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Sample records for reversible cerebellar syndrome

  1. Posterior fossa syndrome after cerebellar stroke.

    PubMed

    Mariën, Peter; Verslegers, Lieven; Moens, Maarten; Dua, Guido; Herregods, Piet; Verhoeven, Jo

    2013-10-01

    Posterior fossa syndrome (PFS) due to vascular etiology is rare in children and adults. To the best of our knowledge, PFS due to cerebellar stroke has only been reported in patients who also underwent surgical treatment of the underlying vascular cause. We report longitudinal clinical, neurocognitive and neuroradiological findings in a 71-year-old right-handed patient who developed PFS following a right cerebellar haemorrhage that was not surgically evacuated. During follow-up, functional neuroimaging was conducted by means of quantified Tc-99m-ECD SPECT studies. After a 10-day period of akinetic mutism, the clinical picture developed into cerebellar cognitive affective syndrome (CCAS) with reversion to a previously learnt accent, consistent with neurogenic foreign accent syndrome (FAS). No psychometric evidence for dementia was found. Quantified Tc-99m-ECD SPECT studies consistently disclosed perfusional deficits in the anatomoclinically suspected but structurally intact bilateral prefrontal brain regions. Since no surgical treatment of the cerebellar haematoma was performed, this case report is presumably the first description of pure, "non-surgical vascular PFS". In addition, reversion to a previously learnt accent which represents a subtype of FAS has never been reported after cerebellar damage. The combination of this unique constellation of poststroke neurobehavioural changes reflected on SPECT shows that the cerebellum is crucially implicated in the modulation of neurocognitive and affective processes. A decrease of excitatory impulses from the lesioned cerebellum to the structurally intact supratentorial network subserving cognitive, behavioural and affective processes constitutes the likely pathophysiological mechanism underlying PFS and CCAS in this patient. PMID:23575947

  2. [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. PMID:24954915

  3. [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.

  4. Cerebellar involvement of Griscelli syndrome type 2

    PubMed Central

    Işikay, Sedat

    2014-01-01

    Griscelli syndrome type 2 is characterised by partial albinism and primary immunodeficiency. We present a case of a 3-year-old girl diagnosed with cerebellar involvement of Griscelli syndrome type 2. Neurological complications may accompany Griscelli syndrome, however, to the best of my knowledge there are only a few case reports of cerebellar involvement of Griscelli syndrome type 2 in the literature. PMID:25315806

  5. Pediatric Neurocutaneous Syndromes with Cerebellar Involvement.

    PubMed

    Bosemani, Thangamadhan; Huisman, Thierry A G M; Poretti, Andrea

    2016-08-01

    Neurocutaneous syndromes encompasses a broad group of genetic disorders with different clinical, genetic, and pathologic features that share developmental lesions of the skin as well as central and peripheral nervous system. Cerebellar involvement has been shown in numerous types of neurocutaneous syndrome. It may help or be needed for the diagnosis and to explain the cognitive and behavioral phenotype of affected children. This article describes various types of neurocutaneous syndrome with cerebellar involvement. For each neurocutaneous disease or syndrome, clinical features, genetic, neuroimaging findings, and the potential role of the cerebellar involvement is discussed. PMID:27423801

  6. 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.

  7. Neuro-Otological Aspects of Cerebellar Stroke Syndrome

    PubMed Central

    2009-01-01

    Cerebellar stroke is a common cause of a vascular vestibular syndrome. Although vertigo ascribed to cerebellar stroke is usually associated with other neurological symptoms or signs, it may mimic acute peripheral vestibulopathy (APV), so called pseudo-APV. The most common pseudo-APV is a cerebellar infarction in the territory of the medial branch of the posterior inferior cerebellar artery (PICA). Recent studies have shown that a normal head impulse result can differentiate acute medial PICA infarction from APV. Therefore, physicians who evaluate stroke patients should be trained to perform and interpret the results of the head impulse test. Cerebellar infarction in the territory of the anterior inferior cerebellar artery (AICA) can produce a unique stroke syndrome in that it is typically accompanied by unilateral hearing loss, which could easily go unnoticed by patients. The low incidence of vertigo associated with infarction involving the superior cerebellar artery distribution may be a useful way of distinguishing it clinically from PICA or AICA cerebellar infarction in patients with acute vertigo and limb ataxia. For the purpose of prompt diagnosis and adequate treatment, it is imperative to recognize the characteristic patterns of the clinical presentation of each cerebellar stroke syndrome. This paper provides a concise review of the key features of cerebellar stroke syndromes from the neuro-otology viewpoint. PMID:19587812

  8. Developmental Cerebellar Cognitive Affective Syndrome in Ex-preterm Survivors Following Cerebellar Injury

    PubMed Central

    Brossard-Racine, Marie; du Plessis, Adre J.; Limperopoulos, Catherine

    2015-01-01

    Cerebellar injury is increasingly recognized as an important complication of very preterm birth. However, the neurodevelopmental consequences of early life cerebellar injury in prematurely born infants have not been well elucidated. We performed a literature search of studies published between 1997 and 2014 describing neurodevelopmental outcomes of preterm infants following direct cerebellar injury or indirect cerebellar injury/underdevelopment. Available data suggests that both direct and indirect mechanisms of cerebellar injury appear to stunt cerebellar growth and adversely affect neurodevelopment. This review also provides important insights into the highly integrated cerebral-cerebellar structural and functional correlates. Finally, this review highlights that early life impairment of cerebellar growth extends far beyond motor impairments and plays a critical, previously underrecognized role in the long-term cognitive, behavioral, and social deficits associated with brain injury among premature infants. These data point to a developmental form of the cerebellar cognitive affective syndrome previously described in adults. Longitudinal prospective studies using serial advanced magnetic resonance imaging techniques are needed to better delineate the full extent of the role of prematurity-related cerebellar injury and topography in the genesis of cognitive, social-behavioral dysfunction. PMID:25241880

  9. 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…

  10. 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

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

    PubMed

    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

    2015-11-01

    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

  12. Cerebellar atrophy in a patient with velocardiofacial syndrome.

    PubMed Central

    Lynch, D R; McDonald-McGinn, D M; Zackai, E H; Emanuel, B S; Driscoll, D A; Whitaker, L A; Fischbeck, K H

    1995-01-01

    Velocardiofacial syndrome and DiGeorge syndrome have not previously been associated with central nervous system degeneration. We report a 34 year old man who presented for neurological evaluation with cerebellar atrophy of unknown aetiology. On historical review, he had neonatal hypocalcaemia, an atrial septal defect, and a corrected cleft palate. His physical examination showed the characteristic facies of velocardiofacial syndrome as well as dysmetria and dysdiadocho-kinesia consistent with cerebellar degeneration. Molecular cytogenetic studies showed a deletion of 22q11.2. This man is the first reported patient with the association of a neurodegenerative disorder and 22q11.2 deletion syndrome. Images PMID:7562973

  13. Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome.

    PubMed

    Bodranghien, Florian; Bastian, Amy; Casali, Carlo; Hallett, Mark; Louis, Elan D; Manto, Mario; Mariën, Peter; Nowak, Dennis A; Schmahmann, Jeremy D; Serrao, Mariano; Steiner, Katharina Marie; Strupp, Michael; Tilikete, Caroline; Timmann, Dagmar; van Dun, Kim

    2016-06-01

    The cerebellum is involved in sensorimotor operations, cognitive tasks and affective processes. Here, we revisit the concept of the cerebellar syndrome in the light of recent advances in our understanding of cerebellar operations. The key symptoms and signs of cerebellar dysfunction, often grouped under the generic term of ataxia, are discussed. Vertigo, dizziness, and imbalance are associated with lesions of the vestibulo-cerebellar, vestibulo-spinal, or cerebellar ocular motor systems. The cerebellum plays a major role in the online to long-term control of eye movements (control of calibration, reduction of eye instability, maintenance of ocular alignment). Ocular instability, nystagmus, saccadic intrusions, impaired smooth pursuit, impaired vestibulo-ocular reflex (VOR), and ocular misalignment are at the core of oculomotor cerebellar deficits. As a motor speech disorder, ataxic dysarthria is highly suggestive of cerebellar pathology. Regarding motor control of limbs, hypotonia, a- or dysdiadochokinesia, dysmetria, grasping deficits and various tremor phenomenologies are observed in cerebellar disorders to varying degrees. There is clear evidence that the cerebellum participates in force perception and proprioceptive sense during active movements. Gait is staggering with a wide base, and tandem gait is very often impaired in cerebellar disorders. In terms of cognitive and affective operations, impairments are found in executive functions, visual-spatial processing, linguistic function, and affective regulation (Schmahmann's syndrome). Nonmotor linguistic deficits including disruption of articulatory and graphomotor planning, language dynamics, verbal fluency, phonological, and semantic word retrieval, expressive and receptive syntax, and various aspects of reading and writing may be impaired after cerebellar damage. The cerebellum is organized into (a) a primary sensorimotor region in the anterior lobe and adjacent part of lobule VI, (b) a second sensorimotor

  14. Cerebellar Cognitive Affective Syndrome Presented as Severe Borderline Personality Disorder

    PubMed Central

    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. PMID:24715924

  15. Spontaneously resolving cerebellar syndrome as a sequelae of dengue viral infection: a case series from Sri Lanka.

    PubMed

    Weeratunga, Praveen N; Caldera, H P Manjula C; Gooneratne, I Kishara; Gamage, Ranjanie; Perera, W Sujith P; Ranasinghe, Gayan V; Niraj, Mahboob

    2014-06-01

    Sri Lanka is hyperendemic for dengue viral infection. Dengue has a wide spectrum of neurological manifestations including previously reported Sri Lankan cases with a 6th nerve palsy and a cerebellar syndrome from a co-infection with dengue and Epstein-Barr virus. This series describes a spontaneously resolving cerebellar syndrome following a dengue viral infection. Dengue is potentially an important cause of cerebellar syndromes in countries hyperendemic for the disease; patients need further studies to identify the responsible serotypes.

  16. XY sex reversal and a nonprogressive neurologic disorder: a new syndrome?

    PubMed

    Mahbubul Huq, A H; Nigro, M A

    2000-10-01

    We report a patient with a unique combination of clinical findings: XY sex reversal, spastic paraplegia, mental retardation, dysmorphism, and infantile-onset olivopontocerebellar hypoplasia. The phenotype of our patient did not coincide with any of the described forms of XY reversal syndromes, hereditary or sporadic spastic paraplegias, or congenital or infantile-onset cerebellar or olivopontocerebellar atrophies or hypoplasias. The disorder of this patient likely represents a genetic condition with pleiotropic effects on brain development and sex determination and adds further evidence for the heterogeneity of spastic paraplegia/infantile olivopontocerebellar hypoplasia syndromes and sex reversal syndromes. PMID:11068172

  17. Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome.

    PubMed

    Ferland, Russell J; Eyaid, Wafaa; Collura, Randall V; Tully, Laura D; Hill, R Sean; Al-Nouri, Doha; Al-Rumayyan, Ahmed; Topcu, Meral; Gascon, Generoso; Bodell, Adria; Shugart, Yin Yao; Ruvolo, Maryellen; Walsh, Christopher A

    2004-09-01

    Joubert syndrome is a congenital brain malformation of the cerebellar vermis and brainstem with abnormalities of axonal decussation (crossing in the brain) affecting the corticospinal tract and superior cerebellar peduncles. Individuals with Joubert syndrome have motor and behavioral abnormalities, including an inability to walk due to severe clumsiness and 'mirror' movements, and cognitive and behavioral disturbances. Here we identified a locus associated with Joubert syndrome, JBTS3, on chromosome 6q23.2-q23.3 and found three deleterious mutations in AHI1, the first gene to be associated with Joubert syndrome. AHI1 is most highly expressed in brain, particularly in neurons that give rise to the crossing axons of the corticospinal tract and superior cerebellar peduncles. Comparative genetic analysis of AHI1 indicates that it has undergone positive evolutionary selection along the human lineage. Therefore, changes in AHI1 may have been important in the evolution of human-specific motor behaviors.

  18. 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…

  19. 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.

  20. 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.

  1. 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.

  2. 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. PMID:26932191

  3. 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

  4. 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.

  5. Reversible Posterior Leukoencephalopathy Syndrome Induced by Pazopanib

    PubMed Central

    2012-01-01

    Background The reversible posterior leukoencephalopathy syndrome is a clinical/radiological syndrome characterized by headache, seizures, impaired vision, acute hypertension, and typical magnetic resonance imaging findings. There are several reports in the literature that depict its occurrence in cancer patients. The list of common anticancer and supportive care drugs that predispose to reversible posterior leukoencephalopathy syndrome is expanding and includes not only a large number of chemotherapeutic agents but also an increased number of new targeted drugs, particularly angiogenesis inhibitors such as bevacizumab,sorefenib and sunitinib. Pazopanib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit which after a positive phase III randomized clinical trial in patients with advanced renal cell cancer received FDA approval for the treatment of advanced renal cell carcinoma. Until now no cases of reversible posterior leukoencephalopathy syndrome induced by pazopanib have been reported. Case report We present the case of a 40 years old female patient with heavily pre-treated metastatic renal cell carcinoma who received pazopanib as salvage treatment. After 21 days of pazopanib therapy the patient referred to the emergency department with epileptic seizure, impaired vision at both eyes and headache. MRI of the brain revealed subcortical oedema at the occipital and parietal lobes bilaterally. She was treated with anticonvulsants, i.v. administration of mannitol and antihypertensives and she recovered completely from her symptoms and was discharged on the tenth hospital day. A brain MRI performed 3 weeks after showed that the subcortical oedema had been subsided. Conclusion In conclusion this is the first case of pazopanib induced reversible posterior leukoencephalopathy syndrome. Although usually reversible, this syndrome is a serious and potentially life threatening adverse

  6. Crossed cerebro-cerebellar atrophy with Dyke Davidoff Masson syndrome.

    PubMed

    Algahtani, Hussein A; Aldarmahi, Ahmed A; Al-Rabia, Mohammed W; Young, G Bryan

    2014-01-01

    Dyke Davidoff Masson syndrome (DDMS) refers to atrophy or hypoplasia of one cerebral hemisphere following a prior fetal or childhood insult. It has characteristics of clinical and radiological changes. These changes include hemiparesis, seizures, facial-asymmetry, and mental retardation. We present a 25-year-old man with crossed cerebrocerebellar atrophy and DDMS. His seizures were well controlled using a combination of antiepileptic drugs.

  7. 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.

  8. 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.

  9. Mutations in SNX14 Cause a Distinctive Autosomal-Recessive Cerebellar Ataxia and Intellectual Disability Syndrome

    PubMed Central

    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

    2014-01-01

    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. PMID:25439728

  10. Saccadic lateropulsion in Wallenberg syndrome: a window to access cerebellar control of saccades?

    PubMed

    Tilikete, Caroline; Koene, Ansgar; Nighoghossian, Norbert; Vighetto, Alain; Pélisson, Denis

    2006-10-01

    Saccadic lateropulsion is characterized by an undershoot of contralaterally directed saccades, an overshoot of ipsilaterally directed saccades and an ipsilateral deviation of vertical saccades. In Wallenberg syndrome, it is thought to result from altered signals in the olivo-cerebellar pathway to the oculomotor cerebellar network. In the current study we aimed to determine whether saccadic lateropulsion results from a cerebellar impairment of motor related signals or visuo-spatial related signals. We studied the trajectory, the accuracy, the direction and the amplitude of a variety of vertical and oblique saccades produced by five patients and nine control subjects. Some results are consistent with previous data suggesting altered motor related signals. Indeed, the horizontal error of contralesional saccades in patients increased with the desired horizontal saccade size. Furthermore, the initial directional error measured during the saccadic acceleration phase was smaller than the global directional error, suggesting that the eye trajectory curved progressively. However, some other results suggest that the processes that specify the horizontal spatial goal of the saccades might be impaired in the patients. Indeed, the horizontal error of ipsilesional saccades in patients did not change significantly with the desired horizontal saccade size. In addition, when comparing saccades with similar intended direction, it was found that the directional error was inversely related to the vertical saccade amplitude. Thus we conclude that the cerebellum might be involved both in controlling the motor execution of saccades and in determining the visuo-spatial information about their goal.

  11. A rare saccade velocity profile in Stiff-Person Syndrome with cerebellar degeneration.

    PubMed

    Zivotofsky, Ari Z; Siman-Tov, Tali; Gadoth, Natan; Gordon, Carlos R

    2006-06-01

    Stiff-Person Syndrome (SPS) is an immune-mediated disorder of the central nervous system characterized by muscle rigidity, episodic muscle spasms, and high titers of antibodies against glutamic acid decarboxylase (GAD). The presence of cerebellar ataxia in SPS is extremely rare, but occurs. Clinical observations of ocular motor abnormalities have been noted in a few SPS patients. The purpose of this study is to provide a detailed quantitative documentation of ocular motor abnormalities in a patient with SPS and progressive cerebellar signs. Detailed clinical assessment of a woman with SPS and precise eye movement recordings using the magnetic search coil technique was performed. In addition to other ocular motor abnormalities that included longer latencies for saccades, downbeat nystagmus, and loss of downward smooth pursuit, a rare saccade velocity profile consisting of multi-component saccades was observed. We postulate that these ocular motor findings are related to impairment of GABAergic neurotransmission because antibodies to glutamic acid decarboxylase (GAD-Abs) have been implicated in the pathogenesis of both SPS and some cases of cerebellar ataxia. In addition, this unusual saccadic velocity profile may have important implications for modeling the saccadic system and furthering a complete understanding of saccade generation. PMID:16725126

  12. 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

  13. 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.

  14. Cerebellar cognitive affective syndrome in Machado Joseph disease: core clinical features.

    PubMed

    Braga-Neto, Pedro; Pedroso, José Luiz; Alessi, Helena; Dutra, Lívia Almeida; Felício, André Carvalho; Minett, Thaís; Weisman, Patrícia; Santos-Galduroz, Ruth F; Bertolucci, Paulo Henrique F; Gabbai, Alberto Alain; Barsottini, Orlando Graziani Povoas

    2012-06-01

    The cerebellum is no longer considered a purely motor control device, and convincing evidence has demonstrated its relationship to cognitive and emotional neural circuits. The aims of the present study were to establish the core cognitive features in our patient population and to determine the presence of Cerebellar Cognitive Affective Syndrome (CCAS) in this group. We recruited 38 patients with spinocerebellar ataxia type 3 (SCA3) or Machado–Joseph disease (MJD)-SCA3/MJD and 31 controls. Data on disease status were recorded (disease duration, age, age at onset, ataxia severity, and CAG repeat length). The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. The neuropsychological assessment consisted of the Mini-Mental State Examination, Clock Drawing Test, Wechsler Adult Intelligence Scale, Rey–Osterrieth Complex Figure, Wisconsin Card Sorting Test, Stroop Color–Word Test, Trail-Making Test, Verbal Paired Associates, and verbal fluency tests. All subjects were also submitted to the Hamilton Anxiety Scale and Beck Depression Inventory. After controlling for multiple comparisons, spatial span, picture completion, symbol search, Stroop Color–Word Test, phonemic verbal fluency, and Trail-Making Tests A and B were significantly more impaired in patients with SCA3/MJD than in controls. Executive and visuospatial functions are impaired in patients with SCA3/MJD, consistent with the symptoms reported in the CCAS. We speculate on a possible role in visual cortical processing degeneration and executive dysfunction in our patients as a model to explain their main cognitive deficit. PMID:21975858

  15. Impaired hypercarbic and hypoxic responses from developmental loss of cerebellar Purkinje neurons: Implications for sudden infant death syndrome

    PubMed Central

    Calton, M.; Dickson, P.; Harper, R.M.; Goldowitz, D.; Mittleman, G.

    2014-01-01

    Impaired responsivity to hypercapnia or hypoxia is commonly considered a mechanism of failure in Sudden Infant Death Syndrome (SIDS). The search for deficient brain structures mediating flawed chemosensitivity typically focuses on medullary regions; however, a network that includes Purkinje cells of the cerebellar cortex and its associated cerebellar nuclei also helps mediate responses to CO2 and O2 challenges, and assists integration of cardiovascular and respiratory interactions. Although cerebellar nuclei contributions to chemoreceptor challenges in adult models are well described, Purkinje cell roles in developing models are unclear. We used a model of developmental cerebellar Purkinje cell loss to determine if such loss influenced compensatory ventilatory responses to hypercapnic and hypoxic challenges. Twenty-four Lurcher mutant mice and wildtype controls were sequentially exposed to 2% increases in CO2 (0%-8%), or 2% reductions in O2 (21%-13%) over four minutes, with return to room air (21% O2 / 79% N2 / 0% CO2) between each exposure. Whole-body plethysmography was used to continuously monitor tidal volume (TV) and breath frequency (f). Increased f to hypercapnia was significantly lower in Mutants, slower to initiate, and markedly lower in compensatory periods, except for very high (8%) CO2 levels. The magnitude of TV changes to increasing CO2 appeared smaller in Mutants, but only approached significance. Smaller, but significant differences emerged in response to hypoxia, with Mutants showing smaller TV when initially exposed to reduced O2, and lower f following exposure to 17% O2. Since cerebellar neuropathology appears in SIDS victims, developmental cerebellar neuropathology may contribute to SIDS vulnerability. PMID:25132500

  16. Posterior Reversible Encephalopathy Syndrome Complicating Traumatic Pancreatitis

    PubMed Central

    Sigurtà, Anna; Terzi, Valeria; Regna-Gladin, Caroline; Fumagalli, Roberto

    2016-01-01

    Abstract We are reporting a case of posterior reversible encephalopathy syndrome (PRES) developed in an unusual clinical scenario without the presence of the most described symptoms. PRES is a neurological and radiological syndrome described in many different clinical conditions. In children it has been mostly reported in association with hematological and renal disorders. Our patient was a 15 years old boy, admitted to our intensive care unit for pancreatitis after blunt abdominal trauma. During the stay in the intensive care unit, he underwent multiple abdominal surgical interventions for pancreatitis complications. He had a difficult management of analgesia and sedation, being often agitated with high arterial pressure, and he developed a bacterial peritonitis. After 29 days his neurological conditions abruptly worsened with neuroimaging findings consistent with PRES. His clinical conditions progressively improved after sedation and arterial pressure control. He was discharged at home with complete resolution of the neurological and imaging signs 2 months later. The pathophysiology of PRES is controversial and involves disordered autoregulation ascribable to hypertension and endothelial dysfunction. In this case both hypertension and endothelial activation, triggered by sepsis and pancreatitis, could represent the culprits of PRES onset. Even if there is no specific treatment for this condition, a diagnosis is mandatory to start antihypertensive and supportive treatment. We are therefore suggesting to consider PRES in the differential diagnosis of a neurological deterioration preceded by hypertension and/or septic state, even without other “typical” clinical features. PMID:27258506

  17. Reversible Posterior Leukoencephalopathy Syndrome Developing After Restart of Sunitinib Therapy for Metastatic Renal Cell Carcinoma

    PubMed Central

    Toyoshima, Yuta; Inoue, Takeshi; Kagebayashi, Yoriaki; Samma, Shoji

    2016-01-01

    A 64-year-old Japanese man had started molecular-targeted therapy with sunitinib for lymph node metastasis 5 years after nephrectomy for left renal cell carcinoma (clear cell carcinoma, G2, pT2N0M0). He was transported to our emergency department because of generalized tonic-clonic seizure, vision loss, and impaired consciousness with acute hypertension after 8 cycles of treatment (2 years after the initiation of sunitinib therapy, including a drug withdrawal period for one year). MRI of the brain (FLAIR images) showed multiple high-intensity lesions in the white matter of the occipital and cerebellar lobes, dorsal brain stem, and left thalamus. Reversible posterior leukoencephalopathy syndrome caused by sunitinib was suspected. In addition to the immediate discontinuation of sunitinib therapy, the administration of antihypertensive agents and anticonvulsants improved the clinical symptoms without neurological damage. Physicians should be aware that sunitinib causes reversible posterior leukoencephalopathy syndrome. The early recognition of reversible posterior leukoencephalopathy syndrome is critical to avoid irreversible neurological damage. PMID:27795711

  18. 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.

  19. Mycophenolate-Induced Posterior Reversible Encephalopathy Syndrome.

    PubMed

    Khajuria, Bhavik; Khajuria, Mansi; Agrawal, Yashwant

    2016-01-01

    A 29-year-old woman presented with diffuse anasarca and shortness of breath. Workup revealed a creatinine of 3.3 and a glomerular filtration rate of 17. The patient was also found to be pancytopenic with evidence of hemolytic anemia. A renal biopsy showed evidence of stage IV lupus nephritis with rapidly progressive glomerulonephritis. Her lupus was further classified as ANA negative and anti-dsDNA positive. Mycophenolate and triweekly hemodialysis were started along with a steroid burst of methylprednisolone 1 g for 3 days followed by prednisone 60 mg daily. Four days after discharge, the patient represented with a witnessed 3-minute seizure involving bowel incontinence, altered mental status, and tongue biting. She was given 2 mg intravenous lorazepam and loaded with 1000 mg levetiracetam for seizure prophylaxis. Magnetic resonance imaging of the head revealed bilateral posterior hemispheric subcortical edema, and the diagnosis of posterior reversible encephalopathy syndrome was made. Mycophenolate was immediately discontinued and replaced with cyclophosphamide. Strict blood pressure control below 140/90 mm Hg was maintained initially with intravenous nicardipine drip and then transitioned to oral nifedipine, clonidine, losartan, and minoxidil. A repeat head magnetic resonance imaging 8 days later showed resolved subcortical edema consistent with the patient's improved mental status. No permanent neurologic sequelae were recorded as a result of this hospital episode. PMID:25933141

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Developmental molecular and functional cerebellar alterations induced by PCP4/PEP19 overexpression: implications for Down syndrome.

    PubMed

    Mouton-Liger, François; Sahún, Ignasi; Collin, Thibault; Lopes Pereira, Patricia; Masini, Debora; Thomas, Sophie; Paly, Evelyne; Luilier, Sabrina; Même, Sandra; Jouhault, Quentin; Bennaï, Soumia; Beloeil, Jean-Claude; Bizot, Jean-Charles; Hérault, Yann; Dierssen, Mara; Créau, Nicole

    2014-03-01

    PCP4/PEP19 is a modulator of Ca(2+)-CaM signaling. In the brain, it is expressed in a very specific pattern in postmitotic neurons. In particular, Pcp4 is highly expressed in the Purkinje cell, the sole output neuron of the cerebellum. PCP4, located on human chromosome 21, is present in three copies in individuals with Down syndrome (DS). In a previous study using a transgenic mouse model (TgPCP4) to evaluate the consequences of 3 copies of this gene, we found that PCP4 overexpression induces precocious neuronal differentiation during mouse embryogenesis. Here, we report combined analyses of the cerebellum at postnatal stages (P14 and adult) in which we identified age-related molecular, electrophysiological, and behavioral alterations in the TgPCP4 mouse. While Pcp4 overexpression at P14 induces an earlier neuronal maturation, at adult stage it induces increase in cerebellar CaMK2alpha and in cerebellar LTD, as well as learning impairments. We therefore propose that PCP4 contributes significantly to the development of Down syndrome phenotypes through molecular and functional changes.

  5. 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.

  6. Developmental molecular and functional cerebellar alterations induced by PCP4/PEP19 overexpression: implications for Down syndrome.

    PubMed

    Mouton-Liger, François; Sahún, Ignasi; Collin, Thibault; Lopes Pereira, Patricia; Masini, Debora; Thomas, Sophie; Paly, Evelyne; Luilier, Sabrina; Même, Sandra; Jouhault, Quentin; Bennaï, Soumia; Beloeil, Jean-Claude; Bizot, Jean-Charles; Hérault, Yann; Dierssen, Mara; Créau, Nicole

    2014-03-01

    PCP4/PEP19 is a modulator of Ca(2+)-CaM signaling. In the brain, it is expressed in a very specific pattern in postmitotic neurons. In particular, Pcp4 is highly expressed in the Purkinje cell, the sole output neuron of the cerebellum. PCP4, located on human chromosome 21, is present in three copies in individuals with Down syndrome (DS). In a previous study using a transgenic mouse model (TgPCP4) to evaluate the consequences of 3 copies of this gene, we found that PCP4 overexpression induces precocious neuronal differentiation during mouse embryogenesis. Here, we report combined analyses of the cerebellum at postnatal stages (P14 and adult) in which we identified age-related molecular, electrophysiological, and behavioral alterations in the TgPCP4 mouse. While Pcp4 overexpression at P14 induces an earlier neuronal maturation, at adult stage it induces increase in cerebellar CaMK2alpha and in cerebellar LTD, as well as learning impairments. We therefore propose that PCP4 contributes significantly to the development of Down syndrome phenotypes through molecular and functional changes. PMID:24291518

  7. 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

  8. 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.

  9. Reversible Cerebral Vasoconstriction Syndrome: A Report on Three Cases.

    PubMed

    Roongpiboonsopit, Duangnapa; Kongbunkiat, Kannikar; Phanthumchinda, Kammant

    2016-01-01

    Reversible cerebral vasoconstriction syndrome (RCVS), a recently recognized syndrome, is defined as an intermittent segmental vasospasm of cerebral arteries accompanied by thunderclap headache. The major complications of RCVS include ischemic or hemorrhagic stroke, which may cause morbidity and mortality. It is important to detect RCVS in clinical practice because misdiagnosis may lead to inappropriate treatment. In Thailand, there are only two reported cases of RCVS, which may reflect an underdiagnosis of this syndrome. To raise awareness of RCVS, we reported a case series of three RCVS cases. Two of the presented cases had interesting precipitating factors, and two cases had an unusual delayed clinical course. PMID:27455831

  10. A Precocious Cerebellar Ataxia and Frequent Fever Episodes in a 16-Month-Old Infant Revealing Ataxia-Telangiectasia Syndrome

    PubMed Central

    Nespoli, Luigi; Tajè, Silvia; Marinoni, Maddalena

    2013-01-01

    Ataxia-telangiectasia (AT) is the most frequent progressive cerebellar ataxia in infancy and childhood. Immunodeficiency which includes both cellular and humoral arms has variable severity. Since the clinical presentation is extremely variable, a high clinical suspicion will allow an early diagnosis. Serum alpha-fetoprotein is elevated in 80–85% of patients and therefore could be used as a screening tool. Here, we present a case of a 5-year-old female infant who was admitted to our department at the age of 16 months because of gait disorders and febrile episodes that had begun at 5 months after the cessation of breastfeeding. Serum alfa-fetoprotein level was elevated. Other investigations showed leukocytopenia with lymphopenia, reduced IgG2 and IgA levels, and low titers of specific postimmunization antibodies against tetanus toxoid and Haemophilus B polysaccharide. Peripheral lymphocytes subsets showed reduction of T cells with a marked predominance of T cells with a memory phenotype and a corresponding reduction of naïve T cells; NK cells were very increased (41%) with normal activity. The characterization of the ATM gene mutations revealed 2 specific mutations (c.5692C > T/c.7630-2A > C) compatible with AT diagnosis. It was concluded that AT syndrome should be considered in children with precocious signs of cerebellar ataxia and recurrent fever episodes. PMID:25374739

  11. Oral administration of PF-01247324, a subtype-selective Nav1.8 blocker, reverses cerebellar deficits in a mouse model of multiple sclerosis.

    PubMed

    Shields, Shannon D; Butt, Richard P; Dib-Hajj, Sulayman D; Waxman, Stephen G

    2015-01-01

    Cerebellar symptoms significantly diminish quality of life in patients with multiple sclerosis (MS). We previously showed that sodium channel Nav1.8, although normally restricted to peripheral somatosensory neurons, is upregulated in the cerebellum in MS, and that Nav1.8 expression is linked to ataxia and MS-like symptoms in mice. Furthermore, intracerebroventricular administration of the Nav1.8 blocker A-803467 temporarily reversed electrophysiological and behavioral manifestations of disease in a mouse MS model; unfortunately A-803467 is not orally bioavailable, diminishing the potential for translation to human patients. In the present study, we assessed the effect of per os (p.o.) dosing of a new orally bioavailable Nav1.8-selective blocker, PF-01247324, in transgenic mice expressing Nav1.8 in Purkinje neurons, and in wildtype mice in the experimental autoimmune encephalomyelitis (EAE) model. PF-01247324 was administered by oral gavage at 1000 mg/kg; control groups received an equal volume of vehicle. Behavioral assays of motor coordination, grip strength, and ataxia were performed. We observed significant improvements in motor coordination and cerebellar-like symptoms in mice that received PF-01247324 compared to control littermates that received vehicle. These preclinical proof-of-concept data suggest that PF-01247324, its derivatives, or other Nav1.8-selective blockers merit further study for providing symptomatic therapy for cerebellar dysfunction in MS and related disorders. PMID:25747279

  12. Three familial midline malformtion syndromes of the central nervous system: agenesis of the corpus callosum and anterior horn-cell disease; agenesis of cerebellar vermis; and atrophy of the cerebellar vermis.

    PubMed

    Andermann, E; Andermann, F; Joubert, M; Melançon, D; Karpati, G; Carpenter, S

    1975-01-01

    Three syndromes are presented in which major midline malformations of the central nervous system were associated with characteristic somatic and neurologic features in 2 or more sibs. The malformations may be suspected on clinical grouds but require confirmation by pneumoencephalography. In 3 French-Canadian sibships from the Saguenay-Lac St. Jean area of Quebec, patients with areflexia, muscular wasting and slowly progressive weakness in a paraparetic distribution were proved to have agenesis of the corpus callosum and anterior horn-cell disease, a syndrome not previously described. In another family, mental retardation, ataxia and episodic hyperpnea were associated with agenesis of the cerebellar vermis in 4 sibs. In yet another French-Canadian family, atrophy of the cerebellar vermis was associated with mental retardation, ataxia and a mild pyramidal syndrome. Because malformations of this nature are usually considered sporadic or multifactorial in origin, recognition of these specific clinical syndromes with probable autosomal recessive inheritance is important from the point of view of genetic counseling and prevention. PMID:1227532

  13. 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.

  14. Reversible cerebral vasoconstriction in Guillain-Barré syndrome.

    PubMed

    Wei, Diana Y; Kao, Justin; Wu, Teddy Y; Pereira, Jennifer A; Anderson, Neil E; Alan Barber, P

    2015-07-01

    We present a 51-year-old woman with clinical and neurophysiological evidence of Guillain-Barré syndrome (GBS) who developed a generalised headache and autonomic dysfunction with sinus tachycardia, hypertension, gastrointestinal motility symptoms and urinary retention. MRI/MRA demonstrated cerebral vasoconstriction and a small convexity subarachnoid haemorrhage which resolved after 3 months. Reversible cerebral vasoconstriction syndrome (RCVS) is characterised by headache, focal neurological deficits or seizures, and reversible cerebral vasoconstriction. To our knowledge, this is the first reported case of RCVS complicating autonomic dysfunction in GBS. This case depicts a rare complication of a common condition and also sheds light on the potential mechanism of RCVS. Neurologists should be aware that autonomic dysfunction can lead to RCVS in GBS.

  15. T-cell reactivity to glutamic acid decarboxylase in stiff-man syndrome and cerebellar ataxia associated with polyendocrine autoimmunity

    PubMed Central

    Costa, M; Saiz, A; Casamitjana, R; Castañer, M FernÁndez; SanmartÍ, A; Graus, F; Jaraquemada, D

    2002-01-01

    Antibodies to glutamic acid decarboxilase (GAD-Abs) are present in the serum of 60–80% of newly diagnosed type 1 diabetes (DM1) patients and patients with autoimmune polyendocrine syndrome (APS) associated with DM1. Higher titre of GAD-Abs are also present in the serum of 60% of patients with stiff-man syndrome (SMS) and all reported patients with cerebellar ataxia associated with polyendocrine autoimmunity (CAPA). Several studies suggest that GAD-Abs may play a critical role in the pathogenesis of SMS and CAPA but little is known about T-cell responsiveness to GAD-65 in these neurological diseases. To analyse cell-mediated responses to GAD, we studied the peripheral blood lymphocyte proliferation and cytokine responses to recombinant human GAD-65 in 5 patients with SMS, 6 with CAPA, 9 with DM1, 8 with APS and 15 control subjects. GAD-65-specific cellular proliferation was significantly higher in SMS than in CAPA, DM1, APS or controls. In contrast, only T cells from CAPA patients showed a significantly high production of interferon-γ after GAD stimulation, compared to all other patients and controls. No differences were found for IL-4 production. These results suggest that, despite similar humoral autoreactivity, cellular responses to GAD are different between SMS and CAPA, with a greater inflammatory response in CAPA, and this difference may be relevant to the pathogenesis of these diseases. PMID:12197888

  16. 4-aminopyridine reverses ataxia and cerebellar firing deficiency in a mouse model of spinocerebellar ataxia type 6.

    PubMed

    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 (SCA6(84Q/+)) 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 (SCA6(84Q/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 SCA6(84Q/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

  17. 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

  18. 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

  19. 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. PMID:27016378

  20. 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.

  1. Cerebellar function in developmental dyslexia.

    PubMed

    Stoodley, Catherine J; Stein, John F

    2013-04-01

    Developmental dyslexia is a genetically based neurobiological syndrome, which is characterized by reading difficulty despite normal or high general intelligence. Even remediated dyslexic readers rarely achieve fast, fluent reading. Some dyslexics also have impairments in attention, short-term memory, sequencing (letters, word sounds, and motor acts), eye movements, poor balance, and general clumsiness. The presence of "cerebellar" motor and fluency symptoms led to the proposal that cerebellar dysfunction contributes to the etiology of dyslexia. Supporting this, functional imaging studies suggest that the cerebellum is part of the neural network supporting reading in typically developing readers, and reading difficulties have been reported in patients with cerebellar damage. Differences in both cerebellar asymmetry and gray matter volume are some of the most consistent structural brain findings in dyslexics compared with good readers. Furthermore, cerebellar functional activation patterns during reading and motor learning can differ in dyslexic readers. Behaviorally, some children and adults with dyslexia show poorer performance on cerebellar motor tasks, including eye movement control, postural stability, and implicit motor learning. However, many dyslexics do not have cerebellar signs, many cerebellar patients do not have reading problems, and differences in dyslexic brains are found throughout the whole reading network, and not isolated to the cerebellum. Therefore, impaired cerebellar function is probably not the primary cause of dyslexia, but rather a more fundamental neurodevelopmental abnormality leads to differences throughout the reading network.

  2. Reversible Cerebral Vasoconstriction Syndrome Presenting With Visual Field Defects.

    PubMed

    Raven, Meisha L; Ringeisen, Alexander L; McAllister, Angela R; Knoch, Daniel W

    2016-06-01

    A 45-year-old woman with a history of depression and anxiety, treated with selective serotonin reuptake inhibitors (SSRIs), experienced acute, recurrent, and severe bifrontal headaches. Over time, she developed a left homonymous hemianopia and mental status changes. MRA revealed segmental vasoconstriction of cerebral arteries in multiple vascular distributions. She was treated with a calcium-channel blocker and magnesium, and there was resolution of her symptoms and cerebrovascular changes. Her clinical course and neuroimaging findings were consistent with reversible cerebral vasoconstriction syndrome. Although rare, this disorder frequently manifests with visual complaints. Although the prognosis is generally favorable, patients with this syndrome require prompt diagnosis and care directed to avoid complications including stroke, seizure, and subarachnoid hemorrhage. PMID:26807800

  3. Reversible posterior leukoencephalopathy syndrome in a child treated with bevacizumab.

    PubMed

    Levy, Carolyn Fein; Oo, Khine Zin; Fireman, Fernando; Pierre, Louisdon; Bania, Marita A; Sadanandan, Swayamprabha; Yamashiro, Darrell J; Glade Bender, Julia L

    2009-05-01

    Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF). Hypertension is a well-recognized, common side effect of VEGF blocking agents. The reversible posterior leukoencephalopathy syndrome (RPLS) has been described as a rare but serious consequence of bevacizumab administration. We present a case of a 6-year-old child with refractory hepatoblastoma who developed hypertensive crisis, seizures and MRI changes consistent with RPLS while receiving bevacizumab with gemcitabine and oxaliplatin. Findings completely resolved without neurologic sequelae with stringent blood-pressure control. Better understanding of risk for RPLS, prompt recognition and aggressive management will be required as bevacizumab gains wider use in pediatrics.

  4. Treatable causes of cerebellar ataxia.

    PubMed

    Ramirez-Zamora, Adolfo; Zeigler, Warren; Desai, Neeja; Biller, José

    2015-04-15

    The cerebellar ataxia syndromes are a heterogeneous group of disorders clinically characterized by the presence of cerebellar dysfunction. Initial assessment of patients with progressive cerebellar ataxia is complex because of an extensive list of potential diagnoses. A detailed history and comprehensive examination are required for an accurate diagnosis and hierarchical diagnostic investigations. Although no cure exists for most of these conditions, a small group of metabolic, hereditary, inflammatory, and immune-mediated etiologies of cerebellar ataxia are amenable to disease-modifying, targeted therapies. Over the past years, disease-specific treatments have emerged. Thus, clinicians must become familiar with these disorders because maximal therapeutic benefit is only possible when done early. In this article, we review disorders in which cerebellar ataxia is a prominent clinical feature requiring targeted treatments along with specific management recommendations.

  5. 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.

  6. Cerebellar Hypoplasia

    MedlinePlus

    ... disorders that begin in early childhood, such as ataxia telangiectasia. In an infant or young child, symptoms of a disorder that features cerebellar hypoplasia might include floppy muscle tone, developmental or ...

  7. Cerebellar Degeneration

    MedlinePlus

    ... Degeneration? Cerebellar degeneration is a process in which neurons in the cerebellum - the area of the brain ... proteins that are necessary for the survival of neurons. Associated diseases: Diseases that are specific to the ...

  8. Boucher-Neuhäuser syndrome: cerebellar degeneration, chorioretinal dystrophy and hypogonadotropic hypogonadism: two novel cases and a review of 40 cases from the literature.

    PubMed

    Tarnutzer, A A; Gerth-Kahlert, C; Timmann, D; Chang, D I; Harmuth, F; Bauer, P; Straumann, D; Synofzik, M

    2015-01-01

    The combination of progressive cerebellar degeneration, hypogonadotropic hypogonadism and chorioretinal dystrophy defines the rare Boucher-Neuhäuser syndrome (BNS), which has recently been linked to autosomal-recessive mutations in the PNPLA6 gene in four index patients. Here we present two novel unrelated patients with BNS, where we identified four recessive PNPLA6 mutations (3 of them novel) as the genetic cause, using a targeted high-throughput approach. This finding provides the first replication from independent families that BNS is caused by PNPLA6 and, moreover, highlights PNPLA6 as the major gene leading to BNS. Given the fact that the major gene causing BNS has thus now been identified, we summarize the spectrum of clinical presentations and phenotype evolution of BNS based on a systematic in-depth review of the literature of previously published cases (n = 40). Both the two cases presented here and our review of the literature propose that the clinical presentation of BNS can be variable regarding both the age (ranging from 1 to 40 years) and the clinical symptoms at onset (cerebellar ataxia in 38 %; vision loss in 36 %; delayed puberty in 26 %). A substantial fraction of BNS cases may present with relatively selective atrophy of the superior and dorsal parts of the cerebellar vermis along with atrophy of the cerebellar hemispheres on MRI, while brainstem or cortical changes on MRI seem to be present only in small fractions. Also in the literature, no other major genetic causes of BNS other than PNPLA6 mutations were identified.

  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. Posterior Reversible Encephalopathy Syndrome (PRES) After Acute Pancreatitis

    PubMed Central

    Murphy, Tara; Al-Sharief, Khalid; Sethi, Vineeta; Ranger, Gurpreet S.

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is an unusual condition typified by acute visual impairment caused by sudden, marked parieto-occipital vasogenic edema. Thought to be inflammatory in origin, it has been described in patients undergoing chemotherapy, with autoimmune disease, and in some infections. We report a case of PRES that occurred one week after an episode of acute pancreatitis in an otherwise healthy 40-year-old female. There was progressive visual impairment over a 24-hour period with almost complete visual loss, with characteristic findings on magnetic resonance imaging. After treatment with steroids, the visual loss recovered. Clinicians should retain an index of suspicion of this rare condition in patients with visual impairment after acute pancreatitis. PMID:26759673

  11. Magnesium for Treatment of Reversible Cerebral Vasoconstriction Syndrome

    PubMed Central

    Mijalski, Christina; Dakay, Katarina; Miller-Patterson, Cameron; Saad, Ali; Silver, Brian

    2015-01-01

    We describe 2 cases of reversible cerebral vasoconstriction syndrome (RCVS) with refractory headache aborted by intravenous magnesium. Case 1 is a 53-year-old woman with subarachnoid hemorrhage due to RCVS presented with refractory headache and persistent vasospasm, despite aggressive treatment with calcium channel blockers (CCBs) and systemic corticosteroids. Subsequently, she experienced dramatic relief of symptoms with intravenous magnesium therapy. She continued oral maintenance therapy and remained symptom free. Case 2 is a 71-year-old female with bilateral temporo-occipital infarcts due to RCVS, presented with refractory headache and persistent vasospasm on transcranial Doppler (TCD), despite aggressive treatment with CCBs. She experienced dramatic relief of symptoms with intravenous magnesium and resolution of vasospasm on TCD. Magnesium may be beneficial for the treatment of refractory headaches in patients with RCVS. Future studies are needed to determine whether it should be considered as a first-line agent. PMID:27366294

  12. Adolescent enrichment partially reverses the social isolation syndrome.

    PubMed

    Hellemans, Kim G C; Benge, Luis C; Olmstead, Mary C

    2004-06-21

    Early environmental experience produces profound neural and behavioural effects. For example, animals reared in isolation show increased anxiety, neophobia, and poorer performance in learning and spatial memory tasks. We investigated whether later enrichment reverses some or all of the deficits induced by isolation rearing. Eighty-four male Long-Evans rats (21 days old) were reared under different conditions: enriched (group housed with toys), isolated (one rat/cage), standard (two rats/cage), isolated-enriched, enriched-isolated, isolated-standard, or enriched-standard. In the latter four conditions, animals were housed in the first environment until adolescence (66 days). Following the 90-day rearing period, all animals were assessed in a battery of behavioural tests and cortical thickness was measured postmortem. Isolation rearing led to significant differences in behavioural tests measuring anxiety, spatial learning, and locomotor activity; switching the rearing condition partially reversed these changes. Rearing condition did not affect pain thresholds in the tail flick test or aversive associative learning in the conditioned taste aversion test. Enriched rats had the thickest cortex; isolated rats the thinnest. None of the switch groups differed significantly from standard-reared rats in this measure. Taken together, these results provide novel and interesting information regarding the effects of pre- or post-adolescent enrichment experience on behavioural and neural expression of the social isolation syndrome. PMID:15158074

  13. Effects of reversible pharmacological shutdown of cerebellar flocculus on the memory of long-term horizontal vestibulo-ocular reflex adaptation in monkeys.

    PubMed

    Anzai, Mari; Kitazawa, Hiromasa; Nagao, Soichi

    2010-11-01

    The adaptation of the horizontal vestibulo-ocular reflex (HVOR) provides an experimental model for motor learning. Two studies, using cats and mice, respectively, have recently suggested pharmacologically that the memory of adaptation is located multiply in the cerebellum and brainstem. Here, we examined the effects of acute cerebellar flocculus shutdown on the adaptation in four monkeys. Two hours of 0.11Hz-10° turntable oscillation while viewing a stationary checked-patterned screen through the left-right reversing prism decreased the HVOR gains by 0.16, and 3 days of prism wearing combined with 2h of daily turntable oscillation decreased the HVOR gains by 0.27. Injections of lidocaine into bilateral flocculi did not affect the nonadapted HVOR gains, but depressed the visual suppression of the HVOR. They recovered the HVOR gains decreased by 2h of training, but very little affected the HVOR gains decreased by previous 2 days of training. Injections of control Ringer's solution did not affect the gains adapted by 2h or 3 days of training. These results are consistent with the previous studies, and suggest that the memory trace of adaptation of the HVOR initially resides in the flocculus but later resides, presumably, in the vestibular nuclei in the monkey.

  14. [Cerebellar stroke].

    PubMed

    Paradowski, Michał; Zimny, Anna; Paradowski, Bogusław

    2015-01-01

    Cerebellar stroke belongs to a group of rare diseases of vascular origin. Cerebellum, supplied by three pairs of arteries (AICA, PICA, SCA) with many anastomoses between them is less susceptible for a stroke, especially ischemic one. Diagnosis of the stroke in this region is harder due to lower sensibility of commonly used CT of the head in case of stroke suspicion. The authors highlight clinical symptoms distinguishing between vascular territories or topographical locations of the stroke, diagnostic procedures, classical and surgical treatment, the most common misdiagnoses are also mentioned. The authors suggest a diagnostic and therapeutic algorithm development, including rtPA treatment criteria for ischemic cerebellar stroke. PMID:26181157

  15. Association of reversible splenial lesion syndrome (RESLES) with Anti-VGKC autoantibody syndrome: a case report.

    PubMed

    Gilder, Thomas R; Hawley, Jason S; Theeler, Brett J

    2016-05-01

    A 50-year-old male presented with complaints of fatigue, confusion, and memory problems. Neurological evaluation revealed altered cognition, unsteady gait, ataxia, dysmetria, and weakness. MRI of the brain was initially unremarkable. Over several days, the patient experienced improvement of symptoms and a follow-up MRI revealed a small lesion in the splenium of the corpus callosum seen on diffusion weighted and T2 sequences. The patient was discovered to have elevated anti-voltage gated potassium channel serum autoantibodies. Follow-up MRI revealed resolution of the splenial lesion. The patient was treated with intravenous immune globulin, and improved back to his pre-treatment baseline. We believe this to be the first case of a reversible splenial lesion syndrome as a manifestation of the anti-voltage gated potassium channel autoantibody syndrome, and propose a pathophysiologic mechanism.

  16. Association of reversible splenial lesion syndrome (RESLES) with Anti-VGKC autoantibody syndrome: a case report.

    PubMed

    Gilder, Thomas R; Hawley, Jason S; Theeler, Brett J

    2016-05-01

    A 50-year-old male presented with complaints of fatigue, confusion, and memory problems. Neurological evaluation revealed altered cognition, unsteady gait, ataxia, dysmetria, and weakness. MRI of the brain was initially unremarkable. Over several days, the patient experienced improvement of symptoms and a follow-up MRI revealed a small lesion in the splenium of the corpus callosum seen on diffusion weighted and T2 sequences. The patient was discovered to have elevated anti-voltage gated potassium channel serum autoantibodies. Follow-up MRI revealed resolution of the splenial lesion. The patient was treated with intravenous immune globulin, and improved back to his pre-treatment baseline. We believe this to be the first case of a reversible splenial lesion syndrome as a manifestation of the anti-voltage gated potassium channel autoantibody syndrome, and propose a pathophysiologic mechanism. PMID:26743064

  17. 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

  18. 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

  19. [Reversible cerebral vasoconstriction syndrome associated with stroke: three case reports].

    PubMed

    Ishi, Yukitomo; Sugiyama, Taku; Echizenya, Sumire; Yokoyama, Yuka; Asaoka, Katsuyuki; Itamoto, Koji

    2014-02-01

    Reversible cerebral vasoconstriction syndrome(RCVS)is characterized by severe headache and diffuse segmental constriction of cerebral arteries that resolves spontaneously within a few months. Although manifestations of stroke are not included in diagnostic criteria of RCVS, it is known that some cases may be associated with stroke, including intracerebral hemorrhage, subarachnoid hemorrhage, or cerebral infarction. We present three cases of RCVS associated with various types of stroke, and then review the literature. Case 1:A 49-year-old woman presented with a headache followed by left hemiparesis and dysarthria. One month before the onset, she was transfused for severe anemia caused by uterus myoma. CT images revealed intracerebral hemorrhages in the right putamen and right occipital lobe. Angiography revealed multiple segmental constrictions of the cerebral arteries. One month after the onset, these vasoconstrictions improved spontaneously. Case 2:A postpartum 38-year-old woman who had a history of migraine presented with thunderclap headache. Imaging revealed a focal subarachnoid hemorrhage in the right postcentral sulcus and segmental vasoconstriction of the right middle cerebral artery. One week after the onset, this vasoconstriction improved spontaneously. Case 3:A 32-year-old woman who had a history of migraine presented with headache followed by left homonymous hemianopsia. Imaging revealed a cerebral infarction of the right occipital lobe and multiple constrictions of the right posterior cerebral artery. These vasoconstrictions gradually improved spontaneously.

  20. Reversible cerebral vasoconstriction syndrome at the emergency department

    PubMed Central

    Kim, Taerim; Ahn, Shin; Sohn, Chang Hwan; Seo, Dong Woo; Kim, Won Young

    2015-01-01

    Objective Reversible cerebral vasoconstriction syndrome (RCVS) is an underestimated cause of thunderclap headache that shares many characteristics with subarachnoid hemorrhage (SAH). This fact makes the two easily confused by emergency physicians. This study evaluated the clinical manifestations, radiological features, and outcomes of patients with RCVS. Methods The electronic medical records of 18 patients meeting the diagnostic criteria of RCVS at our emergency department between January 2013 and December 2014 were retrospectively reviewed. Results The mean patient age was 50.7 years, and 80% were women. Patients with RCVS encountered physicians 4.7 times before receiving an accurate diagnosis. The mean duration of symptoms until diagnosis was 9.3 days. All but one patient experienced severe headache of 8 to 10 on a numerical rating scale. A total of 44% of patients had nausea, and 66% of patients experienced worsening of the headache while gagging, leaning forward, defecating, urinating, or having sexual intercourse. The most frequently affected vessels were the middle cerebral arteries, which demonstrated a characteristic diffuse “string of beads” appearance. Four cases were complicated by SAH. Conclusion Patients with RCVS have a unique set of clinical and imaging features. Emergency physicians should have a high index of suspicion for this clinical entity to improve its rate of detection in patients with thunderclap headache when there is no evidence of aneurysmal SAH. PMID:27752599

  1. Walking unsteadily: a case of acute cerebellar ataxia.

    PubMed

    Simonetta, Federico; Christou, Fotini; Vandoni, Riccardo E; Nierle, Thomas

    2013-01-01

    Acute cerebellar ataxia is an infrequent neurological syndrome in adults especially if complicated by additional neurological deficits. We report the case of a 69-year-old woman who presented with sudden onset of left facial droop, dizziness, slurred speech and impaired balance. Her medical history included paroxysmal atrial fibrillation and a sigmoid diverticular abscess treated with ciprofloxacin and metronidazole. Cranial computed tomographic angiography and MRI showed no signs of acute ischaemia or haemorrhage but demonstrated symmetrically distributed lesions in the cerebellar dentate nuclei. A diagnosis of metronidazole-induced encephalopathy was suspected. Metronidazole was stopped and the patient completely recovered. Metronidazole is a commonly prescribed medication. Clinicians should be aware of the clinical and radiological presentation of metronidazole-induced encephalopathy so that this serious but completely reversible condition can be promptly diagnosed. PMID:23283615

  2. 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.

  3. Early postnatal ataxia and abnormal cerebellar development in mice lacking Xeroderma pigmentosum Group A and Cockayne syndrome Group B DNA repair genes.

    PubMed

    Murai, M; Enokido, Y; Inamura, N; Yoshino, M; Nakatsu, Y; van der Horst, G T; Hoeijmakers, J H; Tanaka, K; Hatanaka, H

    2001-11-01

    Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are rare autosomal recessive disorders associated with a defect in the nucleotide excision repair (NER) pathway required for the removal of DNA damage induced by UV light and distorting chemical adducts. Although progressive neurological dysfunction is one of the hallmarks of CS and of some groups of XP patients, the causative mechanisms are largely unknown. Here we show that mice lacking both the XPA (XP-group A) and CSB (CS-group B) genes in contrast to the single mutants display severe growth retardation, ataxia, and motor dysfunction during early postnatal development. Their cerebella are hypoplastic and showed impaired foliation and stunted Purkinje cell dendrites. Reduced neurogenesis and increased apoptotic cell death occur in the cerebellar external granular layer. These findings suggest that XPA and CSB have additive roles in the mouse nervous system and support a crucial role for these genes in normal brain development. PMID:11687625

  4. Acute cerebellar ataxia

    MedlinePlus

    Cerebellar ataxia; Ataxia - acute cerebellar; Cerebellitis; Post-varicella acute cerebellar ataxia; PVACA ... virus. Viral infections that may cause this include chickenpox , Coxsackie disease, Epstein-Barr, and echovirus . Other causes ...

  5. Normalization of reverse redistribution of thallium-201 with procainamide pretreatment in Wolff-Parkinson-White syndrome

    SciTech Connect

    Nii, T.; Nakashima, Y.; Nomoto, J.; Hiroki, T.; Ohshima, F.; Arakawa, K. )

    1991-03-01

    Stress thallium-201 myocardial perfusion imaging was performed in a patient with Wolff-Parkinson-White syndrome. Reverse redistribution phenomenon was observed in the absence of coronary artery disease. This seems to be the first report of normalization of this phenomenon in association with reversion of accessory pathway to normal atrioventricular conduction after pretreatment with procainamide.

  6. Posterior reversible encephalopathy syndrome (PRES) as a complication of Guillain-Barre' syndrome (GBS).

    PubMed

    Nabi, Sumaira; Rajput, Haris Majid; Badshah, Mazhar; Ahmed, Shahzad

    2016-01-01

    A 17-year-old Pakistani female patient presented with acute onset flaccid quadriparesis with nerve conduction studies showing demyelinating polyneuropathy consistent with Guillain-Barre' syndrome. She was treated with 4 plasmapheresis sessions. She developed raised blood pressure, headache, visual loss and generalised seizures on the 13th day of admission. MRI of the brain on contrast showed findings of altered signals low on T1-weighted image, high on T2-weighted image and fluid-attenuated inversion recovery in the white matter of bilateral occipital, parietal and right frontal lobe consistent with posterior reversible encephalopathy syndrome. The patient was administered antiepileptic and antihypertensive drugs to control seizures and blood pressure. She was discharged in a stable state. On follow-up her visual loss had recovered completely and she had regained full motor strength in all four extremities after 6 weeks. Fresh MRI of the brain revealed complete resolution of lesions. Antihypertensive and antiepileptic medication was discontinued. She is independent in all her daily activities. PMID:27489061

  7. Blood transfusion in sickle cell disease leading to posterior reversible encephalopathy syndrome (PRES).

    PubMed

    Raj, Shashi; Killinger, James; Overby, Philip

    2013-10-01

    Children with sickle cell disease have a very high risk of lifelong neurologic morbidity and mortality. Cerebrovascular accidents are a known complication in children with sickle cell disease. Posterior reversible encephalopathy syndrome is a constellation of acute neurologic findings increasingly recognized in pediatric critical care population with evidence of vasogenic edema on brain imaging possibly due to cerebral vascular endothelial cell dysfunction. This report, for the first time, describes a young adult with sickle cell disease who developed posterior reversible encephalopathy syndrome following blood transfusion. PMID:22899796

  8. Acute headache at emergency department: reversible cerebral vasoconstriction syndrome complicated by subarachnoid haemorrhage and cerebral infarction.

    PubMed

    Yger, M; Zavanone, C; Abdennour, L; Koubaa, W; Clarençon, F; Dupont, S; Samson, Y

    2015-01-01

    Introduction. Reversible cerebral vasoconstriction syndrome is becoming widely accepted as a rare cause of both ischemic and haemorrhagic stroke and should be evocated in case of thunderclap headaches associated with stroke. We present the case of a patient with ischemic stroke associated with cortical subarachnoid haemorrhage (cSAH) and reversible diffuse arteries narrowing, leading to the diagnosis of reversible vasoconstriction syndrome. Case Report. A 48-year-old woman came to the emergency department because of an unusual thunderclap headache. The computed tomography of the brain completed by CT-angiography was unremarkable. Eleven days later, she was readmitted because of a left hemianopsia. One day after her admission, she developed a sudden left hemiparesis. The brain MRI showed ischemic lesions in the right frontal and occipital lobe and diffuse cSAH. The angiography showed vasoconstriction of the right anterior cerebral artery and stenosis of both middle cerebral arteries. Nimodipine treatment was initiated and vasoconstriction completely regressed on day 16 after the first headache. Conclusion. Our case shows a severe reversible cerebral vasoconstriction syndrome where both haemorrhagic and ischemic complications were present at the same time. The history we reported shows that reversible cerebral vasoconstriction syndrome is still underrecognized, in particular in general emergency departments.

  9. [The course of early neurological rehabilitation in a patient with severe posterior reversible encephalopathy syndrome].

    PubMed

    Gdynia, H J; Ampatzis, G; Diaconescu, A; Nowak, D A; Dabitz, R; Pfefferkorn, T

    2014-12-01

    Posterior reversible encephalopathy syndrome (PRES) is widely held to be a benign and potentially reversible disease. However, severe cases have been described in the literature. Data on the long-term outcome of these severe cases are scarce. Furthermore, there are no data focusing on potential benefits of neurological early rehabilitation in these patients. Here we present the clinical picture, neuroimaging features, rehabilitative course and long-term outcome of a patient with severe PRES who underwent early neurological rehabilitation.

  10. Aggressive TAFRO syndrome with reversible cardiomyopathy successfully treated with combination chemotherapy.

    PubMed

    Yasuda, Shunichiro; Tanaka, Keisuke; Ichikawa, Ayako; Watanabe, Ken; Uchida, Emi; Yamamoto, Masahide; Yamamoto, Kouhei; Mizuchi, Daisuke; Miura, Osamu; Fukuda, Tetsuya

    2016-10-01

    TAFRO (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly) syndrome is an atypical manifestation of Castleman's disease. However, the mechanism underlying this very rare syndrome remains unknown, and there is no established standard treatment. Here we report cases of two young females with TAFRO syndrome who showed similar clinical courses. Both cases showed severe anasarca, ascites, and thrombocytopenia. Although high-dose steroids were ineffective, combination chemotherapy showed remarkable effects. However, both patients developed severe but reversible heart failure after CHOP therapy owing to diffuse cardiomyopathy, which was presumably associated with TAFRO syndrome. Therefore, although combination chemotherapy may be very effective in the treatment of TAFRO syndrome, careful observation for cardiomyopathy development is needed, particularly when using adriamycin-containing regimens.

  11. 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

  12. Cerebellar disorders: clinical/radiologic findings and modern imaging tools.

    PubMed

    Manto, Mario; Habas, Christophe

    2016-01-01

    Cerebellar disorders, also called cerebellar ataxias, comprise a large group of sporadic and genetic diseases. Their core clinical features include impaired control of coordination and gait, as well as cognitive/behavioral deficits usually not detectable by a standard neurologic examination and therefore often overlooked. Two forms of cognitive/behavioral syndromes are now well identified: (1) the cerebellar cognitive affective syndrome, which combines an impairment of executive functions, including planning and working memory, deficits in visuospatial skills, linguistic deficiencies such as agrammatism, and inappropriate behavior; and (2) the posterior fossa syndrome, a very acute form of cerebellar cognitive affective syndrome occurring essentially in children. Sporadic ataxias include stroke, toxic causes, immune ataxias, infectious/parainfectious ataxias, traumatic causes, neoplasias and paraneoplastic syndromes, endocrine disorders affecting the cerebellum, and the so-called "degenerative ataxias" (multiple system atrophy, and sporadic adult-onset ataxias). Genetic ataxias include mainly four groups of disorders: autosomal-recessive cerebellar ataxias, autosomal-dominant ataxias (spinocerebellar ataxias and episodic ataxias), mitochondrial disorders, and X-linked ataxias. In addition to biochemical studies and genetic tests, brain imaging techniques are a cornerstone for the diagnosis, clinicoanatomic correlations, and follow-up of cerebellar ataxias. Modern radiologic tools to assess cerebellar ataxias include: functional imaging studies, magnetic resonance spectroscopy, volumetric studies, and tractography. These complementary methods provide a multimodal appreciation of the whole long-range cerebellar network functioning, and allow the extraction of potential biomarkers for prognosis and rating level of recovery after treatment. PMID:27432679

  13. 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

    2015-12-01

    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.

  14. 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

  15. 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

    2015-12-01

    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

  16. Increased excitability and altered action potential waveform in cerebellar granule neurons of the Ts65Dn mouse model of Down syndrome.

    PubMed

    Usowicz, Maria M; Garden, Claire L P

    2012-07-17

    Down syndrome (DS) is characterized by intellectual disability and impaired motor control. Lack of coordinated movement, poor balance, and unclear speech imply dysfunction of the cerebellum, which is known to be reduced in volume in DS. The principal cause of the smaller cerebellum is a diminished number of granule cells (GCs). These neurons form the 'input layer' of the cerebellar cortex, where sensorimotor information carried by incoming mossy fibers is transformed before it is conveyed to Purkinje cells and inhibitory interneurons. However, it is not known how processing of this information is affected in the hypogranular cerebellum that characterizes DS. Here we explore the possibility that the electrical properties of the surviving GCs are changed. We find that in the Ts65Dn mouse model of DS, GCs have a higher input resistance at voltages approaching the threshold for firing, which causes them to be more excitable. In addition, they fire narrower and larger amplitude action potentials. These subtly modified electrical properties may result in atypical transfer of information at the input layer of the cerebellum.

  17. The syndrome of abuse dwarfism (psychosocial dwarfism or reversible hyposomatotropism).

    PubMed

    Money, J

    1977-05-01

    In abuse dwarfism the behavioral signs include some or all of the following: (1) a history of unusual eating and drinking behavior, reversible on change of domicile, such as eating from a garbage can and drinking from a toilet bowl, stealing food, alleged picky eating and rejecting food at the table, polydipsia and polyphagia, possibly alternating with vomiting and possibly also with self-starvation; (2) a history of such behavioral symptoms as enuresis, encopresis, social apathy or inertia, defiant aggressiveness, sudden tantrums, crying spasms, insomnia, eccentric sleeping and waking schedule, pain agnosia, and self-injury, all occurring only in the growth-retarding environment; (3) retarded motor development, with improvement on removal of the child from the domiclle of abuse; (4) retarded intellectual growht, reversible on change of domicile by as much as 30 to 50 IQ points; and (5) a history of pathologic family relationships, including unusual cruelty and neglect, either somatic or psychic or both. PMID:857651

  18. 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…

  19. 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

  20. Reversible man-in-the-barrel syndrome in myasthenia gravis

    PubMed Central

    Shah, Poornima A; Wadia, Pettarusp Murzban

    2016-01-01

    Man-in-the-barrel syndrome (MBS) is an uncommon presentation due to bilateral, predominantly proximal muscle weakness that has not been described to be associated with myasthenia gravis. We describe a case of myasthenia gravis presenting as MBS. Additionally, he had significant wasting of the deltoids bilaterally with fibrillations on electromyography (EMG) at rest and brief duration (3-6 ms) bi/triphasic motor unit potentials (MUPs) on submaximal effort apart from a decremental response on repetitive nerve stimulation (RNS) at 2 Hz. While electrophysiology is an important tool in the diagnosis of myasthenia gravis, pathological EMG patterns do not exclude the diagnosis of myasthenia gravis. PMID:27011638

  1. [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.

  2. Posterior reversible encephalopathy syndrome: the importance of early diagnosis.

    PubMed

    Teotónio, Rute; Marmoto, Dina; Januário, Cristina; Bento, Conceição

    2012-09-17

    A 14-year-old boy was submitted to cardiac transplant due to a dilated cardiomyopathy. On the fourth day of immunosuppression (corticosteroids, mycophenolate mofetil and tacrolimus), he developed right focal seizures and drowsiness. Blood pressure was in the normal range and laboratory findings in cerebral spinal fluid and blood were unremarkable, with drugs in non-toxic levels. The EEG showed a slow background rhythm more pronounced on the right and a seizure onset in the right occipital region. MRI revealed a diffuse hyperintense subcortical white-matter lesion on fluid attenuated inversion recovery, with lesser involvement of left temporal-occipital region. There was no enhancement with gadolinium and MRI diffusion-weighted imaging was consistent with vasogenic oedema. Tacrolimus was stopped with regression of MRI abnormalities and clinical recovery. Posterior reversible encephalopathy associated with tacrolimus is a rare but potentially serious complication of solid organ transplants. A prompt diagnosis and correct treatment is essential to avoid irreversible brain damage.

  3. Immune activation during cerebellar dysfunction following Plasmodium falciparum malaria.

    PubMed

    de Silva, H J; Hoang, P; Dalton, H; de Silva, N R; Jewell, D P; Peiris, J B

    1992-01-01

    Evidence for immune activation was investigated in 12 patients with a rare syndrome of self-limiting, delayed onset cerebellar dysfunction following an attack of falciparum malaria which occurred 18-26 d previously. Concentrations of tumour necrosis factor, interleukin 6 and interleukin 2 were all significantly higher in serum samples of patients during cerebellar ataxia than in recovery sera and in the sera of 8 patients who did not develop delayed cerebellar dysfunction following an attack of falciparum malaria. Cytokine concentrations in the cerebrospinal fluid were also significantly higher in ataxic patients than in controls. These findings suggest that immunological mechanisms may play a role in delayed cerebellar dysfunction following falciparum malaria.

  4. Cerebellar disorders in childhood: cognitive problems.

    PubMed

    Steinlin, Maja

    2008-01-01

    Over the last decade, increasing evidence of cognitive functions of the cerebellum during development and learning processes could be ascertained. Posterior fossa malformations such as cerebellar hypoplasia or Joubert syndrome are known to be related to developmental problems in a marked to moderate extent. More detailed analyses reveal special deficits in attention, processing speed, visuospatial functions, and language. A study about Dandy Walker syndrome states a relationship of abnormalities in vermis lobulation with developmental problems. Further lobulation or volume abnormalities of the cerebellum and/or vermis can be detected in disorders as fragile X syndrome, Downs's syndrome, William's syndrome, and autism. Neuropsychological studies reveal a relation of dyslexia and attention deficit disorder with cerebellar functions. These functional studies are supported by structural abnormalities in neuroimaging in these disorders. Acquired cerebellar or vermis atrophy was found in groups of children with developmental problems such as prenatal alcohol exposure or extreme prematurity. Also, focal lesions during childhood or adolescence such as cerebellar tumor or stroke are related with neuropsychological abnormalities, which are most pronounced in visuospatial, language, and memory functions. In addition, cerebellar atrophy was shown to be a bad prognostic factor considering cognitive outcome in children after brain trauma and leukemia. In ataxia teleangiectasia, a neurodegenerative disorder affecting primarily the cerebellar cortex, a reduced verbal intelligence quotient and problems of judgment of duration are a hint of the importance of the cerebellum in cognition. In conclusion, the cerebellum seems to play an important role in many higher cognitive functions, especially in learning. There is a suggestion that the earlier the incorrect influence, the more pronounced the problems.

  5. [Role of twin reversed arterial perfusion syndrome in the development of fetus acardius].

    PubMed

    Nizyaeva, N V; Kostyukov, K V; Gladkova, K A; Kulikova, G V; Shchegolev, A I

    2016-01-01

    Monochorionic multiple pregnancy has a higher risk for obstetric complications, including those due to the development of twin-to-twin transfusion syndrome and reversed arterial perfusion syndrome (TRAP sequence). The latter occurs in 0.1% of all monochorionic pregnancies. The basis for TRAP sequence is a relationship between arterial and venous anastomoses from the appropriate placental areas, causing a recipient fetus to develop at the expense of a donor fetus. The presence of abnormal anastomoses is considered to be a main cause of acardia. The prognosis for a donor fetus is also unfavorable: the mortality rates in the absence of intrauterine correction are as high as 55%. PMID:27600783

  6. 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

  7. Reversible encephalopathy associated with cholesterol embolism syndrome: magnetic resonance imaging and pathological findings

    PubMed Central

    Andreux, F; Marro, B; Khoury, N EI; Seilhean, D; Alamowitch, S

    2007-01-01

    We describe a patient found to have acute diffuse and reversible encephalopathy on magnetic resonance imaging (MRI) associated with cholesterol emboli syndrome (CES). The initial MRI showed extensive white matter, basal ganglia and cortical damage without evidence of brain infarction. Dramatic clinical and MRI improvement was observed with corticosteroids. Pathologically, cholesterol crystal emboli were found in the lumen of skin and brain arteries and were associated with varying degrees of inflammation of the arteriole wall. This case suggests that CES may be responsible for extensive, acute and reversible encephalopathy underlined by an inflammation of brain arteries. PMID:17229746

  8. 46,XY female sex reversal syndrome with bilateral gonadoblastoma and dysgerminoma

    PubMed Central

    DU, XUE; ZHANG, XUHONG; LI, YONGMEI; HAN, YUKUN

    2014-01-01

    Sex reversal syndrome is a rare congenital condition of complete or disordered gonadal development leading to discordance between the genetic, gonadal and phenotypic sexes, including 46,XX and 46,XY. The gonadoblastoma on the Y-chromosome (GBY) region is associated with an increased risk of developing type II germ cell tumors/cancer. The present study reports a unique case of a phenotypically normal female (age 17 years), presenting with primary amenorrhea and later diagnosed with 46,XY female sex reversal syndrome. Following bilateral gonadectomy, bilateral gonadoblastoma and dysgerminoma were diagnosed. Thus, estrogen replacement therapy was administered periodically to promote the development of secondary sexual characteristics and menstruation, and to prevent osteoporosis. A four year follow-up showed no tumor recurrence and a regular menstrual cycle in this patient. PMID:25187804

  9. Reverse or inverted apical ballooning in a case of refeeding syndrome.

    PubMed

    Robles, Pablo; Monedero, Isabel; Rubio, Amador; Botas, Javier

    2015-06-26

    Takotsubo cardiomyopathy is characterized by the development of transient left ventricular regional wall motion abnormalities, in the absence of significant coronary artery obstruction. This syndrome usually occurs in women and is frequently associated with an intense emotional or physical stress. It usually involves apical segments, but in the recent years atypical forms have been described. Inverted or reverse Takotsubo is a variant in which the basal and midventricular segments are hypokinetic, sparing contractile function of the apex. In this report we describe the case of a 54-year-old woman, with chronic malnutrition, initially admitted because of hypoglycemia and severe electrolyte disturbance due to a refeeding syndrome. Within the next hours she experienced acute cardiac symptoms and developed heart failure with low cardiac output. Electrocardiogram (ECG), elevation of troponin and echocardiographic findings were consistent with inverted Takotsubo cardiomyopathy. To the best of our knowledge, this is the first incidence reported of inverted Takotsubo triggered by refeeding syndrome.

  10. Reverse or inverted apical ballooning in a case of refeeding syndrome

    PubMed Central

    Robles, Pablo; Monedero, Isabel; Rubio, Amador; Botas, Javier

    2015-01-01

    Takotsubo cardiomyopathy is characterized by the development of transient left ventricular regional wall motion abnormalities, in the absence of significant coronary artery obstruction. This syndrome usually occurs in women and is frequently associated with an intense emotional or physical stress. It usually involves apical segments, but in the recent years atypical forms have been described. Inverted or reverse Takotsubo is a variant in which the basal and midventricular segments are hypokinetic, sparing contractile function of the apex. In this report we describe the case of a 54-year-old woman, with chronic malnutrition, initially admitted because of hypoglycemia and severe electrolyte disturbance due to a refeeding syndrome. Within the next hours she experienced acute cardiac symptoms and developed heart failure with low cardiac output. Electrocardiogram (ECG), elevation of troponin and echocardiographic findings were consistent with inverted Takotsubo cardiomyopathy. To the best of our knowledge, this is the first incidence reported of inverted Takotsubo triggered by refeeding syndrome. PMID:26131342

  11. 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

  12. 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. PMID:23500598

  13. Reversible brain atrophy and cognitive impairment in an adolescent Japanese patient with primary adrenal Cushing's syndrome.

    PubMed

    Ohara, Nobumasa; Suzuki, Hiroshi; Suzuki, Akiko; Kaneko, Masanori; Ishizawa, Masahiro; Furukawa, Kazuo; Abe, Takahiro; Matsubayashi, Yasuhiro; Yamada, Takaho; Hanyu, Osamu; Shimohata, Takayoshi; Sone, Hirohito

    2014-01-01

    Endogenous Cushing's syndrome is an endocrine disease resulting from chronic exposure to excessive glucocorticoids produced in the adrenal cortex. Although the ultimate outcome remains uncertain, functional and morphological brain changes are not uncommon in patients with this syndrome, and generally persist even after resolution of hypercortisolemia. We present an adolescent patient with Cushing's syndrome who exhibited cognitive impairment with brain atrophy. A 19-year-old Japanese male visited a local hospital following 5 days of behavioral abnormalities, such as money wasting or nighttime wandering. He had hypertension and a 1-year history of a rounded face. Magnetic resonance imaging (MRI) revealed apparently diffuse brain atrophy. Because of high random plasma cortisol levels (28.7 μg/dL) at 10 AM, he was referred to our hospital in August 2011. Endocrinological testing showed adrenocorticotropic hormone-independent hypercortisolemia, and abdominal computed tomography demonstrated a 2.7 cm tumor in the left adrenal gland. The patient underwent left adrenalectomy in September 2011, and the diagnosis of cortisol-secreting adenoma was confirmed histologically. His hypertension and Cushingoid features regressed. Behavioral abnormalities were no longer observed, and he was classified as cured of his cognitive disturbance caused by Cushing's syndrome in February 2012. MRI performed 8 months after surgery revealed reversal of brain atrophy, and his subsequent course has been uneventful. In summary, the young age at onset and the short duration of Cushing's syndrome probably contributed to the rapid recovery of both cognitive dysfunction and brain atrophy in our patient. Cushing's syndrome should be considered as a possible etiological factor in patients with cognitive impairment and brain atrophy that is atypical for their age.

  14. 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

  15. Iatrogenic Coagulopathy and the Development of Posterior Reversible Encephalopathy Syndrome after L-asparaginase Chemotherapy

    PubMed Central

    Rota, Eugenia; Vallisa, Daniele; Morelli, Nicola; Scagnelli, Paola

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological syndrome mostly related to hypertension, eclampsia, renal failure, or to chemotherapy and/or immunosuppressive drugs. Although the PRES pathophysiology is multifactorial, hypertension and endothelial dysfunction are hypothesized to be the pivotal factors. Here we report a case of PRES in an adult patient after chemotherapy (Escherichia coli L-asparaginase [L-ASP], daunorubicin, vincristine, and intrathecal methotrexate) for acute lymphoblastic leukemia. The development of the PRES was strictly associated with an iatrogenic coagulopathy induced by L-ASP, which inhibits the biosynthesis of hepatic coagulation factors. The nadir of platelet count, antithrombin III (ATIII) and fibrinogen curve was coincident with the onset of the PRES neurological picture; subsequently, the normalization of the ATIII and fibrinogen levels seemed to parallel the good clinical evolution. This case seems to provide new insights into the PRES pathophysiological mechanisms. PMID:27014503

  16. 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.

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

    PubMed

    Ninomiya, S; Narahara, K; Tsuji, K; Yokoyama, Y; Ito, S; Seino, Y

    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-->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. This study suggests that acampomelic CMPD with SR represents a variant of the CMPS1/SRA1 locus disorder. We emphasize the likelihood that CMPS may be a contiguous gene syndrome. PMID:7747782

  18. 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.

  19. 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

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

    PubMed

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

    2016-08-01

    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:27483175

  1. Posterior reversible encephalopathy syndrome in a hypertensive patient with renal failure.

    PubMed

    Aatif, T; El Farouki, M R; Benyahia, M

    2016-03-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinical and neuroimaging entity characterized by headache, visual field deficits, changes in mentation and seizures, and by typical neuro-imaging features such as areas of sub-cortical edema, occasionally cortical, involving predominantly the occipital and parietal lobes of both hemispheres. Hypertension, uremia, immunosuppressive drugs neurotoxicity, preeclampsia or eclampsia, renal disease, and sepsis are the most common etiologies of PRES. Less common, it has been described in the setting of autoimmune disease. We report a case of PRES which was associated with hypertensive crisis in a patient with renal failure. Antihypertensive therapy and hemodialysis resulted in complete recovery.

  2. Reversible posterior encephalopathy syndrome associated with late onset postpartum eclampsia: A case report

    PubMed Central

    Bo, Qi-Yu; Zhao, Xiu-He; Yang, Xue; Wang, Sheng-Jun

    2016-01-01

    Late onset postpartum eclampsia (LPE) is defined by its onset at >48 h after delivery. Reversible posterior encephalopathy syndrome (RPES) associated with LPE is uncommon, with the majority of RPES cases having a late postpartum onset within 4 weeks after childbirth. The present study reported the case of a 15-year old female presenting with convulsions that began 5 weeks after delivery. A magnetic resonance imaging scan of the brain revealed multiple lesions in the cortex, subcortical region and deep white matter of the bilateral cerebellum, and occipital, frontal and parietal lobes. The clinical manifestations and radiological abnormalities were readily resolved subsequent to antihypertension and anticonvulsion treatment. In conclusion, the present rare case indicates that LPE should be considered as a potential diagnosis even at 4 weeks after delivery. Furthermore, clinicians should familiarize with the reversible radioimaging features of RPES, since early recognition and adequate treatment are important to the outcome of patients. PMID:27602098

  3. Reversible posterior encephalopathy syndrome associated with late onset postpartum eclampsia: A case report

    PubMed Central

    Bo, Qi-Yu; Zhao, Xiu-He; Yang, Xue; Wang, Sheng-Jun

    2016-01-01

    Late onset postpartum eclampsia (LPE) is defined by its onset at >48 h after delivery. Reversible posterior encephalopathy syndrome (RPES) associated with LPE is uncommon, with the majority of RPES cases having a late postpartum onset within 4 weeks after childbirth. The present study reported the case of a 15-year old female presenting with convulsions that began 5 weeks after delivery. A magnetic resonance imaging scan of the brain revealed multiple lesions in the cortex, subcortical region and deep white matter of the bilateral cerebellum, and occipital, frontal and parietal lobes. The clinical manifestations and radiological abnormalities were readily resolved subsequent to antihypertension and anticonvulsion treatment. In conclusion, the present rare case indicates that LPE should be considered as a potential diagnosis even at 4 weeks after delivery. Furthermore, clinicians should familiarize with the reversible radioimaging features of RPES, since early recognition and adequate treatment are important to the outcome of patients.

  4. 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.

  5. 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…

  6. [A case of posterior reversible encephalopathy syndrome associated with Takayasu's arteritis].

    PubMed

    Wakida, Kenji; Morita, Hiroyuki; Sakurai, Takeo; Nishida, Hiroshi

    2016-01-01

    A 75-year-old woman presented with a 4-month history of repetitive loss of consciousness, dizziness, and ear fullness. Fluid attenuation inversion recovery magnetic resonance imaging showed high-intensity areas in the right occipital lobe, both frontal lobes, and parietal lobes, and the patient was therefore admitted to our department for further examination. Neurologic findings included a positive Barré sign (right upper extremity), impaired tandem gait, and positive left-sided Babinski reflex. The patient was diagnosed with Takayasu's arteritis owing to a difference in blood pressure between the left and right upper extremity, weakened pulse in the left upper extremity, as well as thickened arterial wall, and delayed enhancement on a contrast-enhanced computed tomography image. The head magnetic resonance imaging findings disappeared within 4 months and the patient was diagnosed with posterior reversible encephalopathy syndrome. Posterior reversible encephalopathy syndrome associated with elderly female Takayasu's arteritis is rare. ; the present case therefore offers valuable information. PMID:26912227

  7. Posterior reversible encephalopathy syndrome following hemodynamic treatment of aneurysmal subarachnoid hemorrhage-induced vasospasm.

    PubMed

    Awori, Jonathan; Rajajee, Venkatakrishna; Gemmete, Joseph J; Chaudhary, Neeraj; Thompson, B Gregory; Pandey, Aditya S

    2016-04-01

    Posterior reversible encephalopathy syndrome (PRES) is an uncommon but significant complication of hemodynamic therapy after aneurysmal subarachnoid hemorrhage (aSAH)-induced vasospasm. We performed a PubMed literature search for the period January 1999 to January 2015 using the search terms "posterior reversible encephalopathy syndrome", "subarachnoid hemorrhage", "vasospasm", and "hypertensive encephalopathy", and identified nine cases of PRES after aSAH-induced vasospasm in the literature. We also present a 63-year-old man with aSAH complicated by vasospasm treated with hemodynamic augmentation who subsequently developed PRES. Imaging following development of PRES symptoms shows vasogenic edema in the white matter of the parietal and occipital lobes. Age, sex, history of hypertension, and baseline blood pressure were variable among patients in the literature review. In all cases, patients improved both from a radiological and clinical perspective following blood pressure reduction. To summarize, PRES is a rare complication of hemodynamic therapy for vasospasm following aSAH. The literature at the time of writing demonstrates no common pattern with regard to patient demographics, medical history, or mode of treatment for symptomatic vasospasm. Given its sporadic and unpredictable nature, considering PRES in the differential diagnosis is important when addressing neurological decline following hemodynamic treatment of vasospasm related to aSAH. PMID:26755456

  8. Diagnosing RCVS Without the CV: The Evolution of Reversible Cerebral Vasoconstriction Syndrome.

    PubMed

    Jacoby, Nuri; Kaunzner, Ulrike; Dinkin, Marc; Safdieh, Joseph

    2016-07-01

    This is a case of a 52-year-old man with a past medical history of 2 episodes of coital thunderclap headaches as well as recent cocaine, marijuana, and pseudoephedrine use, who presented with sudden, sharp, posterior headache associated with photophobia and phonophobia. His initial magnetic resonance imaging (MRI) of the brain, magnetic resonance angiography (MRA) of the head, and magnetic resonance venography (MRV) of the head were all normal as well as a normal lumbar puncture. Given the multiple risk factors for reversible cerebral vasoconstriction syndrome (RCVS), the patient was treated for suspected RCVS, despite the normal imaging. Repeat MRI brain 3 days after hospital admission demonstrated confluent white matter T2 hyperintensities most prominent in the occipital lobes, typical of posterior reversible encephalopathy syndrome (PRES). Repeat MRA of the head 1 day after discharge and 4 days after the abnormal MRI brain showed multisegment narrowing of multiple arteries. This case demonstrates that RCVS may present with PRES on MRI brain and also exemplifies the need to treat suspected RCVS even if imaging is normal, as abnormalities in both the MRI and the MRA may be delayed. PMID:27366300

  9. Reversible cerebral vasoconstriction syndrome as a cause of thunderclap headache: a retrospective case series study.

    PubMed

    Papathanasiou, Athanasios; Zouvelou, Vasiliki; Breen, David P; Phillips, Timothy J; Misbahuddin, Anjum; Chawda, Sanjiv; de Silva, Rajith

    2015-06-01

    Thunderclap headache is a common emergency department presentation. Although subarachnoid hemorrhage (SAH) should be the first diagnosis to exclude, reversible cerebral vasoconstriction syndrome (RCVS) is an important alternative cause, which may be commoner than appreciated. Reversible cerebral vasoconstriction syndrome is characterized by multifocal narrowing of cerebral arteries, typically manifested by acute, severe headache with or without neurologic deficits. To compare and discuss the clinical and radiologic characteristics of patients with RCVS. We report 4 cases of RCVS, presenting at a single unit in 1 year. All presented with thunderclap headache, whereas half of them had additional neurologic symptoms such as right homonymous hemianopia, right-sided weakness, and slurred speech. Brain computed tomography was normal in 2 of our patients, but subsequent cerebrospinal fluid analysis revealed xanthochromia consistent with SAH. The remaining 2 patients demonstrated intracerebral hemorrhage on computed tomography. All of our patients underwent digital subtraction angiography that showed segmental narrowing and dilatation of one or more cerebral arteries without any signs of aneurysm. Repeat digital subtraction angiography after 3 months was entirely normal prompting the diagnosis of RCVS. Thunderclap headache requires urgent workup to identify the underlying cause. Although SAH is the most important diagnosis to exclude in the first instance, emergency physicians should be aware of other causes and how they present, such as RCVS. Early recognition of this condition is important in order to remove precipitants, avoid unnecessary investigations, and inform patients about their prognosis. PMID:25583268

  10. Cerebellar and Brainstem Malformations.

    PubMed

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

    2016-08-01

    The frequency and importance of the evaluation of the posterior fossa have increased significantly over the past 20 years owing to advances in neuroimaging. Conventional and advanced neuroimaging techniques allow detailed evaluation of the complex anatomic structures within the posterior fossa. A wide spectrum of cerebellar and brainstem malformations has been shown. Familiarity with the spectrum of cerebellar and brainstem malformations and their well-defined diagnostic criteria is crucial for optimal therapy, an accurate prognosis, and correct genetic counseling. This article discusses cerebellar and brainstem malformations, with emphasis on neuroimaging findings (including diagnostic criteria), neurologic presentation, systemic involvement, prognosis, and recurrence. PMID:27423798

  11. Reversible magnetic resonance imaging changes in a case of neuroleptic malignant syndrome.

    PubMed

    Jain, Rajendra Singh; Gupta, Pankaj Kumar; Gupta, Ishwar Dayal; Agrawal, Rakesh; Kumar, Sunil; Tejwani, Shankar

    2015-08-01

    Neuroleptic malignant syndrome (NMS) is a life-threatening neurologic emergency associated with the use of mainly typical antipsychotic drugs. It is characterized by fever, altered mental status, generalized rigidity, autonomic instability, myoclonus, raised creatine phosphokinase, rhabdomyolysis, and leukocytosis. Neuroimaging (brain computed tomography/magnetic resonance imaging [MRI]) is usually normal in most of the cases of NMS. Magnetic resonance imaging findings have not been well elucidated in NMS as yet. Very few cases have been reported worldwide. We herein, report a case of a 42-year-old patient of NMS, who presented to us with reversible changes in MRI brain. This case report highlights the possible MRI changes in NMS and their plausible mechanism. PMID:25769796

  12. Posterior reversible encephalopathy syndrome masquerading as progressive multifocal leukoencephalopathy in rituximab treated neuromyelitis optica.

    PubMed

    Berger, Joseph R; Neltner, Janna; Smith, Charles; Cambi, Franca

    2014-11-01

    Both progressive multifocal leukoencephalopathy (PML) and posterior reversible encephalopathy syndrome (PRES) have been reported as complications of rituximab therapy. These disorders may appear indistinguishable on magnetic resonance imaging (MRI). We report on a 42 year old woman with neuromyelitis optica (NMO) of 10 years duration who developed extensive white matter disease affecting chiefly both parietal lobes 6 months after her first and only dose of rituximab. The MRI findings suggested the diagnosis of PML, but her history was more consistent with PRES. Ultimately, a brain biopsy was performed which was consistent with the diagnosis of PRES. PRES and PML may have overlapping symptomatology and be indistinguishable on MRI. An approach to distinguishing between these two disorders is addressed.

  13. 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. PMID:24103665

  14. Subarachnoid hemorrhage due to ruptured intracranial aneurysm following posterior reversible encephalopathy syndrome

    PubMed Central

    Nanba, Takamasa; Kashimura, Hiroshi; Saura, Hiroaki; Takeda, Masaru

    2016-01-01

    Although posterior reversible encephalopathy syndrome (PRES) is rarely associated with subarachnoid hemorrhage, to our knowledge, rupture of a concomitant cerebral aneurysm following PRES has not been reported. We describe a patient with atypical PRES involving the brainstem, thalamus, and periventricular white matter without cortical or subcortical edema of the parietooccipital lobe on magnetic resonance imaging, with rupture of a concomitant cerebral aneurysm. Preexisting extremely high blood pressure may trigger atypical PRES, and failure to lower blood pressure may lead to a concomitant aneurysm rupture. In the future treatment of hypertensive urgency with a recurrence of symptoms and mean arterial blood pressure >150 mmHg, it is advisable to immediately hospitalize the patient for aggressive blood pressure management, especially if PRES is suspected based on clinical and radiological features. PMID:27365964

  15. 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.

  16. 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

  17. Posterior reversible encephalopathy syndrome in malignant hypertension secondary to focal segmental glomerulosclerosis.

    PubMed

    Abdullah, Hafez Mohammad Ammar; Ullah, Waqas; Ahmad, Ejaz; Anwer, Faiz

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a neurological condition that occurs secondary to a variety of causes like autoimmune diseases, uncontrolled hypertension and immunosuppressive agents. We report an unusual association of PRES and malignant hypertension secondary to focal segmental glomerulosclerosis in a young woman, presenting with sudden loss of vision and seizures. She had uncontrolled hypertension and a Glasgow Coma Scale of 6/15. Brain MRI revealed high signals in cortical and subcortical white matter and some involvement of the periventricular areas. She improved dramatically with antihypertensive and antiepileptic medications and was discharged home in a stable condition. It is important to have a high clinical suspicion for this uncommon condition in an appropriate clinical setting, because a timely intervention can prevent long-term complications. PMID:27535734

  18. Habit Reversal Therapy for Body-Focused Repetitive Behaviors in Williams Syndrome: A Case Study

    PubMed Central

    Klein-Tasman, Bonita P.

    2013-01-01

    Williams syndrome (WS) is genetic neurodevelopmental disorder with a well-characterized cognitive and behavioral phenotype. Research has consistently demonstrated high rates of psychopathology in this population; however, little research has examined the use of empirically-supported psychosocial interventions in those with WS. The current case study reports on the use of Habit Reversal Therapy (HRT) to treat multiple body-focused repetitive behaviors in a child with WS. Although HRT is a well-established cognitive-behavioral intervention for body-focused repetitive behaviors, it has been infrequently used in populations with developmental disabilities. An etiologically-informed approach was used to adapt HRT to fit the known behavioral and cognitive phenotype of WS. Results suggest that HRT may be beneficial for this population. Modified treatment elements are described and future research areas highlighted. PMID:24357918

  19. Cerebellar ataxia as presenting feature of hypothyroidism.

    PubMed

    Kotwal, Suman Kumar; Kotwal, Shalija; Gupta, Rohan; Singh, Jang Bhadur; Mahajan, Annil

    2016-04-01

    Symptoms and signs of the hypothyroidism vary in relation to the magnitude and acuteness of the thyroid hormone deficiency. The usual clinical features are constipation, fatigue, cold intolerance and weight gain. Rarely it can present with neurologic problems like reversible cerebellar ataxia, dementia, peripheral neuropathy, psychosis and coma. Hypothyroidism should be suspected in all cases of ataxia, as it is easily treatable. A 40 year-old male presented with the history facial puffiness, hoarseness of voice and gait-ataxia. Investigations revealed frank primary hypothyroidism. Anti-TPO antibody was positive. Thyroxine was started and patient improved completely within eight weeks. Hypothyroidism can present with ataxia as presenting feature. Hypothyroidism should be considered in all cases of cerebellar ataxia as it is a reversible cause of ataxia. PMID:26886095

  20. 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

  1. Reversible phenotype in a mouse model of Hutchinson-Gilford progeria syndrome.

    PubMed

    Sagelius, H; Rosengardten, Y; Schmidt, E; Sonnabend, C; Rozell, B; Eriksson, M

    2008-12-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare progeroid syndrome caused by mutations in the LMNA gene. Currently there is no treatment available for HGPS, but promising results from several studies using farnesyl transferase inhibitors (FTIs) on cells and animal models of HGPS have been published and a clinical trial using FTIs has been started in patients with HGPS. However, the published data from animal models treated with FTIs come from studies where the treatment was started before pronounced disease development. This study used an inducible transgenic animal model of HGPS with abnormalities of the skin and teeth. After phenotype development, the transgenic expression was turned off and a rapid improvement of the phenotype was noted, within 4 weeks of transgenic suppression. After 13 weeks, the skin was almost indistinguishable from wild-type skin. This study shows that in these tissues, expression of the progeria mutation does not cause irreversible damage and that reversal of disease phenotype is possible, which gives promise for a treatment for this disease.

  2. Posterior Reversible Encephalopathy Syndrome Complicating Traumatic Pancreatitis: A Pediatric Case Report.

    PubMed

    Sigurtà, Anna; Terzi, Valeria; Regna-Gladin, Caroline; Fumagalli, Roberto

    2016-05-01

    We are reporting a case of posterior reversible encephalopathy syndrome (PRES) developed in an unusual clinical scenario without the presence of the most described symptoms. PRES is a neurological and radiological syndrome described in many different clinical conditions. In children it has been mostly reported in association with hematological and renal disorders.Our patient was a 15 years old boy, admitted to our intensive care unit for pancreatitis after blunt abdominal trauma.During the stay in the intensive care unit, he underwent multiple abdominal surgical interventions for pancreatitis complications. He had a difficult management of analgesia and sedation, being often agitated with high arterial pressure, and he developed a bacterial peritonitis. After 29 days his neurological conditions abruptly worsened with neuroimaging findings consistent with PRES. His clinical conditions progressively improved after sedation and arterial pressure control.He was discharged at home with complete resolution of the neurological and imaging signs 2 months later.The pathophysiology of PRES is controversial and involves disordered autoregulation ascribable to hypertension and endothelial dysfunction. In this case both hypertension and endothelial activation, triggered by sepsis and pancreatitis, could represent the culprits of PRES onset. Even if there is no specific treatment for this condition, a diagnosis is mandatory to start antihypertensive and supportive treatment. We are therefore suggesting to consider PRES in the differential diagnosis of a neurological deterioration preceded by hypertension and/or septic state, even without other "typical" clinical features. PMID:27258506

  3. 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…

  4. 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

  5. Cerebellar learning mechanisms

    PubMed Central

    Freeman, John H.

    2014-01-01

    The mechanisms underlying cerebellar learning are reviewed with an emphasis on old arguments and new perspectives on eyeblink conditioning. Eyeblink conditioning has been used for decades a model system for elucidating cerebellar learning mechanisms. The standard model of the mechanisms underlying eyeblink conditioning is that there two synaptic plasticity processes within the cerebellum that are necessary for acquisition of the conditioned response: 1) long-term depression (LTD) at parallel fiber-Purkinje cell synapses and 2) long-term potentiation (LTP) at mossy fiber-interpositus nucleus synapses. Additional Purkinje cell plasticity mechanisms may also contribute to eyeblink conditioning including LTP, excitability, and entrainment of deep nucleus activity. Recent analyses of the sensory input pathways necessary for eyeblink conditioning indicate that the cerebellum regulates its inputs to facilitate learning and maintain plasticity. Cerebellar learning during eyeblink conditioning is therefore a dynamic interactive process which maximizes responding to significant stimuli and suppresses responding to irrelevant or redundant stimuli. PMID:25289586

  6. Unilateral cerebellar aplasia.

    PubMed

    Boltshauser, E; Steinlin, M; Martin, E; Deonna, T

    1996-02-01

    We describe three children with unilateral cerebellar aplasia (UCA). Deliveries at term and neonatal periods were uneventful. Pregnancy was normal in one and complicated by mild bleeding (in second and fourth month respectively) in two instances. Presenting signs were delayed motor development with marked contralateral torticollis (n = 1), hemiplegia (n = 1) and unusual head nodding (n = 1). Neuroradiological investigations revealed complete aplasia (n = 1) and subtotal aplasia (n = 2) of one cerebellar hemisphere with only a residual wing-like structure below the tentorium. There was contralateral underdevelopment of the brainstem. The infant with hemiplegic cerebral palsy had an additional supratentorial periventricular parenchymal defect, contralateral to the cerebellar hypoplasia. In view of literature reports, describing similar neuroradiological or neuropathological findings in asymptomatic individuals, it is doubtful whether UCA is responsible for our patient's problems. In our cases UCA has presumably resulted from a prenatal destructive lesion, possibly an infarct, but the timing and exact nature are unknown. PMID:8677027

  7. Horizontal-plane arm movements with direction reversals performed by normal individuals and individuals with down syndrome.

    PubMed

    Almeida, G L; Corcos, D M; Hasan, Z

    2000-10-01

    We examined the systematic variation in shoulder and elbow torque, as well as movement kinematics, for horizontal-plane arm movements with direction reversals performed by normal individuals and individuals with Down syndrome. Eight neurologically normal individuals and eight individuals with Down syndrome performed horizontal, planar reversal movements to four different target locations. The four locations of the targets were chosen such that there is a systematic increase in elbow interaction torque for each of the four different target locations. This systematic increase in interaction torque has previously been shown to lead to progressively larger movement reversal errors, and trajectories that do not show a sharp reversal of direction, for movements to and from the target in patients who have proprioceptive abnormalities. We computed joint torques at the elbow and shoulder and found a high correlation between elbow and shoulder torque for the neurologically normal subjects. The ratio of joint torques varied systematically with target location. These findings extend previously reported findings of a linear synergy between shoulder and elbow joints for a variety of point-to-point movements. There was also a correlation between elbow and shoulder torque in individuals with Down syndrome, but the magnitude of the correlation was less. The ratio of joint torques changed systematically with target direction in individuals with Down syndrome but was slightly different from the ratio observed for neurologically normal individuals. The difference in the ratio was caused by the generation of proportionately more elbow torque than shoulder torque. The fingertip path of individuals with Down syndrome showed a sharp reversal in moving toward and then away from the target. In this respect, they were similar to neurologically normal individuals but dissimilar to individuals with proprioceptive deficits. Finally, we observed that individuals with Down syndrome spend

  8. The comorbidity of reduplicative paramnesia, intermetamorphosis, reverse-intermetamorphosis, misidentification of reflection, and capgras syndrome in an adolescent patient.

    PubMed

    Arısoy, Ozden; Tufan, A Evren; Bilici, Rabia; 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.

  9. 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

  10. The comorbidity of reduplicative paramnesia, intermetamorphosis, reverse-intermetamorphosis, misidentification of reflection, and capgras syndrome in an adolescent patient.

    PubMed

    Arısoy, Ozden; Tufan, A Evren; Bilici, Rabia; 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

  11. The Need for a Rational Approach to Vasoconstrictive Syndromes: Transcranial Doppler and Calcium Channel Blockade in Reversible Cerebral Vasoconstriction Syndrome

    PubMed Central

    Marsh, Elisabeth B.; Ziai, Wendy C.; Llinas, Rafael H.

    2016-01-01

    Introduction Reversible cerebral vasoconstriction syndrome (RCVS) typically affects young patients and left untreated can result in hemorrhage or ischemic stroke. Though the disorder has been well characterized in the literature, the most appropriate way to diagnose, treat, and evaluate therapeutic response remains unclear. In previous studies, transcranial Doppler ultrasound (TCD) has shown elevated velocities indicative of vasospasm. This imaging modality is noninvasive and inexpensive; an attractive option for diagnosis and therapeutic monitoring if it is sensitive enough to detect changes in the acute setting given that RCVS often affects the distal vessels early in the course of disease. There is also limited data that calcium channel blockade may be effective in treating vasospasm secondary to RCVS, though the agent of choice, formulation, and dose are unclear. Methods We report a small cohort of seven patients presenting with thunderclap headache whose vascular imaging was consistent with RCVS. All were treated with calcium channel blockade and monitored with TCD performed every 1–2 days. Results On presentation, TCD correlated with standard neuroimaging findings of vasospasm (on MR, CT, and conventional angiography). TCD was also able to detect improvement in velocities in the acute setting that correlated well with initiation of calcium channel blockade. Long-acting verapamil appeared to have the greatest effect on velocities compared to nimodipine and shorter-acting calcium channel blockers. Conclusion Though small, our cohort demonstrates potential utility of TCD to monitor RCVS, and relative superiority of extended-release verapamil over other calcium channel blockers, illustrating the need for larger randomized trials. PMID:27721780

  12. Reversible cerebral vasoconstriction syndrome associated with fingolimod treatment in relapsing-remitting multiple sclerosis three months after childbirth.

    PubMed

    Kraemer, Markus; Weber, Ralph; Herold, Michèle; Berlit, Peter

    2015-10-01

    Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by acute thunderclap headache, evidence of vasoconstriction in conventional angiography or magnetic resonance angiography and reversibility of these phenomena within 12 weeks. Some triggering factors, for example drugs such as selective serotonin reuptake inhibitors, sumatriptan, tacrolimus, cyclophosphamide and cocaine, or states such as pregnancy, puerperium or migraine have been described. We describe the case of a 29-year-old woman with RCVS associated with fingolimod three months after childbirth. This case represents the first report of RCVS in fingolimod treatment. PMID:26283695

  13. 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.

  14. Posterior reversible encephalopathy syndrome following paroxysmal nocturnal hemoglobinuria: a case report and literature review.

    PubMed

    Ding, Dongxue; Li, Kai; Li, Guoliang; Long, Xiaoyan

    2015-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by hemolytic anemia, marrow failure, and a high incidence of life-threatening venous thrombosis. It is subject to a considerable variety of complications like intestinal obstruction and visceral embolism. The current study firstly presents a 40-year-old male with a previous diagnosis of PNH who developed posterior reversible encephalopathy syndrome (PRES) during treatment with methylprednisolone. He was referred to our department with headache and two episodes of generalized tonic-clonic seizures. Laboratory examination revealed peripheral blood cytopenias and elevated count of reticulocyte. Brain magnetic resonance imaging (MRI) exhibited abnormal signal in the bilateral parieto-occipital lobes with symmetric distribution which confirmed the diagnosis of PRES. After receive treatment of dexamethasone, anti-hypertensive and neurotropic drugs, the patient made a complete clinical recovery; and the abnormal signals of MRI were almost completely absorbed. This case shows that PRES might be a rare complication of PNH. Furthermore, it points out the necessity of rapid diagnosis and treatment of PRES. PMID:26379993

  15. The clinical and radiological spectrum of posterior reversible encephalopathy syndrome: the retrospective Berlin PRES study.

    PubMed

    Liman, T G; Bohner, G; Heuschmann, P U; Endres, M; Siebert, E

    2012-01-01

    The aim of the study was to characterize the clinical and radiological spectrum of posterior reversible encephalopathy syndrome (PRES) in a large cohort. The radiological report data bases of the authors' university hospitals were searched for patients with PRES. Various imaging features at onset of symptoms and on follow-up as well as clinical and paraclinical data were tabulated in those patients fulfilling the criteria for PRES. Exploratory univariate analyses were performed. A total of 96 patients with PRES were included into the study. Wide differences in lesion location, diffusivity, distribution pattern, edema severity, hemorrhage, underlying diseases, symptoms, mean arterial pressure (MAP) and coagulation status were encountered. Hemorrhage occurred significantly more frequently in patients with altered coagulation state and was significantly associated with higher edema grades and with the presence of cytotoxic edema. There was a significant difference in MAP between toxic associations with higher MAP in infection, eclampsy and autoimmune disorders, while lower MAP was found in chemotherapy and immunsupression. In 82% of patients complete or near complete resolution of edema was noted during follow-up. Higher MAP levels were associated with incomplete edema resolution. In 43% of patients residual lesions were seen with a relatively even distribution between focal gliosis, infarction, posthemorrhagic residua, atrophy and laminar necrosis. PRES in this large hospital-based retrospective study comprises a wide radiological and clinical spectrum. Residual lesions were encountered more frequently than commonly expected. Our results point towards a differential contribution of high blood pressure to the course of PRES in different underlying etiologies.

  16. A case of acute post-streptococcal glomerulonephritis that developed posterior reversible encephalopathy syndrome.

    PubMed

    Kasap, Belde; Çarman, Kürşat Bora; Yiş, Uluç

    2014-12-01

    A 10-year male patient presented with swelling in the face, legs and scrotal area which developed 8 days after tonsillitis treatment. Acute post-sterotococcal glomerulonephritis (APSGN) was considered in the patient whose urinalysis revealed hematuria and proteinuria at nephrotic level, whose urea, creatinine, lipid profile and anti-streptolysine O antibody levels were increased, albumin and C3 value were decreased and whose 24-hour urine test revealed proteinuria. Renal biopsy was found to be compatible with APSGN. In the follow-up, severe headache, vomiting and convulsion were observed under antihypertensive and diuretic treatment and when the blood pressure was 130/80 mmHg (the 99(th) percentile for the patient: 129/88 mmHg). During the follow-up, the blood pressure values increased to 160/90 mmHg. The electroencephalogram (EEG) performed was found to be normal and magnetic resonance imaging (MRI) findings were compatible with posterior reversible encephalopathy syndrome (PRES). MRI was found to be normal at the first month following antihypertensive and anticonvulsive treatment. In the first year of the follow-up, the blood pressure, neurological examination and urinalysis findings were found to be normal. This patient was presented to draw attention to the fact that PRES can also present with a blood pressure tending to increase and with blood pressure values which are not so high. PMID:26078688

  17. 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.

  18. The Typical Thunderclap Headache of Reversible Cerebral Vasoconstriction Syndrome and its Various Triggers.

    PubMed

    Ducros, Anne; Wolff, Valérie

    2016-04-01

    During the last 10 years, reversible cerebral vasoconstriction syndrome (RCVS) has emerged as the most frequent cause of thunderclap headache (TCH) in patients without aneurysmal subarachnoid hemorrhage, and as the most frequent cause of recurrent TCHs. The typical TCHs of RCVS are multiple, recurring over a few days to weeks, excruciating, short-lived, and brought up by exertion, sexual activities, emotion, Valsalva maneuvers, or bathing, among other triggers. All these triggers induce sympathetic activation. In a minority of cases with RCVS, TCH heralds stroke and rarely death. Early diagnosis of RCVS in patients who present with isolated headache enables proper management and might reduce the risk of eventual stroke. This review describes the characteristics, triggers, diagnosis, and management of TCH in RCVS. One aim is to underline that the TCH pattern of RCVS is so typical that it enables, according to the 2013 revision of the International Classification of Headache Disorders, the diagnosis of "probable RCVS" in patients with such a headache pattern, normal cerebral angiography, and no other cause. Another objective is to discuss the role of physical and emotional stress in RCVS and in other related conditions involving similar triggers.

  19. 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. PMID:19381433

  20. Reverse Transcription Recombinase Polymerase Amplification Assay for the Detection of Middle East Respiratory Syndrome Coronavirus

    PubMed Central

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

    2013-01-01

    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. PMID:24459611

  1. A rare case of chemotherapy induced reversible cerebral vasoconstriction syndrome in a patient of acute lymphocytic leukemia.

    PubMed

    Sankhe, Shilpa; Kamath, Namita; Sahu, Arpita

    2015-01-01

    Neurotoxic reactions of chemotherapy occur frequently and are often dose limiting side effects of chemotherapy. It is important to differentiate these various nonneoplastic effects from metastases, or sometimes even from each other, since the therapeutic approach differs accordingly. To arrive at a definitive and comprehensive diagnosis, the radiologist should integrate imaging findings, clinical signs, and laboratory results together. Here we present a unique case of chemotherapy induced reversible cerebral vasoconstriction syndrome in a 13-year-old patient of acute lymphoblastic leukemia.

  2. [Bilateral reversed palmaris longus muscle--a rare cause of peripheral median nerve compression syndrome. Case report].

    PubMed

    Giunta, R; Brunner, U; Wilhelm, K

    1993-10-01

    A rare case of median nerve compression syndrome outside the carpal tunnel in the distal forearm is reported. A 21-year-old man suffered while working from symptoms of temporary median nerve compression in both forearms; this was caused by hypertrophy of reversed palmaris longus muscles. Resection of the abnormal muscle bellies relieved the symptoms immediately. Only ten similar cases have been reported in the literature, and this is the first case with bilateral symptoms.

  3. Emotions and their cognitive control in children with cerebellar tumors.

    PubMed

    Hopyan, Talar; Laughlin, Suzanne; Dennis, Maureen

    2010-11-01

    A constellation of deficits, termed the cerebellar cognitive affective syndrome (CCAS), has been reported following acquired cerebellar lesions. We studied emotion identification and the cognitive control of emotion in children treated for acquired tumors of the cerebellum. Participants were 37 children (7-16 years) treated for cerebellar tumors (19 benign astrocytomas (AST), 18 malignant medulloblastomas (MB), and 37 matched controls (CON). The Emotion Identification Task investigated recognition of happy and sad emotions in music. In two cognitive control tasks, we investigated whether children could identify emotion in situations in which the emotion in the music and the emotion in the lyrics was either congruent or incongruent. Children with cerebellar tumors identified emotion as accurately and quickly as controls (p > .05), although there was a significant interaction of emotions and group (p < .01), with the MB group performing less accurately identifying sad emotions, and both cerebellar tumor groups were impaired in the cognitive control of emotions (p < .01). The fact that childhood acquired cerebellar tumors disrupt cognitive control of emotion rather than emotion identification provides some support for a model of the CCAS as a disorder, not so much of emotion as of the regulation of emotion by cognition. PMID:20887648

  4. Metronidazole induced cerebellar ataxia

    PubMed Central

    Hari, Aditya; Srikanth, B. Akshaya; Lakshmi, G. Sriranga

    2013-01-01

    Metronidazole is a widely used antimicrobial usually prescribed by many specialist doctors for a short duration of 10-15 days. Prolonged use of metronidazole is rare. The present case is of a patient who used the drug for 4 months and developed peripheral neuropathy, convulsions, and cerebellar ataxia. He was treated with diazepam and levetiracetam. The patient recovered completely following discontinuation of metronidazole. PMID:23833378

  5. Tardive Syndromes are Rarely Reversible after Discontinuing Dopamine Receptor Blocking Agents: Experience from a University-based Movement Disorder Clinic

    PubMed Central

    Zutshi, Deepti; Cloud, Leslie J.; Factor, Stewart A.

    2014-01-01

    Background Several studies have examined reversibility of tardive syndromes (TS), primarily in psychotic patients who are maintained on dopamine receptor blocking drugs. The results have varied widely. However, few have assessed remission rates after discontinuing the offending agents. This study evaluated reversibility of TS in patients who permanently withdrew the causative agent(s). We also examined for any possible clinical predictors of reversibility. Methods A retrospective cohort of 108 TS patients was studied. Most of the patients were not psychotic; most patients were being treated either for a mood disorder with atypical antipsychotics or for a gastrointestinal disturbance with metoclopramide. Patients were stratified on the basis of reversibility, and statistical tests were used for subgroup comparisons of relevant clinical variables. Logistic regression was undertaken to identify clinical variables predictive of reversibility. Results Only 13% of the cohort experienced reversibility of the TS, 2% without medical intervention. When stratified by reversibility, there were no significant differences in any study variables between subgroups. None of the study variables predicted reversibility in the logistic regression. Discussion Our study demonstrated a low remission rate for TS in a cohort of psychiatric and non-psychiatric patients seen in a movement disorder clinic after the offending agents were completely withdrawn. Such a finding has significant prognostic implications. It is possible that limitations of the retrospective design may have resulted in an underestimation. There is a clear need for prospective, multicenter, clinical trials in populations that can be safely withdrawn from dopamine receptor blocking agents so that true remission rates can be measured. PMID:25374768

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

    PubMed

    Lie, Geoffrey; Morley, Thomas; Chowdhury, Muhammad

    2016-01-01

    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.

  7. 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

  8. Reversible brain atrophy and cognitive impairment in an adolescent Japanese patient with primary adrenal Cushing’s syndrome

    PubMed Central

    Ohara, Nobumasa; Suzuki, Hiroshi; Suzuki, Akiko; Kaneko, Masanori; Ishizawa, Masahiro; Furukawa, Kazuo; Abe, Takahiro; Matsubayashi, Yasuhiro; Yamada, Takaho; Hanyu, Osamu; Shimohata, Takayoshi; Sone, Hirohito

    2014-01-01

    Endogenous Cushing’s syndrome is an endocrine disease resulting from chronic exposure to excessive glucocorticoids produced in the adrenal cortex. Although the ultimate outcome remains uncertain, functional and morphological brain changes are not uncommon in patients with this syndrome, and generally persist even after resolution of hypercortisolemia. We present an adolescent patient with Cushing’s syndrome who exhibited cognitive impairment with brain atrophy. A 19-year-old Japanese male visited a local hospital following 5 days of behavioral abnormalities, such as money wasting or nighttime wandering. He had hypertension and a 1-year history of a rounded face. Magnetic resonance imaging (MRI) revealed apparently diffuse brain atrophy. Because of high random plasma cortisol levels (28.7 μg/dL) at 10 AM, he was referred to our hospital in August 2011. Endocrinological testing showed adrenocorticotropic hormone-independent hypercortisolemia, and abdominal computed tomography demonstrated a 2.7 cm tumor in the left adrenal gland. The patient underwent left adrenalectomy in September 2011, and the diagnosis of cortisol-secreting adenoma was confirmed histologically. His hypertension and Cushingoid features regressed. Behavioral abnormalities were no longer observed, and he was classified as cured of his cognitive disturbance caused by Cushing’s syndrome in February 2012. MRI performed 8 months after surgery revealed reversal of brain atrophy, and his subsequent course has been uneventful. In summary, the young age at onset and the short duration of Cushing’s syndrome probably contributed to the rapid recovery of both cognitive dysfunction and brain atrophy in our patient. Cushing’s syndrome should be considered as a possible etiological factor in patients with cognitive impairment and brain atrophy that is atypical for their age. PMID:25246796

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

    PubMed

    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

  10. 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

  11. 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…

  12. 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

  13. Management of Refractory Noninsulinoma Pancreatogenous Hypoglycemia Syndrome with Gastric Bypass Reversal: A Case Report and Review of the Literature

    PubMed Central

    Rao, Bhavana B.; Click, Benjamin; Eid, George; Codario, Ronald A.

    2015-01-01

    Background. Roux-en-Y gastric bypass (RYGB) is a commonly performed, effective bariatric procedure; however, rarely, complications such as postprandial hypoglycemia due to noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) may ensue. Management of refractory NIPHS is challenging. We report a case that was successfully treated with RYGB reversal. Case Report. A 58-year-old male with history of RYGB nine months earlier for morbid obesity presented for evaluation of postprandial, hypoglycemic seizures. Testing for insulin level, insulin antibodies, oral hypoglycemic agents, pituitary axis hormone levels, and cortisol stimulation was unrevealing. Computed tomography (CT) scan of the abdomen was unremarkable. A 72-hour fast was completed without hypoglycemia. Mixed meal testing demonstrated endogenous hyperinsulinemic hypoglycemia (EHH) and selective arterial calcium stimulation testing (SACST) was positive. Strict dietary modifications, maximal medical therapy, gastrostomy tube feeding, and stomal reduction failed to alleviate symptoms. Ultimately, he underwent laparoscopic reversal of RYGB. Now, 9 months after reversal, he has markedly reduced hypoglycemia burden. Discussion. Hyperfunctioning islets secondary to exaggerated incretin response and altered intestinal nutrient delivery are hypothesized to be causative in NIPHS. For refractory cases, there is increasing skepticism about the safety and efficacy of pancreatic resection. RYGB reversal may be successful. PMID:26523235

  14. Ethanol-Induced Cerebellar Ataxia: Cellular and Molecular Mechanisms.

    PubMed

    Dar, M Saeed

    2015-08-01

    The cerebellum is an important target of ethanol toxicity given that cerebellar ataxia is the most consistent physical manifestation of acute ethanol consumption. Despite the significance of the cerebellum in ethanol-induced cerebellar ataxia (EICA), the cellular and molecular mechanisms underlying EICA are incompletely understood. However, two important findings have shed greater light on this phenomenon. First, ethanol-induced blockade of cerebellar adenosine uptake in rodent models points to a role for adenosinergic A1 modulation of EICA. Second, the consistent observation that intracerebellar administration of nicotine in mice leads to antagonism of EICA provides evidence for a critical role of cerebellar nitric oxide (NO) in EICA reversal. Based on these two important findings, this review discusses the potential molecular events at two key synaptic sites (mossy fiber-granule cell-Golgi cell (MGG synaptic site) and granule cell parallel fiber-Purkinje cell (GPP synaptic site) that lead to EICA. Specifically, ethanol-induced neuronal NOS inhibition at the MGG synaptic site acts as a critical trigger for Golgi cell activation which leads to granule cell deafferentation. Concurrently, ethanol-induced inhibition of adenosine uptake at the GPP synaptic site produces adenosine accumulation which decreases glutamate release and leads to the profound activation of Purkinje cells (PCs). These molecular events at the MGG and GPP synaptic sites are mutually reinforcing and lead to cerebellar dysfunction, decreased excitatory output of deep cerebellar nuclei, and EICA. The critical importance of PCs as the sole output of the cerebellar cortex suggests normalization of PC function could have important therapeutic implications.

  15. 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

  16. [Buspirone in the treatment of cerebellar ataxia].

    PubMed

    Svetel, M; Vojvodić, N; Filipović, S R; Dragasević, N; Sternić, N; Kostić, V S

    1999-01-01

    Ataxia is defined as a disturbance which, quite independent of any motor weakness, alters direction and extent of voluntary movement and impairs the sustained voluntary of reflex muscle contraction necessary for maintaining postiue and equilibrium [1]. Since pathophysiological basis of cerebeller ataxia is still not completely clear, the current therapeutic attempts are mainly symptom-oriented [3]. One possible approach could be a modification of potentially involved neurotransmitter systems of the cerebellum, where particularly interesting is the serotonergic system. However, attempts with levorotatory form of tryptophan (5-HT precursors) proved to be ineffective [4, 5]. Since receptors in the cerebellum are mainly of 5-HTIA subtype, the use of specific agonists might be a more reasonable therapy [6]. The study initially involved 11 patients, but only 9 completed the protocol due to unfavorable side effects. Our open label prospective study lasted for 15 weeks. The patients were tested before the beginning of the treatment (initial visit), at 7th (first visit) and 11th week (second visit) of continuous therapy, and eventually at 15th week (final visit). The daily dose was 40 mg at the first and 60 mg at the second visit. We used the evaluation scale gurposed for cerebellar functions testing (speech, gait, coordination and ocular movements). Significant improvement of cerebellar ataxia in patients under buspiron therapy has been noted. We analyzed the results obtained from our 9 patients (4 females and 5 males), of which 6 patients suffered from cerebellar degeneration, one from multiple sclerosis, one from Ramsey-Hunt syndrome, and one from pontine myelinolysis. At the initial visit the patient score was 18.9 (SD = 7.3), subsequently, at the iirst visit the score was 15.4 (SD = 8), while the second visit yielded the score of 12.9 (SD = 8.2), and finally, after a two-weeks lasting wash-out period, it was 17.7 (SD = 7.1) (Table 1). It was found that patients

  17. Cerebellar abnormalities typical of methylmercury poisoning in a fledged saltmarsh sparrow, Ammodramus caudacutus.

    PubMed

    Scoville, Sheila A; Lane, Oksana P

    2013-05-01

    A fledged, 12-15 day-old saltmarsh sparrow, Ammodramus caudacutus, was collected from an accidental kill on Cinder Island, Long Island, NY, USA. The sparrow was assessed for feather mercury levels and the brain analyzed for cerebellar abnormalities by microscopic examination. In humans, fetal Minamata disease is caused by maternal ingestion of mercury. It is characterized by disrupted and disordered cerebellar neuronal migration in the fetus or infant. Results from this sparrow show cerebellar abnormalities typical of Minamata disease. It is the first known avian or mammalian specimen taken from the wild to show the abnormalities typical of the human fetal syndrome.

  18. Automated cerebellar lobule segmentation with application to cerebellar structural analysis in cerebellar disease.

    PubMed

    Yang, Zhen; Ye, Chuyang; Bogovic, John A; Carass, Aaron; Jedynak, Bruno M; Ying, Sarah H; Prince, Jerry L

    2016-02-15

    The cerebellum plays an important role in both motor control and cognitive function. Cerebellar function is topographically organized and diseases that affect specific parts of the cerebellum are associated with specific patterns of symptoms. Accordingly, delineation and quantification of cerebellar sub-regions from magnetic resonance images are important in the study of cerebellar atrophy and associated functional losses. This paper describes an automated cerebellar lobule segmentation method based on a graph cut segmentation framework. Results from multi-atlas labeling and tissue classification contribute to the region terms in the graph cut energy function and boundary classification contributes to the boundary term in the energy function. A cerebellar parcellation is achieved by minimizing the energy function using the α-expansion technique. The proposed method was evaluated using a leave-one-out cross-validation on 15 subjects including both healthy controls and patients with cerebellar diseases. Based on reported Dice coefficients, the proposed method outperforms two state-of-the-art methods. The proposed method was then applied to 77 subjects to study the region-specific cerebellar structural differences in three spinocerebellar ataxia (SCA) genetic subtypes. Quantitative analysis of the lobule volumes shows distinct patterns of volume changes associated with different SCA subtypes consistent with known patterns of atrophy in these genetic subtypes. PMID:26408861

  19. 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

  20. Reversible palinopsia and the Alice in Wonderland syndrome associated with topiramate use in migraineurs.

    PubMed

    Evans, Randolph W

    2006-05-01

    Two patients are reported who developed palinopsia while taking topiramate for migraine prevention which resolved or decreased in frequency or duration on lower doses, but recurred or increased in frequency or duration on higher doses. Both patients had complete resolution of palinopsia when topiramate was discontinued. A third patient is described who developed the "Alice in Wonderland" syndrome about 1 week after starting topiramate for migraine prevention with complete resolution of symptoms about 1 month after stopping. Topiramate use may cause palinopsia and may be associated with the Alice in Wonderland syndrome through an unknown mechanism. PMID:16643588

  1. 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

  2. The mysterious microcircuitry of the cerebellar nuclei

    PubMed Central

    Uusisaari, Marylka; De Schutter, Erik

    2011-01-01

    Abstract The microcircuitry of cerebellar cortex and, in particular, the physiology of its main element, the Purkinje neuron, has been extensively investigated and described. However, activity in Purkinje neurons, either as single cells or populations, does not directly mediate the cerebellar effects on the motor effector systems. Rather, the result of the entire cerebellar cortical computation is passed to the relatively small cerebellar nuclei that act as the final, integrative processing unit in the cerebellar circuitry. The nuclei ultimately control the temporal and spatial features of the cerebellar output. Given this key role, it is striking that the internal organization and the connectivity with afferent and efferent pathways in the cerebellar nuclei are rather poorly known. In the present review, we discuss some of the many critical shortcomings in the understanding of cerebellar nuclei microcircuitry: the extent of convergence and divergence of the cerebellar cortical pathway to the various cerebellar nuclei neurons and subareas, the possible (lack of) conservation of the finely-divided topographical organization in the cerebellar cortex at the level of the nuclei, as well as the absence of knowledge of the synaptic circuitry within the cerebellar nuclei. All these issues are important for predicting the pattern-extraction and encoding capabilities of the cerebellar nuclei and, until resolved, theories and models of cerebellar motor control and learning may err considerably. PMID:21521761

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

    PubMed

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

    2013-09-01

    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.

  4. [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.

  5. [Posterior reversible encephalopathy syndrome of the midbrain and hypothalamus - a case report of uremic encephalopathy presenting with hypersomnia].

    PubMed

    Shiga, Yuji; Kanaya, Yuhei; Kono, Ryuhei; Takeshima, Shinichi; Shimoe, Yutaka; Kuriyama, Masaru

    2016-01-01

    We report the case of a 73-year-old woman presenting with hypersomnia and loss of appetite. She suffered from diabetic nephropathy without receiving dialysis, in addition to hypertension, which was well controlled without marked fluctuation. There were no objective neurological findings. Her laboratory findings showed renal failure with 3.7 mg/dl of serum creatinine and decreased serum sodium and potassium. Brain magnetic resonance imaging (MRI) showed posterior reversible encephalopathy syndrome (PRES) with vasogenic edema, which was distributed in the dorsal midbrain, medial thalamus, and hypothalamus. After we addressed the electrolyte imbalance and dehydration, her symptoms and MRI findings gradually improved, but faint high signals on MRI were still present 3 months later. Orexin in the cerebrospinal fluid was decreased on admission, but improved 6 months later. We diagnosed uremic encephalopathy with atypical form PRES showing functional disturbance of the hypothalamus. PMID:26640128

  6. Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome and lateralized periodic discharges plus fast activity on EEG.

    PubMed

    Silveira, Diosely C; Bashir, Mahrukh; Daniel, Joshua; Lucena, Michelle H; Bonpietro, Frank

    2016-01-01

    We report on a 20-year-old patient with a 6-month history of recurrent abdominal pain and a 3-day history of vomiting, hypertension, seizures, and encephalopathy. The brain MRI showed posterior reversible encephalopathy syndrome, and continuous EEG (cEEG) monitoring showed lateralized periodic discharges plus fast activity. Comprehensive CSF studies were negative. Because of severe abdominal pain without a definite etiology, we requested urine porphobilinogen and serum and fecal porphyrins, which suggested acute intermittent porphyria (AIP). The patient had a complete resolution of her symptoms with carbohydrate loading and high caloric diet. Acute intermittent porphyria is potentially life-threatening without proper management and prevention of triggers if it is not recognized.

  7. Acute intermittent porphyria presenting with posterior reversible encephalopathy syndrome and lateralized periodic discharges plus fast activity on EEG.

    PubMed

    Silveira, Diosely C; Bashir, Mahrukh; Daniel, Joshua; Lucena, Michelle H; Bonpietro, Frank

    2016-01-01

    We report on a 20-year-old patient with a 6-month history of recurrent abdominal pain and a 3-day history of vomiting, hypertension, seizures, and encephalopathy. The brain MRI showed posterior reversible encephalopathy syndrome, and continuous EEG (cEEG) monitoring showed lateralized periodic discharges plus fast activity. Comprehensive CSF studies were negative. Because of severe abdominal pain without a definite etiology, we requested urine porphobilinogen and serum and fecal porphyrins, which suggested acute intermittent porphyria (AIP). The patient had a complete resolution of her symptoms with carbohydrate loading and high caloric diet. Acute intermittent porphyria is potentially life-threatening without proper management and prevention of triggers if it is not recognized. PMID:27660746

  8. 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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:26858804

  10. Calcineurin Inhibitors Associated Posterior Reversible Encephalopathy Syndrome in Solid Organ Transplantation: Report of 2 Cases and Literature Review.

    PubMed

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

    2016-04-01

    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

  11. [Cerebellar infarctions and their mechanisms].

    PubMed

    Amarenco, P

    1993-01-01

    Cerebellar infarcts have been neglected for a long time and are now shown well by CT and especially MRI. Some infarcts involve the full territory supplied by a cerebellar artery. They are frequently complicated by edema with brain stem compression and supratentorial hydrocephalus, requiring at times emergency surgery, and are often accompanied by other medullary, medial pontine, mesencephalic, thalamic and occipital infarcts. On the other hand, partial territory infarcts are usually confined to the cerebellum and have a benign outcome with total recovery or minimal disability. They are more common than full territory infarcts. However, clinical presentations are similar to those full territory infarcts, differing mainly by the lack of drowsiness or unconsciousness. The main symptoms are vertigo, headache, vomiting, unsteadiness of gait and dysarthria. Signs include ipsilateral limb dysmetria, ipsilateral axial lateropulsion, ataxia and dysarthria. Vertigo is more severe and rotary in posterior inferior cerebellar artery territory infarcts, whereas dysarthria and ataxia are prominent in superior cerebellar artery territory infarcts. A few brain stem signs are sometimes added. In these territorial cerebellar infarcts, cardioembolism is the most common cause. Atherosclerotic occlusion comes next, involving the intracranial part of the vertebral artery and, less frequently, the lower basilar artery, both locations inaccessible to surgery. Other causes are artery to artery embolism from a vertebral artery origin stenosis, or the aortic arch, in situ intracranial branch atherosclerotic occlusion, and vertebral artery dissection. Border zone cerebellar infarcts occur in one third of the cases. They are small cortical or deep infarcts. They have the same symptoms and signs as territorial infarcts except for more frequent postural symptoms occurring over days, weeks or months after the ischemic event. The infarcts mainly have a thromboembolic mechanism, and sometimes have a

  12. Cerebellar neurodegeneration in human hereditary DNA repair disorders.

    PubMed

    Kohji, T; Hayashi, M; Shioda, K; Minagawa, M; Morimatsu, Y; Tamagawa, K; Oda, M

    1998-02-27

    Recent findings have focused attention on the role of apoptosis in neurodegenerative diseases, however, the apoptotic process in child-onset brain disorders has been little investigated. Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are hereditary disorders characterized by impaired DNA repair and neurodegeneration. We investigated apoptotic cell death in the cerebellum of five cases of XP group A (XPA), four cases of CS, and twelve controls, using TdT-mediated DIG-dUTP nick-end labeling (TUNEL) and immunohistochemical staining for bcl-2, bcl-x, p53, bax, BDNF and Trk B. The TUNEL-positive cells were found in the granule cells of the cerebellar cortex of two patients with XPA and two patients with CS, whereas such cells were not detected in the cerebellar cortex in controls. Upregulation of bcl-2 or BDNF was not observed, and bcl-x expression was not altered. Some patients showed nuclear expression of p53 in the granule cells and/or molecular layer, bax-positive glial cells in the cerebellar white matter, and a few Trk B-positive cells in the granular layer. These findings suggest that apoptotic cell death can be involved in the cerebellar degeneration in patients with hereditary defects in DNA repair mechanisms.

  13. Ataxia, dysmetria, tremor. Cerebellar diseases.

    PubMed

    Kornegay, J N

    1991-09-01

    Diseases affecting the cerebellum typically cause ataxia, coupled with dysmetria and tremor. Dysmetria is a condition in which there is improper measuring of distance in muscular acts; hypermetria is overreaching (overstepping) and hypometria is underreaching (understepping). Tremor refers to an involuntary, rhythmic, oscillatory movement of a body part. The tremor of cerebellar disease typically is exaggerated by goal-oriented movements (intention tremor). Cerebellar lesions also often cause loss of the menace response, despite the presence of normal vision. The anatomic basis for this phenomenon is obscure. The principal disease affecting the cerebellum in cats is cerebellar hypoplasia due to in utero infection with the panleukopenia virus. This disease will be discussed here. Neurologic signs of cerebellar involvement also may be seen in association with those diseases that affect the CNS multifocally. In these cats, there may be additional signs indicating involvement of other anatomic areas or the cerebellar deficits may occur alone (see discussion of multifocal diseases in Multiple Neurologic Deficits: Inflammatory Diseases [page 426] and Multiple Neurologic Deficits: Noninfectious Diseases [page 440]). PMID:1802262

  14. Speech prosody in cerebellar ataxia.

    PubMed

    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 speakers and six with ataxia. The speaking task was designed to elicit six different prosodic conditions and four contrastive prosodic events. Distinct prosodic patterns were elicited by the examiner for cerebellar patients and healthy speakers. These utterances were digitally recorded and analysed acoustically and statistically. The healthy speakers showed statistically significant differences among all four prosodic contrasts. The normal model described by the prosodic contrasts provided a sensitive index of cerebellar pathology with quantitative acoustic analyses. A significant interaction between subject groups and prosodic conditions revealed a compromised prosody in cerebellar patients. Significant differences were found for durational parameters, F0 and formant frequencies. The cerebellar speakers demonstrated different patterns of syllable lengthening and syllable reduction from that of the healthy speakers. PMID:17613097

  15. Ataxias and Cerebellar or Spinocerebellar Degeneration

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Ataxias and Cerebellar or Spinocerebellar Degeneration Information Page Synonym(s): ... Publications and Information Publicaciones en Español What are Ataxias and Cerebellar or Spinocerebellar Degeneration? Ataxia often occurs ...

  16. 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.

  17. Reversible Myocarditis and Pericarditis after Black Widow Spider Bite or Kounis Syndrome?

    PubMed Central

    Yaman, Mehmet; Mete, Turkan; Ozer, Ismail; Yaman, Elif; Beton, Osman

    2015-01-01

    Clinical manifestation of black widow spider bite is variable and occasionally leads to death in rural areas. Cases of myocarditis and pericarditis after black widow spider bite are rare and the associated prognostic significance is unknown. Kounis syndrome has been defined as an acute coronary syndrome in the setting of allergic or hypersensitivity and anaphylactic or anaphylactoid insults that manifests as vasospastic angina or acute myocardial infarction or stent thrombosis. Allergic myocarditis is caused by myocardial inflammation triggered by infectious pathogens, toxic, ischemic, or mechanical injuries, such as drug-related inflammation and other immune reactions. A 15-year-old child was admitted to the emergency department with pulmonary edema after spider bite. ST segment depression on ECG, elevated cardiac enzymes and global left ventricular hypokinesia (with ejection fraction of 22%), and local pericardial effusion findings confirmed the diagnosis of myopericarditis. After heart failure and pulmonary edema oriented medical therapy, clinical status improved. Patient showed a progressive improvement and LV functions returned to normal on the sixth day. Myopericarditis complicating spider bite is rare and sometimes fatal. The mechanism is not clearly known. Alpha-latrotoxin of the black widow spider is mostly convicted in these cases. But allergy or hypersensitivity may play a role in myocardial damage. PMID:26509087

  18. 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. PMID:27477572

  19. 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.

  20. The genetics of cerebellar malformations.

    PubMed

    Aldinger, Kimberly A; Doherty, Dan

    2016-10-01

    The cerebellum has long been recognized for its role in motor co-ordination, but it is also increasingly appreciated for its role in complex cognitive behavior. Historically, the cerebellum has been overwhelmingly understudied compared to the neocortex in both humans and model organisms. However, this tide is changing as advances in neuroimaging, neuropathology, and neurogenetics have led to clinical classification and gene identification for numerous developmental disorders that impact cerebellar structure and function associated with significant overall neurodevelopmental dysfunction. Given the broad range in prognosis and associated medical and neurodevelopmental concerns accompanying cerebellar malformations, a working knowledge of these disorders and their causes is critical for obstetricians, perinatologists, and neonatologists. Here we present an update on the genetic causes for cerebellar malformations that can be recognized by neuroimaging and clinical characteristics during the prenatal and postnatal periods. PMID:27160001

  1. 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

  2. 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

  3. [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.

  4. Reverse pupillary block associated with pigment dispersion syndrome after in-the-bag intraocular lens implantation.

    PubMed

    Itagaki, Hideo; Kunikata, Toshio; Hiratsuka, Kentaro; Saito, Junichiro; Oshika, Tetsuro

    2013-12-01

    A 61-year-old man with high myopia who had received a systemic α1A-adrenoceptor antagonist had phacoemulsification and in-the-bag intraocular lens implantation in the right eye. One day postoperatively, marked pigment dispersion in the anterior chamber, posterior bowing of the iris, and iridodonesis were noted associated with a subsequent elevation in intraocular pressure (IOP). Pharmacological pupil dilation was effective in reducing pigment dispersion and IOP, and laser peripheral iridotomy was performed to alleviate posterior bowing of the iris. We hypothesize that dynamic changes in the aqueous humor flow by cataract surgery and latent flaccidity of the iris due to the systemic α1A-adrenoceptor antagonist caused reverse pupillary block. High myopia may be another risk factor for this complication. PMID:24140374

  5. Abnormal ocular motility with brainstem and cerebellar disorders.

    PubMed

    Carlow, T J; Bicknell, J M

    1978-01-01

    The disorders of ocular motility seen in association with brainstem or cerebellar disorders may point to rather specific anatomical or pathological correlations. Pontine gaze palsy reflects involvement of the pontine paramedian reticular formation. Internuclear ophthalmoplegia signifies a lesion in the medial longitudinal fasciculus. Skew deviation may result from a lesion anywhere in the posterior fossa. Ocular bobbing typically results from a pontine lesion. The Sylvian aqueduct syndrome is characteristic of involvement in the upper midbrain-pretectal region, usually a pinealoma. Cerebellar lesions may be manifested by gaze paresis, skew deviation, disturbances of saccadic or smooth pursuit movements, ocular myoclonus, or several characteristic forms of nystagmus. Familiarity with these disorders may be of great help to the physician dealing with a patient with a possible posterior fossa lesion.

  6. R-Baclofen Reverses a Social Behavior Deficit and Elevated Protein Synthesis in a Mouse Model of Fragile X Syndrome

    PubMed Central

    Qin, Mei; Huang, Tianjian; Kader, Michael; Krych, Leland; Xia, Zengyan; Burlin, Thomas; Zeidler, Zachary; Zhao, Tingrui

    2015-01-01

    Background: Fragile X syndrome (FXS) is the most common known inherited form of intellectual disability and the single genomic cause of autism spectrum disorders. It is caused by the absence of a fragile X mental retardation gene (Fmr1) product, FMRP, an RNA-binding translation suppressor. Elevated rates of protein synthesis in the brain and an imbalance between synaptic signaling via glutamate and γ-aminobutyric acid (GABA) are both considered important in the pathogenesis of FXS. In a mouse model of FXS (Fmr1 knockout [KO]), treatment with R-baclofen reversed some behavioral and biochemical phenotypes. A remaining crucial question is whether R-baclofen is also able to reverse increased brain protein synthesis rates. Methods: To answer this question, we measured regional rates of cerebral protein synthesis in vivo with the L-[1-14C]leucine method in vehicle- and R-baclofen–treated wildtype and Fmr1 KO mice. We further probed signaling pathways involved in the regulation of protein synthesis. Results: Acute R-baclofen administration corrected elevated protein synthesis and reduced deficits on a test of social behavior in adult Fmr1 KO mice. It also suppressed activity of the mammalian target of rapamycin pathway, particularly in synaptosome-enriched fractions, but it had no effect on extracellular-regulated kinase 1/2 activity. Ninety min after R-baclofen treatment, we observed an increase in metabotropic glutamate receptor 5 expression in the frontal cortex, a finding that may shed light on the tolerance observed in human studies with this drug. Conclusions: Our results suggest that treatment via activation of the GABA (GABA receptor subtype B) system warrants further study in patients with FXS. PMID:25820841

  7. 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.

  8. Orthostatic tremor: a cerebellar pathology?

    PubMed Central

    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

    2016-01-01

    See Muthuraman et al. (doi:10.1093/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. PMID:27329770

  9. 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…

  10. 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

  11. 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.

  12. Amygdala Modulation of Cerebellar Learning

    PubMed Central

    Farley, Sean J.; Radley, Jason J.

    2016-01-01

    Previous studies showed that amygdala lesions or inactivation slow the acquisition rate of cerebellum-dependent eyeblink conditioning, a type of associative motor learning. The current study was designed to determine the behavioral nature of amygdala–cerebellum interactions, to identify the neural pathways underlying amygdala–cerebellum interactions, and to examine how the amygdala influences cerebellar learning mechanisms in rats. Pharmacological inactivation of the central amygdala (CeA) severely impaired acquisition and retention of eyeblink conditioning, indicating that the amygdala continues to interact with the cerebellum after conditioning is consolidated (Experiment 1). CeA inactivation also substantially reduced stimulus-evoked and learning-related neuronal activity in the cerebellar anterior interpositus nucleus during acquisition and retention of eyeblink conditioning (Experiment 2). A very small proportion of cerebellar neurons responded to the conditioned stimulus (CS) during CeA inactivation. Finally, retrograde and anterograde tracing experiments identified the basilar pontine nucleus at the confluence of outputs from CeA that may support amygdala modulation of CS input to the cerebellum (Experiment 3). Together, these results highlight a role for the CeA in the gating of CS-related input to the cerebellum during motor learning that is maintained even after the conditioned response is well learned. SIGNIFICANCE STATEMENT The current study is the first to demonstrate that the amygdala modulates sensory-evoked and learning-related neuronal activity within the cerebellum during acquisition and retention of associative learning. The findings suggest a model of amygdala–cerebellum interactions in which the amygdala gates conditioned stimulus inputs to the cerebellum through a direct projection from the medial central nucleus to the basilar pontine nucleus. Amygdala gating of sensory input to the cerebellum may be an attention-like mechanism that

  13. Cerebellar Ataxia and Glutamic Acid Decarboxylase Antibodies

    PubMed Central

    Ariño, Helena; Gresa-Arribas, Nuria; Blanco, Yolanda; Martínez-Hernández, Eugenia; Sabater, Lidia; Petit-Pedrol, Mar; Rouco, Idoia; Bataller, Luis; Dalmau, Josep O.; Saiz, Albert; Graus, Francesc

    2016-01-01

    IMPORTANCE Current clinical and immunologic knowledge on cerebellar ataxia (CA) with glutamic acid decarboxylase 65 antibodies (GAD65-Abs) is based on case reports and small series with short-term follow-up data. OBJECTIVE To report the symptoms, additional antibodies, prognostic factors, and long-term outcomes in a cohort of patients with CA and GAD65-Abs. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study and laboratory investigations at a center for autoimmune neurologic disorders among 34 patients with CA and GAD65-Abs, including 25 with long-term follow-up data (median, 5.4 years; interquartile range, 3.1-10.3 years). MAIN OUTCOMES AND MEASURES Analysis of clinicoimmunologic features and predictors of response to immunotherapy. Immunochemistry on rat brain, cultured neurons, and human embryonic kidney cells expressing GAD65, GAD67, α1-subunit of the glycine receptor, and a repertoire of known cell surface autoantigens were used to identify additional antibodies. Twenty-eight patients with stiff person syndrome and GAD65-Abs served as controls. RESULTS The median age of patients was 58 years (range, 33-80 years); 28 of 34 patients (82%) were women. Nine patients (26%) reported episodes of brainstem and cerebellar dysfunction or persistent vertigo several months before developing CA. The clinical presentation was subacute during a period of weeks in 13 patients (38%). Nine patients (26%) had coexisting stiff person syndrome symptoms. Systemic organ-specific autoimmunities (type 1 diabetes mellitus and others) were present in 29 patients (85%). Twenty of 25 patients with long-term follow-up data received immunotherapy (intravenous immunoglobulin in 10 and corticosteroids and intravenous immunoglobulin or other immunosuppressors in 10), and 7 of them (35%) improved. Predictors of clinical response included subacute onset of CA (odds ratio [OR], 0.50; 95% CI, 0.25-0.99; P = .047) and prompt immunotherapy (OR, 0.98; 95% CI, 0.96-0.99; P = .01). Similar

  14. 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.

  15. Reversibility of albuminuria and continuous positive airway pressure compliance in patients of obstructive sleep apnea syndrome.

    PubMed

    Chen, Ning-Hung; Chou, Yu-Ting; Lee, Pei-Hsien; Lin, Shih-Wei; Chuang, Li-Pang; Lin, Yu-Sheng; Yang, Cheng-Ta

    2016-06-01

    A positive correlation between albuminuria and severity of obstructive sleep apnea syndrome (OSAS) has been demonstrated, as indexed by urine albumin-to-creatinine ratios (UACRs). However, the effect of continuous positive airway pressure (CPAP) treatment on albuminuria in OSAS patients has not been established.Sixty subjects, with apnea-hypopnea indices >15 events per hour and no other diagnoses associated with albuminuria, underwent overnight polysomnography for sleep apnea and were examined for UACR at baseline and after 6 months of CPAP therapy. CPAP compliance rates were also recorded.Significant improvement in UACR was found in OSAS patients with good compliance to CPAP treatment after 6 months of therapy (baseline vs 6-month follow-up, 32.0 ± 9.5 vs 19.2 ± 6.5 mg/g, respectively, P = 0.007), whereas slight worsening in UACRs was noted in patients with poor compliance to CPAP treatment (baseline vs 6-month follow-up, respectively, 16.7 ± 4.4 vs 19.1 ± 6.3 mg/g, respectively, P = 0.39). Change in UACR was significant between poor compliance versus good compliance groups (2.4 ± 2.7 vs -12.8 ± 4.4 mg/g, respectively, t = 2.9, P = 0.005). A significant correlation between improvement in UACR and CPAP compliance rates was also noted (Spearman's correlation coefficient: -0.37, P = 0.007). Baseline UACR, good CPAP compliance, and body mass index were independent predictors of changes in UACR.Adequate CPAP treatment improves albuminuria in OSAS patients. In addition to monitoring CPAP adherence and subjective sleepiness, UACR may offer an objective physiological index of CPAP therapeutic effectiveness. PMID:27368036

  16. Reversibility of albuminuria and continuous positive airway pressure compliance in patients of obstructive sleep apnea syndrome

    PubMed Central

    Chen, Ning-Hung; Chou, Yu-Ting; Lee, Pei-Hsien; Lin, Shih-Wei; Chuang, Li-Pang; Lin, Yu-Sheng; Yang, Cheng-Ta

    2016-01-01

    Abstract A positive correlation between albuminuria and severity of obstructive sleep apnea syndrome (OSAS) has been demonstrated, as indexed by urine albumin-to-creatinine ratios (UACRs). However, the effect of continuous positive airway pressure (CPAP) treatment on albuminuria in OSAS patients has not been established. Sixty subjects, with apnea-hypopnea indices >15 events per hour and no other diagnoses associated with albuminuria, underwent overnight polysomnography for sleep apnea and were examined for UACR at baseline and after 6 months of CPAP therapy. CPAP compliance rates were also recorded. Significant improvement in UACR was found in OSAS patients with good compliance to CPAP treatment after 6 months of therapy (baseline vs 6-month follow-up, 32.0 ± 9.5 vs 19.2 ± 6.5 mg/g, respectively, P = 0.007), whereas slight worsening in UACRs was noted in patients with poor compliance to CPAP treatment (baseline vs 6-month follow-up, respectively, 16.7 ± 4.4 vs 19.1 ± 6.3 mg/g, respectively, P = 0.39). Change in UACR was significant between poor compliance versus good compliance groups (2.4 ± 2.7 vs −12.8 ± 4.4 mg/g, respectively, t = 2.9, P = 0.005). A significant correlation between improvement in UACR and CPAP compliance rates was also noted (Spearman's correlation coefficient: −0.37, P = 0.007). Baseline UACR, good CPAP compliance, and body mass index were independent predictors of changes in UACR. Adequate CPAP treatment improves albuminuria in OSAS patients. In addition to monitoring CPAP adherence and subjective sleepiness, UACR may offer an objective physiological index of CPAP therapeutic effectiveness. PMID:27368036

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

    PubMed

    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

  18. 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

  19. A case of acute reversible Charles Bonnet syndrome following postsurgical unilateral eye patch placement.

    PubMed

    Khadavi, Nicole Miriam; Lew, Helen; Goldberg, Robert Alan; Mancini, Ronald

    2010-01-01

    A fully alert 70-year-old male with no significant medical or psychiatric history presented for surgical follow-up after uncomplicated right lower eyelid cicatricial ectropion surgery with postoperative unilateral, eye patch placement complaining of visual hallucinations. Preoperative unaided visual acuity was 20/20 in each eye. The patient described simple, nonformed and complex, formed images that were both static and animated. The images included crystal-like formations that appeared to bubble, green leaves against a vivid magenta backdrop, and an isolated hallucination of a lifelike plant with trembling leaves. These hallucinations began 2 days postoperatively and persisted 2 days following eye patch removal. The patient perceived the hallucinations multiple times a day over the 7-day period, without a stereotyped pattern. The images occurred when the eyes were open and ceased when they were closed. They were prompted by looking at a blank wall or white surface. The patient consistently recognized these images as unreal. They typically persisted for 1 to 2 minutes and could be extinguished by looking away. There were no associated auditory hallucinations, psychosis, or delirium and no history of visual, cognitive, or neurological deficit. The patient denied the use of hallucinogenic medications, including analgesics, or the initiation of any new medications. To the authors' knowledge, this is the first reported case of acute reversible CBS following unilateral eye patch placement. CBS may be a frightening postsurgical consequence of eye patch placement. 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. PMID:20551853

  20. 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. PMID:27037483

  1. 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.

  2. Relationships between edema degree and clinical and biochemical parameters in posterior reversible encephalopathy syndrome: a preliminary study.

    PubMed

    Bo, Gao; Hui, Liang; Feng-Li, Liu; Cui, Lv

    2012-09-01

    The objective of the study was to investigate the associations between the degree of edema with the clinical and biochemical parameters such as serum lactate dehydrogenase (LDH), albumin (ALB) in posterior reversible encephalopathy syndrome (PRES) patients. Forty-nine patients with typical clinical symptoms and characteristic MR imaging findings of PRES were included in this study. Lactate dehydrogenase and ALB were analyzed with the immunoluminometric assays. Fluid-attenuated inversion recovery images were used to evaluate the distribution of the extent or severity of vasogenic edema by two observers. Correlation analysis between the scores of brain edema and the blood pressures, clinical conditions and biochemical parameters was performed. No significant difference of brain edema score was found between patients with eclampsia, chronic renal failure and other clinical condition (P > 0.05). Both mean arterial pressures and LDH level were moderately correlated with the scores of brain edema distribution (Spearman's ρ test, r = 0.405 and 0.497, respectively, P < 0.01). Serum ALB level was not correlated with the scores of brain edema distribution (P > 0.05). Larger and more diffuse lesions may be predicted by higher LDH level and blood pressure. The overall severity of the systemic process might be predicted by the degree of edema expression in PRES.

  3. 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

  4. 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

  5. [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. PMID:26442424

  6. 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

  7. Naive T-cells in myelodysplastic syndrome display intrinsic human telomerase reverse transcriptase (hTERT) deficiency.

    PubMed

    Yang, L; Mailloux, A; Rollison, D E; Painter, J S; Maciejewski, J; Paquette, R L; Loughran, T P; McGraw, K; Makishima, H; Radhakrishnan, R; Wei, S; Ren, X; Komrokji, R; List, A F; Epling-Burnette, P K

    2013-04-01

    Telomeres are specialized structures providing chromosome integrity during cellular division along with protection against premature senescence and apoptosis. Accelerated telomere attrition in patients with myelodysplastic syndrome (MDS) occurs by an undefined mechanism. Although the MDS clone originates within the myeloid compartment, T-lymphocytes display repertoire contraction and loss of naive T-cells. The replicative lifespan of T-cells is stringently regulated by telomerase activity. In MDS cases, we show that purified CD3+ T-cells have significantly shorter telomere length and reduced proliferative capacity upon stimulation compared with controls. To understand the mechanism, telomerase enzymatic activity and telomerase reverse transcriptase (hTERT), gene expression were compared in MDS cases (n=35) and healthy controls (n=42) within different T-cell compartments. Telomerase activity is greatest in naive T-cells illustrating the importance of telomere repair in homeostatic repertoire regulation. Compared with healthy controls, MDS cases had lower telomerase induction (P<0.0001) that correlated with significantly lower hTERT mRNA (P<0.0001), independent of age and disease stratification. hTERT mRNA deficiency affected naive but not memory T-cells, and telomere erosion in MDS occurred without evidence of an hTERT-promoter mutation, copy number variation or deletion. Telomerase insufficiency may undermine homeostatic control within the hematopoietic compartment and promote a change in the T-cell repertoire in MDS.

  8. Specific complications of monochorionic twin pregnancies: twin-twin transfusion syndrome and twin reversed arterial perfusion sequence.

    PubMed

    Chalouhi, G E; Stirnemann, J J; Salomon, L J; Essaoui, M; Quibel, T; Ville, Y

    2010-12-01

    Monochorionic twins are subjected to specific complications which originate in either imbalance or abnormality of the single placenta serving two twins. This unequal placental sharing can cause complications including twin-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), selective intrauterine growth restriction or twin reversed arterial perfusion sequence (TRAP). Monochorionicity also makes the management of these specific complications as well as that of a severe malformation in one twin hazardous since the spontaneous death of one twin exposes the co-twin to a risk of exsanguination into the dead twin and its placenta. The latter is responsible for the death of the co-twin in up to 20% of the cases and in ischemic sequelae in about the same proportions in the survivors. Although the symptoms of all these complications are very different, the keystone of their management comes down to either surgical destruction of the inter-twin anastomoses on the chorionic plate when aiming at dual survival or selective and permanent occlusion of the cord of a severely affected twin aiming at protecting the normal co-twin. This can be best achieved by fetoscopic selective laser coagulation and bipolar forceps cord coagulation respectively. PMID:20855238

  9. 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.

  10. Principal Component Analysis of Cerebellar Shape on MRI Separates SCA Types 2 and 6 into Two Archetypal Modes of Degeneration

    PubMed Central

    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.

    2014-01-01

    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. PMID:22258915

  11. 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. PMID:22258915

  12. Acute hydrocephalus following cerebellar infarct

    PubMed Central

    Epstein, Elliot; Naqvi, Huma

    2010-01-01

    A 59-year-old man was admitted with a diagnosis of acute cerebellar infarct. The next day his level of consciousness deteriorated (Glasgow Coma Score 5) and repeat computed tomography (CT) brain scan showed subtle signs of hydrocephalus. Following neurosurgical intervention, he recovered and is now walking with a frame and assistance. The CT changes of hydrocephalus were subtle and difficult to spot. Recognition of these signs of hydrocephalus and prompt neurosurgical intervention were lifesaving. PMID:22355298

  13. Visuomotor learning in cerebellar patients.

    PubMed

    Timmann, D; Shimansky, Y; Larson, P S; Wunderlich, D A; Stelmach, G E; Bloedel, J R

    1996-11-01

    The aim of the present study was to demonstrate that patients with pathology affecting substantial regions of the cerebellum can improve their performance in a series of two-dimensional tracing tasks, thus supporting the view that this type of motor behavior can be acquired even when the integrity of this structure is compromised. Eight patients with chronic, isolated cerebellar lesions and eight age- and sex-matched healthy controls were tested. Three patients had mild, five had moderate upper limb ataxia. The experiment was divided into two parts. In the first, subjects traced an irregularly shaped outline over 20 consecutive trials ('Trace 1' task). Next, subjects were asked to redraw the object without any underlying template as a guide ('Memory 1' task). In the second part of the study, subjects were asked to trace a different, irregularly shaped outline over 20 consecutive trials ('Trace 2' task). Next, they were required to redraw it by memory with its axis rotated 90 degrees ('Memory 2' task). In each of the memory tasks the template was placed over the drawn image after each trial and shown to the subjects. The error of performance was determined by calculating three different measurements, each focused on different aspects of the task. Based on these measurements, the cerebellar patients showed improvement in both memory tasks. In the 'Memory 1' task the calculated error decreased significantly for the patients with mild ataxia. In the 'Memory 2' task all cerebellar patients improved their performance substantially enough to reduce significantly the magnitude of all three error measurements. The experiments demonstrate that patients with cerebellar lesions are capable of improving substantially their performance of a complex motor task involving the recall of memorized shapes and the visuomotor control of a tracing movement.

  14. 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. PMID:27606347

  15. 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

  16. 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.

  17. 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.

  18. Elevation of serum lactate dehydrogenase at posterior reversible encephalopathy syndrome onset in chemotherapy-treated cancer patients.

    PubMed

    Fitzgerald, Ryan T; Wright, Steven M; Samant, Rohan S; Kumar, Manoj; Ramakrishnaiah, Raghu H; Van Hemert, Rudy; Brown, Aliza T; Angtuaco, Edgardo J

    2014-09-01

    The pathophysiology of posterior reversible encephalopathy syndrome (PRES) is incompletely understood; however, an underlying state of immune dysregulation and endothelial dysfunction has been proposed. We examined alterations of serum lactate dehydrogenase (LDH), a marker of endothelial dysfunction, relative to the development of PRES in patients receiving chemotherapy. A retrospective Institutional Review Board approved database of 88 PRES patients was examined. PRES diagnosis was confirmed by congruent clinical diagnosis and MRI. Clinical features at presentation were recorded. Serum LDH values were collected at three time points: prior to, at the time of, and following PRES diagnosis. Student's t-test was employed. LDH values were available during the course of treatment in 12 patients (nine women; mean age 57.8 years [range 33-75 years]). Chemotherapy-associated PRES patients were more likely to be normotensive (25%) versus the non-chemotherapy group (9%). LDH levels at the time of PRES diagnosis were higher than those before and after (p=0.0263), with a mean difference of 114.8 international units/L. Mean time intervals between LDH measurement prior to and following PRES diagnosis were 44.8 days and 51.4 days, respectively. Mean elapsed time between last chemotherapy administration and PRES onset was 11.1days. In conclusion, serum LDH, a marker of endothelial dysfunction, shows statistically significant elevation at the onset of PRES toxicity in cancer patients receiving chemotherapy. Our findings support a systemic process characterized by endothelial injury/dysfunction as a factor, if not the prime event, in the pathophysiology of PRES.

  19. [Unilateral Posterior Reversible Encephalopathy Syndrome after Ventriculo-Peritoneal Shunt for Normal Pressure Hydrocephalus Following Subarachnoid Hemorrhage: A Case Report].

    PubMed

    Sato, Hiroyuki; Koizumi, Takayuki; Sato, Daisuke; Endo, Shin; Kato, Syunichi

    2016-06-01

    The patient, a 79-year-old man, experienced a Hunt & Kosnik grade IV subarachnoid hemorrhage, presenting with sudden-onset coma and severe left hemiplegia. We performed cranial clipping surgery for a ruptured aneurysm on the right middle cerebral artery the same day. Post-operative recovery proceeded smoothly, with gradual improvements in disturbed consciousness and left hemiplegia. Three weeks post-operation, CT revealed low-density areas in the right frontal and temporal lobe, believed to be due to subarachnoid hemorrhage, as well as hydrocephaly. We then performed a lumbo-peritoneal (L-P) shunt for the hydrocephaly. Two months later, the patient experienced shunt occlusion, and we performed a ventriculo-peritoneal (V-P) shunt revision (pressure: 6 cm H(2)O). Headaches, severe decline in cognitive function, and worsened left hemiplegia were observed seven weeks post-shunt revision. Cranial CT revealed widespread low-density areas in right posterior cerebral white matter. We suspected unilateral posterior reversible encephalopathy syndrome (PRES) after performing cranial MRI and cerebral angiography. Increasing the set pressure of the shunt improved the symptoms and radiographic findings. PRES is typically bilateral, and unilateral incidents are rare. This is the first report of unilateral PRES secondary to shunt operation. Its unilaterality appears to have been caused by unilateral brain damage or adhesions to the brain surface from the subarachnoid cerebral hemorrhage. Overdrainage post-shunt can also induce PRES. Diagnosis of PRES is more difficult in unilateral cases;practitioners must keep PRES in mind as a rare complication post-shunt operation. PMID:27270150

  20. 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

  1. Remote cerebellar hemorrhage following supratentorial cerebrovascular surgery.

    PubMed

    Smith, Ross; Kebriaei, Meysam; Gard, Andrew; Thorell, William; Surdell, Daniel

    2014-04-01

    Three patients with remote cerebellar hemorrhage following supratentorial cerebrovascular surgery are presented. Remote cerebellar hemorrhage is a rare surgical complication that is most often associated with aneurysm clipping or temporal lobectomies. Bleeding occurs on the superior cerebellar cortex and is believed to be venous in origin. The precise pathogenesis of remote cerebellar hemorrhage has yet to be fully elucidated but is generally considered to be a consequence of intraoperative cerebrospinal fluid loss causing caudal displacement of the cerebellum with resultant stretching of the supracerebellar veins. This case series will hopefully shed further light on the incidence, presentation, workup, and treatment of this particular complication of supratentorial surgery. PMID:24238635

  2. Multiple large and small cerebellar infarcts

    PubMed Central

    Canaple, S.; Bogousslavsky, J.

    1999-01-01

    To assess the clinical, topographical, and aetiological features of multiple cerebellar infarcts,18 patients (16.5% of patients with cerebellar infarction) were collected from a prospective acute stroke registry, using a standard investigation protocol including MRI and magnetic resonance angiography. Infarcts in the posterior inferior cerebellar artery (PICA)+superior cerebellar artery (SCA) territory were most common (9/18; 50%), followed by PICA+anterior inferior cerebellar artery (AICA)+SCA territory infarcts (6/18; 33%). One patient had bilateral AICA infarcts. No infarct involved the PICA+AICA combined territory. Other infarcts in the posterior circulation were present in half of the patients and the clinical presentation largely depended on them. Large artery disease was the main aetiology. Our findings emphasised the common occurrence of very small multiple cerebellar infarcts (<2 cm diameter).These very small multiple cerebellar infarcts may occur with (13 patients/18; 72%) or without (3/18; 22%) territorial cerebellar infarcts. Unlike previous series, they could not all be considered junctional infarcts (between two main cerebellar artery territories: 51/91), but also small territorial infarcts (40/91). It is suggested that these very small territorial infarcts may be endzone infarcts, due to the involvement of small distal arterial branches. It is possible that some very small territorial infarcts may be due to a microembolic process, but this hypothesis needs pathological confirmation.

 PMID:10329747

  3. 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.

  4. 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

  5. Crossed Cerebellar Diaschisis in Status Epilepticus.

    PubMed

    Miyazaki, Daigo; Fukushima, Kazuhiro; Nakahara, Asa; Kodaira, Minori; Mochizuki, Katsunori; Kaneko, Kikuko; Kaneko, Tomoki; Sekijima, Yoshiki; Ikeda, Shu-Ichi

    2016-01-01

    Crossed cerebellar diaschisis (CCD) is an interesting phenomenon which classically refers to the depressed blood flow and metabolism affecting one cerebellar hemisphere after a contralateral hemispheric infarction. However, CCD can also be caused by a prolonged seizure. We herein report a case of CCD due to status epilepticus in a patient who showed unique magnetic resonance imaging findings.

  6. 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…

  7. 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.

  8. 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

  9. POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME IN NEUROBLASTOMA PATIENTS RECEIVING ANTI-GD2 3F8 MONOCLONAL ANTIBODY

    PubMed Central

    Kushner, Brian H.; Modak, Shakeel; Basu, Ellen M.; Roberts, Stephen S.; Kramer, Kim; Cheung, Nai-Kong V.

    2014-01-01

    Background Posterior reversible encephalopathy syndrome (PRES) comprises clinical and radiologic findings with rapid onset and potentially dire consequences. Patients experience hypertension, seizures, headache, visual disturbance, and/or altered mentation. Magnetic resonance imaging shows edematous changes in brain (especially parietal and occipital lobes). We report PRES associated with anti-GD2 monoclonal antibody (MoAb) immunotherapy which is now standard for high-risk neuroblastoma but has not previously been implicated in PRES. Methods Successive clinical trials using the anti-GD2 MoAb 3F8 for neuroblastoma patients involved multiple cycles of standard-dose 3F8 (SD-3F8) (20 mg/m2/day, x5 days/cycle) or two cycles of high-dose 3F8 (HD-3F8) (80 mg/m2/day, x5 days/cycle) followed by cycles of SD-3F8. Results PRES was diagnosed in 5/215 (2.3%) patients, including 3/160 (1.9%) patients receiving SD-3F8 and 2/55 (3.6%) patients receiving HD-3F8 (p=0.6). All five patients had a rapid return to clinical-radiologic baseline. PRES occurred in 3/26 (11.5%) patients whose prior treatment included external-beam radiotherapy to the brain (2/6 patients status-post total body irradiation plus 1/20 patients status-post craniospinal irradiation) compared to 2/189 (1.1%) patients without prior brain irradiation (p=0.01). Hypertension, which is strongly linked to PRES, reached grade 3 toxicity in 12/215 (5.6%) patients, including the five patients with PRES and seven patients without PRES. Conclusions Patients receiving anti-GD2 MoAb immunotherapy should be closely monitored for, and undergo urgent treatment or evaluation of, symptoms (e.g., hypertension or headaches) that might herald PRES. Prior brain irradiation may be a predisposing factor for PRES with this immunotherapy. PMID:23633099

  10. 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

  11. Cerebellar Stroke-manifesting as Mania.

    PubMed

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

    2014-07-01

    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

  12. Cerebellar hemangioblastoma manifesting as hearing disturbance.

    PubMed

    Amano, Toshiyuki; Tokunaga, So; Shono, Tadahisa; Mizoguchi, Masahiro; Matsumoto, Kenichi; Yoshida, Fumiaki; Sasaki, Tomio

    2009-09-01

    A 49-year-old man presented with a rare case of cerebellar hemangioblastoma manifesting as only hearing disturbance. He had suffered from hearing difficulty in the right ear for a few months. Magnetic resonance imaging revealed a cystic mass lesion with an internal fluid level and surrounding flow voids in the right cerebellopontine (CP) angle. Cerebral angiography disclosed a vascular-rich tumor fed by both the superior cerebellar and anterior inferior cerebellar arteries. En bloc resection of the tumor was planned under a preoperative diagnosis of cerebellar hemangioblastoma. The tumor protruded into the CP cistern and compressed cranial nerve VIII. The feeding arteries were meticulously coagulated and the tumor was successfully removed. The histological diagnosis was hemangioblastoma. After the operation, the patient's hearing acuity improved dramatically. Cerebellar hemangioblastoma should be considered in the differential diagnosis of CP angle tumors associated with hearing disturbance.

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

    PubMed

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

    2015-11-01

    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

  14. 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

  15. Prenatal diagnosis of Smith-Lemli-Opitz syndrome in a pregnancy with low maternal serum oestriol and a sex-reversed fetus.

    PubMed

    Bick, D P; McCorkle, D; Stanley, W S; Stern, H J; Staszak, P; Berkovitz, G D; Meyers, C M; Kelley, R I

    1999-01-01

    A cytogenetically normal male fetus was subsequently found to have female external genitalia, a cardiac malformation and mid-trimester intra-uterine growth retardation by ultrasound examination. The maternal serum oestriol level was low. The combination of low oestriol and sonographic findings suggested Smith Lemli Opitz syndrome (SLO), which was confirmed by a markedly increased amniotic fluid level of 7-dehydrocholesterol. We review the differential diagnosis of apparent sex reversal in a fetus and low maternal serum oestriol level. To further examine the specificity of low maternal oestriol level as a marker for SLO a follow-up study of 12141 pregnancies screened for Down syndrome using three biochemical markers: alpha-fetoprotein, beta-human chorionic gonadotrophin and oestriol was performed. 26 pregnancies had an oestriol level that was 0.25 MoM or less. SLO was not diagnosed clinically in any of the liveborn children ascertained through a low maternal oestriol level. Nine of the pregnancies ended in spontaneous miscarriage. Although the frequency of SLO in pregnancies with low maternal oestriol levels or sex-reversed fetuses is unknown, the diagnosis of SLO should, nevertheless, be considered in both clinical settings. PMID:10073912

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

    PubMed Central

    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. PMID:27570398

  17. 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. PMID:27570398

  18. A theory of cerebellar cortex.

    PubMed

    Marr, D

    1969-06-01

    1. A detailed theory of cerebellar cortex is proposed whose consequence is that the cerebellum learns to perform motor skills. Two forms of input-output relation are described, both consistent with the cortical theory. One is suitable for learning movements (actions), and the other for learning to maintain posture and balance (maintenance reflexes).2. It is known that the cells of the inferior olive and the cerebellar Purkinje cells have a special one-to-one relationship induced by the climbing fibre input. For learning actions, it is assumed that:(a) each olivary cell responds to a cerebral instruction for an elemental movement. Any action has a defining representation in terms of elemental movements, and this representation has a neural expression as a sequence of firing patterns in the inferior olive; and(b) in the correct state of the nervous system, a Purkinje cell can initiate the elemental movement to which its corresponding olivary cell responds.3. Whenever an olivary cell fires, it sends an impulse (via the climbing fibre input) to its corresponding Purkinje cell. This Purkinje cell is also exposed (via the mossy fibre input) to information about the context in which its olivary cell fired; and it is shown how, during rehearsal of an action, each Purkinje cell can learn to recognize such contexts. Later, when the action has been learnt, occurrence of the context alone is enough to fire the Purkinje cell, which then causes the next elemental movement. The action thus progresses as it did during rehearsal.4. It is shown that an interpretation of cerebellar cortex as a structure which allows each Purkinje cell to learn a number of contexts is consistent both with the distributions of the various types of cell, and with their known excitatory or inhibitory natures. It is demonstrated that the mossy fibre-granule cell arrangement provides the required pattern discrimination capability.5. The following predictions are made.(a) The synapses from parallel fibres

  19. Regional cerebellar volumes predict functional outcome in children with cerebellar malformations.

    PubMed

    Bolduc, Marie-Eve; du Plessis, Adre J; Sullivan, Nancy; Guizard, Nicolas; Zhang, Xun; Robertson, Richard L; Limperopoulos, Catherine

    2012-06-01

    The cerebellum has recently been recognized for its role in high-order functions, including cognition, language, and behavior. Recent studies have also begun to describe a functional topography of the mature cerebellum that includes organization on a mediolateral axis. However, no study to date has examined the relationship between regional cerebellar volume and developmental disabilities in children with cerebellar malformations. The objective of this study was to estimate the extent to which total and regional cerebellar volumes are associated with developmental disabilities in a cohort of children with cerebellar malformations. Children aged 1 to 6 years with a diagnosis of cerebellar malformation underwent standardized outcome measures and quantitative magnetic resonance scanning. The cerebellum was parcellated into seven mediolateral zones (three for each hemisphere plus the vermis) for regional volume analysis. In children with cerebellar malformations, decreased total cerebellar volume was associated with delays in global development, expressive language, cognition, as well as gross and fine motor function. Decreased volume in the right lateral cerebellar hemisphere was related to impaired cognition, expressive language, and gross motor function. Additionally, reduced vermis volume was associated with impaired global development, cognition, expressive language, and gross and fine motor skills, as well as behavior problems and a higher rate of positive autism spectrum screening test. These results begin to define the structural topography of functional outcome in children with cerebellar malformations and should lead to greater accuracy of prognostication as well as timely early developmental interventions.

  20. A dynamical system view of cerebellar function

    NASA Astrophysics Data System (ADS)

    Keeler, James D.

    1990-06-01

    First some previous theories of cerebellar function are reviewed, and deficiencies in how they map onto the neurophysiological structure are pointed out. I hypothesize that the cerebellar cortex builds an internal model, or prediction, of the dynamics of the animal. A class of algorithms for doing prediction based on local reconstruction of attractors are described, and it is shown how this class maps very well onto the structure of the cerebellar cortex. I hypothesize that the climbing fibers multiplex between different trajectories corresponding to different modes of operation. Then the vestibulo-ocular reflex is examined, and experiments to test the proposed model are suggested. The purpose of the presentation here is twofold: (1) To enlighten physiologists to the mathematics of a class of prediction algorithms that map well onto cerebellar architecture. (2) To enlighten dynamical system theorists to the physiological and anatomical details of the cerebellum.

  1. Cognitive, linguistic and affective disturbances following a right superior cerebellar artery infarction: a case study.

    PubMed

    Mariën, Peter; Baillieux, Hanne; De Smet, Hyo Jung; Engelborghs, Sebastiaan; Wilssens, Ineke; Paquier, Philippe; De Deyn, Peter P

    2009-04-01

    The cerebellar cognitive affective syndrome (CCAS) is a neurobehavioral syndrome that may develop after congenital and acquired cerebellar lesions. The syndrome consists of deficits in executive functioning, spatial cognition, visual-spatial memory and language and also involves personality and behavioral changes. We describe a 58-year-old right-handed man who in addition to affective disturbances presented with a unique combination of cognitive and linguistic deficits following an ischemic infarction in the vascular territory of the right superior cerebellar artery (SCA). Neurocognitive and neurolinguistic examinations were performed in the acute phase (10 days post-onset) and lesion phase (four weeks post-onset) of the stroke. A Tc-99m-ECD SPECT study was performed five weeks after the stroke. Acute phase data revealed a generalized cognitive decline and mild transcortical sensory aphasia. In the lesion phase, the neurobehavioral tableau was dominated by executive dysfunctions, disrupted divided attention, disturbed visual-spatial organization and behavioral abnormalities. Neurolinguistic investigations disclosed visual dyslexia and surface dysgraphia. Reading of words and visual lexical decision tasks of words and nonwords were severely defective and predominantly characterized by visual errors. In addition, writing irregular and ambiguous words resulted in regularization errors (phonologically plausible errors based on phoneme-grapheme correspondence rules). In the absence of any structural damage in the supratentorial brain regions, a quantified SPECT study showed a relative hypoperfusion in the right cerebellar hemisphere and the left medial frontal lobe. CCAS is for the first time reported in association with visual dyslexia and surface dysgraphia. We hypothesize that the cognitive and linguistic deficits might result from functional disruption of the cerebellar-encephalic pathways, connecting the cerebellum to the frontal supratentorial areas which subserve

  2. 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

  3. 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.

  4. 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. PMID:26904009

  5. 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

  6. 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

  7. Optogenetic Manipulation of Cerebellar Purkinje Cell Activity In Vivo

    PubMed Central

    Tsubota, Tadashi; Ohashi, Yohei; Tamura, Keita; Sato, Ayana; Miyashita, Yasushi

    2011-01-01

    Purkinje cells (PCs) are the sole output neurons of the cerebellar cortex. Although their anatomical connections and physiological response properties have been extensively studied, the causal role of their activity in behavioral, cognitive and autonomic functions is still unclear because PC activity cannot be selectively controlled. Here we developed a novel technique using optogenetics for selective and rapidly reversible manipulation of PC activity in vivo. We injected into rat cerebellar cortex lentiviruses expressing either the light-activated cationic channel channelrhodopsin-2 (ChR2) or light-driven chloride pump halorhodopsin (eNpHR) under the control of the PC-specific L7 promoter. Transgene expression was observed in most PCs (ChR2, 92.6%; eNpHR, 95.3%), as determined by immunohistochemical analysis. In vivo electrophysiological recordings showed that all light-responsive PCs in ChR2-transduced rats increased frequency of simple spike in response to blue laser illumination. Similarly, most light-responsive PCs (93.8%) in eNpHR-transduced rats decreased frequency of simple spike in response to orange laser illumination. We then applied these techniques to characterize the roles of rat cerebellar uvula, one of the cardiovascular regulatory regions in the cerebellum, in resting blood pressure (BP) regulation in anesthetized rats. ChR2-mediated photostimulation and eNpHR-mediated photoinhibition of the uvula had opposite effects on resting BP, inducing depressor and pressor responses, respectively. In contrast, manipulation of PC activity within the neighboring lobule VIII had no effect on BP. Blue and orange laser illumination onto PBS-injected lobule IX didn't affect BP, indicating the observed effects on BP were actually due to PC activation and inhibition. These results clearly demonstrate that the optogenetic method we developed here will provide a powerful way to elucidate a causal relationship between local PC activity and functions of the cerebellum

  8. 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

  9. 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

  10. 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 Central

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

    2015-01-01

    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. PMID:26130848

  11. 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.

  12. 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.

  13. AMPK activation as a strategy for reversing the endothelial lipotoxicity underlying the increased vascular risk associated with insulin resistance syndrome.

    PubMed

    McCarty, Mark F

    2005-01-01

    The endotheliopathy associated with insulin resistance syndrome appears to result largely from excessive free fatty acid (FFA) exposure that boosts endothelial production of diacylglycerol, thereby activating protein kinase C. This endothelial "lipotoxicity" can be alleviated by very-low-fat diets and by appropriate weight loss. In addition, pharmacological activation of endothelial AMP-activated kinase (AMPK), as with the drug metformin, has the potential to decrease the FFA content of endothelial cells by stimulating fat oxidation; AMPK may also suppress endothelial de novo synthesis of diacylglycerol by inhibiting glycerol-3-phosphate acyltransferase. These considerations may rationalize the superior impact of metformin therapy on the macrovascular health of diabetics. More generally, metformin - or, preferably, better tolerated activators of AMPK - may have considerable potential for promoting vascular health in the large proportion of the adult population afflicted with insulin resistance syndrome. PMID:15823720

  14. Locomotor patterns in cerebellar ataxia.

    PubMed

    Martino, G; Ivanenko, Y P; Serrao, M; Ranavolo, A; d'Avella, A; Draicchio, F; Conte, C; Casali, C; Lacquaniti, F

    2014-12-01

    Several studies have demonstrated how cerebellar ataxia (CA) affects gait, resulting in deficits in multijoint coordination and stability. Nevertheless, how lesions of cerebellum influence the locomotor muscle pattern generation is still unclear. To better understand the effects of CA on locomotor output, here we investigated the idiosyncratic features of the spatiotemporal structure of leg muscle activity and impairments in the biomechanics of CA gait. To this end, we recorded the electromyographic (EMG) activity of 12 unilateral lower limb muscles and analyzed kinematic and kinetic parameters of 19 ataxic patients and 20 age-matched healthy subjects during overground walking. Neuromuscular control of gait in CA was characterized by a considerable widening of EMG bursts and significant temporal shifts in the center of activity due to overall enhanced muscle activation between late swing and mid-stance. Patients also demonstrated significant changes in the intersegmental coordination, an abnormal transient in the vertical ground reaction force and instability of limb loading at heel strike. The observed abnormalities in EMG patterns and foot loading correlated with the severity of pathology [International Cooperative Ataxia Rating Scale (ICARS), a clinical ataxia scale] and the changes in the biomechanical output. The findings provide new insights into the physiological role of cerebellum in optimizing the duration of muscle activity bursts and the control of appropriate foot loading during locomotion.

  15. [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.

  16. Establishment of a novel one-step reverse transcription loop-mediated isothermal amplification assay for rapid identification of RNA from the severe fever with thrombocytopenia syndrome virus.

    PubMed

    Xu, Haihong; Zhang, Lei; Shen, Guangqiang; Feng, Cen; Wang, Xinying; Yan, Jie; Zhang, Yanjun

    2013-12-01

    As an emerging infectious disease, severe fever with thrombocytopenia syndrome virus (SFTSV) infection has been found in many areas of China. Suitable laboratory diagnostic method is urgently needed in clinical detections and epidemiological investigations. In this study, a modified, low-cost and rapid visualized one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for the detection of RNA from the SFTSV has been established. In order to avoid the risk of aerosol contamination and facilitate the naked eye to observe, a microcrystalline wax-dye capsule wrapping the highly sensitive DNA fluorescence dye SYBR Green I was added to the RT-LAMP reaction tube before the initiation of the assay. The detection limit of the established RT-LAMP assay was 10 fg template RNA per reaction mixture. The RT-LAMP assay was confirmed to be high specific to SFTSV, and no cross-reaction was found with the detection of the Chikungunya fever virus, Hemorrhagic Fever with Renal Syndrome virus (HFRSV), and Dengue fever virus. The assay was then applied for the detection of SFTSV RNA in 32 clinical serum samples and showed 94.4% consistence with the detection results of the real-time RT-PCR. The whole process, from sample preparation to result reporting, can be completed within 2h. This adapted, cost efficient and quick visualized RT-LAMP method is feasible for SFTSV field diagnosis in resource-limited field settings.

  17. Establishment of a novel one-step reverse transcription loop-mediated isothermal amplification assay for rapid identification of RNA from the severe fever with thrombocytopenia syndrome virus.

    PubMed

    Xu, Haihong; Zhang, Lei; Shen, Guangqiang; Feng, Cen; Wang, Xinying; Yan, Jie; Zhang, Yanjun

    2013-12-01

    As an emerging infectious disease, severe fever with thrombocytopenia syndrome virus (SFTSV) infection has been found in many areas of China. Suitable laboratory diagnostic method is urgently needed in clinical detections and epidemiological investigations. In this study, a modified, low-cost and rapid visualized one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for the detection of RNA from the SFTSV has been established. In order to avoid the risk of aerosol contamination and facilitate the naked eye to observe, a microcrystalline wax-dye capsule wrapping the highly sensitive DNA fluorescence dye SYBR Green I was added to the RT-LAMP reaction tube before the initiation of the assay. The detection limit of the established RT-LAMP assay was 10 fg template RNA per reaction mixture. The RT-LAMP assay was confirmed to be high specific to SFTSV, and no cross-reaction was found with the detection of the Chikungunya fever virus, Hemorrhagic Fever with Renal Syndrome virus (HFRSV), and Dengue fever virus. The assay was then applied for the detection of SFTSV RNA in 32 clinical serum samples and showed 94.4% consistence with the detection results of the real-time RT-PCR. The whole process, from sample preparation to result reporting, can be completed within 2h. This adapted, cost efficient and quick visualized RT-LAMP method is feasible for SFTSV field diagnosis in resource-limited field settings. PMID:23911296

  18. 9q33.3q34.11 microdeletion: new contiguous gene syndrome encompassing STXBP1, LMX1B and ENG genes assessed using reverse phenotyping.

    PubMed

    Nambot, Sophie; Masurel, Alice; El Chehadeh, Salima; Mosca-Boidron, Anne-Laure; Thauvin-Robinet, Christel; Lefebvre, Mathilde; Marle, Nathalie; Thevenon, Julien; Perez-Martin, Stéphanie; Dulieu, Véronique; Huet, Frédéric; Plessis, Ghislaine; Andrieux, Joris; Jouk, Pierre-Simon; Billy-Lopez, Gipsy; Coutton, Charles; Morice-Picard, Fanny; Delrue, Marie-Ange; Heron, Delphine; Rooryck, Caroline; Goldenberg, Alice; Saugier-Veber, Pascale; Joly-Hélas, Géraldine; Calenda, Patricia; Kuentz, Paul; Manouvrier-Hanu, Sylvie; Dupuis-Girod, Sophie; Callier, Patrick; Faivre, Laurence

    2016-06-01

    The increasing use of array-CGH in malformation syndromes with intellectual disability could lead to the description of new contiguous gene syndrome by the analysis of the gene content of the microdeletion and reverse phenotyping. Thanks to a national and international call for collaboration by Achropuce and Decipher, we recruited four patients carrying de novo overlapping deletions of chromosome 9q33.3q34.11, including the STXBP1, the LMX1B and the ENG genes. We restrained the selection to these three genes because the effects of their haploinsufficency are well described in the literature and easily recognizable clinically. All deletions were detected by array-CGH and confirmed by FISH. The patients display common clinical features, including intellectual disability with epilepsy, owing to the presence of STXBP1 within the deletion, nail dysplasia and bone malformations, in particular patellar abnormalities attributed to LMX1B deletion, epistaxis and cutaneous-mucous telangiectasias explained by ENG haploinsufficiency and common facial dysmorphism. This systematic analysis of the genes comprised in the deletion allowed us to identify genes whose haploinsufficiency is expected to lead to disease manifestations and complications that require personalized follow-up, in particular for renal, eye, ear, vascular and neurological manifestations. PMID:26395556

  19. 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

  20. Disruption of the LTD dialogue between the cerebellum and the cortex in Angelman syndrome model: a timing hypothesis.

    PubMed

    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 Ube3a (m-/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 Ube3a (m-/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 Ube3a (m-/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

  1. 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

  2. Genetics Home Reference: autosomal recessive cerebellar ataxia type 1

    MedlinePlus

    ... Health Conditions ARCA1 autosomal recessive cerebellar ataxia type 1 Enable Javascript to view the expand/collapse boxes. ... Close All Description Autosomal recessive cerebellar ataxia type 1 ( ARCA1 ) is a condition characterized by progressive problems ...

  3. 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...

  4. 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. PMID:25451160

  5. 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.

  6. Long-term consequences of the posterior reversible encephalopathy syndrome in eclampsia and preeclampsia: a review of the obstetric and nonobstetric literature.

    PubMed

    Postma, Ineke R; Slager, Sjoerdtje; Kremer, Hubertus P H; de Groot, Jan Cees; Zeeman, Gerda G

    2014-05-01

    This review summarizes the long-term consequences of the posterior reversible encephalopathy syndrome (PRES) that have been described in the obstetric literature (eclampsia and preeclampsia) and compares these with data from the nonobstetric literature. Preeclampsia is characterized by new-onset hypertension and proteinuria after the 20th week of pregnancy. Neurological symptoms include headache; visual deficits; confusion; seizures; and, in the most severe cases, intracranial hemorrhage. Eclampsia is an acute cerebral complication of preeclampsia, defined as the occurrence of tonic-clonic seizures in pregnant or recently postpartum women. With severe preeclampsia, in conjunction with neurological symptoms, or eclampsia, neuroimaging changes consistent with PRES can be seen. Posterior reversible encephalopathy syndrome is a specific clinicoradiological syndrome presenting with headaches, visual impairment, seizures, and altered mental status. Characteristic neuroimaging features are consistent with cerebral edema predominantly in the parietal and occipital lobes. In addition to preeclampsia/eclampsia, PRES has been associated with various conditions in the nonobstetric population, that is, severe hypertension, transplantation, or autoimmune disease, in combination with immunosuppressive therapy or high-dose chemotherapy for various malignant conditions. Long-term sequelae of both preeclampsia/eclampsia and other PRES-related conditions are poorly described. After eclampsia or preeclampsia, nonspecific white matter lesions may be found on magnetic resonance imaging, which may or may not be related to the PRES episode. Previously (pre)eclamptic women report cognitive failures; however, no neurocognitive impairment has been shown so far. Various nonobstetric PRES-related conditions have been described with long-term neuroimaging abnormalities as well as cognitive problems, epilepsy, or visual impairment. Although no firm conclusions can be drawn because of the

  7. 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

  8. 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.

  9. 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

  10. Mapping cerebellar degeneration in HIV/AIDS.

    PubMed

    Klunder, Andrea D; Chiang, Ming-Chang; Dutton, Rebecca A; Lee, Sharon E; Toga, Arthur W; Lopez, Oscar L; Aizenstein, Howard J; Becker, James T; Thompson, Paul M

    2008-11-19

    Progressive brain atrophy in HIV/AIDS is associated with impaired psychomotor performance, perhaps partly reflecting cerebellar degeneration; yet little is known about how HIV/AIDS affects the cerebellum. We visualized the three-dimensional profile of atrophy in 19 HIV-positive patients (age: 42.9+/-8.3 years) versus 15 healthy controls (age: 38.5+/-12.0 years). We localized consistent patterns of subregional atrophy with an image analysis method that automatically deforms each patient's scan, in three dimensions, to match a reference image. Atrophy was greatest in the posterior cerebellar vermis (14.9% deficit) and correlated with depression severity (P=0.009, corrected), but not with dementia, alcohol/substance abuse, CD4+T-cell counts, or viral load. Profound cerebellar deficits in HIV/AIDS (P=0.007, corrected) were associated with depression, suggesting a surrogate disease marker for antiretroviral trials.

  11. Reversal of mitochondrial defects with CSB-dependent serine protease inhibitors in patient cells of the progeroid Cockayne syndrome

    PubMed Central

    Chatre, Laurent; Biard, Denis S. F.; Sarasin, Alain; Ricchetti, Miria

    2015-01-01

    UV-sensitive syndrome (UVSS) and Cockayne syndrome (CS) are human disorders caused by CSA or CSB gene mutations; both conditions cause defective transcription-coupled repair and photosensitivity. Patients with CS also display neurological and developmental abnormalities and dramatic premature aging, and their cells are hypersensitive to oxidative stress. We report CSA/CSB-dependent depletion of the mitochondrial DNA polymerase-γ catalytic subunit (POLG1), due to HTRA3 serine protease accumulation in CS, but not in UVsS or control fibroblasts. Inhibition of serine proteases restored physiological POLG1 levels in either CS fibroblasts and in CSB-silenced cells. Moreover, patient-derived CS cells displayed greater nitroso-redox imbalance than UVSS cells. Scavengers of reactive oxygen species and peroxynitrite normalized HTRA3 and POLG1 levels in CS cells, and notably, increased mitochondrial oxidative phosphorylation, which was altered in CS cells. These data reveal critical deregulation of proteases potentially linked to progeroid phenotypes in CS, and our results suggest rescue strategies as a therapeutic option. PMID:26038566

  12. A case of human immunodeficiency virus infection with cerebellar ataxia that suggested by an association with autoimmunity.

    PubMed

    Nagao, Shigeto; Kondo, Takayuki; Nakamura, Takashi; Nakagawa, Tomokazu; Matsumoto, Sadayuki

    2016-04-28

    We report a case of human immunodeficiency virus (HIV) infection that showed subacute progressive cerebellar ataxia without HIV encephalopathy or other encephalopathies, including progressive multifocal leukoencephalopathy or encephalitis of other human herpes virus (HHV) infections. A 43-year-old man exhibited unsteady gait. Neurological examination disclosed ataxia of the trunk and lower extremities. Personality change and dementia were absent. Magnetic resonance imaging did not reveal any abnormal finding, including of the cerebellum. The serum HIV-1-RNA was 1.2 × 10(5) copies/ml, and the absolute CD4 lymphocyte count was 141 cells/ml. Remarkably, the serum anti-Yo antibody, as an anti-cerebellar antibody of paraneoplastic syndrome, and anti-gliadin antibody, associated with celiac disease or gluten ataxia, were positive. The cerebrospinal fluid (CSF) immunoglobulin G index was 1.2 (< 0.8), and oligoclonal bands were present. PCR of the CSF was negative for HIV, JC virus, other HHVs, and mycosis. Previous reports presented HIV-infected patients with concurrent autoimmune diseases such as systemic lupus erythematosus, anti-phospholipid syndrome, autoimmune thrombocytopenia, vasculitis, polymyositis and dermatomyositis, sarcoidosis, Graves' disease, and hepatic diseases. These might have been present in patients with a CD4 T lymphocyte count of more than 200 cells/ml. On the other hand, paraneoplastic syndrome, gluten ataxia, cerebellar ataxia associated with anti-glutamic acid decarboxylase antibody, and Hashimoto's encephalopathy might manifest as autoimmune cerebellar ataxia. As regards the association of HIV infection and autoimmune cerebellar ataxia, a previous report suggested that anti-gliadin antibody was detected in about 30% of HIV-infected children, though there is no reference to an association with cerebellar ataxia. Moreover, to our knowledge, detection of anti-Yo antibody in an HIV-infected patient with cerebellar ataxia has not been reported

  13. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients.

    PubMed

    Peterson, K; Rosenblum, M K; Kotanides, H; Posner, J B

    1992-10-01

    We reviewed the clinical findings in 55 patients with cerebellar degeneration associated with the anti-Yo antibody (an anti-Purkinje cell antibody identified in this study by histochemistry and Western blot). The patients were all women, 26 to 85 years old. Fifty-two of them proved to have malignancies, almost exclusively breast or gynecologic cancers and usually confined to the involved organs and local lymph nodes. One woman had adenocarcinoma of the lung, and in three no malignancy has yet been identified. In 34 of 52 patients with cancer, the neurologic syndrome preceded the diagnosis of cancer and in many led to that diagnosis. Patients subacutely developed a pancerebellar disorder that was substantially disabling in most, with 37 of 48 assessable patients being unable to walk or sit unassisted. Laboratory evaluation revealed lymphocytic pleocytosis in 35 patients, with eventual cerebellar atrophy on imaging studies in seventeen. The disabling neurologic syndrome generally did not respond to treatment, but the cancer was often successfully treated. The presence of the anti-Yo antibody in patients with cerebellar symptoms warrants an aggressive approach to diagnosis and treatment of the underlying cancer, as many are curable at the time neurologic symptoms develop.

  14. 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.

  15. Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition.

    PubMed

    McCairn, Kevin W; Iriki, Atsushi; Isoda, Masaki

    2013-01-01

    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.

  16. Non-progressive cerebellar ataxia and previous undetermined acute cerebellar injury: a mysterious clinical condition.

    PubMed

    Pinto, Wladimir Bocca Vieira de Rezende; Pedroso, José Luiz; Souza, Paulo Victor Sgobbi de; Albuquerque, Marcus Vinícius Cristino de; Barsottini, Orlando Graziani Povoas

    2015-10-01

    Cerebellar ataxias represent a wide group of neurological diseases secondary to dysfunctions of cerebellum or its associated pathways, rarely coursing with acute-onset acquired etiologies and chronic non-progressive presentation. We evaluated patients with acquired non-progressive cerebellar ataxia that presented previous acute or subacute onset. Clinical and neuroimaging characterization of adult patients with acquired non-progressive ataxia were performed. Five patients were identified with the phenotype of acquired non-progressive ataxia. Most patients presented with a juvenile to adult-onset acute to subacute appendicular and truncal cerebellar ataxia with mild to moderate cerebellar or olivopontocerebellar atrophy. Establishing the etiology of the acute triggering events of such ataxias is complex. Non-progressive ataxia in adults must be distinguished from hereditary ataxias.

  17. A case of follicular lymphoma associated with paraneoplastic cerebellar degeneration.

    PubMed

    Shimazu, Yayoi; Minakawa, Eiko N; Nishikori, Momoko; Ihara, Masafumi; Hashi, Yuichiro; Matsuyama, Hirofumi; Hishizawa, Masakatsu; Yoshida, Sonoyo; Kitano, Toshiyuki; Kondo, Tadakazu; Ishikawa, Takayuki; Takahashi, Ryosuke; Takaori-Kondo, Akifumi

    2012-01-01

    Paraneoplastic neurological disorders (PND) are neurological effects of malignancy that are recognized as immune-mediated disorders caused by aberrant expression of a tumor antigen that is normally expressed in the nervous system. We report a case of cerebellar ataxia which turned out to be paraneoplastic cerebellar degeneration, a subtype of PND that develops cerebellar symptoms, that was caused by follicular lymphoma. After chemotherapy, the patient attained sufficient improvement of cerebellar symptoms along with complete remission of lymphoma. Paraneoplastic cerebellar degeneration should be recognized as a rare complication of lymphoma as it is important to start proper treatment before the neurological symptoms become irreversible.

  18. Mutation-related differences in exploratory, spatial, and depressive-like behavior in pcd and Lurcher cerebellar mutant mice

    PubMed Central

    Tuma, Jan; Kolinko, Yaroslav; Vozeh, Frantisek; Cendelin, Jan

    2015-01-01

    The cerebellum is not only essential for motor coordination but is also involved in cognitive and affective processes. These functions of the cerebellum and mechanisms of their disorders in cerebellar injury are not completely understood. There is a wide spectrum of cerebellar mutant mice which are used as models of hereditary cerebellar degenerations. Nevertheless, they differ in pathogenesis of manifestation of the particular mutation and also in the strain background. The aim of this work was to compare spatial navigation, learning, and memory in pcd and Lurcher mice, two of the most frequently used cerebellar mutants. The mice were tested in the open field for exploration behavior, in the Morris water maze with visible as well as reversal hidden platform tasks and in the forced swimming test for motivation assessment. Lurcher mice showed different space exploration activity in the open field and a lower tendency to depressive-like behavior in the forced swimming test compared with pcd mice. Severe deficit of spatial navigation was shown in both cerebellar mutants. However, the overall performance of Lurcher mice was better than that of pcd mutants. Lurcher mice showed the ability of visual guidance despite difficulties with the direct swim toward a goal. In the probe trial test, Lurcher mice preferred the visible platform rather than the more recent localization of the hidden goal. PMID:26029065

  19. Cerebellar cortical inhibition and classical eyeblink conditioning.

    PubMed

    Bao, Shaowen; Chen, Lu; Kim, Jeansok J; Thompson, Richard F

    2002-02-01

    The cerebellum is considered a brain structure in which memories for learned motor responses (e.g., conditioned eyeblink responses) are stored. Within the cerebellum, however, the relative importance of the cortex and the deep nuclei in motor learning/memory is not entirely clear. In this study, we show that the cerebellar cortex exerts both basal and stimulus-activated inhibition to the deep nuclei. Sequential application of a gamma-aminobutyric acid type A receptor (GABA(A)R) agonist and a noncompetitive GABA(A)R antagonist allows selective blockade of stimulus-activated inhibition. By using the same sequential agonist and antagonist methods in behaving animals, we demonstrate that the conditioned response (CR) expression and timing are completely dissociable and involve different inhibitory inputs; although the basal inhibition modulates CR expression, the conditioned stimulus-activated inhibition is required for the proper timing of the CR. In addition, complete blockade of cerebellar deep nuclear GABA(A)Rs prevents CR acquisition. Together, these results suggest that different aspects of the memories for eyeblink CRs are encoded in the cerebellar cortex and the cerebellar deep nuclei.

  20. 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.

  1. Cerebellar endocannabinoids: retrograde signaling from purkinje cells.

    PubMed

    Marcaggi, Païkan

    2015-06-01

    The cerebellar cortex exhibits a strikingly high expression of type 1 cannabinoid receptor (CB1), the cannabinoid binding protein responsible for the psychoactive effects of marijuana. CB1 is primarily found in presynaptic elements in the molecular layer. While the functional importance of cerebellar CB1 is supported by the effect of gene deletion or exogenous cannabinoids on animal behavior, evidence for a role of endocannabinoids in synaptic signaling is provided by in vitro experiments on superfused acute rodent cerebellar slices. These studies have demonstrated that endocannabinoids can be transiently released by Purkinje cells and signal at synapses in a direction opposite to information transfer (retrograde). Here, following a description of the reported expression pattern of the endocannabinoid system in the cerebellum, I review the accumulated in vitro data, which have addressed the mechanism of retrograde endocannabinoid signaling and identified 2-arachidonoylglycerol as the mediator of this signaling. The mechanisms leading to endocannabinoid release, the effects of CB1 activation, and the associated synaptic plasticity mechanisms are discussed and the remaining unknowns are pointed. Notably, it is argued that the spatial specificity of this signaling and the physiological conditions required for its induction need to be determined in order to understand endocannabinoid function in the cerebellar cortex. PMID:25520276

  2. Inverse Stochastic Resonance in Cerebellar Purkinje Cells.

    PubMed

    Buchin, Anatoly; Rieubland, Sarah; Häusser, Michael; Gutkin, Boris S; Roth, Arnd

    2016-08-01

    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. Cerebellar Disease in an Adult Cow

    PubMed Central

    Oz, H. H.; Nicholson, S. S.; Al-Bagdadi, F. K.; Zeman, D. H.

    1986-01-01

    This is the report of clinical signs and lesions of a cerebellar disorder in an adult four year old Limousin cow grazing perennial ryegrass (Lolium perenne). The most striking histopathological lesion was a marked paucity of Purkinje cells throughout the cerebellum. ImagesFigure 1.Figure 2. PMID:17422607

  4. 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…

  5. 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

  6. 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

  7. Possible Therapeutic Doses of Cannabinoid Type 1 Receptor Antagonist Reverses Key Alterations in Fragile X Syndrome Mouse Model.

    PubMed

    Gomis-González, Maria; 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

  8. 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

    2015-09-01

    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.

  9. Selective inhibition of caspases in skeletal muscle reverses the apoptotic synaptic degeneration in slow-channel myasthenic syndrome.

    PubMed

    Zhu, Haipeng; Pytel, Peter; Gomez, Christopher M

    2014-01-01

    Slow-channel syndrome (SCS) is a congenital myasthenic disorder caused by point mutations in subunits of skeletal muscle acetylcholine receptor leading to Ca(2+) overload and degeneration of the postsynaptic membrane, nuclei and mitochondria of the neuromuscular junction (NMJ). In both SCS muscle biopsies and transgenic mouse models for SCS (mSCS), the endplate regions are shrunken, and there is evidence of DNA damage in the subsynaptic region. Activated caspase-9, -3 and -7 are intensely co-localized at the NMJ, and the Ca(2+)-activated protease, calpain, and the atypical cyclin-dependent kinase (Cdk5) are overactivated in mSCS. Thus, the true mediator(s) of the disease process is not clear. Here, we demonstrate that selective inhibition of effector caspases, caspase-3 and -7, or initiator caspase, caspase-9, in limb muscle in vivo by localized expression of recombinant inhibitor proteins dramatically decreases subsynaptic DNA damage, increases endplate area and improves ultrastructural abnormalities in SCS transgenic mice. Calpain and Cdk5 are not affected by this treatment. On the other hand, inhibition of Cdk5 by expression of a dominant-negative form of Cdk5 has no effect on the degeneration. Together with previous studies, these results indicate that focal activation of caspase activity at the NMJ is the principal pathological process responsible for the synaptic apoptosis in SCS. Thus, treatments that reduce muscle caspase activity are likely to be of benefit for SCS patients.

  10. Possible Therapeutic Doses of Cannabinoid Type 1 Receptor Antagonist Reverses Key Alterations in Fragile X Syndrome Mouse Model.

    PubMed

    Gomis-González, Maria; Busquets-Garcia, Arnau; Matute, Carlos; Maldonado, Rafael; Mato, Susana; Ozaita, Andrés

    2016-08-31

    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.

  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

    2015-09-01

    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. PMID:26231800

  12. Neuroleptic malignant syndrome due to risperidone treatment in a child with Joubert syndrome.

    PubMed

    Vurucu, Sebahattin; Congologlu, Ayhan; Altun, Demet; Unay, Bulent; Akin, Ridvan

    2009-03-01

    Joubert syndrome is a rare autosomal recessive disease characterized by hypotonia, ataxia, episodic hyperpnea, psychomotor retardation, abnormal ocular movements, cerebellar vermian hypoplasia, and molar tooth sign on magnetic resonance imaging. Neuroleptic malignant syndrome is an uncommon and potentially fatal idiosynchratic reaction of antipsychotic drugs, in which the clinical scenario encompass muscular rigidity, hyperthermia, autonomic dysfunction, altered consciousness, high creatinine phosphokinase levels, and leukocytosis. This report describes a case of neuroleptic malignant syndrome due to risperidone in a child with Joubert syndrome.

  13. Cerebellar circuitry as a neuronal machine.

    PubMed

    Ito, Masao

    2006-01-01

    Shortly after John Eccles completed his studies of synaptic inhibition in the spinal cord, for which he was awarded the 1963 Nobel Prize in physiology/medicine, he opened another chapter of neuroscience with his work on the cerebellum. From 1963 to 1967, Eccles and his colleagues in Canberra successfully dissected the complex neuronal circuitry in the cerebellar cortex. In the 1967 monograph, "The Cerebellum as a Neuronal Machine", he, in collaboration with Masao Ito and Janos Szentágothai, presented blue-print-like wiring diagrams of the cerebellar neuronal circuitry. These stimulated worldwide discussions and experimentation on the potential operational mechanisms of the circuitry and spurred theoreticians to develop relevant network models of the machinelike function of the cerebellum. In following decades, the neuronal machine concept of the cerebellum was strengthened by additional knowledge of the modular organization of its structure and memory mechanism, the latter in the form of synaptic plasticity, in particular, long-term depression. Moreover, several types of motor control were established as model systems representing learning mechanisms of the cerebellum. More recently, both the quantitative preciseness of cerebellar analyses and overall knowledge about the cerebellum have advanced considerably at the cellular and molecular levels of analysis. Cerebellar circuitry now includes Lugaro cells and unipolar brush cells as additional unique elements. Other new revelations include the operation of the complex glomerulus structure, intricate signal transduction for synaptic plasticity, silent synapses, irregularity of spike discharges, temporal fidelity of synaptic activation, rhythm generators, a Golgi cell clock circuit, and sensory or motor representation by mossy fibers and climbing fibers. Furthermore, it has become evident that the cerebellum has cognitive functions, and probably also emotion, as well as better-known motor and autonomic functions

  14. Orthostatic hypotension in acute cerebellar infarction.

    PubMed

    Kim, Hyun-Ah; Lee, Hyung

    2016-01-01

    To investigate the frequency and pattern of orthostatic hypotension (OH) associated with acute isolated cerebellar infarction, and to identify the cerebellar structure(s) potentially responsible for OH, 29 patients (mean age 60.0) with acute isolated cerebellar infarction performed a standard battery of autonomic function tests including the head up tilt test using Finapres for recording of the beat-to-beat BP response during the acute period. Cerebellar infarction related OH was defined as fall in BP (>20 mmHg systolic BP) on tilting in patients without any disease(s) that could potentially cause autonomic dysfunction, or in patients who had a potential cause of autonomic dysfunction, but showed the absence of OH during a follow-up test. The severity and distribution of autonomic dysfunction were measured by the composite autonomic severity score (CASS). Nine patients (31 %) had OH (range 24-53 mmHg) on tilting during the acute period. Most patients (7/9) had a remarkable decrement in systolic BP immediately upon tilting, but OH rapidly normalized. Mean of maximal decrease in systolic BP during head up tilt test was 37.0 mmHg. The OH group showed mild autonomic dysfunctions (CASS, 3.7) with adrenergic sympathetic dysfunction appearing as the most common abnormality. Lesion subtraction analyses revealed that damage to the medial part of the superior semilunar lobule (Crus I) and tonsil was more frequent in OH group compared to non-OH group. Cerebellar infarction may cause a brief episode of OH. The medial part of the superior semilunar lobule and tonsil may participate in regulating the early BP response during orthostasis. PMID:26530504

  15. A Low-Glycemic Nutritional Fitness Program to Reverse Metabolic Syndrome in Professional Firefighters: Results of a Pilot Study

    PubMed Central

    Carey, Mary G.; Al-Zaiti, Salah S.; Liao, Limei; Martin, Heather N.; Butler, Rachael A.

    2011-01-01

    Background The risk for cardiovascular events is higher for those with metabolic syndrome (MetS), and it is known that firefighters have a fourfold risk for cardiovascular events. The purpose of this study was to quantify MetS prevalence and evaluate the effect of a low glycemic nutritional fitness program on the reduction of MetS risk factors among firefighters. Methods Professional firefighters were screened for MetS then enrolled in a low glycemic nutritional fitness program for a 12-week period. Anthropometric and physiologic measurements were obtained at the start and end of the program. Subjects with ≥3 of the following were positive for MetS: waist ≥40 (men) or ≥35 inches (women), BP≥135 (systole) or ≥85 (diastole) mmHg, fasting blood sugar ≥100mg/dl, triglycerides ≥150mg/dl, and high-density lipoproteins <40 (men) or <50 mg/dl (women). Weekly training was provided with low glycemic nutrition and regular fitness and evaluation of individual progress. Results Seventy-five firefighters (age 42+8yrs, mostly Caucasian men) had a total MetS prevalence of 46.7% (p<0.05 vs normal population). One platoon (10 men, age 48±5yrs) was enrolled in the 12-week program. Most (7/10) had MetS at the baseline, but this prevalence decreased significantly after 12 weeks to 3 subjects (p=0.02). On average, subjects had 3.2±1.6 vs 1.9±1.7 MetS risk factors (p<0.01) at baseline and 12 week interval, respectively. Conclusions The prevalence of MetS and MetS risk factors are higher among professional firefighters compared to general population. A short-duration low glycemic fitness program can successfully improve anthropometric and physiologic measures and reduce the prevalence of MetS. PMID:21263343

  16. 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

  17. 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. PMID:26045896

  18. 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. PMID:26334030

  19. [Development of syndrome of inappropriate secretion of ADH and reversible posterior leukoencephalopathy during initial rituximab-CHOP therapy in a patient with diffuse large B-cell lymphoma].

    PubMed

    Mizutani, Minoru; Nakamori, Yoshiki; Sakaguchi, Haruna; Kageyama, Yuki; Oya, Eiko; Ino, Kazuko; Suzuki, Kei; Sekine, Takao

    2013-03-01

    A 61-year-old woman presented with a right mandibular tumor and was diagnosed with DLBCL clinical stage IIIA from the biopsy results of the tumor and CT examination. An initial rituximab was administrated a week after the first CHOP treatment. During the infusion of rituximab, she exhibited disorientation, seizure, and consciousness disturbance. Hyponatremia due to SIADH and hypertension were coincidentally observed. MRI revealed T2 and FLAIR hyperintense signals involving the bilateral occipital, parietal, frontal lobes and the cerebellum that were consistent with reversible posterior leukoencephalopathy syndrome (RPLS). Her consciousness level recovered in parallel with corrections in serum sodium levels and blood pressure. Although she presented with transient cortical blindness, all neurological abnormalities disappeared 40 hours after the occurrence of seizure. She received a further 7 cycles of CHOP followed by 7 cycles of rituximab treatment with no relapse of RPLS. After irradiation for a residual abdominal tumor, she has maintained complete remission for 2 years. Although RPLS is a rare complication of rituximab-CHOP chemotherapy, it should be considered in patients with DLBCL who present with acute neurological deterioration.

  20. Effect of saliva stabilisers on detection of porcine reproductive and respiratory syndrome virus in oral fluid by quantitative reverse transcriptase real-time PCR.

    PubMed

    Decorte, Inge; Van der Stede, Yves; Nauwynck, Hans; De Regge, Nick; Cay, Ann Brigitte

    2013-08-01

    This study evaluated the effect of extraction-amplification methods, storage temperature and saliva stabilisers on detection of porcine reproductive and respiratory syndrome virus (PRRSV) RNA by quantitative reverse transcriptase real-time PCR (qRT-PCR) in porcine oral fluid. The diagnostic performance of different extraction-amplification methods was examined using a dilution series of oral fluid spiked with PRRSV. To determine RNA stability, porcine oral fluid, with or without commercially available saliva stabilisers, was spiked with PRRSV, stored at 4°C or room temperature and tested for the presence of PRRSV RNA by qRT-PCR. PRRSV RNA could be detected in oral fluid using all extraction-amplification combinations, but the limit of detection varied amongst different combinations. Storage temperature and saliva stabilisers had an effect on the stability of PRRSV RNA, which could only be detected for 7 days when PRRSV spiked oral fluid was kept at 4°C or stabilised at room temperature with a commercial mRNA stabiliser.

  1. 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.

  2. Oral administration of diphenylarsinic acid, a degradation product of chemical warfare agents, induces oxidative and nitrosative stress in cerebellar Purkinje cells.

    PubMed

    Kato, Koichi; Mizoi, Mutsumi; An, Yan; Nakano, Masayuki; Wanibuchi, Hideki; Endo, Ginji; Endo, Yoko; Hoshino, Mikio; Okada, Shoji; Yamanaka, Kenzo

    2007-11-10

    A new clinical syndrome with prominent cerebellar symptoms in patients living in Kamisu City, Ibaraki Prefecture, Japan, is described. Since the patients ingested drinking water containing diphenylarsinic acid (DPA), a stable degradation product of both diphenylcyanoarsine and diphenylchloroarsine, which were developed for use as chemical weapons and cause severe vomiting and sneezing, DPA was suspected of being responsible for the clinical syndrome. The purpose of the present study was to elucidate prominent cerebellar symptoms due to DPA. The aim of the study was to determine if single (15 mg/kg) or continuous (5 mg/kg/day for 5 weeks) oral administration of DPA to ICR-strain mice induced oxidative and/or nitrosative stress in their brain. Significantly positive staining with malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) was observed in the cerebellar Purkinje cells by repeated administration (5 mg/kg/day) with DPA for 5 weeks that led to the cerebellar symptoms from a behavioral pharmacology standpoint and by single administration of DPA (15 mg/kg). Furthermore, it is possible that the production of 3-NT was not caused by peroxynitrite formation. The present results suggest the possibility that arsenic-associated novel active species may be a factor underlying the oxidative and nitrosative stress in Purkinje cells due to exposure to DPA, and that the damage may lead to the cerebellar symptoms.

  3. 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.

  4. Cerebellar secretin modulates eyeblink classical conditioning.

    PubMed

    Fuchs, Jason R; Robinson, Gain M; Dean, Aaron M; Schoenberg, Heidi E; Williams, Michael R; Morielli, Anthony D; Green, John T

    2014-12-01

    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.

  5. 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

  6. Discovery of novel human and animal cells infected by the severe acute respiratory syndrome coronavirus by replication-specific multiplex reverse transcription-PCR.

    PubMed

    Gillim-Ross, Laura; Taylor, Jill; Scholl, David R; Ridenour, Jared; Masters, Paul S; Wentworth, David E

    2004-07-01

    The severe acute respiratory syndrome coronavirus (SARS-CoV) is the causative agent of the recent outbreak of severe acute respiratory syndrome. VeroE6 cells, fetal rhesus monkey kidney cells, and human peripheral blood mononuclear cells were the only cells known to be susceptible to SARS-CoV. We developed a multiplex reverse transcription-PCR assay to analyze the susceptibility of cells derived from a variety of tissues and species to SARS-CoV. Additionally, productive infection was determined by titration of cellular supernatants. Cells derived from three species of monkey were susceptible to SARS-CoV. However, the levels of SARS-CoV produced differed by 4 log(10). Mink lung epithelial cells (Mv1Lu) and R-Mix, a mixed monolayer of human lung-derived cells (A549) and mink lung-derived cells (Mv1Lu), are used by diagnostic laboratories to detect respiratory viruses (e.g., influenza virus); they were also infected with SARS-CoV, indicating that the practices of diagnostic laboratories should be examined to ensure appropriate biosafety precautions. Mv1Lu cells produce little SARS-CoV compared to that produced by VeroE6 cells, which indicates that they are a safer alternative for SARS-CoV diagnostics. Evaluation of cells permissive to other coronaviruses indicated that these cell types are not infected by SARS-CoV, providing additional evidence that SARS-CoV binds an alternative receptor. Analysis of human cells derived from lung, kidney, liver, and intestine led to the discovery that human cell lines were productively infected by SARS-CoV. This study identifies new cell lines that may be used for SARS-CoV diagnostics and/or basic research. Our data and other in vivo studies indicate that SARS-CoV has a wide host range, suggesting that the cellular receptor(s) utilized by SARS-CoV is highly conserved and is expressed by a variety of tissues.

  7. The microvasculature of the human cerebellar meninges.

    PubMed

    Nonaka, Hiroko; Akima, Michiko; Hatori, Tsutomu; Nagayama, Tadashi; Zhang, Zean; Ihara, Fumie

    2002-12-01

    The vascular architecture of the human cerebellar meninges was investigated. The surface meninges were poor in vasculature. In the sulci, the meninges were highly vascular but had few capillaries. The venous blood vessels gave long side branches at right angles to the parent vessels in a cruciform pattern, running horizontally along the cerebellar sulci. They were situated at the origin of the secondary or tertiary sulci. Anastomoses between these horizontal branches gave a crosshatched appearance. Short branches often extended to the bases of the sulci, terminating in T-shaped bifurcations with numerous tiny branches, like the roots of a tree. The arteries ran perpendicular to venous branches which were parallel to each other exclusively along the sagittal plane. These arteries bifurcated to straddle the horizontally running veins at the origin of the secondary or tertiary sulci. They gave off many small branches like teeth of a fork from each artery in the secondary or tertiary sulci after they bifurcated to straddle the venous branches and penetrated the cerebellar cortex at the bases of sulci. These fork-like ramifications in the bases of the sulci were most likely responsible for the ready development of pronounced ischemic state. They might also play an important role in the occurrence of ischemic damage at the bases of sulci in cases of severe generalized ischemia.

  8. From cerebellar texture to movement optimization.

    PubMed

    Sultan, Fahad

    2014-10-01

    The cerebellum is a major site for supervised procedural learning and appears to be crucial for optimizing sensorimotor performance. However, the site and origin of the supervising signal are still elusive. Furthermore, its relationship with the prominent neuronal circuitry remains puzzling. In this paper, I will review the relevant information and seek to synthesize a working hypothesis that explains the unique cerebellar structure. The aim of this review was to link the distinctive functions of the cerebellum, as derived from cerebellar lesion studies, with potential elementary computations, as observed by a bottom-up approach from the cerebellar microcircuitry. The parallel fiber geometry is ideal for performing millisecond computations that extract instructive signals. In this scenario, the higher time derivatives of kinematics such as acceleration and/or jerk that occur during motor performance are detected via a tidal wave mechanism and are used (with appropriate gating) as the instructive signal to guide motor smoothing. The advantage of such a mechanism is that movements are optimized by reducing "jerkiness" which, in turn, lowers their energy requirements. PMID:25037239

  9. 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

  10. Isolated lateropulsion of the trunk in cerebellar infarct.

    PubMed

    Shan, D E; Wang, V; Chen, J T

    1995-05-01

    MRI in a 63-year-old male with isolated lateropulsion of the trunk disclosed an infarct in the inferior portion of the right cerebellar hemisphere, suggesting an end-zone type infarct in the lateral branch of the right posterior inferior cerebellar artery (1PICA) or a borderzone infarct between 1PICA and superior cerebellar artery. A close clinico-topographical relationship between isolated lateropulsion of the trunk and lesion in the territory of 1PICA was demonstrated.

  11. 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.

  12. 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. PMID:11532563

  13. Supratentorial arterial ischemic stroke following cerebellar tumor resection in two children.

    PubMed

    Catsman-Berrevoets, Coriene E; van Breemen, Melanie; van Veelen, Marie Lise; Appel, Inge M; Lequin, Maarten H

    2005-01-01

    We describe two children who developed ischemic strokes in the territory of the middle cerebral artery, one 7 days and one 11 days after resection of a cerebellar tumor. In the first child, another infarction occurred in the territory of the contralateral middle cerebral artery 5 days after the first stroke. No specific cause or underlying risk factor other than the surgical procedure was found. The subacute clinical course at stroke onset resembled that of the 'posterior fossa syndrome', suggesting a common underlying mechanism. PMID:16088257

  14. Cerebellar ataxia as the presenting manifestation of Lyme disease.

    PubMed

    Arav-Boger, Ravit; Crawford, Thomas; Steere, Allen C; Halsey, Neal A

    2002-04-01

    A 7-year-old boy from suburban Baltimore who presented with cerebellar ataxia and headaches was found by magnetic resonance imaging to have multiple cerebellar enhancing lesions. He had no history of tick exposure. He was initially treated with steroids for presumptive postinfectious encephalitis. Lyme disease was diagnosed 10 weeks later after arthritis developed. Testing of the cerebrospinal fluid obtained at the time cerebellar ataxia was diagnosed revealed intrathecal antibody production to Borrelia burgdorferi. Treatment with intravenous antibiotics led to rapid resolution of persistent cerebellar findings.

  15. Cerebellar liponeurocytoma in two siblings suggests a possible familial predisposition.

    PubMed

    Pikis, Stylianos; Fellig, Yakov; Margolin, Emil

    2016-10-01

    There is limited data on the genetic origin and natural history of cerebellar liponeurocytoma. To the best of our knowledge there has been only one report of a familial presentation of this rare entity. We report a 72-year-old female with a posterior fossa tumor presenting with progressive cerebellar signs and symptoms. The patient underwent total tumor resection via an uncomplicated sub-occipital craniotomy. Histopathologic examination was diagnostic for cerebellar liponeurocytoma. Her sister was previously treated for a similar tumor. Our report provides further evidence for the possible existence of a hereditary abnormality predisposing afflicted families to cerebellar liponeurocytoma development. PMID:27349466

  16. Discordance between cerebellar metabolism and perfusion: Explanation for SPECT vs. PET differences in the cerebellum

    SciTech Connect

    Meyer, M.; Beltran, M.; Moore, M.

    1994-05-01

    The cerebellum normally has a level of HMPAO uptake that is equal to or greater than nearby frontal cortices on transaxial SPECT sections, whereas FDG PET studies shows the reverse. Since cerebral blood flow is generally coupled to metabolism in normal individuals, this study was performed to test the hypothesis that this difference represents a true discordance between cerebral perfusion and glucose metabolism of the cerebellar cortex. Thirty eight subjects underwent PET imaging after an intravenous bolus of N-13 ammonia (370 MBq) to image cerebral perfusion, later followed by an intravenous bolus of F-18 FDG (3 70 MBq) after the N-13 had disappeared by decay. All studies were acquired with a Siemens 931 ECAT camera with an initial 20 minute transmission scan of the head acquired to apply measured attenuation correction. PET imaging of N-13 ammonia was performed over the first 15 minutes after injection, and FDG imaging was performed between 40 and 55 minutes after injection. Regions of interest for both tracers in each of 38 patients were drawn over the cerebellar cortex from transaxial sections taken at the level of the dentate nuclei, and from the orbitofrontal cortex. Frontal to cerebellar cortex ratios are shown below for perfusion (open square) and metabolism (closed) for each of the 38 patients studied.

  17. Adenosine modulation of [Ca2+]i in cerebellar granular cells: multiple adenosine receptors involved.

    PubMed

    Vacas, Javier; Fernández, Mercedes; Ros, Manuel; Blanco, Pablo

    2003-12-01

    Elimination of adenosine by addition of adenosine deaminase (ADA) to the media leads to alterations in intracellular free calcium concentration ([Ca(2+)](i)) in cerebellar granular cells. Adenosine deaminase brings about increases or decreases in [Ca(2+)](i) depending on the previous activation state of the cell. These effects are dependent on the catalytic activity of adenosine deaminase, since its previous catalytic inactivation with Hg(2+) prevents the above-mentioned changes in intracellular calcium. Extracellular calcium is required for the increase in [Ca(2+)](i) promoted by ADA. This rise is insensitive to thapsigargin, but sensitive to micromolar concentrations of Ni(2+). Toxins specific for L, N and P/Q calcium channels do not overtly reduce this effect. N(6)-Cyclopentyl adenosine (CPA), an A(1) receptor agonist, produces a partial reversion of ADA effects, while CGS21680, A(2A)/A(2B) receptor agonist, slightly enhances them. Expression of A(1), A(2A), A(2B) and A(3) adenosine receptor mRNAs was detected in cerebellar granular cell cultures. These results suggest that adenosine modulate [Ca(2+)](i) in cerebellar granule cells through different adenosine receptor subtypes which, at least in part, seem to act through R-type calcium channels.

  18. 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.

  19. Schmahmann's syndrome - identification of the third cornerstone of clinical ataxiology.

    PubMed

    Manto, Mario; Mariën, Peter

    2015-01-01

    Schmahmann's syndrome represents a novel clinical condition consisting of a constellation of cognitive and affective deficits following cerebellar disease. The complex was first described in 1998 as cerebellar cognitive affective syndrome (CCAS) on the basis of a careful neurological examination, detailed bedside mental state tests, neuropsychological investigations and anatomical neuroimaging of a group of 20 patients with focal cerebellar disorders. The syndrome was characterized by four clusters of symptoms including: (a) impairment of executive functions such as planning, set-shifting, verbal fluency, abstract reasoning and working memory, (b) impaired visuo-spatial cognition, (c) personality changes with blunting of affect or abnormal behaviour, and (d) language deficits including agrammatism, wordfinding disturbances, disruption of language dynamics and dysprosodia. This complex of neurocognitive and behavioural-affective symptoms was ascribed to a functional disruption of the reciprocal pathways that connect the cerebellum with the limbic circuitry and the prefrontal, temporal and parietal association cortices. With the introduction of Schmahmann's syndrome, clinical ataxiology has found its third cornerstone, the two others being the cerebellar motor syndrome (CMS) mainly delineated by the pioneer French and English neurologists of the 19(th) and early 20(th) century, and the vestibulo-cerebellar syndrome (VCS) consisting of ocular instability, deficits of oculomotor movements and ocular misalignment. PMID:26331045

  20. 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.

  1. [Cerebellar Control of Ocular Movements: Application to the Topographical Diagnosis of Cerebellar Lesions].

    PubMed

    Hirose, Genjiro

    2016-03-01

    Over the last decade, substantial information on cerebellar oculomotor control has been provided by the use of sophisticated neuroanatomical, neurophysiological, and imaging techniques. We now know that an intact cerebellum is a prerequisite for normal oculomotor performance. This review clarifies the current knowledge on structure-function correlations of the cerebellum in relation to ocular movements and allows them to be applied to topographical diagnosis of cerebellar lesions. The cerebellar regions most closely related to oculomotor function are: (1) the flocculus/paraflocculus for VOR suppression, cancellation, smooth pursuit eye movement and gaze-holding, (2) the nodulus/ventral uvula for velocity storage and low frequency prolonged vestibular response, and (3) the dorsal oculomotor vermis (declive VI, folium VII) and the posterior portion of the fastigial nucleus (fastigial oculomotor region) for saccades and smooth pursuit initiation. Symptomatically, defects in the flocculus/parflocculus cause saccadic pursuit, downbeat nystagmus, and impairments to visual suppression of the VOR. Lesions of the nodulus/uvula reveal as periodic alternating nystagmus. Lesions of the oculomotor vermis and the fastigial nucleus can induce saccadic dysmetria, while fastigial nucleus lesions may also cause ocular flutter/opsoclonus. A detailed knowledge of cerebellar anatomy and the physiology of eye movements enables localization of lesions to specific areas of the cerebellum. PMID:27001776

  2. Dystonia and Cerebellar Degeneration in the Leaner Mouse Mutant

    PubMed Central

    Raike, Robert S.; Hess, Ellen J.; Jinnah, H.A.

    2015-01-01

    Cerebellar degeneration is traditionally associated with ataxia. Yet, there are examples of both ataxia and dystonia occurring in individuals with cerebellar degeneration. There is also substantial evidence suggesting that cerebellar dysfunction alone may cause dystonia. The types of cerebellar defects that may cause ataxia, dystonia, or both have not been delineated. In the current study, we explored the relationship between cerebellar degeneration and dystonia using the leaner mouse mutant. Leaner mice have severe dystonia that is associated with dysfunctional and degenerating cerebellar Purkinje cells. Whereas the density of Purkinje cells was not significantly reduced in 4 week-old leaner mice, approximately 50% of the neurons were lost by 34 weeks of age. On the other hand, the dystonia and associated functional disability became significantly less severe during this same interval. In other words, dystonia improved as Purkinje cells were lost, suggesting that dysfunctional Purkinje cells, rather than Purkinje cell loss, contribute to the dystonia. These results provide evidence that distorted cerebellar function may cause dystonia and support the concept that different types of cerebellar defects can have different functional consequences. PMID:25791619

  3. 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.

  4. 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…

  5. Molecular markers of neuronal progenitors in the embryonic cerebellar anlage.

    PubMed

    Morales, Daniver; Hatten, Mary E

    2006-11-22

    The cerebellum, like the cerebrum, includes a nuclear structure and an overlying cortical structure. Experiments in the past decade have expanded knowledge beyond the traditional function of the cerebellum to include critical roles in motor learning and memory and sensory discrimination. The initial steps in cerebellar development depend on inductive signaling involving FGF and Wnt proteins produced at the mesencephalic/metencephalic boundary. To address the issue of how individual cerebellar cell fates within the cerebellar territory are specified, we examined the expression of transcription factors, including mammalian homologues of LIM homeodomain-containing proteins, basic helix-loop-helix proteins, and three amino acid loop-containing proteins. The results of these studies show that combinatorial codes of transcription factors define precursors of the cerebellar nuclei, and both Purkinje cells and granule neurons of the cerebellar cortex. Examination of gene expression patterns in several hundred lines of Egfp-BAC (bacterial artificial chromosome) transgenic mice in the GENSAT Project revealed numerous genes with restricted expression in cerebellar progenitor populations, including genes specific for cerebellar nuclear precursors and Purkinje cell precursors. In addition, we identified patterns of gene expression that link granule and Purkinje cells to their precerebellar nuclei. These results identify molecular pathways that offer new insights on the development of the nuclear and cortical structures of the cerebellum, as well as components of the cerebellar circuitry.

  6. [General anesthesia for a girl with Joubert syndrome].

    PubMed

    Matsuura, Kokoro; Takeuchi, Muneyuki; Tachibana, Kazuya; Matsunari, Yasunori; Kinouchi, Keiko

    2010-03-01

    Joubert syndrome is a rare autosomal recessive disorder, which is characterized by absence or underdevelopment of the cerebellar vermis and severe developmental delay. The other common features include ataxia, an abnormal breathing pattern, abnormal eye movements and hypotonia. We report the anesthetic management in a 13-year-old girl with Joubert syndrome, scheduled for cauterization of nasal mucosa under general anesthesia. She had episodes of tachypnea and apnea. Oral midazolam 10 mg and famotidine 20 mg were administered 30 min before surgery. Anesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Vecuronium 2 mg was used to facilitate tracheal intubation. Mechanical ventilation was performed with a low ventilation setting of respiratory rate 5 beats x min(-1) and peak inspiratory pressure 9 cm H2O to maintain normal end-tidal CO2. Flurbiprofen axetil 30 mg was administered intravenously for analgesia, because opioids are not recommended. After reversal of muscle relaxation by atropin 0.5 mg and neostigmine 1.5 mg, her trachea was extubated. She did not develop postoperative apnea. In this patient with Joubert syndrome, midazolam, sevoflurane, nitrous oxide and flurbiprofen axetil were used without any complications. PMID:20229761

  7. 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.

  8. 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

  9. 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.

  10. The physiological basis of therapies for cerebellar ataxias.

    PubMed

    Mitoma, Hiroshi; Manto, Mario

    2016-09-01

    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

  11. 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

  12. Cerebellar ependymal cyst in a dog.

    PubMed

    Wyss-Fluehmann, G; Konar, M; Jaggy, A; Vandevelde, M; Oevermann, A

    2008-11-01

    An 11-week-old, male, Staffordshire Bull Terrier had a history of generalized ataxia and falling since birth. The neurologic findings suggested a localization in the cerebellum. Magnetic resonance imaging of the brain was performed. In all sequences the area of the cerebellum was almost replaced by fluid isointense to cerebrospinal fluid. A complete necropsy was performed after euthanasia. Histologically, the lesion was characterized by extensive loss of cerebellar tissue in both hemispheres and vermis. Toward the surface of the cerebellar defect, the cavity was confined by ruptured and folded membranes consisting of a layer of glial fibrillary acidic (GFAP)-positive glial cells covered multifocally by epithelial cells. Some of these cells bore apical cilia and were cytokeratin and GFAP negative, supporting their ependymal origin. The histopathologic features of our case are consistent with the diagnosis of an ependymal cyst. Its glial and ependymal nature as demonstrated by histopathologic and immunohistochemical examination differs from arachnoid cysts, which have also been reported in dogs. The origin of these cysts remains controversial, but it has been suggested that they develop during embryogenesis subsequent to sequestration of developing neuroectoderm. We speculate that the cyst could have been the result of a pre- or perinatal, possibly traumatic, insult because hemorrhage, and tissue destruction had occurred. To our knowledge, this is the first description of an ependymal cyst in the veterinary literature.

  13. [Surgical decompression for massive cerebellar infarction].

    PubMed

    Ogasawara, K; Koshu, K; Nagamine, Y; Fujiwara, S; Mizoi, K; Yoshimoto, T

    1995-01-01

    The authors report 10 patients with progressive neurological deterioration due to massive cerebellar infarctions. Computerized tomography scans confirmed obstructive hydrocephalus and brain stem compression. All 10 patients (seven men, three women; mean age, 59 years) were treated by external ventricular drainage and decompressive suboccipital craniectomy. After discharge from the hospital, they were followed up (23-101 months) and their functional independence was evaluated by the Barthel Index. The condition of three patients with brain-stem infarction had deteriorated despite decompressive surgery. Two of these died during the acute stage and one because severely disabled. The remaining seven patients showed neurological improvement during the postoperative period. Four patients with preoperative Japan Coma Scale of 100 returned to their previous jobs within the follow-up period and three patients with preoperative Japan Coma Scale of 200 required some assistance in daily activities. It is suggested that decompressive surgery may be beneficial for massive cerebellar infarction. The postoperative prognosis depends mainly on the presence or absence of coexisting brain-stem infarction. It is possible that, without brain-stem infarction, patients who remained in a "dependent" state may have recovered better if they had been operated on earlier.

  14. Insights into cerebellar development and medulloblastoma.

    PubMed

    Bihannic, Laure; Ayrault, Olivier

    2016-01-01

    Cerebellar development is an extensive process that begins during early embryonic stages and persists more than one year after birth in human. Therefore, the cerebellum is susceptible to acquire various developmental abnormalities leading to numerous diseases such as medulloblastoma, the most common pediatric malignant brain tumor. One third of the patients with medulloblastoma are incurable and survivors have a poor quality of life due to the aggressiveness of the broad-spectrum treatments. Within the past few years, it has been highlighted that medulloblastoma is a heterogeneous disease that is divided in four molecular subgroups. This recent advance in the field, combined with the development of associated preclinical models for each subgroup, should enable, in the future, the discovery and use of targeted therapy in clinical treatments for each subtype of medulloblastoma. In this review, we first aim to show how deregulation of cerebellar development can lead to medulloblastoma formation and then to present the advances in the molecular subgrouping of medulloblastoma and the associated preclinical models.

  15. Lgr4 protein deficiency induces ataxia-like phenotype in mice and impairs long term depression at cerebellar parallel fiber-Purkinje cell synapses.

    PubMed

    Guan, Xin; Duan, Yanhong; Zeng, Qingwen; Pan, Hongjie; Qian, Yu; Li, Dali; Cao, Xiaohua; Liu, Mingyao

    2014-09-19

    Cerebellar dysfunction causes ataxia characterized by loss of balance and coordination. Until now, the molecular and neuronal mechanisms of several types of inherited cerebellar ataxia have not been completely clarified. Here, we report that leucine-rich G protein-coupled receptor 4 (Lgr4/Gpr48) is highly expressed in Purkinje cells (PCs) in the cerebellum. Deficiency of Lgr4 leads to an ataxia-like phenotype in mice. Histologically, no obvious morphological changes were observed in the cerebellum of Lgr4 mutant mice. However, the number of PCs was slightly but significantly reduced in Lgr4(-/-) mice. In addition, in vitro electrophysiological analysis showed an impaired long term depression (LTD) at parallel fiber-PC (PF-PC) synapses in Lgr4(-/-) mice. Consistently, immunostaining experiments showed that the level of phosphorylated cAMP-responsive element-binding protein (Creb) was significantly decreased in Lgr4(-/-) PCs. Furthermore, treatment with forskolin, an adenylyl cyclase agonist, rescued phospho-Creb in PCs and reversed the impairment in PF-PC LTD in Lgr4(-/-) cerebellar slices, indicating that Lgr4 is an upstream regulator of Creb signaling, which is underlying PF-PC LTD. Together, our findings demonstrate for first time an important role for Lgr4 in motor coordination and cerebellar synaptic plasticity and provide a potential therapeutic target for certain types of inherited cerebellar ataxia. PMID:25063812

  16. Prenatal Cerebellar Disruptions: Neuroimaging Spectrum of Findings in Correlation with Likely Mechanisms and Etiologies of Injury.

    PubMed

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

    2016-08-01

    There is increasing evidence that the cerebellum is susceptible to prenatal infections and hemorrhages and that congenital morphologic anomalies of the cerebellum may be caused by disruptive (acquired) causes. Starting from the neuroimaging pattern, this report describes a spectrum of prenatal cerebellar disruptions including cerebellar agenesis, unilateral cerebellar hypoplasia, cerebellar cleft, global cerebellar hypoplasia, and vanishing cerebellum in Chiari type II malformation. The neuroimaging findings, possible causative disruptive events, and clinical features of each disruption are discussed. Recognition of cerebellar disruptions and their differentiation from cerebellar malformations is important in terms of diagnosis, prognosis, and genetic counselling. PMID:27423799

  17. Saccadic lateropulsion in Wallenberg's syndrome may be caused by a functional lesion of the fastigial nucleus.

    PubMed

    Helmchen, C; Straube, A; Büttner, U

    1994-06-01

    One of the clinical oculomotor hallmarks of lateral medullary infarction (Wallenberg's syndrome) is the so-called saccadic lateropulsion. In man and in animals, cerebellar lesions lead to dysmetric saccades and underline the importance of cerebellar control on saccadic accuracy. In order to study the lesion site responsible for saccadic lateropulsion we prospectively examined 12 patients with Wallenberg's syndrome who did not show a cerebellar lesion on CT or MRI. All patients consistently showed hypermetric saccades to the ipsilateral side and hypometric contralateral saccades comparable with the effects of cerebellar lesions in monkeys on saccadic accuracy. Based on the most recent experiments involving recordings from saccade-related neurons in the deep cerebellar nuclei of monkeys (oculo-motor region of fastigial nucleus), we hypothesize that saccadic lateropulsion in lateral medullary infarction is essentially identical with cerebellar saccadic dysmetria and results from a disruption of afferent olivocerebellar climbing fibres that gives rise to functional disinhibition of the cerebellar cortex and to increased inhibition of the deep cerebellar nuclei.

  18. 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

  19. Neural correlates of impaired emotional face recognition in cerebellar lesions.

    PubMed

    Adamaszek, Michael; Kirkby, Kenneth C; D'Agata, Fedrico; Olbrich, Sebastian; Langner, Sönke; Steele, Christopher; Sehm, Bernhard; Busse, Stefan; Kessler, Christof; Hamm, Alfons

    2015-07-10

    Clinical and neuroimaging data indicate a cerebellar contribution to emotional processing, which may account for affective-behavioral disturbances in patients with cerebellar lesions. We studied the neurophysiology of cerebellar involvement in recognition of emotional facial expression. Participants comprised eight patients with discrete ischemic cerebellar lesions and eight control patients without any cerebrovascular stroke. Event-related potentials (ERP) were used to measure responses to faces from the Karolinska Directed Emotional Faces Database (KDEF), interspersed in a stream of images with salient contents. Images of faces augmented N170 in both groups, but increased late positive potential (LPP) only in control patients without brain lesions. Dipole analysis revealed altered activation patterns for negative emotions in patients with cerebellar lesions, including activation of the left inferior prefrontal area to images of faces showing fear, contralateral to controls. Correlation analysis indicated that lesions of cerebellar area Crus I contribute to ERP deviations. Overall, our results implicate the cerebellum in integrating emotional information at different higher order stages, suggesting distinct cerebellar contributions to the proposed large-scale cerebral network of emotional face recognition. PMID:25912431

  20. Developmental dyslexia and widespread activation across the cerebellar hemispheres.

    PubMed

    Baillieux, Hanne; Vandervliet, Everhard J M; Manto, Mario; Parizel, Paul M; De Deyn, Peter P; Mariën, Peter

    2009-02-01

    Developmental dyslexia is the most common learning disability in school-aged children with an estimated incidence of five to ten percent. The cause and pathophysiological substrate of this developmental disorder is unclear. Recently, a possible involvement of the cerebellum in the pathogenesis of dyslexia has been postulated. In this study, 15 dyslexic children and 7 age-matched control subjects were investigated by means of functional neuroimaging (fMRI) using a noun-verb association paradigm. Comparison of activation patterns between dyslexic and control subjects revealed distinct and significant differences in cerebral and cerebellar activation. Control subjects showed bilaterally well-defined and focal activation patterns in the frontal and parietal lobes and the posterior regions of the cerebellar hemispheres. The dyslexic children, however, presented widespread and diffuse activations on the cerebral and cerebellar level. Cerebral activations were found in frontal, parietal, temporal and occipital regions. Activations in the cerebellum were found predominantly in the cerebellar cortex, including Crus I, Crus II, hemispheric lobule VI, VII and vermal lobules I, II, III, IV and VII. This preliminary study is the first to reveal a significant difference in cerebellar functioning between dyslexic children and controls during a semantic association task. As a result, we propose a new hypothesis regarding the pathophysiological mechanisms of developmental dyslexia. Given the sites of activation in the cerebellum in the dyslexic group, a defect of the intra-cerebellar distribution of activity is suspected, suggesting a disorder of the processing or transfer of information within the cerebellar cortex. PMID:18986695

  1. Contribution of Cerebellar Sensorimotor Adaptation to Hippocampal Spatial Memory

    PubMed Central

    Passot, Jean-Baptiste; Sheynikhovich, Denis; Duvelle, Éléonore; Arleo, Angelo

    2012-01-01

    Complementing its primary role in motor control, cerebellar learning has also a bottom-up influence on cognitive functions, where high-level representations build up from elementary sensorimotor memories. In this paper we examine the cerebellar contribution to both procedural and declarative components of spatial cognition. To do so, we model a functional interplay between the cerebellum and the hippocampal formation during goal-oriented navigation. We reinterpret and complete existing genetic behavioural observations by means of quantitative accounts that cross-link synaptic plasticity mechanisms, single cell and population coding properties, and behavioural responses. In contrast to earlier hypotheses positing only a purely procedural impact of cerebellar adaptation deficits, our results suggest a cerebellar involvement in high-level aspects of behaviour. In particular, we propose that cerebellar learning mechanisms may influence hippocampal place fields, by contributing to the path integration process. Our simulations predict differences in place-cell discharge properties between normal mice and L7-PKCI mutant mice lacking long-term depression at cerebellar parallel fibre-Purkinje cell synapses. On the behavioural level, these results suggest that, by influencing the accuracy of hippocampal spatial codes, cerebellar deficits may impact the exploration-exploitation balance during spatial navigation. PMID:22485133

  2. Cerebellar Processing of Sensory Inputs Primes Motor Cortex Plasticity

    PubMed Central

    Velayudhan, B.; Hubsch, C.; Pradeep, S.; Roze, E.; Vidailhet, M.; Meunier, S.; Kishore, A.

    2013-01-01

    Plasticity of the human primary motor cortex (M1) has a critical role in motor control and learning. The cerebellum facilitates these functions using sensory feedback. We investigated whether cerebellar processing of sensory afferent information influences the plasticity of the primary motor cortex (M1). Theta-burst stimulation protocols (TBS), both excitatory and inhibitory, were used to modulate the excitability of the posterior cerebellar cortex and to condition an ongoing M1 plasticity. M1 plasticity was subsequently induced in 2 different ways: by paired associative stimulation (PAS) involving sensory processing and TBS that exclusively involves intracortical circuits of M1. Cerebellar excitation attenuated the PAS-induced M1 plasticity, whereas cerebellar inhibition enhanced and prolonged it. Furthermore, cerebellar inhibition abolished the topography-specific response of PAS-induced M1 plasticity, with the effects spreading to adjacent motor maps. Conversely, cerebellar excitation had no effect on the TBS-induced M1 plasticity. This demonstrates the key role of the cerebellum in priming M1 plasticity, and we propose that it is likely to occur at the thalamic or olivo-dentate nuclear level by influencing the sensory processing. We suggest that such a cerebellar priming of M1 plasticity could shape the impending motor command by favoring or inhibiting the recruitment of several muscle representations. PMID:22351647

  3. Neural correlates of impaired emotional face recognition in cerebellar lesions.

    PubMed

    Adamaszek, Michael; Kirkby, Kenneth C; D'Agata, Fedrico; Olbrich, Sebastian; Langner, Sönke; Steele, Christopher; Sehm, Bernhard; Busse, Stefan; Kessler, Christof; Hamm, Alfons

    2015-07-10

    Clinical and neuroimaging data indicate a cerebellar contribution to emotional processing, which may account for affective-behavioral disturbances in patients with cerebellar lesions. We studied the neurophysiology of cerebellar involvement in recognition of emotional facial expression. Participants comprised eight patients with discrete ischemic cerebellar lesions and eight control patients without any cerebrovascular stroke. Event-related potentials (ERP) were used to measure responses to faces from the Karolinska Directed Emotional Faces Database (KDEF), interspersed in a stream of images with salient contents. Images of faces augmented N170 in both groups, but increased late positive potential (LPP) only in control patients without brain lesions. Dipole analysis revealed altered activation patterns for negative emotions in patients with cerebellar lesions, including activation of the left inferior prefrontal area to images of faces showing fear, contralateral to controls. Correlation analysis indicated that lesions of cerebellar area Crus I contribute to ERP deviations. Overall, our results implicate the cerebellum in integrating emotional information at different higher order stages, suggesting distinct cerebellar contributions to the proposed large-scale cerebral network of emotional face recognition.

  4. 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…

  5. Craniotomy for cerebellar hemangioblastoma excision in a patient with von Hippel–Lindau disease complicated by uncontrolled hypertension due to pheochromocytoma

    PubMed Central

    Mizobuchi, Yoshifumi; Kageji, Teruyoshi; Tadashi, Yamaguchi; Nagahiro, Shinji

    2015-01-01

    Introduction This report describes a patient with Von Hippel–Lindau (VHL) syndrome and uncontrolled hypertension due to pheochromocytoma who underwent craniotomy for the excision of a cerebellar hemangioblastoma combined with a laparoscopic adrenalectomy. Case report A 31-year-old man presented with severe headache. MRI showed areas of abnormal enhancement in the left cerebellum that were determined to be hemangioblastoma with mass effect and obstructive hydrocephalus. His blood pressure rose abruptly and could not be controlled. CT of the abdomen revealed bilateral suprarenal tumors, and the patient was diagnosed as having VHL syndrome.On the third day, he presented with increasing headache, a decreased level of consciousness, and hemiparesis. We were not able to perform an craniotomy because abdominal compression in the prone or sitting position resulted in severe hypertension. We performed ventricular drainage to control his ICP. On the fifth day, we first performed a bilateral laparoscopic adrenalectomy to control ICP and then moved the patient to the prone position before performing a craniotomy to remove the left cerebellar hemangioblastoma. Discu ssion & conclusion In patients with pheochromocytoma, the effects of catecholamine oversecretion can cause significant perioperative morbidity and mortality, but these can be prevented by appropriate preoperative medical management. When carrying out an excision of cerebellar hemangioblastomas in patients with intracranial hypertension complicated by abnormal hypertension due to pheochromocytoma whose blood pressure is not sufficiently controlled, tumor resection of the pheochromocytoma prior to cerebellar hemangioblastoma excision in the same surgery may prevent increased ICP and reduce perioperative risk. PMID:26595895

  6. A Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patient

    PubMed Central

    Pedroso, José Luiz; Povoas Barsottini, Orlando Graziani; Lin, Ling; Melberg, Atle; Oliveira, Acary S. B.; Mignot, Emmanuel

    2013-01-01

    Study Objectives: Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is caused by DNMT1 mutations. Diagnosing the syndrome can be difficult, as all clinical features may not be present at onset, HLA-DQB1*06:02 is often negative, and sporadic cases occur. We report on clinical and genetic findings in a 31-year-old woman with cerebellar ataxia, deafness, and narcolepsy, and discuss diagnostic challenges. Design: Clinical and genetic investigation in a patient and family members. Setting: Ataxia clinic, São Paulo, Brazil. Patients or Participants: One patient and her family members. Interventions: N/A. Measurements and Results: Narcolepsy was supported by polysomnographic and multiple sleep latency testing. HLA-DQB1*06:02 was positive. CSF hypocretin-1 was 191 pg/mL (normal values > 200 pg/mL). Mild brain atrophy was observed on MRI, with cerebellar involvement. The patient, her asymptomatic mother, and 3 siblings gave blood samples for genetic analysis. DNMT1 exons 20 and 21 were sequenced. Haplotyping of polymorphic markers surrounding the mutation was performed. The proband had a novel DNMT1 mutation in exon 21, p.Cys596Arg, c.1786T > C. All 4 parental haplotypes could be characterized in asymptomatic siblings without the mutation, indicating that the mutation is de novo in the patient. Conclusions: The Brazilian patient reported here further adds to the worldwide distribution of ADCA-DN. The mutation is novel, and illustrates a sporadic case with de novo mutation. We believe that many more cases with this syndrome are likely to be diagnosed in the near future, mandating knowledge of this condition and consideration of the diagnosis. Citation: Pedroso JL; Barsottini OGP; Lin L; Melberg A; Oliveira ASB; Mignot E. A novel de novo exon 21 DNMT1 mutation causes cerebellar ataxia, deafness, and narcolepsy in a Brazilian patient. SLEEP 2013;36(8):1257-1259. PMID:23904686

  7. The cerebellum is involved in reward-based reversal learning.

    PubMed

    Thoma, Patrizia; Bellebaum, Christian; Koch, Benno; Schwarz, Michael; Daum, Irene

    2008-01-01

    The cerebellum has recently been discussed in terms of a possible involvement in reward-based associative learning. To clarify the cerebellar contribution, eight patients with focal vascular lesions of the cerebellum and a group of 24 healthy subjects matched for age and IQ were compared on a range of different probabilistic outcome-based associative learning tasks, assessing acquisition, reversal, cognitive transfer, and generalization as well as the effect of reward magnitude. Cerebellar patients showed intact acquisition of stimulus contingencies, while reward-based reversal learning was significantly impaired. In addition, the patients showed slower acquisition of new stimulus contingencies in a second reward-based learning task, which might reflect reduced carry-over effects. Reward magnitude affected learning only during initial acquisition, with better learning on trials with high rewards in patients and control subjects. Overall, the findings suggest that the cerebellum is implicated in reversal learning as a dissociable component of reward-based learning. PMID:18592331

  8. Distal myopathy with rimmed vacuoles and cerebellar atrophy.

    PubMed

    Merkli, Hajnalka; Pál, Endre; Gáti, István; Czopf, József

    2006-01-01

    Distal myopathies constitute a clinically and pathologically heterogeneous group of genetically determined neuromuscular disorders, where the distal muscles of the upper or lower limbs are affected. The disease of a 41-year-old male patient started with gait disturbances, when he was 25. The progression was slow, but after 16 years he became seriously disabled. Neurological examination showed moderate to severe weakness in distal muscles of all extremities, marked cerebellar sign and steppage gait. Muscle biopsy resulted in myopathic changes with rimmed vacuoles. Brain MRI scan showed cerebellar atrophy. This case demonstrates a rare association of distal myopathy and cerebellar atrophy.

  9. Cerebellar morphological alterations in rats induced by prenatal ozone exposure.

    PubMed

    Rivas-Manzano, P; Paz, C

    1999-11-26

    The present study analyzes the morphological aspects of the cerebellum of rats with prenatal exposure to ozone. A double blind histological and planimetric analysis was performed studying sagittal sections of the anterior cerebellar lobe at postnatal days 0, 12 and 60. Ozone exposed rats showed cerebellar necrotic signs at age 0, diminished area of the molecular layer with Purkinje cells with pale nucleoli and perinucleolar bodies at age 12, and Purkinje cells showing nuclei with unusual clumps of chromatin in the periphery at age 60. We conclude that exposure to high concentrations of ozone during gestation induces permanent cerebellar damage in rats.

  10. [A case of cerebral gigantism with cerebellar atrophy].

    PubMed

    Kitazawa, K; Ikeda, M; Tsukagoshi, H

    1990-05-01

    A 37-year-old housewife, who had physical characteristics of cerebral gigantism, such as the tall stature, acromegaly, macrocephalia, high arched palate and antimongoloid slant, developed cerebellar ataxia and dysarthria. Her mother, uncle and grandmother were also reported to have slowly progressive gait disturbance. Her mother was also tall. Endocrinological studies failed to show any definite abnormality. CT and MRI revealed remarkable cerebellar atrophy. Though cerebral gigantism is often associated with clumsiness and incoordination, the etiology of the ataxia is poorly understood. This case indicates that the ataxia in cerebral gigantism may be, at least partly, caused by cerebellar atrophy. PMID:2401112

  11. Hereditary Cerebellar Ataxias: A Korean Perspective

    PubMed Central

    Kim, Ji Sun; Cho, Jin Whan

    2015-01-01

    Hereditary ataxia is a heterogeneous disorder characterized by progressive ataxia combined with/without peripheral neuropathy, extrapyramidal symptoms, pyramidal symptoms, seizure, and multiple systematic involvements. More than 35 autosomal dominant cerebellar ataxias have been designated as spinocerebellar ataxia, and there are 55 recessive ataxias that have not been named systematically. Conducting genetic sequencing to confirm a diagnosis is difficult due to the large amount of subtypes with phenotypic overlap. The prevalence of hereditary ataxia can vary among countries, and estimations of prevalence and subtype frequencies are necessary for planning a diagnostic strategy in a specific population. This review covers the various hereditary ataxias reported in the Korean population with a focus on the prevalence and subtype frequencies as the clinical characteristics of the various subtypes. PMID:26090078

  12. 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.

  13. Reversible lacrimal gland-protective regulatory T-cell dysfunction underlies male-specific autoimmune dacryoadenitis in the non-obese diabetic mouse model of Sjögren syndrome.

    PubMed

    Lieberman, Scott M; Kreiger, Portia A; Koretzky, Gary A

    2015-06-01

    CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells are required to maintain immunological tolerance; however, defects in specific organ-protective Treg cell functions have not been demonstrated in organ-specific autoimmunity. Non-obese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity and are a well-characterized model of Sjögren syndrome. Lacrimal gland disease in NOD mice is male-specific, but the role of Treg cells in this sex-specificity is not known. This study aimed to determine if male-specific autoimmune dacryoadenitis in the NOD mouse model of Sjögren syndrome is the result of lacrimal gland-protective Treg cell dysfunction. An adoptive transfer model of Sjögren syndrome was developed by transferring cells from the lacrimal gland-draining cervical lymph nodes of NOD mice to lymphocyte-deficient NOD-SCID mice. Transfer of bulk cervical lymph node cells modelled the male-specific dacryoadenitis that spontaneously develops in NOD mice. Female to female transfers resulted in dacryoadenitis if the CD4(+) CD25(+) Treg-enriched population was depleted before transfer; however, male to male transfers resulted in comparable dacryoadenitis regardless of the presence or absence of Treg cells within the donor cell population. Hormone manipulation studies suggested that this Treg cell dysfunction was mediated at least in part by androgens. Surprisingly, male Treg cells were capable of preventing the transfer of dacryoadenitis to female recipients. These data suggest that male-specific factors promote reversible dysfunction of lacrimal gland-protective Treg cells and, to our knowledge, form the first evidence for reversible organ-protective Treg cell dysfunction in organ-specific autoimmunity.

  14. Cerebellar transcranial direct current stimulation in neurological disease.

    PubMed

    Ferrucci, Roberta; Bocci, Tommaso; Cortese, Francesca; Ruggiero, Fabiana; Priori, Alberto

    2016-01-01

    Several studies have highlighted the therapeutic potential of transcranial direct current stimulation (tDCS) in patients with neurological diseases, including dementia, epilepsy, post-stroke dysfunctions, movement disorders, and other pathological conditions. Because of this technique's ability to modify cerebellar excitability without significant side effects, cerebellar tDCS is a new, interesting, and powerful tool to induce plastic modifications in the cerebellum. In this report, we review a number of interesting studies on the application of cerebellar tDCS for various neurological conditions (ataxia, Parkinson's disease, dystonia, essential tremor) and the possible mechanism by which the stimulation acts on the cerebellum. Study findings indicate that cerebellar tDCS is a promising therapeutic tool in treating several neurological disorders; however, this method's efficacy appears to be limited, given the current data. PMID:27595007

  15. Novel Approaches to Studying the Genetic Basis of Cerebellar Development

    PubMed Central

    Sajan, Samin A.; Waimey, Kathryn E.

    2010-01-01

    The list of genes that when mutated cause disruptions in cerebellar development is rapidly increasing. The study of both spontaneous and engineered mouse mutants has been essential to this progress, as it has revealed much of our current understanding of the developmental processes required to construct the mature cerebellum. Improvements in brain imaging, such as magnetic resonance imaging (MRI) and the emergence of better classification schemes for human cerebellar malformations, have recently led to the identification of a number of genes which cause human cerebellar disorders. In this review we argue that synergistic approaches combining classical molecular techniques, genomics, and mouse models of human malformations will be essential to fuel additional discoveries of cerebellar developmental genes and mechanisms. PMID:20387026

  16. 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

  17. Anomalous Cerebellar Anatomy in Chinese Children with Dyslexia.

    PubMed

    Yang, Ying-Hui; 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

  18. Cerebellar contributions to neurological soft signs in healthy young adults.

    PubMed

    Hirjak, Dusan; Thomann, Philipp A; Kubera, Katharina M; Stieltjes, Bram; Wolf, Robert C

    2016-02-01

    Neurological soft signs (NSS) are frequently found in psychiatric disorders of significant neurodevelopmental origin, e.g., in patients with schizophrenia and autism. Yet NSS are also present in healthy individuals suggesting a neurodevelopmental signature of motor function, probably as a continuum between health and disease. So far, little is known about the neural mechanisms underlying these motor phenomena in healthy persons, and it is even less known whether the cerebellum contributes to NSS expression. Thirty-seven healthy young adults (mean age = 23 years) were studied using high-resolution structural magnetic resonance imaging (MRI) and "resting-state" functional MRI at three Tesla. NSS levels were measured using the "Heidelberg Scale." Cerebellar gray matter volume was investigated using cerebellum-optimized voxel-based analysis methods. Cerebellar function was assessed using regional homogeneity (ReHo), a measure of local network strength. The relationship between cerebellar structure and function and NSS was analyzed using regression models. There was no significant relationship between cerebellar volume and NSS (p < 0.005, uncorrected for height, p < 0.05 corrected for spatial extent). Positive associations with cerebellar lobule VI activity were found for the "motor coordination" and "hard signs" NSS domains. A negative relationship was found between lobule VI activity and "complex motor task" domain (p < 0.005, uncorrected for height, p < 0.05 corrected for spatial extent). The data indicate that in healthy young adults, distinct NSS domains are related to cerebellar activity, specifically with activity of cerebellar subregions with known cortical somatomotor projections. In contrast, cerebellar volume is not predictive of NSS in healthy persons.

  19. Primary cerebellar agenesis presenting as isolated cognitive impairment

    PubMed Central

    Ashraf, Obaid; Jabeen, Shumyla; Khan, Azhar; Shaheen, Feroze

    2016-01-01

    Primary cerebellar agenesis is a rare entity. To the best of our knowledge, eleven living cases have been reported till date. Most of these were associated with some degree of motor impairment. We present a case of cerebellar agenesis in a child who presented with cognitive abnormalities leading to poor performance at school. No motor impairment was seen. Among the eleven cases reported earlier, only one case showed lack of motor impairment.

  20. Primary cerebellar agenesis presenting as isolated cognitive impairment

    PubMed Central

    Ashraf, Obaid; Jabeen, Shumyla; Khan, Azhar; Shaheen, Feroze

    2016-01-01

    Primary cerebellar agenesis is a rare entity. To the best of our knowledge, eleven living cases have been reported till date. Most of these were associated with some degree of motor impairment. We present a case of cerebellar agenesis in a child who presented with cognitive abnormalities leading to poor performance at school. No motor impairment was seen. Among the eleven cases reported earlier, only one case showed lack of motor impairment. PMID:27606028

  1. Oxidative injury in multiple sclerosis cerebellar grey matter.

    PubMed

    Kemp, Kevin; Redondo, Juliana; Hares, Kelly; Rice, Claire; Scolding, Neil; Wilkins, Alastair

    2016-07-01

    Cerebellar dysfunction is a significant contributor to disability in multiple sclerosis (MS). Both white matter (WM) and grey matter (GM) injury occurs within MS cerebellum and, within GM, demyelination, inflammatory cell infiltration and neuronal injury contribute to on-going pathology. The precise nature of cerebellar GM injury is, however, unknown. Oxidative stress pathways with ultimate lipid peroxidation and cell membrane injury occur extensively in MS and the purpose of this study was to investigate these processes in MS cerebellar GM. Post-mortem human cerebellar GM from MS and control subjects was analysed immunohistochemically, followed by semi-quantitative analysis of markers of cellular injury, lipid peroxidation and anti-oxidant enzyme expression. We have shown evidence for reduction in myelin and neuronal markers in MS GM, coupled to an increase in expression of a microglial marker. We also show that the lipid peroxidation product 4-hydroxynonenal co-localises with myelin and its levels negatively correlate to myelin basic protein levels. Furthermore, superoxide dismutase (SOD1 and 2) enzymes, localised within cerebellar neurons, are up-regulated, yet the activation of subsequent enzymes responsible for the detoxification of hydrogen peroxide, catalase and glutathione peroxidase are relatively deficient. These studies provide evidence for oxidative injury in MS cerebellar GM and further help define disease mechanisms within the MS brain. PMID:27086975

  2. Cannabinoids decrease excitatory synaptic transmission and impair long-term depression in rat cerebellar Purkinje cells.

    PubMed

    Lévénés, C; Daniel, H; Soubrié, P; Crépel, F

    1998-08-01

    1. CB-1 cannabinoid receptors are strongly expressed in the molecular layer of the cerebellar cortex. We have analysed, in patch-clamped Purkinje cells (PCs) in rat cerebellar slices, the effect of the selective CB-1 agonists WIN55,212-2 and CP55,940 and of the selective CB-1 antagonist SR141716-A on excitatory synaptic transmission and synaptic plasticity. 2. Bath application of both agonists markedly depressed parallel fibre (PF) EPSCs. This effect was reversed by SR141716-A. In contrast, responses of PCs to ionophoretic application of glutamate were not affected by WIN55, 212-2. 3. The coefficient of variation and the paired-pulse facilitation of these PF-mediated EPSCs increased in the presence of WIN55,212-2. 4. WIN55,212-2 decreased the frequency of miniature EPSCs and of asynchronous synaptic events evoked in the presence of strontium in the bath, but did not affect their amplitude. 5. WIN55, 212-2 did not change the excitability of PFs. 6. WIN55,212-2 impaired long-term depression induced by pairing protocols in PCs. This effect was antagonized by SR141716-A. The same impairment of LTD was produced by 2-chloroadenosine, a compound that decreases the probability of release of glutamate at PF-PC synapses. 7. The present study demonstrates that cannabinoids inhibit synaptic transmission at PF-PC synapses by decreasing the probability of release of glutamate, and thereby impair LTD. These two effects might represent a plausible cellular mechanism underlying cerebellar dysfunction caused by cannabinoids.

  3. Novel metabotropic glutamate receptor negatively coupled to adenylyl cyclase in cultured rat cerebellar astrocytes.

    PubMed

    Kanumilli, Srinivasan; Toms, Nick J; Roberts, Peter J

    2004-04-01

    Several excitatory amino acid ligands were found potently to inhibit forskolin-stimulated cAMP accumulation in rat cultured cerebellar astrocytes: L-cysteine sulfinic acid (L-CSA) = L-aspartate > L-glutamate >/= the glutamate uptake inhibitor, L-PDC. This property did not reflect activation of conventional glutamate receptors, since the selective ionotropic glutamate receptor agonists NMDA, AMPA, and kainate, as well as several mGlu receptor agonists [(1S,3R)-ACPD, (S)-DHPG, DCG-IV, L-AP4, L-quisqualate, and L-CCG-I], were without activity. In addition, the mGlu receptor antagonists, L-AP3, (S)-4CPG, Eglu, LY341495, (RS)-CPPG, and (S)-MCPG failed to reverse 30 microM glutamate-mediated inhibitory responses. L-PDC-mediated inhibition was abolished by the addition of the enzyme glutamate-pyruvate transaminase. This finding suggests that the effect of L-PDC is indirect and that it is mediated through endogenously released L-glutamate. Interestingly, L-glutamate-mediated inhibitory responses were resistant to pertussis toxin, suggesting that G(i)/G(o) type G proteins were not involved. However, inhibition of protein kinase C (PKC, either via the selective PKC inhibitor GF109203X or chronic PMA treatment) augmented glutamate-mediated inhibitory responses. Although mGlu3 receptors (which are negatively coupled to adenylyl cyclase) are expressed in astrocyte populations, in our study Western blot analysis indicated that this receptor type was not expressed in cerebellar astrocytes. We therefore suggest that cerebellar astrocytes express a novel mGlu receptor, which is negatively coupled to adenylyl cyclase, and possesses an atypical pharmacological profile. PMID:14999808

  4. Altered cerebellar connectivity in Parkinson's patients ON and OFF L-DOPA medication.

    PubMed

    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

  5. Defects in the CAPN1 Gene Result in Alterations in Cerebellar Development and Cerebellar Ataxia in Mice and Humans.

    PubMed

    Wang, Yubin; Hersheson, Joshua; Lopez, Dulce; Hammer, Monia; Liu, Yan; Lee, Ka-Hung; Pinto, Vanessa; Seinfeld, Jeff; Wiethoff, Sarah; Sun, Jiandong; Amouri, Rim; Hentati, Faycal; Baudry, Neema; Tran, Jennifer; Singleton, Andrew B; Coutelier, Marie; Brice, Alexis; Stevanin, Giovanni; Durr, Alexandra; Bi, Xiaoning; Houlden, Henry; Baudry, Michel

    2016-06-28

    A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO) mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1), which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans.

  6. 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

  7. Sex differences in cerebellar synaptic transmission and sex-specific responses to autism-linked Gabrb3 mutations in mice.

    PubMed

    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.

  8. Sex differences in cerebellar synaptic transmission and sex-specific responses to autism-linked Gabrb3 mutations in mice.

    PubMed

    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. PMID:27077953

  9. Iron overload-related heart failure in a patient with transfusion-dependent myelodysplastic syndrome reversed by intensive combined chelation therapy.

    PubMed

    Pinto, Valeria; Balocco, Manuela; Ambaglio, Ilaria; Derchi, Giorgio; Malcovati, Luca; Forni, Gian Luca

    2015-11-01

    Patients with transfusion-dependent myelodysplastic syndromes (MDS) have an increased risk of cardiac events, due to both chronic anemia and iron overload. Here, we report the recovery of cardiac function after an intensive iron chelation therapy in a MDS patient who had developed heart failure due to iron overload.

  10. Characteristic diffusion tensor tractography in multiple system atrophy with predominant cerebellar ataxia and cortical cerebellar atrophy.

    PubMed

    Fukui, Yusuke; Hishikawa, Nozomi; Sato, Kota; Nakano, Yumiko; Morihara, Ryuta; Ohta, Yasuyuki; Yamashita, Toru; Abe, Koji

    2016-01-01

    The objective of this study is to determine whether diffusion tensor imaging (DTI) tractography analysis is a potential method for differentiating cerebellar ataxia patients with multiple system atrophy with predominant cerebellar ataxia (MSA-C) and cortical cerebellar atrophy (CCA). Forty-one MSA-C patients (62.7 ± 8.1 years old, mean ± SD) and age- and gender-matched 15 CCA patients (63.0 ± 8.6 years old) were examined.Tractography was performed using the DTI track module provided in the MedINRIA version 1.9.4, and regions of interest were drawn manually to reconstruct an efferent fiber tract and two afferent fiber tracts via the cerebellum. Compared with CCA, MSA-C patients showed significant declines of fractional anisotropy (FA) values of afferent 1 and 2 (p<0.01, respectively) and a significant increase of the radial diffusivity (RD) value in afferent 1 (p<0.05). Receiver-operator characteristic curve analysis showed 85.7 % sensitivity and 75.0 % specificity of FA values in afferent 1 (cutoff value 0.476). Linear regressions showed strong correlations between FA value and disease duration in CCA patients (efferent 1, r = -0.466; afferent 2, r = -0.543; both p<0.05), and between the FA value and the ratio of the standardized scale for the assessment and rating of ataxia (SARA)/disease duration in MSA-C patients (afferent 1, r = -0.407; p<0.01). The present DTI tractography newly showed that the FA values of two afferent fiber tracts showed significant declines in MSA-C patients, and afferent 1 showed good diagnostic sensitivity and specificity. When combining the FA values of efferent 1 with disease duration, the present DTI tractography analysis could be useful for differentiating MSA-C and CCA patients.

  11. 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

  12. Disialotransferrin developmental deficiency syndrome.

    PubMed Central

    Kristiansson, B; Andersson, M; Tonnby, B; Hagberg, B

    1989-01-01

    Seven mentally deficient children and adolescents (three pairs of siblings and one singleton) were studied. A peculiar external appearance, a characteristic neurohepatosubcutaneous tissue impairment syndrome and, as a biological marker, an abnormal sialic acid transferrin pattern were characteristic features. All seven seemed odd from birth and prone to acute cerebral dysfunction during catabolic states. Abnormal lower neurone, cerebellar, and retinal functions dominated from later childhood. The disialotransferrin pattern found in serum and cerebrospinal fluid is thought to be the biological marker of a newly discovered inborn error of glycoprotein metabolism with autosomal recessive inheritance. Images Fig 1 Fig 2 p74-b PMID:2466439

  13. Cerebral gigantism associated with jaw cyst basal cell naevoid syndrome in two families.

    PubMed

    Cramer, H; Niederdellmann, H

    1983-01-01

    We report 9 subjects from 2 families with the syndrome of cerebral gigantism, seven of the patients also had jaw cyst basal cell naevoid syndrome. Neurological, radiological, somatic and biochemical features of this hitherto unreported association are described. Neurological symptoms included mild hydrocephalus, ventricular malformation, cerebellar syndrome, intracranial calcification, oculomotor disturbances, EEG abnormalities and rarely, mild peripheral nervous disorders. A disturbance of calcium metabolism appears to be a prominent feature of the genetically determined nonprogressive syndrome.

  14. Cerebellar development in the absence of Gbx function in zebrafish.

    PubMed

    Su, Chen-Ying; Kemp, Hilary A; Moens, Cecilia B

    2014-02-01

    The midbrain-hindbrain boundary (MHB) is a well-known organizing center during vertebrate brain development. The MHB forms at the expression boundary of Otx2 and Gbx2, mutually repressive homeodomain transcription factors expressed in the midbrain/forebrain and anterior hindbrain, respectively. The genetic hierarchy of gene expression at the MHB is complex, involving multiple positive and negative feedback loops that result in the establishment of non-overlapping domains of Wnt1 and Fgf8 on either side of the boundary and the consequent specification of the cerebellum. The cerebellum derives from the dorsal part of the anterior-most hindbrain segment, rhombomere 1 (r1), which undergoes a distinctive morphogenesis to give rise to the cerebellar primordium within which the various cerebellar neuron types are specified. Previous studies in the mouse have shown that Gbx2 is essential for cerebellar development. Using zebrafish mutants we show here that in the zebrafish gbx1 and gbx2 are required redundantly for morphogenesis of the cerebellar primordium and subsequent cerebellar differentiation, but that this requirement is alleviated by knocking down Otx. Expression of fgf8, wnt1 and the entire MHB genetic program is progressively lost in gbx1-;gbx2- double mutants but is rescued by Otx knock-down. This rescue of the MHB genetic program depends on rescued Fgf signaling, however the rescue of cerebellar primordium morphogenesis is independent of both Gbx and Fgf. Based on our findings we propose a revised model for the role of Gbx in cerebellar development.

  15. 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

  16. Abnormal cerebellar volume in acute and remitted major depression.

    PubMed

    Depping, Malte S; Wolf, Nadine D; Vasic, Nenad; Sambataro, Fabio; Hirjak, Dusan; Thomann, Philipp A; Wolf, Robert C

    2016-11-01

    Abnormal cortical volume is well-documented in patients with major depressive disorder (MDD), but cerebellar findings have been heterogeneous. It is unclear whether abnormal cerebellar structure relates to disease state or medication. In this study, using structural MRI, we investigated cerebellar volume in clinically acute (with and without psychotropic treatment) and remitted MDD patients. High-resolution structural MRI data at 3T were obtained from acute medicated (n=29), acute unmedicated (n=14) and remitted patients (n=16). Data from 29 healthy controls were used for comparison purposes. Cerebellar volume was investigated using cerebellum-optimized voxel-based analysis methods. Patients with an acute MDD episode showed increased volume of left cerebellar area IX, and this was true for both medicated and unmedicated individuals (p<0.05 cluster-corrected). Remitted patients exhibited bilaterally increased area IX volume. In remitted, but not in acutely ill patients, area IX volume was significantly associated with measures of depression severity, as assessed by the Hamilton Depression Rating Scale (HAMD). In addition, area IX volume in remitted patients was significantly related to the duration of antidepressant treatment. In acutely ill patients, no significant relationships were established using clinical variables, such as HAMD, illness or treatment duration and number of depressive episodes. The data suggest that cerebellar area IX, a non-motor region that belongs to a large-scale brain functional network with known relevance to core depressive symptom expression, exhibits abnormal volume in patients independent of clinical severity or medication. Thus, the data imply a possible trait marker of the disorder. However, given bilaterality and an association with clinical scores at least in remitted patients, the current findings raise the possibility that cerebellar volume may be reflective of successful treatment as well.

  17. The Cerebellum and SIDS: Disordered Breathing in a Mouse Model of Developmental Cerebellar Purkinje Cell Loss during Recovery from Hypercarbia

    PubMed Central

    Calton, Michele A.; Howard, Jeremy R.; Harper, Ronald M.; Goldowitz, Dan; Mittleman, Guy

    2016-01-01

    The cerebellum assists coordination of somatomotor, respiratory, and autonomic actions. Purkinje cell alterations or loss appear in sudden infant death and sudden death in epilepsy victims, possibly contributing to the fatal event. We evaluated breathing patterns in 12 wild-type (WT) and Lurcher mutant mice with 100% developmental cerebellar Purkinje cell loss under baseline (room air), and recovery from hypercapnia, a concern in sudden death events. Six mutant and six WT mice were exposed to 4-min blocks of increasing CO2 (2, 4, 6, and 8%), separated by 4-min recovery intervals in room air. Breath-by-breath patterns, including depth of breathing and end-expiratory pause (EEP) durations during recovery, were recorded. No baseline genotypic differences emerged. However, during recovery, EEP durations significantly lengthened in mutants, compared to WT mice, following the relatively low levels of CO2 exposure. Additionally, mutant mice exhibited signs of post-sigh disordered breathing during recovery following each exposure. Developmental cerebellar Purkinje cell loss significantly affects compensatory breathing patterns following mild CO2 exposure, possibly by inhibiting recovery from elevated CO2. These data implicate cerebellar Purkinje cells in the ability to recover from hypercarbia, suggesting that neuropathologic changes or loss of these cells contribute to inadequate ventilatory recovery to increased environmental CO2. Multiple disorders, including sudden infant death syndrome (SIDS) and sudden unexpected death in epilepsy (SUDEP), appear to involve both cardiorespiratory failure and loss or injury to cerebellar Purkinje cells; the findings support the concept that such neuropathology may precede and exert a prominent role in these fatal events. PMID:27242661

  18. Aprosencephaly and cerebellar dysgenesis in SIBS

    SciTech Connect

    Florell, S.R.; Townsend, J.J.; Klatt, E.C.

    1996-06-28

    Aprosencephaly is a rare, lethal malformation sequence of the central nervous system that has been attributed to a postneuralation encephaloclastic process. We describe autopsy findings consistent with aprosencephaly in 2 fetuses conceived from a consanguineous mating (first cousins). Both showed anecephalic manifestations; however, the crania were intact, with fused sutures. The neuropathologic findings were essentially identical. Each fetus had complete absence of the telecephalon and pyramidal tracts, rudimentary diencephalic and mesencephalic structures, primitive cerebellar hemispheres, posterolateral clusters of primitive neural cells in the medullas suggesting an abnormality of neural migration, a normally-formed spinal cord, and retinal dysplasia within normally-formed globes. In addition, both fetuses manifested a peculiar perivascular mesenchymal proliferation seen only within the central nervous system. The similarity of these cases, coupled with parental consanguinity, suggests a primary malformation in brain development due to the homozygous representation of a mutant allele. We hypothesize that these patients may represent a defect in a gene important in brain development, the nature of which has yet to be elucidated. 26 refs., 4 figs., 4 tabs.

  19. Morphological characteristics of the superior cerebellar artery.

    PubMed

    Dodevski, A; Tosovska Lazarova, D; Zhivadinovik, J; Lazareska, M; Stojovska-Jovanovska, E

    2015-01-01

    With the introduction of new techniques in diagnostic and interventional radiology and progress in micro neurosurgery, accurate knowledge of the brain blood vessels is essential for daily clinical work. The aim of this study was to describe the morphological characteristics of the superior cerebellar artery and to emphasize their clinical significance. In this study we examined radiographs of 109 patients who had CT angiography at the University Clinic for Radiology in Skopje, R. Macedonia. This study included 49 females and 60 males, ranging in age from 27 to 83 years; mean age 57.4 ± 11.8 years. In 105 patients SCA arose from the basilar artery on both sides as a single vessel. In two patients SCA arose as a duplicate trunk from the basilar artery. We found unilateral duplication on the right SCA in one patient, and bilateral duplication in one patient. In two patients was noticed origin of the SCA from PCA as a single trunk from adult type of the PCA. Through knowledge of the anatomy and variations of SCA is important for clinicians as well as basic scientists who deal with problems related to intracranial vasculature in daily basis for save performance of diagnostic and interventional procedures. PMID:26076777

  20. α6 integrin subunit regulates cerebellar development

    PubMed Central

    Marchetti, Giovanni; De Arcangelis, Adèle; Pfister, Véronique; Georges-Labouesse, Elisabeth

    2013-01-01

    Mutations in genes encoding several basal lamina components as well as their cellular receptors disrupt normal deposition and remodeling of the cortical basement membrane resulting in a disorganized cerebral and cerebellar cortex. The α6 integrin was the first α subunit associated with cortical lamination defects and formation of neural ectopias. In order to understand the precise role of α6 integrin in the central nervous system (CNS), we have generated mutant mice carrying specific deletion of α6 integrin in neuronal and glia precursors by crossing α6 conditional knockout mice with Nestin-Cre line. Cerebral cortex development occurred properly in the resulting α6fl/fl;nestin-Cre mutant animals. Interestingly, however, cerebellum displayed foliation pattern defects although granule cell (GC) proliferation and migration were not affected. Intriguingly, analysis of Bergmann glial (BG) scaffold revealed abnormalities in fibers morphology associated with reduced processes outgrowth and altered actin cytoskeleton. Overall, these data show that α6 integrin receptors are required in BG cells to provide a proper fissure formation during cerebellum morphogenesis. PMID:23722246

  1. Forebrain-Cerebellar Interactions During Learning

    PubMed Central

    Weible, Aldis P.; Galvez, Roberto; Disterhoft, John F.

    2013-01-01

    The cerebral cortex and cerebellum are high level neural centers that must interact cooperatively to generate coordinated and efficient goal directed movements, including those necessary for a well-timed conditioned response. In this review we describe the progress made in utilizing the forebrain-dependent trace eyeblink conditioning paradigm to understand the neural substrates mediating cerebro-cerebellar interactions during learning and consolidation of conditioned responses. This review expands upon our previous hypothesis that the interaction occurs at sites that project to the pontine nuclei (Weiss & Disterhoft, 1996), by offering more details on the function of the hippocampus and prefrontal cortex during acquisition and the circuitry involved in facilitating pontine input to the cerebellum as a necessary requisite for trace eyeblink conditioning. Our discussion describes the role of the hippocampus, caudal anterior cingulate gyrus, basal ganglia, thalamus, and sensory cortex, including the benefit of utilizing the whisker barrel cortical system. We propose that permanent changes in the sensory cortex, along with input from the caudate and claustrum, and a homologue of the primate dorsolateral prefrontal cortex, serve to bridge the stimulus free trace interval and allow the cerebellum to generate a well-timed conditioned response. PMID:26617664

  2. Morphological characteristics of the superior cerebellar artery.

    PubMed

    Dodevski, A; Tosovska Lazarova, D; Zhivadinovik, J; Lazareska, M; Stojovska-Jovanovska, E

    2015-01-01

    With the introduction of new techniques in diagnostic and interventional radiology and progress in micro neurosurgery, accurate knowledge of the brain blood vessels is essential for daily clinical work. The aim of this study was to describe the morphological characteristics of the superior cerebellar artery and to emphasize their clinical significance. In this study we examined radiographs of 109 patients who had CT angiography at the University Clinic for Radiology in Skopje, R. Macedonia. This study included 49 females and 60 males, ranging in age from 27 to 83 years; mean age 57.4 ± 11.8 years. In 105 patients SCA arose from the basilar artery on both sides as a single vessel. In two patients SCA arose as a duplicate trunk from the basilar artery. We found unilateral duplication on the right SCA in one patient, and bilateral duplication in one patient. In two patients was noticed origin of the SCA from PCA as a single trunk from adult type of the PCA. Through knowledge of the anatomy and variations of SCA is important for clinicians as well as basic scientists who deal with problems related to intracranial vasculature in daily basis for save performance of diagnostic and interventional procedures.

  3. Multiplexed coding by cerebellar Purkinje neurons

    PubMed Central

    Hong, Sungho; Negrello, Mario; Junker, Marc; Smilgin, Aleksandra; Thier, Peter; De Schutter, Erik

    2016-01-01

    Purkinje cells (PC), the sole output neurons of the cerebellar cortex, encode sensorimotor information, but how they do it remains a matter of debate. Here we show that PCs use a multiplexed spike code. Synchrony/spike time and firing rate encode different information in behaving monkeys during saccadic eye motion tasks. Using the local field potential (LFP) as a probe of local network activity, we found that infrequent pause spikes, which initiated or terminated intermittent pauses in simple spike trains, provide a temporally reliable signal for eye motion onset, with strong phase-coupling to the β/γ band LFP. Concurrently, regularly firing, non-pause spikes were weakly correlated with the LFP, but were crucial to linear encoding of eye movement kinematics by firing rate. Therefore, PC spike trains can simultaneously convey information necessary to achieve precision in both timing and continuous control of motion. DOI: http://dx.doi.org/10.7554/eLife.13810.001 PMID:27458803

  4. 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

  5. Acute cerebellar dysfunction with neuromuscular manifestations after scorpionism presumably caused by Tityus obscurus in Santarém, Pará / Brazil.

    PubMed

    Torrez, Pasesa P Q; Quiroga, Mariana M M; Abati, Paulo A M; Mascheretti, Melissa; Costa, Walter Silva; Campos, Luciana P; França, Francisco O S

    2015-03-01

    Scorpionism is a public health problem in many tropical countries, especially in North Africa, South India, Latin America and the Middle East. In Brazil, patients with severe scorpion envenoming have mainly cardiovascular events, including acute heart failure, acute respiratory distress syndrome and shock, death is rare. We described 58 accidents presumably caused by Tityus obscurus in Brazilian Amazonia. Patients reported a sensation of "electric shocks" which could last hours. The vast majority of patients presented a clinical picture compatible with acute cerebellar dysfunction, beginning minutes and lasting up to 2 days after the accident. They presented cerebellar ataxia, dysdiadochokinesia, dysmetry, dysarthria, dyslalia, nausea and vomiting. Besides, some patients presented myoclonus and fasciculation which can also be attributed to cerebellar dysfunction or maybe the result of direct action on skeletal muscle. Two patients had evidence of intense rhabdomyolysis and acute kidney injury. The clinical picture in this scorpion envenoming is mainly characterized by an acute dysfunction of cerebellar activities and abnormal neuromuscular manifestations and in some cases muscle injury which are not described in any other region of the world. This work presents clinical, epidemiologic, laboratory and treatment aspects of this unmatched scorpion envenoming in the state of Pará, northern Brazil. PMID:25549940

  6. Developmental Subchronic Exposure to Diphenylarsinic Acid Induced Increased Exploratory Behavior, Impaired Learning Behavior, and Decreased Cerebellar Glutathione Concentration in Rats

    PubMed Central

    Negishi, Takayuki; Matsunaga, Yuki

    2013-01-01

    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. PMID:24008832

  7. 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

    2007-06-01

    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.

  8. Reversible dementias

    PubMed Central

    Tripathi, Manjari; Vibha, Deepti

    2009-01-01

    In recent years, more attention has been given to the early diagnostic evaluation of patients with dementia which is essential to identify patients with cognitive symptoms who may have treatable conditions. Guidelines suggest that all patients presenting with dementia or cognitive symptoms should be evaluated with a range of laboratory tests, and with structural brain imaging with computed tomography (CT) or magnetic resonance imaging (MRI). While many of the disorders reported as ‘reversible dementias’ are conditions that may well be associated with cognitive or behavioral symptoms, these symptoms are not always sufficiently severe to fulfill the clinical criteria for dementia. Thus, while the etiology of a condition may be treatable it should not be assumed that the associated dementia is fully reversible. Potentially reversible dementias should be identified and treatment considered, even if the symptoms are not sufficiently severe to meet the clinical criteria for dementia, and even if partial or full reversal of the cognitive symptoms cannot be guaranteed. In the literature, the most frequently observed potentially reversible conditions identified in patients with cognitive impairment or dementia are depression, adverse effects of drugs, drug or alcohol abuse, space-occupying lesions, normal pressure hydrocephalus, and metabolic conditions land endocrinal conditions like hypothyroidism and nutritional conditions like vitamin B-12 deficiency. Depression is by far the most common of the potentially reversible conditions. The review, hence addresses the common causes of reversible dementia and the studies published so far. PMID:21416018

  9. 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

  10. 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. PMID:23630472

  11. Cerebellar liponeurocytoma: A case report and review of the literature

    PubMed Central

    WANG, KE; NI, MING; WANG, LIANG; JIA, GUIJUN; WU, ZHEN; ZHANG, LIWEI; ZHANG, JUNTING

    2016-01-01

    Cerebellar liponeurocytoma is rare, and the clinical characteristics and treatment strategy remain unclear. In the present study, a case of cerebellar liponeurocytoma was retrospectively reported and a literature review was performed. A 45-year-old female presented due to occipital headaches, exhibiting a hoarse voice and a broad-based gait. Pre-operative magnetic resonance images revealed a lesion occupying the right hemisphere of the cerebellum and the inferior vermis, compressing the medulla oblongata from the right side, and extending through the foramen magnum to the C2 level. A total resection was performed, and pathological analysis of the lesion showed positivity for synaptophysin, S-100 and neuronal nuclear antigen, partial positivity for Olig-2, and negativity for glial fibrillary acidic protein and epithelial membrane antigen. In addition, the Ki-67 index was low (<5%). Thus, a diagnosis of cerebellar liponeurocytoma was determined. Total resection was successful and the patient was followed up closely. A review of the literature showed that cerebellar liponeurocytoma is mainly located in the cerebellum, with rare extra-cerebellar cases. Certain studies have suggested that the tumor may be located supratentorially and subtentorially, and should be renamed as solely liponeurocytoma. Total resection of the tumor contributes to an improved prognosis, while a subtotal resection and high Ki-67 index lead to recurrence. The tumor is similar to a tumor of low malignancy, with long-term recurrence. Radiation is recommended when there is residual tumor, recurrence or when the Ki-67 is high. PMID:26893691

  12. 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

  13. 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.

  14. 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.

  15. Lateralized cognitive deficits in children following cerebellar lesions.

    PubMed

    Scott, R B; Stoodley, C J; Anslow, P; Paul, C; Stein, J F; Sugden, E M; Mitchell, C D

    2001-10-01

    The aim of this preliminary study was to examine the developing cognitive profiles of children with cerebellar tumours in a consecutive series of clinical patients. MRI and longitudinal intellectual profiles were obtained on seven children (two females, five males; mean age 3 years at diagnosis; mean age 7 years at first assessment). Tumours in three of the children were astrocytomas; of the remaining tumours, two were medulloblastomas, one low-grade glioma, and one ependymoma. In right-handed children, we observed an association between greater damage to right cerebellar structures and a plateauing in verbal and/or literacy skills. In contrast, greater damage to left cerebellar structures was associated with delayed or impaired non-verbal/spatial skills. Long-term cognitive development of the children studied tentatively supports a role for the cerebellum in learning/development. These findings suggest that lateralized cerebellar damage may selectively impair the development of cognitive functions subserved by the contralateral cerebral hemisphere and, in addition, that all children with cerebellar lesions in early childhood should routinely undergo long-term monitoring of their intellectual development. PMID:11665825

  16. Mitotic Events in Cerebellar Granule Progenitor Cells that Expand Cerebellar Surface Area Are Critical for Normal Cerebellar Cortical Lamination in Mice

    PubMed Central

    Chang, Joshua C.; Leung, Mark; Gokozan, Hamza Numan; Gygli, Patrick Edwin; Catacutan, Fay Patsy; Czeisler, Catherine; Otero, José Javier

    2015-01-01

    Late embryonic and postnatal cerebellar folial surface area expansion promotes cerebellar cortical cytoarchitectural lamination. We developed a streamlined sampling scheme to generate unbiased estimates of murine cerebellar surface area and volume using stereological principles. We demonstrate that during the proliferative phase of the external granule layer (EGL) and folial surface area expansion, EGL thickness does not change and thus is a topological proxy for progenitor self-renewal. The topological constraints indicate that during proliferative phases, migration out of the EGL is balanced by self-renewal. Progenitor self-renewal must, therefore, include mitotic events yielding either 2 cells in the same layer to increase surface area (β-events) and mitotic events yielding 2 cells, with 1 cell in a superficial layer and 1 cell in a deeper layer (α-events). As the cerebellum grows, therefore, β-events lie upstream of α-events. Using a mathematical model constrained by the measurements of volume and surface area, we could quantify inter-mitotic times for β-events on a per-cell basis in post-natal mouse cerebellum. Furthermore, we found that loss of CCNA2, which decreases EGL proliferation and secondarily induces cerebellar cortical dyslamination, shows preserved α-type events. Thus, CCNA2-null cerebellar granule progenitor cells are capable of self-renewal of the EGL stem cell niche; this is concordant with prior findings of extensive apoptosis in CCNA2-null mice. Similar methodologies may provide another layer of depth to the interpretation of results from stereological studies. PMID:25668568

  17. 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

  18. 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)

  19. 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

  20. Recurrent cerebellar architecture solves the motor-error problem.

    PubMed Central

    Porrill, John; Dean, Paul; Stone, James V.

    2004-01-01

    Current views of cerebellar function have been heavily influenced by the models of Marr and Albus, who suggested that the climbing fibre input to the cerebellum acts as a teaching signal for motor learning. It is commonly assumed that this teaching signal must be motor error (the difference between actual and correct motor command), but this approach requires complex neural structures to estimate unobservable motor error from its observed sensory consequences. We have proposed elsewhere a recurrent decorrelation control architecture in which Marr-Albus models learn without requiring motor error. Here, we prove convergence for this architecture and demonstrate important advantages for the modular control of systems with multiple degrees of freedom. These results are illustrated by modelling adaptive plant compensation for the three-dimensional vestibular ocular reflex. This provides a functional role for recurrent cerebellar connectivity, which may be a generic anatomical feature of projections between regions of cerebral and cerebellar cortex. PMID:15255096

  1. Cerebellar networks with the cerebral cortex and basal ganglia.

    PubMed

    Bostan, Andreea C; Dum, Richard P; Strick, Peter L

    2013-05-01

    The dominant view of cerebellar function has been that it is exclusively concerned with motor control and coordination. Recent findings from neuroanatomical, behavioral, and imaging studies have profoundly changed this view. Neuroanatomical studies using virus transneuronal tracers have demonstrated that cerebellar output reaches vast areas of the neocortex, including regions of prefrontal and posterior parietal cortex. Furthermore, it has recently become clear that the cerebellum is reciprocally connected with the basal ganglia, which suggests that the two subcortical structures are part of a densely interconnected network. Taken together, these findings elucidate the neuroanatomical substrate for cerebellar involvement in non-motor functions mediated by the prefrontal and posterior parietal cortex, as well as in processes traditionally associated with the basal ganglia. PMID:23579055

  2. Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning.

    PubMed

    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

    2016-02-01

    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

  3. Abnormal Head Impulse Test in a Unilateral Cerebellar Lesion

    PubMed Central

    Baek, Seol-Hee; Jung, Jin-Man; Kwon, Do-Young; Park, Moon Ho; Choi, June; Kim, Ji-Soo

    2015-01-01

    Background The findings of head impulse tests (HIT) are usually normal in cerebellar lesions. Case Report A 46-year-old male presented with progressive dizziness and imbalance of 3 weeks duration. The patient exhibited catch-up saccades during bedside horizontal HIT to either side, which was more evident during the rightward HIT. However, results of bithermal caloric tests and rotatory chair test were normal. MRI revealed a lesion in the inferior cerebellum near the flocculus. Conclusions This case provides additional evidence that damage to the flocculus or its connections may impair the vestibulo-ocular reflex only during high-speed stimuli, especially when the stimuli are applied to the contralesional side. By observing accompanying cerebellar signs, the abnormal HIT findings caused by a cerebellar disorder can be distinguished from those produced by peripheral vestibular disorders. PMID:25749819

  4. 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.

  5. Natural history of Christianson syndrome.

    PubMed

    Schroer, Richard J; Holden, Kenton R; Tarpey, Patrick S; Matheus, Maria Giselle; Griesemer, David A; Friez, Michael J; Fan, Jane Zheng; Simensen, Richard J; Strømme, Petter; Stevenson, Roger E; Stratton, Michael R; Schwartz, Charles E

    2010-11-01

    Christianson syndrome is an X-linked mental retardation syndrome characterized by microcephaly, impaired ocular movement, severe global developmental delay, hypotonia which progresses to spasticity, and early onset seizures of variable types. Gilfillan et al.2008] reported mutations in SLC9A6, the gene encoding the sodium/hydrogen exchanger NHE6, in the family first reported and in three others. They also noted the clinical similarities to Angelman syndrome and found cerebellar atrophy on MRI and elevated glutamate/glutamine in the basal ganglia on MRS. Here we report on nonsense mutations in two additional families. The natural history is detailed in childhood and adult life, the similarities to Angelman syndrome confirmed, and the MRI/MRS findings documented in three affected boys. PMID:20949524

  6. Cerebellar substrates for error correction in motor conditioning.

    PubMed

    Gluck, M A; Allen, M T; Myers, C E; Thompson, R F

    2001-11-01

    The authors evaluate a mapping of Rescorla and Wagner's (1972) behavioral model of classical conditioning onto the cerebellar substrates for motor reflex learning and illustrate how the limitations of the Rescorla-Wagner model are just as useful as its successes for guiding the development of new psychobiological theories of learning. They postulate that the inhibitory pathway that returns conditioned response information from the cerebellar interpositus nucleus back to the inferior olive is the neural basis for the error correction learning proposed by Rescorla and Wagner (Gluck, Myers, & Thompson, 1994; Thompson, 1986). The authors' cerebellar model expects that behavioral processes described by the Rescorla-Wagner model will be localized within the cerebellum and related brain stem structures, whereas behavioral processes beyond the scope of the Rescorla-Wagner model will depend on extracerebellar structures such as the hippocampus and related cortical regions. Simulations presented here support both implications. Several novel implications of the authors' cerebellar error-correcting model are described including a recent empirical study by Kim, Krupa, and Thompson (1998), who verified that suppressing the putative error correction pathway should interfere with the Kamin (1969) blocking effect, a behavioral manifestation of error correction learning. The authors also discuss the model's implications for understanding the limits of cerebellar contributions to associative learning and how this informs our understanding of hippocampal function in conditioning. This leads to a more integrative view of the neural substrates of conditioning in which the authors' real-time circuit-level model of the cerebellum can be viewed as a generalization of the long-term memory module of Gluck and Myers' (1993) trial-level theory of cerebellar-hippocampal interaction in motor conditioning. PMID:11726240

  7. Cerebellar substrates for error correction in motor conditioning.

    PubMed

    Gluck, M A; Allen, M T; Myers, C E; Thompson, R F

    2001-11-01

    The authors evaluate a mapping of Rescorla and Wagner's (1972) behavioral model of classical conditioning onto the cerebellar substrates for motor reflex learning and illustrate how the limitations of the Rescorla-Wagner model are just as useful as its successes for guiding the development of new psychobiological theories of learning. They postulate that the inhibitory pathway that returns conditioned response information from the cerebellar interpositus nucleus back to the inferior olive is the neural basis for the error correction learning proposed by Rescorla and Wagner (Gluck, Myers, & Thompson, 1994; Thompson, 1986). The authors' cerebellar model expects that behavioral processes described by the Rescorla-Wagner model will be localized within the cerebellum and related brain stem structures, whereas behavioral processes beyond the scope of the Rescorla-Wagner model will depend on extracerebellar structures such as the hippocampus and related cortical regions. Simulations presented here support both implications. Several novel implications of the authors' cerebellar error-correcting model are described including a recent empirical study by Kim, Krupa, and Thompson (1998), who verified that suppressing the putative error correction pathway should interfere with the Kamin (1969) blocking effect, a behavioral manifestation of error correction learning. The authors also discuss the model's implications for understanding the limits of cerebellar contributions to associative learning and how this informs our understanding of hippocampal function in conditioning. This leads to a more integrative view of the neural substrates of conditioning in which the authors' real-time circuit-level model of the cerebellum can be viewed as a generalization of the long-term memory module of Gluck and Myers' (1993) trial-level theory of cerebellar-hippocampal interaction in motor conditioning.

  8. Movement Disorders Following Cerebrovascular Lesions in Cerebellar Circuits.

    PubMed

    Choi, Seong-Min

    2016-05-01

    Cerebellar circuitry is important to controlling and modifying motor activity. It conducts the coordination and correction of errors in muscle contractions during active movements. Therefore, cerebrovascular lesions of the cerebellum or its pathways can cause diverse movement disorders, such as action tremor, Holmes' tremor, palatal tremor, asterixis, and dystonia. The pathophysiology of abnormal movements after stroke remains poorly understood. However, due to the current advances in functional neuroimaging, it has recently been described as changes in functional brain networks. This review describes the clinical features and pathophysiological mechanisms in different types of movement disorders following cerebrovascular lesions in the cerebellar circuits. PMID:27240809

  9. The contribution of extrasynaptic signaling to cerebellar information processing

    PubMed Central

    Coddington, Luke T.; Nietz, Angela K.; Wadiche, Jacques I.

    2014-01-01

    The diversity of synapses within the simple modular structure of the cerebellum has been crucial for study of the phasic extrasynaptic signaling by fast neurotransmitters collectively referred to as ‘spillover.’ Additionally, the accessibility of cerebellar components for in vivo recordings and their recruitment by simple behaviors or sensory stimuli has allowed for both direct and indirect demonstrations of the effects of transmitter spillover in the intact brain. The continued study of spillover in the cerebellum not only promotes our understanding of information transfer through cerebellar structures but also how extrasynaptic signaling may be regulated and interpreted throughout the CNS. PMID:24590660

  10. Movement Disorders Following Cerebrovascular Lesions in Cerebellar Circuits

    PubMed Central

    Choi, Seong-Min

    2016-01-01

    Cerebellar circuitry is important to controlling and modifying motor activity. It conducts the coordination and correction of errors in muscle contractions during active movements. Therefore, cerebrovascular lesions of the cerebellum or its pathways can cause diverse movement disorders, such as action tremor, Holmes’ tremor, palatal tremor, asterixis, and dystonia. The pathophysiology of abnormal movements after stroke remains poorly understood. However, due to the current advances in functional neuroimaging, it has recently been described as changes in functional brain networks. This review describes the clinical features and pathophysiological mechanisms in different types of movement disorders following cerebrovascular lesions in the cerebellar circuits. PMID:27240809

  11. Arteriovenous malformations in Cowden syndrome.

    PubMed

    Turnbull, M M; Humeniuk, V; Stein, B; Suthers, G K

    2005-08-01

    Cowden syndrome (OMIM No 158350) is a pleomorphic, autosomal dominant syndrome characterised by hamartomas in tissues derived from the endoderm, mesoderm, and ectoderm. It is caused by germline mutations in the PTEN gene and is allelic to the Bannayan-Riley-Ruvalcaba and Lhermitte-Duclos syndromes. The three syndromes are defined on clinical grounds but there is overlap in their definitions. The clinical features include trichilemmomas, verrucose lesions of the skin, macrocephaly, intellectual disability, cerebellar gangliocytoma, thyroid adenomas, fibroadenomas of the breast, and hamartomatous colonic polyps. Cutaneous haemangiomas are occasionally noted. Malignancies often arise in the affected tissues. Visceral arteriovenous malformations are a recognised component of the Bannayan-Riley-Ruvalcaba syndrome but have been reported rarely in Cowden syndrome. A family is described with a clinical diagnosis of Cowden syndrome, a familial frameshift mutation in the PTEN gene, and large visceral arteriovenous malformations. The association of these pleomorphic syndromes with arteriovenous malformations can be explained by the putative role of the PTEN gene in suppressing angiogenesis. Recognition of arteriovenous malformations as a clinical feature of Cowden syndrome has implications for the clinical management of patients with this disorder. PMID:16061556

  12. 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…

  13. Cerebellar ataxia as a possible complication of babesiosis in two dogs.

    PubMed

    Jacobson, L S

    1994-09-01

    A 6-month-old Miniature Doberman Pinscher was presented with inappetance and cerebellar signs. Babesia canis organisms were found on a capillary bloodsmear. The cerebellar signs resolved rapidly following treatment with diminazene aceturate. A 7-month-old Siberian Husky developed cerebellar signs, blindness and quadriparesis 9 d after presentation with clinical signs typical of uncomplicated canine babesiosis. The dog responded favourably to treatment with prednisolone. Both acute and delayed cerebellar ataxia have been associated with malaria in humans. The clinical signs shown by these dogs were similar to those reported for malaria in humans. Cerebellar ataxia should be considered a possible complication of canine babesiosis.

  14. [Usefulness of molecular genetic analysis of the PRNP gene in patients with cerebellar ataxia: a new case of fatal familial insomnia].

    PubMed

    Marcaud, V; Laplanche, J L; Defontaines, B; Beaudry, P; Vital, A; Vincent, D; Sazdovitch, V; Hauw, J J; Latinville, D; Jung, P; Vecchierini, F; Degos, C F

    2003-02-01

    We report the fifth French case of fatal familial insomnia, characterized by a mutation at codon 178 of prion protein gene and by heterozygoty (Met/Val) at codon 129. The clinical picture included cerebellar ataxia, dysautonomia and frontal lobe syndrome. Prion protein gene analysis was performed in order to support a diagnosis of Creutzfeldt-Jakob disease and assert the diagnosis of fatal familial insomnia. Neuropathologic analysis showed unusual changes including severe neuronal loss in the inferior olive and the dentate nucleus, and absence of obvious lesions in the thalamus. Moreover, spongiform changes were moderate in the superior temporal cortex and the occipital cortex. There was no spongiform change in frontal cortex. Abnormal prion protein (PrP(res)) was mainly evidenced in the parietal cortex. Molecular genetic study of the PRNP gene should be performed in patients who present with a cerebellar ataxia of equivocal origin.

  15. Anterior and posterior inferior cerebellar artery infarction with sudden deafness and vertigo.

    PubMed

    Murakami, Takenobu; Nakayasu, Hiroyuki; Doi, Mitsuru; Fukada, Yasuyo; Hayashi, Miwa; Suzuki, Takeo; Takeuchi, Yuichi; Nakashima, Kenji

    2006-12-01

    We report a patient with anterior and posterior inferior cerebellar artery infarction, which manifested as profound deafness, transient vertigo, and minimal cerebellar signs. We suspect that ischaemia of the left internal auditory artery, which originates from the anterior inferior cerebellar artery, caused the deafness and transient vertigo. A small lesion in the middle cerebellar peduncle in the anterior inferior cerebellar artery territory and no lesion in the dentate nucleus in the posterior inferior cerebellar artery territory are thought to explain the minimal cerebellar signs despite the relatively large size of the infarction. Thus a relatively large infarction of the vertebral-basilar territory can manifest as sudden deafness with vertigo. Neuroimaging, including magnetic resonance imaging, is strongly recommended for patients with sudden deafness and vertigo to exclude infarction of the vertebral-basilar artery territory.

  16. 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…

  17. 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. PMID:17166525

  18. 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

  19. Milder progressive cerebellar atrophy caused by biallelic SEPSECS mutations.

    PubMed

    Iwama, Kazuhiro; Sasaki, Masayuki; Hirabayashi, Shinichi; Ohba, Chihiro; Iwabuchi, Emi; Miyatake, Satoko; Nakashima, Mitsuko; Miyake, Noriko; Ito, Shuichi; Saitsu, Hirotomo; Matsumoto, Naomichi

    2016-06-01

    Cerebellar atrophy is recognized in various types of childhood neurological disorders with clinical and genetic heterogeneity. Genetic analyses such as whole exome sequencing are useful for elucidating the genetic basis of these conditions. Pathological recessive mutations in Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase (SEPSECS) have been reported in a total of 11 patients with pontocerebellar hypoplasia type 2, progressive cerebellocerebral atrophy or progressive encephalopathy, yet detailed clinical features are limited to only four patients. We identified two new families with progressive cerebellar atrophy, and by whole exome sequencing detected biallelic SEPSECS mutations: c.356A>G (p.Asn119Ser) and c.77delG (p.Arg26Profs*42) in family 1, and c.356A>G (p.Asn119Ser) and c.467G>A (p.Arg156Gln) in family 2. Their development was slightly delayed regardless of normal brain magnetic resonance imaging (MRI) in infancy. The progression of clinical symptoms in these families is evidently slower than in previously reported cases, and the cerebellar atrophy milder by brain MRI, indicating that SEPSECS mutations are also involved in milder late-onset cerebellar atrophy. PMID:26888482

  20. 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…

  1. Mapping the development of cerebellar Purkinje cells in zebrafish.

    PubMed

    Hamling, Kyla R; Tobias, Zachary J C; Weissman, Tamily A

    2015-11-01

    The cells that comprise the cerebellum perform a complex integration of neural inputs to influence motor control and coordination. The functioning of this circuit depends upon Purkinje cells and other cerebellar neurons forming in the precise place and time during development. Zebrafish provide a useful platform for modeling disease and studying gene function, thus a quantitative metric of normal zebrafish cerebellar development is key for understanding how gene mutations affect the cerebellum. To begin to quantitatively measure cerebellar development in zebrafish, we have characterized the spatial and temporal patterning of Purkinje cells during the first 2 weeks of development. Differentiated Purkinje cells first emerged by 2.8 days post fertilization and were spatially patterned into separate dorsomedial and ventrolateral clusters that merged at around 4 days. Quantification of the Purkinje cell layer revealed that there was a logarithmic increase in both Purkinje cell number as well as overall volume during the first 2 weeks, while the entire region curved forward in an anterior, then ventral direction. Purkinje cell dendrites were positioned next to parallel fibers as early as 3.3 days, and Purkinje cell diameter decreased significantly from 3.3 to 14 days, possibly due to cytoplasmic reappropriation into maturing dendritic arbors. A nearest neighbor analysis showed that Purkinje cells moved slightly apart from each other from 3 to 14 days, perhaps spreading as the organized monolayer forms. This study establishes a quantitative spatiotemporal map of Purkinje cell development in zebrafish that provides an important metric for studies of cerebellar development and disease.

  2. 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…

  3. 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

  4. 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…

  5. [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.

  6. 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

  7. Grip-load force coordination in cerebellar patients.

    PubMed

    Serrien, D J; Wiesendanger, M

    1999-09-01

    The study examined the anticipatory grip force modulations to load force changes during a drawer-opening task. An impact force was induced by a mechanical stop which abruptly arrested movement of the pulling hand. In performing this task, normal subjects generated a typical grip force profile characterized by an initial force impulse related to drawer movement onset, followed by a ramp-like grip force increase prior to the impending load perturbation. Finally, a reactive response was triggered by the impact. In patients with bilateral cerebellar dysfunction, the drawer-opening task was performed with an alternative control strategy. During pulling, grip force was increased to a high (overestimated) default level. The latter suggests that cerebellar patients were unable to adjust and to scale precisely the grip force according to the load force. In addition, the latency between impact and reactive activity was prolonged in the patients, suggesting an impaired cerebellar transmission of the long-latency responses. In conclusion, these data demonstrate the involvement of cerebellar circuits in both proactive and reactive mechanisms in view of predictable load perturbations during manipulative behavior. PMID:10473743

  8. The history of the development of the cerebellar examination.

    PubMed

    Fine, Edward J; Ionita, Catalina C; Lohr, Linda

    2002-12-01

    The cerebellar examination evolved from observations of experimental lesions made by neurophysiologists and clinical descriptions of patients with trauma to the cerebellum. At the beginning of the 19th century, neurophysiologists such as Luigi Rolando, Marie-Jean-Pierre Flourens, and John Call Dalton, Jr. ablated portions of the cerebellum of a variety of animals and observed staggering gait, clumsiness, and falling from side to side without loss of strength. They concluded that the cerebellum coordinated voluntary movements. In 1899, Joseph Francois Félix Babinski observed that patients with cerebellar lesions could not execute complex movements without breaking down into their elemental movements and described the defect as dysmetria. In 1902, Babinski coined the term dysdiodochokinesis to describe the inability to perform rapid execution of movements requiring alternate contractions of agonist and antagonist muscles. Gordon Holmes in 1904 described the phenomena of rebound, noting that if a limb ipsilateral to a cerebellar lesion is suddenly released from tension, the appendage will flail. In 1917, Gordon Holmes reported hypotonia and dysmetria in men wounded by gunshot wounds to their cerebellum. These observations were rapidly included in descriptions of the cerebellar examination in popular contemporaneous textbooks of neurology. Modern observations have demonstrated that the cerebellum influences such cognitive functions such as planning, verbal fluency, abstract reasoning, prosody, and use of correct grammar.

  9. 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.

  10. Clinical manifestations of cerebellar infarction according to specific lobular involvement.

    PubMed

    Ye, Byoung Seok; Kim, Young Dae; Nam, Hyo Suk; Lee, Hye Sun; Nam, Chung Mo; Heo, Ji Hoe

    2010-12-01

    Lesions in the cerebellum produce various symptoms related to balance and motor coordination. However, the relationship between the exact topographical localization of a lesion and the resulting symptoms is not well understood in humans. In this study, we analyzed 66 consecutive patients with isolated cerebellar infarctions demonstrated on diffusion-weighted magnetic resonance imaging. We identified the involved lobules in these patients using a cross-referencing tool of the picture archiving and communication system, and we investigated the relationships between the sites of the lesions and specific symptoms using χ (2) tests and logistic regression analysis. The most common symptoms in patients with isolated cerebellar infarctions were vertigo (87%) and lateropulsion (82%). Isolated vertigo or lateropulsion without any other symptoms was present in 38% of patients. On the other hand, limb ataxia was a presenting symptom in only 40% of the patients. Lateropulsion, vertigo, and nystagmus were more common in patients with a lesion in the caudal vermis. Logistic regression analysis showed that lesions in the posterior paravermis or nodulus were independently associated with lateropulsion. Lesions in the nodulus were associated with contralateral pulsion, and involvement of the culmen was associated with ipsilateral pulsion and isolated lateropulsion without vertigo. Nystagmus was associated with lesions in the pyramis lobule, while lesions of the anterior paravermis were associated with dysarthria and limb ataxia. Our results showed that the cerebellar lobules are responsible for producing specific symptoms in cerebellar stroke patients.

  11. 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.

  12. PHACE syndrome associated with congenital oculomotor nerve palsy.

    PubMed

    Murthy, Ramesh; Naik, Milind N; Desai, Savari; Honavar, Santosh G

    2009-01-01

    PHACE syndrome is a multisystem disorder presenting with facial hemangiomas, arterial anomalies, cardiac anomalies, posterior fossa malformations and eye abnormalities. The eye abnormalities include microphthalmos, cataracts, optic atrophy and iris hypoplasia. Amongst the neurological anomalies, posterior fossa malformations are common. Fourth nerve palsy has been reported with PHACE syndrome. We report a child presenting with a triad of congenital third nerve palsy, cerebellar hypoplasia and facial capillary hemangioma.

  13. [Peripheral, central and functional vertigo syndromes].

    PubMed

    Strupp, M; Dieterich, M; Zwergal, A; Brandt, T

    2015-12-01

    Depending on the temporal course, three forms of vertigo syndrome can be differentiated: 1) vertigo attacks, e.g. benign paroxysmal positional vertigo (BPPV), Menière's disease and vestibular migraine, 2) acute spontaneous vertigo lasting for days, e.g. acute unilateral vestibulopathy, brainstem or cerebellar infarction and 3) symptoms lasting for months or years, e.g. bilateral vestibulopathy and functional vertigo. The specific therapy of the various syndromes is based on three principles: 1) physical treatment with liberatory maneuvers for BPPV and balance training for vestibular deficits, 2) pharmacotherapy, e.g. for acute unilateral vestibulopathy (corticosteroids) and Menière's disease (transtympanic administration of gentamicin or steroids and high-dose betahistine therapy); placebo-controlled pharmacotherapy studies are currently being carried out for acute unilateral vestibulopathy, vestibular paroxysmia, prophylaxis of BPPV, vestibular migraine, episodic ataxia type 2 and cerebellar ataxia; 3) psychotherapy for functional dizziness.

  14. 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

  15. Automated MRI Cerebellar Size Measurements Using Active Appearance Modeling

    PubMed Central

    Price, Mathew; Cardenas, Valerie A.; Fein, George

    2014-01-01

    Although the human cerebellum has been increasingly identified as an important hub that shows potential for helping in the diagnosis of a large spectrum of disorders, such as alcoholism, autism, and fetal alcohol spectrum disorder, the high costs associated with manual segmentation, and low availability of reliable automated cerebellar segmentation tools, has resulted in a limited focus on cerebellar measurement in human neuroimaging studies. We present here the CATK (Cerebellar Analysis Toolkit), which is based on the Bayesian framework implemented in FMRIB’s FIRST. This approach involves training Active Appearance Models (AAM) using hand-delineated examples. CATK can currently delineate the cerebellar hemispheres and three vermal groups (lobules I–V, VI–VII, and VIII–X). Linear registration with the low-resolution MNI152 template is used to provide initial alignment, and Point Distribution Models (PDM) are parameterized using stellar sampling. The Bayesian approach models the relationship between shape and texture through computation of conditionals in the training set. Our method varies from the FIRST framework in that initial fitting is driven by 1D intensity profile matching, and the conditional likelihood function is subsequently used to refine fitting. The method was developed using T1-weighted images from 63 subjects that were imaged and manually labeled: 43 subjects were scanned once and were used for training models, and 20 subjects were imaged twice (with manual labeling applied to both runs) and used to assess reliability and validity. Intraclass correlation analysis shows that CATK is highly reliable (average test-retest ICCs of 0.96), and offers excellent agreement with the gold standard (average validity ICC of 0.87 against manual labels). Comparisons against an alternative atlas-based approach, SUIT (Spatially Unbiased Infratentorial Template), that registers images with a high-resolution template of the cerebellum, show that our AAM

  16. 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.

  17. 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

  18. 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.

  19. L1 modulates PKD1 phosphorylation in cerebellar granule neurons.

    PubMed

    Chen, Shuang-xi; Hu, Cheng-liang; Liao, Yong-hong; Zhao, Wei-jiang

    2015-01-01

    The neural cell adhesion molecule L1 (L1CAM) is crucial for the development of the nervous system, with an essential role in regulating multiple cellular activities. Protein kinase D1 (PKD1) serves as a key kinase given its diverse array of functions within the cell. Here, we investigated various aspects of the functional relationship between L1 and phosphorylated PKD1 (pPKD1) in cerebellar granule neurons. To study the relationship between L1 and PKD1 phosphorylation, human cerebellar tissue microarrays were subject to immunofluorescence staining. We observed a positive correlation between L1 protein levels and PKD1 phosphorylation. In addition, L1 also co-localized with pPKD1. To analyze the regulatory role of L1 on PKD1 phosphorylation, primary mouse cerebellar granule neurons were treated with various concentrations of rL1 for 48 h. Using Western blot, we revealed that L1 significantly increased PKD1 phosphorylation compared with vehicle control, with the maximal effect observed at 5 nM. ERK1/2 phosphorylation was significantly increased by 2.5 nM and 10nM L1, with no apparent change in SRC phosphorylation. However, SRC expression was markedly reduced by 10nM rL1. AKT1 expression and phosphorylation levels were significantly increased by rL1, with the maximal effect observed at 2.5 and 5 nM, respectively. Our combined data revealed a positive relationship between L1 and pPKD1 in both cultured cerebellar neurons and human cerebellar tissue, suggesting that L1 functions in the modulation of PKD1 phosphorylation. PMID:25445362

  20. Functional Relations of Cerebellar Modules of the Cat

    PubMed Central

    Pong, Milton; Gibson, Alan R.

    2010-01-01

    The cerebellum consists of parasagittal zones that define fundamental modules of neural processing. Each zone receives input from a distinct subdivision of the inferior olive (IO)—activity in one olivary subdivision will affect activity in one cerebellar module. To define functions of the cerebellar modules, we inactivated specific olivary subdivisions in six male cats with a glutamate receptor blocker. Olivary inactivation eliminates Purkinje cell complex spikes, which results in a high rate of Purkinje cell simple spike discharge. The increased simple spike discharge inhibits output from connected regions of the cerebellar nuclei. After inactivation, behavior was evaluated during a reach-to-grasp task and during locomotion. Inactivation of each subdivision produced unique behavioral deficits. Performance of the reach-to-grasp task was affected by inactivation of the rostral dorsal accessory olive (rDAO) and the rostral medial accessory olive (rMAO) and, possibly, the principal olive. rDAO inactivation produced paw drag during locomotion and a deficit in grasping the handle during the reach-to-grasp task. rMAO inactivation caused the cats to reach under the handle and produced severe limb drag during locomotion. Inactivation of the dorsal medial cell column, cell group β, or caudal medial accessory olive produced little deficit in the reach-to-grasp task, but each produced a different deficit during locomotion. In all cases, the cats appeared to have intact sensation, good spatial awareness, and no change of affect. Normal cerebellar function requires low rates of IO discharge, and each cerebellar module has a specific and unique function in sensory–motor integration. PMID:20631170

  1. Adaptive filters and internal models: multilevel description of cerebellar function.

    PubMed

    Porrill, John; Dean, Paul; Anderson, Sean R

    2013-11-01

    Cerebellar function is increasingly discussed in terms of engineering schemes for motor control and signal processing that involve internal models. To address the relation between the cerebellum and internal models, we adopt the chip metaphor that has been used to represent the combination of a homogeneous cerebellar cortical microcircuit with individual microzones having unique external connections. This metaphor indicates that identifying the function of a particular cerebellar chip requires knowledge of both the general microcircuit algorithm and the chip's individual connections. Here we use a popular candidate algorithm as embodied in the adaptive filter, which learns to decorrelate its inputs from a reference ('teaching', 'error') signal. This algorithm is computationally powerful enough to be used in a very wide variety of engineering applications. However, the crucial issue is whether the external connectivity required by such applications can be implemented biologically. We argue that some applications appear to be in principle biologically implausible: these include the Smith predictor and Kalman filter (for state estimation), and the feedback-error-learning scheme for adaptive inverse control. However, even for plausible schemes, such as forward models for noise cancellation and novelty-detection, and the recurrent architecture for adaptive inverse control, there is unlikely to be a simple mapping between microzone function and internal model structure. This initial analysis suggests that cerebellar involvement in particular behaviours is therefore unlikely to have a neat classification into categories such as 'forward model'. It is more likely that cerebellar microzones learn a task-specific adaptive-filter operation which combines a number of signal-processing roles.

  2. Verb generation in children and adolescents with acute cerebellar lesions.

    PubMed

    Frank, B; Schoch, B; Hein-Kropp, C; Dimitrova, A; Hövel, M; Ziegler, W; Gizewski, E R; Timmann, D

    2007-03-14

    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 of the children had received radiation or chemotherapy at or before the time of testing. Eleven age- and education-matched control subjects participated. Subjects had to generate verbs to blocked presentations of photographs of objects. As control condition, the objects had to be named. Furthermore, dysarthria was quantified by means of a sentence production and syllable repetition task. Detailed analysis of individual 3D-MR images revealed that lesions affected cerebellar hemispheres in all children and adolescents. The right cerebellar hemisphere was affected in four and the left hemisphere in five subjects. In the present study, naming and verb generation accuracy were preserved in the majority of subjects with cerebellar lesions. No significant signs of learning deficits were observed, as reduction of reaction times over blocks was not different compared to controls. There was a trend of children and adolescents with right-hemispheric lesions to perform worse compared to controls. In this group, however, significant signs of dysarthria were present. In sum, no significant signs of disordered verb generation were observed in children and adolescents with acute cerebellar lesions. Findings suggest that the role of the cerebellum in verb generation may be less pronounced than previously suggested. Findings need to be confirmed in a larger group of subjects with acute focal lesions.

  3. 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

  4. Adaptive robotic control driven by a versatile spiking cerebellar network.

    PubMed

    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

  5. Sex reversal syndrome in the horse: four new cases of feminization in individuals carrying a 64,XY SRY negative chromosomal complement.

    PubMed

    Anaya, Gabriel; Moreno-Millán, Miguel; Bugno-Poniewierska, Monika; Pawlina, Klaudia; Membrillo, Alberto; Molina, Antonio; Demyda-Peyrás, Sebastián

    2014-12-10

    Horses are characterized as having a greater rate of chromosomal abnormalities than other species, which are mainly related to the sex chromosome pair and produce a series of different anomalies known as disorders in sexual development (DSD). In the present study, three Pura Raza Española (PRE) and one Menorquín (MEN) horses were studied and an incompatibility in their genetic and phenotypic sex were detected. Animals were karyotyped by conventional and molecular cytogenetic analyses and characterized using genomic techniques. Although all individuals, were totally unrelated, these animals had the same abnormality (64,XY SRY negative DSD) despite having an anatomically normal external mare phenotype. Therefore, this syndrome could remain undiagnosed in a large percentage of cases because the physiological and morphological symptoms are rare. In the present study, a slight gonadal dysgenesis was observed only in older individuals. Interestingly this chromosomal abnormality has been previously reported less than twenty times, and never in the PRE or MEN horses. With the present research, it is demonstrated that the use of genetic and cytogenetic diagnostic tools in veterinary practice could be an important complementary test to determine the origin of unexplained reproductive failures among horses.

  6. Sex differences in cerebellar mechanisms involved in pain-related safety learning.

    PubMed

    Labrenz, Franziska; Icenhour, Adriane; Thürling, Markus; Schlamann, Marc; Forsting, Michael; Timmann, Dagmar; Elsenbruch, Sigrid

    2015-09-01

    Recent studies have suggested that the cerebellum contributes to the central processing of pain, including pain-related learning and memory processes. As a complex experience with multiple emotional and cognitive facets, the response to pain and its underlying neural correlates differ between men and women. However, it remains poorly understood whether and to what extent sex differences exist in the cerebellar contribution to pain-related associative learning processes. In the present conditioning study with experimental abdominal pain as unconditioned stimuli (US), we assessed sex-dependent differences in behavioral and neural responses to conditioned warning and safety cues in healthy volunteers. The results revealed that in response to visual stimuli signaling safety from abdominal pain (CS(-)), women showed enhanced cerebellar activation in lobules I-IV, V, VI, VIIIa, IX and X as well as Crus II and the dentate nucleus, which are mostly representative of somatomotor networks. On the other hand, men showed enhanced neural activation in lobules I-IV, VI, VIIb, VIIIb, IX as well as Crus I and II in response to CS(-), which are representative of frontoparietal and ventral attention networks. No sex differences were observed in response to pain-predictive warning signals (CS(+)). Similarly, men and women did not differ in behavioral measures of conditioning, including conditioned changes in CS valence and contingency awareness. Together, we could demonstrate that the cerebellum is involved in associative learning processes of conditioned anticipatory safety from pain and mediates sex differences in the underlying neural processes. Given the high prevalence of chronic pain conditions in women, these results may contribute to improve our understanding of the acquisition and manifestation of chronic abdominal pain syndromes. PMID:26004678

  7. Reduced cerebellar gray matter is a neural signature of physical frailty.

    PubMed

    Chen, Wei-Ta; Chou, Kun-Hsien; Liu, Li-Kuo; Lee, Pei-Lin; Lee, Wei-Ju; Chen, Liang-Kung; Wang, Pei-Ning; Lin, Ching-Po

    2015-09-01

    Physical frailty has been recognized as a clinical syndrome resulting from declines in various physiological systems; however, the role of the central nervous system in the pathophysiology of frailty remains unclear. The I-Lan Longitudinal Aging Study randomly sampled community-dwelling people aged 50 or older for a brain magnetic resonance imaging study. All participants were assessed for frailty status (robust, prefrail, and frail) based on the presence of five frailty components: slow walking speed, muscle weakness, low physical activity, exhaustion and weight loss (Fried criteria). Gray matter volume (GMV) changes associated with frailty status and individual frailty components were examined. Overall, 456 participants (64.0 ± 8.5 years, 47.6% women) were included in this study. The prefrail (n = 178, 39.0%) and frail (n = 19, 4.2%) subjects were grouped for analysis. The prefrail-frail group showed reduced GMV, compared to the robust group (n = 259, 56.8%), in the cerebellum, hippocampi, middle frontal gyri, and several other cerebral regions (corrected P < 0.05). Each frailty component was associated with GMV changes in functionally related brain areas. Hierarchical cluster analysis categorized these components into three subsets. Motor-related components, including weakness, low activity, and slowness, comprised one subset with a common cerebellar involvement. Exhaustion and weight loss were the other two subsets without cerebellar changes. To conclude, physical frailty is associated with a decreased reserve in specific brain regions, especially cerebellum. Further longitudinal studies are needed to explore if the cerebellum- and noncerebellum-based frailty components reflect a distinctive future risk for developing frailty. PMID:26096356

  8. Defects in the CAPN1 Gene Result in Alterations in Cerebellar Development and Cerebellar Ataxia in Mice and Humans.

    PubMed

    Wang, Yubin; Hersheson, Joshua; Lopez, Dulce; Hammer, Monia; Liu, Yan; Lee, Ka-Hung; Pinto, Vanessa; Seinfeld, Jeff; Wiethoff, Sarah; Sun, Jiandong; Amouri, Rim; Hentati, Faycal; Baudry, Neema; Tran, Jennifer; Singleton, Andrew B; Coutelier, Marie; Brice, Alexis; Stevanin, Giovanni; Durr, Alexandra; Bi, Xiaoning; Houlden, Henry; Baudry, Michel

    2016-06-28

    A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO) mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1), which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans. PMID:27320912

  9. Defects in the CAPN1 gene result in alterations in cerebellar development and in cerebellar ataxia in mice and humans

    PubMed Central

    Wang, Yubin; Hersheson, Joshua; Lopez, Dulce; Hamad, Monia Ben; Liu, Yan; Lee, Ka-Hung; Pinto, Vanessa; Seinfeld, Jeff; Wiethoff, Sarah; Sun, Jiandong; Amouri, Rim; Hentati, Faycal; Baudry, Neema; Tran, Jennifer; Singleton, Andrew B; Coutelier, Marie; Brice, Alexis; Stevanin, Giovanni; Durr, Alexandra; Bi, Xiaoning; Houlden, Henry; Baudry, Michel

    2016-01-01

    SUMMARY A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous CAPN1 null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knock-out (KO) mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1 mediated cleavage of PH domain and Leucine rich repeat Protein Phosphatase 1 (PHLPP1), which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis, and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans. PMID:27320912

  10. Vasectomy reversal: a clinical update.

    PubMed

    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

  11. 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

  12. Timing Tasks Synchronize Cerebellar and Frontal Ramping Activity and Theta Oscillations: Implications for Cerebellar Stimulation in Diseases of Impaired Cognition

    PubMed Central

    Parker, Krystal L.

    2016-01-01

    Timing is a fundamental and highly conserved mammalian capability, yet the underlying neural mechanisms are widely debated. Ramping activity of single neurons that gradually increase or decrease activity to encode the passage of time has been speculated to predict a behaviorally relevant temporal event. Cue-evoked low-frequency activity has also been implicated in temporal processing. Ramping activity and low-frequency oscillations occur throughout the brain and could indicate a network-based approach to timing. Temporal processing requires cognitive mechanisms of working memory, attention, and reasoning, which are dysfunctional in neuropsychiatric disease. Therefore, timing tasks could be used to probe cognition in animals with disease phenotypes. The medial frontal cortex and cerebellum are involved in cognition. Cerebellar stimulation has been shown to influence medial frontal activity and improve cognition in schizophrenia. However, the mechanism underlying the efficacy of cerebellar stimulation is unknown. Here, we discuss how timing tasks can be used to probe cerebellar interactions with the frontal cortex and the therapeutic potential of cerebellar stimulation. The goal of this theory and hypothesis manuscript is threefold. First, we will summarize evidence indicating that in addition to motor learning, timing tasks involve cognitive processes that are present within both the cerebellum and medial frontal cortex. Second, we propose methodologies to investigate the connections between these areas in patients with Parkinson’s disease, autism, and schizophrenia. Lastly, we hypothesize that cerebellar transcranial stimulation may rescue medial frontal ramping activity, theta oscillations, and timing abnormalities, thereby restoring executive function in diseases of impaired cognition. This hypothesis could inspire the use of timing tasks as biomarkers for neuronal and cognitive abnormalities in neuropsychiatric disease and promote the therapeutic potential of

  13. Cerebellar Transcranial Direct Current Stimulation (ctDCS): A Novel Approach to Understanding Cerebellar Function in Health and Disease.

    PubMed

    Grimaldi, Giuliana; Argyropoulos, Georgios P; Bastian, Amy; Cortes, Mar; Davis, Nicholas J; Edwards, Dylan J; Ferrucci, Roberta; Fregni, Felipe; Galea, Joseph M; Hamada, Masahi; Manto, Mario; Miall, R Chris; Morales-Quezada, Leon; Pope, Paul A; Priori, Alberto; Rothwell, John; Tomlinson, S Paul; Celnik, Pablo

    2016-02-01

    The cerebellum is critical for both motor and cognitive control. Dysfunction of the cerebellum is a component of multiple neurological disorders. In recent years, interventions have been developed that aim to excite or inhibit the activity and function of the human cerebellum. Transcranial direct current stimulation of the cerebellum (ctDCS) promises to be a powerful tool for the modulation of cerebellar excitability. This technique has gained popularity in recent years as it can be used to investigate human cerebellar function, is easily delivered, is well tolerated, and has not shown serious adverse effects. Importantly, the ability of ctDCS to modify behavior makes it an interesting approach with a potential therapeutic role for neurological patients. Through both electrical and non-electrical effects (vascular, metabolic) ctDCS is thought to modify the activity of the cerebellum and alter the output from cerebellar nuclei. Physiological studies have shown a polarity-specific effect on the modulation of cerebellar-motor cortex connectivity, likely via cerebellar-thalamocortical pathways. Modeling studies that have assessed commonly used electrode montages have shown that the ctDCS-generated electric field reaches the human cerebellum with little diffusion to neighboring structures. The posterior and inferior parts of the cerebellum (i.e., lobules VI-VIII) seem particularly susceptible to modulation by ctDCS. Numerous studies have shown to date that ctDCS can modulate motor learning, and affect cognitive and emotional processes. Importantly, this intervention has a good safety profile; similar to when applied over cerebral areas. Thus, investigations have begun exploring ctDCS as a viable intervention for patients with neurological conditions. PMID:25406224

  14. An antibody to the GM1/GalNAc-GD1a complex correlates with development of pure motor Guillain-Barré syndrome with reversible conduction failure.

    PubMed

    Ogawa, Go; Kaida, Ken-ichi; Kuwahara, Motoi; Kimura, Fumihiko; Kamakura, Keiko; Kusunoki, Susumu

    2013-01-15

    Antibodies to a ganglioside complex consisting of GM1 and GalNAc-GD1a (GM1/GalNAc-GD1a) are found in sera from patients with Guillain-Barré syndrome (GBS). To elucidate the clinical significance of anti-GM1/GalNAc-GD1a antibodies in GBS, clinical features of 58 GBS patients with IgG anti-GM1/GalNAc-GD1a antibodies confirmed by enzyme-linked immunosorbent assay and thin layer chromatography immunostaining were analyzed. Compared to GBS patients without anti-GM1/GalNAc-GD1a antibodies, anti-GM1/GalNAc-GD1a-positive patients more frequently had a preceding respiratory infection (n=38, 66%, p<0.01) and were characterized by infrequency of cranial nerve deficits (n=9, 16%, p<0.01) and sensory disturbances (n=26, 45%, p<0.01). Of the 28 anti-GM1/GalNAc-GD1a-positive patients for whom electrophysiological data were available, 14 had conduction blocks (CBs) at intermediate segments of motor nerves, which were not followed by evident remyelination. Eight of 10 bedridden cases were able to walk independently within one month after the nadir. These results show that the presence of anti-GM1/GalNAc-GD1a antibodies correlated with pure motor GBS characterized by antecedent respiratory infection, fewer cranial nerve deficits, and CBs at intermediate sites of motor nerves. The CB may be generated through alteration of the regulatory function of sodium channels in the nodal axolemma.

  15. Studying Cerebellar Circuits by Remote Control of Selected Neuronal Types with GABAA Receptors

    PubMed Central

    Wisden, William; Murray, Andrew J.; McClure, Christina; Wulff, Peer

    2009-01-01

    Although GABAA receptor-mediated inhibition of cerebellar Purkinje cells by molecular layer interneurons (MLIs) has been studied intensely at the cellular level, it has remained unclear how this inhibition regulates cerebellum-dependent behaviour. We have implemented two complementary approaches to investigate the function of the MLI-Purkinje cell synapse on the behavioural level. In the first approach we permanently disrupted inhibitory fast synaptic transmission at the synapse by genetically removing the postsynaptic GABAA receptors from Purkinje cells (PC-Δγ2 mice). We found that chronic disruption of the MLI-Purkinje cell synapse strongly impaired cerebellar learning of the vestibular occular reflex (VOR), presumably by disrupting the temporal patterns of Purkinje cell activity. However, in PC-Δγ2 mice the baseline VOR reflex was only mildly affected; indeed PC-Δγ2 mice show no ataxia or gait abnormalities, suggesting that MLI control of Purkinje cell activity is either not involved in ongoing motor tasks or that the system compensates for its loss. To investigate the latter possibility we developed an alternative genetic technique; we made the MLI-Purkinje cell synapse selectively sensitive to rapid manipulation with the GABAA receptor modulator zolpidem (PC-γ2-swap mice). Minutes after intraperitoneal zolpidem injection, these PC-γ2-swap mice developed severe motor abnormalities, revealing a substantial contribution of the MLI-Purkinje cell synapses to real time motor control. The cell-type selective permanent knockout of synaptic GABAergic input and the fast reversible modulation of GABAergic input at the same synapse illustrate how pursuing both strategies gives a fuller view. PMID:20076763

  16. Prenatal diagnosis of Chudley-McCullough syndrome.

    PubMed

    Chapman, Teresa; Perez, Francisco A; Ishak, Gisele E; Doherty, Dan

    2016-09-01

    Chudley-McCullough syndrome (CMS) is an autosomal-recessive disorder characterized by a complex brain malformation and profound congenital sensorineural hearing loss. Postnatal brain imaging findings include ventriculomegaly, partial agenesis of corpus callosum, inferior cerebellar dysplasia, arachnoid cysts, and malformations of cortical development including frontal subcortical heterotopia and polymicrogyria. Prenatal diagnosis of CMS is important due to the markedly less severe neurodevelopmental prognosis compared to disorders with similar brain imaging findings. We report prenatal imaging features that help distinguish CMS from other disorders, including slit-like frontal horns, agenesis of the corpus callosum, frontal subcortical heterotopia, arachnoid cysts, and cerebellar dysplasia. © 2016 Wiley Periodicals, Inc. PMID:27312216

  17. Ipsipulsion: A forgotten sign of lateral medullary syndrome.

    PubMed

    Paliwal, Vimal Kumar; Kumar, Surendra; Gupta, Durgesh Kumar; Neyaz, Zafar

    2015-01-01

    Ipsipulsion is a clinical sign specifically seen in lateral medullary syndrome. It is characterized by two involuntary phenomenons. One is static eye deviation ipsilateral to the side of lesion especially in the absence of visual fixation. Second is the saccadic lateropulsion whereby voluntary saccades towards the side of lesion are hypermetric and saccades towards opposite side are hypometric. The vertical saccades may also appear oblique. Ipsipulsion is produced due to damage to the contralateral olivocerebellar pathways that crosses midline in medulla and pass through the ipsilateral inferior cerebellar peduncle to supply ipsilateral cerebellar hemisphere.

  18. Ipsipulsion: A forgotten sign of lateral medullary syndrome

    PubMed Central

    Paliwal, Vimal Kumar; Kumar, Surendra; Gupta, Durgesh Kumar; Neyaz, Zafar

    2015-01-01

    Ipsipulsion is a clinical sign specifically seen in lateral medullary syndrome. It is characterized by two involuntary phenomenons. One is static eye deviation ipsilateral to the side of lesion especially in the absence of visual fixation. Second is the saccadic lateropulsion whereby voluntary saccades towards the side of lesion are hypermetric and saccades towards opposite side are hypometric. The vertical saccades may also appear oblique. Ipsipulsion is produced due to damage to the contralateral olivocerebellar pathways that crosses midline in medulla and pass through the ipsilateral inferior cerebellar peduncle to supply ipsilateral cerebellar hemisphere. PMID:26425003

  19. 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. PMID:3811050

  20. 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.

  1. Human Quadrupeds, Primate Quadrupedalism, and Uner Tan Syndrome

    PubMed Central

    Shapiro, Liza J.; Cole, Whitney G.; Young, Jesse W.; Raichlen, David A.; Robinson, Scott R.; Adolph, Karen E.

    2014-01-01

    Since 2005, an extensive literature documents individuals from several families afflicted with “Uner Tan Syndrome (UTS),” a condition that in its most extreme form is characterized by cerebellar hypoplasia, loss of balance and coordination, impaired cognitive abilities, and habitual quadrupedal gait on hands and feet. Some researchers have interpreted habitual use of quadrupedalism by these individuals from an evolutionary perspective, suggesting that it represents an atavistic expression of our quadrupedal primate ancestry or “devolution.” In support of this idea, individuals with “UTS” are said to use diagonal sequence quadrupedalism, a type of quadrupedal gait that distinguishes primates from most other mammals. Although the use of primate-like quadrupedal gait in humans would not be sufficient to support the conclusion of evolutionary “reversal,” no quantitative gait analyses were presented to support this claim. Using standard gait analysis of 518 quadrupedal strides from video sequences of individuals with “UTS”, we found that these humans almost exclusively used lateral sequence–not diagonal sequence–quadrupedal gaits. The quadrupedal gait of these individuals has therefore been erroneously described as primate-like, further weakening the “devolution” hypothesis. In fact, the quadrupedalism exhibited by individuals with UTS resembles that of healthy adult humans asked to walk quadrupedally in an experimental setting. We conclude that quadrupedalism in healthy adults or those with a physical disability can be explained using biomechanical principles rather than evolutionary assumptions. PMID:25029457

  2. Human quadrupeds, primate quadrupedalism, and Uner Tan Syndrome.

    PubMed

    Shapiro, Liza J; Cole, Whitney G; Young, Jesse W; Raichlen, David A; Robinson, Scott R; Adolph, Karen E

    2014-01-01

    Since 2005, an extensive literature documents individuals from several families afflicted with "Uner Tan Syndrome (UTS)," a condition that in its most extreme form is characterized by cerebellar hypoplasia, loss of balance and coordination, impaired cognitive abilities, and habitual quadrupedal gait on hands and feet. Some researchers have interpreted habitual use of quadrupedalism by these individuals from an evolutionary perspective, suggesting that it represents an atavistic expression of our quadrupedal primate ancestry or "devolution." In support of this idea, individuals with "UTS" are said to use diagonal sequence quadrupedalism, a type of quadrupedal gait that distinguishes primates from most other mammals. Although the use of primate-like quadrupedal gait in humans would not be sufficient to support the conclusion of evolutionary "reversal," no quantitative gait analyses were presented to support this claim. Using standard gait analysis of 518 quadrupedal strides from video sequences of individuals with "UTS", we found that these humans almost exclusively used lateral sequence-not diagonal sequence-quadrupedal gaits. The quadrupedal gait of these individuals has therefore been erroneously described as primate-like, further weakening the "devolution" hypothesis. In fact, the quadrupedalism exhibited by individuals with UTS resembles that of healthy adult humans asked to walk quadrupedally in an experimental setting. We conclude that quadrupedalism in healthy adults or those with a physical disability can be explained using biomechanical principles rather than evolutionary assumptions.

  3. Cerebellar white matter pathways are associated with reading skills in children and adolescents.

    PubMed

    Travis, Katherine E; Leitner, Yael; Feldman, Heidi M; Ben-Shachar, Michal

    2015-04-01

    Reading is a critical life skill in the modern world. The neural basis of reading incorporates a distributed network of cortical areas and their white matter connections. The cerebellum has also been implicated in reading and reading disabilities. However, little is known about the contribution of cerebellar white matter pathways to major component skills of reading. We used diffusion magnetic resonance imaging (dMRI) with tractography to identify the cerebellar peduncles in a group of 9- to 17-year-old children and adolescents born full term (FT, n = 19) or preterm (PT, n = 26). In this cohort, no significant differences were found between fractional anisotropy (FA) measures of the peduncles in the PT and FT groups. FA of the cerebellar peduncles correlated significantly with measures of decoding and reading comprehension in the combined sample of FT and PT subjects. Correlations were negative in the superior and inferior cerebellar peduncles and positive in the middle cerebellar peduncle. Additional analyses revealed that FT and PT groups demonstrated similar patterns of reading associations within the left superior cerebellar peduncle, middle cerebellar peduncle, and left inferior cerebellar peduncle. Partial correlation analyses showed that distinct sub-skills of reading were associated with FA in segments of different cerebellar peduncles. Overall, the present findings are the first to document associations of microstructure of the cerebellar peduncles and the component skills of reading.

  4. In and out of the loop: external and internal modulation of the olivo-cerebellar loop

    PubMed Central

    Libster, Avraham M.; Yarom, Yosef

    2013-01-01

    Cerebellar anatomy is known for its crystal like structure, where neurons and connections are precisely and repeatedly organized with minor variations across the Cerebellar Cortex. The olivo-cerebellar loop, denoting the connections between the Cerebellar cortex, Inferior Olive and Cerebellar Nuclei (CN), is also modularly organized to form what is known as the cerebellar module. In contrast to the relatively organized and static anatomy, the cerebellum is innervated by a wide variety of neuromodulator carrying axons that are heterogeneously distributed along the olivo-cerebellar loop, providing heterogeneity to the static structure. In this manuscript we review modulatory processes in the olivo-cerebellar loop. We start by discussing the relationship between neuromodulators and the animal behavioral states. This is followed with an overview of the cerebellar neuromodulatory signals and a short discussion of why and when the cerebellar activity should be modulated. We then devote a section for three types of neurons where we briefly review its properties and propose possible neuromodulation scenarios. PMID:23626524

  5. Symmetric focal degeneration in the cerebellar and vestibular nuclei in swine caused by ingestion of Aeschynomene indica seeds.

    PubMed

    Riet-Correa, F; Timm, C D; Barros, S S; Summers, B A

    2003-05-01

    A vestibulocerebellar disorder was observed in 2- to 4-month-old swine after consumption of broken rice contaminated with 13% Aeschynomene indica seeds. Affected animals recovered in 2-14 days after removal of the contaminated food. To reproduce the syndrome, 10 pigs were fed 13% A. indica seeds in commercial pig ration or rice. They showed clinical signs similar to those observed in the spontaneous cases, 1 hour to 6 days after ingestion. Three pigs recovered after the withdrawal of the contaminated food. The others were killed. Two pigs that were fed for 25 days with food containing 3% and 6% seeds and two control pigs did not show clinical signs. Histologic lesions were characterized by symmetric focal degeneration in the cerebellar and vestibular nuclei. The initial lesion, observed 24 hours after the first ingestion, was characterized by vacuolation of the neuropil. Subsequently, there was progressive loss of parenchyma, vascular reaction, a few small spheroids, astrocytosis, and accumulation of gitter cells. The brains from four pigs were perfused with a buffered solution of glutaraldehyde-paraformaldehyde 12-48 hours after they started to ingest the seeds. No ultrastructural lesions were observed in the cerebellar nuclei after 12 hours of seed consumption. At 24 hours, endothelial cells and pericytes were separated by empty spaces from astrocyte foot processes, suggesting perivascular edema. The astrocytes were enlarged, consistent with intracellular fluid accumulation. These results suggest that A. indica seeds are toxic, causing functional derangement of the vestibulocerebellar system, followed by alterations in the microvasculature in the cerebellar and vestibular nuclei.

  6. Importance of Nitric Oxide for Local Increases of Blood Flow in Rat Cerebellar Cortex During Electrical Stimulation

    NASA Astrophysics Data System (ADS)

    Akgoren, Nuran; Fabricius, Martin; Lauritzen, Martin

    1994-06-01

    The endothelium-derived relaxing factor, probably nitric oxide (NO), is a potent vasodilator that regulates the vascular tone in several vascular beds, including the brain. We explored the possibility that NO might be of importance for the increase of cerebral blood flow (CBF) associated with activity of the well-defined neuronal circuits of the rat cerebellar cortex. Laser-Doppler flowmetry was used to measure increases of cerebellar blood flow evoked by trains of electrical stimulations of the dorsal surface. The evoked increases of CBF were frequency-dependent, being larger on than off the parallel fiber tracts, suggesting that conduction along parallel fibers and synaptic activation of target cells were important for the increase of CBF. This was verified experimentally since the evoked CBF increases were abolished by tetrodotoxin and reduced by 10 mM Mg2+ and selective antagonists for non-N-methyl-D-aspartate receptors. The cerebellar cortex contains high levels of NO synthase. This raised the possibility that NO was involved in the increase of CBF associated with neuronal activation. NO synthase inhibition by topical application of N^G-nitro-L-arginine attenuated the evoked CBF increase by about 50%. This effect was partially reversed by pretreatment with L-arginine, the natural substrate for the enzyme, while N^G-nitro-D-arginine, the inactive enantiomer, had no effect on the evoked CBF increases. Simultaneous blockade of non-N-methyl-D-aspartate receptors and NO synthase had no further suppressing effect on the blood flow increase than either substance alone, suggesting that the NO-dependent flow rise was dependent on postsynaptic mechanisms. These findings are consistent with the idea that local synthesis of NO is involved in the transduction mechanism between neuronal activity and increased CBF.

  7. Acetylcholine sensitivity of cerebellar neurones in the cat

    PubMed Central

    Crawford, J. M.; Curtis, D. R.; Voorhoeve, P. E.; Wilson, V. J.

    1966-01-01

    1. Cholinomimetics, acetylcholine antagonists and some other compounds of pharmacological interest were administered electrophoretically near neurones within the vermal cerebellar cortex of anaesthetized (pentobarbitone) and unanaesthetized (cerveau isolé) cats. 2. The neurones were identified by position within the cortex, spontaneous activity, and the responses to afferent and antidromic stimulation. 3. Purkinje cells, but neither granule nor basket cells, were excited by cholinomimetics, and the acetylcholine receptors had muscarinic properties. Excitation was often preceded by depression of the spontaneous firing. 4. Intravenously administered atropine and dihydro-β-erythroidine did not depress the synaptic excitation of cerebellar neurones evoked by impulses in mossy, climbing or parallel fibres. 5. Acetylcholine is thus unlikely to be an excitatory transmitter within the feline cerebellum, particularly at mossy fibre-granule cell synapses, despite the presence of relatively high levels of acetylcholinesterase within mossy fibre terminals. PMID:5914249

  8. Propofol effects on cerebellar long-term depression.

    PubMed

    Lee, Kwan Young; Kim, Young Im; Kim, Se Hoon; Park, Hyung Seo; Park, Youn Joon; Ha, Myung Sook; Jin, Yunju; Kim, Dong Kwan

    2015-11-16

    Propofol is an intravenously administered anesthetic that induces γ-aminobutyric acid-mediated inhibition in the central nervous system. It has been implicated in prolonged movement disorders. Since the cerebellum is important for motor coordination and learning, we investigated the potential effects of propofol on cerebellar circuitry. Using the whole-cell patch-clamp technique in Wister rat cerebellar slices, we demonstrated that propofol administration impaired long-term depression from the parallel fiber (PF) to Purkinje cell (PC) synapses (PF-LTD). Also, propofol reduced metabotropic glutamate receptor 1 (mGluR1)-mediated and group I mGluR agonist-induced slow currents in PCs. These results suggest that the propofol-induced PF-LTD impairment may be related to an alteration in mGluR1 signaling, which is essential to motor learning.

  9. Cerebellar networks with the cerebral cortex and basal ganglia

    PubMed Central

    Bostan, Andreea C.; Dum, Richard P.; Strick, Peter L.

    2013-01-01

    The dominant view of cerebellar function has been that it is exclusively concerned with motor control and coordination. Recent results from neuroanatomical, behavioral and imaging studies have profoundly changed this view. Neuroanatomical studies using virus transneuronal tracers have demonstrated that the output from the cerebellum reaches vast areas of the neocortex, including regions of prefrontal and posterior parietal cortex. Furthermore, it has recently become clear that the cerebellum is reciprocally connected with the basal ganglia, indicating that the two subcortical structures are part of a densely interconnected network. Altogether, these results provide the neuroanatomical substrate for cerebellar involvement in non-motor functions mediated by the prefrontal and posterior parietal cortex, as well as in processes traditionally associated with the basal ganglia. PMID:23579055

  10. Maternal Postsecondary Education Associated With Improved Cerebellar Growth After Preterm Birth.

    PubMed

    Stiver, Mikaela L; Kamino, Daphne; Guo, Ting; Thompson, Angela; Duerden, Emma G; Taylor, Margot J; Tam, Emily W Y

    2015-10-01

    The preterm cerebellum is vulnerable to impaired development impacting long-term outcome. Preterm newborns (<32 weeks) underwent serial magnetic resonance imaging (MRI) scans. The association between parental education and cerebellar volume at each time point was assessed, adjusting for age at scan. In 26 infants, cerebellar volumes at term (P = .001), but not birth (P = .4), were associated with 2-year volumes. For 1 cm(3) smaller cerebellar volume (4% total volume) at term, the cerebellum was 3.18 cm(3) smaller (3% total volume) by 2 years. Maternal postsecondary education was not associated with cerebellar volume at term (P = .16). Maternal postsecondary education was a significant confounder in the relationship between term and 2-year cerebellar volumes (P = .016), with higher education associated with improved volumes by 2 years. Although preterm birth has been found to be associated with smaller cerebellar volumes at term, maternal postsecondary education is associated with improved growth detectable by 2 years.

  11. Unexplained neuropsychiatric symptoms in intensive care: A Fahr Syndrome case.

    PubMed

    Calili, Duygu Kayar; Mutlu, Nevzat Mehmet; Mutlu Titiz, Ayse Pinar; Akcaboy, Zeynep Nur; Aydin, Eda Macit; Turan, Isil Ozkocak

    2016-08-01

    Fahr Syndrome is a rare disease where calcium and other minerals are stored bilaterally and symmetrically in the basal ganglia, cerebellar dentate nucleus and white matter. Fahr Syndrome is associated with various metabolic disorders, mainly parathyroid disorders. The presented case discusses a 64-year old male patient admitted to the intensive care unit of our hospital diagnosed with aspiration pneumonia and urosepsis. The cranial tomography examination to explain his nonspecific neurological symptoms showed bilateral calcifications in the temporal, parietal, frontal, occipital lobes, basal ganglia, cerebellar hemisphere and medulla oblongata posteriorly. His biochemical test results also indicated parathormone-calcium metabolic abnormalities. Fahr Syndrome must be considered for a definitive diagnosis in patients with nonspecific neuropsychiatric symptoms and accompanying calcium metabolism disorders in order to control serious morbidity and complications because of neurological damage. PMID:27524543

  12. Clinical Presentations of Coenzyme Q10 Deficiency Syndrome

    PubMed Central

    Quinzii, Catarina M.; Emmanuele, Valentina; Hirano, Michio

    2014-01-01

    Coenzyme Q10 (CoQ10) deficiency is a clinically and genetically heterogeneous syndrome which has been associated with 5 major clinical phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) nephropathy, (4) cerebellar ataxia, and (5) isolated myopathy. Of these phenotypes, cerebellar ataxia and syndromic or isolated nephrotic syndrome are the most common. CoQ10 deficiency predominantly presents in childhood. To date, causative mutations have been identified in a small proportion of patients, making it difficult to identify a phenotype-genotype correlation. Identification of CoQ10 deficiency is important because the disease, in particular muscle symptoms and nephropathy, frequently responds to CoQ10 supplementation. PMID:25126046

  13. Unexplained neuropsychiatric symptoms in intensive care: A Fahr Syndrome case.

    PubMed

    Calili, Duygu Kayar; Mutlu, Nevzat Mehmet; Mutlu Titiz, Ayse Pinar; Akcaboy, Zeynep Nur; Aydin, Eda Macit; Turan, Isil Ozkocak

    2016-08-01

    Fahr Syndrome is a rare disease where calcium and other minerals are stored bilaterally and symmetrically in the basal ganglia, cerebellar dentate nucleus and white matter. Fahr Syndrome is associated with various metabolic disorders, mainly parathyroid disorders. The presented case discusses a 64-year old male patient admitted to the intensive care unit of our hospital diagnosed with aspiration pneumonia and urosepsis. The cranial tomography examination to explain his nonspecific neurological symptoms showed bilateral calcifications in the temporal, parietal, frontal, occipital lobes, basal ganglia, cerebellar hemisphere and medulla oblongata posteriorly. His biochemical test results also indicated parathormone-calcium metabolic abnormalities. Fahr Syndrome must be considered for a definitive diagnosis in patients with nonspecific neuropsychiatric symptoms and accompanying calcium metabolism disorders in order to control serious morbidity and complications because of neurological damage.

  14. Altered corticomotor-cerebellar integrity in young ataxia telangiectasia patients.

    PubMed

    Sahama, Ishani; Sinclair, Kate; Fiori, Simona; Pannek, Kerstin; Lavin, Martin; Rose, Stephen

    2014-09-01

    Magnetic resonance imaging (MRI) research in identifying altered brain structure and function in ataxia-telangiectasia, an autosomal recessive neurodegenerative disorder, is limited. Diffusion-weighted MRI were obtained from 11 ataxia telangiectasia patients (age range, 7-22 years; mean, 12 years) and 11 typically developing age-matched participants (age range, 8-23 years; mean, 13 years). Gray matter volume alterations in patients were compared with those of healthy controls using voxel-based morphometry, whereas tract-based spatial statistics was employed to elucidate white matter microstructure differences between groups. White matter microstructure was probed using quantitative fractional anisotropy and mean diffusivity measures. Reduced gray matter volume in both cerebellar hemispheres and in the precentral-postcentral gyrus in the left cerebral hemisphere was observed in ataxia telangiectasia patients compared with controls (P < 0.05, corrected for multiple comparisons). A significant reduction in fractional anisotropy in the cerebellar hemispheres, anterior/posterior horns of the medulla, cerebral peduncles, and internal capsule white matter, particularly in the left posterior limb of the internal capsule and corona radiata in the left cerebral hemisphere, was observed in patients compared with controls (P < 0.05). Mean diffusivity differences were observed within the left cerebellar hemisphere and the white matter of the superior lobule of the right cerebellar hemisphere (P < 0.05). Cerebellum-localized gray matter changes are seen in young ataxia telangiectasia patients along with white matter tract degeneration projecting from the cerebellum into corticomotor regions. The lack of cortical involvement may reflect early-stage white matter motor pathway degeneration within young patients. PMID:25042086

  15. Evidence for distinct cognitive deficits after focal cerebellar lesions

    PubMed Central

    Gottwald, B; Wilde, B; Mihajlovic, Z; Mehdorn, H

    2004-01-01

    Objectives: Anatomical evidence and lesion studies, as well as functional magnetic resonance imaging (fMRI) studies, indicate that the cerebellum contributes to higher cognitive functions. Cerebellar posterior lateral regions seem to be relevant for cognition, while vermal lesions seem to be associated with changes in affect. However, the results remain controversial. Deficits of patients are sometimes still attributed to motor impairment. Methods: We present data from a detailed neuropsychological examination of 21 patients with cerebellar lesions due to tumour or haematoma, and 21 controls matched for age, sex, and years of education. Results: Patients showed deficits in executive function, and in attentional processes such as working memory and divided attention. Further analysis revealed that patients with right-sided lesions were in general more impaired than those with left-sided lesions. Conclusions: Those hypotheses that suggest that lesions of the right cerebellar hemisphere lead to verbal deficits, while those of the left lead to non-verbal deficits, have in part been confirmed. The generally greater impairment of those patients with a right-sided lesion has been interpreted as resulting from the connection of the right cerebellum to the left cerebral hemisphere, which is dominant for language functions and crucial for right hand movements. Motor impairment was correlated with less than half of the cognitive measures, with no stronger tendency for correlation with cognitive tests that require motor responses discernible. The results are discussed on the basis of an assumption that the cerebellum has a predicting and preparing function, indicating that cerebellar lesions lead to a "dysmetria of thought." PMID:15489381

  16. The cerebellar component of Friedreich’s ataxia

    PubMed Central

    Davis, Ashley N.; Morral, Jennifer A.

    2016-01-01

    Lack of frataxin in Friedreich’s ataxia (FRDA) causes a complex neurological and pathological phenotype. Progressive atrophy of the dentate nucleus (DN) is a major intrinsic central nervous system lesion. Antibodies to neuron-specific enolase (NSE), calbindin, glutamic acid decarboxylase (GAD), and vesicular glutamate transporters 1 and 2 (VGluT1, VGluT2) allowed insight into the disturbed synaptic circuitry of the DN. The available case material included autopsy specimens of 24 patients with genetically defined FRDA and 14 normal controls. In FRDA, the cerebellar cortex revealed intact Purkinje cell somata and dendrites as assessed by calbindin immunore-activity. The DN, however, displayed severe loss of large NSE-reactive neurons. Small neurons remained intact. Labeling of Purkinje cells, basket fibers, Golgi neurons, and Golgi axonal plexuses with antibodies to GAD indicated normal intrinsic circuitry of the cerebellar cortex involving γ-aminobutyric acid (GABA). In contrast, the DN displayed severe loss of GABA-ergic terminals and formation of GAD- and calbindin-reactive grumose degeneration. The surviving small GAD-positive DN neurons provided normal GABA-ergic terminals to intact inferior olivary nuclei. The olives also received normal glutamatergic terminals as shown by VGluT2-reactivity. VGluT1-immunocytochemistry of the cerebellar cortex confirmed normal glutamatergic input to the molecular layer by parallel fibers and the granular layer by mossy fibers. VGluT2-immunoreactivity visualized normal climbing fibers and mossy fiber terminals. The DN, however, showed depletion of VGluT1- and VGluT2-reactive terminals arising from climbing and mossy fiber collaterals. The main functional deficit underlying cerebellar ataxia in FRDA is defective processing of inhibitory and excitatory impulses that converge on the large neurons of the DN. The reason for the selective vulnerability of these nerve cells remains elusive. PMID:21638087

  17. Hippocampal and cerebellar atrophy in patients with Cushing's disease.

    PubMed

    Burkhardt, Till; Lüdecke, Daniel; Spies, Lothar; Wittmann, Linus; Westphal, Manfred; Flitsch, Jörg

    2015-11-01

    OBJECT Cushing's disease (CD) may cause atrophy of different regions of the human brain, mostly affecting the hippocampus and the cerebellum. This study evaluates the use of 3-T MRI of newly diagnosed patients with CD to detect atrophic degeneration with voxel-based volumetry. METHODS Subjects with newly diagnosed, untreated CD were included and underwent 3-T MRI. Images were analyzed using a voxelwise statistical test to detect reduction of brain parenchyma. In addition, an atlas-based volumetric study for regions likely to be affected by CD was performed. RESULTS Nineteen patients with a mean disease duration of 24 months were included. Tumor markers included adrenocorticotropic hormone (median 17.5 pmol/L), cortisol (949.4 nmol/L), and dehydroepiandrosterone sulfate (5.4 μmol/L). The following values are expressed as the mean ± SD. The voxelwise statistical test revealed clusters of significantly reduced gray matter in the hippocampus and cerebellum, with volumes of 2.90 ± 0.26 ml (right hippocampus), 2.89 ± 0.28 ml (left hippocampus), 41.95 ± 4.67 ml (right cerebellar hemisphere), and 42.11 ± 4.59 ml (left cerebellar hemisphere). Healthy control volunteers showed volumes of 3.22 ± 0.25 ml for the right hippocampus, 3.23 ± 0.25 ml for the left hippocampus, 50.87 ± 4.23 ml for the right cerebellar hemisphere, and 50.42 ± 3.97 ml for the left cerebellar hemisphere. CONCLUSIONS Patients with untreated CD show significant reduction of gray matter in the cerebellum and hippocampus. These changes can be analyzed and objectified with the quantitative voxel-based method described in this study.

  18. Bilateral cerebellar activation in unilaterally challenged essential tremor

    PubMed Central

    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.

    2015-01-01

    Background Essential tremor (ET) is one of the most common hyperkinetic movement disorders. Previous research into the pathophysiology of ET suggested underlying cerebellar abnormalities. Objective In this study, we added electromyography as an index of tremor intensity to functional Magnetic Resonance Imaging (EMG-fMRI) to study a group of ET patients selected according to strict criteria to achieve maximal homogeneity. With this approach we expected to improve upon the localization of the bilateral cerebellar abnormalities found in earlier fMRI studies. Methods We included 21 propranolol sensitive patients, who were not using other tremor medication, with a definite diagnosis of ET defined by the Tremor Investigation Group. Simultaneous EMG-fMRI recordings were performed while patients were off tremor medication. Patients performed unilateral right hand and arm extension, inducing tremor, alternated with relaxation (rest). Twenty-one healthy, age- and sex-matched participants mimicked tremor during right arm extension. EMG power variability at the individual tremor frequency as a measure of tremor intensity variability was used as a regressor, mathematically independent of the block regressor, in the general linear model used for fMRI analysis, to find specific tremor-related activations. Results Block-related activations were found in the classical upper-limb motor network, both for ET patients and healthy participants in motor, premotor and supplementary motor areas. In ET patients, we found tremor-related activations bilaterally in the cerebellum: in left lobules V, VI, VIIb and IX and in right lobules V, VI, VIIIa and b, and in the brainstem. In healthy controls we found simulated tremor-related activations in right cerebellar lobule V. Conclusions Our results expand on previous findings of bilateral cerebellar involvement in ET. We have identified specific areas in the bilateral somatomotor regions of the cerebellum: lobules V, VI and VIII. PMID:26909321

  19. Imaging Spectrum of Cerebellar Pathologies: A Pictorial Essay

    PubMed Central

    Arora, Richa

    2015-01-01

    Summary The cerebellum is a crucial structure of hindbrain which helps in maintaining motor tone, posture, gait and also coordinates skilled voluntary movements including eye movements. Cerebellar abnormalities have different spectrum, presenting symptoms and prognosis as compared to supratentorial structures and brainstem. This article intends to review the various pathological processes involving the cerebellum along with their imaging features on MR, which are must to know for all radiologists, neurologists and neurosurgeons for their prompt diagnosis and management. PMID:25806100

  20. Monoallelic and Biallelic Variants in EMC1 Identified in Individuals with Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy.

    PubMed

    Harel, Tamar; Yesil, Gozde; Bayram, Yavuz; Coban-Akdemir, Zeynep; Charng, Wu-Lin; Karaca, Ender; Al Asmari, Ali; Eldomery, Mohammad K; Hunter, Jill V; Jhangiani, Shalini N; Rosenfeld, Jill A; Pehlivan, Davut; El-Hattab, Ayman W; Saleh, Mohammed A; LeDuc, Charles A; Muzny, Donna; Boerwinkle, Eric; Gibbs, Richard A; Chung, Wendy K; Yang, Yaping; Belmont, John W; Lupski, James R

    2016-03-01

    The paradigm of a single gene associated with one specific phenotype and mode of inheritance has been repeatedly challenged. Genotype-phenotype correlations can often be traced to different mutation types, localization of the variants in distinct protein domains, or the trigger of or escape from nonsense-mediated decay. Using whole-exome sequencing, we identified homozygous variants in EMC1 that segregated with a phenotype of developmental delay, hypotonia, scoliosis, and cerebellar atrophy in three families. In addition, a de novo heterozygous EMC1 variant was seen in an individual with a similar clinical and MRI imaging phenotype. EMC1 encodes a member of the endoplasmic reticulum (ER)-membrane protein complex (EMC), an evolutionarily conserved complex that has been proposed to have multiple roles in ER-associated degradation, ER-mitochondria tethering, and proper assembly of multi-pass transmembrane proteins. Perturbations of protein folding and organelle crosstalk have been implicated in neurodegenerative processes including cerebellar atrophy. We propose EMC1 as a gene in which either biallelic or monoallelic variants might lead to a syndrome including intellectual disability and preferential degeneration of the cerebellum. PMID:26942288