Science.gov

Sample records for reversible cerebellar syndrome

  1. [Cerebellar cognitive affective syndrome secondary to a cerebellar tumour].

    PubMed

    Domínguez-Carral, J; Carreras-Sáez, I; García-Peñas, J J; Fournier-Del Castillo, C; Villalobos-Reales, J

    2015-01-01

    Cerebellar cognitive affective syndrome is characterized by disturbances of executive function, impaired spatial cognition, linguistic difficulties, and personality change. The case of an 11 year old boy is presented, with behavior problems, learning difficulties and social interaction problems. In the physical examination he had poor visual contact, immature behavior, reduced expressive language and global motor disability with gait dyspraxia, with no defined cerebellar motor signs. In the neuropsychological evaluation he has a full scale overall intellectual quotient of 84, with signs of cerebellar cognitive affective syndrome. A tumour affecting inferior cerebellar vermis was observed in the magnetic resonance imaging, which had not significantly grown during 5 years of follow up. The cerebellum participates in controlling cognitive and affective functions. Cerebellar pathology must be considered in the differential diagnosis of children with cognitive or learning disorder with associated behavioral and emotional components.

  2. Altered cerebellar feedback projections in Asperger syndrome.

    PubMed

    Catani, Marco; Jones, Derek K; Daly, Eileen; Embiricos, Nitzia; Deeley, Quinton; Pugliese, Luca; Curran, Sarah; Robertson, Dene; Murphy, Declan G M

    2008-07-15

    It has been proposed that the biological basis of autism spectrum disorder includes cerebellar 'disconnection'. However, direct in vivo evidence in support of this is lacking. Here, the microstructural integrity of cerebellar white matter in adults with Asperger syndrome was studied using diffusion tensor magnetic resonance tractography. Fifteen adults with Asperger syndrome and 16 age-IQ-gender-matched healthy controls underwent diffusion tensor magnetic resonance imaging. For each subject, tract-specific measurements of mean diffusivity and fractional anisotropy were made within the inferior, middle, superior cerebellar peduncles and short intracerebellar fibres. No group differences were observed in mean diffusivity. However, people with Asperger syndrome had significantly lower fractional anisotropy in the short intracerebellar fibres (p<0.001) and right superior cerebellar (output) peduncle (p<0.001) compared to controls; but no difference in the input tracts. Severity of social impairment, as measured by the Autistic Diagnostic Interview, was negatively correlated with diffusion anisotropy in the fibres of the left superior cerebellar peduncle. These findings suggest a vulnerability of specific cerebellar neural pathways in people with Asperger syndrome. The localised abnormalities in the main cerebellar outflow pathway may prevent the cerebral cortex from receiving those cerebellar feedback inputs necessary for a successful adaptive social behaviour.

  3. Acute cerebellar ataxia, acute cerebellitis, and opsoclonus-myoclonus syndrome.

    PubMed

    Desai, Jay; Mitchell, Wendy G

    2012-11-01

    Acute cerebellar ataxia and acute cerebellitis represent a process characterized by parainfectious, postinfectious, or postvaccination cerebellar inflammation. There is considerable overlap between these entities. The mildest cases of acute cerebellar ataxia represent a benign condition that is characterized by acute truncal and gait ataxia, variably with appendicular ataxia, nystagmus, dysarthria, and hypotonia. It occurs mostly in young children, presents abruptly, and recovers over weeks. Neuroimaging is normal. Severe cases of cerebellitis represent the other end of the spectrum, presenting with acute cerebellar signs often overshadowed by alteration of consciousness, focal neurological deficits, raised intracranial pressure, hydrocephalus, and even herniation. Neuroimaging is abnormal and the prognosis is less favorable than in acute cerebellar ataxia. Acute disseminated encephalomyelitis may be confused with acute cerebellitis when the clinical findings are predominantly cerebellar, but lesions on neuroimaging are usually widespread. Paraneoplastic opsoclonus-myoclonus syndrome is often initially misdiagnosed as acute cerebellar ataxia, but has very specific features, course, and etiopathogensis.

  4. The Cerebellar Mutism Syndrome and Its Relation to Cerebellar Cognitive Function and the Cerebellar Cognitive Affective Disorder

    ERIC Educational Resources Information Center

    Wells, Elizabeth M.; Walsh, Karin S.; Khademian, Zarir P.; Keating, Robert F.; Packer, Roger J.

    2008-01-01

    The postoperative cerebellar mutism syndrome (CMS), consisting of diminished speech output, hypotonia, ataxia, and emotional lability, occurs after surgery in up to 25% of patients with medulloblastoma and occasionally after removal of other posterior fossa tumors. Although the mutism is transient, speech rarely normalizes and the syndrome is…

  5. Dissociation of locomotor and cerebellar deficits in a murine Angelman syndrome model

    PubMed Central

    Bruinsma, Caroline F.; Schonewille, Martijn; Gao, Zhenyu; Aronica, Eleonora M.A.; Judson, Matthew C.; Philpot, Benjamin D.; Hoebeek, Freek E.; van Woerden, Geeske M.; De Zeeuw, Chris I.; Elgersma, Ype

    2015-01-01

    Angelman syndrome (AS) is a severe neurological disorder that is associated with prominent movement and balance impairments that are widely considered to be due to defects of cerebellar origin. Here, using the cerebellar-specific vestibulo-ocular reflex (VOR) paradigm, we determined that cerebellar function is only mildly impaired in the Ube3am–/p+ mouse model of AS. VOR phase-reversal learning was singularly impaired in these animals and correlated with reduced tonic inhibition between Golgi cells and granule cells. Purkinje cell physiology, in contrast, was normal in AS mice as shown by synaptic plasticity and spontaneous firing properties that resembled those of controls. Accordingly, neither VOR phase-reversal learning nor locomotion was impaired following selective deletion of Ube3a in Purkinje cells. However, genetic normalization of αCaMKII inhibitory phosphorylation fully rescued locomotor deficits despite failing to improve cerebellar learning in AS mice, suggesting extracerebellar circuit involvement in locomotor learning. We confirmed this hypothesis through cerebellum-specific reinstatement of Ube3a, which ameliorated cerebellar learning deficits but did not rescue locomotor deficits. This double dissociation of locomotion and cerebellar phenotypes strongly suggests that the locomotor deficits of AS mice do not arise from impaired cerebellar cortex function. Our results provide important insights into the etiology of the motor deficits associated with AS. PMID:26485287

  6. Cerebellar cognitive affective syndrome presented as severe borderline personality disorder.

    PubMed

    Pesic, Danilo; Peljto, Amir; Lukic, Biljana; Milovanovic, Maja; Svetozarevic, Snezana; Lecic Tosevski, Dusica

    2014-01-01

    An increasing number of findings confirm the significance of cerebellum in affecting regulation and early learning. Most consistent findings refer to association of congenital vermis anomalies with deficits in nonmotor functions of cerebellum. In this paper we presented a young woman who was treated since sixteen years of age for polysubstance abuse, affective instability, and self-harming who was later diagnosed with borderline personality disorder. Since the neurological and neuropsychological reports pointed to signs of cerebellar dysfunction and dysexecutive syndrome, we performed magnetic resonance imaging of brain which demonstrated partially developed vermis and rhombencephalosynapsis. These findings match the description of cerebellar cognitive affective syndrome and show an overlap with clinical manifestations of borderline personality disorder.

  7. Posterior Reversible Encephalopathy Syndrome

    PubMed Central

    Algahtani, Abdulhadi; Aldarmahi, Ahmad; Hmoud, Mohammed; Marzuk, Yousef; Shirah, Bader

    2016-01-01

    Objectives: Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome characterized by headache, altered mental status, seizures, or loss of vision. In this study, we report the largest series of PRES coming from Saudi Arabia and explore the etiology, clinical presentation, and outcome. We also report new imaging findings associated with this condition. Methods: We performed a retrospective study of all cases of PRES admitted to King Abdulaziz Medical City, Jeddah, Saudi Arabia, between the years 2005 and 2015. A neurologist reviewed all charts and analyzed the clinical presentations, etiological factors, and outcomes, and a neuroradiologist reviewed the imaging studies. Only patients with clinical and imaging features consistent with PRES were included in the study. Results: We collected 31 patients who had clinical and radiological features consistent with PRES. Females were more affected than males (18 females and 13 males), and patients’ age ranged from 6 to 95 years, with a mean of 38.3 years. Patients were treated by removing the precipitating causes and treating the underlying conditions. Resolution of neurologic signs occurred within 2 to 3 weeks in all patients. Conclusion: In our opinion, PRES itself is usually a benign condition with complete recovery if the condition is recognized early and managed appropriately. Although clinical signs are nonspecific, the constellation of symptoms including headache, visual problems, seizures, and altered level of consciousness should suggest the possibility of PRES, especially in high-risk group. Abnormalities on magnetic resonance imaging are often characteristic and may be the first clue to the diagnosis. PMID:28042366

  8. Surface-binding autoantibodies to cerebellar neurons in opsoclonus syndrome.

    PubMed

    Blaes, Franz; Fühlhuber, Verena; Korfei, Martina; Tschernatsch, Marlene; Behnisch, Wolfgang; Rostasy, Kevin; Hero, Barbara; Kaps, Manfred; Preissner, Klaus T

    2005-08-01

    Childhood opsoclonus-myoclonus syndrome can occur with or without associated neuroblastoma. An autoimmune pathogenesis has been discussed for both forms. We show here that the majority of children with opsoclonus-myoclonus syndrome (10/14) have autoantibodies binding to the surface of isolated rat cerebellar granular neurons. In some patients, these antibodies are masked by IgG binding to ubiquitous surface antigens, which could be removed by preincubation with the nonneuronal control cell line HEK 293. A newly introduced competitive binding assay showed that the surface binding is directed against the same autoantigen in different patients. Therefore, we hypothesize that opsoclonus-myoclonus syndrome may be the result of an autoimmune process against a neuronal surface protein.

  9. Reversible cortical blindness: posterior reversible encephalopathy syndrome.

    PubMed

    Bandyopadhyay, Sabyasachi; Mondal, Kanchan Kumar; Das, Somnath; Gupta, Anindya; Biswas, Jaya; Bhattacharyya, Subir Kumar; Biswas, Gautam

    2010-11-01

    Cortical blindness is defined as visual failure with preserved pupillary reflexes in structurally intact eyes due to bilateral lesions affecting occipital cortex. Bilateral oedema and infarction of the posterior and middle cerebral arterial territory, trauma, glioma and meningioma of the occipital cortex are the main causes of cortical blindness. Posterior reversible encephalopathy syndrome (PRES) refers to the reversible subtype of cortical blindness and is usually associated with hypertension, diabetes, immunosuppression, puerperium with or without eclampsia. Here, 3 cases of PRES with complete or partial visual recovery following treatment in 6-month follow-up are reported.

  10. Cerebellar Degeneration as a Rare Paraneoplastic Syndrome in a Child With Hodgkin Lymphoma.

    PubMed

    Avramova, Boryana E; Hristova, Tanya; Yordanova, Maya; Vlahova, Irena; Muchinova, Albena; Bojinova, Veneta; Konstantinov, Dobrin

    2016-08-01

    We report a rare case of cerebellar degeneration as a paraneoplastic syndrome in an 8-year-old boy with Hodgkin lymphoma that presented during first-line treatment. Antibodies against Purkinje cells (anti-Tr antibodies) were detected in the serum of the patient. After successful treatment of the lymphoma, the cerebellar symptoms resolved partially. Childhood presentation of paraneoplastic cerebellar degeneration is extremely rare, with only a few reports in the literature. For this reason, the description of all such cases contributes to the enrichment of the medical knowledge and will improve the diagnosis and the treatment of this complication.

  11. A case report of patient with cerebellar variant of stiff person syndrome.

    PubMed

    Maludzińska, Ewa; Rudzińska, Monika; Stępień, Artur; Szczudlik, Andrzej

    2016-01-01

    Stiff person syndrome (SPS) is a rare autoimmune neurological disorder with antibodies against antigens involved in neurotransmission of gamma-aminobutyric acid (GABA). About 10% of patients with SPS may develop ataxia. This cerebellar variant is a distinct subset of SPS with more severe and complex clinical phenotype. We report the clinical, neuropsychological and neuroradiological findings in a 39-year-old female with cerebellar variant of SPS.

  12. Nonsurgical cerebellar mutism (anarthria) in two children.

    PubMed

    Mewasingh, Leena D; Kadhim, Hazim; Christophe, Catherine; Christiaens, Florence J; Dan, Bernard

    2003-01-01

    Cerebellar mutism (anarthria) is a well-described complication of posterior fossa tumor resection. It is accompanied by a characteristic behavior including irritability and autistic features. This syndrome is typically reversible within days to months. Underlying pathophysiology is unknown. We describe two children who presented with a similar clinical finding after nonsurgical cerebellar involvement, hemolytic-uremic syndrome in one and cerebellitis in the other. Postmortem pathologic findings in the first patient indicated cerebellar ischemic necrosis. Single-photon emission computed tomography in the second patient revealed diffuse cerebellar hypoperfusion with no supratentorial abnormalities, refuting a phenomenon of diaschisis between cerebellar and frontal connections. These findings confirm that this clinical syndrome may occur in a nonsurgical, nontraumatic context. They are consistent with recent integrative hypotheses explaining cerebellar anarthria.

  13. Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome: a slowly progressive disorder with stereotypical presentation.

    PubMed

    Cazzato, Daniele; Dalla Bella, Eleonora; Dacci, Patrizia; Mariotti, Caterina; Lauria, Giuseppe

    2016-02-01

    Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a newly described condition with onset in adulthood, characterized by progressive balance impairment and sensory disturbances in the lower limbs, which can severely affect patients' quality of life. Its pathogenesis remains obscure and the diagnosis challenging. We described four patients complaining of slowly progressive gait unbalance and sensory disturbances at the feet followed, after a period ranging 2-6 years, by cerebellar dysfunction. All patients showed gait and limb ataxia, positive Romberg sign, cerebellar dysarthria, gaze-evoked nystagmus, absent deep tendon reflexes, and impaired vibratory sensation. Nerve conduction studies revealed axonal sensory neuropathy, brain magnetic resonance imaging showed cerebellar atrophy, and otoneurological investigation demonstrated bilateral vestibular areflexia with impaired vestibulo-ocular reflexes. The diagnosis of CANVAS should be suspected on clinical ground based on homogeneous course of symptoms and signs, and addressed by video-oculography eye movement recording.

  14. Cerebellar Mutism Syndrome After Posterior Fossa Surgery: A Report of Two Cases of Pilocytic Astrocytoma

    PubMed Central

    GÜNDÜZ, Hasan Burak; YASSA, Mustafa İlker Kuntay; OFLUOĞLU, Ali Ender; POSTALCI, Lütfü; EMEL, Erhan

    2013-01-01

    Cerebellar mutism is a type of syndrome including decreased speech, hypotonia, ataxia and emotional instability which occurs after posterior fossa surgery. It has been first reported by Rekate et al. and Yonemasu in 1985. It is well known that long tract signs and lower cranial nerve involvement are not seen with this syndrome and understanding is preserved. However, the pathophysiology of cerebellar mutism has not been well clarified yet. It is mainly seen in patients with medulloblastoma and brainstem involvement. In this report, we present two extraordinary cases of cerebellar mutism after posterior fossa surgery. They were considered extraordinary because their hystopathological analysis results yielded pilocytic astrocytoma which is out of the predefined risk factors.

  15. Cerebellar cognitive affective syndrome without global mental retardation in two relatives with Gillespie syndrome.

    PubMed

    Mariën, Peter; Brouns, Raf; Engelborghs, Sebastiaan; Wackenier, Peggy; Verhoeven, Jo; Ceulemans, Berten; De Deyn, Peter P

    2008-01-01

    Although previous studies of Gillespie syndrome have systematically reported a generalized delay of cognitive development (mental retardation or oligophrenia), psychometric data to substantiate this view are strikingly absent. In the present study two first degree relatives (mother and daughter) with Gillespie syndrome were neuropsychologically investigated. Aside from a marked asymmetry in the Wechsler-IQ profile, consisting of significantly better results on the verbal [Verbal IQ (VIQ)] than on the nonverbal part [Performance IQ (PIQ)] of the test, cognitive and behavioral assessments revealed a pattern of abnormalities that closely resembles the "cerebellar cognitive and affective syndrome" (CeCAS) (Schmahmann and Sherman, 1998). Aside from prefrontal dysexecutive dysfunctions such as disturbed cognitive planning and set-shifting, parietal lobe involvement was reflected by impaired visuo-spatial memory and visuo-spatial disorganization in constructional tasks. Within the linguistic domain involvement of the prefrontal and temporal language regions was indicated by impaired letter fluency, incidences of agrammatism, apraxia of speech and disrupted language dynamics. With regard to mood and behavior, a number of personality and affective characteristics were found that are typically associated with prefrontal lobe damage and dysfunction of limbic related regions in the cingulate and parahippocampal gyri. Disinhibited symptoms characterized behavior and affect of the mother while the daughter displayed a variety of inhibited symptoms. As a result, behavioral and cognitive findings in these patients do not support the prevailing view of a global mental retardation as a cardinal feature of Gillespie syndrome but primarily reflect cerebellar induced neurobehavioral dysfunctions following disruption of the cerebrocerebellar anatomical circuitry.

  16. Cerebellar Ataxia with Bilateral Vestibulopathy: Description of a Syndrome and Its Characteristic Clinical Sign

    ERIC Educational Resources Information Center

    Migliaccio, Americo A.; Halmagyi, G. Michael; McGarvie, Leigh A.; Cremer, Phillip D.

    2004-01-01

    We report four patients with the syndrome of cerebellar ataxia with bilateral vestibulopathy (CABV) and, using search coil oculography, we validate its characteristic clinical sign, namely impairment of the visually enhanced vestibulo-ocular reflex (VVOR) or doll's head reflex. In our four patients, CABV began in the sixth decade of life; they are…

  17. Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhäuser syndrome.

    PubMed Central

    Rump, R; Hamel, B C; Pinckers, A J; van Dop, P A

    1997-01-01

    We describe two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia, Boucher-Neuhäuser syndrome, a rare but distinct pleiotropic single gene disorder with an autosomal recessive pattern of inheritance. The cases presented illustrate that this syndrome is still poorly recognised. We provide a review and analysis of previously reported cases and the differential diagnosis, which might aid in the identification of additional cases. Images PMID:9321767

  18. Neuropsychological evaluation in an adolescent with cerebellar hypoplasia diagnosed with Asperger's Syndrome.

    PubMed

    Moss, Robert A

    2013-01-01

    There is a growing body of literature describing cases of cognitive impairment associated with both acquired and developmental damage to the cerebellum. The current case study describes such a case involving a 17-year-old male with cerebellar hypoplasia, having incomplete formation of the vermis and atrophy of the interior cerebellar hemispheres. He had previously been diagnosed as having Asperger's Syndrome. A full neuropsychological evaluation was performed, including effort testing. This is followed by a comparison of the current results to previously reported cases, with a discussion of the heterogeneity of deficits associated with developmental cerebellum malformation.

  19. ZNHIT3 is defective in PEHO syndrome, a severe encephalopathy with cerebellar granule neuron loss.

    PubMed

    Anttonen, Anna-Kaisa; Laari, Anni; Kousi, Maria; Yang, Yawei J; Jääskeläinen, Tiina; Somer, Mirja; Siintola, Eija; Jakkula, Eveliina; Muona, Mikko; Tegelberg, Saara; Lönnqvist, Tuula; Pihko, Helena; Valanne, Leena; Paetau, Anders; Lun, Melody P; Hästbacka, Johanna; Kopra, Outi; Joensuu, Tarja; Katsanis, Nicholas; Lehtinen, Maria K; Palvimo, Jorma J; Lehesjoki, Anna-Elina

    2017-03-01

    Progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an early childhood onset, severe autosomal recessive encephalopathy characterized by extreme cerebellar atrophy due to almost total granule neuron loss. By combining homozygosity mapping in Finnish families with Sanger sequencing of positional candidate genes and with exome sequencing a homozygous missense substitution of leucine for serine at codon 31 in ZNHIT3 was identified as the primary cause of PEHO syndrome. ZNHIT3 encodes a nuclear zinc finger protein previously implicated in transcriptional regulation and in small nucleolar ribonucleoprotein particle assembly and thus possibly to pre-ribosomal RNA processing. The identified mutation affects a highly conserved amino acid residue in the zinc finger domain of ZNHIT3. Both knockdown and genome editing of znhit3 in zebrafish embryos recapitulate the patients' cerebellar defects, microcephaly and oedema. These phenotypes are rescued by wild-type, but not mutant human ZNHIT3 mRNA, suggesting that the patient missense substitution causes disease through a loss-of-function mechanism. Transfection of cell lines with ZNHIT3 expression vectors showed that the PEHO syndrome mutant protein is unstable. Immunohistochemical analysis of mouse cerebellar tissue demonstrated ZNHIT3 to be expressed in proliferating granule cell precursors, in proliferating and post-mitotic granule cells, and in Purkinje cells. Knockdown of Znhit3 in cultured mouse granule neurons and ex vivo cerebellar slices indicate that ZNHIT3 is indispensable for granule neuron survival and migration, consistent with the zebrafish findings and patient neuropathology. These results suggest that loss-of-function of a nuclear regulator protein underlies PEHO syndrome and imply that establishment of its spatiotemporal interaction targets will be the basis for developing therapeutic approaches and for improved understanding of cerebellar development.

  20. Diffuse large B-cell lymphoma of stomach presenting with paraneoplastic cerebellar degeneration syndrome.

    PubMed

    Nomani, Ali Zohair; Wazir, Marina; Kashmir, Saba Binte; Qureshi, Muhammad Saleem

    2014-03-01

    Paraneoplastic syndromes are most often diagnosed in the setting of a known malignancy. It is not uncommon for a paraneoplastic disorder to develop before a cancer is identified. While syndrome of cerebellar degeneration has been identified as a paraneoplastic manifestation of Hodgkin's lymphoma, thymoma, lung and breast cancer, ovarian and testicular tumors, melanoma, renal cell carcinoma, follicular lymphoma and adenocarcinoma of stomach, its association with non-Hodgkin's lymphoma and particularly diffuse large B-cell lymphoma has not been established previously. This case report describes the primary presentation with signs of paraneoplastic cerebellar degeneration as the only manifestation of an underlying diffuse large B-cell lymphoma making it the first of its kind to be formally reported. Furthermore, it also includes the identification of associated paraneoplastic antibodies for this particular syndrome.

  1. Reversing the Effects of Fragile X Syndrome

    ERIC Educational Resources Information Center

    Ogren, Marilee P.; Lombroso, Paul J.

    2008-01-01

    A research on how synaptic plasticity is abnormally regulated in fragile X syndrome and how this abnormality can be reversed by therapeutic interventions is presented. Fragile X syndrome is a disorder of synaptic plasticity that contributes to abnormal development and interferes with normal learning and memory.

  2. Neuropathology of a fatal case of posterior reversible encephalopathy syndrome.

    PubMed

    Kheir, John N; Lawlor, Michael W; Ahn, Edward S; Lehmann, Leslie; Riviello, James J; Silvera, V Michelle; McManus, Michael; Folkerth, Rebecca D

    2010-01-01

    The pathology of posterior reversible encephalopathy syndrome (PRES) is undefined, since it is rarely fatal and is biopsied in only exceptional circumstances. We describe rapidly progressive PRES following stem cell transplant for acute lymphoblastic leukemia. After development of altered mental status, this 8-year-old girl had T2 prolongation of the white matter in a posterior-dominant distribution, eventually developing cerebellar edema, hemorrhage, hydrocephalus, and herniation. Despite surgical and medical management, she died 36 hours later. At autopsy, the occipital and cerebellar white matter and focal occipital cortical gray matter showed a spectrum of microvascular changes, including dilated perivascular spaces containing proteinaceous exudates and macrophages, as well as fibrinoid necrosis and acute hemorrhage, in a distribution corresponding to the neuroimaging abnormalities and reminiscent of those seen in patients with acute hypertensive encephalopathy. Of note, similar microvascular changes were not seen in the kidney or other systemic sites. Thus, the findings indicate a brain-specific microvascular compromise as the substrate of PRES, at least in the rare instance of cases progressing to fatal outcome.

  3. Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome

    PubMed Central

    Arbib, Michael A.; Baldassarre, Gianluca

    2017-01-01

    Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area. PMID:28358814

  4. Hind brain agenesis a rare imaging findings in cerebro cerebellar lissencephalic syndrome.

    PubMed

    Mundaganur, Praveen M; Solwalkar, Pradeep; Nimbal, Vishal

    2014-01-01

    A case report of cerebro cerebellar lissencephaly shows complete agenesis of cerebellum and brainstem which is rare imaging finding of group lissencephaly (type I lissencephaly). Though agenesis of cerebellum and brainstem were included in literature, in most of the cases we saw a hypoplasia or atrophy of cerebellum in lissencephaly syndrome. The CT scan findings of this patient shows features of lissencephaly with complete agenesis of brain stem and cerebellum associated with multiple congenital abnormalities.

  5. Holoprosencephaly with cerebellar vermis hypoplasia in 13q deletion syndrome: Critical region for cerebellar dysgenesis within 13q32.2q34.

    PubMed

    Mimaki, Masakazu; Shiihara, Takashi; Watanabe, Mio; Hirakata, Kyoko; Sakazume, Satoru; Ishiguro, Akio; Shimojima, Keiko; Yamamoto, Toshiyuki; Oka, Akira; Mizuguchi, Masashi

    2015-08-01

    We describe two unrelated patients with terminal deletions in the long arm of chromosome 13 showing brain malformation consisting of holoprosencephaly and cerebellar vermis hypoplasia. Array comparative genomic hybridization analysis revealed a pure terminal deletion of 13q31.3q34 in one patient and a mosaic ring chromosome with 13q32.2q34 deletion in the other. Mutations in ZIC2, located within region 13q32, cause holoprosencephaly, whereas the 13q32.2q32.3 region is associated with cerebellar vermis hypoplasia (Dandy-Walker syndrome). The rare concurrence of these major brain malformations in our patients provides further evidence that 13q32.2q32.3 deletion, harboring ZIC2 and ZIC5, leads to cerebellar dysgenesis.

  6. Clinical, neuroradiological and molecular characterization of cerebellar dysplasia with cysts (Poretti-Boltshauser syndrome)

    PubMed Central

    Romani, Marta; Ginevrino, Monia; Mazza, Tommaso; Aiello, Chiara; Zanni, Ginevra; Baumgartner, Bastian; Borgatti, Renato; Brockmann, Knut; Camacho, Ana; Cantalupo, Gaetano; Haeusler, Martin; Hikel, Christiane; Klein, Andrea; Mandrile, Giorgia; Mercuri, Eugenio; Rating, Dietz; Romaniello, Romina; Santorelli, Filippo Maria; Schimmel, Mareike; Spaccini, Luigina; Teber, Serap; von Moers, Arpad; Wente, Sarah; Ziegler, Andreas; Zonta, Andrea; Bertini, Enrico; Boltshauser, Eugen; Valente, Enza Maria

    2016-01-01

    Cerebellar dysplasia with cysts and abnormal shape of the fourth ventricle, in the absence of significant supratentorial anomalies and of muscular involvement, defines recessively inherited Poretti-Boltshauser syndrome (PBS). Clinical features comprise non-progressive cerebellar ataxia, intellectual disability of variable degree, language impairment, ocular motor apraxia and frequent occurrence of myopia or retinopathy. Recently, loss-of-function variants in the LAMA1 gene were identified in six probands with PBS. Here we report the detailed clinical, neuroimaging and genetic characterization of 18 PBS patients from 15 unrelated families. Biallelic LAMA1 variants were identified in 14 families (93%). The only non-mutated proband presented atypical clinical and neuroimaging features, challenging the diagnosis of PBS. Sixteen distinct variants were identified, which were all novel. In particular, the frameshift variant c.[2935delA] recurred in six unrelated families on a shared haplotype, suggesting a founder effect. No LAMA1 variants could be detected in 27 probands with different cerebellar dysplasias or non-progressive cerebellar ataxia, confirming the strong correlate between LAMA1 variants and PBS. PMID:26932191

  7. Clinical, neuroradiological and molecular characterization of cerebellar dysplasia with cysts (Poretti-Boltshauser syndrome).

    PubMed

    Micalizzi, Alessia; Poretti, Andrea; Romani, Marta; Ginevrino, Monia; Mazza, Tommaso; Aiello, Chiara; Zanni, Ginevra; Baumgartner, Bastian; Borgatti, Renato; Brockmann, Knut; Camacho, Ana; Cantalupo, Gaetano; Haeusler, Martin; Hikel, Christiane; Klein, Andrea; Mandrile, Giorgia; Mercuri, Eugenio; Rating, Dietz; Romaniello, Romina; Santorelli, Filippo Maria; Schimmel, Mareike; Spaccini, Luigina; Teber, Serap; von Moers, Arpad; Wente, Sarah; Ziegler, Andreas; Zonta, Andrea; Bertini, Enrico; Boltshauser, Eugen; Valente, Enza Maria

    2016-08-01

    Cerebellar dysplasia with cysts and abnormal shape of the fourth ventricle, in the absence of significant supratentorial anomalies and of muscular involvement, defines recessively inherited Poretti-Boltshauser syndrome (PBS). Clinical features comprise non-progressive cerebellar ataxia, intellectual disability of variable degree, language impairment, ocular motor apraxia and frequent occurrence of myopia or retinopathy. Recently, loss-of-function variants in the LAMA1 gene were identified in six probands with PBS. Here we report the detailed clinical, neuroimaging and genetic characterization of 18 PBS patients from 15 unrelated families. Biallelic LAMA1 variants were identified in 14 families (93%). The only non-mutated proband presented atypical clinical and neuroimaging features, challenging the diagnosis of PBS. Sixteen distinct variants were identified, which were all novel. In particular, the frameshift variant c.[2935delA] recurred in six unrelated families on a shared haplotype, suggesting a founder effect. No LAMA1 variants could be detected in 27 probands with different cerebellar dysplasias or non-progressive cerebellar ataxia, confirming the strong correlate between LAMA1 variants and PBS.

  8. Absence of PAX6 gene mutations in Gillespie syndrome (partial aniridia, cerebellar ataxia, and mental retardation)

    SciTech Connect

    Glaser, T.; Maas, R.L. ); Ton, C.C.T.; Housman, D.E. ); Mueller, R.; Oliver, C. ); Petzl-Erler, M.L. ); Nevin, N.C. )

    1994-01-01

    The PAX6 gene is expressed at high levels in the developing eye and cerebellum and is mutated in patients with autosomal dominant aniridia. The authors have tested the role of PAX6 mutations in three families with Gillespie syndrome, a rare autosomal recessive condition consisting of partial aniridia, cerebellar ataxia, and mental retardation. Single-strand conformational polymorphism analysis of affected individuals revealed no alteration of PAX6 sequences. In two families, the disease trait segregates independently from chromosome 11p markers flanking PAX6. The authors conclude that Gillespie syndrome is genetically distinct from autosomal dominant aniridia. 28 refs., 2 figs., 1 tab.

  9. [Cerebellar hypoplasias].

    PubMed

    Safronova, Marta Maia; Barbot, Clara; Resende Pereira, Jorge

    2010-01-01

    Cerebellar hypoplasias are cerebellar malformations with small but completely formed cerebellum. They can be divided in focal and in diffuse or generalized. It is sometimes difficult to make distinction between cerebellar atrophy (progressive condition) and hipoplasia (not progressive condition). Focal hypoplasias are restricted to one cerebellar hemisphere or to the vermis. Diffuse hypoplasias refer to both cerebellar hemispheres and vermis. If there is associated IVth ventricle enlargement, hypoplasias occur in the context of Dandy-Walker complex, a continuum of posterior fossa cystic anomalies. A revision of cerebellar hypoplasias and associated pathology is done, illustrated with 22 cases tha include focal and diffuse cerebellar hypoplasias, Dandy-Walker malformations and its variant, persistent Blake's pouch cyst, megacisterna magna, PEHO síndrome (progressive encephalopathy with oedema, hipsarrhythmia and optic atrophy), Joubert syndrome, congenital disorder of glycosylation type Ia, pontocerebellar hipoplasias Barth type I and II, diffuse subcortical heterotopia. The imaging finding of structural cerebellar anomalies frequently leads to diagnostic incertainty as the anomalies are mostly unspecific, implying an extenuating analytical and genetic workup. Their knowledge and classification may be useful to decide the patient adjusted laboratorial workup.

  10. Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) - a case report and review of literature.

    PubMed

    Figura, Monika; Gaweł, Małgorzata; Kolasa, Anna; Janik, Piotr

    2014-01-01

    CANVAS (cerebellar ataxia with neuropathy and vestibular areflexia syndrome) is a rare neurological syndrome of unknown etiology. The main clinical features include bilateral vestibulopathy, cerebellar ataxia and sensory neuropathy. An abnormal visually enhanced vestibulo-ocular reflex is the hallmark of the disease. We present a case of 58-year-old male patient who has demonstrated gait disturbance, imbalance and paresthesia of feet for 2 years. On examination ataxia of gait, diminished knee and ankle reflexes, absence of plantar reflexes, fasciculations of thigh muscles, gaze-evoked downbeat nystagmus and abnormal visually enhanced vestibulo-ocular reflex were found. Brain magnetic resonance imaging revealed cerebellar atrophy. Vestibular function testing showed severely reduced horizontal nystagmus in response to bithermal caloric stimulation. Nerve conduction study revealed loss of upper and lower limb sensory nerve action potentials. The course of illness was progressive with ataxic gait and unsteadiness as the most disabling symptoms. We report 4-year follow-up of the patient since the beginning of the disease.

  11. Anti-Ri-associated paraneoplastic cerebellar and brainstem degenerative syndrome.

    PubMed

    Tay, J K; Miller, J; Joshi, A; Athey, R J

    2012-01-01

    We present the case of a female patient with a subacute paraneoplastic brainstem neurological syndrome associated with breast cancer and the development of anti-Ri antineuronal antibodies (ANNAs). It is an important syndrome to identify because of the need for urgent investigation and management to reduce progressive and irreversible neurological deterioration and to recognise the associated risks of bulbar and central respiratory failure. Diagnosis can be confounded if the anticipated normality of imaging and cerebrospinal fluid (CSF) studies is not appreciated. Positive antineuronal screening can provide rapid support for a paraneoplastic aetiology. Urgent and extensive investigation to identify the underlying tumour is imperative since neurological outcome is dependent on the rapidity of commencement and efficacy of tumour therapy. We discuss the symptoms, pathophysiology, diagnosis, treatment and prognosis of paraneoplastic neurological syndromes.

  12. Reversible postural orthostatic tachycardia syndrome.

    PubMed

    Abdulla, Aza; Rajeevan, Thirumagal

    2015-07-16

    Postural orthostatic tachycardia syndrome (POTS) is a relatively rare syndrome recognised since 1940. It is a heterogenous condition with orthostatic intolerance due to dysautonomia and is characterised by rise in heart rate above 30 bpm from base line or to more than 120 bpm within 5-10 min of standing with or without change in blood pressure which returns to base line on resuming supine position. This condition present with various disabling symptoms such as light headedness, near syncope, fatigue, nausea, vomiting, tremor, palpitations and mental clouding, etc. However there are no identifiable signs on clinical examination and patients are often diagnosed to have anxiety disorder. The condition predominantly affects young female between the ages of 15-50 but is rarely described in older people. We describe an older patient who developed POTS which recovered over 12 mo. Recognising this condition is important as there are treatment options available to alleviate the disabling symptoms.

  13. Respective implications of glutamate decarboxylase antibodies in stiff person syndrome and cerebellar ataxia

    PubMed Central

    2011-01-01

    Background To investigate whether Stiff-person syndrome (SPS) and cerebellar ataxia (CA) are associated with distinct GAD65-Ab epitope specificities and neuronal effects. Methods Purified GAD65-Ab from neurological patients and monoclonal GAD65-Ab with distinct epitope specificities (b78 and b96.11) were administered in vivo to rat cerebellum. Effects of intra-cerebellar administration of GAD65-Ab were determined using neurophysiological and neurochemical methods. Results Intra-cerebellar administration of GAD65-Ab from a SPS patient (Ab SPS) impaired the NMDA-mediated turnover of glutamate, but had no effect on NMDA-mediated turnover of glycerol. By contrast, GAD65-Ab from a patient with cerebellar ataxia (Ab CA) markedly decreased the NMDA-mediated turnover of glycerol. Both GAD65-Ab increased the excitability of the spinal cord, as assessed by the F wave/M wave ratios. The administration of BFA, an inhibitor of the recycling of vesicles, followed by high-frequency stimulation of the cerebellum, severely impaired the cerebello-cortical inhibition only when Ab CA was used. Moreover, administration of transcranial direct current stimulation (tDCS) of the motor cortex revealed a strong disinhibition of the motor cortex with Ab CA. Monoclonal antibodies b78 and b96.11 showed distinct effects, with greater effects of b78 in terms of increase of glutamate concentrations, impairment of the adaptation of the motor cortex to repetitive peripheral stimulation, disinhibition of the motor cortex following tDCS, and increase of the F/M ratios. Ab SPS shared antibody characteristics with b78, both in epitope recognition and ability to inhibit enzyme activity, while Ab CA had no effect on GAD65 enzyme activity. Conclusions These results suggest that, in vivo, neurological impairments caused by GAD65-Ab could vary according to epitope specificities. These results could explain the different neurological syndromes observed in patients with GAD65-Ab. PMID:21294897

  14. Sheehan syndrome with reversible dilated cardiomyopathy.

    PubMed

    Laway, Bashir A; Alai, Mohammad S; Gojwari, Tariq; Ganie, Mohd A; Zargar, Abdul Hamid

    2010-01-01

    Cardiac abnormalities in patients with Sheehan syndrome are uncommon. A case of Sheehan syndrome with dilated cardiomyopathy is presented in whom hormone replacement with levothyroxine and prednisolone resulted in complete recovery of cardiomyopathy. A 25-year-old woman presented with lactation failure, secondary amenorrhea, features of hypothyroidism and a hypocortisol state following severe postpartum hemorrhage after her last child birth. She also had smear positive pulmonary tuberculosis. After starting antitubercular treatment, she developed shock, suggestive of hypocortisol crisis. Hormonal investigations revealed evidence of panhypopitutarism and magnetic resonance imaging revealed partial empty sella. Meanwhile echocardiography revealed evidence of dilated cardiomyopathy (DCM). The patient was given replacement therapy in the form of glucocorticoids and levothyroxine in addition to antitubercular treatment. She improved and on follow-up over a period of 7 months, the DCM completely reversed. To our knowledge this is the first report of reversible DCM in a patient with Sheehan syndrome.

  15. Magnetic resonance imaging depiction of acquired Dyke-Davidoff-Masson syndrome with crossed cerebro-cerebellar diaschisis: Report of two cases.

    PubMed

    Gupta, Ranjana; Joshi, Sandeep; Mittal, Amit; Luthra, Ishita; Mittal, Puneet; Verma, Vibha

    2015-01-01

    Acquired Dyke-Davidoff-Masson syndrome, also known as hemispheric atrophy, is characterized by loss of volume of one cerebral hemisphere from an insult in early life. Crossed cerebellar diaschisis refers to dysfunction/atrophy of cerebellar hemisphere which is secondary to contralateral supratentorial insult. We describe magnetic resonance imaging findings in two cases of acquired Dyke-Davidoff-Masson syndrome with crossed cerebro-cerebellar diaschisis.

  16. Breast cancer revealed by a paraneoplastic cerebellar syndrome: about one case and literature review.

    PubMed

    Adama, Dembélé; Moussa, Bambara; Emmanuel, Macoumi; Dennis, Ullmann

    2015-01-01

    To describe a case of breast cancer manifested by cerebellar syndrome and to establish a relationship between breast cancer and Paraneoplastic syndromes through the presence of anti- yo antibodies in serum and cerebrospinal fluid of a patient. Our patient was 52 years old, Multipara with 5 children alive. She had been 3 years post-menopausal under Hormonal Replacement Therapy. Weight: 46.7 Kg; Height: 1.60 m; Body Surface Area: 1.59 m(2). Nil history of alcohol or tobacco smoking. Nil history suggestive of malignancies or autoimmune diseases. Her Blood group was oRh positive, nil presence of irregular agglutinins. She was admitted to the neurology service for vertigo and it was determined an isolated cerebellar syndrome. All tests were negative including tumor markers and radiological imaging. The clinical gynecological examination was perfectly normal. The diagnosis hypothesis was "meningo-encephalocerebellitis of viral origin" but with persistence and aggravation of the cerebellar syndrome, despite treatment. We decided to search, antibodies, anti-Hu, anti-Yo, anti-Ri, and anti Ta. Anti Yo was positive + + + in the cerebrospinal fluid and serum of the patient. The search for a gynecological cancer included a mammography which revealed micro calcifications in the left breast + + +. A lumpectomy of the left breast accompanied with x-ray identification of the micro calcifications was done and the histology showed a High Grade Intraductal carcinoma of the left breast with two homes of 3mm and 1 mm, corresponding to an infiltrating carcinoma of the left breast, grade II tumor of Scarff and Bloom (SBRII, 21 N + / 26, RH +, low Ki 67) and Estrogen and progesterone receptor positive +: multifocal cancer. Following the lumpectomy, mastectomy with ganglion clearing was done with adjuvant chemotherapy (FEC 6 Cycles): histology still showed Infiltrating Intraductal Carcinoma of the left breast, grade II tumor of Scarff and Bloom. Radiotherapy was followed and he patient was

  17. Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome.

    PubMed

    Thomas, Anna C; Williams, Hywel; Setó-Salvia, Núria; Bacchelli, Chiara; Jenkins, Dagan; O'Sullivan, Mary; Mengrelis, Konstantinos; Ishida, Miho; Ocaka, Louise; Chanudet, Estelle; James, Chela; Lescai, Francesco; Anderson, Glenn; Morrogh, Deborah; Ryten, Mina; Duncan, Andrew J; Pai, Yun Jin; Saraiva, Jorge M; Ramos, Fabiana; Farren, Bernadette; Saunders, Dawn; Vernay, Bertrand; Gissen, Paul; Straatmaan-Iwanowska, Anna; Baas, Frank; Wood, Nicholas W; Hersheson, Joshua; Houlden, Henry; Hurst, Jane; Scott, Richard; Bitner-Glindzicz, Maria; Moore, Gudrun E; Sousa, Sérgio B; Stanier, Philip

    2014-11-06

    Intellectual disability and cerebellar atrophy occur together in a large number of genetic conditions and are frequently associated with microcephaly and/or epilepsy. Here we report the identification of causal mutations in Sorting Nexin 14 (SNX14) found in seven affected individuals from three unrelated consanguineous families who presented with recessively inherited moderate-severe intellectual disability, cerebellar ataxia, early-onset cerebellar atrophy, sensorineural hearing loss, and the distinctive association of progressively coarsening facial features, relative macrocephaly, and the absence of seizures. We used homozygosity mapping and whole-exome sequencing to identify a homozygous nonsense mutation and an in-frame multiexon deletion in two families. A homozygous splice site mutation was identified by Sanger sequencing of SNX14 in a third family, selected purely by phenotypic similarity. This discovery confirms that these characteristic features represent a distinct and recognizable syndrome. SNX14 encodes a cellular protein containing Phox (PX) and regulator of G protein signaling (RGS) domains. Weighted gene coexpression network analysis predicts that SNX14 is highly coexpressed with genes involved in cellular protein metabolism and vesicle-mediated transport. All three mutations either directly affected the PX domain or diminished SNX14 levels, implicating a loss of normal cellular function. This manifested as increased cytoplasmic vacuolation as observed in cultured fibroblasts. Our findings indicate an essential role for SNX14 in neural development and function, particularly in development and maturation of the cerebellum.

  18. Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction

    PubMed Central

    Akizu, Naiara; Cantagrel, Vincent; Zaki, Maha S.; Al-Gazali, Lihadh; Wang, Xin; Rosti, Rasim Ozgur; Dikoglu, Esra; Gelot, Antoinette Bernabe; Rosti, Basak; Vaux, Keith K.; Scott, Eric M.; Silhavy, Jennifer L.; Schroth, Jana; Copeland, Brett; Schaffer, Ashleigh E.; Gordts, Philip; Esko, Jeffrey D.; Buschman, Matthew D.; Fields, Seth J.; Napolitano, Gennaro; Ozgul, R. Koksal; Sagiroglu, Mahmut Samil; Azam, Matloob; Ismail, Samira; Aglan, Mona; Selim, Laila; Gamal, Iman; Hadi, Sawsan Abdel; El Badawy, Amera; Sadek, Abdelrahim A.; Mojahedi, Faezeh; Kayserili, Hulya; Masri, Amira; Bastaki, Laila; Temtamy, Samia; Müller, Ulrich; Desguerre, Isabelle; Casanova, Jean-Laurent; Dursun, Ali; Gunel, Murat; Gabriel, Stacey B.; de Lonlay, Pascale; Gleeson, Joseph G.

    2015-01-01

    Pediatric-onset ataxias often present clinically with developmental delay and intellectual disability, with prominent cerebellar atrophy as a key neuroradiographic finding. Here we describe a novel clinically distinguishable recessive syndrome in 12 families with cerebellar atrophy together with ataxia, coarsened facial features and intellectual disability, due to truncating mutations in sorting nexin 14 (SNX14), encoding a ubiquitously expressed modular PX-domain-containing sorting factor. We found SNX14 localized to lysosomes, and associated with phosphatidyl-inositol (3,5)P2, a key component of late endosomes/lysosomes. Patient cells showed engorged lysosomes and slower autophagosome clearance rate upon starvation induction. Zebrafish morphants showed dramatic loss of cerebellar parenchyma, accumulated autophagosomes, and activation of apoptosis. Our results suggest a unique ataxia syndrome due to biallelic SNX14 mutations, leading to lysosome-autophagosome dysfunction. PMID:25848753

  19. Successful neuropsychological rehabilitation in a patient with Cerebellar Cognitive Affective Syndrome.

    PubMed

    Ruffieux, N; Colombo, F; Gentaz, E; Annoni, J-M; Chouiter, L; Roulin Hefti, S; Ruffieux, A; Bihl, T

    2017-01-01

    The objective of this case study was to describe the neuropsychological rehabilitation of a 16-year-old patient who presented a Cerebellar Cognitive Affective Syndrome (CCAS) following a bilateral cerebellar hemorrhage. The patient presented severe and diffuse cognitive deficits, massive behavioral disorders, and emotion regulation difficulties. The cognitive rehabilitation was performed in the chronic phase (one year after the onset of the hemorrhage) using a transdisciplinary neurobehavioral approach based on the patient's favorite interest (soccer). A significant behavioral and cognitive improvement was observed. The patient became progressively independent in all activities of daily living and was discharged home. The Functional Independence Measure at discharge was 124/126 (vs. 37/126 at entry). The patient was able to complete his schooling despite the mild cognitive and behavioral sequelae. This first description of the use of neurobehavioral therapy in a case of chronic CCAS suggests that (a) major clinical improvement can occur more than one year after the onset of the CCAS, showing the importance of long-term and intensive neurorehabilitation; and (b) when the cerebellum cannot properly play its regulator role in cognition, neuropsychological intervention through a behavioral and cognitive approach can be of great help by acting as an external modulator to help the patient regain control over himself.

  20. Joubert syndrome: congenital cerebellar ataxia with the “molar tooth”

    PubMed Central

    Romani, Marta; Micalizzi, Alessia; Valente, Enza Maria

    2013-01-01

    Joubert syndrome (JS) is a congenital cerebellar ataxia with autosomal recessive or X-linked inheritance, which diagnostic hallmark is a unique cerebellar and brainstem malformation recognizable on brain imaging, the “molar tooth sign”. Neurological signs are present from neonatal age and include hypotonia evolving into ataxia, global developmental delay, ocular motor apraxia and breathing dysregulation. These are variably associated with multiorgan involvement, mainly of the retina, kidneys, skeleton and liver. To date, 21 causative genes have been identified, all encoding for proteins of the primary cilium or its apparatus. This is a subcellular organelle that plays key roles in development and in many cellular functions, making JS part of the expanding family of ciliopathies. There is marked clinical and genetic overlap among distinct ciliopathies, which may co-occur even within families. Such variability is likely explained by an oligogenic model of inheritance, in which mutations, rare variants and polymorphisms at distinct loci interplay to modulate the expressivity of the ciliary phenotype. PMID:23870701

  1. Reverse mutations in fragile X syndrome

    SciTech Connect

    Brown, W.T.; Nolin, S.; Houck, G.E.

    1994-09-01

    The fragile X syndrome is the most common inherited form of mental retardation. Yet new mutations have not been described and no affected child has been born to a carrier mother having less than 60 FMR-1 CGG triplet repeats. Reverse mutations also appear to be very rare. We have previously identified the daughter of a premutation mother (95 CGGs) who inherited a normal repeat size of 35 as a reverse mutation. In the process of carrier testing by PCR, we have now identified two additional females with reverse mutations. All three of these reverse mutation women were previously tested by linkage as part of known fragile X families (subsequently confirmed by direct analysis), and assigned a > 99% risk as a carrier. In the second family, the mother carries a premutation allele of 95 repeats and the daughter inherited a 43 repeat allele. Prior to direct DNA testing, she had a positive prenatal diagnosis by linkage (> 99% risk) and cytogenetics with 3/450 cells apparently positive. Subsequent retesting of the products of conception by PCR now reveals a 43 repeat allele from her carrier mother with an 82 repeat allele. Testing with close CA markers (FRAXAC1 and DXS548) confirmed that these women inherited the same chromosome and their full mutation brothers. Further analysis is pending. These examples of reverse mutations are the only ones we have identified in our study of offspring of more than 200 carriers (400+ meioses) examined to date. Therefore, we conclude the frequency of fragile X back mutations is likely to be less than 1%. Retesting of linkage positive carriers is recommended to detect reverse mutations and assure accurate genetic counseling.

  2. Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS): a review of the clinical features and video-oculographic diagnosis.

    PubMed

    Szmulewicz, David J; Waterston, John A; MacDougall, Hamish G; Mossman, Stuart; Chancellor, Andrew M; McLean, Catriona A; Merchant, Saumil; Patrikios, Peter; Halmagyi, G Michael; Storey, Elsdon

    2011-09-01

    The association of bilateral vestibulopathy with cerebellar ataxia was first reported in 1991 and delineated as a distinct syndrome with a characteristic and measurable clinical sign--an absent visually enhanced vestibulo-ocular reflex--in 2004. We reviewed 27 patients with this syndrome and show that a non-length-dependent sensory deficit with absent sensory nerve action potentials is an integral component of this syndrome, which we now call "cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome" (CANVAS). All patients had brain MRI and 22/27 had evidence of cerebellar atrophy involving anterior and dorsal vermis, as well as the hemispheric crus I. Brain and temporal bone pathology in one patient showed marked loss of Purkinje cells and of vestibular, trigeminal, and facial ganglion cells, but not of spiral ganglion cells. There are two sets of sibling pairs, suggesting CANVAS is a late-onset recessive disorder. The characteristic clinical sign-the visual vestibulo-ocular reflex deficit-can be demonstrated and measured clinically using video-oculography.

  3. Decreased tonic inhibition in cerebellar granule cells causes motor dysfunction in a mouse model of Angelman syndrome.

    PubMed

    Egawa, Kiyoshi; Kitagawa, Kyoko; Inoue, Koichi; Takayama, Masakazu; Takayama, Chitoshi; Saitoh, Shinji; Kishino, Tatsuya; Kitagawa, Masatoshi; Fukuda, Atsuo

    2012-12-05

    Angelman syndrome is a neurodevelopmental disorder caused by loss of function of the UBE3A gene encoding a ubiquitin E3 ligase. Motor dysfunction is a characteristic feature of Angelman syndrome, but neither the mechanisms of action nor effective therapeutic strategies have yet been elucidated. We report that tonic inhibition is specifically decreased in cerebellar granule cells of Ube3a-deficient mice, a model of Angelman syndrome. As a mechanism underlying this decrease in tonic inhibition, we show that Ube3a controls degradation of γ-aminobutyric acid (GABA) transporter 1 (GAT1) and that deficiency of Ube3a induces a surplus of GAT1 that results in a decrease in GABA concentrations in the extrasynaptic space. Administering low doses of 4,5,6,7-tetrahydroisothiazolo-[5,4-c]pyridin-3-ol (THIP), a selective extrasynaptic GABA(A) receptor agonist, improves the abnormal firing properties of a population of Purkinje cells in cerebellar brain slices and reduces cerebellar ataxia in Ube3a-deficient mice in vivo. These results suggest that pharmacologically increasing tonic inhibition may be a useful strategy for alleviating motor dysfunction in Angelman syndrome.

  4. Autonomic dysfunction is a major feature of cerebellar ataxia, neuropathy, vestibular areflexia 'CANVAS' syndrome.

    PubMed

    Wu, Teddy Y; Taylor, Jennifer M; Kilfoyle, Dean H; Smith, Andrew D; McGuinness, Ben J; Simpson, Mark P; Walker, Elizabeth B; Bergin, Peter S; Cleland, James C; Hutchinson, David O; Anderson, Neil E; Snow, Barry J; Anderson, Tim J; Paermentier, Laura A F; Cutfield, Nick J; Chancellor, Andrew M; Mossman, Stuart S; Roxburgh, Richard H

    2014-10-01

    Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a recently recognized neurodegenerative ganglionopathy. Prompted by the presence of symptomatic postural hypotension in two patients with CANVAS, we hypothesized that autonomic dysfunction may be an associated feature of the syndrome. We assessed symptoms of autonomic dysfunction and performed autonomic nervous system testing among 26 patients from New Zealand. After excluding three patients with diabetes mellitus, 83% had evidence of autonomic dysfunction; all patients had at least one autonomic symptom and 91% had more than two symptoms. We also found a higher rate of downbeat nystagmus (65%) than previously described in CANVAS. We confirmed that sensory findings on nerve conduction tests were consistent with a sensory ganglionopathy and describe two patients with loss of trigeminal sensation consistent with previous pathological descriptions of trigeminal sensory ganglionopathy. Our results suggest that autonomic dysfunction is a major feature of CANVAS. This has implications for the management of patients with CANVAS as the autonomic symptoms may be amenable to treatment. The findings also provide an important differential diagnosis from multiple system atrophy for patients who present with ataxia and autonomic failure.

  5. Anti-Hu paraneoplastic syndrome presenting with brainstem-cerebellar symptoms and Lambert-Eaton myasthenic syndrome.

    PubMed

    Nagashima, Toshiko; Mizutani, Yasuyuki; Kawahara, Hiromasa; Maguchi, Shiro; Terayama, Yoshihiko; Shinohara, Toshiya; Orba, Yasuko; Chuma, Takayo; Mano, Yukio; Itoh, Tomoo; Sawa, Hirofumi; Sakai, Koichiro; Motomura, Masakatsu; Nagashima, Kazuo

    2003-09-01

    Paraneoplastic syndrome (PNS) with two distinct neurological features was reported in a 50-year-old man who presented initially with vertigo, ataxia, dysarthria, tremor, confusion, urinary retention and hypotension. Pulmonary X-ray findings, class IIIb sputum cytology, and positive anti-Hu antibody established the diagnosis of PNS associated with small-cell lung cancer (SCLC). Two cycles of combined chemotherapy resulted in shrinkage of the lung tumor together with complete recovery of neurological symptoms and disappearance of anti-Hu antibody. Relapse of SCLC 4 months later with re-appearance of anti-Hu antibody required additional chemotherapy and irradiation. Eight months later, when multiple liver metastasis of SCLC was noticed, muscular weakness with positive waxing phenomenon compatible with Lambert-Eaton myasthenic syndrome (LEMS) developed. Postmortem examinations revealed residual SCLC in the primary lung, and massive liver metastasis with generalized lymph node involvement, but no tumors in the CNS. In the cerebellum, there was a slight loss of Purkinje cells with torpedo formation but without apparent lymphocytic infiltration. The present PNS was unique in that the relapse of SCLC was accompanied by the appearance of anti-Hu antibody, and that initial signs of brainstem-cerebellar symptoms, encephalopathy and autonomic failure were replaced by LEMS coinciding with the tumor recurrence.

  6. Reversible posterior leukoencephalopathy syndrome in children with nephrotic syndrome: a case report.

    PubMed

    Liu, Sheng-da; Shen, Qing-min; Lv, Chun-feng

    2014-03-01

    REVERSIBLE posterior leukoencephalopathy syndrome (RPLS) is a rare neurological syndrome characterized by headache, altered mental status, seizures, and visual disturbance, associated with reversible white matter changes.1 It has been commonly reported in patients with severe hypertension and pre-eclampsia. Here we report a case with nephrotic syndrome complicated by RPLS.

  7. Impairments in motor coordination without major changes in cerebellar plasticity in the Tc1 mouse model of Down syndrome.

    PubMed

    Galante, Micaela; Jani, Harsha; Vanes, Lesley; Daniel, Hervé; Fisher, Elizabeth M C; Tybulewicz, Victor L J; Bliss, Timothy V P; Morice, Elise

    2009-04-15

    Down syndrome (DS) is a genetic disorder arising from the presence of a third copy of human chromosome 21 (Hsa21). Recently, O'Doherty et al. [An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science 309 (2005) 2033-2037] generated a trans-species aneuploid mouse line (Tc1) that carries an almost complete Hsa21. The Tc1 mouse is the most complete animal model for DS currently available. Tc1 mice show many features that relate to human DS, including alterations in memory, synaptic plasticity, cerebellar neuronal number, heart development and mandible size. Because motor deficits are one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor behaviour in cerebellum-dependent learning tasks that require high motor coordination and balance. In addition, basic electrophysiological properties of cerebellar circuitry and synaptic plasticity have been investigated. Our results reveal that, compared with controls, Tc1 mice exhibit a higher spontaneous locomotor activity, a reduced ability to habituate to their environments, a different gait and major deficits on several measures of motor coordination and balance in the rota rod and static rod tests. Moreover, cerebellar long-term depression is essentially normal in Tc1 mice, with only a slight difference in time course. Our observations provide further evidence that support the validity of the Tc1 mouse as a model for DS, which will help us to provide insights into the causal factors responsible for motor deficits observed in persons with DS.

  8. Reversible posterior encephalopathy syndrome associated with micronodular adrenocortical disease and Cushing syndrome.

    PubMed

    Lodish, Maya; Patronas, Nicholas J; Stratakis, Constantine A

    2010-01-01

    We report a 6-year-old girl with ACTH-independent Cushing syndrome secondary to bilateral adrenal hyperplasia; she presented with hypertension and seizures, and magnetic resonance imaging shows changes consistent with posterior reversible encephalopathy syndrome.

  9. Reversal of deafness after renal transplantation in Alport's syndrome.

    PubMed

    McDonald, T J; Zincke, H; Anderson, C F; Ott, N T

    1978-01-01

    Six patients (five men and one woman) with Alport's syndrome underwent successful renal transplantation (four received kidneys from cadaver donors and two received allografts from living, related donors). One patient who had received a cadaver kidney had substantial hearing improvement and the others had stabilization of hearing. Hearing loss in Alport's syndrome is progressive. The reversal of deafness in one of our patients and stabilization in the others made us wonder whether an inherited enzymopathy had been reversed, which then mitigated the deafness.

  10. Widespread cerebellar transcriptome changes in Ts65Dn Down syndrome mouse model after lifelong running.

    PubMed

    Walus, Marius; Kida, Elizabeth; Rabe, Ausma; Albertini, Giorgio; Golabek, Adam A

    2016-01-01

    Our previous study showed an improvement in locomotor deficits after voluntary lifelong running in Ts65Dn mice, an animal model for Down syndrome (DS). In the present study, we employed mouse microarrays printed with 55,681 probes in an attempt to identify molecular changes in the cerebellar transcriptome that might contribute to the observed behavioral benefits of voluntary long-term running in Ts65Dn mice. Euploid mice were processed in parallel for comparative purposes in some analyses. We found that running significantly changed the expression of 4,315 genes in the cerebellum of Ts65Dn mice, over five times more than in euploid animals, up-regulating 1,991 and down-regulating 2,324 genes. Functional analysis of these genes revealed a significant enrichment of 92 terms in the biological process category, including regulation of biosynthesis and metabolism, protein modification, phosphate metabolism, synaptic transmission, development, regulation of cell death/apoptosis, protein transport, development, neurogenesis and neuron differentiation. The KEGG pathway database identified 18 pathways that are up-regulated and two that are down-regulated by running that were associated with learning, memory, cell signaling, proteolysis, regeneration, cell cycle, proliferation, growth, migration, and survival. Of six mRNA protein products we tested by immunoblotting, four showed significant running-associated changes in their levels, the most prominent in glutaminergic receptor metabotropic 1, and two showed changes that were close to significant. Thus, unexpectedly, our data point to the high molecular plasticity of Ts65Dn mouse cerebellum, which translated into humans with DS, suggests that the motor deficits of individuals with DS could markedly benefit from prolonged exercise.

  11. Cerebellar Ataxia.

    PubMed

    Perlman

    2000-05-01

    There is nothing more discouraging than for a patient to be given a specific diagnosis, then to be told that there is nothing that can be done. Physicians are equally disheartened to see exponential progress being made in the understanding of the pathophysiology of a complex disorder but few direct benefits resulting for their patients. Over the past 5 years, molecular genetic research has completely revolutionized the way in which the progressive cerebellar ataxias are classified and diagnosed, but it has yet to produce effective gene-based, neuroprotective, or neurorestorative therapies. The treatment of cerebellar ataxia remains primarily a neurorehabilitation challenge, employing physical, occupational, speech, and swallowing therapy; adaptive equipment; driver safety training; and nutritional counseling. Modest additional gains are seen with the use of medications that can improve imbalance, incoordination, or dysarthria (amantadine, buspirone, acetazolamide); cerebellar tremor (clonazepam, propranolol); and cerebellar or central vestibular nystagmus (gabapentin, baclofen, clonazepam). Many of the progressive cerebellar syndromes have associated features involving other neurologic systems (eg, spasticity, dystonia or rigidity, resting or rubral tremor, chorea, motor unit weakness or fatigue, autonomic dysfunction, peripheral or posterior column sensory loss, neuropathic pain or cramping, double vision, vision and hearing loss, dementia, and bowel, bladder, and sexual dysfunction), which can impede the treatment of the ataxic symptoms or can worsen with the use of certain drugs. Treatment of the associated features themselves may in turn worsen the ataxia either directly (as side effects of medication) or indirectly (eg, relaxation of lower limb spasticity that was acting as a stabilizer for an ataxic gait). Secondary complications of progressive ataxia can include deconditioning or immobility, weight loss or gain, skin breakdown, recurrent pulmonary and

  12. Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia

    PubMed Central

    Schmidt, Wolfgang M.; Rutledge, S. Lane; Schüle, Rebecca; Mayerhofer, Benjamin; Züchner, Stephan; Boltshauser, Eugen; Bittner, Reginald E.

    2015-01-01

    Hereditary ataxias comprise a group of genetically heterogeneous disorders characterized by clinically variable cerebellar dysfunction and accompanied by involvement of other organ systems. The molecular underpinnings for many of these diseases are widely unknown. Previously, we discovered the disruption of Scyl1 as the molecular basis of the mouse mutant mdf, which is affected by neurogenic muscular atrophy, progressive gait ataxia with tremor, cerebellar vermis atrophy, and optic-nerve thinning. Here, we report on three human individuals, from two unrelated families, who presented with recurrent episodes of acute liver failure in early infancy and are affected by cerebellar vermis atrophy, ataxia, and peripheral neuropathy. By whole-exome sequencing, compound-heterozygous mutations within SCYL1 were identified in all affected individuals. We further show that in SCYL1-deficient human fibroblasts, the Golgi apparatus is massively enlarged, which is in line with the concept that SCYL1 regulates Golgi integrity. Thus, our findings define SCYL1 mutations as the genetic cause of a human hepatocerebellar neuropathy syndrome. PMID:26581903

  13. Evidence for "Uner Tan Syndrome" as a human model for reverse evolution.

    PubMed

    Tan, Uner

    2006-12-01

    "Uner Tan Syndrome" was further studied in a second family. There was no cerebellar atrophy, except a mild vermial atrophy in MRI scans of the affected individuals. This is not, however, the pathogenesis of the "Uner Tan Syndrome", since in the first and second families there were bipedal men exhibiting very similar MRI scans. The second family may also be considered a live model for reverse evolution in human beings. The present work provided evidence for a reverse evolution: (i) quadrupedality; (ii) primitive mental abilities including language; (iii) curved fingers during wrist-walking of the quadrupedal woman; (iv) arm to leg ratios being close to those of the human-like apes. The quadrupedal individuals were raised in separate places, so that they could not imitate each other, excluding the socio-cultural factors contributing to the habitual quadrupedal gait. The results are consistent with the single gene theory, suggesting a single gene controlling multiple behavioral traits, and the psychomotor theory, and a co-evolution of the human mind, an emergent property of the motor system expressed by human language.

  14. Impairments in motor coordination without major changes in cerebellar plasticity in the Tc1 mouse model of Down syndrome

    PubMed Central

    Galante, Micaela; Jani, Harsha; Vanes, Lesley; Daniel, Hervé; Fisher, Elizabeth M.C.; Tybulewicz, Victor L.J.; Bliss, Timothy V.P.; Morice, Elise

    2009-01-01

    Down syndrome (DS) is a genetic disorder arising from the presence of a third copy of human chromosome 21 (Hsa21). Recently, O'Doherty et al. [An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science 309 (2005) 2033–2037] generated a trans-species aneuploid mouse line (Tc1) that carries an almost complete Hsa21. The Tc1 mouse is the most complete animal model for DS currently available. Tc1 mice show many features that relate to human DS, including alterations in memory, synaptic plasticity, cerebellar neuronal number, heart development and mandible size. Because motor deficits are one of the most frequently occurring features of DS, we have undertaken a detailed analysis of motor behaviour in cerebellum-dependent learning tasks that require high motor coordination and balance. In addition, basic electrophysiological properties of cerebellar circuitry and synaptic plasticity have been investigated. Our results reveal that, compared with controls, Tc1 mice exhibit a higher spontaneous locomotor activity, a reduced ability to habituate to their environments, a different gait and major deficits on several measures of motor coordination and balance in the rota rod and static rod tests. Moreover, cerebellar long-term depression is essentially normal in Tc1 mice, with only a slight difference in time course. Our observations provide further evidence that support the validity of the Tc1 mouse as a model for DS, which will help us to provide insights into the causal factors responsible for motor deficits observed in persons with DS. PMID:19181682

  15. Ethanol impairs Rho GTPase signaling and differentiation of cerebellar granule neurons in a rodent model of fetal alcohol syndrome.

    PubMed

    Joshi, S; Guleria, R S; Pan, J; Bayless, K J; Davis, G E; Dipette, D; Singh, U S

    2006-12-01

    Developmental exposure to ethanol impairs fetal brain development and causes fetal alcohol syndrome. Although the cerebellum is one of the most alcohol-sensitive brain areas, signaling mechanisms underlying the deleterious effects of ethanol on developing cerebellar granule neurons (CGNs) are largely unknown. Here we describe the effects of in vivo ethanol exposure on neurite formation in CGNs and on the activation of Rho GTPases (RhoA and Rac1), regulators of neurite formation. Exposure of 7-day-old rat pups to ethanol for 3 h moderately increased blood alcohol concentration (BAC) ( approximately 40 mM) and inhibited neurite formation and Rac1 activation in CGNs. Longer exposure to ethanol for 5 h resulted in higher BAC ( approximately 80 mM), induced apoptosis, inhibited Rac1, and activated RhoA. Studies demonstrated a regulatory role of Rho GTPases in differentiation of cerebellar neurons, and indicated that ethanol-associated impairment of Rho GTPase signaling might contribute to brain defects observed in fetal alcohol syndrome.

  16. LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders.

    PubMed

    Soós, Zsuzsanna; Salamon, Mónika; Erdei, Katalin; Kaszás, Nóra; Folyovich, András; Szücs, Anna; Barcs, Gábor; Arányi, Zsuzsanna; Skaliczkis, József; Vadasdi, Károly; Winkler, Gábor

    2014-05-30

    Celiac disease--in its typical form--is a chronic immune-mediated enteropathy with typical clinical symptoms that develops against gliadin content of cereal grains, and is often associated with other autoimmune diseases. In cases of atypical manifestation classic symptoms may be absent or mild, and extra-intestinal symptoms or associated syndromes dominate clinical picture. The authors present a longitudinal follow-up of such a case. A 63-years old woman was diagnosed with epilepsy at the age of 19, and with progressive limb ataxia at the age of 36, which was initially thought to be caused by cerebellar atrophy, later probably by stiff person syndrome. At the age 59, her diabetes mellitus manifested with type 2 diabetic phenotype, but based on GAD positivity later was reclassified as type 1 diabetes. Only the last check-up discovered the celiac disease, retrospectively explaining the entire disease course and neurological symptoms. By presenting this case, the authors would like to draw attention to the fact that one should think of the possibility of celiac disease when cerebellar ataxia, progressive neurological symptoms and diabetes are present at the same time. An early diagnosis may help to delay the progression of disease and help better treatment.

  17. Neonatal diabetes mellitus and cerebellar hypoplasia/agenesis: report of a new recessive syndrome

    PubMed Central

    Hoveyda, N.; Shield, J.; Garrett, C.; Chong, W; Beardsall, K.; Bentsi-Enchill, E.; Mallya, H.; Thompson, M.

    1999-01-01

    Classical neonatal diabetes mellitus is defined as hyperglycaemia occurring within the first six weeks of life in term infants. Cerebellar agenesis is rare. We report three cases of neonatal diabetes mellitus, cerebellar hypoplasia/agenesis, and dysmorphism occurring within a highly consanguineous family. This constellation of abnormalities has not previously been described. Two of these cases are sisters and the third case is a female first cousin. The pattern of inheritance suggests this is a previously undescribed autosomal recessive disorder. Prenatal diagnosis of the condition in this family was possible by demonstration of the absence of the cerebellum and severe IUGR.


Keywords: cerebellar agenesis/hypoplasia; neonatal diabetes mellitus; dysmorphic features; autosomal recessive PMID:10507728

  18. Brainstem variant of posterior reversible encephalopathy syndrome: A case report

    PubMed Central

    Caranci, Ferdinando; Belfiore, Maria Paola; Manzi, Francesca; Pagliano, Pasquale; Cirillo, Sossio

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological condition, generally observed in conjunction with severe and acute hypertension, that involves mainly the posterior head areas (occipital and temporal lobes) and anterior “watershed” areas. In this syndrome it is rare to observe a predominant involvement of the brainstem. We describe the clinical and radiological findings in a patient with brainstem involvement, discussing its pathophysiological features and possible differential diagnosis. PMID:26515750

  19. Brainstem variant of posterior reversible encephalopathy syndrome: A case report.

    PubMed

    Tortora, Fabio; Caranci, Ferdinando; Belfiore, Maria Paola; Manzi, Francesca; Pagliano, Pasquale; Cirillo, Sossio

    2015-12-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological condition, generally observed in conjunction with severe and acute hypertension, that involves mainly the posterior head areas (occipital and temporal lobes) and anterior "watershed" areas. In this syndrome it is rare to observe a predominant involvement of the brainstem. We describe the clinical and radiological findings in a patient with brainstem involvement, discussing its pathophysiological features and possible differential diagnosis.

  20. Clinical and methodological confounders in assessing the cerebellar cognitive affective syndrome in adult patients with posterior fossa tumours.

    PubMed

    Omar, Dashne; Ryan, Tracy; Carson, Alan; Bak, Thomas H; Torrens, Lorna; Whittle, Ian

    2014-12-01

    The cerebellar cognitive affective syndrome (CCAS) was first described by Schmahmann and Sherman as a constellation of symptoms including dysexecutive syndrome, spatial cognitive deficit, linguistic deficits and behavioural abnormalities in patients with a lesion in the cerebellum with otherwise normal brain. Neurosurgical patients with cerebellar tumours constitute one of the cohorts in which the CCAS has been described. In this paper, we present a critical review of the literature of this syndrome in neurosurgical patients. Thereafter, we present a prospective clinical study of 10 patients who underwent posterior fossa tumour resection and had a detailed post-operative neuropsychological, neuropsychiatric and neuroradiological assessment. Because our findings revealed a large number of perioperative neuroradiological confounding variables, we reviewed the neuroimaging of a further 20 patients to determine their prevalence. Our literature review revealed that study design, methodological quality and sometimes both diagnostic criteria and findings were inconsistent. The neuroimaging study (pre-operative, n = 10; post-operative, n = 10) showed very frequent neuroradiological confounding complications (e.g. hydrocephalus; brainstem compression; supratentorial lesions and post-operative subdural hygroma); the impact of such features had largely been ignored in the literature. Findings from our clinical study showed various degree of deficits in neuropsychological testing (n = 1, memory; n = 3, verbal fluency; n = 3, attention; n = 2, spatial cognition deficits; and n = 1, behavioural changes), but no patient had full-blown features of CCAS. Our study, although limited, finds no robust evidence of the CCAS following surgery. This and our literature review highlight a need for guidelines regarding study design and methodology when attempting to evaluate neurosurgical cases with regard to the potential CCAS.

  1. Reverse mutations in the fragile X syndrome

    SciTech Connect

    Brown, W.T.; Houck, G.E. Jr.; Ding, Xiaohua

    1996-08-09

    Three females were identified who have apparent reversal of fragile X premutations. Based on haplotype analysis of nearby markers, they were found to have inherited a fragile X chromosome from their premutation carrier mothers, and yet had normal size FMR1 repeat alleles. The changes in repeat sizes from mother to daughter was 95 to 35 in the first, 145 to 43 in the second, and 82 to 33 in the third. In the first family, mutations of the nearby microsatellites FRAXAC2 and DXS548 were also observed. In the other two, only mutations involving the FMR1 repeats were found. We suggest differing mutational mechanisms such as gene conversion versus DNA replication slippage may underlie such reversions. We estimate that such revertants may occur among 1% or less of premutation carrier offspring. Our results indicate that women identified to be carriers by linkage should be retested by direct DNA analysis. 35 refs., 5 figs.

  2. Dyke-Davidoff-Masson Syndrome With Cerebral Hypometabolism and Unique Crossed Cerebellar Diaschisis in 18F-FDG PET/CT.

    PubMed

    Demir, Yusuf; Sürücü, Erdem; Çilingir, Vedat; Bulut, Mehmet Deniz; Tombul, Temel

    2015-09-01

    A 23-year-old man with Dyke-Davidoff-Masson syndrome (DDMS) was admitted to the hospital with increasing frequency of epileptic seizures. Physical examination revealed mental retardation, left facial asymmetry, and left-sided spastic hemiparesis. Dysdiadochokinesia on the left upper limb was detected, and there was no dysmetria. MRI confirmed the well-known radiological features of DDMS. PET/CT demonstrated cerebral and contralateral cerebellar hypometabolism. We present DDMS with crossed cerebellar diaschisis, which was demonstrated by PET/CT.

  3. Acute Cerebellar Syndrome in Infectious Mononucleosis: Documentation of Two Cases With Epstein-Barr Virus Infection

    PubMed Central

    Kramer, David S.; Smitnik, Loretta M.; John, Kuruvilla; Drake, Miles E.

    1985-01-01

    Acute cerebellar ataxia has been described occasionally with infectious mononucleosis. Two additional cases are reported with serologic identification of Epstein-Barr virus (EBV) infection in blood and cerebrospinal fluid. As with previously described cases, the outcome was benign, and examination and laboratory studies did not indicate diffuse neurologic involvement. Visual and brainstem auditory-evoked responses were normal. Electroencephalograms (EEG) demonstrated 14 and 6 per second positive spikes in both patients. This pattern is considered a normal variant and has been recorded from depth electrodes and reported with deep midline lesions. These cases support the prognosis of benign cerebellar involvement in infectious mononucleosis and suggest that evidence of EBV infection be sought in patients with acute ataxia. The significance of 14/sec and 6/sec positive EEG spikes is uncertain. PMID:2987517

  4. Age-related decline in the responsiveness of motor cortex to plastic forces reverses with levodopa or cerebellar stimulation.

    PubMed

    Kishore, Asha; Popa, Traian; James, Praveen; Yahia-Cherif, Lydia; Backer, Febina; Varughese Chacko, Lijo; Govind, Preetha; Pradeep, Salini; Meunier, Sabine

    2014-11-01

    The plasticity of motor cortex is integral for motor memory and skills acquisition but it declines with aging. Forty healthy volunteers, across 6 decades, were tested to examine the (a) age-dependency of motor cortex responsiveness to plasticity induction, as measured from the response to paired associative stimulation (PAS) and the (b) effect of aging on the cerebellar modulation of motor cortex response to PAS. We examined if reduced dopaminergic transmission was involved in the age-related decline of response to PAS by retesting 10 of the older subjects after a single dose of levodopa. There was a substantial decline in the motor cortex response to PAS with aging, which was restored by levodopa in the older subjects. The cerebellar modulation of motor cortex response to PAS was less vulnerable to aging and a single session of cerebellar inhibition reinstated the cortical responsiveness in older subjects. Both levodopa and cerebellar inhibition can be tested for their ability to enhance motor skills acquisition and motor performance in the elderly individuals.

  5. Reverse mutation in fragile X syndrome

    SciTech Connect

    Antinolo, G.; Borrego, S.; Cabeza, J.C.

    1996-01-01

    The fragile X syndrome is the most common cause of familial mental retardation, with an incidence of {approximately}1/1,500 in males and 1/2,500 in females. The clinical expression includes moderate to severe mental retardation, macroorchidism, dysmorphic facial features and behavior disturbances. In 1991, the FMR-1 gene was isolated from the region of the fragile X site. The fragile X phenotype has been found, in most cases, to be characterized at the molecular level by expansion of a (CGG){sub n} repeat and hypermethylation of a CpG island identified in the 5{prime}-UTR of the FMR-1 gene. It has been proposed, and some evidence has been shown, that germ cells carry only premutation alleles and that expansion occurs at a postzygotic stage. A few cases of reduction of the (CGG){sub n} repeat in fragile X syndrome have been reported. These reductions were from a larger premutation to a smaller premutation, in female-to-male transmission, from full mutation to a mosaic pattern, reduction from mosaic full-mutation/premutation females or regression from premutation to normal. We present here the novel observation of a phenotypically normal female carrying a nonmosaic full-mutation allele in somatic cells who transmits a premutation allele to her daughter. This daughter has three mosaic offspring with the full mutation and the premutation. Two of them are monozygotic (MZ) twins sharing a concordant mutation pattern. They are monoamniotic monochorionic, which indicates a late form of twinning. 20 refs., 1 fig.

  6. Management of Posterior Reversible Syndrome in Preeclamptic Women

    PubMed Central

    Poma, S.; Delmonte, M. P.; Gigliuto, C.; Imberti, R.; Delmonte, M.; Arossa, A.; Iotti, G. A.

    2014-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a neurological syndrome associated with a number of conditions including preeclampsia. It is characterized by seizures, alteration of consciousness, visual disturbances, and symmetric white matter abnormalities, typically in the posterior parietooccipital regions of the cerebral hemispheres, at computed tomography (CT) and magnetic resonance (MRI). We report three new cases of PRES in preeclamptic patients and describe the management of these patients. We present a brief review of other cases in the literature, with particular attention to the anesthetic management. PMID:25506009

  7. 4-aminopyridine reverses ataxia and cerebellar firing deficiency in a mouse model of spinocerebellar ataxia type 6

    PubMed Central

    Jayabal, Sriram; Chang, Hui Ho Vanessa; Cullen, Kathleen E.; Watt, Alanna J.

    2016-01-01

    Spinocerebellar ataxia type 6 (SCA6) is a devastating midlife-onset autosomal dominant motor control disease with no known treatment. Using a hyper-expanded polyglutamine (84Q) knock-in mouse, we found that cerebellar Purkinje cell firing precision was degraded in heterozygous (SCA684Q/+) mice at 19 months when motor deficits are observed. Similar alterations in firing precision and motor control were observed at disease onset at 7 months in homozygous (SCA684Q/84Q) mice, as well as a reduction in firing rate. We further found that chronic administration of the FDA-approved drug 4-aminopyridine (4-AP), which targets potassium channels, alleviated motor coordination deficits and restored cerebellar Purkinje cell firing precision to wildtype (WT) levels in SCA684Q/84Q mice both in acute slices and in vivo. These results provide a novel therapeutic approach for treating ataxic symptoms associated with SCA6. PMID:27381005

  8. Reversible posterior leucoencephalopathy syndrome associated with bone marrow transplantation.

    PubMed

    Teive, H A; Brandi, I V; Camargo, C H; Bittencourt, M A; Bonfim, C M; Friedrich, M L; de Medeiros, C R; Werneck, L C; Pasquini, R

    2001-09-01

    Reversible posterior leucoencephalopathy syndrome (RPLS) has previously been described in patients who have renal insufficiency, eclampsia, hypertensive encephalopathy and patients receiving immunosuppressive therapy. The mechanism by which immunosuppressive agents can cause this syndrome is not clear, but it is probably related with cytotoxic effects of these agents on the vascular endothelium. We report eight patients who received cyclosporine A (CSA) after allogeneic bone marrow transplantation or as treatment for severe aplastic anemia (SSA) who developed posterior leucoencephalopathy. The most common signs and symptoms were seizures and headache. Neurological dysfunction occurred preceded by or concomitant with high blood pressure and some degree of acute renal failure in six patients. Computerized tomography studies showed low-density white matter lesions involving the posterior areas of cerebral hemispheres. Symptoms and neuroimaging abnormalities were reversible and improvement occurred in all patients when given lower doses of CSA or when the drug was withdrawn. RPLS may be considered an expression of CSA neurotoxicity.

  9. Reversible electrocardiogram changes and cardiomyopathy secondary to baclofen withdrawal syndrome.

    PubMed

    Kireyev, Dmitriy; Poh, Kian-Keong

    2010-01-01

    Baclofen withdrawal syndrome is a rare and potentially life-threatening condition manifesting with autonomic dysreflexia, high fevers, spasticity, seizures, and multiorgan failure. Reversible cardiomyopathy due to this condition is extremely rare. A high level of suspicion is needed to recognize this condition and start an early intervention to improve patient outcome. Electrocardiographic ST-segment elevation in lead aVR was previously described in association with left main, left anterior descending, and triple-vessel coronary artery disease as well as Takotsubo cardiomyopathy. In this article we present a rare case of reversible cardiomyopathy due to baclofen withdrawal syndrome associated with diffuse ST-segment depressions and ST-segment elevation in lead aVR.

  10. Epinephrine-induced posterior reversible encephalopathy syndrome: a case report.

    PubMed

    Gharabawy, Ramez; Pothula, Vijayasimha R; Rubinshteyn, Vladimir; Silverberg, Michael; Gave, Asaf A

    2011-09-01

    Posterior reversible encephalopathy syndrome (PRES) is a rare disorder that is usually associated with hypertensive crises. It is often missed but may be diagnosed by head computed tomographic (CT) scan or magnetic resonance imaging. An adolescent man presented for elective right shoulder arthroscopic bankart repair. Arthroscopy was performed using a solution of normal saline with 3.3 mg/L of epinephrine for irrigation. Postoperatively, the patient presented with hypertension and epileptiform activity. A CT scan of the head showed PRES.

  11. Posterior reversible encephalopathy syndrome in children: a case series

    PubMed Central

    Emeksiz, Serhat; Kutlu, Nurettin Onur; Çaksen, Hüseyin; Alkan, Gülsüm; Yıkmaz, Hülya Şeker; Tokgöz, Hüseyin

    2016-01-01

    Posterior reversible encephalopathy syndrome is characterized by hypertension, seizure, headache, clouding of consciousness, and visual disturbance, and is diagnosed in the presence of typical lesions on magnetic resonance imaging. We retrospectively evaluated five patients who were diagnosed as having posterior reversible encephalopathy syndrome and followed up in Meram Medical Faculty, Pediatric Intensive Care and Hematology wards, between January 2010 and January 2014. We reviewed the demographic and clinical data, and neuroimaging findings. The primary diseases of the subjects included acute lymphocytic leukemia (n=2), Henoch-Schönlein purpura (n=1), systemic lupus erythematous (n=1), and acute poststreptococcal glomerulonephritis (n=1). The mean age was 10±4.58 years (range, 5–14 years). Acute elevation of blood pressure was found in all patients (n=5). Initial neurologic manifestations included seizure, clouding of consciousness, headache, and visual disturbance. After the diagnosis was made through clinical evaluations and magnetic resonance imaging, complete clinical recovery was obtained in all patients with the appropriate therapeutic approach. In conclusion, posterior reversible encephalopathy syndrome should be considered in the differential diagnosis of patients who present with encephalopathy and underlying diseases such as nephritis, vasculitis, malignancy accompanied by hypertension, and a history of use of medication. PMID:28123335

  12. Differences in cortico-striatal-cerebellar activation during working memory in syndromal and nonsyndromal children with prenatal alcohol exposure.

    PubMed

    Diwadkar, Vaibhav A; Meintjes, Ernesta M; Goradia, Dhruman; Dodge, Neil C; Warton, Christopher; Molteno, Christopher D; Jacobson, Sandra W; Jacobson, Joseph L

    2013-08-01

    Although children with heavy prenatal alcohol exposure may exhibit the distinctive facial dysmorphology seen in full or partial fetal alcohol syndrome (FAS/PFAS), many lack that dysmorphology. This study examined the functional organization of working memory in the brain in three groups of children-those meeting diagnostic criteria for FAS or PFAS, heavily exposed (HE) nonsyndromal children, and healthy controls. A verbal n-back task (1-back and 0-back) was administered to 47 children (17 with FAS/PFAS, 13 HE, and 17 controls) during fMRI. Intra-group one-sample t-tests were used to identify activity regions of interest central to verbal working memory including the dorsal prefrontal cortex (dPFC), inferior frontal gyrus, caudate/putamen, parietal cortex, and cerebellar Crus I/lobule VI and lobule VIIB-IX. Whereas groups did not differ in task sensitivity, fMRI analyses suggested different patterns of sub-network recruitment across groups. Controls primarily recruited left inferior frontal gyrus (Broca's area). By contrast, HE primarily recruited an extensive set of fronto-striatal regions, including left dPFC and left caudate, and the FAS/PFAS group relied primarily on two cerebellar subregions and parietal cortex. This study is, to our knowledge, the first to demonstrate differential recruitment of critical brain regions that subserve basic function in children with different fetal alcohol spectrum disorders compared to controls. The distinct activation patterns seen in the two exposed groups may be related to substantial differences in alcohol dose/occasion to which these groups were exposed in utero.

  13. [Posterior Reversible Encephalopathy Syndrome Associated with Cancer Therapy].

    PubMed

    Mitsuya, Koichi; Nakasu, Yoko; Hayashi, Nakamasa; Yasui, Hirofumi; Ikeda, Takashi; Kuji, Shiho; Onozawa, Yusuke; Endo, Masahiro

    2016-03-01

    Posterior reversible encephalopathy syndrome(PRES)is a subacute neurological syndrome typically manifesting with headache, cortical blindness, and seizures. This syndrome is associated with risk factors such as malignant hypertension, eclampsia, and renal failure. Numerous case reports depict its occurrence in cancer patients. The direct causal mechanisms of PRES in cancer patients have not yet been identified. Cytotoxic chemotherapy may cause direct endothelial damage, which would impact the blood brain barrier. Angiogenesis inhibitors also cause elevation in blood pressure;this is significant, because PRES onset may be solely related to hypertension. An increased number of case reports involving new molecular targeted agent suggests that incidence of PRES as an oncological emergency may increase in the future.

  14. Cerebellar Development and Disease

    PubMed Central

    Gleeson, Joseph G.

    2008-01-01

    Recent Advances The molecular control of cell type specification within the developing cerebellum as well as the genetic causes of the most common human developmental cerebellar disorders have long remained mysterious. Recent genetic lineage and loss-of-function data from mice have revealed unique and non-overlapping anatomical origins for GABAergic neurons from ventricular zone precursors and glutamatergic cell from rhombic lip precursors, mirroring distinct origins for these neurotransmitter-specific cell types in the cerebral cortex. Mouse studies elucidating the role of Ptf1a as a cerebellar ventricular zone GABerigic fate switch were actually preceded by the recognition that PTF1A mutations in humans cause cerebellar agenesis, a birth defect of the human cerebellum. Indeed, several genes for congenital human cerebellar malformations have recently been identified, including genes causing Joubert syndrome, Dandy-Walker malformation and Ponto-cerebellar hypoplasia. These studies have pointed to surprisingly complex roles for transcriptional regulation, mitochondrial function and neuronal cilia in patterning, homeostasis and cell proliferation during cerebellar development. Together mouse and human studies are synergistically advancing our understanding of the developmental mechanisms that generate the uniquely complex mature cerebellum. PMID:18513948

  15. New Recessive Syndrome of Microcephaly, Cerebellar Hypoplasia, and Congenital Heart Conduction Defect

    PubMed Central

    Zaki, Maha S; Salam, Ghada M H Abdel; Saleem, Sahar N; Dobyns, William B; Issa, Mahmoud Y; Sattar, Shifteh; Gleeson, Joseph G

    2011-01-01

    We identified a two-branch consanguineous family in which four affected members (three females and one male) presented with constitutive growth delay, severe psychomotor retardation, microcephaly, cerebellar hypoplasia, and second-degree heart block. They also shared distinct facial features and similar appearance of their hands and feet. Childhood-onset insulin-dependent diabetes mellitus developed in one affected child around the age of 9 years. Molecular analysis excluded mutations in potentially related genes such as PTF1A, EIF2AK3, EOMES, and WDR62. This condition appears to be unique of other known conditions, suggesting a unique clinical entity of autosomal recessive mode of inheritance. © 2011 Wiley Periodicals, Inc. PMID:22002884

  16. Post-operative pediatric cerebellar mutism syndrome and its association with hypertrophic olivary degeneration

    PubMed Central

    Spiteri, Michaela; Kumar, Ram; Lewis, Emma; Harave, Srikrishna; Windridge, David; Ong, Chan; Pizer, Barry

    2016-01-01

    Background The dentato-thalamo-cortical (DTC) pathway is recognized as the anatomical substrate for postoperative pediatric cerebellar mutism (POPCMS), a well-recognized complication affecting up to 31% of children undergoing posterior fossa brain tumour resection. The proximal structures of the DTC pathway also form a segment of the Guillain and Mollaret triangle, a neural network which when disrupted causes hypertrophic olivary degeneration (HOD) of the inferior olivary nucleus (ION). We hypothesize that there is an association between the occurrence of POPCMS and HOD and aim to evaluate this on MR imaging using qualitative and quantitative analysis of the ION in children with and without POPCMS. Methods In this retrospective study we qualitatively analysed the follow up MR imaging in 48 children who underwent posterior fossa tumour resection for presence of HOD. Quantitative analysis of the ION was possible in 28 children and was performed using semi-automated segmentation followed by feature extraction and feature selection techniques and relevance of the features to POPCMS were evaluated. The diagnosis of POPCMS was made independently based on clinical and nursing assessment notes. Results There was significant association between POPCMS and bilateral HOD (P=0.002) but not unilateral HOD. Quantitative analysis showed that hyperintensity in the left ION was the most relevant feature in children with POPCMS. Conclusions Bilateral HOD can serve as a reliable radiological indicator in establishing the diagnosis of POPCMS particularly in equivocal cases. The strong association of signal change due to HOD in the left ION suggests that injury to the right proximal efferent cerebellar pathway plays an important role in the causation of POPCMS. PMID:27942473

  17. [Synchronous appearance and improvement with anticancer chemotherapy of paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome complicated with small cell lung cancer].

    PubMed

    Koriyama, Haruki; Kyoraku, Itaru; Yamashita, Shuichi; Shiomi, Kazutaka; Matsumoto, Nobuhiro; Nakazato, Masamitsu

    2013-01-01

    A 62-year-old man who had suffered from instability of gait and double vision for two months was admitted to our hospital because of weakness of the extremities and ataxia of the extremities and trunk. Chest X-rays and CT scans showed enlargement of the left hilar lymph nodes and a nodular shadow in the left lung. Transbronchial biopsy revealed small cell lung cancer. We diagnosed the patient with two conditions: paraneoplastic cerebellar degeneration (PCD), based on cerebellar ataxia, the presence of Hu antineuronal antibodies, and the absence of cerebellar atrophy and malignancy; and Lambert-Eaton myasthenic syndrome (LEMS), based on weakness of the extremities, the presence of P/Q-type voltage-gated calcium channel antibodies, and waxing in the evoked electromyogram. Anticancer chemoradiation therapy that was started within three months of symptom onset resulted in reductions in size of the hilar lymph nodes and the nodule. Concurrently, cerebellar ataxia, weakness of the extremities, and double vision all disappeared. Anticancer chemotherapy is effective against LEMS while usually less effective against PCD. Early commencement of anticancer chemotherapy is recommended for the treatment of PCD with LEMS.

  18. Reversible Cerebral Vasoconstriction Syndrome Without Typical Thunderclap Headache.

    PubMed

    Wolff, Valérie; Ducros, Anne

    2016-04-01

    Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by severe headache and diffuse segmental intracranial arterial constriction that resolve within three months. Stroke, which is the major complication of RCVS, can result in persistent neurological disability, and rarely causes death. Diagnosis of RCVS early in the clinical course might improve outcomes. Although recurrent thunderclap headache is the clinical hallmark of RCVS, the absence of such a pattern should not lead to discard the diagnosis. Our literature review shows that RCVS can also manifest as an unspecific headache, such as a single severe headache episode, a mild or a progressive headache. Moreover, a subset of patients with severe RCVS presents without any headache, but frequently with seizures, focal neurological deficits, confusion or coma, in the setting of stroke or posterior reversible encephalopathy syndrome. These patients may be aphasic or in comatose state, explaining their inability to give their own medical history. They may have forgotten the headache they had a few days before more dramatic symptoms, or may have a variant of the classical RCVS. By consequence, an RCVS should be suspected in patients with any unusual headache, whether thunderclap or not, and in patients with cryptogenic stroke or convexity subarachnoid hemorrhage, whether the patient also has headache or not. Diagnosis in such cases relies on the demonstration of reversible multifocal intracranial arterial stenosis and the exclusion of other causes.

  19. Acute Pancreatitis and Posterior Reversible Encephalopathy Syndrome: A Case Report.

    PubMed

    Magno Pereira, Vítor; Marote Correia, Luís; Rodrigues, Tiago; Serrão Faria, Gorete

    2016-09-01

    The posterior reversible encephalopathy syndrome is a neurological syndrome characterized by headache, confusion, visual disturbances and seizures associated with identifiable areas of cerebral edema on imaging studies. The authors report the case of a man, 33 years-old, leukodermic with a history of chronic alcohol and tobacco consumption, who is admitted to the emergency department for epigastric pain radiating to the back and vomiting with about six hours of evolution and an intense holocranial headache for two hours. His physical examination was remarkable for a blood pressure of 190/100 mmHg and tenderness in epigastrium. His analytical results revealed emphasis on amylase 193 U/L and lipase 934 U/L. During the observation in the emergency department,he presented a generalized tonic-clonic seizure. Abdominal ultrasonography was performed and suggestive of pancreatitis withoutgallstones signals. Head computed tomography showed subarachnoid haemorrhage and a small right frontal cortical haemorrhage. The brain magnetic resonance imaging done one week after admission showed areas of a bilateral and symmetrical T2 / FLAIR hyperintensities in the subcortical white matter of the parietal and superior frontal regions, suggesting a diagnosis of posterior reversible encephalopathy syndrome. Abdominal computed tomography (10 days after admission) demonstrated a thickened pancreas in connection with inflammation and two small hypodense foci in the anterior part of the pancreas body, translating small foci of necrosis. The investigation of a thrombophilic defect revealed a heterozygous G20210A prothrombin gene mutation. The patient was discharged without neurological sequelae and asymptomatic. The follow-up brain magnetic resonance imaging confirmed the reversal of the lesions, confirming the diagnosis.

  20. Posterior reversible encephalopathy syndrome following a scorpion sting.

    PubMed

    Porcello Marrone, Luiz Carlos; Marrone, Bianca Fontana; Neto, Felipe Kalil; Costa, Francisco Cosme; Thomé, Gustavo Gomes; Aramburu, Martin Brandolt; Schilling, Lucas Porcello; Pascoal, Tharick Ali; Gadonski, Giovani; Huf Marrone, Antônio Carlos; da Costa, Jaderson Costa

    2013-10-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity not yet understood, that is present with transient neurologic symptoms and particular radiological findings. The most common imaging pattern in PRES is the presence of edema in the white matter of the posterior portions of both cerebral hemispheres. The cause of PRES is unclear. We report a case of 13-year-old male who was stung by a scorpion and developed a severe headache, visual disturbance, and seizures and had the diagnosis of PRES with a good outcome. Numerous factors can trigger this syndrome, most commonly: acute elevation of blood pressure, abnormal renal function, and immunosuppressive therapy. There are many cases described showing the relationship between PRES and eclampsia, transplantation, neoplasia and chemotherapy treatment, systemic infections, renal disease acute, or chronic. However, this is the first case of PRES following a scorpion sting.

  1. Posterior reversible encephalopathy syndrome associated with left horizontal gaze palsy

    PubMed Central

    Studyvin, Sarah; Al-Halawani, Moh’d; Amireh, Sawsan; Thawabi, Mohammad

    2017-01-01

    Posterior reversible encephalopathy syndrome (PRES) is characterized by rapid onset of symptoms including headache, seizures, altered consciousness, and visual disturbance, as well as radiologic findings of focal reversible vasogenic edema. Multiple visual disturbances have been described in PRES, such as hemianopia, visual neglect, auras, visual hallucinations, and cortical blindness. However, horizontal gaze palsy has not been previously reported. We report a 72-year-old female who presented with blurred vision, severe headache, lethargy, and later developed seizures. She was found to have left horizontal gaze palsy with intact vestibulo-ocular reflex. Brain magnetic resonance imaging (MRI) showed severe edema throughout the subcortical white matter, and signal in the posterior parietal and occipital lobes. She was diagnosed with PRES associated with supranuclear gaze palsy. PMID:28361069

  2. A reversible posterior leucoencephalopathy syndrome including blindness caused by preeclampsia

    PubMed Central

    Vandenbossche, G; Maquet, J; Vroonen, P; Lambert, G; Nisolle, M; Kridelka, F; Emonts, E

    2016-01-01

    Complications of (pre)eclampsia may involve multiple systems and organs. Neurological symptoms may occur. Visual symptoms concern up to 25% the of patients with severe preeclampsia and 50% of the patients with eclampsia. An uncommon effect of severe preeclampsia is sudden blindness. Blindness may be part of a clinical and radiological presentation named Posterior Reversible Encephalopathy Syndrome (PRES). PRES may lead to permanent neurological deficit, recurrences or death. We report the case of a 24-year-old Caucasian patient, gravida 5 para 2 who developed preeclampsia and PRES complicated with blindness at 32 weeks of gestation. Optimal care allowed visual symptoms to resolve within 24 hours and a favourable maternal outcome and no long- term sequelae. We describe different causes and manifestations of PRES and highlight the need for immediate care in order to optimize the chance of symptoms reversibility. PMID:28003872

  3. Study of Posterior Reversible Encephalopathy Syndrome in Children With Acute Lymphoblastic Leukemia After Induction Chemotherapy.

    PubMed

    Tang, Ji-Hong; Tian, Jian-Mei; Sheng, Mao; Hu, Shao-Yan; Li, Yan; Zhang, Li-Ya; Gu, Qing; Wang, Qi

    2016-03-01

    Increasing occurrence of posterior reversible encephalopathy syndrome has been reported in children with acute lymphoblastic leukemia. However, the etiology of posterior reversible encephalopathy syndrome is not clear. To study the possible pathogenetic mechanisms and treatment of this complication, we reported 11 cases of pediatric acute lymphoblastic leukemia who developed posterior reversible encephalopathy syndrome after induction chemotherapy. After appropriate treatment, the clinical symptoms of posterior reversible encephalopathy syndrome in most cases disappeared even though induction chemotherapy continued. During the 1-year follow-up, no recurrence of posterior reversible encephalopathy syndrome was observed. Although the clinical and imaging features of posterior reversible encephalopathy syndrome may be diverse, posterior reversible encephalopathy syndrome should be recognized as a possible important complication of acute lymphoblastic leukemia when neurologic symptoms appear. In line with previous reports, our study also indicated that posterior reversible encephalopathy syndrome was reversible when diagnosed and treated at an early stage. Thus, the occurrence of posterior reversible encephalopathy syndrome should be considered and investigated to optimize the early induction scheme of acute lymphoblastic leukemia treatment.

  4. Reversible splenial lesion syndrome associated with lobar pneumonia

    PubMed Central

    Li, Chunrong; Wu, Xiujuan; Qi, Hehe; Cheng, Yanwei; Zhang, Bing; Zhou, Hongwei; Lv, Xiaohong; Liu, Kangding; Zhang, Hong-Liang

    2016-01-01

    Abstract Background: Reversible splenial lesion syndrome (RESLES) is a rare clinico-radiological disorder with unclear pathophysiology. Clinically, RESLES is defined as reversible isolated splenial lesions in the corpus callosum, which can be readily identified by magnetic resonance imaging (MRI) and usually resolve completely over a period of time. RESLES could be typically triggered by infection, antiepileptic drugs (AEDs), poisoning, etc. More factors are increasingly recognized. Methods and results: We reported herein an 18-year-old female patient with lobar pneumonia who developed mental abnormalities during hospitalization. An isolated splenial lesion in the corpus callosum was found by head MRI and the lesion disappeared 15 days later. Based on her clinical manifestations and radiological findings, she was diagnosed with lobar pneumonia associated RESLES. We further summarize the up-to-date knowledge about the etiology, possible pathogenesis, clinical manifestations, radiological features, treatment, and prognosis of RESLES. Conclusion: This report contributes to the clinical understanding of RESLES which may present with mental abnormalities after infection. The characteristic imaging of reversible isolated splenial lesions in the corpus callosum was confirmed in this report. The clinical manifestations and lesions on MRI could disappear naturally after 1 month without special treatment. PMID:27684805

  5. Posterior reversible encephalopathy syndrome in patient of severe preeclampsia with Hellp syndrome immediate postpartum.

    PubMed

    Babahabib, Moulay Abdellah; Abdillahi, Ibrahima; Kassidi, Farid; Kouach, Jaouad; Moussaoui, Driss; Dehayni, Mohammed

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a rare clinico-neuroradiologic condition, not commonly reported in the literature. PRES is an uncommon complication of severe preeclampsia/eclampsia. We report the management of one patient with postpartum preeclampsia as an association of HELLP syndrome presenting with status-epileptics. Early diagnosis along with timely supportive therapy resulted in the successful management of this challenging case. Recent understanding on the pathophysiology of this uncommon condition is discussed. We highlight the importance to obstetricians, intensive-care physicians and anesthesiologists of recognizing such cases.

  6. Assessment of Anterior Cingulate Cortex (ACC) and Left Cerebellar Metabolism in Asperger's Syndrome with Proton Magnetic Resonance Spectroscopy (MRS)

    PubMed Central

    Goji, Aya; Ito, Hiromichi; Mori, Kenji; Harada, Masafumi; Hisaoka, Sonoka; Toda, Yoshihiro; Mori, Tatsuo; Abe, Yoko; Miyazaki, Masahito; Kagami, Shoji

    2017-01-01

    Purpose Proton magnetic resonance spectroscopy (1H MRS) is a noninvasive neuroimaging method to quantify biochemical metabolites in vivo and it can serve as a powerful tool to monitor neurobiochemical profiles in the brain. Asperger’s syndrome (AS) is a type of autism spectrum disorder, which is characterized by impaired social skills and restrictive, repetitive patterns of interest and activities, while intellectual levels and language skills are relatively preserved. Despite clinical aspects have been well-characterized, neurometabolic profiling in the brain of AS remains to be clear. The present study used proton magnetic resonance spectroscopy (1H MRS) to investigate whether pediatric AS is associated with measurable neurometabolic abnormalities that can contribute new information on the neurobiological underpinnings of the disorder. Methods Study participants consisted of 34 children with AS (2–12 years old; mean age 5.2 (±2.0); 28 boys) and 19 typically developed children (2–11 years old; mean age 5.6 (±2.6); 12 boys) who served as the normal control group. The 1H MRS data were obtained from two regions of interest: the anterior cingulate cortex (ACC) and left cerebellum. Results In the ACC, levels of N-acetylaspartate (NAA), total creatine (tCr), total choline-containing compounds (tCho) and myo-Inositol (mI) were significantly decreased in children with AS compared to controls. On the other hand, no significant group differences in any of the metabolites were found in the left cerebellum. Neither age nor sex accounted for the metabolic findings in the regions. Conclusion The finding of decreased levels of NAA, tCr, tCho, and mI in the ACC but not in left cerebellar voxels in the AS, suggests a lower ACC neuronal density in the present AS cohort compared to controls. PMID:28060873

  7. Posterior reversible encephalopathy syndrome caused by presumed Takayasu arteritis

    PubMed Central

    Lee, Ki Wuk; Lee, Sang Taek

    2016-01-01

    Takayasu arteritis (TA) is a chronic inflammatory disease of unknown etiology that affects mainly the aorta, main aortic branches, and pulmonary arteries. Diverse neurological manifestations of TA have rarely been reported in children. Posterior reversible encephalopathy syndrome (PRES) is a neuroradiological condition that presents with headache, seizure, visual disturbances, and characteristic lesions on imaging. Inflammatory condition and severe hypertension in TA can cause PRES. We report of a 5-year-old girl with presumed TA who presented with PRES and chronic total occlusion in the renal artery. The findings on magnetic resonance imaging suggested PRES. Left nephrectomy was performed for total occlusion of the left renal artery, and the confirmatory diagnosis of TA was based on the pathologic findings of the renal artery. PMID:28018468

  8. Permanent bilateral cortical blindness due to reversible posterior leukoencephalopathy syndrome.

    PubMed

    Iwama, Mayumi; Takahashi, Hiroshi; Takagi, Ryo; Hiraoka, Miki

    2011-01-01

    Reversible posterior leukoencephalopathy syndrome (RPLS) is induced by acute cerebral edema. Its symptoms include seizures, headache, altered mental status, and visual disturbances. The clinical and radiological findings are usually transient. This report describes a case of RPLS resulting in bilateral total blindness. A 40-year-old man presented with lethargy and bilateral visual loss. He had a 20-year history of hypertension, but had never been treated. On presentation, the left eye was able to perceive light, but the right eye was not. Radiological examination showed diffuse edema in the brain, and ocular fundus examination revealed severe bilateral hypertensive retinopathy. Antihypertensive therapy improved the patient's general condition, including blood pressure. Radiological findings 5 months later showed resolution of most of the abnormal signal areas. However, total blindness had developed in both eyes by day 15, and two courses of pulsed corticosteroid therapy failed to restore the visual loss.

  9. Reversibility of functional deficits in experimental models of Rett syndrome.

    PubMed

    Cobb, Stuart; Guy, Jacky; Bird, Adrian

    2010-04-01

    Mutations in the X-linked MECP2 gene are the primary cause of the severe autism spectrum disorder RTT (Rett syndrome). Deletion of Mecp2 in mice recapitulates many of the overt neurological features seen in humans, and the delayed onset of symptoms is accompanied by deficits in neuronal morphology and synaptic physiology. Recent evidence suggests that reactivation of endogenous Mecp2 in young and adult mice can reverse aspects of RTT-like pathology. In the current perspective, we discuss these findings as well as other genetic, pharmacological and environmental interventions that attempt phenotypic rescue in RTT. We believe these studies provide valuable insights into the tractability of RTT and related conditions and are useful pointers for the development of future therapeutic strategies.

  10. Congenital subclavian steal syndrome with multiple cerebellar infarctions caused by an atypical circumflex retroesophageal right aortic arch with atretic aberrant left subclavian artery.

    PubMed

    Mamopoulos, Apostolos T; Luther, Bernd

    2014-09-01

    A right-sided aortic arch is a rare anomaly with an incidence of 0.1% worldwide and is usually associated with a mirror image of all supra-aortic branches or an aberrant left subclavian artery. The latter is often associated with a Kommerell diverticulum, although it can rarely be hypoplastic or atretic and lead to congenital subclavian steal. In most patients, the situation is well-tolerated. In this report, we present a case of subclavian steal syndrome with multiple cerebellar infarcts in a patient with an atypical right-sided aortic arch and an atretic aberrant left subclavian artery arising from a left-sided descending thoracic aorta.

  11. Anti-Ri-associated paraneoplastic brainstem cerebellar syndrome with coexisting limbic encephalitis in a patient with mixed large cell neuroendocrine lung carcinoma.

    PubMed

    Mitchell, Amber N; Bakhos, Charles T; Zimmerman, Earl A

    2015-02-01

    Paraneoplastic neurologic syndromes (PNS) can be the first manifestations of occult malignancies. If left untreated, PNS often lead to significant morbidity and mortality. Anti-Ri (anti-neuronal nuclear antibody type 2 [ANNA-2]) autoantibodies are commonly associated with breast and small cell lung cancers. Cases of anti-Ri paraneoplastic cerebellar degeneration are reported, but few describe severe nausea and coexisting limbic encephalitis as the major presenting features. We report a 75-year-old woman with medically-intractable emesis, encephalopathy, diplopia, vertigo, and gait ataxia for 3 months. Examination revealed rotary nystagmus, ocular skew deviation, limb dysmetria, and gait ataxia. After two courses of intravenous immunoglobulin, there was minimal improvement. Anti-Ri antibodies were positive in serum only. CT scan identified a 2.0 cm left lung mass, and histopathology revealed large cell neuroendocrine carcinoma with admixed adenocarcinoma non-small cell lung carcinoma (NCSLC). Though the patient achieved nearly complete clinical recovery after tumor resection, anti-Ri levels remained high at 20 months post-resection. To our knowledge this is the first report of a paraneoplastic brainstem cerebellar syndrome with coexisting limbic encephalitis involving anti-Ri positivity and associated mixed neuroendocrine/NSCLC of the lung with marked improvement after tumor resection.

  12. KLK5 Inactivation Reverses Cutaneous Hallmarks of Netherton Syndrome.

    PubMed

    Furio, Laetitia; Pampalakis, Georgios; Michael, Iacovos P; Nagy, Andras; Sotiropoulou, Georgia; Hovnanian, Alain

    2015-09-01

    Netherton Syndrome (NS) is a rare and severe autosomal recessive skin disease which can be life-threatening in infants. The disease is characterized by extensive skin desquamation, inflammation, allergic manifestations and hair shaft defects. NS is caused by loss-of-function mutations in SPINK5 encoding the LEKTI serine protease inhibitor. LEKTI deficiency results in unopposed activities of kallikrein-related peptidases (KLKs) and aberrantly increased proteolysis in the epidermis. Spink5⁻/⁻ mice recapitulate the NS phenotype, display enhanced epidermal Klk5 and Klk7 protease activities and die within a few hours after birth because of a severe skin barrier defect. However the contribution of these various proteases in the physiopathology remains to be determined. In this study, we developed a new murine model in which Klk5 and Spink5 were both knocked out to assess whether Klk5 deletion is sufficient to reverse the NS phenotype in Spink5⁻/⁻ mice. By repeated intercrossing between Klk5⁻/⁻ mice with Spink5⁻/⁻ mice, we generated Spink5⁻/⁻Klk5⁻/⁻ animals. We showed that Klk5 knock-out in Lekti-deficient newborn mice rescues neonatal lethality, reverses the severe skin barrier defect, restores epidermal structure and prevents skin inflammation. Specifically, using in situ zymography and specific protease substrates, we showed that Klk5 knockout reduced epidermal proteolytic activity, particularly its downstream targets proteases KLK7, KLK14 and ELA2. By immunostaining, western blot, histology and electron microscopy analyses, we provide evidence that desmosomes and corneodesmosomes remain intact and that epidermal differentiation is restored in Spink5⁻/⁻Klk5⁻/⁻. Quantitative RT-PCR analyses and immunostainings revealed absence of inflammation and allergy in Spink5⁻/⁻Klk5⁻/⁻ skin. Notably, Il-1β, Il17A and Tslp levels were normalized. Our results provide in vivo evidence that KLK5 knockout is sufficient to reverse NS-like symptoms

  13. Reverse Genetics System for Severe Fever with Thrombocytopenia Syndrome Virus

    PubMed Central

    Brennan, Benjamin; Li, Ping; Zhang, Shuo; Li, Aqian; Liang, Mifang; Li, Dexin

    2014-01-01

    ABSTRACT Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen that was first reported in China in 2009. Phylogenetic analysis of the viral genome showed that SFTS virus represents a new lineage within the Phlebovirus genus, distinct from the existing sandfly fever and Uukuniemi virus groups, in the family Bunyaviridae. SFTS disease is characterized by gastrointestinal symptoms, chills, joint pain, myalgia, thrombocytopenia, leukocytopenia, and some hemorrhagic manifestations with a case fatality rate of about 2 to 15%. Here we report the development of reverse genetics systems to study STFSV replication and pathogenesis. We developed and optimized functional T7 polymerase-based M- and S-segment minigenome assays, which revealed errors in the published terminal sequences of the S segment of the Hubei 29 strain of SFTSV. We then generated recombinant viruses from cloned cDNAs prepared to the antigenomic RNAs both of the minimally passaged virus (HB29) and of a cell culture-adapted strain designated HB29pp. The growth properties, pattern of viral protein synthesis, and subcellular localization of viral N and NSs proteins of wild-type HB29pp (wtHB29pp) and recombinant HB29pp viruses were indistinguishable. We also show that the viruses fail to shut off host cell polypeptide production. The robust reverse genetics system described will be a valuable tool for the design of therapeutics and the development of killed and attenuated vaccines against this important emerging pathogen. IMPORTANCE SFTSV and related tick-borne phleboviruses such as Heartland virus are emerging viruses shown to cause severe disease in humans in the Far East and the United States, respectively. Study of these novel pathogens would be facilitated by technology to manipulate these viruses in a laboratory setting using reverse genetics. Here, we report the generation of infectious SFTSV from cDNA clones and demonstrate that the behavior of recombinant viruses

  14. Rare Case of Posterior Reversible Leukoencephalopathy Syndrome Secondary to Acute Chest Syndrome

    PubMed Central

    Klein, Daniel; El-Sherif, Yasir

    2016-01-01

    We present a case of 29/m with a history of sickle cell disease who presented to the emergency department with sudden onset of chest, trunk, extremity, and back pain, consistent in quality and severity with the patient's usual pain crises. Soon after admission to the medical unit for acute chest syndrome (ACS), the patient developed sudden onset of hypertension associated with left sided hemiplegia, lethargy, dysarthria, aphasia, and left sided facial droop. Neuroimaging revealed that on MRI Brain there was multifocal extensive signal abnormality and a small focal areas of hemorrhage compatible with posterior reversible leukoencephalopathy syndrome (PRES). Patient was treated with levetiracetam and phenytoin and improved soon afterwards, with resolution seen on follow-up MRI two months later. PMID:27957377

  15. Posterior Reversible Encephalopathy Syndrome in Henoch-Schonlein Purpura and Hemolytic Uremic Syndrome

    PubMed Central

    Fidan, Kibriya; Kandur, Yasar; Ucar, Murat; Gucuyener, Kivilcim; Soylemezoglu, Oguz

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological syndrome, composed of symptoms such as headache, seizures, visual disturbances, lethargy, confusion, stupor, focal neurologic findings and radiological findings of bilateral gray and white matter abnormalities suggestive of edema in the posterior regions of the cerebral hemispheres. PRES is associated with significant morbidity and mortality if it is not expeditiously recognized. Magnetic resonance image (MRI) represents the most sensitive imaging technique for recognizing PRES. PRES has been seen in various clinical settings including renal disorders such as acute glomerulonephritis, lupus nephritis, nephrotic syndrome, and drug usage such as calcineurin inhibitors. We aimed to present two study cases for such clinical setting. In this report, we present two patients with PRES in whom the primary diagnosis was hemolytic uremic syndrome (HUS) and Henoch-Schonlein purpura (HSP). Both of them were treated with anticonvulsant and proper antihypertensive drugs. A repeated MRI scan of the head, an ophthalmologic assessment, and a follow-up electroencephalogram produced normal results with no sequelae. Early recognition of PRES as a complication during different diseases and therapies in childhood may facilitate the appropriate treatment, so that intensive treatment should be performed as soon as possible to avoid neurological sequelae. PMID:27298664

  16. Posterior reversible encephalopathy syndrome (PRES) and hypomagnesemia: A frequent association?

    PubMed

    Chardain, A; Mesnage, V; Alamowitch, S; Bourdain, F; Crozier, S; Lenglet, T; Psimaras, D; Demeret, S; Graveleau, P; Hoang-Xuan, K; Levy, R

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a serious neurological condition encountered in various medical fields. Pathophysiological factor(s) common to PRES cases of apparently unrelated etiologies are yet to be found. Based on the hypothesis that hypomagnesemia might participate in the cascade leading to PRES, our study sought to verify whether hypomagnesemia is frequently associated with PRES regardless of etiology. From a retrospective study of a cohort of 57 patients presenting with PRES of different etiologies, presented here are the findings of 19 patients with available serum magnesium levels (SMLs) during PRES. In the acute phase of PRES, hypomagnesemia was present in all 19 patients in spite of differences in etiology (including immunosuppressive drugs, hypertensive encephalopathy, eclampsia, systemic lupus erythematosus, iatrogenic etiology and unknown). SMLs were within normal ranges prior to PRES and below normal ranges during the first 48h of PRES, with a significant decrease in SMLs during the acute phase. In this retrospective study, constant hypomagnesemia was observed during the acute phase of PRES regardless of its etiology. These results now require larger studies to assess the particular importance of acute hypomagnesemia in PRES and especially the possible need to treat PRES with magnesium sulfate.

  17. Reversible dropped head syndrome after hemispheric striatal infarction.

    PubMed

    Funabe, Sayaka; Tanaka, Ryota; Hayashi, Akito; Yamashiro, Kazuo; Shimura, Hideki; Hattori, Nobutaka

    2014-04-01

    We report a rare case of transient "dropped head syndrome" (DHS) after acute ischemic stroke. A 64-year-old man noticed a sudden onset of mild weakness in his left hand and also difficulty in preventing his head from dropping onto his chest without weakness of the neck extensor muscles. Magnetic resonance images showed acute ischemic changes at the right putamen and caudate nucleus. Surface electromyography (EMG) performed 3 days after the stroke showed that both trapeziuses were hypertonic at rest, whereas the activity of the sternocleidomastoids was gradually increased on passive head lifting, indicating dystonia of the neck muscles. His dropped head fully improved by 9 days after the stroke. Re-examination by surface EMG 30 days after the stroke showed no hypertonic activity in the neck muscles. DHS is characterized by an abnormal ante-fixed posture of the neck, usually observed in patients with neurodegenerative disorders such as multiple system atrophy and Parkinson disease. This is the first case of reversible DHS after acute ischemic stroke, and the accumulation of similar cases will be important to elucidate the mechanisms underlying the development of DHS and stroke-associated movement disorders.

  18. [Reversible posterior leukoencephalopathy syndrome associated with carbamazepine-induced hypertension].

    PubMed

    Furuta, Natsumi; Fujita, Yukio; Sekine, Akiko; Ikeda, Masaki; Okamoto, Koichi

    2009-04-01

    A 21-year-old man developed idiopathic trigeminal neuralgia, and was admitted to our hospital. Although neuralgia was promptly resolved after oral carbamazepine (CBZ) administration, he developed arterial hypertension (from 110/60 mmHg to 170/126 mmHg) followed by consciousness disturbance several days after the initiation of carbamazepine. MRI T2-weighted, FLAIR and ADC images demonstrated transient hyperintense lesions of the bilateral fronto-parieto-occipital subcortical white matter. These lesions showed isointensity on diffusion-weighted images. Since these alterations suggested the presence of vasogenic edema induced by hypertension, we diagnosed him as having reversible posterior leukoencephalopathy syndrome (RPLS) induced by hypertension. Persistent hypertension despite the administration of various anti-hypertension drugs finally improved after oral CBZ therapy was discontinued. Therefore, we considered that hypertension was induced by oral CBZ therapy. This is a rare case in which high blood pressure was caused by CBZ. There is no previous report of RPLS induced by CBZ administration. Further investigation to determine whether CBZ is capable of causing arterial hypertension is warranted.

  19. Novel Jbts17 mutant mouse model of Joubert syndrome with cilia transition zone defects and cerebellar and other ciliopathy related anomalies.

    PubMed

    Damerla, Rama Rao; Cui, Cheng; Gabriel, George C; Liu, Xiaoqin; Craige, Branch; Gibbs, Brian C; Francis, Richard; Li, You; Chatterjee, Bishwanath; San Agustin, Jovenal T; Eguether, Thibaut; Subramanian, Ramiah; Witman, George B; Michaud, Jacques L; Pazour, Gregory J; Lo, Cecilia W

    2015-07-15

    Recent studies identified a previously uncharacterized gene C5ORF42 (JBTS17) as a major cause of Joubert syndrome (JBTS), a ciliopathy associated with cerebellar abnormalities and other birth defects. Here we report the first Jbts17 mutant mouse model, Heart Under Glass (Hug), recovered from a forward genetic screen. Exome sequencing identified Hug as a S235P missense mutation in the mouse homolog of JBTS17 (2410089e03rik). Hug mutants exhibit multiple birth defects typical of ciliopathies, including skeletal dysplasia, polydactyly, craniofacial anomalies, kidney cysts and eye defects. Some Hug mutants exhibit congenital heart defects ranging from mild pulmonary stenosis to severe pulmonary atresia. Immunostaining showed JBTS17 is localized in the cilia transition zone. Fibroblasts from Hug mutant mice and a JBTS patient with a JBTS17 mutation showed ciliogenesis defects. Significantly, Hug mutant fibroblasts showed loss of not only JBTS17, but also NPHP1 and CEP290 from the cilia transition zone. Hug mutants exhibited reduced ciliation in the cerebellum. This was associated with reduction in cerebellar foliation. Using a fibroblast wound-healing assay, we showed Hug mutant cells cannot establish cell polarity required for directional cell migration. However, stereocilia patterning was grossly normal in the cochlea, indicating planar cell polarity is not markedly affected. Overall, we showed the JBTS pathophysiology is replicated in the Hug mutant mice harboring a Jbts17 mutation. Our findings demonstrate JBTS17 is a cilia transition zone component that acts upstream of other Joubert syndrome associated transition zone proteins NPHP1 and CEP290, indicating its importance in the pathogenesis of Joubert syndrome.

  20. Cortical blindness after contrast-enhanced CT scan in a patient of sarcoidosis - Is it related to posterior reversible encephalopathy syndrome?

    PubMed

    Suri, Vinit; Agarwal, Ritu; Jadhao, Nilesh; Ahuja, Gulshan K

    2011-10-01

    Transient cortical blindness (TCB) is a well known but rare complication of administration of contrast agent. In this case report, we present a 53-year-old woman who is a follow-up case of sarcoidosis and developed TCB with focal neurological symptoms following contrast-enhanced computed tomography scan. Magnetic resonance imaging revealed bilateral T2/Flair hyperintensities in parieto-occipital, high frontal, and cerebellar hemispheres with involvement of corpus callosum. Clinically and radiologically patient improved significantly in 4 days. The exact mechanism is still speculative and its possible relationship with posterior reversible encephalopathy syndrome is briefly discussed. The patient's symptoms were presumed to be exacerbated by presence of hypertension, underlying autoimmune disorder, sepsis, and high osmolality of contrast agent. Though there is no definite evidence to suggest that a certain treatment regimen improves the natural history of this disease but control of risk factors can possibly prevent this rare but devastating complication.

  1. Posterior reversible encephalopathy syndrome secondary to blood transfusion.

    PubMed

    Singh, Karanbir; Gupta, Rajesh; Kamal, Haris; Silvestri, Nicholas J; Wolfe, Gil I

    2015-03-01

    The appearance of posterior reversible encephalopathy syndrome (PRES) after blood transfusion is rare and has only been reported in three patients to our knowledge. We report a fourth patient with PRES secondary to blood transfusion. A 36-year-old woman with a history of menorrhagia presented to the emergency department with severe fatigue. She had a hemoglobin of 1.7 g/dl and received four units of red blood cells over 15 hours. On day 6 post-transfusion she returned with confusion, headache and a generalized tonic-clonic seizure. The MRI of her brain was consistent with PRES. The following day her confusion worsened, repeat MRI of the brain showed new T2-weighted lesions. Over next 10 days her mental status gradually improved close to her baseline. A repeat MRI of the brain showed resolution of the T2-weighted lesions. The clinical presentation, radiological findings and disease progression in our patient was consistent with PRES. Other than the blood transfusions, there were no apparent risk factors for PRES. The prior three patients with post-transfusion PRES have been reported in middle-aged women with uterine fibroids. It is suspected that these patients have a subacute to chronic anemic state due to ongoing menorrhagia. It is interesting to note that no cases of PRES post-transfusion have been reported in the setting of acute blood loss, such as from trauma. It is postulated that an abrupt increase in hemoglobin causes a rapid rise in blood viscosity and loss of hypoxic vasodilation. Subsequent endothelial damage and brain capillary leakage results in PRES. This constellation of changes may not occur after transfusion in patients with more acute blood loss.

  2. Postinfectious Opsoclonus-Myoclonus Syndrome in a 41-Year-Old Patient-Visualizing Hyperactivation in Deep Cerebellar Nuclei by Cerebral [(18) F]-FDG- PET.

    PubMed

    Mustafa, Mona; Levin, Johannes; Schöberl, Florian; Rominger, Axel

    2015-01-01

    A 41-year-old woman presented with acute onset headache, vertigo, nausea, and gait disorder, initially interpreted as a common cold. Within 2 weeks, she developed a severe opsoclonus-myoclonus syndrome with truncal ataxia. Cerebrospinal fluid examination and serological findings suggested a recent infection with Coxsackie B3 virus. [(18) F]-FDG-PET proved to be the only imaging tool to identify the underlying pathology depicting hyperactivation in the vestibulo- and spinocerebellum as well as hyperactivation of the ocular muscles. At the clinical follow-up 4 months later, the patient's symptoms were considerably improved with only intermittent low-frequency opsoclonus. Corresponding PET findings were able to depict the response to therapy in the ocular muscles and the inferior vermis, whereas the deep cerebellar nuclei were still hyperactivated, however, to a lesser extent. This finding highlights the usefulness of functional/metabolic brain imaging to study the pathophysiology of this type of disorder.

  3. Posterior Reversible Encephalopathy Syndrome in a Postpartum Preeclamptic Woman without Seizure

    PubMed Central

    Ural, Ülkü Mete; Balik, Gülsah; Şentürk, Şenol; Üstüner, Işık; Çobanoğlu, Uğur; Şahin, Figen Kır

    2014-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a cliniconeuroradiological entity presenting with headache, confusion, visual disturbances or blindness, and seizures. Parieto-occipital white matter changes due to vasogenic oedema can be observed on imaging modalities. It rarely occurs without seizures and after delivery. We report a 33-year-old multigravida with a history of preeclampsia in term pregnancy complicated by PRES without seizures at the postpartum period. Clinical improvement with complete resolution without any complications was observed on the 6th day after delivery. Posterior reversible encephalopathy syndrome is reversible when early diagnosis is established and appropriate treatment is started without delay. PMID:24592342

  4. Elevated B-cell activating factor BAFF, but not APRIL, correlates with CSF cerebellar autoantibodies in pediatric opsoclonus-myoclonus syndrome.

    PubMed

    Fühlhuber, V; Bick, S; Kirsten, A; Hahn, A; Gerriets, T; Tschernatsch, M; Kaps, M; Preissner, K T; Blaes, F; Altenkämper, S

    2009-05-29

    Childhood opsoclonus-myoclonus syndrome (OMS) occurs idiopathic or, in association with a neuroblastoma, as a paraneoplastic syndrome. Since autoantibodies were identified in some patients, an autoimmune pathogenesis has been suspected. While the newly discovered B-cell activating factors BAFF and APRIL are involved in systemic autoimmune diseases, their association with neuroimmunological diseases is hardly understood. We here investigated the BAFF and APRIL levels in serum and cerebrospinal fluid (CSF) of OMS patients and their correlation with surface-binding autoantibodies. BAFF and APRIL were both determined by ELISA, and autoantibodies to cerebellar granular neurons (CGN) have been investigated by flow cytometry in 17 OMS patients, 16 neuroblastoma (NB) patients, 13 controls and 11 children with inflammatory neurological diseases (IND). BAFF, but no APRIL, was elevated in the CSF of OMS children and IND children. However, in contrast to IND patients, OMS patients did not have a blood-brain-barrier disturbance, indicating that BAFF was produced intrathecally in OMS patients, but not in IND patients. CSF BAFF levels showed a correlation with CSF CGN autoantibodies (r(2)=0.58, p<0.05). These data indicate that an activated B-cell system in the cerebrospinal fluid is involved in the pathogenesis of OMS, and BAFF may be a candidate parameter for the activation of B-cell immune system.

  5. Posterior reversible encephalopathy syndrome is not associated with mutations in aquaporin-4.

    PubMed

    Matiello, Marcelo; Muralidharan, Rajanandini; Sun, David; Rabinstein, Alejandro A; Weinshenker, Brian G

    2015-08-01

    Posterior reversible encephalopathy syndrome (PRES) is characterized by acute reversible subcortical vasogenic edema that is typically bilateral and self-limiting. It preferentially affects posterior regions of the brain. Clinical manifestations include encephalopathy, seizures, headache, and cortical blindness. PRES may be precipitated by hypertensive crises such as eclampsia and by immunosuppressive agents. The pathophysiology of PRES is incompletely understood. Disordered cerebral autoregulation leading to protein and fluid extravasation is thought to be important.(1) Other theories implicate endothelial dysfunction or vasospasm.(2).

  6. Posterior reversible encephalopathy syndrome in alcoholic hepatitis: Hepatic encephalopathy a common theme.

    PubMed

    John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita

    2017-01-14

    Posterior reversible encephalopathy syndrome (PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome.

  7. Posterior reversible encephalopathy syndrome in alcoholic hepatitis: Hepatic encephalopathy a common theme

    PubMed Central

    John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita

    2017-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome. PMID:28127211

  8. Primary and Reversible Pisa Syndrome in Juvenile Normal Pressure Hydrocephalus

    PubMed Central

    Leon-Sarmiento, Fidias E.; Pradilla, Gustavo; del Rosario Zambrano, Maria

    2012-01-01

    Objective To report a case of Pisa syndrome in a patient with idiopathic normal pressure hydrocephalus, who had never been exposed to psychotropic medications. Methods A 26 years-old, Colombian, male patient, was referred because he had cognitive abnormalities, gait disturbances and urinary incontinence. This patient also displayed pleurothotonos. Neurofunctional evaluation of sensory and motor integration at peripheral and central nervous system levels were done. Results Pisa syndrome disappeared after spinal tap drainage with further gait, balance and behavioral improvement. A brainstem-thalamocortical deregulation of the central sensory and motor programming, due to the chaotic enlargement of brain ventricles was thought to be the pathophysiological mechanism underlying this case. Conclusion NPH must not be longer considered as an exclusive geriatric disorder. Further, uncommon movement disorders may appear with this disorder, which should be carefully approached to avoid iatrogenic and deleterious pharmacological interventions. PMID:23794788

  9. Stimulus-Reward Association and Reversal Learning in Individuals with Asperger Syndrome

    ERIC Educational Resources Information Center

    Zalla, Tiziana; Sav, Anca-Maria; Leboyer, Marion

    2009-01-01

    In the present study, performance of a group of adults with Asperger Syndrome (AS) on two series of object reversal and extinction was compared with that of a group of adults with typical development. Participants were requested to learn a stimulus-reward association rule and monitor changes in reward value of stimuli in order to gain as many…

  10. Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8

    PubMed Central

    Boycott, Kym M.; Beaulieu, Chandree L.; Kernohan, Kristin D.; Gebril, Ola H.; Mhanni, Aziz; Chudley, Albert E.; Redl, David; Qin, Wen; Hampson, Sarah; Küry, Sébastien; Tetreault, Martine; Puffenberger, Erik G.; Scott, James N.; Bezieau, Stéphane; Reis, André; Uebe, Steffen; Schumacher, Johannes; Hegele, Robert A.; McLeod, D. Ross; Gálvez-Peralta, Marina; Majewski, Jacek; Ramaekers, Vincent T.; Nebert, Daniel W.; Innes, A. Micheil; Parboosingh, Jillian S.; Abou Jamra, Rami

    2015-01-01

    Manganese (Mn) and zinc (Zn) are essential divalent cations used by cells as protein cofactors; various human studies and animal models have demonstrated the importance of Mn and Zn for development. Here we describe an autosomal-recessive disorder in six individuals from the Hutterite community and in an unrelated Egyptian sibpair; the disorder is characterized by intellectual disability, developmental delay, hypotonia, strabismus, cerebellar atrophy, and variable short stature. Exome sequencing in one affected Hutterite individual and the Egyptian family identified the same homozygous variant, c.112G>C (p.Gly38Arg), affecting a conserved residue of SLC39A8. The affected Hutterite and Egyptian individuals did not share an extended common haplotype, suggesting that the mutation arose independently. SLC39A8 is a member of the solute carrier gene family known to import Mn, Zn, and other divalent cations across the plasma membrane. Evaluation of these two metal ions in the affected individuals revealed variably low levels of Mn and Zn in blood and elevated levels in urine, indicating renal wasting. Our findings identify a human Mn and Zn transporter deficiency syndrome linked to SLC39A8, providing insight into the roles of Mn and Zn homeostasis in human health and development. PMID:26637978

  11. Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8.

    PubMed

    Boycott, Kym M; Beaulieu, Chandree L; Kernohan, Kristin D; Gebril, Ola H; Mhanni, Aziz; Chudley, Albert E; Redl, David; Qin, Wen; Hampson, Sarah; Küry, Sébastien; Tetreault, Martine; Puffenberger, Erik G; Scott, James N; Bezieau, Stéphane; Reis, André; Uebe, Steffen; Schumacher, Johannes; Hegele, Robert A; McLeod, D Ross; Gálvez-Peralta, Marina; Majewski, Jacek; Ramaekers, Vincent T; Nebert, Daniel W; Innes, A Micheil; Parboosingh, Jillian S; Abou Jamra, Rami

    2015-12-03

    Manganese (Mn) and zinc (Zn) are essential divalent cations used by cells as protein cofactors; various human studies and animal models have demonstrated the importance of Mn and Zn for development. Here we describe an autosomal-recessive disorder in six individuals from the Hutterite community and in an unrelated Egyptian sibpair; the disorder is characterized by intellectual disability, developmental delay, hypotonia, strabismus, cerebellar atrophy, and variable short stature. Exome sequencing in one affected Hutterite individual and the Egyptian family identified the same homozygous variant, c.112G>C (p.Gly38Arg), affecting a conserved residue of SLC39A8. The affected Hutterite and Egyptian individuals did not share an extended common haplotype, suggesting that the mutation arose independently. SLC39A8 is a member of the solute carrier gene family known to import Mn, Zn, and other divalent cations across the plasma membrane. Evaluation of these two metal ions in the affected individuals revealed variably low levels of Mn and Zn in blood and elevated levels in urine, indicating renal wasting. Our findings identify a human Mn and Zn transporter deficiency syndrome linked to SLC39A8, providing insight into the roles of Mn and Zn homeostasis in human health and development.

  12. Reversible Pisa syndrome associated to subdural haematoma: case-report

    PubMed Central

    2014-01-01

    Background Pisa Syndrome or Pleurothotonus is a relatively rare truncal dystonia, characterized by tonic flexion of the trunk and head to one side with slight rotation of the body. Since frequently associated to specific drugs such as antipsychotics and cholinesterase inhibitors or to Parkinson Disease, a pathophysiological role of cholinergic-dopaminergic imbalance has been suggested. We report here the first case of Pisa Syndrome due to an extracerebral pathology as subdural haematoma. Case presentation A hypertensive patient was admitted to Our Department for subacute onset of tonic flexion and slight rotation of the trunk associated to progressive motor deficit in left upper limb after a mild head trauma without loss of consciousness occurred around three month before. No previous or current pharmacological interventions with antidepressant, neuroleptic or anticholinergic drugs were anamnestically retrieved. Familiar and personal history was negative for neurological disorders other than acute cerebrovascular diseases. Acutely performed cerebral MRI with DWI showed a voluminous right subdural haematoma with mild shift of median line. After surgical evacuation, both motor deficit and truncal dystonia were dramatically resolved. At one-year follow up, the patient did not develop any extrapyramidal and cognitive signs or symptoms. Conclusions According to many Authors, the occurrence of truncal dystonia during several pharmacologic treatments and neurodegenerative disorders (such as Alzheimer disease and parkinsonian syndromes) supported the hypothesis that a complex dysregulation of multiple neurotransmitter systems are involved. We suggest a possible role of basal ganglia compression in pathogenesis of truncal dystonia by means of thalamo-cortical trait functional disruption and loss of proprioceptive integration. A further contribution of the subcortical structure displacement that alters motor cortex connectivity to basal ganglia may be postulated. PMID

  13. Acute Reversible Charles Bonnet Syndrome Following Eye Patch Placement.

    PubMed

    Nan, Lian; Yanbin, Hou; Jingping, Zhao

    2013-01-01

    Charles Bonnet syndrome (CBS) is characterised by recurrent vivid visual hallucinations in the presence of normal cognition. We present a case of CBS secondary to eye patching following Pars Plana Vitrectomy with an unusually acute onset in a 48-year-old woman. She presented with formed visual hallucinations that started less than 30 min after patching of her left eye. The patch was removed after 2 d, and these hallucinations persisted 2 d following eye patch removal. It is important that the ophthalmic surgeon be aware of the potential for development of CBS and offer appropriate referral and reassurance should it occur.

  14. Reversible Foix-Chavany-Marie Syndrome in a patient treated for hydrocephalus.

    PubMed

    Kaloostian, P; Chen, H; Harrington, H

    2012-10-01

    The authors report the first known case of Foix-Chavany-Marie Syndrome in a patient with hydrocephalus that reversed with ventriculoperitoneal shunting. A 34-year-old x-ray technician with a history of pilocytic astrocytoma resection and radiotherapy and ventriculoperitoneal shunt placement as a child presented with altered mental status and nausea. She was found to have acute hydrocephalus. Post-operatively she did well and was discharged home. The next day she became acutely altered with anarthria, difficulty speaking, and stiff facial muscles. After multiple revisions, she slowly recovered to her pre-op baseline over the course of next 2 months. This is the first known case of acute hydrocephalus causing Foix-Chavany-Marie Syndrome. Additionally, we show that this unique syndrome is slowly reversible after treatment of hydrocephalus.

  15. [A paraneoplastic Sharp syndrome reversible after resection of a benign schwannoma: a paraneoplastic syndrome?].

    PubMed

    Slimani, S; Sahraoui, M; Bennadji, A; Ladjouze-Rezig, A

    2014-08-01

    Paraneoplastic syndromes commonly occur in malignancies and often precede the first symptoms of the tumor. By definition, paraneoplastic syndromes are only associated with malignancies although some exceptions have been reported, occurring with benign tumors. We report a patient presenting with a clinical and serological Sharp syndrome, followed a few months later by a cervical schwannoma. Curative surgical resection of the mass resulted in a clinical and serological healing from the Sharp syndrome. To our knowledge, this is the first report of a benign schwannoma complicated by a possible paraneoplastic Sharp syndrome.

  16. [Posterior reversible encephalopathy syndrome and cerebrovascular constriction syndrome in the differential diagnosis of post-partum headaches].

    PubMed

    Ruiz López, N; Cano Hernández, B; Balbás Álvarez, S

    2016-02-01

    Postpartum headache can be due to many causes. In a patient with previous epidural analgesia, the headache can be attributed to post-dural puncture headache, even if the symptoms are not typical of this clinical entity. We report a case of a post-partum with accidental dural tap during the insertion of an epidural catheter for labour analgesia, and who referred to headaches in the third post-partum day. Initially, a post-dural puncture headache was suspected, but the subsequent onset of seizures and visual impairment meant that the diagnosis had to be reconsidered. In this case report, the clinical and pathophysiological features of posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome, as well as the differential diagnosis of post-partum headaches are described.

  17. [Clinical study of two cases of traumatic cerebellar injury].

    PubMed

    Yokota, H; Nakazawa, S; Kobayashi, S; Taniguchi, Y; Yukihide, T

    1990-01-01

    Two cases of traumatic cerebellar injury complicated with a traumatic medial longitudinal fasciculus (MLF) syndrome or cerebellar mutism were reported, and the cause of these mechanisms was discussed: Case 1: A 9-year-old boy who struck his head in the occipital region during an automobile accident was operated on for a delayed traumatic intracerebellar hematoma. The operation improved the level of his consciousness but MLF syndrome was noticed. The mechanism of traumatic MLF syndrome was discussed in relation to vascular injury and to neurovascular friction. The outcome of the syndrome including our case, which recovered spontaneously, seemed to support the theory of neurovascular injury. Case 2: A 6-year-old boy who struck his head in the temporooccipital region during an automobile accident was admitted to our hospital without conciousness. On admission, contusion of the temporal lobe and left cerebellar hemisphere was demonstrated by a computerized tomography (CT) and magnetic resonance imaging (MRI). A mute state (cerebellar mutism) was recognized after his recovery of consciousness. The cause of the cerebellar mutism was thought to be an injury of the cerebellar vermis or left cerebellar hemisphere. The findings of CT scan and MRI in our case suggested that the cause of the cerebellar mutism was the contusion of these areas.

  18. Reversal of neurological defects in a mouse model of Rett syndrome.

    PubMed

    Guy, Jacky; Gan, Jian; Selfridge, Jim; Cobb, Stuart; Bird, Adrian

    2007-02-23

    Rett syndrome is an autism spectrum disorder caused by mosaic expression of mutant copies of the X-linked MECP2 gene in neurons. However, neurons do not die, which suggests that this is not a neurodegenerative disorder. An important question for future therapeutic approaches to this and related disorders concerns phenotypic reversibility. Can viable but defective neurons be repaired, or is the damage done during development without normal MeCP2 irrevocable? Using a mouse model, we demonstrate robust phenotypic reversal, as activation of MeCP2 expression leads to striking loss of advanced neurological symptoms in both immature and mature adult animals.

  19. Weaker control of the electrical properties of cerebellar granule cells by tonically active GABAA receptors in the Ts65Dn mouse model of Down’s syndrome

    PubMed Central

    2013-01-01

    Background Down’s syndrome (DS) is caused by triplication of all or part of human chromosome 21 and is characterized by a decrease in the overall size of the brain. One of the brain regions most affected is the cerebellum, in which the number of granule cells (GCs) is markedly decreased. GCs process sensory information entering the cerebellum via mossy fibres and pass it on to Purkinje cells and inhibitory interneurons. How GCs transform incoming signals depends on their input–output relationship, which is adjusted by tonically active GABAA receptor channels. Results We report that in the Ts65Dn mouse model of DS, in which cerebellar volume and GC number are decreased as in DS, the tonic GABAA receptor current in GCs is smaller than in wild-type mice and is less effective in moderating input resistance and raising the minimum current required for action potential firing. We also find that tonically active GABAA receptors curb the height and broaden the width of action potentials in wild-type GCs but not in Ts65Dn GCs. Single-cell real-time quantitative PCR reveals that these electrical differences are accompanied by decreased expression of the gene encoding the GABAA receptor β3 subunit but not genes coding for some of the other GABAA receptor subunits expressed in GCs (α1, α6, β2 and δ). Conclusions Weaker moderation of excitability and action potential waveform in GCs of the Ts65Dn mouse by tonically active GABAA receptors is likely to contribute to atypical transfer of information through the cerebellum. Similar changes may occur in DS. PMID:23870245

  20. Recurarization in a successfully managed case of posterior reversible encephalopathy syndrome (PRES) for emergency caesarean section

    PubMed Central

    Parikh, Suchita; Tavri, Snehlata; Mohite, Shubha

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic syndrome of headache, visual changes, altered mental status and seizures with radiologic findings of posterior cerebral white matter edema. It is seen in hypertensive encephalopathy, renal failure, and autoimmune disorders or in patients on immunosuppressants. We report a case of 24-year-old primigravida who presented at term with sudden onset hypertension, neurological deficits, and an episode of the visual blackout. Magnetic resonance imaging showed features suggestive of PRES. She was posted for emergency lower segment cesarean section. General anesthesia was administered and blood pressure managed with antihypertensives. Postoperatively, she developed acute respiratory depression after prophylactic administration of injection magnesium sulfate. This case highlights that good clinical acumen along with early neuroimaging helps in prompt diagnosis, treatment and prevention of long-term neurological sequelae in PRES and the anesthetic implications of administering magnesium sulfate in the immediate post neuromuscular block reversal phase. PMID:27212776

  1. [Prolonged cerebral salt wasting following craniopharyngioma surgery and posterior reversible encephalopathy syndrome: a case report].

    PubMed

    Ohtonari, Tatsuya; Hashimoto, Masanori; Urasaki, Eiichiro; Yokota, Akira; Araki, Shunsuke; Asayama, Koutaro; Shirahata, Akira

    2005-01-01

    A 9-year-old boy was admitted to our hospital with daytime urinary incontinence for the past one year. MRI showed craniopharyngioma occupying the third ventricle. The tumor was excised by interhemispheric approach. Because hyponatremia and polyuria with high renal loss of sodium were observed on postoperative day 3, hydrocortisone and DDAVP were replaced. On postoperative day 24, successive general convulsions and hyponatremia recurred, and MRI FLAIR imaging showed marked brain edema in the bilateral parieto-occipital lobes. This finding disappeared late in the course of treatment, and the case was diagnosed as posterior reversible encephalopathy syndrome. The pathophysiology of cerebral salt wasting and posterior reversible encephalopathy syndrome in a craniopharyngioma patient are also discussed in the article.

  2. Reversible cerebral vasoconstriction syndrome manifesting as focal seizures without a thunderclap headache: A pediatric case report.

    PubMed

    Kuga, Shuji; Goto, Hironori; Okanari, Kazuo; Maeda, Tomoki; Ihara, Kenji

    2016-10-01

    We report a pediatric case of reversible cerebral vasoconstriction syndrome with focal seizures without a thunderclap headache. A 7-year-old girl had a mild acute headache with nausea after swimming. She subsequently developed hemi-convulsions followed by right hemiplegia. Brain magnetic resonance angiography revealed generalized vasoconstriction of the main cerebral peripheral arteries. Her hemiplegia was spontaneously resolved within 6h. Over the next 24h she suffered from recurrent and transient headaches, which recurred on days 3 and 5. Follow-up magnetic resonance angiography on day 3 documented the multifocal narrowing of the main cerebral arteries, which was observed to have diminished at 12weeks after her initial presentation. She did not have any headaches or neurological deficits after day 5. This case indicates that reversible cerebral vasoconstriction syndrome should be considered in children with focal seizures even when they do not present with thunderclap headaches. The timely and appropriate evaluation by magnetic resonance angiography and imaging is essential for diagnosing reversible cerebral vasoconstriction syndrome.

  3. Perioperative posterior reversible encephalopathy syndrome in 2 pediatric neurosurgery patients with brainstem ependymoma.

    PubMed

    Gephart, Melanie G Hayden; Taft, Bonnie P; Giese, Anne-Katrin; Guzman, Raphael; Edwards, Michael S B

    2011-03-01

    Posterior reversible encephalopathy syndrome (PRES) has been described in pediatric neurooncology patients, although it has not been documented perioperatively in pediatric neurosurgery patients not actively receiving chemotherapy. Recently at the authors' facility, 2 cases of PRES were diagnosed perioperatively in children with brainstem ependymoma. Both patients had presented with hypertension, altered mental status, and seizures and demonstrated MR imaging features consistent with PRES. The patients were treated with antiseizure and antihypertension medications, leading to improvement in both clinical symptoms and neuroimaging findings. These cases are the first to document PRES in perioperative pediatric neurosurgery patients not actively receiving chemotherapy. Both patients had ependymoma involving the brainstem, which may have led to intra- and perioperative hemodynamic instability (including hypertension) and predisposed them to this syndrome. An awareness of PRES in similar scenarios will aid in the prevention, diagnosis, and treatment of pediatric neurosurgery patients with this syndrome.

  4. SMART syndrome: a late reversible complication after radiation therapy for brain tumours.

    PubMed

    Kerklaan, Joost P; Lycklama á Nijeholt, Geert J; Wiggenraad, Ruud G J; Berghuis, Bianca; Postma, Tjeerd J; Taphoorn, Martin J B

    2011-06-01

    With intensified treatment leading to longer survival, complications of therapy for brain tumours are more frequently observed. Regarding radiation therapy, progressive and irreversible white matter disease with cognitive decline is most feared. We report on four patients with reversible clinical and radiological features occurring years after radiation for brain tumours, suggestive for the so called SMART syndrome (stroke-like migraine attacks after radiation therapy). All four patients (males, age 36-60 years) had been treated with focal brain radiation for a primary brain tumour or with whole-brain radiation therapy for brain metastases. Ranging from 2 to 10 years following radiation therapy patients presented with headache and focal neurological deficits, suggestive for tumour recurrence. Two patients also presented with focal seizures. MRI demonstrated typical cortical swelling and contrast enhancement, primarily in the parieto-occipital region. On follow-up both clinical and MRI features improved spontaneously. Three patients eventually proved to have tumour recurrence. The clinical and radiological picture of these patients is compatible with the SMART syndrome, a rare complication of radiation therapy which is probably under recognized in brain tumour patients. The pathophysiology of the SMART syndrome is poorly understood but bears similarities with the posterior reversible encephalopathy syndrome (PRES). These four cases underline that the SMART syndrome should be considered in patients formerly treated with radiation therapy for brain tumours, who present with new neurologic deficits. Before the diagnosis of SMART syndrome can be established other causes, such as local tumour recurrence, leptomeningeal disease or ischemic disease should be ruled out.

  5. Dietary reversal of neuropathy in a murine model of prediabetes and the metabolic syndrome.

    PubMed

    Hinder, Lucy M; O'Brien, Phillipe D; Hayes, John M; Backus, Carey; Solway, Andrew P; Sims-Robinson, Catrina; Feldman, Eva L

    2017-04-05

    Patients with the metabolic syndrome, defined as obesity, dyslipidemia, hypertension, and impaired glucose tolerance (IGT), can develop the same macro- and microvascular complications as patients with type 2 diabetes, including peripheral neuropathy. In type 2 diabetes, glycemic control has little effect on the development and progression of peripheral neuropathy, suggesting that other metabolic syndrome components may contribute to the presence of neuropathy. A parallel phenomenon is observed in patients with prediabetes and the metabolic syndrome, where improvement in weight and dyslipidemia more closely correlates with restoration of nerve function than improvement in glycemic status. The goal of the current study was to develop a murine model that resembles the human condition. We examined longitudinal parameters of the metabolic syndrome and neuropathy development in six mouse strains/genotypes (BKS-wt, BKS-Lepr(db/+), B6-wt, B6-Lepr(db/+), BTBR-wt, and BTBR-Lep(ob/+)) fed a 54% high-fat diet (HFD; from lard). All HFD-fed mice developed large fiber neuropathy and IGT. Changes appeared early and consistently in B6-wt mice, and paralleled the onset of neuropathy. Terminally, B6-wt mice displayed all components of the metabolic syndrome, including obesity, IGT, hyperinsulinemia, dyslipidemia, and oxidized low density lipoproteins (oxLDL). Dietary reversal, whereby B6-wt mice fed HFD from 4-20 weeks of age were switched to standard chow for 4 weeks, completely normalized neuropathy, promoted weight loss, improved insulin sensitivity, and restored LDL-cholesterol and oxLDL by 50% compared to HFD control mice. This dietary reversal model provides the basis for mechanistic studies investigating peripheral nerve damage in the setting of the metabolic syndrome, and ultimately the development of mechanism-based therapies for neuropathy.

  6. Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome.

    PubMed

    Merke, Deborah P; Giedd, Jay N; Keil, Margaret F; Mehlinger, Sarah L; Wiggs, E A; Holzer, Stuart; Rawson, Erin; Vaituzis, A Catherine; Stratakis, Constantine A; Chrousos, George P

    2005-05-01

    Adults with Cushing syndrome frequently develop brain atrophy, memory impairment, and depression, with partial to complete resolution after cure. The effect of excess glucocorticoid exposure on the brain of children has not been systematically studied. Eleven children (six girls, five boys; ages, 8-16 yr) with endogenous Cushing syndrome seen at the National Institutes of Health Clinical Center from 1999-2000 and 10 healthy age- and sex-matched control subjects were studied. Cognitive and psychological evaluations and magnetic resonance imaging of the brain were done before and 1 yr after cure for patients with Cushing syndrome and once for controls. The estimated duration of Cushing syndrome was 4.4 +/- 1.2 yr. When compared with control subjects, children with Cushing syndrome had significantly smaller cerebral volumes (P < 0.001), larger ventricles (P = 0.02), and smaller amygdala (P = 0.004). At baseline, there were no significant differences in IQ between the two groups, and no psychopathology was identified. Despite reversal of cerebral atrophy 1 yr after surgical cure (total cerebral volume, 947 +/- 94 vs.1050 +/- 74 ml, P < 0.001; ventricular volume, 21.4 +/- 12.5 vs. 14.5 +/- 11.6 ml, P < 0.001), children with Cushing syndrome experienced a significant (P < 0.05) decline in Wechsler IQ scores (Full Scale, 112 +/- 19 vs. 98 +/- 14) and a decline in school performance, without any associated psychopathology. The effect of glucocorticoid excess on the brain of children appears to be different from adults. Despite rapid reversibility of cerebral atrophy, children experience a significant decline in cognitive function 1 yr after correction of hypercortisolism.

  7. Cortical subarachnoid hemorrhage associated with reversible cerebral vasoconstriction syndrome after elective triplet cesarean delivery.

    PubMed

    Albano, Beatrice; Del Sette, Massimo; Roccatagliata, Luca; Gandolfo, Carlo; Primavera, Alberto

    2011-06-01

    Reversible cerebral vasoconstriction syndromes (RCVS) comprise a group of disorders characterized by prolonged, but reversible vasoconstriction of the cerebral arteries, usually associated with acute-onset, severe, recurrent headaches, with or without additional neurological signs and symptoms. Various complications of this condition have been observed, such as cortical subarachnoid hemorrhages (cSAH), intracerebral hemorrhages, reversible posterior leukoencephalopathy, ischaemic strokes and transient ischaemic attacks. It is important to include RCVS in thunderclap headache differential diagnosis and among non-aneurismatic subarachnoid hemorrhage causes. In the past years, thanks to the major diffusion of new diagnostic tools such as magnetic resonance, computed tomography and digital subtraction angiography, RCVS have been demonstrated to be more frequent than previously thought. We report an illustrative case of a woman affected by a small cSAH, associated to RCVS, after elective triplet cesarean delivery. To our knowledge, this is the first case of cSAH associated to RCVS after a triplet pregnancy.

  8. The cerebellar serotoninergic system and its possible involvement in cerebellar ataxia.

    PubMed

    Trouillas, P

    1993-05-01

    A review concerning the characteristics of the cerebellar serotoninergic system is presented. In rat, cat and oppossum, the perikarya of origin are located in the brain stem raphe nuclei and in other brainstem structures. The projections to the cerebellar layers and deep nuclei include synaptic connections, but also non synaptic terminals, especially in a diffuse cortical plexus. Serotoninergic receptors have been described: 5-HT1B in the molecular layer and 5-HT2 in the inferior olive. Serotonin exerts neurophysiological effects on several target cells, directly or indirectly, presynaptically or postsynaptically. A modulatory effect on Purkinje cells is well documented. In thiamine deprived animals, a specific serotoninergic cerebellar syndrome includes a selective degeneration of the serotoninergic cerebellar system, an increase of the 5-HIAA cerebellar values and an exaggerated serotoninergic turnover. In human heredoataxias (Friedreich's ataxia and cerebellar cortical atrophy), serotoninergic disturbances have been observed in the CSF, including low 5-HIAA values and an increased serotoninergic turnover. Therapeutic results have been obtained with L-5-HTP, a precursor of serotonin, in several conditions presenting cerebellar ataxia. L-5-HTP resistance of olivopontocerebellar atrophies may be explained by the destruction of serotonin-sensitive target cells, especially Purkinje cells.

  9. Middle cerebellar peduncles: Magnetic resonance imaging and pathophysiologic correlate

    PubMed Central

    Morales, Humberto; Tomsick, Thomas

    2015-01-01

    We describe common and less common diseases that can cause magnetic resonance signal abnormalities of middle cerebellar peduncles (MCP), offering a systematic approach correlating imaging findings with clinical clues and pathologic mechanisms. Myelin abnormalities, different types of edema or neurodegenerative processes, can cause areas of abnormal T2 signal, variable enhancement, and patterns of diffusivity of MCP. Pathologies such as demyelinating disorders or certain neurodegenerative entities (e.g., multiple system atrophy or fragile X-associated tremor-ataxia syndrome) appear to have predilection for MCP. Careful evaluation of concomitant imaging findings in the brain or brainstem; and focused correlation with key clinical findings such as immunosuppression for progressive multifocal leukoencephalopahty; hypertension, post-transplant status or high dose chemotherapy for posterior reversible encephalopathy; electrolyte disorders for myelinolysis or suspected toxic-drug related encephalopathy; would yield an appropriate and accurate differential diagnosis in the majority of cases. PMID:26751508

  10. Memory impairment following right cerebellar infarction: a case study.

    PubMed

    Nakamoto, Fumiko Kusunoki; Tsutsumiuchi, Michiko; Maeda, Meiko Hashimoto; Uesaka, Yoshikazu; Takeda, Katsuhiko

    2015-01-01

    We reported a patient with a right cerebellar infarction who showed anterograde amnesia. Cognitive dysfunction caused by cerebellar lesions was called cerebellar cognitive affective syndrome, and deactivation of the contralateral prefrontal cortex function due to disconnections of cerebello-cerebral fiber tracts have been hypothesized as mechanism underlying the syndrome. The episodic memory impairment, however, could not be supported by the same mechanism because the prefrontal lesions cannot cause amnesia syndrome. The feature of the impairment of our patient was similar to that of diencephalic amnesia, and a single photon emission computed tomography study showed a relative hypoperfusion in the right cerebellar hemisphere and left anterior thalamus. We considered that the memory deficit was caused by the dysfunction of the thalamus, which is a relay center of the cerebello-cerebral connectivity network.

  11. Reversals.

    ERIC Educational Resources Information Center

    National Center on Educational Media and Materials for the Handicapped, Columbus, OH.

    Selected from the National Instructional Materials Information System (NIMIS)--a computer based on-line interactive retrieval system on special education materials--the bibliography covers nine materials for remediating reversals in handicapped students at the early childhood and elementary levels. Entries are presented in order of NIMIS accession…

  12. Spastic paraplegia, optic atrophy, microcephaly with normal intelligence, and XY sex reversal: a new autosomal recessive syndrome?

    PubMed Central

    Teebi, A S; Miller, S; Ostrer, H; Eydoux, P; Colomb-Brockmann, C; Oudjhane, K; Watters, G

    1998-01-01

    Two female sibs of first cousin Iranian parents were found to have the syndrome of spastic paraplegia, optic atrophy with poor vision, microcephaly, and normal cognitive development. Karyotype analysis showed a normal female constitution in one and a male constitution (46,XY) in the other. The XY female showed normal female external genitalia, normal uterus and tubes, and streak gonads. SRY gene sequencing was normal. We conclude that the present family probably represents a new autosomal recessive trait of pleiotropic effects including XY sex reversal and adds further evidence for the heterogeneity of spastic paraplegia syndromes as well as sex reversal syndromes. Images PMID:9733035

  13. Cri-du-chat (5p-) syndrome presenting with cerebellar hypoplasia and hypospadias: prenatal diagnosis and aCGH characterization using uncultured amniocytes.

    PubMed

    Chen, Chih-Ping; Huang, Ming-Chao; Chen, Yi-Yung; Chern, Schu-Rern; Wu, Peih-Shan; Su, Jun-Wei; Town, Dai-Dyi; Wang, Wayseen

    2013-07-25

    We present prenatal diagnosis of a de novo distal deletion involving 5p(5p15.1→pter) using uncultured amniocytes in a pregnancy with cerebellar hypoplasia, hypospadias and facial dysmorphisms in the fetus. We discuss the genotype-phenotype correlation and the consequence of haploinsufficiency of CTNND2, SEMA5A, TERT, SRD5A1 and TPPP. We speculate that haploinsufficiency of SRD5A1 and TPPP may be responsible for hypospadias and cerebellar hypoplasia, respectively, in this case.

  14. Acampomelic campomelic syndrome and sex reversal associated with de novo t(12;17) translocation

    SciTech Connect

    Ninomiya, Shinsuke; Narahara, Kouji; Tsuji, Kazushiro

    1995-03-13

    The association of rare chromosomal rearrangements involving a specific 17q breakpoint with campomelic syndrome (CMPS) and/or sex reversal (SR) has led to an assignment of the CMPS1/SRA1 locus to 17q24.3 {yields} q25.1. We describe a patient with multiple anomalies and SR, who had a de novo t(12;17) translocation. The phenotype was consistent with that of CMPS except for the lack of lower limb bowing and talipes equinovarus. Chromosome painting indicated that the breakpoints appeared to have occurred at 12q21.32 and 17q24.3 or q25.1. CMPD with SR represents a variant of the CMPS1/SRA1 locus disorder. We emphasize the likelihood that CMPS may be a contiguous gene syndrome. 18 refs., 4 figs., 1 tab.

  15. Atypical presentation of posterior reversible encephalopathy syndrome: Clinical and radiological characteristics in eclamptic patients

    PubMed Central

    Aracki-Trenkić, Aleksandra; Stojanov, Dragan; Trenkić, Milan; Radovanović, Zoran; Ignjatović, Jelena; Ristić, Saša; Trenkić-Bozinović, Marija

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is an obstetric emergency frequently occurring in a pregnant or puerperal woman, manifested with an acute headache, consciousness impairment, seizures, and visual deficits and is associated with white matter changes predominantly affecting the posterior parietal and occipital lobes of the brain. Apart from the above-described typical location of the changes, the most common atypical location involves the brain stem and basal ganglia. Since magnetic resonance imaging (MRI) is more sensitive and specific imaging technique compared to computerized tomography, establishing the diagnosis and follow-up in patients with PRES is based mainly on MRI findings. It is particularly important not to exclude PRES as a possible diagnosis when we have the appropriate clinical presentation accompanied by the atypical radiological findings, since this clinical-radiological syndrome can often be manifested with an atypical MRI image. PMID:27322924

  16. The syndrome gelastic seizures-hypothalamic hamartoma: severe, potentially reversible encephalopathy.

    PubMed

    Striano, Salvatore; Striano, Pasquale; Coppola, Antonietta; Romanelli, Pantaleo

    2009-05-01

    Hypothalamic hamartoma (HH) is the pathologic hallmark of a spectrum of epileptic conditions, ranging from a mild form of epilepsy, whose seizures are an urge to laugh without cognitive defects, to the fully developed syndrome of early onset gelastic seizures (GS) associated with precocious puberty and the evolution to a catastrophic epilepsy syndrome. However, a refractory focal or generalized epilepsy develops during the clinical course in nearly all cases. Neurophysiologic and neuroimaging studies have assessed the role of HH in the generation of the GS as well as in the process of secondary epileptogenesis. Electrophysiologic properties of small gamma-aminobutyric acid (GABA)ergic, spontaneously firing neurons might explain the intrinsic epileptogenicity of HH. Surgical ablation of the HH can reverse both epilepsy and encephalopathy. Gamma-knife radiosurgery and image-guided robotic radiosurgery can be useful and safe approaches for treatment, in particular of small HH.

  17. Gemcitabine and Cisplatin induced posterior reversible encephalopathy syndrome: A case report with review of literature

    PubMed Central

    Kabre, Rohit Santosh; Kamble, Krishna Marotirao

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a recently described, scarcely documented clinical entity. PRES is caused by various factors, the most common being hypertension, followed by nonhypertensive causes such as renal diseases and immunosuppressive therapy. Recently, some cases have been reported about the association of increased use of cytotoxic and immunosuppressive agents in cancer patients, and relevant reports have increased with advances in radiological examinations. Here, we report a case of gallbladder cancer with liver metastasis undergoing gemcitabine- and cisplatin-based chemotherapy who presented with complaints of seizures, headache, and bilateral lower limb weakness. Thorough clinical examination, biochemical analysis, and radiological evaluation led to diagnosis of PRES. It is important to recognize this syndrome which will facilitate early diagnosis and prompt symptomatic management. Removal of causative agent is an important aspect of management. Studies are needed to identify factors of adverse prognostic significance and to develop neuroprotective strategies. PMID:27843969

  18. Neuromyelitis Optica in Pregnancy Complicated by Posterior Reversible Encephalopathy Syndrome, Eclampsia and Fetal Death

    PubMed Central

    Igel, Catherine; Garretto, Diana; Robbins, Matthew S; Swerdlow, Michael; Judge, Nancy; Dayal, Ashlesha

    2015-01-01

    Neuromyelitis optica (NMO) is a demyelinating syndrome characterized by optic neuritis and acute myelitis with poor recovery and a progressive course. We report a poor outcome complicated by posterior reversible encephalopathy syndrome (PRES) and eclampsia and review available literature and current evidence for anticipation of adverse fetal and maternal effects. After a pregnancy complicated by multiple admissions for painful NMO exacerbations, a primiparous patient with seropositive NMO presented at 31 + 3/7 weeks with eclampsia, HELLP and subsequent fetal death. MRI confirmed PRES. NMO may be associated with eclampsia and leads to adverse maternal and fetal outcomes. Posited mechanisms include antibody-mediated placental damage and a heightened risk of eclampsia-associated PRES. Further characterization of the course of NMO and its relationship with pregnancy outcomes in larger series would be invaluable. PMID:25584107

  19. Posterior reversible encephalopathy syndrome in a child with Henoch-Schönlein purpura

    PubMed Central

    Sivrioglu, Ali Kemal; Incedayi, Mehmet; Mutlu, Hakan; Meral, Cihan

    2013-01-01

    Henoch-Schönlein purpura (HSP) is a small vessel vasculitis that affects the gastrointestinal and central nervous systems and the kidneys. The disease primarily affects children, but may occur in elderly children with allergic purpura and also in adults. Central nervous system involvement may be the first sign; however, it is rarely encountered. Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome of encephalopathy, headache, visual disturbance and seizures. Its radiological signs can be observed in grey and white matter at the posterior region of the cerebral hemispheres. HSP should be considered in children with PRES in the presence of rash, joint and gastrointestinal symptoms. We reported a 5-year-old patient who developed acute renal failure and PRES by reason of HSP. PMID:23946524

  20. Early-onset Tourette syndrome with reversible autistic behaviour: a dysmaturational disorder.

    PubMed

    Zappella, M

    2002-02-01

    Early-onset Tourette syndrome comorbid with reversible autistic behaviour is described in twelve young males. After a normal gestation, delivery and first-year development, regression set in between the age of one and two with loss of various abilities and the emergence of autistic behaviour. At this time, or slightly later, they showed multiple motor and vocal tics, simple and complex: the latter could also be traced to most of their parents. Following an intervention based on intense cuddling, motor activation and paedagogic guidance, these children's abilities rapidly improved, reaching at follow-up a normal or borderline intellectual functioning and with the disappearance of their initial autistic behaviour. At follow-up tics were present in all, usually with the features of a full-blown Tourette syndrome, often comorbid with ADHD, and in some cases with OCD.

  1. Cortical visual loss in posterior reversible encephalopathy syndrome in late postpartum eclampsia: case series.

    PubMed

    Karuppannasamy, Divya; Vikrant, K; Raghuram, A; Kumaar, T M Sathish

    2014-05-01

    The purpose of this study was to determine the prevalence of visual disturbances in patients with posterior reversible encephalopathy syndrome (PRES) associated with late postpartum eclampsia. We retrospectively reviewed the clinical records of late postpartum eclampsia patients with features of PRES for the presence of visual disturbances and location of radiological abnormalities. We found a higher prevalence of cortical visual loss in patients with PRES associated with late postpartum eclampsia. Bilateral symmetrical vasogenic edema of the parieto-occipital lobe was the most common magnetic resonance imaging (MRI) abnormality noted. No significant differences were observed in the extent of edema in patients with and without visual loss.

  2. Posterior reversible encephalopathy syndrome complicating diabetic ketoacidosis; an important treatable complication.

    PubMed

    Jones, Rachel; Redler, Kasey; Witherick, Jonathan; Fuller, Geraint; Mahajan, Tripti; Wakerley, Benjamin R

    2017-03-01

    Development of acute neurological symptoms secondary to cerebral oedema is well described in diabetic ketoacidosis (DKA) and often has a poor prognosis. We present the clinical and radiological data of a 17-yr-old girl who developed cortical blindness, progressive encephalopathy, and seizures caused by posterior reversible encephalopathy syndrome (PRES) that developed after her DKA had resolved. Vasogenic oedema in PRES resolves if the underlying trigger is identified and eliminated. In this case, hypertension was identified as the likely precipitating factor and following treatment her vision and neurological symptoms rapidly improved. We suggest how recent DKA may have contributed to the development of PRES in this patient.

  3. An unusual presentation of a rare disease: posterior reversible encephalopathy syndrome following abdominal sepsis

    PubMed Central

    Richards, Carly R.N.; McMurray, Robert C.; Criman, Erik T.; Clark, Margaret E.; Gillern, Suzanne

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is an unusual disease of unknown incidence and cause. There are a wide range of associated, predisposing medical causes to include pregnancy, renal failure, immunosuppressive medication administration and hypertension. The diagnosis is made following the radiographic identification of characteristic vasogenic edema in the setting of neurologic impairment. A significant portion of patients will have long-term, if not permanent, sequelae of the disease. We present a patient who developed PRES following a hemicolectomy that was complicated by an anastomotic leak. She went on to a complete recovery following surgical treatment of the leak and supportive care. PMID:27887021

  4. Metformin restores the mitochondrial network and reverses mitochondrial dysfunction in Down syndrome cells.

    PubMed

    Izzo, Antonella; Nitti, Maria; Mollo, Nunzia; Paladino, Simona; Procaccini, Claudio; Faicchia, Deriggio; Calì, Gaetano; Genesio, Rita; Bonfiglio, Ferdinando; Cicatiello, Rita; Polishchuk, Elena; Polishchuk, Roman; Pinton, Paolo; Matarese, Giuseppe; Conti, Anna; Nitsch, Lucio

    2017-01-13

    Alterations in mitochondrial activity and morphology have been demonstrated in human cells and tissues from individuals with Down syndrome (DS), as well as in DS mouse models. An impaired activity of the transcriptional coactivator PGC-1α/PPARGC1Adue to the overexpression of chromosome 21 genes, such as NRIP1/RIP140, has emerged as an underlying cause of mitochondrial dysfunction in DS. We tested the hypothesis that the activation of the PGC-1α pathway might indeed reverse this mitochondrial dysfunction.

  5. Reversible Cerebral Vasoconstriction Syndrome with Intracranial Hypertension: Should Decompressive Craniectomy Be Considered?

    PubMed Central

    Mrozek, Ségolène; Lonjaret, Laurent; Jaffre, Aude; Januel, Anne-Christine; Raposo, Nicolas; Boetto, Sergio; Albucher, Jean-François; Fourcade, Olivier; Geeraerts, Thomas

    2017-01-01

    Background Reversible cerebral vasoconstriction syndrome (RCVS) is a rare cause of intracerebral hemorrhage (ICH) causing intracranial hypertension. Methods Case report. Results We report a case of RCVS-related ICH leading to refractory intracranial hypertension. A decompressive craniectomy was performed to control intracranial pressure. We discuss here the management of RCVS with intracranial hypertension. Decompressive craniectomy was preformed to avoid the risky option of high cerebral perfusion pressure management with the risk of bleeding, hemorrhagic complications, and high doses of norepinephrine. Neurological outcome was good. Conclusion RCVS has a complex pathophysiology and can be very difficult to manage in cases of intracranial hypertension. Decompressive craniectomy should probably be considered. PMID:28203185

  6. Triptan-induced Reversible Cerebral Vasoconstriction Syndrome: Two Case Reports with a Literature Review

    PubMed Central

    Kato, Yuji; Hayashi, Takeshi; Mizuno, Satoko; Horiuchi, Yohsuke; Ohira, Masayuki; Tanahashi, Norio; Takao, Masaki

    2016-01-01

    We encountered two patients with sumatriptan-induced reversible cerebral vasoconstriction syndrome (RCVS). The present patients were taking sumatriptan for the first time because they had been tentatively diagnosed with a migraine. On reviewing the literature, we found nine other cases of triptan-induced RCVS, predominantly among women aged 30 to 40 years. RCVS has been precipitated by triptan at the first ever use, after daily use, and even with long-term use at a normal dose. Patients with acute onset of severe headache should be thoroughly evaluated, and triptan should be administered appropriately. If triptan-induced RCVS is suspected, vascular imaging should be repeated after several days. PMID:27904122

  7. Posterior Reversible Encephalopathy Syndrome with Extensive Deep White Matter Lesions Including the Temporal Pole

    PubMed Central

    Ohira, Junichiro; Mori, Nobuyuki; Kajikawa, Shunsuke; Nakamura, Takeshi; Arisato, Tetsuya; Takahashi, Makio

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) typically affects the posterior subcortical white matter. We report the case of a 55-year-old man with atypical PRES, who had malignant hypertension and renal dysfunction. Magnetic resonance imaging of the brain revealed extensive vasogenic edema in the deep white matter including the temporal pole, as well as in the brainstem and cerebellum. Antihypertensive therapy and hemodialysis contributed to both clinical and radiological improvement. Involvement of the deep white matter including the temporal pole, which is rarely affected in an ischemic stroke, should be recognized as a potential sign of PRES. PMID:27904123

  8. Metabolic anatomy of paraneoplastic cerebellar degeneration

    SciTech Connect

    Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

    1988-06-01

    Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration (PCD)) were evaluated using neuropsychological tests and /sup 18/F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a reverse cerebellar diaschisis.

  9. Posterior reversible encephalopathy syndrome--Insight into pathogenesis, clinical variants and treatment approaches.

    PubMed

    Granata, Guido; Greco, Antonio; Iannella, Giannicola; Granata, Massimo; Manno, Alessandra; Savastano, Ersilia; Magliulo, Giuseppe

    2015-09-01

    Posterior reversible encephalopathy syndrome is a rare clinicoradiological entity characterized by typical MRI findings located in the occipital and parietal lobes, caused by subcortical vasogenic edema. It was first described as a distinctive syndrome by Hinchey in 1996. Etiopathogenesis is not clear, although it is known that it is an endotheliopathy of the posterior cerebral vasculature leading to failed cerebral autoregulation, posterior edema and encephalopathy. A possible pathological activation of the immune system has been recently hypothesized in its pathogenesis. At clinical onset, the most common manifestations are seizures, headache and visual changes. Besides, tinnitus and acute vertigo have been frequently reported. Symptoms can be reversible but cerebral hemorrhage or ischemia may occur. Diagnosis is based on magnetic resonance imaging, in the presence of acute development of clinical neurologic symptoms and signs and arterial hypertension and/or toxic associated conditions with possible endotheliotoxic effects. Mainstay on the treatment is removal of the underlying cause. Further investigation and developments in endothelial cell function and in neuroimaging of cerebral blood flow are needed and will help to increase our understanding of pathophysiology, possibly suggesting novel therapies.

  10. Morphological and functional reversal of phenotypes in a mouse model of Rett syndrome.

    PubMed

    Robinson, Lianne; Guy, Jacky; McKay, Leanne; Brockett, Emma; Spike, Rosemary C; Selfridge, Jim; De Sousa, Dina; Merusi, Cara; Riedel, Gernot; Bird, Adrian; Cobb, Stuart R

    2012-09-01

    Rett syndrome is a neurological disorder caused by mutation of the X-linked MECP2 gene. Mice lacking functional Mecp2 display a spectrum of Rett syndrome-like signs, including disturbances in motor function and abnormal patterns of breathing, accompanied by structural defects in central motor areas and the brainstem. Although routinely classified as a neurodevelopmental disorder, many aspects of the mouse phenotype can be effectively reversed by activation of a quiescent Mecp2 gene in adults. This suggests that absence of Mecp2 during brain development does not irreversibly compromise brain function. It is conceivable, however, that deep-seated neurological defects persist in mice rescued by late activation of Mecp2. To test this possibility, we have quantitatively analysed structural and functional plasticity of the rescued adult male mouse brain. Activation of Mecp2 in ∼70% of neurons reversed many morphological defects in the motor cortex, including neuronal size and dendritic complexity. Restoration of Mecp2 expression was also accompanied by a significant improvement in respiratory and sensory-motor functions, including breathing pattern, grip strength, balance beam and rotarod performance. Our findings sustain the view that MeCP2 does not play a pivotal role in brain development, but may instead be required to maintain full neurological function once development is complete.

  11. Iatrogenic postoperative cerebellar cyst.

    PubMed

    Sharif, Robin; Moscovici, Samuel; Wygoda, Marc; Eliahou, Ruth; Spektor, Sergey

    2016-12-01

    Cerebellar cyst is a known but uncommon entity. It is congenital in most cases, or may develop after brain parenchyma injuries or interventions. To our knowledge, de novo cerebellar cyst after extra-axial tumor excision, has not been described in the literature. We present the first reported case of a de novo cerebellar cyst developing in a 70-year-old woman following retrosigmoid craniotomy for vestibular schwannoma excision, and discuss the possible causes. Following cyst fenestration, there was no clinical or radiological evidence of a residual cyst.

  12. Various Imaging Manifestations of Posterior Reversible Encephalopathy Syndrome (PRES) on Magnetic Resonance Imaging (MRI)

    PubMed Central

    Raman, Rajesh; Devaramane, Radhika; Jagadish, Geetha Mukunda; Chowdaiah, Sanjana

    2017-01-01

    Summary Background Posterior reversible encephalopathy syndrome (PRES), also called the acute hypertensive encephalopathy and reversible posterior leukoencephalopathy syndrome (RPLS), is a neurotoxic syndrome of cerebral vasoregulation classically characterized by bilaterally symmetrical parieto-occipital edema. However, the imaging findings are variable and may occur in other locations such as the frontal lobes, thalami, basal ganglia and brainstem. Most commonly, PRES presents with hyperintense signals on T2 and FLAIR sequences. Restricted diffusion and hemorrhage are rare. This study presents the typical and atypical manifestations of PRES on 3T MR images. Material/Methods It is a retrospective study analyzing a radiology report database and MR images of 92 patients with a clinical and radiological diagnosis of PRES. The brain MRI images of these patients were evaluated. The regions involved and the signal intensity of the affected areas on T1, T2, FLAIR and DW sequences were recorded. The location of the abnormal signal intensity as well as the presence or absence of atypical features such as diffusion restriction and hemorrhage were also recorded. Results The most commonly affected region was the parieto-occipital lobes (100%), however, other atypical regions involved were the frontal lobes (30.4%), temporal lobes (8.69%), basal ganglia (22%), cerebellum(17.39%), brainstem(9%) and thalamus(4%). Some of the cases showed restricted diffusion (43%) and hemorrhage (9%). Conclusions The involvement of the parieto-occipital, frontal and temporal lobes is common in PRES. Occasionally, there may be an involvement of the basal ganglia, cerebellum and brainstem, with or without hemorrhage and restricted diffusion. Radiologists should be aware of the typical and atypical imaging manifestations of PRES in order to make an accurate diagnosis. PMID:28243339

  13. Telomerase reverse-transcriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome

    PubMed Central

    Marrone, Anna; Walne, Amanda; Tamary, Hannah; Masunari, Yuka; Kirwan, Michael; Beswick, Richard; Vulliamy, Tom; Dokal, Inderjeet

    2010-01-01

    Dyskeratosis congenita (DC) is a multisystem bone marrow failure syndrome characterized by a triad of mucocutaneous abnormalities and an increased predisposition to malignancy. X-linked DC is due to mutations in DKC1, while heterozygous mutations in TERC (telomerase RNA component) and TERT (telomerase reverse transcriptase) have been found in autosomal dominant DC. Many patients with DC remain uncharacterized, particularly families displaying autosomal recessive (AR) inheritance. We have now identified novel homozygous TERT mutations in 2 unrelated consanguineous families, where the index cases presented with classical DC or the more severe variant, Hoyeraal-Hreidarsson (HH) syndrome. These TERT mutations resulted in reduced telomerase activity and extremely short telomeres. As these mutations are homozygous, these patients are predicted to have significantly reduced telomerase activity in vivo. Interestingly, in contrast to patients with heterozygous TERT mutations or hemizygous DKC1 mutations, these 2 homozygous TERT patients were observed to have higher-than-expected TERC levels compared with controls. Collectively, the findings from this study demonstrate that homozygous TERT mutations, resulting in a pure but severe telomerase deficiency, produce a phenotype of classical AR-DC and its severe variant, the HH syndrome. PMID:17785587

  14. Lissencephaly with brainstem and cerebellar hypoplasia and congenital cataracts.

    PubMed

    Abumansour, Iman S; Wrogemann, Jens; Chudley, Albert E; Chodirker, Bernard N; Salman, Michael S

    2014-06-01

    Classical lissencephaly may be associated with cerebellar hypoplasia and when significant cerebellar abnormalities occur, defects in proteins encoded by TUBA1A, RELN, and very-low-density lipoprotein receptor (VLDLR) genes have been reported. We present a neonate with a severe neurologic phenotype associated with hypotonia, oropharyngeal incoordination that required a gastric tube for feeding, intractable epilepsy, and congenital cataracts. Her brain magnetic resonance imaging (MRI) showed classical lissencephaly, ventriculomegaly, absent corpus callosum, globular and vertical hippocampi, and severe cerebellar and brainstem hypoplasia. She died at 6 weeks of age. No specific molecular diagnosis was made. This likely represents a previously undescribed genetic lissencephaly syndrome.

  15. Primary cerebellopontine progressive multifocal leukoencephalopathy diagnosed premortem by cerebellar biopsy.

    PubMed

    Jones, H R; Hedley-Whyte, E T; Freidberg, S R; Kelleher, J E; Krolikowski, J

    1982-02-01

    A subacute progressive cerebellar brainstem syndrome developed in a patient with systemic lupus erythematosus in remission. Cerebellar biopsy documented the diagnosis of progressive multifocal leukoencephalopathy (PML). Data from this patient and 10 others in the literature emphasize the need to consider this diagnosis when ataxia develops in any patient with underlying malignancy, chronic infection, or other disease that involves immunological incompetence. Although the ataxic form of PML is not of nosological relevance, early diagnosis may eventually have therapeutic importance.

  16. Acute cerebellar ataxia

    MedlinePlus

    ... Alcohol, medications, and insecticides Bleeding into the cerebellum Multiple sclerosis Strokes of the cerebellum Vaccination ... swelling (inflammation) of the cerebellum (such as from multiple sclerosis) Cerebellar ataxia caused by a recent viral infection ...

  17. Arachnodactyly, aminoaciduria, congenital cataracts, cerebellar ataxia, and delayed developmental milestones

    PubMed Central

    Bhaskar, P. A.; Jagannathan, K.; Valmikinathan, K.

    1974-01-01

    Two male cousins are reported with arachnodactyly, selective aminoaciduria, congenital cataracts, cerebellar ataxia, and delayed developmental milestones, and a distant female relative with similar abnormalities. The syndrome is thought to be previously undescribed, though it has resemblances to Marinesco-Sjögren and Marfan's syndromes. Images PMID:4448994

  18. SCA28: Novel Mutation in the AFG3L2 Proteolytic Domain Causes a Mild Cerebellar Syndrome with Selective Type-1 Muscle Fiber Atrophy.

    PubMed

    Svenstrup, Kirsten; Nielsen, Troels Tolstrup; Aidt, Frederik; Rostgaard, Nina; Duno, Morten; Wibrand, Flemming; Vinther-Jensen, Tua; Law, Ian; Vissing, John; Roos, Peter; Hjermind, Lena Elisabeth; Nielsen, Jørgen Erik

    2017-02-01

    The spinocerebellar ataxias (SCA) are a group of rare inherited neurodegenerative diseases characterized by slowly progressive cerebellar ataxia, resulting in unsteady gait, clumsiness, and dysarthria. The disorders are predominantly inherited in an autosomal dominant manner. Mutations in the gene AFG3L2 that encodes a subunit of the mitochondrial m-AAA protease have previously been shown to cause spinocerebellar ataxia type 28 (SCA28). Here, we present the clinical phenotypes of three patients from a family with autosomal dominant cerebellar ataxia and show by molecular genetics and in silico modelling that this is caused by a novel missense mutation in the AFG3L2 gene. Furthermore, we show, for the first time, fluorodeoxyglucose-positron emission tomography (FDG-PET) scans of the brain and selective type I fiber atrophy of skeletal muscle of SCA28 patients indicating non-nervous-system involvement in SCA28 as well.

  19. [Autosomal recessive cerebellar ataxias].

    PubMed

    Tranchant, Christine; Anheim, Mathieu

    2009-12-01

    Friedreich ataxia is the most frequent recessive cerebral ataxia d should always be researched first. Ataxia with isolated vitamin E deficiency and abetalipoproteinemia have a specific treatment. Associated neurological signs such polyneuroapthy, ophtalmologic or oculomotor signs, pyramidal signs, and cerebellar MRI can lead to the etiological diagnosis. Biological tests should be: vitamin E, cholesterol, alpha-fetoprotein levels, acanthocytes, than phytanic acid, cholestanol, lysosomal enzymes. Numerous autosomal recessive cerebellar ataxia remain without etiology.

  20. Posterior reversible encephalopathy syndrome after intrathecal methotrexate infusion: a case report and literature update

    PubMed Central

    Pavlou, Evangelos; Anastasiou, Athanasia; Pana, Zoi; Tsotoulidou, Vasiliki; Kinali, Maria; Hatzipantelis, Emmanuel

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a rare clinical-radiological entity characterised by seizures, severe headache, mental status instability and visual disturbances. Hypertension is typically present. We report a case of a 13-year old boy with Burkitt lymphoma/leukaemia, who presented with posterior leukoencephalopathy 24 hours after intrathecal methotrexate (MTX) infusion. The child presented with headache, seizures, elevated blood pressure and gradual deterioration of his neurological status. Midazolam, dexamethazone and furosemide were initiated leading to reduction of cerebral oedema and clinical improvement. A thorough literature review is discussed in this report. Pathophysiology of leukoencephalopathy remains unclear. It develops within 5–14 days after intrathecal MTX and resolves within a week usually without permanent neurological sequelae. Broad use of MRI has led to an increasing number of identified cases of PRES. Treatment approach is mainly to manage the underlying cause of PRES. Prognosis is generally benign; however delayed diagnosis and improper management may result in permanent brain insult. PMID:27942481

  1. Cortical blindness and posterior reversible encephalopathy syndrome in an older patient.

    PubMed

    Ait, Sabrina; Gilbert, Thomas; Cotton, Francois; Bonnefoy, Marc

    2012-05-26

    Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity. It associates, to varying extents, neurological symptoms such as headaches, confusion, seizures and visual alterations from haemianopsia to cortical blindness. The diagnosis relies on brain MRI, showing signs of subcortical and cortical oedema in the posterior regions of the brain, with hypersignals in T2/fluid attenuated inversion recovery (FLAIR) or diffusion sequences. With early diagnosis and control of the causal factors, the symptoms and radiological signs can be - as the name implies - totally regressive. PRES can be caused by various heterogeneous factors, such as hypertension, side effect of drug therapies, eclampsia, sepsis or autoimmune diseases. The authors report here the case of an 86-year-old woman, presenting totally regressive cortical blindness and seizures, with compatible imaging.

  2. An unusual case of posterior reversible encephalopathy syndrome in a patient being weaned from intrathecal morphine

    PubMed Central

    Van Aalst, Jasper; Teernstra, Onno P; Weber, Wim E; Rijkers, Kim

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity based on clinical signs, including headache, visual abnormalities, and seizures, and radiological abnormalities mostly consisting of vasogenic brain edema predominantly in the posterior parietal-temporal-occipital regions. PRES typically develops in the setting of a significant “ systemic process”, including preeclampsia, transplantation, infection/sepsis/shock, autoimmune disease, and cancer chemotherapy, in which hypertension often plays an important role. We present a case of PRES in a 63-year-old female patient with an infected intrathecal morphine pump on a cocktail of antibiotics, morphine, clonidine, diazepam, and amitriptyline. It is the first PRES case in a chronic pain patient, which illustrates that PRES can occur in the absence of any of the established risk factors. We hypothesize it may have been caused by antibiotic treatment in our patient. PMID:27274314

  3. Call-fleming syndrome (reversible cerebral artery vasoconstriction) and aneurysm associated with multiple recreational drug use.

    PubMed

    Drazin, Doniel; Alexander, Michael J

    2013-01-01

    Drug abuse represents a significant health issue. Evidence suggests that recreational drug use has a direct effect on the cerebral vasculature and is of greater concern in those with undiagnosed aneurysms or vascular malformations. The authors report a case of thunderclap headache with a negative head CT and equivocal lumbar puncture after a drug-fueled weekend. The patient underwent diagnostic cerebral angiogram which demonstrated multisegmental, distal areas of focal narrowing of the middle, anterior, posterior, and posterior inferior cerebral artery and an incidental aneurysm. It is often difficult to determine the exact origin of symptoms; thus we were left with a bit of a chicken or the egg debate, trying to decipher which part came first. Either the aneurysm ruptured with associated concomitant vasospasm or it is a case of Call-Fleming syndrome (reversible cerebral artery vasoconstriction) with an incidental aneurysm. The authors proposed their management and rationale of this complex case.

  4. Reversible cerebral vasoconstriction syndrome with multivessel cervical artery dissections and a double aortic arch.

    PubMed

    Nouh, Amre; Ruland, Sean; Schneck, Michael J; Pasquale, David; Biller, José

    2014-02-01

    Reversible cerebral vasoconstriction syndrome (RCVS) has been associated with exposure to vasoactive substances and few reports with cervical arterial dissections (CADs). We evaluated a 32-year-old woman with history of depression, migraines without aura, and cannabis use who presented with a thunderclap headache unresponsive to triptans. She was found to have bilateral occipital infarcts, bilateral extracranial vertebral artery dissections, bilateral internal carotid artery dissecting aneurysms, and extensive distal multifocal segmental narrowing of the anterior and posterior intracranial circulation with a "sausage on a string-like appearance" suggestive of RCVS. Subsequently, she was found to have a distal thrombus of the basilar artery, was anticoagulated, and discharged home with no residual deficits. We highlight the potential association of CADs and RCVS. The association of RCVS and a double aortic arch has not been previously reported.

  5. Reversible Cerebral Vasoconstriction Syndrome With Involvement of External Carotid Artery Branches

    PubMed Central

    Shaik, S.; Chhetri, S. K.; Roberts, G.; Wuppalapati, S.

    2014-01-01

    A 44-year-old woman presented with recurrent episodes of thunderclap headache. Neurological examination and computed tomography brain imaging were unremarkable. Cerebrospinal fluid findings were consistent with subarachnoid hemorrhage. Computed tomography angiography of the circle of Willis showed multiple areas of segmental vasoconstriction. This finding was confirmed on cerebral catheter angiography, with segmental vasoconstriction involving bilateral internal carotid, posterior cerebral, and external carotid branches. No aneurysm or other vascular abnormality was identified. She received treatment with nimodipine. A selective serotonin reuptake inhibitor, started 4 weeks earlier, was discontinued. Follow-up angiography after 3 months demonstrated complete resolution of the segmental vasoconstriction, confirming the diagnosis of reversible cerebral vasoconstriction syndrome (RCVS). She remained headache free at follow-up. To our knowledge, external carotid artery branch involvement in RCVS has been described only in one previous occasion. PMID:24982719

  6. The reversible cerebral vasoconstriction syndrome in association with venlafaxine and methenamine.

    PubMed

    Davies, G; Wilson, H; Wilhelm, T; Bowler, J

    2013-06-13

    The reversible cerebral vasoconstriction syndrome (RCVS) is characterised by thunderclap headache and multifocal vasoconstriction of cerebral arteries on angiography. It is often drug induced, but it can occur postpartum, and as a result of a number of other precipitants. To make the diagnosis, it is necessary to exclude other causes of severe headache (such as aneurysmal subarachnoid haemorrhage, carotid dissection and primary angiitis of the central nervous system). However, it is also important to show that the vasoconstriction has resolved with repeat angiography at the 3-month stage. Here we report two cases of RCVS in association with venlafaxine and the urinary antiseptic, methenamine. Serotonin-norepinephrine reuptake inhibitors have recently been reported as a possible precipitant, but this is the first report to implicate methenamine. Although RCVS is relatively uncommon, it should be considered in the differential of those presenting with thunderclap headache.

  7. Calcineurin Inhibitors Associated Posterior Reversible Encephalopathy Syndrome in Solid Organ Transplantation

    PubMed Central

    Song, Turun; Rao, Zhengsheng; Tan, Qiling; Qiu, Yang; Liu, Jinpeng; Huang, Zhongli; Wang, Xianding; Lin, Tao

    2016-01-01

    Abstract Posterior reversible encephalopathy syndrome (PRES) is a rare neurologic side effect of calcineurin inhibitors (CNIs) with poorly understood clinical features. We report cases of 2 patients with PRES developing after kidney transplantation and summarize PRES clinical features through a literature review. The 1st case was a 28-year-old man who received a kidney transplant from a deceased donor. Initial immunosuppressive therapy consisted of tacrolimus/mycophenolate mofetil/prednisolone. He developed headache and blurred vision with visual field loss15 days after transplantation and generalized seizures 4 days later. The 2nd case was a 34-year-old man who received a living kidney transplant. His initial immunosuppressive therapy comprised tacrolimus/mycophenolate mofetil/prednisolone. Two months after transplantation, he developed seizures. Both patients were diagnosed with PRES based on neurological symptoms and magnetic resonance imaging (MRI) findings; they recovered after switching from tacrolimus to either a cyclosporine or a lower tacrolimus dose. CNI-associated PRES is an acute neurological syndrome with seizures, encephalopathy, visual abnormalities, headache, focal neurological deficits, and nausea/vomiting. It is always accompanied by hypertension. A fluid-attenuated inversion recovery signal MRI scan typically shows reversible subcortical white matter changes in the posterior cerebral hemisphere that usually occur within the 1st month after transplantation. CNI-associated PRES has a generally favorable prognosis with early diagnosis and prompt treatment including alternating or discontinuing CNIs and blood pressure control. CNI-associated PRES should be considered in patients exhibiting acute neurological symptoms after transplantation. Early diagnosis and immediate treatment are critical for a favorable prognosis. PMID:27057842

  8. Status Epilepticus and Blindness in a Patient with Carfilzomib-Associated Posterior Reversible Encephalopathy Syndrome

    PubMed Central

    Ebrahem, Rawaa; Cooper, Scott; Manlove, Emily; Lee, Ricky

    2017-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a neurological condition characterized by headaches, visual disturbances, and seizures. A magnetic resonance imaging (MRI) scan of an affected brain typically shows symmetrical white matter edema in the posterior cerebral hemispheres. The onset of PRES can constitute a medical emergency, especially when accompanied by status epilepticus. If promptly recognized and treated, the clinical syndrome and associated radiological findings are usually resolved in a matter of weeks or months. Carfilzomib is a proteasome inhibitor that is newly approved for relapsing myeloma in a patient who has received one or more lines of therapy. In this paper, we report on a 52-year-old female on carfilzomib for multiple myeloma who developed PRES following her second dose of treatment. She was admitted for chronic obstructive pulmonary disease (COPD) exacerbation, and while she was in the hospital, she developed a severe headache, blindness, and status epilepticus. A brain MRI showed signs consistent with PRES. After carfilzomib was discontinued, her symptoms resolved within three days. Unfortunately, the patient passed away shortly after being discharged, so there was no opportunity to perform a repeat MRI. PMID:28357173

  9. A School-Based Application of Modified Habit Reversal for Tourette Syndrome via a Translator: A Case Study

    ERIC Educational Resources Information Center

    Gilman, Rich; Connor, Nancy; Haney, Michelle

    2005-01-01

    A school-based modified habit reversal intervention was utilized with an adolescent diagnosed with Tourette syndrome who recently immigrated from Mexico. Because the student possessed little proficiency of the English language, an interpreter was needed to help implement the procedure. The frequency of motor tics markedly decreased from baseline…

  10. Past, Present and Future Therapeutics for Cerebellar Ataxias

    PubMed Central

    Marmolino, D; Manto, M

    2010-01-01

    Cerebellar ataxias are a group of disabling neurological disorders. Patients exhibit a cerebellar syndrome and can also present with extra-cerebellar deficits, namely pigmentary retinopathy, extrapyramidal movement disorders, pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioural symptoms), and peripheral neuropathy. Recently, deficits in cognitive operations have been unraveled. Cerebellar ataxias are heterogeneous both at the phenotypic and genotypic point of view. Therapeutical trials performed during these last 4 decades have failed in most cases, in particular because drugs were not targeting a deleterious pathway, but were given to counteract putative defects in neurotransmission. The identification of the causative mutations of many hereditary ataxias, the development of relevant animal models and the recent identifications of the molecular mechanisms underlying ataxias are impacting on the development of new drugs. We provide an overview of the pharmacological treatments currently used in the clinical practice and we discuss the drugs under development. PMID:20808545

  11. The Comorbidity of Reduplicative Paramnesia, Intermetamorphosis, Reverse-Intermetamorphosis, Misidentification of Reflection, and Capgras Syndrome in an Adolescent Patient

    PubMed Central

    Arısoy, Ozden; Tufan, A. Evren; Taskiran, Sarper; Topal, Zehra; Demir, Nuran; Cansız, M. Akif

    2014-01-01

    Delusional misidentification syndromes may be superimposed on neurological or psychiatric disorders and include delusional beliefs that the people, objects, or places around the patient change or are made to change with one another. In this paper, an adolescent patient displaying Capgras syndrome, metamorphosis, reverse-intermetamorphosis, misidentification of reflection, and reduplicative paramnesia was presented. The findings that our patient struggled with visuospatial tests applied in the acute phase as well as the observation that she refused to meet her family face-to-face while accepting to speak on the phone may support the role of right hemisphere and visuospatial functions in the development of those syndromes. Further studies or case series evaluated more extensively are needed to reveal the relationship between right hemisphere functions and delusional misidentification syndromes. PMID:25328744

  12. Neurochondrin is a neuronal target antigen in autoimmune cerebellar degeneration

    PubMed Central

    Miske, Ramona; Gross, Catharina C.; Scharf, Madeleine; Golombeck, Kristin S.; Hartwig, Marvin; Bhatia, Urvashi; Schulte-Mecklenbeck, Andreas; Bönte, Kathrin; Strippel, Christine; Schöls, Ludger; Synofzik, Matthis; Lohmann, Hubertus; Dettmann, Inga Madeleine; Deppe, Michael; Mindorf, Swantje; Warnecke, Tobias; Denno, Yvonne; Teegen, Bianca; Probst, Christian; Brakopp, Stefanie; Wandinger, Klaus-Peter; Wiendl, Heinz; Stöcker, Winfried; Meuth, Sven G.

    2016-01-01

    Objective: To report on a novel neuronal target antigen in 3 patients with autoimmune cerebellar degeneration. Methods: Three patients with subacute to chronic cerebellar ataxia and controls underwent detailed clinical and neuropsychological assessment together with quantitative high-resolution structural MRI. Sera and CSF were subjected to comprehensive autoantibody screening by indirect immunofluorescence assay (IFA) and immunoblot. Immunoprecipitation with lysates of hippocampus and cerebellum combined with mass spectrometric analysis was used to identify the autoantigen, which was verified by recombinant expression in HEK293 cells and use in several immunoassays. Multiparameter flow cytometry was performed on peripheral blood and CSF, and peripheral blood was subjected to T-cell receptor spectratyping. Results: Patients presented with a subacute to chronic cerebellar and brainstem syndrome. MRI was consistent with cortical and cerebellar gray matter atrophy associated with subsequent neuroaxonal degeneration. IFA screening revealed strong immunoglobulin G1 reactivity in sera and CSF with hippocampal and cerebellar molecular and granular layers, but not with a panel of 30 recombinantly expressed established neural autoantigens. Neurochondrin was subsequently identified as the target antigen, verified by IFA and immunoblot with HEK293 cells expressing human neurochondrin as well as the ability of recombinant neurochondrin to neutralize the autoantibodies' tissue reaction. Immune phenotyping revealed intrathecal accumulation and activation of B and T cells during the acute but not chronic phase of the disease. T-cell receptor spectratyping suggested an antigen-specific T-cell response accompanying the formation of antineurochondrin autoantibodies. No such neurochondrin reactivity was found in control cohorts of various neural autoantibody-associated neurologic syndromes, relapsing-remitting multiple sclerosis, cerebellar type of multiple system atrophy, hereditary

  13. Location of lesion determines motor vs. cognitive consequences in patients with cerebellar stroke.

    PubMed

    Stoodley, Catherine J; MacMore, Jason P; Makris, Nikos; Sherman, Janet C; Schmahmann, Jeremy D

    2016-01-01

    Cerebellar lesions can cause motor deficits and/or the cerebellar cognitive affective syndrome (CCAS; Schmahmann's syndrome). We used voxel-based lesion-symptom mapping to test the hypothesis that the cerebellar motor syndrome results from anterior lobe damage whereas lesions in the posterolateral cerebellum produce the CCAS. Eighteen patients with isolated cerebellar stroke (13 males, 5 females; 20-66 years old) were evaluated using measures of ataxia and neurocognitive ability. Patients showed a wide range of motor and cognitive performance, from normal to severely impaired; individual deficits varied according to lesion location within the cerebellum. Patients with damage to cerebellar lobules III-VI had worse ataxia scores: as predicted, the cerebellar motor syndrome resulted from lesions involving the anterior cerebellum. Poorer performance on fine motor tasks was associated primarily with strokes affecting the anterior lobe extending into lobule VI, with right-handed finger tapping and peg-placement associated with damage to the right cerebellum, and left-handed finger tapping associated with left cerebellar damage. Patients with the CCAS in the absence of cerebellar motor syndrome had damage to posterior lobe regions, with lesions leading to significantly poorer scores on language (e.g. right Crus I and II extending through IX), spatial (bilateral Crus I, Crus II, and right lobule VIII), and executive function measures (lobules VII-VIII). These data reveal clinically significant functional regions underpinning movement and cognition in the cerebellum, with a broad anterior-posterior distinction. Motor and cognitive outcomes following cerebellar damage appear to reflect the disruption of different cerebro-cerebellar motor and cognitive loops.

  14. The combination of thermal dysregulation and agenesis of corpus callosum: Shapiro's or/and reverse Shapiro's syndrome

    PubMed Central

    Topcu, Yasemin; Bayram, Erhan; Karaoglu, Pakize; Yis, Uluc; Kurul, Semra Hiz

    2013-01-01

    Shapiro syndrome is an extremely rare condition consisting the clinical triad of recurrent hypothermia, hyperhydrosis and agenesis of the corpus callosum. On the other hand, reverse Shapiro's sydrome is characterized periodic hyperthermia and agenesis of the corpus callosum. Here, we describe a 3.5-year-old girl with complete agenesis of corpus callosum presenting with recurrent fever and vomiting. She also had hypothermia attacks with accompanying diaphoresis. To the best of our knowledge, there is no described case with episodes of hyperthermia, hypothermia, and vomiting associated with agenesis of the corpus callosum. Recurrent vomiting may be a newly defined symptom associated with these syndromes. PMID:24339619

  15. Posterior reversible encephalopathy syndrome in setting of postobstructive diuresis and persistent hypocalcemia.

    PubMed

    Gera, Dinesh N; Patil, Sachin B; Parikh, Mitul; Modi, Pranjal R; Kute, Vivek B; Trivedi, Hargovind L

    2012-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiographic entity of heterogenous etiologies, which are grouped together because of similar findings on neuroimaging studies, associated with similar symptom complex of headache, vision loss, altered mentation, and seizures. In this report, we describe a case of PRES in setting of postobstructive diuresis in a 5-year-old male child, whose solitary functioning kidney was obstructed by a 1.6-cm radio-opaque stone, who after percutaneous nephrostomy (PCN) diversion developed persistent hypocalcemia which persisted despite maximum replacement by iv calcium gluconate drip, and the child developed repeated generalized tonic clonic convulsions and became unconscious for 4 days. Computerized tomography (CT) scan of the brain showed typical hypodensities in bilateral occipitoparietal regions suggesting PRES. Ultimately, over a period of 4 days, his hypocalcemia could be corrected and the child was neurologically normal on the 5th day. CT scan of the brain after a month was free of any hypodensities.

  16. Reverse transcription recombinase polymerase amplification assay for the detection of middle East respiratory syndrome coronavirus.

    PubMed

    Abd El Wahed, Ahmed; Patel, Pranav; Heidenreich, Doris; Hufert, Frank T; Weidmann, Manfred

    2013-12-12

    The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the eastern Mediterranean and imported cases to Europe has alerted public health authorities. Currently, detection of MERS-CoV in patient samples is done by real-time RT-PCR. Samples collected from suspected cases are sent to highly-equipped centralized laboratories for screening. A rapid point-of-care test is needed to allow more widespread mobile detection of the virus directly from patient material. In this study, we describe the development of a reverse transcription isothermal Recombinase Polymerase Amplification (RT-RPA) assay for the identification of MERS-CoV. A partial nucleocapsid gene RNA molecular standard of MERS-coronavirus was used to determine the assay sensitivity. The isothermal (42°C) MERS-CoV RT-RPA was as sensitive as real-time RT-PCR (10 RNA molecules), rapid (3-7 minutes) and mobile (using tubescanner weighing 1kg). The MERS-CoV RT-RPA showed cross-detection neither of any of the RNAs of several coronaviruses and respiratory viruses affecting humans nor of the human genome. The developed isothermal real-time RT-RPA is ideal for rapid mobile molecular MERS-CoV monitoring in acute patients and may also facilitate the search for the animal reservoir of MERS-CoV.

  17. Possible overlap between reversible cerebral vasoconstriction syndrome and symptomatic vasospasm after aneurysmal subarachnoid hemorrhage.

    PubMed

    Forget, Patrice; Goffette, Pierre; van de Wyngaert, Françoise; Raftopoulos, Christian; Hantson, Philippe

    2009-08-01

    A 34-year-old woman with a previous history of severe headache ("thunderclap") was admitted with a diagnosis of aneurysmal subarachnoid hemorrhage (SAH). The patient developed symptomatic vasospasm on day 5 that resolved rapidly after having increased arterial blood pressure. She experienced also short-lasting excruciating headache. On day 12, while velocities had normalised, as revealed by transcranial Doppler (TCD), for more than 48 h, she developed aphasia and right hemiplegia associated with diffuse segmental vasospasm on the left middle cerebral artery. Intra-arterial infusion of vasodilatory agents was required. Recurrence of symptomatic vasospasm was noted on day 25, with a great number of territories involved as shown in the cerebral angiogram. A second intra-arterial treatment was needed. The patient complained of multiple episodes of extremely severe headache ("thunderclap"), with also transient dysarthria and hemiparesia on day 30. She was discharged on day 38 after full recovery. The clinical and TCD/radiological findings were consistent with a reversible cerebral vasoconstriction syndrome overlapping SAH related symptomatic vasospasm.

  18. Posterior Reversible Encephelopathy Syndrome Presenting as Quadriparesis in Pregnancy Induced Hypertension

    PubMed Central

    Pranita; Kumar, Ajit; Shahi, Seema

    2015-01-01

    Pregnancy Induced Hypertension (PIH) is a condition characterised by raised blood pressure in pregnancy. It affects approximately one out of every 14 pregnant women. Although PIH more commonly occurs during first pregnancy, it can also occur in subsequent pregnancies. It can present with variable complications related to vasospasm. But focal neurologic deficits are extremely rare in patients with PIH. We report a case of quadriparesis due to posterior reversible encephalopathy syndrome (PRES). A 36 year old full term pregnant female was admitted for emergency lower segment caesarean section (LSCS) as a result of uncontrolled PIH with early clinical signs of left ventricular failure. She was recovering well from pulmonary oedema after being provided with mechanical ventilation. However on 4th day she developed sudden onset quadriparesis without any alteration in sensorium, bladder & bowel disturbance or any sensory deficit. Diffusion weighted neuroimaging (DWI) was carried out which revealed finding suggestive of PRES. The patient was treated with antihypertensive which followed improvement in neurological deficit. Although rare, PRES should be considered as a potential cause of acute onset focal neurological deficit in pregnant females with PIH. With this case report we have tried to create awareness and vigilance about rare but potentially serious yet salvageable condition like PRES. PMID:26023585

  19. [Patient with posterior reversible encephalopathy syndrome with prolonged disturbance of consciousness and convulsion after cerebral aneurysm surgery].

    PubMed

    Ueda, Kayo; Hoshi, Takuo; Yorozu, Shinko; Okazaki, Junko; Motomura, Yuji; Masumoto, Tomohiko; Tsubokawa, Tsunehisa; Tanaka, Makoto

    2011-02-01

    A 73-year-old patient developed convulsion and prolonged disturbance of consciousness after clipping surgery for unruptured cerebral aneurysm. The patient's consciousness improved four days after surgery, and radiological findings suggested posterior reversible encephalopathy syndrome (PRES). The cause of PRES is thought to be dysfunction of blood brain barrier by a sudden increase in blood pressure. In case of unexplained convulsion and decreased level of consciousness, PRES should be considered with radiographic examinations including CT and MRI.

  20. A school-based application of modified habit reversal for Tourette syndrome via a translator: a case study.

    PubMed

    Gilman, Rich; Connor, Nancy; Haney, Michelle

    2005-11-01

    A school-based modified habit reversal intervention was utilized with an adolescent diagnosed with Tourette syndrome who recently immigrated from Mexico. Because the student possessed little proficiency of the English language, an interpreter was needed to help implement the procedure. The frequency of motor tics markedly decreased from baseline to intervention across classroom settings. Results of two follow-up phases revealed that motor tic levels remained below those observed in the baseline phase. Implications and limitations of these findings are noted.

  1. Voltage-gated calcium channel autoimmune cerebellar degeneration

    PubMed Central

    McKasson, Marilyn; Clawson, Susan A.; Hill, Kenneth E.; Wood, Blair; Carlson, Noel; Bromberg, Mark; Greenlee, John E.

    2016-01-01

    Objectives: To describe response to treatment in a patient with autoantibodies against voltage-gated calcium channels (VGCCs) who presented with autoimmune cerebellar degeneration and subsequently developed Lambert-Eaton myasthenic syndrome (LEMS), and to study the effect of the patient's autoantibodies on Purkinje cells in rat cerebellar slice cultures. Methods: Case report and study of rat cerebellar slice cultures incubated with patient VGCC autoantibodies. Results: A 53-year-old man developed progressive incoordination with ataxic speech. Laboratory evaluation revealed VGCC autoantibodies without other antineuronal autoantibodies. Whole-body PET scans 6 and 12 months after presentation detected no malignancy. The patient improved significantly with IV immunoglobulin G (IgG), prednisone, and mycophenolate mofetil, but worsened after IV IgG was halted secondary to aseptic meningitis. He subsequently developed weakness with electrodiagnostic evidence of LEMS. The patient's IgG bound to Purkinje cells in rat cerebellar slice cultures, followed by neuronal death. Reactivity of the patient's autoantibodies with VGCCs was confirmed by blocking studies with defined VGCC antibodies. Conclusions: Autoimmune cerebellar degeneration associated with VGCC autoantibodies may precede onset of LEMS and may improve with immunosuppressive treatment. Binding of anti-VGCC antibodies to Purkinje cells in cerebellar slice cultures may be followed by cell death. Patients with anti-VGCC autoantibodies may be at risk of irreversible neurologic injury over time, and treatment should be initiated early. PMID:27088118

  2. Cerebellar network plasticity: from genes to fast oscillation.

    PubMed

    Cheron, G; Servais, L; Dan, B

    2008-04-22

    The role of the cerebellum has been increasingly recognized not only in motor control but in sensory, cognitive and emotional learning and regulation. Purkinje cells, being the sole output from the cerebellar cortex, occupy an integrative position in this network. Plasticity at this level is known to critically involve calcium signaling. In the last few years, electrophysiological study of genetically engineered mice has demonstrated the topical role of several genes encoding calcium-binding proteins (calretinin, calbindin, parvalbumin). Specific inactivation of these genes results in the emergence of a fast network oscillation (ca. 160 Hz) throughout the cerebellar cortex in alert animals, associated with ataxia. This oscillation is produced by synchronization of Purkinje cells along the parallel fiber beam. It behaves as an electrophysiological arrest rhythm, being blocked by sensorimotor stimulation. Pharmacological manipulations showed that the oscillation is blocked by GABA(A) and NMDA antagonists as well as gap junction blockers. This cerebellar network oscillation has also been documented in mouse models of human conditions with complex developmental cerebellar dysfunction, such as Angelman syndrome and fetal alcohol syndrome. Recent evidence suggests a relationship between fast oscillation and cerebellar long term depression (LTD). This may have major implications for future therapeutic targeting.

  3. Postpartum posterior reversible encephalopathy syndrome (PRES) in a twin pregnancy complicated by preeclampsia-eclampsia: case report.

    PubMed

    Papoutsis, D; El-Attabi, N; Sizer, A

    2014-01-01

    This is the second case in literature of posterior reversible encephalopathy syndrome (PRES) in a twin pregnancy complicated by preeclampsia-eclampsia. A 27-year-old primigravida with dichorionic diamniotic twin pregnancy was admitted at 36 weeks of gestation for induction of labour due to preeclampsia. On the second day postpartum, the patient developed severe hypertension, visual symptoms, confusion, headache, and eclamptic fits. Head computed tomography (CT) showed hypodense basal ganglia lesions. The patient was treated in the intensive treatment unit with hydralazine and labetalol infusions and anticonvulsants. Five days later, there was complete clinical improvement and follow-up magnetic resonance imaging (MRI) was normal. The patient was discharged 11 days post-delivery. Diagnosis of PRES is based on the presence of clinical features of acute neurologic compromise, abnormal neuroimaging findings, and complete reversibility of findings after prompt treatment. Early recognition and proper treatment result in complete reversibility of this condition.

  4. MeCP2 and Rett syndrome: reversibility and potential avenues for therapy.

    PubMed

    Gadalla, Kamal K E; Bailey, Mark E S; Cobb, Stuart R

    2011-10-01

    Mutations in the X-linked gene MECP2 (methyl CpG-binding protein 2) are the primary cause of the neurodevelopmental disorder RTT (Rett syndrome), and are also implicated in other neurological conditions. The expression product of this gene, MeCP2, is a widely expressed nuclear protein, especially abundant in mature neurons of the CNS (central nervous system). The major recognized consequences of MECP2 mutation occur in the CNS, but there is growing awareness of peripheral effects contributing to the full RTT phenotype. MeCP2 is classically considered to act as a DNA methylation-dependent transcriptional repressor, but may have additional roles in regulating gene expression and chromatin structure. Knocking out Mecp2 function in mice recapitulates many of the overt neurological features seen in RTT patients, and the characteristic postnatally delayed onset of symptoms is accompanied by aberrant neuronal morphology and deficits in synaptic physiology. Evidence that reactivation of endogenous Mecp2 in mutant mice, even at adult stages, can reverse aspects of RTT-like pathology and result in apparently functionally mature neurons has provided renewed hope for patients, but has also provoked discussion about traditional boundaries between neurodevelopmental disorders and those involving dysfunction at later stages. In the present paper we review the neurobiology of MeCP2 and consider the various genetic (including gene therapy), pharmacological and environmental interventions that have been, and could be, developed to attempt phenotypic rescue in RTT. Such approaches are already providing valuable insights into the potential tractability of RTT and related conditions, and are useful pointers for the development of future therapeutic strategies.

  5. Real-Time Reverse Transcription-PCR Assay Panel for Middle East Respiratory Syndrome Coronavirus

    PubMed Central

    Lu, Xiaoyan; Whitaker, Brett; Sakthivel, Senthil Kumar K.; Kamili, Shifaq; Rose, Laura E.; Lowe, Luis; Mohareb, Emad; Elassal, Emad M.; Al-sanouri, Tarek; Haddadin, Aktham

    2014-01-01

    A new human coronavirus (CoV), subsequently named Middle East respiratory syndrome (MERS)-CoV, was first reported in Saudi Arabia in September 2012. In response, we developed two real-time reverse transcription-PCR (rRT-PCR) assays targeting the MERS-CoV nucleocapsid (N) gene and evaluated these assays as a panel with a previously published assay targeting the region upstream of the MERS-CoV envelope gene (upE) for the detection and confirmation of MERS-CoV infection. All assays detected ≤10 copies/reaction of quantified RNA transcripts, with a linear dynamic range of 8 log units and 1.3 × 10−3 50% tissue culture infective doses (TCID50)/ml of cultured MERS-CoV per reaction. All assays performed comparably with respiratory, serum, and stool specimens spiked with cultured virus. No false-positive amplifications were obtained with other human coronaviruses or common respiratory viral pathogens or with 336 diverse clinical specimens from non-MERS-CoV cases; specimens from two confirmed MERS-CoV cases were positive with all assay signatures. In June 2012, the U.S. Food and Drug Administration authorized emergency use of the rRT-PCR assay panel as an in vitro diagnostic test for MERS-CoV. A kit consisting of the three assay signatures and a positive control was assembled and distributed to public health laboratories in the United States and internationally to support MERS-CoV surveillance and public health responses. PMID:24153118

  6. Effect of Valsartan on Cerebellar Adrenomedullin System Dysregulation During Hypertension.

    PubMed

    Figueira, Leticia; Israel, Anita

    2017-02-01

    Adrenomedullin (AM) and its receptors components, calcitonin-receptor-like receptor (CRLR), and receptor activity-modifying protein (RAMP1, RAMP2, and RAMP3) are expressed in cerebellum. Cerebellar AM, AM binding sites and receptor components are altered during hypertension, suggesting a role for cerebellar AM in blood pressure regulation. Thus, we assessed the effect of valsartan, on AM and its receptor components expression in the cerebellar vermis of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Additionally, we evaluated AM action on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity, and thiobarbituric acid reactive substances (TBARS) production in cerebellar vermis. Animals were treated with valsartan or vehicle for 11 days. Rats were sacrificed by decapitation; cerebellar vermis was dissected; and AM, CRLR, RAMP1, RAMP2, and RAMP3 expression was quantified by Western blot analysis. CAT, SOD, and GPx activity was determined spectrophotometrically and blood pressure by non-invasive plethysmography. We demonstrate that AM and RAMP2 expression was lower in cerebellum of SHR rats, while CRLR, RAMP1, and RAMP3 expression was higher than those of WKY rats. AM reduced cerebellar CAT, SOD, GPx activities, and TBARS production in WKY rats, but not in SHR rats. Valsartan reduced blood pressure and reversed the altered expression of AM and its receptors components, as well the loss of AM capacity to reduce antioxidant enzyme activity and TBARS production in SHR rats. These findings demonstrate that valsartan is able to reverse the dysregulation of cerebellar adrenomedullinergic system; and they suggest that altered AM system in the cerebellum could represent the primary abnormality leading to hypertension.

  7. Genetics Home Reference: lissencephaly with cerebellar hypoplasia

    MedlinePlus

    ... Conditions lissencephaly with cerebellar hypoplasia lissencephaly with cerebellar hypoplasia Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Lissencephaly with cerebellar hypoplasia (LCH) affects brain development, resulting in the brain ...

  8. Paraneoplastic cerebellar degeneration as a marker of endometrial cancer recurrence.

    PubMed

    Lie, Geoffrey; Morley, Thomas; Chowdhury, Muhammad

    2016-05-18

    An 84-year-old woman developed a cerebellar syndrome having undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrial cancer 1 year previously. She was found to be anti-Yo antibody positive and was diagnosed with paraneoplastic cerebellar degeneration (PCD). A subsequent positron emission tomography scan and lymph node biopsy identified recurrence of her endometrial cancer. This case illustrates how PCD can be an indicator of cancer recurrence, underlines the significance of PCD as a prompt to search for underlying malignancy, and highlights the difficulties PCD poses to the clinician in terms of diagnosis and management.

  9. [Anatomical and clinical correlations in the cerebellar eredodegeneration].

    PubMed

    Pea, Umberto; de Luca, Francesco; Nicola, Massimiliano; Galli, Luigi

    2003-06-01

    Spinocerebellar hereditary degeneration makes up a heterogeneous group of diseases headed by Strumpell-Lorrain syndrome and Friedreich's disease. They are a heterogeneous group characterized by spasticity and paraplegia and related to demyelinization of the pyramidal tract and of the posterior cordons. During a 4-year period, we studied 14 patients (42-61 years old) suffering cerebellar eredodegeneration (hereditary ataxia). The aim of our work was to correlate anatomopathological findings with clinical signs. The important role played by the cerebellum in vesicosphincterial coordination was shown; in particular severe alteration of the ponto-cerebellar bundles could be cause of the abnormal behaviour of the detrusor.

  10. Famotidine-induced reversal of meperidine-related serotonin syndrome: a case report

    PubMed Central

    Joe, Soohyun; Park, Junyi; Lee, Dongwon; Son, Jongchul; Kim, Hyun

    2017-01-01

    Serotonin syndrome is an unexpected fatal adverse event related to serotonergic medication. This case report is the first report describing the possible treatment effect of famotidine on serotonin syndrome. Furthermore, this is the first case report of serotonin syndrome induced by meperidine alone in a patient with no previous history suggesting a susceptibility to serotonin syndrome. A 70-year-old male with no recent history of serotonergic drug use presented with severe serotonin syndrome following ureteroscopy, possibly due to postoperative meperidine administration. The patient's symptoms included hypertension, tachycardia, tachypnea, hyperthermia, myoclonus, diaphoresis, retching, nausea, agitation, and semicoma mentality with no pupillary light reflex. Symptoms began to subside immediately after the administration of intravenous famotidine for prevention of aspiration pneumonia, with mental and neurological symptoms showing improvement initially, followed by autonomic symptoms. This case report suggests that the histamine type 2 receptor antagonist famotidine may be an effective emergency treatment for serotonin syndrome. PMID:28367296

  11. Childhood Cerebellar Ataxia

    PubMed Central

    Fogel, Brent L.

    2012-01-01

    Childhood presentations of ataxia, an impairment of balance and coordination caused by damage to or dysfunction of the cerebellum, can often be challenging to diagnose. Presentations tend to be clinically heterogeneous but key considerations may vary based on the child's age at onset, the course of illness, and subtle differences in phenotype. Systematic investigation is recommended for efficient diagnosis. In this review, we outline common etiologies and describe a comprehensive approach to the evaluation of both acquired and genetic cerebellar ataxia in children. PMID:22764177

  12. Epistatic interactions between Chd7 and Fgf8 during cerebellar development

    PubMed Central

    Basson, M Albert

    2014-01-01

    CHARGE syndrome is a rare, autosomal dominant condition caused by mutations in the CHD7 gene. Although central nervous system defects have been reported, the detailed description and analysis of these anomalies in CHARGE syndrome patients lag far behind the description of other, more easily observed defects. We recently described cerebellar abnormalities in CHARGE syndrome patients and used mouse models to identify the underlying causes. Our studies identified altered expression of the homeobox genes Otx2 and Gbx2 in the developing neural tube of Chd7−/− embryos. Furthermore, we showed that the expression of Fgf8 is sensitive to Chd7 gene dosage and demonstrated an epistatic relationship between these genes during cerebellar vermis development. These findings provided, for the first time, an example of cerebellar vermis hypoplasia in a human syndrome that can be linked to deregulated FGF signaling. I discuss some of these observations and their implications for CHARGE syndrome. PMID:25054096

  13. Palatoglossal fusion with cleft palate and hypoplasia of cerebellar vermis

    PubMed Central

    Solanki, Shailesh; Babu, M. Narendra; Gowrishankar; Ramesh, S.

    2016-01-01

    A new-born male presented within 12 h of birth with respiratory distress. On examination and workup, he had palatoglossal fusion, cleft palate and hypoplasia of the cerebellar vermis. A 2.5 Fr endotracheal tube was inserted into the pharynx through nostril as a nasopharyngeal stent, following which his respiratory distress improved. Once child was optimised, then feeding was started by nasogastric tube and feeds were tolerated well. Elective tracheostomy and gastrostomy were done, followed by release of adhesions between the tongue and palate at a later stage. Review of literature suggests that palatoglossal fusion is uncommon and presents as an emergency. Mostly, these oral synechiae are associated with digital and/or cardiac anomaly. Other disorders associated with intra-oral synechiae include congenital alveolar synechiae, van der Woude syndrome, popliteal pterygium syndrome and oromandibular limb hypogenesis syndrome. The authors report a hitherto undescribed association of palatoglossal fusion with cleft palate and hypoplasia of the cerebellar vermis. PMID:27274132

  14. Dietary nitrite reverses features of postmenopausal metabolic syndrome induced by high fat diet and ovariectomy in mice.

    PubMed

    Ohtake, Kazuo; Ehara, Nobuyuki; Chiba, Hiroshige; Nakano, Genya; Sonoda, Kunihiro; Ito, Junta; Uchida, Hiroyuki; Kobayashi, Jun

    2017-02-14

    Menopausal women are at greater risk of developing metabolic syndrome with reduced endothelial nitric oxide synthase (eNOS) activity. Hormone replacement therapy increases eNOS activity and normalizes some characteristics of metabolic syndrome. We hypothesized that nitric oxide (NO) supplementation should have a therapeutic effect in this syndrome. We examined the effect of dietary nitrite on mice model with postmenopausal metabolic syndrome induced by ovariectomy (OVX) with high fat diet (HF). C57BL/6 female mice were divided into five groups, sham+normal fat diet (NF), sham+ HF, OVX+HF without or with sodium nitrite (50mg and 150mg/L) in drinking water. Daily food intake and weekly body weight were monitored for 18 weeks. OVX and HF significantly reduced plasma levels of nitrate/nitrite (NOx), and developed obesity with visceral hypertrophic adipocytes, and increased transcriptional levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrotizing factor-α (TNF-α) and interleukin-6 (IL-6) in visceral fat tissues. The proinflammatory state in the adipocytes provoked severe hepatosteatosis and insulin resistance in OVX+HF group compared with sham+NF group. However, dietary nitrite significantly suppressed adipocyte hypertrophy and transcriptions of proinflammatory cytokines in visceral fat in a dose dependent manner. The improvement of visceral inflammatory state consequently reversed the hepatosteatosis and insulin resistance observed in OVX+HF mice. These results suggest that endogenous NO defect might underlie postmenopausal metabolic syndrome, and dietary nitrite provides an alternative source of NO, and subsequently compensating for metabolic impairments of this syndrome.

  15. Reversal of Handedness Effects on Bimanual Coordination in Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Mulvey, G. M.; Ringenbach, S. D. R.; Jung, M. L.

    2011-01-01

    Background: Research on unimanual tasks suggested that motor asymmetries between hands may be reduced in people with Down syndrome. Our study examined handedness (as assessed by hand performance) and perceptual-motor integration effects on bimanual coordination. Methods: Adults with Down syndrome (13 non-right-handed, 22 right-handed), along with…

  16. Crossed Cerebellar Diaschisis

    PubMed Central

    Han, Shuguang; Wang, Xiaopeng; Xu, Kai; Hu, Chunfeng

    2016-01-01

    Abstract Crossed cerebellar diaschisis (CCD) describes a depression of oxidative metabolism glucose and blood flow in the cerebellum secondary to a supratentorial lesion in the contralateral cerebral hemisphere. PET/MR has the potential to become a powerful tool for demonstrating and imaging intracranial lesions .We herein report 3 cases of CCD imaging using a tri-modality PET/CT–MR set-up for investigating the value of adding MRI rather than CT to PET in clinical routine. We describe 3 patients with CCD and neurological symptoms in conjunction with abnormal cerebral fluorodeoxyglucose (FDG) positron emission tomography/computed tomography-magnetic resonance imaging (PET/CT–MR) manifestations including arterial spin-labeling (ASL) and T2-weighted images. In all, 18FDG-PET/CT detected positive FDG uptake in supratentorial lesions, and hypometabolism with atrophy in the contralateral cerebellum. More than that, hybrid PET/MRI provided a more accurate anatomic localization and ASL indicated disruption of the cortico-ponto-cerebellar pathway. Using pathology or long-term clinical follow-up to confirm the PET and ASL findings, the supratentorial lesions of the 3 patients were respectively diagnosed with cerebral infarction, recurrent glioma, and metastasis. The reports emphasize the significance of multimodality radiological examinations. Multimodality imaging contributes to proper diagnosis, management, and follow-up of supratentorial lesions with CCD. PMID:26765477

  17. Posterior Reversible Encephalopathy Syndrome and Fatal Cryptococcal Meningitis After Immunosuppression in a Patient With Elderly Onset Inflammatory Bowel Disease

    PubMed Central

    Vasant, Dipesh H.; Limdi, Jimmy K.; Borg-Bartolo, Simon P.; Bonington, Alec

    2016-01-01

    Advanced age and associated comorbidities are-recognized predictors of life-threatening adverse outcomes, such as opportunistic infection following immunosuppressive therapy. We describe the case of an elderly patient with stricturing colonic Crohn’s disease and significant clinical comorbidities, initially controlled with corticosteroid induction followed by infliximab, whose course was complicated by fatal disseminated cryptococcal infection and posterior reversible encephalopathy syndrome. Our patient’s case highlights rare, but serious, complications of immunosuppression. In applying modern treatment paradigms to the elderly, the clinician must consider the potential for more pronounced adverse effects in this potentially vulnerable group, maximizing benefit and minimizing harm. PMID:27807560

  18. Posterior reversible encephalopathy syndrome as a complication of Henoch-Schönlein purpura in a seven-year-old girl.

    PubMed

    Dos Santos, Daiane; Langer, Felipe Welter; Dos Santos, Tatiane; Rafael Tronco Alves, Giordano; Feiten, Marisa; Teixeira de Paula Neto, Walter

    2017-02-01

    Introduction Henoch-Schönlein purpura is a multisystem small vessel vasculitis. Neurologic manifestations are uncommon. Posterior reversible encephalopathy syndrome is a rare complication of Henoch-Schönlein purpura with typical clinical and neuroimaging findings that occurs most commonly in the setting of severe hypertension and renal injury. Case presentation A seven-year-old girl was admitted to our institution presenting with clinical and laboratory findings suggestive of Henoch-Schönlein purpura. Glucocorticoid therapy was initiated, but five days following her admission, she developed altered consciousness, seizures, arterial hypertension, and cortical blindness. Brain MRI scan revealed areas of vasogenic oedema in parieto-occipital lobes, consistent with posterior reversible encephalopathy syndrome. She was immediately initiated on antihypertensives and antiepileptics, which successfully improved her neurologic symptoms. Further laboratory work-up disclosed a rapidly progressive glomerulonephritis secondary to Henoch-Schönlein purpura that was the likely cause of her sudden blood pressure elevation. Immunosuppressive therapy was undertaken, and at one-year follow-up, the patient exhibited complete renal and neurologic recovery. Conclusion Posterior reversible encephalopathy syndrome is a severe complication of Henoch-Schönlein purpura. If promptly diagnosed and treated, children with Henoch-Schönlein purpura presenting with posterior reversible encephalopathy syndrome usually have a good prognosis. Clinicians should be familiar with the characteristic presentation of posterior reversible encephalopathy syndrome and be aware that hypertension and renal injury may predispose Henoch-Schönlein purpura patients to developing this complication.

  19. Sheehan's syndrome with reversible dilated cardiomyopathy: A case report and brief overview.

    PubMed

    Islam, A K M Monwarul; Hasnat, Mohammad A; Doza, Fatema; Jesmin, Humayra

    2014-04-01

    Sheehan's syndrome is a rare condition characterized by post-partal panhypopituitarism due to necrosis of adenohypophysis resulting from severe post-partum hemorrhage. Lethargy, amenorrhea and failure of lactation are the usual presenting features. Cardiac involvement in Sheehan's syndrome is rare. The case presented here describes dilated cardiomyopathy in a 36-year-old lady who failed to respond adequately to the standard anti-failure treatment. Further investigation revealed the diagnosis of Sheehan's syndrome. Besides other manifestations, cardiac function reverted to normal after giving replacement therapy with glucocorticoid, levothyroxine and sex hormone. Physicians, specially those in developing countries, should have high index of suspicion for the diagnosis of Sheehan's syndrome while dealing with a case of 'peripartal dilated cardiomyopathy'. Persistent amenorrhea and failure of lactation may be important clues in this context. Timely diagnosis and appropriate treatment can lessen the sufferings of the patients.

  20. Sheehan’s syndrome with reversible dilated cardiomyopathy: A case report and brief overview

    PubMed Central

    Islam, A.K.M. Monwarul; Hasnat, Mohammad A.; Doza, Fatema; Jesmin, Humayra

    2014-01-01

    Sheehan’s syndrome is a rare condition characterized by post-partal panhypopituitarism due to necrosis of adenohypophysis resulting from severe post-partum hemorrhage. Lethargy, amenorrhea and failure of lactation are the usual presenting features. Cardiac involvement in Sheehan’s syndrome is rare. The case presented here describes dilated cardiomyopathy in a 36-year-old lady who failed to respond adequately to the standard anti-failure treatment. Further investigation revealed the diagnosis of Sheehan’s syndrome. Besides other manifestations, cardiac function reverted to normal after giving replacement therapy with glucocorticoid, levothyroxine and sex hormone. Physicians, specially those in developing countries, should have high index of suspicion for the diagnosis of Sheehan’s syndrome while dealing with a case of ‘peripartal dilated cardiomyopathy’. Persistent amenorrhea and failure of lactation may be important clues in this context. Timely diagnosis and appropriate treatment can lessen the sufferings of the patients. PMID:24719543

  1. Controlateral cavernous syndrome, brainstem congestion and posterior fossa venous thrombosis with cerebellar hematoma related to a ruptured intracavernous carotid artery aneurysm.

    PubMed

    Aldea, Sorin; Guedin, Pierre; Roccatagliata, Luca; Boulin, Anne; Auliac, Stéphanie; Dupuy, Michel; Cerf, Charles; Gaillard, Stéphan; Rodesch, Georges

    2011-06-01

    Intracavernous carotid artery aneurysms (ICCAs) are rarely associated with life-threatening complications. We describe a 55-year-old woman who, after the rupture of an intracavernous carotid artery aneurysm, presented with a contralateral cavernous sinus syndrome and severe posterior fossa and spinal cord symptoms. Following parent artery occlusion, thrombosis of the posterior fossa and spinal cord veins caused a progressive worsening of the neurological status to a "locked-in" state. The patient fully recovered with anticoagulation therapy. Comprehension of the pathophysiological mechanism associated with the rupture of ICCA and early diagnosis of the related symptoms are essential in order to plan a correct treatment that includes the management of the aneurysm rupture and of possible complications related to venous thrombosis.

  2. Reversible cerebral vasoconstriction syndrome (RCVS) in antiphospholipid antibody syndrome (APLA): the role of centrally acting vasodilators. Case series and review of literature.

    PubMed

    Gupta, Sarthak; Zivadinov, Robert; Ramasamy, Deepa; Ambrus, Julian L

    2014-12-01

    Reversible cerebral vasoconstriction syndrome (RCVS) is Raynaud's phenomenon of the brain. Changes in neurological function are dependent upon which areas of the brain are deprived of normal blood flow. Antiphospholipid antibody syndrome (APLA) is a common cause of Raynaud's phenomenon that can occur anywhere in the body, including the brain. Management of CNS vasospasm generally involves the use of centrally acting calcium channel blockers, which have been shown to relieve the associated headaches and transient neurological symptoms associated with it. Three patients with APLA and RCVS from our clinics are illustrated. It is demonstrated that the use of centrally acting calcium channel-blocking drugs, such as nimodipine, which prevent and reverse CNS vasospasm, led to clinical improvement in our patients over the course of 5-9 years. All of them had MRIs done at the initiation of therapy and 5-9 years after being on therapy. MRI measures of T2 lesion volumes (LVs) and number were obtained. All three patients had a good response in controlling clinical symptoms related to CNS vasospasm, Raynaud's phenomenon, visual disturbances, confusion, headaches, and hearing loss. There was also a resolution in the MRI findings of these patients. This case series of three patients shows a clinical improvement and decrease in T2 LV and number in patients with APLA and Raynaud's syndrome on centrally acting calcium channel blockers. RCVS is much more common than that currently appreciated. APLA is the common cause of RCVS. Further studies are needed to determine the optimal methods to diagnose RCVS and optimal therapies to treat it.

  3. Autosomal recessive cerebellar ataxias

    PubMed Central

    Palau, Francesc; Espinós, Carmen

    2006-01-01

    Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia. PMID:17112370

  4. Pediatric cerebellar stroke associated with elevated titer of antibodies to β2-glycoprotein.

    PubMed

    Spalice, Alberto; Del Balzo, Francesca; Perla, Francesco Massimo; Papetti, Laura; Nicita, Francesco; Ursitti, Fabiana; Properzi, Enrico

    2011-06-01

    Antibodies to 2-glycoprotein I (anti-2GPI) have been associated with recurrent thrombosis and pregnancy morbidity. However, the prevalence of anti-2GPI in children suffering from cerebral and cerebellar infarction is unknown. We report on a 10-month-old boy who had an ischemic cerebellar stroke, secondary to antiphospholipid syndrome with high titers of immunoglobulin G anti-2GPI (first titer: 132U) anticardiolipin antibodies and lupus anticoagulant tests were negative. All other causes of infarction were excluded. To our knowledge, this is the first reported case of childhood cerebellar ischemic stroke with only anti-2GPI but no antibodies detectable in standard antiphospholipid assays.

  5. Anti-Yo positive paraneoplastic cerebellar degeneration in the setting of cholangiocarcinoma.

    PubMed

    Bruhnding, Aubree; Notch, Derek; Beard, Albertine

    2017-02-01

    Paraneoplastic neurological syndromes are a rare complication of malignancy. Subacute cerebellar ataxia, or paraneoplastic cerebellar degeneration, usually presents in women with a subcate onset of gait instability, followed by progressive limb and trunk ataxia, dysarthria, diplopia, and dysphagia that occurs in the setting of, or precedes the diagnosis of, a gynecologic or breast malignancy and clinically stabilizes within six months. The most common autoantibody associated with PCD is purkinje cell cytoplasmic antibody type 1, also known as anti-Yo. Here we describe the first reported case of a man with anti-Yo positive paraneoplastic cerebellar degeneration in the setting of occult cholangiocarcinoma.

  6. Reverse split hand syndrome: Dissociated intrinsic hand muscle atrophy pattern in Hirayama disease/brachial monomelic amyotrophy.

    PubMed

    Singh, Ravinder-Jeet; Preethish-Kumar, Veeramani; Polavarapu, Kiran; Vengalil, Seena; Prasad, Chandrajit; Nalini, Atchayaram

    2017-02-01

    Preferential involvement of C7, C8, T1 level anterior horn cells is a typical feature in Hirayama disease/brachial monomelic amyotrophy (BMMA). There are no clinico-electrophysiological studies to substantiate the peculiar pattern of muscle involvement. Thirty subjects, 10 in each group of BMMA, amyotrophic lateral sclerosis (ALS) and age-matched normal healthy subjects underwent detailed clinical and electrophysiological testing. Results showed that the mean age at evaluation for BMMA and ALS patients was 25.8 ± 3.8 and 51.8 ± 9.5 years, respectively; illness duration was 8.1 ± 5.7 years and 11.14 ± 2.85 months, respectively. Clinically, all BMMA patients had reverse of split hand (RSH) syndrome [abductor digiti minimi (ADM) affected more than abductor pollicis brevis (APB)], while 7/10 ALS patients had classical split hand syndrome (APB affected more than ADM). In BMMA, the compound muscle action potential (CMAP) of APB was preserved but reduced/absent in ADM compared to the ALS group which demonstrated reverse findings. APB/ADM ratio was >0.8 in the BMMA group (>1.4 in 80%), around 1.0 in normal controls (none had >1.4) and <0.8 in ALS (70% having values <0.6). In conclusion, RSH syndrome may provide valuable diagnostic clues to differentiate this relatively self-restricted disease from progressive degenerative disease like ALS.

  7. Posterior Reversible Encephalopathy Syndrome (PRES): Restricted Diffusion does not Necessarily Mean Irreversibility

    PubMed Central

    Wagih, Alaa; Mohsen, Laila; Rayan, Moustafa M.; Hasan, Mo’men M.; Al-Sherif, Ashraf H.

    2015-01-01

    Summary Background Restricted diffusion is the second most common atypical presentation of PRES. This has a very important implication, as lesions with cytotoxic edema may progress to infarction. Several studies suggested the role of DWI in the prediction of development of infarctions in these cases. Other studies, however, suggested that PRES is reversible even with cytotoxic patterns. Our aim was to evaluate whether every restricted diffusion in PRES is reversible and what factors affect this reversibility. Material/Methods Thirty-six patients with acute neurological symptoms suggestive of PRES were included in our study. Inclusion criteria comprised imaging features of atypical PRES where DWI images and ADC maps show restricted diffusion. Patients were imaged with 0.2-T and 1.5-T machines. FLAIR images were evaluated for the severity of the disease and a FLAIR/DWI score was used. ADC values were selectively recorded from the areas of diffusion restriction. A follow-up MRI study was carried out in all patients after 2 weeks. Patients were classified according to reversibility into: Group 1 (reversible PRES; 32 patients) and Group 2 (irreversible changes; 4 patients). The study was approved by the University’s research ethics committee, which conforms to the declaration of Helsinki. Results The age and blood pressure did not vary significantly between both groups. The total number of regions involved and the FLAIR/DWI score did not vary significantly between both groups. Individual regions did not reveal any tendency for the development of irreversible lesions. Similarly, ADC values did not reveal any significant difference between both groups. Conclusions PRES is completely reversible in the majority of patients, even with restricted diffusion. None of the variables under study could predict the reversibility of PRES lesions. It seems that this process is individual-dependent. PMID:25960819

  8. Characteristics of reversible and nonreversible COPD and asthma and COPD overlap syndrome patients: an analysis of salbutamol Easyhaler data.

    PubMed

    Müller, Veronika; Gálffy, Gabriella; Orosz, Márta; Kováts, Zsuzsanna; Odler, Balázs; Selroos, Olof; Tamási, Lilla

    2016-01-01

    The choice of inhaler device for bronchodilator reversibility is crucial since suboptimal inhalation technique may influence the result. On the other hand, bronchodilator response also varies from time to time and may depend on patient characteristics. In this study, patients with airway obstruction (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio <70% in chronic obstructive pulmonary disease [COPD]; <80% in asthma) were included (n=121, age: 57.8±17.3 years). Bronchodilator reversibility (American Thoracic Society/European Respiratory Society criteria) was tested in patients with COPD (n=63) and asthma and COPD overlap syndrome (ACOS; n=12). Forty-six asthmatics served as controls. Reversibility was tested with 400 µg salbutamol dry powder inhaler (Buventol Easyhaler, Orion Pharma Ltd, Espoo, Finland). Demographic data and patients' perceptions of Easyhaler compared with β2-agonist pressurized metered dose inhalers (pMDIs) were analyzed. American Thoracic Society/European Respiratory Society guideline defined reversibility was found in 21 out of 63 COPD patients and in two out of 12 ACOS patients. Airway obstruction was more severe in COPD patients as compared with controls (mean FEV1 and FEV1% predicted both P<0.0001). Average response to salbutamol was significantly lower in COPD patients compared with asthma controls (P<0.0001). Reversibility was equally often found in smokers as in never-smokers (33% vs 34%). Nonreversible COPD patients had higher mean weight, body mass index, and FEV1/FVC compared with reversible COPD patients. Most patients preferred Easyhaler and defined its use as simpler and more effective than use of a pMDI. Never-smokers and patients with asthma experienced Easy-haler somewhat easier to use than smokers and patients with COPD. In conclusion, a substantial part of patients with COPD or ACOS showed reversibility to salbutamol dry powder inhaler. Nonreversible patients with COPD were characterized by higher

  9. Characteristics of reversible and nonreversible COPD and asthma and COPD overlap syndrome patients: an analysis of salbutamol Easyhaler data

    PubMed Central

    Müller, Veronika; Gálffy, Gabriella; Orosz, Márta; Kováts, Zsuzsanna; Odler, Balázs; Selroos, Olof; Tamási, Lilla

    2016-01-01

    The choice of inhaler device for bronchodilator reversibility is crucial since suboptimal inhalation technique may influence the result. On the other hand, bronchodilator response also varies from time to time and may depend on patient characteristics. In this study, patients with airway obstruction (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio <70% in chronic obstructive pulmonary disease [COPD]; <80% in asthma) were included (n=121, age: 57.8±17.3 years). Bronchodilator reversibility (American Thoracic Society/European Respiratory Society criteria) was tested in patients with COPD (n=63) and asthma and COPD overlap syndrome (ACOS; n=12). Forty-six asthmatics served as controls. Reversibility was tested with 400 µg salbutamol dry powder inhaler (Buventol Easyhaler, Orion Pharma Ltd, Espoo, Finland). Demographic data and patients’ perceptions of Easyhaler compared with β2-agonist pressurized metered dose inhalers (pMDIs) were analyzed. American Thoracic Society/European Respiratory Society guideline defined reversibility was found in 21 out of 63 COPD patients and in two out of 12 ACOS patients. Airway obstruction was more severe in COPD patients as compared with controls (mean FEV1 and FEV1% predicted both P<0.0001). Average response to salbutamol was significantly lower in COPD patients compared with asthma controls (P<0.0001). Reversibility was equally often found in smokers as in never-smokers (33% vs 34%). Nonreversible COPD patients had higher mean weight, body mass index, and FEV1/FVC compared with reversible COPD patients. Most patients preferred Easyhaler and defined its use as simpler and more effective than use of a pMDI. Never-smokers and patients with asthma experienced Easy-haler somewhat easier to use than smokers and patients with COPD. In conclusion, a substantial part of patients with COPD or ACOS showed reversibility to salbutamol dry powder inhaler. Nonreversible patients with COPD were characterized by

  10. Reversal of experimental Laron Syndrome by xenotransplantation of microencapsulated porcine Sertoli cells.

    PubMed

    Luca, Giovanni; Calvitti, Mario; Mancuso, Francesca; Falabella, Giulia; Arato, Iva; Bellucci, Catia; List, Edward O; Bellezza, Enrico; Angeli, Giovanni; Lilli, Cinzia; Bodo, Maria; Becchetti, Ennio; Kopchick, John J; Cameron, Don F; Baroni, Tiziano; Calafiore, Riccardo

    2013-01-10

    Recombinant human IGF-1 currently represents the only available treatment option for the Laron Syndrome, a rare human disorder caused by defects in the gene encoding growth hormone receptor, resulting in irreversibly retarded growth. Unfortunately, this treatment therapy, poorly impacts longitudinal growth (13% in females and 19% in males), while burdening the patients with severe side effects, including hypoglycemia, in association with the unfair chore of taking multiple daily injections that cause local intense pain. In this study, we have demonstrated that a single intraperitoneal graft of microencapsulated pig Sertoli cells, producing pig insulin-like growth factor-1, successfully promoted significant proportional growth in the Laron mouse, a unique animal model of the human Laron Syndrome. These findings indicate a novel, simply, safe and successful method for the cell therapy-based cure of the Laron Syndrome, potentially applicable to humans.

  11. Redistribution of crossed cerebellar diaschisis

    SciTech Connect

    Kim, S.M.; Park, C.H.; Intenzo, C.M.; Bell, R.

    1989-04-01

    Crossed cerebellar diaschisis refers to a functional decrease in blood flow to the cerebellar hemisphere contralateral to the infarcted or ischemic cerebral hemisphere. This phenomenon can be depicted using PET as well as using SPECT. This condition, seen on early I-123 IMP brain scans, can show redistribution on the three hour delayed scan, presumably due to normal non-specific amine receptor sites of the affected cerebellum. One such case is reported.

  12. Speech prosody in cerebellar ataxia

    NASA Astrophysics Data System (ADS)

    Casper, Maureen

    The present study sought an acoustic signature for the speech disturbance recognized in cerebellar degeneration. Magnetic resonance imaging was used for a radiological rating of cerebellar involvement in six cerebellar ataxic dysarthric speakers. Acoustic measures of the [pap] syllables in contrastive prosodic conditions and of normal vs. brain-damaged patients were used to further our understanding both of the speech degeneration that accompanies cerebellar pathology and of speech motor control and movement in general. Pair-wise comparisons of the prosodic conditions within the normal group showed statistically significant differences for four prosodic contrasts. For three of the four contrasts analyzed, the normal speakers showed both longer durations and higher formant and fundamental frequency values in the more prominent first condition of the contrast. The acoustic measures of the normal prosodic contrast values were then used as a model to measure the degree of speech deterioration for individual cerebellar subjects. This estimate of speech deterioration as determined by individual differences between cerebellar and normal subjects' acoustic values of the four prosodic contrasts was used in correlation analyses with MRI ratings. Moderate correlations between speech deterioration and cerebellar atrophy were found in the measures of syllable duration and f0. A strong negative correlation was found for F1. Moreover, the normal model presented by these acoustic data allows for a description of the flexibility of task- oriented behavior in normal speech motor control. These data challenge spatio-temporal theory which explains movement as an artifact of time wherein longer durations predict more extreme movements and give further evidence for gestural internal dynamics of movement in which time emerges from articulatory events rather than dictating those events. This model provides a sensitive index of cerebellar pathology with quantitative acoustic

  13. Primary therapy for small cell lung cancer reversing the Eaton-Lambert syndrome

    SciTech Connect

    Kalter, S.; Dhingra, H.M.; Farha, P.

    1985-02-01

    A case report is presented of a patient with small cell carcinoma of the lung associated with the classic Eaton-Lambert syndrome. He received intermittent anticholinesterase therapy, with minimal improvement. Combined radiotherapy and chemotherapy for the primary neoplasm produced considerable improvement, with normal EMG findings after complete remission was achieved. 7 references, 1 table.

  14. Effects of stimulus salience on touchscreen serial reversal learning in a mouse model of fragile X syndrome

    PubMed Central

    Dickson, Price E.; Corkill, Beau; McKimm, Eric; Miller, Mellessa M.; Calton, Michele A.; Goldowitz, Daniel; Blaha, Charles D.; Mittleman, Guy

    2013-01-01

    Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in males and the most common genetic cause of autism. Although executive dysfunction is consistently found in humans with FXS, evidence of executive dysfunction in Fmr1 KO mice, a mouse model of FXS, has been inconsistent. One possible explanation for this is that executive dysfunction in Fmr1 KO mice, similar to humans with FXS, is only evident when cognitive demands are high. Using touchscreen operant conditioning chambers, male Fmr1 KO mice and their male wildtype littermates were tested on the acquisition of a pairwise visual discrimination followed by four serial reversals of the response rule. We assessed reversal learning performance under two different conditions. In the first, the correct stimulus was salient and the incorrect stimulus was non-salient. In the second and more challenging condition, the incorrect stimulus was salient and the correct stimulus was non-salient; this increased cognitive load by introducing conflict between sensory-driven (i.e., bottom-up) and task-dependent (i.e., top-down) signals. Fmr1 KOs displayed two distinct impairments relative to wildtype littermates. First, Fmr1 KOs committed significantly more learning-type errors during the second reversal stage, but only under high cognitive load. Second, during the first reversal stage, Fmr1 KOs committed significantly more attempts to collect a reward during the timeout following an incorrect response. These findings indicate that Fmr1 KO mice display executive dysfunction that, in some cases, is only evident under high cognitive load. PMID:23747611

  15. [Aneurysm of the anterior inferior cerebellar artery: case report].

    PubMed

    Adorno, Juan Oscar Alarcón; de Andrade, Guilherme Cabral

    2002-12-01

    The intracranial aneurysms of the posterior circulation have been reported between 5 and 10% of all cerebral aneurysms and the aneurysms of the anterior inferior cerebellar artery (AICA) are considered rare, can cause cerebello pontine angle (CPA) syndrome with or without subarachnoid hemorrhage. Since 1948 few cases were described in the literature. We report on a 33 year-old female patient with subarachnoid hemorrhage due to sacular aneurysm of the left AICA. She was submitted to clipage of the aneurysm without complications.

  16. Size does not always matter: Ts65Dn Down syndrome mice show cerebellum-dependent motor learning deficits that cannot be rescued by postnatal SAG treatment.

    PubMed

    Gutierrez-Castellanos, Nicolas; Winkelman, Beerend H J; Tolosa-Rodriguez, Leonardo; Devenney, Benjamin; Reeves, Roger H; De Zeeuw, Chris I

    2013-09-25

    Humans with Down syndrome (DS) and Ts65Dn mice both show a reduced volume of the cerebellum due to a significant reduction in the density of granule neurons. Recently, cerebellar hypoplasia in Ts65Dn mice was rescued by a single treatment with SAG, an agonist of the Sonic hedgehog pathway, administered on the day of birth. In addition to normalizing cerebellar morphology, this treatment restored the ability to learn a spatial navigation task, which is associated with hippocampal function. It is not clear to what extent this improved performance results from restoration of the cerebellar architecture or a yet undefined role of Sonic hedgehog (Shh) in perinatal hippocampal development. The absence of a clearly demonstrated deficit in cerebellar function in trisomic mice exacerbates the problem of discerning how SAG acts to improve learning and memory. Here we show that phase reversal adaptation and consolidation of the vestibulo-ocular reflex is significantly impaired in Ts65Dn mice, providing for the first time a precise characterization of cerebellar functional deficits in this murine model of DS. However, these deficits do not benefit from the normalization of cerebellar morphology following treatment with SAG. Together with the previous observation that the synaptic properties of Purkinje cells are also unchanged by SAG treatment, this lack of improvement in a region-specific behavioral assay supports the possibility that a direct effect of Shh pathway stimulation on the hippocampus might explain the benefits of this potential approach to the improvement of cognition in DS.

  17. Posterior Reversible Encephalopathy Syndrome Resolving Within 48 Hours in a Normotensive Patient Who Underwent Thoracic Spine Surgery.

    PubMed

    Vakharia, Kunal; Siasios, Ioannis; Dimopoulos, Vassilios G; Pollina, John

    2016-03-01

    Posterior reversible encephalopathy syndrome (PRES) usually manifests with severe headaches, seizures, and visual disturbances due to uncontrollable hypertension. A patient (age in the early 60s) with a history of renal cell cancer presented with lower-extremity weakness and paresthesias. Magnetic resonance imaging (MRI) of the thoracic spine revealed a T8 vertebral body metastatic lesion with cord compression at that level. The patient underwent preoperative embolization of the tumor followed by posterior resection and placement of percutaneous pedicle screws and rods. Postoperatively, the patient experienced decreased visual acuity bilaterally. Abnormal MRI findings consisted of T2 hyperintense lesions and fluid-attenuated inversion recovery changes in both occipital lobes, consistent with the unique brain imaging pattern associated with PRES. The patient's blood pressure was normal and stable from the first day of hospitalization. The patient was kept on high-dose steroid therapy, which was started intraoperatively, and improved within 48 hours after symptom onset.

  18. Defective lamin A-Rb signaling in Hutchinson-Gilford Progeria Syndrome and reversal by farnesyltransferase inhibition.

    PubMed

    Marji, Jackleen; O'Donoghue, Seán I; McClintock, Dayle; Satagopam, Venkata P; Schneider, Reinhard; Ratner, Desiree; Worman, Howard J; Gordon, Leslie B; Djabali, Karima

    2010-06-15

    Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare premature aging disorder caused by a de novo heterozygous point mutation G608G (GGC>GGT) within exon 11 of LMNA gene encoding A-type nuclear lamins. This mutation elicits an internal deletion of 50 amino acids in the carboxyl-terminus of prelamin A. The truncated protein, progerin, retains a farnesylated cysteine at its carboxyl terminus, a modification involved in HGPS pathogenesis. Inhibition of protein farnesylation has been shown to improve abnormal nuclear morphology and phenotype in cellular and animal models of HGPS. We analyzed global gene expression changes in fibroblasts from human subjects with HGPS and found that a lamin A-Rb signaling network is a major defective regulatory axis. Treatment of fibroblasts with a protein farnesyltransferase inhibitor reversed the gene expression defects. Our study identifies Rb as a key factor in HGPS pathogenesis and suggests that its modulation could ameliorate premature aging and possibly complications of physiological aging.

  19. Brief Report: The Association between Autism and Fragile X Syndrome: A Case Report.

    ERIC Educational Resources Information Center

    Lenti, Carlo

    1995-01-01

    This article presents a case report of a male child with Fragile X syndrome, typical autistic behavior, and cerebellar hypoplasia. Questions are raised concerning the possible role and importance of cerebellar abnormalities in relation to autistic symptoms. (DB)

  20. A clinical case study of a Wolfram syndrome-affected family: pattern-reversal visual evoked potentials and electroretinography analysis.

    PubMed

    Langwińska-Wośko, Ewa; Broniek-Kowalik, Karina; Szulborski, Kamil

    2012-04-01

    Wolfram syndrome (WFS), or DIDMOAD, is a rare (1/100 000 to 1/770 000), progressive neurodegenerative disorder. In its early stages, it is characterized by insulin-dependent diabetes mellitus, optic atrophy and loss of sensorineural hearing-this is followed by diabetes insipidus, progressive neurological abnormalities and other endocrine abnormalities, which occur in later years. The aim of this study was to report on the clinical and electrophysiological findings from a family with the WFS1 mutation. The five family members were subjected to a complete ophthalmic examination, which included a flash full-field electroretinogram and pattern-reversal visual evoked potentials (PVEPs) performed according to ISCEV standards. Optic atrophy was confirmed in two homozygotic patients, where P100 latencies were significantly delayed-up to 146 ms in PVEP. P100 latencies were normal in the three heterozygotic patients we examined. Curve morphology abnormalities were observed in all five patients we examined. No literature describing the morphology of PVEP in Wolfram syndrome patients was found. In flash electroretinography, scotopic and photopic responses appeared in normal morphology and value. Diabetic retinopathy was not observed in the diabetes mellitus patients.

  1. Transcranial magnetic stimulation in patients with cerebellar stroke.

    PubMed

    Cruz-Martínez, A; Arpa, J

    1997-01-01

    Conduction time of the central motor pathways (CMCT) by transcranial magnetic stimulation (TMS) was performed within the first two weeks in 7 patients with isolated hemicerebellar lesions after stroke. Cerebellar infarcts were small (< 2 cm in diameter) in 5 patients and no brainstem structure was involved in CT studies. The threshold (3 cases) and CMCT (4 cases) were abnormal or asymmetric by stimulation of the motor cortex contralateral to the impaired hemicerebellum. The follow-up study in 2 patients revealed electrophysiological improvement closely related to clinical cerebellar recovery rate. CMCT was significantly longer by cortex stimulation contralateral to the impaired hemicerebellum than by ipsilateral stimulation. Prolonged CMCT was significantly correlated with the rated severity of cerebellar signs. Increased threshold may be due to depressed facilitating action of the deep cerebellar nuclei on contralateral motor cortex. Abnormal CMCT might result in reduced size and increased dispersion of the efferent volleys. Recovery of electrophysiological results could represent in part true potentially reversible functional deficit. Whichever the pathophysiological mechanisms involved, our results demonstrate that the cerebellum dysfunction plays a role in the abnormalities of CMCT elicited by TMS.

  2. Caytaxin deficiency disrupts signaling pathways in cerebellar cortex.

    PubMed

    Xiao, J; Gong, S; Ledoux, M S

    2007-01-19

    The genetically dystonic (dt) rat, an autosomal recessive model of generalized dystonia, harbors an insertional mutation in Atcay. As a result, dt rats are deficient in Atcay transcript and the neuronally-restricted protein caytaxin. Previous electrophysiological and biochemical studies have defined olivocerebellar pathways, particularly the climbing fiber projection to Purkinje cells, as sites of significant functional abnormality in dt rats. In normal rats, Atcay transcript is abundantly expressed in the granular and Purkinje cell layers of cerebellar cortex. To better understand the consequences of caytaxin deficiency in cerebellar cortex, differential gene expression was examined in dt rats and their normal littermates. Data from oligonucleotide microarrays and quantitative real-time reverse transcriptase-PCR (QRT-PCR) identified phosphatidylinositol signaling pathways, calcium homeostasis, and extracellular matrix interactions as domains of cellular dysfunction in dt rats. In dt rats, genes encoding the corticotropin-releasing hormone receptor 1 (CRH-R1, Crhr1) and plasma membrane calcium-dependent ATPase 4 (PMCA4, Atp2b4) showed the greatest up-regulation with QRT-PCR. Immunocytochemical experiments demonstrated that CRH-R1, CRH, and PMCA4 were up-regulated in cerebellar cortex of mutant rats. Along with previous electrophysiological and pharmacological studies, our data indicate that caytaxin plays a critical role in the molecular response of Purkinje cells to climbing fiber input. Caytaxin may also contribute to maturational events in cerebellar cortex.

  3. rqh1+, a fission yeast gene related to the Bloom's and Werner's syndrome genes, is required for reversible S phase arrest.

    PubMed Central

    Stewart, E; Chapman, C R; Al-Khodairy, F; Carr, A M; Enoch, T

    1997-01-01

    In eukaryotic cells, S phase can be reversibly arrested by drugs that inhibit DNA synthesis or DNA damage. Here we show that recovery from such treatments is under genetic control and is defective in fission yeast rqh1 mutants. rqh1+, previously known as hus2+, encodes a putative DNA helicase related to the Escherichia coli RecQ helicase, with particular homology to the gene products of the human BLM and WRN genes and the Saccharomyces cerevisiae SGS1 gene. BLM and WRN are mutated in patients with Bloom's syndrome and Werner's syndrome respectively. Both syndromes are associated with genomic instability and cancer susceptibility. We show that, like BLM and SGS1, rqh1+ is required to prevent recombination and that in fission yeast suppression of inappropriate recombination is essential for reversible S phase arrest. PMID:9184215

  4. Cerebellar mutism in children: report of six cases and potential mechanisms.

    PubMed

    Koh, S; Turkel, S B; Baram, T Z

    1997-04-01

    Cerebellar mutism is a rare finding associated with resection of posterior fossa tumors or cerebellar hemorrhages. We reviewed the medical records of six children, aged 6 to 12 years, who developed cerebellar mutism after resection of a posterior fossa mass or as a result of posterior fossa trauma. From 1989 to 1994, 210 children underwent posterior fossa resection at our institution, and four developed mutism (an incidence of 1.6%). All four patients had primitive neuroectodermal tumors. The fifth patient experienced trauma, and another patient had an arteriovenous malformation (AVM). In four children, hydrocephalus developed as a result of their tumor or AVM. Four developed cerebellar mutism 24 to 48 hours after surgery or trauma, and one developed cerebellar mutism 5 days after surgery, coincident with hydrocephalus. In one, mutism occurred after a second resection was performed for a recurrence of his posterior fossa tumor. Cerebellar mutism lasted 10 days in one patient and 2 to 8 weeks in the other four. Dysarthria was apparent in four patients during the recovery phase. We suggest trauma to the dentate nucleus and/or its outflow tract, the superior cerebellar peduncle, as a cause of reversible mutism. Because posterior fossa tumors are common in children, mutism should be recognized as an important side effect of surgery.

  5. Alcohol Withdrawal and Cerebellar Mitochondria.

    PubMed

    Jung, Marianna E

    2015-08-01

    Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new

  6. A case of midbrain infarction with acute bilateral cerebellar ataxia visualized by diffusion tensor imaging.

    PubMed

    Maya, Yuka; Kawabori, Masahito; Oura, Daisuke; Niiya, Yoshimasa; Iwasaki, Motoyuki; Mabuchi, Shoji

    2016-08-31

    An 85-year-old woman with hypertension was admitted with a sudden onset of gait disturbance and dysarthria. On admission, the patient showed severe bilateral cerebellar ataxia with moderate right medial longitudinal fasciculus (MLF) syndrome. Magnetic resonance (MR) imaging showed an acute infarction in the lower and medial part of midbrain. Diffusion tensor imaging (DTI) started from both cerebellar peduncles revealed that the lesion of the acute infarction matched the decussation of superior cerebellar peduncle where crossing of tract was seen and a part of its tract was interrupted at the site. Interruption of the cerebellum red nuclear path at the medial part of midbrain was considered to be the reason for bilateral cerebellar ataxia and visualization of cerebellum red nuclear path by DTI can give better understanding of the neurological symptom.

  7. Decreased cerebellar blood flow in postinfectious acute cerebellar ataxia

    PubMed Central

    Nagamitsu, S.; Matsuishi, T.; Ishibashi, M.; Yamashita, Y.; Nishimi, T.; Ichikawa, K.; Yamanishi, K.; Kato, H.

    1999-01-01

    OBJECTIVE—The aim of the present study was to evaluate the regional cerebral blood flow (rCBF) in patients with postinfectious acute cerebellar ataxia using single photon emission computed tomography (SPECT).
METHODS—Five children with postinfectious acute cerebellar ataxia and five control subjects were examined. The distribution of rCBF was measured by SPECT imaging after intravenous administration of 123I-IMP (111 MBq). The rCBF ratio—defined as the ratio of rCBF in the region of interest (ROI) to that in the occipital cortex—was calculated for each cortical and subcortical ROI. The mean rCBF ratio of each region was then compared between the ataxic and control subjects. These patients and all control subjects were also evaluated using MRI.
RESULTS—The rCBF ratio was significantly lower in the cerebellum of the ataxic patients than in the cerebellum of the control subjects (p<0.05). No abnormal cerebellar morphology and no abnormal signal intensities were found on MRI.
CONCLUSION—123I-IMP SPECT clearly demonstrated the decreased rCBF in the cerebellum of all patients with postinfectious acute cerebellar ataxia.

 PMID:10369834

  8. Structural characterization of reverse transcriptase and endonuclease polypeptides of the acquired immunodeficiency syndrome retrovirus.

    PubMed Central

    Lightfoote, M M; Coligan, J E; Folks, T M; Fauci, A S; Martin, M A; Venkatesan, S

    1986-01-01

    Automated N-terminal microsequencing of immune affinity-purified acquired immunodeficiency syndrome retrovirus polypeptides from infected cells was used to locate the N termini of 64-, 51-, and 34-kilodalton (kDa) polypeptides within the pol open reading frame (ORF) of the proviral DNA. The 64- and 51-kDa proteins had identical N termini (Pro-Ile-Ser-Pro-IIe-Glu-Thr-Val-) positioned 156 residues from the beginning of the pol ORF. The N terminus of the 34-kDa pol gene product, Phe-Leu-Asp-Gly-Ile-Asp-Lys-, mapped 716 residues into the pol ORF. These polypeptides were absent in an RT-negative, CD4-negative, persistently infected cell line (8E5) carrying a single defective copy of a constitutively expressed, integrated proviral DNA. Images PMID:2430111

  9. Posterior leukoencephalopathy syndrome as a cause of reversible blindness during pregnancy.

    PubMed

    Onderoglu, Lutfu S; Dursun, Polat; Gultekin, Murat; Celik, Nilufer Y

    2007-08-01

    Cortical blindness is a rare and dramatic complication of pre-eclampsia. The precise nature of the pathogenesis of this condition has not previously been understood. Three preeclamptic patients with unremarkable previous medical history presented with acute blindness between the 28th and 33rd weeks of pregnancy. They were all diagnosed as posterior leukoencephalopathy syndrome (PLES). In all these patients, MRI study revealed the typical feature of gray-white matter edema localized to the temporo-parieto-occipital areas. Vision and MRI findings were restored in all patients after delivery. Although PLES has been described as a puerperal clinicoradiologic entity, it may be seen in preeclamptic-eclamptic patients during the pregnancy. Therefore neuro-imaging studies should be carried out in pregnant patients with visual disturbances in order to exclude PLES. Prompt diagnosis, immediate control of blood pressure, and elimination of possible causes resolves clinical and imaging findings.

  10. Reversible Dilated Cardiomyopathy Caused by a High Burden of Ventricular Arrhythmias in Andersen-Tawil Syndrome.

    PubMed

    Rezazadeh, Saman; Guo, Jiqing; Duff, Henry J; Ferrier, Raechel A; Gerull, Brenda

    2016-12-01

    Andersen-Tawil syndrome (ATS) is caused by mutations in KCNJ2 (Kir2.1). It remains unclear whether dilated cardiomyopathy (DCM) is a primary feature of ATS. We studied a proband with typical physical features of ATS plus DCM and moderate to severe left ventricular dysfunction (left ventricular ejection fraction = 30.5%). Genetic screening revealed a novel mutation in Kir2.1 (c.665T>C, p.L222S). Functional studies showed that this mutation reduced ionic currents in a dominant-negative manner. Suppression of ventricular arrhythmias with bisoprolol led to normalization of left ventricular size and function. We conclude that DCM is likely a secondary phenotype in ATS and is caused by high ventricular arrhythmia burden.

  11. [The neuroscientific work of Justo Gonzalo (1910-1986): the center syndrome and reversal metamorphopsia].

    PubMed

    Arias, M; Gonzalo, I

    2004-10-01

    The Spanish neuroscientist Justo Gonzalo Rodriguez-Leal (Barcelona 1910, Madrid 1986) carried out different studies on cerebral functions, highlighting those made in patients with encephalic injuries suffered during the Spanish civil war. His book "Investigaciones sobre la nueva dinámica cerebral. La actividad cerebral en función de las condiciones de excitabilidad nerviosa", published in two volumes (the first one in 1945 and the second one five years later), gathers some of his fundamental contributions, among which the so-called central syndrome stands out. A dominant parietal lesion (central) equidistant from the visual, sensorial and auditory projection areas can lead to diverse perceptive dysfunctions, among them inversions in visual, tactile and acoustic perception. As the lesion becomes more peripheral, the resulting defect will be more unisensorial and crossed, while when it approaches the central region, the disorders will be bilateral and polysensorial. Justo Gonzalo explained all these phenomena later by a gradient system.

  12. Enhanced antisaccade abilities in children with Tourette syndrome: the Gap-effect Reversal

    PubMed Central

    Tajik-Parvinchi, Diana J.; Sandor, Paul

    2013-01-01

    Tourette Syndrome (TS) is a childhood onset disorder of motor and vocal tics. The neural networks underlying TS overlap with those of saccade eye movements. Thus, deviations on saccadic tasks can provide important information about psychopathology of TS. Tourette syndrome often coexists with Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD). Hence, we manipulated various components of a saccade task to measure its effects on saccades of children with TS-only, TS+ADHD, TS+ADHD+OCD and healthy controls. Children looked toward (prosaccade) or in the opposite direction (antisaccade) of a peripheral target as soon as it appeared. The prosaccade and antisaccade tasks were presented in three conditions. In the Gap200 condition, the fixation dot disappeared 200 ms prior to the appearance of the peripheral target, In the Gap800 condition, the fixation dot disappeared 800 ms prior to the appearance of the peripheral target and in Overlap200 the fixation dot disappeared 200 ms after the appearance of the peripheral target. Fixation-offset manipulations had different effects on each group's antisaccades. The TS+ADHD+OCD group's antisaccade latencies and error rates remained relatively unchanged in the three conditions and displayed a pattern of eye movements that can be interpreted as enhanced. Alternatively, the TS+ADHD group displayed an overall pattern of longer saccadic latencies. Findings corroborate the hypothesis that the combination of tic disorder and ADHD results in unique behavioral profiles. It is plausible that a subgroup of children with TS develop an adaptive ability to control their tics which generalizes to enhanced volitional control of saccadic behavior as well. Supporting evidence and other findings are discussed. PMID:24312038

  13. 'Luxury perfusion syndrome' in a patient with reversible ischemic neurological deficits.

    PubMed

    Banzo, J; Morales, F; Abós, M D; Pascual, L F; Prats, E; Teijeiro, J

    1983-01-01

    A 28-year-old man was admitted to the hospital with difficulty in speech and motor weakness of the right arm of sudden onset. Twelve years previously a grade I oligodendroglioma had been removed. The CT scan showed a low density area without enhancement in the left frontal region that appeared to communicate with the left lateral ventricle. An increased flow through the left middle cerebral-artery and a focal avascular area in the left hemisphere was noted during a dynamic study by angioscintigraphy. A radionuclide cerebral control study showed reduced flow through the left middle cerebral artery. The patient was discharged 25 days after admission with the diagnosis of (1) reversible ischemic neurological deficits associated a hyperperfusion and (2) porencephaly.

  14. Orthostatic tremor: a cerebellar pathology?

    PubMed

    Gallea, Cécile; Popa, Traian; García-Lorenzo, Daniel; Valabregue, Romain; Legrand, André-Pierre; Apartis, Emmanuelle; Marais, Lea; Degos, Bertrand; Hubsch, Cecile; Fernández-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Lehéricy, Stéphane; Meunier, Sabine; Vidailhet, Marie

    2016-08-01

    SEE MUTHURAMAN ET AL DOI101093/AWW164 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Primary orthostatic tremor is characterized by high frequency tremor affecting the legs and trunk during the standing position. Cerebellar defects were suggested in orthostatic tremor without direct evidence. We aimed to characterize the anatomo-functional defects of the cerebellar motor pathways in orthostatic tremor. We used multimodal neuroimaging to compare 17 patients with orthostatic tremor and 17 age- and gender-matched healthy volunteers. Nine of the patients with orthostatic tremor underwent repetitive transcranial stimulation applied over the cerebellum during five consecutive days. We quantified the duration of standing position and tremor severity through electromyographic recordings. Compared to healthy volunteers, grey matter volume in patients with orthostatic tremor was (i) increased in the cerebellar vermis and correlated positively with the duration of the standing position; and (ii) increased in the supplementary motor area and decreased in the lateral cerebellum, which both correlated with the disease duration. Functional connectivity between the lateral cerebellum and the supplementary motor area was abnormally increased in patients with orthostatic tremor, and correlated positively with tremor severity. After repetitive transcranial stimulation, tremor severity and functional connectivity between the lateral cerebellum and the supplementary motor area were reduced. We provide an explanation for orthostatic tremor pathophysiology, and demonstrate the functional relevance of cerebello-thalamo-cortical connections in tremor related to cerebellar defects.

  15. Linking oscillations in cerebellar circuits

    PubMed Central

    Courtemanche, Richard; Robinson, Jennifer C.; Aponte, Daniel I.

    2013-01-01

    In many neuroscience fields, the study of local and global rhythmicity has been receiving increasing attention. These network influences could directly impact on how neuronal groups interact together, organizing for different contexts. The cerebellar cortex harbors a variety of such local circuit rhythms, from the rhythms in the cerebellar cortex per se, or those dictated from important afferents. We present here certain cerebellar oscillatory phenomena that have been recorded in rodents and primates. Those take place in a range of frequencies: from the more known oscillations in the 4–25 Hz band, such as the olivocerebellar oscillatory activity and the granule cell layer oscillations, to the more recently reported slow (<1 Hz oscillations), and the fast (>150 Hz) activity in the Purkinje cell layer. Many of these oscillations appear spontaneously in the circuits, and are modulated by behavioral imperatives. We review here how those oscillations are recorded, some of their modulatory mechanisms, and also identify some of the cerebellar nodes where they could interact. A particular emphasis has been placed on how these oscillations could be modulated by movement and certain neuropathological manifestations. Many of those oscillations could have a definite impact on the way information is processed in the cerebellum and how it interacts with other structures in a variety of contexts. PMID:23908606

  16. Speech Prosody in Cerebellar Ataxia

    ERIC Educational Resources Information Center

    Casper, Maureen A.; Raphael, Lawrence J.; Harris, Katherine S.; Geibel, Jennifer M.

    2007-01-01

    Persons with cerebellar ataxia exhibit changes in physical coordination and speech and voice production. Previously, these alterations of speech and voice production were described primarily via perceptual coordinates. In this study, the spatial-temporal properties of syllable production were examined in 12 speakers, six of whom were healthy…

  17. Modulation of RhoGTPases improves the behavioral phenotype and reverses astrocytic deficits in a mouse model of Rett syndrome.

    PubMed

    De Filippis, Bianca; Fabbri, Alessia; Simone, Daiana; Canese, Rossella; Ricceri, Laura; Malchiodi-Albedi, Fiorella; Laviola, Giovanni; Fiorentini, Carla

    2012-04-01

    RhoGTPases are crucial molecules in neuronal plasticity and cognition, as confirmed by their role in non-syndromic mental retardation. Activation of brain RhoGTPases by the bacterial cytotoxic necrotizing factor 1 (CNF1) reshapes the actin cytoskeleton and enhances neurotransmission and synaptic plasticity in mouse brains. We evaluated the effects of a single CNF1 intracerebroventricular inoculation in a mouse model of Rett syndrome (RTT), a rare neurodevelopmental disorder and a genetic cause of mental retardation, for which no effective therapy is available. Fully symptomatic MeCP2-308 male mice were evaluated in a battery of tests specifically tailored to detect RTT-related impairments. At the end of behavioral testing, brain sections were immunohistochemically characterized. Magnetic resonance imaging and spectroscopy (MRS) were also applied to assess morphological and metabolic brain changes. The CNF1 administration markedly improved the behavioral phenotype of MeCP2-308 mice. CNF1 also dramatically reversed the evident signs of atrophy in astrocytes of mutant mice and restored wt-like levels of this cell population. A partial rescue of the overexpression of IL-6 cytokine was also observed in RTT brains. CNF1-induced brain metabolic changes detected by MRS analysis involved markers of glial integrity and bioenergetics, and point to improved mitochondria functionality in CNF1-treated mice. These results clearly indicate that modulation of brain RhoGTPases by CNF1 may constitute a totally innovative therapeutic approach for RTT and, possibly, for other disorders associated with mental retardation.

  18. Reversible acquired epileptic frontal syndrome and CSWS suppression in a child with congenital hemiparesis treated by hemispherotomy.

    PubMed

    Kallay, Christine; Mayor-Dubois, Claire; Maeder-Ingvar, Malin; Seeck, Margritta; Debatisse, Damien; Deonna, Thierry; Roulet-Perez, Eliane

    2009-09-01

    A boy with a right congenital hemiparesis due to a left pre-natal middle cerebral artery infarct developed focal epilepsy at 33 months and then an insidious and subsequently more rapid, massive cognitive and behavioural regression with a frontal syndrome between the ages of 4 and 5 years with continuous spike-waves during sleep (CSWS) on the EEG. Both the epilepsy and the CSWS were immediately suppressed by hemispherotomy at the age of 5 years and 4 months. A behavioural-cognitive follow-up prior to hemispherotomy, an per-operative EEG and corticography and serial post-operative neuropsychological assessments were performed until the age of 11 years. The spread of the epileptic activity to the "healthy" frontal region was the cause of the reversible frontal syndrome. A later gradual long-term but incomplete cognitive recovery, with moderate mental disability was documented. This outcome is probably explained by another facet of the epilepsy, namely the structural effects of prolonged epileptic discharges in rapidly developing cerebral networks which are, at the same time undergoing the reorganization imposed by a unilateral early hemispheric lesion. Group studies on the outcome of children before and after hemispherectomy using only single IQ measures, pre- and post-operatively, may miss particular epileptic cognitive dysfunctions as they are likely to be different from case to case. Such detailed and rarely available complementary clinical and EEG data obtained in a single case at different time periods in relation to the epilepsy, including per-operative electrophysiological findings, may help to understand the different cognitive deficits and recovery profiles and the limits of full cognitive recovery.

  19. Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells.

    PubMed

    Cao, Kan; Graziotto, John J; Blair, Cecilia D; Mazzulli, Joseph R; Erdos, Michael R; Krainc, Dimitri; Collins, Francis S

    2011-06-29

    Hutchinson-Gilford progeria syndrome (HGPS) is a lethal genetic disorder characterized by premature aging. HGPS is most commonly caused by a de novo single-nucleotide substitution in the lamin A/C gene (LMNA) that partially activates a cryptic splice donor site in exon 11, producing an abnormal lamin A protein termed progerin. Accumulation of progerin in dividing cells adversely affects the integrity of the nuclear scaffold and leads to nuclear blebbing in cultured cells. Progerin is also produced in normal cells, increasing in abundance as senescence approaches. Here, we report the effect of rapamycin, a macrolide antibiotic that has been implicated in slowing cellular and organismal aging, on the cellular phenotypes of HGPS fibroblasts. Treatment with rapamycin abolished nuclear blebbing, delayed the onset of cellular senescence, and enhanced the degradation of progerin in HGPS cells. Rapamycin also decreased the formation of insoluble progerin aggregates and induced clearance through autophagic mechanisms in normal fibroblasts. Our findings suggest an additional mechanism for the beneficial effects of rapamycin on longevity and encourage the hypothesis that rapamycin treatment could provide clinical benefit for children with HGPS.

  20. Motor training compensates for cerebellar dysfunctions caused by oligodendrocyte ablation

    PubMed Central

    Collin, Ludovic; Usiello, Alessandro; Erbs, Eric; Mathis, Carole; Borrelli, Emiliana

    2004-01-01

    The role played by oligodendrocytes (OLs), the myelinating cells of the CNS, during brain development has not been fully explored. We have addressed this question by inducing a temporal and reversible ablation of OLs on postnatal CNS development. OL ablation in newborn mice leads to a profound alteration in the structure of the cerebellar cortex, which can be progressively rescued by newly generated cells, leading to a delayed myelination. Nevertheless, the temporal shift of the OL proliferation and myelinating program cannot completely compensate for developmental defects, resulting in impaired motor functions in the adult. Strikingly, we show that, despite these abnormalities, epigenetic factors, such as motor training, are able to fully rescue cerebellar-directed motor skills. PMID:14694200

  1. Sclerostin inhibition reverses skeletal fragility in an Lrp5-deficient mouse model of OPPG syndrome.

    PubMed

    Kedlaya, Rajendra; Veera, Shreya; Horan, Daniel J; Moss, Rachel E; Ayturk, Ugur M; Jacobsen, Christina M; Bowen, Margot E; Paszty, Chris; Warman, Matthew L; Robling, Alexander G

    2013-11-13

    Osteoporosis pseudoglioma syndrome (OPPG) is a rare genetic disease that produces debilitating effects in the skeleton. OPPG is caused by mutations in LRP5, a WNT co-receptor that mediates osteoblast activity. WNT signaling through LRP5, and also through the closely related receptor LRP6, is inhibited by the protein sclerostin (SOST). It is unclear whether OPPG patients might benefit from the anabolic action of sclerostin neutralization therapy (an approach currently being pursued in clinical trials for postmenopausal osteoporosis) in light of their LRP5 deficiency and consequent osteoblast impairment. To assess whether loss of sclerostin is anabolic in OPPG, we measured bone properties in a mouse model of OPPG (Lrp5(-/-)), a mouse model of sclerosteosis (Sost(-/-)), and in mice with both genes knocked out (Lrp5(-/-);Sost(-/-)). Lrp5(-/-);Sost(-/-) mice have larger, denser, and stronger bones than do Lrp5(-/-) mice, indicating that SOST deficiency can improve bone properties via pathways that do not require LRP5. Next, we determined whether the anabolic effects of sclerostin depletion in Lrp5(-/-) mice are retained in adult mice by treating 17-week-old Lrp5(-/-) mice with a sclerostin antibody for 3 weeks. Lrp5(+/+) and Lrp5(-/-) mice each exhibited osteoanabolic responses to antibody therapy, as indicated by increased bone mineral density, content, and formation rates. Collectively, our data show that inhibiting sclerostin can improve bone mass whether LRP5 is present or not. In the absence of LRP5, the anabolic effects of SOST depletion can occur via other receptors (such as LRP4/6). Regardless of the mechanism, our results suggest that humans with OPPG might benefit from sclerostin neutralization therapies.

  2. Canakinumab reverses overexpression of inflammatory response genes in tumour necrosis factor receptor-associated periodic syndrome

    PubMed Central

    Torene, Rebecca; Nirmala, Nanguneri; Obici, Laura; Cattalini, Marco; Tormey, Vincent; Caorsi, Roberta; Starck-Schwertz, Sandrine; Letzkus, Martin; Hartmann, Nicole; Abrams, Ken; Lachmann, Helen; Gattorno, Marco

    2017-01-01

    Objective To explore whether gene expression profiling can identify a molecular mechanism for the clinical benefit of canakinumab treatment in patents with tumour necrosis factor receptor-associated periodic syndrome (TRAPS). Methods Blood samples were collected from 20 patients with active TRAPS who received canakinumab 150 mg every 4 weeks for 4 months in an open-label proof-of-concept phase II study, and from 20 aged-matched healthy volunteers. Gene expression levels were evaluated in whole blood samples by microarray analysis for arrays passing quality control checks. Results Patients with TRAPS exhibited a gene expression signature in blood that differed from that in healthy volunteers. Upon treatment with canakinumab, many genes relevant to disease pathogenesis moved towards levels seen in the healthy volunteers. Canakinumab downregulated the TRAPS-causing gene (TNF super family receptor 1A (TNFRSF1A)), the drug-target gene (interleukin (IL)-1B) and other inflammation-related genes (eg, MAPK14). In addition, several inflammation-related pathways were evident among the differentially expressed genes. Canakinumab treatment reduced neutrophil counts, but the observed expression differences remained after correction for this. Conclusions These gene expression data support a model in which canakinumab produces clinical benefit in TRAPS by increasing neutrophil apoptosis and reducing pro-inflammatory signals resulting from the inhibition of IL-1β. Notably, treatment normalised the overexpression of TNFRSF1A, suggesting that canakinumab has a direct impact on the main pathogenic mechanism in TRAPS. Trial registration number NCT01242813. PMID:27474763

  3. Gravity-dependent nystagmus and inner-ear dysfunction suggest anterior and posterior inferior cerebellar artery infarct.

    PubMed

    Shaikh, Aasef G; Miller, Benjamin R; Sundararajan, Sophia; Katirji, Bashar

    2014-04-01

    Cerebellar lesions may present with gravity-dependent nystagmus, where the direction and velocity of the drifts change with alterations in head position. Two patients had acute onset of hearing loss, vertigo, oscillopsia, nausea, and vomiting. Examination revealed gravity-dependent nystagmus, unilateral hypoactive vestibulo-ocular reflex (VOR), and hearing loss ipsilateral to the VOR hypofunction. Traditionally, the hypoactive VOR and hearing loss suggest inner-ear dysfunction. Vertigo, nausea, vomiting, and nystagmus may suggest peripheral or central vestibulopathy. The gravity-dependent modulation of nystagmus, however, localizes to the posterior cerebellar vermis. Magnetic resonance imaging in our patients revealed acute cerebellar infarct affecting posterior cerebellar vermis, in the vascular distribution of the posterior inferior cerebellar artery (PICA). This lesion explains the gravity-dependent nystagmus, nausea, and vomiting. Acute onset of unilateral hearing loss and VOR hypofunction could be the manifestation of inner-ear ischemic injury secondary to the anterior inferior cerebellar artery (AICA) compromise. In cases of combined AICA and PICA infarction, the symptoms of peripheral vestibulopathy might masquerade the central vestibular syndrome and harbor a cerebellar stroke. However, the gravity-dependent nystagmus allows prompt identification of acute cerebellar infarct.

  4. Autosomal dominant cerebellar ataxia deafness and narcolepsy.

    PubMed

    Melberg, A; Hetta, J; Dahl, N; Nennesmo, I; Bengtsson, M; Wibom, R; Grant, C; Gustavson, K H; Lundberg, P O

    1995-12-01

    A new autosomal dominant syndrome in a Swedish pedigree is described. Five patients were affected with cerebellar ataxia and sensorineural deafness. Four of these patients had symptoms of narcolepsy. Optic atrophy, other neurological abnormalities and psychiatric symptoms developed with increasing disease duration. Three patients had non-neurological disease in addition, including diabetes mellitus in two and hypertrophic cardiomyopathy in one. Autopsy with neuropathological examination was performed in one case. Molecular studies focused on the short arm of chromosome 6, including the HLA DR2 locus associated with narcolepsy and the (CAG)n repeat at the spinocerebellar ataxia type 1 (SCA1) locus. Biochemical investigation of muscle biopsy of one case indicated mitochondrial dysfunction with selective decrease in ATP production for substrates that normally give the highest rates. The activity of glutamate dehydrogenase was reduced, indicating a low mitochondrial density. We postulate an autosomal dominant genetic factor responsible for this syndrome. Linkage was excluded to HLA DR2, and a normal sized SCA1 repeat was observed. We conclude that a locus predisposing to ataxia, deafness and narcolepsy exists outside this region of chromosome 6.

  5. Deletion of the telomerase reverse transcriptase gene and haploinsufficiency of telomere maintenance in Cri du chat syndrome.

    PubMed

    Zhang, Anju; Zheng, Chengyun; Hou, Mi; Lindvall, Charlotta; Li, Ke-Jun; Erlandsson, Fredrik; Björkholm, Magnus; Gruber, Astrid; Blennow, Elisabeth; Xu, Dawei

    2003-04-01

    Cri du chat syndrome (CdCS) results from loss of the distal portion of chromosome 5p, where the telomerase reverse transcriptase (hTERT) gene is localized (5p15.33). hTERT is the rate-limiting component for telomerase activity that is essential for telomere-length maintenance and sustained cell proliferation. Here, we show that a concomitant deletion of the hTERT allele occurs in all 10 patients with CdCS whom we examined. Induction of hTERT mRNA in proliferating lymphocytes derived from five of seven patients was lower than that in unaffected control individuals (P<.05). The patient lymphocytes exhibited shorter telomeres than age-matched unaffected individuals (P<.0001). A reduction in replicative life span and a high rate of chromosome fusions were observed in cultured patient fibroblasts. Reconstitution of telomerase activity by ectopic expression of hTERT extended the telomere length, increased the population doublings, and prevented the end-to-end fusion of chromosomes. We conclude that hTERT is limiting and haploinsufficient for telomere maintenance in humans in vivo. Accordingly, the hTERT deletion may be one genetic element contributing to the phenotypic changes in CdCS.

  6. Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency

    PubMed Central

    Fuchs, Sebastian; Rensing-Ehl, Anne; Pannicke, Ulrich; Lorenz, Myriam R.; Fisch, Paul; Jeelall, Yogesh; Rohr, Jan; Speckmann, Carsten; Vraetz, Thomas; Farmand, Susan; Schmitt-Graeff, Annette; Krüger, Marcus; Strahm, Brigitte; Henneke, Philipp; Enders, Anselm; Horikawa, Keisuke; Goodnow, Christopher; Schwarz, Klaus

    2015-01-01

    Omenn syndrome (OS) is a severe immunodeficiency associated with erythroderma, lymphoproliferation, elevated IgE, and hyperactive oligoclonal T cells. A restricted T-cell repertoire caused by defective thymic T-cell development and selection, lymphopenia with homeostatic proliferation, and lack of regulatory T cells are considered key factors in OS pathogenesis. We report 2 siblings presenting with cytomegalovirus (CMV) and Pneumocystis jirovecii infections and recurrent sepsis; one developed all clinical features of OS. Both carried homozygous germline mutations in CARD11 (p.Cys150*), impairing NF-κB signaling and IL-2 production. A somatic second-site mutation reverting the stop codon to a missense mutation (p.Cys150Leu) was detected in tissue-infiltrating T cells of the OS patient. Expression of p.Cys150Leu in CARD11-deficient T cells largely reconstituted NF-κB signaling. The reversion likely occurred in a prethymic T-cell precursor, leading to a chimeric T-cell repertoire. We speculate that in our patient the functional advantage of the revertant T cells in the context of persistent CMV infection, combined with lack of regulatory T cells, may have been sufficient to favor OS. This first observation of OS in a patient with a T-cell activation defect suggests that severely defective T-cell development or homeostatic proliferation in a lymphopenic environment are not required for this severe immunopathology. PMID:26289640

  7. A case of posterior reversible encephalopathy syndrome associated with gilenya(®) (fingolimod) treatment for multiple sclerosis.

    PubMed

    Lindå, Hans; von Heijne, Anders

    2015-01-01

    We describe posterior reversible encephalopathy syndrome (PRES) in a woman with multiple sclerosis treated with Gilenya(®) (Fingolimod). The first symptoms appeared after 21 months of fingolimod treatment. She experienced headache, altered mental status, cognitive deficits, seizures, and visual disturbances. Not at any time during the course of the disease could any signs of infection or rheumatic disorder be detected. Test for anti-neuronal antibodies was also negative. Her blood pressure was normal. MRI showed widespread cortical and subcortical changes with some mass-effect in the temporo-occipital-parietal lobes in the left hemisphere. Contrast enhancement was seen in the leptomeninges and, in addition, there were no areas with restricted diffusion and no signs of hemorrhage. Her condition deteriorated until fingolimod was discontinued. Slowly her condition improved and after 8 months, the only symptoms that remained were two small, non-corresponding, right inferior scotomas. We believe that all symptoms, the clinical course, and the MRI findings in this case can all be explained by considering PRES, a probably rare, but serious, side effect of fingolimod treatment.

  8. Reverse transcription recombinase polymerase amplification assay for the rapid detection of type 2 porcine reproductive and respiratory syndrome virus.

    PubMed

    Wang, Jian-Chang; Yuan, Wan-Zhe; Han, Qing-An; Wang, Jin-Feng; Liu, Li-Bing

    2017-05-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogens in pigs, and has tremendous negative economic impact on the swine industry worldwide. PRRSV is classified into the two distinct genotypes: type 1 and type 2, and most of the described PRRSV isolates in China are type 2. Rapid and sensitive detection of PRRSV is of great importance for the disease control and regional eradication programs. Recombinase polymerase amplification (RPA) has emerged as a novel isothermal amplification technology for the molecular diagnosis of infectious diseases. In this study, a fluorescence reverse transcription RPA (RT-RPA) assay was developed to detect the type 2 PRRSV using primers and exo probe specific for the viral nucleocapsid gene. The reaction was performed at 40°C within 20min. The RT-RPA assay could detect both the classical (C-PRRSV) and highly pathogenic PRRSV (HP-PRRSV), but there was no cross-reaction to other pathogens. Using the in vitro transcribed PRRSV RNA as template, the analytical sensitivity of RT-RPA was 690 copies. The assay performance was evaluated by testing 60 field samples and compared to real-time RT-PCR. The detection rate of RT-RPA was 86.6% (52/60), while the detection rate of real-time RT-PCR was 83.3% (50/60). This simple, rapid and reliable method could be potentially applied for rapid detection of PRRSV in point-of-care and rural areas.

  9. Delayed onset of posterior reversible encephalopathy syndrome in a case of scleroderma renal crisis with maintenance hemodialysis

    PubMed Central

    Chen, Ching-Yang; Hung, Shin-Yuan; Lee, Yi-Jer; Lin, Yi-Chan; Pai, Chu-Cheng

    2016-01-01

    Abstract Introduction: In some cases, scleroderma renal crisis (SRC) is not easily distinguishable from other thrombotic microangiopathies such as thrombotic thrombocytopenic purpura, especially when the presentation includes neurological or extra-renal manifestations. Here, we present a case of SRC who developed a rare neurotoxic complication, posterior reversible encephalopathy syndrome (PRES). A 36-year-old man with a history of diffuse cutaneous systemic sclerosis developed SRC and acute-on-chronic renal failure and ultimately required maintenance hemodialysis. Three weeks after starting hemodialysis, the patient presented with confusion and a new-onset seizure disorder. Laboratory examinations revealed thrombocytopenia, a low haptoglobin level, and schizocytes on a blood smear. SRC-related PRES was considered first after PRES was confirmed by brain magnetic resonance imaging. Antihypertensive therapy comprising captopril and amlodipine was administered, and the patient experienced a complete neurological recovery 3 days later without plasma exchange. In all previously reported cases of SRC-associated PRES, PRES developed before hemodialysis. Our report is, therefore, the first to describe a case of onset of SRC-related PRES 3 weeks after the initiation of maintenance hemodialysis. Conclusion: This case demonstrates that microangiopathy and extra-renal manifestations can develop even in SRC patients with end-stage renal disease and that these manifestations can be successfully managed with angiotensin-converting enzyme inhibitors (ACEIs) and aggressive blood pressure control. We recommend continuing ACEI therapy if elevated blood pressure persists after maintenance hemodialysis. PMID:28033278

  10. Habit reversal training and educational group treatments for children with tourette syndrome: A preliminary randomised controlled trial.

    PubMed

    Yates, Rachel; Edwards, Katie; King, John; Luzon, Olga; Evangeli, Michael; Stark, Daniel; McFarlane, Fiona; Heyman, Isobel; İnce, Başak; Kodric, Jana; Murphy, Tara

    2016-05-01

    Quality of life of children with Tourette Syndrome (TS) is impacted greatly by its symptoms and their social consequences. Habit Reversal Training (HRT) is effective but has not, until now, been empirically evaluated in groups. This randomised controlled trial evaluated feasibility and preliminary efficacy of eight HRT group sessions compared to eight Education group sessions. Thirty-three children aged 9-13 years with TS or Chronic Tic Disorder took part. Outcomes evaluated were tic severity and quality of life (QoL). Tic severity improvements were found in both groups. Motor tic severity (Yale Global Tic Severity Scale) showed greatest improvements in the HRT group. Both groups showed a strong tendency toward improvements in patient reported QoL. In conclusion, group-based treatments for TS are feasible and exposure to other children with tics did not increase tic expression. HRT led to greater reductions in tic severity than Education. Implications, such as cost-effectiveness of treatment delivery, are discussed.

  11. A small-molecule inhibitor of SHIP1 reverses age- and diet-associated obesity and metabolic syndrome

    PubMed Central

    Srivastava, Neetu; Iyer, Sonia; Sudan, Raki; Youngs, Christie; Engelman, Robert W.; Howard, Kyle T.; Russo, Christopher M.; Chisholm, John D.; Kerr, William G.

    2016-01-01

    Low-grade chronic inflammation is a key etiological phenomenon responsible for the initiation and perpetuation of obesity and diabetes. Novel therapeutic approaches that can specifically target inflammatory pathways are needed to avert this looming epidemic of metabolic disorders. Genetic and chemical inhibition of SH2-containing inositol 5′ phosphatase 1 (SHIP1) has been associated with systemic expansion of immunoregulatory cells that promote a lean-body state; however, SHIP1 function in immunometabolism has never been assessed. This led us to investigate the role of SHIP1 in metabolic disorders during excess caloric intake in mice. Using a small-molecule inhibitor of SHIP1 (SHIPi), here we show that SHIPi treatment in mice significantly reduces body weight and fat content, improves control of blood glucose and insulin sensitivity, and increases energy expenditure, despite continued consumption of a high-fat diet. Additionally, SHIPi reduces age-associated fat in mice. We found that SHIPi treatment reverses diet-associated obesity by attenuating inflammation in the visceral adipose tissue (VAT). SHIPi treatment increases IL-4–producing eosinophils in VAT and consequently increases both alternatively activated macrophages and myeloid-derived suppressor cells. In addition, SHIPi decreases the number of IFN-γ–producing T cells and NK cells in VAT. Thus, SHIPi represents an approach that permits control of obesity and diet-induced metabolic syndrome without apparent toxicity. PMID:27536730

  12. [Anesthetic Management of a Parturient with Eclampsia, Posterior Reversible Encephalopathy Syndrome and Pulmonary Edema due to Pregnancy-induced Hypertension].

    PubMed

    Aida, Junko; Okutani, Hiroai; Oda, Yutaka; Okutani, Ryu

    2015-08-01

    A 27-year-old woman with mental retardation was admitted to a nearby hospital for an abrupt onset of seizure. Physical examination revealed remarkable hypertension and pregnancy with estimated gestational age of 28th week. Severe pulmonary edema and hypoxia led to a diagnosis of pregnancy-induced hypertension (PIH) accompanied by eclampsia. She was orotracheally intubated because of refractory seizure and hypoxemia, and transferred to our hospital for further treatment. Besides severe hypoxia and hypercapnea, an enhanced lesion was detected in the left posterior cerebrum by brain MRI. No abnormal findings were detected in the fetus, with heart rate of 150 beats x min. She was diagnosed with posterior reversible encephalopathy syndrome (PRES) caused by PIH and emergency cesarean section under general anesthesia was scheduled. A male newborn was delivered with Apgar score of 1/4 (1/5 min), followed by starting continuous infusion of nicardipine for controlling hypertension. Chest X-P on completion of surgery revealed remarkably alleviated pulmonary edema. She received intensive treatment and continued positive pressure ventilation for four days after delivery. She recovered with no neurological deficits and her child was well without any complications.

  13. Reversal of Acute Complex Regional Pain Syndrome Using the Practical Application of Neurodiagnostic Evaluation Process: A Case Study

    PubMed Central

    Anderson, Karen E

    2013-01-01

    In 2005, a patient in my practice developed complex regional pain syndrome type 1 (CRPS 1) after bunion surgery. The condition was properly diagnosed within 4 weeks with a diagnostic technique that I routinely use to diagnose chronic musculoskeletal pain, and it was successfully treated. The tests, which are based on primitive and postural reflexes in infants, were adapted to reflect normal and abnormal motor behaviors in adults after provocation of reflexes of the autonomic nervous system (afferent C fibers in peripheral nerves). Approximately 60 days after my patient’s operation, the tests indicated a positive reflex at the posterior tibial nerve in the operated foot. Surgery to remove an accessory ossicle from the talus adjacent to this nerve resolved the CRPS 1 within 2 weeks. Since CRPS 1 is a dysfunctional state of the autonomic regulatory control of pain, it was postulated that a test based on autonomic nerve function could isolate the source of CRPS 1. The Practical Application of Neurodiagnostic Evaluation process was shown to be diagnostic for the cause of acute CRPS 1 and to allow its reversal. Further evaluation of the test for diagnosis and treatment of CRPS is needed. PMID:24355904

  14. Allometric Analysis Detects Brain Size-Independent Effects of Sex and Sex Chromosome Complement on Human Cerebellar Organization.

    PubMed

    Mankiw, Catherine; Park, Min Tae M; Reardon, P K; Fish, Ari M; Clasen, Liv S; Greenstein, Deanna; Giedd, Jay N; Blumenthal, Jonathan D; Lerch, Jason P; Chakravarty, M Mallar; Raznahan, Armin

    2017-03-17

    The cerebellum is a large hindbrain structure that is increasingly recognized for its contribution to diverse domains of cognitive and affective processing in human health and disease. Although several of these domains are sex-biased, our fundamental understanding of cerebellar sex differences - including their spatial distribution, potential biological determinants, and independence from brain volume variation - lags far behind that for the cerebrum. Here, we harness automated neuroimaging methods for cerebellar morphometrics in 417 individuals to (i) localize normative male-female differences in raw cerebellar volume, (ii) compare these to sex chromosome effects estimated across five rare X-/Y-chromosome aneuploidy (SCA) syndromes, and (iii) clarify brain size-independent effects of sex and SCA on cerebellar anatomy using a generalizable allometric approach which considers scaling relationships between regional cerebellar volume and brain volume in health. Integration of these approaches shows that (i) sex and SCA effects on raw cerebellar volume are large and distributed, but regionally heterogeneous, (ii) human cerebellar volume scales with brain volume in a highly non-linear and regionally heterogeneous fashion that departs from documented patterns of cerebellar scaling in phylogeny, and (iii) cerebellar organization is modified in a brain size-independent manner by sex (relative expansion of total cerebellum, flocculus, and Crus II-lobule VIIIB volumes in males) and SCA (contraction of total cerebellar, lobule IV and Crus I volumes with additional X- or Y-chromosomes; X-specific contraction of Crus II-lobule VIIIB). Our methods and results clarify the shifts in human cerebellar organization that accompany interwoven variations in sex, sex chromosome complement, and brain size.SIGNIFICANCE STATEMENTCerebellar systems are implicated in diverse domains of sex-biased behavior and pathology, but we lack a basic understanding of how sex differences in the human

  15. A Grave Outcome of Posterior Reversible Encephalopathy Syndrome in a Patient Receiving Avastin (Bevacizumab) for Metastatic High-Grade Serous Ovarian Cancer

    PubMed Central

    Elmalik, Hind H.; ElAzzazy, Shereen; Salem, Khaled S.; Bujassoum, Salha

    2015-01-01

    A 45-year-old female developed neurological symptoms and elevated diastolic blood pressure while on bevacizumab (Avastin) and gemcitabine for recurrent carboplatin-resistant high-grade serous ovarian cancer. A brain MRI diagnosed our patient with posterior reversible encephalopathy syndrome. We are discussing her presenting symptoms in this paper as well as the management and the outcome. We emphasize the importance of keeping this rare but very serious complication in all patients receiving bevacizumab. PMID:26351436

  16. Cochlear implantation following cerebellar surgery.

    PubMed

    Saeed, Shahad; Mawman, Deborah; Green, Kevin

    2011-08-01

    Cochlear implantation in patients with known central nervous system conditions can result in wide-ranging outcomes. The aim of this study is to report two cases of cochlear implantation outcomes in patients with acquired cerebellar ataxia following cerebellar surgery. The first is a female implanted with the Nucleus 24 implant in September 2000 and the second is a male implanted with a MED-EL Sonata Flexsoft electro-acoustic stimulation in July 2009. Programming these patients resulted in significant non-auditory stimulation which resulted in less than optimum map fittings. The patients did not gain any open set speech perception benefit although both of them gained an awareness of sound with the device. However, patient 2 elected to become a non-user because of the limited benefit.

  17. 22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.

    PubMed

    Falah, Nadia; Posey, Jennifer E; Thorson, Willa; Benke, Paul; Tekin, Mustafa; Tarshish, Brocha; Lupski, James R; Harel, Tamar

    2017-04-01

    Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH.

  18. The chromatin remodeling factor CHD7 controls cerebellar development by regulating reelin expression

    PubMed Central

    Whittaker, Danielle E.; Riegman, Kimberley L.H.; Kasah, Sahrunizam; Mohan, Conor; Yu, Tian; Sala, Blanca Pijuan; Hebaishi, Husam; Caruso, Angela; Marques, Ana Claudia; Michetti, Caterina; Smachetti, María Eugenia Sanz; Shah, Apar; Sabbioni, Mara; Kulhanci, Omer; Tee, Wee-Wei; Reinberg, Danny; Scattoni, Maria Luisa; McGonnell, Imelda; Wardle, Fiona C.; Fernandes, Cathy

    2017-01-01

    The mechanisms underlying the neurodevelopmental deficits associated with CHARGE syndrome, which include cerebellar hypoplasia, developmental delay, coordination problems, and autistic features, have not been identified. CHARGE syndrome has been associated with mutations in the gene encoding the ATP-dependent chromatin remodeler CHD7. CHD7 is expressed in neural stem and progenitor cells, but its role in neurogenesis during brain development remains unknown. Here we have shown that deletion of Chd7 from cerebellar granule cell progenitors (GCps) results in reduced GCp proliferation, cerebellar hypoplasia, developmental delay, and motor deficits in mice. Genome-wide expression profiling revealed downregulated expression of the gene encoding the glycoprotein reelin (Reln) in Chd7-deficient GCps. Recessive RELN mutations have been associated with severe cerebellar hypoplasia in humans. We found molecular and genetic evidence that reductions in Reln expression contribute to GCp proliferative defects and cerebellar hypoplasia in GCp-specific Chd7 mouse mutants. Finally, we showed that CHD7 is necessary for maintaining an open, accessible chromatin state at the Reln locus. Taken together, this study shows that Reln gene expression is regulated by chromatin remodeling, identifies CHD7 as a previously unrecognized upstream regulator of Reln, and provides direct in vivo evidence that a mammalian CHD protein can control brain development by modulating chromatin accessibility in neuronal progenitors. PMID:28165338

  19. Principal component analysis of cerebellar shape on MRI separates SCA types 2 and 6 into two archetypal modes of degeneration.

    PubMed

    Jung, Brian C; Choi, Soo I; Du, Annie X; Cuzzocreo, Jennifer L; Geng, Zhuo Z; Ying, Howard S; Perlman, Susan L; Toga, Arthur W; Prince, Jerry L; Ying, Sarah H

    2012-12-01

    Although "cerebellar ataxia" is often used in reference to a disease process, presumably there are different underlying pathogenetic mechanisms for different subtypes. Indeed, spinocerebellar ataxia (SCA) types 2 and 6 demonstrate complementary phenotypes, thus predicting a different anatomic pattern of degeneration. Here, we show that an unsupervised classification method, based on principal component analysis (PCA) of cerebellar shape characteristics, can be used to separate SCA2 and SCA6 into two classes, which may represent disease-specific archetypes. Patients with SCA2 (n=11) and SCA6 (n=7) were compared against controls (n=15) using PCA to classify cerebellar anatomic shape characteristics. Within the first three principal components, SCA2 and SCA6 differed from controls and from each other. In a secondary analysis, we studied five additional subjects and found that these patients were consistent with the previously defined archetypal clusters of clinical and anatomical characteristics. Secondary analysis of five subjects with related diagnoses showed that disease groups that were clinically and pathophysiologically similar also shared similar anatomic characteristics. Specifically, Archetype #1 consisted of SCA3 (n=1) and SCA2, suggesting that cerebellar syndromes accompanied by atrophy of the pons may be associated with a characteristic pattern of cerebellar neurodegeneration. In comparison, Archetype #2 was comprised of disease groups with pure cerebellar atrophy (episodic ataxia type 2 (n=1), idiopathic late-onset cerebellar ataxias (n=3), and SCA6). This suggests that cerebellar shape analysis could aid in discriminating between different pathologies. Our findings further suggest that magnetic resonance imaging is a promising imaging biomarker that could aid in the diagnosis and therapeutic management in patients with cerebellar syndromes.

  20. Genetics Home Reference: VLDLR-associated cerebellar hypoplasia

    MedlinePlus

    ... Conditions VLDLR-associated cerebellar hypoplasia VLDLR-associated cerebellar hypoplasia Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description VLDLR -associated cerebellar hypoplasia is an inherited condition that affects the development ...

  1. Calcium-dependent chloride current in rat cerebellar Purkinje cell membranes.

    PubMed

    Vykhareva, E A; Zamoyski, V L; Grigoriev, V V; Bachurin, S O

    2015-01-01

    The presence of calcium-dependent potential-activated chloride currents in the membranes of freshly isolated rat cerebellar Purkinje cells (12-15 days) was shown by the whole-cell patch clamp technique. Chloride currents appeared in a sodium-free external solution and reversibly disappeared in the absence of external chloride and calcium ions.

  2. Paraneoplastic cerebellar degeneration with anti-Yo antibodies - a review.

    PubMed

    Venkatraman, Anand; Opal, Puneet

    2016-08-01

    The ataxic syndrome associated with Anti-Yo antibody, or Purkinje cell cytoplasmic antibody type 1 (PCA1), is the most common variant of paraneoplastic cerebellar degeneration (PCD). The typical presentation involves the subacute development of pancerebellar deficits with a clinical plateau within 6 months. The vast majority of cases have been reported in women with pelvic or breast tumors. Magnetic resonance imaging of the brain is often normal in the early stages, with cerebellar atrophy seen later. The underlying mechanism is believed to be an immunological reaction to cerebellar degeneration-related protein 2 (CDR2), a protein usually found in the cerebellum that is ectopically produced by tumor cells. Although both B- and T-cell abnormalities are seen, there is debate about the relative importance of the autoantibodies and cytotoxic T lymphocytes in the neuronal loss. Cerebrospinal fluid abnormalities, primarily elevated protein, lymphocytic pleocytosis, and oligoclonal bands, are common in the early stages. The low prevalence of this condition has not allowed for large-scale randomized controlled trials. Immunotherapies, such as steroids, intravenous immune globulins, and plasma exchange, have been extensively used in managing this condition, with limited success. Although some reports indicate benefit from antitumor therapies like surgery and chemotherapy, this has not been consistently observed. The prognosis for anti-Yo PCD is almost uniformly poor, with most patients left bedridden. Further studies are required to clarify the pathophysiology and provide evidence-based treatment options.

  3. Inpatient Rehabilitation Performance of Patients with Paraneoplastic Cerebellar Degeneration

    PubMed Central

    Fu, Jack B.; Raj, Vishwa S.; Asher, Arash; Lee, Jay; Guo, Ying; Konzen, Benedict S.; Bruera, Eduardo

    2014-01-01

    Objective To evaluate the functional improvement of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Design Retrospective Review Setting Three tertiary referral based hospitals. Interventions Medical records were retrospectively analyzed for demographic, laboratory, medical and functional data. Main Outcome Measure Functional Independence Measure (FIM) Participants Cancer rehabilitation inpatients admitted to three different cancer centers with a diagnosis of paraneoplastic cerebellar degeneration (n=7). Results All 7 patients were white females. Median age was 62. Primary cancers included ovarian carcinoma (2), small cell lung cancer (2), uterine carcinoma (2), and invasive ductal breast carcinoma. Mean admission total FIM score was 61.0 (SD=23.97). Mean discharge total FIM score was 73.6 (SD=29.35). The mean change in total FIM score was 12.6 (p=.0018). The mean length of rehabilitation stay was 17.1 days. The mean total FIM efficiency was 0.73. 5/7 (71%) patients were discharged home. 1/7 (14%) was discharged to a nursing home. 1/7 (14%) transferred to the primary acute care service. Conclusions This is the first study to demonstrate the functional performance of a group of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Despite the poor neurologic prognosis associated with this syndrome, these patients made significant functional improvements on inpatient rehabilitation. When appropriate, inpatient rehabilitation should be considered. Further studies with larger sample sizes are needed. PMID:25051460

  4. Detection of Middle East respiratory syndrome coronavirus using reverse transcription loop-mediated isothermal amplification (RT-LAMP)

    PubMed Central

    2014-01-01

    Background The first documented case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) occurred in 2012, and outbreaks have continued ever since, mainly in Saudi Arabia. MERS-CoV is primarily diagnosed using a real-time RT-PCR assay, with at least two different genomic targets required for a positive diagnosis according to the case definition of The World Health Organization (WHO) as of 3 July 2013. Therefore, it is urgently necessary to develop as many specific genetic diagnostic methods as possible to allow stable diagnosis of MERS-CoV infections. Methods Reverse transcription-loop-mediated isothermal amplification (RT-LAMP) is a genetic diagnostic method used widely for the detection of viral pathogens, which requires only a single temperature for amplification, and can be completed in less than 1 h. This study developed a novel RT-LAMP assay for detecting MERS-CoV using primer sets targeting a conserved nucleocapsid protein region. Results The RT-LAMP assay was capable of detecting as few as 3.4 copies of MERS-CoV RNA, and was highly specific, with no cross-reaction to other respiratory viruses. Pilot experiments to detect MERS-CoV from medium containing pharyngeal swabs inoculated with pre-titrated viruses were also performed. The RT-LAMP assay exhibited sensitivity similar to that of MERS-CoV real-time RT-PCR. Conclusions These results suggest that the RT-LAMP assay described here is a useful tool for the diagnosis and epidemiologic surveillance of human MERS-CoV infections. PMID:25103205

  5. Synaptic plasticity deficits in an experimental model of rett syndrome: long-term potentiation saturation and its pharmacological reversal.

    PubMed

    Weng, S-M; McLeod, F; Bailey, M E S; Cobb, S R

    2011-04-28

    Rett syndrome (RTT), a disorder caused almost exclusively by mutations in the X-linked gene, MECP2, has a phenotype thought to be primarily of neurological origin. Disruption of Mecp2 in mice results in a prominent RTT-like phenotype. One of the consequences of MeCP2 absence in the brain is altered functional and structural plasticity. We aimed to characterize synaptic effects related to plasticity in the hippocampus further and establish whether plasticity defects are amenable to pharmacological reversal. Using male mice in which Mecp2 expression was prevented by a stop cassette, we assessed synaptic plasticity in area CA1 at different phenotypic stages, scoring the mice weekly for overt RTT-like signs. Strongly symptomatic Mecp2(stop/y) mice displayed reduced long-term potentiation (LTP, 40.2±1.6% of wild-type), post-tetanic potentiation (PTP, 45±18.8% of wild-type) and paired-pulse facilitation (PPF, 78±0.1% of wild type) (all P<0.05), the impairment increasing with symptom severity score. These plasticity impairments were absent in presymptomatic mice. Repeated high frequency stimulation revealed pronounced LTP saturation in symptomatic Mecp2(stop/y) mice, suggesting an LTP 'ceiling' effect. Bath application of the weak NMDA receptor blocker memantine (1 μM) resulted in partial restoration of a short-term plasticity component. These data support that idea that progressive functional synaptic impairment is a key feature in the RTT brain and demonstrate the potential for the pharmacological restoration of plasticity function.

  6. Ethanol attenuates sensory stimulus-evoked responses in cerebellar granule cells via activation of GABA(A) receptors in vivo in mice.

    PubMed

    Wu, Guang; Liu, Heng; Jin, Juan; Hong, Lan; Lan, Yan; Chu, Chun-Ping; Qiu, De-Lai

    2014-02-21

    Acute alcohol intoxication affects cerebellar motor regulation possibly by altering the transfer and integration of external information in cerebellar cortical neurons, resulting in a dysfunction of cerebellar motor regulation or a cerebellar atexia. However, the synaptic mechanisms of ethanol induced impairments of sensory information processing in cerebellar cortical neurons are not fully understand. In the present study, we used electrophysiological and pharmacological methods to study the effects of ethanol on the sensory stimulation-evoked responses in cerebellar granule cells (GCs) in vivo in urethane anesthetized mice. Air-puff stimulation of the ipsilateral whisker-pad evoked stimulus-on (P1) and stimulus-off responses (P2) in GCs of cerebellar Crus II. Cerebellar surface perfusion of ethanol did not alter the onset latency of the sensory stimulation-evoked responses, but reversible reduced the amplitude of P1 and P2. The ethanol-induced reduction of the GCs sensory responses was concentration-dependent. In the presence of ethanol, the mean half-width, area under curve, rise Tau and decay Tau of P1 were significantly decreased. Blockade of gamma-aminobutyric acid type A (GABA(A)) receptors activity induced an increase in amplitude of P1, and abolished the ethanol induced inhibition of the GCs sensory responses. These results indicate that ethanol inhibits the tactile evoked responses in cerebellar GCs through enhancement of GABA(A) receptors activity.

  7. Learning of Sensory Sequences in Cerebellar Patients

    ERIC Educational Resources Information Center

    Frings, Markus; Boenisch, Raoul; Gerwig, Marcus; Diener, Hans-Christoph; Timmann, Dagmar

    2004-01-01

    A possible role of the cerebellum in detecting and recognizing event sequences has been proposed. The present study sought to determine whether patients with cerebellar lesions are impaired in the acquisition and discrimination of sequences of sensory stimuli of different modalities. A group of 26 cerebellar patients and 26 controls matched for…

  8. Acute cerebellar ataxia and infectious mononucleosis.

    PubMed Central

    Wadhwa, N. K.; Ghose, R. R.

    1983-01-01

    A 28-year-old man, who presented with acute cerebellar ataxia, was found to have haematological features of infectious mononucleosis. There was serological evidence of recent infection with Epstein-Barr virus. It is speculated that cerebellar dysfunction results from virus-induced inflammatory changes within the central nervous system. PMID:6312442

  9. Consensus Paper: Management of Degenerative Cerebellar Disorders

    PubMed Central

    Ilg, W.; Bastian, A. J.; Boesch, S.; Burciu, R. G.; Celnik, P.; Claaßen, J.; Feil, K.; Kalla, R.; Miyai, I.; Nachbauer, W.; Schöls, L.; Strupp, M.; Synofzik, M.; Teufel, J.

    2015-01-01

    Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation. PMID:24222635

  10. Down-regulation of cerebellar 5-HT(2C) receptors in pilocarpine-induced epilepsy in rats: therapeutic role of Bacopa monnieri extract.

    PubMed

    Krishnakumar, Amee; Abraham, Pretty Mary; Paul, Jes; Paulose, C S

    2009-09-15

    Epilepsy is a syndrome of episodic brain dysfunction characterized by recurrent unpredictable, spontaneous seizures. Cerebellar dysfunction is a recognized complication of temporal lobe epilepsy and it is associated with seizure generation, motor deficits and memory impairment. Serotonin is known to exert a modulatory action on cerebellar function through 5HT(2C) receptors. 5-HT(2C) receptors are novel targets for developing anti-convulsant drugs. In the present study, we investigated the changes in the 5-HT(2C) receptors binding and gene expression in the cerebellum of control, epileptic and Bacopa monnieri treated epileptic rats. There was a significant down regulation of the 5-HT content (p<0.001), 5-HT(2C) gene expression (p<0.001) and 5-HT(2C) receptor binding (p<0.001) with an increased affinity (p<0.001). Carbamazepine and B. monnieri treatments to epileptic rats reversed the down regulated 5-HT content (p<0.01), 5-HT(2C) receptor binding (p<0.001) and gene expression (p<0.01) to near control level. Also, the Rotarod test confirms the motor dysfunction and recovery by B. monnieri treatment. These data suggest the neuroprotective role of B. monnieri through the upregulation of 5-HT(2C) receptor in epileptic rats. This has clinical significance in the management of epilepsy.

  11. Metronidazole-Induced Cerebellar Toxicity

    PubMed Central

    Agarwal, Amit; Kanekar, Sangam; Sabat, Shyam; Thamburaj, Krishnamurthy

    2016-01-01

    Metronidazole is a very common antibacterial and antiprotozoal with wide usage across the globe, including the least developed countries. It is generally well-tolerated with a low incidence of serious side-effects. Neurological toxicity is fairly common with this drug, however majority of these are peripheral neuropathy with very few cases of central nervous toxicity reported. We report the imaging findings in two patients with cerebellar dysfunction after Metronidazole usage. Signal changes in the dentate and red nucleus were seen on magnetic resonance imaging in these patients. Most of the cases reported in literature reported similar findings, suggesting high predilection for the dentate nucleus in metronidazole induced encephalopathy. PMID:27127600

  12. Reversible Cerebral Vasoconstriction Syndrome Promptly Diagnosed with Magnetic Resonance Imaging Including Magnetic Resonance Angiography During Immunosuppressive Therapy in a 16-Year-Old Girl with Refractory Cytopenia of Childhood

    PubMed Central

    Ueki, Hideaki; Sanayama, Yasushi; Miyajima, Akiyo; Tsuchimochi, Taichiro; Igarashi, Shunji; Sunami, Shosuke

    2016-01-01

    Reversible cerebral vasoconstriction syndrome (RCVS) is a syndrome characterized by severe headache with segmental vasoconstriction of the cerebral arteries that resolves within 12 weeks. A 16-year-old girl with refractory cytopenia of childhood, who was receiving the immunosuppressant cyclosporine, developed severe headache and was diagnosed with RCVS using magnetic resonance imaging, including magnetic resonance angiography (MRA). MRA is a non-invasive and very effective technique for diagnosing RCVS. MRA should be performed at the onset of severe headache during immunosuppressant administration for children with hematological disorders and may prevent sequelae such as posterior reversible encephalopathy syndrome or ischemic attack. PMID:27994838

  13. Cerebellar Stroke-manifesting as Mania

    PubMed Central

    Jagadesan, Venkatesan; Thiruvengadam, Kannapiran R.; Muralidharan, Rengarajalu

    2014-01-01

    Secondary mania resulting from cerebral Cortex are described commonly. But secondary mania produced by cerebellar lesions are relatively uncommon. This case report describes a patient who developed cerebellar stoke and manic features simultaneously. 28 years old male developed giddiness and projectile vomiting. Then he would lie down for about an hour only to find that he could not walk. He became quarrelsome. His Psycho motor activities and speech were increased. He was euphoric and was expressing grandiose ideas. Bender Gestalt Test showed signs of organicity. Score in Young mania relating scale was 32; productivity was low in Rorschach. Neurological examination revealed left cerebellar signs like ataxia and slurring of speech. Computed tomography of brain showed left cerebellar infarct. Relationship between Psychiatric manifestations and cerebellar lesion are discussed. PMID:25035567

  14. Nutritional cerebellar degeneration, with comments on its relationship to Wernicke disease and alcoholism.

    PubMed

    Laureno, Robert

    2012-01-01

    Nutritional cerebellar degeneration occurs in alcoholism and other states that predispose to malnutrition, such as gastric bypass surgery. Gait ataxia is the principal clinical manifestation. Ataxia of the lower limbs is not uncommon, but upper extremity ataxia and nystagmus are rare. Atrophy of the anterior superior vermis is the primary pathological manifestation in established disease. Typically, the onset is subacute. This cerebellar disease is part of the spectrum of the Wernicke-Korsakoff syndrome, i.e. the cerebellar manifestation of Wernicke disease. It may occur with other lesions of Wernicke disease or in isolation. Rarely, with florid disease, lesions may be hemorrhagic. Active disease should be treated with thiamine in the same way that one treats Wernicke disease. Clinicopathologic correlation in this disease has provided the best evidence that the anterior superior vermis is important in coordinating bipedal locomotion.

  15. Cerebellar mutism caused by primary varicella infection in an immunocompetent child.

    PubMed

    Erol, Ilknur; Özkale, Yasemin; Saygi, Semra; Alehan, Füsun

    2014-06-01

    Varicella (chickenpox) is a common childhood infection caused by the varicella-zoster virus, which is often self-limiting and usually benign. Although uncommon, neurologic complications of varicella have been documented that include postinfectious cerebellar ataxia, meningoencephalitis, Reye syndrome, myelitis, optic neuritis, stroke, Guillain-Barré syndrome, seventh cranial nerve palsy, and Ramsay-Hunt syndrome. In this case study, the authors describe a 7-year-old girl who presented with varicella skin rash with unsteady gait and anarthria on day 2, and her condition was attributed to cerebellar mutism. To date, this complication has never been reported in a child with primary varicella infection. Therefore, this case study documents a rare but serious complication of childhood chickenpox.

  16. Novel Association Between the Reverse-Dipper Pattern of Ambulatory Blood Pressure Monitoring and Metabolic Syndrome in Men But Not in Women

    PubMed Central

    Yan, Bin; Yan, Hang; Sun, Lu; Yan, Xin; Peng, Liyuan; Wang, Yuhuan; Wang, Gang

    2015-01-01

    Abstract The aim of this study was to investigate the relationships between nocturnal variations in blood pressure (BP) and metabolic syndrome (MetS) in different gender. This cross-sectional study involved 509 hypertensive patients (254 males and 255 females, 45 to 75 years old) from September 2013 to March 2014. BP values were acquired from ambulatory BP monitoring (ABPM). The dipper pattern of BP was defined as 10% to 20% reduction of the mean systolic BP (SBP) values at night compared with the daytime values. The diagnosis of MetS was made according to NCEP ATP-III definition. Multivariate logistic regression analyses were used to explore the relationships between ABPM results and MetS. In our study, MetS were observed in 29.1% of male and 18.4% of female participants. The prevalence of MetS was higher in the patients with reverse-dipper pattern than in others. After multivariate logistic regression analysis, the reverse-dipper pattern of BP (odds ratio 2.298; P = 0.006) and 24-SBP (odds ratio 1.063; P = 0.021) were independently correlated with MetS in males. However, there was no association between MetS and BP reverse dipping in females. Our cross-sectional study showed that the reverse-dipper pattern of BP is associated with MetS in male, while the underlying mechanism deserves further investigation. PMID:26632731

  17. Viewpoint: reversible nature of platelet binding causing transfusion-related acute lung injury (TRALI) syndrome may explain dyspnea after ticagrelor and elinogrel.

    PubMed

    Serebruany, Victor L

    2012-12-01

    There may be a universal mechanism explaining dyspnea after ticagrelor and elinogrel, namely, transfusion-related acute lung injury (TRALI). Indeed, recent clinical trials with ticagrelor (DISPERSE, DISPERSE-II, and PLATO), and elinogrel (INNOVATE PCI) revealed double-digit rates of dyspnea after novel reversible antiplatelet agents. In contrast, dyspnea is not associated with conventional non-reversible agents such as aspirin, or thienopyridines (ticlopidine, clopidogrel, or prasugrel) suggesting distinct mechanism of shortness of breath after ticagrelor and elinogrel. The adenosine hypothesis has been offered to explain such adverse association. However, despite obvious similarity between ticagrelor and adenosine molecules, the chemical structure of elinogrel is entirely different. In fact, ticagrelor is a cyclopentyl-triazolo-pyrimidine, while elinogrel is a quinazolinedione. Since both agents cause dyspnea, the adenosine hypothesis is no longer valid. In contrast, the reversible nature of platelet inhibition attributable to both ticagrelor and elinogrel causing premature cell ageing, apoptosis, impaired turnover due to sequestration of overloaded, exhausted platelets in the pulmonary circulation are among potential autoimmune mechanism(s) resulting in the development of a TRALI-like reaction, and frequent dyspnea. Despite expected benefit for better bleeding control, further development of reversible antithrombins is severely limited due to the existence of a potentially universal serious adverse event, such as TRALI-syndrome with dyspnea as a predominant clinical manifestation. Since TRALI is an established number one contributor to mortality after blood transfusions, ticagrelor death "benefit" in PLATO is challenged further.

  18. Effects of ethanol on sensory stimulus-evoked responses in the cerebellar molecular layer in vivo in mice.

    PubMed

    Cui, Song-Biao; Cui, Bai-Ri; Liu, Heng; Wu, Mao-Cheng; Xu, Yin-Hua; Bian, Jin-Hua; Chu, Chun-Ping; Qiu, De-Lai

    2014-08-08

    Overdose intake of ethanol can impair cerebellar cortical neurons to integrate and transfer external information, resulting in a dysfunction of cerebellar motor regulation or cerebellar ataxia. However, the mechanisms underlying ethanol-impaired transfer of sensory information from cerebellar cortical molecular layer neurons remain unclear. In the present study, we investigated the effects of ethanol on sensory stimulation-evoked responses in the cerebellar molecular layer of urethane-anesthetized mice, by electrophysiological and pharmacological methods. Our results demonstrated that air-puff stimulation (30 ms, 50-60 psi) of the ipsilateral whisker-pad evoked field potential responses in the molecular layer of the cerebellar cortex folium Crus II, which expressed a negative component (N1) followed by a gamma-aminobutyric acid receptor A (GABAA)-mediated positive component (P1). Cerebellar surface perfusion of ethanol between 2 and 5mM did not change the latency of the evoked responses and the amplitude of N1, but enhanced the amplitude and the area under the curve of P1. Interestingly, high concentrations (>20mM) of ethanol induced a significantly decrease in the amplitude and area under the curve of P1. Furthermore, high concentration ethanol (300 mM) significantly decreased the rise in tau and tau decay value of P1, whereas low concentration ethanol (2-5mM) significantly increased these values of P1. Inhibition of GABAA receptor activity reversed P1 and also abolished the effects of ethanol on sensory stimulation-evoked responses. These results indicated that ethanol induced a bidirectional effect on the sensory stimulation-evoked GABAergic responses in the cerebellar cortical molecular layer, suggesting that acute alcohol intake impacted the sensory information processing of cerebellar cortex.

  19. [Memory transfer in cerebellar motor learning].

    PubMed

    Nagao, Soichi

    2012-01-01

    Most of our motor skills are acquired through learning. Experiments of gain adaptation of ocular reflexes have consistently suggested that the memory of adaptation is initially formed in the cerebellar cortex, and is transferred to the cerebellar (vestibular) nuclei for consolidation to long-term memory after repetitions of training. We have recently developed a new system to evaluate the motor learning in human subjects using prism adaptation of hand reaching movement, by referring to the prism adaptation of dart throwing of Martin et al. (1996). In our system, the subject views the small target presented in the touch-panel screen, and touches it with his/her finger without direct visual feedback. After 15-30 trials of touching wearing prisms, an adaptation occurs in healthy subjects: they became able to touch the target correctly. Meanwhile, such an adaptation was impaired in patients of cerebellar disease. We have proposed a model of human prism adaptation that the memory of adaptation is initially encoded in the cerebellar cortex, and is later transferred to the cerebellar nuclei after repetitions of training. The memory in the cerebellar cortex may be formed and extinguished independently of the memory maintained in the cerebellar nuclei, and these two memories work cooperatively.

  20. Sonic hedgehog patterning during cerebellar development.

    PubMed

    De Luca, Annarita; Cerrato, Valentina; Fucà, Elisa; Parmigiani, Elena; Buffo, Annalisa; Leto, Ketty

    2016-01-01

    The morphogenic factor sonic hedgehog (Shh) actively orchestrates many aspects of cerebellar development and maturation. During embryogenesis, Shh signaling is active in the ventricular germinal zone (VZ) and represents an essential signal for proliferation of VZ-derived progenitors. Later, Shh secreted by Purkinje cells sustains the amplification of postnatal neurogenic niches: the external granular layer and the prospective white matter, where excitatory granule cells and inhibitory interneurons are produced, respectively. Moreover, Shh signaling affects Bergmann glial differentiation and promotes cerebellar foliation during development. Here we review the most relevant functions of Shh during cerebellar ontogenesis, underlying its role in physiological and pathological conditions.

  1. WDR73 missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in a consanguineous family.

    PubMed

    Jiang, Chen; Gai, Nan; Zou, Yongyi; Zheng, Yu; Ma, Ruiyu; Wei, Xianda; Liang, Desheng; Wu, Lingqian

    2017-01-01

    Galloway-Mowat syndrome (GMS) is a very rare autosomal-recessive disorder characterized by nephrotic syndrome associated with microcephaly, and various central nervous system abnormalities, mostly cerebral hypoplasia or cerebellar atrophy, intellectual disability and neural-migration defects. WDR73 is the only gene known to cause GMS, and has never been implicated in other disease. Here we present a Chinese consanguineous family with infantile onset intellectual disability and cerebellar hypoplasia but no microcephaly. Whole exome sequencing identified a WDR73 p.W371G missense mutation. The mutation is confirmed to be segregated in this family by Sanger sequencing according to a recessive inheritance pattern. It is predicted to be deleterious by multiple algorithms and affect highly conserved site. Structural modeling revealed conformational differences between the wild type protein and the p.W371G protein. Real-time PCR and Western blotting revealed altered mRNA and protein levels in mutated samples. Our study indicates the novel WDR73 p.W371G missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in recessive mode of inheritance. Our findings imply that microcephaly is a variable phenotype in WDR73-related disease, suggest WDR73 to be a candidate gene of severe intellectual disability and cerebellar hypoplasia, and expand the molecular spectrum of WDR73-related disease.

  2. Cystic cerebellar astrocytomas in childhood.

    PubMed

    Griffin, T W; Beaufait, D; Blasko, J C

    1979-07-01

    Thirty-nine patients with low grade cystic cerebellar astrocytomas were treated at the University of Washington and Children's Orthopedic Hospital in Seattle, Washington, between 1955 and 1977; 29 were treated with partial or complete resection alone, and 10 received radiation therapy after various types of surgical procedures. With a mean follow-up time of 7 years, the survival rate for patients who had complete resections of their primary disease was 100%. The relapse-free survival rate was 82%. The relapse-free survival rate for patients treated primarily with partial resection alone was 36%. Postoperative irradiation after partial resection for both primary and recurrent disease resulted in a relapse-free survival rate of 83%. If complete tumor excision is not possible, postoperative radiation therapy is recommended following partial resection.

  3. Reversible kallmann syndrome, delayed puberty, and isolated anosmia occurring in a single family with a mutation in the fibroblast growth factor receptor 1 gene.

    PubMed

    Pitteloud, Nelly; Acierno, James S; Meysing, Astrid U; Dwyer, Andrew A; Hayes, Frances J; Crowley, William F

    2005-03-01

    Kallmann syndrome (KS) is a clinically and genetically heterogeneous disorder. Recently, loss-of-function mutations in the fibroblast growth factor receptor 1 (FGFR1) gene have been shown to cause autosomal dominant KS. To date, the detailed reproductive phenotype of KS associated with mutations in the FGFR1 has yet to be described. We report a kindred comprising a male proband with KS and spontaneous reversibility, whose mother had delayed puberty and whose maternal grandfather isolated anosmia. The proband presented at age 18 yr with KS and was subsequently treated with testosterone (T) therapy. Upon discontinuation of T therapy, he recovered from his hypogonadotropic hypogonadism, as evidenced by a normal LH secretion pattern, sustained normal serum T levels, and active spermatogenesis. The three members of this single family harbor the same FGFR1 mutation (Arg(622)X) in the tyrosine kinase domain. This report demonstrates 1) the first genetic cause of the rare variant of reversible KS, 2) the reversal of hypogonadotropic hypogonadism in a proband carrying an FGFR1 mutation suggests a role of FGFR1 beyond embryonic GnRH neuron migration, and 3) a loss of function mutation in the FGFR1 gene causing delayed puberty.

  4. Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

    PubMed Central

    Baldarçara, Leonardo; Currie, Stuart; Hadjivassiliou, M.; Hoggard, Nigel; Jack, Allison; Jackowski, Andrea P.; Mascalchi, Mario; Parazzini, Cecilia; Reetz, Kathrin; Righini, Andrea; Schulz, Jörg B.; Vella, Alessandra; Webb, Sara Jane; Habas, Christophe

    2016-01-01

    Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine. PMID:25382714

  5. Valproate-associated reversible encephalopathy in a 3-year-old girl with Pallister-Killian syndrome.

    PubMed

    Gerstner, Thorsten; Bell, Nellie; Koenig, Stephan A

    2008-06-01

    Valproic acid (VPA) is considered to be a drug of first choice for the therapy of generalized and focal epilepsies, including special epileptic syndromes. The drug is usually well tolerated, rare serious complications may occur in some patients, including hemorrhagic pancreatitis, coagulapathies, bone marrow suppression, VPA-induced hepatotoxicity and encephalopathy. We report a case of VPA-associated encephalopathy without hyperammonemia in a 3-year-old girl with Pallister-Killian-Syndrom, combined with a mild hepatopathy and thrombopathy. After withdrawal of VPA, the clinical symptoms and the electroencephalography-alterations vanished rapidly.

  6. Valproate-associated reversible encephalopathy in a 3-year-old girl with Pallister-Killian syndrome

    PubMed Central

    Gerstner, Thorsten; Bell, Nellie; Koenig, Stephan A

    2008-01-01

    Valproic acid (VPA) is considered to be a drug of first choice for the therapy of generalized and focal epilepsies, including special epileptic syndromes. The drug is usually well tolerated, rare serious complications may occur in some patients, including hemorrhagic pancreatitis, coagulapathies, bone marrow suppression, VPA-induced hepatotoxicity and encephalopathy. We report a case of VPA-associated encephalopathy without hyperammonemia in a 3-year-old girl with Pallister-Killian-Syndrom, combined with a mild hepatopathy and thrombopathy. After withdrawal of VPA, the clinical symptoms and the electroencephalography-alterations vanished rapidly. PMID:18827862

  7. Unusual case of recurrent SMART (stroke-like migraine attacks after radiation therapy) syndrome.

    PubMed

    Ramanathan, Ramnath Santosh; Sreedher, Gayathri; Malhotra, Konark; Guduru, Zain; Agarwal, Deeksha; Flaherty, Mary; Leichliter, Timothy; Rana, Sandeep

    2016-01-01

    Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare delayed complication of cerebral radiation therapy. A 53-year-old female initially presented with headache, confusion and left homonymous hemianopia. Her medical history was notable for cerebellar hemangioblastoma, which was treated with radiation in 1987. Her initial brain MRI (magnetic resonance imaging) revealed cortical enhancement in the right temporo-parieto-occipital region. She improved spontaneously in 2 weeks and follow-up scan at 4 weeks revealed no residual enhancement or encephalomalacia. She presented 6 weeks later with aphasia. Her MRI brain revealed similar contrast-enhancing cortical lesion but on the left side. Repeat CSF studies was again negative other than elevated protein. She was treated conservatively and recovered completely within a week. Before diagnosing SMART syndrome, it is important to rule out tumor recurrence, encephalitis, posterior reversible encephalopathy syndrome (PRES) and stroke. Typically the condition is self-limiting, and gradually resolves.

  8. Antibodies to inositol 1,4,5-triphosphate receptor 1 in patients with cerebellar disease

    PubMed Central

    Fouka, Penelope; Alexopoulos, Harry; Chatzi, Ioanna; Dedos, Skarlatos G.; Samiotaki, Martina; Panayotou, George; Politis, Panagiotis; Tzioufas, Athanasios

    2016-01-01

    Objective: To describe newly identified autoantibodies associated with cerebellar disorders. Design/Methods: We first screened the sera of 15 patients with cerebellar ataxia, without any known associated autoantibodies, with immunocytochemistry on mouse brain. After characterization and validation of a newly identified antibody, 85 additional patients with suspected autoimmune cerebellar disease were screened using a cell-based assay. Results: Immunoglobulin G from one of the first 15 patients demonstrated a distinct staining pattern on Purkinje neurons. This autoantibody, as characterized further by immunoprecipitation and mass spectrometry, was binding inositol 1,4,5-triphosphate receptor 1 (IP3R1), an intracellular channel that mediates the release of Ca2+ from intracellular stores. Anti-IP3R1 specificity was then validated with a cell-based assay. On this basis, screening of 85 other patients with cerebellar disease revealed 2 additional IP3R1-positive patients. All 3 patients presented with cerebellar ataxia; the first was eventually diagnosed with primary progressive multiple sclerosis, the second had a homozygous CAG insertion at the gene TBP, and the third was thought to have a neurodegenerative disease. Conclusions: We independently identified an autoantibody against IP3R1, a protein highly expressed in Purkinje neurons, confirming an earlier report. Because a mouse knockout model for IP3R1 exhibits ataxia and epilepsy, this autoantibody may have a functional role. The heterogeneity of the antibody-positive patients suggests that this antibody may either have a direct involvement in disease pathogenesis or it is a surrogate marker secondary to cerebellar injury. Anti-IP3R1 antibodies should be further explored in various ataxic and epileptic syndromes as they may denote a marker of response to immunotherapies. PMID:27957507

  9. Homozygous Deletion of the Very Low Density Lipoprotein Receptor Gene Causes Autosomal Recessive Cerebellar Hypoplasia with Cerebral Gyral Simplification

    PubMed Central

    Boycott, Kym M.; Flavelle, Shauna; Bureau, Alexandre; Glass, Hannah C.; Fujiwara, T. Mary; Wirrell, Elaine; Davey, Krista; Chudley, Albert E.; Scott, James N.; McLeod, D. Ross; Parboosingh, Jillian S.

    2005-01-01

    An autosomal recessive syndrome of nonprogressive cerebellar ataxia and mental retardation is associated with inferior cerebellar hypoplasia and mild cerebral gyral simplification in the Hutterite population. An identity-by-descent mapping approach using eight patients from three interrelated Hutterite families localized the gene for this syndrome to chromosome region 9p24. Haplotype analysis identified familial and ancestral recombination events and refined the minimal region to a 2-Mb interval between markers D9S129 and D9S1871. A 199-kb homozygous deletion encompassing the entire very low density lipoprotein receptor (VLDLR) gene was present in all affected individuals. VLDLR is part of the reelin signaling pathway, which guides neuroblast migration in the cerebral cortex and cerebellum. To our knowledge, this syndrome represents the first human lipoprotein receptor malformation syndrome and the second human disease associated with a reelin pathway defect. PMID:16080122

  10. Sub-Lethal Dose of Shiga Toxin 2 from Enterohemorrhagic Escherichia coli Affects Balance and Cerebellar Cytoarchitecture

    PubMed Central

    Pinto, Alipio; Cangelosi, Adriana; Geoghegan, Patricia A.; Tironi-Farinati, Carla; Brener, Gabriela J.; Goldstein, Jorge

    2016-01-01

    Shiga toxin producing Escherichia coli may damage the central nervous system before or concomitantly to manifested hemolytic–uremic syndrome symptoms. The cerebellum is frequently damaged during this syndrome, however, the deleterious effects of Shiga toxin 2 has never been integrally reported by ultrastructural, physiological and behavioral means. The aim of this study was to determine the cerebellar compromise after intravenous administration of a sub-lethal dose of Shiga toxin 2 by measuring the cerebellar blood–brain barrier permeability, behavioral task of cerebellar functionality (inclined plane test), and ultrastructural analysis (transmission electron microscope). Intravenous administration of vehicle (control group), sub-lethal dose of 0.5 and 1 ηg of Stx2 per mouse were tested for behavioral and ultrastructural studies. A set of three independent experiments were performed for each study (n = 6). Blood–brain barrier resulted damaged and consequently its permeability was significantly increased. Lower scores obtained in the inclined plane task denoted poor cerebellar functionality in comparison to their controls. The most significant lower score was obtained after 5 days of 1 ηg of toxin administration. Transmission electron microscope micrographs from the Stx2-treated groups showed neurons with a progressive neurodegenerative condition in a dose dependent manner. As sub-lethal intravenous Shiga toxin 2 altered the blood brain barrier permeability in the cerebellum the toxin penetrated the cerebellar parenchyma and produced cell damaged with significant functional implications in the test balance. PMID:26904009

  11. Sub-Lethal Dose of Shiga Toxin 2 from Enterohemorrhagic Escherichia coli Affects Balance and Cerebellar Cytoarchitecture.

    PubMed

    D'Alessio, Luciana; Pinto, Alipio; Cangelosi, Adriana; Geoghegan, Patricia A; Tironi-Farinati, Carla; Brener, Gabriela J; Goldstein, Jorge

    2016-01-01

    Shiga toxin producing Escherichia coli may damage the central nervous system before or concomitantly to manifested hemolytic-uremic syndrome symptoms. The cerebellum is frequently damaged during this syndrome, however, the deleterious effects of Shiga toxin 2 has never been integrally reported by ultrastructural, physiological and behavioral means. The aim of this study was to determine the cerebellar compromise after intravenous administration of a sub-lethal dose of Shiga toxin 2 by measuring the cerebellar blood-brain barrier permeability, behavioral task of cerebellar functionality (inclined plane test), and ultrastructural analysis (transmission electron microscope). Intravenous administration of vehicle (control group), sub-lethal dose of 0.5 and 1 ηg of Stx2 per mouse were tested for behavioral and ultrastructural studies. A set of three independent experiments were performed for each study (n = 6). Blood-brain barrier resulted damaged and consequently its permeability was significantly increased. Lower scores obtained in the inclined plane task denoted poor cerebellar functionality in comparison to their controls. The most significant lower score was obtained after 5 days of 1 ηg of toxin administration. Transmission electron microscope micrographs from the Stx2-treated groups showed neurons with a progressive neurodegenerative condition in a dose dependent manner. As sub-lethal intravenous Shiga toxin 2 altered the blood brain barrier permeability in the cerebellum the toxin penetrated the cerebellar parenchyma and produced cell damaged with significant functional implications in the test balance.

  12. Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLADR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures

    PubMed Central

    Gunn, Shelly R.; Gibson Gunn, G.; Mueller, Francis W.

    2016-01-01

    Patient: Male, 25 Final Diagnosis: Ulcerative colitis and chronic fatigue syndrome Symptoms: Colitis • profound fatigue • multi-joint pain • cognitive impairment • corneal keratitis Medication: — Clinical Procedure: VIP replacement therapy Specialty: Family Medicine Objective: Unusual clinical course Background: Patients with multisymptom chronic conditions, such as refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS), present diagnostic and management challenges for clinicians, as well as the opportunity to recognize and treat emerging disease entities. In the current case we report reversal of co-existing RUC and CFS symptoms arising from biotoxin exposures in a genetically susceptible individual. Case Report: A 25-year-old previously healthy male with new-onset refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS) tested negative for autoimmune disease biomarkers. However, urine mycotoxin panel testing was positive for trichothecene group and air filter testing from the patient’s water-damaged rental house identified the toxic mold Stachybotrys chartarum. HLA-DR/DQ testing revealed a multisusceptible haplotype for development of chronic inflammation, and serum chronic inflammatory response syndrome (CIRS) biomarker testing was positive for highly elevated TGF-beta and a clinically undetectable level of vasoactive intestinal peptide (VIP). Following elimination of biotoxin exposures, VIP replacement therapy, dental extractions, and implementation of a mind body intervention-relaxation response (MBI-RR) program, the patient’s symptoms resolved. He is off medications, back to work, and resuming normal exercise. Conclusions: This constellation of RUC and CFS symptoms in an HLA-DR/DQ genetically susceptible individual with biotoxin exposures is consistent with the recently described CIRS disease pathophysiology. Chronic immune disturbance (turbatio immuno) can be identified with clinically available CIRS biomarkers and

  13. Reversible posterior leukoencephalopathy syndrome following combinatorial cisplatin and pemetrexed therapy for lung cancer in a normotensive patient: A case report and literature review

    PubMed Central

    XIE, CHANGQING; JONES, VOVANTI T.

    2016-01-01

    Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare neurological syndrome of the brain, causing symptoms such as headaches, seizures, altered mental status and visual disturbances. The condition is predominantly associated with hypertension, eclampsia, renal impairment, cytotoxic drugs, immunosuppressive agents and molecular targeted agents, but the precise underlying mechanism of RPLS is not fully understood. The present study describes the case of a 65-year-old female patient with stage IIA non-small cell lung cancer who received cisplatin/pemetrexed treatment at the Leo W. Jenkins Cancer Center. Following 3 cycles of this therapy, the patient was referred to the Emergency Department of Vidant Medical Center with an altered mental status, subsequently presenting with epileptic seizures, a fever and a headache. A neurological examination revealed generalized hyperreflexia and paraparesis, with extensor posturing of the bilateral lower extremities. The lumbar puncture and electroencephalography results were normal, but cranial computed tomography (CT) scans revealed attenuation abnormalities in the bilateral parietal region and the left occipital lobe, with suspected metastasis. Cranial T2-weighted magnetic resonance imaging (MRI) indicated bilateral regions of increased signal intensity in the occipital, temporal and periventricular white matter. The patient was treated with anticonvulsants, steroids and antihypertensive drugs, recovered gradually from the symptoms and regained full consciousness. However, the patient reported residual weakness, presenting with an Eastern Cooperative Oncology Group score of 3, reflective of an inability to independently perform daily activities and self-care. A brain MRI performed 10 days later demonstrated that the subcortical edema had partially subsided. The patient was discharged on day 15 post-admission. A follow-up cranial CT examination 1 month later indicated a partial resolution of the abnormalities. The

  14. Changes in the cerebellar and cerebro-cerebellar circuit in type 2 diabetes.

    PubMed

    Fang, Peng; An, Jie; Tan, Xin; Zeng, Ling-Li; Shen, Hui; Qiu, Shijun; Hu, Dewen

    2017-01-11

    Currently, 422 million adults suffer from diabetes worldwide, leading to tremendous disabilities and a great burden to families and society. Functional and structural MRIs have demonstrated that patients with type 2 diabetes mellitus (T2DM) exhibit abnormalities in brain regions in the cerebral cortex. However, the changes of cerebellar anatomical connections in diabetic patients remains unclear. In the current study, diffusion tensor imaging deterministic tractography and statistical analysis were employed to investigate abnormal cerebellar anatomical connections in diabetic patients. This is the first study to investigate the altered cerebellar anatomical connectivity in T2DM patients. Decreased anatomical connections were found in the cerebellar and cerebro-cerebellar circuits of T2DM patients, providing valuable new insights into the potential neuro-pathophysiology of diabetes-related motor and cognitive deficits.

  15. Diagnosis of twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anaemia-polycythaemia sequence, and twin reversed arterial perfusion sequence.

    PubMed

    Sueters, Marieke; Oepkes, Dick

    2014-02-01

    Monochorionic twin pregnancies are well known to be at risk for a variety of severe complications, a true challenge for the maternal-fetal medicine specialist. With current standards of care, monochorionicity should be established in the first trimester. Subsequently, frequent monitoring using the appropriate diagnostic tools, and in-depth knowledge about the pathophysiology of all possible clinical presentations of monochorionic twin abnormalities, should lead to timely recognition, and appropriate management. Virtually all unique diseases found in monochorionic twins are directly related to placental angio-architecture. This, however, cannot be established reliably before birth. The clinician needs to be aware of the definitions and symptoms of twin-to twin transfusion syndrome, selective fetal growth restriction, twin anaemia-polycythaemia sequence, and twin reversed arterial perfusion sequence, to be able to recognise each disease and take the required action. In this chapter, we address current standards on correct and timely diagnoses of severe complications of monochorionic twin pregnancies.

  16. A global amnesia associated with the specific variant of posterior reversible encephalopathy syndrome (PRES) that developed due to severe preeclampsia and malignant hypertension.

    PubMed

    Borovac, Josip Anđelo; Božić, Joško; Žaja, Nikola; Kolić, Krešimir; Hrboka, Vedran

    2016-04-01

    A case is reported of a 26-year-old primiparous woman in the 32nd week of gestation who presented to the emergency department with the symptoms of a severe headache, nausea and vomiting. The patient was diagnosed with preeclampsia that later progressed to eclampsia. This state was characterized by a sudden onset of a headache and diplopia that advanced to cortical blindness and precipitated significant alterations in mental status, most notable being global amnesia that resolved within 48 h. A post-partum magnetic resonance imaging of the brain in FLAIR mode revealed multiple cortico-subcortical areas of hyperintense signals suggestive of edematous lesions that chiefly involved occipital and parietal lobes with additional atypical manifestations. Such radiologic findings suggested a posterior reversible encephalopathy syndrome variant with the global amnesia as an extraordinary constituent. This unique feature should be acknowledged when treating a preeclamptic or hypertensive patient that exhibits neurological symptomatology and vision disturbances.

  17. Correct the Coagulopathy and Scoop It Out: Complete Reversal of Anuric Renal Failure through the Operative Decompression of Extraperitoneal Hematoma-Induced Abdominal Compartment Syndrome.

    PubMed

    McBeth, Paul B; Dunham, Michael; Ball, Chad G; Kirkpatrick, Andrew W

    2012-01-01

    We report two cases of extraperitoneal compression of the intra-abdominal space resulting in abdominal compartment syndrome (ACS) with overt renal failure, which responded to operative decompression of the extra-peritoneal spaces. This discussion includes patient presentation, clinical course, diagnosis, interventions, and outcomes. Data was collected from the patient's electronic medical record and a radiology database. ACS appears to be a rare but completely reversible complication of both retroperitoneal hematoma (RH) and rectus sheath hematoma (RSH). In patients with large RH or RSH consideration of intra-abdominal pressure (IAP) monitoring combined with aggressive operative drainage after correction of the coagulopathy should be considered. These two cases illustrate how a relatively benign pathology can result in increased IAP, organ failure, and ultimately ACS. Intervention with decompressive laparotomy and evacuation of clot resulted in return to normal physiologic function.

  18. Probe-free real-time reverse transcription polymerase chain reaction assays for the detection and typing of porcine reproductive and respiratory syndrome virus in Canada.

    PubMed

    Eschbaumer, Michael; Li, Wansi May; Wernike, Kerstin; Marshall, Frank; Czub, Markus

    2015-07-01

    Porcine reproductive and respiratory syndrome (PRRS) has tremendous impact on the pork industry in North America. The molecular diagnosis of infection with PRRS virus (PRRSV) is hampered by its considerable strain diversity. In this study, 43 previously published or newly developed primers for probe-free real-time reverse transcription polymerase chain reaction (RT-PCR) were evaluated on their sensitivity, specificity, reproducibility, and repeatability, using a diverse panel of 36 PRRSV strains as well as other arteriviruses and unrelated porcine viruses. Three primer pairs had excellent diagnostic and analytical sensitivity on par with a probe-based reference assay, absolute specificity to virus genotype and species, as well as over 95% reproducibility and repeatability across a wide dynamic range.

  19. A global amnesia associated with the specific variant of posterior reversible encephalopathy syndrome (PRES) that developed due to severe preeclampsia and malignant hypertension

    PubMed Central

    Borovac, Josip Anđelo; Božić, Joško; Žaja, Nikola; Kolić, Krešimir; Hrboka, Vedran

    2016-01-01

    A case is reported of a 26-year-old primiparous woman in the 32nd week of gestation who presented to the emergency department with the symptoms of a severe headache, nausea and vomiting. The patient was diagnosed with preeclampsia that later progressed to eclampsia. This state was characterized by a sudden onset of a headache and diplopia that advanced to cortical blindness and precipitated significant alterations in mental status, most notable being global amnesia that resolved within 48 h. A post-partum magnetic resonance imaging of the brain in FLAIR mode revealed multiple cortico-subcortical areas of hyperintense signals suggestive of edematous lesions that chiefly involved occipital and parietal lobes with additional atypical manifestations. Such radiologic findings suggested a posterior reversible encephalopathy syndrome variant with the global amnesia as an extraordinary constituent. This unique feature should be acknowledged when treating a preeclamptic or hypertensive patient that exhibits neurological symptomatology and vision disturbances. PMID:27099774

  20. [Occipital dermal sinus associated to a cerebellar abscess. Case].

    PubMed

    Costa, J M; de Reina, L; Guillén, A; Claramunt, E

    2004-10-01

    Congenital dermal sinuses are tubular tracts which communicate the skin with deeper structures. It is a manifestation of defective separation of the ectoderm and neuroderm. The incidence is 1/2500-3000 births alive. Almost 10 % of congenital dermal sinuses are localized in the occipitocervical region. They are usually asymptomatic, unless an infectious process is concurrent (meningitis, abscess). We are presenting the case of a 12 months girl with unnoticed cutaneous stigmata in the occipital region, who was admitted with a meningeal syndrome and secondary neurological impairment. She had a cerebellar abscess and was treated with decompression by puncture of the abscess and antibiotics. When infection was resolved, congenital dermal sinus was excised. Process solves without morbidity. We reviewed the clinical and therapeutic features in cases reported previously in the literature.

  1. Acute post-infectious cerebellar ataxia due to co-infection of human herpesvirus-6 and adenovirus mimicking myositis.

    PubMed

    Naselli, Aldo; Pala, Giovanna; Cresta, Federico; Finetti, Martina; Biancheri, Roberta; Renna, Salvatore

    2014-11-26

    Acute cerebellar ataxia (ACA) is a relatively common neurological disease in children. Most common types of ACA are acute post-infectious (APCA) and acute disseminated encephalomyelitis (ADEM). Less common but important causes include opsoclonus-myoclonus syndrome (OMS) and acute cerebellitis. Cerebellar neoplasms and acute hydrocephalus are additional causes of paediatric ataxia. APCA is the most common cause of ACA in children, comprising about 30-50% of total cases. This is a report about an immunocompetent 4-yrs-old male affected by APCA, due to co-infection by human herpesvirus-6 (HHV-6) and adenovirus, with symptoms mimicking myositis.

  2. Cerebellar modules operate at different frequencies

    PubMed Central

    Zhou, Haibo; Lin, Zhanmin; Voges, Kai; Ju, Chiheng; Gao, Zhenyu; Bosman, Laurens WJ; Ruigrok, Tom JH; Hoebeek, Freek E

    2014-01-01

    Due to the uniform cyto-architecture of the cerebellar cortex, its overall physiological characteristics have traditionally been considered to be homogeneous. In this study, we show in awake mice at rest that spiking activity of Purkinje cells, the sole output cells of the cerebellar cortex, differs between cerebellar modules and correlates with their expression of the glycolytic enzyme aldolase C or zebrin. Simple spike and complex spike frequencies were significantly higher in Purkinje cells located in zebrin-negative than zebrin-positive modules. The difference in simple spike frequency persisted when the synaptic input to, but not intrinsic activity of, Purkinje cells was manipulated. Blocking TRPC3, the effector channel of a cascade of proteins that have zebrin-like distribution patterns, attenuated the simple spike frequency difference. Our results indicate that zebrin-discriminated cerebellar modules operate at different frequencies, which depend on activation of TRPC3, and that this property is relevant for all cerebellar functions. DOI: http://dx.doi.org/10.7554/eLife.02536.001 PMID:24843004

  3. Regionalization of the isthmic and cerebellar primordia.

    PubMed

    Narboux-Nême, Nicolas; Louvi, Angeliki; Alexandre, Paula; Wassef, Marion

    2005-01-01

    The complex migrations of neurons born in the dorsal neural tube of the isthmic and rhombomere l (rl) domains complicate the delineation of the cerebellar primordium. We show that Purkinje cells (P) are likely generated over a wide territory before gathering in the future cerebellar primordium under the developing external granular layer. Later expansion of the cerebellum over a restricted ependymal domain could rely on mutual interations between P cells and granule cell progenitors (GCP). P are attracted by GCP and in turn stimulate their proliferation, increasing the surface of the developing cortex. At later stages, regionalization of the developing and adult cerebellar cortex can be detected through regional variations in the distribution of several P cell markers. Whether and how the developmental and adult P subtypes are related is still unknown and it is unclear if they delineate the same sets of cerebellar subdivisions. We provide evidence that the early P regionalization is involved in intrinsic patterning of the cerebellar primordium, in particular it relate to the organization of the corticonuclear connection. We propose that the early P regionalization provides a scaffold to the mature P regionalization but that the development of functional afferent connections induces a period of P plasticity during which the early regional identity of P could be remodeled.

  4. Lung microvascular transport properties measured by multiple indicator dilution methods in patients with adult respiratory distress syndrome. A comparison between patients reversing respiratory failure and those failing to reverse.

    PubMed

    Harris, T R; Bernard, G R; Brigham, K L; Higgins, S B; Rinaldo, J E; Borovetz, H S; Sibbald, W J; Kariman, K; Sprung, C L

    1990-02-01

    We conducted indicator dilution studies on the lungs of patients in the early phases of adult respiratory distress syndrome (ARDS) to test the hypothesis that capillary permeability was increased in patients with respiratory failure. Indicator dilution studies were performed using 51Cr-erythrocytes, 125I-albumin, 14C-urea, and 3H-water as tracers. The injectate was infused as a bolus into a central venous line. Peripheral arterial blood was collected and counted for radioactivity. Mathematical analysis of the indicator curves yielded cardiac output, measures of the product of capillary permeability and surface area for urea (PS and D1/2S), the intravascular lung volume (Vv), and the extravascular lung water volume (Ve). Permeability was separated from surface area by normalizing PS and D1/2S to Vv. Patients could be divided into 16 in whom blood gas determinations and radiologic criteria for ARDS were reversed and 23 in whom they were not. We examined indicator dilution and other measures of lung function in the two groups to determine whether significant differences in microvascular function existed. PS and PS/Vv were significantly higher in the nonreversal patients. Ve was above normal, but not different between groups. Linear regression analysis showed significant correlations for all of the following in the nonreversal group: Ve and all measures of permeability, pulmonary vascular resistance (PVR), and the inverse of permeability-surface area measures and AaDO2 and PVR. Only measures of Ve and PS correlated in the reversal group. These results support the hypothesis that capillary permeability is increased in patients with early ARDS and continuing respiratory failure.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Secondary orthostatic tremor in the setting of cerebellar degeneration.

    PubMed

    Sarva, Harini; Severt, William Lawrence; Jacoby, Nuri; Pullman, Seth L; Saunders-Pullman, Rachel

    2016-05-01

    Orthostatic tremor (OT) and cerebellar ataxia are uncommon and difficult to treat. We present two patients with OT and cerebellar degeneration, one of whom had spinocerebellar ataxia type 2 and a good treatment response.

  6. Neurodevelopmental malformations of the cerebellar vermis in genetically engineered rats

    EPA Science Inventory

    The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformati...

  7. Sodium action potentials in the dendrites of cerebellar Purkinje cells.

    PubMed

    Regehr, W G; Konnerth, A; Armstrong, C M

    1992-06-15

    We report here that in cerebellar Purkinje cells from which the axon has been removed, positive voltage steps applied to the voltage-clamped soma produce spikes of active current. The spikes are inward, are all-or-none, have a duration of approximately 1 ms, and are reversibly eliminated by tetrodotoxin, a Na channel poison. From cell to cell, the amplitude of the spikes ranges from 4 to 20 nA. Spike latency decreases as the depolarizing step is made larger. These spikes clearly arise at a site where the voltage is not controlled, remote from the soma. From these facts we conclude that Purkinje cell dendrites contain a sufficient density of Na channels to generate action potentials. Activation by either parallel fiber or climbing fiber synapses produces similar spikes, suggesting that normal input elicits Na action potentials in the dendrites. These findings greatly alter current views of how dendrites in these cells respond to synaptic input.

  8. A BDNF loop-domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome

    PubMed Central

    Kron, Miriam; Lang, Min; Adams, Ian T.; Sceniak, Michael; Longo, Frank; Katz, David M.

    2014-01-01

    Reduced levels of brain-derived neurotrophic factor (BDNF) are thought to contribute to the pathophysiology of Rett syndrome (RTT), a severe neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). In Mecp2 mutant mice, BDNF deficits have been associated with breathing abnormalities, a core feature of RTT, as well as with synaptic hyperexcitability within the brainstem respiratory network. Application of BDNF can reverse hyperexcitability in acute brainstem slices from Mecp2-null mice, suggesting that therapies targeting BDNF or its receptor, TrkB, could be effective at acute reversal of respiratory abnormalities in RTT. Therefore, we examined the ability of LM22A-4, a small-molecule BDNF loop-domain mimetic and TrkB partial agonist, to modulate synaptic excitability within respiratory cell groups in the brainstem nucleus tractus solitarius (nTS) and to acutely reverse abnormalities in breathing at rest and during behavioral arousal in Mecp2 mutants. Patch-clamp recordings in Mecp2-null brainstem slices demonstrated that LM22A-4 decreases excitability at primary afferent synapses in the nTS by reducing the amplitude of evoked excitatory postsynaptic currents and the frequency of spontaneous and miniature excitatory postsynaptic currents. In vivo, acute treatment of Mecp2-null and -heterozygous mutants with LM22A-4 completely eliminated spontaneous apneas in resting animals, without sedation. Moreover, we demonstrate that respiratory dysregulation during behavioral arousal, a feature of human RTT, is also reversed in Mecp2 mutants by acute treatment with LM22A-4. Together, these data support the hypothesis that reduced BDNF signaling and respiratory dysfunction in RTT are linked, and establish the proof-of-concept that treatment with a small-molecule structural mimetic of a BDNF loop domain and a TrkB partial agonist can acutely reverse abnormal breathing at rest and in response to behavioral arousal

  9. A novel homozygous Fas ligand mutation leads to early protein truncation, abrogation of death receptor and reverse signaling and a severe form of the autoimmune lymphoproliferative syndrome.

    PubMed

    Nabhani, Schafiq; Hönscheid, Andrea; Oommen, Prasad T; Fleckenstein, Bernhard; Schaper, Jörg; Kuhlen, Michaela; Laws, Hans-Jürgen; Borkhardt, Arndt; Fischer, Ute

    2014-12-01

    We report a novel type of mutation in the death ligand FasL that was associated with a severe phenotype of the autoimmune lymphoproliferative syndrome in two patients. A frameshift mutation in the intracellular domain led to complete loss of FasL expression. Cell death signaling via its receptor and reverse signaling via its intracellular domain were completely abrogated. In vitro lymphocyte proliferation induced by weak T cell receptor stimulation could be blocked and cell death was induced by engagement of FasL in T cells derived from healthy individuals and a heterozygous carrier, but not in FasL-deficient patient derived cells. Expression of genes implicated in lymphocyte proliferation and activation (CCND1, NFATc1, NF-κB1) was increased in FasL-deficient T cells and could not be downregulated by FasL engagement as in healthy cells. Our data thus suggest, that deficiency in FasL reverse signaling may contribute to the clinical lymphoproliferative phenotype of ALPS.

  10. Transgene silencing of the Hutchinson-Gilford progeria syndrome mutation results in a reversible bone phenotype, whereas resveratrol treatment does not show overall beneficial effects.

    PubMed

    Strandgren, Charlotte; Nasser, Hasina Abdul; McKenna, Tomás; Koskela, Antti; Tuukkanen, Juha; Ohlsson, Claes; Rozell, Björn; Eriksson, Maria

    2015-08-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder that is most commonly caused by a de novo point mutation in exon 11 of the LMNA gene, c.1824C>T, which results in an increased production of a truncated form of lamin A known as progerin. In this study, we used a mouse model to study the possibility of recovering from HGPS bone disease upon silencing of the HGPS mutation, and the potential benefits from treatment with resveratrol. We show that complete silencing of the transgenic expression of progerin normalized bone morphology and mineralization already after 7 weeks. The improvements included lower frequencies of rib fractures and callus formation, an increased number of osteocytes in remodeled bone, and normalized dentinogenesis. The beneficial effects from resveratrol treatment were less significant and to a large extent similar to mice treated with sucrose alone. However, the reversal of the dental phenotype of overgrown and laterally displaced lower incisors in HGPS mice could be attributed to resveratrol. Our results indicate that the HGPS bone defects were reversible upon suppressed transgenic expression and suggest that treatments targeting aberrant progerin splicing give hope to patients who are affected by HGPS.

  11. Landmark based shape analysis for cerebellar ataxia classification and cerebellar atrophy pattern visualization

    NASA Astrophysics Data System (ADS)

    Yang, Zhen; Abulnaga, S. Mazdak; Carass, Aaron; Kansal, Kalyani; Jedynak, Bruno M.; Onyike, Chiadi; Ying, Sarah H.; Prince, Jerry L.

    2016-03-01

    Cerebellar dysfunction can lead to a wide range of movement disorders. Studying the cerebellar atrophy pattern associated with different cerebellar disease types can potentially help in diagnosis, prognosis, and treatment planning. In this paper, we present a landmark based shape analysis pipeline to classify healthy control and different ataxia types and to visualize the characteristic cerebellar atrophy patterns associated with different types. A highly informative feature representation of the cerebellar structure is constructed by extracting dense homologous landmarks on the boundary surfaces of cerebellar sub-structures. A diagnosis group classifier based on this representation is built using partial least square dimension reduction and regularized linear discriminant analysis. The characteristic atrophy pattern for an ataxia type is visualized by sampling along the discriminant direction between healthy controls and the ataxia type. Experimental results show that the proposed method can successfully classify healthy controls and different ataxia types. The visualized cerebellar atrophy patterns were consistent with the regional volume decreases observed in previous studies, but the proposed method provides intuitive and detailed understanding about changes of overall size and shape of the cerebellum, as well as that of individual lobules.

  12. Landmark Based Shape Analysis for Cerebellar Ataxia Classification and Cerebellar Atrophy Pattern Visualization

    PubMed Central

    Yang, Zhen; Abulnaga, S. Mazdak; Carass, Aaron; Kansal, Kalyani; Jedynak, Bruno M.; Onyike, Chiadi; Ying, Sarah H.; Prince, Jerry L.

    2016-01-01

    Cerebellar dysfunction can lead to a wide range of movement disorders. Studying the cerebellar atrophy pattern associated with different cerebellar disease types can potentially help in diagnosis, prognosis, and treatment planning. In this paper, we present a landmark based shape analysis pipeline to classify healthy control and different ataxia types and to visualize the characteristic cerebellar atrophy patterns associated with different types. A highly informative feature representation of the cerebellar structure is constructed by extracting dense homologous landmarks on the boundary surfaces of cerebellar sub-structures. A diagnosis group classifier based on this representation is built using partial least square dimension reduction and regularized linear discriminant analysis. The characteristic atrophy pattern for an ataxia type is visualized by sampling along the discriminant direction between healthy controls and the ataxia type. Experimental results show that the proposed method can successfully classify healthy controls and different ataxia types. The visualized cerebellar atrophy patterns were consistent with the regional volume decreases observed in previous studies, but the proposed method provides intuitive and detailed understanding about changes of overall size and shape of the cerebellum, as well as that of individual lobules. PMID:27303111

  13. [Study of cerebellar infarction with isolated vertigo].

    PubMed

    Utsumi, Ai; Enomoto, Hiroyuki; Yamamoto, Kaoru; Kimura, Yu; Koizuka, Izumi; Tsukuda, Mamoru

    2010-07-01

    Isolated vertigo is generally attributed to labyrinthine disease, but may also signal otherwise asymptomatic cerebellar infarction. Of 309 subjects admitted between April 2004 and March 2009 for the single symptom of acute vertigo initially thought to be labyrinthine, four were found to have cerebellar infarction of the posterior inferior cerebellar artery area (PICA). All were over 60 years old and had risk factors including hypertension, diabetes mellitus, arrhythmia, and/or hyperlipidemia. Two had trunk ataxia, with magnetic resonance imaging (MRI) showing infarction within a few days. The other two could walk without apparent trunk ataxia, however, it took 4 to 7 days to find the infarction, mainly through neurological, neurootological, and MRI findings. Neurologically, astasia, dysbasia or trunk ataxia were important signs. Neurootologically, nystagmus and electronystagmographic testing involving eye tracking, saccade, and optokinetic patttens were useful.

  14. Reversible Valproate Induced Pisa Syndrome and Parkinsonism in a Neuro-Oncology Patient with Depression and Epilepsy.

    PubMed

    Botturi, Andrea; Silvani, Antonio; Pravettoni, Gabriella; Paoli, Riccardo Augusto; Lucchiari, Claudio

    2016-01-01

    Neurological and psychiatric conditions frequently overlap in neuro-oncology. This overlapping negatively affects patients' quality of life and decreases the ability of providers to manage specific symptoms by therapy modulation, especially when psychopharmacotherapy needs to be prescribed. We describe here a patient with recurrent brain tumor, symptomatic epilepsy and depression who developed Pisa syndrome and parkinsonism after several months of valproic acid use. An accurate recognition of symptoms and treatment side effect allowed an appropriate clinical approach so as to rapidly improve both movement disorder and depression without increasing the risk of developing seizure. This has improved the autonomy and quality of life in a patient with poor prognosis.

  15. Reversible Valproate Induced Pisa Syndrome and Parkinsonism in a Neuro-Oncology Patient with Depression and Epilepsy

    PubMed Central

    Botturi, Andrea; Silvani, Antonio; Pravettoni, Gabriella; Paoli, Riccardo Augusto; Lucchiari, Claudio

    2016-01-01

    Neurological and psychiatric conditions frequently overlap in neuro-oncology. This overlapping negatively affects patients’ quality of life and decreases the ability of providers to manage specific symptoms by therapy modulation, especially when psychopharmacotherapy needs to be prescribed. We describe here a patient with recurrent brain tumor, symptomatic epilepsy and depression who developed Pisa syndrome and parkinsonism after several months of valproic acid use. An accurate recognition of symptoms and treatment side effect allowed an appropriate clinical approach so as to rapidly improve both movement disorder and depression without increasing the risk of developing seizure. This has improved the autonomy and quality of life in a patient with poor prognosis. PMID:27462241

  16. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted cerebellar stimulator. 882.5820 Section... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820 Implanted cerebellar stimulator. (a) Identification. An implanted cerebellar stimulator is a device used to...

  17. Disruption of the LTD dialogue between the cerebellum and the cortex in Angelman syndrome model: a timing hypothesis

    PubMed Central

    Cheron, Guy; Márquez-Ruiz, Javier; Kishino, Tatsuya; Dan, Bernard

    2014-01-01

    Angelman syndrome (AS) is a genetic neurodevelopmental disorder in which cerebellar functioning impairment has been documented despite the absence of gross structural abnormalities. Characteristically, a spontaneous 160 Hz oscillation emerges in the Purkinje cells network of the Ube3am−/p+ Angelman mouse model. This abnormal oscillation is induced by enhanced Purkinje cell rhythmicity and hypersynchrony along the parallel fiber beam. We present a pathophysiological hypothesis for the neurophysiology underlying major aspects of the clinical phenotype of AS, including cognitive, language and motor deficits, involving long-range connection between the cerebellar and the cortical networks. This hypothesis states that the alteration of the cerebellar rhythmic activity impinges cerebellar long-term depression (LTD) plasticity, which in turn alters the LTD plasticity in the cerebral cortex. This hypothesis was based on preliminary experiments using electrical stimulation of the whiskers pad performed in alert mice showing that after a 8 Hz LTD-inducing protocol, the cerebellar LTD accompanied by a delayed response in the wild type (WT) mice is missing in Ube3am−/p+ mice and that the LTD induced in the barrel cortex following the same peripheral stimulation in wild mice is reversed into a LTP in the Ube3am−/p+ mice. The control exerted by the cerebellum on the excitation vs. inhibition balance in the cerebral cortex and possible role played by the timing plasticity of the Purkinje cell LTD on the spike–timing dependent plasticity (STDP) of the pyramidal neurons are discussed in the context of the present hypothesis. PMID:25477791

  18. The use of muscle biopsy in the diagnosis of undefined ataxia with cerebellar atrophy in children

    PubMed Central

    Terracciano, Alessandra; Renaldo, Florence; Zanni, Ginevra; D’Amico, Adele; Pastore, Anna; Barresi, Sabina; Valente, Enza Maria; Piemonte, Fiorella; Tozzi, Giulia; Carrozzo, Rosalba; Valeriani, Massimiliano; Boldrini, Renata; Mercuri, Eugenio; Santorelli, Filippo Maria; Bertini, Enrico

    2012-01-01

    Childhood cerebellar ataxias, and particularly congenital ataxias, are heterogeneous disorders and several remain undefined. We performed a muscle biopsy in patients with congenital ataxia and children with later onset undefined ataxia having neuroimaging evidence of cerebellar atrophy. Significant reduced levels of Coenzyme Q10 (COQ10) were found in the skeletal muscle of 9 out of 34 patients that were consecutively screened. A mutation in the ADCK3/Coq8 gene (R347X) was identified in a female patient with ataxia, seizures and markedly reduced COQ10 levels. In a 2.5-years-old male patient with non syndromic congenital ataxia and autophagic vacuoles in the muscle biopsy we identified a homozygous nonsense mutation R111X mutation in SIL1 gene, leading to early diagnosis of Marinesco-Sjogren syndrome. We think that muscle biopsy is a valuable procedure to improve diagnostic assesement in children with congenital ataxia or other undefined forms of later onset childhood ataxia associated to cerebellar atrophy at MRI. PMID:21873089

  19. Anti-Yo antibody-mediated paraneoplastic cerebellar degeneration in a female patient with pleural malignant mesothelioma.

    PubMed

    Tanriverdi, Ozgur; Meydan, Nezih; Barutca, Sabri; Ozsan, Nazan; Gurel, Duygu; Veral, Ali

    2013-05-01

    Paraneoplastic cerebellar degeneration is a rare non-metastatic complication of malignancies. It presents with acute or subacute onset of ataxia, dysarthria and intention tremor. Paraneoplastic cerebellar degeneration is most commonly associated with malignancies of the ovary, breast and lung. The anti-Yo (anti-Purkinje cells) antibodies that specifically damage the Purkinje cells of the cerebellum are found in the serum and cerebrospinal fluid. Anti-Yo-related paraneoplastic cerebellar degeneration is most commonly found in women with gynecological and breast cancers, but it is reported in other malignancies. Patients with paraneoplastic syndromes most often present with neurologic symptoms before an underlying cancer is detected. We report a case of anti-Yo-related paraneoplastic cerebellar degeneration associated with pleural malignant mesothelioma in a 51-year-old female patient. She presented to our department with a 2-week history after the last chemotherapy of progressive dizziness related to head movement, nausea, vomiting, ataxia and unsteady gait. A western blot assay was negative for anti-Hu, anti-Ri, anti-Ma2, anti-CV2 and anti-amphiphysin paraneoplastic antibody markers but positive for anti-Yo. In conclusion, we report a case of paraneoplastic cerebellar degeneration in a patient with pleural malignant mesothelioma because of the rarity of this neurologic presentation after the diagnosis of malignant mesothelioma and of the association with anti-Yo antibodies.

  20. Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition.

    PubMed

    McCairn, Kevin W; Iriki, Atsushi; Isoda, Masaki

    2013-01-09

    Motor tics, a cardinal symptom of Tourette syndrome (TS), are hypothesized to arise from abnormalities within cerebro-basal ganglia circuits. Yet noninvasive neuroimaging of TS has previously identified robust activation in the cerebellum. To date, electrophysiological properties of cerebellar activation and its role in basal ganglia-mediated tic expression remain unknown. We performed multisite, multielectrode recordings of single-unit activity and local field potentials from the cerebellum, basal ganglia, and primary motor cortex using a pharmacologic monkey model of motor tics/TS. Following microinjections of bicuculline into the sensorimotor putamen, periodic tics occurred predominantly in the orofacial region, and a sizable number of cerebellar neurons showed phasic changes in activity associated with tic episodes. Specifically, 64% of the recorded cerebellar cortex neurons exhibited increases in activity, and 85% of the dentate nucleus neurons displayed excitatory, inhibitory, or multiphasic responses. Critically, abnormal discharges of cerebellar cortex neurons and excitatory-type dentate neurons mostly preceded behavioral tic onset, indicating their central origins. Latencies of pathological activity in the cerebellum and primary motor cortex substantially overlapped, suggesting that aberrant signals may be traveling along divergent pathways to these structures from the basal ganglia. Furthermore, the occurrence of tic movement was most closely associated with local field potential spikes in the cerebellum and primary motor cortex, implying that these structures may function as a gate to release overt tic movements. These findings indicate that tic-generating networks in basal ganglia mediated tic disorders extend beyond classical cerebro-basal ganglia circuits, leading to global network dysrhythmia including cerebellar circuits.

  1. Cerebellar Hypoplasia and Dysmorphia in Neurofibromatosis Type 1.

    PubMed

    Toelle, Sandra P; Poretti, Andrea; Weber, Peter; Seute, Tatjana; Bromberg, Jacoline E C; Scheer, Ianina; Boltshauser, Eugen

    2015-12-01

    Unidentified bright objects (UBO) and tumors are well-known cerebellar abnormalities in neurofibromatosis type 1 (NF1). Literature reports on malformative cerebellar anomalies in neurofibromatosis type 1 (NF1), however, are scant. We retrospectively studied the clinical and neuroimaging findings of 5 patients with NF1 (4 females, age 6 to 29 years at last follow-up) and cerebellar anomalies. Cerebellar symptoms on neurological examination were mild or even not evident whereas learning disabilities were more or less pronounced in four patients. Two patients had cerebellar hypoplasia (diffusely enlarged cerebellar interfoliar spaces) and three cerebellar dysmorphias involving mainly one cerebellar hemisphere. In NF1, malformative cerebellar anomalies are rare (estimated prevalence of about 1%), but most likely underestimated and easily overlooked, because physicians tend to focus on more prevalent, obvious, and well-known findings such as optic pathway gliomas, other tumors, and UBO. This kind of cerebellar anomaly in NF1 has most likely a malformative origin, but the exact pathogenesis is unknown. The individual clinical significance is difficult to determine. We suggest that cerebellar anomalies should be systematically evaluated in neuroimaging studies of NF1 patients.

  2. Inverse Stochastic Resonance in Cerebellar Purkinje Cells

    PubMed Central

    Häusser, Michael; Gutkin, Boris S.; Roth, Arnd

    2016-01-01

    Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability, and also to be involved in network phenomena such as high frequency oscillations and travelling waves. Purkinje cells exhibit type II excitability, which can be revealed by a discontinuity in their f-I curves. We show that this excitability mechanism allows Purkinje cells to be efficiently inhibited by noise of a particular variance, a phenomenon known as inverse stochastic resonance (ISR). While ISR has been described in theoretical models of single neurons, here we provide the first experimental evidence for this effect. We find that an adaptive exponential integrate-and-fire model fitted to the basic Purkinje cell characteristics using a modified dynamic IV method displays ISR and bistability between the resting state and a repetitive activity limit cycle. ISR allows the Purkinje cell to operate in different functional regimes: the all-or-none toggle or the linear filter mode, depending on the variance of the synaptic input. We propose that synaptic noise allows Purkinje cells to quickly switch between these functional regimes. Using mutual information analysis, we demonstrate that ISR can lead to a locally optimal information transfer between the input and output spike train of the Purkinje cell. These results provide the first experimental evidence for ISR and suggest a functional role for ISR in cerebellar information processing. PMID:27541958

  3. Vergence Deficits in Patients with Cerebellar Lesions

    ERIC Educational Resources Information Center

    Sander, T.; Sprenger, A.; Neumann, G.; Machner, B.; Gottschalk, S.; Rambold, H.; Helmchen, C.

    2009-01-01

    The cerebellum is part of the cortico-ponto-cerebellar circuit for conjugate eye movements. Recent animal data suggest an additional role of the cerebellum for the control of binocular alignment and disconjugate, i.e. vergence eye movements. The latter is separated into two different components: fast vergence (to step targets) and slow vergence…

  4. Improving cerebellar segmentation with statistical fusion

    NASA Astrophysics Data System (ADS)

    Plassard, Andrew J.; Yang, Zhen; Prince, Jerry L.; Claassen, Daniel O.; Landman, Bennett A.

    2016-03-01

    The cerebellum is a somatotopically organized central component of the central nervous system well known to be involved with motor coordination and increasingly recognized roles in cognition and planning. Recent work in multiatlas labeling has created methods that offer the potential for fully automated 3-D parcellation of the cerebellar lobules and vermis (which are organizationally equivalent to cortical gray matter areas). This work explores the trade offs of using different statistical fusion techniques and post hoc optimizations in two datasets with distinct imaging protocols. We offer a novel fusion technique by extending the ideas of the Selective and Iterative Method for Performance Level Estimation (SIMPLE) to a patch-based performance model. We demonstrate the effectiveness of our algorithm, Non- Local SIMPLE, for segmentation of a mixed population of healthy subjects and patients with severe cerebellar anatomy. Under the first imaging protocol, we show that Non-Local SIMPLE outperforms previous gold-standard segmentation techniques. In the second imaging protocol, we show that Non-Local SIMPLE outperforms previous gold standard techniques but is outperformed by a non-locally weighted vote with the deeper population of atlases available. This work advances the state of the art in open source cerebellar segmentation algorithms and offers the opportunity for routinely including cerebellar segmentation in magnetic resonance imaging studies that acquire whole brain T1-weighted volumes with approximately 1 mm isotropic resolution.

  5. Improving Cerebellar Segmentation with Statistical Fusion

    PubMed Central

    Plassard, Andrew J.; Yang, Zhen; Prince, Jerry L.; Claassen, Daniel O.; Landman, Bennett A.

    2016-01-01

    The cerebellum is a somatotopically organized central component of the central nervous system well known to be involved with motor coordination and increasingly recognized roles in cognition and planning. Recent work in multi-atlas labeling has created methods that offer the potential for fully automated 3-D parcellation of the cerebellar lobules and vermis (which are organizationally equivalent to cortical gray matter areas). This work explores the trade offs of using different statistical fusion techniques and post hoc optimizations in two datasets with distinct imaging protocols. We offer a novel fusion technique by extending the ideas of the Selective and Iterative Method for Performance Level Estimation (SIMPLE) to a patch-based performance model. We demonstrate the effectiveness of our algorithm, Non-Local SIMPLE, for segmentation of a mixed population of healthy subjects and patients with severe cerebellar anatomy. Under the first imaging protocol, we show that Non-Local SIMPLE outperforms previous gold-standard segmentation techniques. In the second imaging protocol, we show that Non-Local SIMPLE outperforms previous gold standard techniques but is outperformed by a non-locally weighted vote with the deeper population of atlases available. This work advances the state of the art in open source cerebellar segmentation algorithms and offers the opportunity for routinely including cerebellar segmentation in magnetic resonance imaging studies that acquire whole brain T1-weighted volumes with approximately 1 mm isotropic resolution. PMID:27127334

  6. Improving Cerebellar Segmentation with Statistical Fusion.

    PubMed

    Plassard, Andrew J; Yang, Zhen; Prince, Jerry L; Claassen, Daniel O; Landman, Bennett A

    2016-02-27

    The cerebellum is a somatotopically organized central component of the central nervous system well known to be involved with motor coordination and increasingly recognized roles in cognition and planning. Recent work in multi-atlas labeling has created methods that offer the potential for fully automated 3-D parcellation of the cerebellar lobules and vermis (which are organizationally equivalent to cortical gray matter areas). This work explores the trade offs of using different statistical fusion techniques and post hoc optimizations in two datasets with distinct imaging protocols. We offer a novel fusion technique by extending the ideas of the Selective and Iterative Method for Performance Level Estimation (SIMPLE) to a patch-based performance model. We demonstrate the effectiveness of our algorithm, Non-Local SIMPLE, for segmentation of a mixed population of healthy subjects and patients with severe cerebellar anatomy. Under the first imaging protocol, we show that Non-Local SIMPLE outperforms previous gold-standard segmentation techniques. In the second imaging protocol, we show that Non-Local SIMPLE outperforms previous gold standard techniques but is outperformed by a non-locally weighted vote with the deeper population of atlases available. This work advances the state of the art in open source cerebellar segmentation algorithms and offers the opportunity for routinely including cerebellar segmentation in magnetic resonance imaging studies that acquire whole brain T1-weighted volumes with approximately 1 mm isotropic resolution.

  7. Neurochemical, pharmacological, and developmental studies on cerebellar receptors for dicarboxylic amino acids

    SciTech Connect

    Sharif, N.A.; Roberts, P.J.

    1984-01-01

    Specific binding of L-(/sup 3/H)glutamate ((/sup 3/H)Glu) and L(/sup 3/H)Asp) to cerebellar membranes represented a time-, temperature-, pH- and protein-dependent interaction which was both saturable and reversible. Binding sites for both radioligands appeared maximally enriched in synaptosomal fractions isolated by gradient centrifugation. Kinetically derived dissociation constant (K/sub off//K/sub on/ . K/sub d/) for (/sup 3/H)Glu binding to this fraction indicated high-affinity (433 nM). Competition experiments employing analogs of excitatory amino acids, including new antagonists, helped identify binding sites for (/sup 3/H)Glu and (/sup 3/H)Asp as receptors with differential pharmacological specificities. Membrane freezing reduced numbers of both receptor types, but binding activity could be recovered partially by incubation at 37 degrees C. Glu receptors exhibited a pronounced deleterious sensitivity to thiol modifying reagents and L-Glu (50-1000 microM) provided protection against these compounds during co-incubation with cerebellar membranes. It is suggested that cold storage may induce partially reversible receptor inactivation by promoting sulfhydryl group/bond modification. Rat cerebellar glutamatergic function (endogenous Glu content, Glu uptake and receptor sites) exhibited an apparent ontogenetic peak between days 8-12 postpartum with a plateauing profile from day 30 to adulthood. The accelerated development (days 8-12) coincides with the first demonstrable Glu release and kainic acid neurotoxicity, as described previously.

  8. Improved segmentation of cerebellar structures in children

    PubMed Central

    Narayanan, Priya Lakshmi; Boonazier, Natalie; Warton, Christopher; Molteno, Christopher D; Joseph, Jesuchristopher; Jacobson, Joseph L; Jacobson, Sandra W; Zöllei, Lilla; Meintjes, Ernesta M

    2016-01-01

    Background Consistent localization of cerebellar cortex in a standard coordinate system is important for functional studies and detection of anatomical alterations in studies of morphometry. To date, no pediatric cerebellar atlas is available. New method The probabilistic Cape Town Pediatric Cerebellar Atlas (CAPCA18) was constructed in the age-appropriate National Institute of Health Pediatric Database asymmetric template space using manual tracings of 16 cerebellar compartments in 18 healthy children (9–13 years) from Cape Town, South Africa. The individual atlases of the training subjects were also used to implement multi atlas label fusion using multi atlas majority voting (MAMV) and multi atlas generative model (MAGM) approaches. Segmentation accuracy in 14 test subjects was compared for each method to ‘gold standard’ manual tracings. Results Spatial overlap between manual tracings and CAPCA18 automated segmentation was 73% or higher for all lobules in both hemispheres, except VIIb and X. Automated segmentation using MAGM yielded the best segmentation accuracy over all lobules (mean Dice Similarity Coefficient 0.76; range 0.55–0.91). Comparison with existing methods In all lobules, spatial overlap of CAPCA18 segmentations with manual tracings was similar or higher than those obtained with SUIT (spatially unbiased infra-tentorial template), providing additional evidence of the benefits of an age appropriate atlas. MAGM segmentation accuracy was comparable to values reported recently by Park et al. (2014) in adults (across all lobules mean DSC = 0.73, range 0.40–0.89). Conclusions CAPCA18 and the associated multi atlases of the training subjects yield improved segmentation of cerebellar structures in children. PMID:26743973

  9. Reversal of reduced parvalbumin neurons in hippocampus and amygdala of Angelman syndrome model mice by chronic treatment of fluoxetine.

    PubMed

    Godavarthi, Swetha K; Sharma, Ankit; Jana, Nihar Ranjan

    2014-08-01

    Angelman syndrome (AS) is a neuropsychiatric disorder characterized by autism, intellectual disability and motor disturbances. The disease is primarily caused by the loss of function of maternally inherited UBE3A. Ube3a maternal-deficient mice recapitulates many essential feature of AS. These AS mice have been shown to be under chronic stress and exhibits anxiety-like behaviour because of defective glucocorticoid receptor signalling. Here, we demonstrate that chronic stress in these mice could lead to down-regulation of parvalbumin-positive interneurons in the hippocampus and basolateral amygdala from early post-natal days. Down-regulation of parvalbumin-positive interneurons number could be because of decrease in the expression of parvalbumin in these neurons. We also find that treatment with fluoxetine, a selective serotonin reuptake inhibitor, results in restoration of impaired glucocorticoid signalling, elevated serum corticosterone level, parvalbumin-positive interneurons and anxiety-like behaviours. Our findings suggest that impaired glucocorticod signalling in hippocampus and amygdala of AS mice is critical for the decrease in parvalbumin interneurons number, emergence of anxiety and other behavioural deficits and highlights the importance of fluoxetine in the recovery of these abnormalities.

  10. Possible Therapeutic Doses of Cannabinoid Type 1 Receptor Antagonist Reverses Key Alterations in Fragile X Syndrome Mouse Model

    PubMed Central

    Gomis-González, Maria; Busquets-Garcia, Arnau; Matute, Carlos; Maldonado, Rafael; Mato, Susana; Ozaita, Andrés

    2016-01-01

    Fragile X syndrome (FXS) is the most common monogenetic cause of intellectual disability. The cognitive deficits in the mouse model for this disorder, the Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mouse, have been restored by different pharmacological approaches, among those the blockade of cannabinoid type 1 (CB1) receptor. In this regard, our previous study showed that the CB1 receptor antagonist/inverse agonist rimonabant normalized a number of core features in the Fmr1 knockout mouse. Rimonabant was commercialized at high doses for its anti-obesity properties, and withdrawn from the market on the bases of mood-related adverse effects. In this study we show, by using electrophysiological approaches, that low dosages of rimonabant (0.1 mg/kg) manage to normalize metabotropic glutamate receptor dependent long-term depression (mGluR-LTD). In addition, low doses of rimonabant (from 0.01 mg/kg) equally normalized the cognitive deficit in the mouse model of FXS. These doses of rimonabant were from 30 to 300 times lower than those required to reduce body weight in rodents and to presumably produce adverse effects in humans. Furthermore, NESS0327, a CB1 receptor neutral antagonist, was also effective in preventing the novel object-recognition memory deficit in Fmr1 KO mice. These data further support targeting CB1 receptors as a relevant therapy for FXS. PMID:27589806

  11. Impaired adult hippocampal neurogenesis and its partial reversal by chronic treatment of fluoxetine in a mouse model of Angelman syndrome.

    PubMed

    Godavarthi, Swetha K; Dey, Parthanarayan; Sharma, Ankit; Jana, Nihar Ranjan

    2015-09-04

    Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe cognitive and motor deficits, caused by the loss of function of maternally inherited Ube3a. Ube3a-maternal deficient mice (AS model mice) recapitulate many essential features of AS, but how the deficiency of Ube3a lead to such behavioural abnormalities is poorly understood. Here we have demonstrated significant impairment of adult hippocampal neurogenesis in AS mice brain. Although, the number of BrdU and Ki67-positive cell in the hippocampal DG region was nearly equal at early postnatal days among wild type and AS mice, they were significantly reduced in adult AS mice compared to wild type controls. Reduced number of doublecortin-positive immature neurons in this region of AS mice further indicated impaired neurogenesis. Unaltered BrdU and Ki67-positive cells number in the sub ventricular zone of adult AS mice brain along with the absence of imprinted expression of Ube3a in the neural progenitor cell suggesting that Ube3a may not be directly linked with altered neurogenesis. Finally, we show that the impaired hippocampal neurogenesis in these mice can be partially rescued by the chronic treatment of antidepressant fluoxetine. These results suggest that the chronic stress may lead to reduced hippocampal neurogenesis in AS mice and that impaired neurogenesis could contribute to cognitive disturbances observed in these mice.

  12. Cerebello-cortical heterotopia in dentate nucleus, and other microdysgeneses in trisomy D1 (Patau) syndrome.

    PubMed

    Hori, A; Peiffer, J; Pfeiffer, R A; Iizuka, R

    1980-01-01

    Several new histological findings in six cases of the trisomy D1 syndrome are described: hyperplasia of fetal structures (indusium griseum, median raphe of the medulla oblongata) and completely developed cerebellar cortical heterotopia in the dentate nucleus. In one case, a heterotopic pontine nucleus was found within the cerebellar white matter. The coexistence of overdeveloped and remaining fetal structures is emphasized. Several hypotheses regarding cerebellar dysgenesis are discussed.

  13. [Compression of the inferior cerebellar artery-induced compression of the medulla oblongata in Arnold-Chiari malformation as a cause of essential hypertension].

    PubMed

    Makhmudov, U V; Salalykin, V I; Shimanskiĭ, V N; Taniashin, S V; Sidorkin, D V

    2001-01-01

    Cerebrovascular abnormalities (primarily looping of cerebellar arteries) are almost without exception concurrent with the Arnold-Chiari syndrome and hydrocephalus. Persistent essential hypertension may be a manifestation of pathological vessel-brain contact. Customary microvascular decompression may lead to blood pressure stabilization in the postoperative period for a long time. The paper presents a clinical case of a 52-year female patient with the Arnold-Chiari syndrome who underwent microvascular decompression of the left posterior inferior cerebellar artery at the level of the medulla oblongata. Surgical treatment regressed preoperative cerebellar, bulbar, and truncal symptoms, lowered blood pressure from 190/100 to 120/80 mm Hg, and stabilized it at this level.

  14. Reversing the reduced level of endometrial GLUT4 expression in polycystic ovary syndrome: a mechanistic study of metformin action

    PubMed Central

    Li, Xin; Cui, Peng; Jiang, Hong-Yuan; Guo, Yan-Rong; Pishdari, Bano; Hu, Min; Feng, Yi; Billig, Håkan; Shao, Ruijin

    2015-01-01

    Conflicting results have been reported regarding whether or not insulin-regulated glucose transporter 4 (GLUT4) is expressed in human and rodent endometria. There is an inverse relationship between androgen levels and insulin-dependent glucose metabolism in women. Hyperandrogenemia, hyperinsulinemia, and insulin resistance are believed to contribute to endometrial abnormalities in women with polycystic ovary syndrome (PCOS). However, it has been unclear in previous studies if endometrial GLUT4 expression is regulated by androgen-dependent androgen receptors (ARs) and/or the insulin receptor/Akt/mTOR signaling network. In this study, we demonstrate that GLUT4 is expressed in normal endometrial cells (mainly in the epithelial cells) and is down-regulated under conditions of hyperandrogenemia in tissues from PCOS patients and in a 5α-dihydrotestosterone-induced PCOS-like rat model. Western blot analysis revealed reduced endometrial GLUT4 expression and increased AR expression in PCOS patients. However, the reduced GLUT4 level was not always associated with an increase in AR in PCOS patients when comparing non-hyperplasia with hyperplasia. Using a human tissue culture system, we investigated the molecular basis by which GLUT4 regulation in endometrial hyperplasia tissues is affected by metformin in PCOS patients. We show that specific endogenous organic cation transporter isoforms are regulated by metformin, and this suggests a direct effect of metformin on endometrial hyperplasia. Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues. These findings indicate that changes in endometrial GLUT4 expression in PCOS patients involve the androgen-dependent alteration of AR expression and changes in the insulin receptor/PI3K/Akt/mTOR signaling network. PMID:26045896

  15. Reversing the reduced level of endometrial GLUT4 expression in polycystic ovary syndrome: a mechanistic study of metformin action.

    PubMed

    Li, Xin; Cui, Peng; Jiang, Hong-Yuan; Guo, Yan-Rong; Pishdari, Bano; Hu, Min; Feng, Yi; Billig, Håkan; Shao, Ruijin

    2015-01-01

    Conflicting results have been reported regarding whether or not insulin-regulated glucose transporter 4 (GLUT4) is expressed in human and rodent endometria. There is an inverse relationship between androgen levels and insulin-dependent glucose metabolism in women. Hyperandrogenemia, hyperinsulinemia, and insulin resistance are believed to contribute to endometrial abnormalities in women with polycystic ovary syndrome (PCOS). However, it has been unclear in previous studies if endometrial GLUT4 expression is regulated by androgen-dependent androgen receptors (ARs) and/or the insulin receptor/Akt/mTOR signaling network. In this study, we demonstrate that GLUT4 is expressed in normal endometrial cells (mainly in the epithelial cells) and is down-regulated under conditions of hyperandrogenemia in tissues from PCOS patients and in a 5α-dihydrotestosterone-induced PCOS-like rat model. Western blot analysis revealed reduced endometrial GLUT4 expression and increased AR expression in PCOS patients. However, the reduced GLUT4 level was not always associated with an increase in AR in PCOS patients when comparing non-hyperplasia with hyperplasia. Using a human tissue culture system, we investigated the molecular basis by which GLUT4 regulation in endometrial hyperplasia tissues is affected by metformin in PCOS patients. We show that specific endogenous organic cation transporter isoforms are regulated by metformin, and this suggests a direct effect of metformin on endometrial hyperplasia. Moreover, we demonstrate that metformin induces GLUT4 expression and inhibits AR expression and blocks insulin receptor/PI3K/Akt/mTOR signaling in the same hyperplasia human tissues. These findings indicate that changes in endometrial GLUT4 expression in PCOS patients involve the androgen-dependent alteration of AR expression and changes in the insulin receptor/PI3K/Akt/mTOR signaling network.

  16. Low-Dose IL-17 Therapy Prevents and Reverses Diabetic Nephropathy, Metabolic Syndrome, and Associated Organ Fibrosis

    PubMed Central

    Mohamed, Riyaz; Jayakumar, Calpurnia; Chen, Feng; Fulton, David; Stepp, David; Gansevoort, Ron T.

    2016-01-01

    Diabetes is the leading cause of kidney failure, accounting for >45% of new cases of dialysis. Diabetic nephropathy is characterized by inflammation, fibrosis, and oxidant stress, pathologic features that are shared by many other chronic inflammatory diseases. The cytokine IL-17A was initially implicated as a mediator of chronic inflammatory diseases, but recent studies dispute these findings and suggest that IL-17A can favorably modulate inflammation. Here, we examined the role of IL-17A in diabetic nephropathy. We observed that IL-17A levels in plasma and urine were reduced in patients with advanced diabetic nephropathy. Type 1 diabetic mice that are genetically deficient in IL-17A developed more severe nephropathy, whereas administration of low-dose IL-17A prevented diabetic nephropathy in models of type 1 and type 2 diabetes. Moreover, IL-17A administration effectively treated, prevented, and reversed established nephropathy in genetic models of diabetes. Protective effects were also observed after administration of IL-17F but not IL-17C or IL-17E. Notably, tubular epithelial cell-specific overexpression of IL-17A was sufficient to suppress diabetic nephropathy. Mechanistically, IL-17A administration suppressed phosphorylation of signal transducer and activator of transcription 3, a central mediator of fibrosis, upregulated anti-inflammatory microglia/macrophage WAP domain protein in an AMP-activated protein kinase–dependent manner and favorably modulated renal oxidative stress and AMP-activated protein kinase activation. Administration of recombinant microglia/macrophage WAP domain protein suppressed diabetes-induced albuminuria and enhanced M2 marker expression. These observations suggest that the beneficial effects of IL-17 are isoform-specific and identify low-dose IL-17A administration as a promising therapeutic approach in diabetic kidney disease. PMID:26334030

  17. Low-Dose IL-17 Therapy Prevents and Reverses Diabetic Nephropathy, Metabolic Syndrome, and Associated Organ Fibrosis.

    PubMed

    Mohamed, Riyaz; Jayakumar, Calpurnia; Chen, Feng; Fulton, David; Stepp, David; Gansevoort, Ron T; Ramesh, Ganesan

    2016-03-01

    Diabetes is the leading cause of kidney failure, accounting for >45% of new cases of dialysis. Diabetic nephropathy is characterized by inflammation, fibrosis, and oxidant stress, pathologic features that are shared by many other chronic inflammatory diseases. The cytokine IL-17A was initially implicated as a mediator of chronic inflammatory diseases, but recent studies dispute these findings and suggest that IL-17A can favorably modulate inflammation. Here, we examined the role of IL-17A in diabetic nephropathy. We observed that IL-17A levels in plasma and urine were reduced in patients with advanced diabetic nephropathy. Type 1 diabetic mice that are genetically deficient in IL-17A developed more severe nephropathy, whereas administration of low-dose IL-17A prevented diabetic nephropathy in models of type 1 and type 2 diabetes. Moreover, IL-17A administration effectively treated, prevented, and reversed established nephropathy in genetic models of diabetes. Protective effects were also observed after administration of IL-17F but not IL-17C or IL-17E. Notably, tubular epithelial cell-specific overexpression of IL-17A was sufficient to suppress diabetic nephropathy. Mechanistically, IL-17A administration suppressed phosphorylation of signal transducer and activator of transcription 3, a central mediator of fibrosis, upregulated anti-inflammatory microglia/macrophage WAP domain protein in an AMP-activated protein kinase-dependent manner and favorably modulated renal oxidative stress and AMP-activated protein kinase activation. Administration of recombinant microglia/macrophage WAP domain protein suppressed diabetes-induced albuminuria and enhanced M2 marker expression. These observations suggest that the beneficial effects of IL-17 are isoform-specific and identify low-dose IL-17A administration as a promising therapeutic approach in diabetic kidney disease.

  18. Evaluation of Flinders Technology Associates cards for collection and transport of samples for detection of Porcine reproductive and respiratory syndrome virus by reverse transcription polymerase chain reaction.

    PubMed

    Linhares, Daniel C L; Rovira, Albert; Torremorell, Montserrat

    2012-03-01

    Blood, tissue and oral fluid samples collected from experimentally infected animals and field cases were used to evaluate the safety, diagnostic sensitivity and specificity of Flinders Technology Associates (FTA) cards for Porcine reproductive and respiratory syndrome virus (PRRSV) reverse transcription polymerase chain reaction (RT-PCR) diagnostics. The analytical sensitivity of PRRSV RT-PCR from serum and oral fluids in FTA cards was reduced, although the virus could still be detected at concentrations of 10(1) and 10(3) TCID/ml, respectively. The sensitivity and specificity of PRRSV RT-PCR detection from serum, blood, and tissue samples in cards collected from experimentally infected animals were 100%. Sensitivity for oral fluids was 45% (95% CI: 19.97-73.01) compared to fresh. For field samples, sensitivity was 89% (95% CI: 77.35-95.63) and 100% (95% CI: 80.00-100) for serum and lung samples, respectively. The sensitivity was the same for samples stored in cards at room temperature or at 4ºC, and tested overnight or after 14 days. Cards inoculated with PRRSV-positive samples did not yield replicating virus after cell culture. In conclusion, FTA cards proved to be a safe, simple, and sensitive alternative method to transport serum, blood, and tissue samples for PRRSV RT-PCR diagnostics; however, a significant decrease in RT-PCR sensitivity should be expected from oral fluid samples.

  19. Clinical validation of 3 commercial real-time reverse transcriptase polymerase chain reaction assays for the detection of Middle East respiratory syndrome coronavirus from upper respiratory tract specimens.

    PubMed

    Mohamed, Deqa H; AlHetheel, AbdulKarim F; Mohamud, Hanat S; Aldosari, Kamel; Alzamil, Fahad A; Somily, Ali M

    2017-04-01

    Since discovery of Middle East respiratory syndrome coronavirus (MERS-CoV), a novel betacoronavirus first isolated and characterized in 2012, MERS-CoV real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assays represent one of the most rapidly expanding commercial tests. However, in the absence of extensive evaluations of these assays on positive clinical material of different sources, evaluating their diagnostic effectiveness remains challenging. We describe the diagnostic performance evaluation of 3 common commercial MERS-CoV rRT-PCR assays on a large panel (n = 234) of upper respiratory tract specimens collected during an outbreak episode in Saudi Arabia. Assays were compared to the RealStar® MERS-CoV RT-PCR (Alton Diagnostics, Hamburg, Germany) assay as the gold standard. Results showed i) the TIB MolBiol® LightMix UpE and Orf1a assays (TIB MolBiol, Berlin, Germany) to be the most sensitive, followed by ii) the Anyplex™ Seegene MERS-CoV assay (Seegene, Seoul, Korea), and finally iii) the PrimerDesign™ Genesig® HCoV_2012 assay (PrimerDesign, England, United Kingdom). We also evaluate a modified protocol for the PrimerDesign™ Genesig® HCoV_2012 assay.

  20. Aging is a simple deprivation syndrome driven by a quasi-programmed preventable and reversible drift of control system set points due to inappropriate organism-environment interaction.

    PubMed

    Khalyavkin, A V; Krutko, V N

    2014-10-01

    There are two well-known but opposing concepts of the reason for aging. The first supposes that senescence is programmed similarly to the genetic program of development from a zygote up to a mature organism. Genetically determined senile wasting is thought to be associated with the necessity to renovate the population to ensure its adaptation and survival. According to the concept of the stochastic aging (due to accumulation of occasional error and damage), there is no built-in program of aging. There is only a program of development up to the state of maturity, and then the organism should be able to maintain itself limitlessly. However, although the efficiency of repair systems is assumed to be rather high, it is less than 100%. Just this has to result in aging because of accumulation of various errors. We have continued and developed another approach that considers both programmed and stochastic concepts to be incorrect. Aging is a simple deprivation syndrome driven by preventable and even reversible drifts of control systems set points because of an inappropriate "organism-environment" interaction.

  1. Porcine reproductive and respiratory syndrome virus: interlaboratory ring trial to evaluate real-time reverse transcription polymerase chain reaction detection methods.

    PubMed

    Wernike, Kerstin; Bonilauri, Paolo; Dauber, Malte; Errington, Jane; LeBlanc, Neil; Revilla-Fernández, Sandra; Hjulsager, Charlotte; Isaksson, Mats; Stadejek, Tomasz; Beer, Martin; Hoffmann, Bernd

    2012-09-01

    To compare the real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays used for the diagnosis of Porcine reproductive and respiratory syndrome virus (PRRSV), a Europe-wide interlaboratory ring trial was conducted. A variety of PRRSV strains including North American (NA) and European (EU) genotype isolates were analyzed by the participants. Great differences regarding qualitative diagnostics as well as analytical sensitivity were observed between the individual RT-qPCR systems, especially when investigating strains from the EU genotype. None of the assays or commercial kits used in the ring trial could identify all different PRRSV strains with an optimal analytical and diagnostic sensitivity. The genetic variability of the PRRSV strains, which is supposed to hinder the diagnostic of the RT-PCR because of mutations at the primer binding sites, was also confirmed by sequencing and subsequent phylogenetic analysis. In summary, a major problem in PRRSV diagnostics by RT-qPCR is false-negative results. To achieve maximum safety in the molecular diagnosis of PRRSV, the combined usage of different assays or kits is highly recommended.

  2. A probabilistic atlas of the cerebellar white matter.

    PubMed

    van Baarsen, K M; Kleinnijenhuis, M; Jbabdi, S; Sotiropoulos, S N; Grotenhuis, J A; van Cappellen van Walsum, A M

    2016-01-01

    Imaging of the cerebellar cortex, deep cerebellar nuclei and their connectivity are gaining attraction, due to the important role the cerebellum plays in cognition and motor control. Atlases of the cerebellar cortex and nuclei are used to locate regions of interest in clinical and neuroscience studies. However, the white matter that connects these relay stations is of at least similar functional importance. Damage to these cerebellar white matter tracts may lead to serious language, cognitive and emotional disturbances, although the pathophysiological mechanism behind it is still debated. Differences in white matter integrity between patients and controls might shed light on structure-function correlations. A probabilistic parcellation atlas of the cerebellar white matter would help these studies by facilitating automatic segmentation of the cerebellar peduncles, the localization of lesions and the comparison of white matter integrity between patients and controls. In this work a digital three-dimensional probabilistic atlas of the cerebellar white matter is presented, based on high quality 3T, 1.25mm resolution diffusion MRI data from 90 subjects participating in the Human Connectome Project. The white matter tracts were estimated using probabilistic tractography. Results over 90 subjects were symmetrical and trajectories of superior, middle and inferior cerebellar peduncles resembled the anatomy as known from anatomical studies. This atlas will contribute to a better understanding of cerebellar white matter architecture. It may eventually aid in defining structure-function correlations in patients with cerebellar disorders.

  3. Mobious syndrome: MR findings

    PubMed Central

    Srinivas, Maskal Revanna; Vaishali, Dhulappa Mudabasappagol; Vedaraju, Kadaba Shamachar; Nagaraj, Bangalore Rangaswamy

    2016-01-01

    Möbius syndrome is an extremely rare congenital disorder. We report a case of Möbius syndrome in a 2-year-old girl with bilateral convergent squint and left-sided facial weakness. The characteristic magnetic resonance imaging (MRI) findings of Möbius syndrome, which include absent bilateral abducens nerves and absent left facial nerve, were noted. In addition, there was absence of left anterior inferior cerebellar artery (AICA) and absence of bilateral facial colliculi. Clinical features, etiology, and imaging findings are discussed. PMID:28104946

  4. Structural cerebellar correlates of cognitive and motor dysfunctions in cerebellar degeneration.

    PubMed

    Kansal, Kalyani; Yang, Zhen; Fishman, Ann M; Sair, Haris I; Ying, Sarah H; Jedynak, Bruno M; Prince, Jerry L; Onyike, Chiadi U

    2017-03-01

    See King et al. (doi:10.1093/aww348) for a scientific commentary on this article.Detailed mapping of clinical dysfunctions to the cerebellar lobules in disease populations is necessary to establish the functional significance of lobules implicated in cognitive and motor functions in normal subjects. This study constitutes the first quantitative examination of the lobular correlates of a broad range of cognitive and motor phenomena in cerebellar disease. We analysed cross-sectional data from 72 cases with cerebellar disease and 36 controls without cerebellar disease. Cerebellar lobule volumes were derived from a graph-cut based segmentation algorithm. Sparse partial least squares, a variable selection approach, was used to identify lobules associated with motor function, language, executive function, memory, verbal learning, perceptual organization and visuomotor coordination. Motor dysfunctions were chiefly associated with the anterior lobe and posterior lobule HVI. Confrontation naming, noun fluency, recognition, and perceptual organization did not have cerebellar associations. Verb and phonemic fluency, working memory, cognitive flexibility, immediate and delayed recall, verbal learning, and visuomotor coordination were variably associated with HVI, Crus I, Crus II, HVII B and/or HIX. Immediate and delayed recall also showed associations with the anterior lobe. These findings provide preliminary anatomical evidence for a functional topography of the cerebellum first defined in task-based functional magnetic resonance imaging studies of normal subjects and support the hypotheses that (i) cerebellar efferents target frontal lobe neurons involved in forming action representations and new search strategies; (ii) there is greater involvement of the cerebellum when immediate recall tasks involve more complex verbal stimuli (e.g. longer words versus digits); and (iii) it is involved in spontaneous retrieval of long-term memory. More generally, they provide an anatomical

  5. A neural model of cerebellar learning for arm movement control: cortico-spino-cerebellar dynamics.

    PubMed

    Contreras-Vidal, J L; Grossberg, S; Bullock, D

    1997-01-01

    A neural network model of opponent cerebellar learning for arm movement control is proposed. The model illustrates how a central pattern generator in cortex and basal ganglia, a neuromuscular force controller in spinal cord, and an adaptive cerebellum cooperate to reduce motor variability during multijoint arm movements using mono- and bi-articular muscles. Cerebellar learning modifies velocity commands to produce phasic antagonist bursts at interpositus nucleus cells whose feed-forward action overcomes inherent limitations of spinal feedback control of tracking. Excitation of alpha motoneuron pools, combined with inhibition of their Renshaw cells by the cerebellum, facilitate movement initiation and optimal execution. Transcerebellar pathways are opened by learning through long-term depression (LTD) of parallel fiber-Purkinje cell synapses in response to conjunctive stimulation of parallel fibers and climbing fiber discharges that signal muscle stretch errors. The cerebellar circuitry also learns to control opponent muscles pairs, allowing cocontraction and reciprocal inhibition of muscles. Learning is stable, exhibits load compensation properties, and generalizes better across movement speeds if motoneuron pools obey the size principle. The intermittency of climbing fiber discharges maintains stable learning. Long-term potentiation (LTP) in response to uncorrelated parallel fiber signals enables previously weakened synapses to recover. Loss of climbing fibers, in the presence of LTP, can erode normal opponent signal processing. Simulated lesions of the cerebellar network reproduce symptoms of cerebellar disease, including sluggish movement onsets, poor execution of multijoint plans, and abnormally prolonged endpoint oscillations.

  6. A toolbox to visually explore cerebellar shape changes in cerebellar disease and dysfunction

    NASA Astrophysics Data System (ADS)

    Abulnaga, S. Mazdak; Yang, Zhen; Carass, Aaron; Kansal, Kalyani; Jedynak, Bruno M.; Onyike, Chiadi U.; Ying, Sarah H.; Prince, Jerry L.

    2016-03-01

    The cerebellum plays an important role in motor control and is also involved in cognitive processes. Cerebellar function is specialized by location, although the exact topographic functional relationship is not fully understood. The spinocerebellar ataxias are a group of neurodegenerative diseases that cause regional atrophy in the cerebellum, yielding distinct motor and cognitive problems. The ability to study the region-specific atrophy patterns can provide insight into the problem of relating cerebellar function to location. In an effort to study these structural change patterns, we developed a toolbox in MATLAB to provide researchers a unique way to visually explore the correlation between cerebellar lobule shape changes and function loss, with a rich set of visualization and analysis modules. In this paper, we outline the functions and highlight the utility of the toolbox. The toolbox takes as input landmark shape representations of subjects' cerebellar substructures. A principal component analysis is used for dimension reduction. Following this, a linear discriminant analysis and a regression analysis can be performed to find the discriminant direction associated with a specific disease type, or the regression line of a specific functional measure can be generated. The characteristic structural change pattern of a disease type or of a functional score is visualized by sampling points on the discriminant or regression line. The sampled points are used to reconstruct synthetic cerebellar lobule shapes. We showed a few case studies highlighting the utility of the toolbox and we compare the analysis results with the literature.

  7. Crossed Cerebellar Atrophy of the Lateral Cerebellar Nucleus in an Endothelin-1-Induced, Rodent Model of Ischemic Stroke

    PubMed Central

    Chan, Hugh H.; Cooperrider, Jessica L.; Park, Hyun-Joo; Wathen, Connor A.; Gale, John T.; Baker, Kenneth B.; Machado, Andre G.

    2017-01-01

    Crossed cerebellar diaschisis (CCD) is a functional deficit of the cerebellar hemisphere resulting from loss of afferent input consequent to a lesion of the contralateral cerebral hemisphere. It is manifested as a reduction of metabolism and blood flow and, depending on severity and duration, it can result in atrophy, a phenomenon known as crossed cerebellar atrophy (CCA). While CCA has been well-demonstrated in humans, it remains poorly characterized in animal models of stroke. In this study we evaluated the effects of cerebral cortical ischemia on contralateral cerebellar anatomy using an established rodent model of chronic stroke. The effects of cortical ischemia on the cerebellar hemispheres, vermis and deep nuclei were characterized. Intracortical microinjections of endothelin-1 (ET-1) were delivered to the motor cortex of Long Evans rats to induce ischemic stroke, with animals sacrificed 6 weeks later. Naive animals served as controls. Cerebral sections and cerebellar sections including the deep nuclei were prepared for analysis with Nissl staining. Cortical ischemia was associated with significant thickness reduction of the molecular layer at the Crus 1 and parafloccular lobule (PFL), but not in fourth cerebellar lobule (4Cb), as compared to the ipsilesional cerebellar hemisphere. A significant reduction in volume and cell density of the lateral cerebellar nucleus (LCN), the rodent correlate of the dentate nucleus, was also noted. The results highlight the relevance of corticopontocerebellar (CPC) projections for cerebellar metabolism and function, including its direct projections to the LCN. PMID:28261086

  8. Cerebellar Dysfunction in a Patient with HIV.

    PubMed

    Gonzalez-Ibarra, Fernando; Abdul, Waheed; Eivaz-Mohammadi, Sahar; Foscue, Christopher; Gongireddy, Srinivas; Syed, Amer

    2014-01-01

    A 50-year-old AIDS patient with a CD4 T-cell count of 114/mm(3) was admitted with cerebellar symptoms of left CN XI weakness, wide-based gait with left-sided dysmetria, abnormal heel-knee-shin test, and dysdiadochokinesia. MRI showed region of hyperintensity in the left inferior cerebellar hemisphere involving the cortex and underlying white matter. Serological tests for HSV1, HSV2, and syphilis were negative. Her CSF contained high protein content and a WBC of 71/mm(3), predominantly lymphocytes. The CSF was also negative for cryptococcal antigen and VDRL. CSF culture did not grow microbes. CSF PCR assay was negative for HSV1 and HSV2 but was positive for JC virus (1,276 copies). The most likely diagnosis is granule cell neuronopathy (GCN), which can only be definitively confirmed with biopsy and immunohistochemistry.

  9. Marijuana alters the human cerebellar clock.

    PubMed

    O'Leary, Daniel S; Block, Robert I; Turner, Beth M; Koeppel, Julie; Magnotta, Vincent A; Ponto, Laura Boles; Watkins, G Leonard; Hichwa, Richard D; Andreasen, Nancy C

    2003-06-11

    The effects of marijuana on brain perfusion and internal timing were assessed using [15O] water PET in occasional and chronic users. Twelve volunteers who smoked marijuana recreationally about once weekly, and 12 volunteers who smoked daily for a number of years performed a self-paced counting task during PET imaging, before and after smoking marijuana and placebo cigarettes. Smoking marijuana increased rCBF in the ventral forebrain and cerebellar cortex in both groups, but resulted in significantly less frontal lobe activation in chronic users. Counting rate increased after smoking marijuana in both groups, as did a behavioral measure of self-paced tapping, and both increases correlated with rCBF in the cerebellum. Smoking marijuana appears to accelerate a cerebellar clock altering self-paced behaviors.

  10. The visuospatial functions in children after cerebellar low-grade astrocytoma surgery: A contribution to the pediatric neuropsychology of the cerebellum.

    PubMed

    Starowicz-Filip, Anna; Chrobak, Adrian Andrzej; Milczarek, Olga; Kwiatkowski, Stanisław

    2015-12-07

    The aim of this study was to specify whether cerebellar lesions cause visuospatial impairments in children. The study sample consisted of 40 children with low-grade cerebellar astrocytoma, who underwent surgical treatment and 40 healthy controls matched with regard to age and sex. Visuospatial abilities were tested using the spatial WISC-R subtests (Block Design and Object Assembly), Rey-Osterrieth Complex Figure, Benton Judgment of Line Orientation Test, PEBL Mental Rotation Task, and Benton Visual Retention Test. To exclude general diffuse intellectual dysfunction, the WISC-R Verbal Intelligence IQ, Performance IQ, and Full-Scale IQ scores were analysed. Post-surgical medical consequences were measured with the International Cooperative Ataxia Rating Scale. Compared to controls, the cerebellar group manifested problems with mental rotation of objects, visuospatial organization, planning, and spatial construction processes which could not be explained by medical complications or general intellectual retardation. The intensity of visuospatial syndrome highly depends on cerebellar lesion side. Patients with left-sided cerebellar lesions display more severe spatial problems than those with right-sided cerebellar lesions. In conclusion, focal cerebellar lesions in children affect their visuospatial ability. The impairments profile is characterized by deficits in complex spatial processes such as visuospatial organization and mental rotation, requiring reconstruction of visual stimuli using the imagination, while elementary sensory analysis and perception as well as spatial processes requiring direct manipulation of objects are relatively better preserved. This pattern is analogous to the one previously observed in adult population and appears to be typical for cerebellar pathology in general, regardless of age.

  11. Cerebellar secretin modulates eyeblink classical conditioning

    PubMed Central

    Fuchs, Jason R.; Robinson, Gain M.; Dean, Aaron M.; Schoenberg, Heidi E.; Williams, Michael R.; Morielli, Anthony D.

    2014-01-01

    We have previously shown that intracerebellar infusion of the neuropeptide secretin enhances the acquisition phase of eyeblink conditioning (EBC). Here, we sought to test whether endogenous secretin also regulates EBC and to test whether the effect of exogenous and endogenous secretin is specific to acquisition. In Experiment 1, rats received intracerebellar infusions of the secretin receptor antagonist 5-27 secretin or vehicle into the lobulus simplex of cerebellar cortex immediately prior to sessions 1–3 of acquisition. Antagonist-infused rats showed a reduction in the percentage of eyeblink CRs compared with vehicle-infused rats. In Experiment 2, rats received intracerebellar infusions of secretin or vehicle immediately prior to sessions 1–2 of extinction. Secretin did not significantly affect extinction performance. In Experiment 3, rats received intracerebellar infusions of 5-27 secretin or vehicle immediately prior to sessions 1–2 of extinction. The secretin antagonist did not significantly affect extinction performance. Together, our current and previous results indicate that both exogenous and endogenous cerebellar secretin modulate acquisition, but not extinction, of EBC. We have previously shown that (1) secretin reduces surface expression of the voltage-gated potassium channel α-subunit Kv1.2 in cerebellar cortex and (2) intracerebellar infusions of a Kv1.2 blocker enhance EBC acquisition, much like secretin. Kv1.2 is almost exclusively expressed in cerebellar cortex at basket cell–Purkinje cell pinceaus and Purkinje cell dendrites; we propose that EBC-induced secretin release from PCs modulates EBC acquisition by reducing surface expression of Kv1.2 at one or both of these sites. PMID:25403455

  12. Autism and cerebellar dysfunction: Evidence from animal models.

    PubMed

    Tsai, Peter T

    2016-10-01

    Autism is a prevalent neurodevelopmental disorder whose origins are not well understood. Cerebellar involvement has been implicated in the pathogenesis of autism spectrum disorders with increasing evidence from both clinical studies and animal models supporting an important role for cerebellar dysfunction in autism spectrum disorders. This article discusses the various cerebellar contributions to autism spectrum disorders. Both clinical and preclinical studies are discussed and future research directions highlighted.

  13. Cerebro-cerebellar circuits in autism spectrum disorder.

    PubMed

    D'Mello, Anila M; Stoodley, Catherine J

    2015-01-01

    The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural, and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. Further, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD.

  14. Cerebro-cerebellar circuits in autism spectrum disorder

    PubMed Central

    D'Mello, Anila M.; Stoodley, Catherine J.

    2015-01-01

    The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural, and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. Further, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD. PMID:26594140

  15. Acute bilateral cerebellar infarction in the territory of the medial branches of posterior inferior cerebellar arteries.

    PubMed

    Gurer, G; Sahin, G; Cekirge, S; Tan, E; Saribas, O

    2001-10-01

    The most frequent type of cerebellar infarcts involved the posterior inferior cerebellar artery (PICA) and superior cerebellar artery territories but bilateral involvement of lateral or medial branches of PICA is extremely rare. In this report, we present a 55-year-old male who admitted to hospital with vomiting, nausea and dizziness. On examination left-sided hemiparesia and ataxic gait were detected. Infarct on bilateral medial branch of PICA artery territories was found out with cranial magnetic resonance imaging (MRI) technique and 99% stenosis of the left vertebral artery was found out with digital subtraction arteriography. The patient was put on heparin treatment. After 3 weeks, his complaints and symptoms had disappeared except for mild gait ataxia.

  16. [A case of paraneoplastic cerebellar degeneration associated with small cell lung cancer].

    PubMed

    Nakashima, N; Takayama, K; Nakanishi, Y; Ishihara, S; Tanaka, T; Kaneko, Y; Takano, K; Inoue, K; Hara, N

    1999-02-01

    Paraneoplastic cerebellar degeneration (PCD) is a clinical syndrome and known to be occasionally associated with small cell carcinoma of the lung (SCLC). PCD usually affects patients before the cancer is evident. The disorder evolves subacutely, and causes severe pancerebellar dysfunction. In this paper, we report a case of PCD associated with SCLC. A 65-year-old man presenting with 2 weeks of progressive vertigo, gait ataxia, and speech disturbance, was readmitted to our hospital. He had earlier been given a diagnosis of SCLC, oat cell carcinoma, and had undergone high-dose chemotherapy with peripheral blood stem cell transplantation during his first admission. Following that treatment regimen, the tumor disappeared completely and the patient had been in remission. Based on neurological findings and the presence of anti-neuronal antibodies a diagnosis of PCD was made. Although cyclophosphamide (500 mg/m2) was administered, the patient experienced no relief of his cerebellar ataxia. Six months afer readmission, he died of cardiac tamponade due to malignant pericarditis. A histological examination at autopsy found few Purkinje cells and a proliferation of Bergmann's astrocytes in the cerebellar cortex. These findings were consistent with the diagnosis of PCD.

  17. Multiple system atrophy (MSA) with massive macrophage infiltration in the ponto-cerebellar afferent system.

    PubMed

    Yokoyama, Teruo; Hasegawa, Kazuko; Horiuchi, Emiko; Yagishita, Saburou

    2007-08-01

    Multiple system atrophy (MSA) is characterized pathologically by a systemic degeneration of the olivopontocerebellar (OPC), striatonigral (SN) and autonomic systems. Massive glial cytoplasmic inclusions (GCIs) are specific for this disease. Massive lipid-laden macrophage infiltration in the degenerating tracts has not been described up to now. We here report a case of MSA with this rare event in the ponto-cerebellar (cerebellopetal) fibers. The patient, 54-year-old housewife, developed ataxia. At the age of 55 years, she was diagnosed as having MSA by cerebellar ataxia, extrapyramidal signs, autonomic failure and Horner syndrome. She died from asphyxia at the age of 57. The autopsy revealed OPC and SN system atrophy, degeneration and numerous GCIs, compatible with MSA. Numerous lipid-laden macrophages were seen in the pontine nuclei and its transverse fibers including the white matter of the cerebellum, which has not been reported up to now. There was no macrophage infiltration in the other areas. Transient ischemia, infarction and wallerian degeneration do not account for this rare event. The ponto-cerebellar (cerebellopetal) tract pathology, as observed by postmortem neuropathological study, may occur in the context of MSA.

  18. Pitch discrimination in cerebellar patients: evidence for a sensory deficit.

    PubMed

    Parsons, Lawrence M; Petacchi, Augusto; Schmahmann, Jeremy D; Bower, James M

    2009-12-15

    In the last two decades, a growing body of research showing cerebellar involvement in an increasing number of nonmotor tasks and systems has prompted an expansion of speculations concerning the function of the cerebellum. Here, we tested the predictions of a hypothesis positing cerebellar involvement in sensory data acquisition. Specifically, we examined the effect of global cerebellar degeneration on primary auditory sensory function by means of a pitch discrimination task. The just noticeable difference in pitch between two tones was measured in 15 healthy controls and in 15 high functioning patients afflicted with varying degrees of global cerebellar degeneration caused by hereditary, idiopathic, paraneoplastic, or postinfectious pancerebellitis. Participants also performed an auditory detection task assessing sustained attention, a test of verbal auditory working memory, and an audiometric test. Patient pitch discrimination thresholds were on average five and a half times those of controls and were proportional to the degree of cerebellar ataxia assessed independently. Patients and controls showed normal hearing thresholds and similar performance in control tasks in sustained attention and verbal auditory working memory. These results suggest there is an effect of cerebellar degeneration on primary auditory function. The findings are consistent with other recent demonstrations of cerebellar-related sensory impairments, and with robust cerebellar auditorily evoked activity, confirmed by quantitative meta-analysis, across a range of functional neuroimaging studies dissociated from attention, motor, affective, and cognitive variables. The data are interpreted in the context of a sensory hypothesis of cerebellar function.

  19. [A case of brainstem and cerebellar infarctions related to basilar impression].

    PubMed

    Kasai, Takashi; Yoshikawa, Kenji; Tachibana, Shunji; Taniguchi, Takuya; Nakagawa, Masanori

    2004-03-01

    We report a 30-year-old man presenting with medial longitudinal fasciculus (MLF) syndrome after an afternoon nap. Magnetic resonance imaging revealed a right medial pontine tegmental infarction and right cerebellar infarctions. This patient was complicated with basilar impression detected on cervical X-ray and MRI. Three-dimensional CT angiography disclosed that the odontoid process migrated into the posterior fossa, thrusting the bilateral vertebral arteries postero-laterally. The mechanical stress on the bilateral vertebral arteries may have caused infarctions in the territories of the posterior circulation of this patient with basilar impression.

  20. Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments

    PubMed Central

    Badura, Aleksandra; Clopath, Claudia; Schonewille, Martijn; De Zeeuw, Chris I.

    2016-01-01

    Translating neuronal activity to measurable behavioral changes has been a long-standing goal of systems neuroscience. Recently, we have developed a model of phase-reversal learning of the vestibulo-ocular reflex, a well-established, cerebellar-dependent task. The model, comprising both the cerebellar cortex and vestibular nuclei, reproduces behavioral data and accounts for the changes in neural activity during learning in wild type mice. Here, we used our model to predict Purkinje cell spiking as well as behavior before and after learning of five different lines of mutant mice with distinct cell-specific alterations of the cerebellar cortical circuitry. We tested these predictions by obtaining electrophysiological data depicting changes in neuronal spiking. We show that our data is largely consistent with the model predictions for simple spike modulation of Purkinje cells and concomitant behavioral learning in four of the mutants. In addition, our model accurately predicts a shift in simple spike activity in a mutant mouse with a brainstem specific mutation. This combination of electrophysiological and computational techniques opens a possibility of predicting behavioral impairments from neural activity. PMID:27805050

  1. Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments

    NASA Astrophysics Data System (ADS)

    Badura, Aleksandra; Clopath, Claudia; Schonewille, Martijn; de Zeeuw, Chris I.

    2016-11-01

    Translating neuronal activity to measurable behavioral changes has been a long-standing goal of systems neuroscience. Recently, we have developed a model of phase-reversal learning of the vestibulo-ocular reflex, a well-established, cerebellar-dependent task. The model, comprising both the cerebellar cortex and vestibular nuclei, reproduces behavioral data and accounts for the changes in neural activity during learning in wild type mice. Here, we used our model to predict Purkinje cell spiking as well as behavior before and after learning of five different lines of mutant mice with distinct cell-specific alterations of the cerebellar cortical circuitry. We tested these predictions by obtaining electrophysiological data depicting changes in neuronal spiking. We show that our data is largely consistent with the model predictions for simple spike modulation of Purkinje cells and concomitant behavioral learning in four of the mutants. In addition, our model accurately predicts a shift in simple spike activity in a mutant mouse with a brainstem specific mutation. This combination of electrophysiological and computational techniques opens a possibility of predicting behavioral impairments from neural activity.

  2. Distributed Circuit Plasticity: New Clues for the Cerebellar Mechanisms of Learning.

    PubMed

    D'Angelo, Egidio; Mapelli, Lisa; Casellato, Claudia; Garrido, Jesus A; Luque, Niceto; Monaco, Jessica; Prestori, Francesca; Pedrocchi, Alessandra; Ros, Eduardo

    2016-04-01

    The cerebellum is involved in learning and memory of sensory motor skills. However, the way this process takes place in local microcircuits is still unclear. The initial proposal, casted into the Motor Learning Theory, suggested that learning had to occur at the parallel fiber-Purkinje cell synapse under supervision of climbing fibers. However, the uniqueness of this mechanism has been questioned, and multiple forms of long-term plasticity have been revealed at various locations in the cerebellar circuit, including synapses and neurons in the granular layer, molecular layer and deep-cerebellar nuclei. At present, more than 15 forms of plasticity have been reported. There has been a long debate on which plasticity is more relevant to specific aspects of learning, but this question turned out to be hard to answer using physiological analysis alone. Recent experiments and models making use of closed-loop robotic simulations are revealing a radically new view: one single form of plasticity is insufficient, while altogether, the different forms of plasticity can explain the multiplicity of properties characterizing cerebellar learning. These include multi-rate acquisition and extinction, reversibility, self-scalability, and generalization. Moreover, when the circuit embeds multiple forms of plasticity, it can easily cope with multiple behaviors endowing therefore the cerebellum with the properties needed to operate as an effective generalized forward controller.

  3. Abnormal thymic maturation and lymphoproliferation in MRL-Faslpr/lpr mice can be partially reversed by synthetic oligonucleotides: implications for systemic lupus erythematosus and autoimmune lymphoproliferative syndrome.

    PubMed

    Ashman, R F; Singh, N; Lenert, P S

    2016-11-10

    MRL-Fas (lpr/lpr) mice represent an excellent animal model for studying non-malignant lymphoproliferation, regeneration and systemic autoimmunity. Retro-transposon insertion into the second intron of the pro-apoptotic Fas gene appears to be responsible for both lymphoproliferation and autoimmunity, while other genes are more likely to contribute to the regenerative healing characteristic of this mouse strain. Previous studies have shown that neonatal thymectomy can halt the development of abnormal lymphoproliferation. Whereas at four weeks of age primary and secondary lymphoid organs appear to be grossly intact, vigorous lymphoproliferation and autoantibody production subsequently ensues. This is first noticeable at six weeks of age, at which time lymph nodes, spleens and thymuses, but not the bone marrow, become infiltrated with abnormal B220(+)CD3(+)CD4(-)CD8(-) T cells. Around the same time, thymuses show a significant drop in CD4(+)CD8(+)double-positive T cells generating an abnormal ratio between double-positive and single-positive thymocytes. The objective of current study was to evaluate the effect of synthetic oligonucleotides-toll-like receptor antagonists on early lymphoid development in this strain of mice. Herein, we demonstrate the ability of synthetic oligonucleotides made with the nuclease-resistant phosphorothioate backbone to partially reverse abnormal lymphoproliferation and thymic involution in pre-diseased MRL-Fas (lpr/lpr) mice when administered intraperitoneally starting from week four of age. This curative effect of oligonucleotides was primary sequence/secondary oligonucleotide structure-independent, suggesting an effect through the toll-like receptor 7. A similar approach may potentially benefit patients with autoimmune lymphoproliferative syndrome who, like MRL-Fas (lpr/lpr) mice, carry a mutation in the Fas gene.

  4. Comparative Evaluation of Three Homogenization Methods for Isolating Middle East Respiratory Syndrome Coronavirus Nucleic Acids From Sputum Samples for Real-Time Reverse Transcription PCR

    PubMed Central

    Yong, Dongeun; Ki, Chang-Seok; Kim, Jae-Seok; Seong, Moon-Woo; Lee, Hyukmin

    2016-01-01

    Background Real-time reverse transcription PCR (rRT-PCR) of sputum samples is commonly used to diagnose Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Owing to the difficulty of extracting RNA from sputum containing mucus, sputum homogenization is desirable prior to nucleic acid isolation. We determined optimal homogenization methods for isolating viral nucleic acids from sputum. Methods We evaluated the following three sputum-homogenization methods: proteinase K and DNase I (PK-DNase) treatment, phosphate-buffered saline (PBS) treatment, and N-acetyl-L-cysteine and sodium citrate (NALC) treatment. Sputum samples were spiked with inactivated MERS-CoV culture isolates. RNA was extracted from pretreated, spiked samples using the easyMAG system (bioMérieux, France). Extracted RNAs were then subjected to rRT-PCR for MERS-CoV diagnosis (DiaPlex Q MERS-coronavirus, SolGent, Korea). Results While analyzing 15 spiked sputum samples prepared in technical duplicate, false-negative results were obtained with five (16.7%) and four samples (13.3%), respectively, by using the PBS and NALC methods. The range of threshold cycle (Ct) values observed when detecting upE in sputum samples was 31.1–35.4 with the PK-DNase method, 34.7–39.0 with the PBS method, and 33.9–38.6 with the NALC method. Compared with the control, which were prepared by adding a one-tenth volume of 1:1,000 diluted viral culture to PBS solution, the ranges of Ct values obtained by the PBS and NALC methods differed significantly from the mean control Ct of 33.2 (both P<0.0001). Conclusions The PK-DNase method is suitable for homogenizing sputum samples prior to RNA extraction. PMID:27374711

  5. Analytical and Clinical Validation of Six Commercial Middle East Respiratory Syndrome Coronavirus RNA Detection Kits Based on Real-Time Reverse-Transcription PCR

    PubMed Central

    Ko, Young Jin; Seong, Moon-Woo; Kim, Jae-Seok; Shin, Bo-Moon; Sung, Heungsup

    2016-01-01

    Background During the 2015 outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV), six different commercial MERS-CoV RNA detection kits based on real-time reverse-transcription polymerase chain reaction (rRT-PCR) were available in Korea. We performed analytical and clinical validations of these kits. Methods PowerChek (Kogene Biotech, Korea), DiaPlexQ (SolGent, Korea), Anyplex (Seegene, Korea), AccuPower (Bioneer, Korea), LightMix (Roche Molecular Diagnostics, Switzerland), and UltraFast kits (Nanobiosys, Korea) were evaluated. Limits of detection (LOD) with 95% probability values were estimated by testing 16 replicates of upstream of the envelope gene (upE) and open reading frame 1a (ORF1a) RNA transcripts. Specificity was estimated by using 28 nasopharyngeal swabs that were positive for other respiratory viruses. Clinical sensitivity was evaluated by using 18 lower respiratory specimens. The sensitivity test panel and the high inhibition panel were composed of nine specimens each, including eight and six specimens that were positive for MERS-CoV, respectively. Results The LODs for upE ranged from 21.88 to 263.03 copies/reaction, and those for ORF1a ranged from 6.92 to 128.82 copies/reaction. No cross-reactivity with other respiratory viruses was found. All six kits correctly identified 8 of 8 (100%) positive clinical specimens. Based on results from the high inhibition panel, PowerChek and AccuPower were the least sensitive to the presence of PCR inhibition. Conclusions The overall sensitivity and specificity of all six assay systems were sufficient for diagnosing MERS-CoV infection. However, the analytical sensitivity and detection ability in specimens with PCR inhibition could be improved with the use of appropriate internal controls. PMID:27374710

  6. Cerebellar contribution to higher and lower order rule learning and cognitive flexibility in mice.

    PubMed

    Dickson, P E; Cairns, J; Goldowitz, D; Mittleman, G

    2017-03-14

    Cognitive flexibility has traditionally been considered a frontal lobe function. However, converging evidence suggests involvement of a larger brain circuit which includes the cerebellum. Reciprocal pathways connecting the cerebellum to the prefrontal cortex provide a biological substrate through which the cerebellum may modulate higher cognitive functions, and it has been observed that cognitive inflexibility and cerebellar pathology co-occur in psychiatric disorders (e.g., autism, schizophrenia, addiction). However, the degree to which the cerebellum contributes to distinct forms of cognitive flexibility and rule learning is unknown. We tested lurcher↔wildtype aggregation chimeras which lose 0-100% of cerebellar Purkinje cells during development on a touchscreen-mediated attentional set-shifting task to assess the contribution of the cerebellum to higher and lower order rule learning and cognitive flexibility. Purkinje cells, the sole output of the cerebellar cortex, ranged from 0 to 108,390 in tested mice. Reversal learning and extradimensional set-shifting were impaired in mice with⩾95% Purkinje cell loss. Cognitive deficits were unrelated to motor deficits in ataxic mice. Acquisition of a simple visual discrimination and an attentional-set were unrelated to Purkinje cells. A positive relationship was observed between Purkinje cells and errors when exemplars from a novel, non-relevant dimension were introduced. Collectively, these data suggest that the cerebellum contributes to higher order cognitive flexibility, lower order cognitive flexibility, and attention to novel stimuli, but not the acquisition of higher and lower order rules. These data indicate that the cerebellar pathology observed in psychiatric disorders may underlie deficits involving cognitive flexibility and attention to novel stimuli.

  7. Ataxia and tremor due to lesions involving cerebellar projection pathways: a DTI tractographic study in six patients.

    PubMed

    Marek, M; Paus, S; Allert, N; Mädler, B; Klockgether, T; Urbach, H; Coenen, V A

    2015-01-01

    Focal lesions of brainstem, thalamus, and subcortical white matter may cause movement disorders that are clinically indistinguishable from cerebellar symptoms. It is suspected that ataxia in these cases is due to damage of efferent or afferent pathways of the cerebellum. However, the precise anatomical correlate often remains undefined. We used deterministic diffusion tensor magnetic resonance imaging (DTI) tractography to study the anatomical relationship between lesions causing ataxia and efferent cerebellar pathways. Study subjects were six male patients with focal lesions of different etiology (demyelination, hemorrhage, ischemia, neoplasm) outside the cerebellum. Five patients had cerebellar-like ataxia with prominent contralateral upper limb involvement. One patient with an almost midline mesencephalic lesion had a symmetrical ataxic syndrome. We used 3T MRI (Intera, Philips Medical Systems, Best, Netherlands) and DTI tractography (32 directions, StealthViz DTI, Medtronic Navigation, Louisville, USA) to delineate the dentato-rubro-thalamo-cortical tract (DRT). In all patients, tractography demonstrated focal lesions affecting the DRT in different locations. We conclude that in vivo mapping of cerebral pathways using DTI tractography in patients with focal extracerebellar brain lesions may provide direct evidence of circumscribed damage to the DRT, causing unilateral cerebellar-like ataxia. Also, a unilateral mesencephalic lesion at the level of the crossing of the DRT may cause bilateral ataxia.

  8. An integrator circuit in cerebellar cortex.

    PubMed

    Maex, Reinoud; Steuber, Volker

    2013-09-01

    The brain builds dynamic models of the body and the outside world to predict the consequences of actions and stimuli. A well-known example is the oculomotor integrator, which anticipates the position-dependent elasticity forces acting on the eye ball by mathematically integrating over time oculomotor velocity commands. Many models of neural integration have been proposed, based on feedback excitation, lateral inhibition or intrinsic neuronal nonlinearities. We report here that a computational model of the cerebellar cortex, a structure thought to implement dynamic models, reveals a hitherto unrecognized integrator circuit. In this model, comprising Purkinje cells, molecular layer interneurons and parallel fibres, Purkinje cells were able to generate responses lasting more than 10 s, to which both neuronal and network mechanisms contributed. Activation of the somatic fast sodium current by subthreshold voltage fluctuations was able to maintain pulse-evoked graded persistent activity, whereas lateral inhibition among Purkinje cells via recurrent axon collaterals further prolonged the responses to step and sine wave stimulation. The responses of Purkinje cells decayed with a time-constant whose value depended on their baseline spike rate, with integration vanishing at low (< 1 per s) and high rates (> 30 per s). The model predicts that the apparently fast circuit of the cerebellar cortex may control the timing of slow processes without having to rely on sensory feedback. Thus, the cerebellar cortex may contain an adaptive temporal integrator, with the sensitivity of integration to the baseline spike rate offering a potential mechanism of plasticity of the response time-constant.

  9. Neocortical networks entrain neuronal circuits in cerebellar cortex

    PubMed Central

    Roš, Hana; Sachdev, Robert N. S.; Yu, Yuguo; Šestan, Nenad; McCormick, David A.

    2011-01-01

    Activity in neocortex is often characterized by synchronized oscillations of neurons and networks, resulting in the generation of a local field potential and electroencephalogram. Do the neuronal networks of the cerebellum also generate synchronized oscillations and are they under the influence of those in the neocortex? Here we show that in the absence of any overt external stimulus, the cerebellar cortex generates a slow oscillation that is correlated with that of the neocortex. Disruption of the neocortical slow oscillation abolishes the cerebellar slow oscillation, whereas blocking cerebellar activity has no overt effect on the neocortex. We provide evidence that the cerebellar slow oscillation results in part from the activation of granule, Golgi, and Purkinje neurons. In particular, we show that granule and Golgi cells discharge trains of single spikes, and Purkinje cells generate complex spikes, during the Up state of the slow oscillation. Purkinje cell simple spiking is weakly related to the cerebellar and neocortical slow oscillation in a minority of cells. Our results indicate that the cerebellum generates rhythmic network activity that can be recorded as an LFP in the anesthetized animal, which is driven by synchronized oscillations of the neocortex. Furthermore, we show that correlations between neocortical and cerebellar LFPs persist in the awake animal, indicating that neocortical circuits modulate cerebellar neurons in a similar fashion in natural behavioral states. Thus, the projection neurons of the neocortex collectively exert a driving and modulatory influence on cerebellar network activity. PMID:19692605

  10. Acute cerebellar ataxia with human parvovirus B19 infection

    PubMed Central

    Shimizu, Y.; Ueno, T.; Komatsu, H.; Takada, H.; Nunoue, T.

    1999-01-01

    A 2 year old boy developed acute cerebellar ataxia in association with erythema infectiosum. During the disease, genomic DNA and antibodies against human parvovirus B19 were detected in serum but not in cerebrospinal fluid. Parvovirus B19 associated acute cerebellar ataxia might occur due to transient vascular reaction in the cerebellum during infection.

 PMID:10325764

  11. Distinct Critical Cerebellar Subregions for Components of Verbal Working Memory

    ERIC Educational Resources Information Center

    Cooper, Freya E.; Grube, Manon; Von Kriegstein, Katharina; Kumar, Sukhbinder; English, Philip; Kelly, Thomas P.; Chinnery, Patrick F.; Griffiths, Timothy D.

    2012-01-01

    A role for the cerebellum in cognition has been proposed based on studies suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies are limited in the determination of the detailed organisation of cerebellar subregions that are critical for different aspects of cognition. In this study we examined the correlation between…

  12. Humor and laughter in patients with cerebellar degeneration.

    PubMed

    Frank, B; Propson, B; Göricke, S; Jacobi, H; Wild, B; Timmann, D

    2012-06-01

    Humor is a complex behavior which includes cognitive, affective and motor responses. Based on observations of affective changes in patients with cerebellar lesions, the cerebellum may support cerebral and brainstem areas involved in understanding and appreciation of humorous stimuli and expression of laughter. The aim of the present study was to examine if humor appreciation, perception of humorous stimuli, and the succeeding facial reaction differ between patients with cerebellar degeneration and healthy controls. Twenty-three adults with pure cerebellar degeneration were compared with 23 age-, gender-, and education-matched healthy control subjects. No significant difference in humor appreciation and perception of humorous stimuli could be found between groups using the 3 Witz-Dimensionen Test, a validated test asking for funniness and aversiveness of jokes and cartoons. Furthermore, while observing jokes, humorous cartoons, and video sketches, facial expressions of subjects were videotaped and afterwards analysed using the Facial Action Coding System. Using depression as a covariate, the number, and to a lesser degree, the duration of facial expressions during laughter were reduced in cerebellar patients compared to healthy controls. In sum, appreciation of humor appears to be largely preserved in patients with chronic cerebellar degeneration. Cerebellar circuits may contribute to the expression of laughter. Findings add to the literature that non-motor disorders in patients with chronic cerebellar disease are generally mild, but do not exclude that more marked disorders may show up in acute cerebellar disease and/or in more specific tests of humor appreciation.

  13. Distinct critical cerebellar subregions for components of verbal working memory

    PubMed Central

    Cooper, Freya E.; Grube, Manon; Von Kriegstein, Katharina; Kumar, Sukhbinder; English, Philip; Kelly, Thomas P.; Chinnery, Patrick F.; Griffiths, Timothy D.

    2014-01-01

    A role for the cerebellum in cognition has been proposed based on studies suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies are limited in the determination of the detailed organisation of cerebellar subregions that are critical for different aspects of cognition. In this study we examined the correlation between cognitive performance and cerebellar integrity in a specific degeneration of the cerebellar cortex: Spinocerebellar Ataxia type 6 (SCA6). The results demonstrate a critical relationship between verbal working memory and grey matter density in superior (bilateral lobules VI and crus I of lobule VII) and inferior (bilateral lobules VIIIa and VIIIb, and right lobule IX) parts of the cerebellum. We demonstrate that distinct cerebellar regions subserve different components of the prevalent psychological model for verbal working memory based on a phonological loop. The work confirms the involvement of the cerebellum in verbal working memory and defines specific subsystems for this within the cerebellum. PMID:22133495

  14. Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids

    PubMed Central

    Tam, Emily W. Y.; Chau, Vann; Ferriero, Donna M.; Barkovich, A. James; Poskitt, Kenneth J.; Studholme, Colin; Fok, Eric D.-Y.; Grunau, Ruth E.; Glidden, David V.; Miller, Steven P.

    2012-01-01

    With improving survival rates of preterm newborns, adverse cognitive outcomes are increasingly recognized. Adverse cognitive outcomes are associated with decreased cerebellar volumes, and modifiable risk factors for these adverse outcomes should be identified. Animal models demonstrate reduced preterm cerebellar growth after exposure to glucocorticoids. Preterm neonates were prospectively studied with serial MRI examinations near birth and again near term-equivalent age. Adjusting for associated clinical factors, antenatal bethamethasone was not associated with changes in cerebellar volume. Postnatal exposure to clinically routine doses of hydrocortisone or dexamethasone were associated with impaired cerebellar, but not cerebral, growth. Modifying postnatal risk factors for impaired cerebellar development, and particularly glucocorticoid exposure, may help to decrease risk for adverse neurological outcome after preterm birth. PMID:22013125

  15. The physiological basis of therapies for cerebellar ataxias

    PubMed Central

    Mitoma, Hiroshi; Manto, Mario

    2016-01-01

    Cerebellar ataxias represent a group of heterogeneous disorders impacting on activities of daily living and quality of life. Various therapies have been proposed to improve symptoms in cerebellar ataxias. This review examines the physiological background of the various treatments currently administered worldwide. We analyze the mechanisms of action of drugs with a focus on aminopyridines and other antiataxic medications, of noninvasive cerebellar stimulation, and of motor rehabilitation. Considering the cerebellum as a controller, we propose the novel concept of ‘restorable stage’. Because of its unique anatomical architecture and its diffuse connectivity in particular with the cerebral cortex, keeping in mind the anatomophysiology of the cerebellar circuitry is a necessary step to understand the rationale of therapies of cerebellar ataxias and develop novel therapeutic tools. PMID:27582895

  16. Cerebellar vermis plays a causal role in visual motion discrimination.

    PubMed

    Cattaneo, Zaira; Renzi, Chiara; Casali, Stefano; Silvanto, Juha; Vecchi, Tomaso; Papagno, Costanza; D'Angelo, Egidio

    2014-09-01

    Cerebellar patients have been found to show deficits in visual motion discrimination, suggesting that the cerebellum may play a role in visual sensory processing beyond mediating motor control. Here we show that triple-pulse online transcranial magnetic stimulation (TMS) over cerebellar vermis but not over the cerebellar hemispheres significantly impaired motion discrimination. Critically, the interference caused by vermis TMS on motion discrimination did not depend on an indirect effect of TMS over nearby visual areas, as demonstrated by a control experiment in which TMS over V1 but not over cerebellar vermis significantly impaired orientation discrimination. These findings demonstrate the causal role of the cerebellar vermis in visual motion processing in neurologically normal participants.

  17. Cerebellar mass as a location of acute lymphoblastic leukaemia.

    PubMed

    Desideri, Ilaria; Canovetti, Silvia; Pesaresi, Ilaria; Caniglia, Michele; Ciancia, Eugenio; Bartolozzi, Carlo; Puglioli, Michele; Cosottini, Mirco

    2014-09-01

    A 22-year-old man with acute lymphoblastic leukaemia was referred to our observation for headache, cervical pain and sopor. A computed tomography study revealed triventricular obstructive hydrocephalus due to a left cerebellar hyperdense mass impinging on the fourth ventricle. A magnetic resonance study demonstrated an area of hyperintensity on T2-weighted images, hypointensity on T1, restricted diffusivity and contrast enhancement involving the left hemispherical cerebellar cortex and the vermis and causing cerebellar herniation. After surgical excision of the lesion, histological examination revealed an infiltrate of lymphoblastic leukaemia with B cells. Leukaemic intracranial masses are rare. Our report describes a case presenting a cerebellar mass of leukaemic tissue characterized by high cellularity and low apparent diffusion coefficient value comparable to acute ischaemia. Therefore leukaemic intracranial mass has to be considered in the differential diagnosis of cerebellar masses.

  18. New evidence for the cerebellar involvement in personality traits

    PubMed Central

    Picerni, Eleonora; Petrosini, Laura; Piras, Fabrizio; Laricchiuta, Daniela; Cutuli, Debora; Chiapponi, Chiara; Fagioli, Sabrina; Girardi, Paolo; Caltagirone, Carlo; Spalletta, Gianfranco

    2013-01-01

    Following the recognition of its role in sensory-motor coordination and learning, the cerebellum has been involved in cognitive, emotional, and even personality domains. This study investigated the relationships between cerebellar macro- and micro-structural variations and temperamental traits measured by Temperament and Character Inventory (TCI). High resolution T1-weighted, and Diffusion Tensor Images of 100 healthy subjects aged 18–59 years were acquired by 3 Tesla Magnetic Resonance scanner. In multiple regression analyses, cerebellar Gray Matter (GM) or White Matter (WM) volumes, GM Mean Diffusivity (MD), and WM Fractional Anisotropy (FA) were used as dependent variables, TCI scores as regressors, gender, age, and education years as covariates. Novelty Seeking scores were associated positively with the cerebellar GM volumes and FA, and negatively with MD. No significant association between Harm Avoidance, Reward Dependence or Persistence scores and cerebellar structural measures was found. The present data put toward a cerebellar involvement in the management of novelty. PMID:24106465

  19. New evidence for the cerebellar involvement in personality traits.

    PubMed

    Picerni, Eleonora; Petrosini, Laura; Piras, Fabrizio; Laricchiuta, Daniela; Cutuli, Debora; Chiapponi, Chiara; Fagioli, Sabrina; Girardi, Paolo; Caltagirone, Carlo; Spalletta, Gianfranco

    2013-01-01

    Following the recognition of its role in sensory-motor coordination and learning, the cerebellum has been involved in cognitive, emotional, and even personality domains. This study investigated the relationships between cerebellar macro- and micro-structural variations and temperamental traits measured by Temperament and Character Inventory (TCI). High resolution T1-weighted, and Diffusion Tensor Images of 100 healthy subjects aged 18-59 years were acquired by 3 Tesla Magnetic Resonance scanner. In multiple regression analyses, cerebellar Gray Matter (GM) or White Matter (WM) volumes, GM Mean Diffusivity (MD), and WM Fractional Anisotropy (FA) were used as dependent variables, TCI scores as regressors, gender, age, and education years as covariates. Novelty Seeking scores were associated positively with the cerebellar GM volumes and FA, and negatively with MD. No significant association between Harm Avoidance, Reward Dependence or Persistence scores and cerebellar structural measures was found. The present data put toward a cerebellar involvement in the management of novelty.

  20. MCT8 deficiency in Purkinje cells disrupts embryonic chicken cerebellar development.

    PubMed

    Delbaere, Joke; Vancamp, Pieter; Van Herck, Stijn L J; Bourgeois, Nele M A; Green, Mary J; Wingate, Richard J T; Darras, Veerle M

    2017-02-01

    Inactivating mutations in the human SLC16A2 gene encoding the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) result in the Allan-Herndon-Dudley syndrome accompanied by severe locomotor deficits. The underlying mechanisms of the associated cerebellar maldevelopment were studied using the chicken as a model. Electroporation of an MCT8-RNAi vector into the cerebellar anlage of a 3-day-old embryo allowed knockdown of MCT8 in Purkinje cell precursors. This resulted in the downregulation of the thyroid hormone-responsive gene RORα and the Purkinje cell-specific differentiation marker LHX1/5 at day 6. MCT8 knockdown also results in a smaller and less complex dendritic tree at day 18 suggesting a pivotal role of MCT8 for cell-autonomous Purkinje cell maturation. Early administration of the thyroid hormone analogue 3,5,3'-triiodothyroacetic acid partially rescued early Purkinje cell differentiation. MCT8-deficient Purkinje cells also induced non-autonomous effects as they led to a reduced granule cell precursor proliferation, a thinner external germinal layer and a loss of PAX6 expression. By contrast, at day 18, the external germinal layer thickness was increased, with an increase in presence of Axonin-1-positive post-mitotic granule cells in the initial stage of radial migration. The concomitant accumulation of presumptive migrating granule cells in the molecular layer, suggests that inward radial migration to the internal granular layer is stalled. In conclusion, early MCT8 deficiency in Purkinje cells results in both cell-autonomous and non-autonomous effects on cerebellar development and indicates that MCT8 expression is essential from very early stages of development, providing a novel insight into the ontogenesis of the Allan-Herndon-Dudley syndrome.

  1. Mosaic marker chromosome 16 resulting in 16q11.2-q12.1 gain in a child with intellectual disability, microcephaly, and cerebellar cortical dysplasia.

    PubMed

    Zerem, Ayelet; Vinkler, Chana; Michelson, Marina; Leshinsky-Silver, Esther; Lerman-Sagie, Tally; Lev, Dorit

    2011-12-01

    Proximal duplications of the long arm of chromosome 16 are rare and only a few patients have been reported. Clinically, the patients do not have a distinctive syndromic appearance; however they all show some degree of intellectual disability and most have severely delayed speech development. We report on a child presenting with mild-to-moderate intellectual disability, microcephaly, language dyspraxia, and mild dysmorphisms who was found to have a mosaic gain of chromosome 16q (16q11.2-16q12.1). Magnetic resonance imaging done at the age of 4 years demonstrated cerebellar cortical dysplasia involving the vermis and hemispheres. This is the first report of cerebellar anomalies in a patient with partial trisomy 16q. The genes ZNF423 and CBLN1 found in the duplicated region play a role in the development of the cerebellum and may be responsible for the cerebellar cortical dysplasia.

  2. Infantile onset progressive cerebellar atrophy and anterior horn cell degeneration--a late onset variant of PCH-1?

    PubMed

    Lev, Dorit; Michelson-Kerman, Marina; Vinkler, Chana; Blumkin, Lubov; Shalev, Stavit A; Lerman-Sagie, Tally

    2008-03-01

    Despite major recent advances in our understanding of developmental cerebellar disorders, classification and delineation of these disorders remains difficult. The term pontocerebellar hypoplasia is used when there is a structural defect, originating in utero of both pons and cerebellar hemispheres. The term olivopontocerebellar atrophy is used when the disorder starts later in life and the process is a primary degeneration of cerebellar neurons. Pontocerebellar hypoplasia type 1 is associated with spinal anterior horn cell degeneration, congenital contractures, microcephaly, polyhydramnion and respiratory insufficiency leading to early death. However, anterior horn cell degeneration has also been described in cases with later onset pontocerebellar atrophy and recently the spectrum has even been further extended to include the association of anterior horn cell degeneration and cerebellar atrophy without pontine involvement. We describe two siblings from a consanguineous Moslem Arabic family who presented with progressive degeneration of both the cerebellum and the anterior horn cells. The patients presented after 1 year of age with a slow neurodegenerative course that included both cognitive and motor functions. There is considerable phenotypic variability; the sister shows a much milder course. Both children are still alive at 6 and 9 years. The sister could still crawl and speak two word sentences at the age of 3 years while the brother was bedridden and only uttered guttural sounds at the same age. Our cases further extend the phenotype of the cerebellar syndromes with anterior horn cell involvement to include a childhood onset and protracted course and further prove that this neurodegenerative disorder may start in utero or later in life.

  3. A Missense Variant in KCNJ10 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA1)

    PubMed Central

    Mauri, Nico; Kleiter, Miriam; Leschnik, Michael; Högler, Sandra; Dietschi, Elisabeth; Wiedmer, Michaela; Dietrich, Joëlle; Henke, Diana; Steffen, Frank; Schuller, Simone; Gurtner, Corinne; Stokar-Regenscheit, Nadine; O’Toole, Donal; Bilzer, Thomas; Herden, Christiane; Oevermann, Anna; Jagannathan, Vidhya; Leeb, Tosso

    2016-01-01

    Spongy degeneration with cerebellar ataxia (SDCA) is a severe neurodegenerative disease with monogenic autosomal recessive inheritance in Malinois dogs, one of the four varieties of the Belgian Shepherd breed. We performed a genetic investigation in six families and seven isolated cases of Malinois dogs with signs of cerebellar dysfunction. Linkage analysis revealed an unexpected genetic heterogeneity within the studied cases. The affected dogs from four families and one isolated case shared a ∼1.4 Mb common homozygous haplotype segment on chromosome 38. Whole genome sequence analysis of three affected and 140 control dogs revealed a missense variant in the KCNJ10 gene encoding a potassium channel (c.986T>C; p.Leu329Pro). Pathogenic variants in KCNJ10 were reported previously in humans, mice, and dogs with neurological phenotypes. Therefore, we consider KCNJ10:c.986T>C the most likely candidate causative variant for one subtype of SDCA in Malinois dogs, which we propose to term spongy degeneration with cerebellar ataxia 1 (SDCA1). However, our study also comprised samples from 12 Malinois dogs with cerebellar dysfunction which were not homozygous for this variant, suggesting a different genetic basis in these dogs. A retrospective detailed clinical and histopathological analysis revealed subtle neuropathological differences with respect to SDCA1-affected dogs. Thus, our study highlights the genetic and phenotypic complexity underlying cerebellar dysfunction in Malinois dogs and provides the basis for a genetic test to eradicate one specific neurodegenerative disease from the breeding population. These dogs represent an animal model for the human EAST syndrome. PMID:28007838

  4. NF1 regulation of RAS/ERK signaling is required for appropriate granule neuron progenitor expansion and migration in cerebellar development.

    PubMed

    Sanchez-Ortiz, Efrain; Cho, Woosung; Nazarenko, Inga; Mo, Wei; Chen, Jian; Parada, Luis F

    2014-11-01

    Cerebellar development is regulated by a coordinated spatiotemporal interplay between granule neuron progenitors (GNPs), Purkinje neurons, and glia. Abnormal development can trigger motor deficits, and more recent data indicate important roles in aspects of memory, behavior, and autism spectrum disorders (ASDs). Germline mutation in the NF1 tumor suppressor gene underlies Neurofibromatosis type 1, a complex disease that enhances susceptibility to certain cancers and neurological disorders, including intellectual deficits and ASD. The NF1 gene encodes for neurofibromin, a RAS GTPase-activating protein, and thus negatively regulates the RAS signaling pathway. Here, using mouse models to direct conditional NF1 ablation in either embryonic cerebellar progenitors or neonatal GNPs, we show that neurofibromin is required for appropriate development of cerebellar folia layering and structure. Remarkably, neonatal administration of inhibitors of the ERK pathway reversed the morphological defects. Thus, our findings establish a critical cell-autonomous role for the NF1-RAS-ERK pathway in the appropriate regulation of cerebellar development and provide a basis for using neonatal ERK inhibitor-based therapies to treat NF1-induced cerebellar disorders.

  5. Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome.

    PubMed

    Costa, Lara; Sardone, Lara M; Lacivita, Enza; Leopoldo, Marcello; Ciranna, Lucia

    2015-01-01

    Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD) in wild-type (wt) and in Fmr1 KO mice, a mouse model of Fragile X Syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X Syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices. Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X Syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions. The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of Fragile X Syndrome.

  6. Novel agonists for serotonin 5-HT7 receptors reverse metabotropic glutamate receptor-mediated long-term depression in the hippocampus of wild-type and Fmr1 KO mice, a model of Fragile X Syndrome

    PubMed Central

    Costa, Lara; Sardone, Lara M.; Lacivita, Enza; Leopoldo, Marcello; Ciranna, Lucia

    2015-01-01

    Serotonin 5-HT7 receptors are expressed in the hippocampus and modulate the excitability of hippocampal neurons. We have previously shown that 5-HT7 receptors modulate glutamate-mediated hippocampal synaptic transmission and long-term synaptic plasticity. In particular, we have shown that activation of 5-HT7 receptors reversed metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD) in wild-type (wt) and in Fmr1 KO mice, a mouse model of Fragile X Syndrome in which mGluR-LTD is abnormally enhanced, suggesting that 5-HT7 receptor agonists might be envisaged as a novel therapeutic strategy for Fragile X Syndrome. In this perspective, we have characterized the basic in vitro pharmacokinetic properties of novel molecules with high binding affinity and selectivity for 5-HT7 receptors and we have tested their effects on synaptic plasticity using patch clamp on acute hippocampal slices. Here we show that LP-211, a high affinity selective agonist of 5-HT7 receptors, reverses mGluR-LTD in wt and Fmr1 KO mice, correcting a synaptic malfunction in the mouse model of Fragile X Syndrome. Among novel putative agonists of 5-HT7 receptors, the compound BA-10 displayed improved affinity and selectivity for 5-HT7 receptors and improved in vitro pharmacokinetic properties with respect to LP-211. BA-10 significantly reversed mGluR-LTD in the CA3-CA1 synapse in wt and Fmr1KO mice, indicating that BA-10 behaved as a highly effective agonist of 5-HT7 receptors and reduced exaggerated mGluR-LTD in a mouse model of Fragile X Syndrome. On the other side, the compounds RA-7 and PM-20, respectively arising from in vivo metabolism of LP-211 and BA-10, had no effect on mGluR-LTD thus did not behave as agonists of 5-HT7 receptors in our conditions. The present results provide information about the structure-activity relationship of novel 5-HT7 receptor agonists and indicate that LP-211 and BA-10 might be used as novel pharmacological tools for the therapy of Fragile X Syndrome

  7. Cerebellar dentate nuclei lesions alter prefrontal cortex dendritic spine morphology.

    PubMed

    Bauer, David J; Peterson, Todd C; Swain, Rodney A

    2014-01-28

    Anatomical tracing studies in primates have revealed neural tracts from the cerebellar dentate nuclei to prefrontal cortex, implicating a cerebellar role in nonmotor processes. Experiments in rats examining the functional role of this cerebellothalamocortical pathway have demonstrated the development of visuospatial and motivational deficits following lesions of the dentate nuclei, in the absence of motor impairment. These behavioral deficits possibly occur due to structural modifications of the cerebral cortex secondary to loss of cerebellar input. The current study characterized morphological alterations in prefrontal cortex important for visuospatial and motivational processes following bilateral cerebellar dentate nuclei lesions. Rats received either bilateral electrolytic cerebellar dentate nuclei lesions or sham surgery followed by a 30-day recovery. Randomly selected Golgi-impregnated neurons in prefrontal cortex were examined for analysis. Measures of branch length and spine density revealed no differences between lesioned and sham rats in either apical or basilar arbors; however, the proportion of immature to mature spines significantly decreased in lesioned rats as compared to sham controls, with reductions of 33% in the basilar arbor and 28% in the apical arbor. Although expected pruning of branches and spines did not occur, the results are consistent with the hypothesis that cerebellar lesions influence prefrontal morphology and support the possibility that functional deficits following cerebellar dentate nuclei lesions are related to prefrontal morphological alteration.

  8. Abnormal cerebellar morphometry in abstinent adolescent marijuana users

    PubMed Central

    Medina, Krista Lisdahl; Nagel, Bonnie J.; Tapert, Susan F.

    2010-01-01

    Background Functional neuroimaging data from adults have, in general, found frontocerebellar dysfunction associated with acute and chronic marijuana (MJ) use (Loeber & Yurgelun-Todd, 1999). One structural neuroimaging study found reduced cerebellar vermis volume in young adult MJ users with a history of heavy polysubstance use (Aasly et al., 1993). The goal of this study was to characterize cerebellar volume in adolescent chronic MJ users following one month of monitored abstinence. Method Participants were MJ users (n=16) and controls (n=16) aged 16-18 years. Extensive exclusionary criteria included history of psychiatric or neurologic disorders. Drug use history, neuropsychological data, and structural brain scans were collected after 28 days of monitored abstinence. Trained research staff defined cerebellar volumes (including three cerebellar vermis lobes and both cerebellar hemispheres) on high-resolution T1-weighted magnetic resonance images. Results Adolescent MJ users demonstrated significantly larger inferior posterior (lobules VIII-X) vermis volume (p<.009) than controls, above and beyond effects of lifetime alcohol and other drug use, gender, and intracranial volume. Larger vermis volumes were associated with poorer executive functioning (p’s<.05). Conclusions Following one month of abstinence, adolescent MJ users had significantly larger posterior cerebellar vermis volumes than non-using controls. These greater volumes are suggested to be pathological based on linkage to poorer executive functioning. Longitudinal studies are needed to examine typical cerebellar development during adolescence and the influence of marijuana use. PMID:20413277

  9. Fatal remote cerebellar hemorrhage after supratentorial unruptured aneurysm surgery in patient with previous cerebellar infarction

    PubMed Central

    Koh, Eun-Jeong; Park, Jung-Soo

    2017-01-01

    Abstract Rationale: Remote cerebellar hemorrhage (RCH) is a rare complication of supratentorial and spinal surgeries, seldom requiring intervention but occasionally causing significant morbidity or even mortality. Although a number of theories have been proposed, the exact pathophysiology of RCH remains incompletely understood. Patient concerns: We present a 62-year-old patient with RCH encountered following surgical clipping of an unruptured middle cerebral artery bifurcation aneurysm in a patient with previous cerebellar infarction. Lessons: It is extremely rare, but sometimes, RCH can be life-threatening. It is necessary to check the patient's general condition, underlying diseases and medical history. And controlled drainage of the CSF seems to be most important. Arachnoidplasty may be a consideration and the position of the drain string might have to be carefully determined. PMID:28121936

  10. Cerebral venous thrombosis presenting with cerebellar ataxia and cortical blindness.

    PubMed

    Ben Sassi, Samia; Mizouni, Habiba; Nabli, Fatma; Kallel, Lamia; Kefi, Mounir; Hentati, Fayçal

    2010-01-01

    Venous infarction in the cerebellum has been reported only rarely, probably because of the abundant venous collateral drainage in this region. Bilateral occipital infarction is a rare cause of visual loss in cerebral venous thrombosis. We describe a 50-year-old woman with a history of ulcerative colitis who developed acute cerebellar ataxia and cortical blindness. She had bilateral cerebellar and occipital lesions related to sigmoid venous thrombosis and achieved complete recovery with anticoagulation therapy. Cerebral venous thrombosis should be considered in cases of simultaneous cerebellar and occipital vascular lesions.

  11. Cerebellar Mutism Following Closed Head Injury in a Child

    PubMed Central

    Kariyattil, Rajeev; Rahim, Mohamed I. A.; Muthukuttiparambil, Unnikrishnan

    2015-01-01

    Cerebellar mutism is a rare occurrence following paediatric trauma. Although it is quite common after posterior fossa surgery in children, this phenomenon has rarely been reported following other insults, such as trauma, and its pathophysiology remains poorly understood. We report a seven-year-old child who presented to the casualty department of Sultan Qaboos University Hospital in Muscat, Oman, in May 2013 with a traumatic right cerebellar contusion. The child presented with clinical features of cerebellar mutism but underwent a rapid and spontaneous recovery. The possible mechanism of this occurrence is discussed. PMID:25685374

  12. Chronic THC intake modifies fundamental cerebellar functions

    PubMed Central

    Stella, Nephi

    2013-01-01

    Delta9-tetrahydrocannabinol (THC), the principal bioactive component in the Cannabis plant, is truly a captivating drug. Acute and chronic THC intake produces a spectrum of biological effects ranging from transient psychotropic effects to prolonged medicinal benefits, many of which have been fostered for centuries by our society. In the July 2013 issue of the JCI, Cutando et al. combined mouse genetics with classic mouse behavioral analysis to deepen our understanding of the physiological consequence of subchronic THC intake on eyeblink reflexes, a fundamental neuronal adaptive response, revealing that this regimen leads to downregulation of the cannabinoid CB1 receptor (referred to as CB1 in the Cutando et al. article) in cerebellar stress fibers and the activation of microglia, raising provocative new questions about the safety profile of regimented THC intake. PMID:23863631

  13. Classically conditioned postural reflex in cerebellar patients.

    PubMed

    Kolb, F P; Lachauer, S; Maschke, M; Timmann, D

    2004-09-01

    The aim of the current study was to compare postural responses to repetitive platform-evoked perturbations in cerebellar patients with those of healthy subjects using a classical conditioning paradigm. The perturbations consisted of tilting of the platform (unconditioned stimulus: US) at random time intervals, preceded by an auditory signal that represented the conditioning stimulus (CS). Physiological reactions were recorded biomechanically by measuring the vertical ground forces, yielding the center of vertical pressure (CVP), and electrophysiologically by EMG measurements of the main muscle groups of both legs. The recording session consisted of a control section with US-alone trials, a testing section with paired stimuli and a brief final section with US-alone trials. Healthy control subjects were divided into those establishing conditioned responses (CR) in all muscles tested (strategy I) and those with CR in the gastrocnemius muscles only (strategy II), suggesting an associative motor-related process is involved. Patients with a diffuse, non-localized disease were almost unable to establish CR. This was also true for a patient with a focal surgical lesion with no CR on the affected side but who, simultaneously, showed an essentially normal CR incidence on the intact side. During US-alone trials healthy controls exhibited a remarkable decay of the UR amplitude due to a non-associative motor-related process such as habituation. The decay was most prominent in the paired trials section. In contrast, patients showed no significant differences in the UR amplitude throughout the entire recording session. Analysis of the CVP supported the electrophysiological findings, showing CR in the controls only. The differences between the responses of control subjects and those of the cerebellar patients imply strongly that the cerebellum is involved critically in controlling associative and non-associative motor-related processes.

  14. Distal arthrogryposis syndrome

    PubMed Central

    Kulkarni, K. P.; Panigrahi, I.; Ray, M.; Marwaha, R. K.

    2008-01-01

    A 5-month-old male infant presented with weak cry, decreased body movements, tightness of whole body since birth, and one episode of generalized seizure on day 4 of life. He was born at term by elective caesarian section performed for breech presentation. The child had failure to thrive, contractures at elbow and knee joints, hypertonia, microcephaly, small mouth, retrognathia, and camptodactyly. There was global developmental delay. Abdominal examination revealed umbilical and bilateral inguinal hernia. Visual evoked response and brainstem evoked response audiometry were abnormal. Nerve conduction velocity was normal. Magnetic resonance imaging of brain revealed paucity of white matter in bilateral cerebral hemispheres with cerebellar and brain stem atrophy. The differential diagnoses considered in the index patient were distal arthrogryposis (DA) syndrome, cerebroculofacioskeletal syndrome, and Pena Shokier syndrome. The index patient most likely represents a variant of DA: Sheldon Hall syndrome. PMID:20300297

  15. Endovascular Aneurysm Repair Using a Reverse Chimney Technique in a Patient With Marfan Syndrome and Contained Ruptured Chronic Type B Dissection

    SciTech Connect

    Ketelsen, Dominik; Kalender, Guenay; Heuschmid, Martin; Syha, Roland; Mangold, Stefanie; Claussen, Claus D.; Brechtel, Klaus

    2011-10-15

    We report endovascular thoracic and abdominal aneurysm repair (EVAR) with reverse chimney technique in a patient with contained ruptured type B dissection. EVAR seems feasible as a bailout option in Marfan patients with acute life-threatening disease.

  16. Asterixis as a Presentation of Cerebellar Ischemic Stroke

    PubMed Central

    Siniscalchi, Antonio; Gallelli, Luca; Di Benedetto, Olindo; De Sarro, Giovambattista

    2012-01-01

    Asterixis is not yet considered a common neurological sign of cerebellum infarction, and the pathogenic mechanism for asterixis remains elusive. We report a 58-year-old male with moderate hypertension who presented to our emergency department for acute headache in both cervical and occipital regions of the left side. About 2 hours later the patient developed ipsilateral asterixis in the upper left limb; 3 days later the asterixis disappeared. Magnetic resonance imaging of the brain disclosed cerebellar infarctions at the left superior cerebellar artery. In conclusion, we observed that a transitory asterixis associated with ipsilateral headache can be an initial clinical manifestation of ipsilateral cerebellar infarctions in the superior cerebellar artery area. PMID:23359270

  17. Hypocupremia: A Possible Association with Late Cortical Cerebellar Atrophy

    PubMed Central

    Mittal, Shivam Om; Machado, Duarte G.

    2014-01-01

    Background We report a patient, diagnosed with late cortical cerebellar atrophy, who had persistent low serum copper levels. Case report A 48-year-old male developed progressive difficulty with balance, frequent falls, and dysarthric speech, which worsened over a short time span. He had an extensive ataxia work-up, which was unremarkable except for persistent low serum copper levels despite adequate supplementation. Magnetic resonance imaging of the brain showed marked cerebellar atrophy. The patient experienced progressive worsening of symptoms, which did not improve with either oral or parenteral copper supplementation. Discussion To our knowledge, ours is the first case report of late cortical cerebellar atrophy in the setting of low serum copper levels. The current report should trigger further research in mechanisms leading to copper deficiency and its possible role in cerebellar disease. PMID:25247109

  18. Cerebellar blood flow in methylmercury poisoning (Minamata disease).

    PubMed

    Itoh, K; Korogi, Y; Tomiguchi, S; Takahashi, M; Okajima, T; Sato, H

    2001-04-01

    We looked at regional cerebellar blood flow in patients with Minamata disease (MD) using technetium-99m ethyl cysteinate dimer (99m-Tc-ECD). We carried out single-photon emission computed tomography (SPECT) on 15 patients with MD (eight men, seven women, aged 51-78 years, mean 70.5 years) and 11 control subjects (eight men, three women, aged 62-80 years, mean 72.5 years). Regional blood flow was measured in the superior, middle, and inferior portions of the cerebellar hemispheres, and the frontal, temporal and occipital cerebral lobes. The degree of cerebellar atrophy was assessed on MRI. There were significant differences in regional blood flow in all parts of the cerebellum between patients and control, but no significant decrease was observed in the cerebrum. Blood flow was lower in the inferior cerebellum than in the other parts. Even in patients without cerebellar atrophy, flow was significantly decreased regional blood flow in the inferior part.

  19. Anomalous Cerebellar Anatomy in Chinese Children with Dyslexia

    PubMed Central

    Yang, Yang; Chen, Bao-Guo; Zhang, Yi-Wei; Bi, Hong-Yan

    2016-01-01

    The cerebellar deficit hypothesis for developmental dyslexia claims that cerebellar dysfunction causes the failures in the acquisition of visuomotor skills and automatic reading and writing skills. In people with dyslexia in the alphabetic languages, the abnormal activation and structure of the right or bilateral cerebellar lobes have been identified. Using a typical implicit motor learning task, however, one neuroimaging study demonstrated the left cerebellar dysfunction in Chinese children with dyslexia. In the present study, using voxel-based morphometry, we found decreased gray matter volume in the left cerebellum in Chinese children with dyslexia relative to age-matched controls. The positive correlation between reading performance and regional gray matter volume suggests that the abnormal structure in the left cerebellum is responsible for reading disability in Chinese children with dyslexia. PMID:27047403

  20. Malignant cerebellar peduncle lesions - rapid progression and poor outcome

    PubMed Central

    Singla, Navneet; Kapoor, Ankur; Savardekar, Amey; Radotra, B. D.; Chatterjee, Debjyoti; Gupta, Sunil K.

    2016-01-01

    Background: Tumors arising from cerebellar peduncle are extremely rare and behave aggressively. The inclusion of these into either cerebellar or brainstem gliomas is contentious. Case Description: We performed clinicopathological review of three patients treated at our institute and surveyed the literature for previous such reported cases. Mean duration of symptoms in our patients was 2 weeks. Subtotal tumor resection was performed in two patients while the third underwent stereotactic biopsy followed by chemoradiotherapy. Histopathology revealed glioblastoma in initial two patients and medulloblastoma Grade IV in the third. The two patients who underwent surgical excision succumbed to the illness within 2 days and a month, respectively. Conclusion: Malignant cerebellar peduncular lesions have poor overall survival despite surgical debulking. It is not confirmed whether these tumors should be considered as cerebellar lesions or brainstem gliomas due to aggressive clinical behavior, and so the ideal line of management is not yet known. PMID:27057396

  1. Brief Report: Acrocallosal Syndrome and Autism

    ERIC Educational Resources Information Center

    Steiner, Carlos Eduardo; Guerreiro, Marilisa Mantovani; Marques-de-Faria, Antonia Paula

    2004-01-01

    The authors describe a boy presenting with acrocallosal syndrome and autism. Clinical features included craniofacial dysmorphisms, polydactyly, and mental retardation, besides behavioral symptoms compatible with autism. Neuroimaging revealed hypoplasia of the corpus callosum and cerebellar abnormalities. The role of this entity and other…

  2. Non-invasive cerebellar stimulation--a consensus paper.

    PubMed

    Grimaldi, G; Argyropoulos, G P; Boehringer, A; Celnik, P; Edwards, M J; Ferrucci, R; Galea, J M; Groiss, S J; Hiraoka, K; Kassavetis, P; Lesage, E; Manto, M; Miall, R C; Priori, A; Sadnicka, A; Ugawa, Y; Ziemann, U

    2014-02-01

    The field of neurostimulation of the cerebellum either with transcranial magnetic stimulation (TMS; single pulse or repetitive (rTMS)) or transcranial direct current stimulation (tDCS; anodal or cathodal) is gaining popularity in the scientific community, in particular because these stimulation techniques are non-invasive and provide novel information on cerebellar functions. There is a consensus amongst the panel of experts that both TMS and tDCS can effectively influence cerebellar functions, not only in the motor domain, with effects on visually guided tracking tasks, motor surround inhibition, motor adaptation and learning, but also for the cognitive and affective operations handled by the cerebro-cerebellar circuits. Verbal working memory, semantic associations and predictive language processing are amongst these operations. Both TMS and tDCS modulate the connectivity between the cerebellum and the primary motor cortex, tuning cerebellar excitability. Cerebellar TMS is an effective and valuable method to evaluate the cerebello-thalamo-cortical loop functions and for the study of the pathophysiology of ataxia. In most circumstances, DCS induces a polarity-dependent site-specific modulation of cerebellar activity. Paired associative stimulation of the cerebello-dentato-thalamo-M1 pathway can induce bidirectional long-term spike-timing-dependent plasticity-like changes of corticospinal excitability. However, the panel of experts considers that several important issues still remain unresolved and require further research. In particular, the role of TMS in promoting cerebellar plasticity is not established. Moreover, the exact positioning of electrode stimulation and the duration of the after effects of tDCS remain unclear. Future studies are required to better define how DCS over particular regions of the cerebellum affects individual cerebellar symptoms, given the topographical organization of cerebellar symptoms. The long-term neural consequences of non

  3. Isolated cerebellar toxoplasmosis as a complication of HIV infection.

    PubMed

    Pott, H; Castelo, A

    2013-01-01

    Isolated cerebellar mass lesion is an uncommon presentation of toxoplasmosis. The authors report one rare case in a 50-year-old HIV-infected male patient who presented with clipped speech, gait ataxia and incoordination. The cerebellar toxoplasmosis was suspected based on imaging findings, despite the atypical location. This case highlights the need for a high index of clinical suspicion among HIV-infected patients with neurological manifestations and suspicious neuroimaging findings.

  4. Glucose utilization in the inferior cerebellar vermis and ocular myoclonus.

    PubMed

    Yakushiji, Y; Otsubo, R; Hayashi, T; Fukuchi, K; Yamada, N; Hasegawa, Y; Minematsu, K

    2006-07-11

    In a patient with symptomatic ocular myoclonus, the authors observed the regional cerebral metabolic rate of glucose use (rCMRGlu) before and after successful treatment with clonazepam. Even after the symptoms resolved, the rCMRGlu in the hypertrophic olive increased persistently, whereas that in the inferior cerebellar vermis contralateral to the hypertrophic olive decreased. The inferior cerebellar vermis, belonging to the vestibulocerebellar system, may be associated with the generation of symptomatic ocular myoclonus.

  5. The effects of the cerebral, cerebellar and vestibular systems on the head stabilization reflex.

    PubMed

    Bademkiran, Fikret; Uludag, Burhanettin; Guler, Ayse; Celebisoy, Nese

    2016-05-01

    The head stabilization reflex (HSR) is a brain stem reflex which appears in the neck muscles in response to sudden head position changes and brings the head to its previous position. The reflex mechanism has not been understood. The afferent fibers come from cervical muscle spindles, vestibular structures, and the accessory nerve, the efferents from the accessory nerve. In this study, we aim to investigate the roles of supraspinal neural structures and the vestibular system on the HSR. The patient group consisted of 86 patients (33 cerebral cortical lesion, 14 cerebellar syndrome and 39 vestibular inexcitability or hypoexcitability); the control group was composed of 32 healthy volunteers. Concentric needle electrodes were inserted into the sternocleidomastoid muscle (SCM) and the accessory nerves were stimulated with the electrical stimulator. A reflex response of about 45-55 ms was obtained from the contralateral SCM muscle. 50 % of cases had bilateral loss whereas 37 % of cases with unilateral cerebellar lesions had an ipsilateral reflex loss. Bilateral HSR loss was detected in 84 % of cases with bilateral cerebellar lesions. Bilateral reflex loss was observed in 70 % of patients with unilateral cortical lesions and 94 % of those with bilateral vestibular dysfunction. Ipsilateral HSR loss was observed in 55 % of cases with unilateral vestibular dysfunction. It was discovered that supraspinal structures and the vestibular system may have an excitatory effect on HSR. This effect may be lost in supra-segmental and vestibular dysfunctions. The localization value of HSR was found to be rather poor in our study.

  6. Subclinical nigrostriatal dopaminergic denervation in the cerebellar subtype of multiple system atrophy (MSA-C).

    PubMed

    Muñoz, Esteban; Iranzo, Alex; Rauek, Sebastian; Lomeña, Francisco; Gallego, Judith; Ros, Doménec; Santamaría, Joan; Tolosa, Eduardo

    2011-12-01

    Nigrostriatal involvement is considered an additional feature in the new consensus criteria for the diagnosis of the cerebellar variant of multiple system atrophy (MSA-C). However, so far, only a few studies, which include a relative small number of patients, give support to this criterion. Our objective was to assess nigrostriatal dopaminergic innervation in patients with MSA-C without parkinsonism by use of dopamine transporter single photon emission computed tomography (DAT SPECT). Thirteen patients that fulfilled criteria for possible or probable MSA-C and presented no parkinsonian signs, and 12 age-matched healthy controls underwent ((123)I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ([(123)I]FP-CIT) SPECT. Patients were also evaluated through the Unified Multiple System Atrophy Rating Scale (UMSARS) and brain magnetic resonance imaging (MRI). The mean duration of the cerebellar syndrome was 3.8 ± 1.7 years. DAT SPECT showed a significant decrease of striatal [(123)I]FP-CIT uptake ratios in patients (p < 0.001). Radiotracer uptake reduction was 21% in the entire striatum, 19% in putamen, and 24% in caudate nuclei. Striatal binding ratios were within the normal range in 3 patients. We did not find correlation between striatal uptake and disease duration, age of patients, UMSARS-II score, and pontine diameter. [(123)I]FP-CIT SPECT shows that most but not all MSA-C patients without parkinsonism have subclinical nigrostriatal dopaminergic denervation which is not related to disease duration, cerebellar dysfunction, or pontine atrophy.

  7. Paraneoplastic syndromes in olfactory neuroblastoma

    PubMed Central

    Gabrych, Anna; Czapiewski, Piotr; Sworczak, Krzysztof

    2015-01-01

    Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of sinonasal tract, derived from olfactory epithelium. Unilateral nasal obstruction, epistaxis, sinusitis, and headaches are common symptoms. Olfactory neuroblastoma shows neuroendocrine differentiation and similarly to other neuroendocrine tumors can produce several types of peptic substances and hormones. Excess production of these substances can be responsible for different types of endocrinological paraneoplastic syndromes (PNS). Moreover, besides endocrinological, in ONB may also occur neurological PNS, caused by immune cross-reactivity between tumor and normal host tissues in the nervous system. Paraneoplastic syndromes in ONB include: syndrome of inappropriate ADH secretion (SIADH), ectopic ACTH syndrome (EAS), humoral hypercalcemia of malignancy (HHM), hypertension due to catecholamine secretion by tumor, opsoclonus-myoclonus-ataxia (OMA) and paraneoplastic cerebellar degeneration. Paraneoplastic syndromes in ONB tend to have atypical features, therefore diagnosis may be difficult. In this review, we described initial symptoms, patterns of presentation, treatment and outcome of paraneoplastic syndromes in ONB, reported in the literature. PMID:26199564

  8. Proprioceptive Localization Deficits in People With Cerebellar Damage.

    PubMed

    Weeks, Heidi M; Therrien, Amanda S; Bastian, Amy J

    2017-04-01

    It has been hypothesized that an important function of the cerebellum is predicting the state of the body during movement. Yet, the extent of cerebellar involvement in perception of limb state (i.e., proprioception, specifically limb position sense) has yet to be determined. Here, we investigated whether patients with cerebellar damage have deficits when trying to locate their hand in space (i.e., proprioceptive localization), which is highly important for everyday movements. By comparing performance during passive robot-controlled and active self-made multi-joint movements, we were able to determine that some cerebellar patients show improved precision during active movement (i.e., active benefit), comparable to controls, whereas other patients have reduced active benefit. Importantly, the differences in patient performance are not explained by patient diagnosis or clinical ratings of impairment. Furthermore, a subsequent experiment confirmed that active deficits in proprioceptive localization occur during both single-joint and multi-joint movements. As such, it is unlikely that localization deficits can be explained by the multi-joint coordination deficits occurring after cerebellar damage. Our results suggest that cerebellar damage may cause varied impairments to different elements of proprioceptive sense. It follows that proprioceptive localization should be adequately accounted for in clinical testing and rehabilitation of people with cerebellar damage.

  9. Transplantation and Stem Cell Therapy for Cerebellar Degenerations.

    PubMed

    Cendelin, Jan

    2016-02-01

    Stem cell-based and regenerative therapy may become a hopeful treatment for neurodegenerative diseases including hereditary cerebellar degenerations. Neurotransplantation therapy mainly aims to substitute lost cells, but potential effects might include various mechanisms including nonspecific trophic effects and stimulation of endogenous regenerative processes and neural plasticity. Nevertheless, currently, there remain serious limitations. There is a wide spectrum of human hereditary cerebellar degenerations as well as numerous cerebellar mutant mouse strains that serve as models for the development of effective therapy. By now, transplantation has been shown to ameliorate cerebellar function, e.g. in Purkinje cell degeneration mice, Lurcher mutant mice and mouse models of spinocerebellar ataxia type 1 and type 2 and Niemann-Pick disease type C. Despite the lack of direct comparative studies, it appears that there might be differences in graft development and functioning between various types of cerebellar degeneration. Investigation of the relation of graft development to specific morphological, microvascular or biochemical features of the diseased host tissue in various cerebellar degenerations may help to identify factors determining the fate of grafted cells and potential of their functional integration.

  10. Neurodevelopmental Malformations of the Cerebellar Vermis in Genetically Engineered Rats.

    PubMed

    Ramos, Raddy L; Van Dine, Sarah E; Gilbert, Mary E; Leheste, Joerg R; Torres, German

    2015-12-01

    The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformations are almost exclusively found along the primary fissure and are indicative of deficits of neuronal migration during cerebellar development. In the present report, we test the prediction that genetically engineered rats on Sprague-Dawley or Long-Evans backgrounds will also exhibit the same cerebellar malformations. Consistent with our hypothesis, we found that three different transgenic lines on two different backgrounds had cerebellar malformations. Heterotopia in transgenic rats had identical cytoarchitecture as that observed in wild-type rats including altered morphology of Bergmann glia. In light of the possibility that heterotopia could affect results from behavioral studies, these data suggest that histological analyses be performed in studies of cerebellar function or development when using genetically engineered rats on these backgrounds in order to have more careful interpretation of experimental findings.

  11. Clumsiness and disturbed cerebellar development: insights from animal experiments.

    PubMed

    Gramsbergen, Albert

    2003-01-01

    Cerebellar functioning has been implied in the fine adjustments of muscle tone, in the coordination and the feed-forward control of movements and posture, as well as in the establishment and performance of motor skills. The cerebellar cortex in mammals develops late in neuro-ontogeny and an extrapolation from experimental results indicates that in the human the proliferation of the granule cells and the development of circuitry in the cerebellar cortex starts only in the last trimester of pregnancy and lasts until beyond the first birthday. This late development makes the cerebellar development particularly vulnerable to situations like an insufficient supply of nutrients, which may follow placental dysfunction, or to side effects of pharmacological treatments like the administration of corticosteroids in the postnatal period. We studied whether such situations might also lead to motor impairments. In rats, the effects of undernutrition during the brain growth spurt were investigated as well as those of corticosteroids administered in a period that is analogous to the 7th to 8th month of pregnancy in the human. Both these interferences affect cerebellar development and our results in rats indicate that they also lead to retardations in the emergence of certain reflexes, as well as to longer lasting motor impairments during locomotion. Extrapolation of these results strongly suggests that a disturbed cerebellar development should be considered as an important etiological factor in clumsiness in human children.

  12. Action of thyroxine on the survival and neurite maintenance of cerebellar granule neurons in culture.

    PubMed

    Oyanagi, Koshi; Negishi, Takayuki; Tashiro, Tomoko

    2015-04-01

    Developmental hypothyroidism causes severe impairments in the cerebellum. To understand the role of thyroid hormones (THs) in cerebellar development, we examined the effect of three different THs, thyroxine (T4), 3,5,3'-triidothyronine (T3), and 3,3',5'-triiodothyronine (reverse T3; rT3), on the survival and morphology of cerebellar granule neurons (CGNs) in culture and found novel actions specific to T4. Rat CGNs obtained at postnatal day 6 were first cultured for 2 days in serum-containing medium with 25 mM K(+) (K25), then switched to serum-free medium with physiological 5 mM K(+) (K5) or with K25 and cultured for an additional 2 or 4 days. CGNs underwent apoptosis in K5 but survived in K25. Addition of T4 at concentrations of 100-200 nM but not T3 or rT3 rescued CGNs from cell death in K5 in a dose-dependent manner. Furthermore, 200 nM T4 was also effective in maintaining the neurites of CGNs in K5. In K5, T4 suppressed tau phosphorylation at two developmentally regulated sites as well as phosphorylation of c-jun N-terminal kinase (JNK) necessary for its activation and localization to axons. These results suggest that, during cerebellar development, T4 exerts its activity in cell survival and neurite maintenance in a manner distinct from the other two thyroid hormones through regulating the activity and localization of JNK.

  13. Altered cerebellar connectivity in Parkinson's patients ON and OFF L-DOPA medication

    PubMed Central

    Festini, Sara B.; Bernard, Jessica A.; Kwak, Youngbin; Peltier, Scott; Bohnen, Nicolaas I.; Müller, Martijn L. T. M.; Dayalu, Praveen; Seidler, Rachael D.

    2015-01-01

    Although nigrostriatal changes are most commonly affiliated with Parkinson's disease, the role of the cerebellum in Parkinson's has become increasingly apparent. The present study used lobule-based cerebellar resting state functional connectivity to (1) compare cerebellar-whole brain and cerebellar-cerebellar connectivity in Parkinson's patients both ON and OFF L-DOPA medication and controls, and to (2) relate variations in cerebellar connectivity to behavioral performance. Results indicated that, when contrasted to the control group, Parkinson's patients OFF medication had increased levels of cerebellar-whole brain and cerebellar-cerebellar connectivity, whereas Parkinson's patients ON medication had decreased levels of cerebellar-whole brain and cerebellar-cerebellar connectivity. Moreover, analyses relating levels of cerebellar connectivity to behavioral measures demonstrated that, within each group, increased levels of connectivity were most often associated with improved cognitive and motor performance, but there were several instances where increased connectivity was related to poorer performance. Overall, the present study found medication-variant cerebellar connectivity in Parkinson's patients, further demonstrating cerebellar changes associated with Parkinson's disease and the moderating effects of medication. PMID:25954184

  14. Cerebellar-Motor Dysfunction in Schizophrenia and Psychosis-Risk: The Importance of Regional Cerebellar Analysis Approaches

    PubMed Central

    Bernard, Jessica A.; Mittal, Vijay A.

    2014-01-01

    Motor abnormalities in individuals with schizophrenia and those at-risk for psychosis are well documented. An accumulating body of work has also highlighted motor abnormalities related to cerebellar dysfunction in schizophrenia including eye-blink conditioning, timing, postural control, and motor learning. We have also recently found evidence for motor dysfunction in individuals at ultra high-risk for psychosis (1–3). This is particularly relevant as the cerebellum is thought to be central to the cognitive dysmetria model of schizophrenia, and these overt motor signs may point to more general cerebellar dysfunction in the etiology of psychotic disorders. While studies have provided evidence indicative of motor cerebellar dysfunction in at-risk populations and in schizophrenia, findings with respect to the cerebellum have been mixed. One factor potentially contributing to these mixed results is the whole-structure approach taken when investigating the cerebellum. In non-human primates, there are distinct closed-loop circuits between the cerebellum, thalamus, and brain with motor and non-motor cortical regions. Recent human neuroimaging has supported this finding and indicates that there is a cerebellar functional topography (4), and this information is being missed with whole-structure approaches. Here, we review cerebellar-motor dysfunction in individuals with schizophrenia and those at-risk for psychosis. We also discuss cerebellar abnormalities in psychosis, and the cerebellar functional topography. Because of the segregated functional regions of the cerebellum, we propose that it is important to look at the structure regionally in order to better understand its role in motor dysfunction in these populations. This is analogous to approaches taken with the basal ganglia, where each region is considered separately. Such an approach is necessary to better understand cerebellar pathophysiology on a macro-structural level with respect to the pathogenesis of

  15. Anti-Yo Mediated Paraneoplastic Cerebellar Degeneration Associated with Pseudobulbar Affect in a Patient with Breast Cancer

    PubMed Central

    Martin, Allison N.; Jones, David E.; Brenin, David R.; Lapides, David A.

    2017-01-01

    Paraneoplastic cerebellar degeneration (PCD) is a rare anti-Yo mediated paraneoplastic syndromes rarely that is infrequently associated with breast cancer. We present a case of a 52-year-old female presenting with diplopia, gait instability, dysarthria, dysphagia, nystagmus, and, most notably, new onset paroxysmal episodes of uncontrollable crying concerning for pseudobulbar affect (PBA). Serologic testing showed anti-Yo antibodies. The patient was found to have stage IIIA breast cancer as the inciting cause of the paraneoplastic syndrome. The patient was treated with neoadjuvant chemotherapy, modified radical mastectomy, adjuvant Herceptin, and pertuzumab. She was given IVIG for paraneoplastic syndrome, antidepressants, and dextromethorphan-quinidine (Nuedexta), the first FDA-approved therapy for PBA. With multimodality therapy, she demonstrated significant improvement in neurologic and mood symptoms associated with PCD and PBA. PMID:28377827

  16. A case-control proton magnetic resonance spectroscopy study confirms cerebellar dysfunction in benign adult familial myoclonic epilepsy

    PubMed Central

    Long, Lili; Song, Yanmin; Zhang, Linlin; Hu, Chongyu; Gong, Jian; Xu, Lin; Long, Hongyu; Zhou, Luo; Zhang, Yunci; Zhang, Yong; Xiao, Bo

    2015-01-01

    Background Benign adult familial myoclonic epilepsy (BAFME) is a rare form of epilepsy syndrome. The pathogenesis of BAFME remains unclear, though it seems to involve dysfunction of the cerebellum. Objectives The purpose of this study was to use proton magnetic resonance spectroscopy (1H-MRS) to investigate whether neurochemical changes underlie abnormal brain function in BAFME. Methods Twelve BAFME patients from one family and 12 age- and sex-matched healthy controls were enrolled in this study. The ratios of NAA/Cr, NAA/Cho, Cho/Cr, and NAA/(Cr+Cho) were analyzed. Results The BAFME patients exhibited a decreased N-acetylaspartate (NAA)/choline (Cho) ratio in the cerebellar cortex, whereas there were no significant differences in the NAA/creatine (Cr), Cho/Cr, and NAA/(Cr+Cho) ratios compared with healthy controls. There were no significant differences in 1H-MRS values in the frontal cortex or thalamus between the BAFME patients and controls. No correlation was detected between the NAA/Cho ratio in the cerebellar cortex and disease duration, myoclonus severity, or tremor severity. Conclusion Our results indicate clear cerebellar dysfunction in BAFME. 1H-MRS is a useful tool for the diagnosis of BAFME in combination with family history and electrophysiological examination. PMID:25750529

  17. Sex differences in cerebellar synaptic transmission and sex-specific responses to autism-linked Gabrb3 mutations in mice

    PubMed Central

    Mercer, Audrey A; Palarz, Kristin J; Tabatadze, Nino; Woolley, Catherine S; Raman, Indira M

    2016-01-01

    Neurons of the cerebellar nuclei (CbN) transmit cerebellar signals to premotor areas. The cerebellum expresses several autism-linked genes, including GABRB3, which encodes GABAA receptor β3 subunits and is among the maternal alleles deleted in Angelman syndrome. We tested how this Gabrb3 m-/p+ mutation affects CbN physiology in mice, separating responses of males and females. Wild-type mice showed sex differences in synaptic excitation, inhibition, and intrinsic properties. Relative to females, CbN cells of males had smaller synaptically evoked mGluR1/5-dependent currents, slower Purkinje-mediated IPSCs, and lower spontaneous firing rates, but rotarod performances were indistinguishable. In mutant CbN cells, IPSC kinetics were unchanged, but mutant males, unlike females, showed enlarged mGluR1/5 responses and accelerated spontaneous firing. These changes appear compensatory, since mutant males but not females performed indistinguishably from wild-type siblings on the rotarod task. Thus, sex differences in cerebellar physiology produce similar behavioral output, but provide distinct baselines for responses to mutations. DOI: http://dx.doi.org/10.7554/eLife.07596.001 PMID:27077953

  18. WNT3 Inhibits Cerebellar Granule Neuron Progenitor Proliferation and Medulloblastoma Formation via MAPK Activation

    PubMed Central

    Ayrault, Olivier; Kim, Jee Hae; Zhu, Xiaodong; Murphy, David A.; Van Aelst, Linda; Roussel, Martine F.; Hatten, Mary E.

    2013-01-01

    During normal cerebellar development, the remarkable expansion of granule cell progenitors (GCPs) generates a population of granule neurons that outnumbers the total neuronal population of the cerebral cortex, and provides a model for identifying signaling pathways that may be defective in medulloblastoma. While many studies focus on identifying pathways that promote growth of GCPs, a critical unanswered question concerns the identification of signaling pathways that block mitogenic stimulation and induce early steps in differentiation. Here we identify WNT3 as a novel suppressor of GCP proliferation during cerebellar development and an inhibitor of medulloblastoma growth in mice. WNT3, produced in early postnatal cerebellum, inhibits GCP proliferation by down-regulating pro-proliferative target genes of the mitogen Sonic Hedgehog (SHH) and the bHLH transcription factor Atoh1. WNT3 suppresses GCP growth through a non-canonical Wnt signaling pathway, activating prototypic mitogen-activated protein kinases (MAPKs), the Ras-dependent extracellular-signal-regulated kinases 1/2 (ERK1/2) and ERK5, instead of the classical β-catenin pathway. Inhibition of MAPK activity using a MAPK kinase (MEK) inhibitor reversed the inhibitory effect of WNT3 on GCP proliferation. Importantly, WNT3 inhibits proliferation of medulloblastoma tumor growth in mouse models by a similar mechanism. Thus, the present study suggests a novel role for WNT3 as a regulator of neurogenesis and repressor of neural tumors. PMID:24303070

  19. Highly 4-aminopyridine sensitive delayed rectifier current modulates the excitability of guinea pig cerebellar Purkinje cells.

    PubMed

    Etzion, Y; Grossman, Y

    2001-08-01

    The effects of low concentrations of 4-aminopyridine (4-AP) on the membrane properties of guinea pig cerebellar Purkinje cells were investigated in slice preparation using intracellular recordings. It was found that 1-10 microM 4-AP did not affect the resting potential or the input resistance of the cells, but reduced markedly the duration of the slowly depolarizing potential (SDP), and thus the latency to the firing of Ca2+ spikes in response to intracellular current pulses. Intradendritic recordings in the presence of tetrodotoxin, Cd2+, and low [Ca2+]o, which blocked all the regenerative responses, exhibited prominent membrane outward rectification in response to depolarizing current pulses. Under these conditions, the SDP was abolished and, in contrast, a slowly developing hyperpolarization was consistently observed. Application of 10 microM 4-AP reduced the outward membrane rectification in a reversible manner, but did not affect the transient hyperpolarization, which is usually attributed to the activation of potassium "A" current. These results demonstrate, for the first time, the presence of a highly 4-AP sensitive delayed rectifier in guinea pig cerebellar Purkinje cells, which prominently affects their excitability. The results also indicate that the slowly depolarizing potential of guinea pig Purkinje cells does not involve inactivation of transient potassium currents, which has been suggested previously as an underlying mechanism for this phenomenon in turtle Purkinje cells.

  20. Induced pluripotent stem cell technology for modelling and therapy of cerebellar ataxia

    PubMed Central

    Watson, Lauren M.; Wong, Maggie M. K.; Becker, Esther B. E.

    2015-01-01

    Induced pluripotent stem cell (iPSC) technology has emerged as an important tool in understanding, and potentially reversing, disease pathology. This is particularly true in the case of neurodegenerative diseases, in which the affected cell types are not readily accessible for study. Since the first descriptions of iPSC-based disease modelling, considerable advances have been made in understanding the aetiology and progression of a diverse array of neurodegenerative conditions, including Parkinson's disease and Alzheimer's disease. To date, however, relatively few studies have succeeded in using iPSCs to model the neurodegeneration observed in cerebellar ataxia. Given the distinct neurodevelopmental phenotypes associated with certain types of ataxia, iPSC-based models are likely to provide significant insights, not only into disease progression, but also to the development of early-intervention therapies. In this review, we describe the existing iPSC-based disease models of this heterogeneous group of conditions and explore the challenges associated with generating cerebellar neurons from iPSCs, which have thus far hindered the expansion of this research. PMID:26136256

  1. Differential prefrontal-like deficit in children after cerebellar astrocytoma and medulloblastoma tumor

    PubMed Central

    Vaquero, Encarna; Gómez, Carlos M; Quintero, Eliana A; González-Rosa, Javier J; Márquez, Javier

    2008-01-01

    suggest a differential prefrontal-like deficit due to cerebellar lesions and/or cerebellar-frontal diaschisis, as indicate the results in astrocytoma group (without treatments), that also can be generated and/or increased by treatments in the medulloblastoma group. The need for differential rehabilitation strategies for specific clinical groups is remarked. The results are also discussed in the context of the Cerebellar Cognitive Affective Syndrome. PMID:18412947

  2. Imaging calcium waves in cerebellar Bergmann glia.

    PubMed

    Beierlein, Michael

    2013-01-01

    This protocol describes methods for recording synaptically evoked Ca(2+) waves from individual Bergmann glia (BG) in slices of cerebellar cortex. Unlike protoplasmic, star-shaped astrocytes, whose thin processes pose a serious challenge to stable Ca(2+) measurements, BG are large radial cells, with several main processes that run over distances of several hundred micrometers toward the pia and ensheathe thousands of parallel fiber (PF) synapses. Stimulation of PF synapses with brief bursts can trigger long-lasting Ca(2+) responses in BG processes, which can be reliably recorded using a cooled charge-coupled device (CCD) camera. This protocol was developed to enable measurements of Ca(2+) waves in individual BG loaded with a high-affinity Ca(2+) indicator such as Fura-2 for up to 2 h. Because BG recorded in slices rarely display spontaneous (i.e., tetrodotoxin [TTX]-sensitive) or intrinsic Ca(2+) transients, Ca(2+) waves can be evoked repeatedly and reliably, which permits quantitative studies using pharmacological tools. Fluorescence measurements obtained using CCD technology offer a straightforward means of characterizing the mechanisms and potential functional consequences of widespread and long-lasting, store-mediated Ca(2+) increases in astrocytes.

  3. Reversible Sterilization

    ERIC Educational Resources Information Center

    Largey, Gale

    1977-01-01

    Notes that difficult questions arise concerning the use of sterilization for alleged eugenic and euthenic purposes. Thus, how reversible sterilization will be used with relation to the poor, mentally ill, mentally retarded, criminals, and minors, is questioned. (Author/AM)

  4. Understanding and modulating motor learning with Cerebellar stimulation

    PubMed Central

    Celnik, Pablo

    2014-01-01

    Non-invasive brain stimulation techniques are a powerful approach to investigate the physiology and function of the central nervous system. Recent years have seen numerous investigations delivering transcranial magnetic stimulation (TMS) and or transcranial direct current stimulation (tDCS) to the cerebellum to determine its role in motor, cognitive and emotional behaviours. Early studies have shown that it is possible to assess cerebellar-motor cortex (CB-M1) connectivity using a paired-pulse TMS paradigm called cerebellar inhibition (CBI), and indirectly infer the state of cerebellar excitability. Thus, it has been shown that CBI changes proportionally to the magnitude of locomotor learning and in association with reaching adaption tasks. In addition, CBI has been used to demonstrate at a physiological level the effects of applying TMS or tDCS to modulate, up or down, the excitability of cerebellar-M1 connectivity. These studies became the fundamental substrate to newer investigations showing that we can affect motor, cognitive and emotional behaviour when TMS or tDCS targeting the cerebellum is delivered in the context of performance. Furthermore, newer investigations are starting to report the effects of cerebellar non-invasive stimulation to treat symptoms associated with neurological conditions such as stroke and dystonia. Altogether, non-invasive cerebellar stimulation can potentially become a game changer for the management of conditions that affect the cerebellum given the scarcity of current effective therapeutic options. In this brief manuscript, some of the current evidence demonstrating the effects of cerebellar stimulation to modulate motor behaviour and its use to assess physiological processes underlying motor learning are presented. PMID:25283180

  5. A Cerebellar Neuroprosthetic System: Computational Architecture and in vivo Test

    PubMed Central

    Herreros, Ivan; Giovannucci, Andrea; Taub, Aryeh H.; Hogri, Roni; Magal, Ari; Bamford, Sim; Prueckl, Robert; Verschure, Paul F. M. J.

    2014-01-01

    Emulating the input–output functions performed by a brain structure opens the possibility for developing neuroprosthetic systems that replace damaged neuronal circuits. Here, we demonstrate the feasibility of this approach by replacing the cerebellar circuit responsible for the acquisition and extinction of motor memories. Specifically, we show that a rat can undergo acquisition, retention, and extinction of the eye-blink reflex even though the biological circuit responsible for this task has been chemically inactivated via anesthesia. This is achieved by first developing a computational model of the cerebellar microcircuit involved in the acquisition of conditioned reflexes and training it with synthetic data generated based on physiological recordings. Secondly, the cerebellar model is interfaced with the brain of an anesthetized rat, connecting the model’s inputs and outputs to afferent and efferent cerebellar structures. As a result, we show that the anesthetized rat, equipped with our neuroprosthetic system, can be classically conditioned to the acquisition of an eye-blink response. However, non-stationarities in the recorded biological signals limit the performance of the cerebellar model. Thus, we introduce an updated cerebellar model and validate it with physiological recordings showing that learning becomes stable and reliable. The resulting system represents an important step toward replacing lost functions of the central nervous system via neuroprosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region. These results also embody an early example of science-based medicine, where on the one hand the neuroprosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step toward the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term, humans. PMID:25152887

  6. Reversible Cardiomyopathies

    PubMed Central

    Patel, Harsh; Madanieh, Raef; Kosmas, Constantine E; Vatti, Satya K; Vittorio, Timothy J

    2015-01-01

    Cardiomyopathies (CMs) have many etiological factors that can result in severe structural and functional dysregulation. Fortunately, there are several potentially reversible CMs that are known to improve when the root etiological factor is addressed. In this article, we discuss several of these reversible CMs, including tachycardia-induced, peripartum, inflammatory, hyperthyroidism, Takotsubo, and chronic illness–induced CMs. Our discussion also includes a review on their respective pathophysiology, as well as possible management solutions. PMID:26052233

  7. Distributed Cerebellar Motor Learning: A Spike-Timing-Dependent Plasticity Model.

    PubMed

    Luque, Niceto R; Garrido, Jesús A; Naveros, Francisco; Carrillo, Richard R; D'Angelo, Egidio; Ros, Eduardo

    2016-01-01

    Deep cerebellar nuclei neurons receive both inhibitory (GABAergic) synaptic currents from Purkinje cells (within the cerebellar cortex) and excitatory (glutamatergic) synaptic currents from mossy fibers. Those two deep cerebellar nucleus inputs are thought to be also adaptive, embedding interesting properties in the framework of accurate movements. We show that distributed spike-timing-dependent plasticity mechanisms (STDP) located at different cerebellar sites (parallel fibers to Purkinje cells, mossy fibers to deep cerebellar nucleus cells, and Purkinje cells to deep cerebellar nucleus cells) in close-loop simulations provide an explanation for the complex learning properties of the cerebellum in motor learning. Concretely, we propose a new mechanistic cerebellar spiking model. In this new model, deep cerebellar nuclei embed a dual functionality: deep cerebellar nuclei acting as a gain adaptation mechanism and as a facilitator for the slow memory consolidation at mossy fibers to deep cerebellar nucleus synapses. Equipping the cerebellum with excitatory (e-STDP) and inhibitory (i-STDP) mechanisms at deep cerebellar nuclei afferents allows the accommodation of synaptic memories that were formed at parallel fibers to Purkinje cells synapses and then transferred to mossy fibers to deep cerebellar nucleus synapses. These adaptive mechanisms also contribute to modulate the deep-cerebellar-nucleus-output firing rate (output gain modulation toward optimizing its working range).

  8. Distributed Cerebellar Motor Learning: A Spike-Timing-Dependent Plasticity Model

    PubMed Central

    Luque, Niceto R.; Garrido, Jesús A.; Naveros, Francisco; Carrillo, Richard R.; D'Angelo, Egidio; Ros, Eduardo

    2016-01-01

    Deep cerebellar nuclei neurons receive both inhibitory (GABAergic) synaptic currents from Purkinje cells (within the cerebellar cortex) and excitatory (glutamatergic) synaptic currents from mossy fibers. Those two deep cerebellar nucleus inputs are thought to be also adaptive, embedding interesting properties in the framework of accurate movements. We show that distributed spike-timing-dependent plasticity mechanisms (STDP) located at different cerebellar sites (parallel fibers to Purkinje cells, mossy fibers to deep cerebellar nucleus cells, and Purkinje cells to deep cerebellar nucleus cells) in close-loop simulations provide an explanation for the complex learning properties of the cerebellum in motor learning. Concretely, we propose a new mechanistic cerebellar spiking model. In this new model, deep cerebellar nuclei embed a dual functionality: deep cerebellar nuclei acting as a gain adaptation mechanism and as a facilitator for the slow memory consolidation at mossy fibers to deep cerebellar nucleus synapses. Equipping the cerebellum with excitatory (e-STDP) and inhibitory (i-STDP) mechanisms at deep cerebellar nuclei afferents allows the accommodation of synaptic memories that were formed at parallel fibers to Purkinje cells synapses and then transferred to mossy fibers to deep cerebellar nucleus synapses. These adaptive mechanisms also contribute to modulate the deep-cerebellar-nucleus-output firing rate (output gain modulation toward optimizing its working range). PMID:26973504

  9. DTI fiber tractography of cerebro-cerebellar pathways and clinical evaluation of ataxia in childhood posterior fossa tumor survivors.

    PubMed

    Oh, Myung Eun; Driever, Pablo Hernáiz; Khajuria, Rajiv K; Rueckriegel, Stefan Mark; Koustenis, Elisabeth; Bruhn, Harald; Thomale, Ulrich-Wilhelm

    2017-01-01

    Pediatric posterior fossa (PF) tumor survivors experience long-term motor deficits. Specific cerebrocerebellar connections may be involved in incidence and severity of motor dysfunction. We examined the relationship between long-term ataxia as well as fine motor function and alteration of differential cerebellar efferent and afferent pathways using diffusion tensor imaging (DTI) and tractography. DTI-based tractography was performed in 19 patients (10 pilocytic astrocytoma (PA) and 9 medulloblastoma patients (MB)) and 20 healthy peers. Efferent Cerebello-Thalamo-Cerebral (CTC) and afferent Cerebro-Ponto-Cerebellar (CPC) tracts were reconstructed and analyzed concerning fractional anisotropy (FA) and volumetric measurements. Clinical outcome was assessed with the International Cooperative Ataxia Rating Scale (ICARS). Kinematic parameters of fine motor function (speed, automation, variability, and pressure) were obtained by employing a digitizing graphic tablet. ICARS scores were significantly higher in MB patients than in PA patients. Poorer ICARS scores and impaired fine motor function correlated significantly with volume loss of CTC pathway in MB patients, but not in PA patients. Patients with pediatric post-operative cerebellar mutism syndrome showed higher loss of CTC pathway volume and were more atactic. CPC pathway volume was significantly reduced in PA patients, but not in MB patients. Neither relationship was observed between the CPC pathway and ICARS or fine motor function. There was no group difference of FA values between the patients and healthy peers. Reduced CTC pathway volumes in our cohorts were associated with severity of long-term ataxia and impaired fine motor function in survivors of MBs. We suggest that the CTC pathway seems to play a role in extent of ataxia and fine motor dysfunction after childhood cerebellar tumor treatment. DTI may be a useful tool to identify relevant structures of the CTC pathway and possibly avoid surgically induced long

  10. Reversal of focal "misery-perfusion syndrome" by extra-intracranial arterial bypass in hemodynamic cerebral ischemia. A case study with 15O positron emission tomography.

    PubMed

    Baron, J C; Bousser, M G; Rey, A; Guillard, A; Comar, D; Castaigne, P

    1981-01-01

    Tomographic images of cerebral blood flow (CBF) and oxygen extraction fraction (OEF) using the 15O continuous inhalation technique, and positron emission tomography, were obtained from a patient with cerebral ischemia distal to an occluded left internal carotid artery. There was a focal mismatch between CBF and oxygen metabolism in the brain supplied by the middle cerebral artery where CBF was decreased and OEF increased ("misery-perfusion syndrome" as opposed to "luxury-perfusion syndrome"). These abnormalities were most marked in the parieto-occipital watershed area. After left superficial temporal to middle cerebral artery anastomosis, the clinical attacks ceased and a repeat study did not demonstrate the previous CBF and OEF abnormalities. This suggests that this pattern of abnormalities indicates potential viable tissue. The concept of "misery-perfusion" may be of some importance in the pathophysiological mechanisms of hemodynamic cerebral ischemia and serve as a rational basis for revascularization procedures.

  11. Cerebellar cortex and cerebellar nuclei are concomitantly activated during eyeblink conditioning: a 7T fMRI study in humans.

    PubMed

    Thürling, Markus; Kahl, Fabian; Maderwald, Stefan; Stefanescu, Roxana M; Schlamann, Marc; Boele, Henk-Jan; De Zeeuw, Chris I; Diedrichsen, Jörn; Ladd, Mark E; Koekkoek, Sebastiaan K E; Timmann, Dagmar

    2015-01-21

    There are controversies whether learning of conditioned eyeblink responses primarily takes place within the cerebellar cortex, the interposed nuclei, or both. It has also been suggested that the cerebellar cortex may be important during early stages of learning, and that there is a shift to the cerebellar nuclei during later stages. As yet, human studies have provided little to resolve this question. In the present study, we established a setup that allows ultra-high-field 7T functional magnetic resonance imaging (fMRI) of the cerebellar cortex and interposed cerebellar nuclei simultaneously during delay eyeblink conditioning in humans. Event-related fMRI signals increased concomitantly in the cerebellar cortex and nuclei during early acquisition of conditioned eyeblink responses in 20 healthy human subjects. ANOVAs with repeated-measures showed significant effects of time across five blocks of 20 conditioning trials in the cortex and nuclei (p < 0.05, permutation corrected). Activations were most pronounced in, but not limited to, lobules VI and interposed nuclei. Increased activations were most prominent at the first time the maximum number of conditioned responses was achieved. Our data are consistent with a simultaneous and synergistic two-site model of learning during acquisition of classically conditioned eyeblinks. Because increased MRI signal reflects synaptic activity, concomitantly increased signals in the cerebellar nuclei and cortex are consistent with findings of learning related potentiation at the mossy fiber to nuclear cell synapse and mossy fiber to granule cell synapse. Activity related to the expression of conditioned responses, however, cannot be excluded.

  12. Developmental subchronic exposure to diphenylarsinic acid induced increased exploratory behavior, impaired learning behavior, and decreased cerebellar glutathione concentration in rats.

    PubMed

    Negishi, Takayuki; Matsunaga, Yuki; Kobayashi, Yayoi; Hirano, Seishiro; Tashiro, Tomoko

    2013-12-01

    In Japan, people using water from the well contaminated with high-level arsenic developed neurological, mostly cerebellar, symptoms, where diphenylarsinic acid (DPAA) was a major compound. Here, we investigated the adverse effects of developmental exposure to 20mg/l DPAA in drinking water (early period [0-6 weeks of age] and/or late period [7-12]) on behavior and cerebellar development in male rats. In the open field test at 6 weeks of age, early exposure to DPAA significantly increased exploratory behaviors. At 12 weeks of age, late exposure to DPAA similarly increased exploratory behavior independent of the early exposure although a 6-week recovery from DPAA could reverse that change. In the passive avoidance test at 6 weeks of age, early exposure to DPAA significantly decreased the avoidance performance. Even at 12 weeks of age, early exposure to DPAA significantly decreased the test performance, which was independent of the late exposure to DPAA. These results suggest that the DPAA-induced increase in exploratory behavior is transient, whereas the DPAA-induced impairment of passive avoidance is long lasting. At 6 weeks of age, early exposure to DPAA significantly reduced the concentration of cerebellar total glutathione. At 12 weeks of age, late, but not early, exposure to DPAA also significantly reduced the concentration of cerebellar glutathione, which might be a primary cause of oxidative stress. Early exposure to DPAA induced late-onset suppressed expression of NMDAR1 and PSD95 protein at 12 weeks of age, indicating impaired glutamatergic system in the cerebellum of rats developmentally exposed to DPAA.

  13. Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey

    SciTech Connect

    Shimoyama, I.; Dauth, G.W.; Gilman, S.; Frey, K.A.; Penney, J.B. Jr.

    1988-12-01

    Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (1CMRG1c) is decreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral decreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated.

  14. Motor learning of mice lacking cerebellar Purkinje cells

    PubMed Central

    Porras-García, M. Elena; Ruiz, Rocío; Pérez-Villegas, Eva M.; Armengol, José Á.

    2013-01-01

    The cerebellum plays a key role in the acquisition and execution of motor tasks whose physiological foundations were postulated on Purkinje cells' long-term depression (LTD). Numerous research efforts have been focused on understanding the cerebellum as a site of learning and/or memory storage. However, the controversy on which part of the cerebellum participates in motor learning, and how the process takes place, remains unsolved. In fact, it has been suggested that cerebellar cortex, deep cerebellar nuclei, and/or their combination with some brain structures other than the cerebellum are responsible for motor learning. Different experimental approaches have been used to tackle this question (cerebellar lesions, pharmacological agonist and/or antagonist of cerebellar neurotransmitters, virus tract tracings, etc.). One of these approaches is the study of spontaneous mutations affecting the cerebellar cortex and depriving it of its main input–output organizer (i.e., the Purkinje cell). In this review, we discuss the results obtained in our laboratory in motor learning of both Lurcher (Lc/+) and tambaleante (tbl/tbl) mice as models of Purkinje-cell-devoid cerebellum. PMID:23630472

  15. Motor learning of mice lacking cerebellar Purkinje cells.

    PubMed

    Porras-García, M Elena; Ruiz, Rocío; Pérez-Villegas, Eva M; Armengol, José Á

    2013-01-01

    The cerebellum plays a key role in the acquisition and execution of motor tasks whose physiological foundations were postulated on Purkinje cells' long-term depression (LTD). Numerous research efforts have been focused on understanding the cerebellum as a site of learning and/or memory storage. However, the controversy on which part of the cerebellum participates in motor learning, and how the process takes place, remains unsolved. In fact, it has been suggested that cerebellar cortex, deep cerebellar nuclei, and/or their combination with some brain structures other than the cerebellum are responsible for motor learning. Different experimental approaches have been used to tackle this question (cerebellar lesions, pharmacological agonist and/or antagonist of cerebellar neurotransmitters, virus tract tracings, etc.). One of these approaches is the study of spontaneous mutations affecting the cerebellar cortex and depriving it of its main input-output organizer (i.e., the Purkinje cell). In this review, we discuss the results obtained in our laboratory in motor learning of both Lurcher (Lc/+) and tambaleante (tbl/tbl) mice as models of Purkinje-cell-devoid cerebellum.

  16. Modeling the Generation of Output by the Cerebellar Nuclei

    PubMed Central

    Steuber, Volker; Jaeger, Dieter

    2012-01-01

    Functional aspects of network integration in the cerebellar cortex have been studied experimentally and modeled in much detail ever since the early work by theoreticians such as Marr, Albus and Braitenberg more than 40 years ago. In contrast, much less is known about cerebellar processing at the output stage, namely in the cerebellar nuclei (CN). Here, input from Purkinje cells converges to control CN neuron spiking via GABAergic inhibition, before the output from the CN reaches cerebellar targets such as the brainstem and the motor thalamus. In this article we review modeling studies that address how the CN may integrate cerebellar cortical inputs, and what kind of signals may be transmitted. Specific hypotheses in the literature contrast rate coding and temporal coding of information in the spiking output from the CN. One popular hypothesis states that postinhibitory rebound spiking may be an important mechanism by which Purkinje cell inhibition is turned into CN output spiking, but this hypothesis remains controversial. Rate coding clearly does take place, but in what way it may be augmented by temporal codes remains to be more clearly established. Several candidate mechanisms distinct from rebound spiking are discussed, such as the significance of spike time correlations between Purkinje cell pools to determine CN spike timing, irregularity of Purkinje cell spiking as a determinant of CN firing rate, and shared brief pauses between Purkinje cell pools that may trigger individual CN spikes precisely. PMID:23200193

  17. Upregulation of cortico-cerebellar functional connectivity after motor learning.

    PubMed

    Mehrkanoon, Saeid; Boonstra, Tjeerd W; Breakspear, Michael; Hinder, Mark; Summers, Jeffery J

    2016-03-01

    Interactions between the cerebellum and primary motor cortex are crucial for the acquisition of new motor skills. Recent neuroimaging studies indicate that learning motor skills is associated with subsequent modulation of resting-state functional connectivity in the cerebellar and cerebral cortices. The neuronal processes underlying the motor-learning-induced plasticity are not well understood. Here, we investigate changes in functional connectivity in source-reconstructed electroencephalography (EEG) following the performance of a single session of a dynamic force task in twenty young adults. Source activity was reconstructed in 112 regions of interest (ROIs) and the functional connectivity between all ROIs was estimated using the imaginary part of coherence. Significant changes in resting-state connectivity were assessed using partial least squares (PLS). We found that subjects adapted their motor performance during the training session and showed improved accuracy but with slower movement times. A number of connections were significantly upregulated after motor training, principally involving connections within the cerebellum and between the cerebellum and motor cortex. Increased connectivity was confined to specific frequency ranges in the mu- and beta-bands. Post hoc analysis of the phase spectra of these cerebellar and cortico-cerebellar connections revealed an increased phase lag between motor cortical and cerebellar activity following motor practice. These findings show a reorganization of intrinsic cortico-cerebellar connectivity related to motor adaptation and demonstrate the potential of EEG connectivity analysis in source space to reveal the neuronal processes that underpin neural plasticity.

  18. Diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X.

    PubMed

    Miyamoto, T; Kanazawa, N; Kato, S; Kawakami, M; Inoue, Y; Kuhara, T; Inoue, T; Takeshita, K; Tsujino, S

    2001-01-01

    Patients with mitochondrial ornithine transporter deficiency (or HHH syndrome) present with various neurological symptoms, including mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodic disturbance of consciousness or coma due to hyperammonemia. We previously described three novel mutations in the ORNT1 gene in Japanese patients with HHH syndrome. In this article, we report a new patient with HHH syndrome, a 52-year-old woman, who had the typical clinical features, except for an absence of mental retardation. When we screened this patient, as well as a previously described Japanese patient, for mutations in the ORNT1 gene, we found that both were homozygous for a nonsense mutation (R179X). Furthermore, reverse transcription (RT)-polymerase chain reaction (PCR) of fibroblast RNA from one patient showed exon 4 skipping, as had been observed in a previously reported patient with R179X. These results, together with the findings in our previous report, show that, in three of our five reported Japanese HHH patients (six of ten alleles), R179X is present, suggesting that this is a common mutation in Japanese patients with HHH syndrome.

  19. Presynaptic Calcium Signalling in Cerebellar Mossy Fibres

    PubMed Central

    Thomsen, Louiza B.; Jörntell, Henrik; Midtgaard, Jens

    2009-01-01

    Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX)-sensitive fast Na+ spike faithfully followed repetitive depolarizing pulses with little change in spike duration or amplitude, while a strong outward rectification dominated responses to long-lasting depolarizations. High-threshold calcium spikes were uncovered following addition of potassium channel blockers. Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none TTX-sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon appeared to be isolated from one another in terms of calcium signalling. CGP55845 application showed that GABA B receptors mediated presynaptic inhibition of the calcium signal over the entire firing frequency range of mossy fibres. A paired-pulse depression of the calcium signal lasting more than 1 s affected burst firing in mossy fibres; this paired-pulse depression was reduced by GABA B antagonists. While our results indicated that a presynaptic rosette electrophysiologically functioned as a unit, topical GABA application showed that calcium signals in the branches of complex rosettes could be modulated locally, suggesting that cerebellar glomeruli may be dynamically sub-compartmentalized due to ongoing inhibition mediated by Golgi cells. This could provide a fine-grained control of mossy fibre-granule cell information transfer and synaptic plasticity within a mossy fibre rosette. PMID:20162034

  20. Case Report: Acute Cerebellar Thrombosis in an Adult Patient with IgM Nephropathy

    PubMed Central

    Adike, Abimbola; Cherry, Mariyam; Awar, Melina

    2015-01-01

    IgM nephropathy is a relatively rare cause of idiopathic nephrotic syndrome.1 It was initially described by van de Putte,2 then by Cohen and Bhasin in 1978, as a distinctive feature of mesangial proliferative glomerulonephritis.2 It is typically characterized by diffuse IgM deposits on the glomeruli and diffuse mesangial hypercellularity. Little is known about the pathogenesis and treatment of this disease.1,3 We describe a patient who presented with nonspecific symptoms of epigastric pain, nausea, and early satiety. Abdominal imaging and endoscopies were unremarkable. She was found to have significant proteinuria (6.4 g/24 hours), hyperlipidemia, and edema consistent with a diagnosis of nephrotic syndrome. Kidney biopsy was performed and confirmed an IgM nephropathy. Less than 2 weeks after her diagnosis of IgM nephropathy, she presented with an acute cerebellar stroke. Thrombophilia is a well-known complication of nephrotic syndrome, but a review of the literature failed to show an association between IgM nephropathy and acute central nervous system thrombosis. PMID:27057296

  1. Cbln1 downregulates the formation and function of inhibitory synapses in mouse cerebellar Purkinje cells.

    PubMed

    Ito-Ishida, Aya; Kakegawa, Wataru; Kohda, Kazuhisa; Miura, Eriko; Okabe, Shigeo; Yuzaki, Michisuke

    2014-04-01

    The formation of excitatory and inhibitory synapses must be tightly coordinated to establish functional neuronal circuitry during development. In the cerebellum, the formation of excitatory synapses between parallel fibers and Purkinje cells is strongly induced by Cbln1, which is released from parallel fibers and binds to the postsynaptic δ2 glutamate receptor (GluD2). However, Cbln1's role, if any, in inhibitory synapse formation has been unknown. Here, we show that Cbln1 downregulates the formation and function of inhibitory synapses between Purkinje cells and interneurons. Immunohistochemical analyses with an anti-vesicular GABA transporter antibody revealed an increased density of interneuron-Purkinje cell synapses in the cbln1-null cerebellum. Whole-cell patch-clamp recordings from Purkinje cells showed that both the amplitude and frequency of miniature inhibitory postsynaptic currents were increased in cbln1-null cerebellar slices. A 3-h incubation with recombinant Cbln1 reversed the increased amplitude of inhibitory currents in Purkinje cells in acutely prepared cbln1-null slices. Furthermore, an 8-day incubation with recombinant Cbln1 reversed the increased interneuron-Purkinje cell synapse density in cultured cbln1-null slices. In contrast, recombinant Cbln1 did not affect cerebellar slices from mice lacking both Cbln1 and GluD2. Finally, we found that tyrosine phosphorylation was upregulated in the cbln1-null cerebellum, and acute inhibition of Src-family kinases suppressed the increased inhibitory postsynaptic currents in cbln1-null Purkinje cells. These findings indicate that Cbln1-GluD2 signaling inhibits the number and function of inhibitory synapses, and shifts the excitatory-inhibitory balance towards excitation in Purkinje cells. Cbln1's effect on inhibitory synaptic transmission is probably mediated by a tyrosine kinase pathway.

  2. Behavioral effects of neonatal lesions on the cerebellar system.

    PubMed

    Lalonde, Robert; Strazielle, Catherine

    2015-06-01

    Several rodent models with spontaneous mutations causing cerebellar pathology are impaired in motor functions during the neonatal period, including Grid2(Lc), Rora(sg), Dab1(scm), Girk2(Wv), Lmx1a(dr-sst), Myo5a(dn), Inpp4a(wbl), and Cacna1a(rol) mice as well as shaker and dystonic rats. Deficits are also evident in murine null mutants such as Zic1, Fgfr1/FgFr2, and Xpa/Ercc8. Behavioral deficits are time-dependent following X-irradiated- or aspiration-induced lesions of the cerebellum in rats. In addition, motor functions are deficient after lesions in cerebellar-related pathways. As in animal subjects, sensorimotor disturbances have been described in children with cerebellar lesions. These results underline the importance of the cerebellum and its connections in the development of motor functions.

  3. Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning

    PubMed Central

    Gao, Zhenyu; Proietti-Onori, Martina; Lin, Zhanmin; ten Brinke, Michiel M.; Boele, Henk-Jan; Potters, Jan-Willem; Ruigrok, Tom J.H.; Hoebeek, Freek E.; De Zeeuw, Chris I.

    2016-01-01

    Summary Closed-loop circuitries between cortical and subcortical regions can facilitate precision of output patterns, but the role of such networks in the cerebellum remains to be elucidated. Here, we characterize the role of internal feedback from the cerebellar nuclei to the cerebellar cortex in classical eyeblink conditioning. We find that excitatory output neurons in the interposed nucleus provide efference-copy signals via mossy fibers to the cerebellar cortical zones that belong to the same module, triggering monosynaptic responses in granule and Golgi cells and indirectly inhibiting Purkinje cells. Upon conditioning, the local density of nucleocortical mossy fiber terminals significantly increases. Optogenetic activation and inhibition of nucleocortical fibers in conditioned animals increases and decreases the amplitude of learned eyeblink responses, respectively. Our data show that the excitatory nucleocortical closed-loop circuitry of the cerebellum relays a corollary discharge of premotor signals and suggests an amplifying role of this circuitry in controlling associative motor learning. PMID:26844836

  4. Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids.

    PubMed

    Tam, Emily W Y; Chau, Vann; Ferriero, Donna M; Barkovich, A James; Poskitt, Kenneth J; Studholme, Colin; Fok, Eric D-Y; Grunau, Ruth E; Glidden, David V; Miller, Steven P

    2011-10-19

    As survival rates of preterm newborns improve as a result of better medical management, these children increasingly show impaired cognition. These adverse cognitive outcomes are associated with decreases in the volume of the cerebellum. Because animals exhibit reduced preterm cerebellar growth after perinatal exposure to glucocorticoids, we sought to determine whether glucocorticoid exposure and other modifiable factors increased the risk for these adverse outcomes in human neonates. We studied 172 preterm neonatal infants from two medical centers, the University of British Columbia and the University of California, San Francisco, by performing serial magnetic resonance imaging examinations near birth and again near term-equivalent age. After we adjusted for associated clinical factors, antenatal betamethasone was not associated with changes in cerebellar volume. Postnatal exposure to clinically routine doses of hydrocortisone or dexamethasone was associated with impaired cerebellar, but not cerebral, growth. Alterations in treatment after preterm birth, particularly glucocorticoid exposure, may help to decrease risk for adverse neurological outcome after preterm birth.

  5. Cerebellar Development and Autism Spectrum Disorder in Tuberous Sclerosis Complex.

    PubMed

    Sundberg, Maria; Sahin, Mustafa

    2015-12-01

    Approximately 50% of patients with the genetic disease tuberous sclerosis complex present with autism spectrum disorder. Although a number of studies have investigated the link between autism and tuberous sclerosis complex, the etiology of autism spectrum disorder in these patients remains unclear. Abnormal cerebellar function during critical phases of development could disrupt functional processes in the brain, leading to development of autistic features. Accordingly, the authors review the potential role of cerebellar dysfunction in the pathogenesis of autism spectrum disorder in tuberous sclerosis complex. The authors also introduce conditional knockout mouse models of Tsc1 and Tsc2 that link cerebellar circuitry to the development of autistic-like features. Taken together, these preclinical and clinical investigations indicate the cerebellum has a profound regulatory role during development of social communication and repetitive behaviors.

  6. A composite neurobehavioral test to evaluate acute functional deficits after cerebellar haemorrhage in rats.

    PubMed

    McBride, Devin W; Nowrangi, Derek; Kaur, Harpreet; Wu, Guangyong; Huang, Lei; Lekic, Tim; Tang, Jiping; Zhang, John H

    2017-01-01

    Cerebellar haemorrhage accounts for 5-10% of all intracerebral haemorrhages and leads to severe, long-lasting functional deficits. Currently, there is limited research on this stroke subtype, which may be due to the lack of a suitable composite neuroscoring system specific for cerebellar injury in rodents. The purpose of this study is to develop a comprehensive composite neuroscore test for cerebellar injury using a rat model of cerebellar haemorrhage. Sixty male Sprague-Dawley rats were subjected to either sham surgery or cerebellar haemorrhage. Twenty-four hours post-injury, neurological behaviour was evaluated using 17 cost-effective and easy-to-perform tests, and a composite neuroscore was developed. The composite neuroscore was then used to assess functional recovery over seven days after cerebellar haemorrhage. Differences in the composite neuroscore deficits for the mild and moderate cerebellar haemorrhage models were observed for up to five days post-ictus. Until now, a composite neuroscore for cerebellar injury was not available for rodent studies. Herein, using mild and moderate cerebellar haemorrhage rat models a composite neuroscore for cerebellar injury was developed and used to assess functional deficits after cerebellar haemorrhage. This composite neuroscore may also be useful for other cerebellar injury models.

  7. 3D morphometric analysis of human fetal cerebellar development.

    PubMed

    Scott, Julia A; Hamzelou, Kia S; Rajagopalan, Vidya; Habas, Piotr A; Kim, Kio; Barkovich, A James; Glenn, Orit A; Studholme, Colin

    2012-09-01

    To date, growth of the human fetal cerebellum has been estimated primarily from linear measurements from ultrasound and 2D magnetic resonance imaging (MRI). In this study, we use 3D analytical methods to develop normative growth trajectories for the cerebellum in utero. We measured cerebellar volume, linear dimensions, and local surface curvature from 3D reconstructed MRI of the human fetal brain (N = 46). We found that cerebellar volume increased approximately 7-fold from 20 to 31 gestational weeks. The better fit of the exponential curve (R (2) = 0.96) compared to the linear curve (R (2) = 0.92) indicated acceleration in growth. Within-subject cerebellar and cerebral volumes were highly correlated (R (2) = 0.94), though the cerebellar percentage of total brain volume increased from approximately 2.4% to 3.7% (R (2) = 0.63). Right and left hemispheric volumes did not significantly differ. Transcerebellar diameter, vermal height, and vermal anterior to posterior diameter increased significantly at constant rates. From the local curvature analysis, we found that expansion along the inferior and superior aspects of the hemispheres resulted in decreased convexity, which is likely due to the physical constraints of the dura surrounding the cerebellum and the adjacent brainstem. The paired decrease in convexity along the inferior vermis and increased convexity of the medial hemisphere represents development of the paravermian fissure, which becomes more visible during this period. In this 3D morphometric analysis of the human fetal cerebellum, we have shown that cerebellar growth is accelerating at a greater pace than the cerebrum and described how cerebellar growth impacts the shape of the structure.

  8. 3D Morphometric Analysis of Human Fetal Cerebellar Development

    PubMed Central

    Hamzelou, Kia S.; Rajagopalan, Vidya; Habas, Piotr A.; Kim, Kio; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

    2012-01-01

    To date, growth of the human fetal cerebellum has been estimated primarily from linear measurements from ultrasound and 2D magnetic resonance imaging (MRI). In this study, we use 3D analytical methods to develop normative growth trajectories for the cerebellum in utero. We measured cerebellar volume, linear dimensions, and local surface curvature from 3D reconstructed MRI of the human fetal brain (N = 46). We found that cerebellar volume increased approximately 7-fold from 20 to 31 gestational weeks. The better fit of the exponential curve (R2 = 0.96) compared to the linear curve (R2 = 0.92) indicated acceleration in growth. Within-subject cerebellar and cerebral volumes were highly correlated (R2 = 0.94), though the cerebellar percentage of total brain volume increased from approximately 2.4% to 3.7% (R2 = 0.63). Right and left hemispheric volumes did not significantly differ. Transcerebellar diameter, vermal height, and vermal anterior to posterior diameter increased significantly at constant rates. From the local curvature analysis, we found that expansion along the inferior and superior aspects of the hemispheres resulted in decreased convexity, which is likely due to the physical constraints of the dura surrounding the cerebellum and the adjacent brainstem. The paired decrease in convexity along the inferior vermis and increased convexity of the medial hemisphere represents development of the paravermian fissure, which becomes more visible during this period. In this 3D morphometric analysis of the human fetal cerebellum, we have shown that cerebellar growth is accelerating at a greater pace than the cerebrum and described how cerebellar growth impacts the shape of the structure. PMID:22198870

  9. Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome.

    PubMed

    Servais, Laurent; Hourez, Raphaël; Bearzatto, Bertrand; Gall, David; Schiffmann, Serge N; Cheron, Guy

    2007-06-05

    In cerebellum and other brain regions, neuronal cell death because of ethanol consumption by the mother is thought to be the leading cause of neurological deficits in the offspring. However, little is known about how surviving cells function. We studied cerebellar Purkinje cells in vivo and in vitro to determine whether function of these cells was altered after prenatal ethanol exposure. We observed that Purkinje cells that were prenatally exposed to ethanol presented decreased voltage-gated calcium currents because of a decreased expression of the gamma-isoform of protein kinase C. Long-term depression at the parallel fiber-Purkinje cell synapse in the cerebellum was converted into long-term potentiation. This likely explains the dramatic increase in Purkinje cell firing and the rapid oscillations of local field potential observed in alert fetal alcohol syndrome mice. Our data strongly suggest that reversal of long-term synaptic plasticity and increased firing rates of Purkinje cells in vivo are major contributors to the ataxia and motor learning deficits observed in fetal alcohol syndrome. Our results show that calcium-related neuronal dysfunction is central to the pathogenesis of the neurological manifestations of fetal alcohol syndrome and suggest new methods for treatment of this disorder.

  10. Cerebellar cysts in children: a pattern recognition approach.

    PubMed

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

    2015-06-01

    Cerebellar cysts may be seen in selected genetic disorders and acquired anomalies. Here, we review our experience, excluding cystic tumors and parasitic cysts. The pathogenesis is heterogeneous: Cysts may involve/represent normal structures (e.g., Virchow-Robin spaces), be "destructive" (such as in some types of pontocerebellar hypoplasias), "malformative" (such as in some forms of congenital muscular dystrophies and GPR56-related migration disorders), or "disruptive" (such as in some cerebellar dysplasias). The provided checklist may be useful in deciding targeted diagnostic workup.

  11. [Type I Chiari malformation associated with cerebellar atrophy. Case report].

    PubMed

    Moscote-Salazar, Luis Rafael; Calderón-Miranda, Willem Guillermo; Alvis-Miranda, Hernando Raphael; Lee-Aguirre, Ángel; Alcalá-Cerra, Gabriel

    2017-01-01

    Chiari malformation is characterized by caudal displacement of the cerebellar tonsils that penetrate into the spinal canal through the foramen magnum, achieving reach the atlas or axis. trunk and any drop of the fourth ventricle is observed. Typically is seen in young adults. In some cases scoliosis and Syringomyelic cavities may occur. The authors present (as far as they know) the first case in the literature with long term follow-up, of a caucasian woman with an unusual form of cerebellar atrophy and Chiari Type I malformation, suffering from weakness in his upper and lower extremities with rapidly progression. The patient was successfully treated with suboccipital decompression and C1 laminectomy.

  12. Symptomatic cerebellar hemorrhage from recurrent hemangioblastoma during delivery. Case report.

    PubMed

    Hayashi, Shigeto; Takeda, Naoya; Komura, Eiji

    2010-01-01

    A 30-year-old woman suffered cerebellar hemorrhage during the delivery of her first child. She had undergone surgical removal of a symptomatic cerebellar hemangioblastoma 6 years previously. Neuroradiological examinations indicated recurrent hemangioblastoma, confirmed by histological examination of the surgical specimen. She was discharged with no neurological deficit. Hemangioblastomas are benign tumors that are curable with surgical removal, but can grow during pregnancy. Women of reproductive age who have been treated for hemangioblastoma need careful long-term follow up, even if they show no signs of lesion recurrence.

  13. Inside the Thompson laboratory during the "cerebellar years" and the continuing cerebellar story.

    PubMed

    Lavond, D G; Wikgren, J; Nokia, M S

    2011-02-01

    This paper is based on the talk by one of the authors (DL) given at the symposium for the retirement of RF Thompson (RF Thompson: A bridge between 20th and 21st century neuroscience). We first make some informal observations of the historical times and research conditions in the Thompson laboratory when the cerebellum was found to play a critical role in eye lid classical conditioning, the "cerebellar years". These conditions influenced our collaborative international program on the phenomenon known as "transfer of training" or "savings". Our research shows that the appearance of "savings" is an artifact of the order of testing, and depends upon the functioning of the contralateral interpositus nucleus (IPN) in a way that is complementary to the role of the IPN in normal eyelid classical conditioning.

  14. Reversible Computing

    DTIC Science & Technology

    1980-02-01

    will have been introduced. 9. Reversible celular autemata We shall assume the reader to have some familiarity with the concept of cel- lular...10003 Mr. Kin B. Thcmpson 1 copy Technical Director Information Systems Divisia.i Naval Research Laboratory (OP-91T) Technical Information Division

  15. REVERSE OSMOSIS,

    DTIC Science & Technology

    acetate membranes. Mechanisms of the process and porous cellulose acetate membrane technology are briefly reviewed. Based on a general capillary...The reverse osmosis process is discussed with particular reference to systems involving aqueous solutions and Loeb-Sourirajan-type porous cellulose

  16. DNA diagnosis of the fragile X syndrome in a series of 236 mentally retarded subjects and evidence for a reversal of mutation in the FMR-1 gene

    SciTech Connect

    Ouweland, A.M.W. van den; Vries, B.B.A. de; Bakker, P.L.G.; Deelen, W.H.; Graaff, E. de; Hemel, J.O. van; Oostra, B.A.; Niermeijer, M.F.; Halley, D.J.J.

    1994-07-15

    The cloning of the FMR-1 gene and the identification of an expanded CGG repeat in DNA of fragile X patients has made reliable DNA diagnosis feasible. Southern blotting and PCR assays of the CGG repeat in an unselected series of 236 mentally retarded subjects resulted in the identification of 10 new fragile X families. Reevaluation of previously assessed fragile X families resulted in the first observation of the presence of a reversal of mutation in the FMR-1 gene. 21 refs., 1 fig., 1 tab.

  17. Mesothelioma and anti-Ma paraneoplastic syndrome; heterogeneity in immunogenic tumours increases.

    PubMed

    Archer, Hilary Anne; Panopoulou, Aikaterini; Bhatt, Nidhi; Edey, Anthony James; Giffin, Nicola Jane

    2014-02-01

    We present a patient with opsoclonus and diffuse cerebellar signs who had an anti-Ma2 antibody-associated paraneoplastic syndrome secondary to a sarcomatoid mesothelioma. This case highlights the importance of early tumour detection, instigation of therapeutic measures, and the heterogeneity of underlying malignancies in neurological paraneoplastic syndromes.

  18. Dyslexic Children Show Atypical Cerebellar Activation and Cerebro-Cerebellar Functional Connectivity in Orthographic and Phonological Processing.

    PubMed

    Feng, Xiaoxia; Li, Le; Zhang, Manli; Yang, Xiujie; Tian, Mengyu; Xie, Weiyi; Lu, Yao; Liu, Li; Bélanger, Nathalie N; Meng, Xiangzhi; Ding, Guosheng

    2017-04-01

    Previous neuroimaging studies have found atypical cerebellar activation in individuals with dyslexia in either motor-related tasks or language tasks. However, studies investigating atypical cerebellar activation in individuals with dyslexia have mostly used tasks tapping phonological processing. A question that is yet unanswered is whether the cerebellum in individuals with dyslexia functions properly during orthographic processing of words, as growing evidence shows that the cerebellum is also involved in visual and spatial processing. Here, we investigated cerebellar activation and cerebro-cerebellar functional connectivity during word processing in dyslexic readers and typically developing readers using tasks that tap orthographic and phonological codes. In children with dyslexia, we observed an abnormally higher engagement of the bilateral cerebellum for the orthographic task, which was negatively correlated with literacy measures. The greater the reading impairment was for young dyslexic readers, the stronger the cerebellar activation was. This suggests a compensatory role of the cerebellum in reading for children with dyslexia. In addition, a tendency for higher cerebellar activation in dyslexic readers was found in the phonological task. Moreover, the functional connectivity was stronger for dyslexic readers relative to typically developing readers between the lobule VI of the right cerebellum and the left fusiform gyrus during the orthographic task and between the lobule VI of the left cerebellum and the left supramarginal gyrus during the phonological task. This pattern of results suggests that the cerebellum compensates for reading impairment through the connections with specific brain regions responsible for the ongoing reading task. These findings enhance our understanding of the cerebellum's involvement in reading and reading impairment.

  19. Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia

    PubMed Central

    Abbasi, Samira; Abbasi, Ataollah; Sarbaz, Yashar; Shahabi, Parviz

    2016-01-01

    Introduction: Loss of inhibitory output from Purkinje cells leads to hyperexcitability of the Deep Cerebellar Nuclei (DCN), which results in cerebellar ataxia. Also, inhibition of small-conductance calcium-activated potassium (SK) channel increases firing rate of DCN, which could cause cerebellar ataxia. Therefore, SK channel activators can be effective in reducing the symptoms of this disease, and used for the treatment of cerebellar ataxia. In this regard, we hypothesized that blockade of SK channels in different compartments of DCN would increase firing rate with different value. The location of these channels has different effects on increasing firing rate. Methods: In this study, multi-compartment computational model of DCN was used. This computational stimulation allowed us to study the changes in the firing activity of DCN neuron without concerns about interfering parameters in the experiment. Results: The simulation results demonstrated that blockade of somatic and dendritic SK channel increased the firing rate of DCN. In addition, after hyperpolarization (AHP) amplitude increased with blocking SK channel, and its regularity and resting potential changed. However, action potentials amplitude and duration had no significant changes. The simulation results illustrated a more significant contribution of SK channels on the dendritic tree to the DCN firing rate. SK channels in the proximal dendrites have more impact on firing rate compared to distal dendrites. Discussion: Therefore, inhibition of SK channel in DCN can cause cerebellar ataxia, and SK channel openers can have a therapeutic effect on cerebellar ataxia. In addition, the location of SK channels could be important in therapeutic goals. Dendritic SK channels can be a more effective target compared to somatic SK channels. PMID:27303600

  20. Postural Ataxia in Cerebellar Downbeat Nystagmus: Its Relation to Visual, Proprioceptive and Vestibular Signals and Cerebellar Atrophy

    PubMed Central

    Helmchen, Christoph; Kirchhoff, Jan-Birger; Göttlich, Martin; Sprenger, Andreas

    2017-01-01

    Background The cerebellum integrates proprioceptive, vestibular and visual signals for postural control. Cerebellar patients with downbeat nystagmus (DBN) complain of unsteadiness of stance and gait as well as blurred vision and oscillopsia. Objectives The aim of this study was to elucidate the differential role of visual input, gaze eccentricity, vestibular and proprioceptive input on the postural stability in a large cohort of cerebellar patients with DBN, in comparison to healthy age-matched control subjects. Methods Oculomotor (nystagmus, smooth pursuit eye movements) and postural (postural sway speed) parameters were recorded and related to each other and volumetric changes of the cerebellum (voxel-based morphometry, SPM). Results Twenty-seven patients showed larger postural instability in all experimental conditions. Postural sway increased with nystagmus in the eyes closed condition but not with the eyes open. Romberg’s ratio remained stable and was not different from healthy controls. Postural sway did not change with gaze position or graviceptive input. It increased with attenuated proprioceptive input and on tandem stance in both groups but Romberg’s ratio also did not differ. Cerebellar atrophy (vermal lobule VI, VIII) correlated with the severity of impaired smooth pursuit eye movements of DBN patients. Conclusions Postural ataxia of cerebellar patients with DBN cannot be explained by impaired visual feedback. Despite oscillopsia visual feedback control on cerebellar postural control seems to be preserved as postural sway was strongest on visual deprivation. The increase in postural ataxia is neither related to modulations of single components characterizing nystagmus nor to deprivation of single sensory (visual, proprioceptive) inputs usually stabilizing stance. Re-weighting of multisensory signals and/or inappropriate cerebellar motor commands might account for this postural ataxia. PMID:28056109

  1. Whole-Cell Properties of Cerebellar Nuclei Neurons In Vivo.

    PubMed

    Canto, Cathrin B; Witter, Laurens; De Zeeuw, Chris I

    2016-01-01

    Cerebellar nuclei neurons integrate sensorimotor information and form the final output of the cerebellum, projecting to premotor brainstem targets. This implies that, in contrast to specialized neurons and interneurons in cortical regions, neurons within the nuclei encode and integrate complex information that is most likely reflected in a large variation of intrinsic membrane properties and integrative capacities of individual neurons. Yet, whether this large variation in properties is reflected in a heterogeneous physiological cell population of cerebellar nuclei neurons with well or poorly defined cell types remains to be determined. Indeed, the cell electrophysiological properties of cerebellar nuclei neurons have been identified in vitro in young rodents, but whether these properties are similar to the in vivo adult situation has not been shown. In this comprehensive study we present and compare the in vivo properties of 144 cerebellar nuclei neurons in adult ketamine-xylazine anesthetized mice. We found regularly firing (N = 88) and spontaneously bursting (N = 56) neurons. Membrane-resistance, capacitance, spike half-width and firing frequency all widely varied as a continuum, ranging from 9.63 to 3352.1 MΩ, from 6.7 to 772.57 pF, from 0.178 to 1.98 ms, and from 0 to 176.6 Hz, respectively. At the same time, several of these parameters were correlated with each other. Capacitance decreased with membrane resistance (R2 = 0.12, P<0.001), intensity of rebound spiking increased with membrane resistance (for 100 ms duration R2 = 0.1503, P = 0.0011), membrane resistance decreased with membrane time constant (R2 = 0.045, P = 0.031) and increased with spike half-width (R2 = 0.023, P<0.001), while capacitance increased with firing frequency (R2 = 0.29, P<0.001). However, classes of neuron subtypes could not be identified using merely k-clustering of their intrinsic firing properties and/or integrative properties following activation of their Purkinje cell input

  2. Whole-Cell Properties of Cerebellar Nuclei Neurons In Vivo

    PubMed Central

    De Zeeuw, Chris I.

    2016-01-01

    Cerebellar nuclei neurons integrate sensorimotor information and form the final output of the cerebellum, projecting to premotor brainstem targets. This implies that, in contrast to specialized neurons and interneurons in cortical regions, neurons within the nuclei encode and integrate complex information that is most likely reflected in a large variation of intrinsic membrane properties and integrative capacities of individual neurons. Yet, whether this large variation in properties is reflected in a heterogeneous physiological cell population of cerebellar nuclei neurons with well or poorly defined cell types remains to be determined. Indeed, the cell electrophysiological properties of cerebellar nuclei neurons have been identified in vitro in young rodents, but whether these properties are similar to the in vivo adult situation has not been shown. In this comprehensive study we present and compare the in vivo properties of 144 cerebellar nuclei neurons in adult ketamine-xylazine anesthetized mice. We found regularly firing (N = 88) and spontaneously bursting (N = 56) neurons. Membrane-resistance, capacitance, spike half-width and firing frequency all widely varied as a continuum, ranging from 9.63 to 3352.1 MΩ, from 6.7 to 772.57 pF, from 0.178 to 1.98 ms, and from 0 to 176.6 Hz, respectively. At the same time, several of these parameters were correlated with each other. Capacitance decreased with membrane resistance (R2 = 0.12, P<0.001), intensity of rebound spiking increased with membrane resistance (for 100 ms duration R2 = 0.1503, P = 0.0011), membrane resistance decreased with membrane time constant (R2 = 0.045, P = 0.031) and increased with spike half-width (R2 = 0.023, P<0.001), while capacitance increased with firing frequency (R2 = 0.29, P<0.001). However, classes of neuron subtypes could not be identified using merely k-clustering of their intrinsic firing properties and/or integrative properties following activation of their Purkinje cell input

  3. [Intraabdominal metastasis of cerebellar medulloblastoma through ventriculoperitoneal shunt].

    PubMed

    Carrasco Torrents, R; Sancho, M A; Juliá, V; Montaner, A; Costa, J M; Morales, L

    2001-01-01

    We present a 6-year-old girl with cerebellar medulloblastoma causing obstructive hydrocephalus that was treated by ventriculoperitoneal shunting. The patient subsequently underwent surgical excision of the tumor followed by adjuvant craniospinal radiotherapy. Nine months after shunting, multiple intraabdominal metastatic lesions were found. Although the risk is low, ventriculoperitoneal shunting may facilitate the spread of malignant cells.

  4. Cerebro-cerebellar interactions underlying temporal information processing.

    PubMed

    Aso, Kenji; Hanakawa, Takashi; Aso, Toshihiko; Fukuyama, Hidenao

    2010-12-01

    The neural basis of temporal information processing remains unclear, but it is proposed that the cerebellum plays an important role through its internal clock or feed-forward computation functions. In this study, fMRI was used to investigate the brain networks engaged in perceptual and motor aspects of subsecond temporal processing without accompanying coprocessing of spatial information. Direct comparison between perceptual and motor aspects of time processing was made with a categorical-design analysis. The right lateral cerebellum (lobule VI) was active during a time discrimination task, whereas the left cerebellar lobule VI was activated during a timed movement generation task. These findings were consistent with the idea that the cerebellum contributed to subsecond time processing in both perceptual and motor aspects. The feed-forward computational theory of the cerebellum predicted increased cerebro-cerebellar interactions during time information processing. In fact, a psychophysiological interaction analysis identified the supplementary motor and dorsal premotor areas, which had a significant functional connectivity with the right cerebellar region during a time discrimination task and with the left lateral cerebellum during a timed movement generation task. The involvement of cerebro-cerebellar interactions may provide supportive evidence that temporal information processing relies on the simulation of timing information through feed-forward computation in the cerebellum.

  5. Cerebellar Damage Produces Selective Deficits in Verbal Working Memory

    ERIC Educational Resources Information Center

    Ravizza, Susan M.; Mccormick, Cristin A.; Schlerf, John E.; Justus, Timothy; Ivry, Richard B.; Fiez, Julie A.

    2006-01-01

    The cerebellum is often active in imaging studies of verbal working memory, consistent with a putative role in articulatory rehearsal. While patients with cerebellar damage occasionally exhibit a mild impairment on standard neuropsychological tests of working memory, these tests are not diagnostic for exploring these processes in detail. The…

  6. The Contribution of Brainstem and Cerebellar Pathways to Auditory Recognition

    PubMed Central

    McLachlan, Neil M.; Wilson, Sarah J.

    2017-01-01

    The cerebellum has been known to play an important role in motor functions for many years. More recently its role has been expanded to include a range of cognitive and sensory-motor processes, and substantial neuroimaging and clinical evidence now points to cerebellar involvement in most auditory processing tasks. In particular, an increase in the size of the cerebellum over recent human evolution has been attributed in part to the development of speech. Despite this, the auditory cognition literature has largely overlooked afferent auditory connections to the cerebellum that have been implicated in acoustically conditioned reflexes in animals, and could subserve speech and other auditory processing in humans. This review expands our understanding of auditory processing by incorporating cerebellar pathways into the anatomy and functions of the human auditory system. We reason that plasticity in the cerebellar pathways underpins implicit learning of spectrotemporal information necessary for sound and speech recognition. Once learnt, this information automatically recognizes incoming auditory signals and predicts likely subsequent information based on previous experience. Since sound recognition processes involving the brainstem and cerebellum initiate early in auditory processing, learnt information stored in cerebellar memory templates could then support a range of auditory processing functions such as streaming, habituation, the integration of auditory feature information such as pitch, and the recognition of vocal communications. PMID:28373850

  7. Cortical networks of procedural learning: evidence from cerebellar damage.

    PubMed

    Torriero, Sara; Oliveri, Massimiliano; Koch, Giacomo; Lo Gerfo, Emanuele; Salerno, Silvia; Petrosini, Laura; Caltagirone, Carlo

    2007-03-25

    The lateral cerebellum plays a critical role in procedural learning that goes beyond the strict motor control functions attributed to it. Patients with cerebellar damage show marked impairment in the acquisition of procedures, as revealed by their performance on the serial reaction time task (SRTT). Here we present the case of a patient affected by ischemic damage involving the left cerebellum who showed a selective deficit in procedural learning while performing the SRTT with the left hand. The deficit recovered when the cortical excitability of an extensive network involving both cerebellar hemispheres and the dorsolateral prefrontal cortex (DLPFC) was decreased by low-frequency repetitive transcranial magnetic stimulation (rTMS). Although inhibition of the right DLPFC or a control fronto-parietal region did not modify the patient's performance, inhibition of the right (unaffected) cerebellum and the left DLPFC markedly improved task performance. These findings could be explained by the modulation of a set of inhibitory and excitatory connections between the lateral cerebellum and the contralateral prefrontal area induced by rTMS. The presence of left cerebellar damage is likely associated with a reduced excitatory drive from sub-cortical left cerebellar nuclei towards the right DLPFC, causing reduced excitability of the right DLPFC and, conversely, unbalanced activation of the left DLPFC. Inhibition of the left DLPFC would reduce the unbalancing of cortical activation, thus explaining the observed selective recovery of procedural memory.

  8. Early degeneration of the cerebellar cortex, particularly the granular cells.

    PubMed

    Bugiani, O; Berio, A; Di Stefano, A; Mangiante, G; Mancardi, G L; Leonardi, A

    1978-12-07

    An 8 month old infant, who died of severe gastroenteritis, presented a degeneration of the cerebellar cortex involving cells arising from the outer granular layer as well as Purkinje and Golgi II cells. Residual Purkinje cells showed vacuolar change of the cell body and dendritic abnormalities. Related lesions were atrophy of the inferior olives and degeneration of the mossy fibers.

  9. Caytaxin Deficiency Disrupts Signaling Pathways in Cerebellar Cortex

    PubMed Central

    Xiao, Jianfeng; Gong, Suzhen; LeDoux, Mark S.

    2007-01-01

    The genetically dystonic (dt) rat, an autosomal recessive model of generalized dystonia, harbors an insertional mutation in Atcay. As a result, dt rats are deficient in Atcay transcript and the neuronally-restricted protein caytaxin. Previous electrophysiological and biochemical studies have defined olivocerebellar pathways, particularly the climbing fiber projection to Purkinje cells, as a site of significant functional abnormality in dt rats. In normal rats, Atcay transcript is abundantly expressed in the granular and Purkinje cell layers of cerebellar cortex. To better understand the consequences of caytaxin deficiency in cerebellar cortex, differential gene expression was examined in dt rats and their normal littermates. Data from oligonucleotide microarrays and quantitative real-time RT-PCR (QRT-PCR) identified phosphatidylinositol signaling pathways, calcium homeostasis, and extracellular matrix interactions as domains of cellular dysfunction in dt rats. In dt rats, genes encoding the corticotropin-releasing hormone receptor 1 (CRH-R1, Crhr1) and calcium-transporting plasma membrane ATPase 4 (PMCA4, Atp2b4) showed the greatest up-regulation with QRT-PCR. Immunocytochemical experiments demonstrated that CRH-R1, CRH, and PMCA4 were up-regulated in cerebellar cortex of mutant rats. Along with previous electrophysiological and pharmacological studies, our data indicate that caytaxin plays a critical role in the molecular response of Purkinje cells to climbing fiber input. Caytaxin may also contribute to maturational events in cerebellar cortex. PMID:17092653

  10. Speech and Language Findings Associated with Paraneoplastic Cerebellar Degeneration

    ERIC Educational Resources Information Center

    Paslawski, Teresa; Duffy, Joseph R.; Vernino, Steven

    2005-01-01

    Paraneoplastic cerebellar degeneration (PCD) is an autoimmune disease that can be associated with cancer of the breast, lung, and ovary. The clinical presentation of PCD commonly includes ataxia, visual disturbances, and dysarthria. The speech disturbances associated with PCD have not been well characterized, despite general acceptance that…

  11. Cerebellar rTMS disrupts predictive language processing

    PubMed Central

    Lesage, Elise; Morgan, Blaire E.; Olson, Andrew C.; Meyer, Antje S.; Miall, R. Chris

    2012-01-01

    Summary The human cerebellum plays an important role in language, amongst other cognitive and motor functions [1], but a unifying theoretical framework about cerebellar language function is lacking. In an established model of motor control, the cerebellum is seen as a predictive machine, making short-term estimations about the outcome of motor commands. This allows for flexible control, on-line correction, and coordination of movements [2]. The homogeneous cytoarchitecture of the cerebellar cortex suggests that similar computations occur throughout the structure, operating on different input signals and with different output targets [3]. Several authors have therefore argued that this ‘motor’ model may extend to cerebellar nonmotor functions [3–5], and that the cerebellum may support prediction in language processing [6]. However, this hypothesis has never been directly tested. Here, we used the ‘Visual World’ paradigm [7], where on-line processing of spoken sentence content can be assessed by recording the latencies of listeners' eye movements towards objects mentioned. Repetitive transcranial magnetic stimulation (rTMS) was used to disrupt function in the right cerebellum, a region implicated in language [8]. After cerebellar rTMS, listeners showed delayed eye fixations to target objects predicted by sentence content, while there was no effect on eye fixations in sentences without predictable content. The prediction deficit was absent in two control groups. Our findings support the hypothesis that computational operations performed by the cerebellum may support prediction during both motor control and language processing. PMID:23017990

  12. Bilateral cerebellar activation in unilaterally challenged essential tremor.

    PubMed

    Broersma, Marja; van der Stouwe, Anna M M; Buijink, Arthur W G; de Jong, Bauke M; Groot, Paul F C; Speelman, Johannes D; Tijssen, Marina A J; van Rootselaar, Anne-Fleur; Maurits, Natasha M

    2016-01-01

    •We added EMG as an index of tremor intensity to fMRI to study essential tremor.•Block- and tremor-related activations during a unilateral motor task were separated.•Block-related activations were found in the classical motor network.•Tremor-related activations were found in bilateral cerebellar lobules V, VI and VIII.

  13. Cerebellar Zonal Patterning Relies on Purkinje Cell Neurotransmission

    PubMed Central

    White, Joshua J.; Arancillo, Marife; Stay, Trace L.; George-Jones, Nicholas A.; Levy, Sabrina L.; Heck, Detlef H.

    2014-01-01

    Cerebellar circuits are patterned into an array of topographic parasagittal domains called zones. The proper connectivity of zones is critical for motor coordination and motor learning, and in several neurological diseases cerebellar circuits degenerate in zonal patterns. Despite recent advances in understanding zone function, we still have a limited understanding of how zones are formed. Here, we focused our attention on Purkinje cells to gain a better understanding of their specific role in establishing zonal circuits. We used conditional mouse genetics to test the hypothesis that Purkinje cell neurotransmission is essential for refining prefunctional developmental zones into sharp functional zones. Our results show that inhibitory synaptic transmission in Purkinje cells is necessary for the precise patterning of Purkinje cell zones and the topographic targeting of mossy fiber afferents. As expected, blocking Purkinje cell neurotransmission caused ataxia. Using in vivo electrophysiology, we demonstrate that loss of Purkinje cell communication altered the firing rate and pattern of their target cerebellar nuclear neurons. Analysis of Purkinje cell complex spike firing revealed that feedback in the cerebellar nuclei to inferior olive to Purkinje cell loop is obstructed. Loss of Purkinje neurotransmission also caused ectopic zonal expression of tyrosine hydroxylase, which is only expressed in adult Purkinje cells when calcium is dysregulated and if excitability is altered. Our results suggest that Purkinje cell inhibitory neurotransmission establishes the functional circuitry of the cerebellum by patterning the molecular zones, fine-tuning afferent circuitry, and shaping neuronal activity. PMID:24920627

  14. The Contribution of Brainstem and Cerebellar Pathways to Auditory Recognition.

    PubMed

    McLachlan, Neil M; Wilson, Sarah J

    2017-01-01

    The cerebellum has been known to play an important role in motor functions for many years. More recently its role has been expanded to include a range of cognitive and sensory-motor processes, and substantial neuroimaging and clinical evidence now points to cerebellar involvement in most auditory processing tasks. In particular, an increase in the size of the cerebellum over recent human evolution has been attributed in part to the development of speech. Despite this, the auditory cognition literature has largely overlooked afferent auditory connections to the cerebellum that have been implicated in acoustically conditioned reflexes in animals, and could subserve speech and other auditory processing in humans. This review expands our understanding of auditory processing by incorporating cerebellar pathways into the anatomy and functions of the human auditory system. We reason that plasticity in the cerebellar pathways underpins implicit learning of spectrotemporal information necessary for sound and speech recognition. Once learnt, this information automatically recognizes incoming auditory signals and predicts likely subsequent information based on previous experience. Since sound recognition processes involving the brainstem and cerebellum initiate early in auditory processing, learnt information stored in cerebellar memory templates could then support a range of auditory processing functions such as streaming, habituation, the integration of auditory feature information such as pitch, and the recognition of vocal communications.

  15. Hippocampo-cerebellar theta band phase synchrony in rabbits.

    PubMed

    Wikgren, J; Nokia, M S; Penttonen, M

    2010-02-17

    Hippocampal functioning, in the form of theta band oscillation, has been shown to modulate and predict cerebellar learning of which rabbit eyeblink conditioning is perhaps the most well-known example. The contribution of hippocampal neural activity to cerebellar learning is only possible if there is a functional connection between the two structures. Here, in the context of trace eyeblink conditioning, we show (1) that, in addition to the hippocampus, prominent theta oscillation also occurs in the cerebellum, and (2) that cerebellar theta oscillation is synchronized with that in the hippocampus. Further, the degree of phase synchrony (PS) increased both as a response to the conditioning stimuli and as a function of the relative power of hippocampal theta oscillation. However, the degree of PS did not change as a function of either training or learning nor did it predict learning rate as the hippocampal theta ratio did. Nevertheless, theta band synchronization might reflect the formation of transient neural assemblies between the hippocampus and the cerebellum. These findings help us understand how hippocampal function can affect eyeblink conditioning, during which the critical plasticity occurs in the cerebellum. Future studies should examine cerebellar unit activity in relation to hippocampal theta oscillations in order to discover the detailed mechanisms of theta-paced neural activity.

  16. Verb Generation in Children and Adolescents with Acute Cerebellar Lesions

    ERIC Educational Resources Information Center

    Frank, B.; Schoch, B.; Hein-Kropp, C.; Dimitrova, A.; Hovel, M.; Ziegler, W.; Gizewski, E. R.; Timmann, D.

    2007-01-01

    The aim of the present study was to examine verb generation in a larger group of children and adolescents with acute focal lesions of the cerebellum. Nine children and adolescents with cerebellar tumours participated. Subjects were tested a few days after tumour surgery. For comparison, a subgroup was tested also 1 or 2 days before surgery. None…

  17. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implanted cerebellar stimulator. 882.5820 Section 882.5820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820...

  18. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted cerebellar stimulator. 882.5820 Section 882.5820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820...

  19. 21 CFR 882.5820 - Implanted cerebellar stimulator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implanted cerebellar stimulator. 882.5820 Section 882.5820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5820...

  20. Neurodevelopmental Outcomes in Children with Cerebellar Malformations: A Systematic Review

    ERIC Educational Resources Information Center

    Bolduc, Marie-Eve; Limperopoulos, Catherine

    2009-01-01

    Cerebellar malformations are increasingly diagnosed in the fetal period. Consequently, their consideration requires stressful and often critical decisions from both clinicians and families. This has resulted in an emergent need to understand better the impact of these early life lesions on child development. We performed a comprehensive literature…

  1. Predicting and correcting ataxia using a model of cerebellar function

    PubMed Central

    Bhanpuri, Nasir H.; Okamura, Allison M.

    2014-01-01

    Cerebellar damage results in uncoordinated, variable and dysmetric movements known as ataxia. Here we show that we can reliably model single-joint reaching trajectories of patients (n = 10), reproduce patient-like deficits in the behaviour of controls (n = 11), and apply patient-specific compensations that improve reaching accuracy (P < 0.02). Our approach was motivated by the theory that the cerebellum is essential for updating and/or storing an internal dynamic model that relates motor commands to changes in body state (e.g. arm position and velocity). We hypothesized that cerebellar damage causes a mismatch between the brain’s modelled dynamics and the actual body dynamics, resulting in ataxia. We used both behavioural and computational approaches to demonstrate that specific cerebellar patient deficits result from biased internal models. Our results strongly support the idea that an intact cerebellum is critical for maintaining accurate internal models of dynamics. Importantly, we demonstrate how subject-specific compensation can improve movement in cerebellar patients, who are notoriously unresponsive to treatment. PMID:24812203

  2. Is a Cerebellar Deficit the Underlying Cause of Reading Disabilities?

    ERIC Educational Resources Information Center

    Irannejad, Shahrzad; Savage, Robert

    2012-01-01

    This study investigated whether children with dyslexia differed in their performance on reading, phonological, rapid naming, motor, and cerebellar-related tasks and automaticity measures compared to reading age (RA)-matched and chronological age (CA)-matched control groups. Participants were 51 children attending mainstream English elementary…

  3. Early Cerebellar Network Shifting in Spinocerebellar Ataxia Type 6.

    PubMed

    Falcon, M I; Gomez, C M; Chen, E E; Shereen, A; Solodkin, A

    2016-07-01

    Spinocerebellar ataxia 6 (SCA6), an autosomal dominant degenerative disease, is characterized by diplopia, gait ataxia, and incoordination due to severe progressive degeneration of Purkinje cells in the vestibulo- and spinocerebellum. Ocular motor deficits are common, including difficulty fixating on moving objects, nystagmus and disruption of smooth pursuit movements. In presymptomatic SCA6, there are alterations in saccades and smooth-pursuit movements. We sought to assess functional and structural changes in cerebellar connectivity associated with a visual task, hypothesizing that gradual changes would parallel disease progression. We acquired functional magnetic resonance imaging and diffusion tensor imaging data during a passive smooth-pursuit task in 14 SCA6 patients, representing a range of disease duration and severity, and performed a cross-sectional comparison of cerebellar networks compared with healthy controls. We identified a shift in activation from vermis in presymptomatic individuals to lateral cerebellum in moderate-to-severe cases. Concomitantly, effective connectivity between regions of cerebral cortex and cerebellum was at its highest in moderate cases, and disappeared in severe cases. Finally, we noted structural differences in the cerebral and cerebellar peduncles. These unique results, spanning both functional and structural domains, highlight widespread changes in SCA6 and compensatory mechanisms associated with cerebellar physiology that could be utilized in developing new therapies.

  4. Translational Approach to Behavioral Learning: Lessons from Cerebellar Plasticity

    PubMed Central

    Cheron, Guy; Dan, Bernard; Márquez-Ruiz, Javier

    2013-01-01

    The role of cerebellar plasticity has been increasingly recognized in learning. The privileged relationship between the cerebellum and the inferior olive offers an ideal circuit for attempting to integrate the numerous evidences of neuronal plasticity into a translational perspective. The high learning capacity of the Purkinje cells specifically controlled by the climbing fiber represents a major element within the feed-forward and feedback loops of the cerebellar cortex. Reciprocally connected with the basal ganglia and multimodal cerebral domains, this cerebellar network may realize fundamental functions in a wide range of behaviors. This review will outline the current understanding of three main experimental paradigms largely used for revealing cerebellar functions in behavioral learning: (1) the vestibuloocular reflex and smooth pursuit control, (2) the eyeblink conditioning, and (3) the sensory envelope plasticity. For each of these experimental conditions, we have critically revisited the chain of causalities linking together neural circuits, neural signals, and plasticity mechanisms, giving preference to behaving or alert animal physiology. Namely, recent experimental approaches mixing neural units and local field potentials recordings have demonstrated a spike timing dependent plasticity by which the cerebellum remains at a strategic crossroad for deciphering fundamental and translational mechanisms from cellular to network levels. PMID:24319600

  5. Vasectomy reversal.

    PubMed

    Belker, A M

    1987-02-01

    A vasovasostomy may be performed on an outpatient basis with local anesthesia, but also may be performed on an outpatient basis with epidural or general anesthesia. Local anesthesia is preferred by most of my patients, the majority of whom choose this technique. With proper preoperative and intraoperative sedation, patients sleep lightly through most of the procedure. Because of the length of time often required for bilateral microsurgical vasoepididymostomy, epidural or general anesthesia and overnight hospitalization are usually necessary. Factors influencing the preoperative choice for vasovasostomy or vasoepididymostomy in patients undergoing vasectomy reversal are considered. The preoperative planned choice of vasovasostomy or vasoepididymostomy for patients having vasectomy reversal described herein does not have the support of all urologists who regularly perform these procedures. My present approach has evolved as the data reported in Tables 1 and 2 have become available, but it may change as new information is evaluated. However, it offers a logical method for planning choices of anesthesia and inpatient or outpatient status for patients undergoing vasectomy reversal procedures.

  6. Vasectomy reversal: a clinical update

    PubMed Central

    Patel, Abhishek P; Smith, Ryan P

    2016-01-01

    Vasectomy is a safe and effective method of contraception used by 42–60 million men worldwide. Approximately 3%–6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage, or to alleviate the dreaded postvasectomy pain syndrome. Unlike vasectomy, vasectomy reversal is a much more technically challenging procedure that is performed only by a minority of urologists and places a larger financial strain on the patient since it is usually not covered by insurance. Interest in this procedure has increased since the operating microscope became available in the 1970s, which consequently led to improved patency and pregnancy rates following the procedure. In this clinical update, we discuss patient evaluation, variables that may influence reversal success rates, factors to consider in choosing to perform vasovasostomy versus vasoepididymostomy, and the usefulness of vasectomy reversal to alleviate postvasectomy pain syndrome. We also review the use of robotics for vasectomy reversal and other novel techniques and instrumentation that have emerged in recent years to aid in the success of this surgery. PMID:26975488

  7. Adaptive Robotic Control Driven by a Versatile Spiking Cerebellar Network

    PubMed Central

    Casellato, Claudia; Antonietti, Alberto; Garrido, Jesus A.; Carrillo, Richard R.; Luque, Niceto R.; Ros, Eduardo; Pedrocchi, Alessandra; D'Angelo, Egidio

    2014-01-01

    The cerebellum is involved in a large number of different neural processes, especially in associative learning and in fine motor control. To develop a comprehensive theory of sensorimotor learning and control, it is crucial to determine the neural basis of coding and plasticity embedded into the cerebellar neural circuit and how they are translated into behavioral outcomes in learning paradigms. Learning has to be inferred from the interaction of an embodied system with its real environment, and the same cerebellar principles derived from cell physiology have to be able to drive a variety of tasks of different nature, calling for complex timing and movement patterns. We have coupled a realistic cerebellar spiking neural network (SNN) with a real robot and challenged it in multiple diverse sensorimotor tasks. Encoding and decoding strategies based on neuronal firing rates were applied. Adaptive motor control protocols with acquisition and extinction phases have been designed and tested, including an associative Pavlovian task (Eye blinking classical conditioning), a vestibulo-ocular task and a perturbed arm reaching task operating in closed-loop. The SNN processed in real-time mossy fiber inputs as arbitrary contextual signals, irrespective of whether they conveyed a tone, a vestibular stimulus or the position of a limb. A bidirectional long-term plasticity rule implemented at parallel fibers-Purkinje cell synapses modulated the output activity in the deep cerebellar nuclei. In all tasks, the neurorobot learned to adjust timing and gain of the motor responses by tuning its output discharge. It succeeded in reproducing how human biological systems acquire, extinguish and express knowledge of a noisy and changing world. By varying stimuli and perturbations patterns, real-time control robustness and generalizability were validated. The implicit spiking dynamics of the cerebellar model fulfill timing, prediction and learning functions. PMID:25390365

  8. GDNF-induced cerebellar toxicity: A brief review.

    PubMed

    Luz, Matthias; Mohr, Erich; Fibiger, H Christian

    2016-01-01

    Recombinant-methionyl human glial cell line-derived neurotrophic factor (GDNF) is known for its neurorestorative and neuroprotective effects in rodent and primate models of Parkinson's disease (PD). When administered locally into the putamen of Parkinsonian subjects, early clinical studies showed its potential promise as a disease-modifying agent. However, the development of GDNF for the treatment of PD has been significantly clouded by findings of cerebellar toxicity after continuous intraputamenal high-dose administration in a 6-month treatment/3-month recovery toxicology study in rhesus monkeys. Specifically, multifocal cerebellar Purkinje cell loss affecting 1-21% of the cerebellar cortex was observed in 4 of 15 (26.7%; 95% confidence interval [CI]: 10.5-52.4%) animals treated at the highest dose level tested (3000μg/month). No cerebellar toxicity was observed at lower doses (450 and 900μg/month) in the same study, or at similar or higher doses (up to 10,000μg/month) in subchronic or chronic toxicology studies testing intermittent intracerebroventricular administration. While seemingly associated with the use of GDNF, the pathogenesis of the cerebellar lesions has not been fully understood to date. This review integrates available information to evaluate potential pathogenic mechanisms and provide a consolidated assessment of the findings. While other explanations are considered, the existing evidence is most consistent with the hypothesis that leakage of GDNF into cerebrospinal fluid during chronic infusions into the putamen down-regulates GDNF receptors on Purkinje cells, and that subsequent acute withdrawal of GDNF generates the observed lesions. The implications of these findings for clinical studies with GDNF are discussed.

  9. Long lasting cerebellar alterations after perinatal asphyxia in rats.

    PubMed

    Campanille, Verónica; Saraceno, G Ezequiel; Rivière, Stéphanie; Logica, Tamara; Kölliker, Rodolfo; Capani, Francisco; Castilla, Rocío

    2015-07-01

    The developing brain may be particularly vulnerable to injury before, at and after birth. Among possible insults, hypoxia suffered as a consequence of perinatal asphyxia (PA) exhibits the highest incidence levels and the cerebellar circuitry appears to be particularly susceptible, as the cellular makeup and the quantity of inputs change quickly during days and weeks following birth. In this work, we have used a murine model to induce severe global PA in rats at the time of birth. Short-term cerebellar alterations within this PA model have been previously reported but whether such alterations remain in adulthood has not been conclusively determined yet. For this reason, and given the crucial cerebellar role in determining connectivity patterns in the brain, the aim of our work is to unveil long-term cerebellum histomorphology following a PA insult. Morphological and cytological neuronal changes and glial reaction in the cerebellar cortex were analyzed at postnatal 120 (P120) following injury performed at birth. As compared to control, PA animals exhibited: (1) an increase in molecular and granular thickness, both presenting lower cellular density; (2) a disarrayed Purkinje cell layer presenting a higher number of anomalous calbindin-stained cells. (3) focal swelling and marked fragmentation of microtubule-associated protein 2 (MAP-2) in Purkinje cell dendrites and, (4) an increase in glial fibrillary acidic protein (GFAP) expression in Bergmann cells and the granular layer. In conclusion, we demonstrate that PA produces long-term damage in cellular histomorphology in rat cerebellar cortex which could be involved in the pathogenesis of cognitive deficits observed in both animals and humans.

  10. Patterns of regional cerebellar atrophy in genetic frontotemporal dementia

    PubMed Central

    Bocchetta, Martina; Cardoso, M. Jorge; Cash, David M.; Ourselin, Sebastien; Warren, Jason D.; Rohrer, Jonathan D.

    2016-01-01

    Background Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder with a strong genetic component. The cerebellum has not traditionally been felt to be involved in FTD but recent research has suggested a potential role. Methods We investigated the volumetry of the cerebellum and its subregions in a cohort of 44 patients with genetic FTD (20 MAPT, 7 GRN, and 17 C9orf72 mutation carriers) compared with 18 cognitively normal controls. All groups were matched for age and gender. On volumetric T1-weighted magnetic resonance brain images we used an atlas propagation and label fusion strategy of the Diedrichsen cerebellar atlas to automatically extract subregions including the cerebellar lobules, the vermis and the deep nuclei. Results The global cerebellar volume was significantly smaller in C9orf72 carriers (mean (SD): 99989 (8939) mm3) compared with controls (108136 (7407) mm3). However, no significant differences were seen in the MAPT and GRN carriers compared with controls (104191 (6491) mm3 and 107883 (6205) mm3 respectively). Investigating the individual subregions, C9orf72 carriers had a significantly lower volume than controls in lobule VIIa-Crus I (15% smaller, p < 0.0005), whilst MAPT mutation carriers had a significantly lower vermal volume (10% smaller, p = 0.001) than controls. All cerebellar subregion volumes were preserved in GRN carriers compared with controls. Conclusion There appears to be a differential pattern of cerebellar atrophy in the major genetic forms of FTD, being relatively spared in GRN, localized to the lobule VIIa-Crus I in the superior-posterior region of the cerebellum in C9orf72, the area connected via the thalamus to the prefrontal cortex and involved in cognitive function, and localized to the vermis in MAPT, the ‘limbic cerebellum’ involved in emotional processing. PMID:26977398

  11. Ultrastructural pathology of human peritumoural oedematous cerebellar cortex.

    PubMed

    Castejón, O J

    2016-01-01

    Cerebellar cortical biopsies of the peritumoural region of seven patients with cerebellar haemangioma, mesencephalic meningioma, cerebellopontine astrocytoma, cerebellopontine meningioma, and medulloblastoma of cerebellar vermis were examined by means of conventional transmission electron microscopy. Granule cells showed oedematous cytoplasm and mitochondria. Swollen Golgi cells exhibited lipofuscin granules and intranuclear inclusions. Both neuron cell types displayed swollen dendritic digits synapsing with afferent mossy fibre endings. Degenerated myelinated axons corresponding to afferent mossy and climbing fibres and efferent Purkinje cell axons were observed at the granular layer. Dense and clear ischaemic Purkinje cells established degenerated synapses with swollen parallel fibre synaptic varicosities. Degenerated Purkinje cell recurrent axonal collaterals were found at the molecular layer. Swollen and clear Bergmann glial cell cytoplasm was observed closely applied to the oedematous clear and dark Purkinje cell body, dendritic trunk, secondary and tertiary dendritic branches. Swollen climbing fibre endings featured by numerous microtubules and neurofilaments, and a decreased number of synaptic vesicles were observed making degenerated axo-spinodendritic synapses with clear and swollen dendritic spines from Purkinje, Golgi, basket and stellate cell dendrites. Swollen stellate neurons showed oedematous mitochondria. Lipofuscin-rich astrocytes and reactive phagocytic astrocytes were observed. The latter appeared engulfing haematogenous proteinaceous oedema fluid. All cerebellar neurons showed stress endoplasmic reticulum dysfunction featured by focal dilated cisterns and detachment of associated ribosomes. Myelin sheath degeneration was related with oligodendrocyte degenerating hydropic changes. The peritumoural ischaemic cerebellar nerve and glial cell abnormalities were related with neurobehavioral changes, tremor, nystagmus, dismetry and gait disturbance

  12. Neuroimaging Evidence of Cerebellar Involvement in Premenstrual Dysphoric Disorder

    PubMed Central

    Rapkin, Andrea J.; Berman, Steven M.; Mandelkern, Mark A.; Silverman, Daniel H. S.; Morgan, Melinda; London, Edythe D.

    2010-01-01

    Background Premenstrual dysphoric disorder (PMDD) is a debilitating cyclic disorder that is characterized by affective symptoms, including irritability, depression, and anxiety which arise in the luteal phase of the menstrual cycle and resolve soon after the onset of menses. Despite a prevalence of up to 8% in women of reproductive age, few studies have investigated the brain mechanisms that underlie this disorder. Methods We used positron emission tomography with [18F] fluorodeoxyglucose and self-report questionnaires to assess cerebral glucose metabolism and mood in 12 women with PMDD and 12 healthy comparison subjects in the follicular and late luteal phases of the menstrual cycle. The primary biological endpoint was incorporated regional cerebral radioactivity (scaled to the global mean) as an index of glucose metabolism. Relationships between regional brain activity and mood ratings were assessed. Blood samples were taken before each session for assay of plasma estradiol and progesterone concentrations. Results There were no group differences in hormone levels in either the follicular or late luteal phase, but the groups differed in the effect of menstrual phase on cerebellar activity. Women with PMDD, but not comparison subjects, showed an increase in cerebellar activity (particularly in the right cerebellar vermis) from the follicular phase to the late luteal phase (p = 0.003). In the PMDD group, this increase in cerebellar activity was correlated with worsening of mood (p = 0.018). Conclusions These findings suggest that the midline cerebellar nuclei, which have been implicated in other mood disorders, also contribute to negative mood in PMDD. PMID:21092938

  13. Joubert–Boltshauser syndrome with polydactyly in siblings

    PubMed Central

    Egger, J; Bellman, MH; Ross, EM; Baraitser, M

    1982-01-01

    Two siblings are described with clinical features of the Joubert–Boltshauser syndrome. Both had polydactyly and one had fleshy tumours of the tongue. Computed tomography of the brain showed hypoplasia of the cerebellar vermis, associated in one case with a cyst of the fourth ventricle. Images PMID:7131000

  14. Visually Guided Step Descent in Children with Williams Syndrome

    ERIC Educational Resources Information Center

    Cowie, Dorothy; Braddick, Oliver; Atkinson, Janette

    2012-01-01

    Individuals with Williams syndrome (WS) have impairments in visuospatial tasks and in manual visuomotor control, consistent with parietal and cerebellar abnormalities. Here we examined whether individuals with WS also have difficulties in visually controlling whole-body movements. We investigated visual control of stepping down at a change of…

  15. Reversal of Irritable Bowel Syndrome, Sleep Disturbance, and Fatigue With an Elimination Diet, Lifestyle Modification, and Dietary Supplements: A Case Report

    PubMed Central

    Davis, Stephanie

    2016-01-01

    Background A 53-y-old Caucasian patient presented in August 2015 with chief complaints of irritable bowel syndrome (IBS; gas/bloating, gastroesophageal reflux), fatigue, and sleep disturbances. He also noted a history of chronic sinusitis, seasonal allergies, multiple chemical sensitivities, and right knee pain (3 surgeries). His primary care physician, in 2014, diagnosed prediabetes based on an elevated hemoglobin A1c and high-sensitivity C-reactive protein, which was treated with diet and lifestyle modification. Case/Intervention In the course of 6 mo, the patient was treated using an elimination diet, lifestyle modifications, botanicals, and dietary supplements. By addressing the underlying cause of issues, his symptoms decreased and quality of life increased, resulting in the resolution of his IBS symptoms, improved sleep, and increased energy levels. Conclusion This case illustrates the potential diagnostic importance of early testing for gut microbiome imbalances and gastrointestinal infections in the management of IBS as well as the usefulness of a systems-based approach for diagnostic assessment and management of a complex chronic case. PMID:27980496

  16. Temporal disruption of upper-limb anticipatory postural adjustments in cerebellar ataxic patients.

    PubMed

    Bruttini, Carlo; Esposti, Roberto; Bolzoni, Francesco; Vanotti, Alessandra; Mariotti, Caterina; Cavallari, Paolo

    2015-01-01

    Voluntary movements induce postural perturbations, which are counteracted by anticipatory postural adjustments (APAs) that preserve body equilibrium. Little is known about the neural structures generating APAs, but several studies suggested a role of sensory-motor areas, basal ganglia, supplementary motor area and thalamus. However, the role of the cerebellum still remains an open question. The aim of this present paper is to shed further light on the role of cerebellum in APAs organization. Thus, APAs that stabilize the arm when the index finger is briskly flexed were recorded in 13 ataxic subjects (seven sporadic cases, four dominant ataxia type III and two autosomal recessive), presenting a slowly progressive cerebellar syndrome with four-limb dysmetria, and compared with those obtained in 13 healthy subjects. The pattern of postural activity was similar in the two groups [excitation in triceps and inhibition in biceps and anterior deltoid (AD)], but apparent modifications in timing were observed in all ataxic subjects in which, on average, triceps brachii excitation lagged the onset of the prime mover flexor digitorum superficialis by about 27 ms and biceps and AD inhibition were almost synchronous to it. Instead, in normal subjects, triceps onset was synchronous to the prime mover and biceps and AD anticipated it by about 40 ms. The observed disruption of the intra-limb APA organization confirms that the cerebellum is involved in APA control and, considering cerebellar subjects as a model of dysmetria, also supports the view that a proper APA chain may play a crucial role in refining movement metria.

  17. Alzheimer's-related endosome dysfunction in Down syndrome is Abeta-independent but requires APP and is reversed by BACE-1 inhibition.

    PubMed

    Jiang, Ying; Mullaney, Kerry A; Peterhoff, Corrinne M; Che, Shaoli; Schmidt, Stephen D; Boyer-Boiteau, Anne; Ginsberg, Stephen D; Cataldo, Anne M; Mathews, Paul M; Nixon, Ralph A

    2010-01-26

    An additional copy of the beta-amyloid precursor protein (APP) gene causes early-onset Alzheimer's disease (AD) in trisomy 21 (DS). Endosome dysfunction develops very early in DS and AD and has been implicated in the mechanism of neurodegeneration. Here, we show that morphological and functional endocytic abnormalities in fibroblasts from individuals with DS are reversed by lowering the expression of APP or beta-APP-cleaving enzyme 1 (BACE-1) using short hairpin RNA constructs. By contrast, endosomal pathology can be induced in normal disomic (2N) fibroblasts by overexpressing APP or the C-terminal APP fragment generated by BACE-1 (betaCTF), all of which elevate the levels of betaCTFs. Expression of a mutant form of APP that cannot undergo beta-cleavage had no effect on endosomes. Pharmacological inhibition of APP gamma-secretase, which markedly reduced Abeta production but raised betaCTF levels, also induced AD-like endosome dysfunction in 2N fibroblasts and worsened this pathology in DS fibroblasts. T