Sample records for normal brainstem diameters

  1. Long-term survival of an infant with diffuse brainstem lesion diagnosed by prenatal MRI: a case report and review of the literature.

    PubMed

    Suo-Palosaari, M; Rantala, H; Lehtinen, S; Kumpulainen, T; Salokorpi, N

    2016-06-01

    We describe a unique case of expansive diffuse brainstem lesion diagnosed prenatally by magnetic resonance imaging (MRI) with long-term survival. Findings of fetal and postpartum MRI were highly consistent with the characteristics of diffuse brainstem glioma. Diagnosis was based on the features of MRI, and histopathology was not confirmed by biopsy. Although the prognosis of diffuse brainstem tumor is usually poor, this child was asymptomatic at birth and the neurological condition is still normal at 4 years of age without any treatment. During routine imaging follow-up, diameters of the expansion have remained stable, while the size of the lesion compared to the posterior fossa size has diminished. In addition to brainstem tumor, a skin lesion of the back was observed and MRI of the thoracic spine showed a large asymptomatic extradural cystic lesion suggesting an arachnoid cyst. The pontine tumor of this infant, in agreement with a few previously reported cases, suggests a subgroup of beneficial outcome of expansive diffuse brainstem lesions, particularly in the neonatal period. In this article, we discuss the prognosis and characteristics of pediatric brainstem tumors and differential diagnosis of neonatal brainstem lesions.

  2. Age-Related Changes and Reference Values of Bicaudate Ratio and Sagittal Brainstem Diameters on MRI.

    PubMed

    Garbade, Sven F; Boy, Nikolas; Heringer, Jana; Kölker, Stefan; Harting, Inga

    2018-06-05

    Cranial magnetic resonance imaging (MRI) plays an important role in the diagnosis of neurometabolic diseases, and, in addition, temporal patterns of signal and volume changes allow insight into the underlying pathogenesis. While assessment of volume changes by visual inspection is subjective, volumetric approaches are often not feasible with rare neurometabolic diseases, where MRIs are often acquired with different scanners and protocols. Linear surrogate parameters of brain volume, for example, the bicaudate ratio, present a robust alternative that can be derived from standard imaging sequences. Due to the continuing postnatal brain and skull development and later brain involution, it is, however, necessary to compare patient values with age age-adapted normal values.In this article, we present age-dependent normal values derived from 993 standard scans of patients with normal MRI findings (age range: 0-80 years; mean = 19.9; median = 12.8 years) for bicaudate ratio as a measure of global supratentorial volume, as well as the maximal anteroposterior diameters of mesencephalon, pons, and medulla oblongata as parameters of brainstem volume. The provided data allow quantitative, objective assessment of brain volume changes instead of the usually performed visual and therefore subjective assessment. Georg Thieme Verlag KG Stuttgart · New York.

  3. Appearance of fetal posterior fossa at 11-14 weeks in fetuses with Dandy-Walker malformation or chromosomal anomalies.

    PubMed

    Volpe, P; Contro, E; Fanelli, T; Muto, B; Pilu, G; Gentile, M

    2016-06-01

    To describe the sonographic appearance of fetal posterior fossa anatomy at 11-14 weeks of pregnancy and to assess the outcome of fetuses with increased intracranial translucency (IT) and/or brainstem-to-occipital bone (BSOB) diameter. Reference ranges for brainstem (BS), IT and cisterna magna (CM) measurements, BSOB diameter and the BS : BSOB ratio were obtained from the first-trimester ultrasound examination of 233 fetuses with normal postnatal outcome (control group). The intraobserver and interobserver variability of measurements were investigated using 73 stored ultrasound images. In addition, a study group of 17 fetuses with increased IT and/or BSOB diameter was selected to assess outcome. No significant intraobserver or interobserver variability was found for any measurement in the control group. In the study group, IT was increased in all cases and BSOB diameter was above the 95(th) centile of the calculated normal range in all but two (88%) cases. In 13/17 study cases, only two of the three posterior brain spaces were recognized on ultrasound. These 13 fetuses had a larger BSOB diameter than did the four cases that showed all three posterior brain spaces, and had severe associated anomalies including Dandy-Walker malformation (DWM) and/or chromosomal anomalies. Visualization of the fetal posterior fossa anatomy at 11-14 weeks' gestation is feasible. Increased fluid in the posterior brain at 11-14 weeks, particularly in the case of non-visibility of the septation that divides the future fourth ventricle from the CM, is an important risk factor for cystic posterior fossa malformations, in particular DWM, and/or chromosomal aberrations. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  4. Brainstem timing: implications for cortical processing and literacy.

    PubMed

    Banai, Karen; Nicol, Trent; Zecker, Steven G; Kraus, Nina

    2005-10-26

    The search for a unique biological marker of language-based learning disabilities has so far yielded inconclusive findings. Previous studies have shown a plethora of auditory processing deficits in learning disabilities at both the perceptual and physiological levels. In this study, we investigated the association among brainstem timing, cortical processing of stimulus differences, and literacy skills. To that end, brainstem timing and cortical sensitivity to acoustic change [mismatch negativity (MMN)] were measured in a group of children with learning disabilities and normal-learning children. The learning-disabled (LD) group was further divided into two subgroups with normal and abnormal brainstem timing. MMNs, literacy, and cognitive abilities were compared among the three groups. LD individuals with abnormal brainstem timing were more likely to show reduced processing of acoustic change at the cortical level compared with both normal-learning individuals and LD individuals with normal brainstem timing. This group was also characterized by a more severe form of learning disability manifested by poorer reading, listening comprehension, and general cognitive ability. We conclude that abnormal brainstem timing in learning disabilities is related to higher incidence of reduced cortical sensitivity to acoustic change and to deficient literacy skills. These findings suggest that abnormal brainstem timing may serve as a reliable marker of a subgroup of individuals with learning disabilities. They also suggest that faulty mechanisms of neural timing at the brainstem may be the biological basis of malfunction in this group.

  5. Auditory Brainstem Responses in Childhood Psychosis.

    ERIC Educational Resources Information Center

    Gillberg, Christopher; And Others

    1983-01-01

    Auditory brainstem responses (ABR) were compared in 24 autistic children, seven children with other childhood psychoses, and 31 normal children. One-third of the autistic Ss showed abnormal ABR indicating brainstem dysfunction and correlating with muscular hypotonia and severe language impairment. Ss with other psychoses and normal Ss showed…

  6. Brainstem Auditory Evoked Potential Study in Children with Autistic Disorder.

    ERIC Educational Resources Information Center

    Wong, Virginia; Wong, Sik Nin

    1991-01-01

    Brainstem auditory evoked potentials were compared in 109 children with infantile autism, 38 with autistic condition, 19 with mental retardation, and 20 normal children. Children with infantile autism or autistic condition had significantly longer brainstem transmission time than normal children suggesting neurological damage as the basis of…

  7. Noise-induced tinnitus: auditory evoked potential in symptomatic and asymptomatic patients.

    PubMed

    Santos-Filha, Valdete Alves Valentins dos; Samelli, Alessandra Giannella; Matas, Carla Gentile

    2014-07-01

    We evaluated the central auditory pathways in workers with noise-induced tinnitus with normal hearing thresholds, compared the auditory brainstem response results in groups with and without tinnitus and correlated the tinnitus location to the auditory brainstem response findings in individuals with a history of occupational noise exposure. Sixty individuals participated in the study and the following procedures were performed: anamnesis, immittance measures, pure-tone air conduction thresholds at all frequencies between 0.25-8 kHz and auditory brainstem response. The mean auditory brainstem response latencies were lower in the Control group than in the Tinnitus group, but no significant differences between the groups were observed. Qualitative analysis showed more alterations in the lower brainstem in the Tinnitus group. The strongest relationship between tinnitus location and auditory brainstem response alterations was detected in individuals with bilateral tinnitus and bilateral auditory brainstem response alterations compared with patients with unilateral alterations. Our findings suggest the occurrence of a possible dysfunction in the central auditory nervous system (brainstem) in individuals with noise-induced tinnitus and a normal hearing threshold.

  8. Quantitative Magnetic Resonance Diffusion-Weighted Imaging Evaluation of the Supratentorial Brain Regions in Patients Diagnosed with Brainstem Variant of Posterior Reversible Encephalopathy Syndrome: A Preliminary Study.

    PubMed

    Chen, Tai-Yuan; Wu, Te-Chang; Ko, Ching-Chung; Feng, I-Jung; Tsui, Yu-Kun; Lin, Chien-Jen; Chen, Jeon-Hor; Lin, Ching-Po

    2017-07-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity with several causes, characterized by rapid onset of symptoms and typical neuroimaging features, which usually resolve if promptly recognized and treated. Brainstem variant of PRES presents with vasogenic edema in brainstem regions on magnetic resonance (MR) images and there is sparing of the supratentorial regions. Because PRES is usually caused by a hypertensive crisis, which would likely have a systemic effect and global manifestations on the brain tissue, we thus proposed that some microscopic abnormalities of the supratentorial regions could be detected with diffusion-weighted imaging (DWI) using apparent diffusion coefficient (ADC) analysis in brainstem variant of PRES and hypothesized that "normal-looking" supratentorial regions will increase water diffusion. We retrospectively identified patients with PRES who underwent brain magnetic resonance imaging studies. We identified 11 brainstem variants of PRES patients, who formed the study cohort, and 11 typical PRES patients and 20 normal control subjects as the comparison cohorts for this study. Nineteen regions of interest were drawn and systematically placed. The mean ADC values were measured and compared among these 3 groups. ADC values of the typical PRES group were consistently elevated compared with those in normal control subjects. ADC values of the brainstem variant group were consistently elevated compared with those in normal control subjects. ADC values of the typical PRES group and brainstem variant group did not differ significantly, except for the pons area. Quantitative MR DWI may aid in the evaluation of supratentorial microscopic abnormalities in brainstem variant of PRES patients. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  9. Narcolepsy: regional cerebral blood flow during sleep and wakefulness

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sakai, F.; Meyer, J.S.; Karacan, I.

    Serial measurements of regional cerebral blood flow were made by the 135Xe inhalation method during the early stages of sleep and wakefulness in eight normal volunteers and 12 patients with narcolepsy. Electroencephalogram, electro-oculogram, and submental electromyogram were recorded simultaneously. In normals, mean hemispheric gray matter blood flow (Fg) during stages I and II sleep was significantly less than waking values. Maximum regional blood flow decreases during sleep occurred in the brainstem-cerebellar, right inferior temporal, and bilateral frontal regions. In patients with narcolepsy, mean hemispheric Fg while awake was 80.5 +- 13 ml per 100 gm brain per minute. During REMmore » sleep, mean hemispheric Fg increased concurrently with large increases in brainstem-cerebellar region flow. During stages I and II sleep without REM, there were significant increases in mean hemispheric Fg and brainstem-cerebellar Fg, just the opposite of changes in normals. In narcolepsy, there appears to be a reversal of normal cerebral deactivation patterns, particularly involving the brainstem, during stages I and II sleep.« less

  10. Susceptibility-weighted imaging of the venous networks around the brain stem.

    PubMed

    Cai, Ming; Zhang, Xiao-Fen; Qiao, Hui-Huang; Lin, Zhong-Xiao; Ren, Chuan-Gen; Li, Jian-Ce; Chen, Cheng-Chun; Zhang, Nu

    2015-02-01

    The venous network of the brainstem is complex and significant. Susceptibility-weighted imaging (SWI) is a practical technique which is sensitive to veins, especially tiny veins. Our purpose of this study was to evaluate the visualization of the venous network of brainstem by using SWI at 3.0 T. The occurrence rate of each superficial veins of brainstem was evaluated by using SWI on a 3 T MR imaging system in 60 volunteers. The diameter of the lateral mesencephalic vein and peduncular vein were measured by SWI using the reconstructed mIP images in the sagittal view. And the outflow of the veins of brainstem were studied and described according to the reconstructed images. The median anterior pontomesencephalic vein, median anterior medullary vein, peduncular vein, right vein of the pontomesencephalic sulcus, and right lateral anterior pontomesencephalic vein were detected in all the subjects (100%). The outer diameter of peduncular vein was 1.38 ± 0.26 mm (range 0.8-1.8 mm). The lateral mesencephalic vein was found in 75% of the subjects and the mean outer diameter was 0.81 ± 0.2 mm (range 0.5-1.2 mm). The inner veins of mesencephalon were found by using SWI. The venous networks around the brain stem can be visualized by SWI clearly. This result can not only provide data for anatomical study, but also may be available for the surgical planning in the infratentorial region.

  11. [Ultrasound measurement of fetal posterior fossa at 11 to 13⁺⁶ gestational weeks for screening open spina bifida].

    PubMed

    Qin, Feng-Zhen; Li, Sheng-Li; Wen, Hua-Xuan; Ouyang, Yu-Rong; Zheng, Qiong; Bi, Jing-Ru

    2014-06-01

    To establish the normal reference ranges of transabdominal ultrasound measurements of the posterior fossa structure in fetuses at 11 to 13⁺⁶ gestational weeks and explore their clinical value in screening open spina bifida (OSB). Between January, 2013 and September, 541 randomly selected normal fetuses underwent nuchal translucency at the gestational age 11 to 13⁺⁶ weeks. The parameters of the posterior fossa were measured in mid-sagittal view of the fetal face and the axial view of the transverse cerebellum insonated through the anterior fontanel by transabdominal ultrasound to establish the normal reference ranges. The measurements were obtained from 3 fetuses with OSB for comparison with the reference ranges. In normal fetuses, the parameters of the posterior fossa measured in the two views showed no significant differences (P>0.05). Two high echogenic lines were observed in normal fetuses, as compared with one in fetuses with OSB representing the posterior border of the brain stem and the anterior border of the fourth ventricle. The line between the posterior border of the fourth ventricle and the anterior border of the cisterna magna was not displayed in fetuses with OSB. The anteroposterior diameters of the brain stem, the fourth ventricle, and cisterna magna all increased in positive correlation with the crown-lump length in normal fetuses. In the 3 OSB fetuses, the anteroposterior diameter of the brain stem exceeded the 95th percentile and the anteroposterior diameter of fourth ventrical-cisterner magena was below the 5th percentile of the reference range for CRL; the brain stem to fourth ventrical-cisterner magena anteroposterior diameter ratio was increased to above 1. The established normal reference ranges of the parameters of fetal posterior fossa may provide assistance in early OSB detection. The absence of the posterior border of the fourth ventricle and the anterior border of the cisterna magna and a brainstem to fourth ventrical-cisterner magena anteroposterior diameter ratio greater than 1 can be indicative of OSB at 11 to 13⁺⁶ gestational weeks.

  12. The Theoretical Distribution of Evoked Brainstem Activity in Preterm, High-Risk, and Healthy Infants.

    ERIC Educational Resources Information Center

    Salamy, A.

    1981-01-01

    Determines the frequency distribution of Brainstem Auditory Evoked Potential variables (BAEP) for premature babies at different stages of development--normal newborns, infants, young children, and adults. The author concludes that the assumption of normality underlying most "standard" statistical analyses can be met for many BAEP…

  13. Loss of pons-to-hypothalamic white matter tracks in brainstem obesity.

    PubMed

    Purnell, J Q; Lahna, D L; Samuels, M H; Rooney, W D; Hoffman, W F

    2014-12-01

    Hyperphagia and obesity have been reported following damage to the hypothalamus in humans. Other brain sites are also postulated to be involved in the control of food intake and body weight regulation, such as the amygdala and brainstem. The brainstem, however, is thought to primarily integrate short-term meal-related signals but not affect long-term alterations in body weight, which is controlled by higher centers. The objective of this study was to identify structural pathways damaged in a patient with a brainstem cavernoma who experienced sudden onset of hyperphagia and >50 kg weight gain in <1 year following surgical drainage via a midline suboccipital craniotomy. Diffusion tensor imaging revealed loss of nerve fiber connections between her brainstem, hypothalamus and higher brain centers with preservation of motor tracks. Imaging and endocrine testing confirmed normal hypothalamic structure and function. Gastric bypass surgery restored normal appetite and body weight to baseline. This is the first report of 'brainstem obesity' and adds to the brain regions that can determine the long-term body weight set point in humans.

  14. Neurophysiological aspects of brainstem processing of speech stimuli in audiometric-normal geriatric population.

    PubMed

    Ansari, M S; Rangasayee, R; Ansari, M A H

    2017-03-01

    Poor auditory speech perception in geriatrics is attributable to neural de-synchronisation due to structural and degenerative changes of ageing auditory pathways. The speech-evoked auditory brainstem response may be useful for detecting alterations that cause loss of speech discrimination. Therefore, this study aimed to compare the speech-evoked auditory brainstem response in adult and geriatric populations with normal hearing. The auditory brainstem responses to click sounds and to a 40 ms speech sound (the Hindi phoneme |da|) were compared in 25 young adults and 25 geriatric people with normal hearing. The latencies and amplitudes of transient peaks representing neural responses to the onset, offset and sustained portions of the speech stimulus in quiet and noisy conditions were recorded. The older group had significantly smaller amplitudes and longer latencies for the onset and offset responses to |da| in noisy conditions. Stimulus-to-response times were longer and the spectral amplitude of the sustained portion of the stimulus was reduced. The overall stimulus level caused significant shifts in latency across the entire speech-evoked auditory brainstem response in the older group. The reduction in neural speech processing in older adults suggests diminished subcortical responsiveness to acoustically dynamic spectral cues. However, further investigations are needed to encode temporal cues at the brainstem level and determine their relationship to speech perception for developing a routine tool for clinical decision-making.

  15. Dense TRPV2 immunoreactivity defines a subset of motoneurons in the dorsal lateral nucleus of the spinal cord, the nucleus ambiguus and the trigeminal motor nucleus in rat

    PubMed Central

    LeWinter, Robin D.; Scherrer, Grégory; Basbaum, Allan I.

    2008-01-01

    The transient receptor potential cation channel TRPV2 is a member of the TRPV family of proteins and is a homologue of the capsaicin/vanilloid receptor (TRPV1). Like TRPV1, TRPV2 is expressed in a subset of dorsal root ganglia (DRG) neurons that project to superficial laminae of the spinal cord dorsal horn. Because noxious heat (>52°C) activates TRPV2 in transfected cells this channel has been implicated in the processing of high intensity thermal pain messages in vivo. In contrast to TRPV1, however, which is restricted to small diameter DRG neurons, there is significant TRPV2 immunoreactivity in a variety of CNS regions. The present report focuses on a subset of neurons in the brainstem and spinal cord of the rat including the dorsal lateral nucleus (DLN) of the spinal cord, the nucleus ambiguus, and the motor trigeminal nucleus. Double label immunocytochemistry with markers of motoneurons, combined with retrograde labeling, established that these cells are, in fact, motoneurons. With the exception of their smaller diameter, these cells did not differ from other motoneurons, which are only lightly TRPV2-immunoreactive. As for the majority of DLN neurons, the densely-labeled populations co-express androgen receptor and follow normal DLN ontogeny. The functional significance of the very intense TRPV2 expression in these three distinct spinal cord and brainstem motoneurons groups remains to be determined. PMID:18063314

  16. Prospective detection of open spina bifida at 11-13 weeks by assessing intracranial translucency and posterior brain.

    PubMed

    Chaoui, R; Benoit, B; Heling, K S; Kagan, K O; Pietzsch, V; Sarut Lopez, A; Tekesin, I; Karl, K

    2011-12-01

    We describe a case series of six fetuses with open spina bifida (OSB) from four different prenatal units, where the anomaly was detected at the routine 11-13-week ultrasound examination. Crown-rump length ranged from 49 to 78 mm. All cases were first suspected during nuchal translucency thickness measurement in the mid-sagittal plane of the face. OSB was lumbosacral in five fetuses and cervical in one. The intracranial translucency (IT) was obliterated in two cases, but some fluid was found in the other four cases. However, in all cases the typical landmarks of a normal posterior brain and normal IT were absent. In all six cases the ratio of brainstem diameter to brainstem-occipital bone distance was increased (≥ 1). This detection of an abnormal posterior brain led to a targeted examination and detection of the spinal lesion during the same examination in five cases, whereas in one suspicious case the patient was recalled at 17 weeks, when the abnormality was detected. Two fetuses had both multiple anomalies and trisomy 18. These prospective cases demonstrate the feasibility of using the standard mid-sagittal plane commonly used for NT measurement to assess the IT and the posterior brain and to determine the presence of OSB during NT screening. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

  17. Auditory Brainstem Response Thresholds to Air- and Bone-Conducted CE-Chirps in Neonates and Adults

    ERIC Educational Resources Information Center

    Cobb, Kensi M.; Stuart, Andrew

    2016-01-01

    Purpose The purpose of this study was to compare auditory brainstem response (ABR) thresholds to air- and bone-conducted CE-Chirps in neonates and adults. Method Thirty-two neonates with no physical or neurologic challenges and 20 adults with normal hearing participated. ABRs were acquired with a starting intensity of 30 dB normal hearing level…

  18. Binaural fusion and listening effort in children who use bilateral cochlear implants: a psychoacoustic and pupillometric study.

    PubMed

    Steel, Morrison M; Papsin, Blake C; Gordon, Karen A

    2015-01-01

    Bilateral cochlear implants aim to provide hearing to both ears for children who are deaf and promote binaural/spatial hearing. Benefits are limited by mismatched devices and unilaterally-driven development which could compromise the normal integration of left and right ear input. We thus asked whether children hear a fused image (ie. 1 vs 2 sounds) from their bilateral implants and if this "binaural fusion" reduces listening effort. Binaural fusion was assessed by asking 25 deaf children with cochlear implants and 24 peers with normal hearing whether they heard one or two sounds when listening to bilaterally presented acoustic click-trains/electric pulses (250 Hz trains of 36 ms presented at 1 Hz). Reaction times and pupillary changes were recorded simultaneously to measure listening effort. Bilaterally implanted children heard one image of bilateral input less frequently than normal hearing peers, particularly when intensity levels on each side were balanced. Binaural fusion declined as brainstem asymmetries increased and age at implantation decreased. Children implanted later had access to acoustic input prior to implantation due to progressive deterioration of hearing. Increases in both pupil diameter and reaction time occurred as perception of binaural fusion decreased. Results indicate that, without binaural level cues, children have difficulty fusing input from their bilateral implants to perceive one sound which costs them increased listening effort. Brainstem asymmetries exacerbate this issue. By contrast, later implantation, reflecting longer access to bilateral acoustic hearing, may have supported development of auditory pathways underlying binaural fusion. Improved integration of bilateral cochlear implant signals for children is required to improve their binaural hearing.

  19. Cortical auditory evoked potentials in the assessment of auditory neuropathy: two case studies.

    PubMed

    Pearce, Wendy; Golding, Maryanne; Dillon, Harvey

    2007-05-01

    Infants with auditory neuropathy and possible hearing impairment are being identified at very young ages through the implementation of hearing screening programs. The diagnosis is commonly based on evidence of normal cochlear function but abnormal brainstem function. This lack of normal brainstem function is highly problematic when prescribing amplification in young infants because prescriptive formulae require the input of hearing thresholds that are normally estimated from auditory brainstem responses to tonal stimuli. Without this information, there is great uncertainty surrounding the final fitting. Cortical auditory evoked potentials may, however, still be evident and reliably recorded to speech stimuli presented at conversational levels. The case studies of two infants are presented that demonstrate how these higher order electrophysiological responses may be utilized in the audiological management of some infants with auditory neuropathy.

  20. Magnetic resonance imaging differential diagnosis of brainstem lesions in children

    PubMed Central

    Quattrocchi, Carlo Cosimo; Errante, Yuri; Rossi Espagnet, Maria Camilla; Galassi, Stefania; Della Sala, Sabino Walter; Bernardi, Bruno; Fariello, Giuseppe; Longo, Daniela

    2016-01-01

    Differential diagnosis of brainstem lesions, either isolated or in association with cerebellar and supra-tentorial lesions, can be challenging. Knowledge of the structural organization is crucial for the differential diagnosis and establishment of prognosis of pathologies with involvement of the brainstem. Familiarity with the location of the lesions in the brainstem is essential, especially in the pediatric population. Magnetic resonance imaging (MRI) is the most sensitive and specific imaging technique for diagnosing disorders of the posterior fossa and, particularly, the brainstem. High magnetic static field MRI allows detailed visualization of the morphology, signal intensity and metabolic content of the brainstem nuclei, together with visualization of the normal development and myelination. In this pictorial essay we review the brainstem pathology in pediatric patients and consider the MR imaging patterns that may help the radiologist to differentiate among vascular, toxico-metabolic, infective-inflammatory, degenerative and neoplastic processes. Helpful MR tips can guide the differential diagnosis: These include the location and morphology of lesions, the brainstem vascularization territories, gray and white matter distribution and tissue selective vulnerability. PMID:26834941

  1. The human auditory brainstem response to running speech reveals a subcortical mechanism for selective attention.

    PubMed

    Forte, Antonio Elia; Etard, Octave; Reichenbach, Tobias

    2017-10-10

    Humans excel at selectively listening to a target speaker in background noise such as competing voices. While the encoding of speech in the auditory cortex is modulated by selective attention, it remains debated whether such modulation occurs already in subcortical auditory structures. Investigating the contribution of the human brainstem to attention has, in particular, been hindered by the tiny amplitude of the brainstem response. Its measurement normally requires a large number of repetitions of the same short sound stimuli, which may lead to a loss of attention and to neural adaptation. Here we develop a mathematical method to measure the auditory brainstem response to running speech, an acoustic stimulus that does not repeat and that has a high ecological validity. We employ this method to assess the brainstem's activity when a subject listens to one of two competing speakers, and show that the brainstem response is consistently modulated by attention.

  2. Binaural Fusion and Listening Effort in Children Who Use Bilateral Cochlear Implants: A Psychoacoustic and Pupillometric Study

    PubMed Central

    Steel, Morrison M.; Papsin, Blake C.; Gordon, Karen A.

    2015-01-01

    Bilateral cochlear implants aim to provide hearing to both ears for children who are deaf and promote binaural/spatial hearing. Benefits are limited by mismatched devices and unilaterally-driven development which could compromise the normal integration of left and right ear input. We thus asked whether children hear a fused image (ie. 1 vs 2 sounds) from their bilateral implants and if this “binaural fusion” reduces listening effort. Binaural fusion was assessed by asking 25 deaf children with cochlear implants and 24 peers with normal hearing whether they heard one or two sounds when listening to bilaterally presented acoustic click-trains/electric pulses (250 Hz trains of 36 ms presented at 1 Hz). Reaction times and pupillary changes were recorded simultaneously to measure listening effort. Bilaterally implanted children heard one image of bilateral input less frequently than normal hearing peers, particularly when intensity levels on each side were balanced. Binaural fusion declined as brainstem asymmetries increased and age at implantation decreased. Children implanted later had access to acoustic input prior to implantation due to progressive deterioration of hearing. Increases in both pupil diameter and reaction time occurred as perception of binaural fusion decreased. Results indicate that, without binaural level cues, children have difficulty fusing input from their bilateral implants to perceive one sound which costs them increased listening effort. Brainstem asymmetries exacerbate this issue. By contrast, later implantation, reflecting longer access to bilateral acoustic hearing, may have supported development of auditory pathways underlying binaural fusion. Improved integration of bilateral cochlear implant signals for children is required to improve their binaural hearing. PMID:25668423

  3. Calcified pilocytic astrocytoma of the medulla mimicking a brainstem "stone".

    PubMed

    Berhouma, M; Jemel, H; Kchir, N

    2008-10-01

    Brainstem gliomas are a heterogeneous group of tumours commonly found in children, comprising about 10% of central nervous system tumours in paediatric patients, but less than 2% in adults. Pilocytic astrocytomas usually involve the midbrain and the medulla, and their surgical resection, when feasible, is generally curative. Thin calcifications can be normally found within low grade gliomas, but densely calcified pilocytic astrocytomas of the brainstem have been only rarely reported. We present the case of a young man presenting with a large brainstem calcification involving the medulla, which was subtotally resected using a posterior suboccipital approach. The definitive pathological diagnosis was calcified pilocytic astrocytoma.

  4. Audiological and electrophysiological evaluation of children with acquired immunodeficiency syndrome (AIDS).

    PubMed

    Matas, Carla Gentile; Leite, Renata Aparecida; Magliaro, Fernanda Cristina Leite; Gonçalves, Isabela Crivellaro

    2006-08-01

    We examined the peripheral auditory system and the auditory brainstem pathway of children with Acquired Immunodeficiency Syndrome (AIDS). One hundred and one children, 51 with AIDS diagnosis and 50 normal children were evaluated. Audiological assessment included immittance measures, pure tone and speech audiometry and auditory brainstem response (ABR). The children with AIDS more frequently had abnormal results than did their matched controls, presenting either peripheral or auditory brainstem impairment. We suggest that AIDS be considered a risk factor for peripheral and/or auditory brainstem disorders. Further research should be carried out to investigate the auditory effects of HIV infection along the auditory pathway.

  5. Brainstem auditory evoked potential wave V latency-intensity function in normal Dalmatian and Beagle puppies.

    PubMed

    Poncelet, L; Coppens, A; Deltenre, P

    2000-01-01

    This study investigated whether Dalmatian puppies with normal hearing bilaterally had the same click-evoked brainstem auditory potential characteristics as age-matched dogs of another breed. Short-latency brainstem auditory potentials evoked by condensation and rarefaction clicks were recorded in 23 1.5- to 2-month-old Dalmatian puppies with normal hearing bilaterally by a qualitative brainstem auditory evoked potential test and in 16 Beagle dogs of the same age. For each stimulus intensity, from 90 dB normal hearing level down to the wave V threshold, the sum of the potentials evoked by the 2 kinds of stimuli were added, giving an equivalent to the alternate click polarity stimulation. The slope of the L segment of the wave V latency-intensity curve was steeper in Dalmatian (-40 +/- 10 micros/dB) than in Beagles (-28 +/- 5 micros/dB, P < .001) puppies. The hearing threshold was lower in the Beagle puppies (P < .05). These results suggest that interbreed differences may exist at the level of cochlear function in this age class. The wave V latency and wave V-wave I latencies differences at high stimulus intensity were different between the groups of puppies (4.3 +/- 0.2 and 2.5 +/- 0.2 milliseconds, respectively, for Beagles; and 4.1 +/- 0.2 and 2.3 +/- 0.2 milliseconds for Dalmatians, P < .05). A different maturation speed of the neural pathways is one possible explanation of this observation.

  6. Dense transient receptor potential cation channel, vanilloid family, type 2 (TRPV2) immunoreactivity defines a subset of motoneurons in the dorsal lateral nucleus of the spinal cord, the nucleus ambiguus and the trigeminal motor nucleus in rat.

    PubMed

    Lewinter, R D; Scherrer, G; Basbaum, A I

    2008-01-02

    The transient receptor potential cation channel, vanilloid family, type 2 (TRPV2) is a member of the TRPV family of proteins and is a homologue of the capsaicin/vanilloid receptor (transient receptor potential cation channel, vanilloid family, type 1, TRPV1). Like TRPV1, TRPV2 is expressed in a subset of dorsal root ganglia (DRG) neurons that project to superficial laminae of the spinal cord dorsal horn. Because noxious heat (>52 degrees C) activates TRPV2 in transfected cells this channel has been implicated in the processing of high intensity thermal pain messages in vivo. In contrast to TRPV1, however, which is restricted to small diameter DRG neurons, there is significant TRPV2 immunoreactivity in a variety of CNS regions. The present report focuses on a subset of neurons in the brainstem and spinal cord of the rat including the dorsal lateral nucleus (DLN) of the spinal cord, the nucleus ambiguus, and the motor trigeminal nucleus. Double label immunocytochemistry with markers of motoneurons, combined with retrograde labeling, established that these cells are, in fact, motoneurons. With the exception of their smaller diameter, these cells did not differ from other motoneurons, which are only lightly TRPV2-immunoreactive. As for the majority of DLN neurons, the densely-labeled populations co-express androgen receptor and follow normal DLN ontogeny. The functional significance of the very intense TRPV2 expression in these three distinct spinal cord and brainstem motoneurons groups remains to be determined.

  7. Reduced auditory efferent activity in childhood selective mutism.

    PubMed

    Bar-Haim, Yair; Henkin, Yael; Ari-Even-Roth, Daphne; Tetin-Schneider, Simona; Hildesheimer, Minka; Muchnik, Chava

    2004-06-01

    Selective mutism is a psychiatric disorder of childhood characterized by consistent inability to speak in specific situations despite the ability to speak normally in others. The objective of this study was to test whether reduced auditory efferent activity, which may have direct bearings on speaking behavior, is compromised in selectively mute children. Participants were 16 children with selective mutism and 16 normally developing control children matched for age and gender. All children were tested for pure-tone audiometry, speech reception thresholds, speech discrimination, middle-ear acoustic reflex thresholds and decay function, transient evoked otoacoustic emission, suppression of transient evoked otoacoustic emission, and auditory brainstem response. Compared with control children, selectively mute children displayed specific deficiencies in auditory efferent activity. These aberrations in efferent activity appear along with normal pure-tone and speech audiometry and normal brainstem transmission as indicated by auditory brainstem response latencies. The diminished auditory efferent activity detected in some children with SM may result in desensitization of their auditory pathways by self-vocalization and in reduced control of masking and distortion of incoming speech sounds. These children may gradually learn to restrict vocalization to the minimal amount possible in contexts that require complex auditory processing.

  8. Auditory Brainstem Evoked Responses in Newborns with Down Syndrome

    ERIC Educational Resources Information Center

    Kittler, Phyllis M.; Phan, Ha T. T.; Gardner, Judith M.; Miroshnichenko, Inna; Gordon, Anne; Karmel, Bernard Z.

    2009-01-01

    Auditory brainstem evoked responses (ABRs) were compared in 15 newborns with Down syndrome and 15 sex-, age-, and weight-matched control newborns. Participants had normal ABRs based upon values specific to 32- to 42-weeks postconceptional age. Although Wave III and Wave V component latencies and the Wave I-III interpeak latency (IPL) were shorter…

  9. Auditory Brainstem Responses from Children Three Months to Three Years of Age: Normal Patterns of Response II.

    ERIC Educational Resources Information Center

    Gorga, Michael P.; And Others

    1989-01-01

    Auditory brainstem responses (ABR) were measured in 535 children from 3 months to 3 years of age. Results suggested that changes in wave V latency with age are due to central (neural) factors and that age-appropriate norms should be used in evaluations of ABR latencies in children. (Author/DB)

  10. Leigh disease with brainstem involvement in complex I deficiency due to assembly factor NDUFAF2 defect.

    PubMed

    Herzer, M; Koch, J; Prokisch, H; Rodenburg, R; Rauscher, C; Radauer, W; Forstner, R; Pilz, P; Rolinski, B; Freisinger, P; Mayr, J A; Sperl, W

    2010-02-01

    Mitochondrial NADH: ubiquinone oxidoreductase (complex I) deficiency accounts for most defects in mitochondrial oxidative phosphorylation. Pathogenic mutations have been described in all 7 mitochondrial and 12 of the 38 nuclear encoded subunits as well as in assembly factors by interfering with the building of the mature enzyme complex within the inner mitochondrial membrane. We now describe a male patient with a novel homozygous stop mutation in the NDUFAF2 gene. The boy presented with severe apnoea and nystagmus. MRI showed brainstem lesions without involvement of basal ganglia and thalamus, plasma lactate was normal or close to normal. He died after a fulminate course within 2 months after the first crisis. Neuropathology verified Leigh disease. We give a synopsis with other reported patients. Within the clinical spectrum of Leigh disease, patients with mutations in NDUFAF2 present with a distinct clinical pattern with predominantly brainstem involvement on MRI. The diagnosis should not be missed in spite of the normal lactate and lack of thalamus and basal ganglia changes on brain MRI.

  11. The Structural Connectome of the Human Central Homeostatic Network.

    PubMed

    Edlow, Brian L; McNab, Jennifer A; Witzel, Thomas; Kinney, Hannah C

    2016-04-01

    Homeostatic adaptations to stress are regulated by interactions between the brainstem and regions of the forebrain, including limbic sites related to respiratory, autonomic, affective, and cognitive processing. Neuroanatomic connections between these homeostatic regions, however, have not been thoroughly identified in the human brain. In this study, we perform diffusion spectrum imaging tractography using the MGH-USC Connectome MRI scanner to visualize structural connections in the human brain linking autonomic and cardiorespiratory nuclei in the midbrain, pons, and medulla oblongata with forebrain sites critical to homeostatic control. Probabilistic tractography analyses in six healthy adults revealed connections between six brainstem nuclei and seven forebrain regions, several over long distances between the caudal medulla and cerebral cortex. The strongest evidence for brainstem-homeostatic forebrain connectivity in this study was between the brainstem midline raphe and the medial temporal lobe. The subiculum and amygdala were the sampled forebrain nodes with the most extensive brainstem connections. Within the human brainstem-homeostatic forebrain connectome, we observed that a lateral forebrain bundle, whose connectivity is distinct from that of rodents and nonhuman primates, is the primary conduit for connections between the brainstem and medial temporal lobe. This study supports the concept that interconnected brainstem and forebrain nodes form an integrated central homeostatic network (CHN) in the human brain. Our findings provide an initial foundation for elucidating the neuroanatomic basis of homeostasis in the normal human brain, as well as for mapping CHN disconnections in patients with disorders of homeostasis, including sudden and unexpected death, and epilepsy.

  12. The Brainstem Switch for Gaze Shifts in Humans

    DTIC Science & Technology

    2001-10-25

    Page 1 of 4 THE BRAINSTEM SWITCH FOR GAZE SHIFTS IN HUMANS A. N. Kumar1, R. J. Leigh1,2, S. Ramat3 Department of 1Biomedical Engineering, Case...omnipause neurons during gaze shifts. Using the scleral search coil technique, eye movements were measured in seven normal subjects, as they made...voluntary, disjunctive gaze shifts comprising saccades and vergence movements. Conjugate oscillations of small amplitude and high frequency were identified

  13. Microsurgical anatomy of the trochlear nerve.

    PubMed

    Joo, Wonil; Rhoton, Albert L

    2015-10-01

    The trochlear nerve is the cranial nerve with the longest intracranial course, but also the thinnest. It is the only nerve that arises from the dorsal surface of the brainstem and decussates in the superior medullary velum. After leaving the dorsal surface of the brainstem, it courses anterolaterally around the lateral surface of the brainstem and then passes anteriorly just beneath the free edge of the tentorium. It passes forward to enter the cavernous sinus, traverses the superior orbital fissure and terminates in the superior oblique muscle in the orbit. Because of its small diameter and its long course, the trochlear nerve can easily be injured during surgical procedures. Therefore, precise knowledge of its surgical anatomy and its neurovascular relationships is essential for approaching and removing complex lesions of the orbit and the middle and posterior fossae safely. This review describes the microsurgical anatomy of the trochlear nerve and is illustrated with pictures involving the nerve and its surrounding connective and neurovascular structures. © 2015 Wiley Periodicals, Inc.

  14. Speech-evoked auditory brainstem responses in children with hearing loss.

    PubMed

    Koravand, Amineh; Al Osman, Rida; Rivest, Véronique; Poulin, Catherine

    2017-08-01

    The main objective of the present study was to investigate subcortical auditory processing in children with sensorineural hearing loss. Auditory Brainstem Responses (ABRs) were recorded using click and speech/da/stimuli. Twenty-five children, aged 6-14 years old, participated in the study: 13 with normal hearing acuity and 12 with sensorineural hearing loss. No significant differences were observed for the click-evoked ABRs between normal hearing and hearing-impaired groups. For the speech-evoked ABRs, no significant differences were found for the latencies of the following responses between the two groups: onset (V and A), transition (C), one of the steady-state wave (F), and offset (O). However, the latency of the steady-state waves (D and E) was significantly longer for the hearing-impaired compared to the normal hearing group. Furthermore, the amplitude of the offset wave O and of the envelope frequency response (EFR) of the speech-evoked ABRs was significantly larger for the hearing-impaired compared to the normal hearing group. Results obtained from the speech-evoked ABRs suggest that children with a mild to moderately-severe sensorineural hearing loss have a specific pattern of subcortical auditory processing. Our results show differences for the speech-evoked ABRs in normal hearing children compared to hearing-impaired children. These results add to the body of the literature on how children with hearing loss process speech at the brainstem level. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Exploring the Relationship between Physiological Measures of Cochlear and Brainstem Function

    PubMed Central

    Dhar, S.; Abel, R.; Hornickel, J.; Nicol, T.; Skoe, E.; Zhao, W.; Kraus, N.

    2009-01-01

    Objective Otoacoustic emissions and the speech-evoked auditory brainstem response are objective indices of peripheral auditory physiology and are used clinically for assessing hearing function. While each measure has been extensively explored, their interdependence and the relationships between them remain relatively unexplored. Methods Distortion product otoacoustic emissions (DPOAE) and speech-evoked auditory brainstem responses (sABR) were recorded from 28 normal-hearing adults. Through correlational analyses, DPOAE characteristics were compared to measures of sABR timing and frequency encoding. Data were organized into two DPOAE (Strength and Structure) and five brainstem (Onset, Spectrotemporal, Harmonics, Envelope Boundary, Pitch) composite measures. Results DPOAE Strength shows significant relationships with sABR Spectrotemporal and Harmonics measures. DPOAE Structure shows significant relationships with sABR Envelope Boundary. Neither DPOAE Strength nor Structure is related to sABR Pitch. Conclusions The results of the present study show that certain aspects of the speech-evoked auditory brainstem responses are related to, or covary with, cochlear function as measured by distortion product otoacoustic emissions. Significance These results form a foundation for future work in clinical populations. Analyzing cochlear and brainstem function in parallel in different clinical populations will provide a more sensitive clinical battery for identifying the locus of different disorders (e.g., language based learning impairments, hearing impairment). PMID:19346159

  16. The Brainstem Tau Cytoskeletal Pathology of Alzheimer's Disease: A Brief Historical Overview and Description of its Anatomical Distribution Pattern, Evolutional Features, Pathogenetic and Clinical Relevance.

    PubMed

    Rüb, Udo; Stratmann, Katharina; Heinsen, Helmut; Turco, Domenico Del; Seidel, Kay; Dunnen, Wilfred den; Korf, Horst-Werner

    2016-01-01

    The human brainstem is involved in the regulation of the sleep/waking cycle and normal sleep architectonics and is crucial for the performance of a variety of somatomotor, vital autonomic, oculomotor, vestibular, auditory, ingestive and somatosensory functions. It harbors the origins of the ascending dopaminergic, cholinergic, noradrenergic, serotonergic systems, as well the home base of the descending serotonergic system. In contrast to the cerebral cortex the affection of the brainstem in Alzheimer's disease (AD) by the neurofibrillary or tau cytoskeletal pathology was recognized only approximately fourty years ago in initial brainstem studies. Detailed pathoanatomical investigations of silver stained or tau immunostained brainstem tissue sections revealed nerve cell loss and prominent ADrelated cytoskeletal changes in the raphe nuclei, locus coeruleus, and in the compact parts of the substantia nigra and pedunculopontine nucleus. An additional conspicuous AD-related cytoskeletal pathology was also detected in the auditory brainstem system of AD patients (i.e. inferior colliculus, superior olive, dorsal cochlear nucleus), in the oculomotor brainstem network (i.e. rostral interstitial nucleus of the medial longitudinal fascicle, Edinger-Westphal nucleus, reticulotegmental nucleus of pons), autonomic system (i.e. central and periaqueductal grays, parabrachial nuclei, gigantocellular reticular nucleus, dorsal motor vagal and solitary nuclei, intermediate reticular zone). The alterations in these brainstem nuclei offered for the first time adequate explanations for a variety of less understood disease symptoms of AD patients: Parkinsonian extrapyramidal motor signs, depression, hallucinations, dysfunctions of the sleep/wake cycle, changes in sleeping patterns, attentional deficits, exaggerated pupil dilatation, autonomic dysfunctions, impairments of horizontal and vertical saccades, dysfunctional smooth pursuits. The very early occurrence of the AD-related cytoskeletal pathology in some of these brainstem nuclei points to a major and strategic role of the brainstem in the induction and brain spread of the AD-related cytoskeletal pathology.

  17. Brainstem transcription of speech is disrupted in children with autism spectrum disorders

    PubMed Central

    Russo, Nicole; Nicol, Trent; Trommer, Barbara; Zecker, Steve; Kraus, Nina

    2009-01-01

    Language impairment is a hallmark of autism spectrum disorders (ASD). The origin of the deficit is poorly understood although deficiencies in auditory processing have been detected in both perception and cortical encoding of speech sounds. Little is known about the processing and transcription of speech sounds at earlier (brainstem) levels or about how background noise may impact this transcription process. Unlike cortical encoding of sounds, brainstem representation preserves stimulus features with a degree of fidelity that enables a direct link between acoustic components of the speech syllable (e.g., onsets) to specific aspects of neural encoding (e.g., waves V and A). We measured brainstem responses to the syllable /da/, in quiet and background noise, in children with and without ASD. Children with ASD exhibited deficits in both the neural synchrony (timing) and phase locking (frequency encoding) of speech sounds, despite normal click-evoked brainstem responses. They also exhibited reduced magnitude and fidelity of speech-evoked responses and inordinate degradation of responses by background noise in comparison to typically developing controls. Neural synchrony in noise was significantly related to measures of core and receptive language ability. These data support the idea that abnormalities in the brainstem processing of speech contribute to the language impairment in ASD. Because it is both passively-elicited and malleable, the speech-evoked brainstem response may serve as a clinical tool to assess auditory processing as well as the effects of auditory training in the ASD population. PMID:19635083

  18. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org; Merchant, Thomas E.; Gajjar, Amar

    Purpose: To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI). Methods and Materials: We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.4-39.6 Gy) and a cumulative dose of 55.8 Gy to the primary site, followed by four cycles of high-dose chemotherapy. Patients with high-grade gliomas (n = 10) received erlotinib during and after irradiation (54-59.4 Gy). Parametricmore » maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and spatially registered to three-dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age-related benchmark for comparison, 37 DTI studies from 20 healthy volunteers, aged 6 to 25 years, were included in the analysis. Results: The median DTI follow-up time was 3.5 years (range, 1.6-5.0 years). The median mean dose to the pons was 56 Gy (range, 7-59 Gy). Three patterns were seen in longitudinal FA and apparent diffusion coefficient changes: (1) a stable or normal developing time trend, (2) initial deviation from normal with subsequent recovery, and (3) progressive deviation without evidence of complete recovery. The maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long-term recovery patterns. Conclusions: Variations existed among individual patients after therapy in longitudinal evolution of brainstem white matter injury and recovery. Early response in brainstem anisotropy may serve as an indicator of the recovery time trend over 5 years after radiation therapy.« less

  19. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ai, H; Zhang, H

    Purpose: To evaluate normal tissue toxicity in patients with head and neck cancer by calculating average survival fraction (SF) and equivalent uniform dose (EUD) for normal tissue cells. Methods: 20 patients with head and neck cancer were included in this study. IMRT plans were generated using EclipseTM treatment planning system by dosimetrist following clinical radiotherapy treatment guidelines. The average SF for three different normal tissue cells of each concerned structure can be calculated from dose spectrum acquired from differential dose volume histogram (DVH) using linear quadratic model. The three types of normal tissues include radiosensitive, moderately radiosensitive and radio-resistant thatmore » represents 70%, 50% and 30% survival fractions, respectively, for a 2-Gy open field. Finally, EUDs for three types of normal tissue of each structure were calculated from average SF. Results: The EUDs of the brainstem, spinal cord, parotid glands, brachial plexus and etc were calculated. Our analysis indicated that the brainstem can absorb as much as 14.3% of prescription dose to the tumor if the cell line is radiosensitive. In addition, as much as 16.1% and 18.3% of prescription dose were absorbed by the brainstem for moderately radiosensitive and radio-resistant cells, respectively. For the spinal cord, the EUDs reached up to 27.6%, 35.0% and 42.9% of prescribed dose for the three types of radiosensitivities respectively. Three types of normal cells for parotid glands can get up to 65.6%, 71.2% and 78.4% of prescription dose, respectively. The maximum EUDs of brachial plexsus were calculated as 75.4%, 76.4% and 76.7% of prescription for three types of normal cell lines. Conclusion: The results indicated that EUD can be used to quantify and evaluate the radiation damage to surrounding normal tissues. Large variation of normal tissue EUDs may come from variation of target volumes and radiation beam orientations among the patients.« less

  20. SU-F-P-25: Dosimetric Changes of Brainstem Caused by Weight Loss During Intensity-Modulated Radiation Therapy for Nasopharyngeal Carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hu, W; Yu, C; Cai, Y

    Purpose: To explore dosimetric effects of brainstem (BS) caused by weight loss during the course of intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC). Methods: Seventy-seven patients who were diagnosed with NPC by pathology biopsy have been enrolled. Every patients should receive weight measurement weekly and three times of computed tomography (CT) scans and replanning, at the 15th and 25th fraction during the treatment, respectively. The vertical diameter at the level of odontoid process (d1) and cervical vertebra 3 (d2) be measured from CT images (Supporting document Figure 1). All IMRT plans were designed by inverse planning with commercial treatmentmore » planning systems (Corvus 6.2 version, NOMOS Corporation). The dose differences between plan and actual delivery were generated to compare. Results: The weight loss was more in week 4–5 (3.21±2.19kg) than in week 1–3 (1.79±1.83kg) (Supporting document Figure 2). The d1 and d2 decreased was more significantly in week 4–5 than week 1–3, 2.83±1.75mm vs. 0.55±0.75mm and 2.98±2.96mm vs. 1.23±2.09mm, respectively. The maximum dose to the brainstem (BS Dmax) and the percentage of brainstem volume receiving ≥50Gy (BS V50) increased more significantly in week 4–5 than week 1–3, −3.02±5.49Gy vs. −1.85 ±4.88Gy and −1.85±4.88% vs. −0.77±3.32%, respectively. The changes of d1 and d2 and the BS-V50 and BS-Dmax were closely related to weight loss (p≤0.001)(Supporting document Table 1). Conclusion: The study results indicate that weight loss leads to the vertical diameter reduction, which results has a close relationship with dose of the brainstem during IMRT of NPC. This study was supported by Zhejiang Provincial Medicine and Health Foundation (2013KYB290) and Research Foundation of Science and Technology Department of Zhejiang Province 2015C33257.« less

  1. Oxidative stress and Na,K-ATPase activity differential regulation in brainstem and forebrain of Wistar Audiogenic rats may lead to increased seizure susceptibility.

    PubMed

    Parreira, Gabriela Machado; Resende, Maria Daniela Aparecida; Garcia, Israel José Pereira; Sartori, Daniela Bueno; Umeoka, Eduardo Henrique de Lima; Godoy, Lívea Dornela; Garcia-Cairasco, Norberto; Barbosa, Leandro Augusto; Santos, Hérica de Lima; Tilelli, Cristiane Queixa

    2018-01-15

    The Wistar Audiogenic Rat (WAR) is a well-characterized seizure-prone, inbred rodent strain that, when acutely stimulated with high-intensity sounds, develops brainstem-dependent tonic-clonic seizures that can evolve to limbic-like, myoclonic (forebrain) seizures when the acoustic stimuli are presented chronically (audiogenic kindling). In order to investigate possible mechanisms underlying WAR susceptibility to seizures, we evaluated Na,K-ATPase activity, Ca-ATPase activity, Mg-ATPase activity, lipid membrane composition and oxidative stress markers in whole forebrain and whole brainstem samples of naïve WAR, as compared to samples from control Wistar rats. We also evaluated the expression levels of α1 and α3 isoforms of Na,K-ATPase in forebrain samples. We observed increased Na,K-ATPase activity in forebrain samples and increased oxidative stress markers (lipid peroxidation, glutathione peroxidase and superoxide dismutase) in brainstem samples of WAR. The Ca-ATPase activity, Mg-ATPase activity, lipid membrane composition and expression levels of α1 and α3 isoforms of Na,K-ATPase were unaltered. In view of previous data showing that the membrane potentials from naïve WAR's neurons are less negative than that from neurons from Wistar rats, we suggest that Na,K-ATPase increased activity might be involved in a compensatory mechanism necessary to maintain WAR's brains normal activity. Additionally, ongoing oxidative stress in the brainstem could bring Na,K-ATPase activity back to normal levels, which may explain why WAR's present increased susceptibility to seizures triggered by high-intensity sound stimulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. The direct pathway from the brainstem reticular formation to the cerebral cortex in the ascending reticular activating system: A diffusion tensor imaging study.

    PubMed

    Jang, Sung Ho; Kwon, Hyeok Gyu

    2015-10-08

    Precise evaluation of the ascending reticular activating system (ARAS) is important for diagnosis, prediction of prognosis, and management of patients with disorders of impaired consciousness. In the current study, we attempted to reconstruct the direct neural pathway between the brainstem reticular formation (RF) and the cerebral cortex in normal subjects, using diffusion tensor imaging (DTI). Forty-one healthy subjects were recruited for this study. DTIs were performed using a sensitivity-encoding head coil at 1.5Tesla with FMRIB Software Library. For connectivity of the brainstem RF, we used two regions of interest (ROIs) for the brainstem RF (seed ROI) and the thalamus and hypothalamus (exclusion ROI). Connectivity was defined as the incidence of connection between the brainstem RF and target brain regions at the threshold of 5 and 50 streamlines. Regarding the thresholds of 5 and 50, the brainstem RF showed high connectivity to the lateral prefrontal cortex (lPFC, 67.1% and 20.7%) and ventromedial prefrontal cortex (vmPFC, 50.0% and 18.3%), respectively. In contrast, the brainstem RF showed low connectivity to the primary motor cortex (31.7% and 3.7%), premotor cortex (24.4% and 3.7%), primary somatosensory cortex (23.2% and 2.4%), orbitofrontal cortex (17.1% and 7.3%), and posterior parietal cortex (12.2% and 0%), respectively. The brainstem RF was mainly connected to the prefrontal cortex, particularly lPFC and vmPFC. We believe that the methodology and results of this study would be useful to clinicians involved in the care of patients with impaired consciousness and researchers in studies of the ARAS. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Central nervous versus total body thermosensitivity of the duck

    NASA Astrophysics Data System (ADS)

    Simon, E.; Martin, R.; Simon-Oppermann, Ch.

    1981-09-01

    Ducks were chronically implanted with thermodes in the POAH region, the lower brainstem or the vertebral canal. At thermoneutral conditions, lowering the temperature of the spinal cord (Tvc) or the lower brainstem (Tmb) stimulated metabolic heat production (M) with a subsequent rise of core temperature (Tc). Lowering the temperature of the POAH region (Thy) induced a fall of Tc due to paradoxical activation of heat defence and, thus, induced slight to moderate general hypothermia depending on the cooling intensity. When Thy was normalized, the hypothermia temporarily stimulated metabolic heat production until Tc was normalized. Cold sensitivity of the entire body, as revealed by the metabolic response to the hypothermia induced by preceding POAH cooling, and cold sensitivity of the spinal cord and the lower brainstem, as revealed by the metabolic response to local cooling, were quantified by calculating the quotient δM/δT from the maximum metabolic response and the experimentally induced drop of Tc, Tmb and Tvc. With lower brainstem cooling δM/δTmbdid not exceed -0.4 W/(kg · ‡C). With spinal cord cooling, δM/δTvc did not exceed -0.6 W/(kg · ‡C). The mean value of δM/δTc after hypothermia induced by POAH cooling was -4.02 W/(kg · ‡C). The results indicate that the cold sensitivity residing in the CNS of ducks represents only a small fraction of the entire cold sensitivity of the body.

  4. Developmental Emergence of Phenotypes in the Auditory Brainstem Nuclei of Fmr1 Knockout Mice

    PubMed Central

    Rotschafer, Sarah E.

    2017-01-01

    Abstract Fragile X syndrome (FXS), the most common monogenic cause of autism, is often associated with hypersensitivity to sound. Several studies have shown abnormalities in the auditory brainstem in FXS; however, the emergence of these auditory phenotypes during development has not been described. Here, we investigated the development of phenotypes in FXS model [Fmr1 knockout (KO)] mice in the ventral cochlear nucleus (VCN), medial nucleus of the trapezoid body (MNTB), and lateral superior olive (LSO). We studied features of the brainstem known to be altered in FXS or Fmr1 KO mice, including cell size and expression of markers for excitatory (VGLUT) and inhibitory (VGAT) synapses. We found that cell size was reduced in the nuclei with different time courses. VCN cell size is normal until after hearing onset, while MNTB and LSO show decreases earlier. VGAT expression was elevated relative to VGLUT in the Fmr1 KO mouse MNTB by P6, before hearing onset. Because glial cells influence development and are altered in FXS, we investigated their emergence in the developing Fmr1 KO brainstem. The number of microglia developed normally in all three nuclei in Fmr1 KO mice, but we found elevated numbers of astrocytes in Fmr1 KO in VCN and LSO at P14. The results indicate that some phenotypes are evident before spontaneous or auditory activity, while others emerge later, and suggest that Fmr1 acts at multiple sites and time points in auditory system development. PMID:29291238

  5. Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects

    PubMed Central

    Schreiner, Simon J.; Liu, Xinyang; Gietl, Anton F.; Wyss, Michael; Steininger, Stefanie C.; Gruber, Esmeralda; Treyer, Valerie; Meier, Irene B.; Kälin, Andrea M.; Leh, Sandra E.; Buck, Alfred; Nitsch, Roger M.; Pruessmann, Klaas P.; Hock, Christoph; Unschuld, Paul G.

    2014-01-01

    Background: Accumulation of amyloid beta (Aβ) may occur during healthy aging and is a risk factor for Alzheimer Disease (AD). While individual Aβ-accumulation can be measured non-invasively using Pittsburgh Compund-B positron emission tomography (PiB-PET), Fluid-attenuated inversion recovery (FLAIR) is a Magnetic Resonance Imaging (MRI) sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR intensity. Methods: Fourteen healthy elderly subjects without known history of cognitive impairment received 11C-PiB-PET for estimation of regional Aβ-load. In addition, whole brain T1-MPRAGE and FLAIR-MRI sequences were acquired at high field strength of 7 Tesla (7T). Volume-normalized intensities of brain regions were assessed by applying an automated subcortical segmentation algorithm for spatial definition of brain structures. Statistical dependence between FLAIR- and PiB-PET intensities was tested using Spearman's rank correlation coefficient (rho), followed by Holm–Bonferroni correction for multiple testing. Results: Neuropsychological testing revealed normal cognitive performance levels in all participants. Mean regional PiB-PET and FLAIR intensities were normally distributed and independent. Significant correlation between volume-normalized PiB-PET signals and FLAIR intensities resulted for Hippocampus (right: rho = 0.86; left: rho = 0.84), Brainstem (rho = 0.85) and left Basal Ganglia vessel region (rho = 0.82). Conclusions: Our finding of a significant relationship between PiB- and FLAIR intensity mainly observable in the Hippocampus and Brainstem, indicates regional Aβ associated tissue-edema in cognitively normal elderly subjects. Further studies including clinical populations are necessary to clarify the relevance of our findings for estimating individual risk for age-related neurodegenerative processes such as AD. PMID:25249977

  6. Loud Music Exposure and Cochlear Synaptopathy in Young Adults: Isolated Auditory Brainstem Response Effects but No Perceptual Consequences.

    PubMed

    Grose, John H; Buss, Emily; Hall, Joseph W

    2017-01-01

    The purpose of this study was to test the hypothesis that listeners with frequent exposure to loud music exhibit deficits in suprathreshold auditory performance consistent with cochlear synaptopathy. Young adults with normal audiograms were recruited who either did ( n = 31) or did not ( n = 30) have a history of frequent attendance at loud music venues where the typical sound levels could be expected to result in temporary threshold shifts. A test battery was administered that comprised three sets of procedures: (a) electrophysiological tests including distortion product otoacoustic emissions, auditory brainstem responses, envelope following responses, and the acoustic change complex evoked by an interaural phase inversion; (b) psychoacoustic tests including temporal modulation detection, spectral modulation detection, and sensitivity to interaural phase; and (c) speech tests including filtered phoneme recognition and speech-in-noise recognition. The results demonstrated that a history of loud music exposure can lead to a profile of peripheral auditory function that is consistent with an interpretation of cochlear synaptopathy in humans, namely, modestly abnormal auditory brainstem response Wave I/Wave V ratios in the presence of normal distortion product otoacoustic emissions and normal audiometric thresholds. However, there were no other electrophysiological, psychophysical, or speech perception effects. The absence of any behavioral effects in suprathreshold sound processing indicated that, even if cochlear synaptopathy is a valid pathophysiological condition in humans, its perceptual sequelae are either too diffuse or too inconsequential to permit a simple differential diagnosis of hidden hearing loss.

  7. Immunohistochemical localization of calcium-binding proteins in the brainstem vestibular nuclei of the jaundiced Gunn rat.

    PubMed

    Shaia, Wayne T; Shapiro, Steven M; Heller, Andrew J; Galiani, David L; Sismanis, Aristides; Spencer, Robert F

    2002-11-01

    Vestibular gaze and postural abnormalities are major sequelae of neonatal hyperbilirubinemia. The sites and cellular effects of bilirubin toxicity in the brainstem vestibular pathway are not easily detected. Since altered intracellular calcium homeostasis may play a role in neuronal cell death, we hypothesized that altered expression of calcium-binding proteins may occur in brainstem vestibular nuclei of the classic animal model of bilirubin neurotoxicity. The expression of the calcium-binding proteins calbindin-D28k and parvalbumin in the brainstem vestibular pathways and cerebellum of homozygous recessive jaundiced (jj) Gunn rats was examined by light microscopy and immunohistochemistry at 18 days postnatally and compared to the findings obtained from age-matched non-jaundiced heterozygous (Nj) littermate controls. Jaundiced animals exhibited decreased parvalbumin immunoreactivity specifically in synaptic inputs to superior, medial, and inferior vestibular nuclei, and to oculomotor and trochlear nuclei, whereas the neurons retained their normal immunoreactivity. Jaundiced animals also demonstrated a decrease in calbindin expression in the lateral vestibular nuclei and a paucity of calbindin-immunoreactive synaptic endings on the somata of Deiters' neurons. The involved regions are related to the control of the vestibulo-ocular and vestibulospinal reflexes. Decreased expression of calcium-binding proteins in brainstem vestibular neurons may relate to the vestibulo-ocular and vestibulospinal dysfunction seen with clinical kernicterus, and may provide a sensitive new way to assess bilirubin toxicity in the vestibular system.

  8. Expression of amyloid-β protein and amyloid-β precursor protein after primary brain-stem injury in rats.

    PubMed

    Yang, Shudong; Sun, Rongchao; Zhou, Zhiyi; Zhou, Jing; Liang, Jiabei; Mu, Huijun

    2014-09-01

    Amyloid-β (Aβ) protein and its precursor, amyloid-β precursor protein (β-APP), have traditionally been used in the diagnosis of Alzheimer disease. Their use in diagnosis of traumatic brain injury by forensic analysis is becoming more widespread. However, to date, no reliable small animal model exists to evaluate these brain injury indicators. To address this, we have studied primary brain-stem injury in rats to assess the appearance of diffuse axonal injury in brain sections and correlate these findings with appearance of Aβ and relative β-APP mRNA levels. Using an EnVision 2-step immunohistochemical staining method to measure axon diameter, we found that there was significant difference in axon diameters within the medulla oblongata and several time points after brain injury, ranging from 3 to 24 hours. In addition, mRNA expression levels of β-APP increased following brain injury, peaking 3 hours following injury and decreasing back to baseline levels by 24 hours after injury. These results suggest that using immunohistochemistry and reverse transcription-polymerase chain reaction to detect changes in Aβ-associated axonal changes and β-APP mRNA levels, respectively, can be useful for the diagnosis of diffuse axonal injury during autopsy at early time points following fatal brain injury.

  9. Why middle-aged listeners have trouble hearing in everyday settings.

    PubMed

    Ruggles, Dorea; Bharadwaj, Hari; Shinn-Cunningham, Barbara G

    2012-08-07

    Anecdotally, middle-aged listeners report difficulty conversing in social settings, even when they have normal audiometric thresholds [1-3]. Moreover, young adult listeners with "normal" hearing vary in their ability to selectively attend to speech amid similar streams of speech. Ignoring age, these individual differences correlate with physiological differences in temporal coding precision present in the auditory brainstem, suggesting that the fidelity of encoding of suprathreshold sound helps explain individual differences [4]. Here, we revisit the conundrum of whether early aging influences an individual's ability to communicate in everyday settings. Although absolute selective attention ability is not predicted by age, reverberant energy interferes more with selective attention as age increases. Breaking the brainstem response down into components corresponding to coding of stimulus fine structure and envelope, we find that age alters which brainstem component predicts performance. Specifically, middle-aged listeners appear to rely heavily on temporal fine structure, which is more disrupted by reverberant energy than temporal envelope structure is. In contrast, the fidelity of envelope cues predicts performance in younger adults. These results hint that temporal envelope cues influence spatial hearing in reverberant settings more than is commonly appreciated and help explain why middle-aged listeners have particular difficulty communicating in daily life. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Genetics Home Reference: horizontal gaze palsy with progressive scoliosis

    MedlinePlus

    ... to track moving objects. Up-and-down (vertical) eye movements are typically normal. In people with HGPPS , an ... the brainstem is the underlying cause of the eye movement abnormalities associated with the disorder. The cause of ...

  11. Comparison of distortion product otoacoustic emissions with auditory brain-stem response for clinical use in neonatal intensive care unit.

    PubMed

    Ochi, A; Yasuhara, A; Kobayashi, Y

    1998-11-01

    This study compares the clinical usefulness of distortion product otoacoustic emissions (DPOAEs) with the auditory brain-stem response (ABR) for neonates in the neonatal intensive care unit for the evaluation of hearing impairment. Both DPOAEs and ABR were performed on 36 neonates (67 ears) on the same day. We defined neonates as having normal hearing when the thresholds of wave V of ABR were < or =45 dB hearing level. (1) We could not obtain DPOAEs at f2 = 977 Hz in neonates with normal hearing because of high noise floors. DPOAE recording time was 36 min shorter than that of ABR. (2) We defined as normal DPOAEs, the number of frequencies which showed the DPgram-noise floor > or =4 dB was > or =4 at 6 f2 frequencies, from 1416 Hz to 7959 Hz. (3) Normal thresholds of ABR and normal DPOAEs showed the same percentages, i.e. 68.7%, but the percentage of different results between ABR and DPOAEs was 6.0%. Our study indicates that DPOAEs represent a simple procedure, which can be easily performed in the NICU to obtain reliable results in high-risk neonates. Results obtained by DPOAEs were comparable to those obtained by the more complex procedure of ABR.

  12. Basilar artery hypoplasia associated with changes of brainstem potential, transcranial Doppler and perfusion-weighted imaging.

    PubMed

    Zhang, Dao Pei; Yin, Suo; Zhang, Shu Ling; Zhang, Jie Wen; Ma, Qian Kun; Lu, Gui Feng

    2017-07-01

    The aim of this study was to observe brainstem hemodynamic alterations associated with basilar artery hypoplasia (BAH). Nine hundred and fifty-two consecutive patients received emergency multimodal computed tomography; magnetic resonance imaging and magnetic resonance angiogram during the period of January 2011 to December 2014 were included. The vascular risk factors, brainstem auditory evoked potential (BAEP), blink reflex (BR), transcranial Doppler (TCD) and dynamic susceptibility contrast-enhanced perfusion-weighted imaging were completed. There was significant difference in the abnormal rates of TCD and BAEP between BAH and non-BAH patients. A positive correlation between basilar artery diameter and systolic velocity among BAH patients was suggested. V-wave value was used to predict posterior circulation infarction (PCI) with the sensitivity of 0.933 and specificity of 0.50 with the cutoff value of 5.97 s. Abnormal BR rate was also significantly different in BAH and non-BAH patients. The latency of R2 was used to predict PCI with the sensitivity of 0.933 and specificity of 0.50 with the cutoff value of 46.4 ms. The incidence of hypoperfusion was higher in BAH than non-BAH group and it was significant difference. BAH is closely associated with hemodynamic alterations within the pons, which might contribute to vascular vertigo due to regional hypoperfusion.

  13. Audiological characteristics of infants with abnormal transient evoked otoacoustic emission and normal auditory brainstem response.

    PubMed

    Huang, Lihui; Han, Demin; Guo, Ying; Liu, Sha; Cui, Xiaoyan; Mo, Lingyan; Qi, Beier; Cai, Zhenghua; Liu, Hui; En, Hui; Guo, Liansheng

    2008-10-01

    Audiological characteristics were investigated in 81 ears of 53 infants with abnormal transient evoked otoacoustic emission (TEOAE) and normal auditory brainstem response (ABR). The relationship between ABR and other hearing testing methods, including 40Hz auditory event-related potential (40Hz-AERP), auditory steady state response (ASSR), distortion product otoacoustic emission (DPOAE), tympanometry, and acoustic reflex, was analyzed. Of the 81 ears, 18 ears (22.2%) were normal, while 63 ears (77.8%) were abnormal according to the tests. Testing of the 40 Hz AERP (36 ears) and ASSR (45 ears) revealed that 14 ears (38.9%) and 27 ears (60.0%) were abnormal, respectively. Testing of DPOAE in 68 ears revealed that 50 ears (73.5%) were abnormal. Testing of tympanometry in 50 ears and acoustic reflex in 47 ears revealed that 9 ears (18%) and 27 ears (57.4%) were abnormal, respectively. The present data suggests that the hearing of infants cannot be sufficiently evaluated with ABR only and that it must be evaluated with integrative audiological testing methods.

  14. Brainstem dysfunction protects against syncope in multiple sclerosis.

    PubMed

    Habek, Mario; Krbot Skorić, Magdalena; Crnošija, Luka; Adamec, Ivan

    2015-10-15

    The aim of this study was to investigate the correlation between autonomic dysfunction in multiple sclerosis (MS) and brainstem dysfunction evaluated with the vestibular evoked myogenic potentials (VEMP) score and conventional MRI. Forty-five patients with the diagnosis of clinically isolated syndrome (CIS) suggestive of MS were enrolled. VEMP, heart rate, and blood pressure responses to the Valsalva maneuver, heart rate response to deep breathing, and pain provoked head-up tilt table test, as well as brain and spinal cord MRI were performed. There was no difference in the VEMP score between patients with and without signs of sympathetic or parasympathetic dysfunction. However, patients with syncope had significantly lower VEMP score compared to patients without syncope (p<0.01). Patients with orthostatic hypotension (OH) showed a trend of higher VEMP score compared to patients without OH (p=0.06). There was no difference in the presence of lesions in the brainstem or cervical spinal cord between patients with or without any of the studied autonomic parameters. The model consisting of a VEMP score of ≤5 and normal MRI of the midbrain and cervical spinal cord has sensitivity and specificity of 83% for the possibility that the patient with MS can develop syncope. Pathophysiological mechanisms underlying functional and structural disorders of autonomic nervous system in MS differ significantly. While preserved brainstem function is needed for development of syncope, structural disorders like OH could be associated with brainstem dysfunction. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Delayed rotation of the cerebellar vermis: a pitfall in early second-trimester fetal magnetic resonance imaging.

    PubMed

    Pinto, J; Paladini, D; Severino, M; Morana, G; Pais, R; Martinetti, C; Rossi, A

    2016-07-01

    We describe two cases in which delayed rotation of the cerebellar vermis simulated a Dandy-Walker malformation (DWM) on early second-trimester magnetic resonance imaging (MRI). Two pregnant women with suspected fetal posterior fossa anomaly on ultrasound examination underwent fetal MRI at 21 (Case 1) and 19 (Case 2) weeks' gestation. In both cases, upward rotation of the cerebellar vermis was noted; on midsagittal imaging, the brainstem-vermis angle was 28° and 43°, respectively, while cerebellar morphometry showed a reduced vermian anteroposterior diameter compared to reference data. The posterior fossa appeared to be mildly enlarged, while all other findings were normal. Follow-up MRI at 28 + 3 weeks' gestation (Case 1) and at 1 postnatal year (Case 2) showed completely normal findings. Both children had normal psychomotor development and neurological examinations at 1 year of age. Incomplete rotation of the cerebellar vermis can be a physiological finding on early second-trimester fetal MRI examination and can simulate DWM or other forms of cerebellar hypoplasia. Embryologically, delayed permeabilization of Blake's pouch could account for the delayed vermian rotation. Follow-up imaging at a later gestational age is crucial to ensure that this condition is not over-reported and to avoid the potential risk of unnecessary pregnancy interruption. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  16. Are evoked potentials in patients with adult-onset pompe disease indicative of clinically relevant central nervous system involvement?

    PubMed

    Wirsching, Andreas; Müller-Felber, Wolfgang; Schoser, Benedikt

    2014-08-01

    Pompe disease is a multisystem autosomal recessive glycogen storage disease. Autoptic findings in patients with classic infantile and late-onset Pompe disease have proven that accumulation of glycogen can also be found in the peripheral and central nervous system. To assess the functional role of these pathologic findings, multimodal sensory evoked potentials were analyzed. Serial recordings for brainstem auditory, visual, and somatosensory evoked potentials of 11 late-onset Pompe patients were reviewed. Data at the onset of the enzyme replacement therapy with alglucosidase alfa were compared with follow-up recordings at 12 and 24 months. Brainstem auditory evoked potentials showed a delayed peak I in 1/10 patients and an increased I-III and I-V interpeak latency in 1/10 patients, respectively. The III-V interpeak latencies were in the normal range. Visual evoked potentials were completely normal. Median somatosensory evoked potentials showed an extended interpeak latency in 3/9 patients. Wilcoxon tests comparing age-matched subgroups found significant differences in brainstem auditory evoked potentials and visual evoked potentials. We found that the majority of recordings for evoked potentials were within the ranges for standard values, therefore reflecting the lack of clinically relevant central nervous system involvement. Regular surveillance by means of evoked potentials does not seem to be appropriate in late-onset Pompe patients.

  17. Glycosaminoglycan in cerebrum, cerebellum and brainstem of young sheep brain with particular reference to compositional and structural variations of chondroitin-dermatan sulfate and hyaluronan.

    PubMed

    Kilia, Virginia; Skandalis, Spyros S; Theocharis, Achilleas D; Theocharis, Dimitrios A; Karamanos, Nikos K; Papageorgakopoulou, Nickoletta

    2008-09-01

    Recent advances in the structural biology of chondroitin sulfate chains have suggested important biological functions in the development of the brain. Several studies have demonstrated that the composition of chondroitin sulfate chains changes with aging and normal brain maturation. In this study, we determined the concentration of all glycosaminoglycan types, i.e. chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan sulfate, hyaluronan and chondroitin in cerebrum, cerebellum and brainstem of young sheep brain. In all cases, chondroitin sulfate was the predominant glycosaminoglycan type, comprising about 54-58% of total glycosaminoglycans, with hyaluronan being present also in significant amounts of about 19-28%. Of particular interest was the increased presence of the disulfated disaccharides and dermatan sulfate in cerebellum and brainstem, respectively, as well as the detectable and measurable occurrence of chondroitin in young sheep brain. Among the three brain areas, cerebrum was found to be significantly richer in chondroitin sulfate and hyaluronan, two major extracellular matrix components. These findings imply that the extracellular matrix of the cerebrum is different from those of cerebellum and brainstem, and probably this fact is related to the particular histological and functional characteristics of each anatomic area of the brain.

  18. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grantham, K; Santanam, L; Goddu, S

    Purpose: We retrospectively evaluate the dosimetric impact of a 3.5% range uncertainty on CTV coverage and normal organ toxicity for a cohort of brain patients. Methods: Twenty treatment plans involving 20 brain cancer patients treated with Mevions S250 were reviewed. Forty uncertain plans were made by changing the ranges in original plans by ±3.5% while keeping all devices unchanged. Fidelity to the original plans was evaluated with gamma index. Changes in generalized equivalent uniform dose (gEUD) were reported for the following structures: CTV coverage, brainstem, optic chiasm, and optic nerves. Comparisons were made by plotting the relevant endpoints from themore » uncertain plans as a function of the same endpoints from the original clinical plan. Results: Gamma-index analysis resulted in a 50% pass rate of the uncertain plans using a 90% passing rate and 3%/3mm criterion. A 9.5% decrease in the slope of gEUD plot for the CTV was observed for the 3.5% downward range shift. However, the change in slope did not result in a gEUD change greater than 1.1% for the CTV. The slopes of the gEUD plots for normal structures increased by 3.1% 3.9% 2.4% and 0.2% for the chiasm, brainstem, left optic nerve and right optic nerve respectively. The maximum deviation from the gEUD of the clinical plan for normal structures was: 64% in the chiasm, 31% for the brainstem, and 19% for both optic nerves. Conclusion: A retrospective review shows moderate radiobiological impact of range uncertainty in passively scattered proton therapy with sporadic catastrophe. The linear regression analysis on the statistical data indicates a systematic deviation of gEUD from treatment planning in the light of range uncertainty.« less

  19. Interside Latency Differences in Brainstem Auditory and Somatosensory Evoked Potentials. Defining Upper Limits to Determine Asymmetry.

    PubMed

    Moncho, Dulce; Poca, Maria A; Minoves, Teresa; Ferré, Alejandro; Sahuquillo, Juan

    2015-10-01

    Limits of the interside differences are invaluable when interpreting asymmetry in brainstem auditory evoked potentials and somatosensory evoked potentials (SEP) recordings. The aim of this study was to analyze the normal upper limits of interside latency differences of brainstem auditory evoked potentials and SEP from the posterior tibial nerve and median nerve to determine asymmetry. The authors performed a prospective study in 56 healthy subjects aged 15 to 64 years with no neurological or hearing disorders. They analyzed (1) the latencies of I, III, and V waves and I-III, III-V, and I-V intervals and the amplitude ratios V/I and IV/I for brainstem auditory evoked potentials bilaterally; (2) the latencies of N8, N22, N28, and P37 waves and the interval N22-P37 and the amplitude P37 for posterior tibial nerve SEP bilaterally; and (3) the latencies and amplitudes of N9, N13, and N20 waves and N9-N13 and N13-N20 intervals for median nerve SEP bilaterally. The interside differences for these parameters were calculated and analyzed. The authors obtained an upper limit for the interside latency differences from brainstem auditory evoked potentials that was significantly lower than the previously published data. However, the upper limits of interside latency differences for SEP were similar to those previously reported. The findings of this study should be considered when laboratories analyze asymmetry using the normative data published by another center, however temporarily, in organizing new laboratories.

  20. Phrenic nerve deficits and neurological immunopathology associated with acute West Nile virus infection in mice and hamsters.

    PubMed

    Zukor, Katherine; Wang, Hong; Hurst, Brett L; Siddharthan, Venkatraman; Van Wettere, Arnaud; Pilowsky, Paul M; Morrey, John D

    2017-04-01

    Neurological respiratory deficits are serious outcomes of West Nile virus (WNV) disease. WNV patients requiring intubation have a poor prognosis. We previously reported that WNV-infected rodents also appear to have respiratory deficits when assessed by whole-body plethysmography and diaphragmatic electromyography. The purpose of this study was to determine if the nature of the respiratory deficits in WNV-infected rodents is neurological and if deficits are due to a disorder of brainstem respiratory centers, cervical spinal cord (CSC) phrenic motor neuron (PMN) circuitry, or both. We recorded phrenic nerve (PN) activity and found that in WNV-infected mice, PN amplitude is reduced, corroborating a neurological basis for respiratory deficits. These results were associated with a reduction in CSC motor neuron number. We found no dramatic deficits, however, in brainstem-mediated breathing rhythm generation or responses to hypercapnia. PN frequency and pattern parameters were normal, and all PN parameters changed appropriately upon a CO 2 challenge. Histological analysis revealed generalized microglia activation, astrocyte reactivity, T cell and neutrophil infiltration, and mild histopathologic lesions in both the brainstem and CSC, but none of these were tightly correlated with PN function. Similar results in PN activity, brainstem function, motor neuron number, and histopathology were seen in WNV-infected hamsters, except that histopathologic lesions were more severe. Taken together, the results suggest that respiratory deficits in acute WNV infection are primarily due to a lower motor neuron disorder affecting PMNs and the PN rather than a brainstem disorder. Future efforts should focus on markers of neuronal dysfunction, axonal degeneration, and myelination.

  1. Auditory brainstem responses of CBA/J mice with neonatal conductive hearing losses and treatment with GM1 ganglioside.

    PubMed

    Money, M K; Pippin, G W; Weaver, K E; Kirsch, J P; Webster, D B

    1995-07-01

    Exogenous administration of GM1 ganglioside to CBA/J mice with a neonatal conductive hearing loss ameliorates the atrophy of spiral ganglion neurons, ventral cochlear nucleus neurons, and ventral cochlear nucleus volume. The present investigation demonstrates the extent of a conductive loss caused by atresia and tests the hypothesis that GM1 ganglioside treatment will ameliorate the conductive hearing loss. Auditory brainstem responses were recorded from four groups of seven mice each: two groups received daily subcutaneous injections of saline (one group had normal hearing; the other had a conductive hearing loss); the other two groups received daily subcutaneous injections of GM1 ganglioside (one group had normal hearing; the other had a conductive hearing loss). In mice with a conductive loss, decreases in hearing sensitivity were greatest at high frequencies. The decreases were determined by comparing mean ABR thresholds of the conductive loss mice with those of normal hearing mice. The conductive hearing loss induced in the mice in this study was similar to that seen in humans with congenital aural atresias. GM1 ganglioside treatment had no significant effect on ABR wave I thresholds or latencies in either group.

  2. [Changes in brain serotonin biosynthesis in rats with diabetes mellitus induced by streptozocin: effect of insulin treatment].

    PubMed

    Manjarrez-Gutiérrez, G; Rocío Herrera-Márquez, J R; Bueno-Santoyo, S; González-Ramírez, M; Hernández, J

    2000-01-01

    To investigate if the changes in the activity of the tryptophan-5-hydroxylase and in brain serotonin synthesis provoked by diabetes mellitus persist or return to normal in the diabetic rats submitted to treatment with insulin. Diabetes induced by the administration of streptozotocin in rats and their treatment with insulin was the paradigm used. At days 7, 14 and 21 of evolution, the brain serotonergic biosynthetic activity was evaluated. The diabetic rats showed a significant decrease of body weight. Also, they showed a low concentration of I-tryptophan, as well as a diminution in the activity of the key enzyme tryptophan-5-hydroxylase and its product serotonin in the cerebral cortex and brainstem. Interestingly, the activity of the enzyme was higher in the brainstem from day 14, accompanied with an elevation of the neurotransmitter. The diabetic rats submitted to treatment with insulin showed a complete physical recovery and a return to normal of plasma and brain I-tryptophan. The activity of the enzyme not only normalized but was elevated and with an increase of serotonin in the brainstem and cerebral cortex. The present findings confirm that diabetes mellitus produced a chronic anabolic deficit and a decrease in some brain regions of serotonin synthesis. Also, demonstrate that the diabetic rats under specific treatment with insulin had a complete physical recovery and a return to normal of the serotonin precursor in the blood and brain. However, the activity of the limiting enzyme TrpOH case was elevated with an increase of the neurotransmitter in all regions studied. Since the diabetic animal, insulin treated, does recover metabolically, the mechanism of activation of the serotonin biosynthetic path in the brain may not be dependent on the decreased availability of its precursor the free plasma I-tryptophan. Instead, it might be due to a change in the kinetics of tryptophan-5-hydroxylase, since its activity remains significantly increased in spite of plasma and brain normalization of its substrate. Altogether these changes in the biosynthesis of an important brain neurotransmitter may be of relevance in the pathophysiology of the psychoneurological complications in diabetic patients.

  3. Evaluation of peripheral auditory pathways and brainstem in obstructive sleep apnea.

    PubMed

    Matsumura, Erika; Matas, Carla Gentile; Magliaro, Fernanda Cristina Leite; Pedreño, Raquel Meirelles; Lorenzi-Filho, Geraldo; Sanches, Seisse Gabriela Gandolfi; Carvallo, Renata Mota Mamede

    2016-11-25

    Obstructive sleep apnea causes changes in normal sleep architecture, fragmenting it chronically with intermittent hypoxia, leading to serious health consequences in the long term. It is believed that the occurrence of respiratory events during sleep, such as apnea and hypopnea, can impair the transmission of nerve impulses along the auditory pathway that are highly dependent on the supply of oxygen. However, this association is not well established in the literature. To compare the evaluation of peripheral auditory pathway and brainstem among individuals with and without obstructive sleep apnea. The sample consisted of 38 adult males, mean age of 35.8 (±7.2), divided into four groups matched for age and Body Mass Index. The groups were classified based on polysomnography in: control (n=10), mild obstructive sleep apnea (n=11) moderate obstructive sleep apnea (n=8) and severe obstructive sleep apnea (n=9). All study subjects denied a history of risk for hearing loss and underwent audiometry, tympanometry, acoustic reflex and Brainstem Auditory Evoked Response. Statistical analyses were performed using three-factor ANOVA, 2-factor ANOVA, chi-square test, and Fisher's exact test. The significance level for all tests was 5%. There was no difference between the groups for hearing thresholds, tympanometry and evaluated Brainstem Auditory Evoked Response parameters. An association was observed between the presence of obstructive sleep apnea and changes in absolute latency of wave V (p=0.03). There was an association between moderate obstructive sleep apnea and change of the latency of wave V (p=0.01). The presence of obstructive sleep apnea is associated with changes in nerve conduction of acoustic stimuli in the auditory pathway in the brainstem. The increase in obstructive sleep apnea severity does not promote worsening of responses assessed by audiometry, tympanometry and Brainstem Auditory Evoked Response. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  4. Proton spectroscopy in the narcoleptic syndrome. Is there evidence of a brainstem lesion?

    PubMed

    Ellis, C M; Simmons, A; Lemmens, G; Williams, S C; Parkes, J D

    1998-02-01

    There is controversy regarding the relationship of structural or biochemical brainstem lesions to "idiopathic" narcolepsy. Most cases of the narcoleptic syndrome are considered to be idiopathic because no structural lesion is detectable, although some cases of secondary narcolepsy are known to be associated with no structural brainstem lesions. Using proton spectroscopy, we determined levels of ventral pontine metabolite pools in 12 normal subjects and 12 subjects with idiopathic narcolepsy. REM sleep is generated in ventral pontine areas. Proton spectroscopy was used to study levels of N-acetyl aspartate (NAA) as a marker of cell mass, creatine and phosphocreatine (Cr + PCr), and choline (Cho). The intensity of the peaks, as determined by the area under the peak (AUP), was measured. The AUP correlates with the quantity of chemical present. In this study, the ratios of NAA to Cr + PCr were similar in normal subjects and in narcoleptic subjects with idiopathic narcolepsy. No differences in measured metabolic ratio were observed in subjects who slept during the scan procedure compared with those who remained awake. Subjects with "symptomatic" narcolepsy accompanied by an obvious structural brain lesion were not studied. Proton spectroscopy of the brain initiates a new kind of neurochemistry, allowing the noninvasive study of metabolic pools in the living human brain without the use of any kind of tracer or radioactive molecule. In this study, there was no evidence of cell loss in the ventral pontine areas of subjects with the narcoleptic syndrome.

  5. Deletion of beta-2-microglobulin ameliorates spinal cord lesion load and promotes recovery of brainstem NAA levels in a murine model of multiple sclerosis.

    PubMed

    Denic, Aleksandar; Pirko, Istvan; Wootla, Bharath; Bieber, Allan; Macura, Slobodan; Rodriguez, Moses

    2012-09-01

    We used genetic deletion of β2-microglobulin to study the influence of CD8(+) T cells on spinal cord demyelination, remyelination, axonal loss and brainstem N-acetyl aspartate levels during the acute and chronic phases of Theiler's murine encephalomyelitis virus (TMEV) infection. We used β2m(-/-) and β2m(+/+) B10.Q mice (of H-2(q) background) normally susceptible to TMEV-induced demyelination. Over the disease course, β2m(+/+) mice had increasing levels of demyelination and minimal late-onset remyelination. In contrast, β2m(-/-) mice had steady levels of demyelination from 45-390 dpi and remyelination was extensive and more complete. Early in the disease, brainstem NAA levels drop in both strains, but accordingly with remyelination and axonal preservation, NAA recover in β2m(-/-) mice despite equivalent brainstem pathology. At 270 dpi, β2m(+/+) mice had significantly fewer spinal cord axons than β2m(-/-) mice (up to 28% less). In addition, β2m(+/+) mice lost axons of all calibers, whereas β2m(-/-) mice had a modest loss of only medium- and large-caliber axons. This study further supports the hypothesis that CD8(+) T cells are involved in demyelination, and axonal loss following Theiler's virus-induced demyelination. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

  6. Auditory brainstem response to complex sounds predicts self-reported speech-in-noise performance.

    PubMed

    Anderson, Samira; Parbery-Clark, Alexandra; White-Schwoch, Travis; Kraus, Nina

    2013-02-01

    To compare the ability of the auditory brainstem response to complex sounds (cABR) to predict subjective ratings of speech understanding in noise on the Speech, Spatial, and Qualities of Hearing Scale (SSQ; Gatehouse & Noble, 2004) relative to the predictive ability of the Quick Speech-in-Noise test (QuickSIN; Killion, Niquette, Gudmundsen, Revit, & Banerjee, 2004) and pure-tone hearing thresholds. Participants included 111 middle- to older-age adults (range = 45-78) with audiometric configurations ranging from normal hearing levels to moderate sensorineural hearing loss. In addition to using audiometric testing, the authors also used such evaluation measures as the QuickSIN, the SSQ, and the cABR. Multiple linear regression analysis indicated that the inclusion of brainstem variables in a model with QuickSIN, hearing thresholds, and age accounted for 30% of the variance in the Speech subtest of the SSQ, compared with significantly less variance (19%) when brainstem variables were not included. The authors' results demonstrate the cABR's efficacy for predicting self-reported speech-in-noise perception difficulties. The fact that the cABR predicts more variance in self-reported speech-in-noise (SIN) perception than either the QuickSIN or hearing thresholds indicates that the cABR provides additional insight into an individual's ability to hear in background noise. In addition, the findings underscore the link between the cABR and hearing in noise.

  7. The effect of maternal smoking and drinking during pregnancy upon (3)H-nicotine receptor brainstem binding in infants dying of the sudden infant death syndrome: initial observations in a high risk population.

    PubMed

    Duncan, Jhodie R; Randall, Leslie L; Belliveau, Richard A; Trachtenberg, Felicia L; Randall, Bradley; Habbe, Donald; Mandell, Federick; Welty, Thomas K; Iyasu, Solomon; Kinney, Hannah C

    2008-01-01

    The high rate of the sudden infant death syndrome (SIDS) in American Indians in the Northern Plains (3.5/1000) may reflect the high incidence of cigarette smoking and alcohol consumption during pregnancy. Nicotine, a neurotoxic component of cigarettes, and alcohol adversely affect nicotinic receptor binding and subsequent cholinergic development in animals. We measured (3)H-nicotine receptor binding in 16 brainstem nuclei in American Indian SIDS (n = 27) and controls (n = 6). In five nuclei related to cardiorespiratory control, (3)H-nicotinic binding decreased with increasing number of drinks (P < 0.03). There were no differences in binding in SIDS compared with controls, except upon stratification of prenatal exposures. In three mesopontine nuclei critical for arousal there were reductions (P < 0.04) in binding in controls exposed to cigarette smoke compared with controls without exposure; there was no difference between SIDS cases with or without exposure. This study suggests that maternal smoking and alcohol affects (3)H-nicotinic binding in the infant brainstem irrespective of the cause of death. It also suggests that SIDS cases are unable to respond to maternal smoking with the "normal" reduction seen in controls. Future studies are needed to establish the role of adverse prenatal exposures in altered brainstem neurochemistry in SIDS.

  8. Long-Term Survival of a Patient with Brainstem and Recurrent Brain Metastasis from Stage IV Nonsmall Cell Lung Cancer Treated with Multiple Gamma Knife Radiosurgeries and Craniotomies: A Case Report and Review of the Literature

    PubMed Central

    Lamm, Andrew F.; Elaimy, Ameer L.; Mackay, Alexander R.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.; Taylor, Blake S.; Lamoreaux, Wayne T.

    2012-01-01

    The prognosis of patients diagnosed with stage IV nonsmall cell lung cancer that have brain and brainstem metastasis is very poor, with less than a third surviving a year past their initial date of diagnosis. We present the rare case of a 57-year-old man who is a long-term survivor of brainstem and recurrent brain metastasis, after aggressive treatment. He is now five and a half years out from diagnosis and continues to live a highly functional life without evidence of disease. Four separate Gamma Knife stereotactic radiosurgeries in conjunction with two craniotomies were utilized since his initial diagnosis to treat recurrent brain metastasis while chemoradiation therapy and thoracic surgery were used to treat his primary disease in the right upper lung. In his situation, Gamma Knife radiosurgery proved to be a valuable, safe, and effective tool for the treatment of multiply recurrent brain metastases within critical normal structures. PMID:23056973

  9. The Physiological Basis and Clinical Use of the Binaural Interaction Component of the Auditory Brainstem Response

    PubMed Central

    Klump, Georg M.; Tollin, Daniel J.

    2016-01-01

    The auditory brainstem response (ABR) is a sound-evoked non-invasively measured electrical potential representing the sum of neuronal activity in the auditory brainstem and midbrain. ABR peak amplitudes and latencies are widely used in human and animal auditory research and for clinical screening. The binaural interaction component (BIC) of the ABR stands for the difference between the sum of the monaural ABRs and the ABR obtained with binaural stimulation. The BIC comprises a series of distinct waves, the largest of which (DN1) has been used for evaluating binaural hearing in both normal hearing and hearing-impaired listeners. Based on data from animal and human studies, we discuss the possible anatomical and physiological bases of the BIC (DN1 in particular). The effects of electrode placement and stimulus characteristics on the binaurally evoked ABR are evaluated. We review how inter-aural time and intensity differences affect the BIC and, analyzing these dependencies, draw conclusion about the mechanism underlying the generation of the BIC. Finally, the utility of the BIC for clinical diagnoses are summarized. PMID:27232077

  10. Speech Evoked Auditory Brainstem Response in Stuttering

    PubMed Central

    Tahaei, Ali Akbar; Ashayeri, Hassan; Pourbakht, Akram; Kamali, Mohammad

    2014-01-01

    Auditory processing deficits have been hypothesized as an underlying mechanism for stuttering. Previous studies have demonstrated abnormal responses in subjects with persistent developmental stuttering (PDS) at the higher level of the central auditory system using speech stimuli. Recently, the potential usefulness of speech evoked auditory brainstem responses in central auditory processing disorders has been emphasized. The current study used the speech evoked ABR to investigate the hypothesis that subjects with PDS have specific auditory perceptual dysfunction. Objectives. To determine whether brainstem responses to speech stimuli differ between PDS subjects and normal fluent speakers. Methods. Twenty-five subjects with PDS participated in this study. The speech-ABRs were elicited by the 5-formant synthesized syllable/da/, with duration of 40 ms. Results. There were significant group differences for the onset and offset transient peaks. Subjects with PDS had longer latencies for the onset and offset peaks relative to the control group. Conclusions. Subjects with PDS showed a deficient neural timing in the early stages of the auditory pathway consistent with temporal processing deficits and their abnormal timing may underlie to their disfluency. PMID:25215262

  11. Reference tissue normalization in longitudinal (18)F-florbetapir positron emission tomography of late mild cognitive impairment.

    PubMed

    Shokouhi, Sepideh; Mckay, John W; Baker, Suzanne L; Kang, Hakmook; Brill, Aaron B; Gwirtsman, Harry E; Riddle, William R; Claassen, Daniel O; Rogers, Baxter P

    2016-01-15

    Semiquantitative methods such as the standardized uptake value ratio (SUVR) require normalization of the radiotracer activity to a reference tissue to monitor changes in the accumulation of amyloid-β (Aβ) plaques measured with positron emission tomography (PET). The objective of this study was to evaluate the effect of reference tissue normalization in a test-retest (18)F-florbetapir SUVR study using cerebellar gray matter, white matter (two different segmentation masks), brainstem, and corpus callosum as reference regions. We calculated the correlation between (18)F-florbetapir PET and concurrent cerebrospinal fluid (CSF) Aβ1-42 levels in a late mild cognitive impairment cohort with longitudinal PET and CSF data over the course of 2 years. In addition to conventional SUVR analysis using mean and median values of normalized brain radiotracer activity, we investigated a new image analysis technique-the weighted two-point correlation function (wS2)-to capture potentially more subtle changes in Aβ-PET data. Compared with the SUVRs normalized to cerebellar gray matter, all cerebral-to-white matter normalization schemes resulted in a higher inverse correlation between PET and CSF Aβ1-42, while the brainstem normalization gave the best results (high and most stable correlation). Compared with the SUVR mean and median values, the wS2 values were associated with the lowest coefficient of variation and highest inverse correlation to CSF Aβ1-42 levels across all time points and reference regions, including the cerebellar gray matter. The selection of reference tissue for normalization and the choice of image analysis method can affect changes in cortical (18)F-florbetapir uptake in longitudinal studies.

  12. Brainstem encoding of speech and musical stimuli in congenital amusia: evidence from Cantonese speakers

    PubMed Central

    Liu, Fang; Maggu, Akshay R.; Lau, Joseph C. Y.; Wong, Patrick C. M.

    2015-01-01

    Congenital amusia is a neurodevelopmental disorder of musical processing that also impacts subtle aspects of speech processing. It remains debated at what stage(s) of auditory processing deficits in amusia arise. In this study, we investigated whether amusia originates from impaired subcortical encoding of speech (in quiet and noise) and musical sounds in the brainstem. Fourteen Cantonese-speaking amusics and 14 matched controls passively listened to six Cantonese lexical tones in quiet, two Cantonese tones in noise (signal-to-noise ratios at 0 and 20 dB), and two cello tones in quiet while their frequency-following responses (FFRs) to these tones were recorded. All participants also completed a behavioral lexical tone identification task. The results indicated normal brainstem encoding of pitch in speech (in quiet and noise) and musical stimuli in amusics relative to controls, as measured by FFR pitch strength, pitch error, and stimulus-to-response correlation. There was also no group difference in neural conduction time or FFR amplitudes. Both groups demonstrated better FFRs to speech (in quiet and noise) than to musical stimuli. However, a significant group difference was observed for tone identification, with amusics showing significantly lower accuracy than controls. Analysis of the tone confusion matrices suggested that amusics were more likely than controls to confuse between tones that shared similar acoustic features. Interestingly, this deficit in lexical tone identification was not coupled with brainstem abnormality for either speech or musical stimuli. Together, our results suggest that the amusic brainstem is not functioning abnormally, although higher-order linguistic pitch processing is impaired in amusia. This finding has significant implications for theories of central auditory processing, requiring further investigations into how different stages of auditory processing interact in the human brain. PMID:25646077

  13. Brainstem encoding of speech and musical stimuli in congenital amusia: evidence from Cantonese speakers.

    PubMed

    Liu, Fang; Maggu, Akshay R; Lau, Joseph C Y; Wong, Patrick C M

    2014-01-01

    Congenital amusia is a neurodevelopmental disorder of musical processing that also impacts subtle aspects of speech processing. It remains debated at what stage(s) of auditory processing deficits in amusia arise. In this study, we investigated whether amusia originates from impaired subcortical encoding of speech (in quiet and noise) and musical sounds in the brainstem. Fourteen Cantonese-speaking amusics and 14 matched controls passively listened to six Cantonese lexical tones in quiet, two Cantonese tones in noise (signal-to-noise ratios at 0 and 20 dB), and two cello tones in quiet while their frequency-following responses (FFRs) to these tones were recorded. All participants also completed a behavioral lexical tone identification task. The results indicated normal brainstem encoding of pitch in speech (in quiet and noise) and musical stimuli in amusics relative to controls, as measured by FFR pitch strength, pitch error, and stimulus-to-response correlation. There was also no group difference in neural conduction time or FFR amplitudes. Both groups demonstrated better FFRs to speech (in quiet and noise) than to musical stimuli. However, a significant group difference was observed for tone identification, with amusics showing significantly lower accuracy than controls. Analysis of the tone confusion matrices suggested that amusics were more likely than controls to confuse between tones that shared similar acoustic features. Interestingly, this deficit in lexical tone identification was not coupled with brainstem abnormality for either speech or musical stimuli. Together, our results suggest that the amusic brainstem is not functioning abnormally, although higher-order linguistic pitch processing is impaired in amusia. This finding has significant implications for theories of central auditory processing, requiring further investigations into how different stages of auditory processing interact in the human brain.

  14. Neurophysiological responses to music and vibroacoustic stimuli in Rett syndrome.

    PubMed

    Bergström-Isacsson, Märith; Lagerkvist, Bengt; Holck, Ulla; Gold, Christian

    2014-06-01

    People with Rett syndrome (RTT) have severe communicative difficulties. They have as well an immature brainstem that implies dysfunction of the autonomic nervous system. Music plays an important role in their life, is often used as a motivating tool in a variety of situations and activities, and caregivers are often clear about people with RTTs favourites. The aim of this study was to investigate physiological and emotional responses related to six different musical stimuli in people with RTT. The study included 29 participants with RTT who were referred to the Swedish Rett Center for medical brainstem assessment during the period 2006-2007. 11 children with a typical developmental pattern were used as comparison. A repeated measures design was used, and physiological data were collected from a neurophysiological brainstem assessment. The continuous dependent variables measured were Cardiac Vagal Tone (CVT), Cardiac Sensitivity to Baroreflex (CSB), Mean Arterial Blood Pressure (MAP) and the Coefficient of Variation of Mean Arterial Blood Pressure (MAP-CV). These parameters were used to categorise brainstem responses as parasympathetic (calming) response, sympathetic (activating) response, arousal (alerting) response and unclear response. The results showed that all participants responded to the musical stimuli, but not always in the expected way. It was noticeable that both people with and without RTT responded with an arousal to all musical stimuli to begin with. Even though the initial expressions sometimes changed after some time due to poor control functions of their brainstem, the present results are consistent with the possibility that the RTT participants' normal responses to music are intact. These findings may explain why music is so important for individuals with RTT throughout life. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Effects of anesthetic protocol on normal canine brain uptake of 18F-FDG assessed by PET/CT.

    PubMed

    Lee, Min Su; Ko, Jeff; Lee, Ah Ra; Lee, In Hye; Jung, Mi Ae; Austin, Brenda; Chung, Hyunwoo; Nahm, Sangsoep; Eom, Kidong

    2010-01-01

    The purpose of this study was to assess the effects of four anesthetic protocols on normal canine brain uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) using positron emission tomography/computed tomography (PET/CT). Five clinically normal beagle dogs were anesthetized with (1) propofol/isoflurane, (2) medetomidine/pentobarbital, (3) xylazine/ketamine, and (4) medetomidine/tiletamine-zolazepam in a randomized cross-over design. The standard uptake value (SUV) of FDG was obtained in the frontal, parietal, temporal and occipital lobes, cerebellum, brainstem and whole brain, and compared within and between anesthetic protocols using the Friedman test with significance set at P < 0.05. Significant differences in SUVs were observed in various part of the brain associated with each anesthetic protocol. The SUV for the frontal and occipital lobes was significantly higher than in the brainstem in all dogs. Dogs receiving medetomidine/tiletamine-zolazepam also had significantly higher whole brain SUVs than the propofol/isoflurane group. We concluded that each anesthetic protocol exerted a different regional brain glucose uptake pattern. As a result, when comparing brain glucose uptake using PET/CT, one should consider the effects of anesthetic protocols on different regions of the glucose uptake in the dog's brain.

  16. Four cases of acoustic neuromas with normal hearing.

    PubMed

    Valente, M; Peterein, J; Goebel, J; Neely, J G

    1995-05-01

    In 95 percent of the cases, patients with acoustic neuromas will have some magnitude of hearing loss in the affected ear. This paper reports on four patients who had acoustic neuromas and normal hearing. Results from the case history, audiometric evaluation, auditory brainstem response (ABR), electroneurography (ENOG), and vestibular evaluation are reported for each patient. For all patients, the presence of unilateral tinnitus was the most common complaint. Audiologically, elevated or absent acoustic reflex thresholds and abnormal ABR findings were the most powerful diagnostic tools.

  17. Brainstem processing of vestibular sensory exafference: implications for motion sickness etiology

    PubMed Central

    Oman, Charles M.; Cullen, Kathleen E.

    2014-01-01

    The origin of the internal “sensory conflict” stimulus causing motion sickness has been debated for more than four decades. Recent studies show a subclass of neurons in the vestibular nuclei and deep cerebellar nuclei that respond preferentially to passive head movements. During active movement, the semicircular canal and otolith input (“reafference”) to these neurons is cancelled by a mechanism comparing the expected consequences of self-generated movement (estimated with an internal model-presumably located in the cerebellum) with the actual sensory feedback. The un-cancelled component (“exafference”) resulting from passive movement normally helps compensate for unexpected postural disturbances. Notably, the existence of such vestibular “sensory conflict” neurons had been postulated as early as 1982, but their existence and putative role in posture control, motion sickness has been long debated. Here we review the development of “sensory conflict” theories in relation to recent evidence for brainstem and cerebellar reafference cancellation, and identify some open research questions. We propose that conditions producing persistent activity of these neurons, or their targets, stimulates nearby brainstem emetic centers – via an as yet unidentified mechanism. We discuss how such a mechanism is consistent with the notable difference in motion sickness susceptibility of drivers as opposed to passengers, human immunity to normal self-generated movement, and why head restraint or lying horizontal confers relative immunity. Finally, we propose that fuller characterization of these mechanisms, and their potential role in motion sickness could lead to more effective, scientifically based prevention and treatment for motion sickness. PMID:24838552

  18. Comprehensive evaluation of a child with an auditory brainstem implant.

    PubMed

    Eisenberg, Laurie S; Johnson, Karen C; Martinez, Amy S; DesJardin, Jean L; Stika, Carren J; Dzubak, Danielle; Mahalak, Mandy Lutz; Rector, Emily P

    2008-02-01

    We had an opportunity to evaluate an American child whose family traveled to Italy to receive an auditory brainstem implant (ABI). The goal of this evaluation was to obtain insight into possible benefits derived from the ABI and to begin developing assessment protocols for pediatric clinical trials. Case study. Tertiary referral center. Pediatric ABI Patient 1 was born with auditory nerve agenesis. Auditory brainstem implant surgery was performed in December, 2005, in Verona, Italy. The child was assessed at the House Ear Institute, Los Angeles, in July 2006 at the age of 3 years 11 months. Follow-up assessment has continued at the HEAR Center in Birmingham, Alabama. Auditory brainstem implant. Performance was assessed for the domains of audition, speech and language, intelligence and behavior, quality of life, and parental factors. Patient 1 demonstrated detection of sound, speech pattern perception with visual cues, and inconsistent auditory-only vowel discrimination. Language age with signs was approximately 2 years, and vocalizations were increasing. Of normal intelligence, he exhibited attention deficits with difficulty completing structured tasks. Twelve months later, this child was able to identify speech patterns consistently; closed-set word identification was emerging. These results were within the range of performance for a small sample of similarly aged pediatric cochlear implant users. Pediatric ABI assessment with a group of well-selected children is needed to examine risk versus benefit in this population and to analyze whether open-set speech recognition is achievable.

  19. Impact of Morphometry, Myelinization and Synaptic Current Strength on Spike Conduction in Human and Cat Spiral Ganglion Neurons

    PubMed Central

    Rattay, Frank; Potrusil, Thomas; Wenger, Cornelia; Wise, Andrew K.; Glueckert, Rudolf; Schrott-Fischer, Anneliese

    2013-01-01

    Background Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction. Methodology/Principal Findings Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs) along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (∼26 pA) synaptic stimuli. Conclusions/Significance Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea compared to the cat cochlea. PMID:24260179

  20. A clinical analysis of 32 brainstem haemorrhages; with special reference to surviving but severely disabled cases.

    PubMed

    Komiyama, M; Boo, Y E; Yagura, H; Yasui, T; Baba, M; Hakuba, A; Nishimura, S

    1989-01-01

    Thirty-two patients with CT-documented primary brainstem haemorrhage were reviewed retrospectively to obtain a clearer overall clinical picture, especially of the severely disabled survivors. They were divided into 3 groups according to outcome: eleven cases (Group 1) died within 1 month following haemorrhage, 11 cases (Group 2) survived but became bedridden, necessitating full living support, and 10 cases (Group 3) showed minimal neurological deficits and resumed normal activities. Owing to CT and improved critical care, the survival rate was 66% for the whole series. Group 2 comprised 34% of all cases. These patients were mostly alert, quadruplegic, and communicated only with great difficulty. The most common initial symptoms and CT finding in each group were as follows; Group 1: unconsciousness, respiratory disturbance, negative light reflex, tachycardia, and haematoma greater than 3.0 cm; Group 2: disturbance of consciousness, respiratory disturbance, positive light reflex, normal heart rate, and 2.0 greater than haematoma less than 3.5 cm; and Group 3: alertness or only slight disturbance of consciousness, normal respiration, positive light reflex, normal heart rate, haematoma less than 2.5 cm. Although there is an overlap among them, these findings will be useful to distinguish the three groups from each other. Patients with disturbance of consciousness, respiratory disturbance, positive light reflex, normal heart rate, and 2.0 greater than haematoma less than 3.5 cm, have a chance to survive, but in severely disabled condition, if they were treated with vigorous intensive care in the acute stage.

  1. Cranial nerve vascular compression syndromes of the trigeminal, facial and vago-glossopharyngeal nerves: comparative anatomical study of the central myelin portion and transitional zone; correlations with incidences of corresponding hyperactive dysfunctional syndromes.

    PubMed

    Guclu, Bulent; Sindou, Marc; Meyronet, David; Streichenberger, Nathalie; Simon, Emile; Mertens, Patrick

    2011-12-01

    The aim of this study was to evaluate the anatomy of the central myelin portion and the central myelin-peripheral myelin transitional zone of the trigeminal, facial, glossopharyngeal and vagus nerves from fresh cadavers. The aim was also to investigate the relationship between the length and volume of the central myelin portion of these nerves with the incidences of the corresponding cranial dysfunctional syndromes caused by their compression to provide some more insights for a better understanding of mechanisms. The trigeminal, facial, glossopharyngeal and vagus nerves from six fresh cadavers were examined. The length of these nerves from the brainstem to the foramen that they exit were measured. Longitudinal sections were stained and photographed to make measurements. The diameters of the nerves where they exit/enter from/to brainstem, the diameters where the transitional zone begins, the distances to the most distal part of transitional zone from brainstem and depths of the transitional zones were measured. Most importantly, the volume of the central myelin portion of the nerves was calculated. Correlation between length and volume of the central myelin portion of these nerves and the incidences of the corresponding hyperactive dysfunctional syndromes as reported in the literature were studied. The distance of the most distal part of the transitional zone from the brainstem was 4.19  ±  0.81 mm for the trigeminal nerve, 2.86  ±  1.19 mm for the facial nerve, 1.51  ±  0.39 mm for the glossopharyngeal nerve, and 1.63  ±  1.15 mm for the vagus nerve. The volume of central myelin portion was 24.54  ±  9.82 mm(3) in trigeminal nerve; 4.43  ±  2.55 mm(3) in facial nerve; 1.55  ±  1.08 mm(3) in glossopharyngeal nerve; 2.56  ±  1.32 mm(3) in vagus nerve. Correlations (p  < 0.001) have been found between the length or volume of central myelin portions of the trigeminal, facial, glossopharyngeal and vagus nerves and incidences of the corresponding diseases. At present it is rather well-established that primary trigeminal neuralgia, hemifacial spasm and vago-glossopharyngeal neuralgia have as one of the main causes a vascular compression. The strong correlations found between the lengths and volumes of the central myelin portions of the nerves and the incidences of the corresponding diseases is a plea for the role played by this anatomical region in the mechanism of these diseases.

  2. Brainstem auditory evoked potentials with the use of acoustic clicks and complex verbal sounds in young adults with learning disabilities.

    PubMed

    Kouni, Sophia N; Giannopoulos, Sotirios; Ziavra, Nausika; Koutsojannis, Constantinos

    2013-01-01

    Acoustic signals are transmitted through the external and middle ear mechanically to the cochlea where they are transduced into electrical impulse for further transmission via the auditory nerve. The auditory nerve encodes the acoustic sounds that are conveyed to the auditory brainstem. Multiple brainstem nuclei, the cochlea, the midbrain, the thalamus, and the cortex constitute the central auditory system. In clinical practice, auditory brainstem responses (ABRs) to simple stimuli such as click or tones are widely used. Recently, complex stimuli or complex auditory brain responses (cABRs), such as monosyllabic speech stimuli and music, are being used as a tool to study the brainstem processing of speech sounds. We have used the classic 'click' as well as, for the first time, the artificial successive complex stimuli 'ba', which constitutes the Greek word 'baba' corresponding to the English 'daddy'. Twenty young adults institutionally diagnosed as dyslexic (10 subjects) or light dyslexic (10 subjects) comprised the diseased group. Twenty sex-, age-, education-, hearing sensitivity-, and IQ-matched normal subjects comprised the control group. Measurements included the absolute latencies of waves I through V, the interpeak latencies elicited by the classical acoustic click, the negative peak latencies of A and C waves, as well as the interpeak latencies of A-C elicited by the verbal stimulus 'baba' created on a digital speech synthesizer. The absolute peak latencies of waves I, III, and V in response to monoaural rarefaction clicks as well as the interpeak latencies I-III, III-V, and I-V in the dyslexic subjects, although increased in comparison with normal subjects, did not reach the level of a significant difference (p<0.05). However, the absolute peak latencies of the negative wave C and the interpeak latencies of A-C elicited by verbal stimuli were found to be increased in the dyslexic group in comparison with the control group (p=0.0004 and p=0.045, respectively). In the subgroup consisting of 10 patients suffering from 'other learning disabilities' and who were characterized as with 'light' dyslexia according to dyslexia tests, no significant delays were found in peak latencies A and C and interpeak latencies A-C in comparison with the control group. Acoustic representation of a speech sound and, in particular, the disyllabic word 'baba' was found to be abnormal, as low as the auditory brainstem. Because ABRs mature in early life, this can help to identify subjects with acoustically based learning problems and apply early intervention, rehabilitation, and treatment. Further studies and more experience with more patients and pathological conditions such as plasticity of the auditory system, cochlear implants, hearing aids, presbycusis, or acoustic neuropathy are necessary until this type of testing is ready for clinical application. © 2013 Elsevier Inc. All rights reserved.

  3. Motor evoked potential monitoring of the vagus nerve with transcranial electrical stimulation during skull base surgeries.

    PubMed

    Ito, Eiji; Ichikawa, Masahiro; Itakura, Takeshi; Ando, Hitoshi; Matsumoto, Yuka; Oda, Keiko; Sato, Taku; Watanabe, Tadashi; Sakuma, Jun; Saito, Kiyoshi

    2013-01-01

    Dysphasia is one of the most serious complications of skull base surgeries and results from damage to the brainstem and/or cranial nerves involved in swallowing. Here, the authors propose a method to monitor the function of the vagus nerve using endotracheal tube surface electrodes and transcranial electrical stimulation during skull base surgeries. Fifteen patients with skull base or brainstem tumors were enrolled. The authors used surface electrodes of an endotracheal tube to record compound electromyographic responses from the vocalis muscle. Motor neurons were stimulated using corkscrew electrodes placed subdermally on the scalp at C3 and C4. During surgery, the operator received a warning when the amplitude of the vagal motor evoked potential (MEP) decreased to less than 50% of the control level. After surgery, swallowing function was assessed clinically using grading criteria. In 5 patients, vagal MEP amplitude permanently deteriorated to less than 50% of the control level on the right side when meningiomas were dissected from the pons or basilar artery, or when a schwannoma was dissected from the vagal rootlets. These 5 patients had postoperative dysphagia. At 4 weeks after surgery, 2 patients still had dysphagia. In 2 patients, vagal MEPs of one side transiently disappeared when the tumors were dissected from the brainstem or the vagal rootlets. After surgery, both patients had dysphagia, which recovered in 4 weeks. In 7 patients, MEP amplitude was consistent, maintaining more than 50% of the control level throughout the operative procedures. After surgery all 7 patients were neurologically intact with normal swallowing function. Vagal MEP monitoring with transcranial electrical stimulation and endotracheal tube electrode recording was a safe and effective method to provide continuous real-time information on the integrity of both the supranuclear and infranuclear vagal pathway. This method is useful to prevent intraoperative injury of the brainstem corticobulbar tract or the vagal rootlets and to avoid the postoperative dysphagia that is often associated with brainstem or skull base surgeries.

  4. Effect of Brain Stem and Dorsal Vagus Complex Dosimetry on Nausea and Vomiting in Head and Neck Intensity-Modulated Radiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ciura, Katherine; McBurney, Michelle; Nguyen, Baongoc

    Intensity-modulated radiation therapy (IMRT) is becoming the treatment of choice for many head and neck cancer patients. IMRT reduces some toxicities by reducing radiation dose to uninvolved normal tissue near tumor targets; however, other tissues not irradiated using previous 3D techniques may receive clinically significant doses, causing undesirable side effects including nausea and vomiting (NV). Irradiation of the brainstem, and more specifically, the area postrema and dorsal vagal complex (DVC), has been linked to NV. We previously reported preliminary hypothesis-generating dose effects associated with NV in IMRT patients. The goal of this study is to relate brainstem dose to NVmore » symptoms. We retrospectively studied 100 consecutive patients that were treated for oropharyngeal cancer with IMRT. We contoured the brainstem, area postrema, and DVC with the assistance of an expert diagnostic neuroradiologist. We correlated dosimetry for the 3 areas contoured with weekly NV rates during IMRT. NV rates were significantly higher for patients who received concurrent chemotherapy. Post hoc analysis demonstrated that chemoradiation cases exhibited a trend towards the same dose-response relationship with both brainstem mean dose (p = 0.0025) and area postrema mean dose (p = 0.004); however, both failed to meet statistical significance at the p {<=} 0.002 level. Duration of toxicity was also greater for chemoradiation patients, who averaged 3.3 weeks with reported Common Terminology Criteria for Adverse Events (CTC-AE), compared with an average of 2 weeks for definitive RT patients (p = 0.002). For definitive RT cases, no dose-response trend could be ascertained. The mean brainstem dose emerged as a key parameter of interest; however, no one dose parameter (mean/median/EUD) best correlated with NV. This study does not address extraneous factors that would affect NV incidence, including the use of antiemetics, nor chemotherapy dose schedule specifics before and during RT. A prospective study will be required to depict exactly how IMRT dose affects NV.« less

  5. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Paliwal, B; Asprey, W; Yan, Y

    Purpose: In order to take advantage of the high resolution soft tissue imaging available in MR images, we investigated 3D images obtained with the low field 0.35 T MR in ViewRay to serve as an alternative to CT scans for radiotherapy treatment planning. In these images, normal and target structure delineation can be visualized. Assessment is based upon comparison with the CT images and the ability to produce comparable contours. Methods: Routine radiation oncology CT scans were acquired on five patients. Contours of brain, brainstem, esophagus, heart, lungs, spinal cord, and the external body were drawn. The same five patientsmore » were then scanned on the ViewRay TrueFISP-based imaging pulse sequence. The same organs were selected on the MR images and compared to those from the CT scan. Physical volume and the Dice Similarity Coefficient (DSC) were used to assess the contours from the two systems. Image quality stability was quantitatively ensured throughout the study following the recommendations of the ACR MR accreditation procedure. Results: The highest DSC of 0.985, 0.863, and 0.843 were observed for brain, lungs, and heart respectively. On the other hand, the brainstem, spinal cord, and esophagus had the lowest DSC. Volume agreement was most satisfied for the heart (within 5%) and the brain (within 2%). Contour volume for the brainstem and lung (a widely dynamic organ) varied the most (27% and 19%). Conclusion: The DSC and volume measurements suggest that the results obtained from ViewRay images are quantitatively consistent and comparable to those obtained from CT scans for the brain, heart, and lungs. MR images from ViewRay are well-suited for treatment planning and for adaptive MRI-guided radiotherapy. The physical data from 0.35 T MR imaging is consistent with our geometrical understanding of normal structures.« less

  6. HINTS to diagnose stroke in the acute vestibular syndrome: three-step bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging.

    PubMed

    Kattah, Jorge C; Talkad, Arun V; Wang, David Z; Hsieh, Yu-Hsiang; Newman-Toker, David E

    2009-11-01

    Acute vestibular syndrome (AVS) is often due to vestibular neuritis but can result from vertebrobasilar strokes. Misdiagnosis of posterior fossa infarcts in emergency care settings is frequent. Bedside oculomotor findings may reliably identify stroke in AVS, but prospective studies have been lacking. The authors conducted a prospective, cross-sectional study at an academic hospital. Consecutive patients with AVS (vertigo, nystagmus, nausea/vomiting, head-motion intolerance, unsteady gait) with >or=1 stroke risk factor underwent structured examination, including horizontal head impulse test of vestibulo-ocular reflex function, observation of nystagmus in different gaze positions, and prism cross-cover test of ocular alignment. All underwent neuroimaging and admission (generally <72 hours after symptom onset). Strokes were diagnosed by MRI or CT. Peripheral lesions were diagnosed by normal MRI and clinical follow-up. One hundred one high-risk patients with AVS included 25 peripheral and 76 central lesions (69 ischemic strokes, 4 hemorrhages, 3 other). The presence of normal horizontal head impulse test, direction-changing nystagmus in eccentric gaze, or skew deviation (vertical ocular misalignment) was 100% sensitive and 96% specific for stroke. Skew was present in 17% and associated with brainstem lesions (4% peripheral, 4% pure cerebellar, 30% brainstem involvement; chi(2), P=0.003). Skew correctly predicted lateral pontine stroke in 2 of 3 cases in which an abnormal horizontal head impulse test erroneously suggested peripheral localization. Initial MRI diffusion-weighted imaging was falsely negative in 12% (all <48 hours after symptom onset). Skew predicts brainstem involvement in AVS and can identify stroke when an abnormal horizontal head impulse test falsely suggests a peripheral lesion. A 3-step bedside oculomotor examination (HINTS: Head-Impulse-Nystagmus-Test-of-Skew) appears more sensitive for stroke than early MRI in AVS.

  7. [Total brain T2-hyperintense lesion-volume and the axonal damage in the normal-appearing white matter of brainstem in early lapsing-remitting multiple sclerosis].

    PubMed

    Pascual-Lozano, A M; Martínez-Bisbal, M C; Boscá-Blasco, I; Valero-Merino, C; Coret-Ferrer, F; Martí-Bonmatí, L; Martínez-Granados, B; Celda, B; Casanova-Estruch, B

    To evaluate the relationship between the total brain T2-hyperintense lesion volume (TBT2LV) and the axonal damage in the normal-appearing white matter of brainstem measured by 1H-MRS in a group of early relapsing-remitting multiple sclerosis patients. 40 relapsing-remitting multiple sclerosis patients and ten sex- and age-matched healthy subjects were prospectively studied for two years. T2-weighted MR and 1H-MRS imaging were acquired at time of recruitment and at year two. The TBT2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) resonances areas were integrated with jMRUI program and the ratios were calculated for four volume elements that represented the brainstem. At basal study we obtained an axonal loss (as a decrement of NAA/ Cho ratio) in the group of patients compared with controls (p = 0.017); this axonal loss increased at the second year of the follow-up for patients (NAA/Cho decrease, p = 0.004, and NAA/Cr decrease, p = 0.002) meanwhile control subjects had no significant metabolic changes. Higher lesion load was correlated with a poor clinical outcome, being the correlation between the basal TBT2LV and the Expanded Disability Status Scale at second year (r = 0.299; p = 0.05). Besides, axonal loss was not homogeneous for all multiple sclerosis patients, being stronger in the subgroup of patients with high basal TBT2LV (p = 0.043; ANOVA). Our data suggest that axonal damage is early in multiple sclerosis and higher in patients high basal TBT2LV, suggesting a possible relationship between these two phenomena.

  8. Management of a severe forceful breather with Rett syndrome using carbogen.

    PubMed

    Smeets, Eric E J; Julu, Peter O O; van Waardenburg, Dick; Engerström, Ingegerd Witt; Hansen, Stig; Apartopoulos, Flora; Curfs, Leopold M G; Schrander-Stumpel, Connie T R M

    2006-11-01

    We have used a novel neurophysiological technique in the NeuroScope system in combination with conventional electroencephalography (EEG) to monitor both brainstem and cortical activity simultaneously in real-time in a girl with Rett syndrome. The presenting clinical features in our patient were severe sleep disturbances, irregular breathing in the awake state dominated by Valsalva's type of breathing followed by tachypnoea and very frequent attacks of seizures and vacant spells. Our novel neurophysiological data showed that the patient was a Forceful Breather according to the breathing categories in Rett syndrome. She had frequent abnormal spontaneous brainstem activation (ASBA) preceded by severe attacks of hypocapnoea, which was caused by a combination of Valsalva's type of breathing and tachypnoea and all these together were responsible for the seizures and non-epileptic vacant spells. The ASBA was not detectable in conventional EEG and there were no epileptiform changes in the EEG during the seizures and vacant spells caused by the hypocapnic attacks, therefore these were pseudo-seizures. The record of brainstem activity confirmed that these were autonomic events, a kind of "brainstem epilepsy". We successfully treated the sleep disturbance with Pipamperone, a 5-hydroxytryptophan antagonist of receptor type 2 and we prevented the severe hypocapnoea during Valsalva's type of breathing and during tachypnoea using carbogen (a mixture of 5% carbon dioxide and 95% oxygen), which we gave by inhalation. Our treatment drastically reduced the autonomic events, promoted whole night sleep and significantly improved the quality of life in our patient. She can now participate in normal family activity which was previously impossible before treatment.

  9. Mean Normal Portal Vein Diameter Using Sonography among Clients Coming to Radiology Department of Jimma University Hospital, Southwest Ethiopia.

    PubMed

    Geleto, Gemechu; Getnet, Wondim; Tewelde, Tsegaye

    2016-05-01

    Mean portal vein diameter is considered as the best indicator for portal hypertension. However, the cutoff point differs from study to study (above 10-15 mm) despite the existence of normal mean portal vein diameter between 10-15 mm in different settings.This implies the existence of limited evidence on normal portal vein diameter for all populations in all countries prior to setting the cutoff points. Therefore, the aim of this study was sonographic assessment of normal mean portal vein diameter among patients referred to The Department of Radiology in Jimma University Hospital. A facility based cross-sectional study was conducted from November to December 2014 at Jimma University Hospital on a total of 195 clients. Data about portal vein diameter for eligible clients were collected by radiologists using Sonography. Data were edited manually, entered and analyzed using SPSS version 16. Data were collected from a total of 195 participants. Among these, 121(62.1%) were males and the median age of the participants was 35 years. The study revealed a normal mean portal vein diameter of 10.6 mm ±1.8 SD with a respirophasic variation of 25.6%. Likewise, the normal mean portal vein diameter seemed to have varied significantly by age and sex. The study revealed a normal mean portal vein diameter ranging below 13 mm. Hence, decisions made in clinical settings should base on these findings. Besides, there is a need for large scale study to determine portal vein diameter variation by age and sex, controlling other confounders.

  10. Audiological findings in Noonan syndrome.

    PubMed

    Tokgoz-Yilmaz, Suna; Turkyilmaz, Meral Didem; Cengiz, Filiz Basak; Sjöstrand, Alev Pektas; Kose, Serdal Kenan; Tekin, Mustafa

    2016-10-01

    The aim of this study was to evaluate audiologic properties of patients with Noonan syndrome and compare these findings with those of unaffected peers. The study included 17 children with Noonan syndrome and 20 typically developing children without Noonan syndrome. Pure tone and speech audiometry, immitancemetric measurement, otoacoustic emissions measurement and auditory brainstem response tests were applied to all (n = 37) children. Hearing thresholds of children with Noonan syndrome were higher (poorer) than those observed unaffected peers, while the hearing sensitivity of the both groups were normal limits (p = 0.013 for right, p = 0.031 for left ear). Transient evoked otoacoustic emissions amplitudes of the children with Noonan syndrome were lower than the children without Noonan syndrome (p = 0.005 for right, p = 0.002 for left ear). Middle ear pressures and auditory brainstem response values were within normal limits and there was no difference between the two groups (p > 0.05). General benefit of the present study is to characterize the audiologic findings of children with Noonan syndrome, which is beneficial in clinics evaluating children with Noonan syndrome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. [The characteristics of auditory brainstem response in preterm very low birth weight babies].

    PubMed

    Wang, Xiaoya; Luo, Renzhong; Wen, Ruijin; Chen, Qian; Zhou, Jialin; Zou, Yu

    2009-08-01

    To discuss the characteristics of auditory brainstem response in preterm very low birth weight (VLBW) babies and to investigate the correlations between the ABR and clinical characteristics. Fifty-nine VLBW babies (118 ears) were enrolled in the study and 30 term normal babies as the control group. Tympanometry, acoustic reflex, DPOAE, ABR were obtained in all the babies. The prevalence of hearing loss in VLBW babies was higher than normal term babies and babies with perinatal complications higher than those without perinatal complications. There was no correlations between ABR threshold and gestational age, birth weight, postconceptional age, negative correlations between wave I, III and V latencies I - III, III - V and I - V intervals and postconceptional age. Wave I and V latencies, I - III and III - V intervals differed significantly between the two groups. The perinatal complications were the most important causes of the hearing loss in preterm VLBW babies than the gestational age and birth weight. There was a high prevalence of peripheral hearing loss in the preterm VLBW babies. Combining OAE and automated ABR should be applied for hearing screening. Regular follow-up was very important in all the preterm VLBW neonatal.

  12. Comparisons of auditory brainstem response and sound level tolerance in tinnitus ears and non-tinnitus ears in unilateral tinnitus patients with normal audiograms.

    PubMed

    Shim, Hyun Joon; An, Yong-Hwi; Kim, Dong Hyun; Yoon, Ji Eun; Yoon, Ji Hyang

    2017-01-01

    Recently, "hidden hearing loss" with cochlear synaptopathy has been suggested as a potential pathophysiology of tinnitus in individuals with a normal hearing threshold. Several studies have demonstrated that subjects with tinnitus and normal audiograms show significantly reduced auditory brainstem response (ABR) wave I amplitudes compared with control subjects, but normal wave V amplitudes, suggesting increased central auditory gain. We aimed to reconfirm the "hidden hearing loss" theory through a within-subject comparison of wave I and wave V amplitudes and uncomfortable loudness level (UCL), which might be decreased with increased central gain, in tinnitus ears (TEs) and non-tinnitus ears (NTEs). Human subjects included 43 unilateral tinnitus patients (19 males, 24 females) with normal and symmetric hearing thresholds and 18 control subjects with normal audiograms. The amplitudes of wave I and V from the peak to the following trough were measured twice at 90 dB nHL and we separately assessed UCLs at 500 Hz and 3000 Hz pure tones in each TE and NTE. The within-subject comparison between TEs and NTEs showed no significant differences in wave I and wave V amplitude, or wave V/I ratio in both the male and female groups. Individual data revealed increased V/I amplitude ratios > mean + 2 SD in 3 TEs, but not in any control ears. We found no significant differences in UCL at 500 Hz or 3000 Hz between the TEs and NTEs, but the UCLs of both TEs and NTEs were lower than those of the control ears. Our ABR data do not represent meaningful evidence supporting the hypothesis of cochlear synaptopathy with increased central gain in tinnitus subjects with normal audiograms. However, reduced sound level tolerance in both TEs and NTEs might reflect increased central gain consequent on hidden synaptopathy that was subsequently balanced between the ears by lateral olivocochlear efferents.

  13. Comparisons of auditory brainstem response and sound level tolerance in tinnitus ears and non-tinnitus ears in unilateral tinnitus patients with normal audiograms

    PubMed Central

    An, Yong-Hwi; Kim, Dong Hyun; Yoon, Ji Eun; Yoon, Ji Hyang

    2017-01-01

    Objective Recently, “hidden hearing loss” with cochlear synaptopathy has been suggested as a potential pathophysiology of tinnitus in individuals with a normal hearing threshold. Several studies have demonstrated that subjects with tinnitus and normal audiograms show significantly reduced auditory brainstem response (ABR) wave I amplitudes compared with control subjects, but normal wave V amplitudes, suggesting increased central auditory gain. We aimed to reconfirm the “hidden hearing loss” theory through a within-subject comparison of wave I and wave V amplitudes and uncomfortable loudness level (UCL), which might be decreased with increased central gain, in tinnitus ears (TEs) and non-tinnitus ears (NTEs). Subjects and methods Human subjects included 43 unilateral tinnitus patients (19 males, 24 females) with normal and symmetric hearing thresholds and 18 control subjects with normal audiograms. The amplitudes of wave I and V from the peak to the following trough were measured twice at 90 dB nHL and we separately assessed UCLs at 500 Hz and 3000 Hz pure tones in each TE and NTE. Results The within-subject comparison between TEs and NTEs showed no significant differences in wave I and wave V amplitude, or wave V/I ratio in both the male and female groups. Individual data revealed increased V/I amplitude ratios > mean + 2 SD in 3 TEs, but not in any control ears. We found no significant differences in UCL at 500 Hz or 3000 Hz between the TEs and NTEs, but the UCLs of both TEs and NTEs were lower than those of the control ears. Conclusions Our ABR data do not represent meaningful evidence supporting the hypothesis of cochlear synaptopathy with increased central gain in tinnitus subjects with normal audiograms. However, reduced sound level tolerance in both TEs and NTEs might reflect increased central gain consequent on hidden synaptopathy that was subsequently balanced between the ears by lateral olivocochlear efferents. PMID:29253030

  14. Hearing impairment in preterm very low birthweight babies detected at term by brainstem auditory evoked responses.

    PubMed

    Jiang, Z D; Brosi, D M; Wilkinson, A R

    2001-12-01

    Seventy preterm babies who were born with a birthweight <1500 g were studied with brainstem auditory evoked responses (BAER) at 37-42 wk of postconceptional age. The data were compared with those of normal term neonates to determine the prevalence of hearing impairment in preterm very low birthweight (VLBW) babies when they reached term. The BAER was recorded with click stimuli at 21 s(-1). Wave I and V latencies increased significantly (ANOVA p < 0.01 and 0.001). I-V and III-V intervals also increased significantly (p < 0.05 and 0.001). Wave V amplitude and V/I amplitude ratio did not differ significantly from those in the normal term controls. Ten of the 70 VLBW babies had a significant elevation in BAER threshold (>30 dB normal hearing level). Eleven had an increase in I-V interval (>2.5 SD above the mean in the normal controls) and one had a decrease in V/I amplitude ratio (<0.45). These results suggest that 14% (10/70) of the VLBW babies had a peripheral hearing impairment and 17% (12/70) a central impairment. Three babies had both an increase in I-V interval and an elevation in BAER threshold, suggesting that 4% (3/70) had both peripheral and central impairments. Thus, the total prevalence of hearing impairment was 27% (19/70). About one in four preterm VLBW babies has peripheral and/or central hearing impairment at term. VLBW and its associated unfavourable perinatal factors predispose the babies to hearing impairment.

  15. Auditory evoked potentials: predicting speech therapy outcomes in children with phonological disorders.

    PubMed

    Leite, Renata Aparecida; Wertzner, Haydée Fiszbein; Gonçalves, Isabela Crivellaro; Magliaro, Fernanda Cristina Leite; Matas, Carla Gentile

    2014-03-01

    This study investigated whether neurophysiologic responses (auditory evoked potentials) differ between typically developed children and children with phonological disorders and whether these responses are modified in children with phonological disorders after speech therapy. The participants included 24 typically developing children (Control Group, mean age: eight years and ten months) and 23 children clinically diagnosed with phonological disorders (Study Group, mean age: eight years and eleven months). Additionally, 12 study group children were enrolled in speech therapy (Study Group 1), and 11 were not enrolled in speech therapy (Study Group 2). The subjects were submitted to the following procedures: conventional audiological, auditory brainstem response, auditory middle-latency response, and P300 assessments. All participants presented with normal hearing thresholds. The study group 1 subjects were reassessed after 12 speech therapy sessions, and the study group 2 subjects were reassessed 3 months after the initial assessment. Electrophysiological results were compared between the groups. Latency differences were observed between the groups (the control and study groups) regarding the auditory brainstem response and the P300 tests. Additionally, the P300 responses improved in the study group 1 children after speech therapy. The findings suggest that children with phonological disorders have impaired auditory brainstem and cortical region pathways that may benefit from speech therapy.

  16. Hypoxic-ischemic encephalopathy in preterm infants: antecedent factors, brain imaging, and outcome.

    PubMed

    Logitharajah, Pavithra; Rutherford, Mary A; Cowan, Frances M

    2009-08-01

    Our objectives were to establish antecedent factors and patterns of brain injury and their prognostic value in preterm infants with hypoxic-ischemic encephalopathy (HIE). Essential inclusion criteria were gestation (GA) < or =36 wk, Apgar scores <5/<7 at 1/5 min, major resuscitation at birth, and a brain MRI <6 postnatal wk. At least one additional criterion was required of the following: abnormal intrapartum CTG, sentinel event, meconium, cord pH <7.0, neonatal seizures, and multiorgan failure. Antenatal and perinatal data and > or =2 y neurodevelopmental outcome were documented. Fifty-five infants (GA 26-36; median, 35 wk) were eligible; all had 1-6 (median, 3) additional criteria. Placental abruption was the commonest identifiable antecedent event. Evidence of infection was not prominent. Main sites of injury were basal ganglia (BG, 75%), mostly severe, white matter (WM, 89%), mostly mild, brainstem (44%), and cortex (58%). Brainstem injury was associated with severe BG, WM, and cortical injury. Two-year outcome: death (32%), cerebral palsy (26%, mostly severe quadriplegia), mild impairment (10%), and normal (32%). Significant central gray matter and brainstem injury was found in many preterm infants with HIE. Neonatal MRI findings allowed accurate prediction of neurodevelopmental outcome. Early MRI is feasible and a valuable tool in this poorly reported group of infants.

  17. Visual and brainstem auditory evoked potentials in infants with severe vitamin B12 deficiency.

    PubMed

    Demir, Nihat; Koç, Ahmet; Abuhandan, Mahmut; Calik, Mustafa; Işcan, Akin

    2015-01-01

    Vitamin B12 plays an important role in the development of mental, motor, cognitive, and social functions via its role in DNA synthesis and nerve myelination. Its deficiency in infants might cause neuromotor retardation as well as megaloblastic anemia. The objective of this study was to investigate the effects of infantile vitamin B12 deficiency on evoked brain potentials and determine whether improvement could be obtained with vitamin B12 replacement at appropriate dosages. Thirty patients with vitamin B12 deficiency and 30 age-matched healthy controls were included in the study. Hematological parameters, visual evoked potentials, and brainstem auditory evoked potentials tests were performed prior to treatment, 1 week after treatment, and 3 months after treatment. Visual evoked potentials (VEPs) and brainstem auditory evoked potentials (BAEPs) were found to be prolonged in 16 (53.3%) and 15 (50%) patients, respectively. Statistically significant improvements in VEP and BAEP examinations were determined 3 months after treatment. Three months after treatment, VEP and BAEP examinations returned to normal in 81.3% and 53.3% of subjects with prolonged VEPs and BAEPs, respectively. These results demonstrate that vitamin B12 deficiency in infants causes significant impairment in the auditory and visual functioning tests of the brain, such as VEP and BAEP.

  18. Brainstem auditory and somatosensory evoked potentials in relation to clinical and neuroimaging findings in Chiari type 1 malformation.

    PubMed

    Moncho, Dulce; Poca, Maria-Antonia; Minoves, Teresa; Ferré, Alejandro; Rahnama, Kimia; Sahuquillo, Juan

    2015-04-01

    The aim of this study was to describe the abnormalities found in the recordings of evoked potentials (EPs), in particular those of brainstem auditory evoked potentials and somatosensory evoked potentials, in a homogeneous series of patients with Chiari type 1 malformation (CM-1) and study their relationship with clinical symptoms and malformation severity. CM-1 is characterized by cerebellar tonsils that descend below the foramen magnum and may be associated with EP alterations. However, only a small number of authors have described these tests in CM-1, and the patient groups studied to date have been small and heterogeneous. The clinical findings, neuroimages, and EP findings were retrospectively studied in a cohort of 50 patients with CM-1. Seventy percent of patients had EP abnormalities (brainstem auditory evoked potential: 52%, posterior tibial nerve somatosensory evoked potential: 42%, and median nerve somatosensory evoked potential: 34%). The most frequent alteration was an increased central conduction time. Morphometric measurements differed between the normal and pathological groups, although no statistical significance was found when comparing these groups. A high percentage of patients with CM-1 show EP alterations regardless of their clinical or radiological findings, thus highlighting the necessity of performing these tests, especially in patients with few or no symptoms.

  19. Green laser light activates the inner ear

    NASA Astrophysics Data System (ADS)

    Wenzel, Gentiana I.; Balster, Sven; Zhang, Kaiyin; Lim, Hubert H.; Reich, Uta; Massow, Ole; Lubatschowski, Holger; Ertmer, Wolfgang; Lenarz, Thomas; Reuter, Guenter

    2009-07-01

    The hearing performance with conventional hearing aids and cochlear implants is dramatically reduced in noisy environments and for sounds more complex than speech (e. g. music), partially due to the lack of localized sensorineural activation across different frequency regions with these devices. Laser light can be focused in a controlled manner and may provide more localized activation of the inner ear, the cochlea. We sought to assess whether visible light with parameters that could induce an optoacoustic effect (532 nm, 10-ns pulses) would activate the cochlea. Auditory brainstem responses (ABRs) were recorded preoperatively in anesthetized guinea pigs to confirm normal hearing. After opening the bulla, a 50-μm core-diameter optical fiber was positioned in the round window niche and directed toward the basilar membrane. Optically induced ABRs (OABRs), similar in shape to those of acoustic stimulation, were elicited with single pulses. The OABR peaks increased with energy level (0.6 to 23 μJ/pulse) and remained consistent even after 30 minutes of continuous stimulation at 13 μJ, indicating minimal or no stimulation-induced damage within the cochlea. Our findings demonstrate that visible light can effectively and reliably activate the cochlea without any apparent damage. Further studies are in progress to investigate the frequency-specific nature and mechanism of green light cochlear activation.

  20. Radiosurgery for symptomatic cavernous malformations: A multi-institutional retrospective study in Japan

    PubMed Central

    Kida, Yoshihisa; Hasegawa, Toshinori; Iwai, Yoshiyasu; Shuto, Takashi; Satoh, Manabu; Kondoh, Takeshi; Hayashi, Motohiro

    2015-01-01

    Background: A group study for symptomatic cavernous malformation (CM) treated with gamma knife (GK) surgery was performed. Methods: A total of 298 cases collected from 23 GK centers across Japan were included. Hemorrhage was the most common manifestation, followed by seizures and neurological deficits. Most of the lesions were located in the brainstem and basal ganglia, followed by the cerebral or cerebellar hemispheres. The CMs, which had a mean diameter of 14.8 mm, were treated using GK surgery with a mean marginal dose of 14.6 Gy. Results: In terms of hemorrhage-free survival (HFS), a marked dissociation was confirmed between the hemorrhage and seizure groups, while no obvious difference was noted between sexes. Superficial CMs located in cerebellum or lobar regions responded to the treatment better than deeply located CMs in the basal ganglia or brainstem. No significant difference of dose-dependent response was seen for three different ranges of marginal dose: Less than 15 Gy, between 15 and 20 Gy, and more than 20 Gy. Complications were more frequent after a marginal dose of over 15 Gy and in patients with lesions more than 15 mm in diameter. The rates of annual hemorrhage were estimated to be 7.4% during the first 2 years after radiosurgery and 2.8% thereafter. The overall hemorrhage rate after radiosurgery was 4.4%/year/patient. Conclusion: The risk of hemorrhage is considerably reduced after GK treatment. The HFS as well as annual hemorrhage rate after GK treatment was apparently superior to that after conservative treatment for symptomatic CMs. To optimize the success of GK treatment, it is important to reduce the incidence of complications. PMID:26005588

  1. The role of eABR with intracochlear test electrode in decision making between cochlear and brainstem implants: preliminary results.

    PubMed

    Cinar, Betul Cicek; Yarali, Mehmet; Atay, Gamze; Bajin, Munir Demir; Sennaroglu, Gonca; Sennaroglu, Levent

    2017-09-01

    The objective of the study was to discuss the findings of intraoperative electrically evoked auditory brainstem response (eABR) test results with a recently designed intracochlear test electrode (ITE) in terms of their relation to decisions of cochlear or auditory brainstem implantation. This clinical study was conducted in Hacettepe University, Department of Otolaryngology, Head and Neck Surgery and Department of Audiology. Subjects were selected from inner ear malformation (IEM) database. Eleven subjects with profound sensorineural hearing loss were included in the current study with age range from 1 year 3 months to 4 years 3 months for children with prelingual hearing loss. There was only one 42-year-old post-lingual subject. eABR was recorded with an ITE and intraoperatively with an original cochlear implant (CI) electrode in 11 cases with different IEMs. Findings of eABR with ITE and their relation to the decision for CI or auditory brainstem implant (ABI) are discussed. Positive eABR test results were found to be dependent on close to normal cochlear structures and auditory nerve. The probability of positive result decreases with increasing degree of malformation severity. The prediction value of eABR via ITE on decision for hearing restoration was found to be questionable in this study. The results of eABR with ITE have predictive value on what we will get with the actual CI electrode. ITE appears to stimulate the cochlea like an actual CI. If the eABR is positive, the results are reliable. However, if eABR is negative, the results should be evaluated with preoperative audiological testing and MRI findings.

  2. Tyrosine content, influx and accumulation rate, and catecholamine biosynthesis measured in vivo, in the central nervous system and in peripheral organs of the young rat. Influence of neonatal hypo- and hyperthyroidism.

    PubMed

    Diarra, A; Lefauconnier, J M; Valens, M; Georges, P; Gripois, D

    1989-10-01

    The influence of neonatal hypo- and hyperthyroidism on different aspects of tyrosine metabolism in the hypothalamus, striatum, brainstem, adrenal glands, heart and brown adipose tissue (BAT) were studied in 14-day old rats. The synthesis rate of catecholamines (CA) was also determined in vivo after the injection of labelled tyrosine. Hypothyroidism increases tyrosinaemia and endogenous tyrosine concentration in the hypothalamus and BAT. Hyperthyroidism decreases tyrosinaemia and endogenous tyrosine levels in the striatum, adrenals and heart. The accumulation rate of tyrosine determined 30 min after an intravenous injection of the labelled amino acid has been determined in the organs, together with the influx of the amino acid, determined within 20s. Hypothyroidism increases tyrosine accumulation rate in all the organs studied, and tyrosine clearance is decreased in the striatum and brainstem; together with an increased tyrosinaemia, this leads to a normal influx. The influx of tyrosine is increased in the hypothalamus. Hyperthyroidism decreases tyrosine accumulation rate in all the organs except the adrenals. These results indicate that the thyroid status of the young rat can influence tyrosine uptake mechanisms, without modifying an organ's tyrosine content. The fact that hypothyroidism increases tyrosine influx in the hypothalamus without modifying it in the brainstem and striatum reflects an heterogeneous reactivity to the lack of thyroid hormones in different brain structures. Neonatal hypothyroidism decreases the CA synthesis rate in the striatum, the heart and the interscapular brown adipose tissue, while synthesis was enhanced in the brainstem and the adrenals. It is likely that these variations in CA synthesis are due to thyroid hormone modulation of tyrosine hydroxylase activity, the enzyme which catalyses the rate limiting step in CA biosynthesis.

  3. Risk factors for development of postoperative cerebellar mutism syndrome in children after medulloblastoma surgery.

    PubMed

    Pols, San Y C V; van Veelen, Marie Lise C; Aarsen, Femke K; Gonzalez Candel, Antonia; Catsman-Berrevoets, Coriene E

    2017-07-01

    OBJECTIVE Postoperative cerebellar mutism syndrome (pCMS) occurs in 7%-50% of children after cerebellar tumor surgery. Typical features include a latent onset of 1-2 days after surgery, transient mutism, emotional lability, and a wide variety of motor and neurobehavioral abnormalities. Sequelae of this syndrome usually persist long term. The principal causal factor is bilateral surgical damage (regardless of tumor location) to any component of the proximal efferent cerebellar pathway, which leads to temporary dysfunction of cerebral cortical regions as a result of diaschisis. Tumor type, cerebellar midline location, and brainstem involvement are risk factors for pCMS that have been identified repeatedly, but they do not explain its latent onset. Ambiguous or negative results for other factors, such as hydrocephalus, postoperative meningitis, length of vermian incision, and tumor size, have been reached. The aim of this study was to identify perioperative clinical, radiological, and laboratory factors that also increase risk for the development of pCMS. The focus was on factors that might explain the delayed onset of pCMS and thus might provide a time window for taking precautionary measures to prevent pCMS or reduce its severity. The study was focused specifically on children who had undergone surgery for medulloblastoma. METHODS In this single-center retrospective cohort study, the authors included 71 children with medulloblastoma, 28 of whom developed pCMS after primary resection. Clinical and laboratory data were collected prospectively and analyzed systematically. Variables were included for univariate and multivariate analysis. RESULTS Univariate regression analysis revealed 7 variables that had a significant influence on pCMS onset, namely, tumor size, maximum tumor diameter > 5 cm, tumor infiltration or compression of the brainstem, significantly larger decreases in hemoglobin (p = 0.010) and hematocrit (p = 0.003) in the pCMS group after surgery than in the no-pCMS group, significantly more reported incidents of severe bleeding in the tumor bed during surgery in the pCMS group, preoperative hydrocephalus, and a mean body temperature rise of 0.5°C in the first 4 days after surgery in the pCMS group. Multiple regression analysis revealed that tumor size, tumor infiltration into or compression of the brainstem, and higher mean body temperature in the first 4 postoperative days were independent and highly significant predictors for pCMS. CONCLUSIONS The authors confirmed earlier findings that tumor-associated preoperative conditions, such as a maximum tumor diameter ≥ 5 cm and infiltration into or compression of the brainstem, are associated with a higher risk for the development of pCMS. Most importantly, the authors found that a 0.5°C higher mean body temperature in the first 4 postoperative days increased the odds ratio for the development of pCMS almost 5-fold. These data suggest that an important focus for the prevention of pCMS in children who have undergone medulloblastoma surgery might be rigorous maintenance of normothermia as standard care after surgery.

  4. Brainstem ischemic lesions on MRI in children with tuberculous meningitis: with diffusion weighted confirmation.

    PubMed

    van der Merwe, Dirk Johannes; Andronikou, Savvas; Van Toorn, Ronald; Pienaar, Manana

    2009-08-01

    The Western Cape in South Africa has one of the highest incidences of tuberculous meningitis (TBM) in the world. Despite therapy, the outcome in children with advanced TBM remains dismal. Magnetic resonance imaging (MRI) has been shown to be superior to computed tomography (CT) in demonstrating ischemia in TBM, especially of the brainstem. The objective of this study was to characterize brainstem lesions and association with clinical findings in children with TBM by using MRI. CT and multiplanar MRI scans were performed in 30 children with proven TBM. From this group, a subgroup with radiological ischemic changes of the brainstem were identified. Radiological findings in these patients were then correlated with severity of disease, motor deficit, and outcome after 6 months. Radiological brainstem abnormalities were identified in 14 out of 30 children. Thirty-eight brainstem lesions were confirmed to be ischemic. The severity of disease at presentation, degree of motor deficit, and developmental outcome after 6 months of the children with ischemic brainstem lesions was poorer compared to those children without brainstem involvement. However, both sensitivity and specificity of the MRI brainstem lesion detection for clinical outcome proved low. A significant percentage of children with TBM have ischemic brainstem lesions. These are poorly visualized on conventional CT. MRI scanning is more sensitive in detecting these lesions and localizing them. There appears to be some association between MRI-detected brainstem lesions and clinical outcome. The exact meaning of these lesions and their implication for the patient's management require further clarification.

  5. Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity.

    PubMed

    Upadhyayula, Pavan S; Yang, Jason; Yue, John K; Ciacci, Joseph D

    2017-11-07

    Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords "subacute sclerosing panencephalitis" and "brainstem" using the National Library of Medicine PubMed database (March 1981-September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment.

  6. Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder

    PubMed Central

    Feldker, Katharina; Heitmann, Carina Yvonne; Neumeister, Paula; Brinkmann, Leonie; Bruchmann, Maximillan; Zwitserlood, Pienie; Straube, Thomas

    2018-01-01

    Background Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. Methods The present event-related functional MRI (fMRI) study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially non-overlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). Results We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. Limitations The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. Conclusion Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology. PMID:29252163

  7. Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder.

    PubMed

    Feldker, Katharina; Heitmann, Carina Yvonne; Neumeister, Paula; Brinkmann, Leonie; Bruchmann, Maximillan; Zwitserlood, Pienie; Straube, Thomas

    2018-01-01

    Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. The present event-related functional MRI (fMRI) study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially nonoverlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology.

  8. Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder.

    PubMed

    Feldker, Katharina; Heitmann, Carina Yvonne; Neumeister, Paula; Brinkmann, Leonie; Bruchmann, Maximillan; Zwitserlood, Pienie; Straube, Thomas

    2017-09-26

    Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. The present event-related fMRI study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially nonoverlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology.

  9. Visual and vestibular induced eye movements in verbal children and adults with autism

    PubMed Central

    Furman, Joseph M.; Osorio, Maria Joana; Minshew, Nancy J.

    2016-01-01

    This study investigated several types of eye movements that rely on the function of brainstem-cerebellar pathways specifically (vestibular-ocular reflexes) or on widely distributed pathways of the brain (horizontal pursuit and saccade eye movements). Although eye movements that rely on higher brain regions have been studies fairly extensively in autism, eye movements dependent on brainstem and cerebellum have not. This study involved 79 individuals with autism and 62 typical controls aged 5 to 52 years with IQ scores above 70. No differences between the autism and control groups were present on the measures of vestibular ocular reflexes, or on saccade velocity or accuracy. The autism group was significantly slower to initiate saccades, which was most prominent in the 8-18 year old age range. These findings provide the most substantial evidence to date of the functional integrity of brainstem and cerebellar pathways in autism, suggesting that the histopathological abnormalities described in these structures may not be associated with intrinsic dysfunction but rather reflect developmental alterations related to forebrain cortical systems formation. The increase in saccade latency adds to the substantial evidence of altered function and maturation of cortical systems in autism. Objective This study assessed the functionality of vestibular, pursuit and saccade circuitry in autism across a wide age range. Methods Subjects were 79 individuals with autism (AUT) and 62 controls (CON) aged 5 to 52 years with IQ scores > 70. For vestibular testing, earth-vertical axis rotation was performed in darkness and in a lighted visual surround with a fixation target. Ocular motor testing included assessment of horizontal saccades and horizontal smooth pursuit. Results No between-group differences were found in vestibular reflexes or in mean saccade velocity or accuracy. Saccade latency was increased in the AUT group with significant age-related effects in the 8-18 year old subgroups. There was a trend toward decreased pursuit gain without age effects. Conclusions Normal vestibular-induced eye movements and normal saccade accuracy and velocity provide the most substantial evidence to date of the functional integrity of brainstem and cerebellar pathways in autism, suggesting that the histopathological abnormalities described in these structures may not be associated with intrinsic dysfunction but rather reflect developmental alterations related to forebrain cortical systems formation. Increased saccade latency with age effects adds to the extensive existing evidence of altered function and maturation of cortical systems in autism. PMID:25846907

  10. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chau, Ricky; Teo, Peter; Kam, Michael

    The aim of this study is to evaluate the deficiencies in target coverage and organ protection of 2-dimensional radiation therapy (2DRT) in the treatment of advanced T-stage (T3-4) nasopharyngeal carcinoma (NPC), and assess the extent of improvement that could be achieved with intensity modulated radiation therapy (IMRT), with special reference to of the dose to the planning organ-at-risk volume (PRV) of the brainstem and spinal cord. A dosimetric study was performed on 10 patients with advanced T-stage (T3-4 and N0-2) NPC. Computer tomography (CT) images of 2.5-mm slice thickness of the head and neck were acquired with the patient immobilizedmore » in semi-extended-head position. A 2D plan based on Ho's technique, and an IMRT plan based on a 7-coplanar portals arrangement, were established for each patient. 2DRT was planned with the field borders and shielding drawn on the simulator radiograph with reference to bony landmarks, digitized, and entered into a planning computer for reconstruction of the 3D dose distribution. The 2DRT and IMRT treatment plans were evaluated and compared with respect to the dose-volume histograms (DVHs) of the targets and the organs-at-risk (OARs), tumor control probability (TCP), and normal tissue complication probabilities (NTCPs). With IMRT, the dose coverage of the target was superior to that of 2DRT. The mean minimum dose of the GTV and PTV were increased from 33.7 Gy (2DRT) to 62.6 Gy (IMRT), and 11.9 Gy (2DRT) to 47.8 Gy (IMRT), respectively. The D{sub 95} of the GTV and PTV were also increased from 57.1 Gy (2DRT) to 67 Gy (IMRT), and 45 Gy (2DRT) to 63.6 Gy (IMRT), respectively. The TCP was substantially increased to 78.5% in IMRT. Better protection of the critical normal organs was also achieved with IMRT. The mean maximum dose delivered to the brainstem and spinal cord were reduced significantly from 61.8 Gy (2DRT) to 52.8 Gy (IMRT) and 56 Gy (2DRT) to 43.6 Gy (IMRT), respectively, which were within the conventional dose limits of 54 Gy for brainstem and of 45 Gy for spinal cord. The mean maximum doses deposited on the PRV of the brainstem and spinal cord were 60.7 Gy and 51.6 Gy respectively, which were above the conventional dose limits. For the chiasm, the mean dose maximum and the dose to 5% of its volume were reduced from 64.3 Gy (2DRT) to 53.7 Gy (IMRT) and from 62.8 Gy (2DRT) to 48.7 Gy (IMRT), respectively, and the corresponding NTCP was reduced from 18.4% to 2.1%. For the temporal lobes, the mean dose to 10% of its volume (about 4.6 cc) was reduced from 63.8 Gy (2DRT) to 55.4 Gy (IMRT) and the NTCP was decreased from 11.7% to 3.4%. The therapeutic ratio for T3-4 NPC tumors can be significantly improved with IMRT treatment technique due to improvement both in target coverage and the sparing of the critical normal organ. Although the maximum doses delivered to the brainstem and spinal cord in IMRT can be kept at or below their conventional dose limits, the maximum doses deposited on the PRV often exceed these limits due to the close proximity between the target and OARs. In other words, ideal dosimetric considerations cannot be fulfilled in IMRT planning for T3-4 NPC tumors. A compromise of the maximal dose limit to the PRV of the brainstem and spinal cord would need be accepted if dose coverage to the targets is not to be unacceptably compromised. Dosimetric comparison with 2DRT plans show that these dose limits to PRV were also frequently exceeded in 2DRT plans for locally advanced NPC. A dedicated retrospective study on the incidence of clinical injury to neurological organs in a large series of patients with T3-4 NPC treated by 2DRT may provide useful reference data in exploring how far the PRV dose constraints may be relaxed, to maximize the target coverage without compromising the normal organ function.« less

  11. The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults.

    PubMed

    Feng, Jie; Hao, Shuyu; Pan, Changcun; Wang, Yu; Wu, Zhen; Zhang, Junting; Yan, Hai; Zhang, Liwei; Wan, Hong

    2015-11-01

    Brainstem and thalamic gliomas are rare, and they are poorly understood in adults. Genetic aberrations that occur in these tumors are still unknown. In this study, we investigated whether thalamic gliomas have different genetic aberrations and clinical outcomes compared with brainstem gliomas in adults. Forty-three glioma samples were selected, including 28 brainstem and 15 thalamic gliomas. The frequency of the K27M mutation in adult midline gliomas was 58.1%. High-grade gliomas in the thalamus were statistically significantly more numerous than brainstem gliomas. Patients with K27M mutant brainstem gliomas had a significantly shorter overall survival than patients with wild-type tumors (P = .020) by Cox regression after adjustment for other independent risk factors. However, there was no statistical tendency toward a poorer overall survival in thalamic gliomas containing the K27M mutation compared with wild-type tumors. The presence of the K27M mutation significantly corresponded with mutations in TP53 in thalamic gliomas. Interestingly, the K27M mutation was mutually exclusive with mutations in IDH1, which was detected only in brainstem gliomas. The microarray data identified 86 differentially expressed genes between brainstem and thalamic gliomas with the K27M mutation. The cyclin-dependent kinase 6 (CDK6) gene, which plays an important role in cancer pathways, was found to be differentially expressed between brainstem and thalamic gliomas with K27M mutations. Although the K27M mutation was frequently observed in adult brainstem and thalamic gliomas, this mutation tended to be associated with a poorer prognosis in brainstem gliomas but not in thalamic gliomas. Brainstem gliomas may present different genetic aberrations from thalamic gliomas. These differences may provide guidance for therapeutic decisions for the treatment of adult brainstem and thalamic gliomas, which may have different molecular targets. Copyright © 2015. Published by Elsevier Inc.

  12. Congenital brainstem disconnection associated with a syrinx of the brainstem.

    PubMed

    Barth, P G; de Vries, L S; Nikkels, P G J; Troost, D

    2008-02-01

    We report a case of congenital brainstem disconnection including the second detailed autopsy. A full-term newborn presented with irreversible apnoea and died on the fifth day. MRI revealed disconnection of the brainstem. The autopsy included a series of transverse sections of the mesencephalon, medulla oblongata and bridging tissue fragments. A fragile tube walled by mature brainstem tissue could be reconstructed. It enveloped a cylinder of fluid within the ventral pons extending to the mesencephalon and the lower brainstem. The aqueduct was patent and outside the lesion. The basilar artery was represented by a tiny median vessel. The ventral and lateral parts of the posterior brainstem were surrounded by heterotopic glial tissue. The olivary nucleus was absent and the cerebellar dentate nucleus was dysplastic. Considering the maturity of the remaining parts of the pons, the onset of structural decline is likely to be close to the time of birth. Probable causes are progressively insufficient perfusion through an hypoplastic basilar artery, and obstructed venous drainage through an abnormal glial barrier surrounding the posterior brainstem. The morphological findings can be characterized as a syrinx, known from disorders in which brainstem or spinal cord are damaged by a combination of mechanical and circulatory factors.

  13. Vestibular evoked myogenic potentials and MRI in early multiple sclerosis: Validation of the VEMP score.

    PubMed

    Crnošija, Luka; Krbot Skorić, Magdalena; Gabelić, Tereza; Adamec, Ivan; Habek, Mario

    2017-01-15

    To validate the VEMP score as a measure of brainstem dysfunction in patients with the first symptom of multiple sclerosis (MS) (clinically isolated syndrome (CIS)) and to investigate the correlation between VEMP and brainstem MRI results. 121 consecutive CIS patients were enrolled and brainstem functional system score (BSFS) was determined. Ocular VEMP (oVEMP) and cervical VEMP (cVEMP) were analyzed for latencies, conduction block and amplitude asymmetry ratio and the VEMP score was calculated. MRI was analyzed for the presence of brainstem lesions as a whole and separately for the presence of pontine, midbrain and medulla oblongata lesions. Patients with signs of brainstem involvement during the neurological examination (with BSFS ≥1) had a higher oVEMP score compared to patients with no signs of brainstem involvement. A binary logistic regression model showed that patients with brainstem lesion on the MRI are 6.780 times more likely to have BSFS ≥1 (p=0.001); and also, a higher VEMP score is associated with BSFS ≥1 (p=0.042). Furthermore, significant correlations were found between clinical brainstem involvement and brainstem and pontine MRI lesions, and prolonged latencies and/or absent VEMP responses. The VEMP score is a valuable tool in evaluation of brainstem involvement in patients with early MS. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. A new strategic neurosurgical planning tool for brainstem cavernous malformations using interactive computer graphics with multimodal fusion images.

    PubMed

    Kin, Taichi; Nakatomi, Hirofumi; Shojima, Masaaki; Tanaka, Minoru; Ino, Kenji; Mori, Harushi; Kunimatsu, Akira; Oyama, Hiroshi; Saito, Nobuhito

    2012-07-01

    In this study, the authors used preoperative simulation employing 3D computer graphics (interactive computer graphics) to fuse all imaging data for brainstem cavernous malformations. The authors evaluated whether interactive computer graphics or 2D imaging correlated better with the actual operative field, particularly in identifying a developmental venous anomaly (DVA). The study population consisted of 10 patients scheduled for surgical treatment of brainstem cavernous malformations. Data from preoperative imaging (MRI, CT, and 3D rotational angiography) were automatically fused using a normalized mutual information method, and then reconstructed by a hybrid method combining surface rendering and volume rendering methods. With surface rendering, multimodality and multithreshold techniques for 1 tissue were applied. The completed interactive computer graphics were used for simulation of surgical approaches and assumed surgical fields. Preoperative diagnostic rates for a DVA associated with brainstem cavernous malformation were compared between conventional 2D imaging and interactive computer graphics employing receiver operating characteristic (ROC) analysis. The time required for reconstruction of 3D images was 3-6 hours for interactive computer graphics. Observation in interactive mode required approximately 15 minutes. Detailed anatomical information for operative procedures, from the craniotomy to microsurgical operations, could be visualized and simulated three-dimensionally as 1 computer graphic using interactive computer graphics. Virtual surgical views were consistent with actual operative views. This technique was very useful for examining various surgical approaches. Mean (±SEM) area under the ROC curve for rate of DVA diagnosis was significantly better for interactive computer graphics (1.000±0.000) than for 2D imaging (0.766±0.091; p<0.001, Mann-Whitney U-test). The authors report a new method for automatic registration of preoperative imaging data from CT, MRI, and 3D rotational angiography for reconstruction into 1 computer graphic. The diagnostic rate of DVA associated with brainstem cavernous malformation was significantly better using interactive computer graphics than with 2D images. Interactive computer graphics was also useful in helping to plan the surgical access corridor.

  15. Auditory Brainstem Responses in Autism: Brainstem Dysfunction or Peripheral Hearing Loss?

    ERIC Educational Resources Information Center

    Klin, Ami

    1993-01-01

    A review of 11 studies of auditory brainstem response (ABR) in individuals with autism concludes that the ABR data are only suggestive (rather than supportive) of brainstem involvement in autism. The presence of peripheral hearing impairment was observed in some of the autistic individuals. (Author/DB)

  16. Posterior fossa anomalies diagnosed with fetal MRI: associated anomalies and neurodevelopmental outcomes.

    PubMed

    Patek, Kyla J; Kline-Fath, Beth M; Hopkin, Robert J; Pilipenko, Valentina V; Crombleholme, Timothy M; Spaeth, Christine G

    2012-01-01

    The purpose of this study was to describe the relationship between intracranial and extracranial anomalies and neurodevelopmental outcome for fetuses diagnosed with a posterior fossa anomaly (PFA) on fetal MRI. Cases of Dandy-Walker malformation, vermian hypogenesis/hypoplasia, and mega cisterna magna (MCM) were identified through the Fetal Care Center of Cincinnati between January 2004 and December 2010. Parental interview and retrospective chart review were used to assess neurodevelopmental outcome. Posterior fossa anomalies were identified in 59 fetuses; 9 with Dandy-Walker malformation, 36 with vermian hypogenesis/hypoplasia, and 14 with MCM. Cases with isolated PFAs (14/59) had better outcomes than those with additional anomalies (p = 0.00016), with isolated cases of MCM all being neurodevelopmentally normal. Cases with additional intracranial anomalies had a worse outcome than those without intracranial anomalies (p = 0.00017). The presence of extracranial anomalies increased the likelihood of having a poor outcome (p = 0.00014) as did the identification of an abnormal brainstem (p = 0.00018). Intracranial and extracranial anomalies were good predictors of neurodevelopmental outcome in this study. The prognosis was poor for individuals with an abnormal brainstem, whereas those with isolated MCM had normal neurodevelopmental outcome. © 2012 John Wiley & Sons, Ltd.

  17. The Relationship between the Behavioral Hearing Thresholds and Maximum Bilirubin Levels at Birth in Children with a History of Neonatal Hyperbilirubinemia

    PubMed Central

    Panahi, Rasool; Jafari, Zahra; Sheibanizade, Abdoreza; Salehi, Masoud; Esteghamati, Abdoreza; Hasani, Sara

    2013-01-01

    Introduction: Neonatal hyperbilirubinemia is one of the most important factors affecting the auditory system and can cause sensorineural hearing loss. This study investigated the relationship between behavioral hearing thresholds in children with a history of jaundice and the maximum level of bilirubin concentration in the blood. Materials and Methods: This study was performed on 18 children with a mean age of 5.6 years and with a history of neonatal hyperbilirubinemia. Behavioral hearing thresholds, transient evoked emissions and brainstem evoked responses were evaluated in all children. Results: Six children (33.3%) had normal hearing thresholds and the remaining (66.7%) had some degree of hearing loss. There was no significant relationship (r=-0.28, P=0.09) between the mean total bilirubin levels and behavioral hearing thresholds in all samples. A transient evoked emission was seen only in children with normal hearing thresholds however in eight cases brainstem evoked responses had not detected. Conclusion: Increased blood levels of bilirubin at the neonatal period were potentially one of the causes of hearing loss. There was a lack of a direct relationship between neonatal bilirubin levels and the average hearing thresholds which emphasizes on the necessity of monitoring the various amounts of bilirubin levels. PMID:24303432

  18. Are evolutionary hypotheses for motion sickness "just-so" stories?

    PubMed

    Oman, Charles M

    2012-01-01

    Vertebrates have evolved rapidly conditionable nausea and vomiting reflexes mediated by gut and brainstem receptors, clearly as a defense against neurotoxin ingestion. In 1977 Treisman proposed that sensory orientation linkages to emetic centers evolved for the same reason, and that motion sickness was an accidental byproduct. It was an "adaptationist" explanation for motion sickness, since it assumed that evolution has shaped all phenotypic traits for survival advantage. Treisman's "poison" theory is plausible, and frequently cited as the accepted scientific explanation for motion sickness. However, alternative explanations have been proposed. The creation of hypotheses is an essential part of science - provided they are testable. This paper reviews the evidence for the Poison theory and several other adaptationist explanations. These hypotheses are certainly not "just-so stories", but supporting evidence is equivocal, and contradictory evidence exists Parsimony suggests an alternative "pluralistic" view: The vertebrate reticular formation maintains oxygenated blood flow to the brain, discriminates unexpected sensory stimuli- including postural disturbances, and detects and expels ingested neurotoxins. The three systems share neuroarchitectural elements but normally function independently. Brainstem sensory conflict neurons normally discriminate brief postural disturbances, but can be abnormally stimulated during prolonged passive transport (e.g. by boat, beginning about 150-200 generations ago). Sensory conflict signals cross couple into the neurotoxin expulsion and avoidance system, producing an arguably maladaptive emetic phenotype.

  19. SU-E-T-587: Optimal Volumetric Modulated Arc Radiotherapy Treatment Planning Technique for Multiple Brain Metastases with Increasing Number of Arcs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Keeling, V; Hossain, S; Hildebrand, K

    Purpose: To show improvements in dose conformity and normal brain tissue sparing using an optimal planning technique (OPT) against clinically acceptable planning technique (CAP) in the treatment of multiple brain metastases. Methods: A standardized international benchmark case with12 intracranial tumors was planned using two different VMAT optimization methods. Plans were split into four groups with 3, 6, 9, and 12 targets each planned with 3, 5, and 7 arcs using Eclipse TPS. The beam geometries were 1 full coplanar and half non-coplanar arcs. A prescription dose of 20Gy was used for all targets. The following optimization criteria was used (OPTmore » vs. CAP): (No upper limit vs.108% upper limit for target volume), (priority 140–150 vs. 75–85 for normal-brain-tissue), and (selection of automatic sparing Normal-Tissue-Objective (NTO) vs. Manual NTO). Both had priority 50 to critical structures such as brainstem and optic-chiasm, and both had an NTO priority 150. Normal-brain-tissue doses along with Paddick Conformity Index (PCI) were evaluated. Results: In all cases PCI was higher for OPT plans. The average PCI (OPT,CAP) for all targets was (0.81,0.64), (0.81,0.63), (0.79,0.57), and (0.72,0.55) for 3, 6, 9, and 12 target plans respectively. The percent decrease in normal brain tissue volume (OPT/CAP*100) achieved by OPT plans was (reported as follows: V4, V8, V12, V16, V20) (184, 343, 350, 294, 371%), (192, 417, 380, 299, 360%), and (235, 390, 299, 281, 502%) for the 3, 5, 7 arc 12 target plans, respectively. The maximum brainstem dose decreased for the OPT plan by 4.93, 4.89, and 5.30 Gy for 3, 5, 7 arc 12 target plans, respectively. Conclusion: Substantial increases in PCI, critical structure sparing, and decreases in normal brain tissue dose were achieved by eliminating upper limits from optimization, using automatic sparing of normal tissue function with high priority, and a high priority to normal brain tissue.« less

  20. Test-retest reliability of speech-evoked auditory brainstem response in healthy children at a low sensation level.

    PubMed

    Zakaria, Mohd Normani; Jalaei, Bahram

    2017-11-01

    Auditory brainstem responses evoked by complex stimuli such as speech syllables have been studied in normal subjects and subjects with compromised auditory functions. The stability of speech-evoked auditory brainstem response (speech-ABR) when tested over time has been reported but the literature is limited. The present study was carried out to determine the test-retest reliability of speech-ABR in healthy children at a low sensation level. Seventeen healthy children (6 boys, 11 girls) aged from 5 to 9 years (mean = 6.8 ± 3.3 years) were tested in two sessions separated by a 3-month period. The stimulus used was a 40-ms syllable /da/ presented at 30 dB sensation level. As revealed by pair t-test and intra-class correlation (ICC) analyses, peak latencies, peak amplitudes and composite onset measures of speech-ABR were found to be highly replicable. Compared to other parameters, higher ICC values were noted for peak latencies of speech-ABR. The present study was the first to report the test-retest reliability of speech-ABR recorded at low stimulation levels in healthy children. Due to its good stability, it can be used as an objective indicator for assessing the effectiveness of auditory rehabilitation in hearing-impaired children in future studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Short GSM mobile phone exposure does not alter human auditory brainstem response.

    PubMed

    Stefanics, Gábor; Kellényi, Lóránd; Molnár, Ferenc; Kubinyi, Györgyi; Thuróczy, György; Hernádi, István

    2007-11-12

    There are about 1.6 billion GSM cellular phones in use throughout the world today. Numerous papers have reported various biological effects in humans exposed to electromagnetic fields emitted by mobile phones. The aim of the present study was to advance our understanding of potential adverse effects of the GSM mobile phones on the human hearing system. Auditory Brainstem Response (ABR) was recorded with three non-polarizing Ag-AgCl scalp electrodes in thirty young and healthy volunteers (age 18-26 years) with normal hearing. ABR data were collected before, and immediately after a 10 minute exposure to 900 MHz pulsed electromagnetic field (EMF) emitted by a commercial Nokia 6310 mobile phone. Fifteen subjects were exposed to genuine EMF and fifteen to sham EMF in a double blind and counterbalanced order. Possible effects of irradiation was analyzed by comparing the latency of ABR waves I, III and V before and after genuine/sham EMF exposure. Paired sample t-test was conducted for statistical analysis. Results revealed no significant differences in the latency of ABR waves I, III and V before and after 10 minutes of genuine/sham EMF exposure. The present results suggest that, in our experimental conditions, a single 10 minute exposure of 900 MHz EMF emitted by a commercial mobile phone does not produce measurable immediate effects in the latency of auditory brainstem waves I, III and V.

  2. Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity

    PubMed Central

    Yang, Jason; Ciacci, Joseph D.

    2017-01-01

    Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords “subacute sclerosing panencephalitis” and “brainstem” using the National Library of Medicine PubMed database (March 1981–September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment. PMID:29112137

  3. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Giantsoudi, D; Adams, J; MacDonald, S

    Purpose: In proton radiation therapy of posterior fossa tumors, to spare other sensitive structures, the preferred beam geometry results in placing the treatment field distal edge within or just beyond the brainstem, including in at least partially in the treatment volume. Concerns for brainstem toxicity are increased and a controversy exists as to weather the beam’s distal edge should be placed within the brainstem or beyond it, to avoid elevated linear energy transfer (LET) and relative biological effectiveness (RBE) within the brainstem. The dosimetric efficacy of these techniques was examined, accounting for LET- and dose-dependent variable RBE distributions. Methods: Threemore » treatment planning techniques were applied in six ependymoma cases: (a) three-field dose-sparing, with beams’ distal edge within the brainstem; (b) three-field LET-sparing, using same beam directions as (a) but extended field ranges beyond the brainstem; (c) two-posterior-oblique LET-sparing, with extended ranges as (b). Monte Carlo calculated dose, LET and RBE-weighted dose distributions were compared. Results: Lower LET values in the brainstem were accompanied by higher median dose: 53.7 Gy[RBE] and 54.3 Gy[RBE] for techniques (b) and (c) versus 52.1 Gy[RBE] for (a). Accounting for variable RBE, a 15% increase of the brainstem volume receiving at least 60 Gy[RBE] was observed for technique (c) versus (a). Maximum variable-RBE-weighted brainstem dose was comparable for all techniques. Conclusion: Extending the treatment beam range beyond the brainstem, significantly increased its volume receiving high dose radiation, even when accounting for the decreased LET values. The dosimetric benefits of techniques limiting the brainstem dose may outweigh the impact of LET reduction achieved through this technique, especially since clinical consequences of increased LET at the end of range have not been proven yet.« less

  4. Dissociation of spontaneous seizures and brainstem seizure thresholds in mice exposed to eight flurothyl-induced generalized seizures.

    PubMed

    Kadiyala, Sridhar B; Ferland, Russell J

    2017-03-01

    C57BL/6J mice exposed to eight flurothyl-induced generalized clonic seizures exhibit a change in seizure phenotype following a 28-day incubation period and subsequent flurothyl rechallenge. Mice now develop a complex seizure semiology originating in the forebrain and propagating into the brainstem seizure network (a forebrain→brainstem seizure). In contrast, this phenotype change does not occur in seizure-sensitive DBA/2J mice. The underlying mechanism(s) was the focus of these studies. DBA2/J mice were exposed to eight flurothyl-induced seizures (1/day) followed by 24-hour video-electroencephalographic recordings for 28-days. Forebrain and brainstem seizure thresholds were determined in C57BL/6J and DBA/2J mice following one or eight flurothyl-induced seizures, or after eight flurothyl-induced seizures, a 28-day incubation period, and final flurothyl rechallenge. Similar to C57BL/6J mice, DBA2/J mice expressed spontaneous seizures. However, unlike C57BL/6J mice, DBA2/J mice continued to have spontaneous seizures without remission. Because DBA2/J mice do not express forebrain→brainstem seizures following flurothyl rechallenge after a 28-day incubation period, this indicated that spontaneous seizures were not sufficient for the evolution of forebrain→brainstem seizures. Therefore, we determined whether brainstem seizure thresholds were changing during this repeated-flurothyl model and whether this could account for the expression of forebrain→brainstem seizures. Brainstem seizure thresholds were not different between C57BL/6J and DBA/2J mice on day one or on the last induction seizure trial (day eight). However, brainstem seizure thresholds did differ significantly on flurothyl rechallenge (day 28) with DBA/2J mice showing no lowering of their brainstem seizure thresholds. These results demonstrated that DBA/2J mice exposed to the repeated-flurothyl model develop spontaneous seizures without evidence of seizure remission and provide a new model of epileptogenesis. Moreover, these findings indicated that the transition of forebrain ictal discharge into the brainstem seizure network occurs due to changes in brainstem seizure thresholds that are independent of spontaneous seizure expression.

  5. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chang, Chiou-Shiung, E-mail: et000417@gmail.com; Department of Radiation Oncology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan; Hwang, Jing-Min

    Stereotactic radiosurgery (SRS) is a well-established technique that is replacing whole-brain irradiation in the treatment of intracranial lesions, which leads to better preservation of brain functions, and therefore a better quality of life for the patient. There are several available forms of linear accelerator (LINAC)–based SRS, and the goal of the present study is to identify which of these techniques is best (as evaluated by dosimetric outcomes statistically) when the target is located adjacent to brainstem. We collected the records of 17 patients with lesions close to the brainstem who had previously been treated with single-fraction radiosurgery. In all, 5more » different lesion catalogs were collected, and the patients were divided into 2 distance groups—1 consisting of 7 patients with a target-to-brainstem distance of less than 0.5 cm, and the other of 10 patients with a target-to-brainstem distance of ≥ 0.5 and < 1 cm. Comparison was then made among the following 3 types of LINAC-based radiosurgery: dynamic conformal arcs (DCA), intensity-modulated radiosurgery (IMRS), and volumetric modulated arc radiotherapy (VMAT). All techniques included multiple noncoplanar beams or arcs with or without intensity-modulated delivery. The volume of gross tumor volume (GTV) ranged from 0.2 cm{sup 3} to 21.9 cm{sup 3}. Regarding the dose homogeneity index (HI{sub ICRU}) and conformity index (CI{sub ICRU}) were without significant difference between techniques statistically. However, the average CI{sub ICRU} = 1.09 ± 0.56 achieved by VMAT was the best of the 3 techniques. Moreover, notable improvement in gradient index (GI) was observed when VMAT was used (0.74 ± 0.13), and this result was significantly better than those achieved by the 2 other techniques (p < 0.05). For V{sub 4} {sub Gy} of brainstem, both VMAT (2.5%) and IMRS (2.7%) were significantly lower than DCA (4.9%), both at the p < 0.05 level. Regarding V{sub 2} {sub Gy} of normal brain, VMAT plans had attained 6.4 ± 5%; this was significantly better (p < 0.05) than either DCA or IMRS plans, at 9.2 ± 7% and 8.2 ± 6%, respectively. Owing to the multiple arc or beam planning designs of IMRS and VMAT, both of these techniques required higher MU delivery than DCA, with the averages being twice as high (p < 0.05). If linear accelerator is only 1 modality can to establish for SRS treatment. Based on statistical evidence retrospectively, we recommend VMAT as the optimal technique for delivering treatment to tumors adjacent to brainstem.« less

  6. Focal brainstem gliomas

    PubMed Central

    Sabbagh, Abdulrahman J.; Alaqeel, Ahmed M.

    2015-01-01

    Improved neuronavigation guidance as well as intraoperative imaging and neurophysiologic monitoring technologies have enhanced the ability of neurosurgeons to resect focal brainstem gliomas. In contrast, diffuse brainstem gliomas are considered to be inoperable lesions. This article is a continuation of an article that discussed brainstem glioma diagnostics, imaging, and classification. Here, we address open surgical treatment of and approaches to focal, dorsally exophytic, and cervicomedullary brainstem gliomas. Intraoperative neuronavigation, intraoperative neurophysiologic monitoring, as well as intraoperative imaging are discussed as adjunctive measures to help render these procedures safer, more acute, and closer to achieving surgical goals. PMID:25864061

  7. [A case of transient auditory agnosia and schizophrenia].

    PubMed

    Kanzaki, Jin; Harada, Tatsuhiko; Kanzaki, Sho

    2011-03-01

    We report a case of transient functional auditory agnosia and schizophrenia and discuss their relationship. A 30-year-old woman with schizophrenia reporting bilateral hearing loss was found in history taking to be able to hear but could neither understand speech nor discriminate among environmental sounds. Audiometry clarified normal but low speech discrimination. Otoacoustic emission and auditory brainstem response were normal. Magnetic resonance imaging (MRI) elsewhere evidenced no abnormal findings. We assumed that taking care of her grandparents who had been discharged from the hospital had unduly stressed her, and her condition improved shortly after she stopped caring for them, returned home and started taking a minor tranquilizer.

  8. A two-year longitudinal pilot MRI study of the brainstem in autism.

    PubMed

    Jou, Roger J; Frazier, Thomas W; Keshavan, Matcheri S; Minshew, Nancy J; Hardan, Antonio Y

    2013-08-15

    Research has demonstrated the potential role of the brainstem in the pathobiology of autism. Previous studies have suggested reductions in brainstem volume and a relationship between this structure and sensory abnormalities. However, little is known regarding the developmental aspects of the brainstem across childhood and adolescence. The goal of this pilot study was to examine brainstem development via MRI volumetry using a longitudinal research design. Participants included 23 boys with autism and 23 matched controls (age range=8-17 years), all without intellectual disability. Participants underwent structural MRI scans once at baseline and again at two-year follow-up. Brainstem volumetric measurements were performed using the BRAINS2 software package. There were no significant group differences in age, gender, handedness, and total brain volume; however, full-scale IQ was higher in controls. Autism and control groups showed different patterns of growth in brainstem volume. While whole brainstem volume remained stable in controls over the two-year period, the autism group showed increases with age reaching volumes comparable to controls by age 15 years. This increase of whole brainstem volume was primarily driven by bilateral increases in gray matter volume. Findings from this preliminary study are suggestive of developmental brainstem abnormalities in autism primarily involving gray matter structures. These findings are consistent with autism being conceptualized as a neurodevelopmental disorder with alterations in brain-growth trajectories. More longitudinal MRI studies are needed integrating longitudinal cognitive/behavioral data to confirm and elucidate the clinical significance of these atypical growth patterns. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Brainstem blood brain barrier disruption using focused ultrasound: A demonstration of feasibility and enhanced doxorubicin delivery.

    PubMed

    Alli, Saira; Figueiredo, Carlyn A; Golbourn, Brian; Sabha, Nesrin; Wu, Megan Yijun; Bondoc, Andrew; Luck, Amanda; Coluccia, Daniel; Maslink, Colin; Smith, Christian; Wurdak, Heiko; Hynynen, Kullervo; O'Reilly, Meaghan; Rutka, James T

    2018-05-15

    Magnetic Resonance Image-guided Focused Ultrasound (MRgFUS) has been used to achieve transient blood brain barrier (BBB) opening without tissue injury. Delivery of a targeted ultrasonic wave causes an interaction between administered microbubbles and the capillary bed resulting in enhanced vessel permeability. The use of MRgFUS in the brainstem has not previously been shown but could provide value in the treatment of tumours such as Diffuse Intrinsic Pontine Glioma (DIPG) where the intact BBB has contributed to the limited success of chemotherapy. Our primary objective was to determine whether the use of MRgFUS in this eloquent brain region could be performed without histological injury and functional deficits. Our secondary objective was to select an effective chemotherapeutic against patient derived DIPG cell lines and demonstrate enhanced brainstem delivery when combined with MRgFUS in vivo. Female Sprague Dawley rats were randomised to one of four groups: 1) Microbubble administration but no MRgFUS treatment; 2) MRgFUS only; 3) MRgFUS + microbubbles; and 4) MRgFUS + microbubbles + cisplatin. Physiological assessment was performed by monitoring of heart and respiratory rates. Motor function and co-ordination were evaluated by Rotarod and grip strength testing. Histological analysis for haemorrhage (H&E), neuronal nuclei (NeuN) and apoptosis (cleaved Caspase-3) was also performed. A drug screen of eight chemotherapy agents was conducted in three patient-derived DIPG cell lines (SU-DIPG IV, SU-DIPG XIII and SU-DIPG XVII). Doxorubicin was identified as an effective agent. NOD/SCID/GAMMA (NSG) mice were subsequently administered with 5 mg/kg of intravenous doxorubicin at the time of one of the following: 1) Microbubbles but no MRgFUS; 2) MRgFUS only; 3) MRgFUS + microbubbles and 4) no intervention. Brain specimens were extracted at 2 h and doxorubicin quantification was conducted using liquid chromatography mass spectrometry (LC/MS). BBB opening was confirmed by contrast enhancement on T1-weighted MR imaging and positive Evans blue staining of the brainstem. Normal cardiorespiratory parameters were preserved. Grip strength and Rotarod testing demonstrating no decline in performance across all groups. Histological analysis showed no evidence of haemorrhage, neuronal loss or increased apoptosis. Doxorubicin demonstrated cytotoxicity against all three cell lines and is known to have poor BBB permeability. Quantities measured in the brainstem of NSG mice were highest in the group receiving MRgFUS and microbubbles (431.5 ng/g). This was significantly higher than in mice who received no intervention (7.6 ng/g). Our data demonstrates both the preservation of histological and functional integrity of the brainstem following MRgFUS for BBB opening and the ability to significantly enhance drug delivery to the region, giving promise to the treatment of brainstem-specific conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Proposed Toxic and Hypoxic Impairment of a Brainstem Locus in Autism

    PubMed Central

    McGinnis, Woody R.; Audhya, Tapan; Edelson, Stephen M.

    2013-01-01

    Electrophysiological findings implicate site-specific impairment of the nucleus tractus solitarius (NTS) in autism. This invites hypothetical consideration of a large role for this small brainstem structure as the basis for seemingly disjointed behavioral and somatic features of autism. The NTS is the brain’s point of entry for visceral afference, its relay for vagal reflexes, and its integration center for autonomic control of circulatory, immunological, gastrointestinal, and laryngeal function. The NTS facilitates normal cerebrovascular perfusion, and is the seminal point for an ascending noradrenergic system that modulates many complex behaviors. Microvascular configuration predisposes the NTS to focal hypoxia. A subregion—the “pNTS”—permits exposure to all blood-borne neurotoxins, including those that do not readily transit the blood-brain barrier. Impairment of acetylcholinesterase (mercury and cadmium cations, nitrates/nitrites, organophosphates, monosodium glutamate), competition for hemoglobin (carbon monoxide, nitrates/nitrites), and higher blood viscosity (net systemic oxidative stress) are suggested to potentiate microcirculatory insufficiency of the NTS, and thus autism. PMID:24336025

  11. MRI Brain Volume Measurements in Infantile Neuronal Ceroid Lipofuscinosis

    PubMed Central

    Baker, Eva H.; Levin, Sondra W.; Zhang, Zhongjian; Mukherjee, Anil B.

    2016-01-01

    Background Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative storage disease caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. PPT1 deficiency impairs degradation of palmitoylated proteins (constituents of ceroid) by lysosomal hydrolases. Consequent lysosomal ceroid accumulation leads to neuronal injury, resulting in rapid neurodegeneration and childhood demise. As part of a project studying treatment benefits of a combination of cysteamine bitartrate and N-acetylcysteine, we made serial measurements of patients’ brain volumes using MRI. Methods Ten INCL patients participating in a treatment/follow-up study underwent brain MRI that included high resolution T1-weighted images. After manual placement of a mask delineating the surface of the brain, a maximum-likelihood classifier was applied to determine total brain volume, further subdivided as cerebrum, cerebellum, brainstem, and thalamus. Patients’ brain volumes were compared to those of a normal population. Results Major subdivisions of the brain followed similar trajectories with different timing. The cerebrum demonstrated early, rapid volume loss, and may never have been normal postnatally. The thalamus dropped out of the normal range around age 6 months, cerebellum around age 2 years, and brainstem around age 3 years. Discussion Rapid cerebral volume loss was expected based upon previous qualitative reports. Because our study did not include a non-treatment arm, and because progression of brain volumes in INCL has not previously been quantified, we could not determine whether our intervention had a beneficial effect on brain volumes. However, the level of quantitative detail in this study allows it to serve as a reference for evaluation of future therapeutic interventions. PMID:27765741

  12. Brainstem response patterns in deeply-sedated critically-ill patients predict 28-day mortality.

    PubMed

    Rohaut, Benjamin; Porcher, Raphael; Hissem, Tarik; Heming, Nicholas; Chillet, Patrick; Djedaini, Kamel; Moneger, Guy; Kandelman, Stanislas; Allary, Jeremy; Cariou, Alain; Sonneville, Romain; Polito, Andréa; Antona, Marion; Azabou, Eric; Annane, Djillali; Siami, Shidasp; Chrétien, Fabrice; Mantz, Jean; Sharshar, Tarek

    2017-01-01

    Deep sedation is associated with acute brain dysfunction and increased mortality. We had previously shown that early-assessed brainstem reflexes may predict outcome in deeply sedated patients. The primary objective was to determine whether patterns of brainstem reflexes might predict mortality in deeply sedated patients. The secondary objective was to generate a score predicting mortality in these patients. Observational prospective multicenter cohort study of 148 non-brain injured deeply sedated patients, defined by a Richmond Assessment sedation Scale (RASS) <-3. Brainstem reflexes and Glasgow Coma Scale were assessed within 24 hours of sedation and categorized using latent class analysis. The Full Outline Of Unresponsiveness score (FOUR) was also assessed. Primary outcome measure was 28-day mortality. A "Brainstem Responses Assessment Sedation Score" (BRASS) was generated. Two distinct sub-phenotypes referred as homogeneous and heterogeneous brainstem reactivity were identified (accounting for respectively 54.6% and 45.4% of patients). Homogeneous brainstem reactivity was characterized by preserved reactivity to nociceptive stimuli and a partial and topographically homogenous depression of brainstem reflexes. Heterogeneous brainstem reactivity was characterized by a loss of reactivity to nociceptive stimuli associated with heterogeneous brainstem reflexes depression. Heterogeneous sub-phenotype was a predictor of increased risk of 28-day mortality after adjustment to Simplified Acute Physiology Score-II (SAPS-II) and RASS (Odds Ratio [95% confidence interval] = 6.44 [2.63-15.8]; p<0.0001) or Sequential Organ Failure Assessment (SOFA) and RASS (OR [95%CI] = 5.02 [2.01-12.5]; p = 0.0005). The BRASS (and marginally the FOUR) predicted 28-day mortality (c-index [95%CI] = 0.69 [0.54-0.84] and 0.65 [0.49-0.80] respectively). In this prospective cohort study, around half of all deeply sedated critically ill patients displayed an early particular neurological sub-phenotype predicting 28-day mortality, which may reflect a dysfunction of the brainstem.

  13. Correlation of Acute and Late Brainstem Toxicities With Dose-Volume Data for Pediatric Patients With Posterior Fossa Malignancies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nanda, Ronica H., E-mail: rhazari@emory.edu; Ganju, Rohit G.; Schreibmann, Edward

    Purpose: Radiation-induced brainstem toxicity after treatment of pediatric posterior fossa malignancies is incompletely understood, especially in the era of intensity modulated radiation therapy (IMRT). The rates of, and predictive factors for, brainstem toxicity after photon RT for posterior fossa tumors were examined. Methods and Materials: After institutional review board approval, 60 pediatric patients treated at our institution for nonmetastatic infratentorial ependymoma and medulloblastoma with IMRT were included in the present analysis. Dosimetric variables, including the mean and maximum dose to the brainstem, the dose to 10% to 90% of the brainstem (in 10% increments), and the volume of the brainstemmore » receiving 40, 45, 50, and 55 Gy were recorded for each patient. Acute (onset within 3 months) and late (>3 months of RT completion) RT-induced brainstem toxicities with clinical and radiographic correlates were scored using Common Terminology Criteria for Adverse Events, version 4.0. Results: Patients aged 1.4 to 21.8 years underwent IMRT or volumetric arc therapy postoperatively to the posterior fossa or tumor bed. At a median clinical follow-up period of 2.8 years, 14 patients had developed symptomatic brainstem toxicity (crude incidence 23.3%). No correlation was found between the dosimetric variables examined and brainstem toxicity. Vascular injury or ischemia showed a strong trend toward predicting brainstem toxicity (P=.054). Patients with grade 3 to 5 brainstem toxicity had undergone treatment to significant volumes of the posterior fossa. Conclusion: The results of the present series demonstrate a low, but not negligible, risk of brainstem radiation necrosis for pediatric patients with posterior fossa malignancies treated with IMRT. No specific dose-volume correlations were identified; however, modern treatment volumes might help limit the incidence of severe toxicity. Additional work investigating inherent biologic sensitivity might also provide further insight into this clinical problem.« less

  14. [An evaluation of clinical characteristics and prognosis of brain-stem infarction in diabetics].

    PubMed

    Lu, Zheng-qi; Li, Hai-yan; Hu, Xue-qiang; Zhang, Bing-jun

    2011-01-01

    To analyze the relationship between diabetics and the onset, clinical outcomes and prognosis of brainstem infarction, and to evaluate the impact of diabetes on brainstem infarction. Compare 172 cases of acute brainstem infarction in patients with or without diabetes. Analyze the associated risk factors of patients with brain-stem infarction in diabetics by multi-variate logistic regression analysis. Compare the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin scale (mRS) Score, pathogenetic condition and the outcome of the two groups in different times. The systolic blood pressure (SBP), TG, LDL-C, apolipoprotein B (Apo B), glutamyl transpeptidase (γ-GT), fibrinogen (Fb), fasting blood glucose (FPG) and glycosylated hemoglobin(HbA1c)in diabetic group were higher than those in non-diabetic group, which was statistically significant (P < 0.05). From multi-variate logistic regression analysis, γ-GT, Apo B and FPG were the risk predictors of diabetes with brainstem infarction(OR = 1.017, 4.667 and 3.173, respectively), while HDL-C was protective (OR = 0.288). HbA1c was a risk predictor of severity for acute brainstem infarction (OR = 1.299), while Apo A was beneficial (OR = 0.212). Compared with brain-stem infarction in non-diabetic group, NIHSS score and intensive care therapy of diabetic groups on the admission had no statistically significance, while the NIHSS score on discharge and the outcome at 6 months' of follow-up were statistically significant. Diabetes is closely associated with brainstem infarction. Brainstem infarction with diabetes cause more rapid progression, poorer prognosis, higher rates of mortality as well as disability and higher recurrence rate of cerebral infarction.

  15. Brainstem Auditory Evoked Potential in HIV-Positive Adults.

    PubMed

    Matas, Carla Gentile; Samelli, Alessandra Giannella; Angrisani, Rosanna Giaffredo; Magliaro, Fernanda Cristina Leite; Segurado, Aluísio C

    2015-10-20

    To characterize the findings of brainstem auditory evoked potential in HIV-positive individuals exposed and not exposed to antiretroviral treatment. This research was a cross-sectional, observational, and descriptive study. Forty-five HIV-positive individuals (18 not exposed and 27 exposed to the antiretroviral treatment - research groups I and II, respectively - and 30 control group individuals) were assessed through brainstem auditory evoked potential. There were no significant between-group differences regarding wave latencies. A higher percentage of altered brainstem auditory evoked potential was observed in the HIV-positive groups when compared to the control group. The most common alteration was in the low brainstem. HIV-positive individuals have a higher percentage of altered brainstem auditory evoked potential that suggests central auditory pathway impairment when compared to HIV-negative individuals. There was no significant difference between individuals exposed and not exposed to antiretroviral treatment.

  16. Cerebral blood flow in normal and abnormal sleep and dreaming

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Meyer, J.S.; Ishikawa, Y.; Hata, T.

    Measurements of regional or local cerebral blood flow (CBF) by the xenon-133 inhalation method and stable xenon computerized tomography CBF (CTCBF) method were made during relaxed wakefulness and different stages of REM and non-REM sleep in normal age-matched volunteers, narcoleptics, and sleep apneics. In the awake state, CBF values were reduced in both narcoleptics and sleep apneics in the brainstem and cerebellar regions. During sleep onset, whether REM or stage I-II, CBF values were paradoxically increased in narcoleptics but decreased severely in sleep apneics, while in normal volunteers they became diffusely but more moderately decreased. In REM sleep and dreamingmore » CBF values greatly increased, particularly in right temporo-parietal regions in subjects experiencing both visual and auditory dreaming.« less

  17. Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex

    PubMed Central

    Corcoran, Andrea E.; Brust, Rachael D.; Chang, YoonJeung; Nattie, Eugene E.

    2017-01-01

    Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 (Tac1) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1, referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine-N-oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO2. Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei. SIGNIFICANCE STATEMENT Serotonin (5-HT) neurons modulate physiological processes and behaviors as diverse as body temperature, respiration, aggression, and mood. Using genetic tools, we characterize a 5-HT neuron subtype defined by expression of Tachykinin1 and Pet1 (Tac1-Pet1 neurons), mapping soma localization to the caudal medulla primarily and axonal projections to brainstem motor nuclei most prominently, and, when silenced, observed blunting of the ventilatory response to inhaled CO2. Tac1-Pet1 neurons thus appear distinct from and contrast previously described Egr2-Pet1 neurons, which project primarily to chemosensory integration centers and are themselves chemosensitive. PMID:28073937

  18. Familial auditory neuropathy.

    PubMed

    Wang, Qiuju; Gu, Rui; Han, Dongyi; Yang, Weiyan

    2003-09-01

    Auditory neuropathy is a sensorineural hearing disorder characterized by absent or abnormal auditory brainstem responses and normal cochlear outer hair cell function as measured by otoacoustic emission recordings. Many risk factors are thought to be involved in its etiology and pathophysiology. Four Chinese pedigrees with familial auditory neuropathy were presented to demonstrate involvement of genetic factors in the etiology of auditory neuropathy. Probands of the above-mentioned pedigrees, who had been diagnosed with auditory neuropathy, were evaluated and followed in the Department of Otolaryngology-Head and Neck Surgery, China People Liberation Army General Hospital (Beijing, China). Their family members were studied, and the pedigree maps established. History of illness, physical examination, pure-tone audiometry, acoustic reflex, auditory brainstem responses, and transient evoked and distortion-product otoacoustic emissions were obtained from members of these families. Some subjects received vestibular caloric testing, computed tomography scan of the temporal bone, and electrocardiography to exclude other possible neuropathic disorders. In most affected patients, hearing loss of various degrees and speech discrimination difficulties started at 10 to 16 years of age. Their audiological evaluation showed absence of acoustic reflex and auditory brainstem responses. As expected in auditory neuropathy, these patients exhibited near-normal cochlear outer hair cell function as shown in distortion product otoacoustic emission recordings. Pure-tone audiometry revealed hearing loss ranging from mild to profound in these patients. Different inheritance patterns were observed in the four families. In Pedigree I, 7 male patients were identified among 43 family members, exhibiting an X-linked recessive pattern. Affected brothers were found in Pedigrees II and III, whereas in pedigree IV, two sisters were affected. All the patients were otherwise normal without evidence of peripheral neuropathy at the time of writing. Patients with characteristics of nonsyndromic hereditary auditory neuropathy were identified in one large and three smaller Chinese families. Pedigree analysis suggested an X-linked, recessive hereditary pattern in one pedigree and autosomal recessive inheritances in the other three pedigrees. The phenotypes in the study were typical of auditory neuropathy; they were transmitted in different inheritance patterns, indicating clinical and genetic heterogeneity of this disorder. The observed inheritance and clinical audiological findings are different from those previously described for nonsyndromic low-frequency sensorineural hearing loss. This information should facilitate future molecular linkage analyses and positional cloning for the relative genes contributing to auditory neuropathy.

  19. Distribution of CGRP in the minipig brainstem.

    PubMed

    Lisardo Sánchez, Manuel; Vecino, Elena; Coveñas, Rafael

    2014-05-01

    For the first time, an in-depth study has been made of the distribution of fibers and cell bodies containing calcitonin gene-related peptide (CGRP) in the minipig brainstem using an indirect immunoperoxidase technique. The animals studied were not treated with colchicine. Cell bodies containing CGRP were found in 20 nuclei/regions of the brainstem. These perikarya were located in somatomotor, brachiomotor and raphae nuclei, nucleus ambiguus, substantia nigra, nucleus reticularis tegmenti pontis, nucleus prepositus hypoglossi, nuclei olivaris inferior and superior, nuclei pontis, formatio reticularis, nucleus dorsalis tegmenti of Gudden, and in the nucleus reticularis lateralis. Fourteen of the 20 brainstem nuclei showed a high density of immunoreactive cell bodies. In comparison with other species, the minipig, together with the rat, show the most widespread distribution of cell bodies containing CGRP in the mammalian brainstem. Immunoreactive fibers were also observed in the brainstem. However, in the minipig brainstem the density of these fibers is low, as in many brainstem nuclei only single immunoreactive fibers were observed. A high density of immunoreactive fibers was only observed in the pars caudalis of the nucleus tractus spinalis nervi trigemini and in the nucleus ventralis tegmenti of Gudden. According to the observed anatomical distribution of the immunoreactive structures containing CGRP, the peptide could be involved in motor, somatosensory, gustative, and autonomic mechanisms. Copyright © 2014 Wiley Periodicals, Inc.

  20. Transcranial sonography of brainstem structures in panic disorder.

    PubMed

    Šilhán, Petr; Jelínková, Monika; Walter, Uwe; Pavlov Praško, Ján; Herzig, Roman; Langová, Kateřina; Školoudík, David

    2015-10-30

    Panic disorder has been associated with altered serotonin metabolism in the brainstem raphe. The aim of study was to evaluate the BR echogenicity on transcranial sonography (TCS) in panic disorder. A total of 96 healthy volunteers were enrolled in the "derivation" cohort, and 26 healthy volunteers and 26 panic disorder patients were enrolled in the "validation" cohort. TCS echogenicity of brainstem raphe and substantia nigra was assessed on anonymized images visually and by means of digitized image analysis. Significantly reduced brainstem raphe echogenicity was detected more frequently in panic disorder patients than in controls using both visual (68% vs. 31%) and digitized image analysis (52% vs. 12%). The optimal cut-off value of digitized brainstem raphe echogenicity indicated the diagnosis of panic disorder with a sensitivity of 64% and a specificity of 73%, and corresponded to the 30th percentile in the derivation cohort. Reduced brainstem raphe echogenicity was associated with shorter treatment duration, and, by trend, lower severity of anxiety. No relationship was found between echogenicity of brainstem raphe or substantia nigra and age, gender, severity of panic disorder, or severity of depression. Patients with panic disorder exhibit changes of brainstem raphe on TCS suggesting an alteration of the central serotonergic system. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Progressive Changes in a Distributed Neural Circuit Underlie Breathing Abnormalities in Mice Lacking MeCP2.

    PubMed

    Huang, Teng-Wei; Kochukov, Mikhail Y; Ward, Christopher S; Merritt, Jonathan; Thomas, Kaitlin; Nguyen, Tiffani; Arenkiel, Benjamin R; Neul, Jeffrey L

    2016-05-18

    Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Severe breathing abnormalities are common in RTT and are reproduced in mouse models of RTT. Previously, we found that removing MeCP2 from the brainstem and spinal cord in mice caused early lethality and abnormal breathing. To determine whether loss of MeCP2 in functional components of the respiratory network causes specific breathing disorders, we used the Cre/LoxP system to differentially manipulate MeCP2 expression throughout the brainstem respiratory network, specifically within HoxA4-derived tissues, which include breathing control circuitry within the nucleus tractus solitarius and the caudal part of ventral respiratory column but do not include more rostral parts of the breathing control circuitry. To determine whether respiratory phenotypes manifested in animals with MeCP2 removed from specific pons medullary respiratory circuits, we performed whole-body plethysmography and electrophysiological recordings from in vitro brainstem slices from mice lacking MeCP2 in different circuits. Our results indicate that MeCP2 expression in the medullary respiratory network is sufficient for normal respiratory rhythm and preventing apnea. However, MeCP2 expression within components of the breathing circuitry rostral to the HoxA4 domain are neither sufficient to prevent the hyperventilation nor abnormal hypoxic ventilatory response. Surprisingly, we found that MeCP2 expression in the HoxA4 domain alone is critical for survival. Our study reveals that MeCP2 is differentially required in select respiratory components for different aspects of respiratory functions, and collectively for the integrity of this network functions to maintain proper respiration. Breathing abnormalities are a significant clinical feature in Rett syndrome and are robustly reproduced in the mouse models of this disease. Previous work has established that alterations in the function of MeCP2, the protein encoded by the gene mutated in Rett syndrome, within the hindbrain are critical for control of normal breathing. Here we show that MeCP2 function plays distinct roles in specific brainstem regions in the genesis of various aspects of abnormal breathing. This provides insight into the pathogenesis of these breathing abnormalities in Rett syndrome, which could be used to target treatments to improve these symptoms. Furthermore, it provides further knowledge about the fundamental neural circuits that control breathing. Copyright © 2016 the authors 0270-6474/16/365572-15$15.00/0.

  2. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Merchant, Thomas E., E-mail: thomas.merchant@stjude.or; Chitti, Ramana M.; Li Chenghong

    Purpose: To identify risk factors associated with incomplete neurological recovery in pediatric patients with infratentorial ependymoma treated with postoperative conformal radiation therapy (CRT). Methods: The study included 68 patients (median age +- standard deviation of 2.6 +- 3.8 years) who were followed for 5 years after receiving CRT (54-59.4 Gy) and were assessed for function of cranial nerves V to VII and IX to XII, motor weakness, and dysmetria. The mean (+- standard deviation) brainstem dose was 5,487 (+-464) cGy. Patients were divided into four groups representing those with normal baseline and follow-up, those with abnormal baseline and full recovery,more » those with abnormal baseline and partial or no recovery, and those with progressive deficits at 12 (n = 62 patients), 24 (n = 57 patients), and 60 (n = 50 patients) months. Grouping was correlated with clinical and treatment factors. Results: Risk factors (overall risk [OR], p value) associated with incomplete recovery included gender (male vs. female, OR = 3.97, p = 0.036) and gross tumor volume (GTV) (OR/ml = 1.23, p = 0.005) at 12 months, the number of resections (>1 vs. 1; OR = 23.7, p = 0.003) and patient age (OR/year = 0.77, p = 0.029) at 24 months, and cerebrospinal fluid (CSF) shunting (Yes vs. No; OR = 21.9, p = 0.001) and GTV volume (OR/ml = 1.18, p = 0.008) at 60 months. An increase in GTV correlated with an increase in the number of resections (p = 0.001) and CSF shunting (p = 0.035); the number of resections correlated with CSF shunting (p < 0.0001), and male patients were more likely to undergo multiple tumor resections (p = 0.003). Age correlated with brainstem volume (p < 0.0001). There were no differences in outcome based on the absolute or relative volume of the brainstem that received more than 54 Gy. Conclusions: Incomplete recovery of brainstem function after CRT for infratentorial ependymoma is related to surgical morbidity and the volume and the extent of tumor.« less

  3. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jeong, K; Basavatia, A; Mynampati, D

    Purpose: To compare VMAT SRS plans, dynamic conformal arc (DCA) plans, and Brainlab iPlan’s capability of planning and delivering brain SRS plans by employing HybridArc. HybridArc utilizes both DCA and IMRT. Using HybridArc, the amount of DCA versus IMRT needs to be optimized. Methods: Four SRS patients with the aim of reducing brainstem dose were selected for this study. All patients were contoured in iPlan and transferred to Eclipse for VMAT planning. In iPlan, DCA plans were created for each case. Moreover, nine HybridArc plans with DCA-IMRT ratios between 9:1 through 1:9 were created with a single ring structure generatedmore » by subtracting 3 mm expansion of target from a 10 mm expansion of the target. Two static IMRT beams were used in each of the five DCA arcs for HybridArc. The dose was prescribed to DCA only and HybridArc plans and normalized so that the target volume (TV) receives 100% dose to 99.5% of the TV to achieve 120% ∼ 130% max dose within targets. Following metrics were compared: PITV, V12Gy, CGIc, CGIg, CGI, brainstem max dose, and total monitor units (MUs). Results: A brainstem max dose comparable with VMAT from 30% IMRT and less with 50% or more IMRT could be achieved. PITV decreased with increasing IMRT portion and begins to saturate past an IMRT portion of 30%. The CGIg index, which represents how fast the dose falls off, was better with HybridArc in all HybridArc plans. Total MUs increased with increasing IMRT but less than VMAT in all cases. Conclusion: Overall, a lower brainstem max dose and a lower V12Gy with fewer MUs can be achieved with HybridArc. Considering all factors, it would be best to use a DCA-IMRT ratio of either 7:3 or 6:4.« less

  4. Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration.

    PubMed

    Pollard, Amelia Kate; Craig, Emma Louise; Chakrabarti, Lisa

    2016-01-01

    Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70-71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions.

  5. Auditory Brainstem Response Thresholds to Air- and Bone-Conducted CE-Chirps in Neonates and Adults.

    PubMed

    Cobb, Kensi M; Stuart, Andrew

    2016-08-01

    The purpose of this study was to compare auditory brainstem response (ABR) thresholds to air- and bone-conducted CE-Chirps in neonates and adults. Thirty-two neonates with no physical or neurologic challenges and 20 adults with normal hearing participated. ABRs were acquired with a starting intensity of 30 dB normal hearing level (nHL). The lowest stimulus intensity level at which a wave V was identifiable and replicable was considered the ABR threshold. ABR thresholds to air-conducted CE-Chirps were 9.8 dB nHL for neonates and adults. ABR thresholds to bone-conducted CE-Chirps were 3.8 and 13.8 dB nHL for neonates and adults, respectively. The difference in ABR thresholds to bone-conducted CE-Chirps was significantly different (p < .0001, ηp2 = .45). Adults had significantly larger wave V amplitudes to air- (p < .0001, ηp2 = .50) and bone-conducted (p = .013, ηp2 = .15) CE-Chirps at a stimulus intensity of 30 dB nHL. At the same intensity, adults evidenced significantly shorter wave V latencies (p < .0001, ηp2 = .49) only with air-conducted CE-chirps. The difference in ABR thresholds and wave V latencies to air- and bone-conducted CE-Chirps between neonates and adults may be attributed to a disparity in effective signal delivery to the cochlea.

  6. Speech auditory brainstem response (speech ABR) characteristics depending on recording conditions, and hearing status: an experimental parametric study.

    PubMed

    Akhoun, Idrick; Moulin, Annie; Jeanvoine, Arnaud; Ménard, Mikael; Buret, François; Vollaire, Christian; Scorretti, Riccardo; Veuillet, Evelyne; Berger-Vachon, Christian; Collet, Lionel; Thai-Van, Hung

    2008-11-15

    Speech elicited auditory brainstem responses (Speech ABR) have been shown to be an objective measurement of speech processing in the brainstem. Given the simultaneous stimulation and recording, and the similarities between the recording and the speech stimulus envelope, there is a great risk of artefactual recordings. This study sought to systematically investigate the source of artefactual contamination in Speech ABR response. In a first part, we measured the sound level thresholds over which artefactual responses were obtained, for different types of transducers and experimental setup parameters. A watermelon model was used to model the human head susceptibility to electromagnetic artefact. It was found that impedances between the electrodes had a great effect on electromagnetic susceptibility and that the most prominent artefact is due to the transducer's electromagnetic leakage. The only artefact-free condition was obtained with insert-earphones shielded in a Faraday cage linked to common ground. In a second part of the study, using the previously defined artefact-free condition, we recorded speech ABR in unilateral deaf subjects and bilateral normal hearing subjects. In an additional control condition, Speech ABR was recorded with the insert-earphones used to deliver the stimulation, unplugged from the ears, so that the subjects did not perceive the stimulus. No responses were obtained from the deaf ear of unilaterally hearing impaired subjects, nor in the insert-out-of-the-ear condition in all the subjects, showing that Speech ABR reflects the functioning of the auditory pathways.

  7. Prospective longitudinal MRI study of brain volumes and diffusion changes during the first year after moderate to severe traumatic brain injury

    PubMed Central

    Brezova, Veronika; G⊘ran Moen, Kent; Skandsen, Toril; Vik, Anne; Brewer, James B.; Salvesen, Øyvind; Håberg, Asta K.

    2014-01-01

    The objectives of this prospective study in 62 moderate–severe TBI patients were to investigate volume change in cortical gray matter (GM), hippocampus, lenticular nucleus, lobar white matter (WM), brainstem and ventricles using a within subject design and repeated MRI in the early phase (1–26 days) and 3 and 12 months postinjury and to assess changes in GM apparent diffusion coefficient (ADC) in normal appearing tissue in the cortex, hippocampus and brainstem. The impact of Glasgow Coma Scale (GCS) score at admission, duration of post-traumatic amnesia (PTA), and diffusion axonal injury (DAI) grade on brain volumes and ADC values over time was assessed. Lastly, we determined if MRI-derived brain volumes from the 3-month scans provided additional, significant predictive value to 12-month outcome classified with the Glasgow Outcome Scale—Extended after adjusting for GCS, PTA and age. Cortical GM loss was rapid, largely finished by 3 months, but the volume reduction was unrelated to GCS score, PTA, or presence of DAI. However, cortical GM volume at 3 months was a significant independent predictor of 12-month outcome. Volume loss in the hippocampus and lenticular nucleus was protracted and statistically significant first at 12 months. Slopes of volume reduction over time for the cortical and subcortical GGM were significantly different. Hippocampal volume loss was most pronounced and rapid in individuals with PTA > 2 weeks. The 3-month volumes of the hippocampus and lentiform nucleus were the best independent predictors of 12-month outcome after adjusting for GCS, PTA and age. In the brainstem, volume loss was significant at both 3 and 12 months. Brainstem volume reduction was associated with lower GCS score and the presence of DAI. Lobar WM volume was significantly decreased first after 12 months. Surprisingly DAI grade had no impact on lobar WM volume. Ventricular dilation developed predominantly during the first 3 months, and was strongly associated with volume changes in the brainstem and cortical GM, but not lobar WM volume. Higher ADC values were detected in the cortex in individuals with severe TBI, DAI and PTA > 2 weeks, from 3 months. There were no associations between ADC values and brain volumes, and ADC values did not predict outcome. PMID:25068105

  8. Exposures to fine particulate matter (PM2.5) and ozone above USA standards are associated with auditory brainstem dysmorphology and abnormal auditory brainstem evoked potentials in healthy young dogs.

    PubMed

    Calderón-Garcidueñas, Lilian; González-González, Luis O; Kulesza, Randy J; Fech, Tatiana M; Pérez-Guillé, Gabriela; Luna, Miguel Angel Jiménez-Bravo; Soriano-Rosales, Rosa Eugenia; Solorio, Edelmira; Miramontes-Higuera, José de Jesús; Gómez-Maqueo Chew, Aline; Bernal-Morúa, Alexia F; Mukherjee, Partha S; Torres-Jardón, Ricardo; Mills, Paul C; Wilson, Wayne J; Pérez-Guillé, Beatriz; D'Angiulli, Amedeo

    2017-10-01

    Delayed central conduction times in the auditory brainstem have been observed in Mexico City (MC) healthy children exposed to fine particulate matter (PM 2.5 ) and ozone (O 3 ) above the current United States Environmental Protection Agency (US-EPA) standards. MC children have α synuclein brainstem accumulation and medial superior olivary complex (MSO) dysmorphology. The present study used a dog model to investigate the potential effects of air pollution on the function and morphology of the auditory brainstem. Twenty-four dogs living in clean air v MC, average age 37.1 ± 26.3 months, underwent brainstem auditory evoked potential (BAEP) measurements. Eight dogs (4 MC, 4 Controls) were analysed for auditory brainstem morphology and histopathology. MC dogs showed ventral cochlear nuclei hypotrophy and MSO dysmorphology with a significant decrease in cell body size, decreased neuronal packing density with regions in the nucleus devoid of neurons and marked gliosis. MC dogs showed significant delayed BAEP absolute wave I, III and V latencies compared to controls. MC dogs show auditory nuclei dysmorphology and BAEPs consistent with an alteration of the generator sites of the auditory brainstem response waveform. This study puts forward the usefulness of BAEPs to study auditory brainstem neurodegenerative changes associated with air pollution in dogs. Recognition of the role of non-invasive BAEPs in urban dogs is warranted to elucidate novel neurodegenerative pathways link to air pollution and a promising early diagnostic strategy for Alzheimer's Disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. A probabilistic atlas of human brainstem pathways based on connectome imaging data.

    PubMed

    Tang, Yuchun; Sun, Wei; Toga, Arthur W; Ringman, John M; Shi, Yonggang

    2018-04-01

    The brainstem is a critical structure that regulates vital autonomic functions, houses the cranial nerves and their nuclei, relays motor and sensory information between the brain and spinal cord, and modulates cognition, mood, and emotions. As a primary relay center, the fiber pathways of the brainstem include efferent and afferent connections among the cerebral cortex, spinal cord, and cerebellum. While diffusion MRI has been successfully applied to map various brain pathways, its application for the in vivo imaging of the brainstem pathways has been limited due to inadequate resolution and large susceptibility-induced distortion artifacts. With the release of high-resolution data from the Human Connectome Project (HCP), there is increasing interest in mapping human brainstem pathways. Previous works relying on HCP data to study brainstem pathways, however, did not consider the prevalence (>80%) of large distortions in the brainstem even after the application of correction procedures from the HCP-Pipeline. They were also limited in the lack of adequate consideration of subject variability in either fiber pathways or region of interests (ROIs) used for bundle reconstruction. To overcome these limitations, we develop in this work a probabilistic atlas of 23 major brainstem bundles using high-quality HCP data passing rigorous quality control. For the large-scale data from the 500-Subject release of HCP, we conducted extensive quality controls to exclude subjects with severe distortions in the brainstem area. After that, we developed a systematic protocol to manually delineate 1300 ROIs on 20 HCP subjects (10 males; 10 females) for the reconstruction of fiber bundles using tractography techniques. Finally, we leveraged our novel connectome modeling techniques including high order fiber orientation distribution (FOD) reconstruction from multi-shell diffusion imaging and topography-preserving tract filtering algorithms to successfully reconstruct the 23 fiber bundles for each subject, which were then used to calculate the probabilistic atlases in the MNI152 space for public release. In our experimental results, we demonstrate that our method yielded anatomically faithful reconstruction of the brainstem pathways and achieved improved performance in comparison with an existing atlas of cerebellar peduncles based on HCP data. These atlases have been publicly released on NITRIC (https://www.nitrc.org/projects/brainstem_atlas/) and can be readily used by brain imaging researchers interested in studying brainstem pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Brainstem involvement in subacute sclerosing panencephalitis.

    PubMed

    Sharma, Pawan; Singh, Dileep; Singh, Maneesh Kumar; Garg, Ravindra Kumar; Kohli, Neera

    2011-01-01

    The parieto-occipital region of the brain is most frequently and severely affected in subacute sclerosing panencephalitis (SSPE). The basal ganglia, cerebellum and corpus callosum are less commonly involved. Brainstem involvement is rarely described in SSPE, and usually there is involvement of other regions of the brain. We describe a patient with subacute sclerosing panencephalitis with brain magnetic resonance imaging showing extensive brainstem involvement without significant involvement of other cortical structures. Though rarely described in SSPE, one should be aware of such brainstem and cerebellum involvement, and SSPE should be kept in mind when brainstem signal changes are seen in brain MRI with or without involvement of other regions of brain to avoid erroneous reporting.

  11. Brainstem cavernous malformations: anatomical, clinical, and surgical considerations.

    PubMed

    Giliberto, Giuliano; Lanzino, Desiree J; Diehn, Felix E; Factor, David; Flemming, Kelly D; Lanzino, Giuseppe

    2010-09-01

    Symptomatic brainstem cavernous malformations carry a high risk of permanent neurological deficit related to recurrent hemorrhage, which justifies aggressive management. Detailed knowledge of the microscopic and surface anatomy is important for understanding the clinical presentation, predicting possible surgical complications, and formulating an adequate surgical plan. In this article the authors review and illustrate the surgical and microscopic anatomy of the brainstem, provide anatomoclinical correlations, and illustrate a few clinical cases of cavernous malformations in the most common brainstem areas.

  12. Brainstem Encoding of Aided Speech in Hearing Aid Users with Cochlear Dead Region(s).

    PubMed

    Hassaan, Mohammad Ramadan; Ibraheem, Ola Abdallah; Galhom, Dalia Helal

    2016-07-01

    Neural encoding of speech begins with the analysis of the signal as a whole broken down into its sinusoidal components in the cochlea, which has to be conserved up to the higher auditory centers. Some of these components target the dead regions of the cochlea causing little or no excitation. Measuring aided speech-evoked auditory brainstem response elicited by speech stimuli with different spectral maxima can give insight into the brainstem encoding of aided speech with spectral maxima at these dead regions. This research aims to study the impact of dead regions of the cochlea on speech processing at the brainstem level after a long period of hearing aid use. This study comprised 30 ears without dead regions and 46 ears with dead regions at low, mid, or high frequencies. For all ears, we measured the aided speech-evoked auditory brainstem response using speech stimuli of low, mid, and high spectral maxima. Aided speech-evoked auditory brainstem response was producible in all subjects. Responses evoked by stimuli with spectral maxima at dead regions had longer latencies and smaller amplitudes when compared with the control group or the responses of other stimuli. The presence of cochlear dead regions affects brainstem encoding of speech with spectral maxima perpendicular to these regions. Brainstem neuroplasticity and the extrinsic redundancy of speech can minimize the impact of dead regions in chronic hearing aid users.

  13. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gong, G; Liu, C; Liu, C

    Purpose: To analyze the error in contouring the brainstem for patients with head and neck cancer who underwent radiotherapy based on computed tomography (CT) and magnetic resonance (MR) images. Methods: 20 brain tumor and 17 nasopharyngeal cancer patients were randomly selected. Each patient underwent MR and CT scanning. For each patient, one observer contoured the brainstem on CT and MR images for 10 times, and 10 observers from five centers delineated the brainstem on CT and MR images only one time. The inter- and intra-observers volume and outline variations were compared. Results: The volumes of brainstem contoured by inter- andmore » intra-observers on CT and MR images were similar (p>0.05). The reproducibility of contouring brainstem on MR images was better than that on CT images (p<0.05) for both inter- and intra-observer variability. The inter- and intra-observer for contouring on CT images reached mean values of 0.81±0.05 (p>0.05) and of 0.85±0.05 (p>0.05), respectively, while on MR images these respective values were 0.90±0.05 (p>0.05) and 0.92±0.04 (p>0.05). Conclusion: Contouring the brainstem on MR images was more accurate and reproducible than that on CT images. Precise information might be more helpful for protecting the brainstem radiation injury the patients whose lesion were closed to brainstem.« less

  14. [Distribution of human enterovirus 71 in brainstem of infants with brain stem encephalitis and infection mechanism].

    PubMed

    Hao, Bo; Gao, Di; Tang, Da-Wei; Wang, Xiao-Guang; Liu, Shui-Ping; Kong, Xiao-Ping; Liu, Chao; Huang, Jing-Lu; Bi, Qi-Ming; Quan, Li; Luo, Bin

    2012-04-01

    To explore the mechanism that how human enterovirus 71 (EV71) invades the brainstem and how intercellular adhesion molecules-1 (ICAM-1) participates by analyzing the expression and distribution of human EV71, and ICAM-1 in brainstem of infants with brain stem encephalitis. Twenty-two brainstem of infants with brain stem encephalitis were collected as the experimental group and 10 brainstems of fatal congenital heart disease were selected as the control group. The sections with perivascular cuffings were selected to observe EV71-VP1 expression by immunohistochemistry method and ICAM-1 expression was detected for the sections with EV71-VP1 positive expression. The staining image analysis and statistics analysis were performed. The experiment and control groups were compared. (1) EV71-VP1 positive cells in the experimental group were mainly astrocytes in brainstem with nigger-brown particles, and the control group was negative. (2) ICAM-1 positive cells showed nigger-brown. The expression in inflammatory cells (around blood vessels of brain stem and in glial nodules) and gliocytes increased. The results showed statistical difference comparing with control group (P < 0.05). The brainstem encephalitis can be used to diagnose fatal EV71 infection in infants. EV71 can invade the brainstem via hematogenous route. ICAM-1 may play an important role in the pathogenic process.

  15. Combustion of solid carbon rods in zero and normal gravity

    NASA Technical Reports Server (NTRS)

    Spuckler, C. M.; Kohl, F. J.; Miller, R. A.; Stearns, C. A.; Dewitt, K. J.

    1979-01-01

    In order to investigate the mechanism of carbon combustion, spectroscopic carbon rods were resistance ignited and burned in an oxygen environment in normal and zero gravity. Direct mass spectrometric sampling was used in the normal gravity tests to obtain concentration profiles of CO2, CO, and O2 as a function of distance from the carbon surface. The experimental concentrations were compared to those predicted by a stagnant film model. Zero gravity droptower tests were conducted in order to assess the effect of convection on the normal gravity combustion process. The ratio of flame diameter to rod diameter as a function of time for oxygen pressures of 5, 10, 15, and 20 psia was obtained for three different diameter rods. It was found that this ratio was inversely proportional to both the oxygen pressure and the rod diameter.

  16. Improved outcomes in auditory brainstem implantation with the use of near-field electrical compound action potentials.

    PubMed

    Mandalà, Marco; Colletti, Liliana; Colletti, Giacomo; Colletti, Vittorio

    2014-12-01

    To compare the outcomes (auditory threshold and open-set speech perception at 48-month follow-up) of a new near-field monitoring procedure, electrical compound action potential, on positioning the auditory brainstem implant electrode array on the surface of the cochlear nuclei versus the traditional far-field electrical auditory brainstem response. Retrospective study. Tertiary referral center. Among the 202 patients with auditory brainstem implants fitted and monitored with electrical auditory brainstem response during implant fitting, 9 also underwent electrical compound action potential recording. These subjects were matched retrospectively with a control group of 9 patients in whom only the electrical auditory brainstem response was recorded. Electrical compound action potentials were obtained using a cotton-wick recording electrode located near the surface of the cochlear nuclei and on several cranial nerves. Significantly lower potential thresholds were observed with the recording electrode located on the cochlear nuclei surface compared with the electrical auditory brainstem response (104.4 ± 32.5 vs 158.9 ± 24.2, P = .0030). Electrical brainstem response and compound action potentials identified effects on the neighboring cranial nerves on 3.2 ± 2.4 and 7.8 ± 3.2 electrodes, respectively (P = .0034). Open-set speech perception outcomes at 48-month follow-up had improved significantly in the near- versus far-field recording groups (78.9% versus 56.7%; P = .0051). Electrical compound action potentials during auditory brainstem implantation significantly improved the definition of the potential threshold and the number of auditory and extra-auditory waves generated. It led to the best coupling between the electrode array and cochlear nuclei, significantly improving the overall open-set speech perception. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

  17. Anti Ma2-associated myeloradiculopathy: expanding the phenotype of anti-Ma2 associated paraneoplastic syndromes

    PubMed Central

    Murphy, Sinead M; Khan, Usman; Alifrangis, Constantine; Hazell, Steven; Hrouda, David; Blake, Julian; Ball, Joanna; Gabriel, Carolyn; Markarian, Pierre; Rees, Jeremy; Karim, Abid; Seckl, Michael J; Lunn, Michael P; Reilly, Mary M

    2013-01-01

    Anti-Ma2 associated paraneoplastic syndrome usually presents as limbic encephalitis in association with testicular tumours.1, 2 Only four patients have been reported with involvement outside the CNS, two of whom also had limbic or brainstem encephalitis.2, 3 We report a man with anti- Ma2 associated myeloradiculopathy and previous testicular cancer whose neurological syndrome stabilised and anti-Ma2 titres fell following orchidectomy of a microscopically normal testis. PMID:21205983

  18. Responses evoked from man by acoustic stimulation

    NASA Technical Reports Server (NTRS)

    Galambos, R.; Hecox, K.; Picton, T.

    1974-01-01

    Clicks and other acoustic stimuli evoke time-locked responses from the brain of man. The properties of the waves recordable within the interval from 1 to 10 msec after the stimuli strike the eardrum are discussed along with factors influencing the waves in the 100 to 500 msec epoch. So-called brainstem responses from a normal young adult are considered. No waves were observed for clicks to weak to be heard. With increasing stimulus strength the waves become larger in amplitude and their latency shortens.

  19. Early postnatal virus inoculation into the scala media achieved extensive expression of exogenous green fluorescent protein in the inner ear and preserved auditory brainstem response thresholds.

    PubMed

    Wang, Yunfeng; Sun, Yu; Chang, Qing; Ahmad, Shoeb; Zhou, Binfei; Kim, Yeunjung; Li, Huawei; Lin, Xi

    2013-01-01

    Gene transfer into the inner ear is a promising approach for treating sensorineural hearing loss. The special electrochemical environment of the scala media raises a formidable challenge for effective gene delivery at the same time as keeping normal cochlear function intact. The present study aimed to define a suitable strategy for preserving hearing after viral inoculation directly into the scala media performed at various postnatal developmental stages. We assessed transgene expression of green fluorescent protein (GFP) mediated by various types of adeno-associated virus (AAV) and lentivirus (LV) in the mouse cochlea. Auditory brainstem responses were measured 30 days after inoculation to assess effects on hearing. Patterns of GFP expression confirmed extensive exogenous gene expression in various types of cells lining the endolymphatic space. The use of different viral vectors and promoters resulted in specific cellular GFP expression patterns. AAV2/1 with cytomegalovirus promoter apparently gave the best results for GFP expression in the supporting cells. Histological examination showed normal cochlear morphology and no hair cell loss after either AAV or LV injections. We found that hearing thresholds were not significantly changed when the injections were performed in mice younger than postnatal day 5, regardless of the type of virus tested. Viral inoculation and expression in the inner ear for the restoration of hearing must not damage cochlear function. Using normal hearing mice as a model, we have achieved this necessary step, which is required for the treatment of many types of congenital deafness that require early intervention. Copyright © 2013 John Wiley & Sons, Ltd.

  20. High-frequency tone burst-evoked ABR latency-intensity functions.

    PubMed

    Fausti, S A; Olson, D J; Frey, R H; Henry, J A; Schaffer, H I

    1993-01-01

    High-frequency tone burst stimuli (8, 10, 12, and 14 kHz) have been developed and demonstrated to provide reliable and valid auditory brainstem responses (ABRs) in normal-hearing subjects. In this study, latency-intensity functions (LIFs) were determined using these stimuli in 14 normal-hearing individuals. Significant shifts in response latency occurred as a function of stimulus intensity for all tone burst frequencies. For each 10 dB shift in intensity, latency shifts for waves I and V were statistically significant except for one isolated instance. LIF slopes were comparable between frequencies, ranging from 0.020 to 0.030 msec/dB. These normal LIFs for high-frequency tone burst-evoked ABRs suggest the degree of response latency change that might be expected from, for example, progressive hearing loss due to ototoxic insult, although these phenomena may not be directly related.

  1. The relationship of age, gender, and IQ with the brainstem and thalamus in healthy children and adolescents: a magnetic resonance imaging volumetric study

    PubMed Central

    Xie, Yuhuan; Chen, Yian Ann; De Bellis, Michael D.

    2011-01-01

    In healthy children, there is a paucity of information on the growth of the brainstem and thalamus measured by anatomical magnetic resonance imaging. The relationships of age, gender, and age by gender with brainstem and thalamus volumes were analyzed from magnetic resonance brain images of 122 healthy children and adolescents (62 males, 60 females; ages four to seventeen). Results showed that age is a significant predictor of brainstem and thalamus volumes. The volume of the brainstem increases with age, while thalamus volume declines with age. The volumes of right thalami are significantly larger than that of left in both genders with greater rightward asymmetry and greater thalamus/grey matter ratio in females. Males have larger brainstems, but these differences are not significant when covarying for cerebral volumes. Larger thalami were associated with higher verbal IQ. This normative pediatric data is of value to researchers who study these regions in neurodevelopmental disorders. PMID:21954432

  2. The relationship of age, gender, and IQ with the brainstem and thalamus in healthy children and adolescents: a magnetic resonance imaging volumetric study.

    PubMed

    Xie, Yuhuan; Chen, Yian Ann; De Bellis, Michael D

    2012-03-01

    In healthy children, there is a paucity of information on the growth of the brainstem and thalamus measured anatomically magnetic resonance imaging. The relations of age, gender, and age by gender with brainstem and thalamus volumes were analyzed from magnetic resonance brain images of 122 healthy children and adolescents (62 males, 60 females; ages 4 to 17). Results showed that age is a significant predictor of brainstem and thalamus volumes. The volume of the brainstem increases with age, while thalamus volume declines with age. The volume of the right thalamus is significantly larger than that of the left in both genders, with greater rightward asymmetry and greater thalamus to grey matter ratio in females. Males have larger brainstems, but these differences are not significant when covarying for cerebral volume. Larger thalami were associated with higher Verbal IQ. These normative pediatric data are of value to researchers who study these regions in neurodevelopmental disorders.

  3. Dorsally exophytic glioblastoma arising from the medulla oblongata in an adult presenting as 4th ventricular mass.

    PubMed

    Das, Kuntal Kanti; Bettaswamy, Guru Prasad; Mehrotra, Anant; Jaiswal, Sushila; Jaiswal, Awadhesh Kumar; Behari, Sanjay

    2017-01-01

    Brainstem gliomas are relatively rare in adults (<2% of all gliomas). Exophytic gliomas are focal brainstem lesions, which project into the 4 th ventricle or cerebellopontine angles. These exophytic lesions are usually of low-grade histology (pilocytic astrocytoma or ganglioglioma) and have a relatively better outcome compared with brainstem gliomas as a whole. Glioblastoma is the commonest primary glial cell neoplasm and mostly occurs in the supratentorial compartment. It is rather uncommon in the brainstem and seldom has been described as having an exophytic growth pattern. Here we describe an exophytic brainstem glioblastoma arising from the medulla oblongata in a 55-year-old lady who presented with a 4 th ventricular mass, and present a brief review of the literature. Till now, six cases of glioblastoma arising from the medulla oblongata have been reported. So, ours is the seventh such report. To the best of our knowledge, it also happens to be the sixth reported case of dorsally exophytic brainstem glioblastoma till date.

  4. Brainstem Encoding of Aided Speech in Hearing Aid Users with Cochlear Dead Region(s)

    PubMed Central

    Hassaan, Mohammad Ramadan; Ibraheem, Ola Abdallah; Galhom, Dalia Helal

    2016-01-01

    Introduction  Neural encoding of speech begins with the analysis of the signal as a whole broken down into its sinusoidal components in the cochlea, which has to be conserved up to the higher auditory centers. Some of these components target the dead regions of the cochlea causing little or no excitation. Measuring aided speech-evoked auditory brainstem response elicited by speech stimuli with different spectral maxima can give insight into the brainstem encoding of aided speech with spectral maxima at these dead regions. Objective  This research aims to study the impact of dead regions of the cochlea on speech processing at the brainstem level after a long period of hearing aid use. Methods  This study comprised 30 ears without dead regions and 46 ears with dead regions at low, mid, or high frequencies. For all ears, we measured the aided speech-evoked auditory brainstem response using speech stimuli of low, mid, and high spectral maxima. Results  Aided speech-evoked auditory brainstem response was producible in all subjects. Responses evoked by stimuli with spectral maxima at dead regions had longer latencies and smaller amplitudes when compared with the control group or the responses of other stimuli. Conclusion  The presence of cochlear dead regions affects brainstem encoding of speech with spectral maxima perpendicular to these regions. Brainstem neuroplasticity and the extrinsic redundancy of speech can minimize the impact of dead regions in chronic hearing aid users. PMID:27413404

  5. Feasibility of creating a high-resolution 3D diffusion tensor imaging based atlas of the human brainstem: A case study at 11.7T

    PubMed Central

    Aggarwal, Manisha; Zhang, Jiangyang; Pletnikova, Olga; Crain, Barbara; Troncoso, Juan; Mori, Susumu

    2013-01-01

    A three-dimensional stereotaxic atlas of the human brainstem based on high resolution ex vivo diffusion tensor imaging (DTI) is introduced. The atlas consists of high resolution (125–255 μm isotropic) three-dimensional DT images of the formalin-fixed brainstem acquired at 11.7T. The DTI data revealed microscopic neuroanatomical details, allowing three-dimensional visualization and reconstruction of fiber pathways including the decussation of the pyramidal tract fibers, and interdigitating fascicles of the corticospinal and transverse pontine fibers. Additionally, strong grey-white matter contrasts in the apparent diffusion coefficient (ADC) maps enabled precise delineation of grey matter nuclei in the brainstem, including the cranial nerve and the inferior olivary nuclei. Comparison with myelin-stained histology shows that at the level of resolution achieved in this study, the structural details resolved with DTI contrasts in the brainstem were comparable to anatomical delineation obtained with histological sectioning. Major neural structures delineated from DTI contrasts in the brainstem are segmented and three-dimensionally reconstructed. Further, the ex vivo DTI data are nonlinearly mapped to a widely-used in vivo human brain atlas, to construct a high-resolution atlas of the brainstem in the Montreal Neurological Institute (MNI) stereotaxic coordinate space. The results demonstrate the feasibility of developing a 3D DTI based atlas for detailed characterization of brainstem neuroanatomy with high resolution and contrasts, which will be a useful resource for research and clinical applications. PMID:23384518

  6. Determinants and Normal Values of Ascending Aortic Diameter by Age, Gender and Race/Ethnicity in the Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Turkbey, Evrim B.; Jain, Aditya; Johnson, Craig; Redheuil, Alban; Arai, Andrew E.; Gomes, Antoinette S.; Carr, James; Hundley, W. Gregory; Teixido-Tura, Gisela; Eng, John; Lima, Joao A.C.; Bluemke, David A.

    2013-01-01

    PURPOSE To determine the normal size and wall thickness of the ascending thoracic aorta (AA) and its relationship with cardiovascular risk factors in a large population-based study. MATERIALS AND METHODS The mean AA luminal diameter was measured in 3573 Multi-Ethnic Study of Atherosclerosis (MESA) participants (age: 45–84 years), using gradient echo phase contrast cine MRI. Multiple linear regression models were used to evaluate the associations between risk factors and AA diameter. The median and upper normal limit (95th percentile) was defined in a “healthy” subgroup as well as AA wall thickness. RESULTS The upper limits of body surface area indexed AA luminal diameter for age categories of 45–54, 55–64, 65–74, and 75–84 years are 21, 22, 22, and 28 mm/m2 in women and 20, 21, 22, 23 mm/m2 in men, respectively. The mean AA wall thickness was 2.8 mm. Age, gender and body surface area were major determinants of AA luminal diameter (~+1 mm/10 years; ~+1.9 mm in men than women; ~+1 mm/ 0.23 m2; p<0.001). The AA diameter in hypertensive subjects was +0.9 mm larger than in normotensives (p<0.001). CONCLUSION AA diameter increases gradually with aging for both genders, among all race/ethnicities. Normal value of AA diameter is provided. PMID:23681649

  7. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mayo, Charles, E-mail: charles.mayo@umassmemorial.or; Yorke, Ellen; Merchant, Thomas E.

    Publications relating brainstem radiation toxicity to quantitative dose and dose-volume measures derived from three-dimensional treatment planning were reviewed. Despite the clinical importance of brainstem toxicity, most studies reporting brainstem effects after irradiation have fewer than 100 patients. There is limited evidence relating toxicity to small volumes receiving doses above 60-64 Gy using conventional fractionation and no definitive criteria regarding more subtle dose-volume effects or effects after hypofractionated treatment. On the basis of the available data, the entire brainstem may be treated to 54 Gy using conventional fractionation using photons with limited risk of severe or permanent neurological effects. Smaller volumesmore » of the brainstem (1-10 mL) may be irradiated to maximum doses of 59 Gy for dose fractions <=2 Gy; however, the risk appears to increase markedly at doses >64 Gy.« less

  8. Brain magnetic resonance imaging findings and auditory brainstem response in a child with spastic paraplegia 2 due to a PLP1 splice site mutation.

    PubMed

    Kubota, Kazuo; Saito, Yoshiaki; Ohba, Chihiro; Saitsu, Hirotomo; Fukuyama, Tetsuhiro; Ishiyama, Akihiko; Saito, Takashi; Komaki, Hirofumi; Nakagawa, Eiji; Sugai, Kenji; Sasaki, Masayuki; Matsumoto, Naomichi

    2015-01-01

    A boy with spastic paraplegia type 2 (SPG2) due to a novel splice site mutation of PLP1 presented with progressive spasticity of lower limbs, which was first observed during late infancy, when he gained the ability to walk with support. His speech was slow and he had dysarthria. The patient showed mildly delayed intellectual development. Subtotal dysmyelination in the central nervous system was revealed, which was especially prominent in structures known to be myelinated during earlier period, whereas structures that are myelinated later were better myelinated. These findings on the brain magnetic resonance imaging were unusual for subjects with PLP1 mutations. Peaks I and II of the auditory brainstem response (ABR) were normally provoked, but peaks III-V were not clearly demarcated, similarly to the findings in Pelizaeus-Merzbacher disease. These findings of brain MRI and ABR may be characteristic for a subtype of SPG2 patients. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  9. Diprosopia/dicephalia in calves in northern Italy: clinical and aetio-pathological features.

    PubMed

    Biasibetti, E; D'Angelo, A; Bellino, C; Gay, L; Gianella, P; Capucchio, M T

    2011-12-01

    Cephalic parapagia, a rare congenital anomaly caused by the fusion of two monozygotic embryos, is characterized by a single body and a spectrum of duplication of craniofacial structures. The authors describe the clinical and pathological aspects of the parapagus conjoined twin defect in nine calves referred to the Department of Animal Pathology, Turin, between 1999 and 2009. The majority of the calves (eight cases) presented two snouts that shared three or four eyes (diprosopia); one calf presented two separate skulls fused at the foramen magnum (dicephalia). Bilateral inferior brachygnathia was observed in four calves. Post-mortem examination of the skull revealed complete brain duplication with fusion at the caudal portion of the brainstem in all calves. Histological features of the cerebral hemispheres and brainstem were normal; moderate disorganization of the cerebellar cortex was noted in two cases. Cardiac malformations were observed in three calves. No aetiologic cause was determined. This article underscores the importance of diprosopia in cattle species and suggests the need for more detailed investigations to better understand its pathogenesis. © 2011 Blackwell Verlag GmbH.

  10. A direct approach for the design of chirp stimuli used for the recording of auditory brainstem responses

    PubMed Central

    Elberling, Claus; Don, Manuel

    2010-01-01

    A recent study evaluates auditory brainstem responses (ABRs) evoked by chirps of different durations (sweeping rates) [Elberling et al. (2010). J. Acoust. Soc. Am. 128, 215–223]. The study demonstrates that shorter chirps are most efficient at higher levels of stimulation whereas longer chirps are most efficient at lower levels. Mechanisms other than the traveling wave delay, in particular, upward spread of excitation and changes in cochlear-neural delay with level, are suggested to be responsible for these findings. As a consequence, delay models based on estimates of the traveling wave delay are insufficient for the design of chirp stimuli, and another delay model based on a direct approach is therefore proposed. The direct approach uses ABR-latencies from normal-hearing subjects in response to octave-band chirps over a wide range of levels. The octave-band chirps are constructed by decomposing a broad-band chirp, and constitute a subset of the chirp. The delay compensations of the proposed model are similar to those found in the previous experimental study, which thus verifies the results of the proposed model. PMID:21110591

  11. Auditory processing deficits in individuals with primary open-angle glaucoma.

    PubMed

    Rance, Gary; O'Hare, Fleur; O'Leary, Stephen; Starr, Arnold; Ly, Anna; Cheng, Belinda; Tomlin, Dani; Graydon, Kelley; Chisari, Donella; Trounce, Ian; Crowston, Jonathan

    2012-01-01

    The high energy demand of the auditory and visual pathways render these sensory systems prone to diseases that impair mitochondrial function. Primary open-angle glaucoma, a neurodegenerative disease of the optic nerve, has recently been associated with a spectrum of mitochondrial abnormalities. This study sought to investigate auditory processing in individuals with open-angle glaucoma. DESIGN/STUDY SAMPLE: Twenty-seven subjects with open-angle glaucoma underwent electrophysiologic (auditory brainstem response), auditory temporal processing (amplitude modulation detection), and speech perception (monosyllabic words in quiet and background noise) assessment in each ear. A cohort of age, gender and hearing level matched control subjects was also tested. While the majority of glaucoma subjects in this study demonstrated normal auditory function, there were a significant number (6/27 subjects, 22%) who showed abnormal auditory brainstem responses and impaired auditory perception in one or both ears. The finding that a significant proportion of subjects with open-angle glaucoma presented with auditory dysfunction provides evidence of systemic neuronal susceptibility. Affected individuals may suffer significant communication difficulties in everyday listening situations.

  12. Mitochondria-Targeted Antioxidant Mitoquinone Reduces Cisplatin-Induced Ototoxicity in Guinea Pigs.

    PubMed

    Tate, Alan D; Antonelli, Patrick J; Hannabass, Kyle R; Dirain, Carolyn O

    2017-03-01

    Objective To determine if mitoquinone (MitoQ) attenuates cisplatin-induced hearing loss in guinea pigs. Study Design Prospective and controlled animal study. Setting Academic, tertiary medical center. Subjects and Methods Guinea pigs were injected subcutaneously with either 5 mg/kg MitoQ (n = 9) or normal saline (control, n = 9) for 7 days and 1 hour before receiving a single dose of 10 mg/kg cisplatin. Auditory brainstem response thresholds were measured before MitoQ or saline administration and 3 to 4 days after cisplatin administration. Results Auditory brainstem response threshold shifts after cisplatin treatment were smaller by 28 to 47 dB in guinea pigs injected with MitoQ compared with those in the control group at all tested frequencies (4, 8, 16, and 24 kHz, P = .0002 to .04). Scanning electron microscopy of cochlear hair cells showed less outer hair cell loss and damage in the MitoQ group. Conclusion MitoQ reduced cisplatin-induced hearing loss in guinea pigs. MitoQ appears worthy of further investigation as a means of preventing cisplatin ototoxicity in humans.

  13. Longitudinal Development of Distortion Product Otoacoustic Emissions in Infants With Normal Hearing.

    PubMed

    Hunter, Lisa L; Blankenship, Chelsea M; Keefe, Douglas H; Feeney, M Patrick; Brown, David K; McCune, Annie; Fitzpatrick, Denis F; Lin, Li

    2018-01-23

    The purpose of this study was to describe normal characteristics of distortion product otoacoustic emission (DPOAE) signal and noise level in a group of newborns and infants with normal hearing followed longitudinally from birth to 15 months of age. This is a prospective, longitudinal study of 231 infants who passed newborn hearing screening and were verified to have normal hearing. Infants were enrolled from a well-baby nursery and two neonatal intensive care units (NICUs) in Cincinnati, OH. Normal hearing was confirmed with threshold auditory brainstem response and visual reinforcement audiometry. DPOAEs were measured in up to four study visits over the first year after birth. Stimulus frequencies f1 and f2 were used with f2/f1 = 1.22, and the DPOAE was recorded at frequency 2f1-f2. A longitudinal repeated-measure linear mixed model design was used to study changes in DPOAE level and noise level as related to age, middle ear transfer, race, and NICU history. Significant changes in the DPOAE and noise levels occurred from birth to 12 months of age. DPOAE levels were the highest at 1 month of age. The largest decrease in DPOAE level occurred between 1 and 5 months of age in the mid to high frequencies (2 to 8 kHz) with minimal changes occurring between 6, 9, and 12 months of age. The decrease in DPOAE level was significantly related to a decrease in wideband absorbance at the same f2 frequencies. DPOAE noise level increased only slightly with age over the first year with the highest noise levels in the 12-month-old age range. Minor, nonsystematic effects for NICU history, race, and gestational age at birth were found, thus these results were generalizable to commonly seen clinical populations. DPOAE levels were related to wideband middle ear absorbance changes in this large sample of infants confirmed to have normal hearing at auditory brainstem response and visual reinforcement audiometry testing. This normative database can be used to evaluate clinical results from birth to 1 year of age. The distributions of DPOAE level and signal to noise ratio data reported herein across frequency and age in normal-hearing infants who were healthy or had NICU histories may be helpful to detect the presence of hearing loss in infants.

  14. Endoscopic Endonasal Transclival Approach to the Ventral Brainstem: Anatomic Study of the Safe Entry Zones Combining Fiber Dissection Technique with 7 Tesla Magnetic Resonance Guided Neuronavigation.

    PubMed

    Weiss, Alessandro; Perrini, Paolo; De Notaris, Matteo; Soria, Guadalupe; Carlos, Alarcon; Castagna, Maura; Lutzemberger, Lodovico; Santonocito, Orazio Santo; Catapano, Giuseppe; Kassam, Amin; Galino, Alberto Prats

    2018-05-10

    Treatment of intrinsic lesions of the ventral brainstem is a surgical challenge that requires complex skull base antero- and posterolateral approaches. More recently, endoscopic endonasal transclival approach (EETA) has been reported in the treatment of selected ventral brainstem lesions. In this study we explored the endoscopic ventral brainstem anatomy with the aim to describe the degree of exposure of the ventral safe entry zones. In addition, we used a newly developed method combining traditional white matter dissection with high-resolution 7T magnetic resonance imaging (MRI) of the same specimen coregistered using a neuronavigation system. Eight fresh-frozen latex-injected cadaver heads underwent EETA. Additional 8 formalin-fixed brainstems were dissected using Klingler technique guided by ultra-high resolution MRI. The EETA allows a wide exposure of different safe entry zones located on the ventral brainstem: the exposure of perioculomotor zone requires pituitary transposition and can be hindered by superior cerebellar artery. The peritrigeminal zone was barely visible and its exposure required an extradural anterior petrosectomy. The anterolateral sulcus of the medulla was visible in most of specimens, although its close relationship with the corticospinal tract makes it suboptimal as an entry point for intrinsic lesions. In all cases, the use of 7T-MRI allowed the identification of tiny fiber bundles, improving the quality of the dissection. Exposure of the ventral brainstem with EETA requires mastering surgical maneuvers, including pituitary transposition and extradural petrosectomy. The correlation of fiber dissection with 7T-MRI neuronavigation significantly improves the understanding of the brainstem anatomy.

  15. Processing of voices in deafness rehabilitation by auditory brainstem implant.

    PubMed

    Coez, Arnaud; Zilbovicius, Monica; Ferrary, Evelyne; Bouccara, Didier; Mosnier, Isabelle; Ambert-Dahan, Emmanuèle; Kalamarides, Michel; Bizaguet, Eric; Syrota, André; Samson, Yves; Sterkers, Olivier

    2009-10-01

    The superior temporal sulcus (STS) is specifically involved in processing the human voice. Profound acquired deafness by post-meningitis ossified cochlea and by bilateral vestibular schwannoma in neurofibromatosis type 2 patients are two indications for auditory brainstem implantation (ABI). In order to objectively measure the cortical voice processing of a group of ABI patients, we studied the activation of the human temporal voice areas (TVA) by PET H(2)(15)O, performed in a group of implanted deaf adults (n=7) with more than two years of auditory brainstem implant experience, with an intelligibility score average of 17%+/-17 [mean+/-SD]. Relative cerebral blood flow (rCBF) was measured in the three following conditions: during silence, while passive listening to human voice, and to non-voice stimuli. Compared to silence, the activations induced by voice and non-voice stimuli were bilaterally located in the superior temporal regions. However, compared to non-voice stimuli, the voice stimuli did not induce specific supplementary activation of the TVA along the STS. The comparison of ABI group with a normal-hearing controls group (n=7) showed that TVA activations were significantly enhanced among controls group. ABI allowed the transmission of sound stimuli to temporal brain regions but lacked transmitting the specific cues of the human voice to the TVA. Moreover, among groups, during silent condition, brain visual regions showed higher rCBF in ABI group, although temporal brain regions had higher rCBF in the controls group. ABI patients had consequently developed enhanced visual strategies to keep interacting with their environment.

  16. Exposure to low levels of jet-propulsion fuel impairs brainstem encoding of stimulus intensity.

    PubMed

    Guthrie, O'neil W; Xu, Helen; Wong, Brian A; McInturf, Shawn M; Reboulet, Jim E; Ortiz, Pedro A; Mattie, David R

    2014-01-01

    Jet propulsion fuel-8 (JP-8) is a kerosene-based fuel that is used in military jets. The U.S. Armed Services and North Atlantic Treaty Organization countries adopted JP-8 as a standard fuel source and the U.S. military alone consumes more than 2.5 billion gallons annually. Preliminary epidemiologic data suggested that JP-8 may interact with noise to induce hearing loss, and animal studies revealed damage to presynaptic sensory cells in the cochlea. In the current study, Long-Evans rats were divided into four experimental groups: control, noise only, JP-8 only, and JP-8 + noise. A subototoxic level of JP-8 was used alone or in combination with a nondamaging level of noise. Functional and structural assays of the presynaptic sensory cells combined with neurophysiologic studies of the cochlear nerve revealed that peripheral auditory function was not affected by individual exposures and there was no effect when the exposures were combined. However, the central auditory nervous system exhibited impaired brainstem encoding of stimulus intensity. These findings may represent important and major shifts in the theoretical framework that governs current understanding of jet fuel and/or jet fuel + noise-induced ototoxicity. From an epidemiologic perspective, results indicate that jet fuel exposure may exert consequences on auditory function that may be more widespread and insidious than what was previously shown. It is possible that a large population of military personnel who are suffering from the effects of jet fuel exposure may be misidentified because they would exhibit normal hearing thresholds but harbor a "hidden" brainstem dysfunction.

  17. Computational modeling of the human auditory periphery: Auditory-nerve responses, evoked potentials and hearing loss.

    PubMed

    Verhulst, Sarah; Altoè, Alessandro; Vasilkov, Viacheslav

    2018-03-01

    Models of the human auditory periphery range from very basic functional descriptions of auditory filtering to detailed computational models of cochlear mechanics, inner-hair cell (IHC), auditory-nerve (AN) and brainstem signal processing. It is challenging to include detailed physiological descriptions of cellular components into human auditory models because single-cell data stems from invasive animal recordings while human reference data only exists in the form of population responses (e.g., otoacoustic emissions, auditory evoked potentials). To embed physiological models within a comprehensive human auditory periphery framework, it is important to capitalize on the success of basic functional models of hearing and render their descriptions more biophysical where possible. At the same time, comprehensive models should capture a variety of key auditory features, rather than fitting their parameters to a single reference dataset. In this study, we review and improve existing models of the IHC-AN complex by updating their equations and expressing their fitting parameters into biophysical quantities. The quality of the model framework for human auditory processing is evaluated using recorded auditory brainstem response (ABR) and envelope-following response (EFR) reference data from normal and hearing-impaired listeners. We present a model with 12 fitting parameters from the cochlea to the brainstem that can be rendered hearing impaired to simulate how cochlear gain loss and synaptopathy affect human population responses. The model description forms a compromise between capturing well-described single-unit IHC and AN properties and human population response features. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Antinociceptive reflex alteration in acute posttraumatic headache following whiplash injury.

    PubMed

    Keidel, M; Rieschke, P; Stude, P; Eisentraut, R; van Schayck, R; Diener, H

    2001-06-01

    Brainstem-mediated antinociceptive inhibitory reflexes of the temporalis muscle were investigated in 82 patients (47 F, 35 M, mean age 28.3 years, SD 9.4) with acute posttraumatic headache (PH) following whiplash injury but without neurological deficits, bone injury of the cervical spine or a combined direct head trauma on average 5 days after the acceleration trauma. Latencies and durations of the early and late exteroceptive suppression (ES1 and ES2) and the interposed EMG burst (IE) of the EMG of the voluntarily contracted right temporalis muscle evoked by ipsilateral stimulation of the second and third branches of the trigeminal nerve were analyzed and compared to a cohort of 82 normal subjects (43 F, 39 M, mean age 27.7 years, SD 7.1). Highly significant reflex alterations were found in patients with PH with a shortening of ES2 duration with delayed onset and premature ending as the primary parameter of this study, a moderate prolongation of ES1 and IE duration and a delayed onset of IE. The latency of ES1 was not significantly changed. These findings indicate that acute PH in whiplash injury is accompanied by abnormal antinociceptive brainstem reflexes. We conclude that the abnormality of the trigeminal inhibitory temporalis reflex is based on a transient dysfunction of the brainstem-mediated reflex circuit mainly of the late polysynaptic pathways. The reflex abnormalities are considered as a neurophysiological correlate of the posttraumatic (cervico)-cephalic pain syndrome. They point to an altered central pain control in acute PH due to whiplash injury.

  19. Auditory brainstem response latency in forward masking, a marker of sensory deficits in listeners with normal hearing thresholds

    PubMed Central

    Mehraei, Golbarg; Gallardo, Andreu Paredes; Shinn-Cunningham, Barbara G.; Dau, Torsten

    2017-01-01

    In rodent models, acoustic exposure too modest to elevate hearing thresholds can nonetheless cause auditory nerve fiber deafferentation, interfering with the coding of supra-threshold sound. Low-spontaneous rate nerve fibers, important for encoding acoustic information at supra-threshold levels and in noise, are more susceptible to degeneration than high-spontaneous rate fibers. The change in auditory brainstem response (ABR) wave-V latency with noise level has been shown to be associated with auditory nerve deafferentation. Here, we measured ABR in a forward masking paradigm and evaluated wave-V latency changes with increasing masker-to-probe intervals. In the same listeners, behavioral forward masking detection thresholds were measured. We hypothesized that 1) auditory nerve fiber deafferentation increases forward masking thresholds and increases wave-V latency and 2) a preferential loss of low-SR fibers results in a faster recovery of wave-V latency as the slow contribution of these fibers is reduced. Results showed that in young audiometrically normal listeners, a larger change in wave-V latency with increasing masker-to-probe interval was related to a greater effect of a preceding masker behaviorally. Further, the amount of wave-V latency change with masker-to-probe interval was positively correlated with the rate of change in forward masking detection thresholds. Although we cannot rule out central contributions, these findings are consistent with the hypothesis that auditory nerve fiber deafferentation occurs in humans and may predict how well individuals can hear in noisy environments. PMID:28159652

  20. Development of the Brainstem and Cerebellum in Autistic Patients.

    ERIC Educational Resources Information Center

    Hashimoto, Toshiaki; And Others

    1995-01-01

    This study of 102 individuals with autism found that the brainstem and cerebellum increased in size with age but were significantly smaller in autistic patients than in controls. Analysis of the speed of development suggests that brainstem and vermian abnormalities in autism were due to an early insult and hypoplasia rather than to progressive…

  1. Brain-stem laceration and blunt rupture of thoracic aorta: is the intrapleural bleeding postmortem in origin?: an autopsy study.

    PubMed

    Zivković, Vladimir; Nikolić, Slobodan; Babić, Dragan; Juković, Fehim

    2011-12-01

    Some of the fatally injured car occupants could have had both blunt rupture of thoracic aorta with great amount of intrapleural blood, and pontomedullar laceration of brain-stem as well, with both injuries being fatal. The aim of this study was to answer if all intrapleural bleeding in these cases was antemortem, or the bleeding could also be partially postmortem. We observed the group of 66 cases of blunt aortic rupture: 21 case with brain-stem laceration, and 45 cases without it. The average amount of intrapleural bleeding in cases without brain-stem laceration (1993 ± 831 mL) was significantly higher than in those with this injury (1100 ± 708 mL) (t = 4.252, df = 64, P = 0.000). According to our results, in cases of the thoracic aorta rupture with concomitant brain-stem laceration, the amount of intrapleural bleeding less than 1500 mL, should be considered mostly as postmortem in origin, and in such cases, only the brain-stem injury should be considered as cause of death.

  2. Air pollution is associated with brainstem auditory nuclei pathology and delayed brainstem auditory evoked potentials

    PubMed Central

    Calderón-Garcidueñas, Lilian; D’Angiulli, Amedeo; Kulesza, Randy J; Torres-Jardón, Ricardo; Osnaya, Norma; Romero, Lina; Keefe, Sheyla; Herritt, Lou; Brooks, Diane M; Avila-Ramirez, Jose; Delgado-Chávez, Ricardo; Medina-Cortina, Humberto; González-González, Luis Oscar

    2011-01-01

    We assessed brainstem inflammation in children exposed to air pollutants by comparing brainstem auditory evoked potentials (BAEPs) and blood inflammatory markers in children age 96.3± 8.5 months from highly polluted (n=34) versus a low polluted city (n=17). The brainstems of nine children with accidental deaths were also examined. Children from the highly polluted environment had significant delays in wave III (t(50)=17.038; p<0.0001) and wave V (t(50)=19.730; p<0.0001) but no delay in wave I (p=0.548). They also had significantly longer latencies than controls for interwave intervals I–III, III–V, and I–V (all t(50)> 7.501; p<0.0001), consisting with delayed central conduction time of brainstem neural transmission. Highly exposed children showed significant evidence of inflammatory markers and their auditory and vestibular nuclei accumulated α synuclein and/or β amyloid 1–42. Medial superior olive neurons, critically involved in BAEPs, displayed significant pathology. Children’s exposure to urban air pollution increases their risk for auditory and vestibular impairment. PMID:21458557

  3. Huntington’s disease (HD): Degeneration of select nuclei and widespread occurrence of neuronal nuclear and axonal inclusions in the brainstem

    PubMed Central

    Rüb, U; Hentschel, M; Stratmann, K; Brunt, ER; Heinsen, H; Seidel, K; Bouzrou, M; Auburger, G; Paulson, HL; Vonsattel, JP; Lange, HW; Korf, HW; den Dunnen, WF

    2014-01-01

    Huntington’s disease (HD) is a progressive polyglutamine disease that leads to a severe striatal and layer-specific neuronal loss in the cerebral neo-and allocortex. Since some of the clinical symptoms (e.g. oculomotor dysfunctions) suggested a degeneration of select brainstem nuclei we performed a systematic investigation of the brainstem of eight clinically diagnosed and genetically confirmed HD patients. This postmortem investigation revealed a consistent neuronal loss in the substantia nigra, pontine nuclei, reticulotegmental nucleus of the pons, superior and inferior olives, in the area of the excitatory burst neurons for horizontal saccades, raphe interpositus nucleus, and vestibular nuclei. Immunoreactive intranuclear neuronal inclusions were present in all degenerated and apparently spared brainstem nuclei, and immunoreactive axonal inclusions were observed in all brainstem fiber tracts of the HD patients. Degeneration of brainstem nuclei can account for a number of less well understood clinical HD symptoms (i.e. cerebellar, oculomotor and vestibular symptoms), while the formation of axonal aggregates may represent a crucial event in the cascades of pathological events leading to neurodegeneration in HD. PMID:24779419

  4. Magnetization transfer and adiabatic R 1ρ MRI in the brainstem of Parkinson's disease.

    PubMed

    Tuite, Paul J; Mangia, Silvia; Tyan, Andrew E; Lee, Michael K; Garwood, Michael; Michaeli, Shalom

    2012-06-01

    In addition to classic midbrain pathology, Parkinson's disease (PD) is accompanied by changes in pontine and medullary brainstem structures. These additional abnormalities may underlie non-motor features as well as play a role in motor disability. Using novel magnetic resonance imaging (MRI) methods based on rotating frame adiabatic R(1ρ) (i.e., measurements of longitudinal relaxation during adiabatic full passage pulses) and modified magnetization transfer (MT) MRI mapping, we sought to identify brainstem alterations in nine individuals with mild-moderate PD (off medication) and ten age-matched controls at 4 T. We discovered significant differences in MRI parameters between midbrain and medullary brainstem structures in control subjects as compared to PD patients. These findings support the presence of underlying functional/structural brainstem changes in mild-moderate PD. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Evaluating Approaches to Rendering Braille Text on a High-Density Pin Display.

    PubMed

    Morash, Valerie S; Russomanno, Alexander; Gillespie, R Brent; OModhrain, Sile

    2017-10-13

    Refreshable displays for tactile graphics are typically composed of pins that have smaller diameters and spacing than standard braille dots. We investigated configurations of high-density pins to form braille text on such displays using non-refreshable stimuli produced with a 3D printer. Normal dot braille (diameter 1.5 mm) was compared to high-density dot braille (diameter 0.75 mm) wherein each normal dot was rendered by high-density simulated pins alone or in a cluster of pins configured in a diamond, X, or square; and to "blobs" that could result from covering normal braille and high-density multi-pin configurations with a thin membrane. Twelve blind participants read MNREAD sentences displayed in these conditions. For high-density simulated pins, single pins were as quickly and easily read as normal braille, but diamond, X, and square multi-pin configurations were slower and/or harder to read than normal braille. We therefore conclude that as long as center-to-center dot spacing and dot placement is maintained, the dot diameter may be open to variability for rendering braille on a high density tactile display.

  6. Incidence and dosimetric parameters for brainstem necrosis following intensity modulated radiation therapy in nasopharyngeal carcinoma.

    PubMed

    Li, Yang-Chan; Chen, Fo-Ping; Zhou, Guan-Qun; Zhu, Jin-Han; Hu, Jiang; Kang, De-Hua; Wu, Chen-Fei; Lin, Li; Wang, Xiao-Ju; Ma, Jun; Sun, Ying

    2017-10-01

    To clarify the incidence of brainstem toxicity and perform a dose-volume analysis for the brainstem after long-term follow-up of a large cohort of nasopharyngeal carcinoma (NPC) patients who underwent intensity-modulated radiation therapy (IMRT). All patients with NPC treated with IMRT at Sun Yat-sen University Cancer Center between April 2009 and March 2012 were retrospectively reviewed. A total of 1544 patients with follow-up >12months and detailed treatment plan data were included. Radiotherapy was administered using the simultaneous integrated boost technique in 2.0-2.48Gy per fractions/28-33 fractions. Brainstem necrosis was defined as lesions with high signal intensity on T2-weighted images and low signal intensity on T1-weighted images, with or without enhancement after administration of contrast in follow-up MRI. After median follow-up of 79.7months (range, 12.2-85.6months), 2/1544 (0.13%) patients developed brainstem necrosis after intervals of 12.3 and 18.5months. Actuarial incidence of brainstem necrosis was 0.07%, 0.13%, 0.13% and 0.13% after 1, 2, 3 and 5years, respectively. Overall, 384 (24.9%), 153 (9.9%), 67 (4.3%), 39 (2.5%), 78 (5.1%), and 114 (7.4%) patients had excessive doses of D max ≥64Gy, D1cc>59Gy, D2cc>59Gy, aV50>5.9cc, aV55>2.7cc and aV60>0.9cc respectively, of whom only two developed brainstem necrosis. Brainstem necrosis is rare in NPC. The definitive criteria based on conventional radiotherapy cannot accurately predict the occurrence of brainstem necrosis after IMRT, thus more flexible definitive criteria with strict restrictions need to be defined. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The maturation state of the auditory nerve and brainstem in rats exposed to lead acetate and supplemented with ferrous sulfate.

    PubMed

    Zucki, Fernanda; Morata, Thais C; Duarte, Josilene L; Ferreira, Maria Cecília F; Salgado, Manoel H; Alvarenga, Kátia F

    The literature has reported the association between lead and auditory effects, based on clinical and experimental studies. However, there is no consensus regarding the effects of lead in the auditory system, or its correlation with the concentration of the metal in the blood. To investigate the maturation state of the auditory system, specifically the auditory nerve and brainstem, in rats exposed to lead acetate and supplemented with ferrous sulfate. 30 weanling male rats (Rattus norvegicus, Wistar) were distributed into six groups of five animals each and exposed to one of two concentrations of lead acetate (100 or 400mg/L) and supplemented with ferrous sulfate (20mg/kg). The maturation state of the auditory nerve and brainstem was analyzed using Brainstem Auditory Evoked Potential before and after lead exposure. The concentration of lead in blood and brainstem was analyzed using Inductively Coupled Plasma-Mass Spectrometry. We verified that the concentration of Pb in blood and in brainstem presented a high correlation (r=0.951; p<0.0001). Both concentrations of lead acetate affected the maturation state of the auditory system, being the maturation slower in the regions corresponding to portion of the auditory nerve (wave I) and cochlear nuclei (wave II). The ferrous sulfate supplementation reduced significantly the concentration of lead in blood and brainstem for the group exposed to the lowest concentration of lead (100mg/L), but not for the group exposed to the higher concentration (400mg/L). This study indicate that the lead acetate can have deleterious effects on the maturation of the auditory nerve and brainstem (cochlear nucleus region), as detected by the Brainstem Auditory Evoked Potentials, and the ferrous sulphate can partially amend this effect. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. All rights reserved.

  8. Organization, development, and effects of infraorbital nerve transection on galanin binding sites in the trigeminal brainstem complex.

    PubMed

    Bodie, D; Bennett-Clarke, C A; Davis, K; Postelwaite, J P; Chiaia, N L; Rhoades, R W

    1997-01-01

    Previous experiments from this laboratory have indicated that transection of the infraorbital nerve (ION, the trigeminal [V] branch that supplies the mystacial vibrissae follicles) at birth and in adulthood has markedly different effects on galanin immunoreactivity in the V brainstem complex. Adult nerve transection increases galanin immunoreactivity in the superficial layers of V subnucleus caudalis (SpC) only, while neonatal nerve transection results in increased galanin expression in vibrissae-related primary afferents throughout the V brainstem complex. The present study describes the distribution of binding sites for this peptide in the mature and developing V ganglion and brainstem complex and determines the effects of neonatal and adult ION damage and the associated changes in galanin levels upon their distribution and density. Galanin binding sites are densely distributed in all V brainstem subnuclei and are particularly dense in V subnucleus interpolaris and the superficial layers of SpC. They are present at birth (P-0) and their distribution is similar to that in adult animals. Transection of the ION in adulthood and examination of brainstem 7 days later indicated marked reductions in the density of galanin binding sites in the V brainstem complex. With the exception of the superficial laminae of SpC, the same reduction in density remained apparent in rats that survived > 45 days after nerve cuts. Transection of the ION on P-0 resulted in no change in the density of galanin binding sites in the brainstem after either 7 or > 60 days survival. These results indicate that densely distributed galanin binding sites are present in the V brainstem complex of both neonatal and adult rats, that they are located in regions not innervated by galanin-positive axons, and that their density is not significantly influenced by large lesion-induced changes in the primary afferent content of their natural ligand.

  9. Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex.

    PubMed

    Hennessy, Morgan L; Corcoran, Andrea E; Brust, Rachael D; Chang, YoonJeung; Nattie, Eugene E; Dymecki, Susan M

    2017-02-15

    Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 ( Tac1 ) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1 , referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine -N- oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO 2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO 2 Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei. SIGNIFICANCE STATEMENT Serotonin (5-HT) neurons modulate physiological processes and behaviors as diverse as body temperature, respiration, aggression, and mood. Using genetic tools, we characterize a 5-HT neuron subtype defined by expression of Tachykinin1 and Pet1 ( Tac1-Pet1 neurons), mapping soma localization to the caudal medulla primarily and axonal projections to brainstem motor nuclei most prominently, and, when silenced, observed blunting of the ventilatory response to inhaled CO 2 Tac1-Pet1 neurons thus appear distinct from and contrast previously described Egr2-Pet1 neurons, which project primarily to chemosensory integration centers and are themselves chemosensitive. Copyright © 2017 the authors 0270-6474/17/371807-13$15.00/0.

  10. Dose-volume histogram analysis of brainstem necrosis in head and neck tumors treated using carbon-ion radiotherapy.

    PubMed

    Shirai, Katsuyuki; Fukata, Kyohei; Adachi, Akiko; Saitoh, Jun-Ichi; Musha, Atsushi; Abe, Takanori; Kanai, Tatsuaki; Kobayashi, Daijiro; Shigeta, Yuka; Yokoo, Satoshi; Chikamatsu, Kazuaki; Ohno, Tatsuya; Nakano, Takashi

    2017-10-01

    We aimed to evaluate the relationship between brainstem necrosis and dose-volume histograms in patients with head and neck tumors after carbon-ion radiotherapy. We evaluated 85 patients with head and neck tumors who underwent carbon-ion radiotherapy and were followed-up for ≥12months. Brainstem necrosis was evaluated using the Common Terminology Criteria for Adverse Events (version 4.0). The median follow-up was 24months, and four patients developed grade 1 brainstem necrosis, with 2-year and 3-year cumulative rates of 2.8% and 6.5%, respectively. Receiver operating characteristic curve analysis revealed the following significant cut-off values: a maximum brainstem dose of 48Gy (relative biological effectiveness [RBE]), D1cm 3 of 27Gy (RBE), V40Gy (RBE) of 0.1cm 3 , V30Gy (RBE) of 0.7cm 3 , and V20Gy (RBE) of 1.4cm 3 . Multivariate analysis revealed that V30Gy (RBE) was most significantly associated with brainstem necrosis. The 2-year cumulative rates were 33% and 0% for V30Gy (RBE) of ≥0.7cm 3 and <0.7cm 3 , respectively (p<0.001). The present study indicated that the dose constraints might help minimize brainstem necrosis after carbon-ion radiotherapy. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  11. Deviations of the visual upright in three dimensions in disorders of the brainstem: a clinical exploration.

    PubMed

    Frisén, Lars

    2010-12-01

    Deviations of the subjective visual vertical in the roll or fronto-parallel plane occur commonly in disorders of the brainstem and have been extensively explored. In contrast, little is known about deviations in other directions. The present retrospective study focused on deviations in the pitch (sagittal) direction in 176 patients with a wide variety of disorders. The test task was to set a self-illuminated rod in the apparent upright position, in total darkness. Abnormal results (outside ± 4°) were recorded in 58% of the subjects. Negative (top backward) deviations were the most common, particularly with mass lesions in the pineal region, obstructive hydrocephalus, cerebellar lesions and crowding at the craniocervical junction. Positive and negative deviations were about equally common with focal intra-axial lesions. Negative deviations appeared related to dorsal locations of lesions and vice versa. Normal pressure hydrocephalus, Parkinson's disease and progressive supranuclear palsy were associated with smaller deviations, without a clear directional preponderance, and a larger individual variability. Most subjects lacked overt clinical corollaries. The most common ocular signs were aqueduct syndromes (n = 17) and ocular tilt reactions (n = 12), which were associated with deviations in 47 and 92% of instances, respectively. Subjective corollaries of deviation were never reported, not even by those subjects who showed a dramatic improvement upon resolution of the underlying condition. Deviations were also assessed in roll in a subgroup of 40 patients with focal lesions. Thirty subjects returned abnormal results: 13% in roll, 47% in pitch and 40% in pitch and roll. The direction of roll deviation appeared primarily related to laterality, with clockwise deviations with right-sided lesions and vice versa. All subjects with ocular tilt reactions had combined pitch and roll deviations, implying a common neural substrate. Correlation analyses, geometrical modelling and experimental self-observations indicated that deviations in pitch were attributable to cyclotorsional asymmetries between the eyes. The frequent co-existence of abnormal pitch and roll results implies that the true axis of deviation in focal brainstem disorders commonly falls outside traditional reference planes. The term 'visual upright in three dimensions' is suggested to identify unrestricted measurements, preserving the established term 'visual vertical' for measurements confined to the roll plane. Assessment of the visual upright in three dimensions provides a new, quantitative angle on brainstem disorders. The test appears useful for identifying a ubiquitous yet clinically silent feature of brainstem disease and also for monitoring the evolution of underlying conditions. More detailed explorations appear well motivated.

  12. Operative management of brainstem cavernous malformations.

    PubMed

    Asaad, Wael F; Walcott, Brian P; Nahed, Brian V; Ogilvy, Christopher S

    2010-09-01

    Brainstem cavernous malformations (CMs) are complex lesions associated with hemorrhage and neurological deficit. In this review, the authors describe the anatomical nuances relating to the operative techniques for these challenging lesions. The resection of brainstem CMs in properly selected patients has been demonstrated to reduce the risk of rehemorrhage and can be achieved relatively safely in experienced hands.

  13. Functional Ear (A)Symmetry in Brainstem Neural Activity Relevant to Encoding of Voice Pitch: A Precursor for Hemispheric Specialization?

    ERIC Educational Resources Information Center

    Krishnan, Ananthanarayan; Gandour, Jackson T.; Ananthakrishnan, Saradha; Bidelman, Gavin M.; Smalt, Christopher J.

    2011-01-01

    Pitch processing is lateralized to the right hemisphere; linguistic pitch is further mediated by left cortical areas. This experiment investigates whether ear asymmetries vary in brainstem representation of pitch depending on linguistic status. Brainstem frequency-following responses (FFRs) were elicited by monaural stimulation of the left and…

  14. The Role of the Auditory Brainstem in Processing Linguistically-Relevant Pitch Patterns

    ERIC Educational Resources Information Center

    Krishnan, Ananthanarayan; Gandour, Jackson T.

    2009-01-01

    Historically, the brainstem has been neglected as a part of the brain involved in language processing. We review recent evidence of language-dependent effects in pitch processing based on comparisons of native vs. nonnative speakers of a tonal language from electrophysiological recordings in the auditory brainstem. We argue that there is enhancing…

  15. Imaging White Matter in Human Brainstem

    PubMed Central

    Ford, Anastasia A.; Colon-Perez, Luis; Triplett, William T.; Gullett, Joseph M.; Mareci, Thomas H.; FitzGerald, David B.

    2013-01-01

    The human brainstem is critical for the control of many life-sustaining functions, such as consciousness, respiration, sleep, and transfer of sensory and motor information between the brain and the spinal cord. Most of our knowledge about structure and organization of white and gray matter within the brainstem is derived from ex vivo dissection and histology studies. However, these methods cannot be applied to study structural architecture in live human participants. Tractography from diffusion-weighted magnetic resonance imaging (MRI) may provide valuable insights about white matter organization within the brainstem in vivo. However, this method presents technical challenges in vivo due to susceptibility artifacts, functionally dense anatomy, as well as pulsatile and respiratory motion. To investigate the limits of MR tractography, we present results from high angular resolution diffusion imaging of an intact excised human brainstem performed at 11.1 T using isotropic resolution of 0.333, 1, and 2 mm, with the latter reflecting resolution currently used clinically. At the highest resolution, the dense fiber architecture of the brainstem is evident, but the definition of structures degrades as resolution decreases. In particular, the inferred corticopontine/corticospinal tracts (CPT/CST), superior (SCP) and middle cerebellar peduncle (MCP), and medial lemniscus (ML) pathways are clearly discernable and follow known anatomical trajectories at the highest spatial resolution. At lower resolutions, the CST/CPT, SCP, and MCP pathways are artificially enlarged due to inclusion of collinear and crossing fibers not inherent to these three pathways. The inferred ML pathways appear smaller at lower resolutions, indicating insufficient spatial information to successfully resolve smaller fiber pathways. Our results suggest that white matter tractography maps derived from the excised brainstem can be used to guide the study of the brainstem architecture using diffusion MRI in vivo. PMID:23898254

  16. Imaging white matter in human brainstem.

    PubMed

    Ford, Anastasia A; Colon-Perez, Luis; Triplett, William T; Gullett, Joseph M; Mareci, Thomas H; Fitzgerald, David B

    2013-01-01

    The human brainstem is critical for the control of many life-sustaining functions, such as consciousness, respiration, sleep, and transfer of sensory and motor information between the brain and the spinal cord. Most of our knowledge about structure and organization of white and gray matter within the brainstem is derived from ex vivo dissection and histology studies. However, these methods cannot be applied to study structural architecture in live human participants. Tractography from diffusion-weighted magnetic resonance imaging (MRI) may provide valuable insights about white matter organization within the brainstem in vivo. However, this method presents technical challenges in vivo due to susceptibility artifacts, functionally dense anatomy, as well as pulsatile and respiratory motion. To investigate the limits of MR tractography, we present results from high angular resolution diffusion imaging of an intact excised human brainstem performed at 11.1 T using isotropic resolution of 0.333, 1, and 2 mm, with the latter reflecting resolution currently used clinically. At the highest resolution, the dense fiber architecture of the brainstem is evident, but the definition of structures degrades as resolution decreases. In particular, the inferred corticopontine/corticospinal tracts (CPT/CST), superior (SCP) and middle cerebellar peduncle (MCP), and medial lemniscus (ML) pathways are clearly discernable and follow known anatomical trajectories at the highest spatial resolution. At lower resolutions, the CST/CPT, SCP, and MCP pathways are artificially enlarged due to inclusion of collinear and crossing fibers not inherent to these three pathways. The inferred ML pathways appear smaller at lower resolutions, indicating insufficient spatial information to successfully resolve smaller fiber pathways. Our results suggest that white matter tractography maps derived from the excised brainstem can be used to guide the study of the brainstem architecture using diffusion MRI in vivo.

  17. Automated brainstem co-registration (ABC) for MRI.

    PubMed

    Napadow, Vitaly; Dhond, Rupali; Kennedy, David; Hui, Kathleen K S; Makris, Nikos

    2006-09-01

    Group data analysis in brainstem neuroimaging is predicated on accurate co-registration of anatomy. As the brainstem is comprised of many functionally heterogeneous nuclei densely situated adjacent to one another, relatively small errors in co-registration can manifest in increased variance or decreased sensitivity (or significance) in detecting activations. We have devised a 2-stage automated, reference mask guided registration technique (Automated Brainstem Co-registration, or ABC) for improved brainstem co-registration. Our approach utilized a brainstem mask dataset to weight an automated co-registration cost function. Our method was validated through measurement of RMS error at 12 manually defined landmarks. These landmarks were also used as guides for a secondary manual co-registration option, intended for outlier individuals that may not adequately co-register with our automated method. Our methodology was tested on 10 healthy human subjects and compared to traditional co-registration techniques (Talairach transform and automated affine transform to the MNI-152 template). We found that ABC had a significantly lower mean RMS error (1.22 +/- 0.39 mm) than Talairach transform (2.88 +/- 1.22 mm, mu +/- sigma) and the global affine (3.26 +/- 0.81 mm) method. Improved accuracy was also found for our manual-landmark-guided option (1.51 +/- 0.43 mm). Visualizing individual brainstem borders demonstrated more consistent and uniform overlap for ABC compared to traditional global co-registration techniques. Improved robustness (lower susceptibility to outliers) was demonstrated with ABC through lower inter-subject RMS error variance compared with traditional co-registration methods. The use of easily available and validated tools (AFNI and FSL) for this method should ease adoption by other investigators interested in brainstem data group analysis.

  18. Brainstem projections of neurons located in various subdivisions of the dorsolateral hypothalamic area-an anterograde tract-tracing study.

    PubMed

    Papp, Rege S; Palkovits, Miklós

    2014-01-01

    The projections from the dorsolateral hypothalamic area (DLH) to the lower brainstem have been investigated by using biotinylated dextran amine (BDA), an anterograde tracer in rats. The DLH can be divided into 3 areas (dorsomedial hypothalamus, perifornical area, lateral hypothalamic area), and further subdivided into 8 subdivisions. After unilateral stereotaxic injections of BDA into individual DLH subdivisions, the correct sites of injections were controlled histologically, and the distribution patterns of BDA-positive fibers were mapped on serial sections between the hypothalamus and spinal cord in 22 rats. BDA-labeled fibers were observable over 100 different brainstem areas, nuclei, or subdivisions. Injections into the 8 DLH subdivisions established distinct topographical patterns. In general, the density of labeled fibers was low in the lower brainstem. High density of fibers was seen only 4 of the 116 areas: in the lateral and ventrolateral parts of the periaqueductal gray, the Barrington's, and the pedunculopontine tegmental nuclei. All of the biogenic amine cell groups in the lower brainstem (9 noradrenaline, 3 adrenaline, and 9 serotonin cell groups) received labeled fibers, some of them from all, or at least 7 DLH subdivisions, mainly from perifornical and ventral lateral hypothalamic neurons. Some of the tegmental nuclei and nuclei of the reticular formation were widely innervated, although the density of the BDA-labeled fibers was generally low. No definitive descending BDA-positive pathway, but long-run solitaire BDA-labeled fibers were seen in the lower brainstem. These descending fibers joined some of the large tracts or fasciculi in the brainstem. The distribution pattern of BDA-positive fibers of DLH origin throughout the lower brainstem was comparable to patterns of previously published orexin- or melanin-concentrating hormone-immunoreactive fibers with somewhat differences.

  19. Brainstem projections of neurons located in various subdivisions of the dorsolateral hypothalamic area—an anterograde tract-tracing study

    PubMed Central

    Papp, Rege S.; Palkovits, Miklós

    2014-01-01

    The projections from the dorsolateral hypothalamic area (DLH) to the lower brainstem have been investigated by using biotinylated dextran amine (BDA), an anterograde tracer in rats. The DLH can be divided into 3 areas (dorsomedial hypothalamus, perifornical area, lateral hypothalamic area), and further subdivided into 8 subdivisions. After unilateral stereotaxic injections of BDA into individual DLH subdivisions, the correct sites of injections were controlled histologically, and the distribution patterns of BDA-positive fibers were mapped on serial sections between the hypothalamus and spinal cord in 22 rats. BDA-labeled fibers were observable over 100 different brainstem areas, nuclei, or subdivisions. Injections into the 8 DLH subdivisions established distinct topographical patterns. In general, the density of labeled fibers was low in the lower brainstem. High density of fibers was seen only 4 of the 116 areas: in the lateral and ventrolateral parts of the periaqueductal gray, the Barrington's, and the pedunculopontine tegmental nuclei. All of the biogenic amine cell groups in the lower brainstem (9 noradrenaline, 3 adrenaline, and 9 serotonin cell groups) received labeled fibers, some of them from all, or at least 7 DLH subdivisions, mainly from perifornical and ventral lateral hypothalamic neurons. Some of the tegmental nuclei and nuclei of the reticular formation were widely innervated, although the density of the BDA-labeled fibers was generally low. No definitive descending BDA-positive pathway, but long-run solitaire BDA-labeled fibers were seen in the lower brainstem. These descending fibers joined some of the large tracts or fasciculi in the brainstem. The distribution pattern of BDA-positive fibers of DLH origin throughout the lower brainstem was comparable to patterns of previously published orexin- or melanin-concentrating hormone-immunoreactive fibers with somewhat differences. PMID:24904303

  20. Altered Levels of Zinc and N-methyl-D-aspartic Acid Receptor Underlying Multiple Organ Dysfunctions After Severe Trauma

    PubMed Central

    Wang, Guanghuan; Yu, Xiaojun; Wang, Dian; Xu, Xiaohu; Chen, Guang; Jiang, Xuewu

    2015-01-01

    Background Severe trauma can cause secondary multiple organ dysfunction syndrome (MODS) and death. Oxidative stress and/or excitatory neurotoxicity are considered as the final common pathway in nerve cell injuries. Zinc is the cofactor of the redox enzyme, and the effect of the excitatory neurotoxicity is related to N-methyl-D-aspartic acid receptor (NMDAR). Material/Methods We investigated the levels of zinc and brainstem NMDAR in a rabbit model of severe trauma. Zinc and serum biochemical profiles were determined. Immunohistochemistry was used to detect brainstem N-methyl-D-aspartic acid receptor 1 (NR1), N-methyl-D-aspartic acid receptor 2A (NR2A), and N-methyl-D-aspartic acid receptor 2B (NR2B) expression. Results Brain and brainstem Zn levels increased at 12 h, but serum Zn decreased dramatically after the trauma. NR1 in the brainstem dorsal regions increased at 6 h after injury and then decreased. NR2A in the dorsal regions decreased to a plateau at 12 h after trauma. The levels of NR2B were lowest in the death group in the brainstem. Serum zinc was positively correlated with NR2A and 2B and negatively correlated with zinc in the brain. Correlations were also found between the brainstem NR2A and that of the dorsal brainstem, as well as between brainstem NR2A and changes in NR2B. There was a negative correlation between zinc and NR2A. Conclusions Severe trauma led to an acute reduction of zinc enhancing oxidative stress and the changes of NMDAR causing the neurotoxicity of the nerve cells. This may be a mechanism for the occurrence of MODS or death after trauma. PMID:26335029

  1. Gender differences in binaural speech-evoked auditory brainstem response: are they clinically significant?

    PubMed

    Jalaei, Bahram; Azmi, Mohd Hafiz Afifi Mohd; Zakaria, Mohd Normani

    2018-05-17

    Binaurally evoked auditory evoked potentials have good diagnostic values when testing subjects with central auditory deficits. The literature on speech-evoked auditory brainstem response evoked by binaural stimulation is in fact limited. Gender disparities in speech-evoked auditory brainstem response results have been consistently noted but the magnitude of gender difference has not been reported. The present study aimed to compare the magnitude of gender difference in speech-evoked auditory brainstem response results between monaural and binaural stimulations. A total of 34 healthy Asian adults aged 19-30 years participated in this comparative study. Eighteen of them were females (mean age=23.6±2.3 years) and the remaining sixteen were males (mean age=22.0±2.3 years). For each subject, speech-evoked auditory brainstem response was recorded with the synthesized syllable /da/ presented monaurally and binaurally. While latencies were not affected (p>0.05), the binaural stimulation produced statistically higher speech-evoked auditory brainstem response amplitudes than the monaural stimulation (p<0.05). As revealed by large effect sizes (d>0.80), substantive gender differences were noted in most of speech-evoked auditory brainstem response peaks for both stimulation modes. The magnitude of gender difference between the two stimulation modes revealed some distinct patterns. Based on these clinically significant results, gender-specific normative data are highly recommended when using speech-evoked auditory brainstem response for clinical and future applications. The preliminary normative data provided in the present study can serve as the reference for future studies on this test among Asian adults. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  2. Anti-Hu paraneoplastic brainstem encephalitis caused by a pancreatic neuroendocrine tumor presenting with central hypoventilation.

    PubMed

    Najjar, Marc; Taylor, Andrew; Agrawal, Surbhi; Fojo, Tito; Merkler, Alexander E; Rosenblum, Marc K; Lennihan, Laura; Kluger, Michael D

    2017-06-01

    Paraneoplastic neurological syndromes are rare autoimmune manifestations of malignancies associated with specific antibodies. Anti-Hu associated brainstem encephalitis, a well-described syndrome, usually presents subacutely with preferential involvement of the medulla. Anti-Hu antibodies target intraneuronal antigens and are therefore highly correlated with neurological syndromes when present concomitantly with a neoplasm. Reported is a case of anti-Hu brainstem encephalitis associated with a pancreatic neuroendocrine tumor (PNET) presenting with central hypoventilation. This is the first described case of brainstem encephalitis associated with a well-differentiated PNET as well as the first case of Anti-Hu antibodies associated with a PNET. There are no standardized protocols for the treatment of paraneoplastic brainstem encephalitis however, as in the present case, surgical resection and oncological treatment of the tumor is the first line treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Mapping of somatostatin-28 (1-12) in the alpaca (Lama pacos) brainstem.

    PubMed

    De Souza, Eliana; Sánchez, Manuel Lisardo; Aguilar, Luís Ángel; Díaz-Cabiale, Zaida; Narváez, José Ángel; Coveñas, Rafael

    2015-05-01

    Using an indirect immunoperoxidase technique, we studied the distribution of cell bodies and fibers containing somatostatin-28 (1-12) in the alpaca brainstem. Immunoreactive fibers were widely distributed throughout the whole brainstem: 34 brainstem nuclei/regions showed a high or a moderate density of these fibers. Perikarya containing the peptide were widely distributed throughout the mesencephalon, pons and medulla oblongata. Cell bodies containing somatostatin-28 (1-12) were observed in the lateral and medial divisions of the marginal nucleus of the brachium conjunctivum, reticular formation (mesencephalon, pons and medulla oblongata), inferior colliculus, periaqueductal gray, superior colliculus, pericentral division of the dorsal tegmental nucleus, interpeduncular nucleus, nucleus of the trapezoid body, vestibular nucleus, motor dorsal nucleus of the vagus, nucleus of the solitary tract, nucleus praepositus hypoglossi, and in the substantia nigra. This widespread distribution indicates that somatostatin-28 (1-12) is involved in multiple physiological actions in the alpaca brainstem. © 2015 Wiley Periodicals, Inc.

  4. Normal limits in relation to age, body size and gender of two-dimensional echocardiographic aortic root dimensions in persons ≥15 years of age.

    PubMed

    Devereux, Richard B; de Simone, Giovanni; Arnett, Donna K; Best, Lyle G; Boerwinkle, Eric; Howard, Barbara V; Kitzman, Dalane; Lee, Elisa T; Mosley, Thomas H; Weder, Alan; Roman, Mary J

    2012-10-15

    Nomograms to predict normal aortic root diameter for body surface area (BSA) in broad ranges of age have been widely used but are limited by lack of consideration of gender effects, jumps in upper limits of aortic diameter among age strata, and data from older teenagers. Sinus of Valsalva diameter was measured by American Society of Echocardiography convention in normal-weight, nonhypertensive, nondiabetic subjects ≥15 years old without aortic valve disease from clinical or population-based samples. Analyses of covariance and linear regression with assessment of residuals identified determinants and developed predictive models for normal aortic root diameter. In 1,207 apparently normal subjects ≥15 years old (54% women), aortic root diameter was 2.1 to 4.3 cm. Aortic root diameter was strongly related to BSA and height (r = 0.48 for the 2 comparisons), age (r = 0.36), and male gender (+2.7 mm adjusted for BSA and age, p <0.001 for all comparisons). Multivariable equations using age, gender, and BSA or height predicted aortic diameter strongly (R = 0.674 for the 2 comparisons, p <0.001) with minimal relation of residuals to age or body size: for BSA 2.423 + (age [years] × 0.009) + (BSA [square meters] × 0.461) - (gender [1 = man, 2 = woman] × 0.267), SEE 0.261 cm; for height 1.519 + (age [years] × 0.010) + (height [centimeters] × 0.010) - (gender [1 = man, 2 = woman] × 0.247), SEE 0.215 cm. In conclusion, aortic root diameter is larger in men and increases with body size and age. Regression models incorporating body size, age, and gender are applicable to adolescents and adults without limitations of previous nomograms. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. KARS-related diseases: progressive leukoencephalopathy with brainstem and spinal cord calcifications as new phenotype and a review of literature.

    PubMed

    Ardissone, Anna; Tonduti, Davide; Legati, Andrea; Lamantea, Eleonora; Barone, Rita; Dorboz, Imen; Boespflug-Tanguy, Odile; Nebbia, Gabriella; Maggioni, Marco; Garavaglia, Barbara; Moroni, Isabella; Farina, Laura; Pichiecchio, Anna; Orcesi, Simona; Chiapparini, Luisa; Ghezzi, Daniele

    2018-04-04

    KARS encodes lysyl- transfer ribonucleic acid (tRNA) synthetase, which catalyzes the aminoacylation of tRNA-Lys in the cytoplasm and mitochondria. Eleven families/sporadic patients and 16 different mutations in KARS have been reported to date. The associated clinical phenotype is heterogeneous ranging from early onset encephalopathy to isolated peripheral neuropathy or nonsyndromic hearing impairment. Recently additional presentations including leukoencephalopathy as predominant cerebral involvement or cardiomyopathy, isolated or associated with muscular and cerebral involvement, have been reported. A progressive Leukoencephalopathy with brainstem and spinal cord calcifications was previously described in a singleton patient and in two siblings, without the identification of the genetic cause. We reported here about a new severe phenotype associated with biallelic KARS mutations and sharing some common points with the other already reported phenotypes, but with a distinct clinical and neuroimaging picture. Review of KARS mutant patients published to date will be also discussed. Herein, we report the clinical, biochemical and molecular findings of 2 unreported Italian patients affected by developmental delay, acquired microcephaly, spastic tetraparesis, epilepsy, sensory-neural hypoacusia, visual impairment, microcytic hypochromic anaemia and signs of hepatic dysfunction. MRI pattern in our patients was characterized by progressive diffuse leukoencephalopathy and calcifications extending in cerebral, brainstem and cerebellar white matter, with spinal cord involvement. Genetic analysis performed on these 2 patients and in one subject previously described with similar MRI pattern revealed the presence of biallelic mutations in KARS in all 3 subjects. With our report we define the molecular basis of the previously described Leukoencephalopathy with Brainstem and Spinal cord Calcification widening the spectrum of KARS related disorders, particularly in childhood onset disease suggestive for mitochondrial impairment. The review of previous cases does not suggest a strict and univocal genotype/phenotype correlation for this highly heterogeneous entity. Moreover, our cases confirm the usefulness of search for common brain and spine MR imaging pattern and of broad genetic screening, in syndromes clinically resembling mitochondrial disorders in spite of normal biochemical assay.

  6. Cerebellar and Brainstem Malformations.

    PubMed

    Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

    2016-08-01

    The frequency and importance of the evaluation of the posterior fossa have increased significantly over the past 20 years owing to advances in neuroimaging. Conventional and advanced neuroimaging techniques allow detailed evaluation of the complex anatomic structures within the posterior fossa. A wide spectrum of cerebellar and brainstem malformations has been shown. Familiarity with the spectrum of cerebellar and brainstem malformations and their well-defined diagnostic criteria is crucial for optimal therapy, an accurate prognosis, and correct genetic counseling. This article discusses cerebellar and brainstem malformations, with emphasis on neuroimaging findings (including diagnostic criteria), neurologic presentation, systemic involvement, prognosis, and recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. [Forensic application of brainstem auditory evoked potential in patients with brain concussion].

    PubMed

    Zheng, Xing-Bin; Li, Sheng-Yan; Huang, Si-Xing; Ma, Ke-Xin

    2008-12-01

    To investigate changes of brainstem auditory evoked potential (BAEP) in patients with brain concussion. Nineteen patients with brain concussion were studied with BAEP examination. The data was compared to the healthy persons reported in literatures. The abnormal rate of BAEP for patients with brain concussion was 89.5%. There was a statistically significant difference between the abnormal rate of patients and that of healthy persons (P<0.05). The abnormal rate of BAEP in the brainstem pathway for patients with brain concussion was 73.7%, indicating dysfunction of the brainstem in those patients. BAEP might be helpful in forensic diagnosis of brain concussion.

  8. Evidence for a distributed respiratory rhythm generating network in the goldfish (Carsssius auratus).

    PubMed

    Duchcherer, Maryana; Kottick, Andrew; Wilson, R J A

    2010-01-01

    Central pattern generators located in the brainstem regulate ventilatory behaviors in vertebrates. The development of the isolated brainstem preparation has allowed these neural networks to be characterized in a number of aquatic species. The aim of this study was to explore the architecture of the respiratory rhythm-generating site in the goldfish (Carassius auratus) and to determine the utility of a newly developed isolated brainstem preparation, the Sheep Dip. Here we provide evidence for a distributed organization of respiratory rhythm generating neurons along the rostrocaudal axis of the goldfish brainstem and outline the advantages of the Sheep Dip as a tool used to survey neural networks.

  9. Abnormal trajectories in cerebellum and brainstem volumes in carriers of the fragile X premutation.

    PubMed

    Wang, Jun Yi; Hessl, David; Hagerman, Randi J; Simon, Tony J; Tassone, Flora; Ferrer, Emilio; Rivera, Susan M

    2017-07-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder typically affecting male premutation carriers with 55-200 CGG trinucleotide repeat expansions in the FMR1 gene after age 50. The aim of this study was to examine whether cerebellar and brainstem changes emerge during development or aging in late life. We retrospectively analyzed magnetic resonance imaging scans from 322 males (age 8-81 years). Volume changes in the cerebellum and brainstem were contrasted with those in the ventricles and whole brain. Compared to the controls, premutation carriers without FXTAS showed significantly accelerated volume decrease in the cerebellum and whole brain, flatter inverted U-shaped trajectory of the brainstem, and larger ventricles. Compared to both older controls and premutation carriers without FXTAS, carriers with FXTAS exhibited significant volume decrease in the cerebellum and whole brain and accelerated volume decrease in the brainstem. We therefore conclude that cerebellar and brainstem volumes were likely affected during both development and progression of neurodegeneration in premutation carriers, suggesting that interventions may need to start early in adulthood to be most effective. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Air pollution is associated with brainstem auditory nuclei pathology and delayed brainstem auditory evoked potentials.

    PubMed

    Calderón-Garcidueñas, Lilian; D'Angiulli, Amedeo; Kulesza, Randy J; Torres-Jardón, Ricardo; Osnaya, Norma; Romero, Lina; Keefe, Sheyla; Herritt, Lou; Brooks, Diane M; Avila-Ramirez, Jose; Delgado-Chávez, Ricardo; Medina-Cortina, Humberto; González-González, Luis Oscar

    2011-06-01

    We assessed brainstem inflammation in children exposed to air pollutants by comparing brainstem auditory evoked potentials (BAEPs) and blood inflammatory markers in children age 96.3±8.5 months from highly polluted (n=34) versus a low polluted city (n=17). The brainstems of nine children with accidental deaths were also examined. Children from the highly polluted environment had significant delays in wave III (t(50)=17.038; p<0.0001) and wave V (t(50)=19.730; p<0.0001) but no delay in wave I (p=0.548). They also had significantly longer latencies than controls for interwave intervals I-III, III-V, and I-V (all t(50)>7.501; p<0.0001), consisting with delayed central conduction time of brainstem neural transmission. Highly exposed children showed significant evidence of inflammatory markers and their auditory and vestibular nuclei accumulated α synuclein and/or β amyloid(1-42). Medial superior olive neurons, critically involved in BAEPs, displayed significant pathology. Children's exposure to urban air pollution increases their risk for auditory and vestibular impairment. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  11. Electrophysiological Evidence for the Sources of the Masking Level Difference.

    PubMed

    Fowler, Cynthia G

    2017-08-16

    The purpose of this review article is to review evidence from auditory evoked potential studies to describe the contributions of the auditory brainstem and cortex to the generation of the masking level difference (MLD). A literature review was performed, focusing on the auditory brainstem, middle, and late latency responses used in protocols similar to those used to generate the behavioral MLD. Temporal coding of the signals necessary for generating the MLD occurs in the auditory periphery and brainstem. Brainstem disorders up to wave III of the auditory brainstem response (ABR) can disrupt the MLD. The full MLD requires input to the generators of the auditory late latency potentials to produce all characteristics of the MLD; these characteristics include threshold differences for various binaural signal and noise conditions. Studies using central auditory lesions are beginning to identify the cortical effects on the MLD. The MLD requires auditory processing from the periphery to cortical areas. A healthy auditory periphery and brainstem codes temporal synchrony, which is essential for the ABR. Threshold differences require engaging cortical function beyond the primary auditory cortex. More studies using cortical lesions and evoked potentials or imaging should clarify the specific cortical areas involved in the MLD.

  12. A human brain network derived from coma-causing brainstem lesions.

    PubMed

    Fischer, David B; Boes, Aaron D; Demertzi, Athena; Evrard, Henry C; Laureys, Steven; Edlow, Brian L; Liu, Hesheng; Saper, Clifford B; Pascual-Leone, Alvaro; Fox, Michael D; Geerling, Joel C

    2016-12-06

    To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness. © 2016 American Academy of Neurology.

  13. Auditory brainstem activity and development evoked by apical versus basal cochlear implant electrode stimulation in children.

    PubMed

    Gordon, K A; Papsin, B C; Harrison, R V

    2007-08-01

    The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. Responses of the auditory nerve and brainstem, evoked by an apical and a basal implant electrode, were measured over the first year of cochlear implant use in 50 children with early onset severe to profound deafness who used hearing aids prior to implantation. Responses at initial stimulation were of larger amplitude and shorter latency when evoked by the apical electrode. No significant effects of residual hearing or age were found on initial response amplitudes or latencies. With implant use, responses evoked by both electrodes showed decreases in wave and interwave latencies reflecting decreased neural conduction time through the brainstem. Apical versus basal differences persisted with implant experience with one exception; eIII-eV interlatency differences decreased with implant use. Acute stimulation shows prolongation of basally versus apically evoked auditory nerve and brainstem responses in children with severe to profound deafness. Interwave latencies reflecting neural conduction along the caudal and rostral portions of the brainstem decreased over the first year of implant use. Differences in neural conduction times evoked by apical versus basal electrode stimulation persisted in the caudal but not rostral brainstem. Activity-dependent changes of the auditory brainstem occur in response to both apical and basal cochlear implant electrode stimulation.

  14. Right-sided dominance of the bilateral vestibular system in the upper brainstem and thalamus.

    PubMed

    Dieterich, Marianne; Kirsch, V; Brandt, T

    2017-10-01

    MRI diffusion tensor imaging tractography was performed on the bilateral vestibular brainstem pathways, which run from the vestibular nuclei via the paramedian and posterolateral thalamic subnuclei to the parieto-insular vestibular cortex. Twenty-one right-handed healthy subjects participated. Quantitative analysis revealed a rope-ladder-like system of vestibular pathways in the brainstem with crossings at pontine and mesencephalic levels. Three structural types of right-left fiber distributions could be delineated: (1) evenly distributed pathways at the lower pontine level from the vestibular nuclei to the pontine crossing, (2) a moderate, pontomesencephalic right-sided lateralization between the pontine and mesencephalic crossings, and (3) a further increase of the right-sided lateralization above the mesencephalic crossing leading to the thalamic vestibular subnuclei. The increasing lateralization along the brainstem was the result of an asymmetric number of pontine and mesencephalic crossing fibers which was higher for left-to-right crossings. The dominance of the right vestibular meso-diencephalic circuitry in right-handers corresponds to the right-hemispheric dominance of the vestibular cortical network. The structural asymmetry apparent in the upper brainstem might be interpreted in relation to the different functions of the vestibular system depending on their anatomical level: a symmetrical sensorimotor reflex control of eye, head, and body mediated by the lower brainstem; a lateralized right-sided upper brainstem-thalamic function as part of the dominant right-sided cortical/subcortical vestibular system that enables a global percept of body motion and orientation in space.

  15. Brainstem metabotropic glutamate receptors reduce food intake and activate dorsal pontine and medullar structures after peripheral bacterial lipopolysaccharide administration.

    PubMed

    Chaskiel, Léa; Paul, Flora; Gerstberger, Rüdiger; Hübschle, Thomas; Konsman, Jan Pieter

    2016-08-01

    During infection-induced inflammation food intake is reduced. Vagal and brainstem pathways are important both in feeding regulation and immune-to-brain communication. Glutamate is released by vagal afferent terminals in the nucleus of the solitary tract and by its neurons projecting to the parabrachial nuclei. We therefore studied the role of brainstem glutamate receptors in spontaneous food intake of healthy animals and during sickness-associated hypophagia after peripheral administration of bacterial lipopolysaccharides or interleukin-1beta. Brainstem group I and II metabotropic, but not ionotropic, glutamate receptor antagonism increased food intake both in saline- and lipopolysaccharide-treated rats. In these animals, expression of the cellular activation marker c-Fos in the lateral parabrachial nuclei and lipopolysaccharide-induced activation of the nucleus of the solitary tract rostral to the area postrema were suppressed. Group I metabotropic glutamate receptors did not colocalize with c-Fos or neurons regulating gastric function in these structures. Group I metabotropic glutamate receptors were, however, found on raphé magnus neurons that were part of the brainstem circuit innervating the stomach and on trigeminal and hypoglossal motor neurons. In conclusion, our findings show that brainstem metabotropic glutamate receptors reduce food intake and activate the lateral parabrachial nuclei as well as the rostral nucleus of the solitary tract after peripheral bacterial lipopolysaccharide administration. They also provide insight into potential group I metabotropic glutamate receptor-dependent brainstem circuits mediating these effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. A human brain network derived from coma-causing brainstem lesions

    PubMed Central

    Boes, Aaron D.; Demertzi, Athena; Evrard, Henry C.; Laureys, Steven; Edlow, Brian L.; Liu, Hesheng; Saper, Clifford B.; Pascual-Leone, Alvaro; Geerling, Joel C.

    2016-01-01

    Objective: To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. Methods: We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. Results: A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Conclusions: Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness. PMID:27815400

  17. Treatment of a partially thrombosed giant aneurysm of the vertebral artery by aneurysm trapping and direct vertebral artery-posterior inferior cerebellar artery end-to-end anastomosis: technical case report.

    PubMed

    Benes, Ludwig; Kappus, Christoph; Sure, Ulrich; Bertalanffy, Helmut

    2006-07-01

    The purpose of this article is to focus for the first time on the operative management of a direct vertebral artery (VA)-posterior inferior cerebellar artery (PICA) end-to-end anastomosis in a partially thrombosed giant VA-PICA-complex aneurysm and to underline its usefulness as an additional treatment option. The operative technique of a direct VA-PICA end-to-end anatomosis is described in detail. The VA was entering the large aneurysm sack. Distally, the PICA originated from the aneurysm sack-VA-complex. The donor and recipient vessel were cut close to the aneurysm. Whereas the VA was cut in a straight manner, the PICA was cut at an oblique 45-degree angle to enlarge the vascular end diameter. Vessel ends were flushed with heparinized saline and sutured. The thrombotic material inside the aneurysm sack was removed and the distal VA clipped, leaving the anterior spinal artery and brainstem perforators free. The patient regained consciousness without additional morbidity. Magnetic resonance imaging scans revealed a completely decompressed brainstem without infarction. The postoperative angiograms demonstrated a good filling of the anastomosed PICA. Despite the caliber mistmatch of these two vessels the direct VA-PICA end-to-end anastomosis provides an accurate alternative in addition to other anastomoses and bypass techniques, when donor and recipient vessels are suitable and medullary perforators do not have to be disrupted.

  18. Label-Free Ferrocene-Loaded Nanocarrier Engineering for In Vivo Cochlear Drug Delivery and Imaging.

    PubMed

    Youm, Ibrahima; Musazzi, Umberto M; Gratton, Michael Anne; Murowchick, James B; Youan, Bi-Botti C

    2016-10-01

    It is hypothesized that ferrocene (FC)-loaded nanocarriers (FC-NCs) are safe label-free contrast agents for cochlear biodistribution study by transmission electron microscopy (TEM). To test this hypothesis, after engineering, the poly(epsilon-caprolactone)/polyglycolide NCs are tested for stability with various types and ratios of sugar cryoprotectants during freeze-drying. Their physicochemical properties are characterized by UV-visible spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM/EDS). The biodistribution of the FC-NCs in the cochlear tissue after intratympanic injection in guinea pigs is visualized by TEM. Auditory brainstem responses are measured before and after 4-day treatments. These FC-NCs have 153.4 ± 8.7 nm, 85.5 ± 11.2%, and -22.1 ± 1.1 mV as mean diameters, percent drug association efficiency, and zeta potential, respectively (n = 3). The incorporation of FC into the NCs is confirmed by Fourier transform infrared spectroscopy and SEM/EDS spectra. Lactose (3:1 ratio, v/v) is the most effective stabilizer after a 12-day study. The administered NCs are visible by TEM in the scala media cells of the cochlea. Based on auditory brainstem response data, FC-NCs do not adversely affect hearing. Considering the electrondense, radioactive, and magnetic properties of iron inside FC, FC-NCs are promising nanotemplate for future inner ear theranostics. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  19. Neonate Auditory Brainstem Responses to CE-Chirp and CE-Chirp Octave Band Stimuli II: Versus Adult Auditory Brainstem Responses.

    PubMed

    Cobb, Kensi M; Stuart, Andrew

    The purpose of the study was to examine the differences in auditory brainstem response (ABR) latency and amplitude indices to the CE-Chirp stimuli in neonates versus young adults as a function of stimulus level, rate, polarity, frequency and gender. Participants were 168 healthy neonates and 20 normal-hearing young adults. ABRs were obtained to air- and bone-conducted CE-Chirps and air-conducted CE-Chirp octave band stimuli. The effects of stimulus level, rate, and polarity were examined with air-conducted CE-Chirps. The effect of stimulus level was also examined with bone-conducted CE-Chirps and CE-Chirp octave band stimuli. The effect of gender was examined across all stimulus manipulations. In general, ABR wave V amplitudes were significantly larger (p < 0.0001) and latencies were significantly shorter (p < 0.0001) for adults versus neonates for all air-conducted CE-Chirp stimuli with all stimulus manipulations. For bone-conducted CE-Chirps, infants had significantly shorter wave V latencies than adults at 15 dB nHL and 45 dB nHL (p = 0.02). Adult wave V amplitude was significantly larger for bone-conducted CE-Chirps only at 30 dB nHL (p = 0.02). The effect of gender was not statistically significant across all measures (p > 0.05). Significant differences in ABR latencies and amplitudes exist between newborns and young adults using CE-Chirp stimuli. These differences are consistent with differences to traditional click and tone burst stimuli and reflect maturational differences as a function of age. These findings continue to emphasize the importance of interpreting ABR results using age-based normative data.

  20. Benign paroxysmal vertigo of childhood: diagnostic value of vestibular test and high stimulus rate auditory brainstem response test.

    PubMed

    Zhang, Daogong; Fan, Zhaomin; Han, Yuechen; Wang, Mingming; Xu, Lei; Luo, Jianfen; Ai, Yu; Wang, Haibo

    2012-01-01

    To investigate the diagnostic value of vestibular test and high stimulus rate auditory brainstem response (ABR) test and the possible mechanism responsible for benign paroxysmal vertigo of childhood (BPVC). Data of 56 patients with BPVC in vertigo clinic of our hospital from May 2007 to September 2008 were retrospectively analyzed in this study. Patients with BPVC were tested with pure tone audiometry, high stimulus rate auditory brainstem response test (ABR), transcranial Doppler sonography (TCD), bithermal caloric test, and VEMP. The results of the hearing and vestibular function test were compared and analyzed. There were 56 patients with BPVC, including 32 men, 24 women, aged 3-12 years old, with an average of 6.5 years. Among 56 cases of BPVC patients, the results of pure tone audiometry were all normal. High stimulus rate ABR was abnormal in 66.1% (37/56) of cases. TCD showed 57.1% abnormality in 56 cases, including faster flow rate in 28 cases and slower flow rate in 4 cases. High stimulus rate ABR and TCD were both abnormal in 48.2% (27/56) of cases. Bithermal caloric test was abnormal in 14.3% (8/56) of cases. VEMP showed 32.1% abnormality, including amplitude abnormality in 16 cases and latency abnormality in 2 cases. The abnormal rate of VEMP was much higher than that of caloric test. Vascular mechanisms might be involved in the pathogenesis of BPVC and there is strong evidence for close relationship between BPVC and migraine. High stimulus rate ABR is helpful in the diagnosis of BPVC. The inferior vestibular pathway is much more impaired than the superior vestibular pathway in BPVC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. Methamphetamine-related brainstem haemorrhage.

    PubMed

    Chiu, Zelia K; Bennett, Iwan E; Chan, Patrick; Rosenfeld, Jeffrey V

    2016-10-01

    We report the case of an otherwise healthy 29-year-old woman who presented with a brainstem haemorrhage following intravenous methamphetamine use. Extensive investigation did not reveal an underlying pathology, and the development of symptoms was temporally related to methamphetamine injection. Although intracerebral haemorrhage secondary to methamphetamine use is well documented, this report describes a haemorrhage within the brainstem which is a rare location. While animal studies have demonstrated the potential of methamphetamines to produce brainstem haemorrhages, there has only been one previous report describing a haemorrhage in this location due to amphetamine use in humans. We conclude with a brief discussion of the clinical features and aetiology of methamphetamine-related stroke. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Brainstem death: A comprehensive review in Indian perspective

    PubMed Central

    Dhanwate, Anant Dattatray

    2014-01-01

    With the advent of cardiopulmonary resuscitation techniques, the cardiopulmonary definition of death lost its significance in favor of brain death. Brain death is a permanent cessation of all functions of the brain in which though individual organs may function but lack of integrating function of the brain, lack of respiratory drive, consciousness, and cognition confirms to the definition that death is an irreversible cessation of functioning of the organism as a whole. In spite of medical and legal acceptance globally, the concept of brain death and brain-stem death is still unclear to many. Brain death is not promptly declared due to lack of awareness and doubts about the legal procedure of certification. Many brain dead patients are kept on life supporting systems needlessly. In this comprehensive review, an attempt has been made to highlight the history and concept of brain death and brain-stem death; the anatomical and physiological basis of brain-stem death, and criteria to diagnose brain-stem death in India. PMID:25249744

  3. Evaluation of distribution of adenosine A2A receptors in normal human brain measured with [11C]TMSX PET.

    PubMed

    Mishina, Masahiro; Ishiwata, Kiichi; Kimura, Yuichi; Naganawa, Mika; Oda, Keiichi; Kobayashi, Shiro; Katayama, Yasuo; Ishii, Kenji

    2007-09-01

    Adenosine A(2A) receptor (A2AR) is thought to interact with dopamine D(2) receptor. Selective A2AR antagonists have attracted attention as the treatment of Parkinson's disease. In this study, we investigated the distribution of the A2ARs in the living human brain using positron emission tomography (PET) and [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX). We recruited five normal male subjects. A dynamic series of PET scans was performed for 60 min, and the arterial blood was sampled during the scan to measure radioactivity of the parent compound and labeled metabolites. Circular regions of interest of 10-mm diameter were placed in the PET images over the cerebellum, brainstem, thalamus, head of caudate nucleus, anterior and posterior putamen, frontal lobe, temporal lobe, parietal lobe, occipital lobe, and posterior cingulate gyrus for each subject. A two-tissue, three-compartment model was used to estimate K(1), k(2), k(3), and k(4) between metabolite-corrected plasma and tissue time activity of [(11)C]TMSX. The binding potential (BP) was the largest in the anterior (1.25) and posterior putamen (1.20), was next largest in the head of caudate nucleus (1.05) and thalamus (1.03), and was small in the cerebral cortex, especially frontal lobe (0.46). [(11)C]TMSX PET showed the largest BP in the striatum in which A2ARs were enriched as in postmortem and nonhuman studies reported, but that the binding of [(11)C]TMSX was relatively larger in the thalamus to compare with other mammals. To date, [(11)C]TMSX is the only promising PET ligand, which is available to clinical use for mapping the A2ARs in the living human brain.

  4. Neonatal brainstem dysfunction risks infant social engagement

    PubMed Central

    Sopher, Koreen; Kurtzman, Lea; Galili, Giora; Feldman, Ruth; Kuint, Jacob

    2013-01-01

    The role of the brainstem in mediating social signaling in phylogenetic ancestral organisms has been demonstrated. Evidence for its involvement in social engagement in human infants may deepen the understanding of the evolutionary pathway of humans as social beings. In this longitudinal study, neonatal brainstem functioning was measured by auditory brainstem-evoked responses (ABRs) in 125 healthy neonates born prematurely before 35 weeks’ gestational age. At 4 months, infants were tested in a set of structured vignettes that required varying levels of social engagement and cardiac vagal tone was assessed. Data show that neonates with a disrupted I–V waveform, evident mostly by delayed wave V, exhibit shorter latencies to gaze averts in episodes involving direct face-to-face interactions but engage gaze as controls when interacting with masked agents or with agents whose faces are partly veiled by toys. Analysis of variance of infants’ social engagement with ABR, neonatal risk, maternal stress and cardiac vagal tone showed a main effect for ABR and an ABR by gestational age interaction. The integrity of brainstem transmission of sensory information during the final weeks of gestation may scaffold the development of social disengagement, thereby attesting to the brainstem's preserved evolutionary role in developing humans as social organisms prior to engaging in social encounters. PMID:22146141

  5. Curcumin restores diabetes induced neurochemical changes in the brain stem of Wistar rats.

    PubMed

    Kumar, Peeyush T; George, Naijil; Antony, Sherin; Paulose, Cheramadathikudiyil Skaria

    2013-02-28

    Diabetes mellitus, when poorly controlled, leads to debilitating central nervous system (CNS) complications including cognitive deficits, somatosensory and motor dysfunction. The present study investigated curcumin's potential in modulating diabetes induced neurochemical changes in brainstem. Expression analysis of cholinergic, insulin receptor and GLUT-3 in the brainstem of streptozotocin (STZ) induced diabetic rats were studied. Radioreceptor binding assays, gene expression studies and immunohistochemical analysis were done in the brainstem of male Wistar rats. Our result showed that Bmax of total muscarinic and muscarinic M3 receptors were increased and muscarinic M1 receptor was decreased in diabetic rats compared to control. mRNA level of muscarinic M3, α7-nicotinic acetylcholine, insulin receptors, acetylcholine esterase, choline acetyltransferase and GLUT-3 significantly increased and M1 receptor decreased in the brainstem of diabetic rats. Curcumin and insulin treatment restored the alterations and maintained all parameters to near control. The results show that diabetes is associated with significant reduction in brainstem function coupled with altered cholinergic, insulin receptor and GLUT-3 gene expression. The present study indicates beneficial effect of curcumin in diabetic rats by regulating the cholinergic, insulin receptor and GLUT-3 in the brainstem similar to the responses obtained with insulin therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic, and motor systems by high spatial resolution 7-Tesla fMRI.

    PubMed

    Bianciardi, Marta; Toschi, Nicola; Eichner, Cornelius; Polimeni, Jonathan R; Setsompop, Kawin; Brown, Emery N; Hämäläinen, Matti S; Rosen, Bruce R; Wald, Lawrence L

    2016-06-01

    Our aim was to map the in vivo human functional connectivity of several brainstem nuclei with the rest of the brain by using seed-based correlation of ultra-high magnetic field functional magnetic resonance imaging (fMRI) data. We used the recently developed template of 11 brainstem nuclei derived from multi-contrast structural MRI at 7 Tesla as seed regions to determine their connectivity to the rest of the brain. To achieve this, we used the increased contrast-to-noise ratio of 7-Tesla fMRI compared with 3 Tesla and time-efficient simultaneous multi-slice imaging to cover the brain with high spatial resolution (1.1-mm isotropic nominal resolution) while maintaining a short repetition time (2.5 s). The delineated Pearson's correlation-based functional connectivity diagrams (connectomes) of 11 brainstem nuclei of the ascending arousal, motor, and autonomic systems from 12 controls are presented and discussed in the context of existing histology and animal work. Considering that the investigated brainstem nuclei play a crucial role in several vital functions, the delineated preliminary connectomes might prove useful for future in vivo research and clinical studies of human brainstem function and pathology, including disorders of consciousness, sleep disorders, autonomic disorders, Parkinson's disease, and other motor disorders.

  7. Gamma Knife Treatment of Brainstem Metastases

    PubMed Central

    Peterson, Halloran E.; Larson, Erik W.; Fairbanks, Robert K.; MacKay, Alexander R.; Lamoreaux, Wayne T.; Call, Jason A.; Carlson, Jonathan D.; Ling, Benjamin C.; Demakas, John J.; Cooke, Barton S.; Peressini, Ben; Lee, Christopher M.

    2014-01-01

    The management of brainstem metastases is challenging. Surgical treatment is usually not an option, and chemotherapy is of limited utility. Stereotactic radiosurgery has emerged as a promising palliative treatment modality in these cases. The goal of this study is to assess our single institution experience treating brainstem metastases with Gamma Knife radiosurgery (GKRS). This retrospective chart review studied 41 patients with brainstem metastases treated with GKRS. The most common primary tumors were lung, breast, renal cell carcinoma, and melanoma. Median age at initial treatment was 59 years. Nineteen (46%) of the patients received whole brain radiation therapy (WBRT) prior to or concurrent with GKRS treatment. Thirty (73%) of the patients had a single brainstem metastasis. The average GKRS dose was 17 Gy. Post-GKRS overall survival at six months was 42%, at 12 months was 22%, and at 24 months was 13%. Local tumor control was achieved in 91% of patients, and there was one patient who had a fatal brain hemorrhage after treatment. Karnofsky performance score (KPS) >80 and the absence of prior WBRT were predictors for improved survival on multivariate analysis (HR 0.60 (p = 0.02), and HR 0.28 (p = 0.02), respectively). GKRS was an effective treatment for brainstem metastases, with excellent local tumor control. PMID:24886816

  8. Individual differences in brainstem and basal ganglia structure predict postural control and balance loss in young and older adults.

    PubMed

    Boisgontier, Matthieu P; Cheval, Boris; Chalavi, Sima; van Ruitenbeek, Peter; Leunissen, Inge; Levin, Oron; Nieuwboer, Alice; Swinnen, Stephan P

    2017-02-01

    It remains unclear which specific brain regions are the most critical for human postural control and balance, and whether they mediate the effect of age. Here, associations between postural performance and corticosubcortical brain regions were examined in young and older adults using multiple structural imaging and linear mixed models. Results showed that of the regions involved in posture, the brainstem was the strongest predictor of postural control and balance: lower brainstem volume predicted larger center of pressure deviation and higher odds of balance loss. Analyses of white and gray matter in the brainstem showed that the pedunculopontine nucleus area appeared to be critical for postural control in both young and older adults. In addition, the brainstem mediated the effect of age on postural control, underscoring the brainstem's fundamental role in aging. Conversely, lower basal ganglia volume predicted better postural performance, suggesting an association between greater neural resources in the basal ganglia and greater movement vigor, resulting in exaggerated postural adjustments. Finally, results showed that practice, shorter height and heavier weight (i.e., higher body mass index), higher total physical activity, and larger ankle active (but not passive) range of motion were predictive of more stable posture, irrespective of age. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Dyslexia risk gene relates to representation of sound in the auditory brainstem.

    PubMed

    Neef, Nicole E; Müller, Bent; Liebig, Johanna; Schaadt, Gesa; Grigutsch, Maren; Gunter, Thomas C; Wilcke, Arndt; Kirsten, Holger; Skeide, Michael A; Kraft, Indra; Kraus, Nina; Emmrich, Frank; Brauer, Jens; Boltze, Johannes; Friederici, Angela D

    2017-04-01

    Dyslexia is a reading disorder with strong associations with KIAA0319 and DCDC2. Both genes play a functional role in spike time precision of neurons. Strikingly, poor readers show an imprecise encoding of fast transients of speech in the auditory brainstem. Whether dyslexia risk genes are related to the quality of sound encoding in the auditory brainstem remains to be investigated. Here, we quantified the response consistency of speech-evoked brainstem responses to the acoustically presented syllable [da] in 159 genotyped, literate and preliterate children. When controlling for age, sex, familial risk and intelligence, partial correlation analyses associated a higher dyslexia risk loading with KIAA0319 with noisier responses. In contrast, a higher risk loading with DCDC2 was associated with a trend towards more stable responses. These results suggest that unstable representation of sound, and thus, reduced neural discrimination ability of stop consonants, occurred in genotypes carrying a higher amount of KIAA0319 risk alleles. Current data provide the first evidence that the dyslexia-associated gene KIAA0319 can alter brainstem responses and impair phoneme processing in the auditory brainstem. This brain-gene relationship provides insight into the complex relationships between phenotype and genotype thereby improving the understanding of the dyslexia-inherent complex multifactorial condition. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Quantitative Comparison of Retrosigmoid Intradural Suprameatal Approach and Retrosigmoid Transtentorial Approach: Implications for Tumors in the Petroclival Region

    PubMed Central

    Ambekar, Sudheer; Amene, Chiazo; Sonig, Ashish; Guthikonda, Bharat; Nanda, Anil

    2013-01-01

    Background Retrosigmoid transtentorial (RTT) and retrosigmoid intradural suprameatal (RISA) approaches have been used in the treatment of petroclival tumors. Objective To compare the area of exposure of brainstem and petroclival region obtained through RTT and RISA in cadaveric specimens. Methods Five cadaveric specimens with a total of 10 sides were analyzed. RTT and RISA were performed on five sides each. Brainstem and petroclival surface exposure were measured using both the approaches. These values were compared between the two approaches. Results Brainstem area exposure with RTT was 441 ± 63 mm2 and that with RISA was 311 ± 61 mm2. Student's t-test revealed that the difference was significant (p = 0.01). The area of petroclival exposure medial to the Meckel cave through RTT was 696 ± 57 mm2, and that through RISA was 716 ± 51 mm2 (p = 0.69). The area of brainstem exposure between V and VII-VII complex through RTT and RISA was 387 ± 86 mm2 and 378 ± 76 mm2 (p = 0.87). Conclusion The RTT approach is an excellent approach to ventrolateral brainstem and petroclival region. It provides greater superoventral exposure of the ventrolateral brainstem than RISA and provides similar petroclival exposure. PMID:24436928

  11. Experimental Study of Liquid Jet Impingement in Microgravity: The Hydraulic Jump

    NASA Technical Reports Server (NTRS)

    Avedisian, C. T.; Zhao, Z.

    1996-01-01

    A preliminary study of the Circular Hydraulic Jump (CHJ) in microgravity is reported using water as the working fluid. The evolution of the CHJ radius was measured during a sudden transition from normal to microgravity in a drop tower. The downstream height of the CHJ was controlled by submerging the target plate in a tank filled with water to the desired depth, and the measurements are compared with an existing theory for the location of the CHJ. Results showed that the CHJ diameter was larger in microgravity than normal gravity. The adjustment of the CHJ diameter to a sudden change in gravity occurred over a period of about 200 ms for the conditions of the present study, and remained constant thereafter. For flow conditions that a CHJ was not first established at normal gravity but which later appeared during the transition to microgravity, the CHJ diameter was not constant during the period of microgravity but continually changed. Good agreement between the measured and predicted CHJ diameter was found for the normal gravity data, but comparatively poorer agreement was observed for the microgravity measurements.

  12. Progression of brain atrophy in PSP and CBS over 6 months and 1 year.

    PubMed

    Dutt, Shubir; Binney, Richard J; Heuer, Hilary W; Luong, Phi; Attygalle, Suneth; Bhatt, Priyanka; Marx, Gabe A; Elofson, Jonathan; Tartaglia, Maria C; Litvan, Irene; McGinnis, Scott M; Dickerson, Bradford C; Kornak, John; Waltzman, Dana; Voltarelli, Lisa; Schuff, Norbert; Rabinovici, Gil D; Kramer, Joel H; Jack, Clifford R; Miller, Bruce L; Rosen, Howard J; Boxer, Adam L

    2016-11-08

    To examine the utility and reliability of volumetric MRI in measuring disease progression in the 4 repeat tauopathies, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), to support clinical development of new tau-directed therapeutic agents. Six- and 12-month changes in regional MRI volumes and PSP Rating Scale scores were examined in 55 patients with PSP and 33 patients with CBS (78% amyloid PET negative) compared to 30 normal controls from a multicenter natural history study. Longitudinal voxel-based morphometric analyses identified patterns of volume loss, and region-of-interest analyses examined rates of volume loss in brainstem (midbrain, pons, superior cerebellar peduncle), cortical, and subcortical regions based on previously validated atlases. Results were compared to those in a replication cohort of 226 patients with PSP with MRI data from the AL-108-231 clinical trial. Patients with CBS exhibited greater baseline atrophy and greater longitudinal atrophy rates in cortical and basal ganglia regions than patients with PSP; however, midbrain and pontine atrophy rates were similar. Voxel-wise analyses showed distinct patterns of regional longitudinal atrophy in each group as compared to normal controls. The midbrain/pons volumetric ratio differed between diagnoses but remained stable over time. In both patient groups, brainstem atrophy rates were correlated with disease progression measured using the PSP Rating Scale. Volume loss is quantifiable over a period of 6 months in CBS and PSP. Future clinical trials may be able to combine CBS and PSP to measure therapeutic effects. © 2016 American Academy of Neurology.

  13. All in the blink of an eye: new insight into cerebellar and brainstem function in DYT1 and DYT6 dystonia.

    PubMed

    Sadnicka, A; Teo, J T; Kojovic, M; Pareés, I; Saifee, T A; Kassavetis, P; Schwingenschuh, P; Katschnig-Winter, P; Stamelou, M; Mencacci, N E; Rothwell, J C; Edwards, M J; Bhatia, K P

    2015-05-01

    Traditionally dystonia has been considered a disorder of basal ganglia dysfunction. However, recent research has advocated a more complex neuroanatomical network. In particular, there is increasing interest in the pathophysiological role of the cerebellum. Patients with cervical and focal hand dystonia have impaired cerebellar associative learning using the paradigm eyeblink conditioning. This is perhaps the most direct evidence to date that the cerebellum is implicated in patients. Eleven patients with DYT1 dystonia and five patients with DYT6 dystonia were examined and rates of eyeblink conditioning were compared with age-matched controls. A marker of brainstem excitability, the blink reflex recovery, was also studied in the same groups. Patients with DYT1 and DYT6 dystonia have a normal ability to acquire conditioned responses. Blink reflex recovery was enhanced in DYT1 but this effect was not seen in DYT6. If the cerebellum is an important driver in DYT1 and DYT6 dystonia our data suggest that there is specific cerebellar dysfunction such that the circuits essential for conditioning function normally. Our data are contrary to observations in focal dystonia and suggest that the cerebellum may have a distinct role in different subsets of dystonia. Evidence of enhanced blink reflex recovery in all patients with dystonia was not found and recent studies calling for the blink recovery reflex to be used as a diagnostic test for dystonic tremor may require further corroboration. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

  14. Forebrain Mechanisms of Nociception and Pain: Analysis through Imaging

    NASA Astrophysics Data System (ADS)

    Casey, Kenneth L.

    1999-07-01

    Pain is a unified experience composed of interacting discriminative, affective-motivational, and cognitive components, each of which is mediated and modulated through forebrain mechanisms acting at spinal, brainstem, and cerebral levels. The size of the human forebrain in relation to the spinal cord gives anatomical emphasis to forebrain control over nociceptive processing. Human forebrain pathology can cause pain without the activation of nociceptors. Functional imaging of the normal human brain with positron emission tomography (PET) shows synaptically induced increases in regional cerebral blood flow (rCBF) in several regions specifically during pain. We have examined the variables of gender, type of noxious stimulus, and the origin of nociceptive input as potential determinants of the pattern and intensity of rCBF responses. The structures most consistently activated across genders and during contact heat pain, cold pain, cutaneous laser pain or intramuscular pain were the contralateral insula and anterior cingulate cortex, the bilateral thalamus and premotor cortex, and the cerebellar vermis. These regions are commonly activated in PET studies of pain conducted by other investigators, and the intensity of the brain rCBF response correlates parametrically with perceived pain intensity. To complement the human studies, we developed an animal model for investigating stimulus-induced rCBF responses in the rat. In accord with behavioral measures and the results of human PET, there is a progressive and selective activation of somatosensory and limbic system structures in the brain and brainstem following the subcutaneous injection of formalin. The animal model and human PET studies should be mutually reinforcing and thus facilitate progress in understanding forebrain mechanisms of normal and pathological pain.

  15. Possible structural abnormality of the brainstem in unipolar depressive illness: a transcranial ultrasound and diffusion tensor magnetic resonance imaging study.

    PubMed

    Steele, J D; Bastin, M E; Wardlaw, J M; Ebmeier, K P

    2005-11-01

    Most empirically derived antidepressants increase monoamine levels. The nuclei of cells synthesising these monoamines are located in the brainstem, and projection tracts such as the medial forebrain bundle reach virtually all other brain areas. Two studies of unipolar depressive illness using transcranial ultrasound have reported reduced echogenicity of the brainstem midline in unipolar depressed patients. This may be consistent with disruption of white matter tracts, including the medial forebrain bundle, and it has been suggested that the effect of such disruption could be reversed by antidepressants. To replicate these findings in a group of unipolar depressed patients and controls. Fifteen unipolar depressed patients and 15 controls were studied using transcranial ultrasound imaging and diffusion tensor magnetic resonance imaging (DT-MRI). No difference in echogenicity of the brainstem midline of unipolar depressed patients was found. A possible trend (Cohen's d = 0.39) in the direction of previous studies was found. Although the echogenicity of the brainstem midline of the control group was found to be similar to previous reports, there was no reduction in the patient group. Additionally, no structural abnormality of the brainstem was identified using DT-MRI. While these data do not replicate the findings of previous studies reporting a significant reduction in the echogenicity of the brainstem midline in unipolar depressed patients, the ultrasound investigation indicated that there may be a trend in this direction. Given the importance of identifying the causes of depressive illness, it is important that other groups attempt similar studies.

  16. DTI fiber tracking to differentiate demyelinating diseases from diffuse brain stem glioma.

    PubMed

    Giussani, Carlo; Poliakov, Andrew; Ferri, Raymond T; Plawner, Lauren L; Browd, Samuel R; Shaw, Dennis W W; Filardi, Tanya Z; Hoeppner, Corrine; Geyer, J Russell; Olson, James M; Douglas, James G; Villavicencio, Elisabeth H; Ellenbogen, Richard G; Ojemann, Jeffrey G

    2010-08-01

    Intrinsic diffuse brainstem tumors and demyelinating diseases primarily affecting the brainstem can share common clinical and radiological features, sometimes making the diagnosis difficult especially at the time of first clinical presentation. To explore the potential usefulness of new MRI sequences in particular diffusion tensor imaging fiber tracking in differentiating these two pathological entities, we review a series of brainstem tumors and demyelinating diseases treated at our institution. The clinical history including signs and symptoms and MRI findings of three consecutive demyelinating diseases involving the brainstem that presented with diagnostic uncertainty and three diffuse intrinsic brainstem tumors were reviewed, along with a child with a supratentorial tumor for comparison. Fiber tracking of the pyramidal tracts was performed for each patient using a DTI study at the time of presentation. Additionally Fractional Anisotropy values were calculated for each patient in the pons and the medulla oblongata. Routine MR imaging was unhelpful in differentiating between intrinsic tumor and demyelination. In contrast, retrospective DTI fiber tracking clearly differentiated the pathology showing deflection of the pyramidal tracts posteriorly and laterally in the case of intrinsic brainstem tumors and, in the case of demyelinating disease, poorly represented and truncated fibers. Regionalized FA values were variable and of themselves were not predictive either pathology. DTI fiber tracking of the pyramid tracts in patients with suspected intrinsic brainstem tumor or demyelinating disease presents two clearly different patterns that may help in differentiating between these two pathologies when conventional MRI and clinical data are inconclusive. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Relationship between brainstem, cortical and behavioral measures relevant to pitch salience in humans.

    PubMed

    Krishnan, Ananthanarayan; Bidelman, Gavin M; Smalt, Christopher J; Ananthakrishnan, Saradha; Gandour, Jackson T

    2012-10-01

    Neural representation of pitch-relevant information at both the brainstem and cortical levels of processing is influenced by language or music experience. However, the functional roles of brainstem and cortical neural mechanisms in the hierarchical network for language processing, and how they drive and maintain experience-dependent reorganization are not known. In an effort to evaluate the possible interplay between these two levels of pitch processing, we introduce a novel electrophysiological approach to evaluate pitch-relevant neural activity at the brainstem and auditory cortex concurrently. Brainstem frequency-following responses and cortical pitch responses were recorded from participants in response to iterated rippled noise stimuli that varied in stimulus periodicity (pitch salience). A control condition using iterated rippled noise devoid of pitch was employed to ensure pitch specificity of the cortical pitch response. Neural data were compared with behavioral pitch discrimination thresholds. Results showed that magnitudes of neural responses increase systematically and that behavioral pitch discrimination improves with increasing stimulus periodicity, indicating more robust encoding for salient pitch. Absence of cortical pitch response in the control condition confirms that the cortical pitch response is specific to pitch. Behavioral pitch discrimination was better predicted by brainstem and cortical responses together as compared to each separately. The close correspondence between neural and behavioral data suggest that neural correlates of pitch salience that emerge in early, preattentive stages of processing in the brainstem may drive and maintain with high fidelity the early cortical representations of pitch. These neural representations together contain adequate information for the development of perceptual pitch salience. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. The vestibular evoked myogenic potentials (VEMP) score: a promising tool for evaluation of brainstem involvement in multiple sclerosis.

    PubMed

    Gabelić, T; Krbot Skorić, M; Adamec, I; Barun, B; Zadro, I; Habek, M

    2015-02-01

    Concerning the great importance of brainstem involvement in multiple sclerosis (MS), the aim of this study was to explore the role of the newly developed vestibular evoked myogenic potentials (VEMP) score as a possible marker of brainstem involvement in MS patients. This was a prospective case-control study which included 100 MS patients divided into two groups (without and with clinical signs of brainstem involvement) and 50 healthy controls. Ocular VEMP (oVEMP) and cervical VEMP (cVEMP) measurements were performed in all participants and analyzed for latencies, conduction block and amplitude asymmetry ratio. Based on this the VEMP score was calculated and compared with Expanded Disability Status Scale (EDSS), disease duration and magnetic resonance imaging data. Multiple sclerosis patients with clinical signs of brainstem involvement (group 2) had a statistically significant higher percentage of VEMP conduction blocks compared with patients without clinical signs of brainstem involvement (group 1) and healthy controls (P = 0.027 and P < 0.0001, respectively). Similarly, the VEMP score was significantly higher in group 2 compared with group 1 (P = 0.018) and correlated with EDSS and disease duration (P = 0.011 and P = 0.032, respectively). Multivariate linear regression analysis showed that the VEMP score has a statistically significant influence on the EDSS score (P < 0.001, R(2) = 0.239). Interpretation of the oVEMP and cVEMP results in the form of the VEMP score enables better evaluation of brainstem involvement than either of these evoked potentials alone and correlates well with disability. © 2014 EAN.

  19. Cerebral and brainstem electrophysiologic activity during euthanasia with pentobarbital sodium in horses.

    PubMed

    Aleman, M; Williams, D C; Guedes, A; Madigan, J E

    2015-01-01

    An overdose of pentobarbital sodium administered i.v. is the most commonly used method of euthanasia in veterinary medicine. Determining death after the infusion relies on the observation of physical variables. However, it is unknown when cortical electrical activity and brainstem function are lost in a sequence of events before death. To examine changes in the electrical activity of the cerebral cortex and brainstem during an overdose of pentobarbital sodium solution for euthanasia. Our testing hypothesis is that isoelectric pattern of the brain in support of brain death occurs before absence of electrocardiogram (ECG) activity. Fifteen horses requiring euthanasia. Prospective observational study. Horses with neurologic, orthopedic, and cardiac illnesses were selected and instrumented for recording of electroencephalogram, electrooculogram, brainstem auditory evoked response (BAER), and ECG. Physical and neurologic (brainstem reflexes) variables were monitored. Loss of cortical electrical activity occurred during or within 52 seconds after the infusion of euthanasia solution. Cessation of brainstem function as evidenced by a lack of brainstem reflexes and disappearance of the BAER happened subsequently. Despite undetectable heart sounds, palpable arterial pulse, and mean arterial pressure, recordable ECG was the last variable to be lost after the infusion (5.5-16 minutes after end of the infusion). Overdose of pentobarbital sodium solution administered i.v. is an effective, fast, and humane method of euthanasia. Brain death occurs within 73-261 seconds of the infusion. Although absence of ECG activity takes longer to occur, brain death has already occurred. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  20. Convection enhanced delivery of carmustine to the murine brainstem: a feasibility study.

    PubMed

    Sewing, A Charlotte P; Caretti, Viola; Lagerweij, Tonny; Schellen, Pepijn; Jansen, Marc H A; van Vuurden, Dannis G; Idema, Sander; Molthoff, Carla F M; Vandertop, W Peter; Kaspers, Gertjan J L; Noske, David P; Hulleman, Esther

    2014-12-30

    Systemic delivery of therapeutic agents remains ineffective against diffuse intrinsic pontine glioma (DIPG), possibly due to an intact blood-brain-barrier (BBB) and to dose-limiting toxicity of systemic chemotherapeutic agents. Convection-enhanced delivery (CED) into the brainstem may provide an effective local delivery alternative for DIPG patients. The aim of this study is to develop a method to perform CED into the murine brainstem and to test this method using the chemotherapeutic agent carmustine (BiCNU). To this end, a newly designed murine CED catheter was tested in vitro and in vivo. After determination of safety and distribution, mice bearing VUMC-DIPG-3 and E98FM-DIPG brainstem tumors were treated with carmustine dissolved in DW 5% or carmustine dissolved in 10% ethanol. Our results show that CED into the murine brainstem is feasible and well tolerated by mice with and without brainstem tumors. CED of carmustine dissolved in 5% DW increased median survival of mice with VUMC-DIPG-3 and E98FM-DIPG tumors with 35% and 25% respectively. Dissolving carmustine in 10% ethanol further improved survival to 45% in mice with E98FM-DIPG tumors. Since genetically engineered and primary DIPG models are currently only available in mice, murine CED studies have clear advantages over CED studies in other animals. CED in the murine brainstem can be performed safely, is well tolerated and can be used to study efficacy of chemotherapeutic agents orthotopically. These results set the foundation for more CED studies in murine DIPG models. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Preclinical Biosafety Evaluation of Genetically Modified Human Adipose Tissue-Derived Mesenchymal Stem Cells for Clinical Applications to Brainstem Glioma.

    PubMed

    Choi, Seung Ah; Yun, Jun-Won; Joo, Kyeung Min; Lee, Ji Yeoun; Kwak, Pil Ae; Lee, Young Eun; You, Ji-Ran; Kwon, Euna; Kim, Woo Ho; Wang, Kyu-Chang; Phi, Ji Hoon; Kang, Byeong-Cheol; Kim, Seung-Ki

    2016-06-15

    Stem-cell based gene therapy is a promising novel therapeutic approach for inoperable invasive tumors, including brainstem glioma. Previously, we demonstrated the therapeutic potential of human adipose tissue-derived mesenchymal stem cells (hAT-MSC) genetically engineered to express a secreted form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) against brainstem glioma. However, safety concerns should be comprehensively investigated before clinical applications of hAT-MSC.sTRAIL. At first, we injected stereotactically low (1.2 × 10(5) cells/18 μL), medium (2.4 × 10(5)/18 μL), or high dose (3.6 × 10(5)/18 μL) of hAT-MSC.sTRAIL into the brainstems of immunodeficient mice reflecting the plan of the future clinical trial. Local toxicity, systemic toxicity, secondary tumor formation, and biodistribution of hAT-MSC.sTRAIL were investigated. Next, presence of hAT-MSC.sTRAIL was confirmed in the brain and major organs at 4, 9, and 14 weeks in brainstem glioma-bearing mice. In the 15-week subchronic toxicity test, no serious adverse events in terms of body weight, food consumption, clinical symptom, urinalysis, hematology, clinical chemistry, organ weight, and histopathology were observed. In the 26-week tumorigenicity test, hAT-MSC.sTRAIL made no detectable tumors, whereas positive control U-87 MG cells made huge tumors in the brainstem. No remaining hAT-MSC.sTRAIL was observed in any organs examined, including the brainstem at 15 or 26 weeks. In brainstem glioma-bearing mice, injected hAT-MSC.sTRAIL was observed, but gradually decreased over time in the brain. The mRNA of human specific GAPDH and TRAIL was not detected in all major organs. These results indicate that the hAT-MSC.sTRAIL could be applicable to the future clinical trials in terms of biosafety.

  2. The Auditory-Brainstem Response to Continuous, Non-repetitive Speech Is Modulated by the Speech Envelope and Reflects Speech Processing

    PubMed Central

    Reichenbach, Chagit S.; Braiman, Chananel; Schiff, Nicholas D.; Hudspeth, A. J.; Reichenbach, Tobias

    2016-01-01

    The auditory-brainstem response (ABR) to short and simple acoustical signals is an important clinical tool used to diagnose the integrity of the brainstem. The ABR is also employed to investigate the auditory brainstem in a multitude of tasks related to hearing, such as processing speech or selectively focusing on one speaker in a noisy environment. Such research measures the response of the brainstem to short speech signals such as vowels or words. Because the voltage signal of the ABR has a tiny amplitude, several hundred to a thousand repetitions of the acoustic signal are needed to obtain a reliable response. The large number of repetitions poses a challenge to assessing cognitive functions due to neural adaptation. Here we show that continuous, non-repetitive speech, lasting several minutes, may be employed to measure the ABR. Because the speech is not repeated during the experiment, the precise temporal form of the ABR cannot be determined. We show, however, that important structural features of the ABR can nevertheless be inferred. In particular, the brainstem responds at the fundamental frequency of the speech signal, and this response is modulated by the envelope of the voiced parts of speech. We accordingly introduce a novel measure that assesses the ABR as modulated by the speech envelope, at the fundamental frequency of speech and at the characteristic latency of the response. This measure has a high signal-to-noise ratio and can hence be employed effectively to measure the ABR to continuous speech. We use this novel measure to show that the ABR is weaker to intelligible speech than to unintelligible, time-reversed speech. The methods presented here can be employed for further research on speech processing in the auditory brainstem and can lead to the development of future clinical diagnosis of brainstem function. PMID:27303286

  3. Brain volume and fatigue in patients with postpoliomyelitis syndrome.

    PubMed

    Trojan, Daria A; Narayanan, Sridar; Francis, Simon J; Caramanos, Zografos; Robinson, Ann; Cardoso, Mauro; Arnold, Douglas L

    2014-03-01

    Acute paralytic poliomyelitis is associated with encephalitis. Early brain inflammation may produce permanent neuronal injury with brain atrophy, which may result in symptoms such as fatigue. Brain volume has not been assessed in postpoliomyelitis syndrome (PPS). To determine whether brain volume is decreased compared with that in normal controls, and whether brain volume is associated with fatigue in patients with PPS. A cross-sectional study. Tertiary university-affiliated hospital postpolio and multiple sclerosis (MS) clinics. Forty-nine ambulatory patients with PPS, 28 normal controls, and 53 ambulatory patients with MS. We studied the brains of all study subjects with magnetic resonance imaging by using a 1.5 T Siemens Sonata machine. The subjects completed the Fatigue Severity Scale. Multivariable linear regression models were computed to evaluate the contribution of PPS and MS compared with controls to explain brain volume. Normalized brain volume (NBV) was assessed with the automated program Structured Image Evaluation, using Normalization, of Atrophy method from the acquired magnetic resonance images. This method may miss brainstem atrophy. Technically adequate NBV measurements were available for 42 patients with PPS, 27 controls, and 49 patients with MS. The mean (standard deviation) age was 60.9 ± 7.6 years for patients with PPS, 47.0 ± 14.6 years for controls, and 46.2 ± 9.4 years for patients with MS. In a multivariable model adjusted for age and gender, NBV was not significantly different in patients with PPS compared with that in controls (P = .28). As expected, when using a similar model for patients with MS, NBV was significantly decreased compared with that in controls (P = .006). There was no significant association between NBV and fatigue in subjects with PPS (Spearman ρ = 0.23; P = .19). No significant whole-brain atrophy was found, and no association of brain volume with fatigue in PPS. Brain atrophy was confirmed in MS. It is possible that brainstem atrophy was not recognized by this study. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  4. Conjunct SEP and MEP monitoring in resection of infratentorial lesions: lessons learned in a cohort of 210 patients.

    PubMed

    Kodama, Kunihiko; Javadi, Mani; Seifert, Volker; Szelényi, Andrea

    2014-12-01

    During the surgical removal of infratentorial lesions, intraoperative neuromonitoring is mostly focused on cranial nerve assessment and brainstem auditory potentials. Despite the known risk of perforating vessel injury during microdissection within the vicinity of the brainstem, there are few reports about intraoperative neuromonitoring with somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) assessing the medial lemniscus and corticospinal tract. This study analyses the occurrence of intraoperative changes in MEPs and SEPs with regard to lesion location and postoperative neurological outcome. The authors analyzed 210 cases in which patients (mean age 49 ± 13 years, 109 female) underwent surgeries involving the skull base (n = 104), cerebellum (n = 63), fourth ventricle (n = 28), brainstem (n = 12), and foramen magnum (n = 3). Of 210 surgeries, 171 (81.4%) were uneventful with respect to long-tract monitoring. Nine (23%) of the 39 SEP and/or MEP alterations were transient and were only followed by a slight permanent deficit in 1 case. Permanent deterioration only was seen in 19 (49%) of 39 cases; the deterioration was related to tumor dissection in 4 of these cases, and permanent deficit (moderate-severe) was seen in only 1 of these 4 cases. Eleven patients (28%) had losses of at least 1 modality, and in 9 of these 11 cases, the loss was related to surgical microdissection within the vicinity of the brainstem. Four of these 9 patients suffered a moderate-to-severe long-term deficit. For permanent changes, the positive predictive value for neuromonitoring of the long tracts was 0.467, the negative predictive value was 0.989, the sensitivity was 0.875, and the specificity 0.918. Twenty-eight (72%) of 39 SEP and MEP alterations occurred in 66 cases involving intrinsic brainstem tumors or tumors adjacent to the brainstem. Lesion location and alterations in intraoperative neuromonitoring significantly correlated with patients' outcome (p < 0.001, chi-square test). In summary, long-tract monitoring with SEPs and MEPs in infratentorial surgeries has a high sensitivity and negative predictive value with respect to postoperative neurological status. It is recommended especially in those surgeries in which microdissection within and in the vicinity of the brainstem might lead to injury of the brainstem parenchyma or perforating vessels and a subsequent perfusion deficit within the brainstem.

  5. Our first decade of experience in deep brain stimulation of the brainstem: elucidating the mechanism of action of stimulation of the ventrolateral pontine tegmentum.

    PubMed

    Mazzone, Paolo; Vilela Filho, Osvaldo; Viselli, Fabio; Insola, Angelo; Sposato, Stefano; Vitale, Flora; Scarnati, Eugenio

    2016-07-01

    The region of the pedunculopontine tegmental nucleus (PPTg) has been proposed as a novel target for deep brain stimulation (DBS) to treat levodopa resistant symptoms in motor disorders. Recently, the anatomical organization of the brainstem has been revised and four new distinct structures have been represented in the ventrolateral pontine tegmentum area in which the PPTg was previously identified. Given this anatomical reassessment, and considering the increasing of our experience, in this paper we revisit the value of DBS applied to that area. The reappraisal of clinical outcomes in the light of this revisitation may also help to understand the consequences of DBS applied to structures located in the ventrolateral pontine tegmentum, apart from the PPTg. The implantation of 39 leads in 32 patients suffering from Parkinson's disease (PD, 27 patients) and progressive supranuclear palsy (PSP, four patients) allowed us to reach two major conclusions. The first is that the results of the advancement of our technique in brainstem DBS matches the revision of brainstem anatomy. The second is that anatomical and functional aspects of our findings may help to explain how DBS acts when applied in the brainstem and to identify the differences when it is applied either in the brainstem or in the subthalamic nucleus. Finally, in this paper we discuss how the loss of neurons in brainstem nuclei occurring in both PD and PSP, the results of intraoperative recording of somatosensory evoked potentials, and the improvement of postural control during DBS point toward the potential role of ascending sensory pathways and/or other structures in mediating the effects of DBS applied in the ventrolateral pontine tegmentum region.

  6. Mapping of enkephalins and adrenocorticotropic hormone in the squirrel monkey brainstem.

    PubMed

    Duque-Díaz, Ewing; Díaz-Cabiale, Zaida; Narváez, José Angel; Coveñas, Rafael

    2017-03-01

    An immunocytochemical technique has been used to study for the first time the distribution of fibers and cell bodies containing leucine-enkephalin (leu-enk), methionine-enkephalin (met-enk) or adrenocorticotropic hormone (ACTH) in the whole brainstem of the squirrel monkey Saimiri sciureus. Cell bodies containing leu-enk or met-enk were found in the superior colliculus and the formatio reticularis tegmenti mesencephali, respectively. No immunoreactive cell bodies containing ACTH were observed. Leu-enk-immunoreactive fibers were observed in 40 brainstem nuclei/tracts/regions, fibers containing met-enk were found in 38 brainstem nuclei/tracts/regions and fibers containing ACTH were found in 26 nuclei/tracts/regions. In the latter case, the density of immunoreactive fibers was always low. A high/moderate density of leu-enk- or met-enk-immunoreactive fibers were found in 18 and 16 brainstem nuclei/tracts/regions, respectively. The distribution of immunoreactive fibers containing leu-enk or met-enk was quite similar, with both leu-enk and met-enk observed in 82.5 % of the squirrel monkey brainstem nuclei/tracts/regions. This relationship is less marked for met-enk and ACTH (60.5 %) and even lower for leu-enk and ACTH (52.5 %). In 42.5 % of the nuclei/tracts/regions of the squirrel monkey brainstem (colliculus superior, substantia grisea centralis, nucleus interpeduncularis, nucleus tractus spinalis nervi trigemini, nucleus tractus solitarii, nucleus parabrachialis, formatio reticularis, substantia nigra), we observed fibers containing all three neuropeptides. The widespread distribution reported here suggests that enkephalins and ACTH can be involved in several physiological functions. The distribution of the immunoreactive fibers reported here is quite similar to that previously reported for enkephalins and ACTH in Macaca species and humans.

  7. Systematic Morphometry of Catecholamine Nuclei in the Brainstem.

    PubMed

    Bucci, Domenico; Busceti, Carla L; Calierno, Maria T; Di Pietro, Paola; Madonna, Michele; Biagioni, Francesca; Ryskalin, Larisa; Limanaqi, Fiona; Nicoletti, Ferdinando; Fornai, Francesco

    2017-01-01

    Catecholamine nuclei within the brainstem reticular formation (RF) play a pivotal role in a variety of brain functions. However, a systematic characterization of these nuclei in the very same experimental conditions is missing so far. Tyrosine hydroxylase (TH) immune-positive cells of the brainstem correspond to dopamine (DA)-, norepinephrine (NE)-, and epinephrine (E)-containing cells. Here, we report a systematic count of TH-positive neurons in the RF of the mouse brainstem by using stereological morphometry. All these nuclei were analyzed for anatomical localization, rostro-caudal extension, volume, neuron number, neuron density, and mean neuronal area for each nucleus. The present data apart from inherent informative value wish to represent a reference for neuronal mapping in those studies investigating the functional anatomy of the brainstem RF. These include: the sleep-wake cycle, movement control, muscle tone modulation, mood control, novelty orienting stimuli, attention, archaic responses to internal and external stressful stimuli, anxiety, breathing, blood pressure, and innumerable activities modulated by the archaic iso-dendritic hard core of the brainstem RF. Most TH-immune-positive cells fill the lateral part of the RF, which indeed possesses a high catecholamine content. A few nuclei are medial, although conventional nosography considers all these nuclei as part of the lateral column of the RF. Despite the key role of these nuclei in psychiatric and neurological disorders, only a few of them aspired a great attention in biomedical investigation, while most of them remain largely obscure although intense research is currently in progress. A simultaneous description of all these nuclei is not simply key to comprehend the variety of brainstem catecholamine reticular neurons, but probably represents an intrinsically key base for understanding brain physiology and physiopathology.

  8. Systematic Morphometry of Catecholamine Nuclei in the Brainstem

    PubMed Central

    Bucci, Domenico; Busceti, Carla L.; Calierno, Maria T.; Di Pietro, Paola; Madonna, Michele; Biagioni, Francesca; Ryskalin, Larisa; Limanaqi, Fiona; Nicoletti, Ferdinando; Fornai, Francesco

    2017-01-01

    Catecholamine nuclei within the brainstem reticular formation (RF) play a pivotal role in a variety of brain functions. However, a systematic characterization of these nuclei in the very same experimental conditions is missing so far. Tyrosine hydroxylase (TH) immune-positive cells of the brainstem correspond to dopamine (DA)-, norepinephrine (NE)-, and epinephrine (E)-containing cells. Here, we report a systematic count of TH-positive neurons in the RF of the mouse brainstem by using stereological morphometry. All these nuclei were analyzed for anatomical localization, rostro-caudal extension, volume, neuron number, neuron density, and mean neuronal area for each nucleus. The present data apart from inherent informative value wish to represent a reference for neuronal mapping in those studies investigating the functional anatomy of the brainstem RF. These include: the sleep-wake cycle, movement control, muscle tone modulation, mood control, novelty orienting stimuli, attention, archaic responses to internal and external stressful stimuli, anxiety, breathing, blood pressure, and innumerable activities modulated by the archaic iso-dendritic hard core of the brainstem RF. Most TH-immune-positive cells fill the lateral part of the RF, which indeed possesses a high catecholamine content. A few nuclei are medial, although conventional nosography considers all these nuclei as part of the lateral column of the RF. Despite the key role of these nuclei in psychiatric and neurological disorders, only a few of them aspired a great attention in biomedical investigation, while most of them remain largely obscure although intense research is currently in progress. A simultaneous description of all these nuclei is not simply key to comprehend the variety of brainstem catecholamine reticular neurons, but probably represents an intrinsically key base for understanding brain physiology and physiopathology. PMID:29163071

  9. Tracing the neural basis of auditory entrainment.

    PubMed

    Lehmann, Alexandre; Arias, Diana Jimena; Schönwiesner, Marc

    2016-11-19

    Neurons in the auditory cortex synchronize their responses to temporal regularities in sound input. This coupling or "entrainment" is thought to facilitate beat extraction and rhythm perception in temporally structured sounds, such as music. As a consequence of such entrainment, the auditory cortex responds to an omitted (silent) sound in a regular sequence. Although previous studies suggest that the auditory brainstem frequency-following response (FFR) exhibits some of the beat-related effects found in the cortex, it is unknown whether omissions of sounds evoke a brainstem response. We simultaneously recorded cortical and brainstem responses to isochronous and irregular sequences of consonant-vowel syllable /da/ that contained sporadic omissions. The auditory cortex responded strongly to omissions, but we found no evidence of evoked responses to omitted stimuli from the auditory brainstem. However, auditory brainstem responses in the isochronous sound sequence were more consistent across trials than in the irregular sequence. These results indicate that the auditory brainstem faithfully encodes short-term acoustic properties of a stimulus and is sensitive to sequence regularity, but does not entrain to isochronous sequences sufficiently to generate overt omission responses, even for sequences that evoke such responses in the cortex. These findings add to our understanding of the processing of sound regularities, which is an important aspect of human cognitive abilities like rhythm, music and speech perception. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Exploring brainstem function in multiple sclerosis by combining brainstem reflexes, evoked potentials, clinical and MRI investigations.

    PubMed

    Magnano, Immacolata; Pes, Giovanni Mario; Pilurzi, Giovanna; Cabboi, Maria Paola; Ginatempo, Francesca; Giaconi, Elena; Tolu, Eusebio; Achene, Antonio; Salis, Antonio; Rothwell, John C; Conti, Maurizio; Deriu, Franca

    2014-11-01

    To investigate vestibulo-masseteric (VMR), acoustic-masseteric (AMR), vestibulo-collic (VCR) and trigemino-collic (TCR) reflexes in patients with multiple sclerosis (MS); to relate abnormalities of brainstem reflexes (BSRs) to multimodal evoked potentials (EPs), clinical and Magnetic Resonance Imaging (MRI) findings. Click-evoked VMR, AMR and VCR were recorded from active masseter and sternocleidomastoid muscles, respectively; TCR was recorded from active sternocleidomastoid muscles, following electrical stimulation of the infraorbital nerve. EPs and MRI were performed with standard techniques. Frequencies of abnormal BSRs were: VMR 62.1%, AMR 55.1%, VCR 25.9%, TCR 58.6%. Brainstem dysfunction was identified by these tests, combined into a four-reflex battery, in 86.9% of cases, by EPs in 82.7%, MRI in 71.7% and clinical examination in 37.7% of cases. The sensitivity of paired BSRs/EPs (93.3%) was significantly higher than combined MRI/clinical testing (70%) in patients with disease duration ⩽6.4years. BSR alterations significantly correlated with clinical, EP and MRI findings. The four-BSR battery effectively increases the performance of standard EPs in early detection of brainstem impairment, otherwise undetected by clinical examination and neuroimaging. Multiple BSR assessment usefully supplements conventional testing and monitoring of brainstem function in MS, especially in newly diagnosed patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  11. Enterovirus 71 can directly infect the brainstem via cranial nerves and infection can be ameliorated by passive immunization.

    PubMed

    Tan, Soon Hao; Ong, Kien Chai; Wong, Kum Thong

    2014-11-01

    Enterovirus 71 (EV71)-associated hand, foot, and mouth disease may be complicated by encephalomyelitis. We investigated EV71 brainstem infection and whether this infection could be ameliorated by passive immunization in a mouse model. Enterovirus 71 was injected into unilateral jaw/facial muscles of 2-week-old mice, and hyperimmune sera were given before or after infection. Harvested tissues were studied by light microscopy, immunohistochemistry, in situ hybridization, and viral titration. In unimmunized mice, viral antigen and RNA were detected within 24 hours after infection only in ipsilateral cranial nerves, motor trigeminal nucleus, reticular formation, and facial nucleus; viral titers were significantly higher in the brainstem than in the spinal cord samples. Mice given preinfection hyperimmune serum showed a marked reduction of ipsilateral viral antigen/RNA and viral titers in the brainstem in a dose-dependent manner. With optimum hyperimmune serum given after infection, brainstem infection was significantly reduced in a time-dependent manner. A delay in disease onset and a reduction of disease severity and mortality were also observed. Thus, EV71 can directly infect the brainstem, including the medulla, via cranial nerves, most likely by retrograde axonal transport. This may explain the sudden cardiorespiratory collapse in human patients with fatal encephalomyelitis. Moreover, our results suggest that passive immunization may still benefit EV71-infected patients who have neurologic complications.

  12. Expression of cholinergic, insulin, vitamin D receptors and GLUT 3 in the brainstem of streptozotocin induced diabetic rats: effect of treatment with vitamin D₃.

    PubMed

    Peeyush Kumar, T; Paul, Jes; Antony, Sherin; Paulose, C S

    2011-11-01

    Complications arising from diabetes mellitus include cognitive deficits, neurophysiological and structural changes in the brain. The current study investigated the expression of cholinergic, insulin, Vitamin D receptor and GLUT 3 in the brainstem of streptozotocin-induced diabetic rats. Radioreceptor binding assays and gene expression were done in the brainstem of male Wistar rats. Our results showed that B(max) of total muscarinic, muscarinic M3 receptors was increased and muscarinic M1 receptor was decreased in diabetic rats compared to control. A significant increase in gene expression of muscarinic M3, α7 nicotinic acetylcholine, insulin, Vitamin D₃ receptors, acetylcholine esterase, choline acetyl transferase and GLUT 3 were observed in the brainstem of diabetic rats. Immunohistochemistry studies of muscarinic M1, M3 and α7 nicotinic acetylcholine receptors confirmed the gene expression at protein level. Vitamin D₃ and insulin treatment reversed diabetes-induced alterations to near control. This study provides an evidence that diabetes can alter the expression of cholinergic, insulin, Vitamin D receptors and GLUT 3 in brainstem. We found that Vitamin D₃ treatment could modulate the Vitamin D receptors and plays a pivotal role in maintaining the glucose transport and expressional level of cholinergic receptors in the brainstem of diabetic rats. Thus, our results suggest a therapeutic role of Vitamin D₃ in managing neurological disorders associated with diabetes.

  13. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Trifiletti, Daniel M., E-mail: daniel.trifiletti@gmail.com; Lee, Cheng-Chia; Kano, Hideyuki

    Purpose: To pool data across multiple institutions internationally and report on the cumulative experience of brainstem stereotactic radiosurgery (SRS). Methods and Materials: Data on patients with brainstem metastases treated with SRS were collected through the International Gamma Knife Research Foundation. Clinical, radiographic, and dosimetric characteristics were compared for factors prognostic for local control (LC) and overall survival (OS) using univariate and multivariate analyses. Results: Of 547 patients with 596 brainstem metastases treated with SRS, treatment of 7.4% of tumors resulted in severe SRS-induced toxicity (grade ≥3, increased odds with increasing tumor volume, margin dose, and whole-brain irradiation). Local control at 12 monthsmore » after SRS was 81.8% and was improved with increasing margin dose and maximum dose. Overall survival at 12 months after SRS was 32.7% and impacted by age, gender, number of metastases, tumor histology, and performance score. Conclusions: Our study provides additional evidence that SRS has become an option for patients with brainstem metastases, with an excellent benefit-to-risk ratio in the hands of experienced clinicians. Prior whole-brain irradiation increases the risk of severe toxicity in brainstem metastasis patients undergoing SRS.« less

  14. Kavalactones and dihydrokavain modulate GABAergic activity in a rat gastric-brainstem preparation.

    PubMed

    Yuan, Chun-Su; Dey, Lucy; Wang, Anbao; Mehendale, Sangeeta; Xie, Jing-Tian; Aung, Han H; Ang-Lee, Michael K

    2002-12-01

    Using an in vitro neonatal rat gastric-brainstem preparation, the activity of majority neurons recorded in the nucleus tractus solitarius (NTS) of the brainstem were significantly inhibited by GABA A receptor agonist, muscimol (30 microM), and this inhibition was reversed by selective GABA A receptor antagonist, bicuculline (10 microM). Application of kavalactones (300 microg/ml) and dihydrokavain (300 microM) into the brainstem compartment of the preparation also significantly reduced the discharge rate of these NTS neurons (39 % and 32 %, respectively, compared to the control level), and this reduction was partially reversed by bicuculline (10 microM). Kavalactones or dihydrokavain induced inhibitory effects were not reduced after co-application of saclofen (10 microM; a selective GABA B receptor antagonist) or naloxone (100 nM; an opioid receptor antagonist). Pretreatment with kavalactones (300 microg/ml) or dihydrokavain (300 microM) significantly decreased the NTS inhibitory effects induced by muscimol (30 microM), approximately from 51 % to 36 %. Our results demonstrated modulation of brainstem GABAergic mechanism by kavalactones and dihydrokavain, and suggested that these compounds may play an important role in regulation of GABAergic neurotransmission.

  15. Obesity and overweight associated with increased carotid diameter and decreased arterial function in young otherwise healthy men.

    PubMed

    Kappus, Rebecca M; Fahs, Christopher A; Smith, Denise; Horn, Gavin P; Agiovlasitis, Stomatis; Rossow, Lindy; Jae, Sae Y; Heffernan, Kevin S; Fernhall, Bo

    2014-04-01

    Obesity is linked to cardiovascular disease, stroke, increased mortality and vascular remodeling. Although increased arterial diameter is associated with multiple cardiovascular risk factors and obesity, it is unknown whether lumen enlargement is accompanied by unfavorable vascular changes in young and otherwise healthy obese individuals. The purpose of this study was to compare carotid and brachial artery diameter, blood pressure, arterial stiffness, and endothelial function in young, apparently healthy, normal-weight, overweight, and obese male subjects. One hundred sixty-five male subjects (27.39±0.59 years) were divided into 3 groups (normal weight, overweight, and obese) according to body mass index. Subjects underwent cardiovascular measurements to determine arterial diameter, function, and stiffness. After adjusting for age, the obese group had significantly greater brachial, carotid, and aortic pressures, brachial pulse wave velocity, carotid intima media thickness, and carotid arterial diameter compared with both the overweight and normal-weight groups. Obesity is associated with a much worse arterial profile, as an increased carotid lumen size was accompanied by higher blood pressure, greater arterial stiffness, and greater carotid intima media thickness in obese compared with overweight or normal-weight individuals. These data suggest that although obesity may be a factor in arterial remodeling, such remodeling is also accompanied by other hemodynamic and arterial changes consistent with reduced arterial function and increased cardiovascular risk.

  16. Obesity and Overweight Associated With Increased Carotid Diameter and Decreased Arterial Function in Young Otherwise Healthy Men

    PubMed Central

    2014-01-01

    BACKGROUND Obesity is linked to cardiovascular disease, stroke, increased mortality and vascular remodeling. Although increased arterial diameter is associated with multiple cardiovascular risk factors and obesity, it is unknown whether lumen enlargement is accompanied by unfavorable vascular changes in young and otherwise healthy obese individuals. The purpose of this study was to compare carotid and brachial artery diameter, blood pressure, arterial stiffness, and endothelial function in young, apparently healthy, normal-weight, overweight, and obese male subjects. METHODS One hundred sixty-five male subjects (27.39±0.59 years) were divided into 3 groups (normal weight, overweight, and obese) according to body mass index. Subjects underwent cardiovascular measurements to determine arterial diameter, function, and stiffness. RESULTS After adjusting for age, the obese group had significantly greater brachial, carotid, and aortic pressures, brachial pulse wave velocity, carotid intima media thickness, and carotid arterial diameter compared with both the overweight and normal-weight groups. CONCLUSIONS Obesity is associated with a much worse arterial profile, as an increased carotid lumen size was accompanied by higher blood pressure, greater arterial stiffness, and greater carotid intima media thickness in obese compared with overweight or normal-weight individuals. These data suggest that although obesity may be a factor in arterial remodeling, such remodeling is also accompanied by other hemodynamic and arterial changes consistent with reduced arterial function and increased cardiovascular risk. PMID:24048148

  17. Vertigo in brainstem and cerebellar strokes.

    PubMed

    Choi, Kwang-Dong; Lee, Hyung; Kim, Ji-Soo

    2013-02-01

    The aim of this study is to review the recent findings on the prevalence, clinical features, and diagnosis of vertigo from brainstem and cerebellar strokes. Patients with isolated vertigo are at higher risk for stroke than the general population. Strokes involving the brainstem and cerebellum may manifest as acute vestibular syndrome, and acute isolated audiovestibular loss may herald impending infarction in the territory of the anterior inferior cerebellar artery. Appropriate bedside evaluation is superior to MRI for detecting central vestibular syndromes. Recording of vestibular-evoked myogenic potentials is useful for evaluation of the central otolithic pathways in brainstem and cerebellar strokes. Accurate identification of isolated vascular vertigo is very important since misdiagnosis of acute stroke may result in significant morbidity and mortality, whereas overdiagnosis of vascular vertigo would lead to unnecessary costly work-ups and medication.

  18. Shrinking plastic tubing and nonstandard diameters

    NASA Technical Reports Server (NTRS)

    Ruiz, W. V.; Thatcher, C. S.

    1980-01-01

    Process allows larger-than-normal postshrink diameters without splitting. Tetrafluoroethylene tubing on mandrel is supported within hot steel pipe by several small diameter coil sections. Rising temperature of mandrel is measured via thermocouple so assembly can be removed without overshrinking (and splitting) of tubing.

  19. Hemifacial Spasm

    MedlinePlus

    ... nerve at the place where it exits the brainstem. × Definition Hemifacial spasm is a neuromuscular disorder characterized ... nerve at the place where it exits the brainstem. View Full Definition Treatment Surgical treatment in the ...

  20. Clinical Correlates of Brainstem Dysfunction in Autistic Children.

    ERIC Educational Resources Information Center

    Fein, Deborah; And Others

    1981-01-01

    It is suggested that social and attentional pathology may be more specifically associated with the brainstem pathology that may characterize autism than are symptoms in other developmental areas. (Author)

  1. An adult case of mumps brainstem encephalitis.

    PubMed

    Koyama, S; Morita, K; Yamaguchi, S; Fujikane, T; Sasaki, N; Aizawa, H; Kikuchi, K

    2000-06-01

    We present an adult case of mumps brainstem encephalitis. He was successfully treated with steroid pulse therapy and recovered completely except for persistent dysuria. He had not been vaccinated and had no history of acute mumps infection. We consider that encephalitis in this case was caused by a reversible autoimmune process triggered by mumps infection. We emphasize the usefulness of pulse therapy for the treatment of some cases of mumps brainstem encephalitis in addition to the importance of mumps vaccination to prevent such a severe complication as encephalitis.

  2. Learning to Encode Timing: Mechanisms of Plasticity in the Auditory Brainstem

    PubMed Central

    Tzounopoulos, Thanos; Kraus, Nina

    2009-01-01

    Mechanisms of plasticity have traditionally been ascribed to higher-order sensory processing areas such as the cortex, whereas early sensory processing centers have been considered largely hard-wired. In agreement with this view, the auditory brainstem has been viewed as a nonplastic site, important for preserving temporal information and minimizing transmission delays. However, recent groundbreaking results from animal models and human studies have revealed remarkable evidence for cellular and behavioral mechanisms for learning and memory in the auditory brainstem. PMID:19477149

  3. Electron microscopic quantification of collagen fibril diameters in the rabbit medial collateral ligament: a baseline for comparison.

    PubMed

    Frank, C; Bray, D; Rademaker, A; Chrusch, C; Sabiston, P; Bodie, D; Rangayyan, R

    1989-01-01

    To establish a normal baseline for comparison, thirty-one thousand collagen fibril diameters were measured in calibrated transmission electron (TEM) photomicrographs of normal rabbit medial collateral ligaments (MCL's). A new automated method of quantitation was used to compare statistically fibril minimum diameter distributions in one midsubstance location in both MCL's from six animals at 3 months of age (immature) and three animals at 10 months of age (mature). Pooled results demonstrate that rabbit MCL's have statistically different (p less than 0.001) mean minimum diameters at these two ages. Interanimal differences in mean fibril minimum diameters were also significant (p less than 0.001) and varied by 20% to 25% in both mature and immature animals. Finally, there were significant differences (p less than 0.001) in mean diameters and distributions from side-to-side in all animals. These mean left-to-right differences were less than 10% in all mature animals but as much as 62% in some immature animals. Statistical analysis of these data demonstrate that animal-to-animal comparisons using these protocols require a large number of animals with appropriate numbers of fibrils being measured to detect small intergroup differences. With experiments which compare left to right ligaments, far fewer animals are required to detect similarly small differences. These results demonstrate the necessity for rigorous control of sampling, an extensive normal baseline and statistically confirmed experimental designs in any TEM comparisons of collagen fibril diameters.

  4. Altered auditory function in rats exposed to hypergravic fields

    NASA Technical Reports Server (NTRS)

    Jones, T. A.; Hoffman, L.; Horowitz, J. M.

    1982-01-01

    The effect of an orthodynamic hypergravic field of 6 G on the brainstem auditory projections was studied in rats. The brain temperature and EEG activity were recorded in the rats during 6 G orthodynamic acceleration and auditory brainstem responses were used to monitor auditory function. Results show that all animals exhibited auditory brainstem responses which indicated impaired conduction and transmission of brainstem auditory signals during the exposure to the 6 G acceleration field. Significant increases in central conduction time were observed for peaks 3N, 4P, 4N, and 5P (N = negative, P = positive), while the absolute latency values for these same peaks were also significantly increased. It is concluded that these results, along with those for fields below 4 G (Jones and Horowitz, 1981), indicate that impaired function proceeds in a rostro-caudal progression as field strength is increased.

  5. Focal traumatic brain stem injury is a rare type of head injury resulting from assault: a forensic neuropathological study.

    PubMed

    Al-Sarraj, Safa; Fegan-Earl, Ashley; Ugbade, Antonia; Bodi, Istvan; Chapman, Rob; Poole, Simon; Swift, Ben; Jerreat, Peter; Cary, Nat

    2012-04-01

    Brainstem haemorrhage is common in cases of head injury when it is associated with space-occupying lesion and increases in the intracranial pressure (duret haemorrhage), in cases of diffuse axonal injury (in dorso-lateral quadrant) and diffuses vascular injury (in the periventricular tissue). However focal traumatic brainstem injury is rare. We identified 12 cases of focal traumatic brainstem injury from review of 319 case of head injury. The head trauma had been caused by different mechanisms of complex fall from height and assault. 10/12 are associated with skull fracture, 11/12 with contre coup contusions in the frontal and temporal lobes, 5/12 direct contusions to cerebellum, 5/12 haemorrhage in corpus callosum and 2/11 have gliding contusions. None of the cases had pathological evidence of increase in the intracranial pressure. The bleeding in the pons was at the edge in 2/12 and cross the section in 10/12. The majority of patients were unconscious immediately after the incident (10/12) and 9/12 died within one day. Focal traumatic brainstem injury occurs most likely due to direct impact at the back of the head or stretching forces affecting the brainstem in cases of complex fall from height and after assault, particularly those associated with kicks. It is a serious and commonly fatal brain damage, which needed to be differentiated from other causes of brainstem haemorrhages. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  6. A single dose of a neuron-binding human monoclonal antibody improves brainstem NAA concentrations, a biomarker for density of spinal cord axons, in a model of progressive multiple sclerosis.

    PubMed

    Wootla, Bharath; Denic, Aleksandar; Watzlawik, Jens O; Warrington, Arthur E; Rodriguez, Moses

    2015-04-29

    Intracerebral infection of susceptible mouse strains with Theiler's murine encephalomyelitis virus (TMEV) results in chronic demyelinating disease with progressive axonal loss and neurologic dysfunction similar to progressive forms of multiple sclerosis (MS). We previously showed that as the disease progresses, a marked decrease in brainstem N-acetyl aspartate (NAA; metabolite associated with neuronal integrity) concentrations, reflecting axon health, is measured. We also demonstrated stimulation of neurite outgrowth by a neuron-binding natural human antibody, IgM12. Treatment with either the serum-derived or recombinant human immunoglobulin M 12 (HIgM12) preserved functional motor activity in the TMEV model. In this study, we examined IgM-mediated changes in brainstem NAA concentrations and central nervous system (CNS) pathology. (1)H-magnetic resonance spectroscopy (MRS) showed that treatment with HIgM12 significantly increased brainstem NAA concentrations compared to controls in TMEV-infected mice. Pathologic analysis demonstrated a significant preservation of axons in the spinal cord of animals treated with HIgM12. This study links drug efficacy of slowing deficits with axon preservation and NAA concentrations in the brainstem in a model of progressive MS. HIgM12-mediated changes of NAA concentrations in the brainstem are a surrogate marker of axon injury/preservation throughout the spinal cord. This study provides proof-of-concept that a neuron-reactive human IgM can be therapeutic and provides a biomarker for clinical trials.

  7. Hyper-excitability of brainstem pathways in cerebral palsy.

    PubMed

    Smith, Allison Teresa; Gorassini, Monica Ann

    2018-06-27

    Individuals with cerebral palsy (CP) experience impairments in the control of head and neck movements, suggesting dysfunction in brainstem circuitry. To examine if brainstem circuitry is altered in CP we compared reflexes evoked in the sternocleidomastoid (SCM) muscle by trigeminal nerve stimulation in adults with CP and age/sex-matched controls. Increasing the intensity of trigeminal nerve stimulation produced progressive increases in the long-latency suppression of ongoing SCM EMG in controls. In contrast, participants with CP showed progressively increased facilitation around the same reflex window, suggesting heightened excitability of brainstem pathways. We also examined if there was altered activation of cortico-brainstem pathways in response to pre-natal injury of the brain. Motor-evoked potentials (MEPs) in the SCM that were conditioned by a prior trigeminal afferent stimulation were more facilitated in CP compared to controls, especially in ipsilateral MEPs that are likely mediated by cortico-reticulospinal pathways. In some participants with CP, but not in controls, a combined trigeminal nerve and cortical stimulation near threshold intensities produced large, long-lasting responses in both the SCM and biceps brachii muscles. We propose that the enhanced excitatory responses evoked from trigeminal and cortical inputs in CP are produced by heightened excitability of brainstem circuits, resulting in the augmented activation of reticulospinal pathways. Enhanced activation of reticulospinal pathways in response to early injury of the corticospinal tract may provide a compensated activation of the spinal cord, or alternatively, contribute to impairments in the precise control of head and neck functions.

  8. Comparison of Predictable Smooth Ocular and Combined Eye-Head Tracking Behaviour in Patients with Lesions Affecting the Brainstem and Cerebellum

    NASA Technical Reports Server (NTRS)

    Grant, Michael P.; Leigh, R. John; Seidman, Scott H.; Riley, David E.; Hanna, Joseph P.

    1992-01-01

    We compared the ability of eight normal subjects and 15 patients with brainstem or cerebellar disease to follow a moving visual stimulus smoothly with either the eyes alone or with combined eye-head tracking. The visual stimulus was either a laser spot (horizontal and vertical planes) or a large rotating disc (torsional plane), which moved at one sinusoidal frequency for each subject. The visually enhanced Vestibulo-Ocular Reflex (VOR) was also measured in each plane. In the horizontal and vertical planes, we found that if tracking gain (gaze velocity/target velocity) for smooth pursuit was close to 1, the gain of combined eye-hand tracking was similar. If the tracking gain during smooth pursuit was less than about 0.7, combined eye-head tracking was usually superior. Most patients, irrespective of diagnosis, showed combined eye-head tracking that was superior to smooth pursuit; only two patients showed the converse. In the torsional plane, in which optokinetic responses were weak, combined eye-head tracking was much superior, and this was the case in both subjects and patients. We found that a linear model, in which an internal ocular tracking signal cancelled the VOR, could account for our findings in most normal subjects in the horizontal and vertical planes, but not in the torsional plane. The model failed to account for tracking behaviour in most patients in any plane, and suggested that the brain may use additional mechanisms to reduce the internal gain of the VOR during combined eye-head tracking. Our results confirm that certain patients who show impairment of smooth-pursuit eye movements preserve their ability to smoothly track a moving target with combined eye-head tracking.

  9. Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy

    PubMed Central

    Naviaux, J C; Schuchbauer, M A; Li, K; Wang, L; Risbrough, V B; Powell, S B; Naviaux, R K

    2014-01-01

    Autism spectrum disorders (ASDs) now affect 1–2% of the children born in the United States. Hundreds of genetic, metabolic and environmental factors are known to increase the risk of ASD. Similar factors are known to influence the risk of schizophrenia and bipolar disorder; however, a unifying mechanistic explanation has remained elusive. Here we used the maternal immune activation (MIA) mouse model of neurodevelopmental and neuropsychiatric disorders to study the effects of a single dose of the antipurinergic drug suramin on the behavior and metabolism of adult animals. We found that disturbances in social behavior, novelty preference and metabolism are not permanent but are treatable with antipurinergic therapy (APT) in this model of ASD and schizophrenia. A single dose of suramin (20 mg kg−1 intraperitoneally (i.p.)) given to 6-month-old adults restored normal social behavior, novelty preference and metabolism. Comprehensive metabolomic analysis identified purine metabolism as the key regulatory pathway. Correction of purine metabolism normalized 17 of 18 metabolic pathways that were disturbed in the MIA model. Two days after treatment, the suramin concentration in the plasma and brainstem was 7.64 μM pmol μl−1 (±0.50) and 5.15 pmol mg−1 (±0.49), respectively. These data show good uptake of suramin into the central nervous system at the level of the brainstem. Most of the improvements associated with APT were lost after 5 weeks of drug washout, consistent with the 1-week plasma half-life of suramin in mice. Our results show that purine metabolism is a master regulator of behavior and metabolism in the MIA model, and that single-dose APT with suramin acutely reverses these abnormalities, even in adults. PMID:24937094

  10. Neural connectivity of the posterior body of the fornix in the human brain: diffusion tensor imaging study.

    PubMed

    Jang, Sung Ho; Kwon, Hyeok Gyu

    2013-08-09

    Little is known about the neural connectivity of the fornix in the human brain. In the current study, using diffusion tensor imaging, we attempted to investigate the neural connectivity of the posterior body of the fornix in the normal human brain. A total of 43 healthy subjects were recruited for this study. DTIs were acquired using a sensitivity-encoding head coil at 1.5T. For connectivity of the posterior body of the fornix, a seed region of interest was used on the posterior body of the fornix. Connectivity was defined as the incidence of connection between the posterior body of the fornix and any neural structure of the brain at the threshold of 5, 25, and 50 streamline. At the threshold of 5, 25, and 50, the posterior body of the fornix showed connectivity to the precentral gyrus (37%, 19%, and 15%), the postcentral gyrus (25%, 11.5%, and 7%), the posterior parietal cortex (16.5%, 5%, and 5%), the brainstem (12%, 4.5%, and 3.5%), the crus of the fornix (34%, 10.5%, and 7%), the contralateral splenium of the corpus callosum (12.5%, 5%, and 0%), and the ipsilateral splenium of the CC (69.8%%, 33.7%, and 23.3%), respectively. Findings of this study showed that the posterior body of the fornix had connectivity with the cerebral cortex, the brainstem, the fornical crus, and the contralateral splenium through the splenium of the corpus callosum in normal subjects. We believe that the results of this study would be helpful in investigation of the neural network related to memory and recovery mechanisms following fornical injury in the human brain. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Individual Differences in Auditory Brainstem Response Wave Characteristics

    PubMed Central

    Jagadeesh, Anoop; Mauermann, Manfred; Ernst, Frauke

    2016-01-01

    Little is known about how outer hair cell loss interacts with noise-induced and age-related auditory nerve degradation (i.e., cochlear synaptopathy) to affect auditory brainstem response (ABR) wave characteristics. Given that listeners with impaired audiograms likely suffer from mixtures of these hearing deficits and that ABR amplitudes have successfully been used to isolate synaptopathy in listeners with normal audiograms, an improved understanding of how different hearing pathologies affect the ABR source generators will improve their sensitivity in hearing diagnostics. We employed a functional model for human ABRs in which different combinations of hearing deficits were simulated and show that high-frequency cochlear gain loss steepens the slope of the ABR Wave-V latency versus intensity and amplitude versus intensity curves. We propose that grouping listeners according to a ratio of these slope metrics (i.e., the ABR growth ratio) might offer a way to factor out the outer hair cell loss deficit and maximally relate individual differences for constant ratios to other peripheral hearing deficits such as cochlear synaptopathy. We compared the model predictions to recorded click-ABRs from 30 participants with normal or high-frequency sloping audiograms and confirm the predicted relationship between the ABR latency growth curve and audiogram slope. Experimental ABR amplitude growth showed large individual differences and was compared with the Wave-I amplitude, Wave-V/I ratio, or the interwaveI–W latency in the same listeners. The model simulations along with the ABR recordings suggest that a hearing loss profile depicting the ABR growth ratio versus the Wave-I amplitude or Wave-V/I ratio might be able to differentiate outer hair cell deficits from cochlear synaptopathy in listeners with mixed pathologies. PMID:27837052

  12. Effects of Arginase Inhibition in Hypertensive Hyperthyroid Rats.

    PubMed

    Rodríguez-Gómez, Isabel; Manuel Moreno, Juan; Jimenez, Rosario; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Wangensteen, Rosemary; Vargas, Félix

    2015-12-01

    This study analyzed the effects of chronic administration of N[omega]-hydroxy-nor-l-arginine (nor-NOHA), an inhibitor of arginase, on the hemodynamic, oxidative stress, morphologic, metabolic, and renal manifestations of hyperthyroidism in rats. Four groups of male Wistar rats were used: control, nor-NOHA-treated (10 mg/kg/day), thyroxine (T4)-treated (75 μg/rat/day), and thyroxine- plus nor-NOHA-treated rats. All treatments were maintained for 4 weeks. Body weight, tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, morphologic, metabolic, plasma, and renal variables were measured. Arginase I and II protein abundance and arginase activity were measured in aorta, heart, and kidney. The T4 group showed increased arginase I and II protein abundance, arginase activity, SBP, HR, plasma nitrates/nitrites (NOx), brainstem and urinary isoprostanes, proteinuria and cardiac and renal hypertrophy in comparison to control rats. In hyperthyroid rats, chronic nor-NOHA prevented the increase in SBP and HR and decreased proteinuria in association with an increase in plasma NOx and a decrease in brainstem and urinary isoprostanes. In normal rats, nor-NOHA treatment did not significantly change any hemodynamic, morphologic, or renal variables. Acute nor-NOHA administration did not affect renal or systemic hemodynamic variables in normal or T4-treated rats. Hyperthyroidism in rats is associated with the increased expression and activity of arginase in aorta, heart, and kidney. Chronic arginase inhibition with nor-NOHA suppresses the characteristic hemodynamic manifestations of hyperthyroidism in association with a reduced oxidative stress. These results indicate an important role for arginase pathway alterations in the cardiovascular and renal abnormalities of hyperthyroidism. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. A developmental classification of malformations of the brainstem.

    PubMed

    Barkovich, A James; Millen, Kathleen J; Dobyns, William B

    2007-12-01

    With advances in imaging and genetics, malformations of the brainstem are being more commonly identified. We describe and classify brainstem anomalies in 138 patients ascertained over a period of 10 years Magnetic resonance imaging studies and, where available, clinical records of the patients were retrospectively reviewed. Malformations were segregated according to magnetic resonance findings and classified when possible by embryological mechanisms The most common location for anomalies was the pons, which was involved in 114 patients. The midbrain was involved in 45 patients, whereas the medulla was involved in 14. In 53 patients, more than 1 region was affected (all 3 regions in 6 patients, midbrain and pons in 39, and medulla and pons in 8). The malformations were divided into four groups: (1) malformations with abnormal brainstem segmentation, (2) malformations with segmental hypoplasia, (3) postsegmentation malformations, and (4) malformations associated with abnormal cortical organization The malformations of the brainstem identified in this study were diverse and complex. This proposed classification organizes them into groupings based on known genetics and embryological events. Use of this system will help clinicians and scientists to better understand these disorders and, ultimately, to better counsel families of affected patients.

  14. Diffusion tensor imaging demonstrates brainstem and cerebellar abnormalities in congenital central hypoventilation syndrome.

    PubMed

    Kumar, Rajesh; Macey, Paul M; Woo, Mary A; Alger, Jeffry R; Harper, Ronald M

    2008-09-01

    Congenital central hypoventilation syndrome (CCHS) patients show reduced breathing drive during sleep, decreased hypoxic and hypercapnic ventilatory responses, and autonomic and affective deficits, suggesting both brainstem and forebrain injuries. Forebrain damage was previously described in CCHS, but methodological limitations precluded detection of brainstem injury, a concern because genetic mutations in CCHS target brainstem autonomic nuclei. To assess brainstem and cerebellar areas, we used diffusion tensor imaging-based measures, namely axial diffusivity, reflecting water diffusion parallel to fibers, and sensitive to axonal injury, and radial diffusivity, measuring diffusion perpendicular to fibers, and indicative of myelin injury. Diffusion tensor imaging was performed in 12 CCHS and 26 controls, and axial and radial diffusivity maps were compared between groups using analysis of covariance (covariates; age and gender). Increased axial diffusivity in CCHS appeared within the lateral medulla and clusters with injury extended from the dorsal midbrain through the periaqueductal gray, raphé, and superior cerebellar decussation, ventrally to the basal-pons. Cerebellar cortex and deep nuclei, and the superior and inferior cerebellar peduncles showed increased radial diffusivity. Midbrain, pontine, and lateral medullary structures, and the cerebellum and its fiber systems are injured in CCHS, likely contributing to the characteristics found in the syndrome.

  15. Impaired brainstem and thalamic high-frequency oscillatory EEG activity in migraine between attacks.

    PubMed

    Porcaro, Camillo; Di Lorenzo, Giorgio; Seri, Stefano; Pierelli, Francesco; Tecchio, Franca; Coppola, Gianluca

    2017-09-01

    Introduction We investigated whether interictal thalamic dysfunction in migraine without aura (MO) patients is a primary determinant or the expression of its functional disconnection from proximal or distal areas along the somatosensory pathway. Methods Twenty MO patients and twenty healthy volunteers (HVs) underwent an electroencephalographic (EEG) recording during electrical stimulation of the median nerve at the wrist. We used the functional source separation algorithm to extract four functionally constrained nodes (brainstem, thalamus, primary sensory radial, and primary sensory motor tangential parietal sources) along the somatosensory pathway. Two digital filters (1-400 Hz and 450-750 Hz) were applied in order to extract low- (LFO) and high- frequency (HFO) oscillatory activity from the broadband signal. Results Compared to HVs, patients presented significantly lower brainstem (BS) and thalamic (Th) HFO activation bilaterally. No difference between the two cortical HFO as well as in LFO peak activations between the two groups was seen. The age of onset of the headache was positively correlated with HFO power in the right brainstem and thalamus. Conclusions This study provides evidence for complex dysfunction of brainstem and thalamocortical networks under the control of genetic factors that might act by modulating the severity of migraine phenotype.

  16. Distribution of Neurotensin and Somatostatin-28 (1-12) in the Minipig Brainstem.

    PubMed

    Sánchez, M L; Vecino, E; Coveñas, R

    2016-08-01

    Using an indirect immunoperoxidase technique, an in depth study has been carried out for the first time on the distribution of fibres and cell bodies containing neurotensin and somatostatin-28 (1-12) (SOM) in the minipig brainstem. The animals used were not treated with colchicine. The distribution of neurotensin- and SOM-immunoreactive fibres was seen to be quite similar and was moderate in the minipig brainstem: a close anatomical relationship between both neuropeptides was observed. The distribution of cell bodies containing neurotensin or SOM was quite different and restricted. Cell bodies containing neurotensin were found in four brainstem nuclei: nucleus centralis raphae, nucleus dorsalis raphae, in the pars centralis of the nucleus tractus spinalis nervi trigemini and in the nucleus ventralis raphae. Cell bodies containing SOM were found in six nuclei/regions of the brainstem: nucleus ambiguus, nucleus dorsalis motorius nervi vagus, formatio reticularis, nucleus parabrachialis medialis, nucleus reticularis lateralis and nucleus ventralis raphae. According to the observed anatomical distribution of the immunoreactive structures containing neurotensin or SOM, the peptides could be involved in sleep-waking, nociceptive, gustatory, motor, respiratory and autonomic mechanisms. © 2015 Blackwell Verlag GmbH.

  17. Stereotactic radiosurgery for deep intracranial arteriovenous malformations, part 1: Brainstem arteriovenous malformations.

    PubMed

    Cohen-Inbar, Or; Ding, Dale; Chen, Ching-Jen; Sheehan, Jason P

    2016-02-01

    The management of brainstem arteriovenous malformations (AVM) are one of the greatest challenges encountered by neurosurgeons. Brainstem AVM have a higher risk of hemorrhage compared to AVM in other locations, and rupture of these lesions commonly results in devastating neurological morbidity and mortality. The potential morbidity associated with currently available treatment modalities further compounds the complexity of decision making for affected patients. Stereotactic radiosurgery (SRS) has an important role in the management of brainstem AVM. SRS offers acceptable obliteration rates with lower risks of hemorrhage occurring during the latency period. Complex nidal architecture requires a multi-disciplinary treatment approach. Nidi partly involving subpial/epipial regions of the dorsal midbrain or cerebellopontine angle should be considered for a combination of endovascular embolization, micro-surgical resection and SRS. Considering the fact that incompletely obliterated lesions (even when reduced in size) could still cause lethal hemorrhages, additional treatment, including repeat SRS and surgical resection should be considered when complete obliteration is not achieved by first SRS. Patients with brainstem AVM require continued clinical and radiological observation and follow-up after SRS, well after angiographic obliteration has been confirmed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. A pathway in the brainstem for roll-tilt of the subjective visual vertical: evidence from a lesion-behavior mapping study.

    PubMed

    Baier, Bernhard; Thömke, Frank; Wilting, Janine; Heinze, Caroline; Geber, Christian; Dieterich, Marianne

    2012-10-24

    The perceived subjective visual vertical (SVV) is an important sign of a vestibular otolith tone imbalance in the roll plane. Previous studies suggested that unilateral pontomedullary brainstem lesions cause ipsiversive roll-tilt of SVV, whereas pontomesencephalic lesions cause contraversive roll-tilts of SVV. However, previous data were of limited quality and lacked a statistical approach. We therefore tested roll-tilt of the SVV in 79 human patients with acute unilateral brainstem lesions due to stroke by applying modern statistical lesion-behavior mapping analysis. Roll-tilt of the SVV was verified to be a brainstem sign, and for the first time it was confirmed statistically that lesions of the medial longitudinal fasciculus (MLF) and the medial vestibular nucleus are associated with ipsiversive tilt of the SVV, whereas contraversive tilts are associated with lesions affecting the rostral interstitial nucleus of the MLF, the superior cerebellar peduncle, the oculomotor nucleus, and the interstitial nucleus of Cajal. Thus, these structures constitute the anatomical pathway in the brainstem for verticality perception. Present data indicate that graviceptive otolith signals present a predominant role in the multisensory system of verticality perception.

  19. Evaluation of normal abdominal aortic diameters in the Indian population using computed tomography.

    PubMed

    Jasper, A; Harshe, G; Keshava, S N; Kulkarni, G; Stephen, E; Agarwal, S

    2014-01-01

    The aim of this study was to establish normal diameters for the suprarenal and infrarenal abdominal aorta measured at T12 and L3 vertebral levels in the Indian population and to study the variation in aortic diameters with age, sex, height, weight, body mass index (BMI), and body surface area (BSA). One hundred and forty-two patients who underwent helical contrast-enhanced computed tomography (CT) scans of the abdomen for non-cardiovascular reasons were recruited.. The mean internal diameters of the suprarenal and infrarenal abdominal aorta (maximum anteroposterior and transverse diameter) were measured at T12 and L3 vertebral levels and tabulated according to various age groups for both men and women. Pearson correlation coefficient was used to evaluate the correlation between aortic diameters, height, weight, BSA, and BMI. The mean diameters of the suprarenal and infrarenal abdominal aorta measured at T12 and L3 vertebral levels, in men were 19.0 ± 2.3 and 13.8 ± 1.9 mm and in women 17.1 ± 2.3 and 12.0 ± 1.6 mm, respectively. The aortic diameter progressively increased in caliber with increasing age of the patients and was smaller in women than men. A significant positive correlation was found in men between the suprarenal and infrarenal aortic diameters and weight, BSA, and BMI. In women, this correlation was significant in the infrarenal aorta but not in the suprarenal aorta. We obtained a set of normal values for the abdominal aorta in the Indian population. The aortic diameters correlated with age, gender, and body size of the patients as seen with previously published data in the Western population. A brief comparison of data between Indian and Western population showed that the values obtained were less than published elsewhere and hence, this should be considered while formulating intervention protocols.

  20. Effects of acute brainstem compression on auditory brainstem response in the guinea pig.

    PubMed

    Tu, T Y; Yu, L H; Chiu, J H; Shu, C H; Shiao, A S; Lien, C F

    1998-11-01

    The purpose of this study was to establish the norm for parameters of auditory brainstem response (ABR) in the guinea pig and to investigate if acute brainstem compression results in significant changes to these parameters. Thirty-six guinea pigs with positive Preyer's reflex were anesthetized. A craniectomy was performed to remove the right occipital bone and the dura mater was opened to expose the brain, cerebellum and cerebellopontine angle (CPA). A small inflatable balloon was placed into the CPA precisely and slowly. ABR was recorded before incision of the skin as a baseline value, after placement and after inflation of the balloon with water at 0.1-ml intervals. Five stable peaks were recorded in 27 experimental animals. When the balloon was inflated with 0.1 ml water, the absolute latency (AL) of peaks IV and V and the interpeak latency (IPL) of peaks III and IV, and IV and V were prolonged. The amplitude ratios (AR) of peaks II, III, IV and V to peak I decreased. Inflation of the balloon with 0.2 ml of water caused further elongation of ALs of peaks IV and V and decreases in each AR. When the balloon volume increased to 0.3 ml, peak V became unrecognizable and peaks III and IV showed significant elongation of AL; peaks I and II did not show significant change in ALs. Further increase of the balloon volume to 0.4 ml resulted in disappearance of peaks III, IV and V; AL of peak II was also elongated. However, the amplitude and AL of peak I remained unchanged. Similar changes were observed in IPLs. This study establishes the norm of parameters of ABR in guinea pigs and demonstrates that acute brainstem compression causes elongation of ALs and IPLs of peaks II, III, IV and V. This suggests that peaks II, III, IV and V come from the brainstem and that peak I is not generated from the brainstem in the guinea pig.

  1. Exposure to a high-fat high-sugar diet causes strong up-regulation of proopiomelanocortin and differentially affects dopamine D1 and D2 receptor gene expression in the brainstem of rats.

    PubMed

    Alsiö, Johan; Rask-Andersen, Mathias; Chavan, Rohit A; Olszewski, Pawel K; Levine, Allen S; Fredriksson, Robert; Schiöth, Helgi B

    2014-01-24

    A strong link between obesity and dopamine (DA) has been established by studies associating body weight status to variants of genes related to DA signalling. Human and animal studies investigating this relationship have so far focused mainly on the role of DA within the mesolimbic pathway. The aim of this study was to investigate potential DA receptor dysregulation in the brainstem, where these receptors play a potential role in meal termination, during high-fat high-sugar diet (HFHS) exposure. Expression of other key genes, including proopiomelanocortin (POMC), was also analyzed. We randomized rats into three groups; ad libitum access to HFHS (n=24), restricted HFHS access (n=10), or controls (chow-fed, n=10). After 5 weeks, brainstem gene expression was investigated by qRT-PCR. We observed an increase in POMC expression in ad libitum HFHS-fed rats compared to chow-fed controls (p<0.05). Further, expression of DA D2 receptor mRNA was down-regulated in the brainstem of the HFHS ad libitum-fed rats (p<0.05), whereas expression of the DA D1 receptor was upregulated (p<0.05) in these animals compared to chow-fed rats. In control experiments, we observed no effect relative to chow-fed controls on DA-receptor or POMC gene expression in the hypothalamus of HFHS diet-exposed rats, or in the brainstem of acutely food deprived rats. The present findings suggest brainstem POMC to be responsive to palatable foods, and that DA dysregulation after access to energy-dense diets occurs not only in striatal regions, but also in the brainstem, which could be relevant for overeating and for the development and maintenance of obesity. Copyright © 2013. Published by Elsevier Ireland Ltd.

  2. Encoding of speech sounds at auditory brainstem level in good and poor hearing aid performers.

    PubMed

    Shetty, Hemanth Narayan; Puttabasappa, Manjula

    Hearing aids are prescribed to alleviate loss of audibility. It has been reported that about 31% of hearing aid users reject their own hearing aid because of annoyance towards background noise. The reason for dissatisfaction can be located anywhere from the hearing aid microphone till the integrity of neurons along the auditory pathway. To measure spectra from the output of hearing aid at the ear canal level and frequency following response recorded at the auditory brainstem from individuals with hearing impairment. A total of sixty participants having moderate sensorineural hearing impairment with age range from 15 to 65 years were involved. Each participant was classified as either Good or Poor Hearing aid Performers based on acceptable noise level measure. Stimuli /da/ and /si/ were presented through loudspeaker at 65dB SPL. At the ear canal, the spectra were measured in the unaided and aided conditions. At auditory brainstem, frequency following response were recorded to the same stimuli from the participants. Spectrum measured in each condition at ear canal was same in good hearing aid performers and poor hearing aid performers. At brainstem level, better F 0 encoding; F 0 and F 1 energies were significantly higher in good hearing aid performers than in poor hearing aid performers. Though the hearing aid spectra were almost same between good hearing aid performers and poor hearing aid performers, subtle physiological variations exist at the auditory brainstem. The result of the present study suggests that neural encoding of speech sound at the brainstem level might be mediated distinctly in good hearing aid performers from that of poor hearing aid performers. Thus, it can be inferred that subtle physiological changes are evident at the auditory brainstem in a person who is willing to accept noise from those who are not willing to accept noise. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  3. Brainstem evoked response audiometry: an investigatory tool in detecting hepatic encephalopathy in decompensated chronic liver disease.

    PubMed

    Kabali, Balasubramanian; Velayutham, Gowri; Kapali, Suresh Chander

    2014-01-01

    It is estimated that globally there is a marked increase in liver disease with reports of rising morbidity and mortality, particularly in younger age groups. Brainstem auditory evoked potential (BAEP) was recorded in 60 decompensated chronic liver disease (DCLD) subjects who fulfilled the selection criteria and compared to 60 age and gender matched healthy subjects with normal liver functions. DCLD subjects were divided into two inter groups based on presence or absence of hepatic encephalopathy (HE). Group 1 comprises of 30 subjects of grade- I HE and Group 2 included 30 subjects without hepatic encephalopathy (NHE). Absolute and interpeak wave latencies were measured. Results were analysed by student independent t- test using SPSS software 11 version. Statistical significance was tested using P value. From the present study it can be concluded that the central nervous system is involved in liver cirrhosis evidenced by an abnormal BAEP latencies parameters. This shows that there may be progressive demyelination occurring along with axonal loss or dysfunction in liver cirrhosis HE. This study suggests that periodic evaluation of cirrhotic individuals to such test will help in monitoring the progress of encephalopathy. The prime goal of this study is early diagnosis and initiation of treatment before the onset of coma can reduce the fatality rate.

  4. Late radiation side-effects in three patients undergoing parotid irradiation for benign disease.

    PubMed

    Armour, A; Ghanna, P; O'Rielly, B; Habeshaw, T; Symonds, P

    2000-01-01

    We report three patients in whom standard radiation therapy was given and serious late radiation damage was seen. The first patient suffered recurrent parotiditis and a parotid fistula. He was treated initially with 20 Gy in ten fractions via a 300 kV field. Further irradiation was required 1 year later and 40 Gy was given in 2 Gy fractions by an oblique anterior and posterior wedged photon pair. Ten years later he developed localized temporal bone necrosis. The second patient, with pleomorphic salivary adenoma, developed localized temporal bone necrosis 6 years after 60 Gy had been given using standard fractionation and technique. The third patient received 55 Gy in 25 fractions for a pleomorphic salivary adenoma and after 3 years developed temporal bone necrosis. Sixteen years later the same patient developed cerebellar and brainstem necrosis. All patients developed chronic persistent infection during or shortly after the radiation therapy, which increased local tissue sensitivity to late radiation damage. As a result, severe bone, cerebellar and brainstem necrosis was observed at doses that are normally considered safe. We therefore strongly recommend that any infection in a proposed irradiated area should be treated aggressively, with surgical debridement if necessary, before radiotherapy is administered, or that infection developing during or after irradiation is treated promptly.

  5. Oculomotor Neurocircuitry, a Structural Connectivity Study of Infantile Nystagmus Syndrome

    PubMed Central

    Kashou, Nasser H.; Zampini, Angelica R.

    2015-01-01

    Infantile Nystagmus Syndrome (INS) is one of the leading causes of significant vision loss in children and affects about 1 in 1000 to 6000 births. In the present study, we are the first to investigate the structural pathways of patients and controls using diffusion tensor imaging (DTI). Specifically, three female INS patients from the same family were scanned, two sisters and a mother. Six regions of interest (ROIs) were created manually to analyze the number of tracks. Additionally, three ROI masks were analyzed using TBSS (Tract-Based Spatial Statistics). The number of fiber tracks was reduced in INS subjects, compared to normal subjects, by 15.9%, 13.9%, 9.2%, 18.6%, 5.3%, and 2.5% for the pons, cerebellum (right and left), brainstem, cerebrum, and thalamus. Furthermore, TBSS results indicated that the fractional anisotropy (FA) values for the patients were lower in the superior ventral aspects of the pons of the brainstem than in those of the controls. We have identified some brain regions that may be actively involved in INS. These novel findings would be beneficial to the neuroimaging clinical and research community as they will give them new direction in further pursuing neurological studies related to oculomotor function and provide a rational approach to studying INS. PMID:25860806

  6. Pathological laughing as a manifestation in a clinically isolated brainstem syndrome: a case report.

    PubMed

    Kocer, Belgin; Oner, Yusuf; Batur, Hale; Nazliel, Bijen; Cengiz, Bulent; Tali, Turgut

    2009-07-01

    The prevalence of pathological laughing and crying in multiple sclerosis (MS) is 10%. It has been speculated that the anatomical lesion responsible for the pathological laughing is located in the pontine base, prefrontal cortex, and cerebellum. We report an 18-year-old male patient presenting with pathological laughing and hypomania. In his neurological examination, he had a euphoric effect with ataxic walking and dysarthria speech. He had a bilateral conjugated gaze limitation, with a prominent bilateral horizontal nystagmus on left gaze, dysmetria, dysdiadokokinesia, and remarkable dysfunction in a heel-to-shin test on the left. The IgG index in cerebrospinal fluid was normal with an oligoclonal band was present. In cranial MRI, there was a lesion on central pons which was hypointense in T1 images with contrast enhancement and hyperintense in T2 and flair images. Also another lesion in right brachium pontis which did not contrast enhancement but was hyperintense on T2 and flair images was present. There was an elevation of myoinositol/creatine ratio and choline and a reduction of NAA in proton MR spectroscopy. MR spectroscopic evaluation of the patient demonstrated the demyelination process. There has been no report of patients in whom pathological laughter was the presenting symptom of clinically isolated brainstem syndrome.

  7. Specific brainstem and cortico-spinal reflex abnormalities in coexisting essential tremor and Parkinson's disease (ET-PD).

    PubMed

    Yavuz, D; Gündüz, A; Ertan, S; Apaydın, H; Şifoğlu, A; Kiziltan, G; Kiziltan, M E

    2015-05-01

    We aimed to analyze functional changes at brainstem and spinal levels in essential tremor (ET), Parkinson's disease (PD) and coexisting essential tremor and Parkinson's disease (ET-PD). Age- and gender-matched patients with tremor (15 ET, 7 ET with resting tremor, 25 ET-PD and 10 PD) and 12 healthy subjects were enrolled in the study. Diagnosis was established according to standardized clinical criteria. Electrophysiological studies included blink reflex (BR), auditory startle reaction (ASR) and long latency reflex (LLR). Blink reflex was normal and similar in all groups. Probability of ASR was significantly lower in ET-PD group whereas it was similar to healthy subjects in ET and PD (P<0.001). LLR was recorded during voluntary activity in all three groups. LLR II was more common in ET, PD and ET-PD groups. LLR III was far more common in the PD group (n=3, 13.6% in ET; n=4, 16.0% in ET-PD and n=7, 46.7% in PD; p=0.037). Despite the integrity of BR pathways, ASR and LLR show distinctive abnormalities in ET-PD. In our opinion, our electrophysiological findings support the hypothesis that ET-PD is a distinct entity. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Non-random nature of spontaneous mIPSCs in mouse auditory brainstem neurons revealed by recurrence quantification analysis

    PubMed Central

    Leao, Richardson N; Leao, Fabricio N; Walmsley, Bruce

    2005-01-01

    A change in the spontaneous release of neurotransmitter is a useful indicator of processes occurring within presynaptic terminals. Linear techniques (e.g. Fourier transform) have been used to analyse spontaneous synaptic events in previous studies, but such methods are inappropriate if the timing pattern is complex. We have investigated spontaneous glycinergic miniature synaptic currents (mIPSCs) in principal cells of the medial nucleus of the trapezoid body. The random versus deterministic (or periodic) nature of mIPSCs was assessed using recurrence quantification analysis. Nonlinear methods were then used to quantify any detected determinism in spontaneous release, and to test for chaotic or fractal patterns. Modelling demonstrated that this procedure is much more sensitive in detecting periodicities than conventional techniques. mIPSCs were found to exhibit periodicities that were abolished by blockade of internal calcium stores with ryanodine, suggesting calcium oscillations in the presynaptic inhibitory terminals. Analysis indicated that mIPSC occurrences were chaotic in nature. Furthermore, periodicities were less evident in congenitally deaf mice than in normal mice, indicating that appropriate neural activity during development is necessary for the expression of deterministic chaos in mIPSC patterns. We suggest that chaotic oscillations of mIPSC occurrences play a physiological role in signal processing in the auditory brainstem. PMID:16271982

  9. Recovery of Dysphagia in Lateral Medullary Stroke

    PubMed Central

    Gupta, Hitesh; Banerjee, Alakananda

    2014-01-01

    Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function. PMID:25045555

  10. Recovery of Dysphagia in lateral medullary stroke.

    PubMed

    Gupta, Hitesh; Banerjee, Alakananda

    2014-01-01

    Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function.

  11. SU-E-T-491: Influence of Applicator Dimensions On Doses to Bladder, Rectum and Sigmoid in HDR Brachytherapy for Cervical Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dumane, V; Rhome, R; Yuan, Y

    2015-06-15

    Purpose: To study the influence of dimensions of the tandem and ring applicator on bladder D2cc, rectum D2cc and sigmoid D2cc in HDR treatment planning for cervical cancer. Methods: 53 plans from 13 patients treated at our institution with the tandem and ring applicator were retrospectively reviewed. Prescription doses were one of the following: 8 Gy x 3, 7 Gy x 4 and 5.5 Gy x 5. Doses to the D2ccs of the bladder, rectum and the sigmoid were recorded. These doses were normalized to their relative prescriptions doses. Correlations between the normalized bladder D2cc, rectum D2cc and sigmoid D2ccmore » were investigated and linear regression models were developed to study the dependence of these doses on the ring diameter and the applicator angle. Results: Normalized doses to the D2cc of the bladder, rectum and sigmoid showed statistically significant correlation (P < 0.05) to the applicator angle. Significant correlation was also noted for the normalized D2cc of the rectum and the sigmoid with the ring diameter. The normalized bladder D2cc was found to decrease with applicator angle on an average by 22.65% ± 4.43% while the same for the rectum and sigmoid were found to increase on an average by 14.43% ± 1.65% and 14.01% ± 1.42% respectively. Both the rectum and sigmoid D2cc reduced with increasing ring diameter by 12.93% ± 1.95% and 11.27% ± 1.79%. No correlation was observed between the normalized bladder D2cc and the ring diameter. Conclusion: Preliminary regression models developed in this study can potentially aid in the choice of the appropriate applicator angle and ring diameter for tandem and ring implant so as to optimize doses to the bladder, rectum and sigmoid.« less

  12. Visual hallucinations and pontine demyelination in a child: possible REM dissociation?

    PubMed

    Vita, Maria Gabriella; Batocchi, Anna Paola; Dittoni, Serena; Losurdo, Anna; Cianfoni, Alessandro; Stefanini, Maria Chiara; Vollono, Catello; Della Marca, Giacomo; Mariotti, Paolo

    2008-12-15

    An 11 year-old-boy acutely developed complex visual and acoustic hallucinations. Hallucinations, consisting of visions of a threatening, evil character of the Harry Potter saga, persisted for 3 days. Neurological and psychiatric examinations were normal. Ictal EEG was negative. MRI documented 3 small areas of hyperintense signal in the brainstem, along the paramedian and lateral portions of pontine tegmentum, one of which showed post-contrast enhancement. These lesions were likely of inflammatory origin, and treatment with immunoglobulins was started. Polysomnography was normal, multiple sleep latency test showed a mean sleep latency of 8 minutes, with one sleep-onset REM period. The pontine tegmentum is responsible for REM sleep regulation, and contains definite "REM-on" and "REM-off" regions. The anatomical distribution of the lesions permits us to hypothesize that hallucinations in this boy were consequent to a transient impairment of REM sleep inhibitory mechanisms, with the appearance of dream-like hallucinations during wake.

  13. Hyperventilation-induced nystagmus in vestibular schwannoma and unilateral sensorineural hearing loss.

    PubMed

    Mandalà, Marco; Giannuzzi, Annalisa; Astore, Serena; Trabalzini, Franco; Nuti, Daniele

    2013-07-01

    We evaluated the incidence and characteristics of hyperventilation-induced nystagmus (HVN) in 49 patients with gadolinium-enhanced magnetic resonance imaging evidence of vestibular schwannoma and 53 patients with idiopathic unilateral sensorineural hearing loss and normal radiological findings. The sensitivity and specificity of the hyperventilation test were compared with other audio-vestibular diagnostic tests (bedside examination of eye movements, caloric test, auditory brainstem responses) in the two groups of patients. The hyperventilation test scored the highest diagnostic efficiency (sensitivity 65.3 %; specificity 98.1 %) of the four tests in the differential diagnosis of vestibular schwannoma and idiopathic unilateral sensorineural hearing loss. Small tumors with a normal caloric response or caloric paresis were associated with ipsilateral HVN and larger tumors and severe caloric deficits with contralateral HVN. These results confirm that the hyperventilation test is a useful diagnostic test for predicting vestibular schwannoma in patients with unilateral sensorineural hearing loss.

  14. Survey of the Knowledge of Brainstem Death and Attitude Toward Organ Donation Among Relations of Neurosurgical Patients in Nigeria.

    PubMed

    Rabiu, T B; Oshola, H A; Adebayo, B O

    2016-01-01

    Organ transplantation is a developing field in Nigeria, and availability of organs for donation would be a determining factor of the success of the transplant programs. Patients with brainstem death (BSD) are a major source of organs for transplantation. The level of knowledge of BSD as well as attitudes toward organ donation are very important determinants of people's willingness or otherwise to donate organs. We conducted a survey of relations of our in-service neurosurgical patients to assess their knowledge of brainstem death and attitude toward organ donation. To our knowledge, this is the first study of its kind among the growing Nigerian neurosurgery patient and patient-relations population. Convenience sampling of randomly selected relations of neurosurgical patients on admission using interviewer-administered questionnaires was performed. Demographic information and information about brainstem death, attitude toward brainstem death, knowledge of organ donation, and attitude toward organ donation were obtained. The study comprised 127 respondents with a mean age of 36 years (range, 19-72). The majority of the respondents (87, 62.4%) were Christians, 122 (96.1%) were Yorubas, and 66 (52.0%) were women. Eighty-five (66.9%) of the respondents had at least a secondary level of education, and 77 (60.6%) were of low socioeconomic status. Twenty-eight (22.2%) of the respondents had heard of brainstem death. Twenty-six (92.9%) of those who had heard of brainstem death believed that the brain could die long before life finally ceases. One hundred twenty-five (98.4%) of the respondents believed that death only occurs when both breathing and heartbeat stop, and 107 (83.6%) would agree with the physician on a diagnosis of brainstem death in the relation. Sixty-five (51.2%) would want such patients put on a ventilator, and, of these, 43 (66.2%) would want such patients on the ventilator in hope that he or she may recover. One hundred twelve (88.2%) of the relations were aware of organ donation, 109 (85.8%) knew that the kidney can be transplanted, and 27 (21.6%) and 17 (13.4%), respectively, were aware of heart and cornea transplant. One hundred five (82.7%) supported organ transplantation, 85 (66.9%) would donate an organ, and 97 (76.4%) would accept a transplanted organ. The majority of the respondents (76, 59.8%) would generally not allow an organ to be taken from their relation, although 70 (55.1%) would allow organ(s) to be harvested from their relation if the person had consented to it before death. More men are likely to donate organs and allow organs to be harvested from their relations than were women. Likewise, respondents with at least a secondary level of education had better awareness of brainstem death and were more likely to donate organs and allow organs to be harvested from their relations than were their less-educated counterparts. The knowledge of brainstem death was low among respondents, although most of them would agree with the physician if such diagnosis was made for their relation. Most of the respondents were aware of organ donation and supported it, but the majority would not allow an organ to be harvested from their relations. Hence, education of the Nigerian people about brainstem death and organ donation is essential to increase the pool of available organs for transplantation in our community. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Long-term outcome after resection of brainstem hemangioblastomas in von Hippel-Lindau disease

    PubMed Central

    Wind, Joshua J.; Bakhtian, Kamran D.; Sweet, Jennifer A.; Mehta, Gautam U.; Thawani, Jayesh P.; Asthagiri, Ashok R.; Oldfield, Edward H.; Lonser, Russell R.

    2016-01-01

    Object Brainstem hemangioblastomas are frequently encountered in patients with von Hippel-Lindau (VHL) disease. These tumors can cause significant morbidity, and their optimal management has not been defined. To better define the outcome and management of these tumors, the authors analyzed the long-term results in patients who underwent resection of brainstem hemangioblastomas. Methods Consecutive patients with VHL disease who underwent resection of brainstem hemangioblastomas with a follow-up of 12 months or more were included in this study. Serial functional assessments, radiographic examinations, and operative records were analyzed. Results Forty-four patients (17 male and 27 female) underwent 51 operations for resection of 71 brainstem hemangioblastomas. The most common presenting symptoms were headache, swallowing difficulties, singultus, gait difficulties, and sensory abnormalities. The mean follow-up was 5.9 ± 5.0 years (range 1.0–20.8 years). Immediately after 34 operations (66.7%), the patients remained at their preoperative functional status; they improved after 8 operations (15.7%) and worsened after 9 operations (17.6%) as measured by the McCormick scale. Eight (88.9%) of the 9 patients who were worse immediately after resection returned to their preoperative status within 6 months. Two patients experienced functional decline during long-term follow-up (beginning at 2.5 and 5 years postoperatively) caused by extensive VHL disease–associated CNS disease. Conclusions Generally, resection of symptomatic brainstem hemangioblastomas is a safe and effective management strategy in patients with VHL disease. Most patients maintain their preoperative functional status, although long-term decline in functional status may occur due to VHL disease–associated progression. PMID:20932100

  16. 7 Tesla 22-channel wrap-around coil array for cervical spinal cord and brainstem imaging.

    PubMed

    Zhang, Bei; Seifert, Alan C; Kim, Joo-Won; Borrello, Joseph; Xu, Junqian

    2017-10-01

    Increased signal-to-noise ratio and blood oxygenation level-dependent sensitivity at 7 Tesla (T) have the potential to enable high-resolution imaging of the human cervical spinal cord and brainstem. We propose a new two-panel radiofrequency coil design for these regions to fully exploit the advantages of ultra-high field. A two-panel array, containing four transmit/receive and 18 receive-only elements fully encircling the head and neck, was constructed following simulations demonstrating the B1+ and specific absorption rate (SAR) benefits of two-panel over one-panel arrays. This array was compared with a previously reported posterior-only array and tested for safety using a phantom. Its anatomical, functional, and diffusion MRI performance was demonstrated in vivo. The two-panel array produced more uniform B1+ across the brainstem and cervical spinal cord without compromising SAR, and achieved 70% greater receive sensitivity than the posterior-only array. The two-panel design enabled acceleration of R = 2 × 2 in two dimensions or R = 3 in a single dimension. High quality in vivo anatomical, functional, and diffusion images of the human cervical spinal cord and brainstem were acquired. We have designed and constructed a wrap-around coil array with excellent performance for cervical spinal cord and brainstem MRI at 7T, which enables simultaneous human cervical spinal cord and brainstem functional MRI. Magn Reson Med 78:1623-1634, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  17. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nakaya, Kotaro; Department of Neurosurgery, Tokyo Women's Medical University, Tokyo; Niranjan, Ajay

    Purpose: This study evaluated the role of radiosurgery in the management of symptomatic patients with brainstem compression from benign basal tumors. Methods and Materials: Over a 17-year, period 246 patients (202 vestibular schwannomas and 44 meningiomas) with brainstem compression from benign skull-base tumors were managed with Gamma Knife radiosurgery. Median tumor volumes were 3.9 cm{sup 3} (range, 0.8-39.0 mL) and 6.6 mL (range, 1.6-25.1 mL) for vestibular schwannomas and meningiomas, respectively. For both tumors, a median marginal dose of 13 Gy was prescribed. Median follow-up of patients was 65 months for vestibular schwannomas and 60 months for meningiomas. Patients weremore » categorized into four groups on the basis of the tumor-brainstem relationship on neuroimaging. Results: Preservation of function was stratified according to grade of brainstem compression. We analyzed the effect of radiosurgery on symptoms of brainstem compression. The tumor control rate was 100 % for meningioma and 97% for vestibular schwannomas (although 5% required an additional procedure such as a ventriculoperitoneal shunt). In patients with vestibular schwannoma, serviceable hearing was preserved in 72.0%. Balance improved in 31.9%, remained unchanged in 56.5%, and deteriorated in 11.6% of patients who had imbalance at presentation. Balance improved significantly in patients who had less tumor compression (p = 0.0357) after radiosurgery. Symptoms improved in 43.2% of patients with meningioma. Conclusion: Radiosurgery is a minimally invasive option for patients with benign basal tumors that indent or distort the brainstem. A high tumor growth control rate and satisfactory rate of neurological preservation and symptom control can be obtained with radiosurgery.« less

  18. Language-experience plasticity in neural representation of changes in pitch salience

    PubMed Central

    Krishnan, Ananthanarayan; Gandour, Jackson T.; Suresh, Chandan H.

    2016-01-01

    Neural representation of pitch-relevant information at the brainstem and cortical levels of processing is influenced by language experience. A well-known attribute of pitch is its salience. Brainstem frequency following responses and cortical pitch specific responses, recorded concurrently, were elicited by a pitch salience continuum spanning weak to strong pitch of a dynamic, iterated rippled noise pitch contour—homolog of a Mandarin tone. Our aims were to assess how language experience (Chinese, English) affects i) enhancement of neural activity associated with pitch salience at brainstem and cortical levels, ii) the presence of asymmetry in cortical pitch representation, and iii) patterns of relative changes in magnitude along the pitch salience continuum. Peak latency (Fz: Na, Pb, Nb) was shorter in the Chinese than the English group across the continuum. Peak-to-peak amplitude (Fz: Na-Pb, Pb-Nb) of the Chinese group grew larger with increasing pitch salience, but an experience-dependent advantage was limited to the Na-Pb component. At temporal sites (T7/T8), the larger amplitude of the Chinese group across the continuum was both limited to the Na-Pb component and the right temporal site. At the brainstem level, F0 magnitude gets larger as you increase pitch salience, and it too reveals Chinese superiority. A direct comparison of cortical and brainstem responses for the Chinese group reveals different patterns of relative changes in magnitude along the pitch salience continuum. Such differences may point to a transformation in pitch processing at the cortical level presumably mediated by local sensory and/or extrasensory influence overlaid on the brainstem output. PMID:26903418

  19. Macrovascular Decompression of the Brainstem and Cranial Nerves: Evolution of an Anteromedial Vertebrobasilar Artery Transposition Technique.

    PubMed

    Choudhri, Omar; Connolly, Ian D; Lawton, Michael T

    2017-08-01

    Tortuous and dolichoectatic vertebrobasilar arteries can impinge on the brainstem and cranial nerves to cause compression syndromes. Transposition techniques are often required to decompress the brainstem with dolichoectatic pathology. We describe our evolution of an anteromedial transposition technique and its efficacy in decompressing the brainstem and relieving symptoms. To present the anteromedial vertebrobasilar artery transposition technique for macrovascular decompression of the brainstem and cranial nerves. All patients who underwent vertebrobasilar artery transposition were identified from the prospectively maintained database of the Vascular Neurosurgery service, and their medical records were reviewed retrospectively. The extent of arterial displacement was measured pre- and postoperatively on imaging. Vertebrobasilar arterial transposition and macrovascular decompression was performed in 12 patients. Evolution in technique was characterized by gradual preference for the far-lateral approach, use of a sling technique with muslin wrap, and an anteromedial direction of pull on the vertebrobasilar artery with clip-assisted tethering to the clival dura. With this technique, mean lateral displacement decreased from 6.6 mm in the first half of the series to 3.8 mm in the last half of the series, and mean anterior displacement increased from 0.8 to 2.5 mm, with corresponding increases in satisfaction and relief of symptoms. Compressive dolichoectatic pathology directed laterally into cranial nerves and posteriorly into the brainstem can be corrected with anteromedial transposition towards the clivus. Our technique accomplishes this anteromedial transposition from an inferolateral surgical approach through the vagoaccessory triangle, with sling fixation to clival dura using aneurysm clips. Copyright © 2017 by the Congress of Neurological Surgeons

  20. Learning Disability Assessed through Audiologic and Physiologic Measures: A Case Study.

    ERIC Educational Resources Information Center

    Greenblatt, Edward R.; And Others

    1983-01-01

    The report describes a child with central auditory dysfunction, the first reported case where brain-stem dysfunction on audiologic tests were associated with specific electrophysiologic changes in the brain-stem auditory-evoked responses. (Author/CL)

  1. The Influence of Traumatic Axonal Injury in Thalamus and Brainstem on Level of Consciousness at Scene or Admission: A Clinical Magnetic Resonance Imaging Study

    PubMed Central

    Moen, Kent Gøran; Skandsen, Toril; Kvistad, Kjell Arne; Laureys, Steven; Håberg, Asta; Vik, Anne

    2018-01-01

    Abstract The aim of this study was to investigate how traumatic axonal injury (TAI) lesions in the thalamus, basal ganglia, and brainstem on clinical brain magnetic resonance imaging (MRI) are associated with level of consciousness in the acute phase in patients with moderate to severe traumatic brain injury (TBI). There were 158 patients with moderate to severe TBI (7–70 years) with early 1.5T MRI (median 7 days, range 0–35) without mass lesion included prospectively. Glasgow Coma Scale (GCS) scores were registered before intubation or at admission. The TAI lesions were identified in T2*gradient echo, fluid attenuated inversion recovery, and diffusion weighted imaging scans. In addition to registering TAI lesions in hemispheric white matter and the corpus callosum, TAI lesions in the thalamus, basal ganglia, and brainstem were classified as uni- or bilateral. Twenty percent of patients had TAI lesions in the thalamus (7% bilateral), 18% in basal ganglia (2% bilateral), and 29% in the brainstem (9% bilateral). One of 26 bilateral lesions in the thalamus or brainstem was found on computed tomography. The GCS scores were lower in patients with bilateral lesions in the thalamus (median four) and brainstem (median five) than in those with corresponding unilateral lesions (median six and eight, p = 0.002 and 0.022). The TAI locations most associated with low GCS scores in univariable ordinal regression analyses were bilateral TAI lesions in the thalamus (odds ratio [OR] 35.8; confidence interval [CI: 10.5−121.8], p < 0.001), followed by bilateral lesions in basal ganglia (OR 13.1 [CI: 2.0–88.2], p = 0.008) and bilateral lesions in the brainstem (OR 11.4 [CI: 4.0–32.2], p < 0.001). This Trondheim TBI study showed that patients with bilateral TAI lesions in the thalamus, basal ganglia, or brainstem had particularly low consciousness at admission. We suggest these bilateral lesions should be evaluated further as possible biomarkers in a new TAI-MRI classification as a worst grade, because they could explain low consciousness in patients without mass lesions. PMID:29334825

  2. Frequency of postnatal hydronephrosis in infants with a renal anterior-posterior pelvic diameter > 4 mm on midtrimester ultrasound.

    PubMed

    Chou, Ching-Yu; Chen, Li-Ching; Cheong, Mei-Leng; Tsai, Ming-Song

    2015-10-01

    To examine the association of antenatal renal pelvic dilatation observed on midtrimester ultrasound screening with the presence of hydronephrosis in newborn infants. The records of patients who received fetal ultrasound examination at 18-28 weeks' gestation from May 2008 to March 2012 were retrospectively reviewed. A fetal renal pelvic anterior-posterior (AP) diameter > 4 mm was considered abnormal and ≤ 4 mm was considered normal. On postnatal ultrasound, a renal pelvic AP diameter > 3 mm was considered to indicate hydronephrosis and ≤ 3 mm was considered normal. The association of postnatal hydronephrosis with prenatal pelvic AP diameter was determined using binary logistic regression analysis. The study comprised 1310 newborn infants: 684 (52.2%) male and 626 (47.8%) female. Multivariate analysis showed a right or left prenatal AP renal pelvic diameter > 4 mm was associated with a higher risk of postnatal hydronephrosis compared with a right and left prenatal AP renal pelvic diameter ≤ 4 mm. Boys had a higher risk for postnatal hydronephrosis than girls (odds ratio = 2.42, p < 0.05). An antenatal renal pelvic AP diameter > 4 mm on midtrimester ultrasound is predictive of postnatal hydronephrosis. Copyright © 2015. Published by Elsevier B.V.

  3. Wall-to-lumen ratio of intracranial arteries measured by indocyanine green angiography

    PubMed Central

    Nakagawa, Daichi; Shojima, Masaaki; Yoshino, Masanori; Kin, Taichi; Imai, Hideaki; Nomura, Seiji; Saito, Toki; Nakatomi, Hirofumi; Oyama, Hiroshi; Saito, Nobuhito

    2016-01-01

    Background: The wall-to-lumen ratio (WLR) is an important parameter in vascular medicine because it indicates the character of vascular wall as well as the degree of stenosis. Despite the advances in medical imaging technologies, it is still difficult to measure the thin-walled normal intracranial arteries, and the reports on the WLR of normal intracranial artery are limited. It might be possible to calculate the WLR using the indocyanine green (ICG) angiography, which is used to observe intracranial vessels during microsurgery. Purpose: To evaluate the WLR of normal intracranial arteries using ICG angiography. Materials and Methods: From the three cases in which ICG angiography was recorded with a ruler during microsurgery, 20 measurement points were chosen for the analysis. The ICG was injected intravenously with a dose of 0.2 mg/kg, and the vessels were inspected at high magnification using an operating microscope equipped with near-infrared illumination system. The vessel outer diameter and the luminal diameter were measured using the images before and after the ICG arrival based on the pixel ratio method using a ruler as reference, respectively. The WLR was calculated as 0.5 × (vessel outer diameter − vessel luminal diameter). Results: The WLR (mean ± standard deviation) of normal intracranial arteries was 0.086 ± 0.022. The WLR tended to be high in small arteries. Conclusion: The WLR of normal intracranial arteries calculated using ICG angiography was consistent with the WLR reported in the previous reports based on human autopsy. PMID:27695538

  4. Identification of Dynamic Patterns of Speech-Evoked Auditory Brainstem Response Based on Ensemble Empirical Mode Decomposition and Nonlinear Time Series Analysis Methods

    NASA Astrophysics Data System (ADS)

    Mozaffarilegha, Marjan; Esteki, Ali; Ahadi, Mohsen; Nazeri, Ahmadreza

    The speech-evoked auditory brainstem response (sABR) shows how complex sounds such as speech and music are processed in the auditory system. Speech-ABR could be used to evaluate particular impairments and improvements in auditory processing system. Many researchers used linear approaches for characterizing different components of sABR signal, whereas nonlinear techniques are not applied so commonly. The primary aim of the present study is to examine the underlying dynamics of normal sABR signals. The secondary goal is to evaluate whether some chaotic features exist in this signal. We have presented a methodology for determining various components of sABR signals, by performing Ensemble Empirical Mode Decomposition (EEMD) to get the intrinsic mode functions (IMFs). Then, composite multiscale entropy (CMSE), the largest Lyapunov exponent (LLE) and deterministic nonlinear prediction are computed for each extracted IMF. EEMD decomposes sABR signal into five modes and a residue. The CMSE results of sABR signals obtained from 40 healthy people showed that 1st, and 2nd IMFs were similar to the white noise, IMF-3 with synthetic chaotic time series and 4th, and 5th IMFs with sine waveform. LLE analysis showed positive values for 3rd IMFs. Moreover, 1st, and 2nd IMFs showed overlaps with surrogate data and 3rd, 4th and 5th IMFs showed no overlap with corresponding surrogate data. Results showed the presence of noisy, chaotic and deterministic components in the signal which respectively corresponded to 1st, and 2nd IMFs, IMF-3, and 4th and 5th IMFs. While these findings provide supportive evidence of the chaos conjecture for the 3rd IMF, they do not confirm any such claims. However, they provide a first step towards an understanding of nonlinear behavior of auditory system dynamics in brainstem level.

  5. Transcriptional profiling and biomarker identification reveal tissue specific effects of expanded ataxin-3 in a spinocerebellar ataxia type 3 mouse model.

    PubMed

    Toonen, Lodewijk J A; Overzier, Maurice; Evers, Melvin M; Leon, Leticia G; van der Zeeuw, Sander A J; Mei, Hailiang; Kielbasa, Szymon M; Goeman, Jelle J; Hettne, Kristina M; Magnusson, Olafur Th; Poirel, Marion; Seyer, Alexandre; 't Hoen, Peter A C; van Roon-Mom, Willeke M C

    2018-06-22

    Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder caused by expansion of the polyglutamine repeat in the ataxin-3 protein. Expression of mutant ataxin-3 is known to result in transcriptional dysregulation, which can contribute to the cellular toxicity and neurodegeneration. Since the exact causative mechanisms underlying this process have not been fully elucidated, gene expression analyses in brains of transgenic SCA3 mouse models may provide useful insights. Here we characterised the MJD84.2 SCA3 mouse model expressing the mutant human ataxin-3 gene using a multi-omics approach on brain and blood. Gene expression changes in brainstem, cerebellum, striatum and cortex were used to study pathological changes in brain, while blood gene expression and metabolites/lipids levels were examined as potential biomarkers for disease. Despite normal motor performance at 17.5 months of age, transcriptional changes in brain tissue of the SCA3 mice were observed. Most transcriptional changes occurred in brainstem and striatum, whilst cerebellum and cortex were only modestly affected. The most significantly altered genes in SCA3 mouse brain were Tmc3, Zfp488, Car2, and Chdh. Based on the transcriptional changes, α-adrenergic and CREB pathways were most consistently altered for combined analysis of the four brain regions. When examining individual brain regions, axon guidance and synaptic transmission pathways were most strongly altered in striatum, whilst brainstem presented with strongest alterations in the pi-3 k cascade and cholesterol biosynthesis pathways. Similar to other neurodegenerative diseases, reduced levels of tryptophan and increased levels of ceramides, di- and triglycerides were observed in SCA3 mouse blood. The observed transcriptional changes in SCA3 mouse brain reveal parallels with previous reported neuropathology in patients, but also shows brain region specific effects as well as involvement of adrenergic signalling and CREB pathway changes in SCA3. Importantly, the transcriptional changes occur prior to onset of motor- and coordination deficits.

  6. SU-F-T-392: Superior Brainstem and Cochlea Sparing with VMAT for Glioblastoma Multiforme

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Briere, TM; McAleer, MF; Levy, LB

    Purpose: Volumetric arc therapy (VMAT) can provide similar target coverage and normal tissue sparing as IMRT but with shorter treatment times. At our institution VMAT was adopted for the treatment glioblastoma multiforme (GBM) after a small number of test plans demonstrated its non-inferiority. In this study, we compare actual clinical treatment plans for a larger cohort of patients treated with either VMAT or IMRT. Methods: 90 GBM patients were included in this study, 45 treated with IMRT and 45 with VMAT. All planning target volumes (PTVs) were prescribed a dose of 50 Gy, with a simultaneous integrated boost to 60more » Gy. Most IMRT plans used 5 non-coplanar beams, while most VMAT plans used 2 coplanar beams. Statistical analysis was performed using Fisher’s exact test or the Wilcoxon-Mann-Whitney rank sum test. Included in the analysis were patient and treatment characteristics as well as the doses to the target volumes and organs at risk. Results: Treatment times for the VMAT plans were reduced by 5 minutes compared with IMRT. The PTV coverage was similar, with at least 95% covered for all plans, while the median boost PTV dose differed by 0.1 Gy between the IMRT and VMAT cohorts. The doses to the brain, optic chiasm, optic nerves and eyes were not significantly different. The mean dose to the brainstem, however, was 9.4 Gy less with VMAT (p<0.001). The dose to the ipsilateral and contralateral cochleae were respectively 19.7 and 9.5 Gy less (p<0.001). Conclusion: Comparison of clinical treatment plans for separate IMRT and VMAT cohorts demonstrates that VMAT can save substantial treatment time while providing similar target coverage and superior sparing of the brainstem and cochleae. To our knowledge this is the first study to demonstrate this benefit of VMAT in the management of GBM.« less

  7. Binaural interaction in the auditory brainstem response: a normative study.

    PubMed

    Van Yper, Lindsey N; Vermeire, Katrien; De Vel, Eddy F J; Battmer, Rolf-Dieter; Dhooge, Ingeborg J M

    2015-04-01

    Binaural interaction can be investigated using auditory evoked potentials. A binaural interaction component can be derived from the auditory brainstem response (ABR-BIC) and is considered evidence for binaural interaction at the level of the brainstem. Although click ABR-BIC has been investigated thoroughly, data on 500 Hz tone-burst (TB) ABR-BICs are scarce. In this study, characteristics of click and 500 Hz TB ABR-BICs are described. Furthermore, reliability of both click and 500 Hz TB ABR-BIC are investigated. Eighteen normal hearing young adults (eight women, ten men) were included. ABRs were recorded in response to clicks and 500 Hz TBs. ABR-BICs were derived by subtracting the binaural response from the sum of the monaural responses measured in opposite ears. Good inter-rater reliability is obtained for both click and 500 Hz TB ABR-BICs. The most reliable peak in click ABR-BIC occurs at a mean latency of 6.06 ms (SD 0.354 ms). Reliable 500 Hz TB ABR-BIC are obtained with a mean latency of 9.47 ms (SD 0.678 ms). Amplitudes are larger for 500 Hz TB ABR-BIC than for clicks. The most reliable peak in click ABR-BIC occurs at the downslope of wave V. Five hundred Hertz TB ABR-BIC is characterized by a broad positivity occurring at the level of wave V. The ABR-BIC is a useful technique to investigate binaural interaction in certain populations. Examples are bilateral hearing aid users, bilateral cochlear implant users and bimodal listeners. The latter refers to the combination of unilateral cochlear implantation and contralateral residual hearing. The majority of these patients have residual hearing in the low frequencies. The current study suggests that 500 Hz TB ABR-BIC may be a suitable technique to assess binaural interaction in this specific population of cochlear implant users. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  8. Neural Correlates of the Binaural Masking Level Difference in Human Frequency-Following Responses.

    PubMed

    Clinard, Christopher G; Hodgson, Sarah L; Scherer, Mary Ellen

    2017-04-01

    The binaural masking level difference (BMLD) is an auditory phenomenon where binaural tone-in-noise detection is improved when the phase of either signal or noise is inverted in one of the ears (S π N o or S o N π , respectively), relative to detection when signal and noise are in identical phase at each ear (S o N o ). Processing related to BMLDs and interaural time differences has been confirmed in the auditory brainstem of non-human mammals; in the human auditory brainstem, phase-locked neural responses elicited by BMLD stimuli have not been systematically examined across signal-to-noise ratio. Behavioral and physiological testing was performed in three binaural stimulus conditions: S o N o , S π N o , and S o N π . BMLDs at 500 Hz were obtained from 14 young, normal-hearing adults (ages 21-26). Physiological BMLDs used the frequency-following response (FFR), a scalp-recorded auditory evoked potential dependent on sustained phase-locked neural activity; FFR tone-in-noise detection thresholds were used to calculate physiological BMLDs. FFR BMLDs were significantly smaller (poorer) than behavioral BMLDs, and FFR BMLDs did not reflect a physiological release from masking, on average. Raw FFR amplitude showed substantial reductions in the S π N o condition relative to S o N o and S o N π conditions, consistent with negative effects of phase summation from left and right ear FFRs. FFR amplitude differences between stimulus conditions (e.g., S o N o amplitude-S π N o amplitude) were significantly predictive of behavioral S π N o BMLDs; individuals with larger amplitude differences had larger (better) behavioral B MLDs and individuals with smaller amplitude differences had smaller (poorer) behavioral B MLDs. These data indicate a role for sustained phase-locked neural activity in BMLDs of humans and are the first to show predictive relationships between behavioral BMLDs and human brainstem responses.

  9. Nonlinear Processing of Auditory Brainstem Response

    DTIC Science & Technology

    2001-10-25

    Kraków, Poland Abstract: - Auditory brainstem response potentials (ABR) are signals calculated from the EEG signals registered as responses to an...acoustic activation of the auditory system. The ABR signals provide an objective, diagnostic method, widely applied in examinations of hearing organs

  10. [Brainstem auditory evoked potentials (BAEPs) and assessment of personality test in patients with migraine].

    PubMed

    Yang, Y; Li, P; Ye, H C

    2000-02-28

    To explore personality test and brainstem auditory potentials (BAEPs) in patients with migraine. BAEPs and eysenck personality scale were recorded in 30 patients with migraine. The abnormal rate of BAEPs was 53%. The latency of individual wave I, III and V were prolonged, so did the interval of the wave III and wave V. The results of personality test showed that 3 patients(10%) manifested introvert personality, 12 patients (40%) extravert personality, and 17 patients (56%) the intermediate personality. It is indicated that migraine may be related to the disturbance of brainstem disfunction and personality of patients.

  11. Brainstem processing following unilateral and bilateral hearing-aid amplification.

    PubMed

    Dawes, Piers; Munro, Kevin J; Kalluri, Sridhar; Edwards, Brent

    2013-04-17

    Following previous research suggesting hearing-aid experience may induce functional plasticity at the peripheral level of the auditory system, click-evoked auditory brainstem response was recorded at first fitting and 12 weeks after hearing-aid use by unilateral and bilateral hearing-aid users. A control group of experienced hearing-aid users was tested over a similar time scale. No significant alterations in auditory brainstem response latency or amplitude were identified in any group. This does not support the hypothesis of plastic changes in the peripheral auditory system induced by hearing-aid use for 12 weeks.

  12. Differential diagnosis of ventriculomegaly and brainstem kinking on fetal MRI.

    PubMed

    Amir, Tali; Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

    2016-01-01

    Fetal ventriculomegaly is a common and frequently leading neuroimaging finding in complex brain malformations. Here we report on pre- and postnatal neuroimaging findings in three fetuses with prenatal ventriculomegaly and brainstem kinking. We aim to identify key neuroimaging features that may allow the prenatal differentiation between diseases associated with fetal ventriculomegaly and brainstem kinking. All pre- and postnatal magnetic resonance imaging (MRI) data were qualitatively evaluated for infra- and supratentorial abnormalities. Data about clinical features and genetic findings were collected from clinical histories. In all three patients, fetal MRI showed ventriculomegaly and brainstem kinking. In two patients, postnatal MRI also showed supratentorial migration abnormalities and eye abnormalities were found. In these children, the diagnosis of α-dystroglycanopathy was genetically confirmed. In the third patient, basal ganglia had an abnormal shape on MRI suggesting a tubulinopathy. The differential diagnosis of prenatal ventriculomegaly and brainstem kinking includes α-dystroglycanopathies, X-linked hydrocephalus due to mutations in L1CAM, and tubulinopathies. The prenatal differentiation between these diseases may be difficult. The presence of ocular abnormalities on prenatal neuroimaging may favor α-dystroglycanopathies, while dysplastic basal ganglia may suggest a tubulinopathy. However, in some patients the final differentiation between these diseases is possible only postnatally. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  13. Spinal cord stress injury assessment (SCOSIA): clinical applications of mechanical modeling of the spinal cord and brainstem

    NASA Astrophysics Data System (ADS)

    Wong, Kenneth H.; Choi, Jae; Wilson, William; Berry, Joel; Henderson, Fraser C., Sr.

    2009-02-01

    Abnormal stretch and strain is a major cause of injury to the spinal cord and brainstem. Such forces can develop from age-related degeneration, congenital malformations, occupational exposure, or trauma such as sporting accidents, whiplash and blast injury. While current imaging technologies provide excellent morphology and anatomy of the spinal cord, there is no validated diagnostic tool to assess mechanical stresses exerted upon the spinal cord and brainstem. Furthermore, there is no current means to correlate these stress patterns with known spinal cord injuries and other clinical metrics such as neurological impairment. We have therefore developed the spinal cord stress injury assessment (SCOSIA) system, which uses imaging and finite element analysis to predict stretch injury. This system was tested on a small cohort of neurosurgery patients. Initial results show that the calculated stress values decreased following surgery, and that this decrease was accompanied by a significant decrease in neurological symptoms. Regression analysis identified modest correlations between stress values and clinical metrics. The strongest correlations were seen with the Brainstem Disability Index (BDI) and the Karnofsky Performance Score (KPS), whereas the weakest correlations were seen with the American Spinal Injury Association (ASIA) scale. SCOSIA therefore shows encouraging initial results and may have wide applicability to trauma and degenerative disease involving the spinal cord and brainstem.

  14. Speech-evoked brainstem frequency-following responses during verbal transformations due to word repetition.

    PubMed

    Galbraith, G C; Jhaveri, S P; Kuo, J

    1997-01-01

    Speech-evoked brainstem frequency-following responses (FFRs) were recorded to repeated presentations of the same stimulus word. Word repetition results in illusory verbal transformations (VTs) in which word perceptions can differ markedly from the actual stimulus. Previous behavioral studies support an explanation of VTs based on changes in arousal or attention. Horizontal and vertical dipole FFRs were recorded to assess responses with putative origins in the auditory nerve and central brainstem, respectively. FFRs were recorded from 18 subjects when they correctly heard the stimulus and when they reported VTs. Although horizontal and vertical dipole FFRs showed different frequency response patterns, dipoles did not differentiate between perceptual conditions. However, when subjects were divided into low- and high-VT groups (based on percentage of VT trials), a significant Condition x Group interaction resulted. This interaction showed the largest difference in FFR amplitudes during VT trials, with the low-VT group showing increased amplitudes, and the high-VT group showing decreased amplitudes, relative to trials in which the stimulus was correctly perceived. These results demonstrate measurable subject differences in the early processing of complex signals, due to possible effects of attention on the brainstem FFR. The present research shows that the FFR is useful in understanding human language as it is coded and processed in the brainstem auditory pathway.

  15. Morphometric analysis of astrocytes in brainstem respiratory regions.

    PubMed

    Sheikhbahaei, Shahriar; Morris, Brian; Collina, Jared; Anjum, Sommer; Znati, Sami; Gamarra, Julio; Zhang, Ruli; Gourine, Alexander V; Smith, Jeffrey C

    2018-06-11

    Astrocytes, the most abundant and structurally complex glial cells of the central nervous system, are proposed to play an important role in modulating the activities of neuronal networks, including respiratory rhythm-generating circuits of the preBötzinger complex (preBötC) located in the ventrolateral medulla of the brainstem. However, structural properties of astrocytes residing within different brainstem regions are unknown. In this study astrocytes in the preBötC, an intermediate reticular formation (IRF) region with respiratory-related function, and a region of the nucleus tractus solitarius (NTS) in adult rats were reconstructed and their morphological features were compared. Detailed morphological analysis revealed that preBötC astrocytes are structurally more complex than those residing within the functionally distinct neighboring IRF region, or the NTS, located at the dorsal aspect of the medulla oblongata. Structural analyses of the brainstem microvasculature indicated no significant regional differences in vascular properties. We hypothesize that high morphological complexity of preBötC astrocytes reflects their functional role in providing structural/metabolic support and modulation of the key neuronal circuits essential for breathing, as well as constraints imposed by arrangements of associated neurons and/or other local structural features of the brainstem parenchyma. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  16. Relation between cognition and neural connection from injured cingulum to brainstem cholinergic nuclei in chronic patients with traumatic brain injury.

    PubMed

    Yoo, Jin-Sun; Kim, Oh Lyong; Kim, Seong Ho; Kim, Min Su; Jang, Sung Ho

    2014-01-01

    This study investigated the relation between cognition and the neural connection from injured cingulum to brainstem cholinergic nuclei in patients with traumatic brain injury (TBI), using diffusion tensor tractography (DTT). Among 353 patients with TBI, 20 chronic patients who showed discontinuation of both anterior cingulums from the basal forebrain on DTT were recruited for this study. The Wechsler Intelligence Scale and the Memory Assessment Scale (MAS; short-term, verbal, visual and total memory) were used for assessment of cognition. Patients were divided into two groups according to the presence of a neural connection between injured cingulum and brainstem cholinergic nuclei. Eight patients who had a neural connection between injured cingulum and brainstem cholinergic nuclei showed better short-term memory on MAS than 12 patients who did not (p < 0.05). However, other results of neuropsychological testing showed no significant difference (p > 0.05). Better short-term memory in patients who had the neural connection between injured cingulum and brainstem cholinergic nuclei appears to have been attributed to the presence of cholinergic innervation to the cerebral cortex through the neural connection instead of the injured anterior cingulum. The neural connection appears to compensate for the injured anterior cingulum in obtaining cholinergic innervation.

  17. Age-Related Changes in Binaural Interaction at Brainstem Level.

    PubMed

    Van Yper, Lindsey N; Vermeire, Katrien; De Vel, Eddy F J; Beynon, Andy J; Dhooge, Ingeborg J M

    2016-01-01

    Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction. The present study investigates binaural interaction at the level of the auditory brainstem. It is hypothesized that brainstem binaural interaction deteriorates with advancing age. Forty-two subjects of various age participated in the study. Auditory brainstem responses (ABRs) were recorded using clicks and 500 Hz tone-bursts. ABRs were elicited by monaural right, monaural left, and binaural stimulation. Binaural interaction was investigated in two ways. First, grand averages of the binaural interaction component were computed for each age group. Second, wave V characteristics of the binaural ABR were compared with those of the summed left and right ABRs. Binaural interaction in the click ABR was demonstrated by shorter latencies and smaller amplitudes in the binaural compared with the summed monaural responses. For 500 Hz tone-burst ABR, no latency differences were found. However, amplitudes were significantly smaller in the binaural than summed monaural condition. An age-effect was found for 500 Hz tone-burst, but not for click ABR. Brainstem binaural interaction seems to decline with age. Interestingly, these changes seem to be stimulus-dependent.

  18. Immediate, irreversible, posttraumatic coma: a review indicating that bilateral brainstem injury rather than widespread hemispheric damage is essential for its production.

    PubMed

    Rosenblum, William I

    2015-03-01

    Traumatic brain injury may result in immediate long-lasting coma. Much attention has been given to predicting this outcome from the initial examination because these predictions can guide future treatment and interactions with the patient's family. Reports of diffuse axonal injury in these cases have ascribed the coma to widespread damage in the deep white matter that disconnects the hemispheres from the ascending arousal system (AAS). However, brainstem lesions are also present in such cases, and the AAS may be interrupted at the brainstem level. This review examines autopsy and imaging literature that assesses the presence, extent, and predictive value of lesions in both sites. The evidence suggests that diffuse injury to the deep white matter is not the usual cause of immediate long-lasting posttraumatic coma. Instead, brainstem lesions in the rostral pons or midbrain are almost always the cause but only if the lesions are bilateral. Moreover, recovery is possible if critical brainstem inputs to the AAS are spared. The precise localization of the latter is subject to ongoing investigation with advanced imaging techniques using magnets of very high magnetic gradients. Limited availability of this equipment plus the need to verify the findings continue to require meticulous autopsy examination.

  19. Combined preoperative traction with instrumented posterior occipitocervical fusion for severe ventral brainstem compression secondary to displaced os odontoideum: technical report of 2 cases.

    PubMed

    Abd-El-Barr, Muhammad M; Snyder, Brian D; Emans, John B; Proctor, Mark R; Hedequist, Daniel

    2016-12-01

    Severe os odontoideum causing ventral brainstem compression is a rare and difficult entity to treat. It is generally accepted that severe os odontoideum causing ventral brainstem compression and neurological deficits warrants surgical treatment. This often requires both anterior and posterior procedures. Anterior approaches to the craniocervical junction are fraught with complications, including infection and risk of injury to neurovascular structures. External traction systems traditionally require long-term bedrest. The authors report 2 cases of severe ventral brainstem compression secondary to displaced os odontoideum and describe their use of extended preoperative halo vest traction to reduce the severe kyphosis and improve neurological function, followed by posterior occipitocervical fusion. Postoperatively both patients showed remarkable improvements in their neurological function and kyphotic deformity. Preoperative halo vest traction combined with posterior occipitocervical fusion appears to be a safe and effective method to treat brainstem compression by severe os odontoideum. It allows for adequate decompression of ventral neural structures and improvement of neurological function, but it is not hindered by the risks of anterior surgical approaches and does not restrict patients to strict bedrest as traditional traction systems. This method of halo vest traction and posterior-only approaches may be transferable to other cervical instability issues with both anterior and posterior pathologies.

  20. Filter Bed of Packed Spheres

    NASA Technical Reports Server (NTRS)

    Elleman, D. D.; Wang, T. G.

    1986-01-01

    Spheres sized and treated for desired sieve properties. Filter constructed from densely packed spheres restrained by screens. Hollow gas-filled plastic or metal spheres normally used. Manufactured within one percent or better diameter tolerance. Normally, all spheres in filter of same nominal diameter. Filter used as sieve to pass only particles smaller than given size or to retain particles larger than that size. Options available under filter concept make it easy to design for specific applications.

  1. Evaluation and diagnosis of brain death by functional near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Pan, Boan; Zhong, Fulin; Huang, Xiaobo; Pan, Lingai; Lu, Sen; Li, Ting

    2017-02-01

    Brain death, the irreversible and permanent loss of the brain and brainstem functions, is hard to be judged precisely for some clinical reasons. The traditional diagnostic methods are time consuming, expensive and some are even dangerous. Functional near infrared spectroscopy (FNIRS), using the good scattering properties of major component of blood to NIR, is capable of noninvasive monitoring cerebral hemodynamic responses. Here, we attempt to use portable FNIRS under patients' natural state for brain death diagnosis. Ten brain death patients and seven normal subjects participated in FNIRS measurements. All of them were provided different fractional concentration of inspired oxygen (FIO2) in different time periods. We found that the concentration variation of deoxyhemoglobin concentration (Δ[Hb]) presents the trend of decrease in the both brain death patients and normal subjects with the raise of the FIO2, however, the data in the normal subjects is more significant. And the concentration variation of oxyhemoglobins concentration (Δ[HbO2]) emerges the opposite trends. Thus Δ[HbO2]/Δ[Hb] in brain death patients is significantly higher than normal subjects, and emerges the rising trend as time went on. The findings indicated the potential of FNIRS-measured hemodynamic index in diagnosing brain death.

  2. Comparison of characteristics observed in tinnitus patients with unilateral vs bilateral symptoms, with both normal hearing threshold and distortion-product otoacoustic emissions.

    PubMed

    Zagólski, Olaf; Stręk, Paweł

    2017-02-01

    Tinnitus characteristics in normal-hearing patients differ between the groups with unilateral and bilateral complaints. The study was to determine the differences between tinnitus characteristics observed in patients with unilateral vs bilateral symptoms and normal hearing threshold, as well as normal results of distortion-product otoacoustic emissions (DPOAEs). The patients answered questions concerning tinnitus duration, laterality, character, accompanying symptoms, and circumstances of onset. The results of tympanometry, auditory brainstem responses, tinnitus likeness spectrum, minimum masking level (MML), and uncomfortable loudness level were evaluated. Records of 380 tinnitus sufferers were examined. Patients with abnormal audiograms and/or DPOAEs were excluded. The remaining 66 participants were divided into groups with unilateral and bilateral tinnitus. Unilateral tinnitus in normal-hearing patients was diagnosed twice more frequently than bilateral. Tinnitus pitch was higher in the group with bilateral tinnitus (p < .001). MML was lower in unilateral tinnitus (p < .05). Mean age of patients was higher in the unilateral tinnitus group (p < .05). Mean tinnitus duration was longer (p < .05) and hypersensitivity to sound was more frequent (p < .05) in the bilateral tinnitus group. Repeated exposure to excessive noise was the most frequent cause in the bilateral tinnitus group.

  3. Different contributions of primary motor cortex, reticular formation, and spinal cord to fractionated muscle activation.

    PubMed

    Zaaimi, Boubker; Dean, Lauren R; Baker, Stuart N

    2018-01-01

    Coordinated movement requires patterned activation of muscles. In this study, we examined differences in selective activation of primate upper limb muscles by cortical and subcortical regions. Five macaque monkeys were trained to perform a reach and grasp task, and electromyogram (EMG) was recorded from 10 to 24 muscles while weak single-pulse stimuli were delivered through microelectrodes inserted in the motor cortex (M1), reticular formation (RF), or cervical spinal cord (SC). Stimulus intensity was adjusted to a level just above threshold. Stimulus-evoked effects were assessed from averages of rectified EMG. M1, RF, and SC activated 1.5 ± 0.9, 1.9 ± 0.8, and 2.5 ± 1.6 muscles per site (means ± SD); only M1 and SC differed significantly. In between recording sessions, natural muscle activity in the home cage was recorded using a miniature data logger. A novel analysis assessed how well natural activity could be reconstructed by stimulus-evoked responses. This provided two measures: normalized vector length L, reflecting how closely aligned natural and stimulus-evoked activity were, and normalized residual R, measuring the fraction of natural activity not reachable using stimulus-evoked patterns. Average values for M1, RF, and SC were L = 119.1 ± 9.6, 105.9 ± 6.2, and 109.3 ± 8.4% and R = 50.3 ± 4.9, 56.4 ± 3.5, and 51.5 ± 4.8%, respectively. RF was significantly different from M1 and SC on both measurements. RF is thus able to generate an approximation to the motor output with less activation than required by M1 and SC, but M1 and SC are more precise in reaching the exact activation pattern required. Cortical, brainstem, and spinal centers likely play distinct roles, as they cooperate to generate voluntary movements. NEW & NOTEWORTHY Brainstem reticular formation, primary motor cortex, and cervical spinal cord intermediate zone can all activate primate upper limb muscles. However, brainstem output is more efficient but less precise in producing natural patterns of motor output than motor cortex or spinal cord. We suggest that gross muscle synergies from the reticular formation are sculpted and refined by motor cortex and spinal circuits to reach the finely fractionated output characteristic of dexterous primate upper limb movements.

  4. Different contributions of primary motor cortex, reticular formation, and spinal cord to fractionated muscle activation

    PubMed Central

    Dean, Lauren R.

    2018-01-01

    Coordinated movement requires patterned activation of muscles. In this study, we examined differences in selective activation of primate upper limb muscles by cortical and subcortical regions. Five macaque monkeys were trained to perform a reach and grasp task, and electromyogram (EMG) was recorded from 10 to 24 muscles while weak single-pulse stimuli were delivered through microelectrodes inserted in the motor cortex (M1), reticular formation (RF), or cervical spinal cord (SC). Stimulus intensity was adjusted to a level just above threshold. Stimulus-evoked effects were assessed from averages of rectified EMG. M1, RF, and SC activated 1.5 ± 0.9, 1.9 ± 0.8, and 2.5 ± 1.6 muscles per site (means ± SD); only M1 and SC differed significantly. In between recording sessions, natural muscle activity in the home cage was recorded using a miniature data logger. A novel analysis assessed how well natural activity could be reconstructed by stimulus-evoked responses. This provided two measures: normalized vector length L, reflecting how closely aligned natural and stimulus-evoked activity were, and normalized residual R, measuring the fraction of natural activity not reachable using stimulus-evoked patterns. Average values for M1, RF, and SC were L = 119.1 ± 9.6, 105.9 ± 6.2, and 109.3 ± 8.4% and R = 50.3 ± 4.9, 56.4 ± 3.5, and 51.5 ± 4.8%, respectively. RF was significantly different from M1 and SC on both measurements. RF is thus able to generate an approximation to the motor output with less activation than required by M1 and SC, but M1 and SC are more precise in reaching the exact activation pattern required. Cortical, brainstem, and spinal centers likely play distinct roles, as they cooperate to generate voluntary movements. NEW & NOTEWORTHY Brainstem reticular formation, primary motor cortex, and cervical spinal cord intermediate zone can all activate primate upper limb muscles. However, brainstem output is more efficient but less precise in producing natural patterns of motor output than motor cortex or spinal cord. We suggest that gross muscle synergies from the reticular formation are sculpted and refined by motor cortex and spinal circuits to reach the finely fractionated output characteristic of dexterous primate upper limb movements. PMID:29046427

  5. Consciousness and the Brainstem.

    ERIC Educational Resources Information Center

    Parvizi, Josef; Damasio, Antonio

    2001-01-01

    Summarizes a theoretical framework and set of hypotheses aimed at accounting for consciousness in neurobiological terms. Discusses the functional neuroanatomy of nuclei in the brainstem reticular formation. Notes that the views presented are compatible with the idea that the reticular formation modulates the electrophysiological activity of the…

  6. The enigma of the dorsolateral pons as a migraine generator

    PubMed Central

    Borsook, D; Burstein, R

    2013-01-01

    In this editorial, we integrate improved understanding of functional and structural brain stem anatomy with lessons learned from other disciplines on brainstem function to provide an alternative interpretation to the data used to support the brainstem migraine generator theory. PMID:22798640

  7. Advancing functional dysconnectivity and atrophy in progressive supranuclear palsy.

    PubMed

    Brown, Jesse A; Hua, Alice Y; Trujllo, Andrew; Attygalle, Suneth; Binney, Richard J; Spina, Salvatore; Lee, Suzee E; Kramer, Joel H; Miller, Bruce L; Rosen, Howard J; Boxer, Adam L; Seeley, William W

    2017-01-01

    Progressive supranuclear palsy syndrome (PSP-S) results from neurodegeneration within a network of brainstem, subcortical, frontal and parietal cortical brain regions. It is unclear how network dysfunction progresses and relates to longitudinal atrophy and clinical decline. In this study, we evaluated patients with PSP-S (n = 12) and healthy control subjects (n = 20) at baseline and 6 months later. Subjects underwent structural MRI and task-free functional MRI (tf-fMRI) scans and clinical evaluations at both time points. At baseline, voxel based morphometry (VBM) revealed that patients with mild-to-moderate clinical symptoms showed structural atrophy in subcortex and brainstem, prefrontal cortex (PFC; supplementary motor area, paracingulate, dorsal and ventral medial PFC), and parietal cortex (precuneus). Tf-fMRI functional connectivity (FC) was examined in a rostral midbrain tegmentum (rMT)-anchored intrinsic connectivity network that is compromised in PSP-S. In healthy controls, this network contained a medial parietal module, a prefrontal-paralimbic module, and a subcortical-brainstem module. Baseline FC deficits in PSP-S were most severe in rMT network integrative hubs in the prefrontal-paralimbic and subcortical-brainstem modules. Longitudinally, patients with PSP-S had declining intermodular FC between the subcortical-brainstem and parietal modules, while progressive atrophy was observed in subcortical-brainstem regions (midbrain, pallidum) and posterior frontal (perirolandic) cortex. This suggested that later-stage subcortical-posterior cortical change may follow an earlier-stage subcortical-anterior cortical disease process. Clinically, patients with more severe baseline impairment showed greater subsequent prefrontal-parietal cortical FC declines and posterior frontal atrophy rates, while patients with more rapid longitudinal clinical decline showed coupled prefrontal-paralimbic FC decline. VBM and FC can augment disease monitoring in PSP-S by tracking the disease through stages while detecting changes that accompany heterogeneous clinical progression.

  8. A case study of IMRT planning (Plan B) subsequent to a previously treated IMRT plan (Plan A)

    NASA Astrophysics Data System (ADS)

    Cao, F.; Leong, C.; Schroeder, J.; Lee, B.

    2014-03-01

    Background and purpose: Treatment of the contralateral neck after previous ipsilateral intensity modulated radiation therapy (IMRT) for head and neck cancer is a challenging problem. We have developed a technique that limits the cumulative dose to the spinal cord and brainstem while maximizing coverage of a planning target volume (PTV) in the contralateral neck. Our case involves a patient with right tonsil carcinoma who was given ipsilateral IMRT with 70Gy in 35 fractions (Plan A). A left neck recurrence was detected 14 months later. The patient underwent a neck dissection followed by postoperative left neck radiation to a dose of 66 Gy in 33 fractions (Plan B). Materials and Methods: The spinal cord-brainstem margin (SCBM) was defined as the spinal cord and brainstem with a 1.0 cm margin. Plan A was recalculated on the postoperative CT scan but the fluence outside of SCBM was deleted. A further modification of Plan A resulted in a base plan that was summed with Plan B to evaluate the cumulative dose received by the spinal cord and brainstem. Plan B alone was used to evaluate for coverage of the contralateral neck PTV. Results: The maximum cumulative doses to the spinal cord with 0.5cm margin and brainstem with 0.5cm margin were 51.96 Gy and 45.60 Gy respectively. For Plan B, 100% of the prescribed dose covered 95% of PTVb1. Conclusion: The use of a modified ipsilateral IMRT plan as a base plan is an effective way to limit the cumulative dose to the spinal cord and brainstem while enabling coverage of a PTV in the contralateral neck.

  9. The Structural, Functional, and Molecular Organization of the Brainstem

    PubMed Central

    Nieuwenhuys, Rudolf

    2011-01-01

    According to His (1891, 1893) the brainstem consists of two longitudinal zones, the dorsal alar plate (sensory in nature) and the ventral basal plate (motor in nature). Johnston and Herrick indicated that both plates can be subdivided into separate somatic and visceral zones, distinguishing somatosensory and viscerosensory zones within the alar plate, and visceromotor and somatomotor zones within the basal plate. To test the validity of this “four-functional-zones” concept, I developed a topological procedure, surveying the spatial relationships of the various cell masses in the brainstem in a single figure. Brainstems of 16 different anamniote species were analyzed, and revealed that the brainstems are clearly divisible into four morphological zones, which correspond largely with the functional zones of Johnston and Herrick. Exceptions include (1) the magnocellular vestibular nucleus situated in the viscerosensory zone; (2) the basal plate containing a number of evidently non-motor centers (superior and inferior olives). Nevertheless the “functional zonal model” has explanatory value. Thus, it is possible to interpret certain brain specializations related to particular behavioral profiles, as “local hypertrophies” of one or two functional columns. Recent developmental molecular studies on brains of birds and mammals confirmed the presence of longitudinal zones, and also showed molecularly defined transverse bands or neuromeres throughout development. The intersecting boundaries of the longitudinal zones and the transverse bands appeared to delimit radially arranged histogenetic domains. Because neuromeres have been observed in embryonic and larval stages of numerous anamniote species, it may be hypothesized that the brainstems of all vertebrates share a basic organizational plan, in which intersecting longitudinal and transverse zones form fundamental histogenetic and genoarchitectonic units. PMID:21738499

  10. Utility of Brainstem Trigeminal Evoked Potentials in Patients With Primary Trigeminal Neuralgia Treated by Microvascular Decompression.

    PubMed

    Zhu, Jin; Zhang, Xin; Zhao, Hua; Tang, Yin-Da; Ying, Ting-Ting; Li, Shi-Ting

    2017-09-01

    To investigate the characteristics of brainstem trigeminal evoked potentials (BTEP) waveform in patients with and without trigeminal neuralgia (TN), and to discuss the utility of BTEP in patients with primary TN treated by microvascular decompression (MVD). A retrospective review of 43 patients who underwent BTEP between January 2016 and June 2016, including 33 patients with TN who underwent MVD and 10 patients without TN. Brainstem trigeminal evoked potentials characteristics of TN and non-TN were summarized, in particular to compare the BTEP changes between pre- and post-MVD, and to discover the relationship between BTEP changes and surgical outcome. Brainstem trigeminal evoked potentials can be recorded in patients without trigeminal neuralgia. Abnormal BTEP could be recorded when different branches were stimulated. After decompression, the original W2, W3 disappeared and then replaced by a large wave in most patients, or original wave poorly differentiated improved in some patients, showed as shorter latency and (or) amplitude increased. Brainstem trigeminal evoked potentials waveform of healthy side in patients with trigeminal neuralgia was similar to the waveform of patients without TN. In 3 patients, after decompression the W2, W3 peaks increased, and the latency, duration, IPLD did not change significantly. Until discharge, 87.9% (29/33) of the patients presented complete absence of pain without medication (BNI I) and 93.9% (31/33) had good pain control without medication (BNI I-II). Brainstem trigeminal evoked potentials can reflect the conduction function of the trigeminal nerve to evaluate the functional level of the trigeminal nerve conduction pathway. The improvement and restoration of BTEP waveforms are closely related to the postoperative curative effect.

  11. Electrophysiologic Study of a Method of Euthanasia Using Intrathecal Lidocaine Hydrochloride Administered during Intravenous Anesthesia in Horses.

    PubMed

    Aleman, M; Davis, E; Williams, D C; Madigan, J E; Smith, F; Guedes, A

    2015-01-01

    An intravenous (IV) overdose of pentobarbital sodium is the most commonly used method of euthanasia in veterinary medicine. However, this compound is not available in many countries or rural areas resulting in usage of alternative methods such as intrathecal lidocaine administration after IV anesthesia. Its safety and efficacy as a method of euthanasia have not been investigated in the horse. To investigate changes in mean arterial blood pressure and electrical activity of the cerebral cortex, brainstem, and heart during intrathecal administration of lidocaine. Our hypothesis was that intrathecal lidocaine affects the cerebral cortex and brainstem before affecting cardiovascular function. Eleven horses requiring euthanasia for medical reasons. Prospective observational study. Horses were anesthetized with xylazine, midazolam, and ketamine; and instrumented for recording of electroencephalogram (EEG), electrooculogram (EOG), brainstem auditory evoked response (BAER), and electrocardiogram (ECG). Physical and neurological (brainstem reflexes) variables were monitored. Mean arterial blood pressure was recorded throughout the study. Loss of cerebro-cortical electrical activity occurred up to 226 seconds after the end of the infusion of lidocaine solution. Cessation of brainstem function as evidenced by a lack of brainstem reflexes and disappearance of BAER occurred subsequently. Undetectable heart sounds, nonpalpable arterial pulse, and extremely low mean arterial blood pressure supported cardiac death; a recordable ECG was the last variable to disappear after the infusion (300-1,279 seconds). Intrathecal administration of lidocaine is an effective alternative method of euthanasia in anesthetized horses, during which brain death occurs before cardiac death. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

  12. Population calcium imaging of spontaneous respiratory and novel motor activity in the facial nucleus and ventral brainstem in newborn mice

    PubMed Central

    Persson, Karin; Rekling, Jens C

    2011-01-01

    Abstract The brainstem contains rhythm and pattern forming circuits, which drive cranial and spinal motor pools to produce respiratory and other motor patterns. Here we used calcium imaging combined with nerve recordings in newborn mice to reveal spontaneous population activity in the ventral brainstem and in the facial nucleus. In Fluo-8 AM loaded brainstem–spinal cord preparations, respiratory activity on cervical nerves was synchronized with calcium signals at the ventrolateral brainstem surface. Individual ventrolateral neurons at the level of the parafacial respiratory group showed perfect or partial synchrony with respiratory nerve bursts. In brainstem–spinal cord preparations, cut at the level of the mid-facial nucleus, calcium signals were recorded in the dorsal, lateral and medial facial subnuclei during respiratory activity. Strong activity initiated in the dorsal subnucleus, followed by activity in lateral and medial subnuclei. Whole-cell recordings from facial motoneurons showed weak respiratory drives, and electrical field potential recordings confirmed respiratory drive to particularly the dorsal and lateral subnuclei. Putative facial premotoneurons showed respiratory-related calcium signals, and were predominantly located dorsomedial to the facial nucleus. A novel motor activity on facial, cervical and thoracic nerves was synchronized with calcium signals at the ventromedial brainstem extending from the level of the facial nucleus to the medulla–spinal cord border. Cervical dorsal root stimulation induced similar ventromedial activity. The medial facial subnucleus showed calcium signals synchronized with this novel motor activity on cervical nerves, and cervical dorsal root stimulation induced similar medial facial subnucleus activity. In conclusion, the dorsal and lateral facial subnuclei are strongly respiratory-modulated, and the brainstem contains a novel pattern forming circuit that drives the medial facial subnucleus and cervical motor pools. PMID:21486812

  13. Survival, migration, and differentiation of Sox1-GFP embryonic stem cells in coculture with an auditory brainstem slice preparation.

    PubMed

    Glavaski-Joksimovic, Aleksandra; Thonabulsombat, Charoensri; Wendt, Malin; Eriksson, Mikael; Palmgren, Björn; Jonsson, Anna; Olivius, Petri

    2008-03-01

    The poor regeneration capability of the mammalian hearing organ has initiated different approaches to enhance its functionality after injury. To evaluate a potential neuronal repair paradigm in the inner ear and cochlear nerve we have previously used embryonic neuronal tissue and stem cells for implantation in vivo and in vitro. At present, we have used in vitro techniques to study the survival and differentiation of Sox1-green fluorescent protein (GFP) mouse embryonic stem (ES) cells as a monoculture or as a coculture with rat auditory brainstem slices. For the coculture, 300 microm-thick brainstem slices encompassing the cochlear nucleus and cochlear nerve were prepared from postnatal SD rats. The slices were propagated using the membrane interface method and the cochlear nuclei were prelabeled with DiI. After some days in culture a suspension of Sox1 cells was deposited next to the brainstem slice. Following deposition Sox1 cells migrated toward the brainstem and onto the cochlear nucleus. GFP was not detectable in undifferentiated ES cells but became evident during neural differentiation. Up to 2 weeks after transplantation the cocultures were fixed. The undifferentiated cells were evaluated with antibodies against progenitor cells whereas the differentiated cells were determined with neuronal and glial markers. The morphological and immunohistochemical data indicated that Sox1 cells in monoculture differentiated into a higher percentage of glial cells than neurons. However, when a coculture was used a significantly lower percentage of Sox1 cells differentiated into glial cells. The results demonstrate that a coculture of Sox1 cells and auditory brainstem present a useful model to study stem cell differentiation.

  14. Effect of neonatal nociceptin or nocistatin imprinting on the brain concentration of biogenic amines and their metabolites.

    PubMed

    Tekes, Kornélia; Gyenge, Melinda; Sótonyi, Péter; Csaba, György

    2009-04-01

    Noradrenaline (NA), dopamine (DA), homovanillic acid (HA), serotonin (5HT) and 5-hydroxyindole acetic acid (5HIAA) content of five brain regions (hypothalamus, hippocampus, brainstem, striatum and frontal cortex) and the cerebrospinal fluid (CSF) was measured in adult (three months old) male and female rats treated neonatally with a single dose of 10 microg nociceptin (NC) or 10 microg nocistatin (NS) for hormonal imprinting. The biogenic amine and metabolite content of cerebrospinal fluid was also determined. In NC treated animals the serotonergic, dopaminergic as well as noradrenergic systems were influenced by the imprinting. The 5HT level increased in hypothalamus, the 5HIAA tissue levels were found increased in hypothalamus. Hippocampus and striatum and the HVA levels increased highly significantly in brainstem. Dopamine level decreased significantly in striatum, however in frontal cortex both noradrenalin and 5HIAA level decreased. Nevertheless, in NS-treated rats decreased NA tissue levels were found in hypothalamus, brainstem and frontal cortex. Decreased DA levels were found in the hypothalamus, brainstem and striatum. NS imprinting resulted in decreased HVA level, but increased one in the brainstem. The 5HT levels decreased in the hypothalamus, brainstem, striatum and frontal cortex, while 5HIAA content of CSF, and frontal cortex decreased, and that of hypothalamus, hippocampus and striatum increased. There was no significant difference between genders except in the 5HT tissue levels of NC treated rats. Data presented show that neonatal imprinting both by NC and NS have long-lasting and brain area specific effects. In earlier experiments endorphin imprinting also influenced the serotonergic system suggesting that during labour release of pain-related substances may durably affect the serotonergic (dopaminergic, adrenergic) system which can impress the animals' later behavior.

  15. The c-FOS Protein Immunohistological Detection: A Useful Tool As a Marker of Central Pathways Involved in Specific Physiological Responses In Vivo and Ex Vivo

    PubMed Central

    Perrin-Terrin, Anne-Sophie; Jeton, Florine; Pichon, Aurelien; Frugière, Alain; Richalet, Jean-Paul; Bodineau, Laurence; Voituron, Nicolas

    2016-01-01

    Many studies seek to identify and map the brain regions involved in specific physiological regulations. The proto-oncogene c-fos, an immediate early gene, is expressed in neurons in response to various stimuli. The protein product can be readily detected with immunohistochemical techniques leading to the use of c-FOS detection to map groups of neurons that display changes in their activity. In this article, we focused on the identification of brainstem neuronal populations involved in the ventilatory adaptation to hypoxia or hypercapnia. Two approaches were described to identify involved neuronal populations in vivo in animals and ex vivo in deafferented brainstem preparations. In vivo, animals were exposed to hypercapnic or hypoxic gas mixtures. Ex vivo, deafferented preparations were superfused with hypoxic or hypercapnic artificial cerebrospinal fluid. In both cases, either control in vivo animals or ex vivo preparations were maintained under normoxic and normocapnic conditions. The comparison of these two approaches allows the determination of the origin of the neuronal activation i.e., peripheral and/or central. In vivo and ex vivo, brainstems were collected, fixed, and sliced into sections. Once sections were prepared, immunohistochemical detection of the c-FOS protein was made in order to identify the brainstem groups of cells activated by hypoxic or hypercapnic stimulations. Labeled cells were counted in brainstem respiratory structures. In comparison to the control condition, hypoxia or hypercapnia increased the number of c-FOS labeled cells in several specific brainstem sites that are thus constitutive of the neuronal pathways involved in the adaptation of the central respiratory drive. PMID:27167092

  16. FOOD-INTAKE DYSREGULATION IN TYPE 2 DIABETIC GOTO-KAKIZAKI RATS: HYPOTHESIZED ROLE OF DYSFUNCTIONAL BRAINSTEM THYROTROPIN-RELEASING HORMONE AND IMPAIRED VAGAL OUTPUT

    PubMed Central

    Zhao, K.; Ao, Y.; Harper, R.M.; Go, V. L.W.; Yang, H.

    2013-01-01

    Thyrotropin-releasing hormone (TRH), a neuropeptide contained in neural terminals innervating brainstem vagal motor neurons, enhances vagal outflow to modify multisystemic visceral functions and food intake. Type 2 diabetes (T2D) and obesity are accompanied by impaired vagal functioning. We examined the possibility that impaired brainstem TRH action may contribute to the vagal dysregulation of food intake in Goto-Kakizaki (GK) rats, a T2D model with hyperglycemia and impaired central vagal activation by TRH. Food intake induced by intracisternal injection of TRH analog was reduced significantly by 50% in GK rats, compared to Wistar rats. Similarly, natural food intake in the dark phase or food intake after an overnight fast was reduced by 56–81% in GK rats. Fasting (48 h) and refeeding (2 h)-associated changes in serum ghrelin, insulin, peptide YY, pancreatic polypeptide and leptin, and the concomitant changes in orexigenic or anorexigenic peptide expression in the brainstem and hypothalamus, all apparent in Wistar rats, were absent or markedly reduced in GK rats, with hormone release stimulated by vagal activation, such as ghrelin and pancreatic polypeptide, decreased substantially. Fasting-induced Fos expression accompanying endogenous brainstem TRH action decreased by 66% and 91%, respectively, in the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) in GK rats, compared to Wistar rats. Refeeding abolished fasting-induced Fos-expression in the NTS, while that in the DMV remained in Wistar but not GK rats. These findings indicate that dysfunctional brainstem TRH-elicited vagal impairment contributes to the disturbed food intake in T2D GK rats, and may provide a pathophysiological mechanism which prevents further weight gain in T2D and obesity. PMID:23701881

  17. Food-intake dysregulation in type 2 diabetic Goto-Kakizaki rats: hypothesized role of dysfunctional brainstem thyrotropin-releasing hormone and impaired vagal output.

    PubMed

    Zhao, K; Ao, Y; Harper, R M; Go, V L W; Yang, H

    2013-09-05

    Thyrotropin-releasing hormone (TRH), a neuropeptide contained in neural terminals innervating brainstem vagal motor neurons, enhances vagal outflow to modify multisystemic visceral functions and food intake. Type 2 diabetes (T2D) and obesity are accompanied by impaired vagal functioning. We examined the possibility that impaired brainstem TRH action may contribute to the vagal dysregulation of food intake in Goto-Kakizaki (GK) rats, a T2D model with hyperglycemia and impaired central vagal activation by TRH. Food intake induced by intracisternal injection of TRH analog was reduced significantly by 50% in GK rats, compared to Wistar rats. Similarly, natural food intake in the dark phase or food intake after an overnight fast was reduced by 56-81% in GK rats. Fasting (48h) and refeeding (2h)-associated changes in serum ghrelin, insulin, peptide YY, pancreatic polypeptide and leptin, and the concomitant changes in orexigenic or anorexigenic peptide expression in the brainstem and hypothalamus, all apparent in Wistar rats, were absent or markedly reduced in GK rats, with hormone release stimulated by vagal activation, such as ghrelin and pancreatic polypeptide, decreased substantially. Fasting-induced Fos expression accompanying endogenous brainstem TRH action decreased by 66% and 91%, respectively, in the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) in GK rats, compared to Wistar rats. Refeeding abolished fasting-induced Fos-expression in the NTS, while that in the DMV remained in Wistar but not GK rats. These findings indicate that dysfunctional brainstem TRH-elicited vagal impairment contributes to the disturbed food intake in T2D GK rats, and may provide a pathophysiological mechanism which prevents further weight gain in T2D and obesity. Published by Elsevier Ltd.

  18. Quantitative proteomic analysis of the brainstem following lethal sarin exposure.

    PubMed

    Meade, Mitchell L; Hoffmann, Andrea; Makley, Meghan K; Snider, Thomas H; Schlager, John J; Gearhart, Jeffery M

    2015-06-22

    The brainstem represents a major tissue area affected by sarin organophosphate poisoning due to its function in respiratory and cardiovascular control. While the acute toxic effects of sarin on brainstem-related responses are relatively unknown, other brain areas e.g., cortex or cerebellum, have been studied more extensively. The study objective was to analyze the guinea pig brainstem toxicology response following sarin (2×LD50) exposure by proteome pathway analysis to gain insight into the complex regulatory mechanisms that lead to impairment of respiratory and cardiovascular control. Guinea pig exposure to sarin resulted in the typical acute behavior/physiology outcomes with death between 15 and 25min. In addition, brain and blood acetylcholinesterase activity was significantly reduced in the presence of sarin to 95%, and 89%, respectively, of control values. Isobaric-tagged (iTRAQ) liquid chromatography tandem mass spectrometry (LC-MS/MS) identified 198 total proteins of which 23% were upregulated, and 18% were downregulated following sarin exposure. Direct gene ontology (GO) analysis revealed a sarin-specific broad-spectrum proteomic profile including glutamate-mediated excitotoxicity, calcium overload, energy depletion responses, and compensatory carbohydrate metabolism, increases in ROS defense, DNA damage and chromatin remodeling, HSP response, targeted protein degradation (ubiquitination) and cell death response. With regards to the sarin-dependent effect on respiration, our study supports the potential interference of sarin with CO2/H(+) sensitive chemoreceptor neurons of the brainstem retrotrapezoid nucleus (RTN) that send excitatory glutamergic projections to the respiratory centers. In conclusion, this study gives insight into the brainstem broad-spectrum proteome following acute sarin exposure and the gained information will assist in the development of novel countermeasures. Published by Elsevier B.V.

  19. The Sleep Disorder in Anti-lgLON5 Disease.

    PubMed

    Gaig, Carles; Iranzo, Alex; Santamaria, Joan; Graus, Francesc

    2018-05-23

    To review the clinical and polysomnographic features of the sleep disorder occurring in the recently described anti-IgLON5 disease. The hallmark of the disease is the presence of antibodies against IgLON5, a neural cell adhesion molecule of unknown function. The disease presents a robust HLA association, and the neuropathological examination shows a novel neuronal tauopathy with predominant hypothalamic and brainstem involvement. Most patients (> 80%) present sleep-related vocalizations with movements and behaviors and sleep-disordered breathing. Polysomnographic studies show (1) a complex NREM sleep parasomnia at sleep initiation characterized by undifferentiated NREM or poorly structured N2 sleep with sleep-talking or mumbling, and simple or finalistic movements followed by normal periods of N3 or N2 NREM sleep, (2) REM sleep behavior disorder (RBD), and (3) obstructive sleep apnea with stridor. The last two features appear mainly in periods where NREM sleep normalizes. Identification of the anti-IgLON5 sleep disorder is important to suspect the disease. The combination of abnormal NREM sleep initiation, followed by normal periods of NREM sleep and RBD, represents a novel parasomnia.

  20. Neurotoxic effects of n-hexane on the human central nervous system: evoked potential abnormalities in n-hexane polyneuropathy.

    PubMed Central

    Chang, Y C

    1987-01-01

    An outbreak of n-hexane polyneuropathy as a result of industrial exposure occurred in printing factories in Taipei area from December 1983 to February 1985. Multimodality evoked potentials study was performed on 22 of the polyneuropathy cases, five of the subclinical cases, and seven of the unaffected workers. The absolute and interpeak latencies of patterned visual evoked potential (pVEP) in both the polyneuropathy and subclinical groups were longer than in the normal controls. The pVEP interpeak amplitude was also decreased in the polyneuropathy cases. Brainstem auditory evoked potentials (BAEP), showed no difference of wave I latency between factory workers and normal controls, but prolongation of the wave I-V interpeak latencies was noted, corresponding with the severity of the polyneuropathy. In somatosensory evoked potentials (SEPs), both the absolute latencies and central conduction time (CCT) were longer in subclinical and polyneuropathy cases than in the unaffected workers and normal controls. From this evoked potentials study, chronic toxic effects of n-hexane on the central nervous system were shown. PMID:3031221

  1. Impact resistance of fiber composite blades used in aircraft turbine engines

    NASA Technical Reports Server (NTRS)

    Friedrich, L. A.; Preston, J. L., Jr.

    1973-01-01

    Resistance of advanced fiber reinforced epoxy matrix composite materials to ballistic impact was investigated as a function of impacting projectile characteristics, and composite material properties. Ballistic impact damage due to normal impacts, was classified as transverse (stress wave delamination and splitting), penetrative, or structural (gross failure). Steel projectiles were found to be gelatin ice projectiles in causing penetrative damage leading to reduced tensile strength. Gelatin and ice projectiles caused either transverse or structural damage, depending upon projectile mass and velocity. Improved composite transverse tensile strength, use of dispersed ply lay-ups, and inclusion of PRD-49-1 or S-glass fibers correlated with improved resistance of composite materials to transverse damage. In non-normal impacts against simulated blade shapes, the normal velocity component of the impact was used to correlate damage results with normal impact results. Stiffening the leading edge of simulated blade specimens led to reduced ballistic damage, while addition of a metallic leading edge provided nearly complete protection against 0.64 cm diameter steel, and 1.27 cm diameter ice and gelatin projectiles, and partial protection against 2.54 cm diameter projectiles of ice and gelatin.

  2. Brainstem cavernous malformations: Natural history versus surgical management.

    PubMed

    Walcott, Brian P; Choudhri, Omar; Lawton, Michael T

    2016-10-01

    While brainstem cavernous malformations were once considered inoperable, improvements in patient selection, surgical exposures, intraoperative MRI-guidance, MR tractography, and neurophysiologic monitoring have resulted in good outcomes in the majority of operated patients. In a consecutive series of 104 patients with brainstem cavernous malformations, only 14% of patients experienced cranial nerve or motor dysfunction that was worse at late follow-up, relative to their preoperative condition. Outcomes were predicted by several factors, including larger lesion size, lesions that crossed the midline, the presence of a developmental venous anomaly, older age, and greater time interval from lesion hemorrhage to surgery. The 14% of patients who experienced a persistent neurological deficit as a result of surgery, while substantial from any perspective, compares favorably with the risks of observation based on a recent meta-analysis. Curative resection is a safe and effective treatment for brainstem cavernous malformations that will prevent re-hemorrhage in symptomatic patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Pontine hyperperfusion in sporadic hyperekplexia

    PubMed Central

    Vetrugno, Roberto; Mascalchi, Mario; Vella, Alessandra; Nave, Riccardo Della; Guerrini, Laura; Vattimo, Angelo; del Giudice, Emanuele Miraglia; Plazzi, Giuseppe; D'Angelo, Roberto; Greco, Giovanni; Montagna, Pasquale

    2007-01-01

    Objective To explore with neuroimaging techniques the anatomical and functional correlates of sporadic hyperekplexia. Methods Two elderly women with sporadic hyperekplexia underwent neurophysiological assessment, MRI of the brain and proton magnetic resonance spectroscopy (1H‐MRS) of the brainstem and frontal lobes. Regional cerebral blood flow was investigated with single photon emission tomography (SPECT) during evoked startles and at rest. Results Both patients showed excessively large and non‐habituating startle responses. In both patients, MRI showed impingement of the brainstem by the vertebrobasilar artery, lack of frontal or brainstem abnormalities on 1H‐MRS and hyperperfusion in the dorsal pons and cingulate cortex, and superior frontal gyrus at SPECT during evoked startles. Conclusions In our patients with hyperekplexia, the vertebrobasilar arteries were found to impinge on the brainstem. Neurophysiological findings and neurofunctional imaging of evoked startles indicated a pontine origin of the movement disorder modulated by activation in cortical, especially frontal, areas. The neurofunctional correlates of evoked startles in human sporadic hyperekplexia are similar to those observed for the startle circuit in animals. PMID:17702784

  4. Pontine hyperperfusion in sporadic hyperekplexia.

    PubMed

    Vetrugno, Roberto; Mascalchi, Mario; Vella, Alessandra; Della Nave, Riccardo; Guerrini, Laura; Vattimo, Angelo; del Giudice, Emanuele Miraglia; Plazzi, Giuseppe; D'Angelo, Roberto; Greco, Giovanni; Montagna, Pasquale

    2007-09-01

    To explore with neuroimaging techniques the anatomical and functional correlates of sporadic hyperekplexia. Two elderly women with sporadic hyperekplexia underwent neurophysiological assessment, MRI of the brain and proton magnetic resonance spectroscopy (1H-MRS) of the brainstem and frontal lobes. Regional cerebral blood flow was investigated with single photon emission tomography (SPECT) during evoked startles and at rest. Both patients showed excessively large and non-habituating startle responses. In both patients, MRI showed impingement of the brainstem by the vertebrobasilar artery, lack of frontal or brainstem abnormalities on 1H-MRS and hyperperfusion in the dorsal pons and cingulate cortex, and superior frontal gyrus at SPECT during evoked startles. In our patients with hyperekplexia, the vertebrobasilar arteries were found to impinge on the brainstem. Neurophysiological findings and neurofunctional imaging of evoked startles indicated a pontine origin of the movement disorder modulated by activation in cortical, especially frontal, areas. The neurofunctional correlates of evoked startles in human sporadic hyperekplexia are similar to those observed for the startle circuit in animals.

  5. Prospective Characterization of Cognitive Function in Typical and 'Brainstem Predominant'Progressive Supranuclear Palsy Phenotypes.

    PubMed

    Lee, Young-Eun C; Williams, David R; Anderson, Jacqueline F I

    2018-05-01

    Clinicopathological studies over the last decade have broadened the clinical spectrum of progressive supranuclear palsy (PSP) to include several distinct clinical syndromes. We examined the cognitive profiles of patients with PSP-Richardson's syndrome (PSP-RS) and two atypical 'brainstem predominant' PSP phenotypes (PSP-parkinsonism, PSP-P; and PSP-pure akinesia with gait freezing, PSP-PAGF) using a comprehensive neuropsychological battery. Fourteen patients diagnosed as PSP-RS, three patients with PSP-P and four patients with PSP-PAGF were assessed using a comprehensive battery of neuropsychological tests. The typical PSP-RS subgroup demonstrated greater impairments in processing speed [t(19) = -4.10, p = 0.001 (d =1.66)] and executive function [t(19) = -2.63, p = 0.02 (d = 1.20)] compared to the 'brainstem predominant' PSP phenotype. This is the first prospective study to demonstrate that PSP-RS and 'brainstem predominant' PSP phenotypes can be differentiated on cognitive grounds. These differences correspond with variations in pathological profiles reported in the literature.

  6. Corneal Epithelium Thickness Profile in 614 Normal Chinese Children Aged 7-15 Years Old.

    PubMed

    Ma, Yingyan; He, Xiangui; Zhu, Xiaofeng; Lu, Lina; Zhu, Jianfeng; Zou, Haidong

    2016-03-23

    The purpose of the study is to describe the values and distribution of corneal epithelium thickness (CET) in normal Chinese school-aged children, and to explore associated factors with CET. CET maps were measured by Fourier-domain optical coherence tomography (FD-OCT) in normal Chinese children aged 7 to 15 years old from two randomly selected schools in Shanghai, China. Children with normal intraocular pressure were further examined for cycloplegic autorefraction, corneal curvature radius (CCR) and axial length. Central (2-mm diameter area), para-central (2- to 5-mm diameter area), and peripheral (5- to 6-mm diameter area) CET in the superior, superotemporal, temporal, inferotemporal, inferior, inferonasal, nasal, superonasal cornea; minimum, maximum, range, and standard deviation of CET within the 5-mm diameter area were recorded. The CET was thinner in the superior than in the inferior and was thinner in the temporal than in the nasal. The maximum CET was located in the inferior zone, and the minimum CET was in the superior zone. A thicker central CET was associated with male gender (p = 0.009) and older age (p = 0.037) but not with CCR (p = 0.061), axial length (p = 0.253), or refraction (p = 0.351) in the multiple regression analyses. CCR, age, and gender were correlated with para-central and peripheral CET.

  7. Microvascular anatomy of the cerebellar parafloccular perforating space.

    PubMed

    Sosa, Pablo; Dujovny, Manuel; Onyekachi, Ibe; Sockwell, Noressia; Cremaschi, Fabián; Savastano, Luis E

    2016-02-01

    The cerebellopontine angle is a common site for tumor growth and vascular pathologies requiring surgical manipulations that jeopardize cranial nerve integrity and cerebellar and brainstem perfusion. To date, a detailed study of vessels perforating the cisternal surface of the middle cerebellar peduncle-namely, the paraflocculus or parafloccular perforating space-has yet to be published. In this report, the perforating vessels of the anterior inferior cerebellar artery (AICA) in the parafloccular space, or on the cisternal surface of the middle cerebellar peduncle, are described to elucidate their relevance pertaining to microsurgery and the different pathologies that occur at the cerebellopontine angle. Fourteen cadaveric cerebellopontine cisterns (CPCs) were studied. Anatomical dissections and analysis of the perforating arteries of the AICA and posterior inferior cerebellar artery at the parafloccular space were recorded using direct visualization by surgical microscope, optical histology, and scanning electron microscope. A comprehensive review of the English-language and Spanish-language literature was also performed, and findings related to anatomy, histology, physiology, neurology, neuroradiology, microsurgery, and endovascular surgery pertaining to the cerebellar flocculus or parafloccular spaces are summarized. A total of 298 perforating arteries were found in the dissected specimens, with a minimum of 15 to a maximum of 26 vessels per parafloccular perforating space. The average outer diameter of the cisternal portion of the perforating arteries was 0.11 ± 0.042 mm (mean ± SD) and the average length was 2.84 ± 1.2 mm. Detailed schematics and the surgical anatomy of the perforating vessels at the CPC and their clinical relevance are reported. The parafloccular space is a key entry point for many perforating vessels toward the middle cerebellar peduncle and lateral brainstem, and it must be respected and protected during surgical approaches to the cerebellopontine angle.

  8. Regulation of TRPV2 by axotomy in sympathetic, but not sensory neurons.

    PubMed

    Gaudet, Andrew D; Williams, Sarah J; Hwi, Lucy P-R; Ramer, Matt S

    2004-08-13

    Neuropathic pain results from traumatic or disease-related insults to the nervous system. Mechanisms that have been postulated to underlie peripheral neuropathy commonly implicate afferent neurons that have been damaged but still project centrally to the spinal cord, and/or intact neurons that interact with degenerating distal portions of the injured neurons. One pain state that is observed following peripheral nerve injury in the rat is thermal hyperalgesia. The noxious heat-gated ion channel TRPV1 may be responsible for this increased sensitivity, as it is up-regulated in L4 dorsal root ganglion (DRG) neurons following L5 spinal nerve lesion (SpNL). The TRPV1 homologue TRPV2 (or VRL-1) is another member of the TRPV subfamily of TRP ion channels. TRPV2 is a nonselective cation channel activated by high noxious temperatures (>52 degrees C) and is present in a subset of medium- to large-diameter DRG neurons. To establish whether TRPV2 is endogenous to the spinal cord, we examined its expression in the dorsal horn following rhizotomy. We found no significant decrease in TRPV2 immunoreactivity, suggesting that TRPV2 is endogenous to the spinal cord. In order to determine whether TRPV2, like TRPV1, is regulated by peripheral axotomy, we performed L5 SpNL and characterized TRPV2 distribution in the DRG, spinal cord, brainstem, and sympathetic ganglia. Our results show that peripheral axotomy did not regulate TRPV2 in the DRG, spinal cord, or brainstem; however, TRPV2 was up-regulated in sympathetic postganglionic neurons following injury, suggesting a potential role for TRPV2 in sympathetically mediated neuropathic pain.

  9. Diffusion tensor imaging of the brainstem in children with achondroplasia

    PubMed Central

    BOSEMANI, THANGAMADHAN; ORMAN, GUNES; CARSON, KATHRYN A; MEODED, AVNER; HUISMAN, THIERRY A G M; PORETTI, ANDREA

    2014-01-01

    Aim The aims of this study were to compare, using diffusion tensor imaging (DTI) of the brainstem, microstructural integrity of the white matter in children with achondroplasia and age-matched participants and to correlate the severity of craniocervical junction (CCJ) narrowing and neurological findings with DTI scalars in children with achondroplasia. This study also aimed to assess the potential role of fibroblast growth factor receptor type 3 on white matter microstructure. Method Diffusion tensor imaging was performed using a 1.5T magnetic resonance scanner and balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements were obtained from regions of interest, sampled in each pontine corticospinal tract (CST), medial lemniscus, and middle cerebellar peduncle, as well as in the lower brainstem and centrum semiovale, for fractional anisotropy and for mean, axial and radial diffusivity. In addition, a severity score for achondroplasia was assessed by measuring CCJ narrowing. Result Eight patients with achondroplasia (seven males, one female; mean age 5y 6mo, range 1y 1mo–15y 1mo) and eight age- and sex-matched comparison participants (mean age 5y 2mo, range 1y 1mo–14y 11mo) were included in this study. Fractional anisotropy was lower and mean diffusivity and radial diffusivity were higher in the lower brainstem of patients with achondroplasia than in age-matched comparison participants. The CST and middle cerebellar peduncle of the participants showed increases in mean, axial, and radial diffusivity. Fractional anisotropy in the lower brainstem was negatively correlated with the degree of CCJ narrowing. No differences in the DTI metrics of the centrum semiovale were observed between the two groups. Interpretation The reduction in fractional anisotropy and increase in diffusivities in the lower brainstem of participants with achondroplasia may reflect secondary encephalomalacic degeneration and cavitation of the affected white matter tracts as shown by histology. In children with achondroplasia, DTI may serve as a potential biomarker for brainstem white matter injury and aid in the care and management of these patients. PMID:24825324

  10. Diffusion tensor imaging of the brainstem in children with achondroplasia.

    PubMed

    Bosemani, Thangamadhan; Orman, Gunes; Carson, Kathryn A; Meoded, Avner; Huisman, Thierry A G M; Poretti, Andrea

    2014-11-01

    The aims of this study were to compare, using diffusion tensor imaging (DTI) of the brainstem, microstructural integrity of the white matter in children with achondroplasia and age-matched participants and to correlate the severity of craniocervical junction (CCJ) narrowing and neurological findings with DTI scalars in children with achondroplasia. This study also aimed to assess the potential role of fibroblast growth factor receptor type 3 on white matter microstructure. Diffusion tensor imaging was performed using a 1.5T magnetic resonance scanner and balanced pairs of diffusion gradients along 20 non-collinear directions. Measurements were obtained from regions of interest, sampled in each pontine corticospinal tract (CST), medial lemniscus, and middle cerebellar peduncle, as well as in the lower brainstem and centrum semiovale, for fractional anisotropy and for mean, axial, and radial diffusivity. In addition, a severity score for achondroplasia was assessed by measuring CCJ narrowing. Eight patients with achondroplasia (seven males, one female; mean age 5y 6mo, range 1y 1mo-15y 1mo) and eight age- and sex-matched comparison participants (mean age 5y 2mo, range 1y 1mo-14y 11mo) were included in this study. Fractional anisotropy was lower and mean diffusivity and radial diffusivity were higher in the lower brainstem of patients with achondroplasia than in age-matched comparison participants. The CST and middle cerebellar peduncle of the participants showed increases in mean, axial, and radial diffusivity. Fractional anisotropy in the lower brainstem was negatively correlated with the degree of CCJ narrowing. No differences in the DTI metrics of the centrum semiovale were observed between the two groups. The reduction in fractional anisotropy and increase in diffusivities in the lower brainstem of participants with achondroplasia may reflect secondary encephalomalacic degeneration and cavitation of the affected white matter tracts as shown by histology. In children with achondroplasia, DTI may serve as a potential biomarker for brainstem white matter injury and aid in the care and management of these patients. © 2014 Mac Keith Press.

  11. Mechanical Characterization of Immature Porcine Brainstem in Tension at Dynamic Strain Rates.

    PubMed

    Zhao, Hui; Yin, Zhiyong; Li, Kui; Liao, Zhikang; Xiang, Hongyi; Zhu, Feng

    2016-01-21

    Many brain injury cases involve pediatric road traffic accidents, and among these, brainstem injury causes disastrous outcomes. A thorough understanding of the tensile characterization of immature brainstem tissue is crucial in modeling traumatic brain injury sustained by children, but limited experimental data in tension is available for the immature brain tissue at dynamic strain rates. We harvested brainstem tissue from immature pigs (about 4 weeks old, and at a developmental stage similar to that of human toddlers) as a byproduct from a local slaughter house and very carefully prepared the samples. Tensile tests were performed on specimens at dynamic strain rates of 2/s, 20/s, and 100/s using a biological material instrument. The constitutive models, Fung, Ogden, Gent, and exponential function, for immature brainstem tissue material property were developed for the recorded experimental data using OriginPro 8.0 software. The t test was performed for infinitesimal shear modules. The curves of stress-versus-stretch ratio were convex in shape, and inflection points were found in all the test groups at the strain of about 2.5%. The average Lagrange stress of the immature brainstem specimen at the 30% strain at the strain rates of 2, 20, and 100/s was 273±114, 515±107, and 1121±197 Pa, respectively. The adjusted R-Square (R2) of Fung, Ogden, Gent, and exponential model was 0.820≤R2≤0.933, 0.774≤R2≤0.940, 0.650≤R2≤0.922, and 0.852≤R2≤0.981, respectively. The infinitesimal shear modulus of the strain energy functions showed a significant association with the strain rate (p<0.01). The immature brainstem is a rate-dependent material in dynamic tensile tests, and the tissue becomes stiffer with increased strain rate. The reported results may be useful in the study of brain injuries in children who sustain injuries in road traffic accidents. Further research in more detail should be performed in the future.

  12. Ontogeny of cholecystokinin-like immunoreactivity in the Brazilian opossum brain.

    PubMed

    Fox, C A; Jeyapalan, M; Ross, L R; Jacobson, C D

    1991-12-17

    We have studied the anatomical distribution of cholecystokinin-like immunoreactive (CCK-IR) somata and fibers in the brain of the adult and developing Brazilian short-tailed opossum, Monodelphis domestica. Animals ranged in age from the day of birth (1PN) to young adulthood (180PN). A nickel enhanced, avidin-biotin, indirect immunohistochemical technique was used to identify CCK-IR structures. Somata containing CCK immunoreactivity were observed in the cerebral cortex, hippocampus, hypothalamus, thalamus, midbrain, and brainstem in the adult. Cholecystokinin immunoreactive fibers had a wide distribution in the adult Monodelphis brain. The only major region of the brain that did not contain CCK-IR fibers was the cerebellum. The earliest expression of CCK immunoreactivity was found in fibers in the dorsal brainstem of 5-day-old opossum pups. It is possible that the CCK-IR fibers in the brainstem at 5PN are of vagal origin. Cholecystokinin immunoreactive somata were observed in the brainstem on 10PN. The CCK-IR cell bodies observed in the brainstem at 10PN may mark the first expression of CCK-IR elements intrinsic to the brain. A broad spectrum of patterns of onset of CCK expression was observed in the opossum brain. The early occurrence and varied ontogenesis of CCK-IR structures indicates CCK may be involved in the function of a variety of circuits from the brainstem to the cerebral cortex. The early expression of CCK-IR structures in the dorsal brainstem suggests that CCK may modulate feeding behavior in the Monodelphis neonate. Cholecystokinin immunoreactivity in forebrain structures such as the suprachiasmatic nucleus, medial preoptic area, thalamus and cortical structures indicates that CCK may also be involved in circadian rhythmicity, reproductive functions, as well as the state of arousal of the Brazilian opossum. The ontogenic timing of CCK immunoreactivity in specific circuitry also indicates that CCK expression does not occur simultaneously throughout the brain. This pattern of CCK onset may relate to the temporal need for CCK in specific circuits of the central nervous system (CNS) during development.

  13. Clinical anatomy and imaging of the cranial nerves and skull base.

    PubMed

    Jha, Ruchira M; Klein, Joshua P

    2012-09-01

    Evaluation of patients with cranial neuropathies requires an understanding of brainstem anatomy and nerve pathways. Advances in neuroimaging, particularly high spatial resolution magnetic resonance imaging (MRI), have enabled visualization of these tiny structures and their related pathology. This review provides an approach toward using imaging in the evaluation of cranial nerve (CN) and skull base anatomy and pathology. Because brainstem nuclei are inextricably linked to the information contained within CNs, they are briefly mentioned whenever relevant; however, a comprehensive discussion of brainstem syndromes is beyond the scope of this review. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. Auditory Detection of the Human Brainstem Auditory Evoked Response.

    ERIC Educational Resources Information Center

    Kidd, Gerald, Jr.; And Others

    1993-01-01

    This study evaluated whether listeners can distinguish human brainstem auditory evoked responses elicited by acoustic clicks from control waveforms obtained with no acoustic stimulus when the waveforms are presented auditorily. Detection performance for stimuli presented visually was slightly, but consistently, superior to that which occurred for…

  15. Boxing sparring complicated by an acute subdural haematoma and brainstem haemorrhage.

    PubMed

    Hart, Michael G; Trivedi, Rikin A; Hutchinson, Peter J

    2012-10-01

    A professional boxer developed an acute subdural haematoma after boxing sparring. Despite timely surgical decompression, he had a poor overall outcome predominantly from a delayed brainstem haematoma. Magnetic resonance imaging (MRI) was used to elucidate the pathophysiology of the patients' injury and clinical condition.

  16. SEM Imaging for Observation of Morphological Changes in Anaemic Human Blood Cell

    NASA Astrophysics Data System (ADS)

    Datta, Triparna; Roychoudhury, Uttam

    Scanning Electron Microscopy (SEM) is utilized to elucidate the morphological changes in anaemic human red blood cells. Haemoglobin concentration in human blood is in the range of 11.5-13.5 g/dl in healthy adults. Haemoglobin concentration in anaemic red blood is below the lower limit of normal range. Sometimes, the nature of the abnormal shape of the blood cell determines the cause of anaemia. Normally, there occurs a variation in the diameter of the red blood cell (RBC) for different types of anaemia. Increased variation of size in blood cell is termed anisocytosis (a type of anaemia) (Mohan H, Text book of pathology, New Delhi). In case of anisocytosis, diameter of cells larger than normal cell is observed. The classification of anaemia by the size of blood cell is logical, i.e. common morphological abnormality of human blood cell (Davidson's principle and practice of medicine, Publisher Churchill Livingstone, London). Cells are studied under ZEISS SEM with different magnification and applied potential of kV range. Thus the diameters of RBCs in SEM have been compared with RBCs photographed with light microscope. Anaemic cells are observed overlapped with each other with increasing diameter.

  17. Three-dimensional relationship between high-order root-mean-square wavefront error, pupil diameter, and aging

    PubMed Central

    Applegate, Raymond A.; Donnelly, William J.; Marsack, Jason D.; Koenig, Darren E.; Pesudovs, Konrad

    2007-01-01

    We report root-mean-square (RMS) wavefront error (WFE) for individual aberrations and cumulative high-order (HO) RMS WFE for the normal human eye as a function of age by decade and pupil diameter in 1 mm steps from 3 to 7 mm and determine the relationship among HO RMS WFE, mean age for each decade of life, and luminance for physiologic pupil diameters. Subjects included 146 healthy individuals from 20 to 80 years of age. Ocular aberration was measured on the preferred eye of each subject (for a total of 146 eyes through dilated pupils; computed for 3, 4, 5, 6, and 7 mm pupils; and described with a tenth-radial-order normalized Zernike expansion. We found that HO RMS WFE increases faster with increasing pupil diameter for any given age and pupil diameter than it does with increasing age alone. A planar function accounts for 99% of the variance in the 3-D space defined by mean log HO RMS WFE, mean age for each decade of life, and pupil diameter. When physiologic pupil diameters are used to estimate HO RMS WFE as a function of luminance and age, at low luminance (9 cd/m2) HO RMS WFE decreases with increasing age. This normative data set details (1) the 3-D relationship between HO RMS WFE and age for fixed pupil diameters and (2) the 3-D relationship among HO RMS WFE, age, and luminance for physiologic pupil diameters. PMID:17301847

  18. Changes of neurotransmitters in the brainstem of patients with respiratory-pattern disorders during childhood.

    PubMed

    Saito, Y; Ito, M; Ozawa, Y; Obonai, T; Kobayashi, Y; Washizawa, K; Ohsone, Y; Takami, T; Oku, K; Takashima, S

    1999-06-01

    We examined neuropathologically and immunohistochemically the respiratory centers in the brainstem of two patients with Joubert syndrome (JS), three patients with congenital central hypoventilation syndrome (CCHS) and a patient with apneustic breathing (prolonged inspiratory pause) due to unknown etiology. Immunoreactivity (IR) of tryptophan hydroxylase (TPH) was decreased in the dorsal raphe nuclei of two patients with JS compared with age-matched controls, as well as in two patients with Dandy-Walker malformation. The two JS patients showed vermian defect and elongated cerebellar peduncles, and peculiar vascularities in the midline of the whole brainstem were also noted in one of these patients. These findings, as a whole, confirm that the midline structures of brainstem are disordered both structurally and functionally in JS, conceivably resulting in respiratory patterns and psychomotor deficits. IR of serotonin 1A receptor showed no significant changes in the medulla oblongata of these patients, however. In the parabrachial complex, IR of substance P was increased in two patients with CCHS, and one with apneustic breathing. IR of tyrosine hydroxylase was also increased in the latter. The brainstem of these patients showed reactive astrogliosis. These findings suggest preceding hypoxic episodes as well as an increased activity in the parabrachial complex which plays an important role in conducting the driving force to the medullary respiratory neurons from ascending sensory pathways.

  19. Developmental study of vitamin C distribution in children's brainstems by immunohistochemistry.

    PubMed

    Coveñas, R; González-Fuentes, J; Rivas-Infante, E; Lagartos-Donate, M J; Mangas, A; Geffard, M; Arroyo-Jiménez, M M; Cebada-Sánchez, S; Insausti, R; Marcos, P

    2015-09-01

    Vitamin C (Vit C) is an important antioxidant, exerts powerful neuroprotective brain effects and plays a role in neuronal development and maturation. Vit C is present in brain tissue at higher concentrations than in other organs, but its detailed distribution in brain is unknown. Immunohistochemical detection of this vitamin has been performed by using a highly specific antibody against Vit C. The aim of the present work was to analyze the distribution of Vit C in children's brainstems during postnatal development, comparing two groups of ages: younger and older than one year of life. In general, the same areas showing neurons with Vit C in young cases are also immunostained at older ages. The distribution of neurons containing Vit C was broader in the brainstems of older children, suggesting that brainstem neurons maintain or even increase their ability to retain Vit C along the life span. Immunohistochemical labeling revealed only cell bodies containing this vitamin, and no immunoreactive fibers were observed. The distribution pattern of Vit C in children's brainstems suggests a possible role of Vit C in brain homeostatic regulation. In addition, the constant presence of Vit C in neurons of locus coeruleus supports the important role of Vit C in noradrenaline synthesis, which seemed to be maintained along postnatal development. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Comparison between chloral hydrate and propofol-ketamine as sedation regimens for pediatric auditory brainstem response testing.

    PubMed

    Abulebda, Kamal; Patel, Vinit J; Ahmed, Sheikh S; Tori, Alvaro J; Lutfi, Riad; Abu-Sultaneh, Samer

    2017-10-28

    The use of diagnostic auditory brainstem response testing under sedation is currently the "gold standard" in infants and young children who are not developmentally capable of completing the test. The aim of the study is to compare a propofol-ketamine regimen to an oral chloral hydrate regimen for sedating children undergoing auditory brainstem response testing. Patients between 4 months and 6 years who required sedation for auditory brainstem response testing were included in this retrospective study. Drugs doses, adverse effects, sedation times, and the effectiveness of the sedative regimens were reviewed. 73 patients underwent oral chloral hydrate sedation, while 117 received propofol-ketamine sedation. 12% of the patients in the chloral hydrate group failed to achieve desired sedation level. The average procedure, recovery and total nursing times were significantly lower in the propofol-ketamine group. Propofol-ketamine group experienced higher incidence of transient hypoxemia. Both sedation regimens can be successfully used for sedating children undergoing auditory brainstem response testing. While deep sedation using propofol-ketamine regimen offers more efficiency than moderate sedation using chloral hydrate, it does carry a higher incidence of transient hypoxemia, which warrants the use of a highly skilled team trained in pediatric cardio-respiratory monitoring and airway management. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  1. Speech-evoked Brainstem Auditory Responses and Auditory Processing Skills: A Correlation in Adults with Hearing Loss

    PubMed Central

    Sanguebuche, Taissane Rodrigues; Peixe, Bruna Pias; Bruno, Rúbia Soares; Biaggio, Eliara Pinto Vieira; Garcia, Michele Vargas

    2018-01-01

    Introduction  The auditory system consists of sensory structures and central connections. The evaluation of the auditory pathway at a central level can be performed through behavioral and electrophysiological tests, because they are complementary to each other and provide important information about comprehension. Objective  To correlate the findings of speech brainstem-evoked response audiometry with the behavioral tests Random Gap Detection Test and Masking Level Difference in adults with hearing loss. Methods  All patients were submitted to a basic audiological evaluation, to the aforementioned behavioral tests, and to an electrophysiological assessment, by means of click-evoked and speech-evoked brainstem response audiometry. Results  There were no statistically significant values among the electrophysiological test and the behavioral tests. However, there was a significant correlation between the V and A waves, as well as the D and F waves, of the speech-evoked brainstem response audiometry peaks. Such correlations are positive, indicating that the increase of a variable implies an increase in another and vice versa. Conclusion  It was possible to correlate the findings of the speech-evoked brainstem response audiometry with those of the behavioral tests Random Gap Detection and Masking Level Difference. However, there was no statistically significant correlation between them. This shows that the electrophysiological evaluation does not depend uniquely on the behavioral skills of temporal resolution and selective attention. PMID:29379574

  2. Diameter distribution in a Brazilian tropical dry forest domain: predictions for the stand and species.

    PubMed

    Lima, Robson B DE; Bufalino, Lina; Alves, Francisco T; Silva, José A A DA; Ferreira, Rinaldo L C

    2017-01-01

    Currently, there is a lack of studies on the correct utilization of continuous distributions for dry tropical forests. Therefore, this work aims to investigate the diameter structure of a brazilian tropical dry forest and to select suitable continuous distributions by means of statistic tools for the stand and the main species. Two subsets were randomly selected from 40 plots. Diameter at base height was obtained. The following functions were tested: log-normal; gamma; Weibull 2P and Burr. The best fits were selected by Akaike's information validation criterion. Overall, the diameter distribution of the dry tropical forest was better described by negative exponential curves and positive skewness. The forest studied showed diameter distributions with decreasing probability for larger trees. This behavior was observed for both the main species and the stand. The generalization of the function fitted for the main species show that the development of individual models is needed. The Burr function showed good flexibility to describe the diameter structure of the stand and the behavior of Mimosa ophthalmocentra and Bauhinia cheilantha species. For Poincianella bracteosa, Aspidosperma pyrifolium and Myracrodum urundeuva better fitting was obtained with the log-normal function.

  3. A treatment planning comparison between a novel rotating gamma system and robotic linear accelerator based intracranial stereotactic radiosurgery/radiotherapy

    NASA Astrophysics Data System (ADS)

    Fareed, Muhammad M.; Eldib, Ahmed; Weiss, Stephanie E.; Hayes, Shelly B.; Li, Jinsheng; C-M Ma, Charlie

    2018-02-01

    To compare the dosimetric parameters of a novel rotating gamma ray system (RGS) with well-established CyberKnife system (CK) for treating malignant brain lesions. RGS has a treatment head of 16 cobalt-60 sources focused to the isocenter, which can rotate 360° on the ring gantry and swing 35° in the superior direction. We compared several dosimetric parameters in 10 patients undergoing brain stereotactic radiosurgery including plan normalization, number of beams and nodes for CK and shots for RGS, collimators used, estimated treatment time, D 2 cm and conformity index (CI) among two modalities. The median plan normalization for RGS was 56.7% versus 68.5% (p  =  0.002) for CK plans. The median number of shots from RGS was 7.5 whereas the median number of beams and nodes for CK was 79.5 and 46. The median collimator’s diameter used was 3.5 mm for RGS as compared to 5 mm for CK (p  =  0.26). Mean D 2 cm was 5.57 Gy for CyberKnife whereas it was 3.11 Gy for RGS (p  =  0.99). For RGS plans, the median CI was 1.4 compared to 1.3 for the CK treatment plans (p  =  0.98). The average minimum and maximum doses to optic chiasm were 21 and 93 cGy for RGS as compared to 32 and 209 cGy for CK whereas these were 0.5 and 364 cGy by RGS and 18 and 399 cGy by CK to brainstem. The mean V12 Gy for brain predicting for radionecrosis with RGS was 3.75 cm3 as compared to 4.09 cm3 with the CK (p  =  0.41). The dosimetric parameters of a novel RGS with a ring type gantry are comparable with CyberKnife, allowing its use for intracranial lesions and is worth exploring in a clinical setting.

  4. Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

    PubMed

    Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

    2018-04-12

    Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

  5. Neonatal Auditory Brainstem Responses Recorded from Four Electrode Montages.

    ERIC Educational Resources Information Center

    Stuart, Andrew; And Others

    1996-01-01

    Simultaneous auditory brainstem responses (ABRs) to click stimuli at 30 and 60 decibels were recorded from 16 full-term neonates with 4 different electrode arrays. Results indicated that ABR waveforms were morphologically similar to those recorded in adults. Waveform expression was variable with different electrode recording montages. (Author/DB)

  6. Brainstem Correlates of Temporal Auditory Processing in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Basu, Madhavi; Krishnan, Ananthanarayan; Weber-Fox, Christine

    2010-01-01

    Deficits in identification and discrimination of sounds with short inter-stimulus intervals or short formant transitions in children with specific language impairment (SLI) have been taken to reflect an underlying temporal auditory processing deficit. Using the sustained frequency following response (FFR) and the onset auditory brainstem responses…

  7. Positron Emission Tomography in Cochlear Implant and Auditory Brainstem Implant Recipients.

    ERIC Educational Resources Information Center

    Miyamoto, Richard T.; Wong, Donald

    2001-01-01

    Positron emission tomography imaging was used to evaluate the brain's response to auditory stimulation, including speech, in deaf adults (five with cochlear implants and one with an auditory brainstem implant). Functional speech processing was associated with activation in areas classically associated with speech processing. (Contains five…

  8. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER BRAINSTEM AUDITORY EVOKED RESPONSE (BAERS) IN RATS.

    EPA Science Inventory

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in auditory structures in the periphery and the brainstem and is altered following chlorpyrifos exposure. This study e...

  9. [Modification of impulse activity of cat brainstem monoaminergic cells caused by bemitil].

    PubMed

    Kolotilova, O I; Koreniuk, I I; Fokina, Iu O

    2008-01-01

    The study was carried out on brainstem noradrenergetic and serotoninergic neurons of cats and the effect of bemitil (100 mg/kg) introduction was investigated. The results indicate on specific bemitil action on scrotonin- and noradrenergetic neuromediator brain systems. Dose-dependency of the effect of bemitil is revealed.

  10. Relevance of deprivation studies in understanding rapid eye movement sleep

    PubMed Central

    Mehta, Rachna; Khan, Shafa; Mallick, Birendra N

    2018-01-01

    Rapid eye movement sleep (REMS) is a unique phenomenon essential for maintaining normal physiological processes and is expressed at least in species higher in the evolution. The basic scaffold of the neuronal network responsible for REMS regulation is present in the brainstem, which may be directly or indirectly influenced by most other physiological processes. It is regulated by the neurons in the brainstem. Various manipulations including chemical, elec-trophysiological, lesion, stimulation, behavioral, ontogenic and deprivation studies have been designed to understand REMS genesis, maintenance, physiology and functional significance. Although each of these methods has its significance and limitations, deprivation studies have contributed significantly to the overall understanding of REMS. In this review, we discuss the advantages and limitations of various methods used for REMS deprivation (REMSD) to understand neural regulation and physiological significance of REMS. Among the deprivation strategies, the flowerpot method is by far the method of choice because it is simple and convenient, exploits physiological parameter (muscle atonia) for REMSD and allows conducting adequate controls to overcome experimental limitations as well as to rule out nonspecific effects. Notwithstanding, a major criticism that the flowerpot method faces is that of perceived stress experienced by the experimental animals. Nevertheless, we conclude that like most methods, particularly for in vivo behavioral studies, in spite of a few limitations, given the advantages described above, the flowerpot method is the best method of choice for REMSD studies. PMID:29881316

  11. The diagnostic value of earlier and later components of Vestibular Evoked Myogenic Potentials (VEMP) in multiple sclerosis.

    PubMed

    Eleftheriadou, A; Deftereos, S N; Zarikas, V; Panagopoulos, G; Sfetsos, S; Karageorgiou, C L; Ferekidou, E; Kandiloros, D; Korres, S

    2009-01-01

    To evaluate the ability of VEMP to disclose spatial dissemination of Multiple Sclerosis. Forty-six MS patients with auditory and/or vestibular symptoms were studied. Patients were divided in two groups. Group 1 included 24 patients with brainstem MRI findings, and Group 2 included 22 patients without MRI findings. VEMP and BAEP have been recorded and assessed. Abnormal p13n23 wave was observed in 50%, while unilateral absence or bilateral delay of the n34p44 in 43% of the patients. The overall diagnostic value considering abnormal cases suggested by both first and second VEMP waves was increased to 71%. Statistically significant differences revealed between patients and controls for p13 latency (p=0.018). The p13n23 was abnormal in 7 patients, although MRI scanning did not reveal brainstem lesions. In 9 out of 18 MS patients suffering from unilateral hearing loss, n34p44 was present in the unaffected ears and absent in the affected side, although p13n23 was normal. Abnormal VEMP imply the presence of lesions undetected by MRI neuroimaging, which verifies the diagnostic value of the method. Unilateral absence of n34p44 complex was related with sensorineural hearing loss, supporting the hypothesis that n34p44 is of cochlear origin.

  12. Rapid measurement of auditory filter shape in mice using the auditory brainstem response and notched noise.

    PubMed

    Lina, Ioan A; Lauer, Amanda M

    2013-04-01

    The notched noise method is an effective procedure for measuring frequency resolution and auditory filter shapes in both human and animal models of hearing. Briefly, auditory filter shape and bandwidth estimates are derived from masked thresholds for tones presented in noise containing widening spectral notches. As the spectral notch widens, increasingly less of the noise falls within the auditory filter and the tone becomes more detectible until the notch width exceeds the filter bandwidth. Behavioral procedures have been used for the derivation of notched noise auditory filter shapes in mice; however, the time and effort needed to train and test animals on these tasks renders a constraint on the widespread application of this testing method. As an alternative procedure, we combined relatively non-invasive auditory brainstem response (ABR) measurements and the notched noise method to estimate auditory filters in normal-hearing mice at center frequencies of 8, 11.2, and 16 kHz. A complete set of simultaneous masked thresholds for a particular tone frequency were obtained in about an hour. ABR-derived filter bandwidths broadened with increasing frequency, consistent with previous studies. The ABR notched noise procedure provides a fast alternative to estimating frequency selectivity in mice that is well-suited to high through-put or time-sensitive screening. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Relevance of deprivation studies in understanding rapid eye movement sleep.

    PubMed

    Mehta, Rachna; Khan, Shafa; Mallick, Birendra N

    2018-01-01

    Rapid eye movement sleep (REMS) is a unique phenomenon essential for maintaining normal physiological processes and is expressed at least in species higher in the evolution. The basic scaffold of the neuronal network responsible for REMS regulation is present in the brainstem, which may be directly or indirectly influenced by most other physiological processes. It is regulated by the neurons in the brainstem. Various manipulations including chemical, elec-trophysiological, lesion, stimulation, behavioral, ontogenic and deprivation studies have been designed to understand REMS genesis, maintenance, physiology and functional significance. Although each of these methods has its significance and limitations, deprivation studies have contributed significantly to the overall understanding of REMS. In this review, we discuss the advantages and limitations of various methods used for REMS deprivation (REMSD) to understand neural regulation and physiological significance of REMS. Among the deprivation strategies, the flowerpot method is by far the method of choice because it is simple and convenient, exploits physiological parameter (muscle atonia) for REMSD and allows conducting adequate controls to overcome experimental limitations as well as to rule out nonspecific effects. Notwithstanding, a major criticism that the flowerpot method faces is that of perceived stress experienced by the experimental animals. Nevertheless, we conclude that like most methods, particularly for in vivo behavioral studies, in spite of a few limitations, given the advantages described above, the flowerpot method is the best method of choice for REMSD studies.

  14. Brainstem auditory evoked potentials in children with lead exposure.

    PubMed

    Alvarenga, Katia de Freitas; Morata, Thais Catalani; Lopes, Andrea Cintra; Feniman, Mariza Ribeiro; Corteletti, Lilian Cassia Bornia Jacob

    2015-01-01

    Earlier studies have demonstrated an auditory effect of lead exposure in children, but information on the effects of low chronic exposures needs to be further elucidated. To investigate the effect of low chronic exposures of the auditory system in children with a history of low blood lead levels, using an auditory electrophysiological test. Contemporary cross-sectional cohort. Study participants underwent tympanometry, pure tone and speech audiometry, transient evoked otoacoustic emissions, and brainstem auditory evoked potentials, with blood lead monitoring over a period of 35.5 months. The study included 130 children, with ages ranging from 18 months to 14 years, 5 months (mean age 6 years, 8 months ± 3 years, 2 months). The mean time-integrated cumulative blood lead index was 12 μg/dL (SD ± 5.7, range: 2.433). All participants had hearing thresholds equal to or below 20 dBHL and normal amplitudes of transient evoked otoacoustic emissions. No association was found between the absolute latencies of waves I, III, and V, the interpeak latencies I-III, III-V, and I-V, and the cumulative lead values. No evidence of toxic effects from chronic low lead exposures was observed on the auditory function of children living in a lead contaminated area. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  15. Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia.

    PubMed

    DeBoer, Mark D; Zhu, Xin Xia; Levasseur, Peter; Meguid, Michael M; Suzuki, Susumu; Inui, Akio; Taylor, John E; Halem, Heather A; Dong, Jesse Z; Datta, Rakesh; Culler, Michael D; Marks, Daniel L

    2007-06-01

    Cancer cachexia is a debilitating syndrome of anorexia and loss of lean body mass that accompanies many malignancies. Ghrelin is an orexigenic hormone with a short half-life that has been shown to improve food intake and weight gain in human and animal subjects with cancer cachexia. We used a rat model of cancer cachexia and administered human ghrelin and a synthetic ghrelin analog BIM-28131 via continuous infusion using sc osmotic minipumps. Tumor-implanted rats receiving human ghrelin or BIM-28131 exhibited a significant increase in food consumption and weight gain vs. saline-treated animals. We used dual-energy x-ray absorptiometry scans to show that the increased weight was due to maintenance of lean mass vs. a loss of lean mass in saline-treated animals. Also, BIM-28131 significantly limited the loss of fat mass normally observed in tumor-implanted rats. We further performed real-time PCR analysis of the hypothalami and brainstems and found that ghrelin-treated animals exhibited a significant increase in expression of orexigenic peptides agouti-related peptide and neuropeptide Y in the hypothalamus and a significant decrease in the expression of IL-1 receptor-I transcript in the hypothalamus and brainstem. We conclude that ghrelin and a synthetic ghrelin receptor agonist improve weight gain and lean body mass retention via effects involving orexigenic neuropeptides and antiinflammatory changes.

  16. A novel method of brainstem auditory evoked potentials using complex verbal stimuli.

    PubMed

    Kouni, Sophia N; Koutsojannis, Constantinos; Ziavra, Nausika; Giannopoulos, Sotirios

    2014-08-01

    The click and tone-evoked auditory brainstem responses are widely used in clinical practice due to their consistency and predictability. More recently, the speech-evoked responses have been used to evaluate subcortical processing of complex signals, not revealed by responses to clicks and tones. Disyllable stimuli corresponding to familiar words can induce a pattern of voltage fluctuations in the brain stem resulting in a familiar waveform, and they can yield better information about brain stem nuclei along the ascending central auditory pathway. We describe a new method with the use of the disyllable word "baba" corresponding to English "daddy" that is commonly used in many other ethnic languages spanning from West Africa to the Eastern Mediterranean all the way to the East Asia. This method was applied in 20 young adults institutionally diagnosed as dyslexic (10 subjects) or light dyslexic (10 subjects) who were matched with 20 sex, age, education, hearing sensitivity, and IQ-matched normal subjects. The absolute peak latencies of the negative wave C and the interpeak latencies of A-C elicited by verbal stimuli "baba" were found to be significantly increased in the dyslexic group in comparison with the control group. The method is easy and helpful to diagnose abnormalities affecting the auditory pathway, to identify subjects with early perception and cortical representation abnormalities, and to apply the suitable therapeutic and rehabilitation management.

  17. Neural Timing is Linked to Speech Perception in Noise

    PubMed Central

    Samira, Anderson; Erika, Skoe; Bharath, Chandrasekaran; Nina, Kraus

    2010-01-01

    Understanding speech in background noise is challenging for every listener, including those with normal peripheral hearing. This difficulty is due in part to the disruptive effects of noise on neural synchrony, resulting in degraded representation of speech at cortical and subcortical levels as reflected by electrophysiological responses. These problems are especially pronounced in clinical populations such as children with learning impairments. Given the established effects of noise on evoked responses, we hypothesized that listening-in-noise problems are associated with degraded processing of timing information at the brainstem level. Participants (66 children, ages 8 to 14 years, 22 females) were divided into groups based on their performance on clinical measures of speech-in-noise perception (SIN) and reading. We compared brainstem responses to speech syllables between top and bottom SIN and reading groups in the presence and absence of competing multi-talker babble. In the quiet condition, neural response timing was equivalent between groups. In noise, however, the bottom groups exhibited greater neural delays relative to the top groups. Group-specific timing delays occurred exclusively in response to the noise-vulnerable formant transition, not to the more perceptually-robust, steady-state portion of the stimulus. These results demonstrate that neural timing is disrupted by background noise and that greater disruptions are associated with the inability to perceive speech in challenging listening conditions. PMID:20371812

  18. Surgical monitoring with auditory evoked potentials.

    PubMed

    Lüders, H

    1988-07-01

    This comprehensive review of surgical monitoring with auditory evoked potentials (AEPs) includes a detailed discussion of techniques used for recording brainstem auditory evoked potentials, direct eight-nerve potentials, and electrocochleograms. The normal waveform of these different potentials is discussed, and the typical patterns of abnormalities seen with different insults to the peripheral or central auditory pathways are presented. The mechanisms most probably responsible for changes in AEPs during surgical procedures are analyzed. A critical analysis is made of what represents a significant change in AEPs. Also considered is the predictive value of intrasurgical changes of AEPs. Finally, attempts are made to determine whether AEPs monitoring can assist the surgeon in the prevention of postsurgical complications.

  19. Normative growth data for the external diameters of the external and internal iliac arteries in human fetuses--an anatomical, digital and statistical study.

    PubMed

    Szpinda, Michał; Szpinda, Anna

    2012-01-01

    Normative data on the diameters of the aorto-iliac segment are extremely useful in the diagnosis and monitoring of prenatal arterial variants and pathologies. The present study describes age-specific reference intervals and normal growth curves for the external diameters of the external and internal iliac arteries. Using anatomical dissection and digital-image analysis, the normal growth of the external diameters of the external and internal iliac arteries was studied in 124 spontaneously aborted human fetuses, aged 15-34 weeks. Neither sex differences nor laterality differences were found. The external diameters of the external iliac arteries increased from 0.31 +/- 0.06 to 1.41 +/- 0.31 mm on the right, and from 0.29 +/- 0.04 to 1.37 +/- 0.24 mm on the left, and generated the following growth curves of best fit: y = 0.665 - 0.056 x Age + 0.002 x Age2 +/- 0.143 (R2 = 0.82) and y = 0.612 - 0.052 x Age + 0.002 x Age2 +/- 0.118 (R2 = 0.86), respectively. The external diameters of the internal iliac arteries were found to be statistically larger than those of the external iliac arteries (p = 0.0000). The external diameters of the internal iliac arteries ranged from 0.44 +/- 0.07 to 2.04 +/- 0.43 mm on the right, and from 0.44 +/- 0.06 to 1.83 +/- 0.43 mm on the left, and modeled the following quadratic functions: y = 1.524 - 0.127 x Age + 0.004 x Age2 +/- 0.242 (R2 = 0.74), and y = 1.391 - 0.117 x Age + 0.004 x Age2 +/- 0.220 (R2 = 0.76), respectively. The right external iliac arteries (in 71% of the cases) and the right internal iliac arteries (in 65.3% of cases) were larger in external diameter. The values of the external diameters of the external and internal iliac arteries are independent of sex. A strong trend towards higher values for the right external and internal iliac arteries is noted. The external diameter of the internal iliac artery is nearly 1.5 times greater than that of the external iliac artery. Surprisingly, normal growth of the external diameters of the external and internal iliac arteries follows quadratic functions.

  20. Diverse autonomic regulation of pupillary function and the cardiovascular system during alcohol withdrawal.

    PubMed

    Jochum, Thomas; Hoyme, Johannes; Schulz, Steffen; Weißenfels, Markus; Voss, Andreas; Bär, Karl-Jürgen

    2016-02-01

    Previous research indicated the complexity of autonomic dysfunction during acute alcohol withdrawal. This study aimed to investigate the pupillary light reflex as an indicator of midbrain and brainstem regulatory systems in relation to cardiovascular autonomic function. Thirty male patients were included in the study. They were investigated during acute alcohol withdrawal syndrome and 24h later during clomethiazole treatment and compared to healthy controls. Parameters of pupillary light reflex of both eyes as well as heart rate variability, blood pressure variability and baroreflex sensitivity (BRS) were studied. We observed significantly reduced sympathetic (small diameter, e.g., left eye: 5.00 in patients vs. 5.91 mm in controls) and vagal modulation (e.g., prolonged latencies, left eye: 0.28 vs. 0.26 ms) regarding both pupils during acute alcohol withdrawal syndrome. Cardiovascular parameters showed reduced vagal modulation (e.g., b-slope of BRS: 7. 57 vs. 13.59 ms/mm Hg) and mixed results for sympathetic influence. After 24h, autonomic dysfunction improved significantly, both for the pupils (e.g., left diameter: 5.38 mm) and the heart (e.g., b-slope of BRS: 9.34 ms/mm Hg). While parameters obtained from the pupil correlated with cardiac autonomic function (e.g, BRS and left diameter: r=0.564) in healthy controls, no such pattern was observed in patients. Results obtained from the pupil during acute alcohol withdrawal do not simply mirror autonomic dysfunction regarding the heart. Pupillary and cardiovascular changes after 24h indicate state dependencies of the results. The findings are discussed with respect to autonomic mechanisms and potentially involved brain regions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Mechanisms for Adjusting Interaural Time Differences to Achieve Binaural Coincidence Detection

    PubMed Central

    Seidl, Armin H.; Rubel, Edwin W; Harris, David M.

    2010-01-01

    Understanding binaural perception requires detailed analyses of the neural circuitry responsible for the computation of interaural time differences (ITDs). In the avian brainstem, this circuit consists of internal axonal delay lines innervating an array of coincidence detector neurons that encode external ITDs. Nucleus magnocellularis (NM) neurons project to the dorsal dendritic field of the ipsilateral nucleus laminaris (NL) and to the ventral field of the contralateral NL. Contralateral-projecting axons form a delay line system along a band of NL neurons. Binaural acoustic signals in the form of phase-locked action potentials from NM cells arrive at NL and establish a topographic map of sound source location along the azimuth. These pathways are assumed to represent a circuit similar to the Jeffress model of sound localization, establishing a place code along an isofrequency contour of NL. Three-dimensional measurements of axon lengths reveal major discrepancies with the current model; the temporal offset based on conduction length alone makes encoding of physiological ITDs impossible. However, axon diameter and distances between Nodes of Ranvier also influence signal propagation times along an axon. Our measurements of these parameters reveal that diameter and internode distance can compensate for the temporal offset inferred from axon lengths alone. Together with other recent studies these unexpected results should inspire new thinking on the cellular biology, evolution and plasticity of the circuitry underlying low frequency sound localization in both birds and mammals. PMID:20053889

  2. Normal stresses in shear thickening granular suspensions.

    PubMed

    Pan, Zhongcheng; de Cagny, Henri; Habibi, Mehdi; Bonn, Daniel

    2017-05-24

    When subjected to shear, granular suspensions exhibit normal stresses perpendicular to the shear plane but the magnitude and sign of the different components of the normal stresses are still under debate. By performing both oscillatory and rotational rheology measurements on shear thickening granular suspensions and systematically varying the particle diameters and the gap sizes between two parallel-plates, we show that a transition from a positive to a negative normal stress can be observed. We find that frictional interactions which determine the shear thickening behavior of suspensions contribute to the positive normal stresses. Increasing the particle diameters or decreasing the gap sizes leads to a growing importance of hydrodynamic interactions, which results in negative normal stresses. We determine a relaxation time for the system, set by both the pore and the gap sizes, that governs the fluid flow through the inter-particle space. Finally, using a two-fluid model we determine the relative contributions from the particle phase and the liquid phase.

  3. Newborn Auditory Brainstem Evoked Responses (ABRs): Longitudinal Correlates in the First Year.

    ERIC Educational Resources Information Center

    Murray, Ann D.

    1988-01-01

    Aimed to determine to what degree newborns' auditory brainstem evoked responses (ABRs) predict delayed or impaired development during the first year. When 93 infants' ABRs were evaluated at three, six, and nine months, newborn ABR was moderately sensitive for detecting hearing impairment and more sensitive than other indicators in detecting…

  4. Evidence from Auditory Nerve and Brainstem Evoked Responses for an Organic Brain Lesion in Children with Autistic Traits

    ERIC Educational Resources Information Center

    Student, M.; Sohmer, H.

    1978-01-01

    In an attempt to resolve the question as to whether children with autistic traits have an organic nervous system lesion, auditory nerve and brainstem evoked responses were recorded in a group of 15 children (4 to 12 years old) with autistic traits. (Author)

  5. Brainstem Transcription of Speech Is Disrupted in Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Russo, Nicole; Nicol, Trent; Trommer, Barbara; Zecker, Steve; Kraus, Nina

    2009-01-01

    Language impairment is a hallmark of autism spectrum disorders (ASD). The origin of the deficit is poorly understood although deficiencies in auditory processing have been detected in both perception and cortical encoding of speech sounds. Little is known about the processing and transcription of speech sounds at earlier (brainstem) levels or…

  6. Newborn Auditory Brainstem Evoked Responses (ABRs): Prenatal and Contemporary Correlates.

    ERIC Educational Resources Information Center

    Murray, Ann D.

    1988-01-01

    Presented are a literature review and new data on correlates of newborn auditory brainstem evoked responses (ABRs). Concludes that disorders of the central components of the ABR may be more of prenatal than of postnatal origin. The I-V interval had low but reliable correlations with four of 11 Brazelton scale variables. (RH)

  7. Neuronal Determinants of Motor Disability in MS

    DTIC Science & Technology

    2015-10-01

    well as in partial development of fiber tracking techniques for segmentation of motor pathways in the brain, brainstem , and spinal cord. We have...of  motor  neurons  at  the  cortex   and  axons  traversing  the  brain,   brainstem  and  spinal  cord   4 - 6 Dr

  8. The Effect of Otitis Media with Effusion on the Masking-Level Difference and the Auditory Brainstem Response.

    ERIC Educational Resources Information Center

    Hall, Joseph W.; Grose, John H.

    1993-01-01

    This study of 14 children (ages 5-9) with a history of otitis media with effusion found that subjects had significantly reduced masking-level differences (MLD) compared to controls. Results suggest that the reduction in MLD may be related to abnormal brainstem processing. (Author/JDD)

  9. Auditory Brainstem Responses in Young Adults with Down Syndrome.

    ERIC Educational Resources Information Center

    Widen, Judith E.; And Others

    1987-01-01

    In a study of 15 individuals (ages 15-21) with Down Syndrome, auditory brainstem response (ABR) detection levels were elevated, response amplitude reduced, and latency-intensity functions were significantly steeper than for a matched control group. Findings were associated with an impairment in hearing sensitivity at 8000 Hz for the experimental…

  10. Electrophysiological Evidence for the Sources of the Masking Level Difference

    ERIC Educational Resources Information Center

    Fowler, Cynthia G.

    2017-01-01

    Purpose: The purpose of this review article is to review evidence from auditory evoked potential studies to describe the contributions of the auditory brainstem and cortex to the generation of the masking level difference (MLD). Method: A literature review was performed, focusing on the auditory brainstem, middle, and late latency responses used…

  11. Hearing Loss in Middle-Age Persons with Down Syndrome.

    ERIC Educational Resources Information Center

    Evenhuis, H. M.; And Others

    1992-01-01

    This study assessed the hearing function of 35 middle-aged adults with Down's syndrome by means of otoscopy, impedance audiometry, brainstem evoked response audiometry, and pure tone audiometry. The study found brainstem evoked response audiometry useful for routine audiological assessment, as it identified hearing losses of 20 to 90 decibels in…

  12. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hussain, Aamir; Brown, Paul D.; Stafford, Scott L.

    Purpose: Patients with brainstem metastases have limited treatment options. In this study, we reviewed outcomes after stereotactic radiosurgery (SRS) in the management of patients with brainstem metastases. Methods and Materials: Records were reviewed of 22 consecutive patients presenting with brainstem metastases who underwent SRS. The most frequent primary malignancy was the lung (n = 11), followed by breast (n = 3) and kidney (n = 2). Three patients (14%) also underwent whole-brain radiation therapy (WBRT). The median tumor volume was 0.9 mL (range, 0.1-3.3 mL); the median tumor margin dose was 16 Gy (range, 14-23 Gy). Results: Median survival timemore » after SRS was 8.5 months. Although local tumor control was achieved in all patients with imaging follow-up (n = 19), 5 patients died from development and progression of new brain metastases. Two patients (9%) had symptom improvement after SRS, whereas 1 patient (5%) developed a new hemiparesis after SRS. Conclusions: Radiosurgery is safe and provides a high local tumor control rate for patients with small brainstem metastases. Patients with limited systemic disease and good performance status should be strongly considered for SRS.« less

  13. CO2-evoked release of PGE2 modulates sighs and inspiration as demonstrated in brainstem organotypic culture

    PubMed Central

    Forsberg, David; Horn, Zachi; Tserga, Evangelia; Smedler, Erik; Silberberg, Gilad; Shvarev, Yuri; Kaila, Kai; Uhlén, Per; Herlenius, Eric

    2016-01-01

    Inflammation-induced release of prostaglandin E2 (PGE2) changes breathing patterns and the response to CO2 levels. This may have fatal consequences in newborn babies and result in sudden infant death. To elucidate the underlying mechanisms, we present a novel breathing brainstem organotypic culture that generates rhythmic neural network and motor activity for 3 weeks. We show that increased CO2 elicits a gap junction-dependent release of PGE2. This alters neural network activity in the preBötzinger rhythm-generating complex and in the chemosensitive brainstem respiratory regions, thereby increasing sigh frequency and the depth of inspiration. We used mice lacking eicosanoid prostanoid 3 receptors (EP3R), breathing brainstem organotypic slices and optogenetic inhibition of EP3R+/+ cells to demonstrate that the EP3R is important for the ventilatory response to hypercapnia. Our study identifies a novel pathway linking the inflammatory and respiratory systems, with implications for inspiration and sighs throughout life, and the ability to autoresuscitate when breathing fails. DOI: http://dx.doi.org/10.7554/eLife.14170.001 PMID:27377173

  14. Endoscopic third ventriculostomy for hydrocephalus in brainstem glioma: a case series.

    PubMed

    Kobayashi, Natsuki; Ogiwara, Hideki

    2016-07-01

    A brainstem glioma is an incurable brain tumor that can be complicated by hydrocephalus. A ventriculoperitoneal (VP) shunt is generally performed for the control of hydrocephalus. This study aimed to reveal the safety and efficacy of an endoscopic third ventriculostomy (ETV) for hydrocephalus in brainstem gliomas. Six patients who had pontine glioma with hydrocephalus underwent an ETV between May 2010 and November 2015. In all the cases, there were one or more symptoms of hydrocephalus (headache, nausea, vomiting, or lethargy). Retrospective review of these patients was performed using the medical records and neuroimagings. The ETV was performed safely and there were no intraoperative complications in all patients. The mean follow-up period was 12.3 months. An immediate symptomatic relief of hydrocephalus and an adequate control of symptoms were achieved without a VP shunt in all patients. The ETV is considered to be an effective and safe procedure for the treatment of hydrocephalus in brainstem gliomas. Determining the ventriculostomy site according to the preoperative MRI in each case is considered to be important for the safe procedure.

  15. Vessel Sampling and Blood Flow Velocity Distribution With Vessel Diameter for Characterizing the Human Bulbar Conjunctival Microvasculature.

    PubMed

    Wang, Liang; Yuan, Jin; Jiang, Hong; Yan, Wentao; Cintrón-Colón, Hector R; Perez, Victor L; DeBuc, Delia C; Feuer, William J; Wang, Jianhua

    2016-03-01

    This study determined (1) how many vessels (i.e., the vessel sampling) are needed to reliably characterize the bulbar conjunctival microvasculature and (2) if characteristic information can be obtained from the distribution histogram of the blood flow velocity and vessel diameter. Functional slitlamp biomicroscope was used to image hundreds of venules per subject. The bulbar conjunctiva in five healthy human subjects was imaged on six different locations in the temporal bulbar conjunctiva. The histograms of the diameter and velocity were plotted to examine whether the distribution was normal. Standard errors were calculated from the standard deviation and vessel sample size. The ratio of the standard error of the mean over the population mean was used to determine the sample size cutoff. The velocity was plotted as a function of the vessel diameter to display the distribution of the diameter and velocity. The results showed that the sampling size was approximately 15 vessels, which generated a standard error equivalent to 15% of the population mean from the total vessel population. The distributions of the diameter and velocity were not only unimodal, but also somewhat positively skewed and not normal. The blood flow velocity was related to the vessel diameter (r=0.23, P<0.05). This was the first study to determine the sampling size of the vessels and the distribution histogram of the blood flow velocity and vessel diameter, which may lead to a better understanding of the human microvascular system of the bulbar conjunctiva.

  16. Patient-specific Radiation Dose and Cancer Risk for Pediatric Chest CT

    PubMed Central

    Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

    2011-01-01

    Purpose: To estimate patient-specific radiation dose and cancer risk for pediatric chest computed tomography (CT) and to evaluate factors affecting dose and risk, including patient size, patient age, and scanning parameters. Materials and Methods: The institutional review board approved this study and waived informed consent. This study was HIPAA compliant. The study included 30 patients (0–16 years old), for whom full-body computer models were recently created from clinical CT data. A validated Monte Carlo program was used to estimate organ dose from eight chest protocols, representing clinically relevant combinations of bow tie filter, collimation, pitch, and tube potential. Organ dose was used to calculate effective dose and risk index (an index of total cancer incidence risk). The dose and risk estimates before and after normalization by volume-weighted CT dose index (CTDIvol) or dose–length product (DLP) were correlated with patient size and age. The effect of each scanning parameter was studied. Results: Organ dose normalized by tube current–time product or CTDIvol decreased exponentially with increasing average chest diameter. Effective dose normalized by tube current–time product or DLP decreased exponentially with increasing chest diameter. Chest diameter was a stronger predictor of dose than weight and total scan length. Risk index normalized by tube current–time product or DLP decreased exponentially with both chest diameter and age. When normalized by DLP, effective dose and risk index were independent of collimation, pitch, and tube potential (<10% variation). Conclusion: The correlations of dose and risk with patient size and age can be used to estimate patient-specific dose and risk. They can further guide the design and optimization of pediatric chest CT protocols. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101900/-/DC1 PMID:21467251

  17. Patient-specific radiation dose and cancer risk for pediatric chest CT.

    PubMed

    Li, Xiang; Samei, Ehsan; Segars, W Paul; Sturgeon, Gregory M; Colsher, James G; Frush, Donald P

    2011-06-01

    To estimate patient-specific radiation dose and cancer risk for pediatric chest computed tomography (CT) and to evaluate factors affecting dose and risk, including patient size, patient age, and scanning parameters. The institutional review board approved this study and waived informed consent. This study was HIPAA compliant. The study included 30 patients (0-16 years old), for whom full-body computer models were recently created from clinical CT data. A validated Monte Carlo program was used to estimate organ dose from eight chest protocols, representing clinically relevant combinations of bow tie filter, collimation, pitch, and tube potential. Organ dose was used to calculate effective dose and risk index (an index of total cancer incidence risk). The dose and risk estimates before and after normalization by volume-weighted CT dose index (CTDI(vol)) or dose-length product (DLP) were correlated with patient size and age. The effect of each scanning parameter was studied. Organ dose normalized by tube current-time product or CTDI(vol) decreased exponentially with increasing average chest diameter. Effective dose normalized by tube current-time product or DLP decreased exponentially with increasing chest diameter. Chest diameter was a stronger predictor of dose than weight and total scan length. Risk index normalized by tube current-time product or DLP decreased exponentially with both chest diameter and age. When normalized by DLP, effective dose and risk index were independent of collimation, pitch, and tube potential (<10% variation). The correlations of dose and risk with patient size and age can be used to estimate patient-specific dose and risk. They can further guide the design and optimization of pediatric chest CT protocols. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101900/-/DC1. RSNA, 2011

  18. Normal appendiceal diameter in children: does choice of CT oral contrast (VoLumen versus Gastrografin) make a difference?

    PubMed

    Victoria, Teresa; Mahboubi, Soroosh

    2010-09-01

    Appendicitis is a common pediatric emergency and one of the most common causes for surgical exploration in the pediatric patient. Imaging has become an essential tool in the evaluation of the child with suspected appendicitis, aiming to avoid misdiagnosis and to facilitate early surgery, thus decreasing potential morbidity from ruptured appendicitis. The objective of this paper is to compare the luminal diameter of the normal appendix by computed tomography (CT) when utilizing the traditionally used high-attenuation oral contrast material (OCM), Gastrografin, and the relatively new neutral agent VoLumen, with the goal of establishing normal appendiceal size parameters for this neutral OCM. Twenty-six cases of VoLumen-enhanced CT studies of the abdomen and pelvis were identified, of which 13 met the inclusion criteria. These were randomly matched to age control Gastrografin CT examinations. Appendiceal diameters (from wall to wall) were measured in three orthogonal planes and the average of these was recorded. We show that there is no statistical difference between normal appendiceal diameters in patients with a VoLumen-opacified CT versus a Gastrografin-enhanced CT (p = 0.8) being 5.0 +/- 1.3 and 5.1 +/- 1.5 mm, respectively. Chart review revealed no clinical suspicion of appendicitis prior to imaging or on discharge diagnosis in the patients included in this study. The rate of nonvisualization of the appendix with VoLumen in our study was 31%, which equals previously published estimates in children. In summary, as VoLumen use increases in the evaluation of abdominal pathology in the ailing child, we provide guidelines to identify the normal appendix when utilizing this oral contrast agent.

  19. Identification of clinical target areas in the brainstem of prion‐infected mice

    PubMed Central

    Mirabile, Ilaria; Jat, Parmjit S.; Brandner, Sebastian

    2015-01-01

    Aims While prion infection ultimately involves the entire brain, it has long been thought that the abrupt clinical onset and rapid neurological decline in laboratory rodents relates to involvement of specific critical neuroanatomical target areas. The severity and type of clinical signs, together with the rapid progression, suggest the brainstem as a candidate location for such critical areas. In this study we aimed to correlate prion pathology with clinical phenotype in order to identify clinical target areas. Method We conducted a comprehensive survey of brainstem pathology in mice infected with two distinct prion strains, which produce different patterns of pathology, in mice overexpressing prion protein (with accelerated clinical onset) and in mice in which neuronal expression was reduced by gene targeting (which greatly delays clinical onset). Results We identified specific brainstem areas that are affected by prion pathology during the progression of the disease. In the early phase of disease the locus coeruleus, the nucleus of the solitary tract, and the pre‐Bötzinger complex were affected by prion protein deposition. This was followed by involvement of the motor and autonomic centres of the brainstem. Conclusions Neurodegeneration in the locus coeruleus, the nucleus of the solitary tract and the pre‐Bötzinger complex predominated and corresponded to the manifestation of the clinical phenotype. Because of their fundamental role in controlling autonomic function and the overlap with clinical signs in sporadic Creutzfeldt–Jakob disease, we suggest that these nuclei represent key clinical target areas in prion diseases. PMID:25311251

  20. The analgesic agent tapentadol inhibits calcitonin gene-related peptide release from isolated rat brainstem via a serotonergic mechanism.

    PubMed

    Greco, Maria Cristina; Navarra, Pierluigi; Tringali, Giuseppe

    2016-01-15

    In this study we tested the hypothesis that tapentadol inhibits GGRP release from the rat brainstem through a mechanism mediated by the inhibition of NA reuptake; as a second alternative hypothesis, we investigated whether tapentadol inhibits GGRP release via the inhibition of 5-HT reuptake. Rat brainstems were explanted and incubated in short-term experiments. CGRP released in the incubation medium was taken as a marker of CGRP release from the central terminals of trigeminal neurons within the brainstem. CGRP levels were measured by radioimmunoassay under basal conditions or in the presence of tapentadol; NA, 5-HT, clonidine, yohimbine and ondansetron were used as pharmacological tools to investigate the action mechanism of tapentadol. The α2-antagonist yohimbine failed to counteract the effects of tapentadol. Moreover, neither NA nor the α2-agonist clonidine per se inhibited K(+)-stimulated CGRP release, thereby indicating that the effects of tapentadol are nor mediated through the block of NA reuptake. Further experiments showed that 5-HT and tramadol, which inhibits both NA and 5-HT reuptake, significantly reduced K(+)-stimulated CGRP release. Moreover, the 5-HT3 antagonist ondansetron was able to counteract the effects of tapentadol in this system. This study provided pharmacological evidence that tapentadol inhibits stimulated CGRP release from the rat brainstem in vitro through a mechanism involving an increase in 5-HT levels in the system and the subsequent activation of 5-HT3 receptors. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. A challenging entity of endovascular embolization with ONYX for brainstem arteriovenous malformation: Experience from 13 cases.

    PubMed

    Jin, Hengwei; Liu, Zhan; Chang, Qing; Chen, Chang; Ge, Huijian; Lv, Xianli; Li, Youxiang

    2017-10-01

    Objective Brainstem arteriovenous malformations (AVMs) are rare lesions with a high risk of intracranial hemorrhage and are challenging to treat. We present our experience of endovascular embolization with Onyx in these aggressive lesions. Materials and methods Between 2007 and 2016, 13 patients with brainstem AVMs were embolized with Onyx at our center. Twelve patients presented with intracranial hemorrhage and one with headache. Retrospective examinations of patient demographics, clinical presentation, angiographic features, treatment modalities, postoperative complications and outcomes were carried out. Results The AVMs were in the midbrain in 10 patients (one anterior and nine posterior or dorsal), in the posterior pons in two and pontomedullary in one. Complete occlusion was achieved in three patients. Gamma knife radiosurgery was performed in six patients who were near-completely or partially embolized. Postoperative complications, including five cases of ischemia and one case of hemorrhage, resulted in four cases of neurological deterioration and two deaths. Clinical follow-up was obtained in 10 patients at a mean period of 45.2 months (range 3 to 93 months). During the follow-up, good clinical outcomes were observed in seven patients with posterior or dorsal midbrain AVMs, and one patient with a posterior pons AVM that was partially occluded died of intracranial hemorrhage. Conclusion Endovascular embolization for brainstem AVM with Onyx is a technical challenge and the reflux of Onyx may cause severe complications. Individualized treatment is needed based on the specific subtype of brainstem AVM.

  2. Intraparenchymal epidermoid cyst: proper surgical management may lead to satisfactory outcome.

    PubMed

    Zheng, Jian; Wang, Chun; Liu, Fengqiang

    2018-03-12

    Intraparenchymal epidermoid cysts (IECs) are rare lesions, thus the preoperative diagnosis and proper surgical management are still a challenge. We searched the database at our institution and performed a search of English literature in PubMed and Google Scholar. Keywords used were as follows: "intraparenchymal"; "intracerebral"; "intraaxial"; "epidermoid cyst"; "brainstem"; "cholesteatoma"; "pearly tumor". Only cases that were true intraparenchymally located and contained adequate clinical information were included. Six cases of IECs were recorded at our institution. Total removal was achieved in all the six patients with good outcomes. 29 cases meeting the above criteria were found in the literature. Including ours, a total of 35 patients were analyzed. Females were more frequently affected (F/M ratio, 1.9:1). Most of them were located in the brainstem (42.9%) and temporal lobe (22.9%). While in children, all were located in the brainstem. 45.2% showed subtle peripheral enhancement on Magnetic Resonance Imaging (MRI), and all appeared hyperintense on Diffusion Weighted Imaging (DWI). In the subgroup of cerebral lobes and cerebellums, total resection was achieved in 89.5%, and they all showed good outcomes. While in the subgroup of brainstem, 46.7% (seven cases) underwent total resection and 50% (three cases) of them died postoperatively. MRI with DWI is helpful in the preoperative diagnosis. Total resection should be achieved for the IECs located in cerebral lobes and cerebellums, while subtotal resection is a wise and safe strategy for the IECs located in the brainstem.

  3. A Comparison between the Kawase and Extended Retrosigmoid Approaches (Retrosigmoid Transtentorial and Retrosigmoid Intradural Suprameatal Approaches) for Accessing the Petroclival Tumors. A Cadaveric Study

    PubMed Central

    Sharma, Mayur; Ambekar, Sudheer; Guthikonda, Bharat; Nanda, Anil

    2014-01-01

    Background The aim of our study was to compare the area of exposure at the ventral brainstem and petroclival region offered by the Kawase, retrosigmoid transtentorial (RTT), and the retrosigmoid intradural suprameatal (RISA) approaches in cadaveric models. Methods We performed 15 approaches (five each of the Kawase, RISA, and RTT approaches) on silicone-injected adult cadaver heads. Ventral brainstem and petroclival areas of exposure were measured and compared. Results The mean ventral brainstem area exposed by the Kawase approach was 55.00 ± 24.1 mm2, significantly less than that exposed by RTT (441 ± 63.3 mm2) and RISA (311 ± 61 mm2) (p < 0.05). The area of ventral brainstem exposure was significantly more via RTT than through RISA (p = 0.01). The mean petroclival area of exposure through the Kawase approach was significantly smaller than that obtained through the RTT and RISA approaches (101.7 ± 545.01 mm2, 696 ± 57.7 mm2, and 716.7 ± 51.4 mm2, respectively). Conclusion Retrosigmoid approaches provide a greater exposure of the brainstem and petroclival areas. The Kawase approach is ideally suited for lesions around the Meckel cave with an extension into the middle fossa. These approaches can be used in conjunction with one another to access petroclival tumors. PMID:24967151

  4. Association of the Gutta-Induced Microenvironment With Corneal Endothelial Cell Behavior and Demise in Fuchs Endothelial Corneal Dystrophy.

    PubMed

    Kocaba, Viridiana; Katikireddy, Kishore Reddy; Gipson, Ilene; Price, Marianne O; Price, Francis W; Jurkunas, Ula V

    2018-05-31

    The number and size of guttae increase over time in Fuchs endothelial corneal dystrophy (FECD); however, the association between these physical parameters and disease pathogenesis is unclear. To determine the role of guttae in corneal endothelial cell function. In an in vitro model, cells from a human corneal endothelial cell line, HCENC-21T, were seeded on decellularized normal (n = 30) and FECD (n = 70) endothelial basement (Descemet) membranes (DMs). Normal human corneas were sent to our laboratory from 3 sources. The study took place at the Schepens Eye Research Institute, Massachusetts Eye and Ear, Boston, and was performed from September 2015 to July 2017. Normal DMs were obtained from 3 different tissue banks and FECD-DMs were obtained from patients undergoing endothelial keratoplasty in 2 departments. Endothelial cell shape, growth, and migration were assessed by live-cell imaging, and gene expression analysis as a function of guttae diameter was assessed by laser capture microscopy. Mean (SD) age of normal-DMs donors was 65.6 (4.4) years (16 women [53%]), and mean (SD) age of FECD-DMs donors was 68.9 (10.6) years (43 women [61%]). Cells covered a greater area (mean [SD], 97.7% [8.5%]) with a greater mean (SD) number of cells (2083[153] cells/mm2) on the normal DMs compared with the FECD DMs (72.8% [11%]; P = .02 and 1541 [221] cells/mm2 221/mm2; P = .01, respectively). Differences in endothelial cell growth over guttae were observed on FECD DMs depending on the guttae diameter. Guttae with a mean (SD) diameter of 10.5 (2.9) μm did not impede cell growth, whereas those with a diameter of 21.1 (4.9) μm were covered only by the cell cytoplasm. Guttae with the largest mean (SD) diameter, 31.8 (3.8) μm, were not covered by cells, which instead surrounded them in a rosette pattern. Moreover, cells adjacent to large guttae upregulated αSMA, N-cadherin, Snail1, and NOX4 genes compared with ones grown on normal DMs or small guttae. Furthermore, large guttae induced TUNEL-positive apoptosis in a rosette pattern, similar to ex vivo FECD specimens. These findings highlight the important role of guttae in endothelial cell growth, migration, and survival. These data suggest that cell therapy procedures in FECD might be guided by the diameter of the host guttae if subsequent clinical studies confirm these laboratory findings.

  5. Automated estimation of abdominal effective diameter for body size normalization of CT dose.

    PubMed

    Cheng, Phillip M

    2013-06-01

    Most CT dose data aggregation methods do not currently adjust dose values for patient size. This work proposes a simple heuristic for reliably computing an effective diameter of a patient from an abdominal CT image. Evaluation of this method on 106 patients scanned on Philips Brilliance 64 and Brilliance Big Bore scanners demonstrates close correspondence between computed and manually measured patient effective diameters, with a mean absolute error of 1.0 cm (error range +2.2 to -0.4 cm). This level of correspondence was also demonstrated for 60 patients on Siemens, General Electric, and Toshiba scanners. A calculated effective diameter in the middle slice of an abdominal CT study was found to be a close approximation of the mean calculated effective diameter for the study, with a mean absolute error of approximately 1.0 cm (error range +3.5 to -2.2 cm). Furthermore, the mean absolute error for an adjusted mean volume computed tomography dose index (CTDIvol) using a mid-study calculated effective diameter, versus a mean per-slice adjusted CTDIvol based on the calculated effective diameter of each slice, was 0.59 mGy (error range 1.64 to -3.12 mGy). These results are used to calculate approximate normalized dose length product values in an abdominal CT dose database of 12,506 studies.

  6. Coronary artery dimensions in normal Indians.

    PubMed

    Raut, Barendra Kumar; Patil, Vijaysinh Namdeo; Cherian, George

    Diameter of coronary artery is an important predictor of outcome after percutaneous coronary interventions and coronary artery bypass graft surgery. There is very limited data available about coronary artery dimensions in an Indian population. To study the normal dimensions of the coronary artery segments in Indians without coronary artery disease by using quantitative coronary angiography and also to compare the dimensions in Indians with Western. 229 patients who have undergone coronary angiography with entirely normal coronary angiogram were included in our study. This study showed the diameter of vessels in males and females when taken together the left main was larger in size followed by proximal LAD, proximal RCA & proximal LCX respectively (4.08±0.44mm, 3.27±0.23mm, 3.20±0.37mm, 2.97±0.37mm).When the vessel diameter was indexed to body surface area there was no statistical difference between male and female (p value>0.05). The computed value of proximal coronary artery diameter unadjusted for individual body surface area, when compared to Caucasians showed that Caucasians have larger coronary artery dimensions than Indians. But when the proximal vessel diameter was indexed to body surface area there was no statistical significant difference between Indians and Caucasians (p value>0.05). We found that coronary artery size when indexed to body surface area is not statistically different in Indian males and females and compared to Caucasians. However with a smaller body habitus Indians have smaller coronary arteries. Copyright © 2017. Published by Elsevier B.V.

  7. Robust Machine Learning-Based Correction on Automatic Segmentation of the Cerebellum and Brainstem.

    PubMed

    Wang, Jun Yi; Ngo, Michael M; Hessl, David; Hagerman, Randi J; Rivera, Susan M

    2016-01-01

    Automated segmentation is a useful method for studying large brain structures such as the cerebellum and brainstem. However, automated segmentation may lead to inaccuracy and/or undesirable boundary. The goal of the present study was to investigate whether SegAdapter, a machine learning-based method, is useful for automatically correcting large segmentation errors and disagreement in anatomical definition. We further assessed the robustness of the method in handling size of training set, differences in head coil usage, and amount of brain atrophy. High resolution T1-weighted images were acquired from 30 healthy controls scanned with either an 8-channel or 32-channel head coil. Ten patients, who suffered from brain atrophy because of fragile X-associated tremor/ataxia syndrome, were scanned using the 32-channel head coil. The initial segmentations of the cerebellum and brainstem were generated automatically using Freesurfer. Subsequently, Freesurfer's segmentations were both manually corrected to serve as the gold standard and automatically corrected by SegAdapter. Using only 5 scans in the training set, spatial overlap with manual segmentation in Dice coefficient improved significantly from 0.956 (for Freesurfer segmentation) to 0.978 (for SegAdapter-corrected segmentation) for the cerebellum and from 0.821 to 0.954 for the brainstem. Reducing the training set size to 2 scans only decreased the Dice coefficient ≤0.002 for the cerebellum and ≤ 0.005 for the brainstem compared to the use of training set size of 5 scans in corrective learning. The method was also robust in handling differences between the training set and the test set in head coil usage and the amount of brain atrophy, which reduced spatial overlap only by <0.01. These results suggest that the combination of automated segmentation and corrective learning provides a valuable method for accurate and efficient segmentation of the cerebellum and brainstem, particularly in large-scale neuroimaging studies, and potentially for segmenting other neural regions as well.

  8. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Chin-Cheng; Lee, Chen-Chiao, E-mail: joelee168@hotmail.co; Mah, Dennis

    Because of the dose limit for critical structures such as brainstem and spinal cord, administering a dose of 60 Gy to patients with recurrent head and neck cancer is challenging for those who received a previous dose of 60-70 Gy. Specifically, previously irradiated head and neck patients may have received doses close to the tolerance limit to their brainstem and spinal cord. In this study, a reproducible intensity-modulated radiation therapy (IMRT) treatment design is presented to spare the doses to brainstem and spinal cord, with no compromise of prescribed dose delivery. Between July and November 2008, 7 patients with previouslymore » irradiated, recurrent head and neck cancers were treated with IMRT. The jaws of each field were set fixed with the goal of shielding the brainstem and spinal cord at the sacrifice of partial coverage of the planning target volume (PTV) from any particular beam orientation. Beam geometry was arranged to have sufficient coverage of the PTV and ensure that the constraints of spinal cord <10 Gy and brainstem <15 Gy were met. The mean maximum dose to the brainstem was 12.1 Gy (range 6.1-17.3 Gy), and the corresponding mean maximum dose to spinal cord was 10.4 Gy (range 8.2-14.1 Gy). For most cases, 97% of the PTV volume was fully covered by the 95% isodose volume. We found empirically that if the angle of cervical spine curvature (Cobb's angle) was less than {approx}30{sup o}, patients could be treated by 18 fields. Six patients met these criteria and were treated in 25 minutes per fraction. One patient exceeded a 30{sup o} Cobb's angle and was treated by 31 fields in 45 minutes per fraction. We have demonstrated a new technique for retreatment of head and neck cancers. The angle of cervical spine curvature plays an important role in the efficiency and effectiveness of our approach.« less

  9. Robust Machine Learning-Based Correction on Automatic Segmentation of the Cerebellum and Brainstem

    PubMed Central

    Wang, Jun Yi; Ngo, Michael M.; Hessl, David; Hagerman, Randi J.; Rivera, Susan M.

    2016-01-01

    Automated segmentation is a useful method for studying large brain structures such as the cerebellum and brainstem. However, automated segmentation may lead to inaccuracy and/or undesirable boundary. The goal of the present study was to investigate whether SegAdapter, a machine learning-based method, is useful for automatically correcting large segmentation errors and disagreement in anatomical definition. We further assessed the robustness of the method in handling size of training set, differences in head coil usage, and amount of brain atrophy. High resolution T1-weighted images were acquired from 30 healthy controls scanned with either an 8-channel or 32-channel head coil. Ten patients, who suffered from brain atrophy because of fragile X-associated tremor/ataxia syndrome, were scanned using the 32-channel head coil. The initial segmentations of the cerebellum and brainstem were generated automatically using Freesurfer. Subsequently, Freesurfer’s segmentations were both manually corrected to serve as the gold standard and automatically corrected by SegAdapter. Using only 5 scans in the training set, spatial overlap with manual segmentation in Dice coefficient improved significantly from 0.956 (for Freesurfer segmentation) to 0.978 (for SegAdapter-corrected segmentation) for the cerebellum and from 0.821 to 0.954 for the brainstem. Reducing the training set size to 2 scans only decreased the Dice coefficient ≤0.002 for the cerebellum and ≤ 0.005 for the brainstem compared to the use of training set size of 5 scans in corrective learning. The method was also robust in handling differences between the training set and the test set in head coil usage and the amount of brain atrophy, which reduced spatial overlap only by <0.01. These results suggest that the combination of automated segmentation and corrective learning provides a valuable method for accurate and efficient segmentation of the cerebellum and brainstem, particularly in large-scale neuroimaging studies, and potentially for segmenting other neural regions as well. PMID:27213683

  10. Degeneration of ingestion-related brainstem nuclei in spinocerebellar ataxia type 2, 3, 6 and 7.

    PubMed

    Rüb, U; Brunt, E R; Petrasch-Parwez, E; Schöls, L; Theegarten, D; Auburger, G; Seidel, K; Schultz, C; Gierga, K; Paulson, H; van Broeckhoven, C; Deller, T; de Vos, R A I

    2006-12-01

    Dysphagia, which can lead to nutritional deficiencies, weight loss and dehydration, represents a risk factor for aspiration pneumonia. Although clinical studies have reported the occurrence of dysphagia in patients with spinocerebellar ataxia type 2 (SCA2), type 3 (SCA3), type 6 (SCA6) and type 7 (SCA7), there are neither detailed clinical records concerning the kind of ingestive malfunctions which contribute to dysphagia nor systematic pathoanatomical studies of brainstem regions involved in the ingestive process. In the present study we performed a systematic post mortem study on thick serial tissue sections through the ingestion-related brainstem nuclei of 12 dysphagic patients who suffered from clinically diagnosed and genetically confirmed spinocerebellar ataxias assigned to the CAG-repeat or polyglutamine diseases (two SCA2, seven SCA3, one SCA6 and two SCA7 patients) and evaluated their medical records. Upon pathoanatomical examination in all of the SCA2, SCA3, SCA6 and SCA7 patients, a widespread neurodegeneration of the brainstem nuclei involved in the ingestive process was found. The clinical records revealed that all of the SCA patients were diagnosed with progressive dysphagia and showed dysfunctions detrimental to the preparatory phase of the ingestive process, as well as the lingual, pharyngeal and oesophageal phases of swallowing. The vast majority of the SCA patients suffered from aspiration pneumonia, which was the most frequent cause of death in our sample. The findings of the present study suggest (i) that dysphagia in SCA2, SCA3, SCA6 and SCA7 patients may be associated with widespread neurodegeneration of ingestion-related brainstem nuclei; (ii) that dysphagic SCA2, SCA3, SCA6 and SCA7 patients may suffer from dysfunctions detrimental to all phases of the ingestive process; and (iii) that rehabilitative swallow therapy which takes specific functional consequences of the underlying brainstem lesions into account might be helpful in preventing aspiration pneumonia, weight loss and dehydration in SCA2, SCA3, SCA6 and SCA7 patients.

  11. Glycinergic Input to the Mouse Basal Forebrain Cholinergic Neurons

    PubMed Central

    Bardóczi, Zsuzsanna; Pál, Balázs; Kőszeghy, Áron; Wilheim, Tamás; Záborszky, László; Liposits, Zsolt

    2017-01-01

    The basal forebrain (BF) receives afferents from brainstem ascending pathways, which has been implicated first by Moruzzi and Magoun (1949) to induce forebrain activation and cortical arousal/waking behavior; however, it is very little known about how brainstem inhibitory inputs affect cholinergic functions. In the current study, glycine, a major inhibitory neurotransmitter of brainstem neurons, and gliotransmitter of local glial cells, was tested for potential interaction with BF cholinergic (BFC) neurons in male mice. In the BF, glycine receptor α subunit-immunoreactive (IR) sites were localized in choline acetyltransferase (ChAT)-IR neurons. The effect of glycine on BFC neurons was demonstrated by bicuculline-resistant, strychnine-sensitive spontaneous IPSCs (sIPSCs; 0.81 ± 0.25 × 10−1 Hz) recorded in whole-cell conditions. Potential neuronal as well as glial sources of glycine were indicated in the extracellular space of cholinergic neurons by glycine transporter type 1 (GLYT1)- and GLYT2-IR processes found in apposition to ChAT-IR cells. Ultrastructural analyses identified synapses of GLYT2-positive axon terminals on ChAT-IR neurons, as well as GLYT1-positive astroglial processes, which were localized in the vicinity of synapses of ChAT-IR neurons. The brainstem raphe magnus was determined to be a major source of glycinergic axons traced retrogradely from the BF. Our results indicate a direct effect of glycine on BFC neurons. Furthermore, the presence of high levels of plasma membrane glycine transporters in the vicinity of cholinergic neurons suggests a tight control of extracellular glycine in the BF. SIGNIFICANCE STATEMENT Basal forebrain cholinergic (BFC) neurons receive various activating inputs from specific brainstem areas and channel this information to the cortex via multiple projections. So far, very little is known about inhibitory brainstem afferents to the BF. The current study established glycine as a major regulator of BFC neurons by (1) identifying glycinergic neurons in the brainstem projecting to the BF, (2) showing glycine receptor α subunit-immunoreactive (IR) sites in choline acetyltransferase (ChAT)-IR neurons, (3) demonstrating glycine transporter type 2 (GLYT2)-positive axon terminals synapsing on ChAT-IR neurons, and (4) localizing GLYT1-positive astroglial processes in the vicinity of synapses of ChAT-IR neurons. The effect of glycine on BFC neurons was demonstrated by bicuculline-resistant, strychnine-sensitive spontaneous IPSCs recorded in whole-cell conditions. PMID:28874448

  12. Auditory brainstem response as a diagnostic tool for patients suffering from schizophrenia, attention deficit hyperactivity disorder, and bipolar disorder: protocol.

    PubMed

    Wahlström, Viktor; Åhlander, Fredrik; Wynn, Rolf

    2015-02-12

    Psychiatric disorders, such as schizophrenia, attention deficit hyperactivity disorder (ADHD), and bipolar disorder, may sometimes be difficult to diagnose. There is a great need for a valid and reliable diagnostic tool to aid clinicians in arriving at the diagnoses in a timely and accurate manner. Prior studies have suggested that patients suffering from schizophrenia and ADHD may process certain sound stimuli in the brainstem in an unusual manner. When these patient groups have been examined with the electrophysiological method of brainstem audiometry, some studies have found illness-specific aberrations. Such aberrations may also exist for patients suffering from bipolar disorder. In this study, we will examine whether the method of brainstem audiometry can be used as a diagnostic tool for patients suffering from schizophrenia, ADHD, and bipolar disorder. The method includes three steps: (1) auditory stimulation with specific sound stimuli, (2) simultaneous measurement of brainstem activity, and (3) automated interpretation of the resulting brain stem audiograms with data-based signal analysis. We will compare three groups of 12 individuals with confirmed diagnoses of schizophrenia, ADHD, or bipolar disorder with 12 healthy subjects under blinded conditions for a total of 48 participants. The extent to which the method can be used to reach the correct diagnosis will be investigated. The project is now in a recruiting phase. When all patients and controls have been recruited and the measurements have been performed, the data will be analyzed according to a previously arranged algorithm. We expect the recruiting phase and measurements to be completed in early 2015, the analyses to be performed in mid-2015, and the results of the study to be published in early 2016. If the results support previous findings, this will lend strength to the idea that brainstem audiometry can offer objective diagnostic support for patients suffering from schizophrenia, ADHD, and bipolar disorder. A positive result from the study could imply that brainstem audiometry could become an important supportive tool for clinicians in their efforts to diagnose patients with these disorders in a timely and accurate manner. ClinicalTrials.gov NCT01629355; https://clinicaltrials.gov/ct2/show/NCT01629355 (Archived by WebCite at http://www.webcitation.org/6VBfTwx5H).

  13. Neurological assessments after treatment with the antimalarial β-arteether in neonatal and adult rats.

    PubMed

    Erickson, R I; Defensor, E B; Fairchild, D G; Mirsalis, J C; Steinmetz, K L

    2011-08-01

    The World Health Organization currently recommends combinatorial treatment including artemisinins as first-line therapy against drug-resistant Plasmodium falciparum malaria. Although highly efficacious, artemisinin and its derivatives, including β-arteether (βAE), are associated with ototoxicity, tremors, and other autonomic and motor impairments in the clinic. Similar neurological symptoms, as well as brainstem lesions, have been observed in adult laboratory species (mice, rats, dogs, and non human primates) following acute treatment with βAE; however, few long-term, nonclinical studies have been conducted. Furthermore, the majority of deaths attributed to malarial infection occur in children under age five, yet no laboratory studies have been initiated in neonatal or juvenile animals. In the current study, neonatal 7-day-old rats were administered intramuscular doses of 1-90 mg/kg βAE in sesame oil for up to eight treatment cycles (one cycle=7 days treatment+7 days without treatment). Neonates were tested for changes in sensorimotor function, and the same animals were tested as adults in the Functional Observational Battery, for motor activity, and in the 8-arm radial maze. Pups receiving a single cycle of 60 or 90 mg/kg died within a week of treatment but had few behavioral changes and no brainstem pathology. In the long-term study, behavioral and motor changes and brainstem lesions were observed in a dose- and time-related manner. Rats given repeated cycles of 1 or 5mg/kg βAE showed subtle motor abnormalities (e.g., slight loss of righting reflex) while repeated cycles of 10mg/kg βAE treatment resulted in obvious motor and behavioral changes. Rats receiving 1mg/kg βAE had no brainstem lesions whereas some rats treated with 5mg/kg βAE and all rats treated with 10 mg/kg βAE had brainstem lesions. Brainstem lesions were observed after as few as five cycles and were characterized by gliosis, satellitosis and progressive necrosis in motor neurons of the trapezoid, vestibular, and olivary nuclei. This study shows that repeated treatment with clinically relevant doses of βAE causes motor deficits associated with brainstem damage in rodents and suggests that repeated treatment with βAE in children may elicit neurological damage. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Normative biometry of the fetal brain using magnetic resonance imaging.

    PubMed

    Kyriakopoulou, Vanessa; Vatansever, Deniz; Davidson, Alice; Patkee, Prachi; Elkommos, Samia; Chew, Andrew; Martinez-Biarge, Miriam; Hagberg, Bibbi; Damodaram, Mellisa; Allsop, Joanna; Fox, Matt; Hajnal, Joseph V; Rutherford, Mary A

    2017-07-01

    The fetal brain shows accelerated growth in the latter half of gestation, and these changes can be captured by 2D and 3D biometry measurements. The aim of this study was to quantify brain growth in normal fetuses using Magnetic Resonance Imaging (MRI) and to produce reference biometry data and a freely available centile calculator ( https://www.developingbrain.co.uk/fetalcentiles/ ). A total of 127 MRI examinations (1.5 T) of fetuses with a normal brain appearance (21-38 gestational weeks) were included in this study. 2D and 3D biometric parameters were measured from slice-to-volume reconstructed images, including 3D measurements of supratentorial brain tissue, lateral ventricles, cortex, cerebellum and extra-cerebral CSF and 2D measurements of brain biparietal diameter and fronto-occipital length, skull biparietal diameter and occipitofrontal diameter, head circumference, transverse cerebellar diameter, extra-cerebral CSF, ventricular atrial diameter, and vermis height, width, and area. Centiles were constructed for each measurement. All participants were invited for developmental follow-up. All 2D and 3D measurements, except for atrial diameter, showed a significant positive correlation with gestational age. There was a sex effect on left and total lateral ventricular volumes and the degree of ventricular asymmetry. The 5th, 50th, and 95th centiles and a centile calculator were produced. Developmental follow-up was available for 73.1% of cases [mean chronological age 27.4 (±10.2) months]. We present normative reference charts for fetal brain MRI biometry at 21-38 gestational weeks. Developing growth trajectories will aid in the better understanding of normal fetal brain growth and subsequently of deviations from typical development in high-risk pregnancies or following premature delivery.

  15. Theoretical analysis and experimental study on breakaway torque of large-diameter magnetic liquid seal at low temperature

    NASA Astrophysics Data System (ADS)

    Zhang, Haina; Li, Decai; Wang, Qinglei; Zhang, Zhili

    2013-07-01

    The existing researches of the magnetic liquid rotation seal have been mainly oriented to the seal at normal temperature and the seal with the smaller shaft diameter less than 100 mm. However, the large-diameter magnetic liquid rotation seal at low temperature has not been reported both in theory and in application up to now. A key factor restricting the application of the large-diameter magnetic liquid rotation seal at low temperature is the high breakaway torque. In this paper, the factors that influence the breakaway torque including the number of seal stages, the injected quantity of magnetic liquid and the standing time at normal temperature are studied. Two kinds of magnetic liquid with variable content of large particles are prepared first, and a seal feedthrough with 140 mm shaft diameter is used in the experiments. All experiments are carried out in a low temperature chamber with a temperature range from 200°C to -100°C. Different numbers of seal stages are tested under the same condition to study the relation between the breakaway torque and the number of seal stages. Variable quantity of magnetic liquid is injected in the seal gap to get the relation curve of the breakaway torque and the injecting quantity of magnetic liquid. In the experiment for studying the relation between the breakaway torque and the standing time at the normal temperature, the seal feedtrough is laid at normal temperature for different period of time before it is put in the low temperature chamber. The experimental results show that the breakaway torque is proportional to the number of seal stages, the injected quantity of magnetic liquid and the standing time at the normal temperature. Meanwhile, the experimental results are analyzed and the torque formula of magnetic liquid rotation seal at low temperature is deduced from the Navier-Stokes equation on the base of the model of magnetic liquid rotation seal. The presented research can make wider application of the magnetic liquid seal in general. And the large-diameter magnetic liquid rotation seal at low temperature designed by using present research results are to be used in some special fields, such as the military field, etc.

  16. [Magnetic resonance imaging features in two Chinese family with congenital fibrosis of extraocular muscles].

    PubMed

    Wu, Li; Zhou, Lian-Hong; Liu, Chang-Sheng; Cha, Yun-Fei; Wang, Jiong; Xing, Yi-Qiao

    2009-11-01

    The aim of this article was to investigate the structural basis of ocular motility and visual abnormalities in humans with congenital fibrosis of the extraocular muscles (CFEOM). 17 volunteers from 2 CFEOM pedigrees Clinical ophthalmic and motility examed and 18 normal control subjects were correlated with thin-sectioned magnetic resonance imaging (MRI) across the orbit and the brain-stem level. Subjects with CFEOM had severe bilateral blepharoptosis, limited supraduction, and variable ophthalmoplegia. In affected subjects, MRI demonstrated atrophy of the levator palpebrae superioris, all EOMs, and the optic nerves, and small or absent orbital motor nerves. The oculomotor nerve was most severely hypoplastic, but the abducens was also affected. Subjects with CFEOM exhibited subclinical but highly significant reduction from normal in mean optic nerve size (P < 0.05). There are also some difference between the two CFEOM pedigrees. These findings suggest that neuronal disease is primary in CFEOM, with myopathy arising secondary to abnormal innervation and the oculomotor nucleus and trochlear nucleus of the abnormalities defects.

  17. Examining the role of the tectorial membrane in otoacoustic emission generation

    NASA Astrophysics Data System (ADS)

    Cheatham, Marry Ann; Goodyear, Richard J.; Charaziak, Karolina K.; Conklin, Tess; Zheng, Jing; Dallos, Peter; Richardson, Guy P.; Siegel, Jonathan H.

    2015-12-01

    A mouse lacking CEACAM16, a member of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family of proteins, shows changes in tectorial membrane (TM) structure including loss of a defined striated-sheet matrix, absence of Hensen's stripe and increased porosity. In spite of these changes, thresholds for distortion product emissions (DPOAEs) and auditory brainstem responses (ABR) are near normal for most frequencies in the mouse audiogram [11]. In contrast, stimulus frequency emissions (SFOAE) are larger in knockouts (KO) and the incidence of spontaneous emissions (SOAE) is ˜70% [5]. This latter statistic is remarkable considering that SOAEs are uncommon in normal wild-type (WT) mice. In order to understand how the TM might influence emissions, SFOAE magnitude and phase were examined and group delays computed. As in humans, an approximately one-cycle phase change is observed in association with SFOAE fine structure. In addition, CEACAM16 KO mice and their WT controls showed similar group delays/phase slopes indicating no obvious changes in the mechanisms associated with emission generation.

  18. D-METHIONINE REDUCES TOBRAMYCIN-INDUCED OTOTOXICITY WITHOUT ANTIMICROBIAL INTERFERENCE IN ANIMAL MODELS

    PubMed Central

    Fox, Daniel J.; Cooper, Morris D.; Speil, Cristian A.; Roberts, Melissa H.; Yanik, Susan C.; Meech, Robert P.; Hargrove, Tim L.; Verhulst, Steven J.; Rybak, Leonard P.; Campbell, Kathleen C. M.

    2015-01-01

    Background Tobramycin is a critical cystic fibrosis treatment however it causes ototoxicity. This study tested D-methionine protection from tobramycin-induced ototoxicity and potential antimicrobial interference. Methods Auditory brainstem responses (ABR) and outer hair cell (OHC) quantifications measured protection in guinea pigs treated with tobramycin and a range of D-methionine doses. In vitro antimicrobial interference studies tested inhibition and post antibiotic effect assays. In vivo antimicrobial interference studies tested normal and neutropenic E. coli murine survival and intraperitoneal lavage bacterial counts. Results D-methionine conferred significant ABR threshold shift reductions. OHC protection was less robust but significant at 20 kHz in the 420 mg/kg/day group. In vitro studies did not detect D-methionine-induced antimicrobial interference. In vivo studies did not detect D-methionine-induced interference in normal or neutropenic mice. Conclusions D-methionine protects from tobramycin-induced ototoxicity without antimicrobial interference. The study results suggest D-met as a potential otoprotectant from clinical tobramycin use in cystic fibrosis patients. PMID:26166286

  19. Laser treatments of deep-seated brain lesions

    NASA Astrophysics Data System (ADS)

    Ward, Helen A.

    1997-06-01

    The five year survival rate of deep-seated malignant brain tumors after surgery/radiotherapy is virtually 100 percent mortality. Special problems include: (1) Lesions often present late. (2) Position: lesion overlies vital structures, so complete surgical/radiotherapy lesion destruction can damage vital brain-stem functions. (3) Difficulty in differentiating normal brain form malignant lesions. This study aimed to use the unique properties of the laser: (a) to minimize damage during surgical removal of deep-seated brain lesions by operating via fine optic fibers; and (b) to employ the propensity of certain lasers for absorption of dyes and absorption and induction of fluorescence in some brain substances, to differentiate borders of malignant and normal brain, for more complete tumor removal. In the method a fine laser endoscopic technique was devised for removal of brain lesions. The results of this technique, were found to minimize and accurately predict the extent of thermal damage and shock waves to within 1-2mm of the surgical laser beam. Thereby it eliminated the 'popcorn' effect.

  20. d-Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models.

    PubMed

    Fox, Daniel J; Cooper, Morris D; Speil, Cristian A; Roberts, Melissa H; Yanik, Susan C; Meech, Robert P; Hargrove, Tim L; Verhulst, Steven J; Rybak, Leonard P; Campbell, Kathleen C M

    2016-07-01

    Tobramycin is a critical cystic fibrosis treatment however it causes ototoxicity. This study tested d-methionine protection from tobramycin-induced ototoxicity and potential antimicrobial interference. Auditory brainstem responses (ABRs) and outer hair cell (OHC) quantifications measured protection in guinea pigs treated with tobramycin and a range of d-methionine doses. In vitro antimicrobial interference studies tested inhibition and post antibiotic effect assays. In vivo antimicrobial interference studies tested normal and neutropenic Escherichia coli murine survival and intraperitoneal lavage bacterial counts. d-Methionine conferred significant ABR threshold shift reductions. OHC protection was less robust but significant at 20kHz in the 420mg/kg/day group. In vitro studies did not detect d-methionine-induced antimicrobial interference. In vivo studies did not detect d-methionine-induced interference in normal or neutropenic mice. d-Methionine protects from tobramycin-induced ototoxicity without antimicrobial interference. The study results suggest d-met as a potential otoprotectant from clinical tobramycin use in cystic fibrosis patients. Published by Elsevier B.V.

  1. Tinnitus and Auditory Perception After a History of Noise Exposure: Relationship to Auditory Brainstem Response Measures.

    PubMed

    Bramhall, Naomi F; Konrad-Martin, Dawn; McMillan, Garnett P

    2018-01-15

    To determine whether auditory brainstem response (ABR) wave I amplitude is associated with measures of auditory perception in young people with normal distortion product otoacoustic emissions (DPOAEs) and varying levels of noise exposure history. Tinnitus, loudness tolerance, and speech perception ability were measured in 31 young military Veterans and 43 non-Veterans (19 to 35 years of age) with normal pure-tone thresholds and DPOAEs. Speech perception was evaluated in quiet using Northwestern University Auditory Test (NU-6) word lists and in background noise using the words in noise (WIN) test. Loudness discomfort levels were measured using 1-, 3-, 4-, and 6-kHz pulsed pure tones. DPOAEs and ABRs were collected in each participant to assess outer hair cell and auditory nerve function. The probability of reporting tinnitus in this sample increased by a factor of 2.0 per 0.1 µV decrease in ABR wave I amplitude (95% Bayesian confidence interval, 1.1 to 5.0) for males and by a factor of 2.2 (95% confidence interval, 1.0 to 6.4) for females after adjusting for sex and DPOAE levels. Similar results were obtained in an alternate model adjusted for pure-tone thresholds in addition to sex and DPOAE levels. No apparent relationship was found between wave I amplitude and either loudness tolerance or speech perception in quiet or noise. Reduced ABR wave I amplitude was associated with an increased risk of tinnitus, even after adjusting for DPOAEs and sex. In contrast, wave III and V amplitudes had little effect on tinnitus risk. This suggests that changes in peripheral input at the level of the inner hair cell or auditory nerve may lead to increases in central gain that give rise to the perception of tinnitus. Although the extent of synaptopathy in the study participants cannot be measured directly, these findings are consistent with the prediction that tinnitus may be a perceptual consequence of cochlear synaptopathy.

  2. Echocardiography parameters of clinically normal adult captive chimpanzees (Pan troglodytes).

    PubMed

    Sleeper, Meg M; Drobatz, Ken; Lee, D Richard; Lammey, Michael L

    2014-04-15

    To generate reference ranges for echocardiographic variables in clinically normal adult chimpanzees (Pan troglodytes). Retrospective cohort study. 88 clinically normal adult chimpanzees. Echocardiographic data obtained between 2002 and 2011 from chimpanzees at the Alamogordo Primate Facility were reviewed (263 echocardiograms obtained from 158 individuals). Data from clinically normal individuals (33 females and 55 males) were analyzed. Basic cardiac parameters measured in all individuals included aortic root diameter and left atrial diameter in the short and long axis during diastole. Left ventricular measurements included left ventricular internal diameter in systole and diastole and diastolic septal and posterior wall thickness. The E point to septal separation was also measured. Spectral Doppler measurements included the peak flow velocity of the pulmonary artery and aorta and diastolic transmitral flow. The presence of arrhythmias was also noted. Standard echocardiographic findings for a large group of adult female and male chimpanzees were obtained. Female and male chimpanzees were grouped by age in 10-year blocks, and echocardiographic findings were analyzed statistically by 10-year block. In male chimpanzees, cardiac arrhythmias were noted to increase with age. Cardiovascular disease is an important cause of morbidity and death in captive chimpanzees; however, basic echocardiographic measurements from a large cohort of clinically normal animals have not previously been reported. The number of animals in the present study was insufficient to generate reference ranges; however, data from a large cohort of clinically normal animals are presented. This information will be useful for veterinarians working in clinical and research settings with this species.

  3. Vascular corrosion casting of normal and pre-eclamptic placentas.

    PubMed

    Yin, Geping; Chen, Ming; Li, Juan; Zhao, Xiaoli; Yang, Shujun; Li, Xiuyun; Yuan, Zheng; Wu, Aifang

    2017-12-01

    Pre-eclampsia is an important cause of maternal and fetal morbidity and mortality that is associated with decreased placental perfusion. In the present study, vascular corrosion casting was used to investigate the differences in structural changes of the fetoplacental vasculature between normal and pre-eclamptic placentas. An improved epoxy resin vascular casting technique was used in the present study. Casting media were infused into 40 normal and 40 pre-eclamptic placentas through umbilical arteries and veins in order to construct three dimensional fetoplacental vasculatures. The number of branches, diameter, morphology and peripheral artery-to-vein ratio were measured for each specimen. The results indicated that the venous system of normal placentas was divided into 5-7 grades of branches and the volume of the vascular bed was 155.5±45.3 ml. In severe pre-eclamptic placentas, the volume was 106.4±36.1 ml, which was significantly lower compared with normal placentas (P<0.01). The venous system of pre-eclamptic placentas was divided into 4-5 grades of branches, which was much more sparse compared with normal placentas. In additions, the diameters of grade 1-3 veins and grade 2-3 arteries were significantly smaller in severe pre-eclampsia (P<0.05). In conclusion, pre-eclamptic placentas displayed a decreased volume of vascular bed, smaller diameters of grade 1-3 veins and grade 2-3 arteries, and an increased peripheral artery-to-vein ratio, which may be a cause of the placental dysfunction during severe pre-eclampsia.

  4. Morphological Correlates of Hearing Loss after Cochlear Implantation and Electro-Acoustic Stimulation in a Hearing-Impaired Guinea Pig Model

    PubMed Central

    Reiss, Lina A.J.; Stark, Gemaine; Nguyen-Huynh, Anh T.; Spear, Kayce A.; Zhang, Hongzheng; Tanaka, Chiemi; Li, Hongzhe

    2016-01-01

    Hybrid or electro-acoustic stimulation (EAS) cochlear implants (CIs) are designed to provide high-frequency electric hearing together with residual low-frequency acoustic hearing. However, 30-50% of EAS CI recipients lose residual hearing after implantation. The objective of this study was to determine the mechanisms of EAS-induced hearing loss in an animal model with high-frequency hearing loss. Guinea pigs were exposed to 24 hours of noise (12-24 kHz at 116 dB) to induce a high-frequency hearing loss. After recovery, two groups of animals were implanted (n=6 per group), with one group receiving chronic acoustic and electric stimulation for 10 weeks, and the other group receiving no stimulation during this time frame. A third group (n=6) was not implanted, but received chronic acoustic stimulation. Auditory brainstem responses were recorded biweekly to monitor changes in hearing. The organ of Corti was immunolabeled with phalloidin, anti-CtBP2, and anti-GluR2 to quantify hair cells, ribbons and post-synaptic receptors. The lateral wall was immunolabeled with phalloidin and lectin to quantify stria vascularis capillary diameters. Bimodal or trimodal diameter distributions were observed; the number and location of peaks were objectively determined using the Aikake Information Criterion and Expectation Maximization algorithm. Noise exposure led to immediate hearing loss at 16-32 kHz for all groups. Cochlear implantation led to additional hearing loss at 4-8 kHz; this hearing loss was negatively and positively correlated with minimum and maximum peaks of the bimodal or trimodal distributions of stria vascularis capillary diameters, respectively. After chronic stimulation, no significant group changes in thresholds were seen; however, elevated thresholds at 1 kHz in implanted, stimulated animals were significantly correlated with decreased presynaptic ribbon and postsynaptic receptor counts. Inner and outer hair cell counts did not differ between groups and were not correlated with threshold shifts at any frequency. As in the previous study in a normal-hearing model, stria vascularis capillary changes were associated with immediate hearing loss after implantation, while little to no hair cell loss was observed even in cochlear regions with threshold shifts as large as 40-50 dB. These findings again support a role of lateral wall blood flow changes, rather than hair cell loss, in hearing loss after surgical trauma, and implicate the endocochlear potential as a factor in implantation-induced hearing loss. Further, the analysis of the hair cell ribbons and post-synaptic receptors suggest that delayed hearing loss may be linked to synapse or peripheral nerve loss due to stimulation excitotoxicity or inflammation. Further research is needed to separate these potential mechanisms of delayed hearing loss. PMID:26087114

  5. The relationship between perimesencephalic subarachnoid hemorrhage and deep venous system drainage pattern and calibrations.

    PubMed

    Buyukkaya, Ramazan; Yıldırım, Nalan; Cebeci, Hakan; Kocaeli, Hasan; Dusak, Abdürrahim; Ocakoğlu, Gökhan; Erdoğan, Cüneyt; Hakyemez, Bahattin

    2014-01-01

    The purpose of this study is to investigate the relationship between Rosenthal basal vein (BVR) type and diameter and perimesencephalic nonaneurysmal subarachnoid hemorrhage (P-SAH). Aneurysmal subarachnoid hemorrhage (A-SAH), P-SAH, and control groups were evaluated, and BVRs were classified by type. BVR diameters in patients were measured. There was a statistically significant difference of BVR drainage types between groups (P=.002). BVR diameters of patients with normal drainage pattern in P-SAH group were significantly smaller than those in both other groups (P<.001). There is a relationship between P-SAH and BVR primitive drainage type. P-SAH risk increases in parallel with decreasing caliber of BVR in patients with normal drainage pattern. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Two normal incidence collimators designed for the calibration of the extreme ultraviolet explorer

    NASA Technical Reports Server (NTRS)

    Jelinsky, Sharon R.; Welsh, Barry; Jelinsky, Patrick; Spiller, Eberhard

    1988-01-01

    Two Dall-Kirkham, normal incidence collimators have been designed to calibrate the imaging properties of the Extreme Ultraviolet Explorer over the wavelength region from 114 to 2000 A. The mirrors of the short-wavelength, 25-cm diameter collimator are superpolished Zerodur which have been multilayer coated for optimal reflectivity at 114 A. The mirrors of the long-wavelength, 41.25-cm diameter collimator are gold coated Zerodur for high reflectance above 300 A. The design, performance, and future use of these collimators in the extreme ultra-violet is discussed.

  7. The incidental finding of elevated anti GQ1B antibodies in a patient with selective small fiber neuropathy.

    PubMed

    Favoni, Valentina; Liguori, Rocco; Incensi, Alex; Fileccia, Enrico; Donadio, Vincenzo

    2018-05-15

    Small fiber neuropathy (SFN) selectively affects small diameter sensory and/or autonomic axons. Pain and autonomic dysfunctions are the most common symptoms. SFN occurs in several autoimmune diseases and autoantibodies against neuronal proteins may play a role in SFN pathophysiology. Anti-GQ1b antibody has been associated with Miller Fisher syndrome, Bickerstaff's brainstem encephalitis, acute ophthalmoplegia, pharyngeal-cervical-brachial weakness and peripheral neuropathy involving large fibers. Isolated SFN associated with anti-GQ1b antibodies has not been previously reported. Here we report a 45-year-old woman presenting with highly positive anti-GQ1b titer and selective SFN without central nervous system or peripheral large nerve involvement. She improved upon administration of adalizumab. Further studies will clarify a possible pathogenetic role of antiganglioside antibodies in SFN. Moreover, the recognition of antiganglioside antibodies in SFN may have therapeutic consequences with patients who would benefit from immunotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. The Impact of Clinical History on the Threshold Estimation of Auditory Brainstem Response Results for Infants

    ERIC Educational Resources Information Center

    Zaitoun, Maha; Cumming, Steven; Purcell, Alison; O'Brien, Katie

    2017-01-01

    Purpose: This study assesses the impact of patient clinical history on audiologists' performance when interpreting auditory brainstem response (ABR) results. Method: Fourteen audiologists' accuracy in estimating hearing threshold for 16 infants through interpretation of ABR traces was compared on 2 occasions at least 5 months apart. On the 1st…

  9. Effect of High-Pass Filtering on the Neonatal Auditory Brainstem Response to Air- and Bone-Conducted Clicks.

    ERIC Educational Resources Information Center

    Stuart, Andrew; Yang, Edward Y.

    1994-01-01

    Simultaneous 3- channel recorded auditory brainstem responses (ABR) were obtained from 20 neonates with various high-pass filter settings and low intensity levels. Results support the advocacy of less restrictive high-pass filtering for neonatal and infant ABR screening to air-conducted and bone-conducted clicks. (Author/JDD)

  10. The Relationship between Brainstem Temporal Processing and Performance on Tests of Central Auditory Function in Children with Reading Disorders

    ERIC Educational Resources Information Center

    Billiet, Cassandra R.; Bellis, Teri James

    2011-01-01

    Purpose: Studies using speech stimuli to elicit electrophysiologic responses have found approximately 30% of children with language-based learning problems demonstrate abnormal brainstem timing. Research is needed regarding how these responses relate to performance on behavioral tests of central auditory function. The purpose of the study was to…

  11. Infant Temperament and the Brainstem Auditory Evoked Response in Later Childhood.

    ERIC Educational Resources Information Center

    Woodward, Sue A.; McManis, Mark H.; Kagan, Jerome; Deldin, Patricia; Snidman, Nancy; Lewis, Melissa; Kahn, Vali

    2001-01-01

    Evaluated brainstem auditory evoked responses (BAERs) on 10- to 12-year-olds who had been classified as high or low reactive to unfamiliar stimuli at 4 months of age. Found that children previously classified as high reactive at 4 months had larger wave V components than did low reactive children, possibly suggesting greater excitability in…

  12. Auditory Brainstem Response to Complex Sounds Predicts Self-Reported Speech-in-Noise Performance

    ERIC Educational Resources Information Center

    Anderson, Samira; Parbery-Clark, Alexandra; White-Schwoch, Travis; Kraus, Nina

    2013-01-01

    Purpose: To compare the ability of the auditory brainstem response to complex sounds (cABR) to predict subjective ratings of speech understanding in noise on the Speech, Spatial, and Qualities of Hearing Scale (SSQ; Gatehouse & Noble, 2004) relative to the predictive ability of the Quick Speech-in-Noise test (QuickSIN; Killion, Niquette,…

  13. Aberrant Lateralization of Brainstem Auditory Evoked Responses by Individuals with Down Syndrome.

    ERIC Educational Resources Information Center

    Miezejeski, Charles M.; And Others

    1994-01-01

    Brainstem auditory evoked response latencies were studied in 80 males (13 with Down's syndrome). Latencies for waves P3 and P5 were shorter for Down's syndrome subjects, who also showed a different pattern of left versus right ear responses. Results suggest decreased lateralization and receptive and expressive language ability among people with…

  14. Interactions between Brainstem Noradrenergic Neurons and the Nucleus Accumbens Shell in Modulating Memory for Emotionally Arousing Events

    ERIC Educational Resources Information Center

    Kerfoot, Erin C.; Williams, Cedric L.

    2011-01-01

    The nucleus accumbens shell (NAC) receives axons containing dopamine-[beta]-hydroxylase that originate from brainstem neurons in the nucleus of the solitary tract (NTS). Recent findings show that memory enhancement produced by stimulating NTS neurons after learning may involve interactions with the NAC. However, it is unclear whether these…

  15. Language-Dependent Pitch Encoding Advantage in the Brainstem Is Not Limited to Acceleration Rates that Occur in Natural Speech

    ERIC Educational Resources Information Center

    Krishnan, Ananthanarayan; Gandour, Jackson T.; Smalt, Christopher J.; Bidelman, Gavin M.

    2010-01-01

    Experience-dependent enhancement of neural encoding of pitch in the auditory brainstem has been observed for only specific portions of native pitch contours exhibiting high rates of pitch acceleration, irrespective of speech or nonspeech contexts. This experiment allows us to determine whether this language-dependent advantage transfers to…

  16. Screening the High-Risk Newborn for Hearing Loss: The Crib-O-Gram v the Auditory Brainstem Response.

    ERIC Educational Resources Information Center

    Cox, L. Clarke

    1988-01-01

    Presented are a rationale for identifying hearing loss in infancy and a history of screening procedures. The Crib-O-Gram and auditory brainstem response (ABR) tests are evaluated for reliability, validity, and cost-effectiveness. The ABR is recommended, and fully automated ABR instrumentation, which lowers expenses for trained personnel and…

  17. TEN DAY EXPOSURES TO CARBONYL SULFIDE PRODUCE BRAINSTEM LESIONS AND CHANGES IN BRAINSTEM AUDITORY EVOKED RESPONSES IN FISCHER 344N RATS.

    EPA Science Inventory

    Carbonyl sulfide (COS) is a chemical intermediate in the production of pesticides and herbicides, a metabolite of carbon disulfide, a byproduct of the combustion of organic material, and a naturally occurring compound. COS was included in a Toxic Substances Control Act request fo...

  18. Musicians and Tone-Language Speakers Share Enhanced Brainstem Encoding but Not Perceptual Benefits for Musical Pitch

    ERIC Educational Resources Information Center

    Bidelman, Gavin M.; Gandour, Jackson T.; Krishnan, Ananthanarayan

    2011-01-01

    Behavioral and neurophysiological transfer effects from music experience to language processing are well-established but it is currently unclear whether or not linguistic expertise (e.g., speaking a tone language) benefits music-related processing and its perception. Here, we compare brainstem responses of English-speaking musicians/non-musicians…

  19. Acute Tetraparesis with Respiratory Failure after Steroid Administration in a Patient with a Dural Arteriovenous Fistula at the Craniocervical Junction

    PubMed Central

    Takahashi, Hisashi; Ueshima, Taiki; Goto, Daiki; Kimura, Tadashi; Yuki, Natsuko; Inoue, Yasuo; Yoshioka, Akira

    2017-01-01

    A 63-year-old man developed vomiting, paraparesis, dysuria, bulbar palsy, and orthostatic hypotension over a period of 5 months. Neuroradiological examinations showed a swollen lower brainstem with a dural arteriovenous fistula at the craniocervical junction (DAVF-CCJ). A steroid was administered intravenously in the hospital to relieve brainstem edema. A few hours later, however, the patient developed acute tetraparesis with respiratory failure. Recently, there have been several reports describing the acute worsening of paraparesis in patients with a spinal dural arteriovenous fistula after steroid treatment. In addition to these reports, the present case suggests the risk of administering steroids to patients with DAVF-CCJ, especially those with brainstem dysfunction. PMID:29225249

  20. Reduced noise susceptibility in littermate offspring from heterozygous animals of the German waltzing guinea pig.

    PubMed

    Skjönsberg, Åsa; Mannström, Paula

    2015-07-08

    The German waltzing guinea pig is a spontaneously mutated strain with severe auditory and vestibular impairment caused by a so far unknown genetic mutation. The animals are born deaf and show a circling behavior. The heterozygote animals of this guinea pig strain have functionally normal hearing and balance. However, these animals have, in earlier studies, shown an increased resistance to noise compared with normal wild-type guinea pigs. In the present study, we explored the functional hearing with auditory brainstem response thresholds before and at different time points after noise exposure. Symptom-free littermates from heterozygote couples of the German waltzing guinea pigs were exclusively used for the study, which, after the hearing test, were sent back for breeding to confirm their genotype (i.e. heterozygote or normal). The aim of this paper was to ascertain that the previously shown reduced susceptibility to noise trauma in the heterozygote animals of the German waltzing guinea pig was also evident when littermates were used as control animals. The findings are important for further analysis of the heterozygote animals of this strain and for future investigations of the underlying mechanisms behind the diverse susceptibility to exposures of loud sound.

  1. Delayed auditory pathway maturation and prematurity.

    PubMed

    Koenighofer, Martin; Parzefall, Thomas; Ramsebner, Reinhard; Lucas, Trevor; Frei, Klemens

    2015-06-01

    Hearing loss is the most common sensory disorder in developed countries and leads to a severe reduction in quality of life. In this uncontrolled case series, we evaluated the auditory development in patients suffering from congenital nonsyndromic hearing impairment related to preterm birth. Six patients delivered preterm (25th-35th gestational weeks) suffering from mild to profound congenital nonsyndromic hearing impairment, descending from healthy, nonconsanguineous parents and were evaluated by otoacoustic emissions, tympanometry, brainstem-evoked response audiometry, and genetic testing. All patients were treated with hearing aids, and one patient required cochlear implantation. One preterm infant (32nd gestational week) initially presented with a 70 dB hearing loss, accompanied by negative otoacoustic emissions and normal tympanometric findings. The patient was treated with hearing aids and displayed a gradual improvement in bilateral hearing that completely normalized by 14 months of age accompanied by the development of otoacoustic emission responses. Conclusions We present here for the first time a fully documented preterm patient with delayed auditory pathway maturation and normalization of hearing within 14 months of birth. Although rare, postpartum development of the auditory system should, therefore, be considered in the initial stages for treating preterm hearing impaired patients.

  2. Pharmacodynamic action and mechanism of Du Liang soft capsule, a traditional Chinese medicine capsule, on treating nitroglycerin-induced migraine.

    PubMed

    Hou, Min; Tang, Qing; Xue, Qiang; Zhang, Xiaona; Liu, Yang; Yang, Sheng; Chen, Liechun; Xu, Xiaoyu

    2017-01-04

    Du Liang soft capsule (DL) is a traditional Chinese medicine for treating migraines; it is made from two Chinese herbs, including LigusticumstriatumDC., root; Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., root. In the present study, we aimed to elucidate the pharmacodynamic action of DL and its mechanism in an animal model of migraines induced by glyceryl trinitrate (GTN). Sixty rats were randomly divided into six groups, including a normal control group, model control group, positive group (Sumatriptan 0.006gkg -1 ), and three DL groups (0.44, 1.31 and 3.93gkg -1 ). All rats were intragastrically treated with the corresponding treatment for 7 consecutive days, and they were subcutaneously injected with GTN (10mgkg -1 ) 30min after the last treatment, except in the normal control group. After model establishment, the behaviors of all rats, including head scratching, cage climbing, and the development of red ears were observed continuously by digital camera every 30min for 3h. Four hours after GTN treatment, all rats were anaesthetized and the blood and tissue samples were collected. Plasma calcitonin gene related to peptide (CGRP) and endothelin (ET) levels were measured using the radioimmunoassay method, and serum NO was determined by the colorimetric method. Afterwards, the brainstem tissues were dissected and washed with physiological saline, and divided evenly into two parts. One part was used to test the monoamine levels, including levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA), by the fluorometric method, and the other part was used to determine the nuclear factor kappaB (NF-κB) p65, nuclear c-fos, inducible nitric oxide synthase (iNOS), interleukin (IL)-1β (IL-1β), and cyclooxygenase-2 (COX-2) levels by Western blot analysis. In the pharmacodynamic action assay, DL (1.31 and 3.93gkg -1 ) greatly improved the abnormal behaviors of migraine rats, including head scratching and cage climbing, and the development of red ears. In the mechanism assay, compared with the control group, the plasma CGRP and serum NO levels and the brainstem 5-HT, NE and DA levels in the DL administration groups were significantly decreased; and the plasma ET levels were remarkably increased. Moreover, down-regulation of NF-κB p65, c-fos and pro-inflammatory cytokines, including iNOS, IL-1β and COX-2 in the brainstem in the DL administration groups were observed by Western blot analysis. The above results suggested that DL has a therapeutic effect on migraines, and its mechanism may be related to adjusting the level of neurotransmitters and vasoactive substances, consequently relieving neurogenic inflammation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. SU-C-BRA-04: Automated Segmentation of Head-And-Neck CT Images for Radiotherapy Treatment Planning Via Multi-Atlas Machine Learning (MAML)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ren, X; Gao, H; Sharp, G

    Purpose: Accurate image segmentation is a crucial step during image guided radiation therapy. This work proposes multi-atlas machine learning (MAML) algorithm for automated segmentation of head-and-neck CT images. Methods: As the first step, the algorithm utilizes normalized mutual information as similarity metric, affine registration combined with multiresolution B-Spline registration, and then fuses together using the label fusion strategy via Plastimatch. As the second step, the following feature selection strategy is proposed to extract five feature components from reference or atlas images: intensity (I), distance map (D), box (B), center of gravity (C) and stable point (S). The box feature Bmore » is novel. It describes a relative position from each point to minimum inscribed rectangle of ROI. The center-of-gravity feature C is the 3D Euclidean distance from a sample point to the ROI center of gravity, and then S is the distance of the sample point to the landmarks. Then, we adopt random forest (RF) in Scikit-learn, a Python module integrating a wide range of state-of-the-art machine learning algorithms as classifier. Different feature and atlas strategies are used for different ROIs for improved performance, such as multi-atlas strategy with reference box for brainstem, and single-atlas strategy with reference landmark for optic chiasm. Results: The algorithm was validated on a set of 33 CT images with manual contours using a leave-one-out cross-validation strategy. Dice similarity coefficients between manual contours and automated contours were calculated: the proposed MAML method had an improvement from 0.79 to 0.83 for brainstem and 0.11 to 0.52 for optic chiasm with respect to multi-atlas segmentation method (MA). Conclusion: A MAML method has been proposed for automated segmentation of head-and-neck CT images with improved performance. It provides the comparable result in brainstem and the improved result in optic chiasm compared with MA. Xuhua Ren and Hao Gao were partially supported by the NSFC (#11405105), the 973 Program (#2015CB856000), and the Shanghai Pujiang Talent Program (#14PJ1404500).« less

  4. Longitudinal evaluation of corticospinal tract in patients with resected brainstem cavernous malformations using high-definition fiber tractography and diffusion connectometry analysis: preliminary experience.

    PubMed

    Faraji, Amir H; Abhinav, Kumar; Jarbo, Kevin; Yeh, Fang-Cheng; Shin, Samuel S; Pathak, Sudhir; Hirsch, Barry E; Schneider, Walter; Fernandez-Miranda, Juan C; Friedlander, Robert M

    2015-11-01

    Brainstem cavernous malformations (CMs) are challenging due to a higher symptomatic hemorrhage rate and potential morbidity associated with their resection. The authors aimed to preoperatively define the relationship of CMs to the perilesional corticospinal tracts (CSTs) by obtaining qualitative and quantitative data using high-definition fiber tractography. These data were examined postoperatively by using longitudinal scans and in relation to patients' symptomatology. The extent of involvement of the CST was further evaluated longitudinally using the automated "diffusion connectometry" analysis. Fiber tractography was performed with DSI Studio using a quantitative anisotropy (QA)-based generalized deterministic tracking algorithm. Qualitatively, CST was classified as being "disrupted" and/or "displaced." Quantitative analysis involved obtaining mean QA values for the CST and its perilesional and nonperilesional segments. The contralateral CST was used for comparison. Diffusion connectometry analysis included comparison of patients' data with a template from 90 normal subjects. Three patients (mean age 22 years) with symptomatic pontomesencephalic hemorrhagic CMs and varying degrees of hemiparesis were identified. The mean follow-up period was 37.3 months. Qualitatively, CST was partially disrupted and displaced in all. Direction of the displacement was different in each case and progressively improved corresponding with the patient's neurological status. No patient experienced neurological decline related to the resection. The perilesional mean QA percentage decreases supported tract disruption and decreased further over the follow-up period (Case 1, 26%-49%; Case 2, 35%-66%; and Case 3, 63%-78%). Diffusion connectometry demonstrated rostrocaudal involvement of the CST consistent with the quantitative data. Hemorrhagic brainstem CMs can disrupt and displace perilesional white matter tracts with the latter occurring in unpredictable directions. This requires the use of tractography to accurately define their orientation to optimize surgical entry point, minimize morbidity, and enhance neurological outcomes. Observed anisotropy decreases in the perilesional segments are consistent with neural injury following hemorrhagic insults. A model using these values in different CST segments can be used to longitudinally monitor its craniocaudal integrity. Diffusion connectometry is a complementary approach providing longitudinal information on the rostrocaudal involvement of the CST.

  5. Birth-related expression of c-fos, c-jun and substance P mRNAs in the rat brainstem and pia mater: possible relationship to changes in central chemosensitivity.

    PubMed

    Wickström, H R; Holgert, H; Hökfelt, T; Lagercrantz, H

    1999-02-05

    In situ hybridization was used to characterize respiration-related areas of the brainstem activated around the time of birth as well as their postnatal sensitivity to CO2. Levels of mRNA corresponding to the immediate early genes (IEG), c-fos and c-jun, and of substance P precursor, ppt-A, were determined in rat fetuses (E21) and neonatal pups (1 h, 1 day and 6 days after normal birth) and after exposure to hypercapnia (12% CO2 for 1 h). Transient increases in c-fos mRNA were observed in the central chemoreceptor area of the ventral medullary surface (VMS), in the lateral reticular nucleus (LRN), in the nucleus of the solitary tract (NTS), and in the nucleus raphé pallidus (RPA) 1 h after birth. Increased expression of c-fos mRNA in the VMS could also be evoked by hypercapnia and this response was particularly pronounced 1 day after birth. On the other hand, c-jun mRNA could be detected already at E21 in the hypoglossal nucleus (XII) and LRN and these levels were not significantly altered at 1 h after birth. There was, however, an increase in the expression of c-jun mRNA in the pia mater surrounding the brainstem after birth. At 1 day after birth, c-jun mRNA levels had decreased in the LRN and pia mater, and later on (6 days after birth) in XII. Furthermore, the ppt-A mRNA level in NTS increased immediately after birth and remained high 1 and 6 days later. These results suggest that (a) the central chemoreceptor area of the VMS, as well as the NTS, LRN, RPA and pia mater are activated following birth; (b) the VMS, but not the other structures examined, can be activated immediately after birth by hypercapnia; and (c) increased expression of ppt-A mRNA may be related to the transition of respiratory control at birth. Copyright 1998 Elsevier Science B.V.

  6. Generators of the brainstem auditory evoked potential in cat. I. An experimental approach to their identification.

    PubMed

    Melcher, J R; Knudson, I M; Fullerton, B C; Guinan, J J; Norris, B E; Kiang, N Y

    1996-04-01

    This paper is the first in a series aimed at identifying the cellular generators of the brainstem auditory evoked potential (BAEP) in cats. The approach involves (1) developing experimental procedures for making small selective lesions and determining the corresponding changes in BAEP waveforms, (2) identifying brainstem regions involved in BAEP generation by examining the effects of lesions on the BAEP and (3) identifying specific cell populations involved by combining the lesion results with electrophysiological and anatomical information from other kinds of studies. We created lesions in the lower brainstem by injecting kainic acid which is generally toxic for neuronal cell bodies but not for axons and terminals. This first paper describes the justifications for using kainic acid, explains the associated problems, and develops a methodology that addresses the main difficulties. The issues and aspects of the specific methods are generally applicable to physiological and anatomical studies using any neurotoxin, as well as to the present BAEP study. The methods chosen involved (1) measuring the BAEP at regular intervals until it reached a post-injection steady state and perfusing the animals with fixative shortly after the last BAEP recordings were made, (2) using objective criteria to distinguish injection-related BAEP changes from unrelated ones, (3) making control injections to identify effects not due to kainic acid toxicity, (4) verifying the anatomical and functional integrity of axons in lesioned regions, and (5) examining injected brainstems microscopically for cell loss and cellular abnormalities indicating dysfunction. This combination of methods enabled us to identify BAEP changes which are clearly correlated with lesion locations.

  7. A comparison of the brainstem auditory evoked response in healthy ears of unilaterally deaf dogs and bilaterally hearing dogs.

    PubMed

    Plonek, M; Nicpoń, J; Kubiak, K; Wrzosek, M

    2017-03-01

    Auditory plasticity in response to unilateral deafness has been reported in various animal species. Subcortical changes occurring in unilaterally deaf young dogs using the brainstem auditory evoked response have not been evaluated yet. The aim of this study was to assess the brainstem auditory evoked response findings in dogs with unilateral hearing loss, and compare them with recordings obtained from healthy dogs. Brainstem auditory evoked responses (amplitudes and latencies of waves I, II, III, V, the V/I wave amplitude ratio, wave I-V, I-III and III-V interpeak intervals) were studied retrospectively in forty-six privately owned dogs, which were either unilaterally deaf or had bilateral hearing. The data obtained from the hearing ears in unilaterally deaf dogs were compared to values obtained from their healthy littermates. Statistically significant differences in the amplitude of wave III and the V/I wave amplitude ratio at 75 dB nHL were found between the group of unilaterally deaf puppies and the control group. The recordings of dogs with single-sided deafness were compared, and the results showed no statistically significant differences in the latencies and amplitudes of the waves between left- (AL) and right-sided (AR) deafness. The recordings of the brainstem auditory evoked response in canines with unilateral inborn deafness in this study varied compared to recordings from healthy dogs. Future studies looking into electrophysiological assessment of hearing in conjunction with imaging modalities to determine subcortical auditory plasticity and auditory lateralization in unilaterally deaf dogs are warranted.

  8. White matter damage is related to ataxia severity in SCA3.

    PubMed

    Kang, J-S; Klein, J C; Baudrexel, S; Deichmann, R; Nolte, D; Hilker, R

    2014-02-01

    Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem. White matter pathology is generally less severe and thought to occur in the brainstem, spinal cord, and cerebellar white matter. Here, we investigated both grey and white matter pathology in a group of 12 SCA3 patients and matched controls. We used voxel-based morphometry for analysis of tissue loss, and tract-based spatial statistics (TBSS) on diffusion magnetic resonance imaging to investigate microstructural pathology. We analysed correlations between microstructural properties of the brain and ataxia severity, as measured by the Scale for the Assessment and Rating of Ataxia (SARA) score. SCA3 patients exhibited significant loss of both grey and white matter in the cerebellar hemispheres, brainstem including pons and in lateral thalamus. On between-group analysis, TBSS detected widespread microstructural white matter pathology in the cerebellum, brainstem, and bilaterally in thalamus and the cerebral hemispheres. Furthermore, fractional anisotropy in a white matter network comprising frontal, thalamic, brainstem and left cerebellar white matter strongly and negatively correlated with SARA ataxia scores. Tractography identified the thalamic white matter thus implicated as belonging to ventrolateral thalamus. Disruption of white matter integrity in patients suffering from SCA3 is more widespread than previously thought. Moreover, our data provide evidence that microstructural white matter changes in SCA3 are strongly related to the clinical severity of ataxia symptoms.

  9. Brainstem structures are primarily affected in an experimental model of severe scorpion envenomation.

    PubMed

    Guidine, Patrícia Alves Maia; Cash, Diana; Drumond, Luciana Estefani; de Souza E Rezende, Gustavo Henrique; Massensini, André Ricardo; Williams, Steve Charles Rees; Moraes-Santos, Tasso; Moraes, Márcio Flávio Dutra; Mesquita, Michel Bernanos Soares

    2014-01-01

    Severe scorpion envenoming (SSE) is more frequent in children and is characterized by systemic dysfunctions with a mortality rate of up to 9%. Recent evidence shows that the central nervous system (CNS) plays a key role in triggering the cascade of symptoms present in SSE. The age-dependent role of the CNS in SSE lethality may be summarized in 3 hypotheses: (1) the shown increased blood brain barrier permeability of infants to the toxins would especially and primarily compromise neurovegetative control areas, (2) the neurons within these areas have high affinity to the toxins, and (3) the neurovascular interaction is such that SSE metabolically compromises proper function of toxin-targeted areas. A pharmacological magnetic resonance imaging paradigm was used to evaluate localized hemodynamic changes in relative cerebral blood volume (rCBV) for 30 min after the injection of TsTX, the most lethal toxin from the venom of the Tityus serrulatus scorpion. The brainstem showed significant rCBV reduction 1 min after TsTX administration, whereas rostral brain areas had delayed increase in rCBV (confirmed by laser Doppler measurements of cortical cerebral blood flow). Moreover, metabolic activity by 14C-2-deoxyglucose autoradiography showed the highest relative increase at the brainstem. To test whether TsTX has high affinity to brainstem neurons, the lateral ventricle was injected with Alexa Fluor 568 TsTX. Although some neurons showed intense fluorescence, the labeling pattern suggests that specific neurons were targeted. Altogether, these results suggest that brainstem areas involved in neurovegetative control are most likely within the primary structures triggering the cascade of symptoms present in SSE.

  10. Repetitive Diving in Trained Rats Still Increases Fos Production in Brainstem Neurons after Bilateral Sectioning of the Anterior Ethmoidal Nerve

    PubMed Central

    McCulloch, Paul F.; Warren, Erik A.; DiNovo, Karyn M.

    2016-01-01

    This research was designed to investigate the role of the anterior ethmoidal nerve (AEN) during repetitive trained diving in rats, with specific attention to activation of afferent and efferent brainstem nuclei that are part of this reflexive response. The AEN innervates the nose and nasal passages and is thought to be an important component of the afferent limb of the diving response. Male Sprague-Dawley rats (N = 24) were trained to swim and dive through a 5 m underwater maze. Some rats (N = 12) had bilateral sectioning of the AEN, others a Sham surgery (N = 12). Twelve rats (6 AEN cut and 6 Sham) had 24 post-surgical dive trials over 2 h to activate brainstem neurons to produce Fos, a neuronal activation marker. Remaining rats were non-diving controls. Diving animals had significantly more Fos-positive neurons than non-diving animals in the caudal pressor area, ventral medullary dorsal horn, ventral paratrigeminal nucleus, nucleus tractus solitarius, rostral ventrolateral medulla, Raphe nuclei, A5, Locus Coeruleus, and Kölliker-Fuse area. There were no significant differences in brainstem Fos labeling in rats diving with and without intact AENs. Thus, the AENs are not required for initiation of the diving response. Other nerve(s) that innervate the nose and nasal passages, and/or suprabulbar activation of brainstem neurons, may be responsible for the pattern of neuronal activation observed during repetitive trained diving in rats. These results help define the central neuronal circuitry of the mammalian diving response. PMID:27148082

  11. Curvularia abscess of the brainstem.

    PubMed

    Skovrlj, Branko; Haghighi, Maryam; Smethurst, Mark E; Caridi, John; Bederson, Joshua B

    2014-01-01

    To present a unique case of a brainstem Curvularia fungal infection and review the diagnosis and management of this rare phenomenon. A 33-year-old immunocompetent African American male presented with 2 weeks of headache, nausea, and vomiting in a setting of a recent 20-lb weight loss. Neurological examination was positive for multiple cranial nerve palsies, hemisensory loss, and gait instability. Magnetic resonance imaging demonstrated an enhancing medullary lesion. Metastatic and infectious workup revealed a left lung lesion, which on subsequent biopsy was positive for a granuloma yielding no further clues to the etiology of the brainstem lesion. On surgical exploration of the cranial lesion, a puss-filed, encapsulated lesion was encountered that was tightly adherent to the brainstem. Intraoperative biopsy of the lesion capsule was initially negative but on postoperative day 9, fungal hyphae were encountered identified on morphology as Curvularia species. The patient was started on triple antifungal therapy but necessitated a second surgery for lesion debulking and drainage. The patient was discharged home 10 weeks after initial presentation. At the 13-months follow-up the patient is doing very well and his neurological examination continues to improve. This is the first reported case of a brainstem Curvularia infection. This case highlights the importance of an aggressive surgical and antibiotic therapy in the treatment of central nervous system Curvularia infections. There appears to be a strong relationship between heavy marijuana use and Curvularia infection, producing lung granulomas that may extend to other organs such as the central nervous system of immunocompetent patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Potential asphyxia and brainstem abnormalities in sudden and unexpected death in infants.

    PubMed

    Randall, Bradley B; Paterson, David S; Haas, Elisabeth A; Broadbelt, Kevin G; Duncan, Jhodie R; Mena, Othon J; Krous, Henry F; Trachtenberg, Felicia L; Kinney, Hannah C

    2013-12-01

    Sudden and unexplained death is a leading cause of infant mortality. Certain characteristics of the sleep environment increase the risk for sleep-related sudden and unexplained infant death. These characteristics have the potential to generate asphyxial conditions. We tested the hypothesis that infants may be exposed to differing degrees of asphyxia in sleep environments, such that vulnerable infants with a severe underlying brainstem deficiency in serotonergic, γ-aminobutyric acid-ergic, or 14-3-3 transduction proteins succumb even without asphyxial triggers (e.g., supine), whereas infants with intermediate or borderline brainstem deficiencies require asphyxial stressors to precipitate death. We classified cases of sudden infant death into categories relative to a "potential asphyxia" schema in a cohort autopsied at the San Diego County Medical Examiner's Office. Controls were infants who died with known causes of death established at autopsy. Analysis of covariance tested for differences between groups. Medullary neurochemical abnormalities were present in both infants dying suddenly in circumstances consistent with asphyxia and infants dying suddenly without obvious asphyxia-generating circumstances. There were no differences in the mean neurochemical measures between these 2 groups, although mean measures were both significantly lower (P < .05) than those of controls dying of known causes. We found no direct relationship between the presence of potentially asphyxia conditions in the sleep environment and brainstem abnormalities in infants dying suddenly and unexpectedly. Brainstem abnormalities were associated with both asphyxia-generating and non-asphyxia generating conditions. Heeding safe sleep messages is essential for all infants, especially given our current inability to detect underlying vulnerabilities.

  13. Potential Asphyxia and Brainstem Abnormalities in Sudden and Unexpected Death in Infants

    PubMed Central

    Randall, Bradley B.; Paterson, David S.; Haas, Elisabeth A.; Broadbelt, Kevin G.; Duncan, Jhodie R.; Mena, Othon J.; Krous, Henry F.; Trachtenberg, Felicia L.

    2013-01-01

    OBJECTIVE: Sudden and unexplained death is a leading cause of infant mortality. Certain characteristics of the sleep environment increase the risk for sleep-related sudden and unexplained infant death. These characteristics have the potential to generate asphyxial conditions. We tested the hypothesis that infants may be exposed to differing degrees of asphyxia in sleep environments, such that vulnerable infants with a severe underlying brainstem deficiency in serotonergic, γ-aminobutyric acid-ergic, or 14-3-3 transduction proteins succumb even without asphyxial triggers (eg, supine), whereas infants with intermediate or borderline brainstem deficiencies require asphyxial stressors to precipitate death. METHODS: We classified cases of sudden infant death into categories relative to a “potential asphyxia” schema in a cohort autopsied at the San Diego County Medical Examiner’s Office. Controls were infants who died with known causes of death established at autopsy. Analysis of covariance tested for differences between groups. RESULTS: Medullary neurochemical abnormalities were present in both infants dying suddenly in circumstances consistent with asphyxia and infants dying suddenly without obvious asphyxia-generating circumstances. There were no differences in the mean neurochemical measures between these 2 groups, although mean measures were both significantly lower (P < .05) than those of controls dying of known causes. CONCLUSIONS: We found no direct relationship between the presence of potentially asphyxia conditions in the sleep environment and brainstem abnormalities in infants dying suddenly and unexpectedly. Brainstem abnormalities were associated with both asphyxia-generating and non–asphyxia generating conditions. Heeding safe sleep messages is essential for all infants, especially given our current inability to detect underlying vulnerabilities. PMID:24218471

  14. Structural Changes and Lack of HCN1 Channels in the Binaural Auditory Brainstem of the Naked Mole-Rat (Heterocephalus glaber).

    PubMed

    Gessele, Nikodemus; Garcia-Pino, Elisabet; Omerbašić, Damir; Park, Thomas J; Koch, Ursula

    2016-01-01

    Naked mole-rats (Heterocephalus glaber) live in large eu-social, underground colonies in narrow burrows and are exposed to a large repertoire of communication signals but negligible binaural sound localization cues, such as interaural time and intensity differences. We therefore asked whether monaural and binaural auditory brainstem nuclei in the naked mole-rat are differentially adjusted to this acoustic environment. Using antibody stainings against excitatory and inhibitory presynaptic structures, namely the vesicular glutamate transporter VGluT1 and the glycine transporter GlyT2 we identified all major auditory brainstem nuclei except the superior paraolivary nucleus in these animals. Naked mole-rats possess a well structured medial superior olive, with a similar synaptic arrangement to interaural-time-difference encoding animals. The neighboring lateral superior olive, which analyzes interaural intensity differences, is large and elongated, whereas the medial nucleus of the trapezoid body, which provides the contralateral inhibitory input to these binaural nuclei, is reduced in size. In contrast, the cochlear nucleus, the nuclei of the lateral lemniscus and the inferior colliculus are not considerably different when compared to other rodent species. Most interestingly, binaural auditory brainstem nuclei lack the membrane-bound hyperpolarization-activated channel HCN1, a voltage-gated ion channel that greatly contributes to the fast integration times in binaural nuclei of the superior olivary complex in other species. This suggests substantially lengthened membrane time constants and thus prolonged temporal integration of inputs in binaural auditory brainstem neurons and might be linked to the severely degenerated sound localization abilities in these animals.

  15. Tonotopic alterations in inhibitory input to the medial nucleus of the trapezoid body in a mouse model of Fragile X syndrome.

    PubMed

    McCullagh, Elizabeth A; Salcedo, Ernesto; Huntsman, Molly M; Klug, Achim

    2017-11-01

    Hyperexcitability and the imbalance of excitation/inhibition are one of the leading causes of abnormal sensory processing in Fragile X syndrome (FXS). The precise timing and distribution of excitation and inhibition is crucial for auditory processing at the level of the auditory brainstem, which is responsible for sound localization ability. Sound localization is one of the sensory abilities disrupted by loss of the Fragile X Mental Retardation 1 (Fmr1) gene. Using triple immunofluorescence staining we tested whether there were alterations in the number and size of presynaptic structures for the three primary neurotransmitters (glutamate, glycine, and GABA) in the auditory brainstem of Fmr1 knockout mice. We found decreases in either glycinergic or GABAergic inhibition to the medial nucleus of the trapezoid body (MNTB) specific to the tonotopic location within the nucleus. MNTB is one of the primary inhibitory nuclei in the auditory brainstem and participates in the sound localization process with fast and well-timed inhibition. Thus, a decrease in inhibitory afferents to MNTB neurons should lead to greater inhibitory output to the projections from this nucleus. In contrast, we did not see any other significant alterations in balance of excitation/inhibition in any of the other auditory brainstem nuclei measured, suggesting that the alterations observed in the MNTB are both nucleus and frequency specific. We furthermore show that glycinergic inhibition may be an important contributor to imbalances in excitation and inhibition in FXS and that the auditory brainstem is a useful circuit for testing these imbalances. © 2017 Wiley Periodicals, Inc.

  16. Deletion of Fmr1 Alters Function and Synaptic Inputs in the Auditory Brainstem

    PubMed Central

    Rotschafer, Sarah E.; Marshak, Sonya; Cramer, Karina S.

    2015-01-01

    Fragile X Syndrome (FXS), a neurodevelopmental disorder, is the most prevalent single-gene cause of autism spectrum disorder. Autism has been associated with impaired auditory processing, abnormalities in the auditory brainstem response (ABR), and reduced cell number and size in the auditory brainstem nuclei. FXS is characterized by elevated cortical responses to sound stimuli, with some evidence for aberrant ABRs. Here, we assessed ABRs and auditory brainstem anatomy in Fmr1 -/- mice, an animal model of FXS. We found that Fmr1 -/- mice showed elevated response thresholds to both click and tone stimuli. Amplitudes of ABR responses were reduced in Fmr1 -/- mice for early peaks of the ABR. The growth of the peak I response with sound intensity was less steep in mutants that in wild type mice. In contrast, amplitudes and response growth in peaks IV and V did not differ between these groups. We did not observe differences in peak latencies or in interpeak latencies. Cell size was reduced in Fmr1 -/- mice in the ventral cochlear nucleus (VCN) and in the medial nucleus of the trapezoid body (MNTB). We quantified levels of inhibitory and excitatory synaptic inputs in these nuclei using markers for presynaptic proteins. We measured VGAT and VGLUT immunolabeling in VCN, MNTB, and the lateral superior olive (LSO). VGAT expression in MNTB was significantly greater in the Fmr1 -/- mouse than in wild type mice. Together, these observations demonstrate that FXS affects peripheral and central aspects of hearing and alters the balance of excitation and inhibition in the auditory brainstem. PMID:25679778

  17. Block-Dependent Sedation during Epidural Anaesthesia is Associated with Delayed Brainstem Conduction

    PubMed Central

    Wadhwa, Anupama; Shah, Yunus M.; Lin, Chum-Ming; Haugh, Gilbert S.; Sessler, Daniel I.

    2005-01-01

    Neuraxial anaesthesia produces a sedative and anesthetic-sparing effect. Recent evidence suggests that spinal cord anaesthesia modifies reticulo-thalamo-cortical arousal by decreasing afferent sensory transmission. We hypothesized that epidural anaesthesia produces sensory deafferentation-dependent sedation that is associated with impairment of brainstem transmission. We used brainstem auditory evoked potentials (BAEP) to evaluate reticular function in 11 volunteers. Epidural anaesthesia was induced with 2% 2-chloroprocaine. Hemodynamic and respiratory responses, sensory block level, sedation depth and BAEP were assessed throughout induction and resolution of epidural anaesthesia. Sedation was evaluated using verbal rating score (VRS), observer's assessment alertness/sedation (OAA/S) score, and bispectral index (BIS). Prediction probability (PK) was used to associate sensory block with sedation, as well as BIS with other sedation measures. Spearman rank order correlation was used to associate block level and sedation with the absolute and interpeak BAEP latencies. Sensory block level significantly predicted VRS (PK = 0.747), OAA/S score (PK = 0.748) and BIS. Bispectral index predicted VRS and OAA/S score (PK = 0.728). The latency of wave III of BAEP significantly correlated with sedation level (rho = 0.335, P < 0.01) and sensory block (rho = 0.394, P < 0.01). The other BAEP parameters did not change during epidural anaesthesia. Hemodynamic and respiratory responses remained stable throughout the study. Sedation during epidural anaesthesia depends on sensory block level and is associated with detectable block-dependent alterations in the brainstem auditory evoked responses. Sensory deafferentation may reduce CNS alertness through mechanisms related to brainstem neural activity. PMID:15220178

  18. High-resolution computed tomography evaluation of the bronchial lumen to vertebral body diameter and pulmonary artery to vertebral body diameter ratios in anesthetized ventilated normal cats.

    PubMed

    Lee-Fowler, Tekla M; Cole, Robert C; Dillon, A Ray; Tillson, D Michael; Garbarino, Rachel; Barney, Sharron

    2017-10-01

    Objectives Bronchial lumen to pulmonary artery diameter (BA) ratio has been utilized to investigate pulmonary pathology on high-resolution CT images. Diseases affecting both the bronchi and pulmonary arteries render the BA ratio less useful. The purpose of the study was to establish bronchial lumen diameter to vertebral body diameter (BV) and pulmonary artery diameter to vertebral body diameter (AV) ratios in normal cats. Methods Using high-resolution CT images, 16 sets of measurements (sixth thoracic vertebral body [mid-body], each lobar bronchi and companion pulmonary artery diameter) were acquired from young adult female cats and 41 sets from pubertal female cats. Results Young adult and pubertal cat BV ratios were not statistically different from each other in any lung lobe. Significant differences between individual lung lobe BV ratios were noted on combined age group analysis. Caudal lung lobe AV ratios were significantly different between young adult and pubertal cats. All other lung lobe AV ratios were not significantly different. Caudal lung lobe AV ratios were significantly different from all other lung lobes but not from each other in both the young adult and pubertal cats. Conclusions and relevance BV ratio reference intervals determined for individual lung lobes could be applied to both young adult and pubertal cats. Separate AV ratios for individual lung lobes would be required for young adult and pubertal cats. These ratios should allow more accurate evaluation of cats with concurrent bronchial and pulmonary arterial disease.

  19. Experience-Dependent Enhancement of Linguistic Pitch Representation in the Brainstem Is Not Specific to a Speech Context

    ERIC Educational Resources Information Center

    Krishnan, Ananthanarayan; Swaminathan, Jayaganesh; Gandour, Jackson T.

    2009-01-01

    Neural representation of pitch is influenced by lifelong experiences with music and language at both cortical and subcortical levels of processing. The aim of this article is to determine whether neural plasticity for pitch representation at the level of the brainstem is dependent upon specific "dimensions" of pitch contours that commonly occur as…

  20. Descending motor pathways and the spinal motor system - Limbic and non-limbic components

    NASA Technical Reports Server (NTRS)

    Holstege, Gert

    1991-01-01

    Research on descending motor pathways to caudal brainstem and spinal cord in the spinal motor system is reviewed. Particular attention is given to somatic and autonomic motoneurons in the spinal cord and brainstem, local projections to motoneurons, bulbospinal interneurons projecting to motoneurons, descending pathways of somatic motor control systems, and descending pathways involved in limbic motor control systems.

  1. Maturation of Peripheral and Brainstem Auditory Function in the First Year Following Perinatal Asphyxia: A Longitudinal Study.

    ERIC Educational Resources Information Center

    Jiang, Ze D.

    1998-01-01

    A study of 44 infants who suffered asphyxia during the perinatal period examined the influence of perinatal asphyxia on the maturation of auditory pathways by serial recordings of the brainstem auditory evoked potentials (BAEP). The general maturational course of the BAEP following asphyxia was similar to a control group. (Author/CR)

  2. Hearing Screening of High-Risk Newborns with Brainstem Auditory Evoked Potentials: A Follow-Up Study.

    ERIC Educational Resources Information Center

    Shannon, Dorothy A.; And Others

    1984-01-01

    The brainstem auditory evoked potential (BAEP) was evaluated as a hearing screening test in 168 high-risk newborns. The BAEP was found to be a sensitive procedure for the early identification of hearing-impaired newborns. However, the yield of significant hearing abnormalities was less than predicted in other studies using BAEP. (Author/CL)

  3. A Neurobiological Model for the Effects of Early Brainstem Functioning on the Development of Behavior and Emotion Regulation in Infants: Implications for Prenatal and Perinatal Risk

    ERIC Educational Resources Information Center

    Geva, Ronny; Feldman, Ruth

    2008-01-01

    Neurobiological models propose an evolutionary, vertical-integrative perspective on emotion and behavior regulation, which postulates that regulatory functions are processed along three core brain systems: the brainstem, limbic, and cortical systems. To date, few developmental studies applied these models to research on prenatal and perinatal…

  4. Cross-Domain Effects of Music and Language Experience on the Representation of Pitch in the Human Auditory Brainstem

    ERIC Educational Resources Information Center

    Bidelman, Gavin M.; Gandour, Jackson T.; Krishnan, Ananthanarayan

    2011-01-01

    Neural encoding of pitch in the auditory brainstem is known to be shaped by long-term experience with language or music, implying that early sensory processing is subject to experience-dependent neural plasticity. In language, pitch patterns consist of sequences of continuous, curvilinear contours; in music, pitch patterns consist of relatively…

  5. Brainstem auditory evoked responses and ophthalmic findings in llamas and alpacas in eastern Canada

    PubMed Central

    Cullen, Cheryl L.; Lamont, Leigh A.

    2006-01-01

    Abstract Seventeen llamas and 23 alpacas of various coat and iris colors were evaluated for: 1) deafness by using brainstem auditory evoked response testing; and 2) for ocular abnormalities via complete ophthalmic examination. No animals were deaf. The most common ocular abnormalities noted were iris-to-iris persistent pupillary membranes and incipient cataracts. PMID:16536233

  6. Anatomy of the Vestibulo-automatic Outflow to the Gut

    NASA Technical Reports Server (NTRS)

    Torigoe, Y.

    1985-01-01

    Motion sickness can be induced by vestibular effects on the sympathetic portion of the autonomic nervous system. However, the pathways linking the vestibular and autonomic pathways are unknown. As a first step in this analysis, the locations of preganglionic sympathetic neurons (PSN) and dorsal root afferent ganglionic neurons (DRG) which supply sympathetic innervation to major portions of the gastrointestinal tract in rabbits were identified. The objective of a second series of experiments is to determine which of the brainstem nuclei project to the autonomic regions of the spinal cord that control gastrointestinal motility. To achieve this goal, a trans-synaptic retrograde tracer (3H-tetanus toxoid) is applied to the greater splanchnic nerve. This method allows the labeling of neurons within the brainstem that project only to the preganglionic synpathetic neurons. One structure that has been strongly implicated in mediating vestibulo-autonomic control is the cerebellum (i.e., nodulus and uvula). The outflow of these lobules to the autonomic regions of the brainstem is mediated by the fastigial nucleus. To determine the precise projections of the fastigial nucleus to the brainstem nuclei involved in emesis, anterograde tracer (3H-leucine) was injected into the fastigial nucleus in a third series of experiments.

  7. Awake craniotomy for assisting placement of auditory brainstem implant in NF2 patients.

    PubMed

    Zhou, Qiangyi; Yang, Zhijun; Wang, Zhenmin; Wang, Bo; Wang, Xingchao; Zhao, Chi; Zhang, Shun; Wu, Tao; Li, Peng; Li, Shiwei; Zhao, Fu; Liu, Pinan

    2018-06-01

    Auditory brainstem implants (ABIs) may be the only opportunity for patients with NF2 to regain some sense of hearing sensation. However, only a very small number of individuals achieved open-set speech understanding and high sentence scores. Suboptimal placement of the ABI electrode array over the cochlear nucleus may be one of main factors for poor auditory performance. In the current study, we present a method of awake craniotomy to assist with ABI placement. Awake surgery and hearing test via the retrosigmoid approach were performed for vestibular schwannoma resections and auditory brainstem implantations in four patients with NF2. Auditory outcomes and complications were assessed postoperatively. Three of 4 patients who underwent awake craniotomy during ABI surgery received reproducible auditory sensations intraoperatively. Satisfactory numbers of effective electrodes, threshold levels and distinct pitches were achieved in the wake-up hearing test. In addition, relatively few electrodes produced non-auditory percepts. There was no serious complication attributable to the ABI or awake craniotomy. It is safe and well tolerated for neurofibromatosis type 2 (NF2) patients using awake craniotomy during auditory brainstem implantation. This method can potentially improve the localization accuracy of the cochlear nucleus during surgery.

  8. Posterior reversible encephalopathy as the first manifestation of Bickerstaff's brainstem encephalitis.

    PubMed

    Chen, Pei-Ru; Chen, Shih-Pin

    2016-11-08

    Posterior reversible encephalopathy syndrome (PRES) has been associated with Guillain-Barre syndrome in rare cases. Here we report a patient in whom PRES was the presenting manifestation of Bickerstaff's brainstem encephalitis. A 75-year-old woman presented with acute onset of hypertension, headache, blurred vision, and left eyelid drooping. Magnetic resonance imaging of the brain showed characteristic PRES lesions involving the parietal and occipital lobes bilaterally. On the 6th day after symptom onset, the patient developed complete ptosis and external ophthalmoplegia of both eyes, progressive ataxia, and bilateral lower limb weakness. Cerebrospinal fluid analyses revealed albuminocytological dissociation (protein: 66.6 mg/dL, WBC: 0/μl), and nerve conduction studies showed demyelinating sensorimotor polyneuropathy. The patient developed somnolence and a left extensor plantar response on the 8th day. A diagnosis of Bickerstaff's brainstem encephalitis was made. Treatment with plasmapheresis led to a rapid improvement of clinical symptoms. To date, only five similar cases have been reported, but this is the only case in which PRES developed prior to treatment. PRES can be a comorbid condition with Bickerstaff's brainstem encephalitis, either preceding or following treatment; caution should be used in patients with either syndrome who exhibit atypical presentations.

  9. Effects of 12 Months Continuous Positive Airway Pressure on Sympathetic Activity Related Brainstem Function and Structure in Obstructive Sleep Apnea

    PubMed Central

    Henderson, Luke A.; Fatouleh, Rania H.; Lundblad, Linda C.; McKenzie, David K.; Macefield, Vaughan G.

    2016-01-01

    Muscle sympathetic nerve activity (MSNA) is greatly elevated in patients with obstructive sleep apnea (OSA) during normoxic daytime wakefulness. Increased MSNA is a precursor to hypertension and elevated cardiovascular morbidity and mortality. However, the mechanisms underlying the high MSNA in OSA are not well understood. In this study we used concurrent microneurography and magnetic resonance imaging to explore MSNA-related brainstem activity changes and anatomical changes in 15 control and 15 OSA subjects before and after 6 and 12 months of continuous positive airway pressure (CPAP) treatment. We found that following 6 and 12 months of CPAP treatment, resting MSNA levels were significantly reduced in individuals with OSA. Furthermore, this MSNA reduction was associated with restoration of MSNA-related brainstem activity and structural changes in the medullary raphe, rostral ventrolateral medulla, dorsolateral pons, and ventral midbrain. This restoration occurred after 6 months of CPAP treatment and was maintained following 12 months CPAP. These findings show that continual CPAP treatment is an effective long-term treatment for elevated MSNA likely due to its effects on restoring brainstem structure and function. PMID:27013952

  10. Toxicity evaluation of convection-enhanced delivery of small-molecule kinase inhibitors in naïve mouse brainstem.

    PubMed

    Zhou, Zhiping; Ho, Sharon L; Singh, Ranjodh; Pisapia, David J; Souweidane, Mark M

    2015-04-01

    Diffuse intrinsic pontine gliomas (DIPGs) are inoperable and lethal high-grade gliomas lacking definitive therapy. Platelet-derived growth factor receptor (PDGFR) and its downstream signaling molecules are the most commonly overexpressed oncogenes in DIPG. This study tested the effective concentration of PDGFR pathway inhibitors in cell culture and then toxicity of these small-molecule kinase inhibitors delivered to the mouse brainstem via convection-enhanced delivery (CED) for potential clinical application. Effective concentrations of small-molecule kinase inhibitors were first established in cell culture from a mouse brainstem glioma model. Sixteen mice underwent CED, a local drug delivery technique, of saline or of single and multidrug combinations of dasatinib (2 M), everolimus (20 M), and perifosine (0.63 mM) in the pons. Animals were kept alive for 3 days following the completion of infusion. No animals displayed any immediate or delayed neurological deficits postoperatively. Histological analysis revealed edema, microgliosis, acute inflammation, and/or axonal injury in the experimental animals consistent with mild acute drug toxicity. Brainstem CED of small-molecule kinase inhibitors in the mouse did not cause serious acute toxicities. Future studies will be necessary to evaluate longer-term safety to prepare for potential clinical application.

  11. [New opportunities of magnetic-resonance imaging: an algorithm of CSD-HARDI tractography in reconstruction of the brainstem reticular formation fibers].

    PubMed

    Aleksandrova, E V; Batalov, A I; Pogosbekyan, E L; Zakharova, N E; Fadeeva, L M; Kravchuk, A D; Pronin, I N; Potapov, A A

    2018-01-01

    The study purpose was to develop a technique for intravital visualization of the brainstem reticular formation fibers in healthy volunteers using magnetic resonance imaging (MRI). The study included 21 subjects (13 males and 8 females) aged 21 to 62 years. The study was performed on a magnetic resonance imaging scanner with a magnetic field strength of 3 T in T1, T2, T2-FLAIR, DWI, and SWI modes. A CSD-HARDI algorithm was used to identify thin intersecting fibers of the reticular formatio. We developed a technique for reconstructing the reticular formation pathways, tested it in healthy volunteers, and obtained standard quantitative indicators (fractional anisotropy (FA), apparent diffusion coefficient (ACD), fiber length and density, and axial and radial diffusion). We performed a comparative analysis of these indicators in males and females. There was no difference between these groups and between indicators for the right and left brainstem. Our findings will enable comparative analysis of examination results in patients with brain pathology accompanied by brainstem injury, which may help predict the outcome. This work was supported by a grant of the Russian Foundation for Basic Research (#16-04-01472).

  12. Anti-Ma2 paraneoplastic encephalitis associated with testicular germ cell tumor treated by carboplatin, etoposide and bleomycin.

    PubMed

    Kimura, Masaki; Onozawa, Mizuki; Fujisaki, Akira; Arakawa, Takashi; Takeda, Katsuhiko; Dalmau, Joseph; Hattori, Kazunori

    2008-10-01

    Anti-Ma2-associated encephalitis is a paraneoplastic disorder that predominantly affects the limbic system, diencephalon and brainstem, and is usually associated with tumors of the testis. We report a 35-year-old man with a right testicular mass who presented with multiple neurological complains, and clinical, serological and radiological features compatible with anti-Ma2-associated encephalitis. After three courses of carboplatin, etoposide and bleomycin for metastatic testicular germ-cell tumor, all elevated tumor markers normalized and the retroperitoneal metastases disappeared, but the neurological disorder deteriorated. To our knowledge, this is the first case in which orchiectomy followed by carboplatin, etoposide and bleomycin for a testicular tumor with anti-Ma2 encephalitis was performed.

  13. Cardiorespiratory coupling in health and disease.

    PubMed

    Garcia, Alfredo J; Koschnitzky, Jenna E; Dashevskiy, Tatiana; Ramirez, Jan-Marino

    2013-04-01

    Cardiac and respiratory activities are intricately linked both functionally as well as anatomically through highly overlapping brainstem networks controlling these autonomic physiologies that are essential for survival. Cardiorespiratory coupling (CRC) has many potential benefits creating synergies that promote healthy physiology. However, when such coupling deteriorates autonomic dysautonomia may ensue. Unfortunately there is still an incomplete mechanistic understanding of both normal and pathophysiological interactions that respectively give rise to CRC and cardiorespiratory dysautonomia. Moreover, there is also a need for better quantitative methods to assess CRC. This review addresses the current understanding of CRC by discussing: (1) the neurobiological basis of respiratory sinus arrhythmia (RSA); (2) various disease states involving cardiorespiratory dysautonomia; and (3) methodologies measuring heart rate variability and RSA. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Cardiorespiratory Coupling in Health and Disease

    PubMed Central

    Garcia, Alfredo J.; Koschnitzky, Jenna E.; Dashevskiy, Tatiana; Ramirez, Jan-Marino

    2013-01-01

    Cardiac and respiratory activities are intricately linked both functionally as well as anatomically through highly overlapping brainstem networks controlling these autonomic physiologies that are essential for survival. Cardiorespiratory coupling (CRC) has many potential benefits creating synergies that promote healthy physiology. However, when such coupling deteriorates autonomic dysautonomia may ensue. Unfortunately there is still an incomplete mechanistic understanding of both normal and pathophysiological interactions that respectively give rise to CRC and cardiorespiratory dysautonomia. Moreover, there is also a need for better quantitative methods to assess CRC. This review addresses the current understanding of CRC by discussing: (1) the neurobiological basis of respiratory sinus arrhythmia (RSA); (2) various disease states involving cardiorespiratory dysautonomia; and (3) methodologies measuring heart rate variability and RSA. PMID:23497744

  15. A correlation method to predict the surface pressure distribution of an infinite plate or a body of revolution from which a jet is issuing

    NASA Technical Reports Server (NTRS)

    Perkins, S. C., Jr.; Mendenhall, M. R.

    1980-01-01

    A correlation method to predict pressures induced on an infinite plate by a jet exhausting normal to the plate into a subsonic free stream was extended to jets exhausting at angles to the plate and to jets exhausting normal to the surface of a body revolution. The complete method consisted of an analytical method which models the blockage and entrainment properties of the jet and an empirical correlation which accounts for viscous effects. For the flat plate case, the method was applicable to jet velocity ratios up to ten, jet inclination angles up to 45 deg from the normal, and radial distances up to five diameters from the jet. For the body of revolution case, the method was applicable to a body at zero degrees angle of attack, jet velocity ratios 1.96 and 3.43, circumferential angles around the body up to 25 deg from the jet, axial distances up to seven diameters from the jet, and jet-to-body diameter ratios less than 0.1.

  16. Growth and yield of Giant Sequoia

    Treesearch

    David J. Dulitz

    1986-01-01

    Very little information exists concerning growth and yield of giant sequoia (Sequoiadendron giganteum [Lindl.] Buchholz). For old-growth trees, diameter growth is the single factor adding increment since maximum height has been obtained. Diameter growth averages 0.04 inches per year in normal old-growth trees but will fluctuate with changes in the...

  17. Brainstem auditory responses to resolved and unresolved harmonics of a synthetic vowel in quiet and noise.

    PubMed

    Laroche, Marilyn; Dajani, Hilmi R; Prévost, François; Marcoux, André M

    2013-01-01

    This study investigated speech auditory brainstem responses (speech ABR) with variants of a synthetic vowel in quiet and in background noise. Its objectives were to study the noise robustness of the brainstem response at the fundamental frequency F0 and at the first formant F1, evaluate how the resolved/unresolved harmonics regions in speech contribute to the response at F0, and investigate the origin of the response at F0 to resolved and unresolved harmonics in speech. In total, 18 normal-hearing subjects (11 women, aged 18-33 years) participated in this study. Speech ABRs were recorded using variants of a 300 msec formant-synthesized /a/ vowel in quiet and in white noise. The first experiment employed three variants containing the first three formants F1 to F3, F1 only, and F2 and F3 only with relative formant levels following those reported in the literature. The second experiment employed three variants containing F1 only, F2 only, and F3 only, with the formants equalized to the same level and the signal-to-noise ratio (SNR) maintained at -5 dB. Overall response latency was estimated, and the amplitude and local SNR of the envelope following response at F0 and of the frequency following response at F1 were compared for the different stimulus variants in quiet and in noise. The response at F0 was more robust to noise than that at F1. There were no statistically significant differences in the response at F0 caused by the three stimulus variants in both experiments in quiet. However, the response at F0 with the variant dominated by resolved harmonics was more robust to noise than the response at F0 with the stimulus variants dominated by unresolved harmonics. The latencies of the responses in all cases were very similar in quiet, but the responses at F0 due to resolved and unresolved harmonics combined nonlinearly when both were present in the stimulus. Speech ABR has been suggested as a marker of central auditory processing. The results of this study support earlier work on the differential susceptibility to noise of the F0 and F1 components of the evoked response. In the case of F0, the results support the view that in speech, the pitch of resolved harmonics and that of unresolved harmonics are processed in different but interacting pathways that converge in the upper brainstem. Pitch plays an important role in speech perception, and speech ABR can offer a window into the neural extraction of the pitch of speech and how it may change with hearing impairment.

  18. Nailfold capillary patterns in healthy subjects: a real issue in capillaroscopy.

    PubMed

    Ingegnoli, Francesca; Gualtierotti, Roberta; Lubatti, Chiara; Bertolazzi, Chiara; Gutierrez, Marwin; Boracchi, Patrizia; Fornili, Marco; De Angelis, Rossella

    2013-11-01

    Nailfold capillaroscopy has been extensively applied in a broad spectrum of pathologic conditions, but very few data have been published in healthy individuals. The aim of this study was to describe the nailfold capillary findings on a large series of healthy subjects using the video-capillaroscopy technique. Nailfold capillaries were studied based on their morphology, dimensions and density. Then, to evaluate jointly the association between different capillary findings in groups of subjects which were homogeneous for their characteristics, cluster analysis was performed. The results (median) of capillary measurements were as follows: loop length 207μm, external diameter 39μm, internal diameter 17μm, apical diameter 17μm, and intercapillary distance 143μm. Based on the cluster analysis three major "normal" morphologic capillaroscopic patterns were depicted: 1) the "normal" pattern mainly with 2 to 5 U-shaped loops/mm and ≤2 tortuous loops/mm; 2) the "perfect normal" pattern with ≥5 U-shaped loops/mm and 3) the "unusual normal" with at least 1 meandering or bushy loop, or at least 1 microhemorrhage, or with >4 crossed loops/mm. Regarding the loop measurements, the majority of subjects had a median of 7capillaries/mm with a median length of 198μm. © 2013 Elsevier Inc. All rights reserved.

  19. Brainstem conundrum: the Chiari I malformation.

    PubMed

    Mueller, D

    2001-04-01

    To describe the Chairi I Malformation in relation to the anatomy of the brain and spinal cord, the common manifestations of the condition, diagnostic considerations, and management for the primary care provider. Extensive review of the world-wide scientific literature on the condition, supplemented with actual case studies. The adult Chairi I Malformation is an insidious congenital brainstem anomaly that consists of caudal displacement of the cerebellar tonsils, brainstem and fourth ventricle into the upper cervical space, resulting in overcrowding of the posterior fossa. Due to the vague, and often ambiguous presenting symptoms of Chiari I Malformation, many patients are misdiagnosed with conditions such as multiple sclerosis, fibromyalgia, chronic fatigue syndrome, or psychiatric disorders. Patients frequently experience symptoms months to years prior to accurate diagnosis and often incur irreversible neurologic deficits.

  20. Continuous fluidized-bed contactor with recycle of sorbent

    DOEpatents

    Scott, Charles D.; Petersen, James N.; Davison, Brian H.

    1996-01-01

    A continuous fluidized-bed contactor containing sorbent particles is used to remove solutes from liquid solvents. As the sorbent particles, for example gel beads, sorb the solute, for example metal ion species, the sorbent particles tend to decrease in diameter. These smaller loaded sorbent particles rise to the top of the contactor, as larger sorbent particles remain at the bottom of the contactor as a result of normal hydraulic forces. The smaller loaded sorbent particles are then recovered, regenerated, and reintroduced into the contactor. Alternatively, the loaded sorbent particles may also slightly increase in diameter, or exhibit no change in diameter but an increase in density. As a result of normal hydraulic forces the larger loaded sorbent particles fall to the bottom of the contactor. The larger loaded sorbent particles are then recovered, regenerated, and reintroduced into the contactor.

  1. Continuous fluidized-bed contactor with recycle of sorbent

    DOEpatents

    Scott, C.D.; Petersen, J.N.; Davison, B.H.

    1996-07-09

    A continuous fluidized-bed contactor containing sorbent particles is used to remove solutes from liquid solvents. As the sorbent particles, for example gel beads, sorb the solute, for example metal ion species, the sorbent particles tend to decrease in diameter. These smaller loaded sorbent particles rise to the top of the contactor, and larger sorbent particles remain at the bottom of the contactor as a result of normal hydraulic forces. The smaller loaded sorbent particles are then recovered, regenerated, and reintroduced into the contactor. Alternatively, the loaded sorbent particles may also slightly increase in diameter, or exhibit no change in diameter but an increase in density. As a result of normal hydraulic forces the larger loaded sorbent particles fall to the bottom of the contactor. The larger loaded sorbent particles are then recovered, regenerated, and reintroduced into the contactor. 8 figs.

  2. Atlas-based segmentation of brainstem regions in neuromelanin-sensitive magnetic resonance images

    NASA Astrophysics Data System (ADS)

    Puigvert, Marc; Castellanos, Gabriel; Uranga, Javier; Abad, Ricardo; Fernández-Seara, María. A.; Pastor, Pau; Pastor, María. A.; Muñoz-Barrutia, Arrate; Ortiz de Solórzano, Carlos

    2015-03-01

    We present a method for the automatic delineation of two neuromelanin rich brainstem structures -substantia nigra pars compacta (SN) and locus coeruleus (LC)- in neuromelanin sensitive magnetic resonance images of the brain. The segmentation method uses a dynamic multi-image reference atlas and a pre-registration atlas selection strategy. To create the atlas, a pool of 35 images of healthy subjects was pair-wise pre-registered and clustered in groups using an affinity propagation approach. Each group of the atlas is represented by a single exemplar image. Each new target image to be segmented is registered to the exemplars of each cluster. Then all the images of the highest performing clusters are enrolled into the final atlas, and the results of the registration with the target image are propagated using a majority voting approach. All registration processes used combined one two-stage affine and one elastic B-spline algorithm, to account for global positioning, region selection and local anatomic differences. In this paper, we present the algorithm, with emphasis in the atlas selection method and the registration scheme. We evaluate the performance of the atlas selection strategy using 35 healthy subjects and 5 Parkinson's disease patients. Then, we quantified the volume and contrast ratio of neuromelanin signal of these structures in 47 normal subjects and 40 Parkinson's disease patients to confirm that this method can detect neuromelanin-containing neurons loss in Parkinson's disease patients and could eventually be used for the early detection of SN and LC damage.

  3. Role of heat shock protein Hsp25 in the response of the orofacial nuclei motor system to physiological stress

    NASA Technical Reports Server (NTRS)

    Murashov, A. K.; Talebian, S.; Wolgemuth, D. J.

    1998-01-01

    Although expression of the small heat shock protein family member Hsp25 has been previously observed in the central nervous system (CNS), both constitutively and upon induction, its function in the CNS remains far from clear. In the present study we have characterized the spatial pattern of expression of Hsp25 in the normal adult mouse brain as well as the changes in expression patterns induced by subjecting mice to experimental hyperthermia or hypoxia. Immunohistochemical analysis revealed a surprisingly restricted pattern of constitutive expression of Hsp25 in the brain, limited to the facial, trigeminal, ambiguus, hypoglossal and vagal motor nuclei of the brainstem. After hyperthermia or hypoxia treatment, significant increases in the levels of Hsp25 were observed in these same areas and also in fibers of the facial and trigeminal nerve tracts. Immunoblot analysis of protein lysates from brainstem also showed the same pattern of induction of Hsp25. Surprisingly, no other area in the brain showed expression of Hsp25, in either control or stressed animals. The highly restricted expression of Hsp25 implies that this protein may have a specific physiological role in the orofacial motor nuclei, which govern precise coordination between muscles of mastication and the pharynx, larynx, and face. Its rapid induction after stress further suggests that Hsp25 may serve as a specific molecular chaperone in the lower cholinergic motor neurons and along their fibers under conditions of stress or injury. Copyright 1998 Elsevier Science B.V.

  4. Evaluation of the occurrence of canine congenital sensorineural deafness in puppies of predisposed dog breeds using the brainstem auditory evoked response.

    PubMed

    Płonek, Marta; Giza, Elżbieta; Niedźwiedź, Artur; Kubiak, Krzysztof; Nicpoń, Józef; Wrzosek, Marcin

    2016-12-01

    Canine congenital sensorineural deafness (CCSD) affects predisposed breeds of dogs and is primarily caused by an atrophy of the stria vascularis of the organ of Corti. The analysis of the brainstem auditory evoked response (BAER) is a reliable method for the evaluation of hearing in animals as it allows an accurate detection of unilateral or bilateral deafness. The occurrence of unilateral and bilateral deafness using the BAER was determined in a representative group of dogs in Poland, including Bull Terriers (n = 117), Australian Cattle Dogs (n = 62), English Setters (n = 32) and the Dogo Argentino (n = 32). Overall deafness, deafness in each dog breed and an association between deafness and phenotype were studied. Among the 243 dogs tested, 156 (81%) had a normal BAER, 27 (11%) were unilaterally deaf, and 12 (5%) were bilaterally deaf. The amplitudes and latencies of waves I, II, III, V, the V/I wave amplitude ratio, and wave I-V, I-III and III-V inter-peak intervals were recorded for each dog. Unilaterally and bilaterally deaf dogs were present in all the dog breeds studied. There were 17 (14.5%) deaf Bull Terriers, three (4.8%) deaf Australian Cattle Dogs, seven (21.9%) deaf English Setters, and 12 (37.5%) deaf Dogos Argentinos. Preventive BAER screening should be routinely performed in these four breeds to prevent the spread of genes responsible for deafness.

  5. Diagnostic Yield and Safety of Cerebellar and Brainstem Parenchymal Biopsy.

    PubMed

    Tobin, W Oliver; Meyer, Fredric B; Keegan, B Mark

    2015-12-01

    We aimed to determine the diagnostic yield and safety of posterior fossa parenchymal biopsy. One-hundred-thirty-six patients who underwent 137 posterior fossa (brainstem or cerebellar) parenchymal biopsies at Mayo Clinic (Rochester, Minnesota, USA) between 1996 and 2009 were identified by chart review. Case histories; radiologic, surgical, and pathologic reports; and safety outcomes were assessed. Posterior fossa parenchymal biopsies were performed on 78 male and 58 female patients of median age 47 years (interquartile range 28-61). Preoperative clinical diagnosis in the majority of cases was of a malignant neoplasm. Glial neoplasm (51%) was the most common finding followed by lymphoma (7%) and neurosarcoidosis (7%). Normal tissue or nonspecific changes were observed in 28 cases (20%). Three deaths occurred: 2 at the time of biopsy (1%) and 1 due to underlying disease. All deaths occurred in patients who had a cerebellar biopsy. Transient neurologic deficits occurred in 15 patients (11%): worsening of presenting symptoms (4), cardiac arrhythmia (3), vertigo (2), diplopia (2), ataxia (3), seizure (1), decreased consciousness (1), and limb numbness (3). Sustained neurologic deficits occurred in 3 patients: fourth nerve palsy (1), hemiparesis (1), and facial numbness (1). The diagnostic yield of posterior fossa parenchymal biopsy in Mayo Clinic patients with diverse pathologies was 80%. The complication rate was 11% with the majority being transient, but 2 deaths were attributed to biopsy. Evaluation of the diagnostic yield and complication rate at individual neurosurgical centers is needed to determine generalizability of these results. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Dynamic expression of transcription factor Brn3b during mouse cranial nerve development

    PubMed Central

    Sajgo, Szilard; Ali, Seid; Popescu, Octavian; Badea, Tudor Constantin

    2015-01-01

    During development transcription factor combinatorial codes define a large variety of morphologically and physiologically distinct neurons. Such a combinatorial code has been proposed for the differentiation of projection neurons of the somatic and visceral components of cranial nerves. It is possible that individual neuronal cell types are not specified by unique transcription factors, but rather emerge through the intersection of their expression domains. Brn3a, Brn3b and Brn3c, in combination with each other and/or transcription factors of other families, can define subgroups of Retinal Ganglion Cells (RGC), Spiral and Vestibular Ganglia, inner ear and vestibular hair cell neurons in the vestibuloacoustic system, and groups of somatosensory neurons in the Dorsal Root Ganglia (DRG). In the present study we investigated the expression and potential role of the Brn3b transcription factor in cranial nerves and associated nuclei of the brainstem. We report the dynamic expression of Brn3b in the somatosensory component of cranial nerves II, V, VII and VIII and visceromotor nuclei of nerves VII, IX, X, as well as other brainstem nuclei during different stages of development into adult stage. We find that genetically identified Brn3bKO RGC axons show correct but delayed pathfinding during the early stages of embryonic development. However loss of Brn3b does not affect the anatomy of the other cranial nerves normally expressing this transcription factor. PMID:26356988

  7. Comparison of brain MRI findings with language and motor function in the dystroglycanopathies.

    PubMed

    Brun, Brianna N; Mockler, Shelley R H; Laubscher, Katie M; Stephan, Carrie M; Wallace, Anne M; Collison, Julia A; Zimmerman, M Bridget; Dobyns, William B; Mathews, Katherine D

    2017-02-14

    To describe the spectrum of brain MRI findings in a cohort of individuals with dystroglycanopathies (DGs) and relate MRI results to function. All available brain MRIs done for clinical indications on individuals enrolled in a DG natural history study (NCT00313677) were reviewed. Reports were reviewed when MRI was not available. MRIs were categorized as follows: (1) cortical, brainstem, and cerebellar malformations; (2) cortical and cerebellar malformations; or (3) normal. Language development was assigned to 1 of 3 categories by a speech pathologist. Maximal motor function and presence of epilepsy were determined by history or examination. Twenty-five MRIs and 9 reports were reviewed. The most common MRI abnormalities were cobblestone cortex or dysgyria with an anterior-posterior gradient and cerebellar hypoplasia. Seven individuals had MRIs in group 1, 8 in group 2, and 19 in group 3. Language was impaired in 100% of those in MRI groups 1 and 2, and degree of language impairment correlated with severity of imaging. Eighty-five percent of the whole group achieved independent walking, but only 33% did in group 1. Epilepsy was present in 8% of the cohort and rose to 37% of those with an abnormal MRI. Developmental abnormalities of the brain such as cobblestone lissencephaly, cerebellar cysts, pontine hypoplasia, and brainstem bowing are hallmarks of DG and should prompt consideration of these diagnoses. Brain imaging in individuals with DG helps to predict outcomes, especially language development, aiding clinicians in prognostic counseling. © 2017 American Academy of Neurology.

  8. Metronidazole-induced encephalopathy: not always a reversible situation.

    PubMed

    Hobbs, Kyle; Stern-Nezer, Sara; Buckwalter, Marion S; Fischbein, Nancy; Finley Caulfield, Anna

    2015-06-01

    Metronidazole is a nitroimidazole antimicrobial drug prescribed to treat infections caused by anaerobic bacteria and protozoa. Uncommonly, it causes central nervous system (CNS) toxicity manifesting as metronidazole-induced encephalopathy (MIE). Case report. A 65-year-old woman with hepatitis B cirrhosis (Child-Pugh class C, MELD 21) developed progressive encephalopathy to GCS 4 during a 3-week course of metronidazole for cholecystitis. Initial MRI was consistent with CNS metronidazole toxicity, with symmetrical T2 hyperintensity and generally restricted diffusion in bilateral dentate nuclei, corpus callosum, midbrain, superior cerebellar peduncles, internal capsules, and cerebral white matter. Laboratory values did not demonstrate significant electrolyte shifts, and continuous EEG was without seizure. High-dose thiamine was empirically administered. Lumbar puncture was not performed due to coagulopathy and thrombocytopenia. Despite discontinuation of metronidazole and keeping ammonia levels near normal, the patient did not improve. MRI was repeated 1 week after discontinuation of metronidazole. Although there was decreased DWI hyperintensity in the dentate nuclei, diffuse T2 hyperintensity persisted and even progressed in the brainstem, basal ganglia, and subcortical white matter. Petechial hemorrhages developed in bilateral corticospinal tracts and subcortical white matter. T1 hypointensity appeared in the corpus callosum. She was transitioned to comfort measures only and died 12 days later. MIE is an uncommon adverse effect of treatment with metronidazole that characteristically affects the dentate nuclei but may also involve the brainstem, corpus callosum, subcortical white matter, and basal ganglia. While the clinical symptoms and neuroimaging changes are usually reversible, persistent encephalopathy with poor outcome may occur.

  9. A pilot study on predictors of brainstem raphe abnormality in patients with major depressive disorder.

    PubMed

    Kostić, Milutin; Munjiza, Ana; Pesic, Danilo; Peljto, Amir; Novakovic, Ivana; Dobricic, Valerija; Tosevski, Dusica Lecic; Mijajlovic, Milija

    2017-02-01

    Hypo/anechogenicity of the brainstem raphe (BR) structures has been suggested as a possible transcranial parenchymal sonography (TCS) marker associated with depression. The aim of this study was to analyze possible association of the abnormal BR echogenicity in patients with major depression when compared to healthy controls, and to evaluate its clinical and genetic correlates. TCS was performed in 53 patients diagnosed as major depressive disorder (MDD) without psychotic symptoms and in 54 healthy matched controls. The TCS detected BR abnormalities were significantly more frequent in MDD patients (35 out of 53; 66%) in comparison to matched controls (5 out of 56; 9%). The prevalence of short allele (s) homozygocity in the length polymorphism of the promoter region of the serotonin transporter gene (5-HTTLPR) was significantly higher in MDD patients relative to those with normal BR echogenicity. A stepwise statistical discriminant analysis revealed statistically significant separation between MDD patients with and without BR abnormalities groups based on the four predictors combined: the Hamilton Anxiety Rating Scale item 5 ("difficulty in concentration, poor memory"), presence of social phobia, s allele homozygocity of the 5-HTTLPR polymorphism, and presence of generalized anxiety disorder. Cross-sectional design and heterogenous treatment of depressed patients. Reduced BR echogenicity in at least a subgroup of MDD patients may reflect a particular phenotype, characterized by more prevalent comorbid anxiety disorders, associated with particular genetic polymorphisms and neurotransmitter(s) deficits, most probably altered serotonergic mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. The rostral medulla of bullfrog tadpoles contains critical lung rhythmogenic and chemosensitive regions across metamorphosis.

    PubMed

    Reed, Mitchell D; Iceman, Kimberly E; Harris, Michael B; Taylor, Barbara E

    2018-06-08

    The development of amphibian breathing provides insight into vertebrate respiratory control mechanisms. Neural oscillators in the rostral and caudal medulla drive ventilation in amphibians, and previous reports describe ventilatory oscillators and CO 2 sensitive regions arise during different stages of amphibian metamorphosis. However, inconsistent findings have been enigmatic, and make comparisons to potential mammalian counterparts challenging. In the current study we assessed amphibian central CO 2 responsiveness and respiratory rhythm generation during two different developmental stages. Whole-nerve recordings of respiratory burst activity in cranial and spinal nerves were made from intact or transected brainstems isolated from tadpoles during early or late stages of metamorphosis. Brainstems were transected at the level of the trigeminal nerve, removing rostral structures including the nucleus isthmi, midbrain, and locus coeruleus, or transected at the level of the glossopharyngeal nerve, removing the putative buccal oscillator and caudal medulla. Removal of caudal structures stimulated the frequency of lung ventilatory bursts and revealed a hypercapnic response in normally unresponsive preparations derived from early stage tadpoles. In preparations derived from late stage tadpoles, removal of rostral or caudal structures reduced lung burst frequency, while CO 2 responsiveness was retained. Our results illustrate that structures within the rostral medulla are capable of sensing CO 2 throughout metamorphic development. Similarly, the region controlling lung ventilation appears to be contained in the rostral medulla throughout metamorphosis. This work offers insight into the consistency of rhythmic respiratory and chemosensitive capacities during metamorphosis. Copyright © 2018. Published by Elsevier Inc.

  11. Clinical characteristics of acute encephalopathy with acute brain swelling: A peculiar type of acute encephalopathy.

    PubMed

    Nukui, Megumi; Kawawaki, Hisashi; Inoue, Takeshi; Kuki, Ichiro; Okazaki, Shin; Amo, Kiyoko; Togawa, Masao; Ishikawa, Junichi; Rinka, Hiroshi; Shiomi, Masashi

    2018-06-07

    Acute encephalopathy has been observed with acute brain swelling (ABS) that is characterized by rapid progression to whole-brain swelling. The objective of this study was to describe the clinical characteristics of ABS. We encountered four patients with ABS and retrospectively investigated their clinical data with a medical chart review. Three patients had seizure clustering or status epilepticus in the clinical course. Signs of elevated intracranial pressure (ICP) appeared 3-9 h after the first convulsive attack in three patients. In all patients, signs of brainstem involvement appeared 1-8 h after signs of elevated ICP. Mild hyponatremia that progressed after signs of elevated ICP appeared was noted in three patients. Brain CT revealed mild brain swelling in the initial phase, which rapidly progressed to whole-brain swelling. No focal abnormalities were detected on brain MRI in one patient. Continuous electroencephalography was initially normal, but in two patients, high-amplitude slow waves appeared with rapid changes before signs of brainstem involvement. Although recovery was achieved without sequelae in two patients, outcome was fatal for the other two. The pathogenesis of ABS has yet to be clarified, but clinical features in our patients are not consistent with any established subtypes of acute encephalopathy. Therefore, we believe that ABS should be recognized as a new type of acute encephalopathy. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  12. [Development of auditory evoked potentials of the brainstem in relation to age].

    PubMed

    Tarantino, V; Stura, M; Vallarino, R

    1988-01-01

    In order to study the various changes which occur in the waveform, latency and amplitude of the auditory brainstem evoked response (BSER) as a function of age, the authors recorded the BSER from the scalp's surface of 20 newborns and 50 infants, 3 months, 6 months, 1 year and 3 years old as well as from 20 normal adults. The data obtained show that the most reliable waves during the first month of life are waves I, III, V, which is often present even when other vertex-positive peaks are absent. The latencies of the various potential components decreased with maturation. Wave V, evoked by 90 dB sensation level clicks, changed in latency from 7, 12 msec at 1-4 weeks of age to 5,77 msec at 3 years of life. The auditory processes related to peripheral and central transmission were shown to mature at differential rates during the first period of life. By the 6th month, in fact, wave I latency had reached the adult value; in contrast, wave V latency did match that of the adult until approximately 1 year old. One obvious explanation for the age-related latency shift is progressive myelination of the auditory tract in infants, for this is know to occur. The authors conclude that the clinical application of this technique in paediatric patients couldn't provide reliable informations about auditory brain stem activity regardless of evaluation of the relationship between age and characteristics of BSER.

  13. A Novel Method of Brainstem Auditory Evoked Potentials Using Complex Verbal Stimuli

    PubMed Central

    Kouni, Sophia N; Koutsojannis, Constantinos; Ziavra, Nausika; Giannopoulos, Sotirios

    2014-01-01

    Background: The click and tone-evoked auditory brainstem responses are widely used in clinical practice due to their consistency and predictability. More recently, the speech-evoked responses have been used to evaluate subcortical processing of complex signals, not revealed by responses to clicks and tones. Aims: Disyllable stimuli corresponding to familiar words can induce a pattern of voltage fluctuations in the brain stem resulting in a familiar waveform, and they can yield better information about brain stem nuclei along the ascending central auditory pathway. Materials and Methods: We describe a new method with the use of the disyllable word “baba” corresponding to English “daddy” that is commonly used in many other ethnic languages spanning from West Africa to the Eastern Mediterranean all the way to the East Asia. Results: This method was applied in 20 young adults institutionally diagnosed as dyslexic (10 subjects) or light dyslexic (10 subjects) who were matched with 20 sex, age, education, hearing sensitivity, and IQ-matched normal subjects. The absolute peak latencies of the negative wave C and the interpeak latencies of A-C elicited by verbal stimuli “baba” were found to be significantly increased in the dyslexic group in comparison with the control group. Conclusions: The method is easy and helpful to diagnose abnormalities affecting the auditory pathway, to identify subjects with early perception and cortical representation abnormalities, and to apply the suitable therapeutic and rehabilitation management. PMID:25210677

  14. Air and Bone Conduction Frequency-specific Auditory Brainstem Response in Children with Agenesis of the External Auditory Canal

    PubMed Central

    Sleifer, Pricila; Didoné, Dayane Domeneghini; Keppeler, Ísis Bicca; Bueno, Claudine Devicari; Riesgo, Rudimar dos Santos

    2017-01-01

    Introduction  The tone-evoked auditory brainstem responses (tone-ABR) enable the differential diagnosis in the evaluation of children until 12 months of age, including those with external and/or middle ear malformations. The use of auditory stimuli with frequency specificity by air and bone conduction allows characterization of hearing profile. Objective  The objective of our study was to compare the results obtained in tone-ABR by air and bone conduction in children until 12 months, with agenesis of the external auditory canal. Method  The study was cross-sectional, observational, individual, and contemporary. We conducted the research with tone-ABR by air and bone conduction in the frequencies of 500 Hz and 2000 Hz in 32 children, 23 boys, from one to 12 months old, with agenesis of the external auditory canal. Results  The tone-ABR thresholds were significantly elevated for air conduction in the frequencies of 500 Hz and 2000 Hz, while the thresholds of bone conduction had normal values in both ears. We found no statistically significant difference between genders and ears for most of the comparisons. Conclusion  The thresholds obtained by bone conduction did not alter the thresholds in children with conductive hearing loss. However, the conductive hearing loss alter all thresholds by air conduction. The tone-ABR by bone conduction is an important tool for assessing cochlear integrity in children with agenesis of the external auditory canal under 12 months. PMID:29018492

  15. Acoustic fill factors for a 120 inch diameter fairing

    NASA Technical Reports Server (NTRS)

    Lee, Y. Albert

    1992-01-01

    Data from the acoustic test of a 120-inch diameter payload fairing were collected and an analysis of acoustic fill factors were performed. Correction factors for obtaining a weighted spatial average of the interior sound pressure level (SPL) were derived based on this database and a normalized 200-inch diameter fairing database. The weighted fill factors were determined and compared with statistical energy analysis (VAPEPS code) derived fill factors. The comparison is found to be reasonable.

  16. Identifying Candidate Genes that Underlie Cellular pH Sensitivity in Serotonin Neurons Using Transcriptomics: A Potential Role for Kir5.1 Channels

    PubMed Central

    Puissant, Madeleine M.; Mouradian, Gary C.; Liu, Pengyuan; Hodges, Matthew R.

    2017-01-01

    Ventilation is continuously adjusted by a neural network to maintain blood gases and pH. Acute CO2 and/or pH regulation requires neural feedback from brainstem cells that encode CO2/pH to modulate ventilation, including but not limited to brainstem serotonin (5-HT) neurons. Brainstem 5-HT neurons modulate ventilation and are stimulated by hypercapnic acidosis, the sensitivity of which increases with increasing postnatal age. The proper function of brainstem 5-HT neurons, particularly during post-natal development is critical given that multiple abnormalities in the 5-HT system have been identified in victims of Sudden Infant Death Syndrome. Here, we tested the hypothesis that there are age-dependent increases in expression of pH-sensitive ion channels in brainstem 5-HT neurons, which may underlie their cellular CO2/pH sensitivity. Midline raphe neurons were acutely dissociated from neonatal and mature transgenic SSePet-eGFP rats [which have enhanced green fluorescent protein (eGFP) expression in all 5-HT neurons] and sorted with fluorescence-activated cell sorting (FACS) into 5-HT-enriched and non-5-HT cell pools for subsequent RNA extraction, cDNA library preparation and RNA sequencing. Overlapping differential expression analyses pointed to age-dependent shifts in multiple ion channels, including but not limited to the pH-sensitive potassium ion (K+) channel genes kcnj10 (Kir4.1), kcnj16 (Kir5.1), kcnk1 (TWIK-1), kcnk3 (TASK-1) and kcnk9 (TASK-3). Intracellular contents isolated from single adult eGFP+ 5-HT neurons confirmed gene expression of Kir4.1, Kir5.1 and other K+ channels, but also showed heterogeneity in the expression of multiple genes. 5-HT neuron-enriched cell pools from selected post-natal ages showed increases in Kir4.1, Kir5.1, and TWIK-1, fitting with age-dependent increases in Kir4.1 and Kir5.1 protein expression in raphe tissue samples. Immunofluorescence imaging confirmed Kir5.1 protein was co-localized to brainstem neurons and glia including 5-HT neurons as expected. However, Kir4.1 protein expression was restricted to glia, suggesting that it may not contribute to 5-HT neuron pH sensitivity. Although there are caveats to this approach, the data suggest that pH-sensitive Kir5.1 channels may underlie cellular CO2/pH chemosensitivity in brainstem 5-HT neurons. PMID:28270749

  17. Recrystallization and grain growth phenomena in a particle-reinforced aluminum composite

    NASA Astrophysics Data System (ADS)

    van Aken, D. C.; Krajewski, P. E.; Vyletel, G. M.; Allison, J. E.; Jones, J. W.

    1995-06-01

    Recrystallization and grain growth in a 2219/TiC/15p composite were investigated as functions of the amount of deformation and deformation temperature. Both cold and hot deformed samples were annealed at the normal solution treatment temperature of 535 °C. It was shown that large recrystallized grain diameters, relative to the interparticle spacing, could be produced in a narrow range of deformation for samples cold-worked and those hot-worked below 450 °C. For cold-worked samples, between 4 to 6 pct deformation, the recrystallized grain diameters varied from 530 to 66 μm as the amount of deformation increased. Subsequent grain growth was not observed in these recrystallized materials and noncompact grain shapes were observed. For deformations greater than 15 pct, recrystallized grain diameters less than the interparticle spacing were observed and subsequent grain growth produced a pinned grain diameter of 27 μm. The pinned grain diameter agreed well with an empirical model based on three dimensional (3-D) Monte Carlo simulations of grain growth and particle pinning in a two-phase material. Tensile properties were determined as a function of grain size, and it was shown that grain size had a weak influence on yield strength. A maximum in the yield strength was observed at a grain size larger than the normal grain growth and particle-pinned diameter.

  18. Comparison of experimental and theoretical normal-force distributions (including Reynolds number effects) on an ogive-cylinder body at Mach number 1.98

    NASA Technical Reports Server (NTRS)

    Perkins, Edward W; Jorgensen, Leland H

    1956-01-01

    Effects of Reynolds number and angle of attack on the pressure distribution and normal-force characteristics of a body of revolution consisting of a fineness ratio 3 ogival nose tangent to a cylindrical afterbody 7 diameters long have been determined. The test Mach number was 1.98 and the angle-of-attack range from 0 degree to 20 degrees. The Reynolds numbers, based on body diameter, were 0.15 x 10(6) and 0.45 x 10(6). The experimental results are compared with theory.

  19. Auditory Brainstem Response Altered in Humans With Noise Exposure Despite Normal Outer Hair Cell Function

    PubMed Central

    Bramhall, Naomi F.; Konrad-Martin, Dawn; McMillan, Garnett P.; Griest, Susan E.

    2017-01-01

    Objectives Recent animal studies demonstrated that cochlear synaptopathy, a partial loss of inner hair cell-auditory nerve fiber synapses, can occur in response to noise exposure without any permanent auditory threshold shift. In animal models, this synaptopathy is associated with a reduction in the amplitude of wave I of the auditory brainstem response (ABR). The goal of this study was to determine whether higher lifetime noise exposure histories in young people with clinically normal pure-tone thresholds are associated with lower ABR wave I amplitudes. Design Twenty-nine young military Veterans and 35 non Veterans (19 to 35 years of age) with normal pure-tone thresholds were assigned to 1 of 4 groups based on their self-reported lifetime noise exposure history and Veteran status. Suprathreshold ABR measurements in response to alternating polarity tone bursts were obtained at 1, 3, 4, and 6 kHz with gold foil tiptrode electrodes placed in the ear canal. Wave I amplitude was calculated from the difference in voltage at the positive peak and the voltage at the following negative trough. Distortion product otoacoustic emission input/output functions were collected in each participant at the same four frequencies to assess outer hair cell function. Results After controlling for individual differences in sex and distortion product otoacoustic emission amplitude, the groups containing participants with higher reported histories of noise exposure had smaller ABR wave I amplitudes at suprathreshold levels across all four frequencies compared with the groups with less history of noise exposure. Conclusions Suprathreshold ABR wave I amplitudes were reduced in Veterans reporting high levels of military noise exposure and in non Veterans reporting any history of firearm use as compared with Veterans and non Veterans with lower levels of reported noise exposure history. The reduction in ABR wave I amplitude in the groups with higher levels of noise exposure cannot be accounted for by sex or variability in outer hair cell function. This change is similar to the decreased ABR wave I amplitudes observed in animal models of noise-induced cochlear synaptopathy. However, without post mortem examination of the temporal bone, no direct conclusions can be drawn concerning the presence of synaptopathy in the study groups with higher noise exposure histories. PMID:27992391

  20. New Evidence of Cerebellar and Brainstem Hypoplasia in Autistic Infants, Children and Adolescents: The MR Imaging Study by Hashimoto and Colleagues.

    ERIC Educational Resources Information Center

    Courchesne, Eric

    1995-01-01

    In a study by Toshiaki Hashimoto and colleagues (EC 611 142), 10 infants with developmental delay, poor eye contact, and poor facial expression underwent magnetic resonance brain imaging and were later diagnosed with autism. This offered direct evidence of abnormality of the cerebellar vermis and the brainstem at the beginning stages of behavioral…

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