Bundled Postconditioning Therapies Improve Hemodynamics and Neurologic Recovery after 17 Minutes of Untreated Cardiac Arrest

PubMed Central

Bartos, Jason A.; Matsuura, Timothy R.; Sarraf, Mohammad; Youngquist, Scott T.; McKnite, Scott H.; Rees, Jennifer N.; Sloper, Daniel T.; Bates, Frank S.; Segal, Nicolas; Debaty, Guillaume; Lurie, Keith G.; Neumar, Robert W.; Metzger, Joseph M.; Riess, Matthias L.; Yannopoulos, Demetris

2014-01-01

Objective Ischemic postconditioning (stutter CPR) and sevoflurane have been shown to mitigate the effects of reperfusion injury in cardiac tissue after 15 minutes of ventricular fibrillation (VF) cardiac arrest. Poloxamer 188 (P188) has also proven beneficial to neuronal and cardiac tissue during reperfusion injury in human and animal models. We hypothesized that the use of stutter CPR, sevoflurane, and P188 combined with standard advanced life support would improve post-resuscitation cardiac and neurologic function after prolonged VF arrest. Methods Following 17 minutes of untreated VF, 20 pigs were randomized to Control treatment with active compression/decompression (ACD) CPR and impedance threshold device (ITD) (n=8) or Bundle therapy with stutter ACD CPR + ITD + sevoflurane + P188 (n=12). Epinephrine and post-resuscitation hypothermia were given in both groups per standard protocol. Animals that achieved return of spontaneous circulation (ROSC) were evaluated with echocardiography, biomarkers, and a blinded neurologic assessment with a cerebral performance category score. Results Bundle therapy improved hemodynamics during resuscitation, reduced need for epinephrine and repeated defibrillation, reduced biomarkers of cardiac injury and end-organ dysfunction, and increased left ventricular ejection fraction compared to Controls. Bundle therapy also improved rates of ROSC (100% vs. 50%), freedom from major adverse events (50% vs. 0% at 48 hours), and neurologic function (42% with mild or no neurologic deficit and 17% achieving normal function at 48 hours). Conclusions Bundle therapy with a combination of stutter ACD CPR, ITD, sevoflurane, and P188 improved cardiac and neurologic function after 17 minutes of untreated cardiac arrest in pigs. PMID:25447036

Utility of functional MRI in pediatric neurology.

PubMed

Freilich, Emily R; Gaillard, William D

2010-01-01

Functional MRI (fMRI), a tool increasingly used to study cognitive function, is also an important tool for understanding not only normal development in healthy children, but also abnormal development, as seen in children with epilepsy, attention-deficit/hyperactivity disorder, and autism. Since its inception almost 15 years ago, fMRI has seen an explosion in its use and applications in the adult literature. However, only recently has it found a home in pediatric neurology. New adaptations in study design and technologic advances, especially the study of resting state functional connectivity as well as the use of passive task design in sedated children, have increased the utility of functional imaging in pediatrics to help us gain understanding into the developing brain at work. This article reviews the background of fMRI in pediatrics and highlights the most recent literature and clinical applications.

Long-term effects of systemic gene therapy in a canine model of myotubular myopathy.

PubMed

Elverman, Matthew; Goddard, Melissa A; Mack, David; Snyder, Jessica M; Lawlor, Michael W; Meng, Hui; Beggs, Alan H; Buj-Bello, Ana; Poulard, Karine; Marsh, Anthony P; Grange, Robert W; Kelly, Valerie E; Childers, Martin K

2017-11-01

X-linked myotubular myopathy (XLMTM), a devastating pediatric disease caused by the absence of the protein myotubularin, results from mutations in the MTM1 gene. While there is no cure for XLMTM, we previously reported effects of MTM1 gene therapy using adeno-associated virus (AAV) vector on muscle weakness and pathology in MTM1-mutant dogs. Here, we followed 2 AAV-infused dogs over 4 years. We evaluated gait, strength, respiration, neurological function, muscle pathology, AAV vector copy number (VCN), and transgene expression. Four years following AAV-mediated gene therapy, gait, respiratory performance, neurological function and pathology in AAV-infused XLMTM dogs remained comparable to their healthy littermate controls despite a decline in VCN and muscle strength. AAV-mediated gene transfer of MTM1 in young XLMTM dogs results in long-term expression of myotubularin transgene with normal muscular performance and neurological function in the absence of muscle pathology. These findings support a clinical trial in patients. Muscle Nerve 56: 943-953, 2017. © 2017 Wiley Periodicals, Inc.

Between destiny and disease: genetics and molecular pathways of human central nervous system aging.

PubMed

Glorioso, Christin; Sibille, Etienne

2011-02-01

Aging of the human brain is associated with "normal" functional, structural, and molecular changes that underlie alterations in cognition, memory, mood and motor function, amongst other processes. Normal aging also imposes a robust constraint on the onset of many neurological diseases, ranging from late onset neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's diseases (PD), to early onset psychiatric disorders, such as bipolar disorder (BPD) and schizophrenia (SCZ). The molecular mechanisms and genetic underpinnings of age-related changes in the brain are understudied, and, while they share some overlap with peripheral mechanisms of aging, many are unique to the largely non-mitotic brain. Hence, understanding mechanisms of brain aging and identifying associated modulators may have profound consequences for the prevention and treatment of age-related impairments and diseases. Here we review current knowledge on age-related functional and structural changes, their molecular and genetic underpinnings, and discuss how these pathways may contribute to the vulnerability to develop age-related neurological diseases. We highlight recent findings from human post-mortem brain microarray studies, which we hypothesize, point to a potential genetically controlled transcriptional program underlying molecular changes and age-gating of neurological diseases. Finally, we discuss the implications of this model for understanding basic mechanisms of brain aging and for the future investigation of therapeutic approaches. Copyright © 2010 Elsevier Ltd. All rights reserved.

Extracorporeal life support for critical enterovirus 71 rhombencephalomyelitis: long-term neurologic follow-up.

PubMed

Lee, Hsiu-Fen; Chi, Ching-Shiang; Jan, Sheng-Ling; Fu, Yun-Ching; Huang, Fang-Liang; Chen, Po-Yen; Wang, Chung-Chi; Wei, Hao-Ji

2012-04-01

Enterovirus 71 rhombencephalomyelitis with cardiopulmonary dysfunction has become an endemic problem in Taiwan since an epidemic outbreak in 1998. Such cases frequently involve significant morbidity and mortality. From October 2000-June 2008, we collected 10 consecutive patients diagnosed with enterovirus 71 rhombencephalomyelitis complicated by left heart failure, with or without pulmonary edema, and surviving more than 3 months after receiving extracorporeal life support. Follow-up neurologic outcomes were analyzed prospectively. The median duration of neurologic follow-up was 7 years and 2 months. Significant morbidities included bulbar dysfunction, respiratory failure, and flaccid quadriparesis. Eight patients exhibited bulbar dysfunction, and feeding tubes could be removed from four patients (median, 15.5 months). Respiratory failure was observed in seven patients. Three patients were gradually withdrawn from their tracheostomy tube (median period, 30 months). Intelligence tests revealed four patients with normal cognitive function, one with borderline cognitive function, and one with mild mental retardation. Four were bedridden survivors. Extracorporeal life support for critical enterovirus 71 rhombencephalomyelitis demonstrated decreased neurologic sequelae during long-term follow-up, allowing for decannulation of feeding and tracheostomy tubes, and resulting in improved cognitive function. Copyright © 2012 Elsevier Inc. All rights reserved.

Normal carboxyhaemoglobin level in carbon monoxide poisoning treated with hyperbaric oxygen therapy.

PubMed

Helgeson, Scott A; Wilson, Michael E; Guru, Pramod K

2017-07-24

Throughout the world both intentional and inadvertent exposure to carbon monoxide (CO) remains an important public health issue. While CO poisoning can be lethal, the morbidity is predominantly due to nervous system injury. A previously healthy 22-year-old woman was found unconscious at home by her sister. Her parents were found dead in the house with a recent history of a dysfunctional furnace. She was presumed to have CO poisoning despite an initial carboxyhaemoglobin level of 2.5%. Patient had both clinical and radiological evidence of neurological damage. However, with multiple sessions of hyperbaric oxygen (HBO) therapy she recovered to a near normal functional status. There is no consensus that exists among treating physicians about the role of hyperbaric oxygen in management of neurological injury. The case described here has significant neurological damage related to CO exposure but improved after HBO therapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Neurological soft signs in schizophrenia: correlations with age, sex, educational status and psychopathology].

PubMed

Panagiotidis, P; Kaprinis, G; Iacovides, A; Fountoulakis, K

2013-01-01

Though the pathobiology of schizophrenia can be examined in multiple levels, the organic notion of brain disease suggests that neurological features will be present. One straightforward, inexpensive method of investigating brain dysfunction in schizophrenia is thought the bedside assessment of neurological abnormalities with a standard neurological examination. Neurological abnormalities are traditionally classified as "hard signs" (impairments in basic motor, sensory, and reflex behaviors, which do not appear to be affected in schizophrenia) and "soft signs", which refer to more complex phenomena such as abnormalities in motor control, integrative sensory function, sensorimotor integration, and cerebral laterality. Additionally, neurological soft signs (NSS) are minor motor and sensory abnormalities that are considered to be normal in the course of early development but abnormal when elicited in later life or persist beyond childhood. Soft signs also, have no definitive localizing significance but are indicative of subtle brain dysfunction. Most authors believe that they are a reflection not only of deficient integration between the sensory and motor systems, but also of dysfunctional neuronal circuits linking subcortical brain structures such as the basal ganglia, the brain stem, and the limbic system. Throughout the last four decades, studies have consistently shown that NSS are more frequently present in patients with schizophrenia than in normal subjects and non-psychotic psychiatric patients. However, the functional relevance of NSS remains unclear and their specificity has often been challenged, even though there is indication for a relative specificity with regard to diagnosis, or symptomatology. Many studies have considered soft signs as categorical variables thus hampering the evaluation of fluctuation with symptomatology and/or treatment, whereas other studies included insufficient number of assessed signs, or lacked a comprehensive assessment of extrapyramidal symptomatology. Factors such as sex, age or family history of schizophrenia, are said to influence the performance of neurological examination, whereas relative few studies have provided longitudinal follow-up data on neurological soft signs in a sufficient number of patients, in order to address a possible deterioration of neurological functions. Finally, one additional difficulty when analyzing the NSS literature lies in the diversity of symptoms that are evaluated in the studies and/or non-standardized procedures or scoring. We will review some basic issues concerning recurrent difficulties in the measurement and definition of soft signs, as well as controversies on the significance of these signs with respect to clinical subtyping of schizophrenia, and social and demographic variables.

Children with sickle cell anemia with normal transcranial Doppler ultrasounds and without silent infarcts have a low incidence of new strokes.

PubMed

Jordan, Lori C; Roberts Williams, Dionna O; Rodeghier, Mark J; Covert Greene, Brittany V; Ponisio, Maria R; Casella, James F; McKinstry, Robert C; Noetzel, Michael J; Kirkham, Fenella J; Meier, Emily R; Fuh, Beng; McNaull, Melissa; Sarnaik, Sharada; Majumdar, Suvankar; McCavit, Timothy L; DeBaun, Michael R

2018-06-01

In a prospective cohort study, we tested the hypothesis that children with sickle cell anemia (SCA) with normal transcranial Doppler ultrasound (TCD) velocities and without silent cerebral infarcts (SCIs) would have a lower incidence rate of new neurological events (strokes, seizures or transient ischemic attacks) compared to children with normal TCD measurements and SCIs, not receiving regular blood transfusions. Nonrandomized participants from the silent cerebral infarct transfusion (SIT) Trial who had screening magnetic resonance imaging (MRI) of the brain and normal TCD measurements were included. Follow-up ended at the time of first neurological event (stroke, seizure or transient ischemic attack), start of regular blood transfusion, or loss to follow-up, whichever came first. The primary endpoint was a new neurological event. Of 421 participants included, 68 had suspected SCIs. Mean follow-up was 3.6 years. Incidence rates of new neurological events in nontransfused participants with normal TCD values with SCIs and without SCIs were 1.71 and 0.47 neurological events per 100 patient-years, respectively, P = .065. The absence of SCI(s) at baseline was associated with a decreased risk of a new neurological event (hazard ratio 0.231, 95% CI 0.062-0.858; P = .029). Local pediatric neurologists examined 67 of 68 participants with suspected SCIs and identified 2 with overt strokes classified as SCIs by local hematologists; subsequently one had a seizure and the other an ischemic stroke. Children with SCA, without SCIs, and normal TCD measurements have a significantly lower rate of new neurological events when compared to those with SCIs and normal TCD measurements. Pediatric neurology assessment may assist risk stratification. © 2018 Wiley Periodicals, Inc.

A study of the standard brain in Japanese children: morphological comparison with the MNI template.

PubMed

Uchiyama, Hitoshi T; Seki, Ayumi; Tanaka, Daisuke; Koeda, Tatsuya; Jcs Group

2013-03-01

Functional magnetic resonance imaging (MRI) studies involve normalization so that the brains of different subjects can be described using the same coordinate system. However, standard brain templates, including the Montreal Neurological Institute (MNI) template that is most frequently used at present, were created based on the brains of Western adults. Because morphological characteristics of the brain differ by race and ethnicity and between adults and children, errors are likely to occur when data from the brains of non-Western individuals are processed using these templates. Therefore, this study was conducted to collect basic data for the creation of a Japanese pediatric standard brain. Participants in this study were 45 healthy children (contributing 65 brain images) between the ages of 6 and 9 years, who had nothing notable in their perinatal and other histories and neurological findings, had normal physical findings and cognitive function, exhibited no behavioral abnormalities, and provided analyzable MR images. 3D-T1-weighted images were obtained using a 1.5-T MRI device, and images from each child were adjusted to the reference image by affine transformation using SPM8. The lengths were measured and compared with those of the MNI template. The Western adult standard brain and the Japanese pediatric standard brain obtained in this study differed greatly in size, particularly along the anteroposterior diameter and in height, suggesting that the correction rates are high, and that errors are likely to occur in the normalization of pediatric brain images. We propose that the use of the Japanese pediatric standard brain created in this study will improve the accuracy of identification of brain regions in functional brain imaging studies involving children. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

[Early prediction of the neurological result at 12 months in newborns at neurological risk].

PubMed

Herbón, F; Garibotti, G; Moguilevsky, J

2015-08-01

The aim of this study was to evaluate the Amiel-Tison neurological examination (AT) and cranial ultrasound at term for predicting the neurological result at 12 months in newborns with neurological risk. The study included 89 newborns with high risk of neurological damage, who were discharged from the Neonatal Intensive Care of the Hospital Zonal Bariloche, Argentina. The assessment consisted of a neurological examination and cranial ultrasound at term, and neurological examination and evaluation of development at 12 months. The sensitivity, specificity, positive and negative predictor value was calculated. The relationship between perinatal factors and neurodevelopment at 12 month of age was also calculated using logistic regression models. Seventy children completed the follow-up. At 12 months of age, 14% had an abnormal neurological examination, and 17% abnormal development. The neurological examination and the cranial ultrasound at term had low sensitivity to predict abnormal neurodevelopment. At 12 months, 93% of newborns with normal AT showed normal neurological results, and 86% normal development. Among newborns with normal cranial ultrasound the percentages were 90 and 81%, respectively. Among children with three or more perinatal risk factors, the frequency of abnormalities in the neurological response was 5.4 times higher than among those with fewer risk factors, and abnormal development was 3.5 times more frequent. The neurological examination and cranial ultrasound at term had low sensitivity but high negative predictive value for the neurodevelopment at 12 months. Three or more perinatal risk factors were associated with neurodevelopment abnormalities at 12 months of age. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

The neurology of mTOR.

PubMed

Lipton, Jonathan O; Sahin, Mustafa

2014-10-22

The mechanistic target of rapamycin (mTOR) signaling pathway is a crucial cellular signaling hub that, like the nervous system itself, integrates internal and external cues to elicit critical outputs including growth control, protein synthesis, gene expression, and metabolic balance. The importance of mTOR signaling to brain function is underscored by the myriad disorders in which mTOR pathway dysfunction is implicated, such as autism, epilepsy, and neurodegenerative disorders. Pharmacological manipulation of mTOR signaling holds therapeutic promise and has entered clinical trials for several disorders. Here, we review the functions of mTOR signaling in the normal and pathological brain, highlighting ongoing efforts to translate our understanding of cellular physiology into direct medical benefit for neurological disorders.

We "Are" Musical

ERIC Educational Resources Information Center

Welch, Graham F.

2005-01-01

The challenge for music education is to nurture and develop each individual's basic musicality. Assuming normal neurological functioning and development, we are all musical. Our musical development begins pre-birth, with musical behaviours in one form or another being evident across the lifespan. Nevertheless, early enculturation can both foster…

Early school outcomes for extremely preterm infants with transient neurological abnormalities.

PubMed

Harmon, Heidi M; Taylor, H Gerry; Minich, Nori; Wilson-Costello, Deanne; Hack, Maureen

2015-09-01

To determine if transient neurological abnormalities (TNA) at 9 months corrected age predict cognitive, behavioral, and motor outcomes at 6 years of age in extremely preterm infants. A cohort of 124 extremely preterm infants (mean gestational age 25.5wks; 55 males, 69 females), admitted to our unit between 2001 and 2003, were classified based on the Amiel-Tison Neurological Assessment at 9 months and 20 months corrected age as having TNA (n=17), normal neurological assessment (n=89), or neurologically abnormal assessment (n=18). The children were assessed at a mean age of 5 years 11 months (SD 4mo) on cognition, academic achievement, motor ability, and behavior. Compared with children with a normal neurological assessment, children with TNA had higher postnatal exposure to steroids (35% vs 9%) and lower adjusted mean scores on spatial relations (84 [standard error {SE} 5] vs 98 [SE 2]), visual matching (79 [SE 5] vs 91 [SE 2]), letter-word identification (97 [SE 4] vs 108 [SE 1]), and spelling (76 [SE 4] vs 96 [SE 2]) (all p<0.05). Despite a normalized neurological assessment, extremely preterm children with a history TNA are at higher risk for lower cognitive and academic skills than those with normal neurological findings during their first year of school. © 2015 Mac Keith Press.

Early school outcomes for extremely preterm infants with transient neurological abnormalities

PubMed Central

Harmon, Heidi; Taylor, H Gerry; Minich, Nori; Wilson-Costello, Deanne; Hack, Maureen

2015-01-01

AIM To determine if transient neurological abnormalities (TNA) at 9 months corrected age predict cognitive, behavioral, and motor outcomes at 6 years of age in extremely preterm infants. METHOD A cohort of 124 extremely preterm infants (mean gestational age 25.5wk; 55 males, 69 females), admitted to our unit between 2001 and 2003, were classified based on the Amiel-Tison Neurological Assessment at 9 months and 20 months corrected age as having TNA (n=17), normal neurological assessment (n=89), or neurologically abnormal assessment (n=18). The children were assessed at a mean age of 5 years 11 months (SD 4mo) on cognition, academic achievement, motor ability, and behavior. RESULTS Compared with children with a normal neurological assessment, children with TNA had higher postnatal exposure to steroids (35% vs 9%) and lower adjusted mean scores on spatial relations (84 [standard error {SE} 5] vs 98 [SE 2]), visual matching (79 [SE 5] vs 91 [SE 2]), letter–word identification (97 [SE 4] vs 108 [SE 1]), and spelling (76 [SE 4] vs 96 [SE 2]) (all p<0.05). INTERPRETATION Despite a normalized neurological assessment, extremely preterm children with a history TNA are at higher risk for lower cognitive and academic skills than those with normal neurological findings during their first year of school. PMID:26014665

Continuous subcutaneous insulin infusion preserves axonal function in type 1 diabetes mellitus.

PubMed

Kwai, Natalie; Arnold, Ria; Poynten, Ann M; Lin, Cindy S-Y; Kiernan, Matthew C; Krishnan, Arun V

2015-02-01

Diabetic peripheral neuropathy is a common and debilitating complication of diabetes mellitus. Although strict glycaemic control may reduce the risk of developing diabetic peripheral neuropathy, the neurological benefits of different insulin regimens remain relatively unknown. In the present study, 55 consecutive patients with type 1 diabetes mellitus underwent clinical neurological assessment. Subsequently, 41 non-neuropathic patients, 24 of whom were receiving multiple daily insulin injections (MDII) and 17 receiving continuous subcutaneous insulin infusion (CSII), underwent nerve excitability testing, a technique that assesses axonal ion channel function and membrane potential in human nerves. Treatment groups were matched for glycaemic control, body mass index, disease duration and gender. Neurophysiological parameters were compared between treatment groups and those taken from age and sex-matched normal controls. Prominent differences in axonal function were noted between MDII-treated and CSII-treated patients. Specifically, MDII patients manifested prominent abnormalities when compared with normal controls in threshold electrotonus (TE) parameters including depolarizing TE(10-20ms), undershoot and hyperpolarizing TE (90-100 ms) (P < 0.05). Additionally, recovery cycle parameters superexcitability and subexcitability were also abnormal (P < 0.05). In contrast, axonal function in CSII-treated patients was within normal limits when compared with age-matched controls. The differences between the groups were noted in cross-sectional analysis and remained at longitudinal follow-up. Axonal function in type 1 diabetes is maintained within normal limits in patients treated with continuous subcutaneous insulin infusion and not with multiple daily insulin injections. This raises the possibility that CSII therapy may have neuroprotective potential in patients with type 1 diabetes. Copyright © 2014 John Wiley & Sons, Ltd.

Porencephaly

MedlinePlus

... develop only minor neurological problems and have normal intelligence, while others may be severely disabled and die ... develop only minor neurological problems and have normal intelligence, while others may be severely disabled and die ...

What is it like to be a patient with apperceptive agnosia?

PubMed

Vecera, S P; Gilds, K S

1997-01-01

Neuropsychological deficits have been widely used to elucidate normal cognitive functioning. Can patients with such deficits also be used to understand conscious visual experience? In this paper, we ask what it would be like to be a patient with apperceptive agnosia (a deficit in object recognition). Philosophical analyses of such questions have suggested that subjectively experiencing what another person experiences would be impossible. Although such roadblocks into the conscious experience of others exist, the experimental study of both patients and neurologically normal subjects can be used to understand visual processing mechanisms. In order to understand the visual processes damaged in apperceptive agnosia, we first review this syndrome and present a case study of one such patient, patient J.W. We then review several theoretical accounts of apperceptive agnosia, and we conclude that studies of the patients themselves may not allow us to discriminate between the various explanations of the syndrome. To test these accounts, we have simulated apperceptive agnosia in neurologically normal subjects. The implications of our results for understanding both apperceptive agnosia and normal visual processing are discussed.

Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

DTIC Science & Technology

2013-10-01

locomotor recovery. When cystometry was performed at the end of the study, 29/34 (~85%) of mice exhibited partial or complete voluntary bladder...0.05). Following euthanasia , bladders were removed, weighed, and normalized to total bodyweight (Figure 11C). One-way ANOVA demonstrated no

Distribution and function of voltage-gated sodium channels in the nervous system.

PubMed

Wang, Jun; Ou, Shao-Wu; Wang, Yun-Jie

2017-11-02

Voltage-gated sodium channels (VGSCs) are the basic ion channels for neuronal excitability, which are crucial for the resting potential and the generation and propagation of action potentials in neurons. To date, at least nine distinct sodium channel isoforms have been detected in the nervous system. Recent studies have identified that voltage-gated sodium channels not only play an essential role in the normal electrophysiological activities of neurons but also have a close relationship with neurological diseases. In this study, the latest research findings regarding the structure, type, distribution, and function of VGSCs in the nervous system and their relationship to neurological diseases, such as epilepsy, neuropathic pain, brain tumors, neural trauma, and multiple sclerosis, are reviewed in detail.

Neurological and Psychiatric Diseases and Their Unique Cognitive Profiles: Implications for Nursing Practice and Research

PubMed Central

Vance, David E.; Dodson, Joan E.; Watkins, Jason; Kennedy, Bridgett H.; Keltner, Norman L.

2013-01-01

To successfully negotiate and interact with one’s environment, optimal cognitive functioning is needed. Unfortunately, many neurological and psychiatric diseases impede certain cognitive abilities such as executive functioning or speed of processing; this can produce a poor fit between the patient and the cognitive demands of his or her environment. Such non-dementia diseases include bipolar disorder, schizophrenia, post-traumatic stress syndrome, depression, and anxiety disorders, just to name a few. Each of these diseases negatively affects particular areas of the brain, resulting in distinct cognitive profiles (e.g., deficits in executive functioning but normal speed of processing as seen in schizophrenia). In fact, it is from these cognitive deficits in which such behavioral and emotional symptoms may manifest (e.g., delusions, paranoia). This article highlights the distinct cognitive profiles of such common neurological and psychiatric diseases. An understanding of such disease-specific cognitive profiles can assist nurses in providing care to patients by knowing what cognitive deficits are associated with each disease and how these cognitive deficits impact everyday functioning and social interactions. Implications for nursing practice and research are posited within the framework of cognitive reserve and neuroplasticity. PMID:23422693

Left hemisphere regions are critical for language in the face of early left focal brain injury.

PubMed

Raja Beharelle, Anjali; Dick, Anthony Steven; Josse, Goulven; Solodkin, Ana; Huttenlocher, Peter R; Levine, Susan C; Small, Steven L

2010-06-01

A predominant theory regarding early stroke and its effect on language development, is that early left hemisphere lesions trigger compensatory processes that allow the right hemisphere to assume dominant language functions, and this is thought to underlie the near normal language development observed after early stroke. To test this theory, we used functional magnetic resonance imaging to examine brain activity during category fluency in participants who had sustained pre- or perinatal left hemisphere stroke (n = 25) and in neurologically normal siblings (n = 27). In typically developing children, performance of a category fluency task elicits strong involvement of left frontal and lateral temporal regions and a lesser involvement of right hemisphere structures. In our cohort of atypically developing participants with early stroke, expressive and receptive language skills correlated with activity in the same left inferior frontal regions that support language processing in neurologically normal children. This was true independent of either the amount of brain injury or the extent that the injury was located in classical cortical language processing areas. Participants with bilateral activation in left and right superior temporal-inferior parietal regions had better language function than those with either predominantly left- or right-sided unilateral activation. The advantage conferred by left inferior frontal and bilateral temporal involvement demonstrated in our study supports a strong predisposition for typical neural language organization, despite an intervening injury, and argues against models suggesting that the right hemisphere fully accommodates language function following early injury.

Intracerebroventricular gene therapy that delays neurological disease progression is associated with selective preservation of retinal ganglion cells in a canine model of CLN2 disease.

PubMed

Whiting, Rebecca E H; Jensen, Cheryl A; Pearce, Jacqueline W; Gillespie, Lauren E; Bristow, Daniel E; Katz, Martin L

2016-05-01

CLN2 disease is one of a group of lysosomal storage disorders called the neuronal ceroid lipofuscinoses (NCLs). The disease results from mutations in the TPP1 gene that cause an insufficiency or complete lack of the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). TPP1 is involved in lysosomal protein degradation, and lack of this enzyme results in the accumulation of protein-rich autofluorescent lysosomal storage bodies in numerous cell types including neurons throughout the central nervous system and the retina. CLN2 disease is characterized primarily by progressive loss of neurological functions and vision as well as generalized neurodegeneration and retinal degeneration. In children the progressive loss of neurological functions typically results in death by the early teenage years. A Dachshund model of CLN2 disease with a null mutation in TPP1 closely recapitulates the human disorder with a progression from disease onset at approximately 4 months of age to end-stage at 10-11 months. Delivery of functional TPP1 to the cerebrospinal fluid (CSF), either by periodic infusion of the recombinant protein or by a single administration of a TPP1 gene therapy vector to the CSF, significantly delays the onset and progression of neurological signs and prolongs life span but does not prevent the loss of vision or modest retinal degeneration that occurs by 11 months of age. In this study we found that in dogs that received the CSF gene therapy treatment, the degeneration of the retina and loss of retinal function continued to progress during the prolonged life spans of the treated dogs. Eventually the normal cell layers of the retina almost completely disappeared. An exception was the ganglion cell layer. In affected dogs that received TPP1 gene therapy to the CSF and survived an average of 80 weeks, ganglion cell axons were present in numbers comparable to those of normal Dachshunds of similar age. The selective preservation of the retinal ganglion cells suggests that while TPP1 protein delivered via the CSF may protect these cells, preservation of the remainder of the retina will require delivery of normal TPP1 more directly to the retina, probably via the vitreous body. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The myth of the normal, average human brain--the ICBM experience: (1) subject screening and eligibility.

PubMed

Mazziotta, John C; Woods, Roger; Iacoboni, Marco; Sicotte, Nancy; Yaden, Kami; Tran, Mary; Bean, Courtney; Kaplan, Jonas; Toga, Arthur W

2009-02-01

In the course of developing an atlas and reference system for the normal human brain throughout the human age span from structural and functional brain imaging data, the International Consortium for Brain Mapping (ICBM) developed a set of "normal" criteria for subject inclusion and the associated exclusion criteria. The approach was to minimize inclusion of subjects with any medical disorders that could affect brain structure or function. In the past two years, a group of 1685 potential subjects responded to solicitation advertisements at one of the consortium sites (UCLA). Subjects were screened by a detailed telephone interview and then had an in-person history and physical examination. Of those who responded to the advertisement and considered themselves to be normal, only 31.6% (532 subjects) passed the telephone screening process. Of the 348 individuals who submitted to in-person history and physical examinations, only 51.7% passed these screening procedures. Thus, only 10.7% of those individuals who responded to the original advertisement qualified for imaging. The most frequent cause for exclusion in the second phase of subject screening was high blood pressure followed by abnormal signs on neurological examination. It is concluded that the majority of individuals who consider themselves normal by self-report are found not to be so by detailed historical interviews about underlying medical conditions and by thorough medical and neurological examinations. Recommendations are made with regard to the inclusion of subjects in brain imaging studies and the criteria used to select them.

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice

PubMed Central

Avraham, Y; Grigoriadis, NC; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, EM

2011-01-01

BACKGROUND AND PURPOSE Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT1A, on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. EXPERIMENTAL APPROACH Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. KEY RESULTS Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. CONCLUSIONS AND IMPLICATIONS Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. PMID:21182490

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice.

PubMed

Avraham, Y; Grigoriadis, Nc; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, Em

2011-04-01

Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT(1A) , on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

False-normal vitamin B12 results in a patient with pernicious anaemia.

PubMed

Wainwright, P; Narayanan, S; Cook, P

2015-12-01

Pernicious anaemia is a common autoimmune disorder with a prevalence of approximately 4% amongst Europeans. If untreated, it can result in permanent neurological disability or death. Central to the diagnosis is establishing the presence of vitamin B12 deficiency. Concern has been raised recently regarding false-normal results obtained with competitive-binding vitamin B12 assays performed on automated biochemistry platforms in patients with pernicious anaemia due to the presence of interfering anti-intrinsic factor antibodies in the patient sample. We report a case in which diagnosis of pernicious anaemia was delayed due to false-normal vitamin B12 results. Questioning the results in light of high pre-test probability, and knowledge of the role of functional markers of vitamin B12 deficiency enabled the correct diagnosis to be made so that effective treatment could be initiated. It is crucial that those who frequently request vitamin B12 are aware of the potential problems with the available assays and how these problems can be addressed. We suggest that all patients with normal vitamin B12 levels where there is a high clinical suspicion for deficiency such as a macrocytic anaemia, neurological symptoms or megaloblastic bone marrow should have a functional assay of vitamin B12 (plasma homocysteine or methylmalonic acid) checked to further investigate for vitamin B12 deficiency. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Superior cerebral protection with profound hypothermia during circulatory arrest.

PubMed

Gillinov, A M; Redmond, J M; Zehr, K J; Troncoso, J C; Arroyo, S; Lesser, R P; Lee, A W; Stuart, R S; Reitz, B A; Baumgartner, W A

1993-06-01

The optimal temperature for cerebral protection during hypothermic circulatory arrest is not known. This study was undertaken to test the hypothesis that deeper levels of cerebral hypothermia (< 10 degrees C) confer better protection against neurologic injury during prolonged hypothermic circulatory arrest ("colder is better"). Twelve male dogs (20 to 25 kg) were placed on closed-chest cardiopulmonary bypass via femoral artery and femoral/external jugular vein. Using surface and core cooling, tympanic membrane temperature was lowered to 18 degrees to 20 degrees C (deep hypothermia, n = 6) or 5 degrees to 7 degrees C (profound hypothermia, n = 6). After 2 hours of hypothermic circulatory arrest, animals were rewarmed to 35 degrees to 37 degrees C on cardiopulmonary bypass. All were mechanically ventilated and monitored in an intensive care unit setting for 20 hours. Neurologic assessment was performed every 12 hours using a species-specific behavior scale that yielded a neurodeficit score ranging from 0% to 100%, where 0 = normal and 100% = brain dead. After 72 hours, animals were sacrificed and examined histologically for neurologic injury. Histologic injury scores were assigned to each animal (range, 0 [normal] to 100 [severe injury]). At the end of the observation period, profoundly hypothermic animals had better neurologic function (neurodeficit score, 5.7% +/- 4.0%) compared with deeply hypothermic animals (neurodeficit score, 41% +/- 9.3%; p < 0.006). Every animal had histologic evidence of neurologic injury, but profoundly hypothermic animals had significantly less injury (histologic injury score, 19.2 +/- 1.2 versus 48.3 +/- 1.5; p < 0.0001).

Therapeutic Effect of Steroids in Osmotic Demyelination of Infancy.

PubMed

Bansal, Lalit R

2018-01-01

An 11-month-old male presented with acute gastroenteritis, seizures, and altered mental status. Laboratory workup revealed serum sodium of 177 mmol/L. Magnetic resonance imaging of the brain showed reduced diffusion in the supratentorial white matter, T2 hyperintensities in the left central pons and midbrain, subacute stroke in the right occipital lobe, and bilateral cerebellar hemorrhagic infarcts. The child was presumed to have hypernatremia-induced central pontine and extrapontine myelinolysis. He received 5 days of high-dose methylprednisolone for persistent encephalopathy and spastic quadriparesis with rapid recovery of his cognitive function and neurological examination. The child remained seizure-free and achieved normal development at 3-month and 2-year follow-ups. Osmotic demyelination of infancy may leave children with a significant neurological deficit. For favorable neurological outcome, early steroids should be considered.

[Quantification of the gnostic sensitivity via measurement of the vibration threshold and of finger tip sensation].

PubMed

Oosterhuis, H J; Bouwsma, C; van Halsema, B; Hollander, R A; Kros, C J; Tombroek, I

1992-10-03

Quantification of vibration perception and fingertip sensation in routine neurological examination. Neurological Clinic, University Hospital, Groningen, the Netherlands. Prospective, controlled investigation. Vibration perception and fingertip sensation were quantified in a large group of normal control persons of various ages and in neurological patients and compared with the usual sensory tests at routine neurological examination. The vibration perception limit was measured with a biothesiometer without accelerometer, the fingertip sensation with a device for two-point discrimination slightly modified according to Renfrew ('Renfrew meter'). Concordance of the tests was studied by calculating kappa values. The normal values of both sensory qualities had a log-normal distribution and increased with age. The values obtained with the Renfrew meter correlated well with those of the two-point discrimination and stereognosis but were systematically higher than those indicated by Renfrew. Both methods appear useful at routine neurological examination if certain measuring precautions are taken.

Cybernetic anthropomorphic machine systems

NASA Technical Reports Server (NTRS)

Gray, W. E.

1974-01-01

Functional descriptions are provided for a number of cybernetic man machine systems that augment the capacity of normal human beings in the areas of strength, reach or physical size, and environmental interaction, and that are also applicable to aiding the neurologically handicapped. Teleoperators, computer control, exoskeletal devices, quadruped vehicles, space maintenance systems, and communications equipment are considered.

Comparison of stationary and personal air sampling with an air dispersion model for children’s ambient exposure to manganese

EPA Science Inventory

Manganese (Mn) is ubiquitous in the environment and essential for normal growth and development, yet excessive exposure can lead to impairments in neurological function. This study modeled ambient Mn concentrations as an alternative to stationary and personal air sampling to asse...

Utility of behavioral versus cognitive measures in differentiating between subtypes of frontotemporal lobar degeneration and Alzheimer's disease.

PubMed

Heidler-Gary, Jennifer; Gottesman, Rebecca; Newhart, Melissa; Chang, Shannon; Ken, Lynda; Hillis, Argye E

2007-01-01

We hypothesized that a modified version of the Frontal Behavioral Inventory (FBI-mod), along with a few cognitive tests, would be clinically useful in distinguishing between clinically defined Alzheimer's disease (AD) and subtypes of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (dysexecutive type), progressive nonfluent aphasia, and semantic dementia. We studied 80 patients who were diagnosed with AD (n = 30) or FTLD (n = 50), on the basis of a comprehensive neuropsychological battery, imaging, neurological examination, and history. We found significant between-group differences on the FBI-mod, two subtests of the Rey Auditory Verbal Learning Test (verbal learning and delayed recall), and the Trail Making Test Part B (one measure of 'executive functioning'). AD was characterized by relatively severe impairment in verbal learning, delayed recall, and executive functioning, with relatively normal scores on the FBI-mod. Frontotemporal dementia was characterized by relatively severe impairment on the FBI-mod and executive functioning in the absence of severe impairment in verbal learning and recall. Progressive nonfluent aphasia was characterized by severe impairment in executive functioning with relatively normal scores on verbal learning and recall and FBI-mod. Finally, semantic dementia was characterized by relatively severe deficits in delayed recall, but relatively normal performance on new learning, executive functioning, and on FBI-mod. Discriminant function analysis confirmed that the FBI-mod, in conjunction with the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B categorized the majority of patients as subtypes of FTLD or AD in the same way as a full neuropsychological battery, neurological examination, complete history, and imaging. These tests may be useful for efficient clinical diagnosis, although progressive nonfluent aphasia and semantic dementia are likely to be best distinguished by language tests not included in standard neuropsychological test batteries.

The prevalence of abnormal preoperative neurological examination in Scheuermann kyphosis: correlation with X-ray, magnetic resonance imaging, and surgical outcome.

PubMed

Cho, Woojin; Lenke, Lawrence G; Bridwell, Keith H; Hu, Guangxun; Buchowski, Jacob M; Dorward, Ian G; Pahys, Joshua M; Cho, Samuel K; Kang, Matthew M; Zebala, Lukas P; Koester, Linda A

2014-10-01

Retrospective. The purpose of this study was to report the prevalence of abnormal neurological findings detected by physical examination in Scheuermann kyphosis and to correlate it to radiographs, magnetic resonance imaging (MRI) findings, and results of operative treatment. There have been sporadic reports about abnormal neurological findings in patients with Scheuermann kyphosis. Among 82 patients with Scheuermann kyphosis who underwent corrective surgery, 69 primary cases were selected. Patients' charts were reviewed retrospectively in terms of pre and postoperative neurological examinations. Sensory or motor change was defined as an abnormal neurological examination. Their duration, associated problems, and various parameters on preoperative radiographs and MRI examinations were also measured to search for any atypical findings associated with an abnormal neurological examination. There were 6 cases (9%) (group AbN), with an abnormal neurological examination ranging from severe myelopathy to a subtle change (e.g., sensory paresthesias on trunk). Five patients recovered to a normal neurological examination after corrective surgery. The remaining 1 patient with severe myelopathy also showed marked improvement and was ambulatory unassisted by 2-year follow-up. In patients with a normal neurological examination (group N, n = 63), only 1 patient had neurological sequelae because of anterior spinal artery syndrome after combined anterior-posterior correction. No preoperative radiographical parameters were significantly different between groups. Average age was 21.3 (AbN) and 18.6 (N) years (P = 0.55). Average preoperative T5-12 kyphosis was 69.0° (AbN) and 72.5° (N) (P = 0.61). Forty-two magnetic resonance images were obtained and all showed typical findings of Scheuermann kyphosis. Five patients in the AbN group (1 patient underwent computed tomography/myelography) and 37 patients in the N group underwent an MRI. The prevalence of abnormal neurological findings in Scheuermann kyphosis was 9%, emphasizing the importance of performing a detailed preoperative neurological examination. If congenital stenosis or a herniated thoracic disc is present, myelopathy can occur. No radiographical findings correlated with the abnormal preoperative neurological examinations. A normal MRI can exist in the face of an abnormal neurological examination, and conversely, a normal neurological examination can be seen with an abnormal MRI. Surgery was successful in alleviating abnormal neurological issues. 4.

Underlying neurological dysfunction in children with language, speech or learning difficulties and a verbal IQ--performance IQ discrepancy.

PubMed

Meulemans, J; Goeleven, A; Zink, I; Loyez, L; Lagae, L; Debruyne, F

2012-01-01

We investigated the relationship between possible underlying neurological dysfunction and a significant discrepancy between verbal IQ/performance IQ (VIQ-PIQ) in children with language, speech or learning difficulties. In a retrospective study, we analysed data obtained from intelligence testing and neurological evaluation in 49 children with a significant VIQ-PIQ discrepancy (> or = 25 points) who were referred because of language, speech or learning difficulties to the Multidisciplinary University Centre for Logopedics and Audiology (MUCLA) of the University Hospitals of Leuven, Belgium. The group of children broke down into a group of 35 children with PIQ > VIQ and a group of 14 children with VIQ > PIQ. In the first group, neurological data were present for 24 children. The neurological history and clinical neurological examination were normal in all cases. Brain MRI was performed in 15 cases and proved to be normal in all children. Brain activity was assessed with long-term video EEG monitoring in ten children. In two children, the EEG results were abnormal: there was an epileptic focus in one child and a manifest alteration in the EEG typical of Landau-Kleffner syndrome in the other. In the second group of 14 children whose VIQ was higher than the PIQ, neurological data were available for ten children. Neurological history and clinical neurological examination were normal in all cases. Brain MRI was performed in five cases and was normal in all children. EEG monitoring was performed in one child. This revealed benign childhood epilepsy with centrotemporal spikes. In a small number of children (9%) with speech, language and learning difficulties and a discrepancy between VIQ and PIQ, an underlying neurological abnormality is present. We recommend referring children with a significant VIQ-PIQ mismatch to a paediatric neurologist. As an epileptic disorder seems to be the most common underlying neurological pathology in this specific group of children, EEG monitoring should be recommended in these children. Neuro-imaging should only be used in selected patients.

Ramus marginalis mandibulae nervus facialis palsy in hemifacial microsomia.

PubMed

Silvestri, A; Mariani, G; Vernucci, R A

2008-12-01

The paralysis of the ramus marginalis mandibulae nervus facialis may occur in Hemifacial Microsomia (HM); the combination of both HM and palsy contributes to an elongation of the mandibular body. This study explores a possible correlation between neurological deficit, muscular atony, and structural deficiency. Of 58 patients with HM who had come to the University of Rome (Sapienza) Pre-surgical Orthodontics Unit, 4 patients were afflicted with Hemifacial Microsomia and ramus marginalis mandibulae nervus palsy; these patients underwent physical, neurological, opthamologic and systemic examinations. The results were then analysed in order to determine a possible correlation between neuro-muscular and structural deficit. Electroneurographic and electromyographic examinations were performed to estimate facial nerve and muscles involvement. Neuroelectrographic exam showed a damage of the nervous motor fibres of the facial nerve ipsilateral to HM, with an associated damage of the muscular function, while neuro-muscular functions on the healthy side were normal. The peripheral nervous and muscular deficits affect the function of facial soft tissues and the growth of mandibular body with an asymmetry characterised by a hypodevelopment of the ramus (due to the HM) and by an elongation of the mandibular body (due to ramus marginalis mandibulae nerve palsy), so that the chin deviation is contralateral to HM. In these forms, a neurological examination is necessary to assess the neurological damage on the HM side. Neuromuscular deficiency can also contribute to a relapse tendency after a surgical-orthodontic treatment.

Systemic lupus erythematosus with organic brain syndrome: serial electroencephalograms accurately evaluate therapeutic efficacy.

PubMed

Kato, Takashi; Shiratori, Kyoji; Kobashigawa, Tsuyoshi; Hidaka, Yuji

2006-01-01

A 48-year-old man with systemic lupus erythematosus developed organic brain syndrome. High-dose prednisolone was ineffective, and somnolence without focal signs rapidly developed. Electroencephalogram (EEG) demonstrated a slow basic rhythm (3 Hz), but brain magnetic resonance imaging was normal. Somnolence resolved soon after performing plasma exchange (two sessions). However, memory dysfunction persisted, with EEG demonstrating mild abnormalities (7-8 Hz basic rhythm). Double-filtration plasmapheresis (three sessions) was done, followed by intravenous cyclophosphamide. Immediately after the first plasmapheresis session, memory dysfunction began to improve. After the second dose of cyclophosphamide, intellectual function resolved completely and EEG findings also normalized (basic rhythm of 10 Hz waves). Serial EEG findings precisely reflected the neurological condition and therapeutic efficacy in this patient. In contrast, protein levels in cerebrospinal fluid remained high and did not seem to appropriately reflect the neurological condition in this patient.

Thyroid-related neurological disorders and complications in children.

PubMed

Nandi-Munshi, Debika; Taplin, Craig E

2015-04-01

Thyroid hormones exert critical roles throughout the body and play an important and permissive role in neuroendocrine, neurological, and neuromuscular function. We performed a PubMed search through June 2014 with search terms including "hypothyroidism," "hyperthyroidism," "neurological complications," "neuropathy," "myopathy," "congenital hypothyroidism," and "encephalopathy." Relevant publications reviewed included case series, individual case reports, systematic reviews, retrospective analyses, and randomized controlled trials. The neurological outcomes of congenital hypothyroidism were reviewed, along with the clinical features of associated neuromuscular syndromes of both hypothyroidism and hyperthyroidism, including other autoimmune conditions. Evidence for, and pathophysiological controversies surrounding, Hashimoto encephalopathy was also reviewed. The establishment of widespread newborn screening programs has been highly successful in attenuating or preventing early and irreversible neurological harm resulting from congenital thyroid hormone deficiency, but some children continue to display neuromuscular, sensory, and cognitive defects in later life. Acquired disorders of thyroid function such as Hashimoto thyroiditis and Graves' disease are associated with a spectrum of central nervous system and/or neuromuscular dysfunction. However, considerable variation in clinical phenotype is described, and much of our knowledge of the role of thyroid disease in childhood neurological disorders is derived from adult case series. Early and aggressive normalization of thyroxine levels in newborn infants with congenital hypothyroidism is important in minimizing neurological sequelae, but maternal thyroid hormone sources are also critically important to the early developing brain. A spectrum of neurological disorders has been reported in older children with acquired thyroid disease, but the frequency with which these occur remains poorly defined in the literature, and much must be extrapolated from adult data. A high index of suspicion for acquired thyroid disease is paramount in the investigation of many neurological disorders of youth, as many reported sequelae of hypothyroidism and hyperthyroidism are reversible with appropriate endocrine management. Copyright © 2015 Elsevier Inc. All rights reserved.

Central nervous system involvement in severe congenital neutropenia: neurological and neuropsychological abnormalities associated with specific HAX1 mutations.

PubMed

Carlsson, G; van't Hooft, I; Melin, M; Entesarian, M; Laurencikas, E; Nennesmo, I; Trebińska, A; Grzybowska, E; Palmblad, J; Dahl, N; Nordenskjöld, M; Fadeel, B; Henter, J-I

2008-10-01

Homozygous mutations in the HAX1 gene were recently identified in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden. Our observations suggested that these patients also develop neurological and neuropsychological symptoms. Detailed clinical studies and mutation analyses were performed in the surviving patients belonging to the Kostmann kindred and in two patients not related to this family, along with studies of HAX1 splice variant expression in normal human tissues. Five of six Kostmann family patients and one other patient from northern Sweden harboured homozygous HAX1 mutations (568C-->T, Q190X) and one carried a heterozygous ELA2 gene mutation. One Swedish patient of Kurdish extraction carried alternative homozygous HAX1 mutations (131G-->A, W44X). All the three patients with Q190X mutations who were alive and available for evaluation developed neurological disease with decreased cognitive function, and three of four patients who reached 10 years developed epilepsy. In contrast, the patients with the ELA2 and W44X HAX1 mutations, respectively, showed no obvious neurological abnormalities. Moreover, two alternative HAX1 splice variants were identified in normal human tissues, including the brain. Both transcripts contained exon 5, harbouring the Q190X mutation, whereas the 5' end of exon 2 containing the W44X mutation was spliced out from the second transcript. We describe neurological and neuropsychological abnormalities for the first time in Kostmann disease patients. These central nervous system symptoms appear to be associated with specific HAX1 mutations.

Short and long-term outcomes in children with suspected acute encephalopathy.

PubMed

Nishiyama, Masahiro; Nagase, Hiroaki; Tanaka, Tsukasa; Fujita, Kyoko; Kusumoto, Mayumi; Kajihara, Shinsuke; Yamaguchi, Yoshimichi; Maruyama, Azusa; Takeda, Hiroki; Uetani, Yoshiyuki; Tomioka, Kazumi; Toyoshima, Daisaku; Taniguchi-Ikeda, Mariko; Morioka, Ichiro; Takada, Satoshi; Iijima, Kazumoto

2016-09-01

The time-dependent changes that occur in children after acute encephalopathy are not clearly understood. Therefore, we assessed changes in brain function after suspected acute encephalopathy over time. We created a database of children admitted to the pediatric intensive care unit at Kobe Children's Hospital because of convulsions or impaired consciousness with fever between 2002 and 2013. Clinical courses and outcomes were reviewed and patients who met the following criteria were included in the study: (1) 6months to 15years of age, (2) no neurological abnormality before onset, (3) treated for suspected acute encephalopathy, and (4) followed after 1 (0-2) month and 12 (10-17) months of onset. Outcomes were assessed using the Pediatric Cerebral Performance Category (PCPC) scale, with a score of 1 representing normal performance; 2, mild disability; 3, moderate disability; 4, severe disability; 5, vegetative state; and 6, brain death. A total of 78 children (32 male) with a median (range) age at onset of 20 (6-172) months were enrolled. Fifty-one cases scored 1 on the PCPC, 13 scored 2, three scored 3, five scored 4, one scored 5, and five cases scored 6 at discharge. Whereas seven of the 13 cases that scored a 2 on the PCPC recovered normal brain function after 12months, none of the nine cases that scored a 3-5 on the PCPC recovered normal function. Our findings suggest moderate to severe disability caused by acute encephalopathy had lasting consequences on brain function, whereas mild disability might result in improved function. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Protein O-Mannosyltransferases Affect Sensory Axon Wiring and Dynamic Chirality of Body Posture in the Drosophila Embryo.

PubMed

Baker, Ryan; Nakamura, Naosuke; Chandel, Ishita; Howell, Brooke; Lyalin, Dmitry; Panin, Vladislav M

2018-02-14

Genetic defects in protein O-mannosyltransferase 1 (POMT1) and POMT2 underlie severe muscular dystrophies. POMT genes are evolutionarily conserved in metazoan organisms. In Drosophila , both male and female POMT mutants show a clockwise rotation of adult abdominal segments, suggesting a chirality of underlying pathogenic mechanisms. Here we described and analyzed a similar phenotype in POMT mutant embryos that shows left-handed body torsion. Our experiments demonstrated that coordinated muscle contraction waves are associated with asymmetric embryo rolling, unveiling a new chirality marker in Drosophila development. Using genetic and live-imaging approaches, we revealed that the torsion phenotype results from differential rolling and aberrant patterning of peristaltic waves of muscle contractions. Our results demonstrated that peripheral sensory neurons are required for normal contractions that prevent the accumulation of torsion. We found that POMT mutants show abnormal axonal connections of sensory neurons. POMT transgenic expression limited to sensory neurons significantly rescued the torsion phenotype, axonal connectivity defects, and abnormal contractions in POMT mutant embryos. Together, our data suggested that protein O-mannosylation is required for normal sensory feedback to control coordinated muscle contractions and body posture. This mechanism may shed light on analogous functions of POMT genes in mammals and help to elucidate the etiology of neurological defects in muscular dystrophies. SIGNIFICANCE STATEMENT Protein O-mannosyltransferases (POMTs) are evolutionarily conserved in metazoans. Mutations in POMTs cause severe muscular dystrophies associated with pronounced neurological defects. However, neurological functions of POMTs remain poorly understood. We demonstrated that POMT mutations in Drosophila result in abnormal muscle contractions and cause embryo torsion. Our experiments uncovered a chirality of embryo movements and a unique POMT -dependent mechanism that maintains symmetry of a developing system affected by chiral forces. Furthermore, POMTs were found to be required for proper axon connectivity of sensory neurons, suggesting that O-mannosylation regulates the sensory feedback controlling muscle contractions. This novel POMT function in the peripheral nervous system may shed light on analogous functions in mammals and help to elucidate pathomechanisms of neurological abnormalities in muscular dystrophies. Copyright © 2018 the authors 0270-6474/18/381850-16$15.00/0.

Pan-brachial plexus neuropraxia following lightning: A rare case report.

PubMed

Patnaik, Ashis; Mahapatra, Ashok Kumar; Jha, Menka

2015-01-01

Neurological complications following lightning are rare and occur in form of temporary neurological deficits of central origin. Involvement of peripheral nervous system is extremely rare and only a few cases have been described in the literature. Isolated unilateral pan-brachial plexus neuropraxia has never been reported in the literature. Steroids have long been used for treatment of neuropraxia. However, their use in lightning neural injury is unique and requires special mention. We report a rare case of lightning-induced unilateral complete flaccid paralysis along with sensory loss in a young patient. Lightning typically causes central nervous involvement in various types of motor and sensory deficit. Surprisingly, the nerve conduction study showed the involvement of peripheral nervous system involvement. Steroids were administered and there was significant improvement in neurological functions within a short span of days. Patients' functions in the affected limb were normal in one month. Our case was interesting since it is the first such case in the literature where lightning has caused such a rare instance of unilateral pan-brachial plexus lesion. Such cases when seen, raises the possibility of more common central nervous system pathology rather than peripheral involvement. However, such lesions can be purely benign forms of peripheral nerve neuropraxia, which can be managed by steroid treatment without leaving any long-term neurological deficits.

Spectrum of gross motor function in extremely low birth weight children with cerebral palsy at 18 months of age.

PubMed

Vohr, Betty R; Msall, Michael E; Wilson, Dee; Wright, Linda L; McDonald, Scott; Poole, W Kenneth

2005-07-01

The purpose of this study was to evaluate the relationship between cerebral palsy (CP) diagnoses as measured by the topographic distribution of the tone abnormality with level of function on the Gross Motor Function Classification System (GMFCS) and developmental performance on the Bayley Scales of Infant Development II (BSID-II). It was hypothesized that (1) the greater the number of limbs involved, the higher the GMFCS and the lower the BSID-II Motor Scores and (2) there would be a spectrum of function and skill achievement on the GMFCS and BSID-II Motor Scores for children in each of the CP categories. A multicenter, longitudinal cohort study was conducted of 1860 extremely low birth weight (ELBW) infants who were born between August 1, 1995 and February 1, 1998, and evaluated at 18 to 22 months' corrected age. Children were categorized into impairment groups on the basis of the typography of neurologic findings: spastic quadriplegia, triplegia, diplegia, hemiplegia, monoplegia, hypotonic and/or athetotic CP, other abnormal neurologic findings, and normal. The neurologic category then was compared with GMFCS level and BSID-II Motor Scores. A total of 282 (15.2%) of the 1860 children evaluated had CP. Children with more limbs involved had more abnormal GMFCS levels and lower BSID-II scores, reflecting more severe functional limitations. However, for each CP diagnostic category, there was a spectrum of gross motor functional levels and BSID-II scores. Although more than 1 (26.6%) in 4 of the children with CP had moderate to severe gross motor functional impairment, 1 (27.6%) in 4 had motor functional skills that allowed for ambulation. Given the range of gross motor skill outcomes for specific types of CP, the GMFCS is a better indicator of gross motor functional impairment than the traditional categorization of CP that specifies the number of limbs with neurologic impairment. The neurodevelopmental assessment of young children is optimized by combining a standard neurologic examination with measures of gross and fine motor function (GMFCS and Bayley Psychomotor Developmental Index). Additional studies to examine longer term functional motor and adaptive-functional developmental skills are required to devise strategies that delineate therapies to optimize functional performance.

Altered Activation and Functional Asymmetry of Exner's Area but not the Visual Word Form Area in a Child with Sudden-onset, Persistent Mirror Writing.

PubMed

Linke, Annika; Roach-Fox, Elizabeth; Vriezen, Ellen; Prasad, Asuri Narayan; Cusack, Rhodri

2018-06-02

Mirror writing is often produced by healthy children during early acquisition of literacy, and has been observed in adults following neurological disorders or insults. The neural mechanisms responsible for involuntary mirror writing remain debated, but in healthy children, it is typically attributed to the delayed development of a process of overcoming mirror invariance while learning to read and write. We present an unusual case of sudden-onset, persistent mirror writing in a previously typical seven-year-old girl. Using her dominant right hand only, she copied and spontaneously produced all letters, words and sentences, as well as some numbers and objects, in mirror image. Additionally, she frequently misidentified letter orientations in perceptual assessments. Clinical, neuropsychological, and functional neuroimaging studies were carried out over sixteen months. Neurologic and ophthalmologic examinations and a standard clinical MRI scan of the head were normal. Neuropsychological testing revealed average scores on most tests of intellectual function, language function, verbal learning and memory. Visual perception and visual reasoning were average, with the exception of below average form constancy, and mild difficulties on some visual memory tests. Activation and functional connectivity of the reading and writing network was assessed with fMRI. During a reading task, the VWFA showed a strong response to words in mirror but not in normal letter orientation - similar to what has been observed in typically developing children previously - but activation was atypically reduced in right primary visual cortex and Exner's Area. Resting-state connectivity within the reading and writing network was similar to that of age-matched controls, but hemispheric asymmetry between the balance of motor-to-visual input was found for Exner's Area. In summary, this unusual case suggests that a disruption to visual-motor integration rather than to the VWFA can contribute to sudden-onset, persistent mirror writing in the absence of clinically detectable neurological insult. Copyright © 2018. Published by Elsevier Ltd.

The impact of epilepsy on preschool children and their families.

PubMed

Tanriverdi, Müberra; Mutluay, Fatma Karantay; Tarakçi, Devrim; Güler, Serhat; Iscan, Akin

2016-09-01

This study investigated the possible presence of sensory-motor developmental impairments in preschool children with epilepsy and explored epilepsy impact on their activities and quality of life and on the stress load of their family. Study participants were children aged 2-6years diagnosed with epilepsy without any other comorbidities (epi-only children). The instruments used for assessment included the Neurological, Sensory, Motor, Developmental Assessment (NSMDA) scale for sensory-motor development, the Impact of Childhood Neurologic Disability Scale (ICNDS), and the Impact of Pediatric Epilepsy Scale (IPES) for disease impact on disability and Quality of Life (QoL), as well as the Pediatric Outcomes Data Collection Instrument (PODCI) for functional health status, and the Parental Stress Scale (PSS) for the family stress load. Required data were obtained from direct testing or observation of children's activities and mother-supplied answers to questions. Eighty-two children were investigated. The NSMDA scores were in the normal development range 6-8. Significant moderate impact of the disease on disability and QoL was estimated with the ICNDS and IPES instruments. The PODCI scores were similar to healthy population levels except for the happiness dimension which was better for children with epilepsy. PSS were significantly above normal. The functional health and QoL of the children as well as their family stress were found to be positively correlated with increasing age. It is found that epilepsy does not degrade neuromotor development and functional health status of preschool epi-only children, though it has a significant impact on their neurological disability and QoL and the stress level of their families; this impact seems to decrease with age. Copyright © 2016 Elsevier Inc. All rights reserved.

Lower urinary tract and sexual dysfunction in neurological patients.

PubMed

Vodušek, David B

2014-01-01

Lower urinary tract dysfunction (LUTD) and sexual dysfunction (SD) are common in neurological patients due to a combination of lesions affecting relevant neural control, constraints imposed by sensorimotor and cognitive deficits and--particularly for SD--psychosocial consequences of chronic neurological disease. This review summarizes the etiology, diagnosis and treatment of LUTD and SD in neurological patients. LUTD may lead to serious health problems; both LUTD and SD significantly affect quality of life. Management of patients with spinal cord injury and dysraphism is undertaken in specialized centers according to established guidelines. Treatment of neurological patients with noncomplicated neurogenic LUTD or SD should preferentially be guided by a neurologist. For rational treatment of urinary symptoms, an accurate assessment is mandatory; the bladder and the sphincter need to be defined as normal, over- or underactive. Urodynamic testing is the gold standard for functional diagnosis; assessment of residual urine and uroflow are the minimal requirements before considering management. Dysfunction of desire, arousal and orgasm (ejaculation) may be diagnosed by medical history and are amenable to counselling and treatment, which is--in the case of erectile dysfunction--evidence based. Further high-quality studies are necessary to test the best approaches for diagnosing and managing particular types of neurogenic LUTD and SD in the different neurological patient populations. © 2014 S. Karger AG, Basel.

The emerging link between O-GlcNAcylation and neurological disorders.

PubMed

Ma, Xiaofeng; Li, He; He, Yating; Hao, Junwei

2017-10-01

O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is involved in the regulation of many cellular cascades and neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In the brain, the expression of O-GlcNAcylation is notably heightened, as is that of O-linked N-acetylglucosaminyltransferase (OGT) and β-N-acetylglucosaminidase (OGA), the presence of which is prominent in many regions of neurological importance. Most importantly, O-GlcNAcylation is believed to contribute to the normal functioning of neurons; conversely, its dysregulation participates in the pathogenesis of neurological disorders. In neurodegenerative diseases, O-GlcNAcylation of the brain's key proteins, such as tau and amyloid-β, interacts with their phosphorylation, thereby triggering the formation of neurofibrillary tangles and amyloid plaques. An increase of O-GlcNAcylation by pharmacological intervention prevents neuronal loss. Additionally, O-GlcNAcylation is stress sensitive, and its elevation is cytoprotective. Increased O-GlcNAcylation ameliorated brain damage in victims of both trauma-hemorrhage and stroke. In this review, we summarize the current understanding of O-GlcNAcylation's physiological and pathological roles in the nervous system and provide a foundation for development of a therapeutic strategy for neurological disorders.

Right Fronto-Parietal Dysfunction in Children with ADHD and Developmental Dyslexia as Determined by Line Bisection Judgements

ERIC Educational Resources Information Center

Waldie, Karen E.; Hausmann, Markus

2010-01-01

Visual line bisection is a reliable and valid laterality task that is typically used with patients with acquired brain damage to assess right hemisphere functioning. Neurologically normal individuals tend to bisect lines to the left of the objective midline whereas those with right parietal damage bisect lines to the right. In this study children…

On compensatory strategies and computational models: the case of pure alexia.

PubMed

Shallice, Tim

2014-01-01

The article is concerned with inferences from the behaviour of neurological patients to models of normal function. It takes the letter-by-letter reading strategy common in pure alexic patients as an example of the methodological problems involved in making such inferences that compensatory strategies produce. The evidence is discussed on the possible use of three ways the letter-by-letter reading process might operate: "reversed spelling"; the use of the phonological input buffer as a temporary holding store during word building; and the use of serial input to the visual word-form system entirely within the visual-orthographic domain such as in the model of Plaut [1999. A connectionist approach to word reading and acquired dyslexia: Extension to sequential processing. Cognitive Science, 23, 543-568]. The compensatory strategy used by, at least, one pure alexic patient does not fit with the third of these possibilities. On the more general question, it is argued that even if compensatory strategies are being used, the behaviour of neurological patients can be useful for the development and assessment of first-generation information-processing models of normal function, but they are not likely to be useful for the development and assessment of second-generation computational models.

Motor outcome at the age of one after perinatal hypoxic-ischemic encephalopathy.

PubMed

van Schie, P E M; Becher, J G; Dallmeijer, A J; Barkhof, F; Weissenbruch, M M; Vermeulen, R J

2007-04-01

The aim of this report is to describe the motor outcome in one year-old children who were born at full-term with perinatal hypoxic-ischemic encephalopathy (HIE). Relationships between motor ability tests and neurological examination at one year, and between these tests and neonatal brain magnetic resonance imaging (MRI) were investigated. 32 surviving children, born full-term with perinatal HIE, are included in this report. All children had a neonatal MRI. At one year, motor ability was assessed with the Alberta Infant Motor Scale and the Bayley Scales of Infant Development (2nd version). Neurological examinations included the neurological optimality score (NOS). At one year, 14 children (44%) had normal motor ability, nine (28%) had mildly delayed, and nine had significantly delayed motor ability. The NOS ranged from 14.6-27 points. All children with normal motor ability had (near) optimal NOS, however, not all children with high NOS had normal motor ability. Eleven children (34%) had normal neonatal MRI; at one year, six of them had normal, and five had mildly delayed motor ability. Eight children with normal motor ability showed abnormalities on neonatal MRI. Neonatal brain MRI does not predict motor outcome at one year. Motor ability tests and neurological examinations should be used in a complementary manner to describe outcome after HIE.

Acute transient hemiparesis induced by lightning strike.

PubMed

Rahmani, Seyed Hesam; Faridaalaee, Gholamreza; Jahangard, Samira

2015-07-01

According to data from the National Oceanic and Atmospheric Administration,in the years from 1959 to 1994, lightning was responsible for more than 3000 deaths and nearly 10,000 casualties. The most important characteristic features of lightning injuries are multisystem involvement and widely variable severity. Lightning strikes are primarily a neurologic injury that affects all 3 components of the nervous system: central, autonomic,and peripheral. Neurologic complications of lightning strikes vary from transient benign symptoms to permanent disability. Many patients experience a temporary paralysis called keraunoparalysis. Here we reported a 22-year-old mountaineer man with complaining of left sided hemiparesis after being hit by a lightning strike in the mountain 3 hours ago. There was no loss of consciousness at hitting time. On arrival the patient was alert, awake and hemodynamically stable. In neurologic examination cranial nerves were intact, left sided upper and lower extremity muscle force was I/V with a combination of complete sensory loss, and right-sided muscle force and sensory examination were normal. There is not any evidence of significant vascular impairment in the affected extremities. Brain MRI and CT scan and cervical MRI were normal. During 2 days of admission, with intravenous hydration, heparin 5000 unit SC q12hr and physical therapy of the affected limbs, motor and sensory function improved and was normal except mild paresthesia. He was discharged 1 day later for outpatient follow up while vitamin B1 100mg orally was prescribed.Paresthesia improved after 3 days without further sequels.

One-stage posterior transforaminal lumbar debridement, 360° interbody fusion, and posterior instrumentation in treating lumbosacral spinal tuberculosis.

PubMed

Pang, Xiaoyang; Wu, Ping; Shen, Xiongjie; Li, Dongzhe; Luo, Chenke; Wang, Xiyang

2013-08-01

Retrospective analysis of the clinical study efficacy and feasibility of one-stage posterior transforaminal lumbar debridement, 360° interbody fusion, and posterior instrumentation in treating lumbosacral spinal tuberculosis. A total of 21 patients with lumbosacral tuberculosis (TB) collected from January 2004 to January 2010, underwent one-stage posterior transforaminal lumbar debridement, 360° interbody fusion, and posterior instrumentation. In addition, the clinical efficacy was evaluated based on the data on the lumbo-sacral angle, neuro-logical status that was recorded by American Spinal Injury Association (ASIA) Impairment Scale, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), which were collected at specific time points. All cases were followed up for 16-36 months (average 24.9 ± 6.44 months). 18 patients suffered from evident neurological deficits preoperatively, of which 16 patients returned to normal at the final follow-up. Two patients with neurological dysfunction aggravated postoperative, experienced significant partial neurological recovery. With an effective and standard anti-TB chemotherapy treated, the values of ESR and CRP returned to normal levels 3-month later postoperative and maintained till the final follow-up. Preoperative lumbosacral angle was 20.89 ± 2.32° and returned 29.62 ± 1.41° postoperative. During long-term follow-up, there was only 1-3° lumbosacral angle loss. There was a significant difference between preoperative and postoperative lumbosacral angles. With effective and standard anti-TB chemotherapy, one-stage posterior transforaminal lumbar debridement, 360° interbody fusion, and posterior instrumentation for lumbosacral tuberculosis can effectively relieve pain symptoms, improve neurological function, and reconstruct the spinal stability.

Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer's disease.

PubMed

Kirova, Anna-Mariya; Bays, Rebecca B; Lagalwar, Sarita

2015-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by deficits in episodic memory, working memory (WM), and executive function. Examples of executive dysfunction in AD include poor selective and divided attention, failed inhibition of interfering stimuli, and poor manipulation skills. Although episodic deficits during disease progression have been widely studied and are the benchmark of a probable AD diagnosis, more recent research has investigated WM and executive function decline during mild cognitive impairment (MCI), also referred to as the preclinical stage of AD. MCI is a critical period during which cognitive restructuring and neuroplasticity such as compensation still occur; therefore, cognitive therapies could have a beneficial effect on decreasing the likelihood of AD progression during MCI. Monitoring performance on working memory and executive function tasks to track cognitive function may signal progression from normal cognition to MCI to AD. The present review tracks WM decline through normal aging, MCI, and AD to highlight the behavioral and neurological differences that distinguish these three stages in an effort to guide future research on MCI diagnosis, cognitive therapy, and AD prevention.

Oscillatory Activities in Neurological Disorders of Elderly: Biomarkers to Target for Neuromodulation.

PubMed

Giovanni, Assenza; Capone, Fioravante; di Biase, Lazzaro; Ferreri, Florinda; Florio, Lucia; Guerra, Andrea; Marano, Massimo; Paolucci, Matteo; Ranieri, Federico; Salomone, Gaetano; Tombini, Mario; Thut, Gregor; Di Lazzaro, Vincenzo

2017-01-01

Non-invasive brain stimulation (NIBS) has been under investigation as adjunct treatment of various neurological disorders with variable success. One challenge is the limited knowledge on what would be effective neuronal targets for an intervention, combined with limited knowledge on the neuronal mechanisms of NIBS. Motivated on the one hand by recent evidence that oscillatory activities in neural systems play a role in orchestrating brain functions and dysfunctions, in particular those of neurological disorders specific of elderly patients, and on the other hand that NIBS techniques may be used to interact with these brain oscillations in a controlled way, we here explore the potential of modulating brain oscillations as an effective strategy for clinical NIBS interventions. We first review the evidence for abnormal oscillatory profiles to be associated with a range of neurological disorders of elderly (e.g., Parkinson's disease (PD), Alzheimer's disease (AD), stroke, epilepsy), and for these signals of abnormal network activity to normalize with treatment, and/or to be predictive of disease progression or recovery. We then ask the question to what extent existing NIBS protocols have been tailored to interact with these oscillations and possibly associated dysfunctions. Our review shows that, despite evidence for both reliable neurophysiological markers of specific oscillatory dis-functionalities in neurological disorders and NIBS protocols potentially able to interact with them, there are few applications of NIBS aiming to explore clinical outcomes of this interaction. Our review article aims to point out oscillatory markers of neurological, which are also suitable targets for modification by NIBS, in order to facilitate in future studies the matching of technical application to clinical targets.

Oscillatory Activities in Neurological Disorders of Elderly: Biomarkers to Target for Neuromodulation

PubMed Central

Assenza, Giovanni; Capone, Fioravante; di Biase, Lazzaro; Ferreri, Florinda; Florio, Lucia; Guerra, Andrea; Marano, Massimo; Paolucci, Matteo; Ranieri, Federico; Salomone, Gaetano; Tombini, Mario; Thut, Gregor; Di Lazzaro, Vincenzo

2017-01-01

Non-invasive brain stimulation (NIBS) has been under investigation as adjunct treatment of various neurological disorders with variable success. One challenge is the limited knowledge on what would be effective neuronal targets for an intervention, combined with limited knowledge on the neuronal mechanisms of NIBS. Motivated on the one hand by recent evidence that oscillatory activities in neural systems play a role in orchestrating brain functions and dysfunctions, in particular those of neurological disorders specific of elderly patients, and on the other hand that NIBS techniques may be used to interact with these brain oscillations in a controlled way, we here explore the potential of modulating brain oscillations as an effective strategy for clinical NIBS interventions. We first review the evidence for abnormal oscillatory profiles to be associated with a range of neurological disorders of elderly (e.g., Parkinson’s disease (PD), Alzheimer’s disease (AD), stroke, epilepsy), and for these signals of abnormal network activity to normalize with treatment, and/or to be predictive of disease progression or recovery. We then ask the question to what extent existing NIBS protocols have been tailored to interact with these oscillations and possibly associated dysfunctions. Our review shows that, despite evidence for both reliable neurophysiological markers of specific oscillatory dis-functionalities in neurological disorders and NIBS protocols potentially able to interact with them, there are few applications of NIBS aiming to explore clinical outcomes of this interaction. Our review article aims to point out oscillatory markers of neurological, which are also suitable targets for modification by NIBS, in order to facilitate in future studies the matching of technical application to clinical targets. PMID:28659788

The Myth of the Normal, Average Human Brain—The ICBM Experience: (1) Subject Screening and Eligibility

PubMed Central

Mazziotta, John C.; Woods, Roger; Iacoboni, Marco; Sicotte, Nancy; Yaden, Kami; Tran, Mary; Bean, Courtney; Kaplan, Jonas; Toga, Arthur W.

2009-01-01

In the course of developing an atlas and reference system for the normal human brain throughout the human age span from structural and functional brain imaging data, the International Consortium for Brain Mapping (ICBM) developed a set of “normal” criteria for subject inclusion and the associated exclusion criteria. The approach was to minimize inclusion of subjects with any medical disorders that could affect brain structure or function. In the past two years, a group of 1,685 potential subjects responded to solicitation advertisements at one of the consortium sites (UCLA). Subjects were screened by a detailed telephone interview and then had an in-person history and physical examination. Of those who responded to the advertisement and considered themselves to be normal, only 31.6% (532 subjects) passed the telephone screening process. Of the 348 individuals who submitted to in-person history and physical examinations, only 51.7% passed these screening procedures. Thus, only 10.7% of those individuals who responded to the original advertisement qualified for imaging. The most frequent cause for exclusion in the second phase of subject screening was high blood pressure followed by abnormal signs on neurological examination. It is concluded that the majority of individuals who consider themselves normal by self-report are found not to be so by detailed historical interviews about underlying medical conditions and by thorough medical and neurological examinations. Recommendations are made with regard to the inclusion of subjects in brain imaging studies and the criteria used to select them. PMID:18775497

EEG correlates of the alcohol-induced organic brain syndrome in man.

PubMed

Zilm, D H; Huszar, L; Carlen, P L; Kaplan, H L; Wilkinson, D A

1980-05-01

Fourteen chronic alcoholics were studied within 1 to 3 weeks of beginning abstinence for a duration of 6 to 10 weeks. Patients were drug-free during the study. Electroencephalograms were recorded on admission, and twice at 2- to 3-week intervals. Neurologic examinations were performed during the same week as EEGs, and patients received a psychologic examination and CT scan within 3 weeks. Two groups could be identified. One group had high neurologic impairment scores, low alpha production, high 20 to 30 Hz power, impaired gait, and mental performance, while the other had low scores, normal alpha rhythm, and reduced degree of mental dysfunction. The impaired group showed marked improvement in neurologic scores, alpha rhythm, and 20 to 30 Hz power within 4 to 6 weeks, in contrast to no change for the unimpaired group. There was no evidence that age, duration of drinking, time from last drink, or cortical atrophy were involved in predisposing alcoholics to demonstrate the observed changes. It is submitted that spontaneous recovery in brain function of neurologically impaired alcoholics accompanies abstinence from chronic alcohol consumption.

Establishing Mouse Models for Zika Virus-induced Neurological Disorders Using Intracerebral Injection Strategies: Embryonic, Neonatal, and Adult.

PubMed

Herrlinger, Stephanie A; Shao, Qiang; Ma, Li; Brindley, Melinda; Chen, Jian-Fu

2018-04-26

The Zika virus (ZIKV) is a flavivirus currently endemic in North, Central, and South America. It is now established that the ZIKV can cause microcephaly and additional brain abnormalities. However, the mechanism underlying the pathogenesis of ZIKV in the developing brain remains unclear. Intracerebral surgical methods are frequently used in neuroscience research to address questions about both normal and abnormal brain development and brain function. This protocol utilizes classical surgical techniques and describes methods that allow one to model ZIKV-associated human neurological disease in the mouse nervous system. While direct brain inoculation does not model the normal mode of virus transmission, the method allows investigators to ask targeted questions concerning the consequence after ZIKV infection of the developing brain. This protocol describes embryonic, neonatal, and adult stages of intraventricular inoculation of ZIKV. Once mastered, this method can become a straightforward and reproducible technique that only takes a few hours to perform.

Brain endothelial TAK1 and NEMO safeguard the neurovascular unit

PubMed Central

Ridder, Dirk A.; Wenzel, Jan; Müller, Kristin; Töllner, Kathrin; Tong, Xin-Kang; Assmann, Julian C.; Stroobants, Stijn; Weber, Tobias; Niturad, Cristina; Fischer, Lisanne; Lembrich, Beate; Wolburg, Hartwig; Grand’Maison, Marilyn; Papadopoulos, Panayiota; Korpos, Eva; Truchetet, Francois; Rades, Dirk; Sorokin, Lydia M.; Schmidt-Supprian, Marc; Bedell, Barry J.; Pasparakis, Manolis; Balschun, Detlef; D’Hooge, Rudi; Löscher, Wolfgang; Hamel, Edith

2015-01-01

Inactivating mutations of the NF-κB essential modulator (NEMO), a key component of NF-κB signaling, cause the genetic disease incontinentia pigmenti (IP). This leads to severe neurological symptoms, but the mechanisms underlying brain involvement were unclear. Here, we show that selectively deleting Nemo or the upstream kinase Tak1 in brain endothelial cells resulted in death of endothelial cells, a rarefaction of brain microvessels, cerebral hypoperfusion, a disrupted blood–brain barrier (BBB), and epileptic seizures. TAK1 and NEMO protected the BBB by activating the transcription factor NF-κB and stabilizing the tight junction protein occludin. They also prevented brain endothelial cell death in a NF-κB–independent manner by reducing oxidative damage. Our data identify crucial functions of inflammatory TAK1–NEMO signaling in protecting the brain endothelium and maintaining normal brain function, thus explaining the neurological symptoms associated with IP. PMID:26347470

Aciclovir-induced acute kidney injury in patients with 'suspected viral encephalitis' encountered on a liaison neurology service.

PubMed

Bogdanova-Mihaylova, Petya; Burke, David; O'Dwyer, John P; Bradley, David; Williams, Jennifer A; Cronin, Simon J; Smyth, Shane; Murphy, Raymond P; Murphy, Sinead M; Wall, Catherine; McCabe, Dominick J H

2018-01-06

Patients with 'suspected viral encephalitis' are frequently empirically treated with intravenous aciclovir. Increasing urea and creatinine are 'common', but rapidly progressive renal failure is reported to be 'very rare'. To describe the clinical course and outcome of cases of aciclovir-induced acute kidney injury (AKI) encountered by the Liaison Neurology Service at AMNCH and to highlight the importance of surveillance and urgent treatment of this iatrogenic complication. Retrospectively and prospectively collected data from the Liaison Neurology Service at AMNCH on patients who received IV aciclovir for suspected viral encephalitis and developed AKI were analysed. Aciclovir-induced AKI was defined by a consultant nephrologist in all cases as a rise in serum creatinine of > 26 μmol/L in 48 h or by ≥ 1.5 times the baseline value. Renal function, haematocrit, and fluid balance were monitored following AKI onset. Data from 10 patients were analysed. Median time to AKI onset was 3.5 days (range: 1-6 days). Aciclovir was stopped or the dose adjusted. All patients recovered with IV normal saline, aiming for a urine output > 100-150 ml/h. The interval between first rise in creatinine and return to normal levels varied between 5 and 19 days. Liaison neurologists and general physicians need to be aware that aciclovir may cause AKI attributed to distal intra-tubular crystal nephropathy. Daily fluid balance and renal function monitoring are essential because AKI may arise even with intensive pre-hydration. Prognosis is good if identified early and actively treated.

When novel sentences spoken or heard for the first time in the history of the universe are not enough: toward a dual-process model of language.

PubMed

Van Lancker Sidtis, Diana

2004-01-01

Although interest in the language sciences was previously focused on newly created sentences, more recently much attention has turned to the importance of formulaic expressions in normal and disordered communication. Also referred to as formulaic expressions and made up of speech formulas, idioms, expletives, serial and memorized speech, slang, sayings, clichés, and conventional expressions, non-propositional language forms a large proportion of every speaker's competence, and may be differentially disturbed in neurological disorders. This review aims to examine non-propositional speech with respect to linguistic descriptions, psycholinguistic experiments, sociolinguistic studies, child language development, clinical language disorders, and neurological studies. Evidence from numerous sources reveals differentiated and specialized roles for novel and formulaic verbal functions, and suggests that generation of novel sentences and management of prefabricated expressions represent two legitimate and separable processes in language behaviour. A preliminary model of language behaviour that encompasses unitary and compositional properties and their integration in everyday language use is proposed. Integration and synchronizing of two disparate processes in language behaviour, formulaic and novel, characterizes normal communicative function and contributes to creativity in language. This dichotomy is supported by studies arising from other disciplines in neurology and psychology. Further studies are necessary to determine in what ways the various categories of formulaic expressions are related, and how these categories are processed by the brain. Better understanding of how non-propositional categories of speech are stored and processed in the brain can lead to better informed treatment strategies in language disorders.

Paraneoplastic Neurological Disorder in Nasopharyngeal Carcinoma.

PubMed

Ng, Sze Yin; Kongg, Min Han; Yunus, Mohd Razif Mohamad

2017-03-01

Paraneoplastic neurological disorder (PND) is a condition due to immune cross-reactivity between the tumour cells and the normal tissue, whereby the "onconeural" antibodies attack the normal host nervous system. It can present within weeks to months before or after the diagnosis of malignancies. Nasopharyngeal carcinoma is associated with paraneoplastic syndrome, for example, dermatomyositis, and rarely with a neurological disorder. We report on a case of nasopharyngeal carcinoma with probable PND. Otolaryngologists, oncologists and neurologists need to be aware of this condition in order to make an accurate diagnosis and to provide prompt treatment.

Developing a 3-choice serial reaction time task for examining neural and cognitive function in an equine model.

PubMed

Roberts, Kirsty; Hemmings, Andrew J; McBride, Sebastian D; Parker, Matthew O

2017-12-01

Large animal models of human neurological disorders are advantageous compared to rodent models due to their neuroanatomical complexity, longevity and their ability to be maintained in naturalised environments. Some large animal models spontaneously develop behaviours that closely resemble the symptoms of neural and psychiatric disorders. The horse is an example of this; the domestic form of this species consistently develops spontaneous stereotypic behaviours akin to the compulsive and impulsive behaviours observed in human neurological disorders such as Tourette's syndrome. The ability to non-invasively probe normal and abnormal equine brain function through cognitive testing may provide an extremely useful methodological tool to assess brain changes associated with certain human neurological and psychiatric conditions. An automated operant system with the ability to present visual and auditory stimuli as well as dispense salient food reward was developed. To validate the system, ten horses were trained and tested using a standard cognitive task (three choice serial reaction time task (3-CSRTT)). All animals achieved total learning criterion and performed six probe sessions. Learning criterion was met within 16.30±0.79 sessions over a three day period. During six probe sessions, level of performance was maintained at 80.67±0.57% (mean±SEM) accuracy. This is the first mobile fully automated system developed to examine cognitive function in the horse. A fully-automated operant system for mobile cognitive function of a large animal model has been designed and validated. Horses pose an interesting complementary model to rodents for the examination of human neurological dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Volunteers for biomedical research. Recruitment and screening of normal controls.

PubMed

Shtasel, D L; Gur, R E; Mozley, P D; Richards, J; Taleff, M M; Heimberg, C; Gallacher, F; Gur, R C

1991-11-01

We examined the process of accruing healthy control subjects for biomedical research on brain function. Of 1670 responders to newspaper advertising, 23.1% were uninterested when learning more about the studies, and 50.9% of those remaining were found by structured telephone screening to meet exclusionary criteria for having a history of psychiatric, neurologic, or medical disease that might affect brain function. Of 312 volunteers passing the telephone screening who came to an in-person evaluation by a physician and agreed to participate, 49.7% were found to meet exclusionary criteria, and only 157 were admitted to the study. This underscores the importance of attending to the issue of screening and assessment of "normal volunteers." Alternative strategies should be considered for enriching the pool.

The role of emotion in decision-making: evidence from neurological patients with orbitofrontal damage.

PubMed

Bechara, Antoine

2004-06-01

Most theories of choice assume that decisions derive from an assessment of the future outcomes of various options and alternatives through some type of cost-benefit analyses. The influence of emotions on decision-making is largely ignored. The studies of decision-making in neurological patients who can no longer process emotional information normally suggest that people make judgments not only by evaluating the consequences and their probability of occurring, but also and even sometimes primarily at a gut or emotional level. Lesions of the ventromedial (which includes the orbitofrontal) sector of the prefrontal cortex interfere with the normal processing of "somatic" or emotional signals, while sparing most basic cognitive functions. Such damage leads to impairments in the decision-making process, which seriously compromise the quality of decisions in daily life. The aim of this paper is to review evidence in support of "The Somatic Marker Hypothesis," which provides a systems-level neuroanatomical and cognitive framework for decision-making and suggests that the process of decision-making depends in many important ways on neural substrates that regulate homeostasis, emotion, and feeling. The implications of this theoretical framework for the normal and abnormal development of the orbitofrontal cortex are also discussed.

Bridging Neuroanatomy, Neuroradiology and Neurology: Three-Dimensional Interactive Atlas of Neurological Disorders

PubMed Central

Nowinski, W.L.; Chua, B.C.

2013-01-01

Understanding brain pathology along with the underlying neuroanatomy and the resulting neurological deficits is of vital importance in medical education and clinical practice. To facilitate and expedite this understanding, we created a three-dimensional (3D) interactive atlas of neurological disorders providing the correspondence between a brain lesion and the resulting disorder(s). The atlas contains a 3D highly parcellated atlas of normal neuroanatomy along with a brain pathology database. Normal neuroanatomy is divided into about 2,300 components, including the cerebrum, cerebellum, brainstem, spinal cord, arteries, veins, dural sinuses, tracts, cranial nerves (CN), white matter, deep gray nuclei, ventricles, visual system, muscles, glands and cervical vertebrae (C1-C5). The brain pathology database contains 144 focal and distributed synthesized lesions (70 vascular, 36 CN-related, and 38 regional anatomy-related), each lesion labeled with the resulting disorder and associated signs, symptoms, and/or syndromes compiled from materials reported in the literature. The initial view of each lesion was preset in terms of its location and size, surrounding surface and sectional (magnetic resonance) neuroanatomy, and labeling of lesion and neuroanatomy. In addition, a glossary of neurological disorders was compiled and for each disorder materials from textbooks were included to provide neurological description. This atlas of neurological disorders is potentially useful to a wide variety of users ranging from medical students, residents and nurses to general practitioners, neuroanatomists, neuroradiologists and neurologists, as it contains both normal (surface and sectional) brain anatomy and pathology correlated with neurological disorders presented in a visual and interactive way. PMID:23859280

Bridging neuroanatomy, neuroradiology and neurology: three-dimensional interactive atlas of neurological disorders.

PubMed

Nowinski, W L; Chua, B C

2013-06-01

Understanding brain pathology along with the underlying neuroanatomy and the resulting neurological deficits is of vital importance in medical education and clinical practice. To facilitate and expedite this understanding, we created a three-dimensional (3D) interactive atlas of neurological disorders providing the correspondence between a brain lesion and the resulting disorder(s). The atlas contains a 3D highly parcellated atlas of normal neuroanatomy along with a brain pathology database. Normal neuroanatomy is divided into about 2,300 components, including the cerebrum, cerebellum, brainstem, spinal cord, arteries, veins, dural sinuses, tracts, cranial nerves (CN), white matter, deep gray nuclei, ventricles, visual system, muscles, glands and cervical vertebrae (C1-C5). The brain pathology database contains 144 focal and distributed synthesized lesions (70 vascular, 36 CN-related, and 38 regional anatomy-related), each lesion labeled with the resulting disorder and associated signs, symptoms, and/or syndromes compiled from materials reported in the literature. The initial view of each lesion was preset in terms of its location and size, surrounding surface and sectional (magnetic resonance) neuroanatomy, and labeling of lesion and neuroanatomy. In addition, a glossary of neurological disorders was compiled and for each disorder materials from textbooks were included to provide neurological description. This atlas of neurological disorders is potentially useful to a wide variety of users ranging from medical students, residents and nurses to general practitioners, neuroanatomists, neuroradiologists and neurologists, as it contains both normal (surface and sectional) brain anatomy and pathology correlated with neurological disorders presented in a visual and interactive way.

Brain disease, connectivity, plasticity and cognitive therapy: A neurological view of mental disorders.

PubMed

Lubrini, G; Martín-Montes, A; Díez-Ascaso, O; Díez-Tejedor, E

2018-04-01

Our conception of the mind-brain relationship has evolved from the traditional idea of dualism to current evidence that mental functions result from brain activity. This paradigm shift, combined with recent advances in neuroimaging, has led to a novel definition of brain functioning in terms of structural and functional connectivity. The purpose of this literature review is to describe the relationship between connectivity, brain lesions, cerebral plasticity, and functional recovery. Assuming that brain function results from the organisation of the entire brain in networks, brain dysfunction would be a consequence of altered brain network connectivity. According to this approach, cognitive and behavioural impairment following brain damage result from disrupted functional organisation of brain networks. However, the dynamic and versatile nature of these circuits makes recovering brain function possible. Cerebral plasticity allows for functional reorganisation leading to recovery, whether spontaneous or resulting from cognitive therapy, after brain disease. Current knowledge of brain connectivity and cerebral plasticity provides new insights into normal brain functioning, the mechanisms of brain damage, and functional recovery, which in turn serve as the foundations of cognitive therapy. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain

PubMed Central

Liang, Winnie S.; Dunckley, Travis; Beach, Thomas G.; Grover, Andrew; Mastroeni, Diego; Walker, Douglas G.; Caselli, Richard J.; Kukull, Walter A.; McKeel, Daniel; Morris, John C.; Hulette, Christine; Schmechel, Donald; Alexander, Gene E.; Reiman, Eric M.; Rogers, Joseph; Stephan, Dietrich A.

2008-01-01

In this article, we have characterized and compared gene expression profiles from laser capture microdissected neurons in six functionally and anatomically distinct regions from clinically and histopathologically normal aged human brains. These regions, which are also known to be differentially vulnerable to the histopathological and metabolic features of Alzheimer’s disease (AD), include the entorhinal cortex and hippocampus (limbic and paralimbic areas vulnerable to early neurofibrillary tangle pathology in AD), posterior cingulate cortex (a paralimbic area vulnerable to early metabolic abnormalities in AD), temporal and prefrontal cortex (unimodal and heteromodal sensory association areas vulnerable to early neuritic plaque pathology in AD), and primary visual cortex (a primary sensory area relatively spared in early AD). These neuronal profiles will provide valuable reference information for future studies of the brain, in normal aging, AD and other neurological and psychiatric disorders. PMID:17077275

Neurologic outcome after thoracolumbar partial lateral corpectomy for intervertebral disc disease in 72 dogs.

PubMed

Salger, Florian; Ziegler, Luisa; Böttcher, Irene Christine; Oechtering, Gerhard; Böttcher, Peter; Flegel, Thomas

2014-07-01

To determine neurologic outcome and factors influencing outcome after thoracolumbar partial lateral corpectomy (PLC) in dogs with intervertebral disc disease (IVDD) causing ventral spinal cord compression. Retrospective case series. Dogs with IVDD (n = 72; 87 PLC). Dogs with IVDD between T9 and L5 were included if treated by at least 1 PLC. Exclusion criteria were: previous spinal surgery, combination of PLC with another surgical procedure. Neurologic outcome was assessed by: (1) modified Frankel score (MFS) based on neurologic examinations at 4 time points (before surgery, immediately after PLC, at discharge and 4 weeks after PLC); and (2) owner questionnaire. The association of the following factors with neurologic outcome was analyzed: age, body weight, duration of current neurologic dysfunction (acute, chronic), IVDD localization, breed (chondrodystrophic, nonchondrodystrophic), number of PLCs, degree of presurgical spinal cord compression and postsurgical decompression, slot depth, presurgical MFS. Presurgical spinal cord compression was determined by CT myelography (71 dogs) or MRI (1 dog), whereas postsurgical decompression and slot depth were determined on CT myelography (69 dogs). MFS was improved in 18.7%, 31.7%, and 64.2% of dogs at the 3 postsurgical assessments, whereas it was unchanged in 62.6%, 52.8%, and 32.0% at corresponding time points. Based on owner questionnaire, 91.4% of dogs were ambulatory 6 months postsurgically with 74.5% having a normal gait. Most improvement in neurologic function developed within 6 months after surgery. Presurgical MFS was the only variable significantly associated with several neurologic outcome measurements (P < .01). PLC is an option for decompression in ventrally compressing thoracolumbar IVDD. Prognosis is associated with presurgical neurologic condition. © Copyright 2014 by The American College of Veterinary Surgeons.

Are sporadic fidgety movements as clinically relevant as is their absence?

PubMed

Einspieler, Christa; Yang, Hong; Bartl-Pokorny, Katrin D; Chi, Xia; Zang, Fei-Fei; Marschik, Peter B; Guzzetta, Andrea; Ferrari, Fabrizio; Bos, Arend F; Cioni, Giovanni

2015-04-01

Infants with normal fidgety movements at 3 to 5 months after term are very likely to show neurologically normal development, while the absence of fidgety movements is an early marker for an adverse neurological outcome, mainly cerebral palsy (CP). The clinical significance of so-called sporadic fidgety movements (i.e., fidgety movements occur isolated in a few body parts and are of 1- to 3-second-duration) is not yet known. Our objective was to determine whether infants who had developed CP and had sporadic fidgety movements have a better outcome than infants who did not have fidgety movements. Longitudinal study. Retrospective analysis of prospectively collected data. 61 infants who developed CP (46 male, 15 female; 29 infants born preterm; videoed for the assessment of movements and postures at 9 to 16 weeks post-term age). The Gross Motor Function Classification System (GMFCS) was applied at 3 to 5 years of age. There was no difference between children diagnosed with CP who had sporadic fidgety movements at 9 to 16 weeks post-term age (n = 9) and those who never developed fidgety movements (n = 50) with regard to their functional mobility and activity limitation at 3 to 5 years of age. One infant had normal FMs and developed unilateral CP, GMFCS Level I; the remaining infant had abnormal FMs and developed bilateral CP, GMFCS Level II. There is no evidence that the occurrence of occasional isolated fidgety bursts indicates a milder type of CP. Copyright © 2015. Published by Elsevier Ireland Ltd.

Comparison of Quantitative Characteristics of Early Post-resuscitation EEG Between Asphyxial and Ventricular Fibrillation Cardiac Arrest in Rats.

PubMed

Chen, Bihua; Chen, Gang; Dai, Chenxi; Wang, Pei; Zhang, Lei; Huang, Yuanyuan; Li, Yongqin

2018-04-01

Quantitative electroencephalogram (EEG) analysis has shown promising results in studying brain injury and functional recovery after cardiac arrest (CA). However, whether the quantitative characteristics of EEG, as potential indicators of neurological prognosis, are influenced by CA causes is unknown. The purpose of this study was designed to compare the quantitative characteristics of early post-resuscitation EEG between asphyxial CA (ACA) and ventricular fibrillation CA (VFCA) in rats. Thirty-two Sprague-Dawley rats of both sexes were randomized into either ACA or VFCA group. Cardiopulmonary resuscitation was initiated after 5-min untreated CA. Characteristics of early post-resuscitation EEG were compared, and the relationships between quantitative EEG features and neurological outcomes were investigated. Compared with VFCA, serum level of S100B, neurological deficit score and brain histopathologic damage score were dramatically higher in the ACA group. Quantitative measures of EEG, including onset time of EEG burst, time to normal trace, burst suppression ratio, and information quantity, were significantly lower for CA caused by asphyxia and correlated with the 96-h neurological outcome and survival. Characteristics of earlier post-resuscitation EEG differed between cardiac and respiratory causes. Quantitative measures of EEG not only predicted neurological outcome and survival, but also have the potential to stratify CA with different causes.

RNase alleviates neurological dysfunction in mice undergoing cardiac arrest and cardiopulmonary resuscitation

PubMed Central

Ma, Ye; Chen, Chan; Zhang, Shu; Wang, Qiao; Chen, Hai; Dong, Yuanlin; Zhang, Zheng; Li, Yan; Niu, Zhendong; Zhu, Tao; Yu, Hai; Liu, Bin

2017-01-01

Cardiac arrest (CA) is one of the leading lethal factors. Despite cardiopulmonary resuscitation (CPR) procedure has been consecutively improved and lots of new strategies have been developed, neurological outcome of the patients experienced CPR is still disappointing. Ribonuclease (RNase) has been demonstrated to have neuroprotective effects in acute stroke and postoperative cognitive impairment, possibly through acting against endogenous RNA that released from damaged tissue. However, the role of RNase in post-cardiac arrest cerebral injury is unknown. In the present study, we investigated the role of RNase in neurological outcome of mice undergoing 5 minutes of CA and followed by CPR. RNase or the same dosage of normal saline was administrated. We found that RNase administration could: 1) improve neurologic score on day 1 and day 3 after CA/CPR performance; 2) improve memory and learning ability on day 3 after training in contextual fear-conditioning test; 3) reduce extracellular RNA (exRNA) level in plasma and hippocampus tissue, and hippocampal cytokines mRNA production on day 3 after CA/CPR procedure; 4) attenuate autophagy levels in hippocampus tissue on day 3 after CA/CPR procedure. In conclusion, RNase could improve neurological function by reducing inflammation response and autophagy in mice undergoing CA/CPR. PMID:28881795

Neurological bypass for sensory innervation of the penis in patients with spina bifida.

PubMed

Overgoor, Max L E; Kon, Moshe; Cohen-Kettenis, Peggy T; Strijbos, Saskia A M; de Boer, Niels; de Jong, Tom P V M

2006-09-01

Most male patients with spina bifida have normal sexual desires. During puberty they begin to realize that they can achieve erection and sexual intercourse but without any sensation in the penis. We hypothesized that restored sensation in the penis would greatly contribute to their quality of life and sexual health. In this prospective study we investigated the outcome of a new operative neurological bypass procedure in patients with spina bifida. In 3 patients who were 17, 18 and 21 years old with a spinal lesion at L5, L4 and L3-L4, respectively, the sensory ilioinguinal nerve (L1) was cut distal in the groin and joined by microneurorrhaphy to the divided ipsilateral dorsal nerve of the penis (S2-4) at the base of the penis. All patients underwent preoperative and postoperative neurological and psychological evaluations. By 15 months postoperatively all patients had achieved excellent sensation on the operated side of the glans penis. They were unequivocally positive about the results and the penis had become more integrated into the body image. In 2 patients masturbation became more meaningful and 1 became more sexually active with and without his partner. The newly designed neurological bypass procedure in patients with spina bifida resulted in excellent sensibility in the glans penis. The new sensation appeared to contribute to the quality of the patient sexuality and sexual functioning as well as to the feeling of being a more normal and complete individual who is more conscious of the penis. This new operation might become standard treatment in patients with spina bifida in the future.

Cerebral fat embolism syndrome after long bone fracture due to gunshot injury.

PubMed

Duran, Latif; Kayhan, Servet; Kati, Celal; Akdemir, Hizir Ufuk; Balci, Kemal; Yavuz, Yucel

2014-03-01

Cerebral fat embolism syndrome is a lethal complication of long-bone fractures and clinically manifasted with respiratory distress, altered mental status, and petechial rash. We presented a 20-year-old male admitted with gun-shot wounds to his left leg. Twenty-four hours after the event, he had generalized tonic clonic seizures, decorticate posture and a Glascow Coma Scale of seven with localization of painful stimuli. Subsequent magnetic resonance imaging of the brain showed a star-field pattern defining multiple lesions of restricted diffusion. On a 4-week follow-up, he had returned to normal neurological function. Despite the severity of the neurological condition upon initial presentation, the case cerebral fat embolism illustrates that, cerebral dysfunction associated with cerebral fat embolism illustrates reversible.

Impaired growth and neurological abnormalities in branched-chain α-keto acid dehydrogenase kinase-deficient mice

PubMed Central

Joshi, Mandar A.; Jeoung, Nam Ho; Obayashi, Mariko; Hattab, Eyas M.; Brocken, Eric G.; Liechty, Edward A.; Kubek, Michael J.; Vattem, Krishna M.; Wek, Ronald C.; Harris, Robert A.

2006-01-01

The BCKDH (branched-chain α-keto acid dehydrogenase complex) catalyses the rate-limiting step in the oxidation of BCAAs (branched-chain amino acids). Activity of the complex is regulated by a specific kinase, BDK (BCKDH kinase), which causes inactivation, and a phosphatase, BDP (BCKDH phosphatase), which causes activation. In the present study, the effect of the disruption of the BDK gene on growth and development of mice was investigated. BCKDH activity was much greater in most tissues of BDK−/− mice. This occurred in part because the E1 component of the complex cannot be phosphorylated due to the absence of BDK and also because greater than normal amounts of the E1 component were present in tissues of BDK−/− mice. Lack of control of BCKDH activity resulted in markedly lower blood and tissue levels of the BCAAs in BDK−/− mice. At 12 weeks of age, BDK−/− mice were 15% smaller than wild-type mice and their fur lacked normal lustre. Brain, muscle and adipose tissue weights were reduced, whereas weights of the liver and kidney were greater. Neurological abnormalities were apparent by hind limb flexion throughout life and epileptic seizures after 6–7 months of age. Inhibition of protein synthesis in the brain due to hyperphosphorylation of eIF2α (eukaryotic translation initiation factor 2α) might contribute to the neurological abnormalities seen in BDK−/− mice. BDK−/− mice show significant improvement in growth and appearance when fed a high protein diet, suggesting that higher amounts of dietary BCAA can partially compensate for increased oxidation in BDK−/− mice. Disruption of the BDK gene establishes that regulation of BCKDH by phosphorylation is critically important for the regulation of oxidative disposal of BCAAs. The phenotype of the BDK−/− mice demonstrates the importance of tight regulation of oxidative disposal of BCAAs for normal growth and neurological function. PMID:16875466

Ataxia Telangiectasia

MedlinePlus

... A-T usually have normal or above normal intelligence. × Definition Ataxia-telangiectasia is a rare, childhood neurological ... A-T usually have normal or above normal intelligence. View Full Definition Treatment There is no cure ...

Control of Abnormal Synchronization in Neurological Disorders

PubMed Central

Popovych, Oleksandr V.; Tass, Peter A.

2014-01-01

In the nervous system, synchronization processes play an important role, e.g., in the context of information processing and motor control. However, pathological, excessive synchronization may strongly impair brain function and is a hallmark of several neurological disorders. This focused review addresses the question of how an abnormal neuronal synchronization can specifically be counteracted by invasive and non-invasive brain stimulation as, for instance, by deep brain stimulation for the treatment of Parkinson’s disease, or by acoustic stimulation for the treatment of tinnitus. On the example of coordinated reset (CR) neuromodulation, we illustrate how insights into the dynamics of complex systems contribute to successful model-based approaches, which use methods from synergetics, non-linear dynamics, and statistical physics, for the development of novel therapies for normalization of brain function and synaptic connectivity. Based on the intrinsic multistability of the neuronal populations induced by spike timing-dependent plasticity (STDP), CR neuromodulation utilizes the mutual interdependence between synaptic connectivity and dynamics of the neuronal networks in order to restore more physiological patterns of connectivity via desynchronization of neuronal activity. The very goal is to shift the neuronal population by stimulation from an abnormally coupled and synchronized state to a desynchronized regime with normalized synaptic connectivity, which significantly outlasts the stimulation cessation, so that long-lasting therapeutic effects can be achieved. PMID:25566174

Extreme hyponatraemia with intact neurological outcome in a young child with Addison’s disease

PubMed Central

Smith, John-Paul; Burren, Christine; Cherinet, Yonas

2011-01-01

The authors present the case of a 6-year-old boy with a good neurological outcome from extreme hyponatraemia caused by autoimmune hypoadrenalism. He presented with 1 week of reduced appetite, lethargy, vomiting and one episode of diarrhoea. He was described as being slightly unsteady on his feet. Clinically he was alert, although intermittently confused, with dry mucous membranes and sunken eyes. Serum sodium was 96 mmol/l with normal serum potassium and renal function. He was initially treated with 3% saline intravenously, and his serum sodium increased to 128 mmol/l by day 3. He developed slurred speech and ataxia on day 4, although MRI brain showed no evidence of pontine myelinosis, and the symptoms resolved over 1 week. A Synacthen test on day 10 confirmed a diagnosis of Addison’s disease and he was commenced on hydrocortisone and fludrocortisone replacement therapy. At 5 months follow-up there are no obvious neurological or developmental sequelae. PMID:22679234

Cognitive, emotional, and neural benefits of musical leisure activities in aging and neurological rehabilitation: A critical review.

PubMed

Särkämö, Teppo

2017-04-28

Music has the capacity to engage auditory, cognitive, motor, and emotional functions across cortical and subcortical brain regions and is relatively preserved in aging and dementia. Thus, music is a promising tool in the rehabilitation of aging-related neurological illnesses, such as stroke and Alzheimer disease. As the population ages and the incidence and prevalence of these illnesses rapidly increases, music-based interventions that are enjoyable and effective in the everyday care of the patients are needed. In addition to formal music therapy, musical leisure activities, such as music listening and singing, which patients can do on their own or with a caregiver, are a promising way to support psychological well-being during aging and in neurological rehabilitation. This review article provides an overview of current evidence on the cognitive, emotional, and neural effects of musical leisure activities both during normal aging and in the rehabilitation and care of stroke patients and people with dementia. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

ATP7A-related copper transport diseases-emerging concepts and future trends.

PubMed

Kaler, Stephen G

2011-01-01

This Review summarizes recent advances in understanding copper-transporting ATPase 1 (ATP7A), and examines the neurological phenotypes associated with dysfunction of this protein. Involvement of ATP7A in axonal outgrowth, synapse integrity and neuronal activation underscores the fundamental importance of copper metabolism to neurological function. Defects in ATP7A cause Menkes disease, an infantile-onset, lethal condition. Neonatal diagnosis and early treatment with copper injections enhance survival in patients with this disease, and can normalize clinical outcomes if mutant ATP7A molecules retain small amounts of residual activity. Gene replacement rescues a mouse model of Menkes disease, suggesting a potential therapeutic approach for patients with complete loss-of-function ATP7A mutations. Remarkably, a newly discovered ATP7A disorder-isolated distal motor neuropathy-has none of the characteristic clinical or biochemical abnormalities of Menkes disease or its milder allelic variant occipital horn syndrome (OHS), instead resembling Charcot-Marie-Tooth disease type 2. These findings indicate that ATP7A has a crucial but previously unappreciated role in motor neuron maintenance, and that the mechanism underlying ATP7A-related distal motor neuropathy is distinct from Menkes disease and OHS pathophysiology. Collectively, these insights refine our knowledge of the neurology of ATP7A-related copper transport diseases and pave the way for further progress in understanding ATP7A function.

Neurological Soft Signs in Indian Children with Specific Developmental Disorders of Scholastic Skills

ERIC Educational Resources Information Center

Sadhu, Raja; Mehta, Manju; Kalra, Veena; Sagar, Rajesh; Mongia, Monica

2008-01-01

Aim: To compare the occurrence of neurological soft signs (NSS) in children with specific developmental disorders of scholastic skills (SDDSS) and normal children. Methods: 36 cases of SDDSS were compared with 30 control children regarding sociodemographic and clinical variables and neurological soft signs. Results: Children with SDDSS had…

Neurological soft signs in persons with amnestic mild cognitive impairment and the relationships to neuropsychological functions.

PubMed

Li, Hui-Jie; Wang, Peng-Yun; Jiang, Yang; Chan, Raymond C K; Wang, Hua-Li; Li, Juan

2012-06-07

Neurological abnormalities have been reported in people with amnestic mild cognitive impairment (aMCI). The current study aimed to examine the prevalence of neurological soft signs (NSS) in this clinical group and to examine the relationship of NSS to other neuropsychological performances. Twenty-nine people with aMCI and 28 cognitively healthy elderly people were recruited for the present study. The NSS subscales (motor coordination, sensory integration, and disinhibition) of the Cambridge Neurological Inventory and a set of neuropsychological tests were administered to all the participants. People with aMCI exhibited significantly more motor coordination signs, disinhibition signs, and total NSS than normal controls. Correlation analysis showed that the motor coordination subscale score and total score of NSS were significantly inversely correlated with the combined Z-score of neuropsychological tests in aMCI group. These preliminary findings suggested that people with aMCI demonstrated a higher prevalence of NSS compared to healthy elderly people. Moreover, NSS was found to be inversely correlated with the neuropsychological performances in persons with aMCI. When taken together, these findings suggested that NSS may play a potential important role and serve as a tool to assist in the early detection of aMCI.

Paraspinal muscle impingement causing acute Brown-Sequard syndrome after posterior cervical decompression.

PubMed

Jost, Patrick W; Marawar, Satyajit; O'Leary, Patrick F

2010-04-01

A case report. To present a previously unreported cause of neurologic compromise after cervical spine surgery. Several different causes of postoperative neurologic deficit have been reported in the literature. The authors present a case of acute postoperative paralysis after posterior cervical decompression by a mechanism that has not yet been reported in the literature. A 54-year-old muscular, short-statured man underwent posterior cervical laminectomy from C3-C5 without instrumentation and left C5 foraminotomy. Within hours of leaving the operating room, he began to develop postoperative neurologic deficits in his extremities, which progressed to a classic Brown-Sequard syndrome. Magnetic resonance imaging revealed regional kyphosis and large swollen paraspinal muscles impinging on the spinal cord without epidural hematoma. Emergent operative re-exploration confirmed these findings; large, swollen paraspinal muscles, a functioning drain, and no hematoma were found. The patient was treated with immediate corticosteroids at the time of initial diagnosis, and emergent re-exploration and debulking of the paraspinal muscles. The patient had complete recovery of neurologic function to his preoperative baseline after the second procedure but required a third procedure in which anterior discectomy and fusion at C4-C5 was performed, which led to improvement of his preoperative symptoms. When performing posterior cervical decompression, surgeons must be aware of the potential for loss of normal lordosis and anterior displacement of paraspinal muscles against the spinal cord, especially in muscular patients.

Successful treatment of refractory seizures with phenobarbital, propofol, and medetomidine following congenital portosystemic shunt ligation in a dog.

PubMed

Heidenreich, Dorothee C; Giordano, Paola; Kirby, Barbara M

2016-11-01

To report a case of refractory seizures following congenital portosystemic shunt (CPSS) ligation that regained normal neurologic and hepatic function with novel treatment. Medical care included constant rate infusions (CRI) of propofol and medetomidine in conjunction with phenobarbital and supportive intensive care. A 2-year-old neutered male Bichon Frise was diagnosed with a single extrahepatic CPSS based on typical clinical signs, laboratory data, abdominal ultrasound, and computed tomographic angiography. Following initiation of standard medical treatment, a complete surgical ligation of the CPSS was performed. Recovery was uneventful until postligation neurologic dysfunction developed 54 hours after surgery. Seizures were controlled with phenobarbital (6 mg/kg IM q 12 h) and propofol CRI (0.3-0.6 mg/kg/min). Attempts to wean the dog from the propofol CRI resulted in recurrence of seizure activity until the addition of medetomidine CRI (0.016 μg/kg/min) 76 hours after initiation of drug-induced coma allowed gradual discontinuation of the propofol CRI. The dog regained full neurologic and hepatic function and had no further seizure activity apart from a small number of seizure episodes 5 and 22 months later. Adjustments in antiepileptic treatment resulted in no further neurologic dysfunction at 27-month follow-up. This report highlights the potential benefit of medetomidine CRI for treatment of postattenuation refractory seizures, which to date have proven impossible to predict and difficult to treat with high mortality rates and persistent neurological deficits in surviving animals. Neuroprotective, drug-sparing, and anti-hypertensive features of medetomidine might improve outcome in postligation refractory seizures. Further investigation and clinical application of medetomidine CRI may improve outcome in this complication of CPSS attenuation. © Veterinary Emergency and Critical Care Society 2015.

Proteomics of vitamin B12 processing.

PubMed

Hannibal, Luciana; DiBello, Patricia M; Jacobsen, Donald W

2013-03-01

The causes of cobalamin (B12, Cbl) deficiency are multifactorial. Whether nutritional due to poor dietary intake, or functional due to impairments in absorption or intracellular processing and trafficking events, the major symptoms of Cbl deficiency include megaloblastic anemia, neurological deterioration and in extreme cases, failure to thrive and death. The common biomarkers of Cbl deficiency (hyperhomocysteinemia and methylmalonic acidemia) are extremely valuable diagnostic indicators of the condition, but little is known about the changes that occur at the protein level. A mechanistic explanation bridging the physiological changes associated with functional B12 deficiency with its intracellular processers and carriers is lacking. In this article, we will cover the effects of B12 deficiency in a cblC-disrupted background (also referred to as MMACHC) as a model of functional Cbl deficiency. As will be shown, major protein changes involve the cytoskeleton, the neurological system as well as signaling and detoxification pathways. Supplementation of cultured MMACHC-mutant cells with hydroxocobalamin (HOCbl) failed to restore these variants to the normal phenotype, suggesting that a defective Cbl processing pathway produces irreversible changes at the protein level.

Grey matter abnormalities in children and adolescents with functional neurological symptom disorder.

PubMed

Kozlowska, Kasia; Griffiths, Kristi R; Foster, Sheryl L; Linton, James; Williams, Leanne M; Korgaonkar, Mayuresh S

2017-01-01

Functional neurological symptom disorder refers to the presence of neurological symptoms not explained by neurological disease. Although this disorder is presumed to reflect abnormal function of the brain, recent studies in adults show neuroanatomical abnormalities in brain structure . These structural brain abnormalities have been presumed to reflect long-term adaptations to the disorder, and it is unknown whether child and adolescent patients, with illness that is typically of shorter duration, show similar deficits or have normal brain structure. High-resolution, three-dimensional T1-weighted magnetic resonance images (MRIs) were acquired in 25 patients (aged 10-18 years) and 24 healthy controls. Structure was quantified in terms of grey matter volume using voxel-based morphometry. Post hoc, we examined whether regions of structural difference related to a measure of motor readiness to emotional signals and to clinical measures of illness duration, illness severity, and anxiety/depression. Patients showed greater volumes in the left supplementary motor area (SMA) and right superior temporal gyrus (STG) and dorsomedial prefrontal cortex (DMPFC) (corrected p < 0.05). Previous studies of adult patients have also reported alterations of the SMA. Greater SMA volumes correlated with faster reaction times in identifying emotions but not with clinical measures. The SMA, STG, and DMPFC are known to be involved in the perception of emotion and the modulation of motor responses. These larger volumes may reflect the early expression of an experience-dependent plasticity process associated with increased vigilance to others' emotional states and enhanced motor readiness to organize self-protectively in the context of the long-standing relational stress that is characteristic of this disorder.

Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome.

PubMed

Vootla, Vamshidhar R; Daniel, Myrta

2015-01-01

Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome.

[Eyelid retraction of neurologic origin: Report of three cases].

PubMed

Cartier R, Luis; Guzmán S, Jorge; Pasquali F, Renzo

2017-02-01

Eyelid retraction, has received limited attention and it has passively been interpreted as the result of an overactive levator palpebrae superioris muscle secondary to midbrain injury. However, eyelid retractions can occur in other neurological diseases, not directly related with the midbrain. We report three patients who developed eyelid retraction. One patient had a bilateral eyelid retraction, related with Creutzfeldt-Jakob disease (CJD). Another patient had a unilateral right eyelid retraction associated with a thalamic-mesencephalic infarct. The third patient had a bilateral pontine infarction on magnetic resonance imaging. In the patient with CJD, eyelid retraction did not subside. Among patients with infarctions, the retraction persisted after focal symptoms had subsided, showing an evolution that was apparently independent of the basic process. The analysis of these patients allows us to conclude that the pathogenesis of eyelid retraction includes supranuclear mechanisms in both the development and maintenance of the phenomenon. Unilateral or bilateral eyelid retraction does not alter the normal function of eyelid, which ever had normal close eye blink. In these reported cases, a hyperactivity of levator palpebrae superioris muscle was clinically ruled out.

Long-term neurodevelopmental outcome and exercise capacity after corrective surgery for tetralogy of Fallot or ventricular septal defect in infancy.

PubMed

Hövels-Gürich, Hedwig H; Konrad, Kerstin; Skorzenski, Daniela; Nacken, Claudia; Minkenberg, Ralf; Messmer, Bruno J; Seghaye, Marie-Christine

2006-03-01

The purpose of this prospective study was to assess whether neurodevelopmental status and exercise capacity of children 5 to 10 years after corrective surgery for tetralogy of Fallot or ventricular septal defect in infancy was different compared with normal children and influenced by the preoperative condition of hypoxemia or cardiac insufficiency. Forty unselected children, 20 with tetralogy of Fallot and hypoxemia and 20 with ventricular septal defect and cardiac insufficiency, operated on with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass at a mean age of 0.7 +/- 0.3 years (mean +/- SD), underwent, at mean age 7.4 +/- 1.6 years, standardized evaluation of neurologic status, gross motor function, intelligence, academic achievement, language, and exercise capacity. Results were compared between the groups and related to preoperative, perioperative, and postoperative status and management. Rate of mild neurologic dysfunction was increased compared with normal children, but not different between the groups. Exercise capacity and socioeconomic status were not different compared with normal children and between the groups. Compared with the normal population, motor function, formal intelligence, academic achievement, and expressive and receptive language were significantly reduced (p < 0.01 to p < 0.001) in the whole group and in the subgroups, except for normal intelligence in ventricular septal defect patients. Motor dysfunction was significantly higher in the Fallot group compared with the ventricular septal defect group (p < 0.01) and correlated with neurologic dysfunction, lower intelligence, and reduced expressive language (p < 0.05 each). Reduced New York Heart Association functional class was correlated with lower exercise capacity and longer duration of cardiopulmonary bypass (p < 0.05 each). Reduced socioeconomic status significantly influenced dysfunction in formal intelligence (p < 0.01) and academic achievement (p < 0.05). Preoperative risk factors such as prenatal hypoxia, perinatal asphyxia, and preterm birth, factors of perioperative management such as cardiac arrest, lowest nasopharyngeal temperature, and age at surgery, and postoperative risk factors as postoperative cardiocirculatory insufficiency and duration of mechanical ventilation were not different between the groups and had no influence on outcome. Degree of hypoxemia in Fallot patients and degree of cardiac insufficiency in ventricular septal defect patients did not influence the outcome within the subgroups. Children with preoperative hypoxemia in infancy are at higher risk for motor dysfunction than children with cardiac insufficiency. Corrective surgery in infancy for tetralogy of Fallot or ventricular septal defect with combined circulatory arrest and low flow bypass is associated with reduced neurodevelopmental outcome, but not with reduced exercise capacity in childhood. In our experience, the general risk of long-term neurodevelopmental impairment is related to unfavorable effects of the global perioperative management. Socioeconomic status influences cognitive capabilities.

Few CT Scan Abnormalities Found Even in Neurologically Impaired Learning Disabled Children.

ERIC Educational Resources Information Center

Denckla, Martha Bridge; And Others

1985-01-01

Most of 32 learning disabled children (seven to 14 years old) with neurological lateralization characteristics marked by right and left hemispheres had a normal CT (computerized tomography) scan. (CL)

Cpd-1 Null Mice Display a Subtle Neurological Phenotype

PubMed Central

Kular, Rupinder K.; Gogliotti, Rocky G.; Opal, Puneet

2010-01-01

Background CPD1 (also known as ANP32-E) belongs to a family of evolutionarily conserved acidic proteins with leucine rich repeats implicated in a variety of cellular processes regulating gene expression, vesicular trafficking, intracellular signaling and apoptosis. Because of its spatiotemporal expression pattern, CPD1 has been proposed to play an important role in brain morphogenesis and synaptic development. Methodology/Principal Findings We have generated CPD1 knock-out mice that we have subsequently characterized. These mice are viable and fertile. However, they display a subtle neurological clasping phenotype and mild motor deficits. Conclusions/Significance CPD1 is not essential for normal development; however, it appears to play a role in the regulation of fine motor functions. The minimal phenotype suggests compensatory biological mechanisms. PMID:20844742

Cerebral fat embolism syndrome after long bone fracture due to gunshot injury

PubMed Central

Duran, Latif; Kayhan, Servet; Kati, Celal; Akdemir, Hizir Ufuk; Balci, Kemal; Yavuz, Yucel

2014-01-01

Cerebral fat embolism syndrome is a lethal complication of long-bone fractures and clinically manifasted with respiratory distress, altered mental status, and petechial rash. We presented a 20-year-old male admitted with gun-shot wounds to his left leg. Twenty-four hours after the event, he had generalized tonic clonic seizures, decorticate posture and a Glascow Coma Scale of seven with localization of painful stimuli. Subsequent magnetic resonance imaging of the brain showed a star-field pattern defining multiple lesions of restricted diffusion. On a 4-week follow-up, he had returned to normal neurological function. Despite the severity of the neurological condition upon initial presentation, the case cerebral fat embolism illustrates that, cerebral dysfunction associated with cerebral fat embolism illustrates reversible. PMID:24701067

Anterior temporal lobes mediate semantic representation: Mimicking semantic dementia by using rTMS in normal participants

PubMed Central

Pobric, Gorana; Jefferies, Elizabeth; Ralph, Matthew A. Lambon

2007-01-01

Studies of semantic dementia and PET neuroimaging investigations suggest that the anterior temporal lobes (ATL) are a critical substrate for semantic representation. In stark contrast, classical neurological models of comprehension do not include ATL, and likewise functional MRI studies often fail to show activations in the ATL, reinforcing the classical view. Using a novel application of low-frequency, repetitive transcranial magnetic stimulation (rTMS) over the ATL, we demonstrate that the behavioral pattern of semantic dementia can be mirrored in neurologically intact participants: Specifically, we show that temporary disruption to neural processing in the ATL produces a selective semantic impairment leading to significant slowing in both picture naming and word comprehension but not to other equally demanding, nonsemantic cognitive tasks. PMID:18056637

Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking.

PubMed

Metzler, Martina; Li, Bo; Gan, Lu; Georgiou, John; Gutekunst, Claire-Anne; Wang, Yushan; Torre, Enrique; Devon, Rebecca S; Oh, Rosemary; Legendre-Guillemin, Valerie; Rich, Mark; Alvarez, Christine; Gertsenstein, Marina; McPherson, Peter S; Nagy, Andras; Wang, Yu Tian; Roder, John C; Raymond, Lynn A; Hayden, Michael R

2003-07-01

Huntingtin interacting protein 1 (HIP1) is a recently identified component of clathrin-coated vesicles that plays a role in clathrin-mediated endocytosis. To explore the normal function of HIP1 in vivo, we created mice with targeted mutation in the HIP1 gene (HIP1(-/-)). HIP1(-/-) mice develop a neurological phenotype by 3 months of age manifest with a failure to thrive, tremor and a gait ataxia secondary to a rigid thoracolumbar kyphosis accompanied by decreased assembly of endocytic protein complexes on liposomal membranes. In primary hippocampal neurons, HIP1 colocalizes with GluR1-containing AMPA receptors and becomes concentrated in cell bodies following AMPA stimulation. Moreover, a profound dose-dependent defect in clathrin-mediated internalization of GluR1-containing AMPA receptors was observed in neurons from HIP1(-/-) mice. Together, these data provide strong evidence that HIP1 regulates AMPA receptor trafficking in the central nervous system through its function in clathrin-mediated endocytosis.

Error-related processing following severe traumatic brain injury: An event-related functional magnetic resonance imaging (fMRI) study

PubMed Central

Sozda, Christopher N.; Larson, Michael J.; Kaufman, David A.S.; Schmalfuss, Ilona M.; Perlstein, William M.

2011-01-01

Continuous monitoring of one’s performance is invaluable for guiding behavior towards successful goal attainment by identifying deficits and strategically adjusting responses when performance is inadequate. In the present study, we exploited the advantages of event-related functional magnetic resonance imaging (fMRI) to examine brain activity associated with error-related processing after severe traumatic brain injury (sTBI). fMRI and behavioral data were acquired while 10 sTBI participants and 12 neurologically-healthy controls performed a task-switching cued-Stroop task. fMRI data were analyzed using a random-effects whole-brain voxel-wise general linear model and planned linear contrasts. Behaviorally, sTBI patients showed greater error-rate interference than neurologically-normal controls. fMRI data revealed that, compared to controls, sTBI patients showed greater magnitude error-related activation in the anterior cingulate cortex (ACC) and an increase in the overall spatial extent of error-related activation across cortical and subcortical regions. Implications for future research and potential limitations in conducting fMRI research in neurologically-impaired populations are discussed, as well as some potential benefits of employing multimodal imaging (e.g., fMRI and event-related potentials) of cognitive control processes in TBI. PMID:21756946

Error-related processing following severe traumatic brain injury: an event-related functional magnetic resonance imaging (fMRI) study.

PubMed

Sozda, Christopher N; Larson, Michael J; Kaufman, David A S; Schmalfuss, Ilona M; Perlstein, William M

2011-10-01

Continuous monitoring of one's performance is invaluable for guiding behavior towards successful goal attainment by identifying deficits and strategically adjusting responses when performance is inadequate. In the present study, we exploited the advantages of event-related functional magnetic resonance imaging (fMRI) to examine brain activity associated with error-related processing after severe traumatic brain injury (sTBI). fMRI and behavioral data were acquired while 10 sTBI participants and 12 neurologically-healthy controls performed a task-switching cued-Stroop task. fMRI data were analyzed using a random-effects whole-brain voxel-wise general linear model and planned linear contrasts. Behaviorally, sTBI patients showed greater error-rate interference than neurologically-normal controls. fMRI data revealed that, compared to controls, sTBI patients showed greater magnitude error-related activation in the anterior cingulate cortex (ACC) and an increase in the overall spatial extent of error-related activation across cortical and subcortical regions. Implications for future research and potential limitations in conducting fMRI research in neurologically-impaired populations are discussed, as well as some potential benefits of employing multimodal imaging (e.g., fMRI and event-related potentials) of cognitive control processes in TBI. Copyright © 2011 Elsevier B.V. All rights reserved.

Neurocognitive functions and brain atrophy after proven neuroborreliosis: a case-control study.

PubMed

Schmidt, Holger; Djukic, Marija; Jung, Klaus; Holzgraefe, Manfred; Dechent, Peter; von Steinbüchel, Nicole; Blocher, Joachim; Eiffert, Helmut; Schmidt-Samoa, Carsten

2015-08-19

Patients often report neurocognitive difficulties after neuroborreliosis (NB). The frequency and extent of cognitive problems in European patients have been studied incompletely. Sixty patients received a neurological and neuropsychological work-up 6 months or longer after treatment for proven NB. Quality of life, psychiatric symptom load, and brain atrophy were measured. All results were compared with a group of 30 healthy control persons adapted for age, gender and education being serologically negative for Borrelia burgdorferi senso latu. A cognitive sum score and a global sum score including cognitive, psychological results and quality of life data was calculated for both groups. Patients after NB showed a lower (i.e. more impaired) score on the Scripps Neurological rating scale (SNRS), but the observed neurological deficits were generally mild (mean ± SD: 97.1 ± 4.7 vs. 99.1 ± 2.4, p = 0.02). The mean neuropsychological domain results of the NB group were all within the normal range. However, a lower performance was found for the frontal executive function z-values (mean ± SD -0.29 ± 0.60 vs. 0.09 ± 0.60; p = 0.0059) of NB patients. Comparing the global sum score (mean ± SD 11.3 ± 4.2 NB vs. 14.3 ± 2.9 control , p = 0.001) and the cognitive sum score of the NB group with those of the control group (mean ± SD -0.15 ± 0.42 NB vs. 0.08 ± 0.31 control , p = 0.0079), both differences were statistically different. The frequencies of impaired global sum scores and those of the pathological cognitive sum scores (p = 0.07) did not differ statistically. No significant differences were found for health-related quality of life (hrQoL), sleep, psychiatric symptom load, or brain atrophy. The mean cognitive functions of patients after proven NB were in the normal range. However, we were able to demonstrate a lower performance for the domain of frontal executive functions, for the mean cognitive sum score and the global sum score as a sign of subtle but measurable sequelae of neuroborreliosis. Brain atrophy is not a common consequence of neuroborreliosis.

Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke

PubMed Central

Zavaglia, Melissa; Forkert, Nils D.; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C.

2015-01-01

Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a ‘map of stroke’. PMID:26448908

Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke.

PubMed

Zavaglia, Melissa; Forkert, Nils D; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C

2015-01-01

Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a 'map of stroke'.

Personality dimensions of people who suffer from visual stress.

PubMed

Hollis, J; Allen, P M; Fleischmann, D; Aulak, R

2007-11-01

Personality dimensions of participants who suffer from visual stress were compared with those of normal participants using the Eysenck Personality Inventory. Extraversion-Introversion scores showed no significant differences between the participants who suffered visual stress and those who were classified as normal. By contrast, significant differences were found between the normal participants and those with visual stress in respect of Neuroticism-Stability. These differences accord with Eysenck's personality theory which states that those who score highly on the neuroticism scale do so because they have a neurological system with a low threshold such that their neurological system is easily activated by external stimuli. The findings also relate directly to the theory of visual stress proposed by Wilkins which postulates that visual stress results from an excess of neural activity. The data may indicate that the excess activity is likely to be localised at particular neurological regions or neural processes.

Hyperintense White Matter Lesions in 50 High-Altitude Pilots with Neurologic Decompression Sickness

DTIC Science & Technology

2012-12-01

Environ Med 2004 ; 75 : 969 – 72 . 4. Bartzokis G, Tishler TA, Shin IS, Lu PH, Cummings JL . Brain ferritin iron as a risk factor for...Coyle T, Lancaster J, et al. Can structural MRI indices of cerebral integrity track cognitive trends in executive control function during normal...Digital brain atlases . Trends Neurosci 1995 ; 18 : 210 – 1 . 28. Miura K, Soyama Y, Morikawa Y, Nishijo M, Nakanishi Y, et al

Diminished brain resilience syndrome: A modern day neurological pathology of increased susceptibility to mild brain trauma, concussion, and downstream neurodegeneration.

PubMed

Morley, Wendy A; Seneff, Stephanie

2014-01-01

The number of sports-related concussions has been steadily rising in recent years. Diminished brain resilience syndrome is a term coined by the lead author to describe a particular physiological state of nutrient functional deficiency and disrupted homeostatic mechanisms leading to increased susceptibility to previously considered innocuous concussion. We discuss how modern day environmental toxicant exposure, along with major changes in our food supply and lifestyle practices, profoundly reduce the bioavailability of neuro-critical nutrients such that the normal processes of homeostatic balance and resilience are no longer functional. Their diminished capacity triggers physiological and biochemical 'work around' processes that result in undesirable downstream consequences. Exposure to certain environmental chemicals, particularly glyphosate, the active ingredient in the herbicide, Roundup(®), may disrupt the body's innate switching mechanism, which normally turns off the immune response to brain injury once danger has been removed. Deficiencies in serotonin, due to disruption of the shikimate pathway, may lead to impaired melatonin supply, which reduces the resiliency of the brain through reduced antioxidant capacity and alterations in the cerebrospinal fluid, reducing critical protective buffering mechanisms in impact trauma. Depletion of certain rare minerals, overuse of sunscreen and/or overprotection from sun exposure, as well as overindulgence in heavily processed, nutrient deficient foods, further compromise the brain's resilience. Modifications to lifestyle practices, if widely implemented, could significantly reduce this trend of neurological damage.

Use of the Progressive Figures Test in evaluating brain-damaged children, children with academic problems, and normal controls.

PubMed

Reitan, Ralph M; Wolfson, Deborah

2004-03-01

This study explores the use of the Progressive Figures Test as an instrument for broad initial screening of children in the 6- through 8-year age range with respect to the possible need for more definitive neuropsychological evaluation. Considering earlier results obtained in comparison of brain-damaged and control children [Clinical Neuropsychology: Current Applications, Hemisphere Publishing Corp., Washington, DC, 1974, p. 53; Proceedings of the Conference on Minimal Brain Dysfunction, New York Academy of Sciences, New York, 1973, p. 65], the Progressive Figures Test seemed potentially useful as a first step in determining whether a comprehensive neuropsychological evaluation is indicated. In this investigation, three groups were studied: (1) children with definitive evidence of brain damage or disease who, when compared with normal controls, help to establish the limits of neuropsychological functioning, (2) a group of children who had normal neurological examinations but also had academic problems of significant concern to both parents and teachers, and (3) a normal control group. Statistically significant differences were present in comparing each pair of groups, with the brain-damaged children performing most poorly and the controls performing best. Score distributions for the three groups make it possible to identify a score-range that represented a borderline or "gray" area and to suggest a cutting score that identified children whose academic problems might have a neurological basis and for whom additional neuropsychological evaluation appeared to be indicated.

Immune response to Sarcocystis neurona infection in naturally infected horses with equine protozoal myeloencephalitis.

PubMed

Yang, Jibing; Ellison, Siobhan; Gogal, Robert; Norton, Heather; Lindsay, David S; Andrews, Frank; Ward, Daniel; Witonsky, Sharon

2006-06-15

Equine protozoal myeloencephalitis (EPM) is one of the most common neurologic diseases of horses in the United States. The primary etiologic agent is Sarcocystis neurona. Currently, there is limited knowledge regarding the protective or pathophysiologic immune response to S. neurona infection or the subsequent development of EPM. The objectives of this study were to determine whether S. neurona infected horses with clinical signs of EPM had altered or suppressed immune responses compared to neurologically normal horses and if blood sample storage would influence these findings. Twenty clinically normal horses and 22 horses with EPM, diagnosed by the presence of S. neurona specific antibodies in the serum and/or cerebrospinal (CSF) and clinical signs, were evaluated for differences in the immune cell subsets and function. Our results demonstrated that naturally infected horses had significantly (P<0.05) higher percentages of CD4 T-lymphocytes and neutrophils (PMN) in separated peripheral blood leukocytes than clinically normal horses. Leukocytes from naturally infected EPM horses had significantly lower proliferation responses, as measured by thymidine incorporation, to a non-antigen specific mitogen than did clinically normal horses (P<0.05). Currently, studies are in progress to determine the role of CD4 T cells in disease and protection against S. neurona in horses, as well as to determine the mechanism associated with suppressed in vitro proliferation responses. Finally, overnight storage of blood samples appears to alter T lymphocyte phenotypes and viability among leukocytes.

Prevalence and Burden of Gait Disorders in Elderly Men and Women Aged 60–97 Years: A Population-Based Study

PubMed Central

Mahlknecht, Philipp; Kiechl, Stefan; Bloem, Bastiaan R.; Willeit, Johann; Scherfler, Christoph; Gasperi, Arno; Rungger, Gregorio; Poewe, Werner; Seppi, Klaus

2013-01-01

Background Although gait disorders are common in the elderly, the prevalence and overall burden of these disorders in the general community is not well defined. Methods In a cross-sectional investigation of the population-based Bruneck Study cohort, 488 community-residing elderly aged 60–97 years underwent a thorough neurological assessment including a standardized gait evaluation. Gait disorders were classified according to an accepted scheme and their associations to falls, neuropsychological measures, and quality of life were explored. Results Overall, 32.2% (95% confidence interval [CI] 28.2%–36.4%) of participants presented with impaired gait. Prevalence increased with age (p<0.001), but 38.3% (95%CI 30.1%–47.3%) of the subjects aged 80 years or older still had a normally preserved gait. A total of 24.0% (95%CI 20.4%–28.0%) manifested neurological gait disorders, 17.4% (14.3%–21.0%) non-neurological gait problems, and 9.2% (6.9%–12.1%) a combination of both. While there was no association of neurological gait disorders with gender, non-neurological gait disorders were more frequent in women (p = 0.012). Within the group of neurological gait disorders 69.2% (95%CI 60.3%–76.9%) had a single distinct entity and 30.8% (23.1%–39.7%) had multiple neurological causes for gait impairment. Gait disorders had a significant negative impact on quantitative gait measures, but only neurological gait disorders were associated with recurrent falls (odds ratio 3.3; 95%CI 1.4–7.5; p = 0.005 for single and 7.1; 2.7–18.7; p<0.001 for multiple neurological gait disorders). Finally, we detected a significant association of gait disorders, in particular neurological gait disorders, with depressed mood, cognitive dysfunction, and compromised quality of life. Conclusions Gait disorders are common in the general elderly population and are associated with reduced mobility. Neurological gait disorders in particular are associated with recurrent falls, lower cognitive function, depressed mood, and diminished quality of life. PMID:23894511

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.

Neurocognitive profile of a young adolescent with DK phocomelia/von Voss phocomelia/von Voss Cherstvoy syndrome.

PubMed

Antonini, Tanya N; Van Horn Kerne, Valerie; Axelrad, Marni E; Karaviti, Lefkothea P; Schwartz, David D

2015-07-01

DK phocomelia/von Voss Cherstvoy syndrome is a rare condition characterized by upper limb and urogenital abnormalities and various brain anomalies. Previously reported cases have noted significant developmental delays, although no formal testing of cognitive abilities has been reported. In this paper we describe results from a comprehensive neuropsychological evaluation of a 12-year-old male with DK phocomelia syndrome. Test findings indicated mild impairment in intellectual functioning, with more significant impairment in adaptive skills and academic achievement. The neuropsychological profile converged with neurological findings, showing a distinct pattern of strengths and weaknesses that suggests functional compromise of posterior brain regions with relatively well-preserved functioning of more anterior regions. Specifically, impairments were evident in perceptual reasoning, visual perception, and visuomotor integration, whereas normal or near normal functioning was evident in memory, receptive language, social cognition, attention, and most aspects of executive functioning. To our knowledge this is the first report to describe the neurocognitive profile of an individual with DK phocomelia syndrome. © 2015 Wiley Periodicals, Inc.

Effect of Intrafix® SafeSet infusion apparatus on phlebitis in a neurological intensive care unit: a case-control study.

PubMed

Liu, F; Chen, D; Liao, Y; Diao, L; Liu, Y; Wu, M; Xue, X; You, C; Kang, Y

2012-01-01

To investigate the effect of the Intrafix(®) SafeSet infusion apparatus on the incidence of phlebitis in patients being intravenously infused in a neurological intensive care unit (ICU). Patients aged > 12 years, with no history of diabetes mellitus and no existing phlebitis, requiring a daily peripheral intravenous infusion of ≥ 8 h with the total period lasting ≥ 3 days, were enrolled. Infusions were performed using the Intrafix(®) SafeSet or normal infusion apparatus. Incidence of phlebitis (scored according to the Infusion Nursing Standards of Practice of the American Infusion Nurses Society) was analysed. Patients (n = 1545) were allocated to Intrafix(®) SafeSet (n = 709) or normal infusion (n = 836) groups, matched for age, gender and preliminary diagnosis. Incidence of phlebitis was significantly higher using normal infusion apparatus compared with the Intrafix(®) SafeSet (23.4% versus 17.9%, respectively). Intrafix(®) SafeSet infusion apparatus significantly reduced the incidence of phlebitis in patients in the neurological ICU, compared with normal infusion apparatus, and may be suitable for use in routine clinical practice.

Ischemia may be the primary cause of the neurologic deficits in classic migraine

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

Skyhoj Olsen, T.; Friberg, L.; Lassen, N.A.

1987-02-01

This study investigates whether the cerebral blood flow reduction occurring in attacks of classic migraine is sufficient to cause neurologic deficits. Regional cerebral blood flow measured with the xenon 133 intracarotid injection technique was analyzed in 11 patients in whom a low-flow area developed during attacks of classic migraine. When measured with this technique, regional cerebral blood flow in focal low-flow areas will be overestimated because of the effect of scattered radiation (Compton scatter) on the recordings. In this study, this effect was particularly taken into account when evaluating the degree of blood flow reduction. During attacks of classic migraine,more » cerebral blood flow reductions averaging 52% were observed focally in the 11 patients. Cerebral blood flow levels known to be insufficient for normal cortical function (less than 16 to 23 mL/100 g/min) were measured in seven patients during the attacks. This was probably also the case in the remaining four patients, but the effect of scattered radiation made a reliable evaluation of blood flow impossible. It is concluded that the blood flow reduction that occurs during attacks of classic migraine is sufficient to cause ischemia and neurologic deficits. Hence, this study suggests a vascular origin of the prodromal neurologic deficits that may accompany attacks of classic migraine.« less

Prognostic significance of electrophysiological tests for facial nerve outcome in vestibular schwannoma surgery.

PubMed

van Dinther, J J S; Van Rompaey, V; Somers, T; Zarowski, A; Offeciers, F E

2011-01-01

To assess the prognostic significance of pre-operative electrophysiological tests for facial nerve outcome in vestibular schwannoma surgery. Retrospective study design in a tertiary referral neurology unit. We studied a total of 123 patients with unilateral vestibular schwannoma who underwent microsurgical removal of the lesion. Nine patients were excluded because they had clinically abnormal pre-operative facial function. Pre-operative electrophysiological facial nerve function testing (EPhT) was performed. Short-term (1 month) and long-term (1 year) post-operative clinical facial nerve function were assessed. When pre-operative facial nerve function, evaluated by EPhT, was normal, the outcome from clinical follow-up at 1-month post-operatively was excellent in 78% (i.e. HB I-II) of patients, moderate in 11% (i.e. HB III-IV), and bad in 11% (i.e. HB V-VI). After 1 year, 86% had excellent outcomes, 13% had moderate outcomes, and 1% had bad outcomes. Of all patients with normal clinical facial nerve function, 22% had an abnormal EPhT result and 78% had a normal result. No statistically significant differences could be observed in short-term and long-term post-operative facial function between the groups. In this study, electrophysiological tests were not able to predict facial nerve outcome after vestibular schwannoma surgery. Tumour size remains the best pre-operative prognostic indicator of facial nerve function outcome, i.e. a better outcome in smaller lesions.

[Intracranial pressure monitoring and CSF dynamics in patients with neurological disorders: indications and practical considerations].

PubMed

Poca, M; Sahuquillo, J

2001-01-01

The study of cerebrospinal fluid (CSF) dynamics is central to the diagnosis of adult chronic hydrocephalus (ACH). At present, many neurology and neurosurgery departments use one or more tests to guide diagnosis of this syndrome and to predict patient response to shunting. In specialised centres, the study of CSF dynamics is combined with continuous intracranial pressure (ICP) monitoring. Determination of several variables of CSF dynamics and definitions of qualitative and quantitative characteristics of ICP can be used to establish whether the hydrocephalus is active, compensated or arrested. CSF dynamics and ICP monitoring can also be used to check the correct functioning of the shunt and can be of use in the clinical management of patients with pseudotumor cerebri. Moreover, ICP monitoring is used to guide the treatment of several acute neurological processes. The aim of this review is to describe the fundamentals of CSF dynamics studies and the bases of continuous ICP monitoring. The advantages and disadvantages of several hydrodynamic tests that can be performed by lumbar puncture, as well as the normal and abnormal characteristics of an ICP recording, are discussed.

Magnetic Resonance Guided Focused Ultrasound Surgery: Part 2 – A Review of Current and Future Applications

PubMed Central

Medel, Ricky; Monteith, Stephen J.; Elias, W. Jeffrey; Eames, Matthew; Snell, John; Sheehan, Jason P.; Wintermark, Max; Jolesz, Ferenc A.; Kassell, Neal F.

2014-01-01

Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) represents a novel combination of technologies that is actively being realized as a non-invasive therapeutic tool for a myriad of conditions. These applications are reviewed with a focus on neurological utilization. A combined search of Pubmed and Medline was performed to identify the key events and current status of MRgFUS, with a focus on neurological applications. MRgFUS signifies a potentially ideal device for the treatment of neurological diseases. As it is nearly real-time, it allows monitored provision of treatment location and energy deposition, is noninvasive, thereby limiting or eliminating disruption of normal tissue, provides focal delivery of therapeutic agents, enhances radiation delivery, and permits modulation of neural function. Multiple clinical applications are currently in clinical use and many more are under active preclinical investigation. The therapeutic potential of MRgFUS is expanding rapidly. Although clinically in its infancy, preclinical and early phase I clinical trials in neurosurgery suggest a promising future for MRgFUS. Further investigation is necessary to define its true potential and impact. PMID:22791029

(Putative) Sex differences in neuroimmune modulation of memory

PubMed Central

Tronson, Natalie C.; Collette, Katie M.

2016-01-01

The neuroimmune system is significantly sexually dimorphic, with sex differences evident in the number and activation states of microglia, in the activation of astrocytes, and in cytokine release and function. Neuroimmune cells and signaling are now recognized as critical for many neural functions throughout the lifespan, including synaptic plasticity and memory function. Here we address the question of how cytokines, astrocytes, and microglia contribute to memory, and specifically how neuroimmune modulation of memory differentially affects males and females. Understanding sex differences in both normal memory processes and dysregulation of memory in psychiatric and neurological disorders is critical for developing treatment and preventive strategies for memory disorders that are effective for both men and women. PMID:27870428

Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome

PubMed Central

Vootla, Vamshidhar R.; Daniel, Myrta

2015-01-01

Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome. PMID:26351414

Cognitive and motor function of neurologically impaired extremely low birth weight children.

PubMed

Bernardo, Janine; Friedman, Harriet; Minich, Nori; Taylor, H Gerry; Wilson-Costello, Deanne; Hack, Maureen

2015-01-01

Rates of neurological impairment among extremely low birth weight children (ELBW [<1 kg]) have decreased since 2000; however, their functioning is unexamined. To compare motor and cognitive functioning of ELBW children with neurological impairment, including cerebral palsy and severe hypotonia/hypertonia, between two periods: 1990 to 1999 (n=83) and 2000 to 2005 (n=34). Measures of function at 20 months corrected age included the Mental and Psychomotor Developmental Indexes of the Bayley Scales of Infant Development and the Gross Motor Functional Classification System as primary outcomes and individual motor function items as secondary outcomes. Analysis failed to reveal significant differences for the primary outcomes, although during 2000 to 2005, sitting significantly improved in children with neurological impairment (P=0.003). Decreases in rates of neurological impairment among ELBW children have been accompanied by a suggestion of improved motor function, although cognitive function has not changed.

The role of cerebral hyperperfusion in postoperative neurologic dysfunction after left ventricular assist device implantation for end-stage heart failure.

PubMed

Lietz, Katherine; Brown, Kevin; Ali, Syed S; Colvin-Adams, Monica; Boyle, Andrew J; Anderson, David; Weinberg, Alan D; Miller, Leslie W; Park, Soon; John, Ranjit; Lazar, Ronald M

2009-04-01

Cerebral hyperperfusion is a life-threatening syndrome that can occur in patients with chronically hypoperfused cerebral vasculature whose normal cerebral circulation was re-established after carotid endarterectomy or angioplasty. We sought to determine whether the abrupt restoration of perfusion to the brain after left ventricular assist device (LVAD) implantation produced similar syndromes. We studied the role of increased systemic flow after LVAD implantation on neurologic dysfunction in 69 consecutive HeartMate XVE LVAD (Thoratec, Pleasanton, Calif) recipients from October 2001 through June 2006. Neurologic dysfunction was defined as postoperative permanent or transient central change in neurologic status, including confusion, focal neurologic deficits, visual changes, seizures, or coma for more than 24 hours within 30 days after LVAD implantation. We found that 19 (27.5%) patients had neurologic dysfunction, including encephalopathy (n = 11), coma (n = 3), and other complications (n = 5). The multivariate analysis showed that an increase in cardiac index from the preoperative baseline value (relative risk, 1.33 per 25% cardiac index increase; P = .01) and a previous coronary bypass operation (relative risk, 4.53; P = .02) were the only independent predictors of neurologic dysfunction. Reduction of left ventricular assist device flow in 16 of the 19 symptomatic patients led to improvement of symptoms in 14 (87%) patients. Our findings showed that normal flow might overwhelm cerebral autoregulation in patients with severe heart failure, suggesting that cerebral hyperperfusion is possible in recipients of mechanical circulatory support with neurologic dysfunction.

Hydrogen-rich saline attenuates spinal cord hemisection-induced testicular injury in rats.

PubMed

Ge, Li; Wei, Li-Hua; Du, Chang-Qing; Song, Guo-Hua; Xue, Ya-Zhuo; Shi, Hao-Shen; Yang, Ming; Yin, Xin-Xin; Li, Run-Ting; Wang, Xue-Er; Wang, Zhen; Song, Wen-Gang

2017-06-27

To study how hydrogen-rich saline (HS) promotes the recovery of testicular biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a right hemisection was performed at the T11-T12 of the spinal cord in Wistar rats. Animals were divided into four groups: normal group; vehicle group: sham-operated rats administered saline; hSCI group: subjected to hSCI and administered saline; HRST group: subjected to hSCI and administered HS. Hind limb neurological function, testis index, testicular morphology, mean seminiferous tubular diameter (MSTD) and seminiferous epithelial thickness (MSET), the expression of heme oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1), cell ultrastructure, and apoptosis of spermatogenic cells were studied. The results indicated that hSCI significantly decreased the hind limb neurological function, testis index, MSTD, and MSET, and induced severe testicular morphological injury. The MFN-2 level was decreased, and HO-1 and HMGB-1 were overexpressed in testicular tissues. In addition, hSCI accelerated the apoptosis of spermatogenic cells and the ultrastructural damage of cells in the hypophysis and testis. After HS administration, all these parameters were considerably improved, and the characteristics of hSCI testes were similar to those of normal control testes. Taken together, HS administration can promote the recovery of testicular biological function by anti-oxidative, anti-inflammatory, and anti-apoptotic action. More importantly, HS can inhibit the hSCI-induced ultrastructural changes in gonadotrophs, ameliorate the abnormal regulation of the hypothalamic-pituitary-testis axis, and thereby promote the recovery of testicular injury. HS administration also inhibited the hSCI-induced ultrastructural changes in testicular spermatogenic cells, Sertoli cells and interstitial cells.

Hydrogen-rich saline attenuates spinal cord hemisection-induced testicular injury in rats

PubMed Central

Ge, Li; Wei, Li-Hua; Du, Chang-Qing; Song, Guo-Hua; Xue, Ya-Zhuo; Shi, Hao-Shen; Yang, Ming; Yin, Xin-Xin; Li, Run-Ting; Wang, Xue-er; Wang, Zhen; Song, Wen-Gang

2017-01-01

To study how hydrogen-rich saline (HS) promotes the recovery of testicular biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a right hemisection was performed at the T11–T12 of the spinal cord in Wistar rats. Animals were divided into four groups: normal group; vehicle group: sham-operated rats administered saline; hSCI group: subjected to hSCI and administered saline; HRST group: subjected to hSCI and administered HS. Hind limb neurological function, testis index, testicular morphology, mean seminiferous tubular diameter (MSTD) and seminiferous epithelial thickness (MSET), the expression of heme oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1), cell ultrastructure, and apoptosis of spermatogenic cells were studied. The results indicated that hSCI significantly decreased the hind limb neurological function, testis index, MSTD, and MSET, and induced severe testicular morphological injury. The MFN-2 level was decreased, and HO-1 and HMGB-1 were overexpressed in testicular tissues. In addition, hSCI accelerated the apoptosis of spermatogenic cells and the ultrastructural damage of cells in the hypophysis and testis. After HS administration, all these parameters were considerably improved, and the characteristics of hSCI testes were similar to those of normal control testes. Taken together, HS administration can promote the recovery of testicular biological function by anti-oxidative, anti-inflammatory, and anti-apoptotic action. More importantly, HS can inhibit the hSCI-induced ultrastructural changes in gonadotrophs, ameliorate the abnormal regulation of the hypothalamic-pituitary-testis axis, and thereby promote the recovery of testicular injury. HS administration also inhibited the hSCI-induced ultrastructural changes in testicular spermatogenic cells, Sertoli cells and interstitial cells. PMID:28404953

Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function

PubMed Central

Mak, Angel C. Y.; Pullinger, Clive R.; Tang, Ling Fung; Wong, Jinny S.; Deo, Rahul C.; Schwarz, Jean-Marc; Gugliucci, Alejandro; Movsesyan, Irina; Ishida, Brian Y.; Chu, Catherine; Poon, Annie; Kim, Phillip; Stock, Eveline O.; Schaefer, Ernst J.; Asztalos, Bela F.; Castellano, Joseph M.; Wyss-Coray, Tony; Duncan, Jacque L.; Miller, Bruce L.; Kane, John P.; Kwok, Pui-Yan; Malloy, Mary J.

2016-01-01

IMPORTANCE The identification of a patient with a rare form of severe dysbetalipoproteinemia allowed the study of the consequences of total absence of apolipoprotein E (apoE). OBJECTIVES To discover the molecular basis of this rare disorder and to determine the effects of complete absence of apoE on neurocognitive and visual function and on lipoprotein metabolism. DESIGN, SETTING, AND PARTICIPANTS Whole-exome sequencing was performed on the patient’s DNA. He underwent detailed neurological and visual function testing and lipoprotein analysis. Lipoprotein analysis was also performed in the Cardiovascular Research Institute, University of California, San Francisco, on blood samples from the proband’s mother, wife, 2 daughters, and normolipidemic control participants. MAIN OUTCOME MEASURES Whole-exome sequencing, lipoprotein analysis, and neurocognitive function. RESULTS The patient was homozygous for an ablative APOE frameshift mutation (c.291del, p.E97fs). No other mutations likely to contribute to the phenotype were discovered, with the possible exception of two, in ABCC2 (p.I670T) and LIPC (p.G137R). Despite complete absence of apoE, he had normal vision, exhibited normal cognitive, neurological, and retinal function, had normal findings on brain magnetic resonance imaging, and had normal cerebrospinal fluid levels of β-amyloid and tau proteins. He had no significant symptoms of cardiovascular disease except a suggestion of myocardial ischemia on treadmill testing and mild atherosclerosis noted on carotid ultrasonography. He had exceptionally high cholesterol content (760 mg/dL; to convert to millimoles per liter, multiply by 0.0259) and a high cholesterol to triglycerides ratio (1.52) in very low-density lipoproteins with elevated levels of small-diameter high-density lipoproteins, including high levels of prebeta-1 high-density lipoprotein. Intermediate-density lipoproteins, low-density lipoproteins, and very low-density lipoproteins contained elevated apoA-I and apoA-IV levels. The patient’s apoC-III and apoC-IV levels were decreased in very low-density lipoproteins. Electron microscopy revealed large lamellar particles having electron-opaque cores attached to electron-lucent zones in intermediate-density and low-density lipoproteins. Low-density lipoprotein particle diameters were distributed bimodally. CONCLUSIONS AND RELEVANCE Despite a profound effect on lipoprotein metabolism, detailed neurocognitive and retinal studies failed to demonstrate any defects. This suggests that functions of apoE in the brain and eye are not essential or that redundant mechanisms exist whereby its role can be fulfilled. Targeted knockdown of apoE in the central nervous system might be a therapeutic modality in neurodegenerative disorders. PMID:25111166

Autism Spectrum Disorder in a Girl with a De Novo X;19 Balanced Translocation

PubMed Central

Baruffi, Marcelo Razera; de Souza, Deise Helena; Bicudo da Silva, Rosana Aparecida; Ramos, Ester Silveira; Moretti-Ferreira, Danilo

2012-01-01

Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with a de novo X;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed a de novo balanced translocation, with the karyotype 46,X,t(X;19)(p21.2;q13.4). Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY). Although abnormal phenotypes associated with de novo balanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process. PMID:23074688

Proteins with neomorphic moonlighting functions in disease.

PubMed

Jeffery, Constance J

2011-07-01

One gene can encode multiple protein functions because of RNA splice variants, gene fusions during evolution, promiscuous enzyme activities, and moonlighting protein functions. In addition to these types of multifunctional proteins, in which both functions are considered "normal" functions of a protein, some proteins have been described in which a mutation or conformational change imparts a second function on a protein that is not a "normal" function of the protein. We propose to call these new functions "neomorphic moonlighting functions". The most common examples of neomorphic moonlighting functions are due to conformational changes that impart novel protein-protein interactions resulting in the formation of protein aggregates in Alzheimers, Parkinsons disease, and the systemic amyloidoses. Other changes that can result in a neomorphic moonlighting function include a mutation in SMAD4 that causes the protein to bind to new promoters and thereby alter gene transcription patterns, mutations in two isocitrate dehydrogenase isoforms that impart a new catalytic activity, and mutations in dihydrolipoamide dehydrogenase that activate a hidden protease activity. These neomorphic moonlighting functions were identified because of their connection to disease. In the cases described herein, the new functions cause cancers or severe neurological impairment, although in most cases the mechanism by which the new function leads to disease is unknown. Copyright © 2011 Wiley Periodicals, Inc.

Advanced Connectivity Analysis (ACA): a Large Scale Functional Connectivity Data Mining Environment.

PubMed

Chen, Rong; Nixon, Erika; Herskovits, Edward

2016-04-01

Using resting-state functional magnetic resonance imaging (rs-fMRI) to study functional connectivity is of great importance to understand normal development and function as well as a host of neurological and psychiatric disorders. Seed-based analysis is one of the most widely used rs-fMRI analysis methods. Here we describe a freely available large scale functional connectivity data mining software package called Advanced Connectivity Analysis (ACA). ACA enables large-scale seed-based analysis and brain-behavior analysis. It can seamlessly examine a large number of seed regions with minimal user input. ACA has a brain-behavior analysis component to delineate associations among imaging biomarkers and one or more behavioral variables. We demonstrate applications of ACA to rs-fMRI data sets from a study of autism.

Matrix Metalloproteinases as a Therapeutic Target to Improve Neurologic Recovery After Spinal Cord Injury

DTIC Science & Technology

2013-10-01

the BMS scale where a score of 0 indicates hindlimb paralysis and a score of 9 reflects normal hindlimb locomotor function. The more mildly injured...graded levels of injury severity based upon the BMS scale . Urologic status shows injury severity-dependent changes with UICs being most pronounced...BMS scale . Exclusion criteria were as follows: any animal showing an average score of > 0.5 at 8 hours post- injury or morbidity as defined in UCSF

Thoracolumbar vertebral osteochondroma in a young dog.

PubMed

Santen, D R; Payne, J T; Pace, L W; Kroll, R A; Johnson, G C

1991-10-15

Osteosarcoma was diagnosed in a 7-month-old female German Shepherd Dog with hind limb paresis. Radiography revealed a circumscribed calcified mass in the dorsal vertebral lamina at T13-L1 resulting in extradural compression of the spinal cord. Surgical excision of the mass resulted in gradual return to normal neurologic function. Four weeks after surgery, the dog became severely atactic after rolling onto its back. A chip fracture of T13 was identified, and the dog was euthanatized at the owners' request.

Increased pediatric functional neurological symptom disorders after the Boston marathon bombings: a case series.

PubMed

Guerriero, Réjean M; Pier, Danielle B; de Gusmão, Claudio M; Bernson-Leung, Miya E; Maski, Kiran P; Urion, David K; Waugh, Jeff L

2014-11-01

Functional neurological symptom disorders are frequently the basis for acute neurological consultation. In children, they are often precipitated by high-frequency everyday stressors. The extent to which a severe traumatic experience may also precipitate functional neurological abnormalities is unknown. For the 2-week period after the Boston Marathon bombings, we prospectively collected data on patients whose presentation suggested a functional neurological symptom disorder. We assessed clinical and demographic variables, duration of symptoms, extent of educational impact, and degree of connection to the Marathon bombing. We contacted all patients at 6 months after presentation to determine the outcome and accuracy of the diagnosis. In a parallel study, we reported a baseline of 2.6 functional neurological presentations per week in our emergency room. In the week after the Marathon bombings, this frequency tripled. Ninety-one percent of presentations were delayed by 1 week, with onset around the first school day after a city-wide lockdown. Seventy-three percent had a history of a prior psychiatric diagnosis. At the 6 months follow-up, no functional neurological symptom disorder diagnoses were overturned and no new organic diagnosis was made. Pediatric functional neurological symptom disorder may be precipitated by both casual and high-intensity stressors. The 3.4-fold increase in incidence after the Boston Marathon bombings and city-wide lockdown demonstrates the marked effect that a community-wide tragedy can have on the mental health of children. Care providers must be aware of functional neurological symptom disorders after stressful community events in vulnerable patient populations, particularly those with prior psychiatric diagnoses. Copyright © 2014 Elsevier Inc. All rights reserved.

[Difficulties in the diagnosis in the case of subacute paraplegia in a woman with Addison-Biermer disease].

PubMed

Szupień, Elzbieta; Ositek, Bozena; Pniewski, Jarosław

2004-01-01

The following paper presents a case of presently rare serious and non-typical subacutely progressing neurological complications in Addison-Biermer disease in a period before the diagnosis, and effective treatment with vitamin B12 in the advanced process of the nervous system impairment. The patient was a 52-year-old woman with the following (increasingly severe) symptoms occurring over a period of 5 weeks, after an earlier non-related operation: paresis of lower limbs (up to paraplegia), slight paresis of upper limbs, sphincters disorder, numbness and the loss of sensation in the upper and lower limbs, and finally mental deterioration. The woman was admitted to a neurological clinic with the suspected Guillain-Bare syndrome. After an interview and medical examination, with the help of some additional tests and resulting clinical picture, it was diagnosed as the Addison-Biermer disorder. A typical treatment was started with vitamin B12 injections, with a neurological improvement within a week, and further gradual improvement over the following 5 weeks of treatment in the clinic (improvement in the strength, sensation in the limbs, functionality of the sphincters, and normalization of the cognitive functions). After 2 months of continuous pharmacological treatment and physical rehabilitation, the patient started to walk with the help of a walker, and after further 2 months, she was able to walk on her own with a crutch.

Extraneuronal pathology in a canine model of CLN2 neuronal ceroid lipofuscinosis after intracerebroventricular gene therapy that delays neurological disease progression.

PubMed

Katz, M L; Johnson, G C; Leach, S B; Williamson, B G; Coates, J R; Whiting, R E H; Vansteenkiste, D P; Whitney, M S

2017-04-01

CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1, which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Studies using a canine model for this disorder demonstrated that delivery of TPP1 enzyme to the cerebrospinal fluid (CSF) by intracerebroventricular administration of an AAV-TPP1 vector resulted in substantial delays in the onset and progression of neurological signs and prolongation of life span. We hypothesized that the treatment may not deliver therapeutic levels of this protein to tissues outside the central nervous system that also require TPP1 for normal lysosomal function. To test this hypothesis, dogs treated with CSF administration of AAV-TPP1 were evaluated for the development of non-neuronal pathology. Affected treated dogs exhibited progressive cardiac pathology reflected by elevated plasma cardiac troponin-1, impaired cardiac function and development of histopathological myocardial lesions. Progressive increases in the plasma activity levels of alanine aminotransferase and creatine kinase indicated development of pathology in the liver and muscles. The treatment also did not prevent disease-related accumulation of lysosomal storage bodies in the heart or liver. These studies indicate that optimal treatment outcomes for CLN2 disease may require delivery of TPP1 systemically as well as directly to the central nervous system.

Extraneuronal pathology in a canine model of CLN2 neuronal ceroid lipofuscinosis after intracerebroventricular gene therapy that delays neurological disease progression

PubMed Central

Katz, M L; Johnson, G C; Leach, S B; Williamson, B G; Coates, J R; Whiting, R E H; Vansteenkiste, D P; Whitney, M S

2017-01-01

CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1, which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Studies using a canine model for this disorder demonstrated that delivery of TPP1 enzyme to the cerebrospinal fluid (CSF) by intracerebroventricular administration of an AAV-TPP1 vector resulted in substantial delays in the onset and progression of neurological signs and prolongation of life span. We hypothesized that the treatment may not deliver therapeutic levels of this protein to tissues outside the central nervous system that also require TPP1 for normal lysosomal function. To test this hypothesis, dogs treated with CSF administration of AAV-TPP1 were evaluated for the development of non-neuronal pathology. Affected treated dogs exhibited progressive cardiac pathology reflected by elevated plasma cardiac troponin-1, impaired cardiac function and development of histopathological myocardial lesions. Progressive increases in the plasma activity levels of alanine aminotransferase and creatine kinase indicated development of pathology in the liver and muscles. The treatment also did not prevent disease-related accumulation of lysosomal storage bodies in the heart or liver. These studies indicate that optimal treatment outcomes for CLN2 disease may require delivery of TPP1 systemically as well as directly to the central nervous system. PMID:28079862

Cortical localization of cognitive function by regression of performance on event-related potentials

NASA Technical Reports Server (NTRS)

Montgomery, R. W.; Montgomery, L. D.; Guisado, R.

1992-01-01

This paper demonstrates a new method of mapping cortical localization of cognitive function, using electroencephalographic data. Cross-subject regression analyses are used to identify cortical sites and post-stimulus latencies where there is a high correlation between subjects' performance and their cognitive event-related potential amplitude. The procedure was tested using a mental arithmetic task and was found to identify essentially the same cortical regions that have been associated with such tasks on the basis of research with patients suffering localized cortical lesions. Thus, it appears to offer an inexpensive, noninvasive tool for exploring the dynamics of localization in neurologically normal subjects.

Zuo-Gui and You-Gui pills, two traditional Chinese herbal formulas, downregulated the expression of NogoA, NgR, and RhoA in rats with experimental autoimmune encephalomyelitis.

PubMed

Kou, Shuang; Zheng, Qi; Wang, Yizhou; Zhao, Hui; Zhang, Qiuxia; Li, Ming; Qi, Fang; Fang, Ling; Liu, Lei; Ouyang, Junyao; Zhao, Haiyu; Wang, Lei

2014-12-02

Zuo-Gui pills (ZGPs) and You-Gui pills (YGPs) are 2 traditional Chinese herbal formulas used for treating multiple sclerosis (MS) in the clinical setting and have been shown to have neuroprotective effects in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The aim of this study was to explore the mechanisms underlying the neuroprotective functions of ZGPs and YGPs. Female Lewis rats were randomly divided into normal control, EAE model, 2g/kg ZGP-treated EAE, 3g/kg YGP-treated EAE, and prednisone acetate-treated groups. EAE model was induced by subcutaneous injection of MBP68-86 antigen. The neurological function scores were estimated. Histological structures of the brains and spinal cords were observed, and myelinated and axons imaged. NogoA, Nogo receptor (NgR), and RhoA transcript and protein levels were measured by real-time quantitative RT-PCR and western blotting on postimmunization (PI) days 14 (acute stage) and 28 (remission stage). ZGPs and YGPs significantly reduced neurological functions scores and abrogated inflammatory infiltrates, demyelination, and axonal damage. Furthermore, treatment with ZGPs and YGPs inhibited NogoA, NgR, and RhoA mRNA and protein expression in rats at both the acute and remission stages. ZGPs exhibited stronger effects on NogoA and RhoA expressions, as well as neurological function, during the acute stage of EAE, while YGPs caused greater reductions in NogoA expression during the remission stage. Our findings suggested that ZGPs and YGPs exerted neuroprotective effects by downregulation of NogoA, NgR, and RhoA pathways, with differences in response times and targets observed between ZGPs and YGPs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Utilization of Veno-Arterial Extracorporeal Membrane Oxygenation for Massive Pulmonary Embolism.

PubMed

Pasrija, Chetan; Kronfli, Anthony; George, Praveen; Raithel, Maxwell; Boulos, Francesca; Herr, Daniel L; Gammie, James S; Pham, Si M; Griffith, Bartley P; Kon, Zachary N

2018-02-01

The management of massive pulmonary embolism remains challenging, with a considerable mortality rate. Although veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for massive pulmonary embolism has been reported, its use as salvage therapy has been associated with poor outcomes. We reviewed our experience utilizing an aggressive, protocolized approach of VA-ECMO to triage, optimize, and treat these patients. All patients with a massive pulmonary embolism who were placed on VA-ECMO, as an initial intervention determined by protocol, were retrospectively reviewed. ECMO support was continued until organ optimization was achieved or neurologic status was determined. At that time, if the thrombus burden resolved, decannulation was performed. If substantial clot burden was still present with evidence of right ventricular (RV) strain, operative therapy was undertaken. Twenty patients were identified. Before cannulation, all patients had an RV-to-left ventricular ratio greater than 1.0 and severe RV dysfunction. The median duration of ECMO support was 5.1 days, with significant improvement in end-organ function. Ultimately, 40% received anticoagulation alone, 5% underwent catheter-directed therapy, and 55% underwent surgical pulmonary embolectomy. Care was withdrawn in 1 patient with a prolonged pre-cannulation cardiac arrest after confirmation of neurologic death. In-hospital and 90-day survival was 95%. At discharge, 18 of 19 patients had normal RV function, and 1 patient, who received catheter-directed therapy, had mild dysfunction. VA-ECMO appears to be an effective tool to optimize end-organ function as a bridge to recovery or intervention, with excellent outcomes. This approach may allow clinicians to better triage patients with massive pulmonary embolism to the appropriate therapy on the basis of recovery of RV function, residual thrombus burden, operative risk, and neurologic status. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Functional Performance and Associations between Performance Tests and Neurological Assessment Differ in Men and Women with Parkinson's Disease.

PubMed

Medijainen, Kadri; Pääsuke, Mati; Lukmann, Aet; Taba, Pille

2015-01-01

Neurological assessment of a patient with Parkinson's disease (PD) is expected to reflect upon functional performance. As women are known to report more limitations even for same observed functional performance level, present study was designed to examine whether associations between neurological assessments and functional performance differ across genders. 14 men and 14 women with PD participated. Functional performance was assessed by measuring walking speeds on 10-meter walk test (10MWT) and by performing timed-up-and-go-test (TUG). Neurological assessment included Hoehn and Yahr Scale (HY), Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Schwab and England Activities of Daily Living Scale (S-E), and Mini Mental State Examination (MMSE). In women with PD, Kendall's tau-b correlation analyses revealed significant correlations between functional performance tests and neurological assessment measures, with the exception in MMSE. No corresponding associations were found for men, although they demonstrated better functional performance, as expected. Men in similar clinical stage of the PD perform better on functional tests than women. Disease severity reflects upon functional performance differently in men and women with PD. Results indicate that when interpreting the assessment results of both functional performance and neurological assessment tests, the gender of the patient should be taken into consideration.

Vitamin B-12 status and neurologic function in older people: a cross-sectional analysis of baseline trial data from the Older People and Enhanced Neurological Function (OPEN) study.

PubMed

Miles, Lisa M; Allen, Elizabeth; Mills, Kerry; Clarke, Robert; Uauy, Ricardo; Dangour, Alan D

2016-09-01

Aging is associated with a progressive decline in vitamin B-12 status. Overt vitamin B-12 deficiency causes neurologic disturbances in peripheral and central motor and sensory systems, but the public health impact for neurologic disease of moderately low vitamin B-12 status in older people is unclear. Evidence from observational studies is limited by heterogeneity in the definition of vitamin B-12 status and imprecise measures of nerve function. We aimed to determine whether vitamin B-12 status is associated with electrophysiologic indexes of peripheral or central neurologic function in asymptomatic older people with moderately low vitamin B-12 status. We used a cross-sectional analysis of baseline data from the Older People and Enhanced Neurological Function study conducted in Southeast England. This trial investigated the effectiveness of vitamin B-12 supplementation on electrophysiologic indexes of neurologic function in asymptomatic older people (mean age: 80 y) with moderately low vitamin B-12 status (serum vitamin B-12 concentrations ≥107 and <210 pmol/L without anemia, n = 201). Vitamin B-12 status was assessed with the use of total vitamin B-12, holotranscobalamin, and a composite indicator of vitamin B-12 status (cB-12). Electrophysiologic measures of sensory and motor components of peripheral and central nerve function were assessed in all participants by a single observer. In multivariate models, there was no evidence of an association of vitamin B-12, holotranscobalamin, or cB-12 with any nerve conduction outcome. There was also no evidence of an association of vitamin B-12 status with clinical markers of neurologic function. This secondary analysis of high-quality trial data did not show any association of any measure of vitamin B-12 status with either peripheral or central neurologic function or any clinical markers of neurologic function in older people with moderately low vitamin B-12 status. The results of this study are unlikely to be generalizable to a less healthy older population with more severe vitamin B-12 deficiency. This trial was registered at www.controlled-trials.com as ISRCTN54195799. © 2016 American Society for Nutrition.

Dissociative amnesia: Disproportionate retrograde amnesia, stressful experiences and neurological circumstances.

PubMed

Thomas-Antérion, C

Dissociative amnesias have been reported in neurological episodes mild enough to not cause any visible lesions on morphological examination. Disproportionate retrograde amnesia with or without identity loss happens in the context of psychological trauma (known or not). In metabolic imaging studies, some authors have reported functional alterations, particularly in the bilateral hippocampus, right temporal regions and inferolateral prefrontal cortex, despite normal morphological imaging. To avoid the presumption of an organic, psychogenic or mixed origin for such changes, De Renzi et al. suggested the term 'functional amnesia' to describe the condition. Patients have sometimes recovered during events similar to those preceding the amnesia in either a spectacular fashion or never. Also, in some cases, distraction or sedation may trigger the start of recovery. During psychotherapy, one patient remembered seeing a car on fire when he was a boy, and his amnesia started when his house was on fire. This suggests control by the frontal cortex, with repression blocking amnesic traces in the new emotional and biological context. Copyright © 2017. Published by Elsevier Masson SAS.

[Brain metastases: Focal treatment (surgery and radiation therapy) and cognitive consequences].

PubMed

Reygagne, Emmanuelle; Du Boisgueheneuc, Foucaud; Berger, Antoine

2017-04-01

Brain metastases represent the first cause of malignant brain tumor. Without radiation therapy, prognosis was poor with fast neurological deterioration, and a median overall survival of one month. Nowadays, therapeutic options depend on brain metastases presentation, extra brain disease, performance status and estimated prognostic (DS GPA). Therefore, for oligometastatic brain patients with a better prognosis, this therapeutic modality is controversial. In fact, whole-brain radiation therapy improves neurological outcomes, but it can also induce late neuro-cognitive sequelae for long-term survivors of brain metastases. Thus, in this strategy for preserving good cognitive functions, stereotactic radiation therapy is a promising treatment. Delivering precisely targeted radiation in few high-doses in one to four brain metastases, allows to reduce radiation damage to normal tissues and it should allow to decrease radiation-induced cognitive decline. In this paper, we will discuss about therapeutic strategies (radiation therapy and surgery) with their neuro-cognitive consequences for brain metastases patients and future concerning preservation of cognitive functions. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking

PubMed Central

Metzler, Martina; Li, Bo; Gan, Lu; Georgiou, John; Gutekunst, Claire-Anne; Wang, Yushan; Torre, Enrique; Devon, Rebecca S.; Oh, Rosemary; Legendre-Guillemin, Valerie; Rich, Mark; Alvarez, Christine; Gertsenstein, Marina; McPherson, Peter S.; Nagy, Andras; Wang, Yu Tian; Roder, John C.; Raymond, Lynn A.; Hayden, Michael R.

2003-01-01

Huntingtin interacting protein 1 (HIP1) is a recently identified component of clathrin-coated vesicles that plays a role in clathrin-mediated endocytosis. To explore the normal function of HIP1 in vivo, we created mice with targeted mutation in the HIP1 gene (HIP1–/–). HIP1–/– mice develop a neurological phenotype by 3 months of age manifest with a failure to thrive, tremor and a gait ataxia secondary to a rigid thoracolumbar kyphosis accompanied by decreased assembly of endocytic protein complexes on liposomal membranes. In primary hippocampal neurons, HIP1 colocalizes with GluR1-containing AMPA receptors and becomes concentrated in cell bodies following AMPA stimulation. Moreover, a profound dose-dependent defect in clathrin-mediated internalization of GluR1-containing AMPA receptors was observed in neurons from HIP1–/– mice. Together, these data provide strong evidence that HIP1 regulates AMPA receptor trafficking in the central nervous system through its function in clathrin-mediated endocytosis. PMID:12839988

Neuropsychological Differences Among Subtypes of Schizophrenia

ERIC Educational Resources Information Center

Goldstein, Gerald; Halperin, Keith M.

1977-01-01

A common pool of schizophrenic subjects was subdivided and analyzed three separate times on the basis of three sets of criteria: paranoid versus nonparanoid, neurologically normal versus neurologically abnormal, and long-term institutionalization versus short-term institutionalization. Differences in ability levels and patterns were determined for…

Cognitive-analytical therapy for a patient with functional neurological symptom disorder-conversion disorder (psychogenic myopia): A case study.

PubMed

Nasiri, Hamid; Ebrahimi, Amrollah; Zahed, Arash; Arab, Mostafa; Samouei, Rahele

2015-05-01

Functional neurological symptom disorder commonly presents with symptoms and defects of sensory and motor functions. Therefore, it is often mistaken for a medical condition. It is well known that functional neurological symptom disorder more often caused by psychological factors. There are three main approaches namely analytical, cognitive and biological to manage conversion disorder. Any of such approaches can be applied through short-term treatment programs. In this case, study a 12-year-old boy with the diagnosed functional neurological symptom disorder (psychogenic myopia) was put under a cognitive-analytical treatment. The outcome of this treatment modality was proved successful.

Multicenter validation of a bedside antisaccade task as a measure of executive function

PubMed Central

Hellmuth, J.; Mirsky, J.; Heuer, H.W.; Matlin, A.; Jafari, A.; Garbutt, S.; Widmeyer, M.; Berhel, A.; Sinha, L.; Miller, B.L.; Kramer, J.H.

2012-01-01

Objective: To create and validate a simple, standardized version of the antisaccade (AS) task that requires no specialized equipment for use as a measure of executive function in multicenter clinical studies. Methods: The bedside AS (BAS) task consisted of 40 pseudorandomized AS trials presented on a laptop computer. BAS performance was compared with AS performance measured using an infrared eye tracker in normal elders (NE) and individuals with mild cognitive impairment (MCI) or dementia (n = 33). The neuropsychological domain specificity of the BAS was then determined in a cohort of NE, MCI, and dementia (n = 103) at UCSF, and the BAS was validated as a measure of executive function in a 6-center cohort (n = 397) of normal adults and patients with a variety of brain diseases. Results: Performance on the BAS and laboratory AS task was strongly correlated and BAS performance was most strongly associated with neuropsychological measures of executive function. Even after controlling for disease severity and processing speed, BAS performance was associated with multiple assessments of executive function, most strongly the informant-based Frontal Systems Behavior Scale. Conclusions: The BAS is a simple, valid measure of executive function in aging and neurologic disease. PMID:22573640

Cephalic Disorders

MedlinePlus

... level. Some may have near-normal development and intelligence. Many will die before the age of 2. ... develop only minor neurological problems and have normal intelligence, while others may be severely disabled. Others may ...

A tool for classifying individuals with chronic back pain: using multivariate pattern analysis with functional magnetic resonance imaging data.

PubMed

Callan, Daniel; Mills, Lloyd; Nott, Connie; England, Robert; England, Shaun

2014-01-01

Chronic pain is one of the most prevalent health problems in the world today, yet neurological markers, critical to diagnosis of chronic pain, are still largely unknown. The ability to objectively identify individuals with chronic pain using functional magnetic resonance imaging (fMRI) data is important for the advancement of diagnosis, treatment, and theoretical knowledge of brain processes associated with chronic pain. The purpose of our research is to investigate specific neurological markers that could be used to diagnose individuals experiencing chronic pain by using multivariate pattern analysis with fMRI data. We hypothesize that individuals with chronic pain have different patterns of brain activity in response to induced pain. This pattern can be used to classify the presence or absence of chronic pain. The fMRI experiment consisted of alternating 14 seconds of painful electric stimulation (applied to the lower back) with 14 seconds of rest. We analyzed contrast fMRI images in stimulation versus rest in pain-related brain regions to distinguish between the groups of participants: 1) chronic pain and 2) normal controls. We employed supervised machine learning techniques, specifically sparse logistic regression, to train a classifier based on these contrast images using a leave-one-out cross-validation procedure. We correctly classified 92.3% of the chronic pain group (N = 13) and 92.3% of the normal control group (N = 13) by recognizing multivariate patterns of activity in the somatosensory and inferior parietal cortex. This technique demonstrates that differences in the pattern of brain activity to induced pain can be used as a neurological marker to distinguish between individuals with and without chronic pain. Medical, legal and business professionals have recognized the importance of this research topic and of developing objective measures of chronic pain. This method of data analysis was very successful in correctly classifying each of the two groups.

A Tool for Classifying Individuals with Chronic Back Pain: Using Multivariate Pattern Analysis with Functional Magnetic Resonance Imaging Data

PubMed Central

Callan, Daniel; Mills, Lloyd; Nott, Connie; England, Robert; England, Shaun

2014-01-01

Chronic pain is one of the most prevalent health problems in the world today, yet neurological markers, critical to diagnosis of chronic pain, are still largely unknown. The ability to objectively identify individuals with chronic pain using functional magnetic resonance imaging (fMRI) data is important for the advancement of diagnosis, treatment, and theoretical knowledge of brain processes associated with chronic pain. The purpose of our research is to investigate specific neurological markers that could be used to diagnose individuals experiencing chronic pain by using multivariate pattern analysis with fMRI data. We hypothesize that individuals with chronic pain have different patterns of brain activity in response to induced pain. This pattern can be used to classify the presence or absence of chronic pain. The fMRI experiment consisted of alternating 14 seconds of painful electric stimulation (applied to the lower back) with 14 seconds of rest. We analyzed contrast fMRI images in stimulation versus rest in pain-related brain regions to distinguish between the groups of participants: 1) chronic pain and 2) normal controls. We employed supervised machine learning techniques, specifically sparse logistic regression, to train a classifier based on these contrast images using a leave-one-out cross-validation procedure. We correctly classified 92.3% of the chronic pain group (N = 13) and 92.3% of the normal control group (N = 13) by recognizing multivariate patterns of activity in the somatosensory and inferior parietal cortex. This technique demonstrates that differences in the pattern of brain activity to induced pain can be used as a neurological marker to distinguish between individuals with and without chronic pain. Medical, legal and business professionals have recognized the importance of this research topic and of developing objective measures of chronic pain. This method of data analysis was very successful in correctly classifying each of the two groups. PMID:24905072

Is There Chronic Brain Damage in Retired NFL Players? Neuroradiology, Neuropsychology, and Neurology Examinations of 45 Retired Players

PubMed Central

Casson, Ira R.; Viano, David C.; Haacke, E. Mark; Kou, Zhifeng; LeStrange, Danielle G.

2014-01-01

Background: Neuropathology and surveys of retired National Football League (NFL) players suggest that chronic brain damage is a frequent result of a career in football. There is limited information on the neurological statuses of living retired players. This study aimed to fill the gap in knowledge by conducting in-depth neurological examinations of 30- to 60-year-old retired NFL players. Hypothesis: In-depth neurological examinations of 30- to 60-year-old retired players are unlikely to detect objective clinical abnormalities in the majority of subjects. Study Design: A day-long medical examination was conducted on 45 retired NFL players, including state-of-the-art magnetic resonance imaging (MRI; susceptibility weighted imaging [SWI], diffusion tensor imaging [DTI]), comprehensive neuropsychological and neurological examinations, interviews, blood tests, and APOE (apolipoprotein E) genotyping. Level of Evidence: Level 3. Methods: Participants’ histories focused on neurological and depression symptoms, exposure to football, and other factors that could affect brain function. The neurological examination included Mini-Mental State Examination (MMSE) evaluation of cognitive function and a comprehensive search for signs of dysarthria, pyramidal system dysfunction, extrapyramidal system dysfunction, and cerebellar dysfunction. The Beck Depression Inventory (BDI) and Patient Health Questionnaire (PHQ) measured depression. Neuropsychological tests included pen-and-paper and ImPACT evaluation of cognitive function. Anatomical examination SWI and DTI MRI searched for brain injuries. The results were statistically analyzed for associations with markers of exposure to football and related factors, such as body mass index (BMI), ethanol use, and APOE4 status. Results: The retired players’ ages averaged 45.6 ± 8.9 years (range, 30-60 years), and they had 6.8 ± 3.2 years (maximum, 14 years) of NFL play. They reported 6.9 ± 6.2 concussions (maximum, 25) in the NFL. The majority of retired players had normal clinical mental status and central nervous system (CNS) neurological examinations. Four players (9%) had microbleeds in brain parenchyma identified in SWI, and 3 (7%) had a large cavum septum pellucidum with brain atrophy. The number of concussions/dings was associated with abnormal results in SWI and DTI. Neuropsychological testing revealed isolated impairments in 11 players (24%), but none had dementia. Nine players (20%) endorsed symptoms of moderate or severe depression on the BDI and/or met criteria for depression on PHQ; however, none had dementia, dysarthria, parkinsonism, or cerebellar dysfunction. The number of football-related concussions was associated with isolated abnormalities on the clinical neurological examination, suggesting CNS dysfunction. The APOE4 allele was present in 38% of the players, a larger number than would be expected in the general male population (23%-26%). Conclusion: MRI lesions and neuropsychological impairments were found in some players; however, the majority of retired NFL players had no clinical signs of chronic brain damage. Clinical Relevance: These results need to be reconciled with the prevailing view that a career in football frequently results in chronic brain damage. PMID:25177413

Anterior Z-plate and titanic mesh fixation for acute burst thoracolumbar fracture.

PubMed

Xu, Jian-Guang; Zeng, Bing-Fang; Zhou, Wei; Kong, Wei-Qing; Fu, Yi-Shan; Zhao, Bi-Zeng; Zhang, Tao; Lian, Xiao-Feng

2011-04-01

A retrospective study. To evaluate the clinical outcome, effectiveness, and security of the surgical management of acute thoracolumbar burst fracture with corpectomy, titanic mesh autograft, and Z-plate fixation by anterior approach. Many surgical methods were adopted to treat acute burst thoracolumbar fracture. But the optimal surgical management remains controversial. A retrospective review of a consecutive series of 48 patients with thoracolumbar burst fracture treated with anterior corpectomy, titanic mesh autograft, and Z-plate internal fixation was carried out. Preoperative clinical and radiographic data of all cases were originally collected. Surgical indications were motor neurologic deficit and thoracolumbar column instability. Twenty-two patients (45.8%) with acute thoracolumbar burst fractures presented with a neurologic deficit. The postoperative recovery of neural function, restoration of anterior cortex collapse, kyphotic angle, and spinal canal compromise were observed. The preoperative kyphotic angle was improved to a mean of 5.6°, radiographic height restored to 95.8% of the adjacent normal levels, and canal compromise was 0%. None of the patients had neurologic deterioration. Mean follow-up time was 32.4 months (range, 24-47 months). All 22 patients with neurologic deficit demonstrated at least one Frankel grade improvement on final observation, with 16 (73%) patients had accomplished complete neurologic recovery. Forty-six (96%) patients reported minimal or no pain at final follow-up observation, and 40 (83%) patients who had been working before injury returned to original work. The authors considered spinal cord decompression with anterior corpectomy and stability reconstruction with titanic mesh autograft and Z-plate fixation at same time in one incision as an effective technique for unstable thoracolumbar burst fracture with and without neurologic deficit.

The neurological safety of epidural parecoxib in rats.

PubMed

Kim, Yang Hyun; Lee, Pyung Bok; Park, Jeongmi; Lim, Young Jin; Kim, Yong Chul; Lee, Sang Chul; Ahn, Wonsik

2011-12-01

Epidural injection of cyclooxygenase-2 inhibitors has been suggested as a useful therapeutic modality in pain management in animal studies and clinical settings. Direct epidural administration of parecoxib, a highly selective cyclooxygenase-2 inhibitor, may have advantages over its parenteral administration regarding required dose, side effects, and efficacy. However, no animal studies have been performed to investigate the possible neurotoxicity of epidurally injected parecoxib. Therefore, the present study was performed to assess the neurotoxicity of epidurally injected parecoxib in rats. Rats (n=45) were randomly divided into three groups: normal saline group (group N, n=15), ethanol group (group E, n=15), and parecoxib group (group P, n=15). 0.3 mL of epidural parecoxib (6 mg) and the same volume of epidural ethanol or normal saline were injected into the epidural space. Neurologic assessment was performed 3, 7 and 21 days after the injection by pinch toe testing. Histologic changes were evaluated for vacuolation of the dorsal funiculus, chromatolytic changes of the motor neurons, neuritis, and meningeal inflammation. All rats in groups N and P showed normal response to pinch-toe testing and had a normal gait at each observation point. Histological examination showed no evidence suggestive of neuronal body or axonal lesions, gliosis, or myelin sheet damage in group N or P at any time. However, all rats in group E showed sensory-motor dysfunction, behavioral change, or histopathological abnormalities. No neurotoxicity on the spinal cord or abnormalities in sensorimotor function or behavior was noted in rats that received epidural parecoxib. Copyright © 2011 Elsevier Inc. All rights reserved.

Creatine and guanidinoacetate reference values in a French population.

PubMed

Joncquel-Chevalier Curt, Marie; Cheillan, David; Briand, Gilbert; Salomons, Gajja S; Mention-Mulliez, Karine; Dobbelaere, Dries; Cuisset, Jean-Marie; Lion-François, Laurence; Des Portes, Vincent; Chabli, Allel; Valayannopoulos, Vassili; Benoist, Jean-François; Pinard, Jean-Marc; Simard, Gilles; Douay, Olivier; Deiva, Kumaran; Tardieu, Marc; Afenjar, Alexandra; Héron, Delphine; Rivier, François; Chabrol, Brigitte; Prieur, Fabienne; Cartault, François; Pitelet, Gaëlle; Goldenberg, Alice; Bekri, Soumeya; Gerard, Marion; Delorme, Richard; Porchet, Nicole; Vianey-Saban, Christine; Vamecq, Joseph

2013-11-01

Creatine and guanidinoacetate are biomarkers of creatine metabolism. Their assays in body fluids may be used for detecting patients with primary creatine deficiency disorders (PCDD), a class of inherited diseases. Their laboratory values in blood and urine may vary with age, requiring that reference normal values are given within the age range. Despite the long known role of creatine for muscle physiology, muscle signs are not necessarily the major complaint expressed by PCDD patients. These disorders drastically affect brain function inducing, in patients, intellectual disability, autistic behavior and other neurological signs (delays in speech and language, epilepsy, ataxia, dystonia and choreoathetosis), being a common feature the drop in brain creatine content. For this reason, screening of PCDD patients has been repeatedly carried out in populations with neurological signs. This report is aimed at providing reference laboratory values and related age ranges found for a large scale population of patients with neurological signs (more than 6 thousand patients) previously serving as a background population for screening French patients with PCDD. These reference laboratory values and age ranges compare rather favorably with literature values for healthy populations. Some differences are also observed, and female participants are discriminated from male participants as regards to urine but not blood values including creatine on creatinine ratio and guanidinoacetate on creatinine ratio values. Such gender differences were previously observed in healthy populations; they might be explained by literature differential effects of testosterone and estrogen in adolescents and adults, and by estrogen effects in prepubertal age on SLC6A8 function. Finally, though they were acquired on a population with neurological signs, the present data might reasonably serve as reference laboratory values in any future medical study exploring abnormalities of creatine metabolism and transport. © 2013 Elsevier Inc. All rights reserved.

[Before you diagnose a patient with a conversion disorder, perform a thorough general medical and neurological examination. Case study].

PubMed

Pawełczyk, Tomasz; Pawełczyk, Agnieszka; Rabe-Jabłońska, Jolanta

2012-01-01

Dissociative and conversion disorders are classified together according to ICD-10 as states that are not confirmed by the presence of somatic diseases, which they suggest. According to the DSM-IV, both disorders are classified separately. Conversion disorders are a group of psychiatric disorders whose symptoms mimic the presence of malfunction or loss of motor or sensory function, whereas the nature and dynamics of the observed symptoms is not fully explained by the results of objective assessments and consultations, nor is the direct effect of a psychoactive substance. Impaired mental integration of different functions which normally interact simultaneously in the perception of reality and inner experience of the individual is found in dissociative disorders. The article describes the case of 25-year old man, in whom after initial suspicion of myasthenia gravis and its exclusion, a diagnosis of conversion disorder was made on the basis of the clinical picture and treatment with an SSRI antidepressant and individual psychotherapy were recommended. No improvement in mental and neurological status after six month therapy resulted in an in-depth diagnostics in a clinical setting and diagnosis of brain stem tumor (aastrocytoma fibrillare). (a) Neuroimaging is a source of important clinical data and in many cases should constitute an inherent element of a psychiatric diagnosis. (b) Diagnosis of conversion (dissociative) disorders requires a precise differential diagnosis, excluding the somatic causes of observed neurological ailments. (c) A late diagnosis of neurological or somatic causes of symptoms which arouse a suspicion of conversion (dissociative) disorders may make a radical treatment impossible or may considerably aggravate the remote prognosis and quality of the patients' life.

Neurologic improvement without angiographic improvement after antithyroid therapy in a patient with Moyamoya syndrome.

PubMed

Ishigami, Akiko; Toyoda, Kazunori; Suzuki, Rieko; Miyashita, Fumio; Iihara, Koji; Minematsu, Kazuo

2014-01-01

Moyamoya disease with special complications, including Graves' disease, is called as moyamoya syndrome. A 22-year-old Japanese woman had left middle cerebral artery (MCA) territory infarction complicated with Graves' disease. She had right-sided hemiparesis that deteriorated on day 8 with the infarct growth and thyrotoxicosis. On angiogram, the left MCA was occluded at the origin without moyamoya vessels. Positron emission tomography (PET) revealed misery-perfusion phenomenon in the left MCA territory. After initiation of the antithyroid therapy, her hemiparesis became milder. Seventeen months later, her thyroid function was normalized and net-like collateral moyamoya vessels proliferated in the left MCA territory. Misery-perfusion phenomenon persisted on PET. This report is unique in the point of neurologic recovery of the moyamoya patient right after initiation of antithyroid medication without radiological improvement. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A locus for the nystagmus-associated form of episodic ataxia maps to an 11-cM region on chromosome 19p

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

Kramer, P.L.; Gancher, S.T.; Nutt, J.G.

1995-07-01

Episodic ataxia (EA) is a rare neurological disorder characterized by attacks of generalized ataxia and near-normal neurological function between attacks. Most inherited cases are the result of an autosomal dominant condition with unknown neuropathology. It is heterogeneous and includes at least two distinct forms. In EA-1, attacks last minutes and interictal myokymia may be present. In EA-2, attacks may last hours and interictal nystagmus may occur. We reported linkage in four EA-1 families to chromosome 12p13 and identified mutations in these families in a potassium channel gene, KCNA1. Recently, we reported linkage in two EA-2 families to a 30-cM regionmore » on chromosome 19p. This report is based on members of the same two families and one additional kindred. 18 refs., 1 fig., 1 tab.« less

The impact of cognitive impairment, neurological soft signs and subdepressive symptoms on functional outcome in bipolar disorder.

PubMed

Baş, Tuba Öcek; Poyraz, Cana Aksoy; Baş, Alper; Poyraz, Burç Çağrı; Tosun, Musa

2015-03-15

Cognitive impairments and subsyndromal depressive symptoms are present during euthymic periods of bipolar disorder (BD). Most studies have determined that cognitive impairments and residual depressive symptoms have major impacts on psychosocial functioning. The aim of the present study was to identify the major factor responsible for low psychosocial functioning in a subgroup of patients with BD despite clinical recovery. Sixty patients with bipolar I disorder and 41 healthy subjects were enrolled in this study. Cognitive performance, neurological soft signs (NSSs), psychosocial functioning, residual mood symptoms and illness characteristics were assessed. Using the median value of the Functioning Assessment Short Test (FAST) as the cut-off point, the patients were divided into two groups, high- (n=29) or low-functioning (n=31), and they were compared based on total NSS, residual depressive symptoms, cognitive performance and clinical variables. Performances on the verbal memory tests and social functioning were significantly worse in the euthymic patients with BD. Increased rates of NSS were identified in the patients compared with the normal controls. The low-functioning patients performed significantly worse on verbal memory, and their NSS and residual depressive symptoms were significantly higher compared to high-functioning patients. In the regression analysis, subsyndromal depressive symptoms and verbal learning measures were identified as the best predictors of psychosocial functioning. The patients were artificially separated into two groups based on a FAST score cut-off. In this study, residual depressive symptoms and verbal memory impairments were the most prominent factors associated with the level of functioning. Copyright © 2014 Elsevier B.V. All rights reserved.

Using the social amoeba Dictyostelium to study the functions of proteins linked to neuronal ceroid lipofuscinosis.

PubMed

Huber, Robert J

2016-11-24

Neuronal ceroid lipofuscinosis (NCL), also known as Batten disease, is a debilitating neurological disorder that affects both children and adults. Thirteen genetically distinct genes have been identified that when mutated, result in abnormal lysosomal function and an excessive accumulation of ceroid lipofuscin in neurons, as well as other cell types outside of the central nervous system. The NCL family of proteins is comprised of lysosomal enzymes (PPT1/CLN1, TPP1/CLN2, CTSD/CLN10, CTSF/CLN13), proteins that peripherally associate with membranes (DNAJC5/CLN4, KCTD7/CLN14), a soluble lysosomal protein (CLN5), a protein present in the secretory pathway (PGRN/CLN11), and several proteins that display different subcellular localizations (CLN3, CLN6, MFSD8/CLN7, CLN8, ATP13A2/CLN12). Unfortunately, the precise functions of many of the NCL proteins are still unclear, which has made targeted therapy development challenging. The social amoeba Dictyostelium discoideum has emerged as an excellent model system for studying the normal functions of proteins linked to human neurological disorders. Intriguingly, the genome of this eukaryotic soil microbe encodes homologs of 11 of the 13 known genes linked to NCL. The genetic tractability of the organism, combined with its unique life cycle, makes Dictyostelium an attractive model system for studying the functions of NCL proteins. Moreover, the ability of human NCL proteins to rescue gene-deficiency phenotypes in Dictyostelium suggests that the biological pathways regulating NCL protein function are likely conserved from Dictyostelium to human. In this review, I will discuss each of the NCL homologs in Dictyostelium in turn and describe how future studies can exploit the advantages of the system by testing new hypotheses that may ultimately lead to effective therapy options for this devastating and currently untreatable neurological disorder.

Morning Glory Syndrome with Carotid and Middle Cerebral Artery Vasculopathy.

PubMed

Nezzar, Hachemi; Mbekeani, Joyce N; Dalens, Helen

2015-12-01

To report a case of incidental asymptomatic atypical morning glory syndrome (MGS) with concomitant ipsilateral carotid and middle cerebral dysgenesis. A 6-year-old child was discovered to have incidental findings of MGS, with atypia. All visual functions were normal including vision and stereopsis. Neuroimaging revealed ipsilateral carotid and middle cerebral vascular narrowing without associated collateral vessels or cerebral ischemia commonly seen in Moyamoya disease. Subsequent annual examinations have been stable, without signs of progression. This case demonstrates disparity between structural aberrations and final visual and neurological function and reinforces the association between MGS and intracranial vascular disruption. Full ancillary ophthalmic and neuroimaging studies should be performed in all patients with MGS with interval reassessments, even when the patient is asymptomatic and functionally intact.

Hypokalemia-induced pseudoischemic electrocardiographic changes and quadriplegia.

PubMed

Mirijello, Antonio; Rinninella, Emanuele; De Leva, Francesca; Tosoni, Alberto; Vassallo, Gabriele; Antonelli, Mariangela; Addolorato, Giovanni; Landolfi, Raffaele

2014-03-01

Hypokalemia is a common biochemical abnormality. Severe hypokalemia can produce cardiac rhythm alterations and neurologic manifestations. Early detection and treatment allow clinician to prevent morbidity and mortality from cardiac arrhythmias and respiratory failure. Here, we describe a case of severe hypokalemia inducing pseudoischemic electrocardiographic (ECG) alterations and quadriplegia, in a patient affected by chronic diarrhea. Electrocardiographic alterations and neurologic manifestations completely disappeared after potassium replacement; however, prolonged potassium supplementation was required to achieve the normalization of plasmatic potassium levels. Consecutive figures show ECG improvement until normalization of ECG findings.

Homozygous EEF1A2 mutation causes dilated cardiomyopathy, failure to thrive, global developmental delay, epilepsy and early death.

PubMed

Cao, Siqi; Smith, Laura L; Padilla-Lopez, Sergio R; Guida, Brandon S; Blume, Elizabeth; Shi, Jiahai; Morton, Sarah U; Brownstein, Catherine A; Beggs, Alan H; Kruer, Michael C; Agrawal, Pankaj B

2017-09-15

Eukaryotic elongation factor 1A (EEF1A), is encoded by two distinct isoforms, EEF1A1 and EEF1A2; whereas EEF1A1 is expressed almost ubiquitously, EEF1A2 expression is limited such that it is only detectable in skeletal muscle, heart, brain and spinal cord. Currently, the role of EEF1A2 in normal cardiac development and function is unclear. There have been several reports linking de novo dominant EEF1A2 mutations to neurological issues in humans. We report a pair of siblings carrying a homozygous missense mutation p.P333L in EEF1A2 who exhibited global developmental delay, failure to thrive, dilated cardiomyopathy and epilepsy, ultimately leading to death in early childhood. A third sibling also died of a similar presentation, but DNA was unavailable to confirm the mutation. Functional genomic analysis was performed in S. cerevisiae and zebrafish. In S. cerevisiae, there was no evidence for a dominant-negative effect. Previously identified putative de novo mutations failed to complement yeast strains lacking the EEF1A ortholog showing a major growth defect. In contrast, the introduction of the mutation seen in our family led to a milder growth defect. To evaluate its function in zebrafish, we knocked down eef1a2 expression using translation blocking and splice-site interfering morpholinos. EEF1A2-deficient zebrafish had skeletal muscle weakness, cardiac failure and small heads. Human EEF1A2 wild-type mRNA successfully rescued the morphant phenotype, but mutant RNA did not. Overall, EEF1A2 appears to be critical for normal heart function in humans, and its deficiency results in clinical abnormalities in neurologic function as well as in skeletal and cardiac muscle defects. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Educational Programming for Pupils with Neurologically Based Language Disorders. Final Report.

ERIC Educational Resources Information Center

Zedler, Empress Y.

To investigate procedures whereby schools may achieve maximal results with otherwise normal underachieving pupils with neurologically based language-learning disorders, 100 such subjects were studied over a 2-year period. Fifty experimental subjects remained in regular classes in school and received individualized teaching outside of school hours…

Neurological Disease associated with Folate Deficiency

PubMed Central

Reynolds, E. H.; Rothfeld, P.; Pincus, Jonathen H.

1973-01-01

In a general medical hospital population the neurological status of 24 patients with severe folate deficiency was compared with that of a control group of 21 patients with normal serum folate. A significant increase of organic brain syndrome and pyramidal tract damage was found in the folate-deficient group. These findings were independent of the degree of anaemia or the presence of alcoholism. These data are consistent with the view that severe folate deficiency may cause neurological deficits. PMID:4703098

The impact of systemic cortical alterations on perception

NASA Astrophysics Data System (ADS)

Zhang, Zheng

2011-12-01

Perception is the process of transmitting and interpreting sensory information, and the primary somatosensory (SI) area in the human cortex is the main sensory receptive area for the sensation of touch. The elaborate neuroanatomical connectivity that subserves the neuronal communication between adjacent and near-adjacent regions within sensory cortex has been widely recognized to be essential to normal sensory function. As a result, systemic cortical alterations that impact the cortical regional interaction, as associated with many neurological disorders, are expected to have significant impact on sensory perception. Recently, our research group has developed a novel sensory diagnostic system that employs quantitative sensory testing methods and is able to non-invasively assess central nervous system healthy status. The intent of this study is to utilize quantitative sensory testing methods that were designed to generate discriminable perception to objectively and quantitatively assess the impacts of different conditions on human sensory information processing capacity. The correlation between human perceptions with observations from animal research enables a better understanding of the underlying neurophysiology of human perception. Additional findings on different subject populations provide valuable insight of the underlying mechanisms for the development and maintenance of different neurological diseases. During the course of the study, several protocols were designed and utilized. And this set of sensory-based perceptual metrics was employed to study the effects of different conditions (non-noxious thermal stimulation, chronic pain stage, and normal aging) on sensory perception. It was found that these conditions result in significant deviations of the subjects' tactile information processing capacities from normal values. Although the observed shift of sensory detection sensitivity could be a result of enhanced peripheral activity, the changes in the effects of adaptation most likely reflect changes in central nervous system. The findings in this work provide valuable information for better understanding the underlying mechanisms involved in the development and maintenance of different neurological conditions.

Non-Stationarity in the “Resting Brain’s” Modular Architecture

PubMed Central

Jones, David T.; Vemuri, Prashanthi; Murphy, Matthew C.; Gunter, Jeffrey L.; Senjem, Matthew L.; Machulda, Mary M.; Przybelski, Scott A.; Gregg, Brian E.; Kantarci, Kejal; Knopman, David S.; Boeve, Bradley F.; Petersen, Ronald C.; Jack, Clifford R.

2012-01-01

Task-free functional magnetic resonance imaging (TF-fMRI) has great potential for advancing the understanding and treatment of neurologic illness. However, as with all measures of neural activity, variability is a hallmark of intrinsic connectivity networks (ICNs) identified by TF-fMRI. This variability has hampered efforts to define a robust metric of connectivity suitable as a biomarker for neurologic illness. We hypothesized that some of this variability rather than representing noise in the measurement process, is related to a fundamental feature of connectivity within ICNs, which is their non-stationary nature. To test this hypothesis, we used a large (n = 892) population-based sample of older subjects to construct a well characterized atlas of 68 functional regions, which were categorized based on independent component analysis network of origin, anatomical locations, and a functional meta-analysis. These regions were then used to construct dynamic graphical representations of brain connectivity within a sliding time window for each subject. This allowed us to demonstrate the non-stationary nature of the brain’s modular organization and assign each region to a “meta-modular” group. Using this grouping, we then compared dwell time in strong sub-network configurations of the default mode network (DMN) between 28 subjects with Alzheimer’s dementia and 56 cognitively normal elderly subjects matched 1∶2 on age, gender, and education. We found that differences in connectivity we and others have previously observed in Alzheimer’s disease can be explained by differences in dwell time in DMN sub-network configurations, rather than steady state connectivity magnitude. DMN dwell time in specific modular configurations may also underlie the TF-fMRI findings that have been described in mild cognitive impairment and cognitively normal subjects who are at risk for Alzheimer’s dementia. PMID:22761880

Functional progression of patients with neurological diseases in a tertiary paediatric intensive care unit: Our experience.

PubMed

Madurga Revilla, P; López Pisón, J; Samper Villagrasa, P; García Íñiguez, J P; Garcés Gómez, R; Domínguez Cajal, M; Gil Hernández, I

2017-11-23

Neurological diseases explain a considerable proportion of admissions to paediatric intensive care units (PICU), and are a significant cause of morbidity and mortality. This study aims to analyse the functional progression of children with critical neurological conditions. Retrospective descriptive study of children admitted to PICU with neurological diseases over a period of 3 years (2012-2014), assessing vital and functional prognosis at PICU discharge and at one year according to the Pediatric Cerebral and Overall Performance Category scales (PCPC-POPC) and the Functional Status Scale (FSS). The results are compared with our previous data (1990-1999), and those of the international multicentre PANGEA study. A total of 266 children were studied. The mortality rate was 3%; the PRISM-III and PIM2 models did not show predictive ability. Clinically significant worsening was observed in functional health at discharge in 30% of the sample, according to POPC, 15% according to PCPC, and 5% according to FSS. After one year, functional performance improved according to PCPC-POPC, but not according to FSS. Children with no underlying neurological disease had a higher degree of functional impairment; this was prolonged over time. We observed a decrease in overall and neurocritical mortality compared with our previous data (5.60 vs. 2.1%, P=.0003, and 8.44 vs. 2.63%, P=.0014, respectively). Compared with the PANGEA study, both mortality and cerebral functional impairment in neurocritical children were lower in our study (1.05 vs. 13.32%, P<.0001, and 10.47% vs. 23.79%, P<.0001, respectively). Nearly one-third of critically ill children have neurological diseases. A significant percentage, mainly children without underlying neurological diseases, had a clinically significant functional impact at PICU discharge and after a year. Neuromonitoring and neuroprotection measures and the evaluation of functional progression are necessary to improve critical child care. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

A systematic review and meta-analysis of neurological soft signs in relatives of people with schizophrenia

PubMed Central

2011-01-01

Background Neurological soft signs are subtle but observable impairments in motor and sensory functions that are not localized to a specific area of the brain. Neurological soft signs are common in schizophrenia. It has been established that soft signs meet two of five criteria for an endophenotype, namely: association with the illness, and state independence. This review investigated whether soft signs met a further criterion for an endophenotype, namely familial association. It was hypothesized that if familial association were present then neurological soft signs would be: (a) more common in first-degree relatives of people with schizophrenia than in controls; and (b) more common in people with schizophrenia than in their first-degree relatives. Method A systematic search identified potentially eligible studies in the EMBASE (1980-2011), OVID - MEDLINE (1950-2011) and PsycINFO (1806-2011) databases. Studies were included if they carried out a three-way comparison of levels of soft signs between people with schizophrenia, their first-degree relatives, and normal controls. Data were extracted independently by two reviewers and cross-checked by double entry. Results After screening 8678 abstracts, seven studies with 1553 participants were identified. Neurological soft signs were significantly more common in first-degree relatives of people with schizophrenia than in controls (pooled standardised mean difference (SMD) 1.24, 95% confidence interval (c.i) 0.59-1.89). Neurological soft signs were also significantly more common in people with schizophrenia than in their first-degree relatives (SMD 0.92, 95% c.i 0.64-1.20). Sensitivity analyses examining the effects of age and group blinding did not significantly alter the main findings. Conclusions Both hypotheses were confirmed, suggesting that the distribution of neurological soft signs in people with schizophrenia and their first-degree relatives is consistent with the endophenotype criterion of familial association. PMID:21859445

Male sexual dysfunction and infertility associated with neurological disorders

PubMed Central

Fode, Mikkel; Krogh-Jespersen, Sheila; Brackett, Nancy L; Ohl, Dana A; Lynne, Charles M; Sønksen, Jens

2012-01-01

Normal sexual and reproductive functions depend largely on neurological mechanisms. Neurological defects in men can cause infertility through erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Among the major conditions contributing to these symptoms are pelvic and retroperitoneal surgery, diabetes, congenital spinal abnormalities, multiple sclerosis and spinal cord injury. Erectile dysfunction can be managed by an increasingly invasive range of treatments including medications, injection therapy and the surgical insertion of a penile implant. Retrograde ejaculation is managed by medications to reverse the condition in mild cases and in bladder harvest of semen after ejaculation in more severe cases. Anejaculation might also be managed by medication in mild cases while assisted ejaculatory techniques including penile vibratory stimulation and electroejaculation are used in more severe cases. If these measures fail, surgical sperm retrieval can be attempted. Ejaculation with penile vibratory stimulation can be done by some spinal cord injured men and their partners at home, followed by in-home insemination if circumstances and sperm quality are adequate. The other options always require assisted reproductive techniques including intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection. The method of choice depends largely on the number of motile sperm in the ejaculate. PMID:22138899

Management and outcomes of spinal epidural hematoma during vertebroplasty: Case series.

PubMed

Fang, Miao; Zhou, Jiaojiao; Yang, Dongjun; He, Yu; Xu, Yong; Liu, Xin; Zeng, Yong

2018-05-01

Spinal cord injury (SCI) is one of the common complications of spinal surgery. There is no definite treatment and time of decompression for spinal cord induced by epidural hematoma during vertebroplasty. A total of 6 patients with SCI during vertebroplasty were included in our research. All of them occurred sensory disturbance and motor dysfunction due to a lower or same level operative vertebral body lesion in vertebroplasty. Neurological manifestations during vertebroplasty, postoperative magnetic resonance imaging and computed tomography. Once SCI occurred in vertebroplasty, four patients were underwent spinal cord decompression immediately, and two patients were done after 14 and 22 hours, respectively. Before decompression operation, one patient was Frankel A, three were Frankel B, and two were Frankel C. One day after evacuation of the SEH, three patients recovered to normal neurological function (Frankel E), one to Frankel C, and one to Frankel D, but the other one did not recover. At the last follow-up, five patients had recovered to Frankel E and one patient to Frankel D. According to our experience, when SCI occurs during vertebroplasty, neurological deficits are always secondary to acute SEH. Timely decompression, particularly transfer surgery, can shorten recovery time.

Prediction of 3- to 5-Month Outcomes from Signs of Acute Bilirubin Toxicity in Newborn Infants.

PubMed

El Houchi, Salma Z; Iskander, Iman; Gamaleldin, Rasha; El Shenawy, Amira; Seoud, Iman; Abou-Youssef, Hazem; Wennberg, Richard P

2017-04-01

To evaluate the ability of the bilirubin-induced neurologic dysfunction (BIND) score to predict residual neurologic and auditory disability and to document the relationship of BIND score to total serum bilirubin (TSB) concentration. The BIND score (assessing mental status, muscle tone, and cry patterns) was obtained serially at 6- to 8-hour intervals in 220 near-term and full-term infants with severe hyperbilirubinemia. Neurologic and/or auditory outcomes at 3-5 months of age were correlated with the highest calculated BIND score. The BIND score was also correlated with TSB. Follow-up neurologic and auditory examinations were performed for 145/202 (72%) surviving infants. All infants with severe acute bilirubin encephalopathy (BIND scores 7-9) either died or suffered residual neurologic and auditory impairment. Of 24 cases with moderate encephalopathy (BIND 4-6), 15 (62.5%) resolved following aggressive intervention and were normal at follow-up. Three of 73 infants with mild encephalopathy (BIND scores 1-3) but severe jaundice (TSB ranging 33.5-38 mg/dL; 573-650 µmol/L) had residual neurologic and/or auditory impairment. A BIND score ≥4 had a specificity of 87.3% and a sensitivity of 97.4% for predicting poor neurologic outcomes (receiver operating characteristic analysis). BIND scores trended higher with severe hyperbilirubinemia (r 2  = 0.54, P < .005), but 5/39 (13%) infants with TSB ≥36.5 mg/dL (624 µmol/L) had BIND scores ≤3, and normal outcomes at 3-5 months. The BIND score can be used to evaluate the severity of acute bilirubin encephalopathy and predict residual neurologic and hearing dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology.

PubMed

Wijdicks, Eelco F M; Varelas, Panayiotis N; Gronseth, Gary S; Greer, David M

2010-06-08

To provide an update of the 1995 American Academy of Neurology guideline with regard to the following questions: Are there patients who fulfill the clinical criteria of brain death who recover neurologic function? What is an adequate observation period to ensure that cessation of neurologic function is permanent? Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death? What is the comparative safety of techniques for determining apnea? Are there new ancillary tests that accurately identify patients with brain death? A systematic literature search was conducted and included a review of MEDLINE and EMBASE from January 1996 to May 2009. Studies were limited to adults. In adults, there are no published reports of recovery of neurologic function after a diagnosis of brain death using the criteria reviewed in the 1995 American Academy of Neurology practice parameter. Complex-spontaneous motor movements and false-positive triggering of the ventilator may occur in patients who are brain dead. There is insufficient evidence to determine the minimally acceptable observation period to ensure that neurologic functions have ceased irreversibly. Apneic oxygenation diffusion to determine apnea is safe, but there is insufficient evidence to determine the comparative safety of techniques used for apnea testing. There is insufficient evidence to determine if newer ancillary tests accurately confirm the cessation of function of the entire brain.

Comparison of Psychomotor Development Screening Test and Clinical Assessment of Psychomotor Development

PubMed

Radmilović, Goranka; Matijević, Valentina; Zavoreo, Iris

2016-12-01

Numerous adverse factors are acting in the prenatal, perinatal and postnatal period of life and may be the cause of later mild or severe deviations from normal psychomotor development. Therefore, it is crucial to identify infants with neurological risk factors and infants that already have a delay from orderly development, in order to immediately initiate the rehabilitation process. The aim of this study was to determine whether there is difference in the assessment of psychomotor development in neurological risk children based on the psychomotor development test (Croatian, Razvoj psihomotorike, RPM test) and clinical evaluation of neuromotor development. RPM test is designed for rough estimate of psychomotor development in children in the first two years of life. The study included 15 full term children (8 male and 7 female) with clinical diagnosis of mild paraparesis and mild deviation from normal psychological and social development, and 15 full term children (8 male and 7 female) without neurological risk factors and deviations from normal psychomotor development, all at the age of 12-24 months. Of the 15 children diagnosed with mild paraparesis, none had delayed psychomotor development, 6.7% had suspect development and 93.3% had normal development on RPM test. All children in the control group had normal development on RPM test. According to the results, the RPM test is not sensitive enough to detect mild neurodevelopmental disorders.

Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke

PubMed Central

Liu, Zhongwu; Chopp, Michael

2015-01-01

Astrocytes are the most abundant cell type within the central nervous system. They play essential roles in maintaining normal brain function, as they are a critical structural and functional part of the tripartite synapses and the neurovascular unit, and communicate with neurons, oligodendrocytes and endothelial cells. After an ischemic stroke, astrocytes perform multiple functions both detrimental and beneficial, for neuronal survival during the acute phase. Aspects of the astrocytic inflammatory response to stroke may aggravate the ischemic lesion, but astrocytes also provide benefit for neuroprotection, by limiting lesion extension via anti-excitotoxicity effects and releasing neurotrophins. Similarly, during the late recovery phase after stroke, the glial scar may obstruct axonal regeneration and subsequently reduce the functional outcome; however, astrocytes also contribute to angiogenesis, neurogenesis, synaptogenesis, and axonal remodeling, and thereby promote neurological recovery. Thus, the pivotal involvement of astrocytes in normal brain function and responses to an ischemic lesion designates them as excellent therapeutic targets to improve functional outcome following stroke. In this review, we will focus on functions of astrocytes and astrocyte-mediated events during stroke and recovery. We will provide an overview of approaches on how to reduce the detrimental effects and amplify the beneficial effects of astrocytes on neuroprotection and on neurorestoration post stroke, which may lead to novel and clinically relevant therapies for stroke. PMID:26455456

Regional CBF in chronic stable TBI treated with hyperbaric oxygen.

PubMed

Barrett, K F; Masel, B; Patterson, J; Scheibel, R S; Corson, K P; Mader, J T

2004-01-01

To investigate whether Hyperbaric Oxygen Therapy (HBO2) could improve neurologic deficits and regional cerebral blood flow (rCBF) in chronic traumatic brain injuries (TBI), the authors employed a nonrandomized control pilot trial. Five subjects, at least three years post head injury, received HBO2. Five head injured controls (HIC) were matched for age, sex, and type of injury. Five healthy subjects served as normal controls. Sixty-eight normal volunteers comprised a reference data bank against which to compare SPECT brain scans. HBO2 subjects received 120 HBO2 in blocks of 80 and 40 treatments with an interval five-month break. Normal controls underwent a single SPECT brain scan, HBO2, and repeat SPECT battery. TBI subjects were evaluated by neurologic, neuropsychometric, exercise testing, and pre and post study MRIs, or CT scans if MRI was contraindicated. Statistical Parametric Mapping was applied to SPECT scans for rCBF analysis. There were no significant objective changes in neurologic, neuropsychometric, exercise testing, MRIs, or rCBF. In this small pilot study, HBO2 did not effect clinical or regional cerebral blood flow improvement in TBI subjects.

Cell biology of spinocerebellar ataxia.

PubMed

Orr, Harry T

2012-04-16

Ataxia is a neurological disorder characterized by loss of control of body movements. Spinocerebellar ataxia (SCA), previously known as autosomal dominant cerebellar ataxia, is a biologically robust group of close to 30 progressive neurodegenerative diseases. Six SCAs, including the more prevalent SCA1, SCA2, SCA3, and SCA6 along with SCA7 and SCA17 are caused by expansion of a CAG repeat that encodes a polyglutamine tract in the affected protein. How the mutated proteins in these polyglutamine SCAs cause disease is highly debated. Recent work suggests that the mutated protein contributes to pathogenesis within the context of its "normal" cellular function. Thus, understanding the cellular function of these proteins could aid in the development of therapeutics.

Disruption of striatal-enriched protein tyrosine phosphatase (STEP) function in neuropsychiatric disorders

PubMed Central

Karasawa, Takatoshi; Lombroso, Paul J.

2014-01-01

Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific tyrosine phosphatase that plays a major role in the development of synaptic plasticity. Recent findings have implicated STEP in several psychiatric and neurological disorders, including Alzheimer’s disease, schizophrenia, fragile X syndrome, Huntington’s disease, stroke/ischemia, and stress-related psychiatric disorders. In these disorders, STEP protein expression levels and activity are dysregulated, contributing to the cognitive deficits that are present. In this review, we focus on the most recent findings on STEP, discuss how STEP expression and activity are maintained during normal cognitive function, and how disruptions in STEP activity contribute to a number of illnesses. PMID:25218562

Characterization and functional analysis of cellular immunity in mice with biotinidase deficiency.

PubMed

Pindolia, Kirit; Li, Hong; Cardwell, Cisley; Wolf, Barry

2014-05-01

Biotinidase deficiency is an autosomal recessively inherited metabolic disorder that can be easily and effectively treated with pharmacological doses of the vitamin, biotin. Untreated children with profound biotinidase deficiency may exhibit neurological, cutaneous and cellular immunological abnormalities, specifically candida infections. To better understand the immunological dysfunction in some symptomatic individuals with biotinidase deficiency, we studied various aspects of immunological function in a genetically engineered knock-out mouse with biotinidase deficiency. The mouse has no detectable biotinidase activity and develops neurological and cutaneous symptoms similar to those seen in symptomatic children with the disorder. Mice with profound biotinidase deficiency on a biotin-restricted diet had smaller thymuses and spleens than identical mice fed a biotin-replete diet or wildtype mice on either diet; however, the organ to body weight ratios were not significantly different. Thymus histology was normal. Splenocyte subpopulation study showed a significant increase in CD4 positive cells. In addition, in vitro lymphocyte proliferation assays consistently showed diminished proliferation in response to various immunological stimuli. Not all symptomatic individuals with profound biotinidase deficiency develop immunological dysfunction; however, our results do show significant alterations in cellular immunological function that may contribute and/or provide a mechanism(s) for the cellular immunity abnormalities in individuals with biotinidase deficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

Encephalopathy in acute liver failure resulting from acetaminophen intoxication: new observations with potential therapy.

PubMed

Brusilow, Saul W; Cooper, Arthur J L

2011-11-01

Hyperammonemia is a major contributing factor to the encephalopathy associated with liver disease. It is now generally accepted that hyperammonemia leads to toxic levels of glutamine in astrocytes. However, the mechanism by which excessive glutamine is toxic to astrocytes is controversial. Nevertheless, there is strong evidence that glutamine-induced osmotic swelling, especially in acute liver failure, is a contributing factor: the osmotic gliopathy theory. The object of the current communication is to present evidence for the osmotic gliopathy theory in a hyperammonemic patient who overdosed on acetaminophen. Case report. Johns Hopkins Hospital. A 22-yr-old woman who, 36 hrs before admission, ingested 15 g acetaminophen was admitted to the Johns Hopkins Hospital. She was treated with N-acetylcysteine. Physical examination was unremarkable; her mental status was within normal limits and remained so until approximately 72 hrs after ingestion when she became confused, irritable, and agitated. She was intubated, ventilated, and placed on lactulose. Shortly thereafter, she was noncommunicative, unresponsive to painful stimuli, and exhibited decerebrate posturing. A clinical diagnosis of cerebral edema and increased intracranial pressure was made. She improved very slowly until 180 hrs after ingestion when she moved all extremities. She woke up shortly thereafter. Despite the fact that hyperammonemia is a major contributing factor to the encephalopathy observed in acute liver failure, the patient's plasma ammonia peaked when she exhibited no obvious neurologic deficit. Thereafter, her plasma ammonia decreased precipitously in parallel with a worsening neurologic status. She was deeply encephalopathic during a period when her liver function and plasma ammonia had normalized. Plasma glutamine levels in this patient were high but began to normalize several hours after plasma ammonia had returned to normal. The patient only started to recover as her plasma glutamine began to return to normal. We suggest that the biochemical data are consistent with the osmotic gliopathy theory--high plasma ammonia leads to high plasma glutamine--an indicator of excess glutamine in astrocytes (the site of brain glutamine synthesis). This excess glutamine leads to osmotic stress in these cells. The lag in recovery of brain function presumably reflects time taken for the astrocyte glutamine concentration to return to normal. We hypothesize that an inhibitor of brain glutamine synthesis may be an effective treatment modality for acute liver failure.

Encephalopathy in acute liver failure resulting from acetaminophen intoxication: New observations with potential therapy

PubMed Central

Brusilow, Saul W; Cooper, Arthur J.L.

2011-01-01

Objective Hyperammonemia is a major contributing factor to the encephalopathy associated with liver disease. It is now generally accepted that hyperammonemia leads to toxic levels of glutamine in astrocytes. However, the mechanism by which excessive glutamine is toxic to astrocytes is controversial. Nevertheless, there is strong evidence that glutamine-induced osmotic swelling, especially in acute liver failure (ALF), is a contributing factor – the osmotic gliopathy theory. The object of the current communication is to present evidence for the osmotic gliopathy theory in a hyperammonemic patient who overdosed on acetaminophen. Design Case report. Setting Johns Hopkins Hospital. Patient A 22-year old white female who, 36 hours prior to admission, ingested 15 grams of acetaminophen was admitted to the Johns Hopkins Hospital. Physical examination was unremarkable; her mental status was within normal limits and remained so until approximately 72 hours after ingestion when she became confused, irritable and agitated. Interventions She was intubated, ventilated and placed on lactulose. Shortly thereafter she was non-communicative, unresponsive to painful stimuli and exhibited decerebrate posturing. A clinical diagnosis of cerebral edema and increased intracranial pressure (ICP) was made. She improved very slowly until 180 hours after ingestion when she moved all extremities. She woke up shortly thereafter. Measurements and main results Despite the fact that hyperammonemia is a major contributing factor to the encephalopathy observed in ALF the patient’s plasma ammonia peaked when she exhibited no obvious neurological deficit. Thereafter, her plasma ammonia decreased precipitously in parallel with a worsening neurological status. She was deeply encephalopathic during a period when her liver function and plasma ammonia had normalized. Plasma glutamine levels in this patient were high, but began to normalize several hours after plasma ammonia had returned to normal. The patient only commenced to recover as her plasma glutamine began to return to normal. Conclusions We suggest that the biochemical data are consistent with the osmotic gliopathy theory – high plasma ammonia leads to high plasma glutamine – an indicator of excess glutamine in astrocytes (the site of brain glutamine synthesis). This excess glutamine leads to osmotic stress in these cells. The lag in recovery of brain function presumably reflects time taken for the astrocyte glutamine concentration to return to normal. We hypothesize that an inhibitor of brain glutamine synthesis may be an effective treatment modality for ALF. PMID:21705899

Motor Imitation Abilities and Neurological Signs in Autistic Children.

ERIC Educational Resources Information Center

Jones, Vicki; Prior, Margot

1985-01-01

Ten autistic children were compared with 10 chronologically and mentally normal children on two tests of motor imitation and on the Herzig Battery for Non-Focal Neurological Signs. Results indicated that autistic Ss had significant handicaps in the neurodevelopmental area, with very poor performance on motor imitation tasks and a universal and…

NEUROLOGICAL AND MEDICAL FACTORS DISCRIMINATING BETWEEN NORMAL CHILDREN AND THOSE WITH LEARNING DISABILITY.

ERIC Educational Resources Information Center

FORREST, THOMAS

COMPREHENSIVE NEUROLOGICAL EXAMINATIONS WERE ADMINISTERED TO THE 264 CHILDREN DIVIDED INTO FOUR GROUPS--EDUCATIONALLY HANDICAPPED (EH), SUCCESSFUL ACADEMIC (SA) CONTROLS, AND THE SIBLINGS OF EACH GROUP (EHS AND SAS). ON SEVERAL MEASURES AND TASKS THE EH CHILDREN WERE DIFFERENTIATED FROM THE SA CHILDREN, AND STRONG SIMILARITIES WERE ALSO FOUND…

Temporal resolution in individuals with neurological disorders

PubMed Central

Rabelo, Camila Maia; Weihing, Jeffrey A; Schochat, Eliane

2015-01-01

OBJECTIVE: Temporal processing refers to the ability of the central auditory nervous system to encode and detect subtle changes in acoustic signals. This study aims to investigate the temporal resolution ability of individuals with mesial temporal sclerosis and to determine the sensitivity and specificity of the gaps-in-noise test in identifying this type of lesion. METHOD: This prospective study investigated differences in temporal resolution between 30 individuals with normal hearing and without neurological lesions (G1) and 16 individuals with both normal hearing and mesial temporal sclerosis (G2). Test performances were compared, and the sensitivity and specificity were calculated. RESULTS: There was no difference in gap detection thresholds between the two groups, although G1 revealed better average thresholds than G2 did. The sensitivity and specificity of the gaps-in-noise test for neurological lesions were 68% and 98%, respectively. CONCLUSIONS: Temporal resolution ability is compromised in individuals with neurological lesions caused by mesial temporal sclerosis. The gaps-in-noise test was shown to be a sensitive and specific measure of central auditory dysfunction in these patients. PMID:26375561

Resting-state activity in development and maintenance of normal brain function.

PubMed

Pizoli, Carolyn E; Shah, Manish N; Snyder, Abraham Z; Shimony, Joshua S; Limbrick, David D; Raichle, Marcus E; Schlaggar, Bradley L; Smyth, Matthew D

2011-07-12

One of the most intriguing recent discoveries concerning brain function is that intrinsic neuronal activity manifests as spontaneous fluctuations of the blood oxygen level-dependent (BOLD) functional MRI signal. These BOLD fluctuations exhibit temporal synchrony within widely distributed brain regions known as resting-state networks. Resting-state networks are present in the waking state, during sleep, and under general anesthesia, suggesting that spontaneous neuronal activity plays a fundamental role in brain function. Despite its ubiquitous presence, the physiological role of correlated, spontaneous neuronal activity remains poorly understood. One hypothesis is that this activity is critical for the development of synaptic connections and maintenance of synaptic homeostasis. We had a unique opportunity to test this hypothesis in a 5-y-old boy with severe epileptic encephalopathy. The child developed marked neurologic dysfunction in association with a seizure disorder, resulting in a 1-y period of behavioral regression and progressive loss of developmental milestones. His EEG showed a markedly abnormal pattern of high-amplitude, disorganized slow activity with frequent generalized and multifocal epileptiform discharges. Resting-state functional connectivity MRI showed reduced BOLD fluctuations and a pervasive lack of normal connectivity. The child underwent successful corpus callosotomy surgery for treatment of drop seizures. Postoperatively, the patient's behavior returned to baseline, and he resumed development of new skills. The waking EEG revealed a normal background, and functional connectivity MRI demonstrated restoration of functional connectivity architecture. These results provide evidence that intrinsic, coherent neuronal signaling may be essential to the development and maintenance of the brain's functional organization.

Circular RNA: a new star in neurological diseases.

PubMed

Li, Tao-Ran; Jia, Yan-Jie; Wang, Qun; Shao, Xiao-Qiu; Lv, Rui-Juan

2017-08-01

Circular RNAs (circRNAs) are novel endogenous non-coding RNAs characterized by the presence of a covalent bond linking the 3' and 5' ends generated by backsplicing. In this review, we summarize a number of the latest theories regarding the biogenesis, properties and functions of circRNAs. Specifically, we focus on the advancing characteristics and functions of circRNAs in the brain and neurological diseases. CircRNAs exhibit the characteristics of species conservation, abundance and tissue/developmental-stage-specific expression in the brain. We also describe the relationship between circRNAs and several neurological diseases and highlight their functions in neurological diseases.

Impaired angiogenesis in aminopeptidase N-null mice

PubMed Central

Rangel, Roberto; Sun, Yan; Guzman-Rojas, Liliana; Ozawa, Michael G.; Sun, Jessica; Giordano, Ricardo J.; Van Pelt, Carolyn S.; Tinkey, Peggy T.; Behringer, Richard R.; Sidman, Richard L.; Arap, Wadih; Pasqualini, Renata

2007-01-01

Aminopeptidase N (APN, CD13; EC 3.4.11.2) is a transmembrane metalloprotease with several functions, depending on the cell type and tissue environment. In tumor vasculature, APN is overexpressed in the endothelium and promotes angiogenesis. However, there have been no reports of in vivo inactivation of the APN gene to validate these findings. Here we evaluated, by targeted disruption of the APN gene, whether APN participates in blood vessel formation and function under normal conditions. Surprisingly, APN-null mice developed with no gross or histological abnormalities. Standard neurological, cardiovascular, metabolic, locomotor, and hematological studies revealed no alterations. Nonetheless, in oxygen-induced retinopathy experiments, APN-deficient mice had a marked and dose-dependent deficiency of the expected retinal neovascularization. Moreover, gelfoams embedded with growth factors failed to induce functional blood vessel formation in APN-null mice. These findings establish that APN-null mice develop normally without physiological alterations and can undergo physiological angiogenesis but show a severely impaired angiogenic response under pathological conditions. Finally, in addition to vascular biology research, APN-null mice may be useful reagents in other medical fields such as malignant, cardiovascular, immunological, or infectious diseases. PMID:17360568

A Korean patient with glutaric aciduria type 1 with a novel mutation in the glutaryl CoA dehydrogenase gene.

PubMed

Kim, Hee Su; Yu, Hee Joon; Lee, Jeehun; Park, Hyung-Doo; Kim, Ji Hye; Shin, Hyung-Jin; Jin, Dong Kyu; Lee, Munhyang

2014-01-01

Mutations in the glutaryl-CoA dehydrogenase gene can result in Glutaric aciduria type 1(GA 1) by accumulation of glutaric acid, 3-hydroxyglutaric acid (3-OH-GA), and glutarylcarnitine (C5DC). GA 1 is characterized by macrocephaly, subdural hemorrhage (SDH), and dystonic movement disorder after acute encephalopathic crisis. We report a Korean patient with GA1 and a novel mutation. A 16-month-old boy presented with SDH, macrocephaly, and developmental delay. In the neurologic examination, the patient had mild axial hypotonia, but otherwise normal neurologic functions. The brain MRI showed large amounts of bilateral SDH and high signal intensity in both basal ganglia and thalamus. Metabolic screening tests detected highly elevated urinary GA levels but 3-OH-glutaric acid was normal. C5DC was 0.94 μM/L (reference range < 0.3 μM/L). The patient had compound heterozygous mutations of the GCDH gene: p.Arg257Gln (c.770G>A) and p.Cys308Arg (c.922T>C). p.Cys308Arg is a novel mutation; reports of p.Arg257Gln were also rare both in Caucasians and Asian populations. In summary, we hereby report one Korean patient with GA1 with clinical, biochemical, and radiologic characteristics confirmed by genetic analysis.

Sulcal depth-based cortical shape analysis in normal healthy control and schizophrenia groups

NASA Astrophysics Data System (ADS)

Lyu, Ilwoo; Kang, Hakmook; Woodward, Neil D.; Landman, Bennett A.

2018-03-01

Sulcal depth is an important marker of brain anatomy in neuroscience/neurological function. Previously, sulcal depth has been explored at the region-of-interest (ROI) level to increase statistical sensitivity to group differences. In this paper, we present a fully automated method that enables inferences of ROI properties from a sulcal region- focused perspective consisting of two main components: 1) sulcal depth computation and 2) sulcal curve-based refined ROIs. In conventional statistical analysis, the average sulcal depth measurements are employed in several ROIs of the cortical surface. However, taking the average sulcal depth over the full ROI blurs overall sulcal depth measurements which may result in reduced sensitivity to detect sulcal depth changes in neurological and psychiatric disorders. To overcome such a blurring effect, we focus on sulcal fundic regions in each ROI by filtering out other gyral regions. Consequently, the proposed method results in more sensitive to group differences than a traditional ROI approach. In the experiment, we focused on a cortical morphological analysis to sulcal depth reduction in schizophrenia with a comparison to the normal healthy control group. We show that the proposed method is more sensitivity to abnormalities of sulcal depth in schizophrenia; sulcal depth is significantly smaller in most cortical lobes in schizophrenia compared to healthy controls (p < 0.05).

Relationships between brain and body temperature, clinical and imaging outcomes after ischemic stroke

PubMed Central

Karaszewski, Bartosz; Carpenter, Trevor K; Thomas, Ralph G R; Armitage, Paul A; Lymer, Georgina Katherine S; Marshall, Ian; Dennis, Martin S; Wardlaw, Joanna M

2013-01-01

Pyrexia soon after stroke is associated with severe stroke and poor functional outcome. Few studies have assessed brain temperature after stroke in patients, so little is known of its associations with body temperature, stroke severity, or outcome. We measured temperatures in ischemic and normal-appearing brain using 1H-magnetic resonance spectroscopy and its correlations with body (tympanic) temperature measured four-hourly, infarct growth by 5 days, early neurologic (National Institute of Health Stroke Scale, NIHSS) and late functional outcome (death or dependency). Among 40 patients (mean age 73 years, median NIHSS 7, imaged at median 17 hours), temperature in ischemic brain was higher than in normal-appearing brain on admission (38.6°C-core, 37.9°C-contralateral hemisphere, P=0.03) but both were equally elevated by 5 days; both were higher than tympanic temperature. Ischemic lesion temperature was not associated with NIHSS or 3-month functional outcome; in contrast, higher contralateral normal-appearing brain temperature was associated with worse NIHSS, infarct expansion and poor functional outcome, similar to associations for tympanic temperature. We conclude that brain temperature is higher than body temperature; that elevated temperature in ischemic brain reflects a local tissue response to ischemia, whereas pyrexia reflects the systemic response to stroke, occurs later, and is associated with adverse outcomes. PMID:23571281

PET evaluation of the dopamine system of the human brain

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

Volkow, N.D.; Fowler, J.S.; Gatley, S.

1996-07-01

Dopamine plays a pivotal role in the regulation and control of movement, motivation and cognition. It also is closely linked to reward, reinforcement and addiction. Abnormalities in brain dopamine are associated with many neurological and psychiatric disorders including Parkinson`s disease, schizophrenia and substance abuse. This close association between dopamine and neurological and psychiatric diseases and with substance abuse make it an important topic in research in the neurosciences and an important molecular target in drug development. PET enables the direct measurement of components of the dopamine system in the living human brain. It relies on radiotracers which label dopamine receptors,more » dopamine transporters, precursors of dopamine or compounds which have specificity for the enzymes which degrade dopamine. Additionally, by using tracers that provide information on regional brain metabolism or blood flow as well as neurochemically specific pharmacological interventions, PET can be used to assess the functional consequences of change in brain dopamine activity. PET dopamine measurements have been used to investigate the normal human brain and its involvement in psychiatric and neurological diseases. It has also been used in psychopharmacological research to investigate dopamine drugs used in the treatment of Parkinson`s disease and of schizophrenia as well as to investigate the effects of drugs of abuse on the dopamine system. Since various functional and neurochemical parameters can be studied in the same subject, PET enables investigation of the functional integrity of the dopamine system in the human brain and investigation of the interactions of dopamine with other neurotransmitters. This paper summarizes the different tracers and experimental strategies developed to evaluate the various elements of the dopamine system in the human brain with PET and their applications to clinical research. 254 refs., 7 figs., 3 tabs.« less

Quantitative somatosensory testing of the penis: optimizing the clinical neurological examination.

PubMed

Bleustein, Clifford B; Eckholdt, Haftan; Arezzo, Joseph C; Melman, Arnold

2003-06-01

Quantitative somatosensory testing, including vibration, pressure, spatial perception and thermal thresholds of the penis, has demonstrated neuropathy in patients with a history of erectile dysfunction of all etiologies. We evaluated which measurement of neurological function of the penis was best at predicting erectile dysfunction and examined the impact of location on the penis for quantitative somatosensory testing measurements. A total of 107 patients were evaluated. All patients were required to complete the erectile function domain of the International Index of Erectile Function (IIEF) questionnaire, of whom 24 had no complaints of erectile dysfunction and scored within the "normal" range on the IIEF. Patients were subsequently tested on ventral middle penile shaft, proximal dorsal midline penile shaft and glans penis (with foreskin retracted) for vibration, pressure, spatial perception, and warm and cold thermal thresholds. Mixed models repeated measures analysis of variance controlling for age, diabetes and hypertension revealed that method of measurement (quantitative somatosensory testing) was predictive of IIEF score (F = 209, df = 4,1315, p <0.001), while site of measurement on the penis was not. To determine the best method of measurement, we used hierarchical regression, which revealed that warm temperature was the best predictor of erectile dysfunction with pseudo R(2) = 0.19, p <0.0007. There was no significant improvement in predicting erectile dysfunction when another test was added. Using 37C and greater as the warm thermal threshold yielded a sensitivity of 88.5%, specificity 70.0% and positive predictive value 85.5%. Quantitative somatosensory testing using warm thermal threshold measurements taken at the glans penis can be used alone to assess the neurological status of the penis. Warm thermal thresholds alone offer a quick, noninvasive accurate method of evaluating penile neuropathy in an office setting.

Awake craniotomy and electrophysiological mapping for eloquent area tumours.

PubMed

Chacko, Ari George; Thomas, Santhosh George; Babu, K Srinivasa; Daniel, Roy Thomas; Chacko, Geeta; Prabhu, Krishna; Cherian, Varghese; Korula, Grace

2013-03-01

An awake craniotomy facilitates radical excision of eloquent area gliomas and ensures neural integrity during the excision. The study describes our experience with 67 consecutive awake craniotomies for the excision of such tumours. Sixty-seven patients with gliomas in or adjacent to eloquent areas were included in this study. The patient was awake during the procedure and intraoperative cortical and white matter stimulation was performed to safely maximize the extent of surgical resection. Of the 883 patients who underwent craniotomies for supratentorial intraaxial tumours during the study period, 84 were chosen for an awake craniotomy. Sixty-seven with a histological diagnosis of glioma were included in this study. There were 55 men and 12 women with a median age of 34.6 years. Forty-two (62.6%) patients had positive localization on cortical stimulation. In 6 (8.9%) patients white matter stimulation was positive, five of whom had responses at the end of a radical excision. In 3 patients who developed a neurological deficit during tumour removal, white matter stimulation was negative and cessation of the surgery did not result in neurological improvement. Sixteen patients (24.6%) had intraoperative neurological deficits at the time of wound closure, 9 (13.4%) of whom had persistent mild neurological deficits at discharge, while the remaining 7 improved to normal. At a mean follow-up of 40.8 months, only 4 (5.9%) of these 9 patients had persistent neurological deficits. Awake craniotomy for excision of eloquent area gliomas enable accurate mapping of motor and language areas as well as continuous neurological monitoring during tumour removal. Furthermore, positive responses on white matter stimulation indicate close proximity of eloquent cortex and projection fibres. This should alert the surgeon to the possibility of postoperative deficits to change the surgical strategy. Thus the surgeon can resect tumour safely, with the knowledge that he has not damaged neurological function up to that point in time thus maximizing the tumour resection and minimizing neurological deficits. Copyright © 2012 Elsevier B.V. All rights reserved.

Harnessing plasticity for the treatment of neurosurgical disorders: an overview.

PubMed

Chen, H Isaac; Attiah, Mark; Baltuch, Gordon; Smith, Douglas H; Hamilton, Roy H; Lucas, Timothy H

2014-11-01

Plasticity is fundamental to normal central nervous system function and its response to injury. Understanding this adaptive capacity is central to the development of novel surgical approaches to neurologic disease. These innovative interventions offer the promise of maximizing functional recovery for patients by harnessing targeted plasticity. Developing novel therapies will require the unprecedented integration of neuroscience, bioengineering, molecular biology, and physiology. Such synergistic approaches will create therapeutic options for patients previously outside of the scope of neurosurgery, such as those with permanent disability after traumatic brain injury or stroke. In this review, we synthesize the rapidly evolving field of plasticity and explore ways that neurosurgeons may enhance functional recovery in the future. We conclude that understanding plasticity is fundamental to modern neurosurgical education and practice. Copyright © 2014 Elsevier Inc. All rights reserved.

Systematic changes in position sense accompany normal aging across adulthood.

PubMed

Herter, Troy M; Scott, Stephen H; Dukelow, Sean P

2014-03-25

Development of clinical neurological assessments aimed at separating normal from abnormal capabilities requires a comprehensive understanding of how basic neurological functions change (or do not change) with increasing age across adulthood. In the case of proprioception, the research literature has failed to conclusively determine whether or not position sense in the upper limb deteriorates in elderly individuals. The present study was conducted a) to quantify whether upper limb position sense deteriorates with increasing age, and b) to generate a set of normative data that can be used for future comparisons with clinical populations. We examined position sense in 209 healthy males and females between the ages of 18 and 90 using a robotic arm position-matching task that is both objective and reliable. In this task, the robot moved an arm to one of nine positions and subjects attempted to mirror-match that position with the opposite limb. Measures of position sense were recorded by the robotic apparatus in hand-and joint-based coordinates, and linear regressions were used to quantify age-related changes and percentile boundaries of normal behaviour. For clinical comparisons, we also examined influences of sex (male versus female) and test-hand (dominant versus non-dominant) on all measures of position sense. Analyses of hand-based parameters identified several measures of position sense (Variability, Shift, Spatial Contraction, Absolute Error) with significant effects of age, sex, and test-hand. Joint-based parameters at the shoulder (Absolute Error) and elbow (Variability, Shift, Absolute Error) also exhibited significant effects of age and test-hand. The present study provides strong evidence that several measures of upper extremity position sense exhibit declines with age. Furthermore, this data provides a basis for quantifying when changes in position sense are related to normal aging or alternatively, pathology.

Vestibular-evoked myogenic potential (VEMP) in the evaluation of schistosomal myeloradiculopathy.

PubMed

Felipe, Lilian; Gonçalves, Denise Utsch; Tavares, Maurício Campelo; Sousa-Pereira, Sílvio Roberto; Antunes, Carlos Maurício de Figueiredo; Lambertucci, José Roberto

2009-10-01

Schistosomal myeloradiculopathy (SMR) is the most severe and disabling form of schistosomiasis. The diagnosis is based on clinical, laboratory, and image data. Vestibular-evoked myogenic potential (VEMP) is a neurophysiologic test that assesses the vestibulospinal pathway through acoustic or galvanic stimuli. The aim of this study was to evaluate cervical spinal abnormalities in patients with SMR. Fifty-two subjects were evaluated, of whom 29 had SMR and 30 did not (normal control). Normal VEMP was observed in all volunteers without SMR. Abnormal VEMP was recorded in 34% of the group with SMR. After treatment, abnormal VEMP was found in 80% of those with persistent neurologic abnormalities. VEMP is a functional test, and the alteration may precede image abnormalities. This procedure may be useful for early diagnosis of schistosomal cervical spinal cord involvement.

A neural network model for transference and repetition compulsion based on pattern completion.

PubMed

Javanbakht, Arash; Ragan, Charles L

2008-01-01

In recent years because of the fascinating growth of the body of neuroscientific knowledge, psychoanalytic scientists have worked on models for the neurological substrates of key psychoanalytic concepts. Transference is an important example. In this article, the psychological process of transference is described, employing the neurological function of pattern completion in hippocampal and thalamo-cortical pathways. Similarly, repetition compulsion is seen as another type of such neurological function; however, it is understood as an attempt for mastery of the unknown, rather than simply for mastery of past experiences and perceptions. Based on this suggested model of neurological function, the myth of the psychoanalyst as blank screen is seen as impossible and ineffective, based on neurofunctional understandings of neuropsychological process. The mutative effect of psychoanalytic therapy, correcting patterns of pathological relatedness, is described briefly from conscious and unconscious perspectives. While cognitive understanding (insight) helps to modify transferentially restored, maladaptive patterns of relatedness, the development of more adaptive patterns is also contingent upon an affective experience (working through), which alters the neurological substrates of unconscious, pathological affective patterns and their neurological functional correlates.

Dichotic listening and otoacoustic emissions: shared variance between cochlear function and dichotic listening performance in adults with normal hearing.

PubMed

Markevych, Vladlena; Asbjørnsen, Arve E; Lind, Ola; Plante, Elena; Cone, Barbara

2011-07-01

The present study investigated a possible connection between speech processing and cochlear function. Twenty-two subjects with age range from 18 to 39, balanced for gender with normal hearing and without any known neurological condition, were tested with the dichotic listening (DL) test, in which listeners were asked to identify CV-syllables in a nonforced, and also attention-right, and attention-left condition. Transient evoked otoacoustic emissions (TEOAEs) were recorded for both ears, with and without the presentation of contralateral broadband noise. The main finding was a strong negative correlation between language laterality as measured with the dichotic listening task and of the TEOAE responses. The findings support a hypothesis of shared variance between central and peripheral auditory lateralities, and contribute to the attentional theory of auditory lateralization. The results have implications for the understanding of the cortico-fugal efferent control of cochlear activity. 2011 Elsevier Inc. All rights reserved.

[Association between polymorphism of dopamine β-hydroxylase and neurological dysfunction hereditary susceptibility of electric welders].

PubMed

Chen, Wen-wen; Shao, Hua

2010-09-01

To investigate the relationship between genetic polymorphism of dopamine β-hydroxylase (DBH) and manganese-induced nerve injury. In a cross-sectional study, 402 electric welders who had worked over one year in relatively fixed sites were recruited, and the concentration of manganese in which they worked was stable. These samples was divided into high exposure group (CEI > 1) and low exposure group (CEI < 1) by CEI. Between the two groups, the groups were divided into abnormal group and normal group according to the result of neurologic check (there were 81 workers with abnormal neurological dysfunction in high exposure group and 28 workers in low exposure group, P < 0.05). Polymorphism of DBH gene was analyzed with polymerase chain reaction-restriction fragment length polymorphism. The distribution of A2A2 genotype and A2 allele of DBH was significantly different. In high exposure group, the distribution of A2A2 genotype and A2 allele of DBH in abnormal group was significantly wider than in normal group (A2A2 genotype, OR = 1.248, P < 0.05, A2 allele, OR = 1.103, P < 0.05). In low exposure group, the distribution of A2 allele of DBH in abnormal group was significantly wider than in normal group (OR = 1.176, P < 0.05). The individuals who carry A2A2 genotype and A2 allele of DBH have increased risk of neurological dysfunction after explosion to manganese for a certain time, which suggests that polymorphism of DBH (intron 5 Taq I) would play a great role in hereditary susceptibility of neurological dysfunction cause by manganese.

Improved Neuropsychological and Neurological Functioning Across Three Antiretroviral Regimens in Diverse Resource-Limited Settings: AIDS Clinical Trials Group Study A5199, the International Neurological Study

PubMed Central

Robertson, K.; Jiang, H.; Kumwenda, J.; Supparatpinyo, K.; Evans, S.; Campbell, T. B.; Price, R.; Tripathy, S.; Kumarasamy, N.; La Rosa, A.; Santos, B.; Silva, M. T.; Montano, S.; Kanyama, C.; Faesen, S.; Murphy, R.; Hall, C.; Marra, C. M.; Marcus, C.; Berzins, B.; Allen, R.; Housseinipour, M.; Amod, F.; Sanne, I.; Hakim, J.; Walawander, A.; Nair, A.

2012-01-01

Background. AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings. Methods. Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations. Results. The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01). Conclusions. The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization –recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction. Clinical trials registration.  NCT00096824. PMID:22661489

Speech Motor Sequence Learning: Acquisition and Retention in Parkinson Disease and Normal Aging

ERIC Educational Resources Information Center

Whitfield, Jason A.; Goberman, Alexander M.

2017-01-01

Purpose: The aim of the current investigation was to examine speech motor sequence learning in neurologically healthy younger adults, neurologically healthy older adults, and individuals with Parkinson disease (PD) over a 2-day period. Method: A sequential nonword repetition task was used to examine learning over 2 days. Participants practiced a…

Short report

PubMed Central

Quinn, P. T.; Andrews, Gavin

1977-01-01

Stuttering associated with neurological pathology in normal adult speakers is uncommon, has no consistent clinicopathological picture, and its significance is too easily dismissed. A case is reported showing that stuttering may be a presenting symptom of progressive neurological disease, and another case demonstrates that a speech disorder which is indistinguishable from common stuttering may follow cerebral follow injury in adulthood. PMID:915515

Resuscitation with Lyophilized Plasma Is Safe and Improves Neurological Recovery in a Long-Term Survival Model of Swine Subjected to Traumatic Brain Injury, Hemorrhagic Shock, and Polytrauma.

PubMed

Georgoff, Patrick E; Nikolian, Vahagn C; Halaweish, Ihab; Chtraklin, Kiril; Bruhn, Peter J; Eidy, Hassan; Rasmussen, Monica; Li, Yongqing; Srinivasan, Ashok; Alam, Hasan B

2017-07-01

We have shown previously that fresh frozen plasma (FFP) and lyophilized plasma (LP) decrease brain lesion size and improve neurological recovery in a swine model of traumatic brain injury (TBI) and hemorrhagic shock (HS). In this study, we examine whether these findings can be validated in a clinically relevant model of severe TBI, HS, and polytrauma. Female Yorkshire swine were subjected to TBI (controlled cortical impact), hemorrhage (40% volume), grade III liver and splenic injuries, rib fracture, and rectus abdominis crush. The animals were maintained in a state of shock (mean arterial pressure 30-35 mm Hg) for 2 h, and then randomized to resuscitation with normal saline (NS), FFP, or LP (n = 5 swine/group). Animals were recovered and monitored for 30 d, during which time neurological recovery was assessed. Brain lesion sizes were measured via magnetic resonance imaging (MRI) on post-injury days (PID) three and 10. Animals were euthanized on PID 30. The severity of shock and response to resuscitation was similar in all groups. When compared with NS-treated animals, plasma-treated animals (FFP and LP) had significantly lower neurologic severity scores (PID 1-7) and a faster return to baseline neurological function. There was no significant difference in brain lesion sizes between groups. LP treatment was well tolerated and similar to FFP. In this clinically relevant large animal model of severe TBI, HS, and polytrauma, we have shown that plasma-based resuscitation strategies are safe and result in neurocognitive recovery that is faster than recovery after NS-based resuscitation.

Evaluative procedures to detect, characterize, and assess the severity of diabetic neuropathy.

PubMed

Dyck, P J

1991-01-01

Minimal criteria for diabetic neuropathy need to be defined and universally applied. Standardized evaluative procedures need to be agreed and normal ranges determined from healthy volunteers. Types and stages of neuropathy should be established and assessments performed on representative populations of both Type 1 and Type 2 diabetic patients. Potential minimal criteria include absent ankle reflexes and vibratory sensation, and abnormalities of nerve conduction. However, the preferred criterion is the identification of more than two statistically defined abnormalities among symptoms and deficits, nerve conduction, quantitative sensory examination or quantitative autonomic examination. Various evaluative procedures are available. Symptoms should be assessed and scores can be assigned to neurological deficits. However, assessments of nerve conduction provide the most specific, objective, sensitive, and repeatable procedures, although these may be the least meaningful. Many techniques are available for quantitative sensory examination, but are poorly standardized and normal values are not available. For quantitative autonomic examination, tests are available for the adequacy of cardiovascular and peripheral vascular reflexes and increasingly for other autonomic functions. In any assessment of nerve function the conditions should be optimized and standardized, and stimuli defined. Specific instructions should be given and normal ranges established in healthy volunteers.

Modern network science of neurological disorders.

PubMed

Stam, Cornelis J

2014-10-01

Modern network science has revealed fundamental aspects of normal brain-network organization, such as small-world and scale-free patterns, hierarchical modularity, hubs and rich clubs. The next challenge is to use this knowledge to gain a better understanding of brain disease. Recent developments in the application of network science to conditions such as Alzheimer's disease, multiple sclerosis, traumatic brain injury and epilepsy have challenged the classical concept of neurological disorders being either 'local' or 'global', and have pointed to the overload and failure of hubs as a possible final common pathway in neurological disorders.

Thyroid function and the risk of dementia: The Rotterdam Study.

PubMed

Chaker, Layal; Wolters, Frank J; Bos, Daniel; Korevaar, Tim I M; Hofman, Albert; van der Lugt, Aad; Koudstaal, Peter J; Franco, Oscar H; Dehghan, Abbas; Vernooij, Meike W; Peeters, Robin P; Ikram, M Arfan

2016-10-18

To study the role of thyroid function in dementia, cognitive function, and subclinical vascular brain disease with MRI. Analyses were performed within the Rotterdam Study (baseline 1997), a prospective, population-based cohort. We evaluated the association of thyroid-stimulating hormone (TSH) and free thyroxine with incident dementia using Cox models adjusted for age, sex, cardiovascular risk factors, and education. Absolute risks were calculated accounting for death as a competing risk factor. Associations of thyroid function with cognitive test scores and subclinical vascular brain disease (white matter lesions, lacunes, and microbleeds) were assessed with linear or logistic regression. Additionally, we stratified by sex and restricted analyses to normal thyroid function. We included 9,446 participants with a mean age of 65 years. During follow-up (mean 8.0 years), 601 participants had developed dementia. Higher TSH was associated with lower dementia risk in both the full and normal ranges of thyroid function (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.83-0.98; and HR 0.76, 95% CI 0.64-0.91, respectively). This association was independent of cardiovascular risk factors. Dementia risk was higher in individuals with higher free thyroxine (HR 1.04, 95% CI 1.01-1.07). Absolute 10-year dementia risk decreased from 15% to 10% with higher TSH in older women. Higher TSH was associated with better global cognitive scores (p = 0.021). Thyroid function was not related to subclinical vascular brain disease as indicated by MRI. High and high-normal thyroid function is associated with increased dementia risk. Thyroid function is not related to vascular brain disease as assessed by MRI, suggesting a role for thyroid hormone in nonvascular pathways leading to dementia. © 2016 American Academy of Neurology.

Brain magnetic resonance imaging and motor and intellectual functioning in 86 patients born at term with spastic diplegia.

PubMed

Numata, Yurika; Onuma, Akira; Kobayashi, Yasuko; Sato-Shirai, Ikuko; Tanaka, Soichiro; Kobayashi, Satoru; Wakusawa, Keisuke; Inui, Takehiko; Kure, Shigeo; Haginoya, Kazuhiro

2013-02-01

To investigate the association between magnetic resonance imaging (MRI) patterns and motor function, epileptic episodes, and IQ or developmental quotient in patients born at term with spastic diplegia. Eighty-six patients born at term with cerebral palsy (CP) and spastic diplegia (54 males, 32 females; median age 20 y, range 7-42 y) among 829 patients with CP underwent brain MRI between 1990 and 2008. The MRI and clinical findings were analysed retrospectively. Intellectual disability was classified according to the Enjoji developmental test or the Wechsler Intelligence Scale for Children (3rd edition). The median ages at diagnosis of CP, assignment of Gross Motor Function Classification System (GMFCS) level, cognitive assessment, and MRI were 2 years (range 5 mo-8 y), 6 years (2 y 8 mo-19 y), 6 years (1 y 4 mo-19 y), and 7 years (10 mo-30 y) respectively. MRI included normal findings (41.9%), periventricular leukomalacia, hypomyelination, and porencephaly/periventricular venous infarction. The frequency of patients in GMFCS levels III to V and intellectual disability did not differ between those with normal and abnormal MRI findings. Patients with normal MRI findings had significantly fewer epileptic episodes than those with abnormal ones (p=0.001). Varied MRI findings, as well as the presence of severe motor dysfunction and intellectual disability (despite normal MRI), suggest that patients born at term with spastic diplegia had heterogeneous and unidentified pathophysiology. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

Cingulo-insular structural alterations associated with psychogenic symptoms, childhood abuse and PTSD in functional neurological disorders.

PubMed

Perez, David L; Matin, Nassim; Barsky, Arthur; Costumero-Ramos, Victor; Makaretz, Sara J; Young, Sigrid S; Sepulcre, Jorge; LaFrance, W Curt; Keshavan, Matcheri S; Dickerson, Bradford C

2017-06-01

Adverse early-life events are predisposing factors for functional neurological disorder (FND) and post-traumatic stress disorder (PTSD). Cingulo-insular regions are implicated in the biology of both conditions and are sites of stress-mediated neuroplasticity. We hypothesised that functional neurological symptoms and the magnitude of childhood abuse would be associated with overlapping anterior cingulate cortex (ACC) and insular volumetric reductions, and that FND and PTSD symptoms would map onto distinct cingulo-insular areas. This within-group voxel-based morphometry study probes volumetric associations with self-report measures of functional neurological symptoms, adverse life events and PTSD symptoms in 23 mixed-gender FND patients. Separate secondary analyses were also performed in the subset of 18 women with FND to account for gender-specific effects. Across the entire cohort, there were no statistically significant volumetric associations with self-report measures of functional neurological symptom severity or childhood abuse. In women with FND, however, parallel inverse associations were observed between left anterior insular volume and functional neurological symptoms as measured by the Patient Health Questionnaire-15 and the Screening for Somatoform Symptoms Conversion Disorder subscale. Similar inverse relationships were also appreciated between childhood abuse burden and left anterior insular volume. Across all subjects, PTSD symptom severity was inversely associated with dorsal ACC volume, and the magnitude of lifetime adverse events was inversely associated with left hippocampal volume. This study reveals distinct cingulo-insular alterations for FND and PTSD symptoms and may advance our understanding of FND. Potential biological convergence between stress-related neuroplasticity, functional neurological symptoms and reduced insular volume was identified. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Psychogenic amnesia: syndromes, outcome, and patterns of retrograde amnesia.

PubMed

Harrison, Neil A; Johnston, Kate; Corno, Federica; Casey, Sarah J; Friedner, Kimberley; Humphreys, Kate; Jaldow, Eli J; Pitkanen, Mervi; Kopelman, Michael D

2017-09-01

There are very few case series of patients with acute psychogenic memory loss (also known as dissociative/functional amnesia), and still fewer studies of outcome, or comparisons with neurological memory-disordered patients. Consequently, the literature on psychogenic amnesia is somewhat fragmented and offers little prognostic value for individual patients. In the present study, we reviewed the case records and neuropsychological findings in 53 psychogenic amnesia cases (ratio of 3:1, males:females), in comparison with 21 consecutively recruited neurological memory-disordered patients and 14 healthy control subjects. In particular, we examined the pattern of retrograde amnesia on an assessment of autobiographical memory (the Autobiographical Memory Interview). We found that our patients with psychogenic memory loss fell into four distinct groups, which we categorized as: (i) fugue state; (ii) fugue-to-focal retrograde amnesia; (iii) psychogenic focal retrograde amnesia following a minor neurological episode; and (iv) patients with gaps in their memories. While neurological cases were characterized by relevant neurological symptoms, a history of a past head injury was actually more common in our psychogenic cases (P = 0.012), perhaps reflecting a 'learning episode' predisposing to later psychological amnesia. As anticipated, loss of the sense of personal identity was confined to the psychogenic group. However, clinical depression, family/relationship problems, financial/employment problems, and failure to recognize the family were also statistically more common in that group. The pattern of autobiographical memory loss differed between the psychogenic groups: fugue cases showed a severe and uniform loss of memories for both facts and events across all time periods, whereas the two focal retrograde amnesia groups showed a 'reversed' temporal gradient with relative sparing of recent memories. After 3-6 months, the fugue patients had improved to normal scores for facts and near-normal scores for events. By contrast, the two focal retrograde amnesia groups showed less improvement and continued to show a reversed temporal gradient. In conclusion, the outcome in psychogenic amnesia, particularly those characterized by fugue, is better than generally supposed. Findings are interpreted in terms of Markowitsch's and Kopelman's models of psychogenic amnesia, and with respect to Anderson's neuroimaging findings in memory inhibition. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Biodex Fall Risk Assessment in the Elderly With Ataxia: A New Age-Dependent Derived Index in Rehabilitation: An Observational Study.

PubMed

Prometti, Paola; Olivares, Adriana; Gaia, Giuseppina; Bonometti, Giampietro; Comini, Laura; Scalvini, Simonetta

2016-03-01

The aim of this study was to evaluate if the Biodex Fall Risk Assessment could provide an age-adjusted index useful for classifying patients at "risk of fall."This was a cohort study conducted on 61 chronic patients, in stable conditions, having a history of ataxia, difficulty in walking or loss of balance, and aged >64 years. These patients were coming from home to our Institute undergoing a period of in-hospital standard rehabilitation. Assessment of clinical parameters was performed at entry. Functional scales (Functional Independence Measure [FIM] for motor and cognitive function, Barthel G, Tinetti POMA), and the Biodex Fall Risk Index (FRI) were performed at entry and discharge. The Normalized FRI, obtained adjusting FRI to the reported maximum predictive FRI for the relevant age, identified 2 types of patients: those with a greater risk of fall than expected for that age, labeled Case 1 (Normalized FRI>1); and those with an equal or even lesser risk of fall than expected for that age, labeled Case 0 (Normalized FRI≤1).FRI, Normalized FRI as well as independent variables as age, sex, pathology group, FIM, BarthelG, were considered in a multiple regression analysis to predict the functional improvement (i.e., delta Tinetti Total score) after rehabilitation.Normalized FRI is useful in assessing patients at risk of falls both before and after rehabilitation. At admission, the Normalized FRI evidenced high fall risk in 46% of patients (Case 1) which decreased to 12% after rehabilitation, being greater than age-predicted in 7 patients (Case 1-1) despite the functional improvement observed after the rehabilitation treatment. Normalized FRI evidenced Case 1-1 patients as neurological, "very old" (86% in age-group 75-84 years), and with serious events at 18 to 24 months' follow-up. Normalized FRI, but not FRI, at admission was a predictor of improvement in Tinetti Total scores.The normalized FRI effectively indicated patients at higher risk of fall, in whom health deterioration, falls, or cognitive decline was later documented at follow-up. The normalized FRI could be a standardized measure for identifying frailer patients becoming a further criterium of discharge home and marker of fall risk at home.

[Charles Miller Fisher: the grandmaster of neurological observation].

PubMed

Fukutake, Toshio

2014-11-01

Charles Miller Fisher is widely regarded as the father of modern stroke neurology. He discovered almost all pathomechanisms of cerebral infarction, including embolism from atrial fibrillation, carotid artery disease, and lacunar infarcts and their syndromes, by the most meticulous clinico-pathological observations. Moreover, his work provided the basis for treatments such as anticoagulation, antiplatelet therapy, and carotid endarterectomy. He also contributed greatly to several topics of General Neurology; for example, migraine, normal pressure hydrocephalus, and Miller Fisher syndrome. In his late years, he tried to expand the neurological field to the more complex disorders of human behavior, including hysteria, dementia, and ill-defined pain syndromes. He thus became known as the grandmaster of refined neurological observation. His lifelong detailed studies were crucially important in helping neurologists all over the world recognize disorders and syndromes that had not previously been understood.

Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.

PubMed

Sun, Bao-Liang; Wang, Li-Hua; Yang, Tuo; Sun, Jing-Yi; Mao, Lei-Lei; Yang, Ming-Feng; Yuan, Hui; Colvin, Robert A; Yang, Xiao-Yi

2017-09-10

The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes. Brain lymphatic drainage helps maintain water and ion balance of the ISF, waste clearance, and reabsorption of macromolecular solutes. A second physiological function includes communication with the immune system modulating immune surveillance and responses of the brain. These physiological functions are influenced by aging, genetic phenotypes, sleep-wake cycle, and body posture. The impairment and dysfunction of the brain lymphatic system has crucial roles in age-related changes of brain function and the pathogenesis of neurovascular, neurodegenerative, and neuroinflammatory diseases, as well as brain injury and tumors. In this review, we summarize the key component elements (regions, cells, and water transporters) of the brain lymphatic system and their regulators as potential therapeutic targets in the treatment of neurologic diseases and their resulting complications. Finally, we highlight the clinical importance of ependymal route-based targeted gene therapy and intranasal drug administration in the brain by taking advantage of the unique role played by brain lymphatic pathways in the regulation of CSF flow and ISF/CSF exchange. Copyright © 2017. Published by Elsevier Ltd.

Evaluation of central nervous system in patients with glycogen storage disease type 1a.

PubMed

Aydemir, Yusuf; Gürakan, Figen; Saltık Temizel, İnci Nur; Demir, Hülya; Oğuz, Kader Karlı; Yalnızoğlu, Dilek; Topçu, Meral; Özen, Hasan; Yüce, Aysel

2016-01-01

We aimed to evaluate structure and functions of central nervous system (CNS) in children with glycogen storage disease (GSD) type 1a. Neurological examination, psychometric tests, electroencephalography (EEG), magnetic resonance imaging (MRI), visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) were performed. The results were compared between patients with good and poor metabolic control and healthy children. Twenty-three patients with GSD type 1a were studied. Twelve patients were in poor metabolic control group and 11 patients in good metabolic control group. Five patients had intellectual disability, 10 had EEG abnormalities, seven had abnormal VEP and two had abnormal BAEP results. MRI was abnormal in five patients. There was significant correlation between the number of hypoglycemic attacks and MRI abnormalities. Central nervous system may be affected in GSD type 1a even in patients with normal neurologic examination. Accumulation of abnormal results in patients with poor metabolic control supports the importance of metabolic control in GSD type 1a.

Three families with mild PMM2-CDG and normal cognitive development.

PubMed

Vals, Mari-Anne; Morava, Eva; Teeäär, Kai; Zordania, Riina; Pajusalu, Sander; Lefeber, Dirk J; Õunap, Katrin

2017-06-01

Congenital disorders of glycosylation (CDG) are caused by defective glycosylation of proteins and lipids. PMM2-CDG is the most common subtype among the CDG. The severity of PMM2-CDG is variable. Patients often have a recognizable phenotype with neurological and multisystem symptoms that might cause early death. We report six patients from three families who are diagnosed with a clinically mild PMM2-CDG and have normal cognitive development. All these patients had delayed gross motor skills with mild-to-moderate neurological findings. Cerebellar hypoplasia was detected in all siblings for whom brain MRI was performed. In 5/6 children the Wechsler Intelligence Scale for Children (WISC) showed normal cognitive development with full scale IQ scores ranging from borderline to average. Four patients were diagnosed with PMM2-CDG at the age of 8 years or later as their neurological symptoms were quite mild and they had been able to participate in regular school programs. We report patients with p.Val231Met/p.Arg239Trp and p.Ile120Thr/p.Gly228Cys genotypes which may cause milder variants of PMM2-CDG. © 2017 Wiley Periodicals, Inc.

Genetic neurological channelopathies: molecular genetics and clinical phenotypes.

PubMed

Spillane, J; Kullmann, D M; Hanna, M G

2016-01-01

Evidence accumulated over recent years has shown that genetic neurological channelopathies can cause many different neurological diseases. Presentations relating to the brain, spinal cord, peripheral nerve or muscle mean that channelopathies can impact on almost any area of neurological practice. Typically, neurological channelopathies are inherited in an autosomal dominant fashion and cause paroxysmal disturbances of neurological function, although the impairment of function can become fixed with time. These disorders are individually rare, but an accurate diagnosis is important as it has genetic counselling and often treatment implications. Furthermore, the study of less common ion channel mutation-related diseases has increased our understanding of pathomechanisms that is relevant to common neurological diseases such as migraine and epilepsy. Here, we review the molecular genetic and clinical features of inherited neurological channelopathies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Artistic creativity, style and brain disorders.

PubMed

Bogousslavsky, Julien

2005-01-01

The production of novel, motivated or useful material defines creativity, which appears to be one of the higher, specific, human brain functions. While creativity can express itself in virtually any domain, art might particularly well illustrate how creativity may be modulated by the normal or pathological brain. Evidence emphasizes global brain functioning in artistic creativity and output, but critical steps which link perception processing to execution of a work, such as extraction-abstraction, as well as major developments of non-esthetic values attached to art also underline complex activation and inhibition processes mainly localized in the frontal lobe. Neurological diseases in artists provide a unique opportunity to study brain-creativity relationships, in particular through the stylistic changes which may develop after brain lesion. (c) 2005 S. Karger AG, Basel

Anatomo-clinical overlapping maps (AnaCOM): a new method to create anatomo-functional maps from neuropsychological tests and structural MRI scan of subjects with brain lesions

NASA Astrophysics Data System (ADS)

Kinkingnehun, Serge R. J.; du Boisgueheneuc, Foucaud; Golmard, Jean-Louis; Zhang, Sandy X.; Levy, Richard; Dubois, Bruno

2004-04-01

We have developed a new technique to analyze correlations between brain anatomy and its neurological functions. The technique is based on the anatomic MRI of patients with brain lesions who are administered neuropsychological tests. Brain lesions of the MRI scans are first manually segmented. The MRI volumes are then normalized to a reference map, using the segmented area as a mask. After normalization, the brain lesions of the MRI are segmented again in order to redefine the border of the lesions in the context of the normalized brain. Once the MRI is segmented, the patient's score on the neuropsychological test is assigned to each voxel in the lesioned area, while the rest of the voxels of the image are set to 0. Subsequently, the individual patient's MRI images are superimposed, and each voxel is reassigned the average score of the patients who have a lesion at that voxel. A threshold is applied to remove regions having less than three overlaps. This process leads to an anatomo-functional map that links brain areas to functional loss. Other maps can be created to aid in analyzing the functional maps, such as one that indicates the 95% confidence interval of the averaged scores for each area. This anatomo-clinical overlapping map (AnaCOM) method was used to obtain functional maps from patients with lesions in the superior frontal gyrus. By finding particular subregions more responsible for a particular deficit, this method can generate new hypotheses to be tested by conventional group methods.

Human Neurological Development: Past, Present and Future

NASA Technical Reports Server (NTRS)

Pelligra, R. (Editor)

1978-01-01

Neurological development is considered as the major human potential. Vision, vestibular function, intelligence, and nutrition are discussed as well as the treatment of neurological disfunctions, coma, and convulsive seizures.

Language systems in normal and aphasic human subjects: functional imaging studies and inferences from animal studies.

PubMed

Wise, Richard J S

2003-01-01

The old neurological model of language, based on the writings of Broca, Wernicke and Lichtheim in the 19th century, is now undergoing major modifications. Observations on the anatomy and physiology of auditory processing in non-human primates are giving strong indicators as to how speech perception is organised in the human brain. In the light of this knowledge, functional activation studies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are achieving a new level of precision in the investigation of language organisation in the human brain, in a manner not possible with observations on patients with aphasic stroke. Although the use of functional imaging to inform methods of improving aphasia rehabilitation remains underdeveloped, there are strong indicators that this methodology will provide the means to research a very imperfectly developed area of therapy.

Language-learning impairments: a 30-year follow-up of language-impaired children with and without psychiatric, neurological and cognitive difficulties.

PubMed

Elbro, Carsten; Dalby, Mogens; Maarbjerg, Stine

2011-01-01

This study investigated the long-term consequences of language impairments for academic, educational and socio-economic outcomes. It also assessed the unique contributions of childhood measures of speech and language, non-verbal IQ, and of psychiatric and neurological problems. The study was a 30-year follow-up of 198 participants originally diagnosed with language impairments at 3-9 years. Childhood diagnoses were based on language and cognitive abilities, social maturity, motor development, and psychiatric and neurological signs. At follow-up the participants responded to a questionnaire about literacy, education, employment, economic independence and family status. The response rate was 42% (198/470). At follow-up a majority of the participants reported literacy difficulties, unemployment and low socio-economic status-at rates significantly higher than in the general population. Participants diagnosed as children with specific language impairments had significantly better outcomes than those with additional diagnoses, even when non-verbal IQ was normal or statistically controlled. Childhood measures accounted for up to 52% of the variance in adult outcomes. Psychiatric and neurological comorbidity is relevant for adult outcomes of language impairments even when non-verbal IQ is normal. © 2011 Royal College of Speech & Language Therapists.

Peripheral neuropathy as a complication of diabetic ketoacidosis in a child with newly diagnosed diabetes type 1 - case report.

PubMed

Baszyńska-Wilk, Marta; Wysocka-Mincewicz, Marta; Świercz, Anna; Świderska, Jolanta; Marszał, Magdalena; Szalecki, Mieczysław

2017-12-08

Neurological complications of diabetic ketoacidosis are considered to be very serious clinical problem. The most common complication is cerebral edema. However this group includes also less common syndromes such as ischemic or hemorrhagic stroke, cerebral venous and sinus thrombosis or very rare peripheral neuropathy. We present a case of 9-year old girl with new onset type 1 diabetes, diabetic ketoacidosis, cerebral edema, multifocal vasogenic brain lesions and lower limbs peripheral paresis. The patient developed polydipsia and polyuria one week before admission to the hospital. In laboratory tests initial blood glucose level 1136 mg/dl and acidosis (pH 7.1; BE-25.9) were noted. She was admitted to the hospital in a critical condition and required treatment in intensive care unit. Computed tomography scan showed brain edema and hipodense lesion in the left temporal region. Brain MRI revealed more advanced multifocal brain lesions Nerve conduction studies demonstrated damage of the motor neuron in both lower extremities with dysfunction in both peroneal nerves and the right tibial nerve. As a result of diabetological, neurological treatment and physiotherapy patient's health state gradually improved. Acute neuropathy after ketoacidosis is rare complication and its pathomechanism is not clear. Patients with DKA require careful monitoring of neurological functions even after normalization of glycemic parameters.

Antibodies against the voltage-dependent anion channel (VDAC) and its protective ligand hexokinase I in children with autism

PubMed Central

Gonzalez-Gronow, Mario; Cuchacovich, Miguel; Francos, Rina; Cuchacovich, Stephanie; Fernandez, Maria del Pilar; Blanco, Angel; Bowers, Edith V.; Kaczowka, Steven; Pizzo, Salvatore V.

2010-01-01

Autistic children show elevated serum levels of autoantibodies to several proteins essential for the function of normal brains. The voltage-dependent anion channel, VDAC, and hexokinase-I, a VDAC protective ligand, were identified as targets of this autoimmunity in autistic children. These autoantibodies were purified using immunoaffinity chromatographic techniques. Both antibodies induce apoptosis of cultured human neuroblastoma cells. Because VDAC and hexokinase-I are essential for brain protection from ischemic damage, the presence of these autoantibodies suggests a possible causal role in the neurologic pathogenesis of autism. PMID:20576296

Clinical, magnetic resonance imaging, and histopathologic findings in 6 dogs with surgically resected extraparenchymal spinal cord hematomas.

PubMed

Hague, D W; Joslyn, S; Bush, W W; Glass, E N; Durham, A C

2015-01-01

Extraparenchymal spinal cord hematoma has been described in veterinary medicine in association with neoplasia, intervertebral disk disease, and snake envenomation. There are rare reports of spontaneous extraparenchymal spinal cord hematoma formation with no known cause in human medicine. Multiple cases of spontaneous extraparenchymal spinal cord hematoma have not been described previously in veterinary medicine. To describe the signalment, clinical findings, magnetic resonance imaging (MRI) features, and surgical outcomes in histopathologically confirmed extraparenchymal spinal cord hematomas in dogs with no identified underlying etiology. Six dogs had MRI of the spinal cord, decompressive spinal surgery, and histopathologic confirmation of extraparenchymal spinal cord hematoma not associated with an underlying cause. Multi-institutional retrospective study. Six patients had spontaneous extraparenchymal spinal cord hematoma formation. MRI showed normal signal within the spinal cord parenchyma in all patients. All hematomas had T2-weighted hyperintensity and the majority (5/6) had no contrast enhancement. All dogs underwent surgical decompression and most patients (5/6) returned to normal or near normal neurologic function postoperatively. Follow-up of the patients (ranging between 921 and 1,446 days) showed no progression of neurologic clinical signs or any conditions associated with increased bleeding tendency. Before surgery and histopathology confirming extraparenchymal hematoma, the primary differential in most cases was neoplasia, based on the MRI findings. This retrospective study reminds clinicians of the importance of the combination of advanced imaging combined with histopathologic diagnosis. The prognosis for spontaneous spinal cord extraparenchymal hematoma with surgical decompression appears to be favorable in most cases. Copyright © 2015 by the American College of Veterinary Internal Medicine.

Biochemical properties of beta-glucosidase in leukocytes from patients and obligated heterozygotes for Gaucher disease carriers.

PubMed

Michelin, Kristiane; Wajner, Alessandro; Bock, Hugo; Fachel, Angela; Rosenberg, Roberto; Pires, Ricardo Flores; Pereira, Maria Luiza Saraiva; Giugliani, Roberto; Coelho, Janice Carneiro

2005-12-01

Gaucher's disease (GD) is a disorder caused by the deficiency of lysosomal beta-glucosidase, an enzyme that participates in the degradation of glycosphingolipids. Deficiency of this enzyme results in the storage of glucocerebrosides in lysosomes of macrophage. No studies are available in the literature comparing biochemical and kinetic behavior of this enzyme in leukocytes and fibroblasts from normal individuals, obligate heterozygotes and patients with GD. The behavior of beta-glu in terms of optimum pH, heat stability, Km and Vmax in leukocytes from patients with GD and obligated heterozygotes with different genotypes and normal individuals were characterized. Optimum pH was similar in all groups analyzed. In terms of Km and Vmax, several differences among heterozygotes and homozygotes groups and among these groups and normal enzyme were observed. Enzyme from all groups were inactivated when preincubated at 60 degrees C, but some enzymes were more stable than other. Results showed a different behavior of the enzyme in the 3 groups under analysis. Such behavior varied according to individual mutation. The catalytic gradient presented by beta-glu allowed the correlation of N370S mutation-which presented more stable biochemical properties-with the non-neurological clinical condition of the disease and the catalytically less stable mutation (D409H), with the neurological clinical condition of GD. This study contributes to a better understanding of the repercussion of the different mutations on the protein function, thus allowing to predict the severity of such complex metabolic disorder and to anticipate the most appropriate intervention for each case specifically.

Decreased heart rate and enhanced sinus arrhythmia during interictal sleep demonstrate autonomic imbalance in generalized epilepsy

PubMed Central

Sivakumar, Siddharth S.; Namath, Amalia G.; Tuxhorn, Ingrid E.; Lewis, Stephen J.

2016-01-01

We hypothesized that epilepsy affects the activity of the autonomic nervous system even in the absence of seizures, which should manifest as differences in heart rate variability (HRV) and cardiac cycle. To test this hypothesis, we investigated ECG traces of 91 children and adolescents with generalized epilepsy and 25 neurologically normal controls during 30 min of stage 2 sleep with interictal or normal EEG. Mean heart rate (HR) and high-frequency HRV corresponding to respiratory sinus arrhythmia (RSA) were quantified and compared. Blood pressure (BP) measurements from physical exams of all subjects were also collected and analyzed. RSA was on average significantly stronger in patients with epilepsy, whereas their mean HR was significantly lower after adjusting for age, body mass index, and sex, consistent with increased parasympathetic tone in these patients. In contrast, diastolic (and systolic) BP at rest was not significantly different, indicating that the sympathetic tone is similar. Remarkably, five additional subjects, initially diagnosed as neurologically normal but with enhanced RSA and lower HR, eventually developed epilepsy, suggesting that increased parasympathetic tone precedes the onset of epilepsy in children. ECG waveforms in epilepsy also displayed significantly longer TP intervals (ventricular diastole) relative to the RR interval. The relative TP interval correlated positively with RSA and negatively with HR, suggesting that these parameters are linked through a common mechanism, which we discuss. Altogether, our results provide evidence for imbalanced autonomic function in generalized epilepsy, which may be a key contributing factor to sudden unexpected death in epilepsy. PMID:26888110

The classification of conversion disorder (functional neurologic symptom disorder) in ICD and DSM.

PubMed

Levenson, J L; Sharpe, M

2016-01-01

The name given to functional neurologic symptoms has evolved over time in the different editions of the International Classification of Diseases (ICD) and the Diagnostic and Statistical Manual of Mental Disorders (DSM), reflecting a gradual move away from an etiologic conception rooted in hysterical conversion to an empiric phenomenologic one, emphasizing the central role of the neurologic examination and testing in demonstrating that the symptoms are incompatible with recognized neurologic disease pathophysiology, or are internally inconsistent. © 2016 Elsevier B.V. All rights reserved.

Flaccid quadriplegia due to thyrotoxic myopathy.

PubMed

Couillard, Philippe; Wijdicks, Eelco F M

2014-04-01

Acute flaccid paralysis is an important clinical problem in neurological critical care. After implementing life-supporting measures, it is imperative to identify the correct diagnosis to provide timely appropriate care. Thyrotoxicosis is a recognized cause of myopathy, but rarely of quadriplegia. Here, we report a case of hyperthyroidism with severe weakness. Case report and video demonstration of clinical examination. We describe a case of a 59-year-old woman with Grave's disease who presented to the hospital with progressive shortness of breath secondary to atrial fibrillation with rapid ventricular response. Following contrast administration, she had a pulseless electrical activity arrest from which she recovered without cognitive sequelae, but with flaccid quadriplegia, facial diplegia, and hypophonia. CK was mildly elevated and electrolytes were essentially normal. Nerve conduction studies and electromyography demonstrated features supporting an acute myopathy without evidence of neuromuscular junction conduction abnormality. Normalization of thyroid hormones resulted in slow, but steady improvement over months after which she regained ambulation. Acute flaccid quadriplegia can result from thyrotoxicosis. With normalization of thyroid function, recovery can be expected.

Cerebrovascular Accidents Associated with Sorafenib in Hepatocellular Carcinoma

PubMed Central

Saif, Muhammad W.; Isufi, Iris; Peccerillo, Jennifer; Syrigos, Kostas N.

2011-01-01

Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. Laboratory data were noncontributory. The head CT scan did not reveal acute abnormalities. No hemodynamically significant stenosis was visible in the carotid ultrasound, and the echocardiogram showed normal size of the heart chambers and normal systolic function of the left ventricle. Sorafenib was discontinued in both cases. Physicians should monitor patients receiving sorafenib for neurologic symptoms, and in the absence of other etiology, prompt discontinuation of this drug should be considered. PMID:21687621

Cerebrovascular accidents associated with sorafenib in hepatocellular carcinoma.

PubMed

Saif, Muhammad W; Isufi, Iris; Peccerillo, Jennifer; Syrigos, Kostas N

2011-01-01

Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. Laboratory data were noncontributory. The head CT scan did not reveal acute abnormalities. No hemodynamically significant stenosis was visible in the carotid ultrasound, and the echocardiogram showed normal size of the heart chambers and normal systolic function of the left ventricle. Sorafenib was discontinued in both cases. Physicians should monitor patients receiving sorafenib for neurologic symptoms, and in the absence of other etiology, prompt discontinuation of this drug should be considered.

Head Impact Exposure and Neurologic Function of Youth Football Players.

PubMed

Munce, Thayne A; Dorman, Jason C; Thompson, Paul A; Valentine, Verle D; Bergeron, Michael F

2015-08-01

Football players are subjected to repetitive impacts that may lead to brain injury and neurologic dysfunction. Knowledge about head impact exposure (HIE) and consequent neurologic function among youth football players is limited. This study aimed to measure and characterize HIE of youth football players throughout one season and explore associations between HIE and changes in selected clinical measures of neurologic function. Twenty-two youth football players (11-13 yr) wore helmets outfitted with a head impact telemetry (HIT) system to quantify head impact frequency, magnitude, duration, and location. Impact data were collected for each practice (27) and game (9) in a single season. Selected clinical measures of balance, oculomotor performance, reaction time, and self-reported symptoms were assessed before and after the season. The median individual head impacts per practice, per game, and throughout the entire season were 9, 12, and 252, respectively. Approximately 50% of all head impacts (6183) had a linear acceleration between 10g and 20g, but nearly 2% were greater than 80g. Overall, the head impact frequency distributions in this study population were similar in magnitude and location as in high school and collegiate football, but total impact frequency was lower. Individual changes in neurologic function were not associated with cumulative HIE. This study provides a novel examination of HIE and associations with short-term neurologic function in youth football and notably contributes to the limited HIE data currently available for this population. Whereas youth football players can experience remarkably similar head impact forces as high school players, cumulative subconcussive HIE throughout one youth football season may not be detrimental to short-term clinical measures of neurologic function.

[Brain function recovery after prolonged posttraumatic coma].

PubMed

Klimash, A V; Zhanaidarov, Z S

2016-01-01

To explore the characteristics of brain function recovery in patients after prolonged posttraumatic coma and with long-unconscious states. Eighty-seven patients after prolonged posttraumatic coma were followed-up for two years. An analysis of a clinical/neurological picture after a prolonged episode of coma was based on the dynamics of vital functions, neurological status and patient's reactions to external stimuli. Based on the dynamics of the clinical/neurological picture that shows the recovery of functions of the certain brain areas, three stages of brain function recovery after a prolonged episode of coma were singled out: brain stem areas, diencephalic areas and telencephalic areas. These functional/anatomic areas of brain function recovery after prolonged coma were compared to the present classifications.

Fate of patients with spinal cord ischemia complicating thoracic endovascular aortic repair.

PubMed

DeSart, Kenneth; Scali, Salvatore T; Feezor, Robert J; Hong, Michael; Hess, Philip J; Beaver, Thomas M; Huber, Thomas S; Beck, Adam W

2013-09-01

Spinal cord ischemia (SCI) is a potentially devastating complication of thoracic endovascular aortic repair (TEVAR) that can result in varying degrees of short-term and permanent disability. This study was undertaken to describe the clinical outcomes, long-term functional impact, and influence on survival of SCI after TEVAR. A retrospective review of all TEVAR patients at the University of Florida from 2000 to 2011 was performed to identify individuals experiencing SCI, defined by any new lower extremity neurologic deficit not attributable to another cause. SCI was dichotomized into immediate or delayed onset, with immediate onset defined as SCI noted upon awakening from anesthesia, and delayed characterized as a period of normal function, followed by development of neurologic injury. Ambulatory status was determined using database query, record review, and phone interviews with patients and/or family. Mortality was estimated using life-table analysis. A total of 607 TEVARs were performed for various indications, with 57 patients (9.4%) noted to have postoperative SCI (4.3% permanent). SCI patients were more likely to be older (63.9 ± 15.6 vs 70.5 ± 11.2 years; P = .002) and have a number of comorbidities, including chronic obstructive pulmonary disease, hypertension, dyslipidemia, and cerebrovascular disease (P < .0001). At some point in their care, a cerebrospinal fluid drain was placed in 54 patients (95%), with 54% placed postoperatively. In-hospital mortality was 8.8% for the entire cohort (SCI vs no SCI; P = .45). SCI developed immediately in 12 patients, delayed onset in 40, and indeterminate in five patients due to indiscriminate timing from postoperative sedation. Three patients (25%) with immediate SCI had measurable functional improvement (FI), whereas 28 (70%) of the delayed-onset patients experienced some degree of neurologic recovery (P = .04). Of the 34 patients with complete data available, 26 (76%) reported quantifiable FI, but only 13 (38%) experienced return to their preoperative baseline. Estimated mean (± standard error) survival for patients with and without SCI was 37.2 ± 4.5 and 71.6 ± 3.9 months (P < .0006), respectively. Patients with FI had a mean survival of 53.9 ± 5.9 months compared with 9.6 ± 3.6 months for those without improvement (P < .0001). Survival and return of neurologic function were not significantly different when patients with preoperative and postoperative cerebrospinal fluid drains were compared. The minority of patients experience complete return to baseline function after SCI with TEVAR, and outcomes in patients without early functional recovery are particularly dismal. Patients experiencing delayed SCI are more likely to have FI and may anticipate similar life-expectancy with neurologic recovery compared with patients without SCI. Timing of drain placement does not appear to have an impact on postdischarge FI or long-term mortality. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Resilient protein co-expression network in male orbitofrontal cortex layer 2/3 during human aging.

PubMed

Pabba, Mohan; Scifo, Enzo; Kapadia, Fenika; Nikolova, Yuliya S; Ma, Tianzhou; Mechawar, Naguib; Tseng, George C; Sibille, Etienne

2017-10-01

The orbitofrontal cortex (OFC) is vulnerable to normal and pathologic aging. Currently, layer resolution large-scale proteomic studies describing "normal" age-related alterations at OFC are not available. Here, we performed a large-scale exploratory high-throughput mass spectrometry-based protein analysis on OFC layer 2/3 from 15 "young" (15-43 years) and 18 "old" (62-88 years) human male subjects. We detected 4193 proteins and identified 127 differentially expressed (DE) proteins (p-value ≤0.05; effect size >20%), including 65 up- and 62 downregulated proteins (e.g., GFAP, CALB1). Using a previously described categorization of biological aging based on somatic tissues, that is, peripheral "hallmarks of aging," and considering overlap in protein function, we show the highest representation of altered cell-cell communication (54%), deregulated nutrient sensing (39%), and loss of proteostasis (35%) in the set of OFC layer 2/3 DE proteins. DE proteins also showed a significant association with several neurologic disorders; for example, Alzheimer's disease and schizophrenia. Notably, despite age-related changes in individual protein levels, protein co-expression modules were remarkably conserved across age groups, suggesting robust functional homeostasis. Collectively, these results provide biological insight into aging and associated homeostatic mechanisms that maintain normal brain function with advancing age. Copyright © 2017 Elsevier Inc. All rights reserved.

Correlation between hypertension and cognitive function in elderly

NASA Astrophysics Data System (ADS)

Fitri, F. I.; Rambe, A. S.

2018-03-01

Hypertension and cognitive impairment are common disorders among elderly adults, and their prevalences tend to rise as the population ages. This study aimed to determine the correlation between hypertension and cognitive function in elderly. It was a cross-sectional study involving 62 elderly subjects. All subjects underwent physical and neurologic examination and Montreal Cognitive Assessment-Indonesian Version (MoCA-INA) to assess cognitive function. This study included 62 subjects consisted of 26 males (41.9%) and 36 females (58.1%). There were 24 subjects (38.2%) with hypertension and 38 (61.3%) normal elderly subjects. The mean age was 65.71±4.49 years old. There were no significant differences in demographic characteristics, total MoCA-INA scores, and scores based on cognitive domains between two groups, except for visuospatial and executive function (p=0.026). There was a significant correlation between hypertension and visuospatial and executive function (r=0.301, p=0.017). Hypertension is correlated with cognitive impairment mainly on visuospatial and executive function in elderly.

[The child's brain: normal (unaltered) development and development altered by perinatal injury].

PubMed

Marín-Padilla, Miguel

2013-09-06

In this study we analyse some of the morphological and functional aspects of normal and altered development (the latter due to perinatal injury) in the child's brain. Both normal and altered development are developmental processes that progressively interconnect the different regions. The neuropathological development of subpial and periventricular haemorrhages, as well as that of white matter infarct, are analysed in detail. Any kind of brain damage causes a local lesion with possible remote repercussions. All the components (neurons, fibres, blood capillaries and neuroglias) of the affected region undergo alterations. Those that are destroyed are eliminated by the inflammatory process and those that survive are transformed. The pyramidal neurons with amputated apical dendrites are transformed and become stellate cells, the axonal terminals and those of the radial glial cells are regenerated and the region involved is reinnervated and revascularised with an altered morphology and function (altered local corticogenesis). The specific microvascular system of the grey matter protects its neurons from infarction of the white matter. Although it survives, the grey matter is left disconnected from the afferent and efferent fibres, amputated by the infarct with alterations affecting its morphology and possibly its functioning (altered local corticogenesis). Any local lesion can modify the morphological and functional development of remote regions that are functionally interconnected with it (altered remote corticogenesis). We suggest that any local brain injury can alter the morphology and functioning of the regions that are morphologically and functionally interconnected with it and thus end up affecting the child's neurological and psychological development. These changes can cross different regions of the brain (epileptic auras) and, if they eventually reach the motor region, will give rise to the motor storm that characterises epilepsy.

Cystic fibrosis transmembrane conductance regulator protein (CFTR) expression in the developing human brain: comparative immunohistochemical study between patients with normal and mutated CFTR.

PubMed

Marcorelles, Pascale; Friocourt, Gaëlle; Uguen, Arnaud; Ledé, Françoise; Férec, Claude; Laquerrière, Annie

2014-11-01

Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein has recently been shown to be expressed in the human adult central nervous system (CNS). As CFTR expression has also been documented during embryonic development in several organs, such as the respiratory tract, the intestine and the male reproductive system, suggesting a possible role during development we decided to investigate the expression of CFTR in the human developing CNS. In addition, as some, although rare, neurological symptoms have been reported in patients with CF, we compared the expression of normal and mutated CFTR at several fetal stages. Immunohistochemistry was performed on brain and spinal cord samples of foetuses between 13 and 40 weeks of gestation and compared with five patients with cystic fibrosis (CF) of similar ages. We showed in this study that CFTR is only expressed in neurons and has an early and widespread distribution during development. Although we did not observe any cerebral abnormality in patients with CF, we observed a slight delay in the maturation of several brain structures. We also observed different expression and localization of CFTR depending on the brain structure or the cell maturation stage. Our findings, along with a literature review on the neurological phenotypes of patients with CF, suggest that this gene may play previously unsuspected roles in neuronal maturation or function. © The Author(s) 2014.

Coronary gas embolism during a dive: a case report.

PubMed

Villela, Alvarez; Weaver, Lindell K; Ritesh, Dhar

2015-01-01

A healthy scuba diver presented with a NSTEMI (non-ST segment elevation myocardial infarction), pneumothorax and pneumomediastinum after diving. A 34-year-old woman with no significant medical history presented to the emergency department after an episode of loss of consciousness and seizure-like activity after an uncontrolled ascent during a dive in a freshwater lake at 5,700 feet of altitude. A chest radiograph showed pneumothorax, pneumomediastinum and pneumopericardium. She had septal infarction as indicated by ECG, and elevated troponin. Echocardiogram revealed a mildly depressed left ventricular ejection fraction (LVEF) with apical akinesis. Coronary angiogram showed normal coronary arteries. Hyperbaric oxygen was not given since evaluation occurred 28 hours after the event: The patient had a pneumothorax, and was neurologically normal. She was discharged on angiotensin-converting enzyme inhibitors (ACE-I) and opioids for chest pain. Cardiac function normalized on transthoracic echocardiogram (TTE) two weeks later, but she continued to complain of chest pain that was treated with dihydropyridine calcium channel blockers. She then developed pericarditis confirmed by CMRI, requiring treatment with non-steroidal anti-inflammatory drugs (NSAIDS), colchicine and steroids. Five months after the accident, she was asymptomatic, with excellent exercise function and normal exercise stress echocardiogram. Reports of myocardial injury caused by arterial gas embolism from diving are rare. This case shows coronary air embolism complicating pulmonary barotrauma and may be the first report of pericarditis complicating myocardial injury after an AGE.

Cognitive Decline in Patients with Chronic Hydrocephalus and Normal Aging: ‘Growing into Deficits’

PubMed Central

de Beer, Marlijn H.; Scheltens, Philip

2016-01-01

Background/Aim To explore the theory of ‘growing into deficits’, a concept known from developmental neurology, in a series of cases with chronic hydrocephalus (CH). Methods Patients were selected from the Amsterdam Dementia Cohort and underwent extensive dementia screening. Results Twelve patients with CH were selected, in whom Alzheimer's disease was considered unlikely, based on biomarker information and follow-up. Mean Mini-Mental State Examination score was 24 (range 7-30). Most patients were functioning on a level of mild dementia [Clinical Dementia Rating score of 0.5 in 8/11 (66.7%) patients]. On neuropsychological examination, memory and executive functions, as well as processing speed were most frequently impaired. Conclusion In our opinion, the theory of ‘growing into deficits’ shows a parallel with the clinical course of CH and normal aging when Alzheimer's disease was considered very unlikely, because most of these patients were functioning well for a very large part of their lives. The altered cerebrospinal fluid dynamics might make the brain more vulnerable to aging-related changes, leading to a faster cognitive decline in CH patients compared to healthy subjects, especially in case of concomitant brain damage such as traumatic brain injury or meningitis. PMID:27920793

Severe rhabdomyolysis and acute renal failure in an adolescent with hypothyroidism.

PubMed

Comak, Elif; Koyun, Mustafa; Kiliçarslan-Akkaya, Bahar; Bircan, Iffet; Akman, Sema

2011-01-01

Hypothyroidism has been reported rarely as the cause of rhabdomyolysis in adults and children. We present here a non-compliant adolescent with a diagnosis of hypothyroidism who developed rhabdomyolysis and acute renal failure with no additional predisposing factor. A 13-year-old girl with a previous history of hypothyroidism due to thyroid hypoplasia presented with generalized myalgia, malaise, vomiting, and oliguria lasting for three days. Neurological examination revealed bilateral marked weakness and tenderness of muscles of both lower and upper extremities. Urine had bloody appearance and urine analysis showed blood reaction with dipstick test, but there were no erythrocytes on microscopic examination. Serum creatine phosphokinase and myoglobin levels were elevated. Thyroid stimulating hormone (TSH) levels were high, and free thyroxine (T4) and triiodothyronine (T3) levels were low, compatible with uncontrolled hypothyroidism. Renal function tests showed acute renal failure. Other causes of rhabdomyolysis such as muscular trauma, drugs, toxins, infections, vigorous exercise, and electrolyte abnormalities were excluded. Hemodialysis was administered for 24 sessions. After L-thyroxine therapy, thyroid function tests normalized, muscle strength improved, serum muscle enzyme levels returned to normal levels, and renal function tests recovered. One must be aware that rhabdomyolysis may develop in a non-compliant patient with hypothyroidism.

Perceptual consequences of disrupted auditory nerve activity.

PubMed

Zeng, Fan-Gang; Kong, Ying-Yee; Michalewski, Henry J; Starr, Arnold

2005-06-01

Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique contribution of neural synchrony to sensory perception but also provide guidance for translational research in terms of better diagnosis and management of human communication disorders.

High serum uric acid levels are a protective factor against unfavourable neurological functional outcome in patients with ischaemic stroke.

PubMed

Wang, Yu-Fang; Li, Jiao-Xing; Sun, Xun-Sha; Lai, Rong; Sheng, Wen-Li

2018-05-01

Objective We aimed to evaluate the association between serum uric acid levels at the onset and prognostic outcome in patients with acute ischaemic stroke. Methods We retrospectively analysed the outcomes of 1166 patients with ischaemic stroke who were hospitalized in our centre during August 2008 to November 2012. Correlations of serum uric acid levels and prognostic outcomes were analysed. Results Men had higher serum uric acid levels and better neurological functional outcomes compared with women. There was a strong negative correlation between serum uric acid levels and unfavourable neurological functional outcomes. Generalized estimated equation analysis showed that a higher serum uric acid level (>237 µmol/L) was a protective factor for neurological functional outcome in male, but not female, patients. Among five trial of ORG 10172 in acute stroke treatment classification subtypes, only patients with the large-artery atherosclerosis subtype had a significant protective effect of serum uric acid levels on neurological outcome. Conclusions Our study shows that high serum uric acid levels are a significant protective factor in men and in the large-artery atherosclerosis subtype in patients with ischaemic stroke. This is helpful for determining the prognostic value of serum uric acid levels for neurological outcome of acute ischaemic stroke.

17-Year Outcome of Preterm Infants with Diverse Neonatal Morbidities: Part 1, Impact on Physical, Neurological, and Psychological Health Status

PubMed Central

Sullivan, Mary C.; Msall, Michael E.; Miller, Robin J.

2012-01-01

Purpose The purpose of this study was to comprehensively examine physical, neurological, and psychological health in a U.S. sample of 180 infants at age 17. Design & Methods The World Health Organization International Classification of Functioning, Disability and Health model framed the health-related domains and contextual factors. Assessments included growth, chronic conditions, neurological status, and psychological health. Results Physical health, growth, and neurological outcomes were poorer in the preterm groups. Minor neurological impairment was related to integrative function. Preterm survivors reported higher rates of depression, anxiety, and inattention/hyperactivity. Practice Implications Complex health challenges confront preterm survivors at late adolescence suggesting the necessity of continued health surveillance. PMID:22734876

Neurological function, information-motivation-behavioral skills factors, and risk behaviors among HIV-positive alcohol users.

PubMed

Malow, Robert M; Dévieux, Jessy G; Stein, Judith A; Rosenberg, Rhonda; Lerner, Brenda G; Attonito, Jennifer; Villalba, Karina

2012-11-01

The purpose of this study was to examine neurological impairment in combination with information-motivation-behavioral skills (IMB) variables. The study tests the role of IMB variables as mediators of antecedent variables of demographics, life stress, social support, and neurological impairment with outcome measures of HIV preventive and risk behaviors in a sample of HIV-positive, alcohol-using adults (n = 250) with a history of alcohol abuse/dependence. Neurological impairment was measured with the Color Trails Test (CTT). Average performance on the CTT by the sample was substantially worse than established norms. In a directional latent variable model, neurological impairment directly predicted lower transmission knowledge scores and poorer performance on an observational condom skills assessment. Greater neurological impairment was significantly associated with greater age. Future interventions geared toward HIV+ adults who use alcohol should take into consideration HIV-related and age-related neurological functioning which may impede the facilitation of safe sex behaviors.

Neurologic manifestations of electrolyte disturbances.

PubMed

Riggs, Jack E

2002-02-01

Electrolyte disturbances occur commonly and are associated with a variety of characteristic neurologic manifestations involving both the central and peripheral nervous systems. Electrolyte disturbances are essentially always secondary processes. Effective management requires identification and treatment of the underlying primary disorder. Since neurological symptoms of electrolyte disorders are generally functional rather than structural, the neurologic manifestations of electrolyte disturbances are typically reversible. The neurologic manifestations of serum sodium, potassium, calcium, and magnesium disturbances are reviewed.

Addison disease presenting with acute neurologic deterioration: a rare presentation yields new lessons from old observations in primary adrenal failure.

PubMed

Myers, Kenneth A; Kline, Gregory A

2010-01-01

To report a rare case of Addison disease presenting with acute neurologic deterioration, and to discuss previous reports and illustrative clinical lessons drawn from the case. We detail the clinical presentation and sequence of events leading to diagnosis of Addison disease in a 20-year-old man whose initial symptoms were those of acute neurologic deterioration. A 20-year-old man presented with acute, rapid neurologic deterioration. The patient required intubation, but his condition responded very well to mannitol and dexamethasone. Head computed tomography showed a fourth ventricle reduced in size and basal cistern effacement, changes consistent with mild cerebral edema. Primary adrenal insufficiency was diagnosed after a low morning cortisol concentration prompted a corticotropin-stimulation test and serum aldosterone measurement (undetectable). The diagnosis was almost missed because of suspected confounders of dexamethasone and etomidate use. Subsequently, the patient tested positive for anti-21- hydroxylase antibodies. Cerebral edema rarely occurs with Addison disease and is most likely secondary to hyponatremia. Diagnosis in such cases may be complicated by resuscitative therapies; however, low cortisol levels should always be thoroughly investigated. This patient's presentation was also unique in that he maintained a normal electrolyte profile despite hypoaldosteronism, a phenomenon that may be explained by enhanced mineralocorticoid activity of exogenous cortisol. The diagnosis of primary adrenal insufficiency may not be suspected in the absence of classic hyperpigmentation and hyperkalemia, but should remain in the differential diagnosis of acute confusion. While the use of dexamethasone and etomidate in initial resuscitation can transiently suppress adrenal function, any unusually low cortisol level merits thorough investigation.

Neurological function after total en bloc spondylectomy for thoracic spinal tumors.

PubMed

Murakami, Hideki; Kawahara, Norio; Demura, Satoru; Kato, Satoshi; Yoshioka, Katsuhito; Tomita, Katsuro

2010-03-01

Total en bloc spondylectomy (TES) for thoracic spinal tumors may in theory produce neurological dysfunction as a result of ischemic or mechanical damage to the spinal cord. Potential insults include preoperative embolization at 3 levels, intraoperative ligation of segmental arteries, nerve root ligation, and circumferential dural dissection. The purpose of this study was to assess neurological function after thoracic TES. The authors performed a retrospective review of 79 patients with thoracic-level spinal tumors that had been treated with TES between 1989 and 2006. Neurological function was retrospectively analyzed according to the Frankel grading system. Of the 79 cases, 26 involved primary tumors and 53 involved metastatic tumors. The number of excised vertebrae was 1 in 60 cases, 2 in 13, and >or= 3 in 6. The Frankel grade before surgery was B in 1 case, C in 16, D in 29, and E in 33. At the follow-up, the Frankel grade was C in 2 cases, D in 24, and E in 53. Of 46 cases with neurological deficits before surgery, neurological improvement of at least 1 Frankel grade was achieved in 25 cases (54.3%). Although the Frankel grade did not change in 21 patients, improvement in neurological symptoms within the same Frankel grade did occur in these patients. There were no cases of neurological deterioration. There was no neurological deterioration due to preoperative embolization, ligation of segmental arteries, or ligation of thoracic nerve roots. Each of the cases with preoperative neurological deficits showed improvement in neurological symptoms. Data in the current study clinically proved that TES is a safe operation with respect to spinal cord blood flow. In TES, the spinal cord is circumferentially decompressed and the spinal column is shortened. An increase in spinal cord blood flow due to spinal shortening in addition to decompression was considered to have brought about a resolution of neurological symptoms with TES.

Transcriptome profiling of UPF3B/NMD-deficient lymphoblastoid cells from patients with various forms of intellectual disability

PubMed Central

Nguyen, LS; Jolly, L; Shoubridge, C; Chan, WK; Huang, L; Laumonnier, F; Raynaud, M; Hackett, A; Field, M; Rodriguez, J; Srivastava, AK; Lee, Y; Long, R; Addington, AM; Rapoport, JL; Suren, S; Hahn, CN; Gamble, J; Wilkinson, MF; Corbett, MA; Gecz, J

2014-01-01

The nonsense-mediated mRNA decay (NMD) pathway was originally discovered by virtue of its ability to rapidly degrade aberrant mRNAs with premature termination codons. More recently, it was shown that NMD also directly regulates subsets of normal transcripts, suggesting that NMD has roles in normal biological processes. Indeed, several NMD factors have been shown to regulate neurological events (for example, neurogenesis and synaptic plasticity) in numerous vertebrate species. In man, mutations in the NMD factor gene UPF3B, which disrupts a branch of the NMD pathway, cause various forms of intellectual disability (ID). Using Epstein Barr virus—immortalized B cells, also known as lymphoblastoid cell lines (LCLs), from ID patients that have loss-of-function mutations in UPF3B, we investigated the genome-wide consequences of compromised NMD and the role of NMD in neuronal development and function. We found that ~5% of the human transcriptome is impacted in UPF3B patients. The UPF3B paralog, UPF3A, is stabilized in all UPF3B patients, and partially compensates for the loss of UPF3B function. Interestingly, UPF3A protein, but not mRNA, was stabilised in a quantitative manner that inversely correlated with the severity of patients’ phenotype. This suggested that the ability to stabilize the UPF3A protein is a crucial modifier of the neurological symptoms due to loss of UPF3B. We also identified ARHGAP24, which encodes a GTPase-activating protein, as a canonical target of NMD, and we provide evidence that deregulation of this gene inhibits axon and dendrite outgrowth and branching. Our results demonstrate that the UPF3B-dependent NMD pathway is a major regulator of the transcriptome and that its targets have important roles in neuronal cells. PMID:22182939

Quantifying pediatric neuro-oncology risk factors: development of the neurological predictor scale.

PubMed

Micklewright, Jackie L; King, Tricia Z; Morris, Robin D; Krawiecki, Nicolas

2008-04-01

Pediatric neuro-oncology researchers face methodological challenges associated with quantifying the influence of tumor and treatment-related risk factors on child outcomes. The Neurological Predictor Scale was developed to serve as a cumulative index of a child's exposure to risk factors. The clinical utility of the Neurological Predictor Scale was explored in a sample of 25 children with heterogeneous brain tumors. Consistent with expectation, a series of regression analyses demonstrated that the Neurological Predictor Scale significantly predicted composite intellectual functioning (r(2) = 0.21, p < .05), short-term memory (r(2) = 0.16, p = .05), and abstract visual reasoning abilities (r(2) = 0.28, p < .05). With the exception of chemotherapy, the Neurological Predictor Scale accounted for a significant amount of the variance in child intellectual functioning above and beyond individually examined variables. The Neurological Predictor Scale can be used to quickly quantify the cumulative risk factors associated with pediatric brain tumor diagnoses.

Neurological development of children born to liver transplant recipients.

PubMed

Schreiber-Zamora, J; Kociszewska-Najman, B; Borek-Dzięcioł, B; Drozdowska-Szymczak, A; Czaplińska, N; Pawlik, O; Cyganek, A; Pietrzak, B; Wielgoś, M

2014-10-01

Immunosuppressive treatment used in pregnant liver recipients may have a negative impact on fetal development and successively a child. The aim of the study was to make a neurological assessment of infants and children born to liver transplant recipients (LTRs) born between December 4, 2001, and February 11, 2013, in the 1(st) Department of Obstetrics and Gynecology, Medical University of Warsaw. The study involved 88 children, of whom 44 children were born to LTR mothers, and 44 children born to women who were not organ recipients and delivered at a similar gestational age. The gestational age of neonates ranged from 33 to 41 weeks, and the birth weight ranged from 1420 g to 4100 g. The neurological examination was performed in children from 7 weeks to 10 years of age. The neurological development was assessed by a specialist in pediatric neurology. The results of the examination were divided according to the following criteria: 1) normal development, 2) slight disorders, 3) moderate disorders, and 4) severe disorders. The Fisher's exact test was used for statistical analysis. Normal development was found in 35 of 44 (79.54%) children in the LTR group and 39 of 44 (88.63%) children in the control group (P = .3827). Slight disorders were observed in 6 of 44 (13.63%) children in LTR group and 5 of 44 (11.36%) children in the control group. Moderate disorders were found only in 3 of 44 (6.81%) children in the LTR group. No severe disorders were observed in both groups. Neurological development of children born to the liver recipients who were exposed to chronic immunosuppressive treatment in their fetal lives is the same as that of children whose mothers have not undergone organ transplantation.

Functional and clinical neuroanatomy of morality.

PubMed

Fumagalli, Manuela; Priori, Alberto

2012-07-01

Morality is among the most sophisticated features of human judgement, behaviour and, ultimately, mind. An individual who behaves immorally may violate ethical rules and civil rights, and may threaten others' individual liberty, sometimes becoming violent and aggressive. In recent years, neuroscience has shown a growing interest in human morality, and has advanced our understanding of the cognitive and emotional processes involved in moral decisions, their anatomical substrates and the neurology of abnormal moral behaviour. In this article, we review research findings that have provided a key insight into the functional and clinical neuroanatomy of the brain areas involved in normal and abnormal moral behaviour. The 'moral brain' consists of a large functional network including both cortical and subcortical anatomical structures. Because morality is a complex process, some of these brain structures share their neural circuits with those controlling other behavioural processes, such as emotions and theory of mind. Among the anatomical structures implicated in morality are the frontal, temporal and cingulate cortices. The prefrontal cortex regulates activity in subcortical emotional centres, planning and supervising moral decisions, and when its functionality is altered may lead to impulsive aggression. The temporal lobe is involved in theory of mind and its dysfunction is often implicated in violent psychopathy. The cingulate cortex mediates the conflict between the emotional and the rational components of moral reasoning. Other important structures contributing to moral behaviour include the subcortical nuclei such as the amygdala, hippocampus and basal ganglia. Brain areas participating in moral processing can be influenced also by genetic, endocrine and environmental factors. Hormones can modulate moral behaviour through their effects on the brain. Finally, genetic polymorphisms can predispose to aggressivity and violence, arguing for a genetic-based predisposition to morality. Because abnormal moral behaviour can arise from both functional and structural brain abnormalities that should be diagnosed and treated, the neurology of moral behaviour has potential implications for clinical practice and raises ethical concerns. Last, since research has developed several neuromodulation techniques to improve brain dysfunction (deep brain stimulation, transcranial magnetic stimulation and transcranial direct current stimulation), knowing more about the 'moral brain' might help to develop novel therapeutic strategies for neurologically based abnormal moral behaviour.

Regional cerebral blood flow and anxiety: a correlation study in neurologically normal patients

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

Rodriguez, G.; Cogorno, P.; Gris, A.

1989-06-01

Regional CBF (rCBF) was evaluated by the /sup 133/Xe inhalation method in 60 neurologically normal patients (30 men and 30 women) and hemispheric and regional values were correlated with anxiety measurements collected by a self-rating questionnaire before and after the examination. Statistically significant negative correlations between rCBF and anxiety measures were found. rCBF reduction for high anxiety levels is in line with results previously reported by others and could be related to lower performance levels for moderately high anxiety scores as those reported in the present population. This could perhaps be explained by rearrangement of flow from cortical zones tomore » deeper areas of the brain, classically known to be implicated in the control of emotions. However, these results should be interpreted cautiously, since they were obtained in patients and not in normal subjects.« less

Clinical NMR imaging of the brain in children: normal and neurologic disease

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

Johnson, M.A,; Pennock, J.M.; Bydder, G.M.

1983-11-01

The results of initial clinical nuclear magnetic resonance imaging of the brain in eight normal and 52 children with a wide variety of neurologic diseases were reviewed. The high level of gray-white matter contrast available with inversion-recovery sequences provided a basis for visualizing normal myelination as well as delays or deficits in this process. The appearances seen in cases of parenchymal hemorrhage, cerebral infarction, and proencephalic cysts are described. Ventricular enlargement was readily identified and marginal edema was demonstrated with spin-echo sequences. Abnormalities were seen in cerebral palsy, congenital malformations, Hallervorden-Spatz disease, aminoaciduria, and meningitis. Space-occupying lesions were identified bymore » virtue of their increased relaxation times and mass effects. Nuclear magnetic resonance imaging has considerable potential in pediatric neuroradiologic practice, in some conditions supplying information not available by computed tomography or sonography.« less

Hemiparesis is a clinical correlate of general adaptive dysfunction in children and adolescents with Sturge-Weber syndrome.

PubMed

Reesman, Jennifer; Gray, Robert; Suskauer, Stacy J; Ferenc, Lisa M; Kossoff, Eric H; Lin, Doris D M; Turin, Elizabeth; Comi, Anne M; Brice, Patrick J; Zabel, T Andrew

2009-06-01

This study sought to identify neurologic correlates of adaptive functioning in individuals with Sturge-Weber syndrome. A total of 18 children, adolescents, and young adults with Sturge-Weber syndrome with brain involvement were recruited from our Sturge-Weber center. All underwent neurologic examination (including review of clinical brain magnetic resonance imaging) and neuropsychological assessment. Neuropsychological assessment included measures of intellectual ability and standardized parent report of adaptive functioning. Overall, Full Scale IQ and ratings of global adaptive functioning were both lower than the population-based norms (P < .05). Negative correlations were identified between adaptive functioning ratings, clinician ratings of cortical abnormality, and ratings of neurologic status. Hemiparesis (minimal versus prominent) was the only individual component of the rating scales that differentiated between individuals with nonimpaired and impaired adaptive functioning scores. Information obtained during neurological examination of children and adolescents with Sturge-Weber syndrome particularly hemiparetic status is useful for identifying children who may need additional intervention.

Epigenetic mechanisms in the development of memory and their involvement in certain neurological diseases.

PubMed

Rosales-Reynoso, M A; Ochoa-Hernández, A B; Juárez-Vázquez, C I; Barros-Núñez, P

Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases. Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Advances in urea cycle neuroimaging: Proceedings from the 4th International Symposium on urea cycle disorders, Barcelona, Spain, September 2013.

PubMed

Pacheco-Colón, Ileana; Fricke, Stanley; VanMeter, John; Gropman, Andrea L

2014-01-01

Our previous imaging research performed as part of a Urea Cycle Rare Disorders Consortium (UCRDC) grant, has identified specific biomarkers of neurologic injury in ornithine transcarbamylase deficiency, OTCD. While characterization of mutations can be achieved in most cases, this information does not necessarily predict the severity of the underlying neurological syndrome. The biochemical consequences of any mutation may be modified additionally by a large number of factors, including contributions of other enzymes and transport systems that mediate flux through the urea cycle, diet and other environmental factors. These factors likely vary from one patient to another, and they give rise to heterogeneity of clinical severity. Affected cognitive domains include non-verbal learning, fine motor processing, reaction time, visual memory, attention, and executive function. Deficits in these capacities may be seen in symptomatic patients, as well as asymptomatic carriers with normal IQ and correlate with variances in brain structure and function in these patients. Using neuroimaging we can identify biomarkers that reflect the downstream impact of UCDs on cognition. This manuscript is a summary of the presentation from the 4th International Consortium on urea cycle disorders held in, Barcelona, Spain, September 2, 2014. Copyright © 2014 Elsevier Inc. All rights reserved.

Neural Control and Physiology of Sexual Function: Effect of Spinal Cord Injury.

PubMed

Krassioukov, Andrei; Elliott, Stacy

2017-01-01

Objective: To present the current understanding of normal anatomy, physiology, sexual physiology, pathophysiology and the consequential sexual changes and dysfunctions following a spinal cord injury (SCI). Methods: Narrative review of the latest literature. Results: Peripheral innervations of the pelvis involve 3 sets of efferent neurons coordinated though the pelvic plexus (somatic, thoracolumbar sympathetic, and sacral parasympathetic), and these are under cerebral descending excitatory and inhibitory control. SCI, depending on the level of lesion and completeness, can alter this cerebral control, affecting the psychological and reflexogenic potential for genital arousal and also ejaculation and orgasm. During arousal, nitric oxide is the main neurotransmitter for smooth muscle relaxation in both male and female erectile tissue. In men, erection, ejaculation, and orgasm are under separate neurological control and can be individually affected by SCI. Conclusions: Since sexual function is rated amongst the highest priorities by individuals living with SCI, methods employed to affect the neurological changes to maximize sexual neurophysiology prior to initiating medical therapies including paying attention to sexual sensate areas and visceral signals with mindfulness techniques, practicing body mapping, and sexual stimulation of sensate areas to encourage neuroplasticity. Attention should be paid to the biopsychosocial sexual contexts within which persons with SCI live to maximize their sexual and fertility rehabilitation.

Neural Control and Physiology of Sexual Function: Effect of Spinal Cord Injury

PubMed Central

Elliott, Stacy

2017-01-01

Objective: To present the current understanding of normal anatomy, physiology, sexual physiology, pathophysiology and the consequential sexual changes and dysfunctions following a spinal cord injury (SCI). Methods: Narrative review of the latest literature. Results: Peripheral innervations of the pelvis involve 3 sets of efferent neurons coordinated though the pelvic plexus (somatic, thoracolumbar sympathetic, and sacral parasympathetic), and these are under cerebral descending excitatory and inhibitory control. SCI, depending on the level of lesion and completeness, can alter this cerebral control, affecting the psychological and reflexogenic potential for genital arousal and also ejaculation and orgasm. During arousal, nitric oxide is the main neurotransmitter for smooth muscle relaxation in both male and female erectile tissue. In men, erection, ejaculation, and orgasm are under separate neurological control and can be individually affected by SCI. Conclusions: Since sexual function is rated amongst the highest priorities by individuals living with SCI, methods employed to affect the neurological changes to maximize sexual neurophysiology prior to initiating medical therapies including paying attention to sexual sensate areas and visceral signals with mindfulness techniques, practicing body mapping, and sexual stimulation of sensate areas to encourage neuroplasticity. Attention should be paid to the biopsychosocial sexual contexts within which persons with SCI live to maximize their sexual and fertility rehabilitation. PMID:29339872

Sirtuin 3 mediates neuroprotection of ketones against ischemic stroke

PubMed Central

Yin, Junxiang; Han, Pengcheng; Tang, Zhiwei; Liu, Qingwei; Shi, Jiong

2015-01-01

Stroke is one of the leading causes of death. Growing evidence indicates that ketone bodies have beneficial effects in treating stroke, but their underlying mechanism remains unclear. Our previous study showed ketone bodies reduced reactive oxygen species by using NADH as an electron donor, thus increasing the NAD+/NADH ratio. In this study, we investigated whether mitochondrial NAD+-dependent Sirtuin 3 (SIRT3) could mediate the neuroprotective effects of ketone bodies after ischemic stroke. We injected mice with either normal saline or ketones (beta-hydroxybutyrate and acetoacetate) at 30 minutes after ischemia induced by transient middle cerebral artery (MCA) occlusion. We found that ketone treatment enhanced mitochondria function, reduced oxidative stress, and therefore reduced infarct volume. This led to improved neurologic function after ischemia, including the neurologic score and the performance in Rotarod and open field tests. We further showed that ketones' effects were achieved by upregulating NAD+-dependent SIRT3 and its downstream substrates forkhead box O3a (FoxO3a) and superoxide dismutase 2 (SOD2) in the penumbra region since knocking down SIRT3 in vitro diminished ketones' beneficial effects. These results provide us a foundation to develop novel therapeutics targeting this SIRT3-FoxO3a-SOD2 pathway. PMID:26058697

Intraoperative visualisation of functional structures facilitates safe frameless stereotactic biopsy in the motor eloquent regions of the brain.

PubMed

Zhang, Jia-Shu; Qu, Ling; Wang, Qun; Jin, Wei; Hou, Yuan-Zheng; Sun, Guo-Chen; Li, Fang-Ye; Yu, Xin-Guang; Xu, Ban-Nan; Chen, Xiao-Lei

2017-12-20

For stereotactic brain biopsy involving motor eloquent regions, the surgical objective is to enhance diagnostic yield and preserve neurological function. To achieve this aim, we implemented functional neuro-navigation and intraoperative magnetic resonance imaging (iMRI) into the biopsy procedure. The impact of this integrated technique on the surgical outcome and postoperative neurological function was investigated and evaluated. Thirty nine patients with lesions involving motor eloquent structures underwent frameless stereotactic biopsy assisted by functional neuro-navigation and iMRI. Intraoperative visualisation was realised by integrating anatomical and functional information into a navigation framework to improve biopsy trajectories and preserve eloquent structures. iMRI was conducted to guarantee the biopsy accuracy and detect intraoperative complications. The perioperative change of motor function and biopsy error before and after iMRI were recorded, and the role of functional information in trajectory selection and the relationship between the distance from sampling site to nearby eloquent structures and the neurological deterioration were further analyzed. Functional neuro-navigation helped modify the original trajectories and sampling sites in 35.90% (16/39) of cases to avoid the damage of eloquent structures. Even though all the lesions were high-risk of causing neurological deficits, no significant difference was found between preoperative and postoperative muscle strength. After data analysis, 3mm was supposed to be the safe distance for avoiding transient neurological deterioration. During surgery, the use of iMRI significantly reduced the biopsy errors (p = 0.042) and potentially increased the diagnostic yield from 84.62% (33/39) to 94.87% (37/39). Moreover, iMRI detected intraoperative haemorrhage in 5.13% (2/39) of patients, all of them benefited from the intraoperative strategies based on iMRI findings. Intraoperative visualisation of functional structures could be a feasible, safe and effective technique. Combined with intraoperative high-field MRI, it contributed to enhance the biopsy accuracy and lower neurological complications in stereotactic brain biopsy involving motor eloquent areas.

Connectomics and other novel methods for examining neural systems.

PubMed

Wurtman, Richard J

2017-04-01

Novel approaches for studying the brain and relating its activities to mental phenomena have come into use during the past decade (Bargmann, 2015). These include both new laboratory methods - involving, among others, generation of isolated cells which retain neuronal characteristics in vivo; the selective stimulation of neurons by light in vivo; and direct electrical stimulation of specific brain regions to restore a system's balance of excitation and inhibition - and a new organizing principle, "connectomics", which recognizes that networks, and not simply a key nucleus or region, underlie most brain functions and malfunctions. Its application has already improved our comprehension of how the brain normally functions and our ability to help patients with such poorly treated neurologic and psychiatric diseases as Alzheimer's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

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…

Compelling Evidence that Exposure Therapy for PTSD Normalizes Brain Function.

PubMed

Roy, Michael J; Costanzo, Michelle E; Blair, James R; Rizzo, Albert A

2014-01-01

Functional magnetic resonance imaging (fMRI) is helping us better understand the neurologic pathways involved in posttraumatic stress disorder (PTSD). We previously reported that military service members with PTSD after deployment to Iraq or Afghanistan demonstrated significant improvement, or normalization, in the fMRI-measured activation of the amygdala, prefrontal cortex and anterior cingulate gyrus following exposure therapy for PTSD. However, our original study design did not include repeat scans of control participants, rendering it difficult to discern how much of the observed normalization in brain activity is attributable to treatment, rather than merely a practice effect. Using the same Affective Stroop task paradigm, we now report on a larger sample of PTSD-positive combat veterans that we treated with exposure therapy, as well as a combat-exposed control group of service members who completed repeat scans at 3-4 month intervals. Findings from the treatment group are similar to our prior report. Combat controls showed no significant change on repeat scanning, indicating that the observed differences in the intervention group were in fact due to treatment. We continue to scan additional study participants, in order to determine whether virtual reality exposure therapy has a different impact on regional brain activation than other therapies for PTSD.

Residual neurological function after sacral root resection during en-bloc sacrectomy: a systematic review.

PubMed

Zoccali, Carmine; Skoch, Jesse; Patel, Apar S; Walter, Christina M; Maykowski, Philip; Baaj, Ali A

2016-12-01

Sacrectomy is a highly demanding surgery representing the main treatment for primary tumors arising in the sacrum and pelvis. Unfortunately, it is correlated with loss of important function depending on the resection level and nerve roots sacrificed. The current literature regarding residual function after sacral resection comes from several small case series. The goal of this review is to appraise residual motor function and gait, sensitivity, bladder, bowel, and sexual function after sacrectomies, with consideration to the specific roots sacrificed. An exhaustive literature search was conducted. All manuscripts published before May 2015 regarding residual function after sacrectomy were considered; if a clear correlation between root level and functioning was not present, the paper was excluded. The review identified 15 retrospective case series, totaling 244 patients; 42 patients underwent sacrectomies sparing L4/L4, L4/L5 and L5/L5; 45 sparing both L5 and one or both S1 roots; 8 sparing both S1 and one S2; 48 sparing both S2; 11 sparing both S2 and one S3, 54 sparing both S3, 9 sparing both S3 and one or both S4, and 27 underwent unilateral variable resection. Patients who underwent a sacrectomy maintained functionally normal ambulation in 56.2 % of cases when both S2 roots were spared, 94.1 % when both S3 were spared, and in 100 % of more distal resections. Normal bladder and bowel function were not present when both S2 were cut. When one S2 root was spared, normal bladder function was present in 25 % of cases; when both S2 were spared, 39.9 %; when one S3 was spared, 72.7 %; and when both S3 were spared, 83.3 %. Abnormal bowel function was present in 12.5 % of cases when both S1 and one S2 were spared; in 50.0 % of cases when both S2 were spared; and in 70 % of cases when one S3 was spared; if both S3 were spared, bowel function was normal in 94 % of cases. When even one S4 root was spared, normal bladder and bowel function were present in 100 % of cases. Unilateral sacral nerve root resection preserved normal bladder function in 75 % of cases and normal bowel function in 82.6 % of cases. Motor function depended on S1 root involvement. Total sacrectomy is associated with compromising important motor, bladder, bowel, sensitivity, and sexual function. Residual motor function is dependent on sparing L5 and S1 nerve roots. Bladder and bowel function is consistently compromised in higher sacrectomies; nevertheless, the probability of maintaining sufficient function increases progressively with the roots spared, especially when S3 nerve roots are spared. Unilateral resection is usually associated with more normal function. To the best of our knowledge, this is the first comprehensive literature review to analyze published reports of residual sacral nerve root function after sacrectomy.

Mutations in UNC80, Encoding Part of the UNC79-UNC80-NALCN Channel Complex, Cause Autosomal-Recessive Severe Infantile Encephalopathy

PubMed Central

Shamseldin, Hanan E.; Faqeih, Eissa; Alasmari, Ali; Zaki, Maha S.; Gleeson, Joseph G.; Alkuraya, Fowzan S.

2016-01-01

Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. PMID:26708753

What Is Orofacial Fatigue and How Does It Affect Function for Swallowing and Speech?

PubMed Central

Solomon, Nancy Pearl

2012-01-01

Speech-language pathologists are likely to encounter patients who report symptoms of fatigue, but there are few clinical procedures to assess this phenomenon. Furthermore, it is difficult to determine whether fatigue contributes to a patient's dysphagia or dysarthria. This article reviews orofacial muscles, including the muscles of the tongue, lips, and cheeks, highlighting in particular their role in swallowing and speaking. It provides definitions of fatigue and describes assessment procedures. The author's research has focused on assessing fatigue, especially of the tongue, and elucidating the effects of exercising the tongue on speech and nonspeech tasks. Most of this work involves people who have Parkinson's disease and neurologically normal adults; results generally support heightened fatigue in Parkinson's disease. However, the effect of fatigue on functional activities remains unclear. Literature regarding the effects of orofacial fatigue on swallowing and speaking is notably sparse, but preliminary evidence indicates that these functions are rather robust. PMID:17117353

The mGluR theory of fragile X mental retardation.

PubMed

Bear, Mark F; Huber, Kimberly M; Warren, Stephen T

2004-07-01

Many of the diverse functional consequences of activating group 1 metabotropic glutamate receptors require translation of pre-existing mRNA near synapses. One of these consequences is long-term depression (LTD) of transmission at hippocampal synapses. Loss of fragile X mental retardation protein (FMRP), the defect responsible for fragile X syndrome in humans, increases LTD in mouse hippocampus. This finding is consistent with the growing evidence that FMRP normally functions as a repressor of translation of specific mRNAs. Here we present a theory that can account for diverse neurological and psychiatric aspects of fragile X syndrome, based on the assumption that many of the protein-synthesis-dependent functions of metabotropic receptors are exaggerated in fragile X syndrome. The theory suggests new directions for basic research as well as novel therapeutic approaches for the treatment of humans with fragile X, the most frequent inherited cause of mental retardation and an identified cause of autism.

Do (epi)genetics impact the brain in functional neurologic disorders?

PubMed

Frodl, T

2016-01-01

Advances in neuropsychiatric research are supposed to lead to significant improvements in understanding functional neurologic disorders and their diagnosis. However, epigenetic and genetic research on conversion disorders and somatoform disorders is only at its start. This review demonstrates the current state within this field and tries to bridge a gap from what is known on gene-stress interactions in other psychiatric disorders like depression. The etiology of conversion disorders is hypothesized to be multifactorial. These considerations also suggest that potential etiologic factors lead to alterations in brain function, either episodically or chronically, eventually leading to structural brain changes. In particular, the knowledge of how the environment influences brain structure and function, e.g., via epigenetic regulation, may be interesting for future research in functional neurologic disorders. Reviewing the literature results in evidence that childhood adversities play a role in the development of functional neurologic disorders, whereby at present no reports exist about the interactive effect between childhood adversity and genetic factors or about the impact of epigenetics. © 2016 Elsevier B.V. All rights reserved.

The feasibility of establishing a free clinic for uninsured patients with neurologic disorders.

PubMed

Taylor, Joseph J; Larrew, Thomas; Omole, Armina; Roberts, Mallory; Kornegay, Adam; Kornegay, Kelly; Yamada, Lidia; Revuelta, Gonzalo J; Sohn, Mimi; Hughes, Thomas; Edwards, Jonathan C

2015-08-01

The Dream Center Neurology Clinic (DCNC) is a free specialty clinic associated with the Medical University of South Carolina that provides health care for uninsured patients with neurologic disorders. Routine neurologic care is often neglected by free primary care clinics, leaving indigent and uninsured patients to suffer from treatable neurologic ailments. The DCNC was established by supplementing existing resources from a free primary care facility called the Dream Center. Our strategy of building a high-need specialty service into a preexisting primary care infrastructure may provide a blueprint for neurologists who are eager to address the neurologic needs of the underserved in their local communities. According to local charge estimates, the DCNC has provided roughly $120,000 worth of outpatient neurologic care over the past year. The clinic runs through the collaborative effort of medical students as well as academic and private health care providers. Donated services such as EEG, diagnostic lab work, botulinum toxin, supplies, and imaging are also critical to clinic operations. In addition to providing the uninsured with services that are normally inaccessible to them, the DCNC provides a unique educational opportunity for medical students, residents, and all volunteers who are eager to help and learn.

Undiagnosed neurological disease as a potential cause of male lower urinary tract symptoms.

PubMed

Wei, Diana Y; Drake, Marcus J

2016-01-01

In the central nervous system there are many regulatory processes controlling the lower urinary tract. This review considers the possibility that urinary dysfunction may precede diagnosis of neurological disease. Lower urinary tract symptoms (LUTS) occur early in multiple system atrophy, Parkinson's disease and normal pressure hydrocephalus, and may present before neurological diagnosis. Some people present with LUTS and subsequently are diagnosed with multiple sclerosis or a spinal condition. In male LUTS, the symptoms could reflect early stages of a neurological disease, which has not yet been diagnosed ('occult neurology'). Key symptoms include erectile dysfunction, retrograde ejaculation, enuresis, loss of filling sensation or unexplained stress urinary incontinence. Directed questioning should enquire about visual symptoms, back pain, anosmia, bowel dysfunction and incontinence, or memory loss. Examination features can include resting tremor, 'croaky' speech, abnormal gait, orthostatic hypotension, ataxia, or altered perineal sensation. Imaging, such as MRI scan, should only be requested after expert neurological examination, to ensure the correct parts of the central nervous system are scanned with appropriate radiological protocols. Urologists should consider an undiagnosed neurological condition can be present in a few cases. Any finding should be further evaluated by colleagues with relevant expertise.

Quadriplegia due to lead-contaminated opium--case report.

PubMed

Beigmohammadi, Mohammad Taghi; Aghdashi, Moosa; Najafi, Atabak; Mojtahedzadeh, Mojtaba; Karvandian, Kassra

2008-10-01

Utilization of lead-contaminated opium may lead to severe motor neuron impairment and quadriplegia. Forty years oriented old male, opium addict, was admitted to the ICU, with headache, nausea and abdominal pain, and weakness in his lower and upper extremities without definitive diagnosis. The past medical and occupational history was negative. Laboratory investigation showed; anemia (Hb 7.7 g/dl), slightly elevated liver function tests, elevated total bilirubin, and ESR. Abdominal sonography and brain CT scan were normal. EMG and NCV results and neurologic examination were suggestive for Guillain-Barre. He underwent five sessions of plasmapheresis. Blood lead level was > 200 microg/dl. He received dimercaprol (BAL) and calcium disodium edetate (CaEDTA) for two five days session. Upon discharge from ICU all laboratory tests were normal and blood lead level was reduced, but he was quadriplegic. The delayed treatment of lead poisoning may lead to irreversible motor neuron defect.

Crosstalk between metabolic and neuropsychiatric disorders

PubMed Central

Cha, Danielle S.

2012-01-01

Evidence supporting the concurrence of metabolic disturbances (e.g. insulin resistance, diabetes and obesity) and neuropsychiatric disorders has been demonstrated in both human and animal studies, suggesting the possibility that they have shared pathophysiological mechanisms. During the past decade, our understanding for the role of insulin in both normal and abnormal central nervous system (CNS) processes has become increasingly refined. Evidence indicates that insulin is a pleiotropic peptide, critical to neurotrophism, neuroplasticity, and neuromodulation. Moreover, the role of insulin underscores its importance in the development of several neuropsychiatric disorders, including, but not limited to, mechanisms involved in the pathogenesis and progression towards diabetes, obesity, and neurodegenerative disorders, such as Alzheimer's disease. This review focuses on the insulin-mediated effects on normal and abnormal brain function and discusses why targeting insulin-related pathways in the brain may emerge as a new approach for refining treatment of neurological and psychiatric disorders. PMID:22802875

Crosstalk between metabolic and neuropsychiatric disorders.

PubMed

Kaidanovich-Beilin, Oksana; Cha, Danielle S; McIntyre, Roger S

2012-01-01

Evidence supporting the concurrence of metabolic disturbances (e.g. insulin resistance, diabetes and obesity) and neuropsychiatric disorders has been demonstrated in both human and animal studies, suggesting the possibility that they have shared pathophysiological mechanisms. During the past decade, our understanding for the role of insulin in both normal and abnormal central nervous system (CNS) processes has become increasingly refined. Evidence indicates that insulin is a pleiotropic peptide, critical to neurotrophism, neuroplasticity, and neuromodulation. Moreover, the role of insulin underscores its importance in the development of several neuropsychiatric disorders, including, but not limited to, mechanisms involved in the pathogenesis and progression towards diabetes, obesity, and neurodegenerative disorders, such as Alzheimer's disease. This review focuses on the insulin-mediated effects on normal and abnormal brain function and discusses why targeting insulin-related pathways in the brain may emerge as a new approach for refining treatment of neurological and psychiatric disorders.

Koumine exhibits anxiolytic properties without inducing adverse neurological effects on functional observation battery, open-field and Vogel conflict tests in rodents.

PubMed

Chen, Chao-Jie; Zhong, Zhi-Feng; Xin, Zhi-Ming; Hong, Long-Hui; Su, Yan-Ping; Yu, Chang-Xi

2017-04-01

Koumine, an active alkaloid of neurotoxic plant Gelsemium, has been focused on its therapeutic uses, especially in central nervous system. Nevertheless, less is known about the neurological effects of koumine, which hampers its potential therapeutic exploitation. Moreover, as the anxiolytic potential of Gelsemium has raised many critical issues, its active principles on the anxiolytic and other neurological effects need to be further investigated. Here, we used functional observation battery (FOB) of mice to systematically measure the neurological effects of koumine at the effective doses, and then further confirmed its anxiolytic properties in open-field test (OFT) of mice and Vogel conflict test (VCT) of rats. Koumine exhibited anxiolytic-like activities but did not affect other autonomic, neurological and physical functions in FOB. Furthermore, koumine released anxiolytic responses and anti-punishment action in a manner similar to diazepam in OFT and VCT, respectively. The results constitutes solid set of fundamental data further demonstrating anxiolytic properties of koumine at the therapeutic doses without inducing adverse neurological effects, which supports the perspectives for the development of safe and effective koumine medicine against pathological anxiety.

[Neurological soft signs in pervasive developmental disorders].

PubMed

Halayem, S; Bouden, A; Halayem, M B; Tabbane, K; Amado, I; Krebs, M O

2010-09-01

Many studies have focused on specific motor signs in autism and Asperger's syndrome, but few has been published on the complete range of neurological soft signs (NSS) in children with pervasive developmental disorder (PDD). Scarce are the studies evaluating NSS in children suffering from PDD not otherwise specified (PDDNOS). This study compared performance of 11 autistic children (AD) and 10 children with PDDNOS, with controls matched on age, sex and cognitive performance on Krebs et al.'s NSS scale. Because of the duration of the assessments and specific difficulties encountered in managing some items, an adaptation of the scale had to be made during a pilot study with the agreement of the author. To be eligible, patients had to meet the following inclusion criteria: an age range of 6-16 years, a diagnosis of autistic disorder or PDDNOS based on the DSM IV criteria (American Psychiatric Association 1994). The autism diagnostic interview-revised (ADI-R) was used in order to confirm the diagnosis and to evaluate the association of the symptoms to the severity of the NSS. The childhood autism rating scale (CARS) was completed for the patients in order to evaluate symptoms at the time of the NSS examination. Cognitive ability was assessed with Raven's progressive matrices. Were excluded patients with: history of cerebral palsy, congenital anomaly of the central nervous system, epilepsy, known genetic syndrome, tuberous sclerosis, neurofibromatosis, antecedent of severe head trauma, Asperger's syndrome, obvious physical deformities or sensory deficits that would interfere with neurological assessment, deep mental retardation and recent or chronic substance use or abuse. Healthy controls shared the same exclusion criteria, with no personal history of neurological, psychiatric disorder or substance abuse, no family history of psychiatric disorder and normal or retardation in schooling. All study procedures were approved by the local Ethics Committee (Comité d'éthique, Razi Hospital), according to the declaration of Helsinki. There was no difference between patients and controls with respect to sex, age and cognitive function. All children had an IQ higher than 81. Significant differences were found between AD children and control group in the motor integration function and sensory integration function. Different NSS scores were significantly higher in the PDDNOS group than in controls: the total scores, motor coordination, motor integration function, sensory integration and abnormal movements. Lower performance in motor coordination skills was associated with higher ADI-R communication score in the AD group. No relationship was found between NSS and CARS' total sore. This study confirms the impaired neurological functioning in autistic as well as PDDNOS children. The association of motor impairment with autistic symptoms highlights the argument that motor control problems can be part of the autism spectrum disorders. The lack of relationship between NSS and intellectual aptitude in the clinical sample provides new elements for the neurodevelopment model of the autism spectrum. Copyright © 2010 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

The evidence for urodynamic investigation of patients with symptoms of urinary incontinence

PubMed Central

2013-01-01

Urodynamic studies are the gold standard to objectively diagnose dysfunction of the lower urinary tract. The widely available evidence for the clinical relevance is, however, fragmented. This article summarizes the published knowledge supporting the use of urodynamic studies in urinary incontinence in female, male and frail patients, as well as patients with relevant neurological disease. Five technological innovations are discussed briefly. Standard urodynamic cystometry can, on the basis of a solid body of evidence, objectively unveil the entire function of the lower urinary tract in all patients with urinary incontinence, regardless of the patients' perception of (ab-)normality of signs and or symptoms. PMID:23513180

[The complex approach to the rehabilitation of post-stroke patients with movement disorders in the early rehabilitation period].

PubMed

Khabirov, F A; Khaĭbullin, T I; Grigor'eva, O V

2011-01-01

We studied 110 patients, aged 34-71 years, in the early rehabilitation period after stroke who were admitted to a rehabilitation neurologic department of Kazan. The rehabilitation approach was based on the combination of several methods: kinesitherapy, transcranial magnetic stimulation and cerebrolysin treatment. This complex reanimation allowed to achieve the marked functional restoration of movement abilities in many cases that was correlated with the normalization of brain bioelectric activity (the increase of alpha-rhythm spectral power, the decrease of slow-wave EEG components). The combined use of these three methods was more effective than a combination of any two of them.

Outcome of tyrosinaemia type III.

PubMed

Ellaway, C J; Holme, E; Standing, S; Preece, M A; Green, A; Ploechl, E; Ugarte, M; Trefz, F K; Leonard, J V

2001-12-01

Tyrosinaemia type III is a rare disorder caused by a deficiency of 4-hydroxyphenylpyruvate dioxygenase, the second enzyme in the catabolic pathway of tyrosine. The majority of the nine previously reported patients have presented with neurological symptoms after the neonatal period, while others detected by neonatal screening have been asymptomatic. All have had normal liver and renal function and none has skin or eye abnormalities. A further four patients with tyrosinaemia type III are described. It is not clear whether a strict low tyrosine diet alters the natural history of tyrosinaemia type III, although there remains a suspicion that treatment may be important, at least in infancy.

Effects of Speaking Rate on Word Recognition in Parkinson’s Disease and Normal Aging

PubMed Central

Forrest, Karen; Nygaard, Lynne; Pisoni, David B.; Siemers, Eric

2011-01-01

Current theories of basal ganglia function emphasize their role in the integration of sensory information into motor activities, particularly in the control of movement timing. People with basal ganglia disorders such as Parkinson’s disease exhibit poor temporal control of movements, in general and articulation in particular, as demonstrated by irregular speaking rate, reduced stress contrasts, and reduced movement durations and velocities. Previous research has implicated sensory deficits as contributory factors in limb movement control in patients with Parkinson’s disease; however, the relation between sensory deficits and speech-movement abnormalities has not been documented. In the present study, the existence of perceptual processing difficulties of speaking rate was investigated in subjects with Parkinsonian dysarthria (PD). Comparisons in perception were made between subjects with PD, neurologically normal geriatrics (GN) and neurologically normal young adults (YN) for accuracy in identification of words presented at different speaking rates. We hypothesized that word-identification scores would be lower for PD and GN subjects compared to the YN subjects, an effect that was supported by the data. We also expected that there would be differences between the GN and PD subjects in their accuracy of word identification at a faster speaking rate, an hypothesis that was not supported by the data. Rather, GN and PD subjects differed in identification scores for words spoken at a slow rate. PD subjects who had faster habitual speaking rates (HSR) had significantly lower word-identification scores in the slow compared to conversational rate conditions, a relation that was significant r = +0.64). These data suggest the need to consider perceptual deficits as an additional factor that contributes to rate variations in PD speech. PMID:21637728

A voxel-based analysis of FDG-PET in traumatic brain injury: regional metabolism and relationship between the thalamus and cortical areas.

PubMed

García-Panach, Javier; Lull, Nuria; Lull, Juan José; Ferri, Joan; Martínez, Carlos; Sopena, Pablo; Robles, Montserrat; Chirivella, Javier; Noé, Enrique

2011-09-01

The objective was to study the correlations and the differences in glucose metabolism between the thalamus and cortical structures in a sample of severe traumatic brain injury (TBI) patients with different neurological outcomes. We studied 49 patients who had suffered a severe TBI and 10 healthy control subjects using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). The patients were divided into three groups: a vegetative or minimally-conscious state (MCS&VS) group (n=17), which included patients who were in a vegetative or a minimally conscious state; an In-post-traumatic amnesia (In-PTA) group (n=12), which included patients in PTA; and an Out-PTA group (n=20), which included patients who had recovered from PTA. SPM5 software was used to determine the metabolic differences between the groups. FDG-PET images were normalized and four regions of interest were generated around the thalamus, precuneus, and the frontal and temporal lobes. The groups were parameterized using Student's t-test. Principal component analysis was used to obtain an intensity-estimated-value per subject to correlate the function between the structures. Differences in glucose metabolism in all structures were related to the neurological outcome, and the most severe patients showed the most severe hypometabolism. We also found a significant correlation between the cortico-thalamo-cortical metabolism in all groups. Voxel-based analysis suggests a functional correlation between these four areas, and decreased metabolism was associated with less favorable outcomes. Higher levels of activation of the cortico-cortical connections appear to be related to better neurological condition. Differences in the thalamo-cortical correlations between patients and controls may be related to traumatic dysfunction due to focal or diffuse lesions.

Neurogranin, a synaptic protein, is associated with memory independent of Alzheimer biomarkers.

PubMed

Casaletto, Kaitlin B; Elahi, Fanny M; Bettcher, Brianne M; Neuhaus, John; Bendlin, Barbara B; Asthana, Sanjay; Johnson, Sterling C; Yaffe, Kristine; Carlsson, Cynthia; Blennow, Kaj; Zetterberg, Henrik; Kramer, Joel H

2017-10-24

To determine the association between synaptic functioning as measured via neurogranin in CSF and cognition relative to established Alzheimer disease (AD) biomarkers in neurologically healthy older adults. We analyzed CSF concentrations of neurogranin, β-amyloid (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau) among 132 neurologically normal older adults (mean 64.5, range 55-85), along with bilateral hippocampal volumes and a measure of episodic memory (Auditory Verbal Learning Test, delayed recall). Univariable analyses examined the relationship between neurogranin and the other AD-related biomarkers. Multivariable regression models examined the relationship between neurogranin and delayed recall, adjusting for age and sex, and interaction terms (neurogranin × AD biomarkers). Higher neurogranin concentrations were associated with older age (ρ = 0.20, p = 0.02), lower levels of p-tau and t-tau, and smaller hippocampal volumes ( p < 0.03), but not with CSF Aβ42 ( p = 0.18). In addition, CSF neurogranin demonstrated a significant relationship with memory performance independent of the AD-related biomarkers; individuals with the lowest CSF neurogranin concentrations performed better on delayed recall than those with medium or high CSF neurogranin concentrations ( p < 0.01). Notably, CSF p-tau, t-tau, and Aβ42 and hippocampal volumes were not significantly associated with delayed recall scores ( p > 0.40), and did not interact with neurogranin to predict memory ( p > 0.10). Synaptic dysfunction (assessed via neurogranin) may be an early pathologic process in age-related neurodegeneration, and a sensitive marker of age-related cognitive abilities, potentially preceding or even acting independently from AD pathogenesis. Synaptic functioning may be a useful early marker of cognitive aging and possibly a target for future brain aging interventions. © 2017 American Academy of Neurology.

Gastroesophageal Reflux in Neurologically Impaired Children: What Are the Risk Factors?

PubMed

Kim, Seung; Koh, Hong; Lee, Joon Soo

2017-03-15

Neurologically impaired patients frequently suffer from gastrointestinal tract problems, such as gastroesophageal reflux disease (GERD). In this study, we aimed to define the risk factors for GERD in neurologically impaired children. From May 2006 to March 2014, 101 neurologically impaired children who received 24-hour esophageal pH monitoring at Severance Children's Hospital were enrolled in the study. The esophageal pH finding and the clinical characteristics of the patients were analyzed. The reflux index was higher in patients with abnormal electroencephalography (EEG) results than in those with normal EEG results (p=0.027). Mitochondrial disease was associated with a higher reflux index than were epileptic disorders or cerebral palsy (p=0.009). Patient gender, feeding method, scoliosis, tracheostomy, and baclofen use did not lead to statistical differences in reflux index. Age of onset of neurological impairment was inversely correlated with DeMeester score and reflux index. Age at the time of examination, the duration of the disease, and the number of antiepileptic drugs were not correlated with GER severity. Early-onset neurological impairment, abnormal EEG results, and mitochondrial disease are risk factors for severe GERD.

Functional genomics reveals an essential and specific role for Stat1 in protection of the central nervous system following herpes simplex virus corneal infection.

PubMed

Pasieka, Tracy Jo; Cilloniz, Cristian; Carter, Victoria S; Rosato, Pamela; Katze, Michael G; Leib, David A

2011-12-01

Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), and Δvhs, an avirulent recombinant lacking the virion host shutoff (vhs) function. In addition, two mouse strains were used: strain 129 (control) and a Stat1-deficient (Stat1(-/-)) strain. Using combinations of these virus and mouse strains, we established a model of infection resulting in three different outcomes: viral clearance without neurological disease (Δvhs infection of control mice), neurological disease followed by viral clearance (Δvhs infection of Stat1(-/-) mice and WT infection of control mice), or neurological disease followed by death (WT infection of Stat1(-/-) mice). Through the use of functional genomics on the infected brain stems, we determined gene signatures that were representative of the three infection outcomes. We demonstrated a pathological signature in the brain stem of Stat1-deficient mice characterized by upregulation of transcripts encoding chemokine receptors, inflammatory markers, neutrophil chemoattractants, leukocyte adhesion proteins, and matrix metalloproteases. Additionally, there was a greater than 100-fold increase in the inflammatory markers interleukin 1β (IL-1β) and IL-6. Consistent with this gene signature, we demonstrated profound CNS inflammation with a concomitant lethal breach of the BBB. Taken together, our results indicated an essential role for normal Stat1-dependent signaling in mediating a nonpathological immune response to viral CNS infection.

The relationship between subconcussive impacts and concussion history on clinical measures of neurologic function in collegiate football players.

PubMed

Gysland, Sonia M; Mihalik, Jason P; Register-Mihalik, Johna K; Trulock, Scott C; Shields, Edgar W; Guskiewicz, Kevin M

2012-01-01

Concussions sustained during college and professional football careers have been associated with both acute and chronic neurologic impairment. The contribution of subconcussive impacts to this impairment has not been adequately studied. Therefore, we investigated the relationship between subconcussive impacts and concussion history on clinical measures of neurologic function. Forty-six collegiate football players completed five clinical measures of neurologic function commonly employed in the evaluation of concussion before and after a single season. These tests included the Automated Neuropsychological Assessment Metrics, Sensory Organization Test, Standardized Assessment of Concussion, Balance Error Scoring System, and Graded Symptom Checklist. The Head Impact Telemetry (HIT) System recorded head impact data including the frequency, magnitude, and location of impacts. College football players sustain approximately 1,000 subconcussive impacts to the head over the course of a season, but for the most part, do not demonstrate any clinically meaningful changes from preseason to postseason on measures of neurologic function. Changes in performance were mostly independent of prior concussion history, and the total number, magnitude and location of sustained impacts over one season as observed R(2) values ranged between 0.30 and 0.35. Repetitive subconcussive head impacts over a single season do not appear to result in short-term neurologic impairment, but these relationships should be further investigated for a potential dose-response over a player's career.

Free-Radical Scavenger Edaravone Treatment Confers Neuroprotection Against Traumatic Brain Injury in Rats

PubMed Central

Wang, Guo-Hua; Li, Yong-Cai; Li, Xia; Shi, Hong; Gao, Yan-Qin; Vosler, Peter S.

2011-01-01

Abstract Traumatic brain injury (TBI) is one of the leading causes of neurological disability in young adults. Edaravone, a novel synthetic small-molecule free-radical scavenger, has been shown to have a neuroprotective effect in both animal models of cerebral ischemia and stroke patients; however, the underlying mechanism is poorly understood. In this report, we investigated the potential mechanisms of edaravone treatment in a rat model of TBI. TBI was induced in the right cerebral cortex of male adult rats using Feeney's weight-drop method. Edaravone (0.75, 1.5, or 3 mg/kg) or vehicle (normal saline) was intravenously administered at 2 and 12 h after TBI. Edaravone treatment significantly decreased hippocampal CA3 neuron loss, reduced oxidative stress, and decreased neuronal programmed cell death compared to vehicle treatment. The protective effects of edaravone treatment were also related to the pathology of TBI on non-neuronal cells, as edaravone decreased astrocyte and glial activation. Lastly, edaravone treatment significantly reduced the presence of inflammatory cytokines, cerebral edema, blood–brain barrier (BBB) permeability, and, importantly, neurological deficits following TBI. Our results suggest that edaravone exerts a neuroprotective effect in the rat model of TBI. The likely mechanism is via inhibiting oxidative stress, leading to a decreased inflammatory response and glial activation, and thereby reducing neuronal death and improving neurological function. PMID:21732763

Gastrointestinal and nutritional problems in neurologically impaired children.

PubMed

Quitadamo, Paolo; Thapar, Nikhil; Staiano, Annamaria; Borrelli, Osvaldo

2016-11-01

The current increasing survival of children with severe central nervous system damage has created a major challenge for medical care. Gastrointestinal and nutritional problems in neurologically impaired children have been recently recognized as an integral part of their disease, often leading to growth failure and worsened quality of life for both children and caregivers. Nutritional support is essential for the optimal care of these children. Undernourished handicapped children might not respond properly to intercurrent diseases and suffer unnecessarily. On the other hand, restoring a normal nutritional status results in a better quality of life in many. The easiest and least invasive method to increase energy intake is to improve oral intake. However, oral intake can be maintained as long as there is no risk of aspiration, the child is growing well and the time required to feed the child remains within acceptable limits. When oral intake is unsafe, insufficient or too time consuming, enteral nutrition should be initiated. Damage to the developing central nervous system may result in significant dysfunction in the gastrointestinal tract and is reflected in impairment in oral-motor function, rumination, gastro-oesophageal reflux (GER), with or without aspiration, delayed gastric emptying and constipation. These problems can all potentially contribute to feeding difficulty in disabled children, carrying further challenging long-term management issues. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Polynitroxyl albumin and albumin therapy after pediatric asphyxial cardiac arrest: effects on cerebral blood flow and neurologic outcome

PubMed Central

Manole, Mioara D; Kochanek, Patrick M; Foley, Lesley M; Hitchens, T Kevin; Bayır, Hülya; Alexander, Henry; Garman, Robert; Ma, Li; Hsia, Carleton J C; Ho, Chien; Clark, Robert S B

2012-01-01

Postresuscitation cerebral blood flow (CBF) disturbances and generation of reactive oxygen species likely contribute to impaired neurologic outcome after pediatric cardiac arrest (CA). Hence, we determined the effects of the antioxidant colloid polynitroxyl albumin (PNA) versus albumin or normal saline (NS) on CBF and neurologic outcome after asphyxial CA in immature rats. We induced asphyxia for 9 minutes in male and female postnatal day 16 to 18 rats randomized to receive PNA, albumin, or NS at resuscitation from CA or sham surgery. Regional CBF was measured serially from 5 to 150 minutes after resuscitation by arterial spin-labeled magnetic resonance imaging. We assessed motor function (beam balance and inclined plane), spatial memory retention (water maze), and hippocampal neuronal survival. Polynitroxyl albumin reduced early hyperemia seen 5 minutes after CA. In contrast, albumin markedly increased and prolonged hyperemia. In the delayed period after resuscitation (90 to 150 minutes), CBF was comparable among groups. Both PNA- and albumin-treated rats performed better in the water maze versus NS after CA. This benefit was observed only in males. Hippocampal neuron survival was similar between injury groups. Treatment of immature rats with PNA or albumin resulted in divergent acute changes in CBF, but both improved spatial memory retention in males after asphyxial CA. PMID:22126915

Validity assessment and the neurological physical examination.

PubMed

Zasler, Nathan D

2015-01-01

The assessment of any patient or examinee with neurological impairment, whether acquired or congenital, provides a key set of data points in the context of developing accurate diagnostic impressions and implementing an appropriate neurorehabilitation program. As part of that assessment, the neurological physical exam is an extremely important component of the overall neurological assessment. In the aforementioned context, clinicians often are confounded by unusual, atypical or unexplainable physical exam findings that bring into question the organicity, veracity, and/or underlying cause of the observed clinical presentation. The purpose of this review is to provide readers with general directions and specific caveats regarding validity assessment in the context of the neurological physical exam. It is of utmost importance for health care practitioners to be aware of assessment methodologies that may assist in determining the validity of the neurological physical exam and differentiating organic from non-organic/functional impairments. Maybe more importantly, the limitations of many commonly used strategies for assessment of non-organicity should be recognized and consider prior to labeling observed physical findings on neurological exam as non-organic or functional.

Neurological Research on Language and the Implications for Teaching Bilingual Children to Read. Occasional Papers on Linguistics, No. 1.

ERIC Educational Resources Information Center

Giordano, Gerard

Neurological data indicate that the universal aptitude for functional language is biologically based, species specific, and developmental. The universality of functional oral speech is indisputable. Everyone, however, does not exhibit similar expertise in processing oral and visual language. Many people can speak two languages functionally but…

Dysprosody nonassociated with neurological diseases--a case report.

PubMed

Pinto, José Antonio; Corso, Renato José; Guilherme, Ana Cláudia Rocha; Pinho, Sílvia Rebelo; Nóbrega, Monica de Oliveira

2004-03-01

Dysprosody also known as pseudo-foreign dialect, is the rarest neurological speech disorder. It is characterized by alterations in intensity, in the timing of utterance segments, and in rhythm, cadency, and intonation of words. The terms refers to changes as to duration, fundamental frequency, and intensity of tonic and atonic syllables of the sentences spoken, which deprive an individual's particular speech of its characteristics. The cause of this disease is usually associated with neurological pathologies such as brain vascular accidents, cranioencephalic traumatisms, and brain tumors. The authors report a case of dysprosody attended to at the Núcleo de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço de São Paulo (NOSP). It is about a female patient with bilateral III degree Reinke's edema and normal neurological examinations that started presenting characteristics of the German dialect following a larynx microsurgery.

Maternal influences on fetal microbial colonization and immune development

PubMed Central

Romano-Keeler, Joann; Weitkamp, Jörn-Hendrik

2014-01-01

While critical for normal development, the exact timing of establishment of the intestinal microbiome is unknown. For example, although preterm labor and birth have been associated with bacterial colonization of the amniotic cavity and fetal membranes for many years, the prevailing dogma of a sterile intrauterine environment during normal term pregnancies has been challenged more recently. While found to be a key contributor of evolution in the animal kingdom, maternal transmission of commensal bacteria may also constitute a critical process during healthy pregnancies in humans with yet unclear developmental importance. Metagenomic sequencing has elucidated a rich placental microbiome in normal term pregnancies likely providing important metabolic and immune contributions to the growing fetus. Conversely, an altered microbial composition during pregnancy may produce aberrant metabolites impairing fetal brain development and life-long neurological outcomes. Here we review the current understanding of microbial colonization at the feto-maternal interface and explain how normal gut colonization drives a balanced neonatal mucosal immune system, while dysbiosis contributes to aberrant immune function early in life and beyond. We discuss how maternal genetics, diet, medications, and probiotics inform the fetal microbiome in preparation for perinatal and postnatal bacterial colonization. PMID:25310759

Recent advances in applying mass spectrometry and systems biology to determine brain dynamics.

PubMed

Scifo, Enzo; Calza, Giulio; Fuhrmann, Martin; Soliymani, Rabah; Baumann, Marc; Lalowski, Maciej

2017-06-01

Neurological disorders encompass various pathologies which disrupt normal brain physiology and function. Poor understanding of their underlying molecular mechanisms and their societal burden argues for the necessity of novel prevention strategies, early diagnostic techniques and alternative treatment options to reduce the scale of their expected increase. Areas covered: This review scrutinizes mass spectrometry based approaches used to investigate brain dynamics in various conditions, including neurodegenerative and neuropsychiatric disorders. Different proteomics workflows for isolation/enrichment of specific cell populations or brain regions, sample processing; mass spectrometry technologies, for differential proteome quantitation, analysis of post-translational modifications and imaging approaches in the brain are critically deliberated. Future directions, including analysis of cellular sub-compartments, targeted MS platforms (selected/parallel reaction monitoring) and use of mass cytometry are also discussed. Expert commentary: Here, we summarize and evaluate current mass spectrometry based approaches for determining brain dynamics in health and diseases states, with a focus on neurological disorders. Furthermore, we provide insight on current trends and new MS technologies with potential to improve this analysis.

Gastrointestinal problems in the neurologically impaired child.

PubMed

Sullivan, P B

1997-09-01

Damage to the developing central nervous system may result in significant dysfunction in the gastrointestinal tract and is reflected in impairment in oral-motor function, rumination, gastro-oesophageal reflux, with or without aspiration, delayed gastric emptying and constipation. These problems can all potentially contribute to feeding difficulty in disabled children. Early recognition of an infant with neurological impairment that is compromising the normal feeding process is crucial. Detailed assessment of the nature of the feeding difficulties will help to predict the anticipated future nutritional needs and will allow decisions to be made about the appropriateness of input from different professionals (speech therapy, dietitians, gastroenterologists). Only when such information has been carefully assembled will rational and directed medical and surgical therapy be possible. Nutritional rehabilitation of disabled children can be associated with increased mortality and morbidity secondary to gastro-oesophageal reflux, retching, dumping syndrome or aspiration. It may also entail an increased work for care givers and increase costs of care. It is therefore necessary to document the impact of such rehabilitation on growth and quality of life for both patient and care giver.

Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia

NASA Technical Reports Server (NTRS)

Zeitzer, J. M.; Ayas, N. T.; Shea, S. A.; Brown, R.; Czeisler, C. A.

2000-01-01

The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.

SUMOylation in Neurological Diseases.

PubMed

Liu, F-Y; Liu, Y-F; Yang, Y; Luo, Z-W; Xiang, J-W; Chen, Z-G; Qi, R-L; Yang, T-H; Xiao, Y; Qing, W-J; Li, D W-C

2017-01-01

Since the discovery of SUMOs (small ubiquitin-like modifiers) over 20 years ago, sumoylation has recently emerged as an important posttranslational modification involved in almost all aspects of cellular physiology. In neurons, sumoylation dynamically modulates protein function and consequently plays an important role in neuronal maturation, synapse formation and plasticity. Thus, the dysfunction of sumoylation pathway is associated with many different neurological disorders. Hundreds of different proteins implicated in the pathogenesis of neurological disorders are SUMO-modified, indicating the importance of sumoylation involved in the neurological diseases. In this review, we summarize the growing findings on protein sumoylation in neuronal function and dysfunction. It is essential to have a thorough understanding on the mechanism how sumoylation contributes to neurological diseases in developing efficient therapy for these diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of core body temperature on changes in spinal somatosensory-evoked potential in acute spinal cord compression injury: an experimental study in the rat.

PubMed

Jou, I M

2000-08-01

Acute spinal cord injury was induced by a clip compression model in rats to approximate spinal cord injury encountered in spinal surgery. Spinal somatosensory-evoked potential neuromonitoring was used to study the electrophysiologic change. To compare and correlate changes in evoked potential after acute compression at different core temperatures with postoperative neurologic function and histologic change, to evaluate current intraoperative neuromonitoring warning criteria for neural damage, and to confirm the protective effect of hypothermia in acute spinal cord compression injury by electrophysiologic, histologic, and clinical observation. With the increase in aggressive correction of spinal deformities, and the invasiveness of surgical instruments, the incidence of neurologic complication appears to have increased despite the availability of sensitive intraoperative neuromonitoring techniques designed to alert surgeons to impending neural damage. Many reasons have been given for the frequent failures of neuromonitoring, but the influence of temperature-a very important and frequently encountered factor-on evoked potential has not been well documented. Specifically, decrease in amplitude and elongation of latency seem not to have been sufficiently taken into account when intraoperative neuromonitoring levels were interpreted and when acceptable intraoperative warning criteria were determined. Experimental acute spinal cord injury was induced in rats by clip compression for two different intervals and at three different core temperatures. Spinal somatosensory-evoked potential, elicited by stimulating the median nerve and recorded from the cervical interspinous C2-C3, was monitored immediately before and after compression, and at 15-minute intervals for 1 hour. Spinal somatosensory-evoked potential change is almost parallel to temperature-based amplitude reduction and latency elongation. Significant neurologic damage induced by acute compression of the cervical spinal cord produced a degree of effect on the amplitude of spinal somatosensory-evoked potential in normothermic conditions that differed from the effect in moderately hypothermic conditions. Using the same electromonitoring criteria,moderately hypothermic groups showed a significantly higher false-negative rate statistically (35%) than normothermic groups (10%). Systemic cooling may protect against the detrimental effects of aggressive spinal surgical procedures. There is still not enough published information available to establish statistically and ethically acceptable intraoperative neuromonitoring warning and intervention criteria conclusively. Therefore, an urgent need exists for further investigation. Although a reduction of more than 50% in evoked potential still seems acceptable as an indicator of impending neural function loss, maintenance of more than 50% of baseline evoked potential is no guarantee of normal postoperative neural function, especially at lower than normal temperatures.

Strain map of the tongue in normal and ALS speech patterns from tagged and diffusion MRI

NASA Astrophysics Data System (ADS)

Xing, Fangxu; Prince, Jerry L.; Stone, Maureen; Reese, Timothy G.; Atassi, Nazem; Wedeen, Van J.; El Fakhri, Georges; Woo, Jonghye

2018-03-01

Amyotrophic Lateral Sclerosis (ALS) is a neurological disease that causes death of neurons controlling muscle movements. Loss of speech and swallowing functions is a major impact due to degeneration of the tongue muscles. In speech studies using magnetic resonance (MR) techniques, diffusion tensor imaging (DTI) is used to capture internal tongue muscle fiber structures in three-dimensions (3D) in a non-invasive manner. Tagged magnetic resonance images (tMRI) are used to record tongue motion during speech. In this work, we aim to combine information obtained with both MR imaging techniques to compare the functionality characteristics of the tongue between normal and ALS subjects. We first extracted 3D motion of the tongue using tMRI from fourteen normal subjects in speech. The estimated motion sequences were then warped using diffeomorphic registration into the b0 spaces of the DTI data of two normal subjects and an ALS patient. We then constructed motion atlases by averaging all warped motion fields in each b0 space, and computed strain in the line of action along the muscle fiber directions provided by tractography. Strain in line with the fiber directions provides a quantitative map of the potential active region of the tongue during speech. Comparison between normal and ALS subjects explores the changing volume of compressing tongue tissues in speech facing the situation of muscle degradation. The proposed framework provides for the first time a dynamic map of contracting fibers in ALS speech patterns, and has the potential to provide more insight into the detrimental effects of ALS on speech.

Strain Map of the Tongue in Normal and ALS Speech Patterns from Tagged and Diffusion MRI.

PubMed

Xing, Fangxu; Prince, Jerry L; Stone, Maureen; Reese, Timothy G; Atassi, Nazem; Wedeen, Van J; El Fakhri, Georges; Woo, Jonghye

2018-02-01

Amyotrophic Lateral Sclerosis (ALS) is a neurological disease that causes death of neurons controlling muscle movements. Loss of speech and swallowing functions is a major impact due to degeneration of the tongue muscles. In speech studies using magnetic resonance (MR) techniques, diffusion tensor imaging (DTI) is used to capture internal tongue muscle fiber structures in three-dimensions (3D) in a non-invasive manner. Tagged magnetic resonance images (tMRI) are used to record tongue motion during speech. In this work, we aim to combine information obtained with both MR imaging techniques to compare the functionality characteristics of the tongue between normal and ALS subjects. We first extracted 3D motion of the tongue using tMRI from fourteen normal subjects in speech. The estimated motion sequences were then warped using diffeomorphic registration into the b0 spaces of the DTI data of two normal subjects and an ALS patient. We then constructed motion atlases by averaging all warped motion fields in each b0 space, and computed strain in the line of action along the muscle fiber directions provided by tractography. Strain in line with the fiber directions provides a quantitative map of the potential active region of the tongue during speech. Comparison between normal and ALS subjects explores the changing volume of compressing tongue tissues in speech facing the situation of muscle degradation. The proposed framework provides for the first time a dynamic map of contracting fibers in ALS speech patterns, and has the potential to provide more insight into the detrimental effects of ALS on speech.

Auditory analysis of xeroderma pigmentosum 1971–2012: hearing function, sun sensitivity and DNA repair predict neurological degeneration

PubMed Central

Totonchy, Mariam B.; Tamura, Deborah; Pantell, Matthew S.; Zalewski, Christopher; Bradford, Porcia T.; Merchant, Saumil N.; Nadol, Joseph; Khan, Sikandar G.; Schiffmann, Raphael; Pierson, Tyler Mark; Wiggs, Edythe; Griffith, Andrew J.; DiGiovanna, John J.; Brewer, Carmen C.

2013-01-01

To assess the role of DNA repair in maintenance of hearing function and neurological integrity, we examined hearing status, neurological function, DNA repair complementation group and history of acute burning on minimal sun exposure in all patients with xeroderma pigmentosum, who had at least one complete audiogram, examined at the National Institutes of Health from 1971 to 2012. Seventy-nine patients, aged 1–61 years, were diagnosed with xeroderma pigmentosum (n = 77) or xeroderma pigmentosum/Cockayne syndrome (n = 2). A total of 178 audiograms were included. Clinically significant hearing loss (>20 dB) was present in 23 (29%) of 79 patients. Of the 17 patients with xeroderma pigmentosum-type neurological degeneration, 13 (76%) developed hearing loss, and all 17 were in complementation groups xeroderma pigmentosum type A or type D and reported acute burning on minimal sun exposure. Acute burning on minimal sun exposure without xeroderma pigmentosum-type neurological degeneration was present in 18% of the patients (10/55). Temporal bone histology in a patient with severe xeroderma pigmentosum-type neurological degeneration revealed marked atrophy of the cochlear sensory epithelium and neurons. The 19-year mean age of detection of clinically significant hearing loss in the patients with xeroderma pigmentosum with xeroderma pigmentosum-type neurological degeneration was 54 years younger than that predicted by international norms. The four frequency (0.5/1/2/4 kHz) pure-tone average correlated with degree of neurodegeneration (P < 0.001). In patients with xeroderma pigmentosum, aged 4–30 years, a four-frequency pure-tone average ≥10 dB hearing loss was associated with a 39-fold increased risk (P = 0.002) of having xeroderma pigmentosum-type neurological degeneration. Severity of hearing loss parallels neurological decline in patients with xeroderma pigmentosum-type neurological degeneration. Audiometric findings, complementation group, acute burning on minimal sun exposure and age were important predictors of xeroderma pigmentosum-type neurological degeneration. These results provide evidence that DNA repair is critical in maintaining neurological integrity of the auditory system. PMID:23365097

Auditory analysis of xeroderma pigmentosum 1971-2012: hearing function, sun sensitivity and DNA repair predict neurological degeneration.

PubMed

Totonchy, Mariam B; Tamura, Deborah; Pantell, Matthew S; Zalewski, Christopher; Bradford, Porcia T; Merchant, Saumil N; Nadol, Joseph; Khan, Sikandar G; Schiffmann, Raphael; Pierson, Tyler Mark; Wiggs, Edythe; Griffith, Andrew J; DiGiovanna, John J; Kraemer, Kenneth H; Brewer, Carmen C

2013-01-01

To assess the role of DNA repair in maintenance of hearing function and neurological integrity, we examined hearing status, neurological function, DNA repair complementation group and history of acute burning on minimal sun exposure in all patients with xeroderma pigmentosum, who had at least one complete audiogram, examined at the National Institutes of Health from 1971 to 2012. Seventy-nine patients, aged 1-61 years, were diagnosed with xeroderma pigmentosum (n = 77) or xeroderma pigmentosum/Cockayne syndrome (n = 2). A total of 178 audiograms were included. Clinically significant hearing loss (>20 dB) was present in 23 (29%) of 79 patients. Of the 17 patients with xeroderma pigmentosum-type neurological degeneration, 13 (76%) developed hearing loss, and all 17 were in complementation groups xeroderma pigmentosum type A or type D and reported acute burning on minimal sun exposure. Acute burning on minimal sun exposure without xeroderma pigmentosum-type neurological degeneration was present in 18% of the patients (10/55). Temporal bone histology in a patient with severe xeroderma pigmentosum-type neurological degeneration revealed marked atrophy of the cochlear sensory epithelium and neurons. The 19-year mean age of detection of clinically significant hearing loss in the patients with xeroderma pigmentosum with xeroderma pigmentosum-type neurological degeneration was 54 years younger than that predicted by international norms. The four frequency (0.5/1/2/4 kHz) pure-tone average correlated with degree of neurodegeneration (P < 0.001). In patients with xeroderma pigmentosum, aged 4-30 years, a four-frequency pure-tone average ≥10 dB hearing loss was associated with a 39-fold increased risk (P = 0.002) of having xeroderma pigmentosum-type neurological degeneration. Severity of hearing loss parallels neurological decline in patients with xeroderma pigmentosum-type neurological degeneration. Audiometric findings, complementation group, acute burning on minimal sun exposure and age were important predictors of xeroderma pigmentosum-type neurological degeneration. These results provide evidence that DNA repair is critical in maintaining neurological integrity of the auditory system.

Phenotypic consequences of deletion of the {gamma}{sub 3}, {alpha}{sub 5}, or {beta}{sub 3} subunit of the type A {gamma}-aminobutyric acid receptor in mice

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

Culia, C.T.; Stubbs, L.J.; Montgomery, C.S.

1994-03-29

Three genes (Gabrg3, Gabra5, and Gabrb3) encoding the {gamma}{sub 3}, {alpha}{sub 5}, and {beta}{sub 3} subunits of the type A {gamma}-aminobutyric acid receptor, respectively, are known to map near the pink-eyed dilution (p) locus in mouse chromosome 7. This region shares homology with a segment of human chromosome 15 that is implicated in Angelman syndrome, an inherited neurobehavioral disorder. By mapping Gabrg3-Gabra5-Gabrb3-telomere. Like Gabrb3, neither the Gabra5 nor Gabrg3 gene is functionally imprinted in adult mouse brain. Mice deleted for all three subunits die at birth with a cleft palate, although there are rare survivors ({approximately} 5%) that do notmore » have a cleft palate but do exhibit a neurological abnormality characterized by tremor, jerky gait, and runtiness. The authors have previously suggested that deficiency of the {beta}{sub 3} subunit may be responsible for the clefting defect. Most notably, however, in this report they describe mice carrying two overlapping, complementing p deletions that fail to express the {gamma}{sub 3} transcript, as well as mice from another line that express neither the {gamma}{sub 3} nor {alpha}{sub 5} transcripts. Surprisingly, mice from both of these lines are phenotypically normal and do not exhibit any of the neurological symptoms characteristic of the rare survivors that are deleted for all three ({gamma}{sub 3}, {alpha}{sub 5}, and {beta}{sub 3}) subunits. These mice therefore provide a whole-organism type A {gamma}-aminobutyric-acid receptor background that is devoid of any receptor subtypes that normally contain the {gamma}{sub 3} and/or {alpha}{sub 5} subunits. The absence of an overt neurological phenotype in mice lacking the {gamma}{sub 3} and/or {alpha}{sub 5} subunits also suggests that mutations in these genes are unlikely to provide useful animal models for Angelman syndrome in humans.« less

Impairment of executive function in Kenyan children exposed to severe falciparum malaria with neurological involvement.

PubMed

Kariuki, Symon M; Abubakar, Amina; Newton, Charles R J C; Kihara, Michael

2014-09-16

Persistent neurocognitive impairments occur in a fifth of children hospitalized with severe falciparum malaria. There is little data on the association between different neurological phenotypes of severe malaria (seizures, impaired consciousness and prostration) and impairments in executive function. Executive functioning of children exposed to severe malaria with different neurological phenotypes (N = 58) and in those unexposed (N = 56) was examined using neuropsychological tests such as vigilance test, test for everyday attention test for children (TEA-Ch), contingency naming test (CNT) and self-ordered pointing test (SOPT). Linear regression was used to determine the association between neurological phenotypes of severe malaria and executive function performance scores, accounting for potential confounders. Children with complex seizures in severe malaria performed more poorly than unexposed controls in the vigilance (median efficiency scores (interquartile range) = 4.84 (1.28-5.68) vs. 5.84 (4.71-6.42), P = 0.030) and SOPT (mean errors (standard deviation) = 29.50 (8.82) vs. 24.80 (6.50), P = 0.029) tests, but no differences were observed in TEA-Ch and CNT tests. Performance scores for other neurological phenotypes of severe malaria were similar with those of unexposed controls. After accounting for potential confounders, such as child's age, sex, schooling; maternal age, schooling and economic activity; perinatal factors and history of seizures, complex seizures remained associated with efficiency scores in the vigilance test (beta coefficient (β) (95% confidence interval (CI)) = -0.40 (-0.67, -0.13), P = 0.006) and everyday attention scores of the TEA-Ch test (β (95% CI) = -0.57 (-1.04, -0.10), P = 0.019); the association with SOPT error scores was weak (β (95% CI) = 4.57 (-0.73-9.89), P = 0.089). Combined neurological phenotypes were not significantly associated with executive function performance scores. Executive function impairment in children with severe malaria is associated with specific neurological phenotypes, particularly complex seizures. Effective prophylaxis and management of malaria-associated acute seizures may improve executive functioning performance scores of children.

Clinical characteristics of children with severe visual impairment but favorable retinal structural outcomes from the Early Treatment for Retinopathy of Prematurity (ETROP) study.

PubMed

Siatkowski, R Michael; Good, William V; Summers, C Gail; Quinn, Graham E; Tung, Betty

2013-04-01

To describe visual function and associated characteristics at the 6-year examination in children enrolled in the Early Treatment for Retinopathy of Prematurity Study who had unfavorable visual outcomes despite favorable structural outcomes in one or both eyes. The clinical examination records of children completing the 6-year follow-up examination were retrospectively reviewed. Eligible subjects were those with visual acuity of ≤20/200 in each eye (where recordable) and a normal fundus or straightening of the temporal retinal vessels with or without macular ectopia in at least one eye. Data regarding visual function, retinal structure, presence of nystagmus, optic atrophy, optic disk cupping, seizures/shunts, and Functional Independence Measure for Children (ie, WeeFIM: pediatric functional independence measure) developmental test scores were reviewed. Of 342 participants who completed the 6-year examination, 39 (11%) met inclusion criteria. Of these, 29 (74%) had normal retinal structure, 18 (46%) had optic atrophy, and 3 (8%) had increased cupping of the optic disk in at least one eye. Latent and/or manifest nystagmus occurred in 30 children (77%). The presence of nystagmus was not related to the presence of optic atrophy. Of the 39 children, 28 (72%) had a below-normal WeeFIM score. In 25 participants (7%) completing the 6-year examination, cortical visual impairment was considered the primary cause of visual loss. The remainder likely had components of both anterior and posterior visual pathway disease. Clinical synthesis of ocular anatomy and visual and neurologic function is required to determine the etiology of poor vision in these children. Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Forthergillian Lecture. Imaging human brain function.

PubMed

Frackowiak, R S

The non-invasive brain scanning techniques introduced a quarter of a century ago have become crucial for diagnosis in clinical neurology. They have also been used to investigate brain function and have provided information about normal activity and pathogenesis. They have been used to investigate functional specialization in the brain and how specialized areas communicate to generate complex integrated functions such as speech, memory, the emotions and so on. The phenomenon of brain plasticity is poorly understood and yet clinical neurologists are aware, from everyday observations, that spontaneous recovery from brain lesions is common. An improved understanding of the mechanisms of recovery may generate new therapeutic strategies and indicate ways of modulating mechanisms that promote plastic compensation for loss of function. The main methods used to investigate these issues are positron emission tomography and magnetic resonance imaging (M.R.I.). M.R.I. is also used to map brain structure. The techniques of functional brain mapping and computational morphometrics depend on high performance scanners and a validated set of analytic statistical procedures that generate reproducible data and meaningful inferences from brain scanning data. The motor system presents a good paradigm to illustrate advances made by scanning towards an understanding of plasticity at the level of brain areas. The normal motor system is organized in a nested hierarchy. Recovery from paralysis caused by internal capsule strokes involves functional reorganization manifesting itself as changed patterns of activity in the component brain areas of the normal motor system. The pattern of plastic modification depends in part on patterns of residual or disturbed connectivity after brain injury. Therapeutic manipulations in patients with Parkinson's disease using deep brain stimulation, dopaminergic agents or fetal mesencephalic transplantation provide a means to examine mechanisms underpinning plastic change. Other models of plastic change, such as normal visuospatial learning or re-establishing speech comprehension after cochlear implantation in the deaf illustrate how patterns of brain function adapt over time. Limitations of the scanning techniques and prospects for the future are discussed in relation to new developments in the neuroimaging field.

Colour vision impairment is associated with disease severity in multiple sclerosis.

PubMed

Martínez-Lapiscina, Elena H; Ortiz-Pérez, Santiago; Fraga-Pumar, Elena; Martínez-Heras, Eloy; Gabilondo, Iñigo; Llufriu, Sara; Bullich, Santiago; Figueras, Marc; Saiz, Albert; Sánchez-Dalmau, Bernardo; Villoslada, Pablo

2014-08-01

Colour vision assessment correlates with damage of the visual pathway and might be informative of overall brain damage in multiple sclerosis (MS). The objective of this paper is to investigate the association between impaired colour vision and disease severity. We performed neurological and ophthalmic examinations, as well as magnetic resonance imaging (MRI) and optical coherence tomography (OCT) analyses, on 108 MS patients, both at baseline and after a follow-up of one year. Colour vision was evaluated by Hardy, Rand and Rittler plates. Dyschromatopsia was defined if colour vision was impaired in either eye, except for participants with optic neuritis (ON), for whom only the unaffected eye was considered. We used general linear models adjusted for sex, age, disease duration and MS treatment for comparing presence of dyschromatopsia and disease severity. Impaired colour vision in non-ON eyes was detected in 21 out of 108 patients at baseline. At baseline, patients with dyschromatopsia had lower Multiple Sclerosis Functional Composite (MSFC) scores and Brief Repeatable Battery-Neuropsychology executive function scores than those participants with normal colour vision. In addition, these patients had thinner retinal nerve fiber layer (RNFL), and smaller macular volume, normalized brain volume and normalized gray matter volume (NGMV) at baseline. Moreover, participants with incident dyschromatopsia after one-year follow-up had a greater disability measured by the Expanded Disability Status Scale and MSFC-20 and a greater decrease in NGMV than participants with normal colour vision. Colour vision impairment is associated with greater MS severity. © The Author(s) 2013.

Is early adulthood a critical developmental stage for psychosis proneness? A survey of delusional ideation in normal subjects.

PubMed

Verdoux, H; van Os, J; Maurice-Tison, S; Gay, B; Salamon, R; Bourgeois, M

1998-02-09

It has been hypothesized that late adolescence and early adulthood might be a brain developmental stage favoring the clinical expression of psychotic symptoms in psychiatric or neurological diseases. The aim of the present survey was to examine the relationship between age and delusional ideation in a sample of subjects with no psychiatric disorder. The survey was carried out with the Aquitaine Sentinel Network of general practitioners. Consecutive practice attenders were invited to complete the PDI-21 (Peters Delusional Inventory 21 items), a self-report questionnaire designed to measure delusional ideation in the normal population. The study concerned 444 patients who had no lifetime history of psychiatric disorder and who completed the PDI-21. A principal component analysis of the PDI-21 items was performed in order to identify delusional dimensions. An age-related decrease in the likelihood to report delusional ideas was found, younger subjects scoring higher on most dimensions of delusional ideation, such as 'persecution', 'thought disturbance', 'grandiosity' and 'paranormal beliefs'. 'Religiosity' was the only dimension positively associated with age. The results suggest that there may be a physiological neurodevelopmental stage favouring the expression of psychosis proneness in normal subjects, and support the hypothesis that the association between age and positive psychotic symptoms in functional and organic psychoses may be linked to the interaction between normal brain maturational processes and cerebral abnormalities involved in the aetiology of functional and organic psychoses.

Prosopo-affective agnosia associated with chronic organic brain syndrome.

PubMed

Kurucz, J; Feldmar, G; Werner, W

1979-02-01

Impairment of the ability to recognize facially expressed emotions was studied in 14 chronically disoriented patients with chronic organic brain syndrome (CBS). This impairment was named prosopo-affective agnosia (PAA). A diagnostic requirement was relatively intact neurologic functioning in underlying perceptual-verbal-motor processing. A test was designed for facial-affect recognition in the accurate differentiation of normal persons from chronically disoriented CBS patients. No normal subject made any errors in this test. Despite decades of illness and hospital living, patients with a history of schizophrenia or major affective disorders scored almost at a normal level (95 vs. 100 percent) in this test, and significantly higher (95 vs. 66 percent) than did the disoriented CBS patients. The social and therapeutic implications of the findings are stressed. CBS patients may be impaired with respect to receiving and appreciating elementary aspects of social communications such as recognizing a smile, anger, sadness or disapproval on the faces of people who surround them. This disability requires understanding and a special attitude on the part of the therapeutic team toward such patients.

Photodynamic therapy: a review of applications in neurooncology and neuropathology

NASA Astrophysics Data System (ADS)

Uzdensky, Anatoly B.; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Marya; Rudkovskii, Mikhail; Sharifulina, Svetlana

2015-06-01

Photodynamic therapy (PDT) effect is a promising adjuvant modality for diagnosis and treatment of brain cancer. It is of importance that the bright fluorescence of most photosensitizers provides visualization of brain tumors. This is successfully used for fluorescence-guided tumor resection according to the principle "to see and to treat." Non-oncologic application of PDT effect for induction of photothrombotic infarct of the brain tissue is a well-controlled and reproducible stroke model, in which a local brain lesion is produced in the predetermined brain area. Since normal neurons and glial cells may also be damaged by PDT and this can lead to unwanted neurological consequences, PDT effects on normal neurons and glial cells should be comprehensively studied. We overviewed the current literature data on the PDT effect on a range of signaling and epigenetic proteins that control various cell functions, survival, necrosis, and apoptosis. We hypothesize that using cell-specific inhibitors or activators of some signaling proteins, one can selectively protect normal neurons and glia, and simultaneously exacerbate photodynamic damage of malignant gliomas.

Physical Therapy for Neurological Conditions in Geriatric Populations.

PubMed

Carmeli, Eli

2017-01-01

With more of the world's population surviving longer, individuals often face age-related neurology disorders and decline of function that can affect lifestyle and well-being. Despite neurophysiological changes affecting the brain function and structure, the aged brain, in some degree, can learn and relearn due to neuroplasticity. Recent advances in rehabilitation techniques have produced better functional outcomes in age-related neurological conditions. Physical therapy (PT) of the elderly individual focuses in particular on sensory-motor impairments, postural control coordination, and prevention of sarcopenia. Geriatric PT has a significant influence on quality of life, independent living, and life expectancy. However, in many developed and developing countries, the profession of PT is underfunded and understaffed. This article provides a brief overview on (a) age-related disease of central nervous system and (b) the principles, approaches, and doctrines of motor skill learning and point out the most common treatment models that PTs use for neurological patients.

Clinical review: Neuromonitoring - an update

PubMed Central

2013-01-01

Critically ill patients are frequently at risk of neurological dysfunction as a result of primary neurological conditions or secondary insults. Determining which aspects of brain function are affected and how best to manage the neurological dysfunction can often be difficult and is complicated by the limited information that can be gained from clinical examination in such patients and the effects of therapies, notably sedation, on neurological function. Methods to measure and monitor brain function have evolved considerably in recent years and now play an important role in the evaluation and management of patients with brain injury. Importantly, no single technique is ideal for all patients and different variables will need to be monitored in different patients; in many patients, a combination of monitoring techniques will be needed. Although clinical studies support the physiologic feasibility and biologic plausibility of management based on information from various monitors, data supporting this concept from randomized trials are still required. PMID:23320763

Physical Therapy for Neurological Conditions in Geriatric Populations

PubMed Central

Carmeli, Eli

2017-01-01

With more of the world’s population surviving longer, individuals often face age-related neurology disorders and decline of function that can affect lifestyle and well-being. Despite neurophysiological changes affecting the brain function and structure, the aged brain, in some degree, can learn and relearn due to neuroplasticity. Recent advances in rehabilitation techniques have produced better functional outcomes in age-related neurological conditions. Physical therapy (PT) of the elderly individual focuses in particular on sensory–motor impairments, postural control coordination, and prevention of sarcopenia. Geriatric PT has a significant influence on quality of life, independent living, and life expectancy. However, in many developed and developing countries, the profession of PT is underfunded and understaffed. This article provides a brief overview on (a) age-related disease of central nervous system and (b) the principles, approaches, and doctrines of motor skill learning and point out the most common treatment models that PTs use for neurological patients. PMID:29270402

Application of Atomic Dielectric Resonance Spectroscopy for the screening of blood samples from patients with clinical variant and sporadic CJD

PubMed Central

Fagge, Timothy J; Barclay, G Robin; Stove, G Colin; Stove, Gordon; Robinson, Michael J; Head, Mark W; Ironside, James W; Turner, Marc L

2007-01-01

Background Sub-clinical variant Creutzfeldt-Jakob disease (vCJD) infection and reports of vCJD transmission through blood transfusion emphasise the need for blood screening assays to ensure the safety of blood and transplanted tissues. Most assays aim to detect abnormal prion protein (PrPSc), although achieving required sensitivity is a challenge. Methods We have used innovative Atomic Dielectric Resonance Spectroscopy (ADRS), which determines dielectric properties of materials which are established by reflectivity and penetration of radio/micro waves, to analyse blood samples from patients and controls to identify characteristic ADR signatures unique to blood from vCJD and to sCJD patients. Initial sets of blood samples from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) were screened as training samples to determine group-specific ADR characteristics, and provided a basis for classification of blinded sets of samples. Results Blood sample groups from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) screened by ADRS were classified with 100% specificity and sensitivity, discriminating these by a co-variance expert analysis system. Conclusion ADRS appears capable of recognising and discriminating serum samples from vCJD, sCJD, non-CJD neurological diseases, and normal healthy adults, and might be developed to provide a system for primary screening or confirmatory assay complementary to other screening systems. PMID:17760958

Recurrent somnolence in a 17-month-old infant: late-onset ornithine transcarbamylase (OTC) deficiency due to the novel hemizygous mutation c.535C > T (p.Leu179Phe).

PubMed

Fantur, Michaela; Karall, Daniela; Scholl-Buergi, Sabine; Häberle, Johannes; Rauchenzauner, Markus; Fruehwirth, Martin

2013-01-01

Herein, we describe a case of a now 28-month-old boy who presented at the age of 17 months with four episodes of recurrent vomiting and somnolence during a period of four months with increasing severity. A comprehensive clinical and metabolic evaluation revealed normal blood pH and blood glucose, normal cerebral computed tomography and electroencephalogram but an elevated plasma ammonia concentration, which raised the suspicion of a urea cycle disorder. The combination of elevated urinary orotic acid and plasma glutamine with normal citrulline suggested the diagnosis of ornithine transcarbamylase (OTC) deficiency, which was confirmed by molecular genetic testing revealing the novel hemizygous mutation c.535C > T (p.Leu179Phe) of the OTC gene. After restitution of anabolism by administration of parenteral glucose, substitution of citrulline and detoxification of ammonia with sodium benzoate, the patient recovered rapidly and is in a stable metabolic and neurological state since then. This case underlines that the diagnosis of a urea cycle defect should be considered in the differential diagnosis of recurrent idiopathic vomiting in combination with unexplained neurological symptoms also beyond the neonatal period due to the possibility of mild or atypical late-onset presentation (e.g. OTC deficiency in hemizygous males). Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The Neurologic Assessment in Neuro-Oncology (NANO) scale: a tool to assess neurologic function for integration into the Response Assessment in Neuro-Oncology (RANO) criteria

PubMed Central

DeAngelis, Lisa M.; Brandes, Alba A.; Peereboom, David M.; Galanis, Evanthia; Lin, Nancy U.; Soffietti, Riccardo; Macdonald, David R.; Chamberlain, Marc; Perry, James; Jaeckle, Kurt; Mehta, Minesh; Stupp, Roger; Muzikansky, Alona; Pentsova, Elena; Cloughesy, Timothy; Iwamoto, Fabio M.; Tonn, Joerg-Christian; Vogelbaum, Michael A.; Wen, Patrick Y.; van den Bent, Martin J.; Reardon, David A.

2017-01-01

Abstract Background. The Macdonald criteria and the Response Assessment in Neuro-Oncology (RANO) criteria define radiologic parameters to classify therapeutic outcome among patients with malignant glioma and specify that clinical status must be incorporated and prioritized for overall assessment. But neither provides specific parameters to do so. We hypothesized that a standardized metric to measure neurologic function will permit more effective overall response assessment in neuro-oncology. Methods. An international group of physicians including neurologists, medical oncologists, radiation oncologists, and neurosurgeons with expertise in neuro-oncology drafted the Neurologic Assessment in Neuro-Oncology (NANO) scale as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. The scale was subsequently tested in a multicenter study to determine its overall reliability, inter-observer variability, and feasibility. Results. The NANO scale is a quantifiable evaluation of 9 relevant neurologic domains based on direct observation and testing conducted during routine office visits. The score defines overall response criteria. A prospective, multinational study noted a >90% inter-observer agreement rate with kappa statistic ranging from 0.35 to 0.83 (fair to almost perfect agreement), and a median assessment time of 4 minutes (interquartile range, 3–5). Conclusion. The NANO scale provides an objective clinician-reported outcome of neurologic function with high inter-observer agreement. It is designed to combine with radiographic assessment to provide an overall assessment of outcome for neuro-oncology patients in clinical trials and in daily practice. Furthermore, it complements existing patient-reported outcomes and cognition testing to combine for a global clinical outcome assessment of well-being among brain tumor patients. PMID:28453751

Late onset Pott's paraplegia in patients with upper thoracic sharp kyphosis.

PubMed

Zhang, Zhengfeng

2012-02-01

The purpose of this study was to determine the clinical results of patients with late onset upper thoracic sharp Pott's kyphosis and to predict the prognosis for Pott's paraplegics. The study included five patients who developed late onset upper thoracic (T1-T4) sharp Pott's kyphosis/kyphoscoliosis within a period from 19 to 37 years after the active disease was healed. The kyphosis angle of the patients ranged from 95° to 105°. Among them, three patients suffered onset of paraplegia ranging from 26 to 31 years after spinal tuberculosis was healed. The duration of neurological deterioration before surgery ranged from four to five years. All patients underwent decompressive surgery with an attempt to correct the curve. Neurological status was evaluated using the ASIA impairment classification and the motor score. Postoperatively, kyphosis correction ranged from 20° to 30° for five patients. No neurological deficit occurred in two patients with normal neurological status. Two ASIA D paraplegics remained unchanged after surgery and no further improvement was found at one year follow-up. One ASIA C paralysis deteriorated neurologically to ASIA B after surgery and persisted to a deterioration of neurological status at one year follow-up. Upper thoracic sharp Pott's kyphosis and neurological deficits occur progressively. The neurological recovery or improvement of Pott's paraplegics with upper thoracic severe sharp kyphosis results in poor prognosis after decompressive surgery.

Complex and differential glial responses in Alzheimer's disease and ageing.

PubMed

Rodríguez, José J; Butt, Arthur M; Gardenal, Emanuela; Parpura, Vladimir; Verkhratsky, Alexei

2016-01-01

Glial cells and their association with neurones are fundamental for brain function. The emergence of complex neurone-glial networks assures rapid information transfer, creating a sophisticated circuitry where both types of neural cells work in concert, serving different activities. All glial cells, represented by astrocytes, oligodendrocytes, microglia and NG2-glia, are essential for brain homeostasis and defence. Thus, glia are key not only for normal central nervous system (CNS) function, but also to its dysfunction, being directly associated with all forms of neuropathological processes. Therefore, the progression and outcome of neurological and neurodegenerative diseases depend on glial reactions. In this review, we provide a concise account of recent data obtained from both human material and animal models demonstrating the pathological involvement of glia in neurodegenerative processes, including Alzheimer's disease (AD), as well as physiological ageing.

Metabolic Changes Following Perinatal Asphyxia: Role of Astrocytes and Their Interaction with Neurons.

PubMed

Logica, Tamara; Riviere, Stephanie; Holubiec, Mariana I; Castilla, Rocío; Barreto, George E; Capani, Francisco

2016-01-01

Perinatal Asphyxia (PA) represents an important cause of severe neurological deficits including delayed mental and motor development, epilepsy, major cognitive deficits and blindness. The interaction between neurons, astrocytes and endothelial cells plays a central role coupling energy supply with changes in neuronal activity. Traditionally, experimental research focused on neurons, whereas astrocytes have been more related to the damage mechanisms of PA. Astrocytes carry out a number of functions that are critical to normal nervous system function, including uptake of neurotransmitters, regulation of pH and ion concentrations, and metabolic support for neurons. In this work, we aim to review metabolic neuron-astrocyte interactions with the purpose of encourage further research in this area in the context of PA, which is highly complex and its mechanisms and pathways have not been fully elucidated to this day.

Metabolic Changes Following Perinatal Asphyxia: Role of Astrocytes and Their Interaction with Neurons

PubMed Central

Logica, Tamara; Riviere, Stephanie; Holubiec, Mariana I.; Castilla, Rocío; Barreto, George E.; Capani, Francisco

2016-01-01

Perinatal Asphyxia (PA) represents an important cause of severe neurological deficits including delayed mental and motor development, epilepsy, major cognitive deficits and blindness. The interaction between neurons, astrocytes and endothelial cells plays a central role coupling energy supply with changes in neuronal activity. Traditionally, experimental research focused on neurons, whereas astrocytes have been more related to the damage mechanisms of PA. Astrocytes carry out a number of functions that are critical to normal nervous system function, including uptake of neurotransmitters, regulation of pH and ion concentrations, and metabolic support for neurons. In this work, we aim to review metabolic neuron-astrocyte interactions with the purpose of encourage further research in this area in the context of PA, which is highly complex and its mechanisms and pathways have not been fully elucidated to this day. PMID:27445788

Nonsurgical management of an extensive spontaneous spinal epidural hematoma causing quadriplegia and respiratory distress in a choledocholithiasis patient

PubMed Central

Raasck, Kyle; Khoury, Jason; Aoude, Ahmed; Abduljabbar, Fahad; Jarzem, Peter

2017-01-01

Abstract Rationale: Spontaneous spinal epidural hematoma (SSEH) manifests from blood accumulating in the epidural space, compressing the spinal cord, and leading to acute neurological deficits. The disease's cloudy etiology and rarity contribute to dangerously suboptimal therapeutic principles. These neural deficits can be permanent, even fatal, if the SSEH is not treated in a timely and appropriate manner. Standard therapy is decompressive laminectomy, though nonsurgical management is a viable course of action for patients who meet a criterion that is continuously being refined. Patient concerns: A 76-year-old woman on warfarin for a past pulmonary embolism presented to the emergency room with jaundice, myalgia, hematuria, neck pain, and an International Normalized Ratio (INR) of 14. Upon admission, she rapidly developed quadriplegia and respiratory distress that necessitated intubation. Diagnoses: T2-weighted magnetic resonance imaging (MRI) revealed an epidural space-occupying hyperintensity from C2 to S5 consistent with a spinal epidural hematoma. An incidental finding of dilated intrahepatic and common bile ducts prompted an endoscopic retrograde cholangiopancreatography, which demonstrated choledocholithiasis. Interventions: The patient's INR was normalized with Vitamin K and Beriplex. Upon transfer to the surgical spine team for assessment of a possible intervention, the patient began to demonstrate recovery of neural functions. The ensuing sustained motor improvement motivated the team's preference for close neurologic monitoring and continued medical therapy over surgery. Thirteen hours after the onset of her symptoms, the patient was extubated. A sphincterotomy was later performed, removing 81 common bile duct stones. Outcomes: MRI demonstrated complete resorption of the SSEH and the patient maintained full neurological function at final follow-up. Lessons: Nonsurgical management of SSEH should be considered in the context of early and sustained recovery. Severe initial neural deficit does not necessitate surgical decompression. Choledocholithiasis and subsequent Vitamin K deficiency, particularly when coupled with anticoagulant use, can increase INR and is a novel proposed risk factor for SSEH. Furthermore, coagulopathies should be medically corrected before surgical intervention within a given timeframe, as spontaneous recovery may manifest. This should be favored over surgery in patients demonstrating early and sustained recovery, as nonsurgical management is 25% more effective in achieving full recovery. PMID:29390530

Nonsurgical management of an extensive spontaneous spinal epidural hematoma causing quadriplegia and respiratory distress in a choledocholithiasis patient: A case report.

PubMed

Raasck, Kyle; Khoury, Jason; Aoude, Ahmed; Abduljabbar, Fahad; Jarzem, Peter

2017-12-01

Spontaneous spinal epidural hematoma (SSEH) manifests from blood accumulating in the epidural space, compressing the spinal cord, and leading to acute neurological deficits. The disease's cloudy etiology and rarity contribute to dangerously suboptimal therapeutic principles. These neural deficits can be permanent, even fatal, if the SSEH is not treated in a timely and appropriate manner. Standard therapy is decompressive laminectomy, though nonsurgical management is a viable course of action for patients who meet a criterion that is continuously being refined. A 76-year-old woman on warfarin for a past pulmonary embolism presented to the emergency room with jaundice, myalgia, hematuria, neck pain, and an International Normalized Ratio (INR) of 14. Upon admission, she rapidly developed quadriplegia and respiratory distress that necessitated intubation. T2-weighted magnetic resonance imaging (MRI) revealed an epidural space-occupying hyperintensity from C2 to S5 consistent with a spinal epidural hematoma. An incidental finding of dilated intrahepatic and common bile ducts prompted an endoscopic retrograde cholangiopancreatography, which demonstrated choledocholithiasis. The patient's INR was normalized with Vitamin K and Beriplex. Upon transfer to the surgical spine team for assessment of a possible intervention, the patient began to demonstrate recovery of neural functions. The ensuing sustained motor improvement motivated the team's preference for close neurologic monitoring and continued medical therapy over surgery. Thirteen hours after the onset of her symptoms, the patient was extubated. A sphincterotomy was later performed, removing 81 common bile duct stones. MRI demonstrated complete resorption of the SSEH and the patient maintained full neurological function at final follow-up. Nonsurgical management of SSEH should be considered in the context of early and sustained recovery. Severe initial neural deficit does not necessitate surgical decompression. Choledocholithiasis and subsequent Vitamin K deficiency, particularly when coupled with anticoagulant use, can increase INR and is a novel proposed risk factor for SSEH. Furthermore, coagulopathies should be medically corrected before surgical intervention within a given timeframe, as spontaneous recovery may manifest. This should be favored over surgery in patients demonstrating early and sustained recovery, as nonsurgical management is 25% more effective in achieving full recovery. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

[The carrier model of neurology in Hungary: a proposal for the solution until 2020].

PubMed

Bereczki, Dániel; Csiba, László; Komoly, Sámuel; Vécsei, László; Ajtay, András

2011-11-30

Based on our previous survey on the capacities of neurological services and on the predictable changes in the neurologist workforce in Hungary, we present a proposal for the organization of the structure of neurological services in the future. We discuss the diagnostic groups treated by neurologists, the neurological services and their progressive organization. Using the current capacities as baseline, we propose patient groups to be treated by neurologists in the future, and the levels of services. Based on the tendencies seen in the last years we suggest to consider to allocate acute stroke services exclusively to stroke units in neurological departments, and we identify a few other diagnostic groups where neurology should have a larger share in patient care. We define three levels for inpatient care: university departments, regional/county hospitals, city hospitals. Instead of minimum criteria we assign outpatient and inpatient standards that are functional from the economic point of view as well. University departments cover all areas of neurological services, have a function in graduate and postgraduate training, and on a regional basis they participate in professional quality assurance activities at the county and city hospital levels, and would have a more independent role in residency training. As far as patient care is concerned, the task of the regional/county hospitals would be similar to that of university departments - without the exclusively university functions. A general neurological service would be offered at the city hospital level - the representation of all subspecialties of neurology is not required. Neurorehabilitation would be organized at special units of neurological wards at the city hospital level, at independent neurorehabilitation wards in regional/county hospitals, and also as an outpatient service offered at the patients' home. The most significant organizational change would affect the outpatient neurological services. In addition to the special outpatient units associated with university departments and regional/county hospitals, the general neurological outpatient services would be organized as private practices, similarly to the current system of general practitioners, where the individual practices contract independently with the health insurance fund. Their task would be a general neurological service offered 30 hours per week, and also basic, screening neurophysiological and neurosonological examinations, with proper equipment and trained assistance. A transformation in residency training and a change in financing is needed for this plan to fulfill.

EEG in Sarcoidosis Patients Without Neurological Findings.

PubMed

Bilgin Topçuoğlu, Özgür; Kavas, Murat; Öztaş, Selahattin; Arınç, Sibel; Afşar, Gülgün; Saraç, Sema; Midi, İpek

2017-01-01

Sarcoidosis is a multisystem granulomatous disease affecting nervous system in 5% to 10% of patients. Magnetic resonance imaging (MRI) is accepted as the most sensitive method for detecting neurosarcoidosis. However, the most common findings in MRI are the nonspecific white matter lesions, which may be unrelated to sarcoidosis and can occur because of hypertension, diabetes mellitus, smoking, and other inflammatory or infectious disorders, as well. Autopsy studies report more frequent neurological involvement than the ante mortem studies. The aim of this study is to assess electroencephalography (EEG) in sarcoidosis patients without neurological findings in order to display asymptomatic neurological dysfunction. We performed EEG on 30 sarcoidosis patients without diagnosis of neurosarcoidosis or prior neurological comorbidities. Fourteen patients (46.7%) showed intermittant focal and/or generalized slowings while awake and not mentally activated. Seven (50%) of these 14 patients with EEG slowings had nonspecific white matter changes while the other half showed EEG slowings in the absence of MRI changes. We conclude that EEG slowings, when normal variants (psychomotor variant, temporal theta of elderly, frontal theta waves) are eliminated, may be an indicator of dysfunction in brain activity even in the absence of MRI findings. Hence, EEG may contribute toward detecting asymptomatic neurological dysfunction or probable future neurological involvement in sarcoidosis patients. © EEG and Clinical Neuroscience Society (ECNS) 2016.

Neurologic emergencies in HIV-negative immunosuppressed patients.

PubMed

Guzmán-De-Villoria, J A; Fernández-García, P; Borrego-Ruiz, P J

HIV-negative immunosuppressed patients comprise a heterogeneous group including transplant patients, patients undergoing treatment with immunosuppressors, uremic patients, alcoholics, undernourished patients, diabetics, patients on dialysis, elderly patients, and those diagnosed with severe or neoplastic processes. Epileptic seizures, focal neurologic signs, and meningoencephalitis are neurologic syndromes that require urgent action. In most of these situations, neuroimaging tests are necessary, but the findings can be different from those observed in immunocompetent patients in function of the inflammatory response. Infectious disease is the first diagnostic suspicion, and the identification of an opportunistic pathogen should be oriented in function of the type and degree of immunosuppression. Other neurologic emergencies include ischemic stroke, cerebral hemorrhage, neoplastic processes, and pharmacological neurotoxicity. This article reviews the role of neuroimaging in HIV-negative immunodepressed patients with a neurologic complication that requires urgent management. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Symptomatic treatment of neurologic symptoms in Wilson disease.

PubMed

Litwin, Tomasz; Dušek, Petr; Członkowska, Anna

2017-01-01

Wilson disease (WD) is a potentially treatable neurodegenerative disorder. In the majority of cases, treatment with drugs that induce a negative copper balance (usually chelators or zinc salts) leads to improvements in liver function and neurologic signs. However, some patients show severe neurologic symptoms at diagnosis, such as tremor, dystonia, parkinsonism, and chorea. In this patient group, some neurologic deficits may persist despite adequate treatment, and further neurologic deterioration may be observed after treatment initiation. Such patients may require additional treatment to alleviate neurologic symptoms. Apart from general recommendations for WD anticopper treatment, there are currently no guidelines for managing neurologic symptoms in WD. The aim of this chapter is to summarize possible treatments of neurologic symptoms in WD based on the presently available medical literature. © 2017 Elsevier B.V. All rights reserved.

Intellectual disability and bleeding diathesis due to deficient CMP--sialic acid transport.

PubMed

Mohamed, Miski; Ashikov, Angel; Guillard, Mailys; Robben, Joris H; Schmidt, Samuel; van den Heuvel, B; de Brouwer, Arjan P M; Gerardy-Schahn, Rita; Deen, Peter M T; Wevers, Ron A; Lefeber, Dirk J; Morava, Eva

2013-08-13

To identify the underlying genetic defect in a patient with intellectual disability, seizures, ataxia, macrothrombocytopenia, renal and cardiac involvement, and abnormal protein glycosylation. Genetic studies involved homozygosity mapping by 250K single nucleotide polymorphism array and SLC35A1 sequencing. Functional studies included biochemical assays for N-glycosylation and mucin-type O-glycosylation and SLC35A1-encoded cytidine 5'-monophosphosialic acid (CMP-sialic acid) transport after heterologous expression in yeast. We performed biochemical analysis and found combined N- and O-glycosylation abnormalities and specific reduction in sialylation in this patient. Homozygosity mapping revealed homozygosity for the CMP-sialic acid transporter SLC35A1. Mutation analysis identified a homozygous c.303G > C (p.Gln101His) missense mutation that was heterozygous in both parents. Functional analysis of mutant SLC35A1 showed normal Golgi localization but 50% reduction in transport activity of CMP-sialic acid in vitro. We confirm an autosomal recessive, generalized sialylation defect due to mutations in SLC35A1. The primary neurologic presentation consisting of ataxia, intellectual disability, and seizures, in combination with bleeding diathesis and proteinuria, is discriminative from a previous case described with deficient sialic acid transporter. Our study underlines the importance of sialylation for normal CNS development and regular organ function.

Respiratory insufficiency with preserved diaphragmatic function in amyotrophic lateral sclerosis.

PubMed

Yamauchi, Rika; Imai, Tomihiro; Tsuda, Emiko; Hozuki, Takayoshi; Yamamoto, Daisuke; Shimohama, Shun

2014-01-01

We performed a longitudinal study to elucidate the correlation between respiratory insufficiency and respiratory biomarkers, including diaphragmatic compound muscle action potential (DCMAP), at the initiation of noninvasive ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS). The patients were assessed at least every six months. Additional assessments were performed at the start of respiratory therapy when the patients met the criteria for the initiation of NIV. Each assessment consisted of a full neurological examination, a phrenic nerve conduction study, respiratory function tests, and nocturnal pulsed oximetry. We enrolled 43 patients with either definite or probable ALS as defined by the revised El Escorial criteria. The patients were divided into two groups according to the timing of the initiation of respiratory therapy. Seventeen patients (group A) met the criteria for NIV initiation when their DCMAP remained normal. Twenty-six patients (group B) met the criteria when their DCMAP decreased below normal limits. Although respiratory function parameters were significantly worse in group B compared with group A at NIV initiation, more than 80% of the patients in both groups developed nocturnal desaturation during sleep. DCMAP is not always a reliable indicator for determining the optimal timing for NIV initiation during the progression of respiratory insufficiency in ALS. Physicians should be aware of the risk of respiratory insufficiency during sleep in patients with ALS.

Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C: an observational cohort study.

PubMed

Patterson, Marc C; Mengel, Eugen; Vanier, Marie T; Schwierin, Barbara; Muller, Audrey; Cornelisse, Peter; Pineda, Mercè

2015-05-28

Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat. The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption >28 days) were included in this analysis. Disability was measured using a scale rating the four domains, ambulation, manipulation, language and swallowing from 0 (normal) to 1 (worst). Neurological disease progression was analysed in all patients based on: 1) annual progression rates between enrolment and last follow up, and; 2) categorical analysis with patients categorised as 'improved/stable' if ≥3/4 domain scores were lower/unchanged, and as 'progressed' if <3 scores were lower/unchanged between enrolment and last follow-up visit. In total, 283 patients were enrolled from 28 centers in 13 European countries, Canada and Australia between September 2009 and October 2013; 92 patients received continuous miglustat therapy. The mean (SD) miglustat exposure during the observation period (enrolment to last follow-up) was 2.0 (0.7) years. Among 84 evaluable patients, 9 (11 %) had early-infantile (<2 years), 27 (32 %) had late-infantile (2 to <6 years), 30 (36 %) had juvenile (6 to <15 years) and 18 (21 %) had adolescent/adult (≥15 years) onset of neurological manifestations. The mean (95%CI) composite disability score among all patients was 0.37 (0.32,0.42) at enrolment and 0.44 (0.38,0.50) at last follow-up visit, and the mean annual progression rate was 0.038 (0.018,0.059). Progression of composite disability scores appeared highest among patients with neurological onset during infancy or childhood and lowest in those with adolescent/adult-onset. Overall, 59/86 evaluable patients (69 %) were categorized as improved/stable and the proportion of improved/stable patients increased with age at neurological onset. Safety findings were consistent with previous data. Disability status was improved/stable in the majority of patients who received continuous miglustat therapy for an average period of 2 years.

Sleep Disorders in Childhood Neurological Diseases

PubMed Central

Liu, Zhao

2017-01-01

Sleep problems are frequently addressed as a primary or secondary concern during the visit to the pediatric neurology clinic. Sleep disorders can mimic other neurologic diseases (e.g., epilepsy and movement disorders), and this adds challenges to the diagnostic process. Sleep disorders can significantly affect the quality of life and functionality of children in general and those with comorbid neurological diseases in particular. Understanding the pathophysiology of sleep disorders, recognizing the implications of sleep disorder in children with neurologic diseases and behavioral difficulties, and early intervention continue to evolve resulting in better neurocognitive outcomes. PMID:28937639

Pilot randomized trial of therapeutic hypothermia with serial cranial ultrasound and 18-22 month follow-up for neonatal encephalopathy in a low resource hospital setting in Uganda: study protocol.

PubMed

Robertson, Nicola J; Hagmann, Cornelia F; Acolet, Dominique; Allen, Elizabeth; Nyombi, Natasha; Elbourne, Diana; Costello, Anthony; Jacobs, Ian; Nakakeeto, Margaret; Cowan, Frances

2011-06-04

There is now convincing evidence that in industrialized countries therapeutic hypothermia for perinatal asphyxial encephalopathy increases survival with normal neurological function. However, the greatest burden of perinatal asphyxia falls in low and mid-resource settings where it is unclear whether therapeutic hypothermia is safe and effective. Under the UCL Uganda Women's Health Initiative, a pilot randomized controlled trial in infants with perinatal asphyxia was set up in the special care baby unit in Mulago Hospital, a large public hospital with ~20,000 births in Kampala, Uganda to determine:(i) The feasibility of achieving consent, neurological assessment, randomization and whole body cooling to a core temperature 33-34°C using water bottles(ii) The temperature profile of encephalopathic infants with standard care(iii) The pattern, severity and evolution of brain tissue injury as seen on cranial ultrasound and relation with outcome(iv) The feasibility of neurodevelopmental follow-up at 18-22 months of age Ethical approval was obtained from Makerere University and Mulago Hospital. All infants were in-born. Parental consent for entry into the trial was obtained. Thirty-six infants were randomized either to standard care plus cooling (target rectal temperature of 33-34°C for 72 hrs, started within 3 h of birth) or standard care alone. All other aspects of management were the same. Cooling was performed using water bottles filled with tepid tap water (25°C). Rectal, axillary, ambient and surface water bottle temperatures were monitored continuously for the first 80 h. Encephalopathy scoring was performed on days 1-4, a structured, scorable neurological examination and head circumference were performed on days 7 and 17. Cranial ultrasound was performed on days 1, 3 and 7 and scored. Griffiths developmental quotient, head circumference, neurological examination and assessment of gross motor function were obtained at 18-22 months. We will highlight differences in neonatal care and infrastructure that need to be taken into account when considering a large safety and efficacy RCT of therapeutic hypothermia in low and mid resource settings in the future. Current controlled trials ISRCTN92213707.

The nature of primary vocal tremor.

PubMed

Hachinski, V C; Thomsen, I V; Buch, N H

1975-08-01

Three elderly women with marked progressive voice tremor, without other neurological symptoms, and negative family histories were investigated. All had a 4-5 Hz respiratory tremor in expiration and, to a lesser degree, in inspiration; and all had vocal tremulousness synchronous with their respiratory irregularity. Articulation of phonemes was normal. In two cases the neurological examination was otherwise normal; in the third case there was a minimal 71/2 Hz tremor in the left thumb and index finger. Simultaneous speech and vocal air pressure recordings, as well as cinematographic studies of the vocal apparatus and diaphragm were carried out. It is suggested that these cases represent primarily an action tremor of respiration, that they belong in the spectrum of essential tremor, and hence may be amenable to treatment with propranolol.

Xenon-delayed postconditioning attenuates spinal cord ischemia/reperfusion injury through activation AKT and ERK signaling pathways in rats.

PubMed

Liu, Shiyao; Yang, Yanwei; Jin, Mu; Hou, Siyu; Dong, Xiuhua; Lu, Jiakai; Cheng, Weiping

2016-09-15

Previous studies have shown that xenon-delayed postconditioning for up to 2h after reperfusion provides protection against spinal cord ischemia/reperfusion (I/R) injury in rats. This study was designed to determine the roles of phosphatidylinositol 3-kinase (PI3K)-Akt and extracellular signal-regulated kinase (ERK) in this neuroprotection. The rats were randomly assigned to the following nine groups (n=16∗9): 1) I/R+N2 group, 2) I/R+Xe group, 3) I/R+PD98059+N2 group (ERK blocking agent), 4) I/R+wortmannin+N2 group (PI3K-Akt blocking agent), 5) I/R+PD98059+Xe group, 6) I/R+wortmannin+Xe group, 7) I/R+DMSO+Xe group (dimethyl sulfoxide, vehicle control), 8) I/R+DMSO+N2 group, and 9) sham group (no spinal cord ischemia and no xenon). Spinal cord ischemia was induced for 25min in male Sprague-Dawley rats. Neurological function was assessed using the Basso, Beattie, and Bresnahan (BBB) open-field locomotor scale at 6, 12, 24 and 48h after reperfusion. Histological examination of the lumbar spinal cord was performed using Nissl staining and TUNEL staining at 4 (n=8) and 48 (n=8)h after reperfusion. Western blotting was performed to evaluate p-Akt and p-ERK expression in the spinal cord at 4 (n=8) and 48 (n=8) h after reperfusion. Compared with the sham group, all rats in the I/R groups had lower BBB scores, fewer normal motor neurons, more apoptotic neurons and lower p-Akt and p-ERK levels at each time point (P<0.05). Compared with the I/R group, rats in the I/R+Xe group had higher neurological scores, more normal motor neurons, fewer apoptotic neurons and significantly higher levels of p-Akt and p-ERK at each time point (P<0.05). Compared with the I/R+Xe group, the I/R+PD98059+Xe and I/R+wortmannin+Xe groups showed worse neurological outcomes and less p-Akt and p-ERK at each time point (P<0.05). These results suggest that xenon-delayed postconditioning improves neurological outcomes to spinal cord I/R injury in rats through the activation of the AKT and ERK signaling pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

[Incidence and follow-up characteristics of neurologically relevant psychogenic symptoms].

PubMed

Franz, M; Schellberg, D; Reister, G; Schepank, H

1993-06-01

The author reports on the prevalence and stability of the course of neurologically relevant psychogenic symptoms as well as their dependence on age and sex. Altogether 240 probands from the Mannheim Cohort Study on the epidemiology of psychogenic disorders were examined for psychogenic impairment over a 10-year period during three investigation periods. On the whole, seven neurologically relevant groups of symptoms (headache, lumbar and cervical vertebral complaints, non-systematic vertigo, functional hyperkinesia, functional paresis, sleep disturbances, concentration disturbances) differ clearly in frequency, characteristics of the course and clinical relevance.

HaNDL syndrome: Correlation between focal deficits topography and EEG or SPECT abnormalities in a series of 5 new cases.

PubMed

Barón, J; Mulero, P; Pedraza, M I; Gamazo, C; de la Cruz, C; Ruiz, M; Ayuso, M; Cebrián, M C; García-Talavera, P; Marco, J; Guerrero, A L

2016-06-01

Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) is characterised by migraine-like headache episodes accompanied by neurological deficits consisting of motor, sensory, or aphasic symptoms. Electroencephalogram (EEG) and single photon emission computed tomography (SPECT) may show focal abnormalities that correspond to the neurological deficits. We aim to evaluate the correlation between focal deficit topography and EEG or SPECT abnormalities in 5 new cases. We retrospectively reviewed patients attended in a tertiary hospital (January 2010-May 2014) and identified 5 patients (3 men, 2 women) with a mean age of 30.6 ± 7.7 (21-39) years. They presented 3.4 ± 2.6 episodes of headache (range, 2-8) of moderate to severe intensity and transient neurological deficits over a maximum of 5 weeks. Pleocytosis was detected in CSF in all cases (70 to 312 cells/mm3, 96.5-100% lymphocytes) with negative results from aetiological studies. At least one EEG was performed in 4 patients and SPECT in 3 patients. Patient 1: 8 episodes; 4 left hemisphere, 3 right hemisphere, and 1 brainstem; 2 EEGs showing left temporal and bilateral temporal slowing; normal SPECT. Patient 2: 2 episodes, left hemisphere and right hemisphere; SPECT showed decreased left temporal blood flow. Patient 3: 3 left hemisphere deficits; EEG with bilateral frontal and temporal slowing. Patient 4: 2 episodes with right parieto-occipital topography and right frontal slowing in EEG. Patient 5: 2 episodes, right hemisphere and left hemisphere, EEG with right temporal slowing; normal SPECT. The neurological deficits accompanying headache in HaNDL demonstrate marked clinical heterogeneity. SPECT abnormalities and most of all EEG abnormalities were not uncommon in our series and they did not always correlate to the topography of focal déficits. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Assessment and evaluation of the high risk neonate: the NICU Network Neurobehavioral Scale.

PubMed

Lester, Barry M; Andreozzi-Fontaine, Lynne; Tronick, Edward; Bigsby, Rosemarie

2014-08-25

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. The NNNS assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The NNNS is a noninvasive neonatal assessment tool with demonstrated validity as a predictor, not only of medical outcomes such as cerebral palsy diagnosis, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ. The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible. The video shows the NNNS procedures, shows examples of normal and abnormal performance and the various clinical populations in which the exam can be used.

Posterior thalamic hemorrhage induces "pusher syndrome".

PubMed

Karnath, Hans-Otto; Johannsen, Leif; Broetz, Doris; Küker, Wilhelm

2005-03-22

Recent findings argue for a pathway in humans for sensing the orientation of gravity and controlling upright body posture, separate from the one for orientation perception of the visual world. Stroke patients with contraversive pushing were shown to experience their body as oriented upright when actually tilted about 20 degrees to the ipsilesional side, in spite of normal visual-vestibular functioning. A recent study suggested the involvement of posterolateral thalamus typically associated with the disorder. To evaluate the relationship between pushing behavior and thalamic function. Over a 3-year period the authors prospectively investigated 40 patients with left- or right-sided thalamic strokes. Twenty-eight percent showed contraversive pushing. The authors found a strong relationship between etiology, vascular territory, lesion size, and neurologic disorders associated with contraversive pushing. Pusher patients had larger lesions that typically were caused by hemorrhage (vs infarcts) located in the posterior thalamus (vs anterior thalamic lesions in those patients without pushing behavior). A paresis of the contralesional extremities was more frequent and more severe in pusher patients. Further, these patients showed more additional spatial neglect with right thalamic lesions, while they tended to be more aphasic with left thalamic lesions. Posterior thalamus seems to be fundamentally involved in our control of upright body posture. Higher pressure, swelling, and other secondary pathologic processes associated with posterior thalamic hemorrhage (vs thalamic infarction) may provoke contraversive pushing in combination with additional neurologic symptoms.

Out-of-Hospital Hypertonic Resuscitation Following Severe Traumatic Brain Injury: A Randomized Controlled Trial

PubMed Central

Bulger, Eileen M.; May, Susanne; Brasel, Karen J.; Schreiber, Martin; Kerby, Jeffrey D.; Tisherman, Samuel A.; Newgard, Craig; Slutsky, Arthur; Coimbra, Raul; Emerson, Scott; Minei, Joseph P.; Bardarson, Berit; Kudenchuk, Peter; Baker, Andrew; Christenson, Jim; Idris, Ahamed; Davis, Daniel; Fabian, Timothy C.; Aufderheide, Tom P.; Callaway, Clifton; Williams, Carolyn; Banek, Jane; Vaillancourt, Christian; van Heest, Rardi; Sopko, George; Hata, J. Steven; Hoyt, David B.

2010-01-01

Context Hypertonic fluids restore cerebral perfusion with reduced cerebral edema and modulate inflammatory response to reduce subsequent neuronal injury and thus have potential benefit in resuscitation of patients with traumatic brain injury (TBI). Objective To determine whether out-of-hospital administration of hypertonic fluids improves neurologic outcome following severe TBI. Design, Setting, and Participants Multicenter, double-blind, randomized, placebo-controlled clinical trial involving 114 North American emergency medical services agencies within the Resuscitation Outcomes Consortium, conducted between May 2006 and May 2009 among patients 15 years or older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less who did not meet criteria for hypovolemic shock. Planned enrollment was 2122 patients. Intervention A single 250-mL bolus of 7.5% saline/6% dextran 70 (hypertonic saline/dextran), 7.5% saline (hypertonic saline), or 0.9% saline (normal saline) initiated in the out-of-hospital setting. Main Outcome Measure Six-month neurologic outcome based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4). Results The study was terminated by the data and safety monitoring board after randomization of 1331 patients, having met prespecified futility criteria. Among the 1282 patients enrolled, 6-month outcomes data were available for 1087 (85%). Baseline characteristics of the groups were equivalent. There was no difference in 6-month neurologic outcome among groups with regard to proportions of patients with severe TBI (GOSE ≤4) (hypertonic saline/dextran vs normal saline: 53.7% vs 51.5%; difference, 2.2% [95% CI, −4.5% to 9.0%]; hypertonic saline vs normal saline: 54.3% vs 51.5%; difference, 2.9% [95% CI, −4.0% to 9.7%]; P=.67). There were no statistically significant differences in distribution of GOSE category or Disability Rating Score by treatment group. Survival at 28 days was 74.3% with hypertonic saline/dextran, 75.7% with hypertonic saline, and 75.1% with normal saline (P=.88). Conclusion Among patients with severe TBI not in hypovolemic shock, initial resuscitation with either hypertonic saline or hypertonic saline/dextran, compared with normal saline, did not result in superior 6-month neurologic outcome or survival. Trial Registration clinicaltrials.gov Identifier: NCT00316004 PMID:20924011

Neurotechnology: a new approach for treating brain disorders.

PubMed

Robson, John A; Davenport, R John

2014-05-01

Advances in neuroscience, engineering and computer technologies are creating opportunities to connect the brain directly to devices to treat a variety of disorders, both neurological and psychiatric. They are opening a new field of neuroscience called "neurotechnology." This article reviews efforts in this area that are ongoing at Brown University and the hospitals affiliated with Brown's Alpert Medical School. Two general approaches are being used. One uses advanced electrodes to "sense" the activity of many individual neurons in the cerebral cortex and then use that activity for therapeutic purposes. The other uses various types of devices to stimulate specific networks in the brain in order to restore normal function and alleviate symptoms.

76 FR 6625 - Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Neurological Devices Panel of the Medical Devices Advisory Committee. General Function of the Committee: To...

Zolpidem Overdose: A Medical and Ethical Dilemma.

PubMed

Shuaib, Waqas; Beatrice, Cristina; Abazid, Ahmad G

Acute altered mental status can be caused by a broad range of etiologies, including cerebrovascular, neurologic, traumatic, metabolic, infectious, psychiatric, medications, etc. We present a case of a 53-year-old healthcare professional with an acute altered mental status after a trip to Africa. The patient was extensively worked up for infectious, cardiovascular, and neurologic etiologies, and all results were within normal limits. Further history revealed an overdose of a self-medicated hypnotic (zolpidem) for insomnia. The patient was conservatively managed and discharged on trazadone for insomnia.

Facial expression perception correlates with verbal working memory function in schizophrenia.

PubMed

Hagiya, Kumiko; Sumiyoshi, Tomiki; Kanie, Ayako; Pu, Shenghong; Kaneko, Koichi; Mogami, Tamiko; Oshima, Sachie; Niwa, Shin-ichi; Inagaki, Akiko; Ikebuchi, Emi; Kikuchi, Akiko; Yamasaki, Syudo; Iwata, Kazuhiko; Nakagome, Kazuyuki

2015-12-01

Facial emotion perception is considered to provide a measure of social cognition. Numerous studies have examined the perception of emotion in patients with schizophrenia, and the majority has reported impaired ability to recognize facial emotion perception. We aimed to investigate the correlation between facial expression recognition and other domains of social cognition and neurocognition in Japanese patients with schizophrenia. Participants were 52 patients with schizophrenia and 53 normal controls with no history of psychiatric diseases. All participants completed the Hinting Task and the Social Cognition Screening Questionnaire. The Brief Assessment of Cognition in Schizophrenia was administered only to the patients. Facial emotion perception measured by the Facial Emotion Selection Test (FEST) was compared between the patients and normal controls. Patients performed significantly worse on the FEST compared to normal control subjects. The FEST total score was significantly positively correlated with scores of the Brief Assessment of Cognition in Schizophrenia attention subscale, Hinting Task, Social Cognition Screening Questionnaire Verbal Working Memory and Metacognition subscales. Stepwise multiple regression analysis revealed that verbal working memory function was positively related to the facial emotion perception ability in patients with schizophrenia. These results point to the concept that facial emotion perception and some types of working memory use common cognitive resources. Our findings may provide implications for cognitive rehabilitation and related interventions in schizophrenia. © 2015 The Authors. Psychiatry and Clinical Neurosciences © 2015 Japanese Society of Psychiatry and Neurology.

Continuous Amplitude-Integrated Electroencephalographic Monitoring Is a Useful Prognostic Tool for Hypothermia-Treated Cardiac Arrest Patients.

PubMed

Oh, Sang Hoon; Park, Kyu Nam; Shon, Young-Min; Kim, Young-Min; Kim, Han Joon; Youn, Chun Song; Kim, Soo Hyun; Choi, Seung Pill; Kim, Seok Chan

2015-09-22

Modern treatments have improved the survival rate following cardiac arrest, but prognostication remains a challenge. We examined the prognostic value of continuous electroencephalography according to time by performing amplitude-integrated electroencephalography on patients with cardiac arrest receiving therapeutic hypothermia. We prospectively studied 130 comatose patients treated with hypothermia from September 2010 to April 2013. We evaluated the time to normal trace (TTNT) as a neurological outcome predictor and determined the prognostic value of burst suppression and status epilepticus, with a particular focus on their time of occurrence. Fifty-five patients exhibited a cerebral performance category score of 1 to 2. The area under the curve for TTNT was 0.97 (95% confidence interval, 0.92-0.99), and the sensitivity and specificity of TTNT<24 hours after resuscitation as a threshold for predicting good neurological outcome were 94.6% (95% confidence interval, 84.9%-98.9%) and 90.7% (95% confidence interval, 81.7%-96.2%), respectively. The threshold displaying 100% specificity for predicting poor neurological outcome was TTNT>36 hours. Burst suppression and status epilepticus predicted poor neurological outcome (positive predictive value of 98.3% and 96.4%, respectively). The combination of these factors predicted a negative outcome at a median of 6.2 hours after resuscitation (sensitivity and specificity of 92.0% and 96.4%, respectively). A TTNT<24 hours was associated with good neurological outcome. The lack of normal trace development within 36 hours, status epilepticus, and burst suppression were predictors of poor outcome. The combination of these negative predictors may improve their prognostic performance at an earlier stage. © 2015 The Authors.

Neurological Development of Children With Isolated Robin Sequence Treated With Nasopharyngeal Intubation in Early Infancy.

PubMed

Alencar, Tatiane Romanini Rodrigues; Marques, Ilza Lazarini; Bertucci, Alvaro; Prado-Oliveira, Rosana

2017-05-01

The study assessed the neurodevelopment of children with isolated Robin sequence (IRS) and evaluated if children treated exclusively with nasopharyngeal intubation (NPI) present delay in neurological development. The prospective and cross-sectional study was conducted at the Hospital for Rehabilitation of Craniofacial Anomalies, Brazil. Children with IRS were divided into two groups according to the type of treatment in early infancy: 38 were treated with NPI (more severe cases) and 24 with postural treatment (less severe cases). Regarding interventions, children were assessed at 2 to 6 years of age using the Denver II Developmental Screening Test (Denver II) and Neurological Evolutionary Examination (NEE). According to Denver II, 73.7% in the NPI group and 79.2% in the postural group presented normal development. This result was similar to the results of different studies in the literature with typical population. Considering all areas of development, there were no significant differences in Denver II between the NPI and postural groups (P = .854). In the NPI group, 89.5% of children and 87.5% in the postural group presented normal development in NEE. Language was the most affected area, as 18.4% and 20.8% of children in NPI and postural group, respectively, presented risk for delay in the Denver II. The increased risk for delay in language area was probably due to anatomical conditions of the muscles involved in speech, and to hearing oscillations, as 47.4% in NPI group and 58.3% in postural group underwent myringotomy. IRS treated with NPI had neurological development similar to those in less severe cases. Children treated exclusively with NPI did not present delay in neurological development.

Clinical presentation of anti-N-methyl-d-aspartate receptor and anti-voltage-gated potassium channel complex antibodies in children: A series of 24 cases.

PubMed

Konuskan, Bahadir; Yildirim, Mirac; Topaloglu, Haluk; Erol, Ilknur; Oztoprak, Ulkuhan; Tan, Huseyin; Gocmen, Rahsan; Anlar, Banu

2018-01-01

The symptomatology and paraclinical findings of antibody-mediated encephalitis, a relatively novel disorder, are still being characterized in adults and children. A high index of suspicion is needed in order to identify these cases among children presenting with various neurological symptoms. The aim of this study is to examine the clinical, demographic and laboratory findings and outcome of children with anti-NMDAR and anti-VGKC encephalitis for any typical or distinctive features. Cases diagnosed with anti-N-Methyl d-aspartate receptor (NMDAR) and anti-voltage gated potassium channel (VGKC) antibody-mediated encephalopathy in four major child neurology centers are described. In four years, 16 children with NMDAR and 8 children with VGKC antibody-associated disease were identified in the participating centers. The most frequent initial manifestation consisted of generalized seizures and cognitive symptoms in both groups. Movement abnormalities were frequent in anti-NMDAR patients and autonomic symptoms, in anti-VGKC patients. Cerebrospinal fluid (CSF) protein, cell count and IgG index were normal in 9/15 anti-NMDAR and 5/8 anti-VGKC patients tested. EEG and MRI findings were usually nonspecific and non-contributory. The rate and time of recovery was not related to age, sex, acute or subacute onset, antibody type, MRI, EEG or CSF results. Treatment within 3 months of onset was associated with normal neurological outcome. Our results suggest anti-NMDAR and VGKC encephalopathies mostly present with non-focal neurological symptoms longer than 3 weeks. In contrast with adult cases, routine CSF testing, MRI and EEG did not contribute to the diagnosis in this series. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Quantitative methods in assessment of neurologic function.

PubMed

Potvin, A R; Tourtellotte, W W; Syndulko, K; Potvin, J

1981-01-01

Traditionally, neurologists have emphasized qualitative techniques for assessing results of clinical trials. However, in recent years qualitative evaluations have been increasingly augmented by quantitative tests for measuring neurologic functions pertaining to mental state, strength, steadiness, reactions, speed, coordination, sensation, fatigue, gait, station, and simulated activities of daily living. Quantitative tests have long been used by psychologists for evaluating asymptomatic function, assessing human information processing, and predicting proficiency in skilled tasks; however, their methodology has never been directly assessed for validity in a clinical environment. In this report, relevant contributions from the literature on asymptomatic human performance and that on clinical quantitative neurologic function are reviewed and assessed. While emphasis is focused on tests appropriate for evaluating clinical neurologic trials, evaluations of tests for reproducibility, reliability, validity, and examiner training procedures, and for effects of motivation, learning, handedness, age, and sex are also reported and interpreted. Examples of statistical strategies for data analysis, scoring systems, data reduction methods, and data display concepts are presented. Although investigative work still remains to be done, it appears that carefully selected and evaluated tests of sensory and motor function should be an essential factor for evaluating clinical trials in an objective manner.

Critical Thinking, Executive Functions and Their Potential Relationship

ERIC Educational Resources Information Center

Lizarraga, Maria Luisa Sanz de Acedo; Baquedano, Maria Teresa Sanz de Acedo; Villanueva, Oscar Ardaiz

2012-01-01

The central issue of this paper is to review the possible relationships between the constructs of critical thinking and executive functions. To do this, we first analyse the essential components of critical thinking from a psychological and neurological point of view. Second, we examine the scope of the cognitive and neurological nature of…

Enhanced detection threshold for in vivo cortical stimulation produced by Hebbian conditioning

NASA Astrophysics Data System (ADS)

Rebesco, James M.; Miller, Lee E.

2011-02-01

Normal brain function requires constant adaptation, as an organism learns to associate important sensory stimuli with the appropriate motor actions. Neurological disorders may disrupt these learned associations and require the nervous system to reorganize itself. As a consequence, neural plasticity is a crucial component of normal brain function and a critical mechanism for recovery from injury. Associative, or Hebbian, pairing of pre- and post-synaptic activity has been shown to alter stimulus-evoked responses in vivo; however, to date, such protocols have not been shown to affect the animal's subsequent behavior. We paired stimulus trains separated by a brief time delay to two electrodes in rat sensorimotor cortex, which changed the statistical pattern of spikes during subsequent behavior. These changes were consistent with strengthened functional connections from the leading electrode to the lagging electrode. We then trained rats to respond to a microstimulation cue, and repeated the paradigm using the cue electrode as the leading electrode. This pairing lowered the rat's ICMS-detection threshold, with the same dependence on intra-electrode time lag that we found for the functional connectivity changes. The timecourse of the behavioral effects was very similar to that of the connectivity changes. We propose that the behavioral changes were a consequence of strengthened functional connections from the cue electrode to other regions of sensorimotor cortex. Such paradigms might be used to augment recovery from a stroke, or to promote adaptation in a bidirectional brain-machine interface.

New Therapeutic Drugs from Bioactive Natural Molecules: the Role of Gut Microbiota Metabolism in Neurodegenerative Diseases.

PubMed

Di Meo, Francesco; Donato, Stella; Di Pardo, Alba; Maglione, Vittorio; Filosa, Stefania; Crispi, Stefania

2018-04-03

The gut-brain axis is considered a neuroendocrine system, which connects brain and gastrointestinal tract and plays an important role in stress response. The homeostasis of gut-brain axis is important for healthy conditions and its alterations are associated to neurological disorders and neurodegenerative diseases. Gut microbiota is a dynamic ecosystem that can be altered by external factors such as diet composition, antibiotics or xenobiotics. Recent advances in gut microbiota analyses indicate that the gut bacterial community plays a key role in maintaining normal brain functions. Recent metagenomic analyses have elucidated that the relationship between gut and brain, either in normal or in pathological conditions, reflects the existence of a "microbiota-gut-brain" axis. Gut microbiota composition can be influenced by dietary ingestion of probiotics or natural bioactive molecules such as prebiotics and polyphenols. Their derivatives coming from microbiota metabolism can affect both gut bacterial composition and brain biochemistry. Modifications of microbiota composition by natural bioactive molecules could be used to restore the altered brain functions, which characterize neurodegenerative diseases, leading to consider these compounds as novel therapeutic strategies for the treatment of neuropathologies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

NASA Astrophysics Data System (ADS)

Lee, Kendall H.; Lujan, J. Luis; Trevathan, James K.; Ross, Erika K.; Bartoletta, John J.; Park, Hyung Ook; Paek, Seungleal Brian; Nicolai, Evan N.; Lee, Jannifer H.; Min, Hoon-Ki; Kimble, Christopher J.; Blaha, Charles D.; Bennet, Kevin E.

2017-04-01

There has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy.

VOLTAGE-GATED POTASSIUM CHANNELS AT THE CROSSROADS OF NEURONAL FUNCTION, ISCHEMIC TOLERANCE, AND NEURODEGENERATION

PubMed Central

Shah, Niyathi Hegde; Aizenman, Elias

2013-01-01

Voltage-gated potassium (Kv) channels are widely expressed in the central and peripheral nervous system, and are crucial mediators of neuronal excitability. Importantly, these channels also actively participate in cellular and molecular signaling pathways that regulate the life and death of neurons. Injury-mediated increased K+ efflux through Kv2.1 channels promotes neuronal apoptosis, contributing to widespread neuronal loss in neurodegenerative disorders such as Alzheimer’s disease and stroke. In contrast, some forms of neuronal activity can dramatically alter Kv2.1 channel phosphorylation levels and influence their localization. These changes are normally accompanied by modifications in channel voltage-dependence, which may be neuroprotective within the context of ischemic injury. Kv1 and Kv7 channel dysfunction leads to neuronal hyperexcitability that critically contributes to the pathophysiology of human clinical disorders such as episodic ataxia and epilepsy. This review summarizes the neurotoxic, neuroprotective, and neuroregulatory roles of Kv channels, and highlights the consequences of Kv channel dysfunction on neuronal physiology. The studies described in this review thus underscore the importance of normal Kv channel function in neurons, and emphasize the therapeutic potential of targeting Kv channels in the treatment of a wide range of neurological diseases. PMID:24323720

Controlling specific locomotor behaviors through multidimensional monoaminergic modulation of spinal circuitries

PubMed Central

Musienko, Pavel; van den Brand, Rubia; Märzendorfer, Olivia; Roy, Roland R.; Gerasimenko, Yury; Edgerton, V. Reggie; Courtine, Grégoire

2012-01-01

Descending monoaminergic inputs markedly influence spinal locomotor circuits, but the functional relationships between specific receptors and the control of walking behavior remain poorly understood. To identify these interactions, we manipulated serotonergic, dopaminergic, and noradrenergic neural pathways pharmacologically during locomotion enabled by electrical spinal cord stimulation in adult spinal rats in vivo. Using advanced neurobiomechanical recordings and multidimensional statistical procedures, we reveal that each monoaminergic receptor modulates a broad but distinct spectrum of kinematic, kinetic and EMG characteristics, which we expressed into receptor–specific functional maps. We then exploited this catalogue of monoaminergic tuning functions to devise optimal pharmacological combinations to encourage locomotion in paralyzed rats. We found that, in most cases, receptor-specific modulatory influences summed near algebraically when stimulating multiple pathways concurrently. Capitalizing on these predictive interactions, we elaborated a multidimensional monoaminergic intervention that restored coordinated hindlimb locomotion with normal levels of weight bearing and partial equilibrium maintenance in spinal rats. These findings provide new perspectives on the functions of and interactions between spinal monoaminergic receptor systems in producing stepping, and define a framework to tailor pharmacotherapies for improving neurological functions after CNS disorders. PMID:21697376

Current Concepts in Diagnosis and Treatment of Functional Neurological Disorders.

PubMed

Espay, Alberto J; Aybek, Selma; Carson, Alan; Edwards, Mark J; Goldstein, Laura H; Hallett, Mark; LaFaver, Kathrin; LaFrance, W Curt; Lang, Anthony E; Nicholson, Tim; Nielsen, Glenn; Reuber, Markus; Voon, Valerie; Stone, Jon; Morgante, Francesca

2018-06-04

Functional neurological disorders (FND) are common sources of disability in medicine. Patients have often been misdiagnosed, correctly diagnosed after lengthy delays, and/or subjected to poorly delivered diagnoses that prevent diagnostic understanding and lead to inappropriate treatments, iatrogenic harm, unnecessary and costly evaluations, and poor outcomes. Functional Neurological Symptom Disorder/Conversion Disorder was adopted by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, replacing the term psychogenic with functional and removing the criterion of psychological stress as a prerequisite for FND. A diagnosis can now be made in an inclusionary manner by identifying neurological signs that are specific to FNDs without reliance on presence or absence of psychological stressors or suggestive historical clues. The new model highlights a wider range of past sensitizing events, such as physical trauma, medical illness, or physiological/psychophysiological events. In this model, strong ideas and expectations about these events correlate with abnormal predictions of sensory data and body-focused attention. Neurobiological abnormalities include hypoactivation of the supplementary motor area and relative disconnection with areas that select or inhibit movements and are associated with a sense of agency. Promising evidence has accumulated for the benefit of specific physical rehabilitation and psychological interventions alone or in combination, but clinical trial evidence remains limited. Functional neurological disorders are a neglected but potentially reversible source of disability. Further research is needed to determine the dose and duration of various interventions, the value of combination treatments and multidisciplinary therapy, and the therapeutic modality best suited for each patient.

The Effectiveness of Singing or Playing a Wind Instrument in Improving Respiratory Function in Patients with Long-Term Neurological Conditions: A Systematic Review.

PubMed

Ang, Kexin; Maddocks, Matthew; Xu, Huiying; Higginson, Irene J

2017-03-01

Many long-term neurological conditions adversely affect respiratory function. Singing and playing wind instruments are relatively inexpensive interventions with potential for improving respiratory function; however, synthesis of current evidence is needed to inform research and clinical use of music in respiratory care. To critically appraise, analyze, and synthesize published evidence on the effectiveness of singing or playing a wind instrument to improve respiratory function in people with long-term neurological conditions. Systematic review of published randomized controlled trials and observational studies examining singing or playing wind instruments to improve respiratory function in individuals with long-term neurological conditions. Articles meeting specified inclusion criteria were identified through a search of the Medline, Embase, PsycINFO, Cochrane Library, CINAHL, Web of Science, CAIRSS for Music, WHO International Clinical Trials Registry Platform Search Portal, and AMED databases as early as 1806 through March 2015. Information on study design, clinical populations, interventions, and outcome measures was extracted and summarized using an electronic standardized coding form. Methodological quality was assessed and summarized across studies descriptively. From screening 584 references, 68 full texts were reviewed and five studies included. These concerned 109 participants. The studies were deemed of low quality, due to evidence of bias, in part due to intervention complexity. No adverse effects were reported. Overall, there was a trend toward improved respiratory function, but only one study on Parkinson's disease had significant between-group differences. The positive trend in respiratory function in people with long-term neurological conditions following singing or wind instrument therapy is of interest, and warrants further investigation. © the American Music Therapy Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Role of the gluten-free diet on neurological-EEG findings and sleep disordered breathing in children with celiac disease.

PubMed

Parisi, P; Pietropaoli, N; Ferretti, A; Nenna, R; Mastrogiorgio, G; Del Pozzo, M; Principessa, L; Bonamico, M; Villa, M P

2015-02-01

To determine whether celiac children are at risk for EEG-neurological features and sleep disordered breathing (SDB), and whether an appropriate gluten-free diet (GFD) influences these disorders. We consecutively enrolled 19 children with a new biopsy-proven celiac disease (CD) diagnosis. At CD diagnosis and after 6 months of GFD, each patient underwent a general and neurological examination, an electroencephalogram, a questionnaire about neurological features, and a validated questionnaire about SDB: OSA (obstructive sleep apnea) scores<0 predict normality; values>0 predict OSA. At CD diagnosis, 37% of patients complained headache that affected daily activities and 32% showed positive OSA score. The EEG examinations revealed abnormal finding in 48% of children. After 6 months of GFD headache disappeared in 72% of children and EEG abnormalities in 78%; all children showed negative OSA score. According to our preliminary data, in the presence of unexplained EEG abnormalities and/or other neurological disorders/SDB an atypical or silent CD should also be taken into account. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

CDKL5 variants: Improving our understanding of a rare neurologic disorder.

PubMed

Hector, Ralph D; Kalscheuer, Vera M; Hennig, Friederike; Leonard, Helen; Downs, Jenny; Clarke, Angus; Benke, Tim A; Armstrong, Judith; Pineda, Mercedes; Bailey, Mark E S; Cobb, Stuart R

2017-12-01

To provide new insights into the interpretation of genetic variants in a rare neurologic disorder, CDKL5 deficiency, in the contexts of population sequencing data and an updated characterization of the CDKL5 gene. We analyzed all known potentially pathogenic CDKL5 variants by combining data from large-scale population sequencing studies with CDKL5 variants from new and all available clinical cohorts and combined this with computational methods to predict pathogenicity. The study has identified several variants that can be reclassified as benign or likely benign. With the addition of novel CDKL5 variants, we confirm that pathogenic missense variants cluster in the catalytic domain of CDKL5 and reclassify a purported missense variant as having a splicing consequence. We provide further evidence that missense variants in the final 3 exons are likely to be benign and not important to disease pathology. We also describe benign splicing and nonsense variants within these exons, suggesting that isoform hCDKL5_5 is likely to have little or no neurologic significance. We also use the available data to make a preliminary estimate of minimum incidence of CDKL5 deficiency. These findings have implications for genetic diagnosis, providing evidence for the reclassification of specific variants previously thought to result in CDKL5 deficiency. Together, these analyses support the view that the predominant brain isoform in humans (hCDKL5_1) is crucial for normal neurodevelopment and that the catalytic domain is the primary functional domain.

Epigenetic mechanisms during ageing and neurogenesis as novel therapeutic avenues in human brain disorders.

PubMed

Delgado-Morales, Raúl; Agís-Balboa, Roberto Carlos; Esteller, Manel; Berdasco, María

2017-01-01

Ageing is the main risk factor for human neurological disorders. Among the diverse molecular pathways that govern ageing, epigenetics can guide age-associated decline in part by regulating gene expression and also through the modulation of genomic instability and high-order chromatin architecture. Epigenetic mechanisms are involved in the regulation of neural differentiation as well as in functional processes related to memory consolidation, learning or cognition during healthy lifespan. On the other side of the coin, many neurodegenerative diseases are associated with epigenetic dysregulation. The reversible nature of epigenetic factors and, especially, their role as mediators between the genome and the environment make them exciting candidates as therapeutic targets. Rather than providing a broad description of the pathways epigenetically deregulated in human neurological disorders, in this review, we have focused on the potential use of epigenetic enzymes as druggable targets to ameliorate neural decline during normal ageing and especially in neurological disorders. We will firstly discuss recent progress that supports a key role of epigenetic regulation during healthy ageing with an emphasis on the role of epigenetic regulation in adult neurogenesis. Then, we will focus on epigenetic alterations associated with ageing-related human disorders of the central nervous system. We will discuss examples in the context of psychiatric disorders, including schizophrenia and posttraumatic stress disorders, and also dementia or Alzheimer's disease as the most frequent neurodegenerative disease. Finally, methodological limitations and future perspectives are discussed.

A Symptomatic Case of Thoracic Vertebral Hemangioma Causing Lower Limb Spastic Paresis.

PubMed

Alfawareh, Mohammad; Alotaibi, Tariq; Labeeb, Abdallah; Audat, Ziad

2016-10-31

BACKGROUND Despite being the most common tumor of the spine, vertebral hemangioma is rarely symptomatic in adults. In fact, only 0.9-1.2% of all vertebral hemangiomas may be symptomatic. When hemangiomas occur in the thoracic vertebrae, they are more likely to be symptomatic due to the narrow vertebral canal dimensions that mandate more aggressive management prior to the onset of severe neurological sequelae. CASE REPORT An 18-year-old male presented to the emergency room with a one-month history of mild to moderate mid-thoracic back pain, radiating to both lower limbs. It was associated with both lower limb weakness and decreased sensation. There was no history of bowel or bladder incontinence. Neurological examination revealed lower limb weakness with power 3/5, exaggerated deep tendon reflexes, bilateral sustained clonus, impaired sensation below the umbilicus, spasticity, and a positive Babinski sign. A CT scan showed a diffuse body lesion at the 8th thoracic vertebra with coarse trabeculations, corduroy appearance, or jail-bar sign. The patient underwent decompression and fixation. Biopsy of permanent samples showed proliferation of blood vessels with dilated spaces and no malignant cells, consistent with hemangioma. Postoperatively, spasticity improved, and the patient regained normal power. CONCLUSIONS Symptomatic vertebral hemangiomas are rare but should be considered as a differential diagnosis. They can present with severe neurological symptoms. When managed appropriately, patients regain full motor and sensory function. Decompression resulted in quick relief of symptoms, which was followed by an extensive rehabilitation program.

Nmf9 Encodes a Highly Conserved Protein Important to Neurological Function in Mice and Flies.

PubMed

Zhang, Shuxiao; Ross, Kevin D; Seidner, Glen A; Gorman, Michael R; Poon, Tiffany H; Wang, Xiaobo; Keithley, Elizabeth M; Lee, Patricia N; Martindale, Mark Q; Joiner, William J; Hamilton, Bruce A

2015-07-01

Many protein-coding genes identified by genome sequencing remain without functional annotation or biological context. Here we define a novel protein-coding gene, Nmf9, based on a forward genetic screen for neurological function. ENU-induced and genome-edited null mutations in mice produce deficits in vestibular function, fear learning and circadian behavior, which correlated with Nmf9 expression in inner ear, amygdala, and suprachiasmatic nuclei. Homologous genes from unicellular organisms and invertebrate animals predict interactions with small GTPases, but the corresponding domains are absent in mammalian Nmf9. Intriguingly, homozygotes for null mutations in the Drosophila homolog, CG45058, show profound locomotor defects and premature death, while heterozygotes show striking effects on sleep and activity phenotypes. These results link a novel gene orthology group to discrete neurological functions, and show conserved requirement across wide phylogenetic distance and domain level structural changes.

Functional (psychogenic) movement disorders: merging mind and brain.

PubMed

Edwards, Mark J; Bhatia, Kailash P

2012-03-01

Functional (psychogenic) movement disorders (FMD) are part of the wide spectrum of functional neurological disorders, which together account for over 16% of patients referred to neurology clinics. FMD have been described as a "crisis for neurology" and cause major challenges in terms of diagnosis and treatment. As with other functional disorders, a key issue is the absence of pathophysiological understanding. There has been an influential historical emphasis on causation by emotional trauma, which is not supported by epidemiological studies. The similarity between physical signs in functional disorders and those that occur in feigned illness has also raised important challenges for pathophysiological understanding and has challenged health professionals' attitudes toward patients with these disorders. However, physical signs and selected investigations can help clinicians to reach a positive diagnosis, and modern pathophysiological research is showing an appreciation of the importance of both physical and psychological factors in FMD. Copyright © 2012 Elsevier Ltd. All rights reserved.

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…

Developmental outcomes of cord blood transplantation for Krabbe disease: A 15-year study.

PubMed

Wright, Matthew D; Poe, Michele D; DeRenzo, Anthony; Haldal, Shilpa; Escolar, Maria L

2017-09-26

To describe long-term outcomes of children with early-infantile Krabbe disease who underwent hematopoietic stem cell transplantation (HSCT) in the first 7 weeks of life. In this prospective longitudinal study, evaluations performed at baseline and follow-up included brain imaging, neurodiagnostic tests, and neurobehavioral evaluations. Of the 18 patients in this study (11 girls, 7 boys; mean follow-up 9.5 years, range 4-15), 5 died (3 of peritransplant complications, 1 of a surgical complication unrelated to Krabbe disease, 1 of disease progression). One of the surviving patients has normal cognitive function and 10 continue to develop cognitive skills at a slightly slower rate than normal. All surviving patients continue to gain receptive language skills, with 7 falling within the normal range. Ten patients receive speech therapy, and 2 of these patients require augmentative communication devices. Gross motor development varies widely, but 3 patients can walk independently, and 7 walk with assistive devices. Spasticity ranges from mild to severe, and 12 patients wear orthotics. Fine motor skills are generally preserved. Brain myelination and atrophy stabilized in 8 patients, improved in 4 patients, and worsened in 1 patient. Nerve conduction velocities initially improved but continue to be abnormal in most patients. The surviving patients function at a much higher level than untreated children or symptomatic children who underwent HSCT. These results show that early HSCT changes the natural history of this disease by improving both lifespan and functional abilities. This study provides Class IV evidence that for children with early-infantile Krabbe disease, early HSCT improves lifespan and functional abilities. © 2017 American Academy of Neurology.

Right ventricular dysfunction after resuscitation predicts poor outcomes in cardiac arrest patients independent of left ventricular function.

PubMed

Ramjee, Vimal; Grossestreuer, Anne V; Yao, Yuan; Perman, Sarah M; Leary, Marion; Kirkpatrick, James N; Forfia, Paul R; Kolansky, Daniel M; Abella, Benjamin S; Gaieski, David F

2015-11-01

Determination of clinical outcomes following resuscitation from cardiac arrest remains elusive in the immediate post-arrest period. Echocardiographic assessment shortly after resuscitation has largely focused on left ventricular (LV) function. We aimed to determine whether post-arrest right ventricular (RV) dysfunction predicts worse survival and poor neurologic outcome in cardiac arrest patients, independent of LV dysfunction. A single-center, retrospective cohort study at a tertiary care university hospital participating in the Penn Alliance for Therapeutic Hypothermia (PATH) Registry between 2000 and 2012. 291 in- and out-of-hospital adult cardiac arrest patients at the University of Pennsylvania who had return of spontaneous circulation (ROSC) and post-arrest echocardiograms. Of the 291 patients, 57% were male, with a mean age of 59 ± 16 years. 179 (63%) patients had LV dysfunction, 173 (59%) had RV dysfunction, and 124 (44%) had biventricular dysfunction on the initial post-arrest echocardiogram. Independent of LV function, RV dysfunction was predictive of worse survival (mild or moderate: OR 0.51, CI 0.26-0.99, p<0.05; severe: OR 0.19, CI 0.06-0.65, p=0.008) and neurologic outcome (mild or moderate: OR 0.33, CI 0.17-0.65, p=0.001; severe: OR 0.11, CI 0.02-0.50, p=0.005) compared to patients with normal RV function after cardiac arrest. Echocardiographic findings of post-arrest RV dysfunction were equally prevalent as LV dysfunction. RV dysfunction was significantly predictive of worse outcomes in post-arrest patients after accounting for LV dysfunction. Post-arrest RV dysfunction may be useful for risk stratification and management in this high-mortality population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Microbiota and neurologic diseases: potential effects of probiotics.

PubMed

Umbrello, Giulia; Esposito, Susanna

2016-10-19

The microbiota colonizing the gastrointestinal tract have been associated with both gastrointestinal and extra-gastrointestinal diseases. In recent years, considerable interest has been devoted to their role in the development of neurologic diseases, as many studies have described bidirectional communication between the central nervous system and the gut, the so-called "microbiota-gut-brain axis". Considering the ability of probiotics (i.e., live non-pathogenic microorganisms) to restore the normal microbial population and produce benefits for the host, their potential effects have been investigated in the context of neurologic diseases. The main aims of this review are to analyse the relationship between the gut microbiota and brain disorders and to evaluate the current evidence for the use of probiotics in the treatment and prevention of neurologic conditions. Overall, trials involving animal models and adults have reported encouraging results, suggesting that the administration of probiotic strains may exert some prophylactic and therapeutic effects in a wide range of neurologic conditions. Studies involving children have mainly focused on autism spectrum disorder and have shown that probiotics seem to improve neuro behavioural symptoms. However, the available data are incomplete and far from conclusive. The potential usefulness of probiotics in preventing or treating neurologic diseases is becoming a topic of great interest. However, deeper studies are needed to understand which formulation, dosage and timing might represent the optimal regimen for each specific neurologic disease and what populations can benefit. Moreover, future trials should also consider the tolerability and safety of probiotics in patients with neurologic diseases.

The neurological basis of occupation.

PubMed

Gutman, Sharon A; Schindler, Victoria P

2007-01-01

The purpose of the present paper was to survey the literature about the neurological basis of human activity and its relationship to occupation and health. Activities related to neurological function were organized into three categories: those that activate the brain's reward system; those that promote the relaxation response; and those that preserve cognitive function into old age. The results from the literature review correlating neurological evidence and activities showed that purposeful and meaningful activities could counter the effects of stress-related diseases and reduce the risk for dementia. Specifically, it was found that music, drawing, meditation, reading, arts and crafts, and home repairs, for example, can stimulate the neurogical system and enhance health and well-being, Prospective research studies are needed to examine the effects of purposeful activities on reducing stress and slowing the rate of cognitive decline.

A Morpholino Strategy to Assess TSC Gene Function in Zebrafish

DTIC Science & Technology

2006-11-01

ABSTRACT Tuberous sclerosis complex (TSC) is a genetic disorder associated with severe neurological symptoms including mental retardation, autism ...ABSTRACT Tuberous sclerosis complex (TSC) is a genetic disorder associated with severe neurological symptoms including mental retardation, autism ...devastating autosomal dominant disease that results in severe neurological symptoms including mental retardation, autism , and seizures (DiMario, 2004

Abnormalities on the Neurological Examination and EEG in Young Children with Pervasive Developmental Disorders

ERIC Educational Resources Information Center

Akshoomoff, Natacha; Farid, Nikdokht; Courchesne, Eric; Haas, Richard

2007-01-01

This study examined the nature and frequency of neurological and EEG abnormalities in 60 young children (ages 2-6 years) with pervasive developmental disorders. A number of standard neurological functions could not be adequately assessed due to the young age of the children and/or limited comprehension and cooperation. The most common neurological…

Detection of third and sixth cranial nerve palsies with a novel method for eye tracking while watching a short film clip

PubMed Central

Samadani, Uzma; Farooq, Sameer; Ritlop, Robert; Warren, Floyd; Reyes, Marleen; Lamm, Elizabeth; Alex, Anastasia; Nehrbass, Elena; Kolecki, Radek; Jureller, Michael; Schneider, Julia; Chen, Agnes; Shi, Chen; Mendhiratta, Neil; Huang, Jason H.; Qian, Meng; Kwak, Roy; Mikheev, Artem; Rusinek, Henry; George, Ajax; Fergus, Robert; Kondziolka, Douglas; Huang, Paul P.; Smith, R. Theodore

2015-01-01

OBJECT Automated eye movement tracking may provide clues to nervous system function at many levels. Spatial calibration of the eye tracking device requires the subject to have relatively intact ocular motility that implies function of cranial nerves (CNs) III (oculomotor), IV (trochlear), and VI (abducent) and their associated nuclei, along with the multiple regions of the brain imparting cognition and volition. The authors have developed a technique for eye tracking that uses temporal rather than spatial calibration, enabling detection of impaired ability to move the pupil relative to normal (neurologically healthy) control volunteers. This work was performed to demonstrate that this technique may detect CN palsies related to brain compression and to provide insight into how the technique may be of value for evaluating neuropathological conditions associated with CN palsy, such as hydrocephalus or acute mass effect. METHODS The authors recorded subjects’ eye movements by using an Eyelink 1000 eye tracker sampling at 500 Hz over 200 seconds while the subject viewed a music video playing inside an aperture on a computer monitor. The aperture moved in a rectangular pattern over a fixed time period. This technique was used to assess ocular motility in 157 neurologically healthy control subjects and 12 patients with either clinical CN III or VI palsy confirmed by neuro-ophthalmological examination, or surgically treatable pathological conditions potentially impacting these nerves. The authors compared the ratio of vertical to horizontal eye movement (height/width defined as aspect ratio) in normal and test subjects. RESULTS In 157 normal controls, the aspect ratio (height/width) for the left eye had a mean value ± SD of 1.0117 ± 0.0706. For the right eye, the aspect ratio had a mean of 1.0077 ± 0.0679 in these 157 subjects. There was no difference between sexes or ages. A patient with known CN VI palsy had a significantly increased aspect ratio (1.39), whereas 2 patients with known CN III palsy had significantly decreased ratios of 0.19 and 0.06, respectively. Three patients with surgically treatable pathological conditions impacting CN VI, such as infratentorial mass effect or hydrocephalus, had significantly increased ratios (1.84, 1.44, and 1.34, respectively) relative to normal controls, and 6 patients with supratentorial mass effect had significantly decreased ratios (0.27, 0.53, 0.62, 0.45, 0.49, and 0.41, respectively). These alterations in eye tracking all reverted to normal ranges after surgical treatment of underlying pathological conditions in these 9 neurosurgical cases. CONCLUSIONS This proof of concept series of cases suggests that the use of eye tracking to detect CN palsy while the patient watches television or its equivalent represents a new capacity for this technology. It may provide a new tool for the assessment of multiple CNS functions that can potentially be useful in the assessment of awake patients with elevated intracranial pressure from hydrocephalus or trauma. PMID:25495739

Detection of third and sixth cranial nerve palsies with a novel method for eye tracking while watching a short film clip.

PubMed

Samadani, Uzma; Farooq, Sameer; Ritlop, Robert; Warren, Floyd; Reyes, Marleen; Lamm, Elizabeth; Alex, Anastasia; Nehrbass, Elena; Kolecki, Radek; Jureller, Michael; Schneider, Julia; Chen, Agnes; Shi, Chen; Mendhiratta, Neil; Huang, Jason H; Qian, Meng; Kwak, Roy; Mikheev, Artem; Rusinek, Henry; George, Ajax; Fergus, Robert; Kondziolka, Douglas; Huang, Paul P; Smith, R Theodore

2015-03-01

Automated eye movement tracking may provide clues to nervous system function at many levels. Spatial calibration of the eye tracking device requires the subject to have relatively intact ocular motility that implies function of cranial nerves (CNs) III (oculomotor), IV (trochlear), and VI (abducent) and their associated nuclei, along with the multiple regions of the brain imparting cognition and volition. The authors have developed a technique for eye tracking that uses temporal rather than spatial calibration, enabling detection of impaired ability to move the pupil relative to normal (neurologically healthy) control volunteers. This work was performed to demonstrate that this technique may detect CN palsies related to brain compression and to provide insight into how the technique may be of value for evaluating neuropathological conditions associated with CN palsy, such as hydrocephalus or acute mass effect. The authors recorded subjects' eye movements by using an Eyelink 1000 eye tracker sampling at 500 Hz over 200 seconds while the subject viewed a music video playing inside an aperture on a computer monitor. The aperture moved in a rectangular pattern over a fixed time period. This technique was used to assess ocular motility in 157 neurologically healthy control subjects and 12 patients with either clinical CN III or VI palsy confirmed by neuro-ophthalmological examination, or surgically treatable pathological conditions potentially impacting these nerves. The authors compared the ratio of vertical to horizontal eye movement (height/width defined as aspect ratio) in normal and test subjects. In 157 normal controls, the aspect ratio (height/width) for the left eye had a mean value ± SD of 1.0117 ± 0.0706. For the right eye, the aspect ratio had a mean of 1.0077 ± 0.0679 in these 157 subjects. There was no difference between sexes or ages. A patient with known CN VI palsy had a significantly increased aspect ratio (1.39), whereas 2 patients with known CN III palsy had significantly decreased ratios of 0.19 and 0.06, respectively. Three patients with surgically treatable pathological conditions impacting CN VI, such as infratentorial mass effect or hydrocephalus, had significantly increased ratios (1.84, 1.44, and 1.34, respectively) relative to normal controls, and 6 patients with supratentorial mass effect had significantly decreased ratios (0.27, 0.53, 0.62, 0.45, 0.49, and 0.41, respectively). These alterations in eye tracking all reverted to normal ranges after surgical treatment of underlying pathological conditions in these 9 neurosurgical cases. This proof of concept series of cases suggests that the use of eye tracking to detect CN palsy while the patient watches television or its equivalent represents a new capacity for this technology. It may provide a new tool for the assessment of multiple CNS functions that can potentially be useful in the assessment of awake patients with elevated intracranial pressure from hydrocephalus or trauma.

Functional Neuroanatomy and Neurophysiology of Functional Neurological Disorders (Conversion Disorder).

PubMed

Voon, Valerie; Cavanna, Andrea E; Coburn, Kerry; Sampson, Shirlene; Reeve, Alya; LaFrance, W Curt

2016-01-01

Much is known regarding the physical characteristics, comorbid symptoms, psychological makeup, and neuropsychological performance of patients with functional neurological disorders (FNDs)/conversion disorders. Gross neurostructural deficits do not account for the patients' deficits or symptoms. This review describes the literature focusing on potential neurobiological (i.e. functional neuroanatomic/neurophysiological) findings among individuals with FND, examining neuroimaging and neurophysiological studies of patients with the various forms of motor and sensory FND. In summary, neural networks and neurophysiologic mechanisms may mediate "functional" symptoms, reflecting neurobiological and intrapsychic processes.

Chickenpox and Shingles Tests

MedlinePlus

... Time and International Normalized Ratio (PT/INR) PSEN1 Quantitative Immunoglobulins Red Blood Cell (RBC) Antibody Identification Red ... of Neurological Disorders and Stroke: Shingles, Hope Through Research CDC: Shingles MedlinePlus Medical Encyclopedia: Chickenpox March of ...

Pathobiology of Christianson Syndrome: Linking Disrupted Endosomal-Lysosomal Function with Intellectual Disability and Sensory Impairments.

PubMed

Kerner-Rossi, Mallory; Gulinello, Maria; Walkley, Steven; Dobrenis, Kostantin

2018-05-14

Christianson syndrome (CS) is a recently described rare neurogenetic disorder presenting early in life with a broad range of neurological symptoms, including severe intellectual disability with nonverbal status, hyperactivity, epilepsy, and progressive ataxia due to cerebellar atrophy. CS is due to loss-of-function mutations in SLC9A6, encoding NHE6, a sodium-hydrogen exchanger involved in the regulation of early endosomal pH. Here we review what is currently known about the neuropathogenesis of CS, based on insights from experimental models, which to date have focused on mechanisms that affect the CNS, specifically the brain. In addition, parental reports of sensory disturbances in their children with CS, including an apparent insensitivity to pain, led us to explore sensory function and related neuropathology in Slc9a6 KO mice. We present new data showing sensory deficits in Slc9a6 KO mice, which had reduced behavioral responses to noxious thermal and mechanical stimuli (Hargreaves and Von Frey assays, respectively) compared to wild type (WT) littermates. Immunohistochemical and ultrastructural analysis of the spinal cord and peripheral nervous system revealed intracellular accumulation of the glycosphingolipid GM2 ganglioside in KO but not WT mice. This cellular storage phenotype was most abundant in neurons of lamina I-II of the dorsal horn, a major relay site in the processing of painful stimuli. Spinal cords of KO mice also exhibited changes in astroglial and microglial populations throughout the gray matter suggestive of a neuroinflammatory process. Our findings establish the Slc9a6 KO mouse as a relevant tool for studying the sensory deficits in CS, and highlight selective vulnerabilities in relevant cell populations that may contribute to this phenotype. How NHE6 loss of function leads to such a multifaceted neurological syndrome is still undefined, and it is likely that NHE6 is involved with many cellular processes critical to normal nervous system development and function. In addition, the sensory issues exhibited by Slc9a6 KO mice, in combination with our neuropathological findings, are consistent with NHE6 loss of function impacting the entire nervous system. Sensory dysfunction in intellectually disabled individuals is challenging to assess and may impair patient safety and quality of life. Further mechanistic studies of the neurological impairments underlying CS and other genetic intellectual disability disorders must also take into account mechanisms affecting broader nervous system function in order to understand the full range of associated disabilities. Copyright © 2018. Published by Elsevier Inc.

Unusual Presentation of Spasm of Near Reflex Mimicking Large-Angle Acute Acquired Comitant Esotropia

PubMed Central

Shanker, Varshini; Nigam, Vishal

2015-01-01

Abstract We report the case of an 11-year-old boy who presented with sudden esotropia, binocular diplopia, and blurred vision. The patient was neurologically normal. He had a large, constant, comitant, alternating esotropia associated with minimal accommodative spasm. Ocular motility and pupillary reactions were normal. He was diagnosed to have spasm of the near reflex presenting as acute onset of esotropia. The esotropia was persistent despite treatment and eventually resolved with prolonged cycloplegic therapy. This unusual case illustrates that spasm of the near reflex can have unique and variable presentations. Spasm of the near reflex needs to be considered in the differential diagnosis of every case of acute, acquired, comitant esotropia. This is the first case of spasm of the near reflex where persistent esotropia is reported in the absence of any neurological disorder. PMID:27928354

Cold aortic flush and chest compressions enable good neurologic outcome after 15 mins of ventricular fibrillation in cardiac arrest in pigs.

PubMed

Janata, Andreas; Weihs, Wolfgang; Schratter, Alexandra; Bayegan, Keywan; Holzer, Michael; Frossard, Martin; Sipos, Wolfgang; Springler, Gregor; Schmidt, Peter; Sterz, Fritz; Losert, Udo M; Laggner, Anton N; Kochanek, Patrick M; Behringer, Wilhelm

2010-08-01

The induction of deep cerebral hypothermia via ice-cold saline aortic flush during prolonged ventricular fibrillation cardiac arrest, followed by hypothermic stasis and delayed resuscitation (emergency preservation and resuscitation), improved neurologic outcome after cardiac arrest in pigs, as compared to conventional resuscitation. We hypothesized that emergency preservation and resuscitation with chest compressions would further improve outcome in the same model. Prospective experimental study. University research laboratory. : Twenty-four female, large, white breed pigs (27-37 kg). Fifteen minutes of ventricular fibrillation cardiac arrest were followed by 20 mins of resuscitation with chest compressions (control, n = 8), deep cerebral hypothermia via 200 mL/kg 4 degrees C saline aortic flush and hypothermic stasis (emergency preservation and resuscitation, n = 8), and emergency preservation and resuscitation combined with chest compressions (emergency preservation and resuscitation plus chest compressions, n = 8). At 35 mins after cardiac arrest, cardiopulmonary bypass was initiated, followed by defibrillation. Mild hypothermia was continued for 20 hrs. Pigs were evaluated after 9 days using a neurologic deficit (neurologic deficit score: 100% = brain dead; 0%-10% = normal) and an overall performance category score (overall performance category score: 1 = normal; 2 = slightly handicapped; 3 = severely handicapped; 4 = comatose; 5 = dead/brain dead). Brain temperature decreased from 38.5 degrees C to 15.3 degrees C +/- 3.3 degrees C in the emergency preservation and resuscitation group, and to 11.3 degrees C +/- 1.2 degrees C in the emergency preservation and resuscitation plus chest compressions group. In the control group, restoration of spontaneous circulation was achieved in four out of eight pigs, and one survived to 9 days. In the emergency preservation and resuscitation group, restoration of spontaneous circulation was achieved in seven out of eight pigs and five survived; in the emergency preservation and resuscitation plus chest compressions group, all had restoration of spontaneous circulation and seven survived (restoration of spontaneous circulation, p = .08). Neurologic outcome for (median and interquartile range) the control group included overall performance category score of 3, neurologic deficit score of 45%; for the emergency preservation and resuscitation group, overall performance category score was 3 (2-5) and neurologic deficit score was 45% (36; 50) and in the emergency preservation and resuscitation plus chest compressions group, overall performance category score was 2 (1-3) and neurologic deficit score was 13% (5; 21) (overall performance category score, p = .04; neurologic deficit score emergency preservation and resuscitation vs. emergency preservation and resuscitation plus chest compressions, p = .003). Emergency preservation and resuscitation by deep cerebral hypothermia combined with chest compressions during prolonged cardiac arrest in pigs are feasible and improve neurologic outcome.

Neurological and neurocognitive functions from intrauterine methylmercury exposure.

PubMed

Yorifuji, Takashi; Kado, Yoko; Diez, Midory Higa; Kishikawa, Toshihiro; Sanada, Satoshi

2016-05-03

In the 1950s, large-scale food poisoning caused by methylmercury was identified in Minamata, Japan. Although severe intrauterine exposure cases (ie, congenital Minamata disease patients) are well known, possible impacts of methylmercury exposure in utero among residents, which is likely at lower levels than in congenital Minamata disease patients, are rarely explored. In 2014, the authors examined neurological and neurocognitive functions among 18 exposed participants in Minamata, focusing on fine motor, visuospatial construction, and executive functions. More than half of the participants had some fine motor and coordination difficulties. In addition, several participants had lower performance for neurocognitive function tests (the Rey-Osterrieth Complex Figure test and Keio version of the Wisconsin card sorting test). These deficits imply diffuse brain damage. This study suggests possible neurological and neurocognitive impacts of prenatal exposure to methylmercury among exposed residents of Minamata.

Sudden post-traumatic sciatica caused by a thoracic spinal meningioma.

PubMed

Mariniello, Giuseppe; Malacario, Francesca; Dones, Flavia; Severino, Rocco; Ugga, Lorenzo; Russo, Camilla; Elefante, Andrea; Maiuri, Francesco

2016-10-01

Spinal meningiomas usually present with slowly progressive symptoms of cord and root compression, while a sudden clinical onset is very rare. A 35-year-old previously symptom-free woman presented sudden right sciatica and weakness of her right leg following a fall with impact to her left foot. A neurological examination showed paresis of the right quadriceps, tibial and sural muscles, increased bilateral knee and ankle reflexes and positive Babinski sign. Magnetic resonance imaging (MRI) revealed the presence of a spinal T11 meningioma in the left postero-lateral compartment of the spinal canal; at this level, the spinal cord was displaced to the contralateral side with the conus in the normal position. At surgery, a meningioma with dural attachment of the left postero-lateral dural surface was removed. The intervention resulted in rapid remission of both pain and neurological deficits. Spinal meningiomas may exceptionally present with sudden pain and neurological deficits as result of tumour bleeding or post-traumatic injury of the already compressed nervous structures, both in normal patients and in those with conus displacement or tethered cord. In this case, the traumatic impact of the left foot was transmitted to the spine, resulting in stretching of the already compressed cord and of the contralateral lombosacral roots. This case suggests that low thoracic cord compression should be suspected in patients with post-traumatic radicular leg pain with normal lumbar spine MRI. © The Author(s) 2016.

Leukocyte glutamate dehydrogenase activity in patients with degenerative neurological disorders.

PubMed Central

Aubby, D; Saggu, H K; Jenner, P; Quinn, N P; Harding, A E; Marsden, C D

1988-01-01

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 39 normal subjects, 32 neurological controls, 66 patients with progressive ataxic disorders, 32 with multiple system atrophy, 40 with Parkinson's disease, eight with Steele-Richardson-Olszewski syndrome, eight with juvenile Parkinsonism and four with the dystonia-Parkinsonism syndrome. GDH activity was reproducible to within 10% in leukocyte pellets stored at -70 degrees C for up to 9 months, and did not vary with sex or age in control subjects. There was marked variation in the relative proportions of heat stable and heat labile forms of GDH between control subjects and on repeated assay in the same subject. Total leukocyte GDH activity was similar in normal subjects and neurological controls. Mean total GDH activity was reduced in all patient groups by between 15 to 29% compared with controls. Fourteen patients had total GDH activity below 50% of the control mean, but low values were not specific for any one disease (five had ataxic disorders, four Parkinson's disease, three multiple system atrophy, one juvenile Parkinsonism, and one dystonia-Parkinsonism). The heat labile fraction of GDH represented about 20% of total activity in control subjects, and 27% in the patients with reduced total GDH activity. Thus low GDH activity was not disease-specific in this study, and the heat-labile GDH fraction was not selectively affected. "Reduced" leucocyte GDH activity in some patients may represent no more than the lower end of a normal distribution. PMID:3204397

Mutations in UNC80, Encoding Part of the UNC79-UNC80-NALCN Channel Complex, Cause Autosomal-Recessive Severe Infantile Encephalopathy.

PubMed

Shamseldin, Hanan E; Faqeih, Eissa; Alasmari, Ali; Zaki, Maha S; Gleeson, Joseph G; Alkuraya, Fowzan S

2016-01-07

Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Profile of cognitive function in adults with duchenne muscular dystrophy.

PubMed

Ueda, Yukihiko; Suwazono, Shugo; Maedo, Sino; Higuchi, Itsuro

2017-03-01

Several studies have examined intellectual functioning of boys with duchenne muscular dystrophy (DMD). However, little is known about the remaining cognitive weaknesses in adults with DMD. The purpose of this study was to investigate the profile of cognitive functioning that is characteristics of adults with DMD. Twenty-four subscales from the Wechsler Adult Intelligence Scale III (WAIS-III), the Clinical Assessment for Attention (CAT), and the Wechsler Memory Scale Revised (WMS-R) were used to assess participants with DMD (N=15; mean age=30.4years). Scores for Picture Completion, Arithmetic, Matrix Reasoning, Symbol Search, Letter-Number Sequencing, and Digit Span of the WAIS-III; all CAT scores, and Logical Memory and Delayed Logical Memory from the WMS-R were significantly deficient in adults with DMD in comparison to the normal population. The ability to sequentially process auditory and visual information remains impaired in adults with DMD. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Decreased functional connectivity to posterior cingulate cortex in major depressive disorder.

PubMed

Yang, Rui; Gao, Chengge; Wu, Xiaoping; Yang, Junle; Li, Shengbin; Cheng, Hu

2016-09-30

The default mode network (DMN) and its interaction with other key networks such as the salience network and executive network are keys to understand psychiatric and neurological disorders including major depressive disorder (MDD). In this study, we combined independent component analysis and seed based connectivity analysis to study the posterior default mode network between 20 patients with MDD and 25 normal controls, as well as pre-treatment and post-treatment conditions of the patients. Both correlated and anti-correlated networks centered at the posterior cingulate cortex (PCC) were examined (PCC+ and PCC-). Our results showed aberrant functional connectivity of the PCC+ and PCC- networks between patients and normal controls. Specifically, normal controls exhibited significantly higher connectivity between the PCC and frontal/temporal regions for the PCC+ network and stronger connectivity strength between the PCC and the insula/middle frontal cortex for the PCC- network. The overall connectivity strength of the PCC+ and PCC- networks was also significantly lower in MDD. Because the PCC is a hub in the DMN that interacts with other networks, our result suggested a stronger interaction between the DMN and the salience network but a weak interaction between the DMN and the executive network in MDD. The treatment using sertraline did increase the functional connectivity strength, especially in the PCC+ network. Despite a large inter-subject variability in the overall connectivity strengths and change of the PCC network in response to the treatment, a high correlation between change of connectivity strength and the Hamilton depression score was observed for both the PCC+ and PCC- network. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effect of dual tasking on foot kinematics in people with functional ankle instability.

PubMed

Tavakoli, Sanam; Forghany, Saeed; Nester, Christopher

2016-09-01

Some cases of repeated inversion ankle sprains are thought to have a neurological basis and are termed functional ankle instability (FAI). In addition to factors local to the ankle, such as loss of proprioception, cognitive demands have the ability to influence motor control and may increase the risk of repetitive lateral sprains. The purpose of this study was to investigate the effect of cognitive demand on foot kinematics in physically active people with functional ankle instability. 21 physically active participants with FAI and 19 matched healthy controls completed trials of normal walking (single task) and normal walking while performing a cognitive task (dual task). Foot motion relative to the shank was recorded. Cognitive performance, ankle kinematics and movement variability in single and dual task conditions was characterized. During normal walking, the ankle joint was significantly more inverted in FAI compared to the control group pre and post initial contact. Under dual task conditions, there was a statistically significant increase in frontal plane foot movement variability during the period 200ms pre and post initial contact in people with FAI compared to the control group (p<0.05). Dual task also significantly increased plantar flexion and inversion during the period 200ms pre and post initial contact in the FAI group (p<0.05). participants with FAI demonstrated different ankle movement patterns and increased movement variability during a dual task condition. Cognitive load may increase risk of ankle instability in these people. Copyright © 2016 Elsevier B.V. All rights reserved.

Outcomes of fetuses with small head circumference on second-trimester ultrasonography.

PubMed

Deloison, Benjamin; Chalouhi, Gihad E; Bernard, Jean-Pierre; Ville, Yves; Salomon, Laurent J

2012-09-01

We examined the outcomes of pregnancies in which the fetal head circumference (HC) was below the 5(th) centile at the routine second-trimester scan. We retrospectively analysed outcomes of 18,377 women according to HC Z scores at second-trimester ultrasound examination between 2001 and 2008. We collected all major malformations, intrauterine deaths and other abnormal outcomes. Six hundred seventy-four fetuses (3.7%) had an HC below the 5(th) centile. Twenty-one major malformations were noted, consisting mainly of neurological abnormalities (3.1%). There were seven intra uterine fetal death (1.3%). Of all the fetuses, 26% were lost to follow-up. Outcome and neurological development was normal in 467 cases, based on neonatal examination and/or parent or general practitioner reports. Major abnormalities were noted in respectively 26.2%, 3.0% and 1.1% of fetuses with Z scores < -2.5, -2.5 to -2.0, and -2 to -1.645, compared with 0.3% of fetuses with normal HC (p < 10(-4)). A head circumference below the 5(th) centile at second-trimester scan is associated with various abnormalities, especially neurological disorders. The outcome was worse when the HC was smaller. An HC Z score below -2.5 was strongly associated with neurological and chromosomal abnormalities. Conversely, an HC Z score below -1.645 but above -2, excluding cases with prenatally diagnosed malformations, seems to be reassuring for favorable neonatal outcome. © 2012 John Wiley & Sons, Ltd.

Driver landmark and traffic sign identification in early Alzheimer's disease.

PubMed

Uc, E Y; Rizzo, M; Anderson, S W; Shi, Q; Dawson, J D

2005-06-01

To assess visual search and recognition of roadside targets and safety errors during a landmark and traffic sign identification task in drivers with Alzheimer's disease. 33 drivers with probable Alzheimer's disease of mild severity and 137 neurologically normal older adults underwent a battery of visual and cognitive tests and were asked to report detection of specific landmarks and traffic signs along a segment of an experimental drive. The drivers with mild Alzheimer's disease identified significantly fewer landmarks and traffic signs and made more at-fault safety errors during the task than control subjects. Roadside target identification performance and safety errors were predicted by scores on standardised tests of visual and cognitive function. Drivers with Alzheimer's disease are impaired in a task of visual search and recognition of roadside targets; the demands of these targets on visual perception, attention, executive functions, and memory probably increase the cognitive load, worsening driving safety.

The first familial case of inherited 2q37.3 interstitial deletion with isolated skeletal abnormalities including brachydactyly type E and short stature.

PubMed

Jean-Marçais, Nolwenn; Decamp, Matthieu; Gérard, Marion; Ribault, Virginie; Andrieux, Joris; Kottler, Marie-Laure; Plessis, Ghislaine

2015-01-01

Albright hereditary osteodystrophy (AHO)-like syndrome is also known as brachydactyly-mental retardation syndrome (BDMR; OMIM 60040). This disorder includes intellectual disability in all patients, skeletal abnormalities, including brachydactyly E (BDE) in approximately half, obesity, and facial dysmorphism. Patients with 2q37 microdeletion or HDAC4 mutation are defined as having an AHO-like phenotype with normal stimulatory G (Gs) function. HDAC4 is involved in neurological, cardiac, and skeletal function. This paper reports the first familial case of 2q37.3 interstitial deletion affecting two genes, HDAC4 and TWIST2. Patients presented with BDE and short stature without intellectual disability, showing that haploinsufficiency of the HDAC4 critical region may lead to a spectrum of phenotypes, ranging from isolated brachydactyly type E to BDMR. © 2014 Wiley Periodicals, Inc.

CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

PubMed Central

Lee, J.-M.; Ramos, E.M.; Lee, J.-H.; Gillis, T.; Mysore, J.S.; Hayden, M.R.; Warby, S.C.; Morrison, P.; Nance, M.; Ross, C.A.; Margolis, R.L.; Squitieri, F.; Orobello, S.; Di Donato, S.; Gomez-Tortosa, E.; Ayuso, C.; Suchowersky, O.; Trent, R.J.A.; McCusker, E.; Novelletto, A.; Frontali, M.; Jones, R.; Ashizawa, T.; Frank, S.; Saint-Hilaire, M.H.; Hersch, S.M.; Rosas, H.D.; Lucente, D.; Harrison, M.B.; Zanko, A.; Abramson, R.K.; Marder, K.; Sequeiros, J.; Paulsen, J.S.; Landwehrmeyer, G.B.; Myers, R.H.; MacDonald, M.E.; Durr, Alexandra; Rosenblatt, Adam; Frati, Luigi; Perlman, Susan; Conneally, Patrick M.; Klimek, Mary Lou; Diggin, Melissa; Hadzi, Tiffany; Duckett, Ayana; Ahmed, Anwar; Allen, Paul; Ames, David; Anderson, Christine; Anderson, Karla; Anderson, Karen; Andrews, Thomasin; Ashburner, John; Axelson, Eric; Aylward, Elizabeth; Barker, Roger A.; Barth, Katrin; Barton, Stacey; Baynes, Kathleen; Bea, Alexandra; Beall, Erik; Beg, Mirza Faisal; Beglinger, Leigh J.; Biglan, Kevin; Bjork, Kristine; Blanchard, Steve; Bockholt, Jeremy; Bommu, Sudharshan Reddy; Brossman, Bradley; Burrows, Maggie; Calhoun, Vince; Carlozzi, Noelle; Chesire, Amy; Chiu, Edmond; Chua, Phyllis; Connell, R.J.; Connor, Carmela; Corey-Bloom, Jody; Craufurd, David; Cross, Stephen; Cysique, Lucette; Santos, Rachelle Dar; Davis, Jennifer; Decolongon, Joji; DiPietro, Anna; Doucette, Nicholas; Downing, Nancy; Dudler, Ann; Dunn, Steve; Ecker, Daniel; Epping, Eric A.; Erickson, Diane; Erwin, Cheryl; Evans, Ken; Factor, Stewart A.; Farias, Sarah; Fatas, Marta; Fiedorowicz, Jess; Fullam, Ruth; Furtado, Sarah; Garde, Monica Bascunana; Gehl, Carissa; Geschwind, Michael D.; Goh, Anita; Gooblar, Jon; Goodman, Anna; Griffith, Jane; Groves, Mark; Guttman, Mark; Hamilton, Joanne; Harrington, Deborah; Harris, Greg; Heaton, Robert K.; Helmer, Karl; Henneberry, Machelle; Hershey, Tamara; Herwig, Kelly; Howard, Elizabeth; Hunter, Christine; Jankovic, Joseph; Johnson, Hans; Johnson, Arik; Jones, Kathy; Juhl, Andrew; Kim, Eun Young; Kimble, Mycah; King, Pamela; Klimek, Mary Lou; Klöppel, Stefan; Koenig, Katherine; Komiti, Angela; Kumar, Rajeev; Langbehn, Douglas; Leavitt, Blair; Leserman, Anne; Lim, Kelvin; Lipe, Hillary; Lowe, Mark; Magnotta, Vincent A.; Mallonee, William M.; Mans, Nicole; Marietta, Jacquie; Marshall, Frederick; Martin, Wayne; Mason, Sarah; Matheson, Kirsty; Matson, Wayne; Mazzoni, Pietro; McDowell, William; Miedzybrodzka, Zosia; Miller, Michael; Mills, James; Miracle, Dawn; Montross, Kelsey; Moore, David; Mori, Sasumu; Moser, David J.; Moskowitz, Carol; Newman, Emily; Nopoulos, Peg; Novak, Marianne; O'Rourke, Justin; Oakes, David; Ondo, William; Orth, Michael; Panegyres, Peter; Pease, Karen; Perlman, Susan; Perlmutter, Joel; Peterson, Asa; Phillips, Michael; Pierson, Ron; Potkin, Steve; Preston, Joy; Quaid, Kimberly; Radtke, Dawn; Rae, Daniela; Rao, Stephen; Raymond, Lynn; Reading, Sarah; Ready, Rebecca; Reece, Christine; Reilmann, Ralf; Reynolds, Norm; Richardson, Kylie; Rickards, Hugh; Ro, Eunyoe; Robinson, Robert; Rodnitzky, Robert; Rogers, Ben; Rosenblatt, Adam; Rosser, Elisabeth; Rosser, Anne; Price, Kathy; Price, Kathy; Ryan, Pat; Salmon, David; Samii, Ali; Schumacher, Jamy; Schumacher, Jessica; Sendon, Jose Luis Lópenz; Shear, Paula; Sheinberg, Alanna; Shpritz, Barnett; Siedlecki, Karen; Simpson, Sheila A.; Singer, Adam; Smith, Jim; Smith, Megan; Smith, Glenn; Snyder, Pete; Song, Allen; Sran, Satwinder; Stephan, Klaas; Stober, Janice; Sü?muth, Sigurd; Suter, Greg; Tabrizi, Sarah; Tempkin, Terry; Testa, Claudia; Thompson, Sean; Thomsen, Teri; Thumma, Kelli; Toga, Arthur; Trautmann, Sonja; Tremont, Geoff; Turner, Jessica; Uc, Ergun; Vaccarino, Anthony; van Duijn, Eric; Van Walsem, Marleen; Vik, Stacie; Vonsattel, Jean Paul; Vuletich, Elizabeth; Warner, Tom; Wasserman, Paula; Wassink, Thomas; Waterman, Elijah; Weaver, Kurt; Weir, David; Welsh, Claire; Werling-Witkoske, Chris; Wesson, Melissa; Westervelt, Holly; Weydt, Patrick; Wheelock, Vicki; Williams, Kent; Williams, Janet; Wodarski, Mary; Wojcieszek, Joanne; Wood, Jessica; Wood-Siverio, Cathy; Wu, Shuhua; Yastrubetskaya, Olga; de Yebenes, Justo Garcia; Zhao, Yong Qiang; Zimbelman, Janice; Zschiegner, Roland; Aaserud, Olaf; Abbruzzese, Giovanni; Andrews, Thomasin; Andrich, Jurgin; Antczak, Jakub; Arran, Natalie; Artiga, Maria J. Saiz; Bachoud-Lévi, Anne-Catherine; Banaszkiewicz, Krysztof; di Poggio, Monica Bandettini; Bandmann, Oliver; Barbera, Miguel A.; Barker, Roger A.; Barrero, Francisco; Barth, Katrin; Bas, Jordi; Beister, Antoine; Bentivoglio, Anna Rita; Bertini, Elisabetta; Biunno, Ida; Bjørgo, Kathrine; Bjørnevoll, Inga; Bohlen, Stefan; Bonelli, Raphael M.; Bos, Reineke; Bourne, Colin; Bradbury, Alyson; Brockie, Peter; Brown, Felicity; Bruno, Stefania; Bryl, Anna; Buck, Andrea; Burg, Sabrina; Burgunder, Jean-Marc; Burns, Peter; Burrows, Liz; Busquets, Nuria; Busse, Monica; Calopa, Matilde; Carruesco, Gemma T.; Casado, Ana Gonzalez; Catena, Judit López; Chu, Carol; Ciesielska, Anna; Clapton, Jackie; Clayton, Carole; Clenaghan, Catherine; Coelho, Miguel; Connemann, Julia; Craufurd, David; Crooks, Jenny; Cubillo, Patricia Trigo; Cubo, Esther; Curtis, Adrienne; De Michele, Giuseppe; De Nicola, A.; de Souza, Jenny; de Weert, A. Marit; de Yébenes, Justo Garcia; Dekker, M.; Descals, A. Martínez; Di Maio, Luigi; Di Pietro, Anna; Dipple, Heather; Dose, Matthias; Dumas, Eve M.; Dunnett, Stephen; Ecker, Daniel; Elifani, F.; Ellison-Rose, Lynda; Elorza, Marina D.; Eschenbach, Carolin; Evans, Carole; Fairtlough, Helen; Fannemel, Madelein; Fasano, Alfonso; Fenollar, Maria; Ferrandes, Giovanna; Ferreira, Jaoquim J.; Fillingham, Kay; Finisterra, Ana Maria; Fisher, K.; Fletcher, Amy; Foster, Jillian; Foustanos, Isabella; Frech, Fernando A.; Fullam, Robert; Fullham, Ruth; Gago, Miguel; García, RocioGarcía-Ramos; García, Socorro S.; Garrett, Carolina; Gellera, Cinzia; Gill, Paul; Ginestroni, Andrea; Golding, Charlotte; Goodman, Anna; Gørvell, Per; Grant, Janet; Griguoli, A.; Gross, Diana; Guedes, Leonor; BascuñanaGuerra, Monica; Guerra, Maria Rosalia; Guerrero, Rosa; Guia, Dolores B.; Guidubaldi, Arianna; Hallam, Caroline; Hamer, Stephanie; Hammer, Kathrin; Handley, Olivia J.; Harding, Alison; Hasholt, Lis; Hedge, Reikha; Heiberg, Arvid; Heinicke, Walburgis; Held, Christine; Hernanz, Laura Casas; Herranhof, Briggitte; Herrera, Carmen Durán; Hidding, Ute; Hiivola, Heli; Hill, Susan; Hjermind, Lena. E.; Hobson, Emma; Hoffmann, Rainer; Holl, Anna Hödl; Howard, Liz; Hunt, Sarah; Huson, Susan; Ialongo, Tamara; Idiago, Jesus Miguel R.; Illmann, Torsten; Jachinska, Katarzyna; Jacopini, Gioia; Jakobsen, Oda; Jamieson, Stuart; Jamrozik, Zygmunt; Janik, Piotr; Johns, Nicola; Jones, Lesley; Jones, Una; Jurgens, Caroline K.; Kaelin, Alain; Kalbarczyk, Anna; Kershaw, Ann; Khalil, Hanan; Kieni, Janina; Klimberg, Aneta; Koivisto, Susana P.; Koppers, Kerstin; Kosinski, Christoph Michael; Krawczyk, Malgorzata; Kremer, Berry; Krysa, Wioletta; Kwiecinski, Hubert; Lahiri, Nayana; Lambeck, Johann; Lange, Herwig; Laver, Fiona; Leenders, K.L.; Levey, Jamie; Leythaeuser, Gabriele; Lezius, Franziska; Llesoy, Joan Roig; Löhle, Matthias; López, Cristobal Diez-Aja; Lorenza, Fortuna; Loria, Giovanna; Magnet, Markus; Mandich, Paola; Marchese, Roberta; Marcinkowski, Jerzy; Mariotti, Caterina; Mariscal, Natividad; Markova, Ivana; Marquard, Ralf; Martikainen, Kirsti; Martínez, Isabel Haro; Martínez-Descals, Asuncion; Martino, T.; Mason, Sarah; McKenzie, Sue; Mechi, Claudia; Mendes, Tiago; Mestre, Tiago; Middleton, Julia; Milkereit, Eva; Miller, Joanne; Miller, Julie; Minster, Sara; Möller, Jens Carsten; Monza, Daniela; Morales, Blas; Moreau, Laura V.; Moreno, Jose L. López-Sendón; Münchau, Alexander; Murch, Ann; Nielsen, Jørgen E.; Niess, Anke; Nørremølle, Anne; Novak, Marianne; O'Donovan, Kristy; Orth, Michael; Otti, Daniela; Owen, Michael; Padieu, Helene; Paganini, Marco; Painold, Annamaria; Päivärinta, Markku; Partington-Jones, Lucy; Paterski, Laurent; Paterson, Nicole; Patino, Dawn; Patton, Michael; Peinemann, Alexander; Peppa, Nadia; Perea, Maria Fuensanta Noguera; Peterson, Maria; Piacentini, Silvia; Piano, Carla; Càrdenas, Regina Pons i; Prehn, Christian; Price, Kathleen; Probst, Daniela; Quarrell, Oliver; Quiroga, Purificacion Pin; Raab, Tina; Rakowicz, Maryla; Raman, Ashok; Raymond, Lucy; Reilmann, Ralf; Reinante, Gema; Reisinger, Karin; Retterstol, Lars; Ribaï, Pascale; Riballo, Antonio V.; Ribas, Guillermo G.; Richter, Sven; Rickards, Hugh; Rinaldi, Carlo; Rissling, Ida; Ritchie, Stuart; Rivera, Susana Vázquez; Robert, Misericordia Floriach; Roca, Elvira; Romano, Silvia; Romoli, Anna Maria; Roos, Raymond A.C.; Røren, Niini; Rose, Sarah; Rosser, Elisabeth; Rosser, Anne; Rossi, Fabiana; Rothery, Jean; Rudzinska, Monika; Ruíz, Pedro J. García; Ruíz, Belan Garzon; Russo, Cinzia Valeria; Ryglewicz, Danuta; Saft, Carston; Salvatore, Elena; Sánchez, Vicenta; Sando, Sigrid Botne; Šašinková, Pavla; Sass, Christian; Scheibl, Monika; Schiefer, Johannes; Schlangen, Christiane; Schmidt, Simone; Schöggl, Helmut; Schrenk, Caroline; Schüpbach, Michael; Schuierer, Michele; Sebastián, Ana Rojo; Selimbegovic-Turkovic, Amina; Sempolowicz, Justyna; Silva, Mark; Sitek, Emilia; Slawek, Jaroslaw; Snowden, Julie; Soleti, Francesco; Soliveri, Paola; Sollom, Andrea; Soltan, Witold; Sorbi, Sandro; Sorensen, Sven Asger; Spadaro, Maria; Städtler, Michael; Stamm, Christiane; Steiner, Tanja; Stokholm, Jette; Stokke, Bodil; Stopford, Cheryl; Storch, Alexander; Straßburger, Katrin; Stubbe, Lars; Sulek, Anna; Szczudlik, Andrzej; Tabrizi, Sarah; Taylor, Rachel; Terol, Santiago Duran-Sindreu; Thomas, Gareth; Thompson, Jennifer; Thomson, Aileen; Tidswell, Katherine; Torres, Maria M. Antequera; Toscano, Jean; Townhill, Jenny; Trautmann, Sonja; Tucci, Tecla; Tuuha, Katri; Uhrova, Tereza; Valadas, Anabela; van Hout, Monique S.E.; van Oostrom, J.C.H.; van Vugt, Jeroen P.P.; vanm, Walsem Marleen R.; Vandenberghe, Wim; Verellen-Dumoulin, Christine; Vergara, Mar Ruiz; Verstappen, C.C.P.; Verstraelen, Nichola; Viladrich, Celia Mareca; Villanueva, Clara; Wahlström, Jan; Warner, Thomas; Wehus, Raghild; Weindl, Adolf; Werner, Cornelius J.; Westmoreland, Leann; Weydt, Patrick; Wiedemann, Alexandra; Wild, Edward; Wild, Sue; Witjes-Ané, Marie-Noelle; Witkowski, Grzegorz; Wójcik, Magdalena; Wolz, Martin; Wolz, Annett; Wright, Jan; Yardumian, Pam; Yates, Shona; Yudina, Elizaveta; Zaremba, Jacek; Zaugg, Sabine W.; Zdzienicka, Elzbieta; Zielonka, Daniel; Zielonka, Euginiusz; Zinzi, Paola; Zittel, Simone; Zucker, Birgrit; Adams, John; Agarwal, Pinky; Antonijevic, Irina; Beck, Christopher; Chiu, Edmond; Churchyard, Andrew; Colcher, Amy; Corey-Bloom, Jody; Dorsey, Ray; Drazinic, Carolyn; Dubinsky, Richard; Duff, Kevin; Factor, Stewart; Foroud, Tatiana; Furtado, Sarah; Giuliano, Joe; Greenamyre, Timothy; Higgins, Don; Jankovic, Joseph; Jennings, Dana; Kang, Un Jung; Kostyk, Sandra; Kumar, Rajeev; Leavitt, Blair; LeDoux, Mark; Mallonee, William; Marshall, Frederick; Mohlo, Eric; Morgan, John; Oakes, David; Panegyres, Peter; Panisset, Michel; Perlman, Susan; Perlmutter, Joel; Quaid, Kimberly; Raymond, Lynn; Revilla, Fredy; Robertson, Suzanne; Robottom, Bradley; Sanchez-Ramos, Juan; Scott, Burton; Shannon, Kathleen; Shoulson, Ira; Singer, Carlos; Tabbal, Samer; Testa, Claudia; van, Kammen Dan; Vetter, Louise; Walker, Francis; Warner, John; Weiner, illiam; Wheelock, Vicki; Yastrubetskaya, Olga; Barton, Stacey; Broyles, Janice; Clouse, Ronda; Coleman, Allison; Davis, Robert; Decolongon, Joji; DeLaRosa, Jeanene; Deuel, Lisa; Dietrich, Susan; Dubinsky, Hilary; Eaton, Ken; Erickson, Diane; Fitzpatrick, Mary Jane; Frucht, Steven; Gartner, Maureen; Goldstein, Jody; Griffith, Jane; Hickey, Charlyne; Hunt, Victoria; Jaglin, Jeana; Klimek, Mary Lou; Lindsay, Pat; Louis, Elan; Loy, Clemet; Lucarelli, Nancy; Malarick, Keith; Martin, Amanda; McInnis, Robert; Moskowitz, Carol; Muratori, Lisa; Nucifora, Frederick; O'Neill, Christine; Palao, Alicia; Peavy, Guerry; Quesada, Monica; Schmidt, Amy; Segro, Vicki; Sperin, Elaine; Suter, Greg; Tanev, Kalo; Tempkin, Teresa; Thiede, Curtis; Wasserman, Paula; Welsh, Claire; Wesson, Melissa; Zauber, Elizabeth

2012-01-01

Objective: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. Methods: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. Results: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. Conclusions: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. Neurology® 2012;78:690–695 PMID:22323755

Effects of Normal Aging on Visuo-Motor Plasticity

NASA Technical Reports Server (NTRS)

Roller, Carrie A.; Cohen, Helen S.; Kimball, Kay T.; Bloomberg, Jacob J.

2001-01-01

Normal aging is associated with declines in neurologic function. Uncompensated visual and vestibular problems may have dire consequences including dangerous falls. Visuomotor plasticity is a form of behavioral neural plasticity which is important in the process of adapting to visual or vestibular alteration, including those changes due to pathology, pharmacotherapy, surgery or even entry into a microgravity or underwater environment. In order to determine the effects of aging on visuomotor plasticity, we chose the simple and easily measured paradigm of visual-motor re-arrangement created by using visual displacement prisms while throwing small balls at a target. Subjects threw balls before, during and after wearing a set of prisms which displace the visual scene by twenty degrees to the right. Data obtained during adaptation were modeled using multilevel analyses for 73 subjects aged 20 to 80 years. We found no statistically significant difference in measures of visuomotor plasticity with advancing age. Further studies are underway examining variable practice training as a potential mechanism for enhancing this form of behavioral neural plasticity.

Effects of normal aging on visuo-motor plasticity

NASA Technical Reports Server (NTRS)

Roller, Carrie A.; Cohen, Helen S.; Kimball, Kay T.; Bloomberg, Jacob J.

2002-01-01

Normal aging is associated with declines in neurologic function. Uncompensated visual and vestibular problems may have dire consequences including dangerous falls. Visuo-motor plasticity is a form of behavioral neural plasticity, which is important in the process of adapting to visual or vestibular alteration, including those changes due to pathology, pharmacotherapy, surgery or even entry into microgravity or an underwater environment. To determine the effects of aging on visuo-motor plasticity, we chose the simple and easily measured paradigm of visual-motor rearrangement created by using visual displacement prisms while throwing small balls at a target. Subjects threw balls before, during and after wearing a set of prisms which displace the visual scene by twenty degrees to the right. Data obtained during adaptation were modeled using multilevel modeling techniques for 73 subjects, aged 20 to 80 years. We found no statistically significant difference in measures of visuo-motor plasticity with advancing age. Further studies are underway examining variable practice training as a potential mechanism for enhancing this form of behavioral neural plasticity.

New daily persistent headache with isolated sphenoiditis in children

PubMed Central

Lee, Jeongho; Rhee, Minhee

2015-01-01

Isolated sphenoid sinusitis is a rare disease in children, and its symptoms are often nonspecific and confusing. Rarely, severe headache can be the first or only symptom of isolated sphenoid sinusitis. New daily persistent headache (NDPH) is a form of chronic daily headache that may have features of both migraines and tension-type headaches. NDPH is difficult to diagnose and requires a multifaceted approach. Here, we report on a 10-year-old boy and an 11-year-old girl who both presented with typical NDPH symptoms. These patients had no nasal symptoms or signs of infection. Neither nonsteroidal anti-inflammatory drugs nor topiramate had any effect on the headaches. Their neurological and ophthalmological examinations were normal. The results of routine blood work, including thyroid function tests, inflammatory markers, complete blood count, tests for viral infection, and a metabolic panel, were normal. A brain magnetic resonance imaging scan showed isolated sphenoid sinusitis. Both patients' symptoms resolved completely after approximately 1 month of oral antibiotics for sinusitis. PMID:25774200

New daily persistent headache with isolated sphenoiditis in children.

PubMed

Lee, Jeongho; Rhee, Minhee; Suh, Eun Sook

2015-02-01

Isolated sphenoid sinusitis is a rare disease in children, and its symptoms are often nonspecific and confusing. Rarely, severe headache can be the first or only symptom of isolated sphenoid sinusitis. New daily persistent headache (NDPH) is a form of chronic daily headache that may have features of both migraines and tension-type headaches. NDPH is difficult to diagnose and requires a multifaceted approach. Here, we report on a 10-year-old boy and an 11-year-old girl who both presented with typical NDPH symptoms. These patients had no nasal symptoms or signs of infection. Neither nonsteroidal anti-inflammatory drugs nor topiramate had any effect on the headaches. Their neurological and ophthalmological examinations were normal. The results of routine blood work, including thyroid function tests, inflammatory markers, complete blood count, tests for viral infection, and a metabolic panel, were normal. A brain magnetic resonance imaging scan showed isolated sphenoid sinusitis. Both patients' symptoms resolved completely after approximately 1 month of oral antibiotics for sinusitis.

The Neurologic Assessment in Neuro-Oncology (NANO) scale: a tool to assess neurologic function for integration into the Response Assessment in Neuro-Oncology (RANO) criteria.

PubMed

Nayak, Lakshmi; DeAngelis, Lisa M; Brandes, Alba A; Peereboom, David M; Galanis, Evanthia; Lin, Nancy U; Soffietti, Riccardo; Macdonald, David R; Chamberlain, Marc; Perry, James; Jaeckle, Kurt; Mehta, Minesh; Stupp, Roger; Muzikansky, Alona; Pentsova, Elena; Cloughesy, Timothy; Iwamoto, Fabio M; Tonn, Joerg-Christian; Vogelbaum, Michael A; Wen, Patrick Y; van den Bent, Martin J; Reardon, David A

2017-05-01

The Macdonald criteria and the Response Assessment in Neuro-Oncology (RANO) criteria define radiologic parameters to classify therapeutic outcome among patients with malignant glioma and specify that clinical status must be incorporated and prioritized for overall assessment. But neither provides specific parameters to do so. We hypothesized that a standardized metric to measure neurologic function will permit more effective overall response assessment in neuro-oncology. An international group of physicians including neurologists, medical oncologists, radiation oncologists, and neurosurgeons with expertise in neuro-oncology drafted the Neurologic Assessment in Neuro-Oncology (NANO) scale as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. The scale was subsequently tested in a multicenter study to determine its overall reliability, inter-observer variability, and feasibility. The NANO scale is a quantifiable evaluation of 9 relevant neurologic domains based on direct observation and testing conducted during routine office visits. The score defines overall response criteria. A prospective, multinational study noted a >90% inter-observer agreement rate with kappa statistic ranging from 0.35 to 0.83 (fair to almost perfect agreement), and a median assessment time of 4 minutes (interquartile range, 3-5). The NANO scale provides an objective clinician-reported outcome of neurologic function with high inter-observer agreement. It is designed to combine with radiographic assessment to provide an overall assessment of outcome for neuro-oncology patients in clinical trials and in daily practice. Furthermore, it complements existing patient-reported outcomes and cognition testing to combine for a global clinical outcome assessment of well-being among brain tumor patients. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The effect of vertebral fracture on the early neurologic recovery in patients with central cord syndrome.

PubMed

Schroeder, Gregory D; Kepler, Christopher K; Hjelm, Nik; Vaccaro, Alexander R; Weinstein, Michael S

2015-05-01

To compare early changes in the ASIA Motor Score (AMS) between patients with central cord syndrome (CCS) from an acute fracture to patients without a fracture. Patients with CCS were identified and stratified based on the presence of a fracture. The AMS through the first week of the patients' hospitalization was obtained. Initial injury severity as well as early neurologic recovery was measured using the AMS. Analysis of variance was performed to determine if age, gender, rectal tone at presentation, congenital stenosis, or surgery within 24 h significantly effected the change in AMS. A strong trend (p = 0.0504) towards a more severe initial neurologic injury in patients with a fracture (AMS 59.7) than in patients without a fracture (AMS 70.2) was identified. However, in the week after injury, patients with a fracture had an improvement in their neurologic function (ΔAMS +4.8) while patients without a fracture demonstrated neurologic decline (ΔAMS -5.9). The change in AMS between patients with and without a fracture was nearly significant (p = 0.06). Patients with central cord syndrome present with similar symptoms, but injuries with and without a fracture may be associated with a different early neurologic recovery. Patients with a fracture have a more severe injury at initial presentation, but tend to have neurologic improvement in the first week; conversely patients without a fracture have a less severe initial neurologic injury, but tend to have a slight decline in neurologic function over the first week.

Searching for a neurologic injury's Wechsler Adult Intelligence Scale-Third Edition profile.

PubMed

Gonçalves, Marta A; Moura, Octávio; Castro-Caldas, Alexandre; Simões, Mário R

2017-01-01

This study aimed to investigate the presence of a Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) cognitive profile in a Portuguese neurologic injured sample. The Portuguese WAIS-III was administered to 81 mixed neurologic patients and 81 healthy matched controls selected from the Portuguese standardization sample. Although the mixed neurologic injury group performed significantly lower than the healthy controls for the majority of the WAIS-III scores (i.e., composite measures, discrepancies, and subtests), the mean scores were within the normal range and, therefore, at risk of being unobserved in a clinical evaluation. ROC curves analysis showed poor to acceptable diagnostic accuracy for the WAIS-III composite measures and subtests (Working Memory Index and Digit Span revealed the highest accuracy for discriminating between participants, respectively). Multiple regression analysis showed that both literacy and the presence of brain injury were significant predictors for all of the composite measures. In addition, multiple regression analysis also showed that literacy, age of injury onset, and years of survival predicted all seven composite measures for the mixed neurologic injured group. Despite the failure to find a WAIS-III cognitive profile for mixed neurologic patients, the results showed a significant influence of brain lesion and literacy in the performance of the WAIS-III.

[The importance of neurological examinations in the age of the technological revolution].

PubMed

Berbel-García, A; González-Spínola, J; Martínez-Salio, A; Porta-Etessam, J; Pérez-Martínez, D A; de Toledo, M; Sáiz-Díaz, R A

Neurologic practice and care have been modified in many important ways during the past ten years, to adapt to the explosion of new information and new technology. Students, residents and practicing physicians have been continuing programs to a model that focuses almost exclusively on the applications to neurologic disorders of the new knowledge obtained from biomedical research. On the other hand high demand for outpatient neurologic care prevents adequate patient's evaluation. Case 1: 65 years old female. Occipital headache diagnosed of tensional origin (normal computerized tomography). Two months later is re-evaluated due to intractable pain and hypoglossal lesion. An amplified computerized tomography revealed a occipital condyle metastasis. Case 2: 21 years old female. Clinical suspicion of demyelinating disease due to repeated facial paresis and sensitive disorder. General exploration and computerized tomography revealed temporo-mandibular joint. Case 3: 60 years old female. Valuation of anticoagulant therapy due to repeated transient ischemic attacks. She suffered from peripheral facial palsy related to auditory cholesteatoma. Neurologic education is nowadays orientated to new technologies. On the other hand, excessive demand prevents adequate valuation and a minute exploration is substituted by complementary evaluations. These situations generate diagnostic mistakes or iatrogenic. It would be important a consideration of the neurologic education profiles and fulfillment of consultations time recommendations for outpatients care.

Markers for human brain pericytes and smooth muscle cells.

PubMed

Smyth, Leon C D; Rustenhoven, Justin; Scotter, Emma L; Schweder, Patrick; Faull, Richard L M; Park, Thomas I H; Dragunow, Mike

2018-06-07

Brain pericytes and vascular smooth muscle cells (vSMCs) are a critical component of the neurovascular unit and are important in regulating cerebral blood flow and blood-brain barrier integrity. Identification of subtypes of mural cells in tissue and in vitro is important to any study of their function, therefore we identified distinct mural cell morphologies in neurologically normal post-mortem human brain. Further, the distribution of mural cell markers platelet-derived growth factor receptor-β (PDGFRβ), α-smooth muscle actin (αSMA), CD13, neural/glial antigen-2 (NG2), CD146 and desmin was examined. We determined that PDGFRβ, NG2, CD13, and CD146 were expressed in capillary-associated pericytes. NG2, and CD13 were also present on vSMCs in large vessels, however abundant CD146 and desmin staining was also detected in vSMCs on large vessels, co-labelling with αSMA. To determine whether cultures recapitulated observations from tissue, primary human brain pericytes derived from neurologically normal autopsies were analysed for the presence of pericyte markers by immunocytochemistry, western blotting and qPCR. The proteins observed in brain pericytes in tissue (PDGFRβ, αSMA, desmin, CD146, CD13, and NG2) were present in vitro, validating a panel of proteins that can be used to label brain pericytes and vSMCs in tissue and in vitro. Finally, we showed that the proteins CD146 and desmin that are expressed on large vessels in situ, are also selective markers of a smooth muscle cell phenotype in vitro. Copyright © 2018 Elsevier B.V. All rights reserved.

Lower Urinary Tract Urological Abnormalities and Urodynamic Findings of Physiological Urinary Incontinence Versus Non-mono Symptomatic Nocturnal Enuresis in Children.

PubMed

Naseri, Mitra

2014-03-01

Although 98% of children attain daytime bladder control by three years of age, urinary incontinence is regarded physiological up to the fifth year of life. This study aimed to assess whether lower urinary tract urological abnormalities and abnormal urodynamic findings are infrequent in children with physiological urinary incontinence in contrast to those with non-monosymptomatic nocturnal enuresis (NMNE). During a three-year period (2007-2009), 66 neurologically normal children including 51 children (34 girls, 17 boys) older than five years of age with NMNE and intermittent daytime incontinence, and 15 children with physiological urinary incontinence (eight girls and seven boys) aged four to five years of age without any known urological abnormalities were enrolled in the study. Patients with neurologic deficits or known urological anomalies were excluded from the study. Kidney-bladder ultrasonography, voiding cystourethrography (VCUG), and urodynamic studies were performed to evaluate the anatomy of urinary tract and bladder function. Urinary tract infection was found in 23 (34.8%) children, 17 (33.3%) and 6 (40%) patients with NMNE and physiological urinary incontinence, respectively. Out of 48 patients who underwent VCUG, vesicoureteral reflux (VUR) was found in seven and eight children younger and older than five years of age, respectively. Abnormal urodynamic findings were reported in 5 (62.5%) of eight children younger than five-year-old, and 14 (63.6%) of 22 patients older than 5-year-old. VUR might be more frequent in children with physiological urinary incontinence than the normal population, and might be as common as NMNE with intermittent daytime incontinence.

Chronic choline supplementation improves cognitive and motor performance via modulating oxidative and neurochemical status in rats.

PubMed

Tabassum, Saiqa; Haider, Saida; Ahmad, Saara; Madiha, Syeda; Parveen, Tahira

2017-08-01

Choline, an essential nutrient, accounts for multiple functions in the body and brain. While its beneficial effects on healthy adults are not clear, choline supplementation is important during pregnancy for brain development, in elderly patients for support of cognitive performance and in patients with neurological disorders to reduce memory deficits. Thus, the aim of this study is to investigate whether choline administration in healthy adult rats beneficially impacts cognitive and locomotor performance, and associated oxidative and neurochemical outcomes. Two groups, control and choline, received tap water and choline bitartrate, respectively at the dose equivalent to adequate intake for five weeks. Food intake and body weight were monitored daily. Behavioral analysis comprising assessment of cognitive performance (by novel object recognition, passive avoidance and Morris Water Maze test) and locomotor performance (by Open field, Kondziela's inverted screen and beam walking test) were performed. Following testing, rats were decapitated and brain samples were collected for estimation of acetylcholine, redox profile and monoamine measurements. The results showed that chronic choline administration significantly improves cognitive and locomotor performance accompanied by a reduction in oxidative stress, enhanced cholinergic neurotransmission and monoamine levels in the brain of healthy adult rats. Hence, chronic choline intake was found to improve behavioral, oxidative and neurochemical outcomes in the normal population, so it can be suggested that choline tablets can be used as a safe and effective supplement for improving the neurological health of normal individuals and that they might also be beneficial in preventing cognitive and motor disorders later in life. Copyright © 2017 Elsevier Inc. All rights reserved.

Awake craniotomy for glioma resection: Technical aspects and initial results in a single institution.

PubMed

Trimble, Gillian; McStravick, Clodagh; Farling, Peter; Megaw, Katie; McKinstry, Steven; Smyth, Graham; Law, Gillian; Courtney, Heather; Quigley, Gavin; Flannery, Thomas

2015-01-01

Although variations in the technique of awake craniotomy (AC) have been widely reported, a key member of this interdisciplinary procedure is the healthcare professional performing assessments of neurological function during resection. The expertise of the latter will depend on the neurological function to be tested and on available resources of the institution. This report details our initial experience of an AC service utilizing the expertise of a speech and language therapist (SLT) and an experienced neuro-physiotherapist (NP) to monitor patient function during glioma resection. Forty-five patients underwent 50 AC procedures for eloquently located gliomas over a 3-year period. Patients with a glioma involving speech or sensorimotor areas were assessed preoperatively by the SLT/NP respectively. The same therapist monitored the patient's neurological function intraoperatively and executed a rehabilitation program tailored to the needs of the patient in the postoperative period. Three patients underwent biopsy only, due to intraoperative seizures precluding intraoperative mapping (2 cases) or speech arrest on stimulation of a small recurrent tumor. The remaining 47 cases were suitable for repetitive neurological assessment "awake" during tumor debulking. One patient with a large sensorimotor tumor developed intraoperative hemiparesis due to outward brain herniation (which recovered postoperatively). Ten patients developed a new or worsened neurological deficit in the initial postoperative period (6 were detected intraoperatively), of which 5 eventually had resolution and returned to baseline function within 2 weeks. In our initial experience based anecdotally on a previous similar "non-awake" caseload, we have found AC with the input of the SLT/NP to be a key component in ensuring optimal functional outcomes for patients with gliomas in eloquently located areas.

Image analysis of neuropsychological test responses

NASA Astrophysics Data System (ADS)

Smith, Stephen L.; Hiller, Darren L.

1996-04-01

This paper reports recent advances in the development of an automated approach to neuropsychological testing. High performance image analysis algorithms have been developed as part of a convenient and non-invasive computer-based system to provide an objective assessment of patient responses to figure-copying tests. Tests of this type are important in determining the neurological function of patients following stroke through evaluation of their visuo-spatial performance. Many conventional neuropsychological tests suffer from the serious drawback that subjective judgement on the part of the tester is required in the measurement of the patient's response which leads to a qualitative neuropsychological assessment that can be both inconsistent and inaccurate. Results for this automated approach are presented for three clinical populations: patients suffering right hemisphere stroke are compared with adults with no known neurological disorder and a population comprising normal school children of 11 years is presented to demonstrate the sensitivity of the technique. As well as providing a more reliable and consistent diagnosis this technique is sufficiently sensitive to monitor a patient's progress over a period of time and will provide the neuropsychologist with a practical means of evaluating the effectiveness of therapy or medication administered as part of a rehabilitation program.

Adverse Influence of Pre-Stroke Dementia on Short-Term Functional Outcomes in Patients with Acute Ischemic Stroke: The Fukuoka Stroke Registry.

PubMed

Wakisaka, Yoshinobu; Matsuo, Ryu; Hata, Jun; Kuroda, Junya; Kitazono, Takanari; Kamouchi, Masahiro; Ago, Tetsuro

2017-01-01

Dementia and stroke are major causes of disability in the elderly. However, the association between pre-stroke dementia and functional outcome after stoke remains unresolved. We aimed to determine this association in patients with acute ischemic stroke. Among patients registered in the Fukuoka Stroke Registry from June 2007 to May 2015, 4,237 patients with ischemic stroke within 24 h of onset, who were functionally independent before the onset, were enrolled in this study. Pre-stroke dementia was defined as any type of dementia that was present prior to the index stroke. Primary and secondary study outcomes were poor functional outcome (modified Rankin Scale 3-6) at 3 months after the stroke onset and neurological deterioration (≥2-point increases on the National Institutes of Health Stroke Scale score during hospitalization), respectively. For propensity score (PS)-matched cohort study to control confounding variables for pre-stroke dementia, 318 pairs of patients with and without pre-stroke dementia were also selected on the basis of 1:1 matching. Multivariable logistic regression models and conditional logistic regression analysis were used to quantify associations between pre-stroke dementia and study outcomes. Of all 4,237 participants, 347 (8.2%) had pre-stroke dementia. The frequencies of neurological deterioration and poor functional outcome were significantly higher in patients with pre-stroke dementia than in those without pre-stroke dementia (neurological deterioration, 16.1 vs. 7.1%, p < 0.01; poor functional outcome, 63.7 vs. 27.1%, p < 0.01). Multivariable analysis showed that pre-stroke dementia was significantly associated with neurological deterioration (OR 1.67; 95% CI 1.14-2.41; p < 0.01) and poor functional outcome (OR 2.91; 95% CI 2.17-3.91; p < 0.01). In the PS-matched cohort study, the same trends were observed between the pre-stroke dementia and neurological deterioration (OR 2.60; 95% CI 1.17-5.78; p < 0.01) and between the dementia and poor functional outcome (OR 3.62; 95% CI 1.89-6.95; p < 0.01). Pre-stroke dementia was significantly associated with higher risks for poor functional outcome at 3 months after stroke onset as well as for neurological deterioration during hospitalization in patients with acute ischemic stroke. © 2016 S. Karger AG, Basel.

Radial extracorporeal shock wave therapy improves cerebral blood flow and neurological function in a rat model of cerebral ischemia.

PubMed

Kang, Nan; Zhang, Jing; Yu, Xiaotong; Ma, Yuewen

2017-01-01

We performed middle cerebral artery occlusion (MCAO) in rats to investigate the effect and some of the underlying mechanisms of radial extracorporeal shock wave therapy (rESWT) in cerebral ischemia rats. We measured neurological function and cerebral blood flow (CBF) using a full-field laser perfusion imager and brain infarct volume on days 3, 12, and 30. Immunofluorescence, western blot, and real-time polymerase chain reaction (PCR) techniques were used to detect the expression of vascular endothelial growth factor (VEGF), neuron-specific enolase (NSE), nestin, Wnt3a, and β-catenin in the ischemic hemisphere. The dose of rESWT used on the head revealed remarkable advantages over sham rESWT, as demonstrated by improved neurological function scores, increased CBF, and reduced brain infarct volume. Furthermore, applying rESWT to the head and limbs enhanced short-term neurological function. Our results confirmed that rESWT can induce VEGF expression over an extended period with a profound effect, which may be the primary reason for CBF recovery. High NSE and nestin expression levels suggest that rESWT enhanced the number of neurons and neural stem cells (NSCs). Wnt3a and β-catenin expression were up-regulated in the ischemic hemisphere, indicating that rESWT promoted NSC proliferation and differentiation via the Wnt/β-catenin pathway. Overall, our findings suggest that an appropriate rESWT dose delivered to the head of rats helps restore neurological function and CBF, and additional application of rESWT to the limbs is more effective than treating the head alone.

Remote Physical Activity Monitoring in Neurological Disease: A Systematic Review.

PubMed

Block, Valerie A J; Pitsch, Erica; Tahir, Peggy; Cree, Bruce A C; Allen, Diane D; Gelfand, Jeffrey M

2016-01-01

To perform a systematic review of studies using remote physical activity monitoring in neurological diseases, highlighting advances and determining gaps. Studies were systematically identified in PubMed/MEDLINE, CINAHL and SCOPUS from January 2004 to December 2014 that monitored physical activity for ≥24 hours in adults with neurological diseases. Studies that measured only involuntary motor activity (tremor, seizures), energy expenditure or sleep were excluded. Feasibility, findings, and protocols were examined. 137 studies met inclusion criteria in multiple sclerosis (MS) (61 studies); stroke (41); Parkinson's Disease (PD) (20); dementia (11); traumatic brain injury (2) and ataxia (1). Physical activity levels measured by remote monitoring are consistently low in people with MS, stroke and dementia, and patterns of physical activity are altered in PD. In MS, decreased ambulatory activity assessed via remote monitoring is associated with greater disability and lower quality of life. In stroke, remote measures of upper limb function and ambulation are associated with functional recovery following rehabilitation and goal-directed interventions. In PD, remote monitoring may help to predict falls. In dementia, remote physical activity measures correlate with disease severity and can detect wandering. These studies show that remote physical activity monitoring is feasible in neurological diseases, including in people with moderate to severe neurological disability. Remote monitoring can be a psychometrically sound and responsive way to assess physical activity in neurological disease. Further research is needed to ensure these tools provide meaningful information in the context of specific neurological disorders and patterns of neurological disability.

The Trail Making test: a study of its ability to predict falls in the acute neurological in-patient population.

PubMed

Mateen, Bilal Akhter; Bussas, Matthias; Doogan, Catherine; Waller, Denise; Saverino, Alessia; Király, Franz J; Playford, E Diane

2018-05-01

To determine whether tests of cognitive function and patient-reported outcome measures of motor function can be used to create a machine learning-based predictive tool for falls. Prospective cohort study. Tertiary neurological and neurosurgical center. In all, 337 in-patients receiving neurosurgical, neurological, or neurorehabilitation-based care. Binary (Y/N) for falling during the in-patient episode, the Trail Making Test (a measure of attention and executive function) and the Walk-12 (a patient-reported measure of physical function). The principal outcome was a fall during the in-patient stay ( n = 54). The Trail test was identified as the best predictor of falls. Moreover, addition of other variables, did not improve the prediction (Wilcoxon signed-rank P < 0.001). Classical linear statistical modeling methods were then compared with more recent machine learning based strategies, for example, random forests, neural networks, support vector machines. The random forest was the best modeling strategy when utilizing just the Trail Making Test data (Wilcoxon signed-rank P < 0.001) with 68% (± 7.7) sensitivity, and 90% (± 2.3) specificity. This study identifies a simple yet powerful machine learning (Random Forest) based predictive model for an in-patient neurological population, utilizing a single neuropsychological test of cognitive function, the Trail Making test.

Evidence for the absence of cerebral glucose-6-phosphatase activity in glycogen storage disease type I (Von Gierke's disease)

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

Phelps, M.E.; Mazziotta, J.C.; Hawkins, R.A.

1981-01-01

Glycogen storage disease type I (GSD-I) is characterized by a functional deficit in glucose-6-phosphatase that normally hydrolyzes glucose-6-PO/sub 4/ to glucose. This enzyme is primarily found in liver, kidney, and muscle but it is also present in brain, where it appears to participate in the regulation of cerebral tissue glucose. Since most neurological symptoms in GSD-I patients involve systemic hypoglycemia, previous reports have not examined possible deficiencies in phosphatase activity in the brain. Positron computed tomography, F-18-labeled 2-fluorodeoxyglucose (FDG) and a tracer kinetic model for FDG were used to measure the cortical plasma/tissue forward and reverse transport, phosphorylation and dephosphorylationmore » rate constants, tissue/plasma concentration gradient, tissue concentration turnover rate for this competitive analog of glucose, and the cortical metabolic rates for glucose. Studies were carried out in age-matched normals (N = 13) and a single GSD-I patient. The dephosphorylation rate constant in the GSD-I patient was about one tenth the normal value indicating a low level of cerebral phosphatase activity. The other measured parameters were within normal limits except for the rate of glucose phosphorylation which reflected a cortical glucose metabolic rate one half the normal value. Since glucose transport and tissue glucose concentration was normal, the reduced cortical glucose metabolism probably results from the use of alternative substrates (..beta..-hydroxybutyrate and acetoacetate) which are consistently elevated in the plasma of GSD-I patients.« less

Nitrite therapy after cardiac arrest reduces ROS generation, improves cardiac and neurological function and enhances survival via reversible inhibition of mitochondrial complex I

PubMed Central

Dezfulian, Cameron; Shiva, Sruti; Alekseyenko, Aleksey; Pendyal, Akshay; Beiser, DG; Munasinghe, Jeeva P.; Anderson, Stasia A.; Chesley, Christopher F.; Hoek, TL Vanden; Gladwin, Mark T.

2009-01-01

Background Three-fourths of cardiac arrest survivors die prior to hospital discharge or suffer significant neurological injury. Excepting therapeutic hypothermia and revascularization, no novel therapies have been developed that improve survival or cardiac and neurological function after resuscitation. Nitrite (NO2−) increases cellular resilience to focal ischemia-reperfusion injury in multiple organs. We hypothesized that nitrite therapy may improve outcomes after the unique global ischemia-reperfusion insult of cardiopulmonary arrest. Methods and Results We developed a mouse model of cardiac arrest characterized by 12-minutes of normothermic asystole and a high cardiopulmonary resuscitation (CPR) rate. In this model, global ischemia and CPR was associated with blood and organ nitrite depletion, reversible myocardial dysfunction, impaired alveolar gas exchange, neurological injury and an approximate 50% mortality. A single low dose of intravenous nitrite (50 nmol=1.85 μmol/kg=0.13 mg/kg) compared to blinded saline placebo given at CPR initiation with epinephrine improved cardiac function, survival and neurological outcomes. From a mechanistic standpoint, nitrite treatment restored intracardiac nitrite and increased S-nitrosothiol levels, decreased pathological cardiac mitochondrial oxygen consumption due to reactive oxygen species formation and prevented oxidative enzymatic injury via reversible specific inhibition of respiratory chain complex I. Conclusion Nitrite therapy after resuscitation from 12-minutes of asystole rapidly and reversibly modulated mitochondrial reactive oxygen species generation during early reperfusion, limiting acute cardiac dysfunction and death, as well as neurological impairment in survivors. PMID:19704094

Neural correlates of improvements in personality and behavior following a neurological event.

PubMed

King, Marcie L; Manzel, Kenneth; Bruss, Joel; Tranel, Daniel

2017-11-21

Research on changes in personality and behavior following brain damage has focused largely on negative outcomes, such as increased irritability, moodiness, and social inappropriateness. However, clinical observations suggest that some patients may actually show positive personality and behavioral changes following a neurological event. In the current work, we investigated neuroanatomical correlates of positive personality and behavioral changes following a discrete neurological event (e.g., stroke, benign tumor resection). Patients (N = 97) were rated by a well-known family member or friend on five domains of personality and behavior: social behavior, irascibility, hypo-emotionality, distress, and executive functioning. Ratings were acquired during the chronic epoch of recovery, when psychological status was stabilized. We identified patients who showed positive changes in personality and behavior in one or more domains of functioning. Lesion analyses indicated that positive changes in personality and behavior were most consistently related to damage to the bilateral frontal polar regions and the right anterior dorsolateral prefrontal region. These findings support the conclusion that improvements in personality and behavior can occur after a neurological event, and that such changes have systematic neuroanatomical correlates. Patients who showed positive changes in personality and behavior following a neurological event were rated as having more disturbed functioning prior to the event. Our study may be taken as preliminary evidence that improvements in personality and behavior following a neurological event may involve dampening of (premorbidly) more extreme expressions of emotion. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pediatric neurological syndromes and inborn errors of purine metabolism.

PubMed

Camici, Marcella; Micheli, Vanna; Ipata, Piero Luigi; Tozzi, Maria Grazia

2010-02-01

This review is devised to gather the presently known inborn errors of purine metabolism that manifest neurological pediatric syndromes. The aim is to draw a comprehensive picture of these rare diseases, characterized by unexpected and often devastating neurological symptoms. Although investigated for many years, most purine metabolism disorders associated to psychomotor dysfunctions still hide the molecular link between the metabolic derangement and the neurological manifestations. This basically indicates that many of the actual functions of nucleosides and nucleotides in the development and function of several organs, in particular central nervous system, are still unknown. Both superactivity and deficiency of phosphoribosylpyrophosphate synthetase cause hereditary disorders characterized, in most cases, by neurological impairments. The deficiency of adenylosuccinate lyase and 5-amino-4-imidazolecarboxamide ribotide transformylase/IMP cyclohydrolase, both belonging to the de novo purine synthesis pathway, is also associated to severe neurological manifestations. Among catabolic enzymes, hyperactivity of ectosolic 5'-nucleotidase, as well as deficiency of purine nucleoside phosphorylase and adenosine deaminase also lead to syndromes affecting the central nervous system. The most severe pathologies are associated to the deficiency of the salvage pathway enzymes hypoxanthine-guanine phosphoribosyltransferase and deoxyguanosine kinase: the former due to an unexplained adverse effect exerted on the development and/or differentiation of dopaminergic neurons, the latter due to a clear impairment of mitochondrial functions. The assessment of hypo- or hyperuricemic conditions is suggestive of purine enzyme dysfunctions, but most disorders of purine metabolism may escape the clinical investigation because they are not associated to these metabolic derangements. This review may represent a starting point stimulating both scientists and physicians involved in the study of neurological dysfunctions caused by inborn errors of purine metabolism with the aim to find novel therapeutical approaches. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Neurological development of children born to mothers after kidney transplantation.

PubMed

Schreiber-Zamora, Joanna; Szpotanska-Sikorska, Monika; Drozdowska-Szymczak, Agnieszka; Czaplinska, Natalia; Pietrzak, Bronisława; Wielgos, Miroslaw; Kociszewska-Najman, Bozena

2017-12-03

Pregnancies after kidney transplantation are at high risk of complications such as preterm birth and foetal growth restriction. Until now, the impact of these factors on neurological development of children born to transplant mothers has not been established. A comparison of neurological examinations performed in 36 children of kidney transplant women (study group) and 36 children born to healthy mothers (control group). The children from both groups were born at a similar gestational age and in the similar time period from 12/1996 to 09/2012. Neurological examinations were performed from 07/2010 to 11/2013. Each examination was adjusted to the patient's age and performed after the neonatal period. Three years later children were re-consulted, if they presented neurological deviations or were less than 12 months old at the time of the first examination. Normal neurological development was found in 86% of children in both groups (p = .999). Mild neurological deviations were observed in four (11%) children born to kidney transplant mothers and in five (14%) children born to healthy mothers (p = .999). Moderate deviations were diagnosed in one premature child born to transplant mother, whose pregnancy was complicated with a severe preeclampsia and foetal growth restriction. In the study population, no severe neurological disorders were found. Almost all (8/10) children with neurological deviations were born prematurely in good general conditions. The neurological deviations observed in the first year of life were mild and transient. In children over 1 year of age, deviations were more pronounced and continued to maintain. The neurological development of children of kidney transplant women is similar to that of the general population and possible deviations seem to be the result of intrauterine hypotrophy and prematurity. Therefore, in clinical practice, it is necessary to plan post-transplant pregnancies especially in women at high risk of these complications.

Gamma Knife radiosurgery for facial nerve schwannomas: a multicenter study.

PubMed

Sheehan, Jason P; Kano, Hideyuki; Xu, Zhiyuan; Chiang, Veronica; Mathieu, David; Chao, Samuel; Akpinar, Berkcan; Lee, John Y K; Yu, James B; Hess, Judith; Wu, Hsiu-Mei; Chung, Wen-Yuh; Pierce, John; Missios, Symeon; Kondziolka, Douglas; Alonso-Basanta, Michelle; Barnett, Gene H; Lunsford, L Dade

2015-08-01

Facial nerve schwannomas (FNSs) are rare intracranial tumors, and the optimal management of these tumors remains unclear. Resection can be undertaken, but the tumor's intimate association with the facial nerve makes resection with neurological preservation quite challenging. Stereotactic radiosurgery (SRS) has been used to treat FNSs, and this study evaluates the outcome of this approach. At 8 medical centers participating in the North American Gamma Knife Consortium (NAGKC), 42 patients undergoing SRS for an FNS were identified, and clinical and radiographic data were obtained for these cases. Males outnumbered females at a ratio of 1.2:1, and the patients' median age was 48 years (range 11-76 years). Prior resection was performed in 36% of cases. The mean tumor volume was 1.8 cm(3), and a mean margin dose of 12.5 Gy (range 11-15 Gy) was delivered to the tumor. At a median follow-up of 28 months, tumor control was achieved in 36 (90%) of the 40 patients with reliable radiographic follow-up. Actuarial tumor control was 97%, 97%, 97%, and 90% at 1, 2, 3, and 5 years postradiosurgery. Preoperative facial nerve function was preserved in 38 of 42 patients, with 60% of evaluable patients having House-Brackmann scores of 1 or 2 at last follow-up. Treated patients with a House-Brackmann score of 1 to 3 were more likely to demonstrate this level of facial nerve function at last evaluation (OR 6.09, 95% CI 1.7-22.0, p = 0.006). Avoidance of temporary or permanent neurological symptoms was more likely to be achieved in patients who received a tumor margin dose of 12.5 Gy or less (log-rank test, p = 0.024) delivered to a tumor of ≤ 1 cm(3) in volume (log-rank test, p = 0.01). Stereotactic radiosurgery resulted in tumor control and neurological preservation in most FNS patients. When the tumor is smaller and the patient exhibits favorable normal facial nerve function, SRS portends a better result. The authors believe that early, upfront SRS may be the treatment of choice for small FNSs, but it is an effective salvage treatment for residual/recurrent tumor that remain or progress after resection.

Human-robot cooperative movement training: learning a novel sensory motor transformation during walking with robotic assistance-as-needed.

PubMed

Emken, Jeremy L; Benitez, Raul; Reinkensmeyer, David J

2007-03-28

A prevailing paradigm of physical rehabilitation following neurologic injury is to "assist-as-needed" in completing desired movements. Several research groups are attempting to automate this principle with robotic movement training devices and patient cooperative algorithms that encourage voluntary participation. These attempts are currently not based on computational models of motor learning. Here we assume that motor recovery from a neurologic injury can be modelled as a process of learning a novel sensory motor transformation, which allows us to study a simplified experimental protocol amenable to mathematical description. Specifically, we use a robotic force field paradigm to impose a virtual impairment on the left leg of unimpaired subjects walking on a treadmill. We then derive an "assist-as-needed" robotic training algorithm to help subjects overcome the virtual impairment and walk normally. The problem is posed as an optimization of performance error and robotic assistance. The optimal robotic movement trainer becomes an error-based controller with a forgetting factor that bounds kinematic errors while systematically reducing its assistance when those errors are small. As humans have a natural range of movement variability, we introduce an error weighting function that causes the robotic trainer to disregard this variability. We experimentally validated the controller with ten unimpaired subjects by demonstrating how it helped the subjects learn the novel sensory motor transformation necessary to counteract the virtual impairment, while also preventing them from experiencing large kinematic errors. The addition of the error weighting function allowed the robot assistance to fade to zero even though the subjects' movements were variable. We also show that in order to assist-as-needed, the robot must relax its assistance at a rate faster than that of the learning human. The assist-as-needed algorithm proposed here can limit error during the learning of a dynamic motor task. The algorithm encourages learning by decreasing its assistance as a function of the ongoing progression of movement error. This type of algorithm is well suited for helping people learn dynamic tasks for which large kinematic errors are dangerous or discouraging, and thus may prove useful for robot-assisted movement training of walking or reaching following neurologic injury.

When the left brain is not right the right brain may be left: report of personal experience of occipital hemianopia

PubMed Central

Cole, M.

1999-01-01

OBJECTIVES—To make a personal report of a hemianopia due to an occipital infarct, sustained by a professor of neurology.
METHODS—Verbatim observation of neurological phenomena recorded during the acute illness.
RESULTS—Hemianopia, visual hallucinations, and non-occipital deficits without extraoccipital lesions on MRI, are described and discussed.
CONCLUSIONS—Hemianopia, due to an occipital infarct, without alexia, is not a disability which precludes a normal professional career. Neurorehabilitation has not been necessary.

 PMID:10406983

Pernicious anaemia presenting as catatonia without signs of anaemia or macrocytosis.

PubMed

Jauhar, Sameer; Blackett, Allison; Srireddy, Pavan; McKenna, Peter J

2010-09-01

Pernicious anaemia can present with psychiatric symptoms before haematological or neurological manifestations appear. We describe a young woman who presented with insidious onset catatonia without evidence of psychosis or depression. Blood count and mean cell volume were normal and neurological findings were equivocal. Low B(12) levels and intrinsic factor antibodies were found only by chance when they were included in a battery of further investigations. B(12) replacement was followed by prompt improvement. This case provides an argument for wider screening for B(12) deficiency in certain individuals with psychiatric disorders.

Chorea in a patient with cryopyrin-associated periodic syndrome.

PubMed

Schwarzbach, Christopher J; Schmitt, Wilhelm H; Szabo, Kristina; Bäzner, Hansjoerg; Hennerici, Michael G; Blahak, Christian

2016-01-19

To describe a patient with cryopyrin-associated periodic syndrome (CAPS) with an uncommon neurologic phenotype and a rare underlying genetic mutation. Our patient had CAPS with a rare NLPR3 missense mutation (p.Tyr859Cys) in exon 6 with chorea as the major symptom. Clinical symptoms were associated with persistent inflammatory changes of the CSF and serum and included elevated anticardiolipin immunoglobulin G; MRI showed prolonged gadolinium enhancement of 2 chronic inflammatory lesions. Conventional immunosuppressive treatment with prednisolone and hydroxychloroquine was insufficient. Neurologic symptoms, laboratory/chemical measures, and MRI abnormalities almost completely normalized following interleukin (IL)-1β blockade with anakinra. This case is unique for its uncommon neurologic phenotype, the rare underlying genetic mutation, and the long course of the disease as well as almost complete recovery following appropriate therapy. In addition, the chronic inflammatory white matter lesions observed on brain MRI and the responsiveness to IL-1β blockade with anakinra are unusual. © 2015 American Academy of Neurology.

Molecular genetics in fetal neurology.

PubMed

Huang, Jin; Wah, Isabella Y M; Pooh, Ritsuko K; Choy, Kwong Wai

2012-12-01

Brain malformations, particularly related to early brain development, are a clinically and genetically heterogeneous group of fetal neurological disorders. Fetal cerebral malformation, predominantly of impaired prosencephalic development namely agenesis of the corpus callosum and septo-optic dysplasia, is the main pathological feature in fetus, and causes prominent neurodevelopmental retardation, and associated with congenital facial anomalies and visual disorders. Differential diagnosis of brain malformations can be extremely difficult even through magnetic resonance imaging. Advances in genomic and molecular genetics technologies have led to the identification of the sonic hedgehog pathways and genes critical to the normal brain development. Molecular cytogenetic and genetic studies have identified numeric and structural chromosomal abnormalities as well as mutations in genes important for the etiology of fetal neurological disorders. In this review, we update the molecular genetics findings of three common fetal neurological abnormalities, holoprosencephaly, lissencephaly and agenesis of the corpus callosum, in an attempt to assist in perinatal and prenatal diagnosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Inpatient Assessment and Management of Motor Functional Neurological Disorders: An Interdisciplinary Perspective.

PubMed

McKee, Kathleen; Glass, Sean; Adams, Caitlin; Stephen, Christopher D; King, Franklin; Parlman, Kristin; Perez, David L; Kontos, Nicholas

2018-01-08

Motor functional neurologic disorders (FND)-previously termed "hysteria" and later "conversion disorder"-are exceedingly common and frequently encountered in the acute hospital setting. Despite their high prevalence, patients with motor FND can be challenging to diagnose accurately and manage effectively. To date, there is limited guidance on the inpatient approach to the neuropsychiatric evaluation of patients with functional (psychogenic) neurologic symptoms. The authors outline an inpatient multidisciplinary approach, involving neurology, psychiatry, and physical therapy, for the assessment and acute inpatient management of motor FND. A vignette of a patient with motor FND is presented followed by a discussion of general assessment principles. Thereafter, a detailed description of the neurologic and psychiatric assessments is outlined. Delivery of a "rule-in" diagnosis is emphasized and specific guidance for what can be accomplished postdiagnosis in the hospital is suggested. We encourage an interdisciplinary approach beginning at the early stages of the diagnostic assessment once an individual is suspected of having motor FND. Practical suggestions for the inpatient assessment of motor FND are presented. It is also important to individualize the diagnostic assessment. Future research should be conducted to test best practices for motor FND management in the acute inpatient hospital setting. Copyright © 2018 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.

Functional neurological symptom disorder (conversion disorder): A role for microglial-based plasticity mechanisms?

PubMed

Stephenson, Chris P; Baguley, Ian J

2018-02-01

Functional Neurological Symptom Disorder (FND) is a relatively common neurological condition, accounting for approximately 3-6% of neurologist referrals. FND is considered a transient disorder of neuronal function, sometimes linked to physical trauma and psychological stress. Despite this, chronic disability is common, for example, around 40% of adults with motor FND have permanent disability. Building on current theoretical models, this paper proposes that microglial dysfunction could perpetuate functional changes within acute motor FND, thus providing a pathophysiological mechanism underlying the chronic stage of the motor FND phenotypes seen clinically. Core to our argument is microglia's dual role in modulating neuroimmunity and their control of synaptic plasticity, which places them at a pathophysiological nexus wherein coincident physical trauma and psychological stress could cause long-term change in neuronal networks without producing macroscopic structural abnormality. This model proposes a range of hypotheses that are testable with current technologies. Copyright © 2017. Published by Elsevier Ltd.

Nystagmus using video-oculography in psychiatric patients.

PubMed

Kiyomizu, Kensuke; Matsuda, Keiji; Torihara, Koji; Nakayama, Meiho; Komaki, Shogo; Tono, Tetsuya; Ishida, Yasushi; Yoshida, Kensei; Kimitsuki, Takashi

2009-08-01

To evaluate whether nystagmus has clinical significance in psychiatric patients who have functional and/or organic brain dysfunction. We performed gaze, positional and positioning nystagmus tests on 227 patients with psychiatric diseases (144 men, 83 women, with an average age +/- SD of 62.5 +/- 14.0 years) in order to evaluate the frequency and characteristics of nystagmus. Patients were classified according to the underlying disease. Normal control subjects were 107 subjects (26 men, 81 women, with an average age +/- SD of 35.6 +/- 10.0 years). Nystagmus was observed in 56 (24.7%) of 227 cases. Nystagmus was seen in 16 (59.3%) of 27 cases of alcoholism, 14 (22.2%) of 63 cases of organic psychiatric disorders, 25 (20.2%) of 124 cases of schizophrenia, 1 (20.0%) of 5 cases of excited mental retardation, 0 (0.0%) of 7 cases of mood disorders, 0 (0.0%) of 1 case of anxiety disorders and 1 (0.9%) of 107 subjects of normal control. There was a significant difference between psychiatric diseases and normal control. These results indicate that nystagmus may also be a very important clinical finding not only in patients with neurological and neuro-otological diseases, but also in patients with psychiatric diseases.

The connection between acute otitis media and the acute abdomen.

PubMed

Masood, Imran; Hendriksz, Tami

2017-06-22

A female aged 9 years with a recent episode of acute otitis media (AOM) presented to her primary care physician with complaints of severe abdominal pain with right lower quadrant rebound tenderness, suggestive of an acute surgical abdomen. Neurological examination was normal on presentation. She was transferred to the local children's hospital for workup of appendicitis, during which she began exhibiting ataxia and slurred speech. Further evaluation revealed mastoiditis, venous sinus thrombosis and subdural empyema. Appendicitis was ruled out. We describe the first documented case of neurological complications of AOM presenting as an acute surgical abdomen without initial neurological findings. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Quasi-periodic patterns (QPP): large-scale dynamics in resting state fMRI that correlate with local infraslow electrical activity.

PubMed

Thompson, Garth John; Pan, Wen-Ju; Magnuson, Matthew Evan; Jaeger, Dieter; Keilholz, Shella Dawn

2014-01-01

Functional connectivity measurements from resting state blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) are proving a powerful tool to probe both normal brain function and neuropsychiatric disorders. However, the neural mechanisms that coordinate these large networks are poorly understood, particularly in the context of the growing interest in network dynamics. Recent work in anesthetized rats has shown that the spontaneous BOLD fluctuations are tightly linked to infraslow local field potentials (LFPs) that are seldom recorded but comparable in frequency to the slow BOLD fluctuations. These findings support the hypothesis that long-range coordination involves low frequency neural oscillations and establishes infraslow LFPs as an excellent candidate for probing the neural underpinnings of the BOLD spatiotemporal patterns observed in both rats and humans. To further examine the link between large-scale network dynamics and infraslow LFPs, simultaneous fMRI and microelectrode recording were performed in anesthetized rats. Using an optimized filter to isolate shared components of the signals, we found that time-lagged correlation between infraslow LFPs and BOLD is comparable in spatial extent and timing to a quasi-periodic pattern (QPP) found from BOLD alone, suggesting that fMRI-measured QPPs and the infraslow LFPs share a common mechanism. As fMRI allows spatial resolution and whole brain coverage not available with electroencephalography, QPPs can be used to better understand the role of infraslow oscillations in normal brain function and neurological or psychiatric disorders. © 2013.

Quasi-periodic patterns (QPP): large-scale dynamics in resting state fMRI that correlate with local infraslow electrical activity

PubMed Central

Thompson, Garth John; Pan, Wen-Ju; Magnuson, Matthew Evan; Jaeger, Dieter; Keilholz, Shella Dawn

2013-01-01

Functional connectivity measurements from resting state blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) are proving a powerful tool to probe both normal brain function and neuropsychiatric disorders. However, the neural mechanisms that coordinate these large networks are poorly understood, particularly in the context of the growing interest in network dynamics. Recent work in anesthetized rats has shown that the spontaneous BOLD fluctuations are tightly linked to infraslow local field potentials (LFPs) that are seldom recorded but comparable in frequency to the slow BOLD fluctuations. These findings support the hypothesis that long-range coordination involves low frequency neural oscillations and establishes infraslow LFPs as an excellent candidate for probing the neural underpinnings of the BOLD spatiotemporal patterns observed in both rats and humans. To further examine the link between large-scale network dynamics and infraslow LFPs, simultaneous fMRI and microelectrode recording were performed in anesthetized rats. Using an optimized filter to isolate shared components of the signals, we found that time-lagged correlation between infraslow LFPs and BOLD is comparable in spatial extent and timing to a quasi-periodic pattern (QPP) found from BOLD alone, suggesting that fMRI-measured QPPs and the infraslow LFPs share a common mechanism. As fMRI allows spatial resolution and whole brain coverage not available with electroencephalography, QPPs can be used to better understand the role of infraslow oscillations in normal brain function and neurological or psychiatric disorders. PMID:24071524

Plasticity of language-related brain function during recovery from stroke.

PubMed

Thulborn, K R; Carpenter, P A; Just, M A

1999-04-01

This study was undertaken to correlate functional recovery from aphasia after acute stroke with the temporal evolution of the anatomic, physiological, and functional changes as measured by MRI. Blood oxygenation level-dependent contrast and echo-planar MRI were used to map language comprehension in 6 normal adults and in 2 adult patients during recovery from acute stroke presenting with aphasia. Perfusion, diffusion, sodium, and conventional anatomic MRI were used to follow physiological and structural changes. The normal activation pattern for language comprehension showed activation predominately in left-sided Wernicke's and Broca's areas, with laterality ratios of 0.8 and 0.3, respectively. Recovery of the patient confirmed as having a completed stroke affecting Broca's area occurred rapidly with a shift of activation to the homologous region in the right hemisphere within 3 days, with continued rightward lateralization over 6 months. In the second patient, in whom mapping was performed fortuitously before stroke, recovery of a Wernicke's aphasia showed a similar increasing rightward shift in activation recruitment over 9 months after the event. Recovery of aphasia in adults can occur rapidly and is concomitant with an activation pattern that changes from left to a homologous right hemispheric pattern. Such recovery occurs even when the stroke evolves to completion. Such plasticity must be considered when evaluating stroke interventions based on behavioral and neurological measurements.

The potential role of melatonin on sleep deprivation-induced cognitive impairments: implication of FMRP on cognitive function.

PubMed

Kwon, K J; Lee, E J; Kim, M K; Jeon, S J; Choi, Y Y; Shin, C Y; Han, S-H

2015-08-20

While prolonged sleep deprivation (SD) could lead to profound negative health consequences, such as impairments in vital biological functions of immunity and cognition, melatonin possesses powerful ameliorating effects against those harmful insults. Melatonin has strong antioxidant and anti-inflammatory effects that help to restore body's immune and cognitive functions. In this study, we investigated the possible role of melatonin in reversing cognitive dysfunction induced by SD in rats. Our experimental results revealed that sleep-deprived animals exhibited spatial memory impairment in the Morris water maze tasks compared with the control groups. Furthermore, there was an increased glial activation most prominent in the hippocampal region of the SD group compared to the normal control (NC) group. Additionally, markers of oxidative stress such as 4-hydroxynonenal (4-HNE) and 7,8-dihydro-8-oxo-deoxyguanine (8-oxo-dG) were significantly increased, while fragile X-mental retardation protein (FMRP) expression was decreased in the SD group. Interestingly, melatonin treatment normalized these events to control levels following SD. Our data demonstrate that SD induces oxidative stress through glial activation and decreases FMRP expression in the neurons. Furthermore, our results suggest the efficacy of melatonin for the treatment of sleep-related neuronal dysfunction, which occurs in neurological disorders such as Alzheimer's disease and autism. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Illuminating Neural Circuits: From Molecules to MRI.

PubMed

Lee, Jin Hyung; Kreitzer, Anatol C; Singer, Annabelle C; Schiff, Nicholas D

2017-11-08

Neurological disease drives symptoms through pathological changes to circuit functions. Therefore, understanding circuit mechanisms that drive behavioral dysfunction is of critical importance for quantitative diagnosis and systematic treatment of neurological disease. Here, we describe key technologies that enable measurement and manipulation of neural activity and neural circuits. Applying these approaches led to the discovery of circuit mechanisms underlying pathological motor behavior, arousal regulation, and protein accumulation. Finally, we discuss how optogenetic functional magnetic resonance imaging reveals global scale circuit mechanisms, and how circuit manipulations could lead to new treatments of neurological diseases. Copyright © 2017 the authors 0270-6474/17/3710817-09$15.00/0.

Social Cognition Deficits: Current Position and Future Directions for Neuropsychological Interventions in Cerebrovascular Disease.

PubMed

Njomboro, Progress

2017-01-01

Neuropsychological assessments of cognitive dysfunction in cerebrovascular illness commonly target basic cognitive functions involving aspects of memory, attention, language, praxis, and number processing. Here, I highlight the clinical importance of often-neglected social cognition functions. These functions recruit a widely distributed neural network, making them vulnerable in most cerebrovascular diseases. Sociocognitive deficits underlie most of the problematic social conduct observed in patients and are associated with more negative clinical outcomes (compared to nonsocial cognitive deficits). In clinical settings, social cognition deficits are normally gleaned from collateral information from caregivers or from indirect inferences made from patients' performance on standard nonsocial cognitive tests. Information from these sources is however inadequate. I discuss key social cognition functions, focusing initially on deficits in emotion perception and theory of mind, two areas that have gained sizeable attention in neuroscientific research, and then extend the discussion into relatively new, less covered but crucial functions involving empathic behaviour, social awareness, social judgements, and social decision making. These functions are frequently impaired following neurological change. At present, a wide range of psychometrically robust social cognition tests is available, and this review also makes the case for their inclusion in neuropsychological assessments.

Social Cognition Deficits: Current Position and Future Directions for Neuropsychological Interventions in Cerebrovascular Disease

PubMed Central

2017-01-01

Neuropsychological assessments of cognitive dysfunction in cerebrovascular illness commonly target basic cognitive functions involving aspects of memory, attention, language, praxis, and number processing. Here, I highlight the clinical importance of often-neglected social cognition functions. These functions recruit a widely distributed neural network, making them vulnerable in most cerebrovascular diseases. Sociocognitive deficits underlie most of the problematic social conduct observed in patients and are associated with more negative clinical outcomes (compared to nonsocial cognitive deficits). In clinical settings, social cognition deficits are normally gleaned from collateral information from caregivers or from indirect inferences made from patients' performance on standard nonsocial cognitive tests. Information from these sources is however inadequate. I discuss key social cognition functions, focusing initially on deficits in emotion perception and theory of mind, two areas that have gained sizeable attention in neuroscientific research, and then extend the discussion into relatively new, less covered but crucial functions involving empathic behaviour, social awareness, social judgements, and social decision making. These functions are frequently impaired following neurological change. At present, a wide range of psychometrically robust social cognition tests is available, and this review also makes the case for their inclusion in neuropsychological assessments. PMID:28729755

Non-fluent aphasia and neural reorganization after speech therapy: insights from human sleep electrophysiology and functional magnetic resonance imaging.

PubMed

Sarasso, S; Santhanam, P; Määtta, S; Poryazova, R; Ferrarelli, F; Tononi, G; Small, S L

2010-09-01

Stroke is associated with long-term functional deficits. Behavioral interventions are often effective in promoting functional recovery and plastic changes. Recent studies in normal subjects have shown that sleep, and particularly slow wave activity (SWA), is tied to local brain plasticity and may be used as a sensitive marker of local cortical reorganization after stroke. In a pilot study, we assessed the local changes induced by a single exposure to a therapeutic session of IMITATE (Intensive Mouth Imitation and Talking for Aphasia Therapeutic Effects), a behavioral therapy used for recovery in patients with post-stroke aphasia. In addition, we measured brain activity changes with functional magnetic resonance imaging (fMRI) in a language observation task before, during and after the full IMITATE rehabilitative program. Speech production improved both after a single exposure and the full therapy program as measured by the Western Aphasia Battery (WAB) Repetition subscale. We found that IMITATE induced reorganization in functionally-connected, speech-relevant areas in the left hemisphere. These preliminary results suggest that sleep hd-EEGs, and the topographical analysis of SWA parameters, are well suited to investigate brain plastic changes underpinning functional recovery in neurological disorders.

[Clinical techniques for use in neurological physical examinations. II. Motor and reflex functions].

PubMed

Rodríguez-García, P L; Rodríguez-Pupo, L; Rodríguez-García, D

The aim of this study is to highlight the chief practical aspects of the techniques used in the neurological physical examination of the motor and reflex functions. We recommend clinicians to carry out a brief but consistent and effective exploration in a systematic, flexible and orderly manner to check for abnormalities in the motor and reflex functions of the nervous system. Should any anomalies be detected, then a more detailed and thorough neurological exploration must be performed selectively. We present a detailed review of the practical aspects of the main techniques used in the physical examination of these neurological categories. The motor function is explored using techniques that examine muscle tone, muscle strength, muscle fatigability, hypokinesia, tremor, coordination and gait. Lastly, in this category several manoeuvres that are useful in hysterical or mimicking paralyses are also dealt with. Reflexes to examination are usually divided into: 1. Myotatic reflexes; 2. Cutaneomucous reflexes; 3. Spinal cord or defence automatism reflexes; 4. Posture and attitude reflexes. We also add the study of primitive pathological reflexes, remote reflexes, synkinesias and signs of meningeal irritation. We present a detailed description of the main clinical techniques used in the neurological physical examination of motility and reflexes, as well as an approach that allows them to be performed on adult patients. In addition, we underline the importance of physically examining the nervous system in contemporary medicine and the need to continually perfect the way these techniques are performed in order to achieve an efficient clinical practice.

75 FR 22596 - Proposed Collection; Comment Request; NIH Toolbox for Assessment of Neurological and Behavioral...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-29

... methods and measures of four domains of neurological and behavioral functioning (cognitive, emotional... Neuroscience, National Institute on Aging, NIH, DHHS, 7201 Wisconsin Avenue, Suite 350, Bethesda, Maryland...

Noopept reduces the postischemic functional and metabolic disorders in the brain of rats with different sensitivity to hypoxia.

PubMed

Zarubina, I V; Shabanov, P D

2009-03-01

Chronic cerebral ischemia was induced by ligation of both common carotid arteries in Wistar rats, divided by sensitivity to hypoxia into highly sensitive and low-sensitive. Noopept (peptide preparation), injected (0.5 mg/kg) during 7 days after occlusion of the carotid arteries, reduced the neurological disorders in rats with high and low sensitivity to hypoxia and improved their survival during the postischemic period. Noopept normalized behavior disordered by cerebral ischemia (according to the open field and elevated plus maze tests), prevented accumulation of LPO products and inhibition of antioxidant systems in the brain of rats with high and low sensitivity to hypoxia. Hence, noopept exhibited a neuroprotective effect in cerebral ischemia.

[Catastrophic antiphospholipid syndrome in the immediate puerperium].

PubMed

Ortiz, P; Castro, A; Vallés, M; Coll, E; Casas, M; Mauri, J M

2003-01-01

We describe a female previously diagnosed of primary antiphospholipid antibody syndrome who presented a preclampsia in the second pregnancy. An urgent caesaria was made because of a worsening high blood pressure and oliguria. In the immediated puerperium she showed low platelets and persistent high blood pressure. Afterwards acute renal failure and neurological signs with a severe aortic valvulopathy were diagnosed. An haemolytic anemia was also detected. Definitive diagnosis was made by kidney biopsy with the result of a thrombotic microangiopathy. Treatment with low weight heparin and aspirin and systemic corticosteroids was started in the immediate puerperium and fresh frozen plasma was then added with a good response to treatment. Actually she is still with high blood pressure, aortic valvulopathy. Renal function is normal one year later.

Computed tomographic diagnosis of unilateral cavernous sinus syndrome caused by a chondrosarcoma in a dog: a case report.

PubMed

Hernández-Guerra, Angel María; Del Mar López-Murcia, María; Planells, Alicia; Corpa, Juan Manuel; Liste, Fernando

2007-07-01

An eight-year old Rottweiler dog was presented with signs of enophthalmia, ptosis, anisocoria and mydriasis of the right eye, which showed visual disturbance, reduced or absent reflexes, and ophthalmoplegia. Consensual pupillary light reflex was also absent in the left eye. These neurological deficits were compatible with cavernous sinus syndrome. Computed tomography images of the cavernous sinus and the optical fissure revealed a mildly calcified mass arising from the right presphenoid bone extending further caudally into the orbital foramina. This extension of the mass affected the normal function of several cranial nerves. The dog was euthanased within one year of the initial presentation following development of forebrain signs. A chondrosarcoma was diagnosed histologically after necropsy.

Persistence of neurological damage induced by dietary vitamin B-12 deficiency in infancy

PubMed Central

von Schenck, U.; Bender-Gotze, C.; Koletzko, B.

1997-01-01

Accepted 9 April 1997
 A case is reported of a 14 month old boy with severe dietary vitamin B-12 deficiency caused by his mother's vegan diet. Cinical, electroencephalography (EEG), and haematological findings are described. Cranial magnetic resonance imaging (MRI) showed severe frontal and frontoparietal cranial atrophy. Vitamin B-12 supplements led to a rapid improvement of haematological and neurological symptoms. Serum vitamin B-12 and urinary methylmalonate excretion were normal 10 days after treatment began. After six weeks, EEG was normal and cranial MRI after 10 weeks showed complete disappearance of all structural abnormalities. Cognitive and language development, however, remained seriously retarded at the age of 2 years. It is concluded that infantile vitamin B-12 deficiency induced by maternal vegan diets may cause lasting neurodisability even though vitamin B-12 supplementation leads to rapid resolution of cerebral atrophy and electroencephalographic abnormality.

 PMID:9301352

Girl with signs of Pelizaeus-Merzbacher disease heterozygous for a mutation in exon 2 of the proteolipid protein gene

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

Hodes, M.E.; DeMyer, W.E.; Pratt, V.M.

1995-02-13

We studied a female infant with clinical signs of Pelizaeus-Merzbacher disease (PMD), who has a familial mutation (C{sup 41}{r_arrow}T) in exon 2 of the proteolipid protein gene (PLP), and selected relatives. While the carrier mother and grandmother of the proposita currently are neurologically normal and show normal T2 magnetic resonance imaging (MRI) of the brain, the infant has a neurological picture, MRIs, and brain auditory evoked response (BAER) consistent with that diagnosis. The data here presented show that PMD can occur in females carrying a mutation in the PLP gene. Our experience with the MRIs of this patient, her mothermore » and grandmother, and those of a previously reported family show that molecular genetic analysis and not MRI is the appropriate means for carrier detection. 22 refs., 5 figs.« less

Neurophysiological model of the normal and abnormal human pupil

NASA Technical Reports Server (NTRS)

Krenz, W.; Robin, M.; Barez, S.; Stark, L.

1985-01-01

Anatomical, experimental, and computer simulation studies were used to determine the structure of the neurophysiological model of the pupil size control system. The computer simulation of this model demonstrates the role played by each of the elements in the neurological pathways influencing the size of the pupil. Simulations of the effect of drugs and common abnormalities in the system help to illustrate the workings of the pathways and processes involved. The simulation program allows the user to select pupil condition (normal or an abnormality), specific site along the neurological pathway (retina, hypothalamus, etc.) drug class input (barbiturate, narcotic, etc.), stimulus/response mode, display mode, stimulus type and input waveform, stimulus or background intensity and frequency, the input and output conditions, and the response at the neuroanatomical site. The model can be used as a teaching aid or as a tool for testing hypotheses regarding the system.

The cerebral hemodynamics of normotensive hypovolemia during lower-body negative pressure

NASA Technical Reports Server (NTRS)

Giller, C. A.; Levine, B. D.; Meyer, Y.; Buckey, J. C.; Lane, L. D.; Borchers, D. J.

1992-01-01

Although severe hypovolemia can lead to hypotension and neurological decline, many patients with neurosurgical disorders experience a significant hypovolemia while autonomic compensatory mechanisms maintain a normal blood pressure. To assess the effects of normotensive hypovolemia upon cerebral hemodynamics, transcranial Doppler ultrasound monitoring of 13 healthy volunteers was performed during graded lower-body negative pressure of up to -50 mm Hg, an accepted laboratory model for reproducing the physiological effects of hypovolemia. Middle cerebral artery flow velocity declined by 16% +/- 4% (mean +/- standard error of the mean) and the ratio between transcranial Doppler ultrasound pulsatility and systemic pulsatility rose 22% +/- 8%, suggesting cerebral small-vessel vasoconstriction in response to the sympathetic activation unmasked by lower-body negative pressure. This vasoconstriction may interfere with the autoregulatory response to a sudden fall in blood pressure, and may explain the common observation of neurological deficit during hypovolemia even with a normal blood pressure.

Osthole attenuates spinal cord ischemia-reperfusion injury through mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction in rats.

PubMed

Zhou, Yue-fei; Li, Liang; Feng, Feng; Yuan, Hua; Gao, Da-kuan; Fu, Luo-an; Fei, Zhou

2013-12-01

Osthole, the main bioactive compounds isolated from the traditional Chinese medical herb broad Cnidium monnieri (L.) cusson, has been shown to exert spectrum of pharmacologic activities. The aim of this study was to investigate the potential neuroprotective effects of osthole against spinal cord ischemia-reperfusion injury in rats. Osthole was administrated at the concentration of 0.1, 1, 10, 50, or 200 mg/kg (intraperitoneally) 1 h before spinal cord ischemia. The effects on spinal cord injury were measured by spinal cord water content, infarct volume, hematoxylin and eosin staining, and neurologic assessment. Mitochondria were purified from injured spinal cord tissue to determine mitochondrial function. We found that treatment with osthole (10 and 50 mg/kg) significantly decreased spinal cord water content and infarct volume, preserved normal motor neurons, and improved neurologic functions. These protective effects can be also observed even if the treatment was delayed to 4 h after reperfusion. Osthole treatment preserved mitochondrial membrane potential level, reduced reactive oxygen species production, increased adenosine triphosphate generation, and inhibited cytochrome c release in mitochondrial samples. Moreover, osthole increased mitochondria respiratory chain complex activities in spinal cord tissue, with no effect on mitochondrial DNA content and the expression of mitochondrial-specific transcription factors. All these findings demonstrate the neuroprotective effect of osthole in spinal cord ischemia-reperfusion injury model and suggest that oshtole-induced neuroprotection was mediated by mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

NIRS in clinical neurology - a 'promising' tool?

PubMed

Obrig, Hellmuth

2014-01-15

Near-infrared spectroscopy (NIRS) has become a relevant research tool in neuroscience. In special populations such as infants and for special tasks such as walking, NIRS has asserted itself as a low resolution functional imaging technique which profits from its ease of application, portability and the option to co-register other neurophysiological and behavioral data in a 'near natural' environment. For clinical use in neurology this translates into the option to provide a bed-side oximeter for the brain, broadly available at comparatively low costs. However, while some potential for routine brain monitoring during cardiac and vascular surgery and in neonatology has been established, NIRS is largely unknown to clinical neurologists. The article discusses some of the reasons for this lack of use in clinical neurology. Research using NIRS in three major neurologic diseases (cerebrovascular disease, epilepsy and headache) is reviewed. Additionally the potential to exploit the established position of NIRS as a functional imaging tool with regard to clinical questions such as preoperative functional assessment and neurorehabilitation is discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Is the Charcot and Bernard case (1883) of loss of visual imagery really based on neurological impairment?

PubMed

Zago, Stefano; Allegri, Nicola; Cristoffanini, Marta; Ferrucci, Roberta; Porta, Mauro; Priori, Alberto

2011-11-01

INTRODUCTION. The Charcot and Bernard case of visual imagery, Monsieur X, is a classic case in the history of neuropsychology. Published in 1883, it has been considered the first case of visual imagery loss due to brain injury. Also in recent times a neurological valence has been given to it. However, the presence of analogous cases of loss of visual imagery in the psychiatric field have led us to hypothesise functional origins rather than organic. METHODS. In order to assess the validity of such an inference, we have compared the symptomatology of Monsieur X with that found in cases of loss of visual mental images, both psychiatric and neurological, presented in literature. RESULTS. The clinical findings show strong assonances of the Monsieur X case with the symptoms manifested over time by the patients with functionally based loss of visual imagery. CONCLUSION. Although Monsieur X's damage was initially interpreted as neurological, reports of similar symptoms in the psychiatric field lead us to postulate a functional cause for his impairment as well.

A study in persons later after stroke of the relationships between social participation, environmental factors and depression.

PubMed

Zhang, Lifang; Sui, Minghong; Yan, Tiebin; You, Liming; Li, Kun; Gao, Yan

2017-03-01

To explore the impacts of social participation and the environment on depression among people with stroke. Cross-sectional survey. Structured interviews in the participants' homes. Community-dwelling persons with stroke in the rural areas of China ( N = 639). Not applicable. Depression (Hamilton Rating Scale for Depression-6), activity and social participation (Chinese version of the World Health Organization's Disability Assessment Schedule 2.0), environmental barriers (Craig Hospital Inventory of Environmental Factors), neurological function (Canadian Neurological Scale). A total of 42% of the variance in depression was explained by the environmental barriers, neurological function, activity, and social participation factors studied. Social participation, services/assistance, and attitudes/support were directly related to depression; their standardized regression coefficients were 0.530, 0.162, and 0.092, respectively ( p ⩽ 0.01). The physical environment, policies, and neurological function indirectly impacted depression. Depression influences social participation in turn, with a standardized regression coefficient of 0.29 ( p ⩽ 0.01). Depression and social participation are inversely related. The physical environment, services/assistance, attitudes/support, and policies all impact post-stroke depression.

Interruption of spinal cord microglial signaling by alpha-2 agonist dexmedetomidine in a murine model of delayed paraplegia.

PubMed

Bell, Marshall T; Agoston, Viktor A; Freeman, Kirsten A; Puskas, Ferenc; Herson, Paco S; Mares, Joshua; Fullerton, David A; Reece, T Brett

2014-04-01

Despite investigation into preventable pharmacologic adjuncts, paraplegia continues to complicate thoracoabdominal aortic interventions. The alpha 2a adrenergic receptor agonist, dexmedetomidine, has been shown to preserve neurologic function and neuronal viability in a murine model of spinal cord ischemia reperfusion, although the mechanism remains elusive. We hypothesize that dexmedetomidine will blunt postischemic inflammation in vivo following thoracic aortic occlusion with in vitro demonstration of microglial inhibition following lipopolysaccharide (LPS) stimulation. Adult male C57BL/6 mice underwent 4 minutes of aortic occlusion. Mice received 25 μg/kg intraperitoneal dexmedetomidine (n = 8) or 0.9% normal saline (n = 7) at reperfusion and 12-hour intervals postoperatively until 48 hours. Additionally, sham mice (n = 3), which had aortic arch exposed with no occlusion, were included for comparison. Functional scoring was done at 6 hours following surgery and 12-hour intervals until 60 hours when spinal cords were removed and examined for neuronal viability and cytokine production. Additional analysis of microglia activation was done in 12 hours following surgery. Age- and sex-matched mice had spinal cord removed for microglial isolation culture. Cells were grown to confluence and stimulated with toll-like receptor-4 agonist LPS 100 ng/mL in presence of dexmedetomidine or vehicle control for 24 hours. Microglia and media were then removed for analysis of protein expression. Dexmedetomidine treatment at reperfusion significantly preserved neurologic function with mice in treatment group having a Basso Score of 6.3 in comparison to 2.3 in ischemic control group. Treatment was associated with a significant reduction in microglia activation and in interleukin-6 production. Microglial cells in isolation when stimulated with LPS had an increased production of proinflammatory cytokines and markers of activation. Treatment with dexmedetomidine significantly attenuated microglial activation and proinflammatory cytokine production in vitro with a greater than twofold reduction in tumor necrosis factor-α. Alpha 2a agonist, dexmedetomidine treatment at reperfusion preserved neurologic function and neuronal viability. Furthermore, dexmedetomidine treatment resulted in an attenuation of microglial activation and proinflammatory cytokine production both in vivo and in vitro following LPS stimulation. This finding lends insight into the mechanism of paralysis following thoracic aortic interventions and may guide future pharmacologic targets for attenuating spinal cord ischemia and reperfusion. Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Stressful life events and maltreatment in conversion (functional neurological) disorder: systematic review and meta-analysis of case-control studies.

PubMed

Ludwig, Lea; Pasman, Joëlle A; Nicholson, Timothy; Aybek, Selma; David, Anthony S; Tuck, Sharon; Kanaan, Richard A; Roelofs, Karin; Carson, Alan; Stone, Jon

2018-04-01

Stressful life events and maltreatment have traditionally been considered crucial in the development of conversion (functional neurological) disorder, but the evidence underpinning this association is not clear. We aimed to assess the association between stressors and functional neurological disorder. We systematically reviewed controlled studies reporting stressors occurring in childhood or adulthood, such as stressful life events and maltreatment (including sexual, physical abuse, and emotional neglect) and functional neurological disorder. We did a meta-analysis, with assessments of methodology, sources of bias, and sensitivity analyses. 34 case-control studies, with 1405 patients, were eligible. Studies were of moderate-to-low quality. The frequency of childhood and adulthood stressors was increased in cases compared with controls. Odds ratios (OR) were higher for emotional neglect in childhood (49% for cases vs 20% for controls; OR 5·6, 95% CI 2·4-13·1) compared with sexual abuse (24% vs 10%; 3·3, 2·2-4·8) or physical abuse (30% vs 12%; 3·9, 2·2-7·2). An association with stressful life events preceding onset (OR 2·8, 95% CI 1·4-6·0) was stronger in studies with better methods (interviews; 4·3, 1·4-13·2). Heterogeneity was significant between studies (I 2 21·1-90·7%). 13 studies that specifically ascertained that the participants had not had either severe life events or any subtype of maltreatment all found a proportion of patients with functional neurological disorder reporting no stressor. Stressful life events and maltreatment are substantially more common in people with functional neurological disorder than in healthy controls and patient controls. Emotional neglect had a higher risk than traditionally emphasised sexual and physical abuse, but many cases report no stressors. This outcome supports changes to diagnostic criteria in DSM-5; stressors, although relevant to the cause in many patients, are not a core diagnostic feature. This result has implications for ICD-11. None. Copyright © 2018 Elsevier Ltd. All rights reserved.

RAX and anophthalmia in humans: Evidence of brain anomalies

PubMed Central

Youssef, Mohamed A.; Bayoumi, Nader; ElShakankiri, Nihal; Marzouk, Iman; Hauser, Philippe; Schorderet, Daniel F.

2012-01-01

Purpose To report the clinical and genetic study of two families of Egyptian origin with clinical anophthalmia. To further determine the role of the retina and anterior neural fold homeobox gene (RAX) in anophthalmia and associated cerebral malformations. Methods Three patients with clinical anophthalmia and first-degree relatives from two consanguineous families of Egyptian origin underwent full ophthalmologic, general and neurologic examination, and blood tests. Cerebral magnetic resonance imaging (MRI) was performed in the index cases of both families. Genomic DNA was prepared from venous leukocytes, and direct sequencing of all the exons and intron-exon junctions of RAX was performed after PCR amplification. Results Clinical bilateral anophthalmia was observed in all three patients. General and neurologic examinations were normal; obesity and delay in psychomotor development were observed in the isolated case. Orbital MRI showed a hypoplastic orbit with present but rudimentary extraocular muscles and normal lacrimal glands. Cerebral MRI showed agenesis of the optic nerves, optic tracts, and optic chiasma. In the index case of family A, the absence of the frontal and sphenoidal sinuses was also noted. In the index case of family B, only the sphenoidal sinus was absent, and there was significant cortical atrophy. The three patients carried a novel homozygous c.543+3A>G mutation (IVS2+3A>G) in RAX. Parents were healthy heterozygous carriers. No mutations were detected in orthodenticle homeobox 2 (OTX2), ventral anterior homeobox 1 (VAX1), or sex determining region Y-box 2 (SOX2). Conclusions This is the first report of a homozygous splicing RAX mutation associated with autosomal recessive bilateral anophthalmia. To our knowledge, only two isolated cases of anophthalmia, three null and one missense case affecting nuclear localization or the DNA-binding homeodomain, have been found to be caused by compound heterozygote RAX mutations. A novel missense RAX mutation was identified in three patients with bilateral anophthalmia and a distinct systemic and neurologic phenotype. The mutation potentially affects splicing of the last exon and is thought to result in a protein that has an aberrant homeodomain and no paired-tail domain. Functional consequences of this change still need to be characterized. PMID:22736936

RAX and anophthalmia in humans: evidence of brain anomalies.

PubMed

Abouzeid, Hana; Youssef, Mohamed A; Bayoumi, Nader; ElShakankiri, Nihal; Marzouk, Iman; Hauser, Philippe; Schorderet, Daniel F

2012-01-01

To report the clinical and genetic study of two families of Egyptian origin with clinical anophthalmia. To further determine the role of the retina and anterior neural fold homeobox gene (RAX) in anophthalmia and associated cerebral malformations. Three patients with clinical anophthalmia and first-degree relatives from two consanguineous families of Egyptian origin underwent full ophthalmologic, general and neurologic examination, and blood tests. Cerebral magnetic resonance imaging (MRI) was performed in the index cases of both families. Genomic DNA was prepared from venous leukocytes, and direct sequencing of all the exons and intron-exon junctions of RAX was performed after PCR amplification. Clinical bilateral anophthalmia was observed in all three patients. General and neurologic examinations were normal; obesity and delay in psychomotor development were observed in the isolated case. Orbital MRI showed a hypoplastic orbit with present but rudimentary extraocular muscles and normal lacrimal glands. Cerebral MRI showed agenesis of the optic nerves, optic tracts, and optic chiasma. In the index case of family A, the absence of the frontal and sphenoidal sinuses was also noted. In the index case of family B, only the sphenoidal sinus was absent, and there was significant cortical atrophy. The three patients carried a novel homozygous c.543+3A>G mutation (IVS2+3A>G) in RAX. Parents were healthy heterozygous carriers. No mutations were detected in orthodenticle homeobox 2 (OTX2), ventral anterior homeobox 1 (VAX1), or sex determining region Y-box 2 (SOX2). This is the first report of a homozygous splicing RAX mutation associated with autosomal recessive bilateral anophthalmia. To our knowledge, only two isolated cases of anophthalmia, three null and one missense case affecting nuclear localization or the DNA-binding homeodomain, have been found to be caused by compound heterozygote RAX mutations. A novel missense RAX mutation was identified in three patients with bilateral anophthalmia and a distinct systemic and neurologic phenotype. The mutation potentially affects splicing of the last exon and is thought to result in a protein that has an aberrant homeodomain and no paired-tail domain. Functional consequences of this change still need to be characterized.

Functional abnormalities in normally appearing athletes following mild traumatic brain injury: a functional MRI study

PubMed Central

Slobounov, Semyon M.; Zhang, K.; Pennell, D.; Ray, W.; Johnson, B.; Sebastianelli, W.

2010-01-01

Memory problems are one of the most common symptoms of sport-related mild traumatic brain injury (MTBI), known as concussion. Surprisingly, little research has examined spatial memory in concussed athletes given its importance in athletic environments. Here, we combine functional magnetic resonance imaging (fMRI) with a virtual reality (VR) paradigm designed to investigate the possibility of residual functional deficits in recently concussed but asymptomatic individuals. Specifically, we report performance of spatial memory navigation tasks in a VR environment and fMRI data in 15 athletes suffering from MTBI and 15 neurologically normal, athletically active age matched controls. No differences in performance were observed between these two groups of subjects in terms of success rate (94 and 92%) and time to complete the spatial memory navigation tasks (mean = 19.5 and 19.7 s). Whole brain analysis revealed that similar brain activation patterns were observed during both encoding and retrieval among the groups. However, concussed athletes showed larger cortical networks with additional increases in activity outside of the shared region of interest (ROI) during encoding. Quantitative analysis of blood oxygen level dependent (BOLD) signal revealed that concussed individuals had a significantly larger cluster size during encoding at parietal cortex, right dorsolateral prefrontal cortex, and right hippocampus. In addition, there was a significantly larger BOLD signal percent change at the right hippocampus. Neither cluster size nor BOLD signal percent change at shared ROIs was different between groups during retrieval. These major findings are discussed with respect to current hypotheses regarding the neural mechanism responsible for alteration of brain functions in a clinical setting. PMID:20039023

Blood-Brain Barrier Function and Biomarkers of Central Nervous System Injury in Rickettsial Versus Other Neurological Infections in Laos.

PubMed

Dittrich, Sabine; Sunyakumthorn, Piyanate; Rattanavong, Sayaphet; Phetsouvanh, Rattanaphone; Panyanivong, Phonepasith; Sengduangphachanh, Amphonsavanh; Phouminh, Phonelavanh; Anantatat, Tippawan; Chanthongthip, Anisone; Lee, Sue J; Dubot-Pérès, Audrey; Day, Nicholas P J; Paris, Daniel H; Newton, Paul N; Turner, Gareth D H

2015-08-01

Blood-brain barrier (BBB) function and cerebrospinal fluid (CSF) biomarkers were measured in patients admitted to hospital with severe neurological infections in the Lao People's Democratic Republic (N = 66), including bacterial meningitis (BM; N = 9) or tuberculosis meningitis (TBM; N = 11), Japanese encephalitis virus (JEV; N = 25), and rickettsial infections (N = 21) including murine and scrub typhus patients. The albumin index (AI) and glial fibrillary acidic protein (GFAP) levels were significantly higher in BM and TBM than other diseases but were also raised in individual rickettsial patients. Total tau protein was significantly raised in the CSF of JEV patients. No differences were found between clinical or neurological symptoms, AI, or biomarker levels that allowed distinction between severe neurological involvement by Orientia tsutsugamushi compared with Rickettsia species. © The American Society of Tropical Medicine and Hygiene.

[Awake craniotomy for brain tumours].

PubMed

Milos, Peter; Metcalf, Kerstin; Vigren, Patrick; Lindehammar, Hans; Nilsson, Malin; Boström, Sverre

2016-10-11

Awake craniotomy for brain tumours  Awake neurosurgery is a useful method in lesions near eloquent brain areas, particularly low-grade gliomas.The aim is to maximise tumour resection and preserve neurological function. We performed 40 primary awake surgeries and 8 residual surgeries. Patients were operated awake throughout the procedure or with a laryngeal mask and general anaesthesia during the opening stage and then awake during intracerebral surgery. Language and motor function were mapped with direct cortical stimulation, motor evoked potential and standardised neurological testing. Radiologically, complete resection was achieved in 18 out of 40 patients in the primary surgeries. Full neurological recovery at three months was observed in 29 patients. Of the 11 patients with persisting neurological deficits at three months, symptoms were present preoperatively in 9 patients. We conclude that awake surgery, combined with intraoperative neurophysiological methods, is a safe method to improve treatment for low-grade gliomas.

Neuropsychiatry. An old discipline in a new gestalt bridging biological psychiatry, neuropsychology, and cognitive neurology.

PubMed

Northoff, Georg

2008-06-01

The recent developments of psychiatry getting better insight into the biological basis of psychiatric disorders questions the old division between psychiatry and neurology. The present paper focus on the concept of neuropsychiatry, its historical antecedents and closely associated disciplines like biological psychiatry, behavioral neurology and neuropsychology. A special emphasis is put on the question of function and localization; the suggestions are made that the concept of neuronal integration may bridge the often discussed gap between localization and holism in the relation between function and brain regions. Examples of different mechanisms of neuronal integration are discussed and applied to specific neuropsychiatric disorders. It is concluded that the concept of neuronal integration may offer an appropriate conceptual tool to establish the concept of neuropsychiatry in a new and meaningful gestalt at the interface between biological psychiatry, neuropsychology and cognitive neurology.

Mitochondria in neuroplasticity and neurological disorders.

PubMed

Mattson, Mark P; Gleichmann, Marc; Cheng, Aiwu

2008-12-10

Mitochondrial electron transport generates the ATP that is essential for the excitability and survival of neurons, and the protein phosphorylation reactions that mediate synaptic signaling and related long-term changes in neuronal structure and function. Mitochondria are highly dynamic organelles that divide, fuse, and move purposefully within axons and dendrites. Major functions of mitochondria in neurons include the regulation of Ca(2+) and redox signaling, developmental and synaptic plasticity, and the arbitration of cell survival and death. The importance of mitochondria in neurons is evident in the neurological phenotypes in rare diseases caused by mutations in mitochondrial genes. Mitochondria-mediated oxidative stress, perturbed Ca(2+) homeostasis, and apoptosis may also contribute to the pathogenesis of prominent neurological diseases including Alzheimer's, Parkinson's, and Huntington's diseases; stroke; amyotrophic lateral sclerosis; and psychiatric disorders. Advances in understanding the molecular and cell biology of mitochondria are leading to novel approaches for the prevention and treatment of neurological disorders.

Neurologic examination and instrument-based measurements in the evaluation of ulnar neuropathy at the elbow.

PubMed

Omejec, Gregor; Podnar, Simon

2018-06-01

The aim of the study was to compare the utility of instrument-based assessment of peripheral nerve function with the neurologic examination in ulnar neuropathy at the elbow (UNE). We prospectively recruited consecutive patients with suspected UNE, performed a neurologic examination, and performed instrument-based measurements (muscle cross-sectional area by ultrasonography, muscle strength by dynamometry, and sensation using monofilaments). We found good correlations between clinical estimates and corresponding instrument-based measurements, with similar ability to diagnose UNE and predict UNE pathophysiology. Although instrument-based methods provide quantitative evaluation of peripheral nerve function, we did not find them to be more sensitive or specific in the diagnosis of UNE than the standard neurologic examination. Likewise, instrument-based methods were not better able to differentiate between groups of UNE patients with different pathophysiologies. Muscle Nerve 57: 951-957, 2018. © 2017 Wiley Periodicals, Inc.

Sustained attention in school-age children with congenital hypothyroidism: Influence of episodes of overtreatment in the first three years of life.

PubMed

García Morales, L; Rodríguez Arnao, M D; Rodríguez Sánchez, A; Dulín Íñiguez, E; Álvarez González, M A

2017-11-20

Children with congenital hypothyroidism (CH) are at risk of developing mild cognitive impairment despite normal overall intellectual performance. These deficits may be caused by disease-related and treatment-related factors. This study explores the impact of abnormal thyroid function during the first 3 years of life on attention performance at school age. We included 49 children diagnosed with CH and receiving treatment for the condition: 14 boys (mean age 9.5±2.8 years) and 35 girls (9.6±2.6 years). The number of episodes of normal, under-, and overtreatment were estimated based on TSH levels during their first 3 years of life (at 12, 18, 24, 30, and 36 months). Children were assessed using a computerised version of a Sustained attention test. General linear models were calculated with the attention index as the dependent variable and sex, aetiology, and number of episodes of normal, under-, and overtreatment as independent variables. Higher numbers of episodes of overtreatment (low TSH level) were associated with poorer attention performance at school age (P=.005, r=-0.45). Children with CH should be monitored closely during the first 3 years of life in order to prevent not only hypothyroidism but also any adverse effects of overtreatment that may affect attentional function at school age. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Functional assessment of a series of paediatric patients receiving neurointensive treatment: New Functional status scale.

PubMed

Madurga-Revilla, P; López-Pisón, J; Samper-Villagrasa, P; Garcés-Gómez, R; García-Íñiguez, J P; Domínguez-Cajal, M; Gil-Hernández, I; Viscor-Zárate, S

2017-11-01

Functional health, a reliable parameter of the impact of disease, should be used systematically to assess prognosis in paediatric intensive care units (PICU). Developing scales for the assessment of functional health is therefore essential. The Paediatric Overall and Cerebral Performance Category (POPC, PCPC) scales have traditionally been used in paediatric studies. The new Functional Status Scale (FSS) was designed to provide more objective results. This study aims to confirm the validity of the FSS compared to the classic POPC and PCPC scales, and to evaluate whether it may also be superior to the latter in assessing of neurological function. We conducted a retrospective descriptive study of 266 children with neurological diseases admitted to intensive care between 2012 and 2014. Functional health at discharge and at one year after discharge was evaluated using the PCPC and POPC scales and the new FSS. Global FSS scores were found to be well correlated with all POPC scores (P<.001), except in category 5 (coma/vegetative state). Global FSS score dispersion increases with POPC category. The neurological versions of both scales show a similar correlation. Comparison with classic POPC and PCPC categories suggests that the new FSS scale is a useful method for evaluating functional health in our setting. The dispersion of FSS values underlines the poor accuracy of POPC-PCPC compared to the new FSS scale, which is more disaggregated and objective. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Investigating the necessity of computed tomographic scans in children with headaches: a retrospective review.

PubMed

Gandhi, Rohit; Lewis, Evan Cole; Evans, Jeanette W; Sell, Erick

2015-03-01

Headaches are a common problem in the pediatric population. In 2002, the American Academy of Neurology (AAN) developed guidelines on neuroimaging for patients presenting with headache. Our objective was to determine the frequency of computed tomographic (CT) scanning ordered by a range of medical practitioners for pediatric patients presenting with primary headache. A retrospective chart review was conducted at the Children's Hospital of Eastern Ontario (CHEO), a tertiary care centre in Ontario. One hundred fifty-one records of patients referred to the outpatient neurology clinic at CHEO with ''headache'' or ''migraine'' as the primary complaint from 2004 to 2009 were randomly selected. Ninety-nine patients with normal neurologic examinations were ultimately included. Thirty-four patients (34%; 95% CI 25-45) had undergone CT scanning. None of the 34 CT scans (0%; 95% CI 0-10) showed significant findings, and none changed the headache diagnosis or management. Eleven (32%) of the CT scans were ordered by CHEO neurologists, 15 (44%) by community physicians, and 8 (24%) by CHEO emergency physicians. A high proportion of children presenting with primary headaches and a normal neurologic examination undergo CT scanning, despite well-established AAN guidelines regarding neuroimaging. Most of these CT scans do not appear to alter diagnosis and management. A variety of non-evidencebased factors may be encouraging physicians to overinvestigate this population and, as a result, increasing the risk of adverse events due to radiation exposure. Implementing initiatives at a site-based level that promote the use of established guidelines before performing CT scanning in this population may be beneficial.

Dihydrofolate Reductase Deficiency Due to a Homozygous DHFR Mutation Causes Megaloblastic Anemia and Cerebral Folate Deficiency Leading to Severe Neurologic Disease

PubMed Central

Cario, Holger; Smith, Desirée E.C.; Blom, Henk; Blau, Nenad; Bode, Harald; Holzmann, Karlheinz; Pannicke, Ulrich; Hopfner, Karl-Peter; Rump, Eva-Maria; Ayric, Zuleya; Kohne, Elisabeth; Debatin, Klaus-Michael; Smulders, Yvo; Schwarz, Klaus

2011-01-01

The importance of intracellular folate metabolism is illustrated by the severity of symptoms and complications caused by inborn disorders of folate metabolism or by folate deficiency. We examined three children of healthy, distantly related parents presenting with megaloblastic anemia and cerebral folate deficiency causing neurologic disease with atypical childhood absence epilepsy. Genome-wide homozygosity mapping revealed a candidate region on chromosome 5 including the dihydrofolate reductase (DHFR) locus. DHFR sequencing revealed a homozygous DHFR mutation, c.458A>T (p.Asp153Val), in all siblings. The patients' folate profile in red blood cells (RBC), plasma, and cerebrospinal fluid (CSF), analyzed by liquid chromatography tandem mass spectrometry, was compatible with DHFR deficiency. DHFR activity and fluorescein-labeled methotrexate (FMTX) binding were severely reduced in EBV-immortalized lymphoblastoid cells of all patients. Heterozygous cells displayed intermediate DHFR activity and FMTX binding. RT-PCR of DHFR mRNA revealed no differences between wild-type and DHFR mutation-carrying cells, whereas protein expression was reduced in cells with the DHFR mutation. Treatment with folinic acid resulted in the resolution of hematological abnormalities, normalization of CSF folate levels, and improvement of neurological symptoms. In conclusion, the homozygous DHFR mutation p.Asp153Val causes DHFR deficiency and leads to a complex hematological and neurological disease that can be successfully treated with folinic acid. DHFR is necessary for maintaining sufficient CSF and RBC folate levels, even in the presence of adequate nutritional folate supply and normal plasma folate. PMID:21310277

Brain ultrasound findings in neonates treated with intrauterine transfusion for fetal anaemia.

PubMed

Leijser, Lara M; Vos, Nikki; Walther, Frans J; van Wezel-Meijler, Gerda

2012-09-01

The main causes of severe fetal anaemia are red-cell allo-immunization, parvo B19 virus infection and feto-maternal haemorrhage. Treatment consists of intrauterine transfusion (IUT). Neuro-imaging studies in surviving neonates treated with IUT are scarce. To assess if neonates treated with IUT for fetal anaemia are at risk for cerebral injury, report the incidence and severity of brain ultrasound (US) abnormalities and explore the relation between brain US findings and perinatal parameters and neurological outcome. Brain US scans of neonates born alive between 2001 and 2008 with at least one IUT were retrospectively reviewed and classified as normal, mildly or moderately/severely abnormal. Incidences of abnormalities were calculated for full-term and preterm neonates. Presence and severity of abnormalities were related to clinical and IUT related parameters and to neurological outcome around 2 years of age (adverse: moderate or severe disability; favourable: normal or mild disability). A total of 127 neonates (82 born preterm) were included. Median number of IUTs was 3 (range 1-6) and of brain US 2 (1-6). Median gestational age and weight at birth were 36.6 (26.0-41.1) weeks and 2870 (1040-3950)g. In 72/127 (57%) neonates ≥1 abnormality was seen on brain US, classified as moderate/severe in 30/127 (24%). Neurological outcome was adverse in 5 infants. Presence of brain US abnormalities was not significantly related to any of the perinatal parameters or to neurological outcome. Neonates undergoing IUT for fetal anaemia are at high risk of brain injury. Copyright © 2012 Elsevier Ltd. All rights reserved.

Publication performance and research output of Neurology and Neurosurgery training institutes in India: A 5-year analysis.

PubMed

Madhugiri, Venkatesh S

2015-01-01

Scientific publications are a reflection of the quality of the clinical and academic work being carried out in an institute. Training in the process of research and scientific writing are important components of the residency curriculum. The publication performance and research output of institutes training residents in neurology and neurosurgery were evaluated. Internet-based study. This study was based on the data available on the websites of the Medical Council of India and the National Board of Examinations. The PubMed search interface was used to determine the publication output of institutes over the past 5 years (2010-2014). Google Scholar was used to determine the citation performance of each paper. The publication parameters were normalized to the number of faculty members in each institute as listed on the institutional web page. The normalized publication performance for an institute was computed by comparing the figures for that institute with the national average. Institutes could be ranked on several criteria. There was a high degree of clustering of output from the top 5% of the institutes. About 13% of the neurology intake and 30.9% of neurosurgery intake over the past 5 years has been into the institutes that have not published a single paper during this period. This evaluation of the publication performance and research output of neurology and neurosurgery training institutes would serve as a baseline data for future evaluations and comparisons. The absence of any publication and research output from several training institutes is a matter of concern.

Changes in Body Temperature in Incomplete Spinal Cord Injury by Digital Infrared Thermographic Imaging

PubMed Central

Song, Yun-Gyu; Won, Yu Hui; Park, Sung-Hee; Ko, Myoung-Hwan

2015-01-01

Objective To investigate changes in the core temperature and body surface temperature in patients with incomplete spinal cord injuries (SCI). In incomplete SCI, the temperature change is difficult to see compared with complete spinal cord injuries. The goal of this study was to better understand thermal regulation in patients with incomplete SCI. Methods Fifty-six SCI patients were enrolled, and the control group consisted of 20 healthy persons. The spinal cord injuries were classified according to International Standards for Neurological Classification of Spinal Cord Injury. The patients were classified into two groups: upper (neurological injury level T6 or above) and lower (neurological injury level T7 or below) SCIs. Body core temperature was measured using an oral thermometer, and body surface temperature was measured using digital infrared thermographic imaging. Results Twenty-nine patients had upper spinal cord injuries, 27 patients had lower SCIs, and 20 persons served as the normal healthy persons. Comparing the skin temperatures of the three groups, the temperatures at the lower abdomen, anterior thigh and anterior tibia in the patients with upper SCIs were lower than those of the normal healthy persons and the patients with lower SCIs. No significant temperature differences were observed between the normal healthy persons and the patients with lower SCIs. Conclusion In our study, we found thermal dysregulation in patients with incomplete SCI. In particular, body surface temperature regulation was worse in upper SCIs than in lower injuries. Moreover, cord injury severity affected body surface temperature regulation in SCI patients. PMID:26605167

Remote Physical Activity Monitoring in Neurological Disease: A Systematic Review

PubMed Central

Block, Valerie A. J.; Pitsch, Erica; Tahir, Peggy; Cree, Bruce A. C.; Allen, Diane D.; Gelfand, Jeffrey M.

2016-01-01

Objective To perform a systematic review of studies using remote physical activity monitoring in neurological diseases, highlighting advances and determining gaps. Methods Studies were systematically identified in PubMed/MEDLINE, CINAHL and SCOPUS from January 2004 to December 2014 that monitored physical activity for ≥24 hours in adults with neurological diseases. Studies that measured only involuntary motor activity (tremor, seizures), energy expenditure or sleep were excluded. Feasibility, findings, and protocols were examined. Results 137 studies met inclusion criteria in multiple sclerosis (MS) (61 studies); stroke (41); Parkinson's Disease (PD) (20); dementia (11); traumatic brain injury (2) and ataxia (1). Physical activity levels measured by remote monitoring are consistently low in people with MS, stroke and dementia, and patterns of physical activity are altered in PD. In MS, decreased ambulatory activity assessed via remote monitoring is associated with greater disability and lower quality of life. In stroke, remote measures of upper limb function and ambulation are associated with functional recovery following rehabilitation and goal-directed interventions. In PD, remote monitoring may help to predict falls. In dementia, remote physical activity measures correlate with disease severity and can detect wandering. Conclusions These studies show that remote physical activity monitoring is feasible in neurological diseases, including in people with moderate to severe neurological disability. Remote monitoring can be a psychometrically sound and responsive way to assess physical activity in neurological disease. Further research is needed to ensure these tools provide meaningful information in the context of specific neurological disorders and patterns of neurological disability. PMID:27124611

Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect

PubMed Central

Fassihi, Hiva; Sethi, Mieran; Fawcett, Heather; Wing, Jonathan; Chandler, Natalie; Mohammed, Shehla; Craythorne, Emma; Morley, Ana M. S.; Lim, Rongxuan; Turner, Sally; Henshaw, Tanya; Garrood, Isabel; Giunti, Paola; Hedderly, Tammy; Abiona, Adesoji; Naik, Harsha; Harrop, Gemma; McGibbon, David; Jaspers, Nicolaas G. J.; Botta, Elena; Nardo, Tiziana; Stefanini, Miria; Young, Antony R.; Sarkany, Robert P. E.; Lehmann, Alan R.

2016-01-01

Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins. PMID:26884178

Temporary divergence paralysis in viral meningitis.

PubMed

Bakker, Stef L M; Gan, Ivan M

2008-06-01

A 43-year-old woman who reported diplopia and headache was found to have comitant esotropia at distance fixation and normal alignment at reading distance (divergence paralysis). Eye movement, including abduction, was normal as was the rest of the neurologic examination. Brain MRI was normal. Lumbar puncture showed an elevated opening pressure and a cerebrospinal fluid formula consistent with viral meningitis. The patient was treated with intravenous fluids and analgesics and with a temporary prism to alleviate diplopia. Within 3 weeks, she had fully recovered. This is the first report of divergence palsy in viral meningitis.

Dose-effect relationships between manganese exposure and neurological, neuropsychological and pulmonary function in confined space bridge welders.

PubMed

Bowler, Rosemarie M; Roels, Harry A; Nakagawa, Sanae; Drezgic, Marija; Diamond, Emily; Park, Robert; Koller, William; Bowler, Russell P; Mergler, Donna; Bouchard, Maryse; Smith, Donald; Gwiazda, Roberto; Doty, Richard L

2007-03-01

Although adverse neuropsychological and neurological health effects are well known among workers with high manganese (Mn) exposures in mining, ore-processing and ferroalloy production, the risks among welders with lower exposures are less well understood. Confined space welding in construction of a new span of the San Francisco-Oakland Bay Bridge without adequate protection was studied using a multidisciplinary method to identify the dose-effect relationship between adverse health effects and Mn in air or whole blood. Bridge welders (n = 43) with little or no personal protection equipment and exposed to a welding fume containing Mn, were administered neurological, neuropsychological, neurophysiological and pulmonary tests. Outcome variables were analysed in relation to whole blood Mn (MnB) and a Cumulative Exposure Index (CEI) based on Mn-air, duration and type of welding. Welders performed a mean of 16.5 months of welding on the bridge, were on average 43.8 years of age and had on average 12.6 years of education. The mean time weighted average of Mn-air ranged from 0.11-0.46 mg/m(3) (55% >0.20 mg/m(3)). MnB >10 microg/l was found in 43% of the workers, but the concentrations of Mn in urine, lead in blood and copper and iron in plasma were normal. Forced expiratory volume at 1s: forced vital capacity ratios (FEV(1)/FVC) were found to be abnormal in 33.3% of the welders after about 1.5 years of welding at the bridge. Mean scores of bradykinesia and Unified Parkinson Disease Rating Scale exceeded 4 and 6, respectively. Computer assisted tremor analysis system hand tremor and body sway tests, and University of Pennsylvania Smell Identification Test showed impairment in 38.5/61.5, 51.4 and 88% of the welders, respectively. Significant inverse dose-effect relationships with CEI and/or MnB were found for IQ (p

Neurologic music therapy in upper-limb rehabilitation in children with severe bilateral cerebral palsy: a randomized controlled trial.

PubMed

Marrades-Caballero, Eugenio; Santonja-Medina, Clara S; Sanz-Mengibar, Jose M; Santonja-Medina, Fernando

2018-02-26

After receiving neurologic music therapy, functional improvements in children with severe bilateral cerebral palsy have not been found in the literature. Musical training with instruments allows interrelationships between movement, emotions and cognition for task-based learning, in order to improve motor control. To understand whether neurologic music therapy has an impact on the functionality of children with severe cerebral palsy. A randomized controlled assessor-blind trial was carried out. Children were recruited and treated in their own community center. Eighteen children with severe bilateral cerebral palsy between 4 and 16 years old were studied. The intervention group (n=18) received music therapy for 16 weeks, in addition to its usual physiotherapy input. Two music therapists implemented a neurologic music therapy program of therapeutic instrumental music performance. The control group (n=9) received its usual therapeutic input, similar to the intervention group, but not neurologic music therapy. Overall and specific "Chailey levels of Ability" were quantified, as well as the Locomotor Stages. Significant improvements in the overall and specific "arm and hand position" as well as "activities" from the Chailey Levels of Ability and the Locomotor Stages were observed (p<.05) in the group which received the music therapy (corregir si se acepta en la editing proofs). All these improvements persisted after 4 months. The control group showed no improvements after a four-month follow-up. Optimized intervention of neurologic music therapy can improve the functionality of children with severe bilateral cerebral palsy. Music therapy is a useful tool in rehabilitation and its positive effects remain four months after completing the treatment.

A new kid on the block: The Memory Validity Profile (MVP) in children with neurological conditions.

PubMed

Brooks, Brian L; Fay-McClymont, Taryn B; MacAllister, William S; Vasserman, Marsha; Sherman, Elisabeth M S

2018-06-06

Determining the validity of obtained data is an inherent part of a neuropsychological assessment. The purpose of this study was investigate the failure rate of the Memory Validity Profile (MVP) in a large clinical sample of children and adolescents with neurological diagnoses. Data were obtained from 261 consecutive patients (mean age = 12.0, SD = 3.9, range = 5-19) who were referred for a neuropsychological assessment in a tertiary care pediatric hospital and were administered the MVP. In this sample, 4.6% of youth failed the MVP. Mean administration time for the MVP was 7.4 min, although time to complete was not associated with failure rates. Failure rates were held relatively consistent at approximately 5% across age ranges, diagnoses, and psychomotor processing speed abilities. Having very low, below normal, or above normal intellectual abilities did not alter failure rate on the MVP. However, those with intellectual disability (i.e., IQ<70) had a higher fail rate at 12% on MVP Total Score, but only 6% on the MVP Visual portion. Failure rates on the MVP were associated with lower scores on memory tests. This study provides support for using the MVP in children as young as 5 years with neurological diagnoses.

Vestibular and oculomotor findings in neurologically-normal, non-concussed children.

PubMed

Corwin, Daniel J; Zonfrillo, Mark R; Wiebe, Douglas J; Master, Christina L; Grady, Matthew F; Arbogast, Kristy B

2018-01-01

To determine the proportion of non-concussed, neurologically normal children with failures on a vestibular and oculomotor examination for concussion performed in an acute setting. This was a cross-sectional study of subjects 6-18 years old presenting to a paediatric emergency department with non-neurologic chief complaints. The examination was administered by a paediatric emergency medicine physician, and includes assessments of dysmetria, nystagmus, smooth pursuits, saccades, gaze stability, near-point of convergence, and gait/balance testing. Of the 295 subjects enrolled, 24% failed at least one element of testing. About 13% had >1 failed element and 5% had >2 failed elements. About 29% of females and 19% of males had failed examinations. By age, 15% of subjects 6-8 years old, 32% 9-11 years, 32% 12-14 years, and 26% 15-18 years had failed examinations. Overall, 10% were unable to complete the exam due to developmental age. The provider should be aware that a proportion of non-concussed children may demonstrate failure on a single element of the vestibular and oculomotor exam. While this testing is of benefit to the acute care provider in diagnosing paediatric concussion, its utility is greatest in the context of an injury history with acute onset of concussion symptoms.

Nonrhinologic headache in a tertiary rhinology practice.

PubMed

Perry, Brian F; Login, Ivan S; Kountakis, Stilianos E

2004-04-01

Our goal was to determine the etiology of headache in patients who were referred for sinus evaluation but were found to have no evidence of rhinosinusitis on computed tomography (CT) of the sinuses and on endoscopic examination. Data were collected prospectively from 100 patients with headache but with normal sinus CT and endoscopic examination. Headache and 20-Item Sino-Nasal Outcomes Test (SNOT-20) scores of patients with the chief complaint of headache and who requested further neurologic evaluation (group I) were compared with the scores of patients who did not list headache as a significant symptom (group II) and with the scores of patients without headache (group III). The most common neurologic diagnosis for group I patients (n = 36) was migraine headaches (58%). These patients also had higher mean SNOT-20 scores (24 +/- 3.3) compared to group II patients with mild headache (14.6 +/- 2.3) or group III patients without headache (12.4 +/- 2.1). Migraine was the most common type of headache in patients with normal sinus CT treated for presumed rhinosinusitis as the cause of the headache. Patients with headache as their chief complaint that required further neurologic evaluation had overall higher SNOT-20 scores than nonheadache patients, indicating greater disability of their overall quality of life index.

Impact of Early Vasopressor Administration on Neurological Outcomes after Prolonged Out-of-Hospital Cardiac Arrest.

PubMed

Hubble, Michael W; Tyson, Clark

2017-06-01

Introduction Vasopressors are associated with return of spontaneous circulation (ROSC), but no long-term benefit has been demonstrated in randomized trials. However, these trials did not control for the timing of vasopressor administration which may influence outcomes. Consequently, the objective of this study was to develop a model describing the likelihood of favorable neurological outcome (cerebral performance category [CPC] 1 or 2) as a function of the public safety answering point call receipt (PSAP)-to-pressor-interval (PPI) in prolonged out-of-hospital cardiac arrest. Hypothesis The likelihood of favorable neurological outcome declines with increasing PPI. This investigation was a retrospective study of cardiac arrest using linked data from the Cardiac Arrest Registry to Enhance Survival (CARES) database (Centers for Disease Control and Prevention [Atlanta, Georgia USA]; American Heart Association [Dallas, Texas USA]; and Emory University Department of Emergency Medicine [Atlanta, Georgia USA]) and the North Carolina (USA) Prehospital Medical Information System. Adult patients suffering a bystander-witnessed, non-traumatic cardiac arrest between January 2012 and June 2014 were included. Logistic regression was used to calculate the adjusted odds ratio (OR) of neurological outcome as a function of PPI, while controlling for patient age, gender, and race; endotracheal intubation (ETI); shockable rhythm; layperson cardiopulmonary resuscitation (CPR); and field hypothermia. Of the 2,100 patients meeting inclusion criteria, 913 (43.5%) experienced ROSC, 618 (29.4%) survived to hospital admission, 187 (8.9%) survived to hospital discharge, and 155 (7.4%) were discharged with favorable neurological outcomes (CPC 1 or 2). Favorable neurological outcome was less likely with increasing PPI (OR=0.90; P<.01) and increasing age (OR=0.97; P<.01). Compared to patients with non-shockable rhythms, patients with shockable rhythms were more likely to have favorable neurological outcomes (OR=7.61; P<.01) as were patients receiving field hypothermia (OR=2.13; P<.01). Patient gender, non-Caucasian race, layperson CPR, and ETI were not independent predictors of favorable neurological outcome. In this evaluation, time to vasopressor administration was significantly associated with favorable neurological outcome. Among adult, witnessed, non-traumatic arrests, the odds of hospital discharge with CPC 1 or 2 declined by 10% for every one-minute delay between PSAP call-receipt and vasopressor administration. These retrospective observations support the notion of a time-dependent function of vasopressor effectiveness on favorable neurological outcome. Large, prospective studies are needed to verify this relationship. Hubble MW , Tyson C . Impact of early vasopressor administration on neurological outcomes after prolonged out-of-hospital cardiac arrest. Prehosp Disaster Med. 2017; 32(3):297-304.

Laryngotracheal Stenosis in Children and Infants With Neurological Disorders: Management and Outcome.

PubMed

Nicollas, Richard; Moreddu, Eric; Le Treut-Gay, Claire; Roman, Stéphane; Mancini, Julien; Triglia, Jean-Michel

2016-12-01

The goal of this retrospective study is to compare the management and outcome of surgical treatment of laryngotracheal stenosis in children and infants with and without an associated neurological disorder. In a series of children operated on for subglottic stenosis (SGS), patients with an associated neurological disorder were identified. The following criteria were compared in children with and without neurological disease: grade of stenosis, age, technique (Crico-Tracheal Resection (CTR), Laryngo-Tracheo-Plasty (LTP) in single and 2 stage, laser), analyzing duration, preoperative tracheostomy, decannulation rate, preoperative gastrostomy, and number of days in intensive care unit and in hospital. Two hundred twenty-three children were operated on for subglottic stenosis, of whom 68 (30.5%) had an associated neurological disorder. Some criteria were found to be statistically different between the 2 populations: mean age of 43 months in neurological population versus 13 months (P < .001). The distribution of the grades of SGS appeared similar in the 2 groups (P = .088), and the mean duration of stay in hospital and in ICU were not statistically different (respectively, P = .186 and P = .056) between the 2 groups; a 2-stage procedure was performed more frequently than 1-stage in the cases with associated neurological disorder-66.6% versus 36.5% (P = .013); the median duration of stenting was 20 days in those with neurological disease versus 12 (P = .021). Preoperative tracheotomy was noted in 75% of neurological patients versus 47.7% of the others (P < .001). The outcome was considered to be good (decannulation and no further treatment) following a single procedure in 82.4% of patients with neurological disorder, as against 86.5% of neurologically unimpaired subjects. The difference in outcome of surgery was not statistically different (P = .392) between the 2 groups. It appears that subglottic stenosis in children with associated neurological disorder is not more severe than in neurologically normal patients. In three-quarters of the neurologically impaired cases, a preoperative tracheostomy was needed, but the rates of failure of postoperative decannulation are not statistically significant between the 2 groups. In our experience, 2-stage techniques are more often performed than single stage in this population in order to allow airway safety, for example after feeding. If properly managed, the final results are similar in the 2 populations. © The Author(s) 2016.

Perinatal asphyxia in the guinea pig leads to morphologic but not neurologic, cognitive, or behavioral changes.

PubMed

Hoeger, Harald; Bubna-Littitz, Herrmann; Engelmann, Mario; Schwerdtner, Ingrid; Schmid, Diethard; Lahoda, Robert; Seidl, Rainer; Lubec, Gert; Lubec, Barbara

2003-07-01

In a recent publication, we described neurodegeneration along with neurotransmitter deficits and impaired differentiation in the guinea pig 3 months following severe perinatal asphyxia (PA). We were therefore interested in the clinical features in terms of neurology, cognitive functions, and behavior. We tested the long-term effects of PA in an animal model, which in the rat are well documented and resemble the clinical situation. Examinations consisted of an observational battery for motor and reflex functions and the acoustic startle response setting. We tested cognitive functions in the multiple T-maze and evaluated behavior using the elevated plus maze and open field studies. No neurologic deficits were observed in the observational battery, including the acoustic startle response. Cognitive functions of memory and learning were not impaired in the multiple T-maze. In the open field and in the elevated plus maze, the system to test anxiety-related behavior, guinea pigs performed well. Our findings of patent neurology, cognitive functions, and behavior do not reflect the prominent morphologic findings of neurodegeneration. This is in agreement with corresponding studies on PA in the rat at the identical time point. We learned from this study that both test systems, although representing the standard in neuroscience, are either not sensitive enough or central nervous system lesions are clinically fully compensated.

Neurological soft signs discriminate schizophrenia from bipolar disorder.

PubMed

Rigucci, Silvia; Dimitri-Valente, Giorgia; Mandarelli, Gabriele; Manfredi, Giovanni; Comparelli, Anna; De Filippis, Sergio; Gherardelli, Simona; Bersani, Giuseppe; Girardi, Paolo; Ferracuti, Stefano

2014-03-01

Although neurological soft signs have been consistently described in patients with schizophrenia, their diagnostic specificity is not well clarified. To test the hypothesis that neurological soft signs are specifically related to schizophrenia, we examined 305 subjects (patients with schizophrenia-spectrum disorder, n=167; patients with bipolar I disorder, n=88; controls, n=50). Neurological soft signs were assessed using the Neurological Evaluation Scale (NES). Multiple logistic regression analysis was used to compute the diagnostic predictive power of neurological soft signs. Patients in the schizophrenia-spectrum disorder group were found to have significantly greater neurological impairment (NES total score=23.9, standard deviation [SD] 11.2) than those in the bipolar disorder group (NES total score=18.2, SD 7.6; p<0.001). Neurological functioning was closely associated with psychopathology (all p<0.001). The NES total score reliably distinguished patients with schizophrenia spectrum disorders from those with bipolar disorder in 68.7% of the cases (p<0.001). Moreover, a particular set of neurological soft signs showed specificity for the schizophrenia-spectrum disorder diagnostic group. Our findings suggest that schizophrenia and bipolar disorder can be distinguished in terms of neurological impairment. Furthermore, we recommend the utility of neurological soft signs as a useful, quantifiable, sensitive, and inexpensive tool for the diagnostic work-up of schizophrenia.

Use of the interRAI CHESS scale to predict mortality among persons with neurological conditions in three care settings.

PubMed

Hirdes, John P; Poss, Jeffrey W; Mitchell, Lori; Korngut, Lawrence; Heckman, George

2014-01-01

Persons with certain neurological conditions have higher mortality rates than the population without neurological conditions, but the risk factors for increased mortality within diagnostic groups are less well understood. The interRAI CHESS scale has been shown to be a strong predictor of mortality in the overall population of persons receiving health care in community and institutional settings. This study examines the performance of CHESS as a predictor of mortality among persons with 11 different neurological conditions. Survival analyses were done with interRAI assessments linked to mortality data among persons in home care (n = 359,940), complex continuing care hospitals/units (n = 88,721), and nursing homes (n = 185,309) in seven Canadian provinces/territories. CHESS was a significant predictor of mortality in all 3 care settings for the 11 neurological diagnostic groups considered after adjusting for age and sex. The distribution of CHESS scores varied between diagnostic groups and within diagnostic groups in different care settings. CHESS is a valid predictor of mortality in neurological populations in community and institutional care. It may prove useful for several clinical, administrative, policy-development, evaluation and research purposes. Because it is routinely gathered as part of normal clinical practice in jurisdictions (like Canada) that have implemented interRAI assessment instruments, CHESS can be derived without additional need for data collection.

The Infant Motor Profile: a standardized and qualitative method to assess motor behaviour in infancy.

PubMed

Heineman, Kirsten R; Bos, Arend F; Hadders-Algra, Mijna

2008-04-01

A reliable and valid instrument to assess neuromotor condition in infancy is a prerequisite for early detection of developmental motor disorders. We developed a video-based assessment of motor behaviour, the Infant Motor Profile (IMP), to evaluate motor abilities, movement variability, ability to select motor strategies, movement symmetry, and fluency. The IMP consists of 80 items and is applicable in children from 3 to 18 months. The present study aimed to test intra- and interobserver reliability and concurrent validity of the IMP with the Alberta Infant Motor Scale (AIMS) and Touwen neurological examination. The study group consisted of 40 low-risk term (median gestational age [GA] 40 wks, range 38-42 wks) and 40 high-risk preterm infants (median GA 29.6 wks, range 26-33 wks) with corrected ages 4 to 18 months (31 females, 49 males). Intra- and interobserver agreement of the IMP were satisfactory (Spearman's rho=0.9). Concurrent validity of IMP and AIMS was good (Spearman's rho=0.8, p<0.005). The IMP was able to differentiate between infants with normal neurological condition, simple minor neurological dysfunction (MND), complex MND, and abnormal neurological condition (p<0.005). This means that the IMP may be a promising tool to evaluate neurological integrity during infancy, a suggestion that needs confirmation by means of assessment of larger groups of infants with heterogeneous neurological conditions.

Brain transcriptome perturbations in the Hfe(-/-) mouse model of genetic iron loading.

PubMed

Johnstone, Daniel; Graham, Ross M; Trinder, Debbie; Delima, Roheeth D; Riveros, Carlos; Olynyk, John K; Scott, Rodney J; Moscato, Pablo; Milward, Elizabeth A

2012-04-11

Severe disruption of brain iron homeostasis can cause fatal neurodegenerative disease, however debate surrounds the neurologic effects of milder, more common iron loading disorders such as hereditary hemochromatosis, which is usually caused by loss-of-function polymorphisms in the HFE gene. There is evidence from both human and animal studies that HFE gene variants may affect brain function and modify risks of brain disease. To investigate how disruption of HFE influences brain transcript levels, we used microarray and real-time reverse transcription polymerase chain reaction to assess the brain transcriptome in Hfe(-/-) mice relative to wildtype AKR controls (age 10 weeks, n≥4/group). The Hfe(-/-) mouse brain showed numerous significant changes in transcript levels (p<0.05) although few of these related to proteins directly involved in iron homeostasis. There were robust changes of at least 2-fold in levels of transcripts for prominent genes relating to transcriptional regulation (FBJ osteosarcoma oncogene Fos, early growth response genes), neurotransmission (glutamate NMDA receptor Grin1, GABA receptor Gabbr1) and synaptic plasticity and memory (calcium/calmodulin-dependent protein kinase IIα Camk2a). As previously reported for dietary iron-supplemented mice, there were altered levels of transcripts for genes linked to neuronal ceroid lipofuscinosis, a disease characterized by excessive lipofuscin deposition. Labile iron is known to enhance lipofuscin generation which may accelerate brain aging. The findings provide evidence that iron loading disorders can considerably perturb levels of transcripts for genes essential for normal brain function and may help explain some of the neurologic signs and symptoms reported in hemochromatosis patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Examination of Physiological Function and Biochemical Disorders in a Rat Model of Prolonged Asphyxia-Induced Cardiac Arrest followed by Cardio Pulmonary Bypass Resuscitation

PubMed Central

Kim, Junhwan; Yin, Tai; Yin, Ming; Zhang, Wei; Shinozaki, Koichiro; Selak, Mary A.; Pappan, Kirk L.; Lampe, Joshua W.; Becker, Lance B.

2014-01-01

Background Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion. Method A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition. Results After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue. Conclusion The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage. PMID:25383962

Examination of physiological function and biochemical disorders in a rat model of prolonged asphyxia-induced cardiac arrest followed by cardio pulmonary bypass resuscitation.

PubMed

Kim, Junhwan; Yin, Tai; Yin, Ming; Zhang, Wei; Shinozaki, Koichiro; Selak, Mary A; Pappan, Kirk L; Lampe, Joshua W; Becker, Lance B

2014-01-01

Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion. A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition. After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue. The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage.

Functional speech disorders: clinical manifestations, diagnosis, and management.

PubMed

Duffy, J R

2016-01-01

Acquired psychogenic or functional speech disorders are a subtype of functional neurologic disorders. They can mimic organic speech disorders and, although any aspect of speech production can be affected, they manifest most often as dysphonia, stuttering, or prosodic abnormalities. This chapter reviews the prevalence of functional speech disorders, the spectrum of their primary clinical characteristics, and the clues that help distinguish them from organic neurologic diseases affecting the sensorimotor networks involved in speech production. Diagnosis of a speech disorder as functional can be supported by sometimes rapidly achieved positive outcomes of symptomatic speech therapy. The general principles of such therapy are reviewed. © 2016 Elsevier B.V. All rights reserved.

Ketone bodies protection against HIV-1 Tat-induced neurotoxicity.

PubMed

Hui, Liang; Chen, Xuesong; Bhatt, Dhaval; Geiger, Nicholas H; Rosenberger, Thad A; Haughey, Norman J; Masino, Susan A; Geiger, Jonathan D

2012-07-01

HIV-1-associated neurocognitive disorder (HAND) is a syndrome that ranges clinically from subtle neuropsychological impairments to profoundly disabling HIV-associated dementia. Not only is the pathogenesis of HAND unclear, but also effective treatments are unavailable. The HIV-1 transactivator of transcription protein (HIV-1 Tat) is strongly implicated in the pathogenesis of HAND, in part, because of its well-characterized ability to directly excite neurons and cause neurotoxicity. Consistent with previous findings from others, we demonstrate here that HIV-1 Tat induced neurotoxicity, increased intracellular calcium, and disrupted a variety of mitochondria functions, such as reducing mitochondrial membrane potential, increasing levels of reactive oxygen species, and decreasing bioenergetic efficiency. Of therapeutic importance, we show that treatment of cultured neurons with ketone bodies normalized HIV-1 Tat induced changes in levels of intracellular calcium, mitochondrial function, and neuronal cell death. Ketone bodies are normally produced in the body and serve as alternative energy substrates in tissues including brain and can cross the blood-brain barrier. Ketogenic strategies have been used clinically for treatment of neurological disorders and our current results suggest that similar strategies may also provide clinical benefits in the treatment of HAND. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Effect of Chinese Herbal Medicine on Molecular Imaging of Neurological Disorders.

PubMed

Yao, Yao; Chen, Ting; Huang, Jing; Zhang, Hong; Tian, Mei

2017-01-01

Chinese herbal medicine has been used to treat a wide variety of neurological disorders including stroke, Alzheimer's disease, and Parkinson's disease. However, its mechanism behind the effectiveness remains unclear. Recently, molecular imaging technology has been applied for this purpose, since it can assess the cellular or molecular function in a living subject by using specific imaging probes and/or radioactive tracers, which enable efficient analysis and monitoring the therapeutic response repetitively. This chapter reviews the in vivo functional and metabolic changes after administration of Chinese herbal medicine in various neurological disorders and provides perspectives on the future evaluations of therapeutic response of Chinese herbal medicine. © 2017 Elsevier Inc. All rights reserved.

Impact of bilirubin-induced neurologic dysfunction on neurodevelopmental outcomes

PubMed Central

Loe, Irene M.

2015-01-01

Bilirubin-induced neurologic dysfunction (BIND) is the constellation of neurologic sequelae following milder degrees of neonatal hyperbilirubinemia than are associated with kernicterus. Clinically, BIND may manifest after the neonatal period as developmental delay, cognitive impairment, disordered executive function, and behavioral and psychiatric disorders. However, there is controversy regarding the relative contribution of neonatal hyperbilirubinemia versus other risk factors to the development of later neurodevelopmental disorders in children with BIND. In this review, we focus on the empiric data from the past 25 years regarding neurodevelopmental outcomes and BIND, including specific effects on developmental delay, cognition, speech and language development, executive function, and th neurobehavioral disorders, such as attention deficit/hyperactivity disorder and autism. PMID:25585889

Language deficits, localization, and grammar: evidence for a distributive model of language breakdown in aphasic patients and neurologically intact individuals.

PubMed

Dick, F; Bates, E; Wulfeck, B; Utman, J A; Dronkers, N; Gernsbacher, M A

2001-10-01

Selective deficits in aphasic patients' grammatical production and comprehension are often cited as evidence that syntactic processing is modular and localizable in discrete areas of the brain (e.g., Y. Grodzinsky, 2000). The authors review a large body of experimental evidence suggesting that morpho-syntactic deficits can be observed in a number of aphasic and neurologically intact populations. They present new data showing that receptive agrammatism is found not only over a range of aphasic groups, but is also observed in neurologically intact individuals processing under stressful conditions. The authors suggest that these data are most compatible with a domain-general account of language, one that emphasizes the interaction of linguistic distributions with the properties of an associative processor working under normal or suboptimal conditions.

Music for the ageing brain: Cognitive, emotional, social, and neural benefits of musical leisure activities in stroke and dementia.

PubMed

Särkämö, Teppo

2017-01-01

Music engages an extensive network of auditory, cognitive, motor, and emotional processing regions in the brain. Coupled with the fact that the emotional and cognitive impact of music is often well preserved in ageing and dementia, music is a powerful tool in the care and rehabilitation of many ageing-related neurological diseases. In addition to formal music therapy, there has been a growing interest in self- or caregiver-implemented musical leisure activities or hobbies as a widely applicable means to support psychological wellbeing in ageing and in neurological rehabilitation. This article reviews the currently existing evidence on the cognitive, emotional, and neural benefits of musical leisure activities in normal ageing as well as in the rehabilitation and care of two of the most common and ageing-related neurological diseases: stroke and dementia.

Methods for Functional Connectivity Analyses

DTIC Science & Technology

2012-12-13

motor , or hand motor function (green, red, or blue shading, respectively). Thus, this work produced the first comprehensive analysis of ECoG...Computer Engineering, University of Texas at El Paso , TX, USA 3Department of Neurology, Albany Medical College, Albany, NY, USA 4Department of Computer...Department of Health, Albany, NY, USA bDepartment of Electrical and Computer Engineering, University of Texas at El Paso , TX, USA cDepartment of Neurology

[The use of a robot-assisted Gait Trainer GT1 in patients in the acute period of cerebral stroke: a pilot study].

PubMed

Skvortsova, V I; Ivanova, G E; Kovrazhkina, E A; Rumiantseva, N A; Staritsyn, A N; Suvorov, A Iu; Sogomonian, E K

2008-01-01

An aim of the study was to evaluate efficacy of using Gait Trainer GT1, a robot-assisted gait trainer with a system of body-weight support, for the rehabilitation of gait in patients in the acute period of cerebral stroke. A main group included 30 patients in the acute period of ischemic and hemorrhage stroke and a control group--20 age- and sex matched patients. Patients of both groups had daily kinesitherapy sessions with a rehabilitator. Patients of the main group had additional sessions on the Gait Trainer GT1 from the moment of functional readiness to adequate orthostatic probe. Efficacy of rehabilitation was assessed in the four following phases: the first verticalization of patient in the standing position, adaptation of patient to the standing position, walking with assistance, independent walking. Muscular power (scores) in all muscles of low extremities, muscle tonus (the Ashfort scale), amplitude of tendinous reflexes on the reflexes scale, sensory disturbances and discoordination syndromes (specially elaborated scales), pathological positions in the axial muscular system and extremities, functional status (a steadiness scale, the Berg balance scale, the Barthel scale, 5 m test) were assessed in each phase. Stabilometry was conducted for objective evaluation of vertical balance function. The duration of sessions on GT1 and a number of exercises were depended on the patient's tolerability to physical activity. Percentage of relief was determined by the ability of a patient to balance in the standing position. Each patient had 8-10 sessions. A significant improvement of the functional status: ability to balance in standing position, walking, increase of self-care skills were observed in both groups. No significant differences in the level of functional improvements were found compared to the control group. However some peculiarities of the rehabilitation of primary neurologic deficit were observed during CT1-trainings: the normalization of muscle tonus both in spastic and hypotonic muscles, predominate rehabilitation of flexor muscular system (p = 0.005), significant improvement of deep and surface sensitivity (p < 0.005). The stabilometric data revealed the normalization of strategy of vertical posture support--from hip to ankle (p = 0.001), proprioceptive control of balance by the Romberg coefficient (p = 0.005). Robot-assisted gait trainers are commonly used in trainings of step patterns in highly disabled patients who are not able to walk without assistance. These peculiarities of the rehabilitation of primary neurologic deficit during the GT-trainings allowed to use a differential approach to a candidate selection for the sessions.

Role of cerebral ultrasound and magnetic resonance imaging in newborns with congenital cytomegalovirus infection.

PubMed

Capretti, Maria Grazia; Lanari, Marcello; Tani, Giovanni; Ancora, Gina; Sciutti, Rita; Marsico, Concetta; Lazzarotto, Tiziana; Gabrielli, Liliana; Guerra, Brunella; Corvaglia, Luigi; Faldella, Giacomo

2014-03-01

To assess the diagnostic and prognostic value of cerebral magnetic resonance imaging (cMRI) in comparison with that of cerebral ultrasound (cUS) in predicting neurodevelopmental outcome in newborns with congenital cytomegalovirus (CMV) infection. Forty CMV-congenitally infected newborns underwent cUS and cMRI within the first month of life. Clinical course, laboratory findings, visual/hearing function and neurodevelopmental outcome were documented. Thirty newborns showed normal cMRI, cUS and hearing/visual function in the first month of life; none showed CMV-related abnormalities at follow-up. Six newborns showed pathological cMRI and cUS findings (pseudocystis, ventriculomegaly, calcifications, cerebellar hypoplasia) but cMRI provided additional information (white matter abnormalities in three cases, lissencephaly/polymicrogyria in one and a cyst of the temporal lobe in another one); cerebral calcifications were detected in 3/6 infants by cUS but only in 2/6 by cMRI. Four of these 6 infants showed severe neurodevelopmental impairment and five showed deafness during follow-up. Three newborns had a normal cUS, but cMRI documented white matter abnormalities and in one case also cerebellar hypoplasia; all showed neurodevelopmental impairment and two were deaf at follow-up. One more newborn showed normal cUS and cMRI, but brainstem auditory evoked responses were abnormal; psychomotor development was normal at follow-up. Compared with cUS, cMRI disclosed additional pathological findings in CMV-congenitally infected newborns. cUS is a readily available screening tool useful in the identification of infected newborns with major cerebral involvement. Further studies with a larger sample size are needed to determine the prognostic role of MRI, particularly regarding isolated white matter lesions. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Increased Functional MEG Connectivity as a Hallmark of MRI-Negative Focal and Generalized Epilepsy.

PubMed

Li Hegner, Yiwen; Marquetand, Justus; Elshahabi, Adham; Klamer, Silke; Lerche, Holger; Braun, Christoph; Focke, Niels K

2018-05-15

Epilepsy is one of the most prevalent neurological diseases with a high morbidity. Accumulating evidence has shown that epilepsy is an archetypical neural network disorder. Here we developed a non-invasive cortical functional connectivity analysis based on magnetoencephalography (MEG) to assess commonalities and differences in the network phenotype in different epilepsy syndromes (non-lesional/cryptogenic focal and idiopathic/genetic generalized epilepsy). Thirty-seven epilepsy patients with normal structural brain anatomy underwent a 30-min resting state MEG measurement with eyes closed. We only analyzed interictal epochs without epileptiform discharges. The imaginary part of coherency was calculated as an indicator of cortical functional connectivity in five classical frequency bands. This connectivity measure was computed between all sources on individually reconstructed cortical surfaces that were surface-aligned to a common template. In comparison to healthy controls, both focal and generalized epilepsy patients showed widespread increased functional connectivity in several frequency bands, demonstrating the potential of elevated functional connectivity as a common pathophysiological hallmark in different epilepsy types. Furthermore, the comparison between focal and generalized epilepsies revealed increased network connectivity in bilateral mesio-frontal and motor regions specifically for the generalized epilepsy patients. Our study indicated that the surface-based normalization of MEG sources of individual brains enables the comparison of imaging findings across subjects and groups on a united platform, which leads to a straightforward and effective disclosure of pathological network characteristics in epilepsy. This approach may allow for the definition of more specific markers of different epilepsy syndromes, and increased MEG-based resting-state functional connectivity seems to be a common feature in MRI-negative epilepsy syndromes.

Neurogranin as a predictor of memory and executive function decline in MCI patients.

PubMed

Headley, Alison; De Leon-Benedetti, Andres; Dong, Chuanhui; Levin, Bonnie; Loewenstein, David; Camargo, Christian; Rundek, Tatjana; Zetterberg, Henrik; Blennow, Kaj; Wright, Clinton B; Sun, Xiaoyan

2018-03-06

To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313, p = 0.0068 and β = -0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ 42 ) were controlled for in these analyses. High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ 42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD. © 2018 American Academy of Neurology.

Using Multivariate Base Rates to Interpret Low Scores on an Abbreviated Battery of the Delis-Kaplan Executive Function System.

PubMed

Karr, Justin E; Garcia-Barrera, Mauricio A; Holdnack, James A; Iverson, Grant L

2017-05-01

Executive function consists of multiple cognitive processes that operate as an interactive system to produce volitional goal-oriented behavior, governed in large part by frontal microstructural and physiological networks. Identification of deficits in executive function in those with neurological or psychiatric conditions can be difficult because the normal variation in executive function test scores, in healthy adults when multiple tests are used, is largely unknown. This study addresses that gap in the literature by examining the prevalence of low scores on a brief battery of executive function tests. The sample consisted of 1,050 healthy individuals (ages 16-89) from the standardization sample for the Delis-Kaplan Executive Function System (D-KEFS). Seven individual test scores from the Trail Making Test, Color-Word Interference Test, and Verbal Fluency Test were analyzed. Low test scores, as defined by commonly used clinical cut-offs (i.e., ≤25th, 16th, 9th, 5th, and 2nd percentiles), occurred commonly among the adult portion of the D-KEFS normative sample (e.g., 62.8% of the sample had one or more scores ≤16th percentile, 36.1% had one or more scores ≤5th percentile), and the prevalence of low scores increased with lower intelligence and fewer years of education. The multivariate base rates (BR) in this article allow clinicians to understand the normal frequency of low scores in the general population. By use of these BRs, clinicians and researchers can improve the accuracy with which they identify executive dysfunction in clinical groups, such as those with traumatic brain injury or neurodegenerative diseases. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Effect of neurological monitoring in postoperative 5-15 days residual thyroidectomy after primary thyroid cancer surgery.

PubMed

Long, Miao-Yun; Diao, Fei-Yu; Peng, Li-Na; Tan, Lang-Ping; Zhu, Yue; Huang, Kai; Li, Hong-Hao

2018-05-16

To explore the application of intraoperative neurological monitoring in residual thyroidectomy 5-15 days after thyroid cancer operation and the influence on postoperative serum thyroglobulin (Tg), recurrent laryngeal nerve and function of parathyroid glands. Material of patients receiving thyroid surgery from January 2010 to December 2016 was retrospectively analyzed. Cases meeting with standards were enrolled for analysis and the patients were divided into neurological monitoring group and non-neurological monitoring group in line with the use of neurological monitoring during the operation. Recurrent laryngeal nerve-injured hoarseness, hypoparathyroidism and concentration of serum Tg before and after the surgery were collected and analyzed. Four-hundred and thirty-five patients met with standards, among which 227 from neurological monitoring group and 208 from non-neurological monitoring group. Temporary hoarseness rate of non-neurological monitoring group and neurological monitoring group was 8.67% and 2.2%. Permanent hoarseness rate of non-neurological monitoring group and neurological monitoring group was 1.92% and 0.44%. Temporary hypoparathyroidism rate of non-neurological monitoring group and neurological monitoring group was 18.75% and 7.48%. Permanent hypoparathyroidism rate of non-neurological monitoring group and neurological monitoring group was 1.92% and 0.88%. Average Tg concentration 1 month after the surgery in non-neurological monitoring group and neurological monitoring group was 2.82 and 1.37 ng/mL, respectively. Rate of average Tg concentration less than 1 ng/mL 1 month after the surgery in non-neurological monitoring group and neurological monitoring group was 45.06% and 67.4%. Intraoperative neurological monitoring can be adopted in residual thyroidectomy in postoperative 5-15 days after primary thyroid cancer surgery, as to reduce incidence rate of recurrent laryngeal nerve injury and hypoparathyroidism and to enhance thorough removal of thyroid tissues and cancer tissues. © 2018 John Wiley & Sons Australia, Ltd.

Batten's Disease: Determining Educational Interventions.

ERIC Educational Resources Information Center

Johnson, Barbara; Jochum, Julie

1996-01-01

This article presents basic information on the causes, physical and emotional characteristics, diagnosis and treatment, and educational implications of Batten's Disease, a degenerative neurological disorder which strikes children and adults, causes progressive loss of neurological function, and leads to eventual premature death. Discussion also…

Symptomatic vertebral hemangioma in pregnancy treated antepartum. A case report with review of literature.

PubMed

Vijay, Kamath; Shetty, Ajoy P; Rajasekaran, S

2008-09-01

Pregnancy related compressive myelopathy secondary to vertebral hemangioma is a rare occurrence and its treatment antepartum is rare. We report a 22-year-old lady in her 26th-week of pregnancy who was treated in two stages--antepartum with a laminectomy and posterior stabilization. This resulted in complete recovery of the neurological deficits. She delivered a normal baby after 3 months, following which a corpectomy and fusion was performed. This two-staged approach appears safe and effective in treating symptomatic vertebral haemangiomas causing neurological deficits during pregnancy. A review of relevant literature has been done.

Predicting autism at birth.

PubMed

Steinman, Gary

2013-07-01

The amounts of at least three biochemical factors are more often abnormal in autistic people than neurologically normal ones. They include insulin-like growth factor, anti-myelin basic protein, and serotonin. This may explain why processes initiated in utero which hinder normal neurogenesis, especially myelination, continue after delivery. Quantitation of these parameters may make possible the calculation of an autism index, anticipating at birth which children will ultimately develop overt autism. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparison for aphasic and control subjects of eye movements hypothesized in neurolinguistic programming.

PubMed

Dooley, K O; Farmer, A

1988-08-01

Neurolinguistic programming's hypothesized eye movements were measured independently using videotapes of 10 nonfluent aphasic and 10 control subjects matched for age and sex. Chi-squared analysis indicated that eye-position responses were significantly different for the groups. Although earlier research has not supported the hypothesized eye positions for normal subjects, the present findings support the contention that eye-position responses may differ between neurologically normal and aphasic individuals.

When to consider thyroid dysfunction in the neurology clinic.

PubMed

Mistry, Niraj; Wass, John; Turner, Martin R

2009-06-01

There are many neurological manifestations of thyroid disease, and thyroid function has taken its place in the "routine bloods" of neurology practice. However, although conditions such as carpal tunnel syndrome prompt thyroid testing despite any clear evidence for this approach, other symptoms of potential significance in terms of thyroid disease may be overlooked in the busy general neurology clinic, or abnormal thyroid tests may be assumed to be incidental. Psychiatric disorders, loss of consciousness, movement disorders and weakness may all be manifestations of primary thyroid disease. This is a symptom-based review where we will consider the evidence (or lack of it) for the association of various neurological problems with thyroid dysfunction, and also the pitfalls in interpretation of the biochemical tests.

The motor repertoire in 3- to 5-month old infants with Down syndrome.

PubMed

Herrero, Dafne; Einspieler, Christa; Panvequio Aizawa, Carolina Y; Mutlu, Akmer; Yang, Hong; Nogolová, Alice; Pansy, Jasmin; Nielsen-Saines, Karin; Marschik, Peter B

2017-08-01

Even though Down syndrome is the most common chromosomal cause of intellectual disability, studies on early development are scarce. To describe movements and postures in 3- to 5-month-old infants with Down syndrome and assess the relation between pre- and perinatal risk factors and the eventual motor performance. Exploratory study; 47 infants with Down syndrome (26 males, 27 infants born preterm, 22 infants with congenital heart disease) were videoed at 10-19 weeks post-term (median=14 weeks). We assessed their Motor Optimality Score (MOS) based on postures and movements (including fidgety movements) and compared it to that of 47 infants later diagnosed with cerebral palsy and 47 infants with a normal neurological outcome, matched for gestational and recording ages. The MOS (median=13, range 10-28) was significantly lower than in infants with a normal neurological outcome (median=26), but higher than in infants later diagnosed with cerebral palsy (median=6). Fourteen infants with Down syndrome showed normal fidgety movements, 13 no fidgety movements, and 20 exaggerated, too fast or too slow fidgety movements. A lack of movements to the midline and several atypical postures were observed. Neither preterm birth nor congenital heart disease was related to aberrant fidgety movements or reduced MOS. The heterogeneity in fidgety movements and MOS add to an understanding of the large variability of the early phenotype of Down syndrome. Studies on the predictive values of the early spontaneous motor repertoire, especially for the cognitive outcome, are warranted. The significance of this exploratory study lies in its minute description of the motor repertoire of infants with Down syndrome aged 3-5 months. Thirty percent of infants with Down syndrome showed age-specific normal fidgety movements. The rate of abnormal fidgety movements (large amplitude, high/slow speed) or a lack of fidgety movements was exceedingly high. The motor optimality score of infants with Down syndrome was lower than in infants with normal neurological outcome but higher than in infants who were later diagnosed with cerebral palsy. Neither preterm birth nor congenital heart disease were related to the motor performance at 3-5 months. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Electroacupuncture modulates stromal cell-derived factor-1α expression and mobilization of bone marrow endothelial progenitor cells in focal cerebral ischemia/reperfusion model rats.

PubMed

Xie, Chenchen; Gao, Xiang; Luo, Yong; Pang, Yueshan; Li, Man

2016-10-01

Stromal cell-derived factor-1α(SDF-1α) plays a crucial role in regulating the mobilization, migration and homing of endothelial progenitor cells(EPCs). Electroacupuncture(EA), a modern version of Traditional Chinese Medicine, can improve neurological recovery and angiogenesis in cerebral ischemic area. This study aimed to investigate the effects of electroacupuncture(EA) on the mobilization and migration of bone marrow EPCs and neurological functional recovery in rats model after focal cerebral ischemia/reperfusion and the potentially involved mechanisms. Sprague-Dawley rats received filament occlusion of the right middle cerebral artery for 2h followed by reperfusion for 12h, 1d, 2d, 3d, 7d respectively. Rats were randomly divided into sham group, model group and EA group. After 2h of the reperfusion, EA was given at the "Baihui" (GV 20)/Siguan ("Hegu" (LI 4)/"Taichong" (LR 3)) acupoints in the EA group. Modified neurological severity score (mNSS) was used to assess the neurological functional recovery. EPCs number and SDF-1α level in bone marrow(BM) and peripheral blood(PB) were detected by using fluorescence-activated cell sorting (FACS) analysis and quantitative real time polymerase chain reaction (qRT-PCR) respectively. An mNSS test showed that EA treatment significantly improved the neurological functional outcome. EPCs number in PB and BM were obviously increased in the EA group. After cerebral ischemia, the SDF-1α level was decreased in BM while it was increased in PB, which implied a gradient of SDF-1α among BM and PB after ischemia. It suggested that the forming of SDF-1α concentration gradient can induce the mobilization and homing of EPCs. Eletroacupuncture as a treatment can accelerate and increase the forming of SDF-1α concentration gradient to further induce the mobilization of EPCs and angiogenesis in ischemic brain and improve the neurological function recovery. Copyright © 2016 Elsevier B.V. All rights reserved.