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Paraneoplastic cerebellar ataxia associated with anti-Hu antibodies and benign ganglioneuroma.
We describe a case of cerebellar ataxia associated with anti-Hu antibodies and benign ganglioneuroma. A 28-year-old woman developed progressive ataxia with hyporeflexia at the age of 19. Brain MRI showed progressive cerebellar atrophy. Neurophysiological studies, screening of immune-mediated ataxias, oncological markers, vitamin E and genetic tests for spinocerebellar ataxia types 1,2,3, Friedreich ataxia and POLG1 were negative. Anti-Hu antibodies were positive in Western blot and indirect immunofluorescence (1:640). Total-body computed tomography revealed a mediastinum mass; the histological diagnosis was maturing gangli...
Source: Functional Neurology - January 25, 2015 Category: Neurology Tags: Funct Neurol Source Type: research

Friedreich Ataxia: Failure of GABA-ergic and Glycinergic Synaptic Transmission in the Dentate Nucleus
Abstract: Atrophy of large neurons in the dentate nucleus (DN) is an important pathologic correlate of neurologic disability in patients with Friedreich ataxia (FA). Thinning of the DN was quantified in 29 autopsy cases of FA and 2 carriers by measuring the thickness of the gray matter ribbon on stains with anti–glutamic acid decarboxylase, the rate-limiting enzyme in the biosynthesis of γ-amino-butyric acid (GABA). The DN was thinner than normal in all cases of FA, and atrophy correlated inversely with disease duration but not with age at onset or length of the homozygous guanine-adenine-adenine trinucleotide expansion...
Source: Journal of Neuropathology and Experimental Neurology - January 23, 2015 Category: Neurology Tags: Original Articles Source Type: research

Reduced cortical activation in inferior frontal junction in Unverrich-Lundborg disease (EPM1) a motor fMRI study
Unverricht-Lundborg disease (EPM1) is the most common form of the progressive myoclonus epilepsies. It is an autosomal recessively inherited disorder caused by mutations in the cystatin B gene (CSTB). EPM1 is characterized by stimulus-sensitive and action-activated myoclonus, tonic-clonic seizures and ataxia. Although the epileptic seizures can be relatively well managed with anti-epileptic medications, the myoclonus is much more resistant to treatment (Kälviäinen et al., 2008), and thus it is the most incapacitating symptom of the disease. (Source: Epilepsy Research)
Source: Epilepsy Research - January 23, 2015 Category: Neurology Authors: Mervi Könönen, Nils Danner, Päivi Koskenkorva, Reetta Kälviäinen, Jelena Hyppönen, Esa Mervaala, Pasi Karjalainen, Ritva Vanninen, Eini Niskanen Source Type: research

Joint preserving surgery versus arthrodesis in operative treatment of patients with neuromuscular polyneuropathy: questionnaire assessment
Abstract The purpose of the paper was to present the results of surgical treatment of foot deformities in peripheral neuropathies using bone procedures: both joint preserving and with joint arthrodesis. The study included 26 patients, 14 males and 12 females (43 feet). The age of the patients at surgery ranged from 5 to 55 years (average 23 years). The follow-up ranged from 0.5 to 15 years (average 4.3 years). Seventeen patients presented Charcot–Marie–Tooth disease, three Friedreich’s ataxia and six peripheral motor and sensory neuropathies of undetermined nature. Sixteen patients had bilateral proce...
Source: European Journal of Orthopaedic Surgery and Traumatology - January 21, 2015 Category: Orthopaedics Source Type: research

Bovine hepatic differential gene expression in response to perennial ryegrass staggers
The objective of this study was to characterise differential gene expression in the liver of animals fed lolitrem B-containing feed over an extended period of time. Eighteen steers were fed one of three rations (n=6/group) containing lolitrem B (247, 1,554 or 2,256 μg/kg (dry matter basis)) over 64 days in a double-blind study. Microarray and confirmatory qPCR were performed to evaluate the hepatic gene expression profile from biopsies taken on days 0 and 64. Widespread perturbation of gene expression was observed in all groups receiving lolitrem B, with a total of 152 differential genes identified (false discovery rate ...
Source: World Mycotoxin Journal - January 21, 2015 Category: Toxicology Tags: World Mycotoxin Journal Source Type: research

Variable Activation of the DNA Damage Response Pathways in Patients Undergoing Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging [Radiation and Medical Imaging]
Conclusions— Our findings showed that SPECT MPI resulted in a variable activation of the DNA damage response pathways. Although only a small subset of patients had increased protein phosphorylation and elevated gene expression postimaging, continued care should be taken to reduce radiation exposure to both the patients and operators. (Source: Circulation: Cardiovascular Imaging)
Source: Circulation: Cardiovascular Imaging - January 21, 2015 Category: Radiology Authors: Hee Lee, W., Nguyen, P., Hu, S., Liang, G., Ong, S.-G., Han, L., Sanchez-Freire, V., Lee, A. S., Vasanawala, M., Segall, G., Wu, J. C. Tags: Imaging, Nuclear cardiology and PET Radiation and Medical Imaging Source Type: research

Spinocerebellar Ataxia Type 7: A Neurodegenerative Disorder with Peripheral Neuropathy
Background: Autosomal dominant spinocerebellar ataxias (SCA) are a group of inherited neurodegenerative disorders that typically show peripheral neuropathy. SCA7 is one of the rarest forms of SCA ( (Source: European Neurology)
Source: European Neurology - January 20, 2015 Category: Neurology Source Type: research

Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV)
Abstract Background Since the identification of the first case of infection with the Middle East respiratory syndrome corona virus (MERS-CoV) in Saudi Arabia in June 2012, the number of laboratory-confirmed cases has exceeded 941 cases globally, of which 347 died. The disease presents as severe respiratory infection often with shock, acute kidney injury, and coagulopathy. Recently, we observed three cases who presented with neurologic symptoms. These are so far the first reported cases of neurologic injury associated with MERS-CoV infection. Methods Data...
Source: Infection - January 20, 2015 Category: Infectious Diseases Source Type: research

Neuropathy target esterase impairments cause Oliver-McFarlane and Laurence-Moon syndromes
Conclusions Previously, PNPLA6 mutations have been associated with spastic paraplegia type 39, Gordon–Holmes syndrome and Boucher–Neuhäuser syndromes. Discovery of these additional PNPLA6-opathies further elucidates a spectrum of neurodevelopmental and neurodegenerative disorders associated with NTE impairment and suggests a unifying mechanism with diagnostic and prognostic importance. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - January 19, 2015 Category: Genetics & Stem Cells Authors: Hufnagel, R. B., Arno, G., Hein, N. D., Hersheson, J., Prasad, M., Anderson, Y., Krueger, L. A., Gregory, L. C., Stoetzel, C., Jaworek, T. J., Hull, S., Li, A., Plagnol, V., Willen, C. M., Morgan, T. M., Prows, C. A., Hegde, R. S., Riazuddin, S., Grabowsk Tags: Eye Diseases, Reproductive medicine, Pituitary disorders Genotype-phenotype correlations Source Type: research

Identification of 46 CAG repeats within as probably the shortest pathogenic allele for SCA12
Spinocerebellar ataxia type 12 (SCA12) is predominantly characterized by action tremor, followed by slowly progressive cerebellar dysfunction. It is a very rare disorder and only identified in certain countries so far. The current appreciation for phenotypic and genotypic features of SCA12 is still limited. (Source: Parkinsonism and Related Disorders)
Source: Parkinsonism and Related Disorders - January 17, 2015 Category: Neurology Authors: Yi Dong, Jian-Jun Wu, Zhi-Ying Wu Tags: Short communication Source Type: research

Role of ataxia-telangiectasia mutated (ATM) in porcine oocyte in vitro maturation.
Abstract Ataxia-telangiectasia mutated (ATM) is critical for the DNA damage response, cell cycle checkpoints, and apoptosis. Significant effort has focused on elucidating the relationship between ATM and other nuclear signal transducers; however, little is known about the connection between ATM and oocyte meiotic maturation. We investigated the function of ATM in porcine oocytes. ATM was expressed at all stages of oocyte maturation and localized predominantly in the nucleus. Furthermore, the ATM-specific inhibitor KU-55933 blocked porcine oocyte maturation, reducing the percentages of oocytes that underwent germina...
Source: Cell Biology International - January 17, 2015 Category: Cytology Authors: Lin ZL, Kim NH Tags: Cell Biol Int Source Type: research

Molecular characterization and functional expression of the Apis mellifera voltage-dependent Ca(2+) channels.
Abstract Voltage-gated Ca(2+) channels allow the influx of Ca(2+) ions from the extracellular space upon membrane depolarization and thus serve as a transducer between membrane potential and cellular events initiated by Ca(2+) transients. Most insects are predicted to possess three genes encoding Cavα, the main subunit of Ca(2+) channels, and several genes encoding the two auxiliary subunits, Cavβ and Cavα2δ; however very few of these genes have been cloned so far. Here, we cloned three full-length cDNAs encoding the three Cavα subunits (AmelCav1a, AmelCav2a and AmelCav3a), a cDNA encoding a novel variant of t...
Source: Insect Biochemistry and Molecular Biology - January 17, 2015 Category: Biochemistry Authors: Cens T, Rousset M, Collet C, Charreton M, Garnery L, Le Conte Y, Chahine M, Sandoz JC, Charnet P Tags: Insect Biochem Mol Biol Source Type: research

Friedreich Ataxia: Failure of GABA-ergic and Glycinergic Synaptic Transmission in the Dentate Nucleus
AbstractAtrophy of large neurons in the dentate nucleus (DN) is an important pathologic correlate of neurologic disability in patients with Friedreich ataxia (FA). Thinning of the DN was quantified in 29 autopsy cases of FA and 2 carriers by measuring the thickness of the gray matter ribbon on stains with anti–glutamic acid decarboxylase, the rate-limiting enzyme in the biosynthesis of γ-amino-butyric acid (GABA). The DN was thinner than normal in all cases of FA, and atrophy correlated inversely with disease duration but not with age at onset or length of the homozygous guanine-adenine-adenine trinucleotide expansions....
Source: Journal of Neuropathology and Experimental Neurology - January 16, 2015 Category: Neurology Tags: Original Articles Source Type: research

Role of Evaluating MGMT Status and 1p36 Deletion in Radiosurgery-Induced Anaplastic Ependymoma That Rapidly and Completely Resolved by Temozolomide Alone: Case Report and Review of the Literature
J Neurol Surg RepDOI: 10.1055/s-0034-1396657Stereotactic gamma knife surgery (GKS)-induced brain tumors are extremely rare, and no ependymal tumors induced by GKS have been reported. Therefore, little is known about their clinical, pathologic, and genetic features. In addition, a regimen of adjuvant chemotherapy for anaplastic ependymoma (AE) has not been established. A 77-year-old man presented with a gait disturbance and left-side cerebellar ataxia more than 19 years after GKS performed for a cerebellar arteriovenous malformation. Imaging studies demonstrated an enhancing mass in the irradiated field with signs of intrav...
Source: Journal of Neurological Surgery Reports - January 16, 2015 Category: Neurosurgery Authors: Hirono, SeiichiroIwadate, YasuoKambe, MichiyoHiwasa, TakakiTakiguchi, MasakiNakatani, YukioSaeki, Naokatsu Tags: Case Report Source Type: research

Clinical and Neuropathological Features of Spastic Ataxia in a Spanish Family with Novel Compound Heterozygous Mutations in STUB1.
PMID: 25592071 [PubMed - as supplied by publisher] (Source: Cerebellum)
Source: Cerebellum - January 16, 2015 Category: Neuroscience Authors: Bettencourt C, de Yébenes JG, López-Sendón JL, Shomroni O, Zhang X, Qian SB, Bakker IM, Heetveld S, Ros R, Quintáns B, Sobrido MJ, Bevova MR, Jain S, Bugiani M, Heutink P, Rizzu P Tags: Cerebellum Source Type: research

Substantia Nigra Echogenicity in Hereditary Ataxias With and Without Nigrostriatal Pathology: a Pilot Study.
We examined 12 patients with nigrostriatal ataxia (11 SCA3 and 1 SCA6), 12 nigrostriatal healthy control patients, 7 patients with non-nigrostriatal ataxia (5 FRDA and 2 SCA7), and 7 non-nigrostriatal healthy control patients. The median (IQR) SN area (cm(2)) was greater in the nigrostriatal ataxias compared with the controls (right SN, 0.43 [0.44] vs. 0.11 [0.25]; P = 0.001; left SN, 0.32 [0.25] vs. 0.11 [0.16]; P = 0.001), but was similar among the non-nigrostriatal ataxias and controls. There were no statistically significant differences in the SN area between the nigrostriatal and non-nigrostriatal ataxias, alt...
Source: Cerebellum - January 16, 2015 Category: Neuroscience Authors: Martínez-Sánchez P, Cazorla-García R, Sanz-Gallego I, Correas-Callero E, Pulido-Valdeolivas I, Arpa J Tags: Cerebellum Source Type: research

Substantia Nigra Echogenicity in Hereditary Ataxias With and Without Nigrostriatal Pathology: a Pilot Study
We examined 12 patients with nigrostriatal ataxia (11 SCA3 and 1 SCA6), 12 nigrostriatal healthy control patients, 7 patients with non-nigrostriatal ataxia (5 FRDA and 2 SCA7), and 7 non-nigrostriatal healthy control patients. The median (IQR) SN area (cm2) was greater in the nigrostriatal ataxias compared with the controls (right SN, 0.43 [0.44] vs. 0.11 [0.25]; P = 0.001; left SN, 0.32 [0.25] vs. 0.11 [0.16]; P = 0.001), but was similar among the non-nigrostriatal ataxias and controls. There were no statistically significant differences in the SN area between the nigrostriatal and non-nigrostriatal ataxias, altho...
Source: The Cerebellum - January 15, 2015 Category: Neurology Source Type: research

Clinical and Neuropathological Features of Spastic Ataxia in a Spanish Family with Novel Compound Heterozygous Mutations in STUB1
(Source: The Cerebellum)
Source: The Cerebellum - January 15, 2015 Category: Neurology Source Type: research

ATM gene mutations in sporadic breast cancer patients from Brazil
Conclusions: Our results corroborate the hypothesis that sporadic breast tumors may occur in carriers of low penetrance ATM mutant alleles and these mutations confer different levels of breast cancer risk. (Source: BioMed Central)
Source: BioMed Central - January 15, 2015 Category: Journals (General) Authors: Flavia MangoneElisabete C MiraccaHarriet E FeilotterLois M MulliganMaria Nagai Source Type: research

ATDC induces an invasive switch in KRAS-induced pancreatic tumorigenesis [Research Papers]
The initiation of pancreatic ductal adenocarcinoma (PDA) is linked to activating mutations in KRAS. However, in PDA mouse models, expression of oncogenic mutant KRAS during development gives rise to tumors only after a prolonged latency or following induction of pancreatitis. Here we describe a novel mouse model expressing ataxia telangiectasia group D complementing gene (ATDC, also known as TRIM29 [tripartite motif 29]) that, in the presence of oncogenic KRAS, accelerates pancreatic intraepithelial neoplasia (PanIN) formation and the development of invasive and metastatic cancers. We found that ATDC up-regulates CD44 in m...
Source: Genes and Development - January 15, 2015 Category: Genetics & Stem Cells Authors: Wang, L., Yang, H., Abel, E. V., Ney, G. M., Palmbos, P. L., Bednar, F., Zhang, Y., Leflein, J., Waghray, M., Owens, S., Wilkinson, J. E., Prasad, J., Ljungman, M., Rhim, A. D., Pasca di Magliano, M., Simeone, D. M. Tags: Research Papers Source Type: research

Inactivation of PNKP by Mutant ATXN3 Triggers Apoptosis by Activating the DNA Damage-Response Pathway in SCA3
We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-δ pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach ...
Source: PLoS Genetics - January 15, 2015 Category: Genetics & Stem Cells Authors: Rui Gao et al. Source Type: research

ATR and ATM Loss-of-Function
Mechanisms to maintain genomic integrity are essential for cells to remain viable. Not surprisingly, disruption of key DNA damage response pathway factors, such as ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia and RAD3-related (ATR) results in loss of genomic integrity. Here, a synthetic lethal siRNA-screening approach not only confirmed ATM but identified additional replication checkpoint proteins, when ablated, enhanced ATR inhibitor (ATRi) response in a high-content -H2AX assay. Cancers with inactivating ATM mutations exhibit impaired DNA double-stranded break (DSB) repair and rely on compensatory repair pat...
Source: Molecular Cancer Research - January 15, 2015 Category: Cancer & Oncology Authors: Menezes, D. L., Holt, J., Tang, Y., Feng, J., Barsanti, P., Pan, Y., Ghoddusi, M., Zhang, W., Thomas, G., Holash, J., Lees, E., Taricani, L. Tags: DNA Damage and Repair Source Type: research

Anti-Ri-associated paraneoplastic brainstem cerebellar syndrome with coexisting limbic encephalitis in a patient with mixed large cell neuroendocrine lung carcinoma
We report a 75-year-old woman with medically-intractable emesis, encephalopathy, diplopia, vertigo, and gait ataxia for 3months. Examination revealed rotary nystagmus, ocular skew deviation, limb dysmetria, and gait ataxia. After two courses of intravenous immunoglobulin, there was minimal improvement. Anti-Ri antibodies were positive in serum only. CT scan identified a 2.0cm left lung mass, and histopathology revealed large cell neuroendocrine carcinoma with admixed adenocarcinoma non-small cell lung carcinoma (NCSLC). Though the patient achieved nearly complete clinical recovery after tumor resection, anti-Ri levels rema...
Source: Journal of Clinical Neuroscience - January 14, 2015 Category: Neuroscience Source Type: research

CLIPPERS: Induction and maintenance of remission using hydroxychloroquine
We describe a patient with CLIPPERS in whom treatment with hydroxychloroquine was successful in inducing and maintaining the remission of symptoms confirmed by radiologic resolution. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 14, 2015 Category: Neurology Authors: Tan, B. L., Agzarian, M., Schultz, D. W. Tags: MRI, Autoimmune diseases, Class IV, Gait disorders/ataxia Clinical/Scientific Notes Source Type: research

Ethanol-Induced Cerebellar Ataxia: Cellular and Molecular Mechanisms
Abstract 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 administ...
Source: The Cerebellum - January 13, 2015 Category: Neurology Source Type: research

Peripheral neuropathy and parkinsonism: a large clinical and pathogenic spectrum
This article reviews conditions in which PN may coexist with parkinsonism. (Source: Journal of the Peripheral Nervous System)
Source: Journal of the Peripheral Nervous System - January 13, 2015 Category: Neurology Authors: Anne Vital, Sebastien Lepreux, Claude Vital Tags: Review Source Type: research

Ethanol-Induced Cerebellar Ataxia: Cellular and Molecular Mechanisms.
Abstract 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 administr...
Source: Cerebellum - January 13, 2015 Category: Neuroscience Authors: Dar MS Tags: Cerebellum Source Type: research

Gliomatosis cerebri in a Twelve-year Old
A 12 year-old previously healthy male was admitted with subacute onset of right-sided facial droop, deteriorating handwriting, and frequent falls. Examination revealed mild hemiparesis, lower motor neuron facial palsy and positive Babinski reflex on the right side. He also had ataxia and bilateral dysmetria. The patient progressively developed quadriparesis, bilateral internuclear ophthalmoplegia, multiple cranial nerve palsies, a pseudobulbar affect and a hyperreflexic neurogenic bladder over the next few months. (Source: Pediatric Neurology)
Source: Pediatric Neurology - January 13, 2015 Category: Neurology Authors: Young Ah Lee, William Kupsky, Deniz Altinok, Zhihong Joanne Wang, Lalitha Sivaswamy Tags: Visual Diagnosis Source Type: research

Ipsilesional limb ataxia and truncal ipsipulsion in isolated infarction of the superior cerebellar peduncle
The clinical features of a lesion confined to the superior cerebellar peduncle (SCP) have not been defined well in human. A 92-year-old woman suddenly developed mild dysarthria and severe imbalance from an isolated unilateral SCP infarction, and examination showed ipsiversive ocular torsion, severe ipsilesional limb ataxia, and truncal ipsipulsion. These findings are well consistent with those observed in monkeys when the SCP was severed. In addition to the dentate-rubro-thalamic projections, the SCP appears to contain the fibers involved in the control of eye motion in the roll plane. (Source: Journal of the Neurological Sciences)
Source: Journal of the Neurological Sciences - January 13, 2015 Category: Neurology Authors: Sun-Uk Lee, Hee-Joon Bae, Ji-Soo Kim Tags: Short communication Source Type: research

Macro- and Microstructural Changes in Patients with Spinocerebellar Ataxia Type 6: Assessment of Phylogenetic Subdivisions of the Cerebellum and the Brain Stem [BRAIN]
CONCLUSIONS: We found characteristic macro- and microstructural changes, depending on phylogenetic regions of the infratentorial brain, that strongly correlated with clinical symptoms in patients with spinocerebellar ataxia type 6. (Source: American Journal of Neuroradiology)
Source: American Journal of Neuroradiology - January 13, 2015 Category: Radiology Authors: Sato, K., Ishigame, K., Ying, S. H., Oishi, K., Miller, M. I., Mori, S. Tags: BRAIN Source Type: research

In vitro study of the neuropathic potential of the organophosphorus compounds trichlorfon and acephate.
Abstract Organophosphorus-induced delayed neuropathy (OPIDN) is a central and peripheral distal axonopathy characterized by ataxia and paralysis. Trichlorfon and acephate are two organophosphorus compounds (OPs) used worldwide as insecticide and which cause serious effects to non-target species. Despite that, the neuropathic potential of these OPs remains unclear. The present study addressed the neurotoxic effects and the neuropathic potential of trichlorfon and acephate in SH-SY5Y human neuroblastoma cells, by evaluating inhibition and aging of neuropathy target esterase (NTE), inhibition of acetylcholinesterase (...
Source: Toxicology in Vitro - January 13, 2015 Category: Toxicology Authors: Fernandes LS, Emerick GL, Dos Santos NA, Paula ES, Barbosa F, Santos AC Tags: Toxicol In Vitro Source Type: research

[Series] Treatment of progressive multiple sclerosis: what works, what does not, and what is needed
Disease-modifying drugs have mostly failed as treatments for progressive multiple sclerosis. Management of the disease therefore solely aims to minimise symptoms and, if possible, improve function. The degree to which this approach is based on empirical data derived from studies of progressive disease or whether treatment decisions are based on what is known about relapsing-remitting disease remains unclear. Symptoms rated as important by patients with multiple sclerosis include balance and mobility impairments, weakness, reduced cardiovascular fitness, ataxia, fatigue, bladder dysfunction, spasticity, pain, cognitive defi...
Source: Lancet Neurology - January 12, 2015 Category: Neurology Authors: Anthony Feinstein, Jenny Freeman, Albert C Lo Tags: Series Source Type: research

[In Context] Friedreich's footprint
Nikolaus Friedreich (1825–1882) was a German neurologist, who is probably best remembered for giving his name to the rare progressive autosomal neurodegenerative disease Friedreich's ataxia, but he was also interested in several other branches of medicine. He was instrumental in the establishment of clinicopathological correlations for brain tumours, muscular dystrophies, and spinal ataxias.1 (Source: Lancet Neurology)
Source: Lancet Neurology - January 12, 2015 Category: Neurology Authors: Steven Goodrick Tags: In Context Source Type: research

Excessive brain iron accumulation in spinocerebellar ataxia type 17
A 60-year-old man had a 3-year history of cerebellar ataxia and dementia, without a family history. T1-weighted MRI showed cerebellar atrophy (figure, A). Susceptibility-weighted images (SWI) revealed hypointensities of the basal ganglia and mesencephalic and cerebellar nuclei (figure, B, a–c), suggesting neurodegeneration with brain iron accumulation.1 Serum copper, iron, ferritin, transferrin, and ceruloplasmin levels were normal. Genetic testing revealed a CAG/CAA repeat expansion of 1 allele with 44 repeats (normal range 25–42), within the reduced penetrance range (43–48 repeats) in the TATA box bindi...
Source: Neurology - January 12, 2015 Category: Neurology Authors: Claassen, J., Gerding, W. M., Kastrup, O., Uslar, E., Goericke, S., Timmann, D. Tags: MRI, All Clinical Neurology, Spinocerebellar ataxia NEUROIMAGES Source Type: research

Treatment of progressive multiple sclerosis: what works, what does not, and what is needed
Publication date: February 2015 Source:The Lancet Neurology, Volume 14, Issue 2 Author(s): Anthony Feinstein , Jenny Freeman , Albert C Lo Disease-modifying drugs have mostly failed as treatments for progressive multiple sclerosis. Management of the disease therefore solely aims to minimise symptoms and, if possible, improve function. The degree to which this approach is based on empirical data derived from studies of progressive disease or whether treatment decisions are based on what is known about relapsing-remitting disease remains unclear. Symptoms rated as important by patients with multiple sclerosis include balan...
Source: The Lancet Neurology - January 12, 2015 Category: Neurology Source Type: research

Sacs knockout mice present pathophysiological defects underlying autosomal recessive spastic ataxia of Charlevoix-Saguenay
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS [MIM 270550]) is an early-onset neurodegenerative disorder caused by mutations in the SACS gene. Over 170 SACS mutations have been reported worldwide and are thought to cause loss of function of sacsin, a poorly characterized and massive 520 kDa protein. To establish an animal model and to examine the pathophysiological basis of ARSACS, we generated Sacs knockout (Sacs–/–) mice. Null animals displayed an abnormal gait with progressive motor, cerebellar and peripheral nerve dysfunctions highly reminiscent of ARSACS. These clinical features were ac...
Source: Human Molecular Genetics - January 12, 2015 Category: Genetics & Stem Cells Authors: Lariviere, R., Gaudet, R., Gentil, B. J., Girard, M., Conte, T. C., Minotti, S., Leclerc-Desaulniers, K., Gehring, K., McKinney, R. A., Shoubridge, E. A., McPherson, P. S., Durham, H. D., Brais, B. Tags: ARTICLES Source Type: research

Expression of a pathogenic mutation of SOD1 sensitizes aprataxin-deficient cells and mice to oxidative stress and triggers hallmarks of premature ageing
We report a delayed population doubling and accelerated senescence in Aptx–/– primary mouse fibroblasts, which is not due to detectable telomere instability or cell cycle deregulation but is associated with a reduction in transcription recovery following oxidative stress. Expression of SOD1G93A uncovers a survival defect ex vivo in cultured cells and in vivo in tissues lacking Aptx. The surviving neurons feature numerous and deep nuclear envelope invaginations, a hallmark of cellular stress. Furthermore, they possess an elevated number of high-density nuclear regions and a concomitant increase in histone H3 K9 ...
Source: Human Molecular Genetics - January 12, 2015 Category: Genetics & Stem Cells Authors: Carroll, J., Page, T. K. W., Chiang, S.-C., Kalmar, B., Bode, D., Greensmith, L., Mckinnon, P. J., Thorpe, J. R., Hafezparast, M., El-Khamisy, S. F. Tags: ARTICLES Source Type: research

Mechanisms of ATM Activation.
Abstract The ataxia-telangiectasia mutated (ATM) protein kinase is a master regulator of the DNA damage response, and it coordinates checkpoint activation, DNA repair, and metabolic changes in eukaryotic cells in response to DNA double-strand breaks and oxidative stress. Loss of ATM activity in humans results in the pleiotropic neurodegeneration disorder ataxia-telangiectasia. ATM exists in an inactive state in resting cells but can be activated by the Mre11-Rad50-Nbs1 (MRN) complex and other factors at sites of DNA breaks. In addition, oxidation of ATM activates the kinase independently of the MRN complex. This re...
Source: Annual Review of Biochemistry - January 12, 2015 Category: Biochemistry Authors: Paull TT Tags: Annu Rev Biochem Source Type: research

Ataxia telangiectasia mutated inhibits oxidative stress-induced apoptosis by regulating heme oxygenase-1 expression.
In conclusion, ATM induces HO-1 expression via activation of PKC-δ and NF-κB and inhibits oxidative stress-induced apoptosis. A loss of HO-1 induction may explain why AT patients are vulnerable to oxidative stress. PMID: 25592228 [PubMed - as supplied by publisher] (Source: The International Journal of Biochemistry and Cell Biology)
Source: The International Journal of Biochemistry and Cell Biology - January 12, 2015 Category: Biochemistry Authors: Yu JH, Cho SO, Lim JW, Kim N, Kim H Tags: Int J Biochem Cell Biol Source Type: research

Clinical aspects of envenomation caused by Tityus obscurus (Gervais, 1843) in two distinct regions of Pará state, Brazilian Amazon basin: a prospective case series
Conclusion : The present study shows that two regions of Para state differ in the clinical manifestations and severity of confirmed envenomation by T. obscurus which suggests a toxicity variation resulting from the diversity of T. obscurus venom in different areas of the Brazilian Amazon basin, and that T. serrulatus antivenom can be successfully used against T. obscurus. (Source: Journal of Venomous Animals and Toxins including Tropical Diseases)
Source: Journal of Venomous Animals and Toxins including Tropical Diseases - January 11, 2015 Category: Tropical Medicine Source Type: research

D-lactic acidosis mediated neuronal encephalopathy in acute lymphoblastic leukemia patient: An under diagnosis
We present here a case of D-lactic acidosis in a patient with acute lymphoblastic leukemia (ALL) who developed severe neurological symptoms and metabolic acidosis due to vancomycin-resistant enterococci (VRE) infection, and elevated D-lactic acid. (Source: Clinica Chimica Acta)
Source: Clinica Chimica Acta - January 11, 2015 Category: Laboratory Medicine Source Type: research

Isoliquiritigenin causes DNA damage and inhibits ATM expression leading to G2/M phase arrest and apoptosis in oral squamous cell carcinoma
Conclusions: ATM was cleaved by ISL‐activated caspase, thus inhibiting DNA repair in OSCC cells. Therefore, ISL is a promising chemopreventive agent against oral cancer. This article is protected by copyright. All rights reserved. (Source: Head and Neck)
Source: Head and Neck - January 10, 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

Ubiquitin-specific protease 14 regulates c-Jun N-terminal kinase signaling at the neuromuscular junction
Conclusions: USP14's catalytic activity is required for nervous system structure and function and has an ongoing role in NMJ synaptic transmission. By regulating the ubiquitination status of protein kinases, USP14 can coordinate the activity of intracellular signaling pathways that control the development and activity of the NMJ. (Source: BioMed Central)
Source: BioMed Central - January 10, 2015 Category: Journals (General) Authors: Jada H VadenBula J BhattacharyyaPing-Chung ChenJennifer A WatsonAndrea G MarshallScott E PhillipsJulie A WilsonGwendalyn D KingRichard J MillerScott M Wilson Source Type: research

From Ventriculomegaly to severe muscular atrophy: Expansion of the clinical spectrum related to mutations in AIFM1
We report here on a further patient thereby expanding the clinical and mutation spectrum. In addition, we review the known phenotypes related to AIFM1 mutations. The clinical course in the male patient described here was characterized by phases with rapid deterioration and long phases without obvious progression of disease. At age 2.5years he developed hearing loss and severe ataxia and at age 10years muscle wasting, swallowing difficulties, respiratory insufficiency and external opthamoplegia. By next generation sequencing of whole exome we identified a hemizygous missense mutation in the AIFM1 gene, c.727G>T (p.Va...
Source: Mitochondrion - January 10, 2015 Category: Biochemistry Source Type: research

Tandem gait performance in essential tremor patients correlates with cognitive function
Conclusions: More cognitive difficulty was associated with more tandem gait difficulty in ET. Ambulation often requires the concurrent use of both cognitive and motor neural systems; hence it is possible that the cognitive and gait problems in ET reflect an underlying pervasive disorder affecting both cognitive and motor circuits. (Source: BioMed Central)
Source: BioMed Central - January 10, 2015 Category: Journals (General) Authors: Elan D LouisAshwini K Rao Source Type: research

Novel ATM mutation in a German patient presenting as generalized dystonia without classical signs of ataxia-telangiectasia
(Source: Journal of Neurology)
Source: Journal of Neurology - January 8, 2015 Category: Neurology Source Type: research

A novel frameshift mutation in FGF14 causes an autosomal dominant episodic ataxia
Abstract Episodic ataxias (EAs) are a heterogeneous group of neurological disorders characterized by recurrent attacks of ataxia. Mutations in KCNA1 and CACNA1A account for the majority of EA cases worldwide. We recruited a two-generation family affected with EA of unknown subtype and performed whole-exome sequencing on two affected members. This revealed a novel heterozygous mutation c.211_212insA (p.I71NfsX27) leading to a premature stop codon in FGF14. Mutations in FGF14 are known to cause spinocerebellar ataxia type 27 (SCA27). Sanger sequencing confirmed segregation within the family. Our findings expand the ...
Source: Neurogenetics - January 8, 2015 Category: Genetics & Stem Cells Source Type: research

Prevalence and characteristics of tremor in the NARCOMS multiple sclerosis registry: a cross-sectional survey
Conclusions Tremor is common among NARCOMS registrants and severely disabling for some. Both ADL-based and symptom-descriptive measures of tremor severity can be used to stratify patients. (Source: BMJ Open)
Source: BMJ Open - January 8, 2015 Category: Journals (General) Authors: Rinker, J. R., Salter, A. R., Walker, H., Amara, A., Meador, W., Cutter, G. R. Tags: Open access, Epidemiology, Neurology Research Source Type: research

Gait and Balance in Adults with Friedreich's Ataxia
Friedreich's Ataxia (FA) is an autosomal recessive, neurodegenerative disease characterized by progressive lower extremity muscle weakness and areflexia, decreased vibratory and proprioceptive sense, imbalance and gait ataxia. [1]. FA is considered a sensory ataxia due to early involvement of the dorsal root ganglia and spinal cord dorsal columns with later involvement of the cerebellum [2]. Rating scales such as the International Cooperative Ataxia Rating Scale or the Friedreich's Ataxia Rating Scale (FARS) are often used clinically and in research to evaluate the severity and progression of FA [3]. (Source: Gait and Posture)
Source: Gait and Posture - January 8, 2015 Category: Orthopaedics Authors: Jeannie Stephenson, Theresa Zesiewicz, Clifton Gooch, Lynn Wecker, Kelly Sullivan, Israt Jahan, Seok Hun Kim Source Type: research

Visual consciousness explained by its impairments
Purpose of review: The scientific study of the visual consciousness has been marked by significant recent achievements, resulting from an interaction between the exploration of cognition in both brain-damaged patients and healthy individuals. Several neuropsychological syndromes contain marked dissociations which permit the identification of principles related to the neurophysiology of consciousness. The generality of these principles can then be evaluated in healthy individuals using a combination of experimental psychology paradigms, and functional brain-imaging tools. Recent findings: In this article, I review major fin...
Source: Current Opinion in Neurology - January 6, 2015 Category: Neurology Tags: NEURO-OPHTHALMOLOGY AND NEUROOTOLOGY: Edited by Jose-Alain Sahel and Joseph Furman Source Type: research