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Dejerine Hand Phenomenon
A man in his mid-60s had a 6-week progression of motor and sensitive disturbances in all 4 limbs. He had a history of episodic cervicalgia but no active neck pain. Examination revealed distal 3/5 paresis in the arms, distal 4/5 paresis in the legs, paresthesia-hypoesthesia in all limbs without radicular pain, 3/4 hyperreflexia, Ashworth 1 spasticity with mild clonus, and sensitive gait ataxia. Lhermitte sign was absent. Bilateral Hoffmann, Babinski, and Dejerine reflexes were present. (Source: JAMA Neurology)
Source: JAMA Neurology - June 29, 2015 Category: Neurology Source Type: research

Towards therapeutic targets for SCA3: insight into the role of Machado-Joseph disease protein ataxin-3 in misfolded proteins clearance
Publication date: Available online 27 June 2015 Source:Progress in Neurobiology Author(s): Xiaoling Li , Hongmei Liu , Paula L. Fischhaber , Tie-Shan Tang Machado-Joseph disease (MJD, also known as spinocerebellar ataxia type 3, SCA3), an autosomal dominant neurological disorder, is caused by an abnormal expanded polyglutamine (polyQ) repeat in the ataxin-3 protein. The length of the expanded polyQ stretch correlates positively with the severity of the disease and inversely with the age at onset. To date, we cannot fully explain the mechanism underlying neurobiological abnormalities of this disease. Yet, accumulating rep...
Source: Progress in Neurobiology - June 27, 2015 Category: Neuroscience Source Type: research

Characterization of Gastric Mucosa Biopsies Reveals Alterations in Huntington’s Disease
Introduction Most studies into the pathology of Huntington’s disease (HD) focus on the basal ganglia and cerebral cortex1. However, mutant huntingtin is expressed throughout the body and abnormalities have been noted in peripheral tissues, not considered secondary to neuronal damage2,3,4. Weight loss is one of the most common peripheral features of HD5,6. The underlying mechanisms are not, however, entirely known. Studies have indicated that weight loss is not secondary to inadequate nutrition, nor to hyperactivity5. Studies have instead suggested that loss of body weight results from changes in metabolism7 and also th...
Source: PLOS Currents Huntington Disease - June 26, 2015 Category: Neurology Authors: Andrew C McCourt Source Type: research

Cognitive impairment before changes appear on [18F]‐fluoro‐D‐glucose positron emission tomography images in a patient with possible early‐stage cerebellar‐predominant multiple system atrophy
Abstract Multiple system atrophy (MSA) is a sporadic, rapidly progressive neurodegenerative disorder characterized by autonomic dysfunction combined with parkinsonism or cerebellar ataxia. Patients with MSA typically suffer from cognitive disorders and rapid eye movement sleep behaviour disorder. 18F‐fluorodeoxyglucose‐positron emission tomography is used to assess MSA. However, the relationship between the clinical features and findings on 18F‐fluorodeoxyglucose‐positron emission tomography in patients with MSA has not yet been investigated. Here we report a case of possible early‐stage cerebellar‐type MSA. We...
Source: Psychogeriatrics - June 26, 2015 Category: Geriatrics Authors: Masahiko Takaya, Masahiko Atsumi, Tomoyuki Hirose, Kazunari Ishii, Osamu Shirakawa Tags: Case Report Source Type: research

Severe childhood Guillain‐Barré syndrome associated with Mycoplasma pneumoniae infection: a case series
We report 7 children with recent M. pneumoniae infection and severe GBS that presented to two European medical centers from 1992–2012. Severe GBS was defined as the occurrence of respiratory failure, central nervous system (CNS) involvement, or death. Five children had GBS, one Bickerstaff brain stem encephalitis (BBE), and one acute‐onset chronic inflammatory demyelinating polyneuropathy (A‐CIDP). The 5 patients with severe GBS were derived from an original cohort of 66 children with GBS. In this cohort, 17 children (26%) had a severe form of GBS and 47% of patients with M. pneumoniae infection presented with severe...
Source: Journal of the Peripheral Nervous System - June 26, 2015 Category: Neurology Authors: Patrick M. Meyer Sauteur, Joyce Roodbol, Annette Hackenberg, Marie‐Claire Y. de Wit, Cornelis Vink, Christoph Berger, Enno Jacobs, Annemarie M.C. van Rossum, Bart C. Jacobs Tags: RESEARCH REPORT Source Type: research

PMCA3 Mutation and Cerebellar Ataxia [Signal Transduction]
The particular importance of Ca2+ signaling to neurons demands its precise regulation within their cytoplasm. Isoform 3 of the plasma membrane Ca2+ ATPase (the PMCA3 pump), which is highly expressed in brain and cerebellum, plays an important role in the regulation of neuronal Ca2+. A genetic defect of the PMCA3 pump has been described in one family with X-linked congenital cerebellar ataxia. Here we describe a novel mutation in the ATP2B3 gene in a patient with global developmental delay, generalized hypotonia and cerebellar ataxia. The mutation (a R482H replacement) impairs the Ca2+ ejection function of the pump. It redu...
Source: Journal of Biological Chemistry - June 25, 2015 Category: Chemistry Authors: Cali, T., Lopreiato, R., Shimony, J., Vineyard, M., Frizzarin, M., Zanni, G., Zanotti, G., Brini, M., Shinawi, M., Carafoli, E. Tags: Molecular Bases of Disease Source Type: research

Concurrent idiopathic vestibular syndrome and facial nerve paralysis in a cat
ConclusionVestibular dysfunction and concurrent facial nerve paralysis have previously been reported in the cat, but not of an idiopathic nature. (Source: Australian Veterinary Journal)
Source: Australian Veterinary Journal - June 25, 2015 Category: Veterinary Research Authors: AR Fraser, SN Long, MA Chevoir Tags: SMALL ANIMALS Source Type: research

ILAE type 3 hippocampal sclerosis in patients with anti-GAD-related epilepsy
Conclusions: These cases suggest that ILAE type 3 hippocampal sclerosis may be immunologically related to and may exist as part of a broader anti-GAD–related neurologic syndrome in some instances. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - June 25, 2015 Category: Neurology Authors: Glover, R. L., DeNiro, L. V., Lasala, P. A., Weidenheim, K. M., Graber, J. J., Boro, A. Tags: Epilepsy surgery, Hippocampal sclerosis, Autoimmune diseases, Gait disorders/ataxia, Stiff person syndrome Article Source Type: research

Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome
Abstract 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, reductio...
Source: The Cerebellum - June 24, 2015 Category: Neurology Source Type: research

NKX2.1-Related Disorders: a novel mutation with mild clinical presentation
Conclusions: The frequency of congenital hypothyroidism cases associated with NKX2.1 mutations is expected to be higher in a subgroup of patients, selected according to the neurological presentation. In these patients the analysis of NKX2.1 mutational status is recommended. (Source: Italian Journal of Pediatrics)
Source: Italian Journal of Pediatrics - June 24, 2015 Category: Pediatrics Authors: Sara MontiAnnalisa NicolettiAntonella CantasanoHeiko KrudeAlessandra Cassio Source Type: research

NKX2.1 -Related Disorders: a novel mutation with mild clinical presentation
Conclusions The frequency of congenital hypothyroidism cases associated with NKX2.1 mutations is expected to be higher in a subgroup of patients, selected according to the neurological presentation. In these patients the analysis of NKX2.1 mutational status is recommended. (Source: Italian Journal of Pediatrics)
Source: Italian Journal of Pediatrics - June 24, 2015 Category: Pediatrics Source Type: research

Treatment of EBV‐associated nodular sclerosing Hodgkin lymphoma in a patient with ataxia telangiectasia with brentuximab vedotin and reduced COPP plus rituximab
Patients with ataxia telangiectasia (AT) with malignancies face poor prognosis due to increased treatment‐related toxicity. Here, we report a 14‐year‐old male with AT and Hodgkin lymphoma (HL) who received brentuximab vedotin and reduced COPP plus rituximab courses. This treatment resulted in complete remission and showed no severe toxicity. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)
Source: Pediatric Blood and Cancer - June 24, 2015 Category: Cancer & Oncology Authors: Michael T. Meister, Sandra Voss, Dirk Schwabe Tags: Brief Report Source Type: research

Coexistance of Autosomal Recessive Spastic Ataxia of Charlevoix Saguenay and Spondyloepiphyseal Dysplasia in a Turkish patient
Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is a distinct form of hereditary early-onset spastic ataxia and is related to progressive degeneration of the cerebellum and spinal cord [3]. People with ARSACS typically have abnormal tensing of the muscles (spasticity), difficulty coordinating movements (ataxia), muscle wasting (amyotrophy), involuntary eye movements (nystagmus), and speech difficulties (dysarthria). (Source: Journal of the Neurological Sciences)
Source: Journal of the Neurological Sciences - June 24, 2015 Category: Neurology Authors: Semiha Kurt, Ece Kartal, Durdane Aksoy, Betul Cevik, Asli Gundogdu Eken, Irmak Sahbaz, A. Nazli Basak Tags: Letter to the Editor Source Type: research

The spectrum of epilepsy caused by POLG mutations
Abstract Mutations in POLG are increasingly recognized as a cause of refractory occipital lobe epilepsy (OLE) and status epilepticus (SE). Our aim was to describe the epilepsy syndrome in seven patients with POLG mutations. We retrospectively reviewed the medical records of seven patients with POLG mutations and epilepsy. Mutation analysis was performed by direct sequencing of the coding exons of the POLG gene. Disease onset was at a median age of 18 years (range 12–26). Epilepsy was the presenting problem in six patients. All had focal seizures, with motor (n = 6) and visual (n = 6) phenomena. Six pati...
Source: Acta Neurologica Belgica - June 24, 2015 Category: Neurology Source Type: research

Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome.
Abstract 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...
Source: Cerebellum - June 24, 2015 Category: Neuroscience Authors: Bodranghien F, Bastian A, Casali C, Hallett M, Louis ED, Manto M, Mariën P, Nowak DA, Schmahmann JD, Serrao M, Steiner KM, Strupp M, Tilikete C, Timmann D, van Dun K Tags: Cerebellum Source Type: research

Coexistence of autosomal recessive spastic ataxia of Charlevoix Saguenay and spondyloepiphyseal dysplasia in a Turkish patient
Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is a distinct form of hereditary early-onset spastic ataxia and is related to progressive degeneration of the cerebellum and spinal cord [3]. People with ARSACS typically have abnormal tensing of the muscles (spasticity), difficulty coordinating movements (ataxia), muscle wasting (amyotrophy), involuntary eye movements (nystagmus), and speech difficulties (dysarthria). (Source: Journal of the Neurological Sciences)
Source: Journal of the Neurological Sciences - June 24, 2015 Category: Neurology Authors: Semiha Kurt, Ece Kartal, Durdane Aksoy, Betul Cevik, Asli Gundogdu Eken, Irmak Sahbaz, A. Nazli Basak Tags: Letter to the Editor Source Type: research

De novo point mutations in patients diagnosed with ataxic cerebral palsy
Cerebral palsy is a sporadic disorder with multiple likely aetiologies, but frequently considered to be caused by birth asphyxia. Genetic investigations are rarely performed in patients with cerebral palsy and there is little proven evidence of genetic causes. As part of a large project investigating children with ataxia, we identified four patients in our cohort with a diagnosis of ataxic cerebral palsy. They were investigated using either targeted next generation sequencing or trio-based exome sequencing and were found to have mutations in three different genes, KCNC3, ITPR1 and SPTBN2. All the mutations were de novo and...
Source: Brain - June 23, 2015 Category: Neurology Authors: Parolin Schnekenberg, R., Perkins, E. M., Miller, J. W., Davies, W. I. L., D'Adamo, M. C., Pessia, M., Fawcett, K. A., Sims, D., Gillard, E., Hudspith, K., Skehel, P., Williams, J., O'Regan, M., Jayawant, S., Jefferson, R., Hughes, S., Lustenberger, A., R Tags: Original Articles Source Type: research

Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome
Abstract Leigh syndrome (LS) is a rare heterogeneous progressive neurodegenerative disorder usually presenting in infancy or early childhood. Clinical presentation is variable and includes psychomotor delay or regression, acute neurological or acidotic episodes, hypotonia, ataxia, spasticity, movement disorders, and corresponding anomalies of the basal ganglia and brain stem on magnetic resonance imaging. To date, 35 genes have been associated with LS, mostly involved in mitochondrial respiratory chain function and encoded in either nuclear or mitochondrial DNA. We used whole-exome sequencing to identify disease-c...
Source: Human Genetics - June 23, 2015 Category: Genetics & Stem Cells Source Type: research

Mitigation of Cerebellar Neuropathy in Globoid Cell Leukodystrophy Mice by AAV-Mediated Gene Therapy.
In this study, the efficacy of cerebellum-targeted gene therapy on the cerebellar neuropathology in twitcher mice (a murine model of GLD) has been validated. We observed degeneration of Purkinje cells, Bergmann glia, and granule cells in addition to astrocytosis and demyelination in the cerebellum of the twitcher mice. Ultrastructural analysis revealed dark cell degeneration and disintegration of the cellular composition of Purkinje cells in untreated twitcher mice. In addition, the expressions of neurotrophic factors CNTF, GDNF and IGF-I were up-regulated and the expression of BDNF was down-regulated. Intracerebellar-medi...
Source: Gene - June 23, 2015 Category: Genetics & Stem Cells Authors: Lin DS, Hsiao CD, Lee AY, Ho CS, Liu HL, Wang TJ, Jian YR, Hsu JC, Huang ZD, Lee TH, Chiang MF Tags: Gene Source Type: research

Metabolic annotation of 2-ethylhydracrylic acid.
Abstract Increased levels of the organic acid, 2-ethylhydracrylic acid (2-EHA) occur in urine of subjects with impaired L(+)-isoleucine metabolism. Chiral intermediates formed during isoleucine degradation are (S) enantiomers. Blockage of (S) pathway flux drives racemization of (2S, 3S) L(+)-isoleucine and its (2S, 3R) stereoisomer, L(+)-alloisoleucine. This non-protein amino acid is metabolized to (R)-2-methylbutyryl CoA via enzymes common to branched chain amino acid degradation. Subsequently, (R) intermediates serve as alternate substrates for three valine metabolic enzymes, generating 2-EHA. Once formed, 2-EHA ...
Source: International Journal of Clinical Chemistry - June 23, 2015 Category: Chemistry Authors: Ryan RO Tags: Clin Chim Acta Source Type: research

Association of PRPS1 Mutations with Disease Phenotypes.
Authors: Mittal R, Patel K, Mittal J, Chan B, Yan D, Grati M, Liu XZ Abstract Phosphoribosylpyrophosphate synthetase 1 (PRPS1) codes for PRS-I enzyme that catalyzes the first step of nucleotide synthesis. PRPS1 gene mutations have been implicated in a number of human diseases. Recently, new mutations in PRPS1 have been identified that have been associated with novel phenotypes like diabetes insipidus expanding the spectrum of PRPS1-related diseases. The purpose of this review is to evaluate current literature on PRPS1-related syndromes and summarize potential therapies. The overexpression of PRPS1 results in PRS-I ...
Source: Disease Markers - June 22, 2015 Category: Laboratory Medicine Tags: Dis Markers Source Type: research

Proteolytic cleavage of ataxin-7 promotes SCA7 retinal degeneration and neurological dysfunction
The neurodegenerative disorder spinocerebellar ataxia type 7 (SCA7) is caused by a polyglutamine (polyQ) expansion in the ataxin-7 protein, categorizing SCA7 as one member of a large class of heritable neurodegenerative proteinopathies. Cleavage of ataxin-7 by the protease caspase-7 has been demonstrated in vitro, and the accumulation of proteolytic cleavage products in SCA7 patients and mouse models has been identified as an early pathological change. However, it remains unknown whether a causal relationship exists between ataxin-7 proteolysis and in vivo SCA7 disease progression. To determine whether caspase cleavage is ...
Source: Human Molecular Genetics - June 22, 2015 Category: Genetics & Stem Cells Authors: Guyenet, S. J., Mookerjee, S. S., Lin, A., Custer, S. K., Chen, S. F., Sopher, B. L., La Spada, A. R., Ellerby, L. M. Tags: ARTICLES Source Type: research

The mutant Moonwalker TRPC3 channel links calcium signaling to lipid metabolism in the developing cerebellum
The Moonwalker (Mwk) mouse is a model of dominantly inherited cerebellar ataxia caused by a gain-of-function mutation in the transient receptor potential (TRP) channel TRPC3. Here, we report impairments in dendritic growth and synapse formation early on during Purkinje cell development in the Mwk cerebellum that are accompanied by alterations in calcium signaling. To elucidate the molecular effector pathways that regulate Purkinje cell dendritic arborization downstream of mutant TRPC3, we employed transcriptomic analysis of developing Purkinje cells isolated by laser-capture microdissection. We identified significant gene ...
Source: Human Molecular Genetics - June 22, 2015 Category: Genetics & Stem Cells Authors: Dulneva, A., Lee, S., Oliver, P. L., Di Gleria, K., Kessler, B. M., Davies, K. E., Becker, E. B. E. Tags: ARTICLES Source Type: research

Paraneoplastic Disorders and Glutamic Acid Decarboxylase Antibodies
An increasing number of antineural IgG antibodies have been detected since the 1980s in patients with autoimmune central nervous system disease. Antibodies to intracellular antigens were initially found and antibodies to antigens on the neural surface have now been identified. Antibodies to the intracellular enzyme glutamic acid decarboxylase (GAD) were one of the earliest antibodies discovered. However, not all antibodies have the same value. This means that not all are pathogenic, specific for defined syndromes, and indicative for responsiveness to immunological treatment. Antibodies to the N-methyl-d-aspartate receptor ...
Source: JAMA Neurology - June 22, 2015 Category: Neurology Source Type: research

A Gain‐of‐Function Mutation in NALCN in a Child with Intellectual Disability, Ataxia, and Arthrogryposis
We report a de novo heterozygous mutation in NALCN (p.R1181Q), which codes for a Na+‐leak channel, in a girl with intellectual disability, episodic and persistent ataxia and arthrogryposis.Interestingly, her episodes of ataxia were abolished by the administration of acetazolamide. Functional studies in C. elegans indicated that p.R1181Q confers a gain‐of‐function to NALCN, suggesting that dominant mutations in NALCN cause a neuro‐developmental phenotype that overlaps with, while being mostly distinct from that associated with recessive mutations in the same gene. (Source: Human Mutation)
Source: Human Mutation - June 22, 2015 Category: Genetics & Stem Cells Authors: Kyota Aoyagi, Elsa Rossignol, Fadi F. Hamdan, Ben Mulcahy, Lin Xie, Shinya Nagamatsu, Guy A. Rouleau, Mei Zhen, Jacques L. Michaud Tags: Brief Report Source Type: research

Comparison of Different Symptom Assessment Scales for Multiple System Atrophy
Abstract To identify the most sensitive scale for use in clinical trials on multiple system atrophy (MSA), a short and sensitive scale is needed for MSA clinical trials. Potential candidates are the Unified MSA Rating Scale (UMSARS), Scale for the Assessment and Rating of Ataxia (SARA), Berg Balance Scale (BBS), MSA Health-Related Quality of Life scale (MSA-QoL), and Scales for Outcomes in Parkinson’s Disease–Autonomic questionnaire (SCOPA-AUT). We enrolled patients with MSA from eight hospitals in Hokkaido, Japan. Board-certified neurologists assessed each patient at 6-month intervals and scored them on the U...
Source: The Cerebellum - June 21, 2015 Category: Neurology Source Type: research

Comparison of Different Symptom Assessment Scales for Multiple System Atrophy.
Abstract To identify the most sensitive scale for use in clinical trials on multiple system atrophy (MSA), a short and sensitive scale is needed for MSA clinical trials. Potential candidates are the Unified MSA Rating Scale (UMSARS), Scale for the Assessment and Rating of Ataxia (SARA), Berg Balance Scale (BBS), MSA Health-Related Quality of Life scale (MSA-QoL), and Scales for Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-AUT). We enrolled patients with MSA from eight hospitals in Hokkaido, Japan. Board-certified neurologists assessed each patient at 6-month intervals and scored them on the UMSARS...
Source: Cerebellum - June 21, 2015 Category: Neuroscience Authors: Matsushima M, Yabe I, Oba K, Sakushima K, Mito Y, Takei A, Houzen H, Tsuzaka K, Yoshida K, Maruo Y, Sasaki H Tags: Cerebellum Source Type: research

Longitudinal changes in cerebellar and subcortical volumes in adult-onset Niemann–Pick disease type C patients treated with miglustat
This study explored how changes in cerebellar grey and white matter volumes, and in subcortical volumes, related to patient treatment status and disability and ataxia ratings. Nine adult-onset NPC patients and 17 matched controls underwent T1-weighted MRI. One patient was not receiving miglustat, and pre-treatment data were available for a further patient. Semi-automated cerebellar and subcortical segmentation was undertaken, and the rates of change in putamen, hippocampal, thalamic and caudal volumes, and grey and white matter cerebellar volumes, were compared to rates of change in Iturriaga disability score, Brief Ataxia...
Source: Journal of Neurology - June 20, 2015 Category: Neurology Source Type: research

Stroke of a cardiac myxoma origin
Conclusion: Cardiac myxoma stroke is rare. Often does it affect young females. For an improved diagnostic accuracy, magnetic resonance imaging of the brain and echocardiography are imperative for young stroke patients in identifying the cerebral infarct and determining the stroke of a cardiac origin. Immediate thrombolytic therapy may completely resolve the cerebral stroke and improve the neurologic function of the patients. An early surgical resection of cardiac myxoma is recommended in patients with not large territory cerebral infarct. Resumo Objetivo: As características clínicas do acidente vascular cerebral causado ...
Source: Revista Brasileira de Cirurgia Cardiovascular - June 19, 2015 Category: Cardiovascular & Thoracic Surgery Source Type: research

Genome-Engineering Tools to Establish Accurate Reporter Cell Lines That Enable Identification of Therapeutic Strategies to Treat Friedreich's Ataxia
Friedreich’s ataxia is a neurodegenerative disease caused by deficiency of the mitochondrial protein frataxin. This deficiency results from expansion of a trinucleotide repeat in the first intron of the frataxin gene. Because this repeat expansion resides in an intron and hence does not alter the amino acid sequence of the frataxin protein, gene reactivation could be of therapeutic benefit. High-throughput screening for frataxin activators has so far met with limited success because current cellular models may not accurately assess endogenous frataxin gene regulation. Here we report the design and validation of genom...
Source: Journal of Biomolecular Screening - June 19, 2015 Category: Molecular Biology Authors: Villasenor, R., Miraglia, L., Romero, A., Tu, B., Punga, T., Knuckles, P., Duss, S., Orth, T., Buhler, M. Tags: Original Research Source Type: research

Total intravenous anaesthesia in adult mules
Conclusions and clinical relevanceThe combination of xylazine–diazepam–ketamine provides effective short‐term anaesthesia in mules under field conditions. (Source: Veterinary Anaesthesia and Analgesia)
Source: Veterinary Anaesthesia and Analgesia - June 19, 2015 Category: Veterinary Research Authors: Khadim H Dar, Ajay K Gupta Tags: Short Communication Source Type: research

Activation and Inhibition of ATM by Phytochemicals: Awakening and Sleeping the Guardian Angel Naturally
Abstract Double-stranded breaks (DSBs) are cytotoxic DNA lesions caused by oxygen radicals, ionizing radiation, and radiomimetic chemicals. Increasing understanding of DNA damage signaling has provided an ever-expanding list of modulators reported to orchestrate DNA damage repair and ataxia telangiectasia mutated (ATM) is the master regulator and main transducer of the DSB response. Increasingly, it is being realized that DNA damage response is a synchronized and branched network that functionalizes different molecular cascades to activate special checkpoints, thus temporarily arresting progression of the cell cyc...
Source: Archivum Immunologiae et Therapiae Experimentalis - June 19, 2015 Category: Allergy & Immunology Source Type: research

Multiple nocardial abscesses of the brainstem and spinal cord diagnosed after an open biopsy through a cervical partial central corpectomy: case report.
Abstract Nocardiosis of the central nervous system is a challenging and difficult diagnosis for the clinician. The combination of infections of the brain and spinal cord is even more rare. The authors report on a patient with multiple lesions in the brainstem and cervical spinal cord. This 81-year-old immunocompetent woman presented with symptoms of progressive walking difficulty and ataxia. The results of an extensive workup with laboratory investigation, MRI, lumbar puncture, positron emission tomography (PET), and bone marrow biopsy remained inconclusive. Only after an open biopsy of a cervical lesion by an ante...
Source: Journal of Neurosurgery.Spine - June 19, 2015 Category: Neurosurgery Authors: Peeters I, Casselman JW, Vandecasteele SJ, Janssen A, Regaert B, Vantomme N, Vanopdenbosch LJ Tags: J Neurosurg Spine Source Type: research

GAA triplet-repeats cause nucleosome depletion in the human genome.
Abstract Although there have been many investigations into how trinucleotide repeats affect nucleosome formation and local chromatin structure, the nucleosome positioning of GAA triplet-repeats in the human genome has remained elusive. In this work, the nucleosome occupancy around GAA triplet-repeats across the human genome was computed statistically. The results showed a nucleosome-depleted region in the vicinity of GAA triplet-repeats in activated and resting CD4(+) T cells. Furthermore, the A-tract was frequently adjacent to the upstream region of GAA triplet-repeats and could enhance the depletion surrounding G...
Source: Genomics - June 19, 2015 Category: Genetics & Stem Cells Authors: Zhao H, Xing Y, Liu G, Chen P, Zhao X, Li G, Cai L Tags: Genomics Source Type: research

A new cellular model to follow Friedreich's ataxia development in a time-resolved way [RESEARCH ARTICLE]
ABSTRACT Friedreich's ataxia (FRDA) is a recessive autosomal ataxia caused by reduced levels of frataxin (FXN), an essential mitochondrial protein that is highly conserved from bacteria to primates. The exact role of frataxin and its primary function remain unclear although this information would be very valuable to design a therapeutic approach for FRDA. A main difficulty encountered so far has been that of establishing a clear temporal relationship between the different observations that could allow a distinction between causes and secondary effects, and provide a clear link between aging and disease development. To appr...
Source: DMM Disease Models and Mechanisms - June 18, 2015 Category: Biomedical Science Authors: Vannocci, T., Faggianelli, N., Zaccagnino, S., della Rosa, I., Adinolfi, S., Pastore, A. Tags: RESEARCH ARTICLE Source Type: research

Exome Sequencing reveals a novel WDR45 frameshift mutation and inherited POLR3A heterozygous variants in a female with a complex phenotype and mixed brain MRI findings.
We report on a female child with severe intellectual disability, aphasia, short stature, ataxia, failure to thrive and structural brain abnormalities. Brain MRI obtained in late infancy showed hypomyelination involving the central periventricular white matter and thinning of the corpus callosum with no evidence of iron accumulation. Brain MRI obtained in childhood showed stable hypomyelination, with progressive iron accumulation in the basal ganglia, in particular in the globus pallidus and substantia nigra. Whole Exome Sequencing (WES) identified a novel WDR45 frameshift deleterious mutation in Exon 9 (c.587-588del) and a...
Source: European Journal of Medical Genetics - June 18, 2015 Category: Genetics & Stem Cells Authors: Khalifa M, Naffaa L Tags: Eur J Med Genet Source Type: research

Ataxia mouse model: Eye blink conditioning for early diagnosis of human disease SCA6
Scientists have established a mouse model for the human disease SCA6. SCA6 is characterized by movement deficits and caused by similar genetic alterations as Chorea Huntington. The mouse model will be used to investigate the disease mechanisms. Experiments suggest that an impairment of eye blink conditioning could be an early disease symptom. (Source: ScienceDaily Headlines)
Source: ScienceDaily Headlines - June 17, 2015 Category: Science Source Type: news

Preferential Recruitment of Neutrophils into the Cerebellum and Brainstem Contributes to the Atypical Experimental Autoimmune Encephalomyelitis Phenotype.
In this study, we provide a detailed analysis of this model, demonstrating that the atypical EAE observed in LysMCre-SOCS3(fl/fl) mice is characterized by extensive neutrophil infiltration into the cerebellum and brainstem, increased inducible NO synthase levels in the cerebellum and brainstem, and prominent axonal damage. Importantly, infiltrating SOCS3-deficient neutrophils produce high levels of CXCL2, CCL2, CXCL10, NO, TNF-α, and IL-1β. Kinetic studies demonstrate that neutrophil infiltration into the cerebellum and brainstem of LysMCre-SOCS3(fl/fl) mice closely correlates with atypical EAE clinical symptoms. Ab-medi...
Source: Journal of Immunology - June 17, 2015 Category: Allergy & Immunology Authors: Liu Y, Holdbrooks AT, Meares GP, Buckley JA, Benveniste EN, Qin H Tags: J Immunol Source Type: research

Isoliquiritigenin as a cause of DNA damage and inhibitor of ataxia‐telangiectasia mutated expression leading to G2/M phase arrest and apoptosis in oral squamous cell carcinoma
ConclusionATM was cleaved by ISL‐activated caspase, thus inhibiting DNA repair in OSCC cells. Therefore, ISL is a promising chemopreventive agent against oral cancer. © 2015 Wiley Periodicals, Inc. Head Neck, 2015 (Source: Head and Neck)
Source: Head and Neck - June 16, 2015 Category: ENT & OMF Authors: Shih‐Min Hsia, Cheng‐Chia Yu, Yin‐Hua Shih, Michael Yuanchien Chen, Tong‐Hong Wang, Yu‐Ting Huang, Tzong‐Ming Shieh Tags: Original Article Source Type: research

Clinical findings and diagnosis in genetic prion diseases in Germany
Abstract To describe the clinical syndrome and diagnostic tests in patients with genetic prion diseases (gPD) in Germany. Clinical features, MRI, EEG, and CSF markers were studied in 91 patients (28 D178N, 20 E200K, 17 inserts, 13 V210I, 8 P102L, 5 E196K). Dementia (35 %) and ataxia (29 %) were the most common initial symptoms and signs. A wide variety and high frequency of neurological/psychiatric symptoms and signs was found during disease course in all patients independently of the type of the mutation. Psychiatric manifestations were frequent (87 %). Neuropsychological abnormalities were observed in 67 %, ...
Source: European Journal of Epidemiology - June 15, 2015 Category: Epidemiology Source Type: research

β-elemene enhances both radiosensitivity and chemosensitivity of glioblastoma cells through the inhibition of the ATM signaling pathway.
Authors: Liu S, Zhou L, Zhao Y, Yuan Y Abstract Glioblastoma multiforme (GBM), a tumor associated with poor prognosis, is known to be resistant to radiotherapy and alkylating agents such as temozolomide (TMZ). β-elemene, a monomer found in Chinese traditional herbs extracted from Curcuma wenyujin, is currently being used as an antitumor drug for different types of tumors including GBM. In the present study, we investigated the roles of β-elemene in the radiosensitivity and chemosensitivity of GBM cells. Human GBM cell lines U87-MG, T98G, U251, LN229 and rat C6 cells were treated with β-elemene combined with radi...
Source: Oncology Reports - June 15, 2015 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

Cognitive Impairment and Brain Imaging Characteristics of Patients with Congenital Cataracts, Facial Dysmorphism, Neuropathy Syndrome.
Abstract Congenital cataracts, facial dysmorphism, neuropathy (CCFDN) syndrome is a complex autosomal recessive multisystem disorder. The aim of the current study is to evaluate the degree of cognitive impairment in a cohort of 22 CCFDN patients and its correlation with patients' age, motor disability, ataxia, and neuroimaging changes. Twenty-two patients with genetically confirmed diagnosis of CCFDN underwent a detailed neurological examination. Verbal and nonverbal intelligence, memory, executive functions, and verbal fluency wеre assessed in all the patients aged 4 to 47 years. Brain magnetic resonance imaging ...
Source: Behavioural Neurology - June 13, 2015 Category: Neurology Authors: Chamova T, Zlatareva D, Raycheva M, Bichev S, Kalaydjieva L, Tournev I Tags: Behav Neurol Source Type: research

Psychiatric disorders, spinocerebellar ataxia type 3 and CAG expansion
Abstract Few studies have investigated the association between spinocerebellar ataxia type 3 (SCA3) and psychiatric disorders, using mainly screening scales to assess signs and symptoms of depression and anxiety. With these limitations in mind, we assessed the prevalence of DSM-IV Axis I psychiatric disorders in SCA3 patients and their possible associations with the length of CAG repeats and socio-demographic characteristics, highlighting potential risk factors. DNA samples were collected from 59 adults diagnosed with SCA3 for the quantification of CAG repeats. Next, the patients were assessed in respect to the pr...
Source: Journal of Neurology - June 13, 2015 Category: Neurology Source Type: research

‘SARAgraph’: A proposed graphic system for representing ataxia progression
Publication date: Available online 11 June 2015 Source:Neurología (English Edition) Author(s): I. Pulido-Valdeolivas , D. Gómez-Andrés , I. Sanz-Gallego , J. Arpa-Gutiérrez (Source: Neurologia)
Source: Neurologia - June 12, 2015 Category: Neurology Source Type: research

ALG8-CDG: novel patients and review of the literature
Conclusion: In ALG8-CDG, isoelectric focusing of transferrin in serum or plasma shows an abnormal sialotransferrin pattern. The diagnosis is confirmed by mutation analysis in ALG8; all patients reported so far had point mutations or small deletions. The prognosis is generally poor. Thus, a timely and correct diagnosis is important for counselling. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - June 12, 2015 Category: Internal Medicine Authors: Michaela HöckKarina WegleiterElisabeth RalserUrsula Kiechl-KohlendorferSabine Scholl-BürgiChristine FauthElisabeth SteichenKarin PichlerDirk LefeberGert MatthjisLiesbeth KeldermansKathrin MaurerJohannes ZschockeDaniela Karall Source Type: research

Molecular and clinical study of a cohort of 110 Algerian patients with autosomal recessive ataxia
Conclusion: We report here a large cohort of patients with genetically determined autosomal recessive ataxia and the first study of the genetic context of ARCA in Algeria. This study showed that in Algerian patients, the two most common types of ataxia (Friedreich ataxia and ataxia with isolated vitamin E deficiency) coexist with forms that may be less common or underdiagnosed. To refine the genotype/phenotype correlation in rare and heteregeneous diseases as autosomal recessive ataxias, more extensive epidemiological investigations and reports are necessary as well as more accurate and detailed clinical characterizations....
Source: BMC Medical Genetics - June 12, 2015 Category: Genetics & Stem Cells Authors: Wahiba HamzaLamia Ali PachaTarik HamadoucheJean MullerNathalie DrouotFarida FerratSamira MakriMalika ChaouchMeriem TazirMichel KoenigTraki Benhassine Source Type: research

ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion
Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse x...
Source: eLife - June 12, 2015 Category: Biomedical Science Authors: Chen, W.-T., Ebelt, N. D., Stracker, T. H., Xhemalce, B., Van Den Berg, C. L., Miller, K. M. Tags: Genes and chromosomes Source Type: research

Severe phenotypic spectrum of biallelic mutations in PRRT2 gene
Conclusions Our observations expand the phenotype related to PRRT2 insufficiency, and highlight the complexity of the phenotype associated with biallelic mutations, which represents a severe neurological disease with various paroxysmal disorders and frequent developmental disabilities. (Source: Journal of Neurology, Neurosurgery and Psychiatry)
Source: Journal of Neurology, Neurosurgery and Psychiatry - June 12, 2015 Category: Neurosurgery Authors: Delcourt, M., Riant, F., Mancini, J., Milh, M., Navarro, V., Roze, E., Humbertclaude, V., Korff, C., Des Portes, V., Szepetowski, P., Doummar, D., Echenne, B., Quintin, S., Leboucq, N., Singh Amrathlal, R., Rochette, J., Roubertie, A. Tags: Genetics, Child and adolescent psychiatry Movement disorders Source Type: research

Modifications of resting state networks in spinocerebellar ataxia type 2
Abstract We aimed to investigate the integrity of the Resting State Networks in spinocerebellar ataxia type 2 (SCA2) and the correlations between the modification of these networks and clinical variables. Resting‐state functional magnetic resonance imaging (RS‐fMRI) data from 19 SCA2 patients and 29 healthy controls were analyzed using an independent component analysis and dual regression, controlling at voxel level for the effect of atrophy by co‐varying for gray matter volume. Correlations between the resting state networks alterations and disease duration, age at onset, number of triplets, and clinical score were ...
Source: Movement Disorders - June 12, 2015 Category: Neurology Authors: Sirio Cocozza, Francesco Saccà, Amedeo Cervo, Angela Marsili, Cinzia Valeria Russo, Sara Maria delle Acque Giorgio, Giuseppe De Michele, Alessandro Filla, Arturo Brunetti, Mario Quarantelli Tags: Research Article Source Type: research