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Portal–Left Atrium Shunt Leading to Stroke
A 37-year-old man presented acutely with a stroke, ataxia, and left upper limb weakness. His medical history was positive for congenital low-grade liver fibrosis and for a single episode of paresthesia of the left upper limb (4 y previously). Magnetic resonance imaging showed acute ischemic lesions in the right cerebellum and temporal region (). Chest radiography, blood tests, and echocardiography were normal. Computed tomography demonstrated dilatation of the portal vein and gastroesophageal varix arising from the left gastric vein (arrowhead) and reaching the left atrium (arrow), which is partially contrasted in the veno...
Source: Journal of Vascular and Interventional Radiology : JVIR - February 27, 2014 Category: Radiology Authors: Umberto G. Rossi, Giovanni Gandini, Maurizio Cariati Source Type: research
Altered structural brain connectome in young adult fragile X premutation carriers
Abstract Fragile X premutation carriers (fXPC) are characterized by 55–200 CGG trinucleotide repeats in the 5′ untranslated region on the Xq27.3 site of the X chromosome. Clinically, they are associated with the fragile X‐Associated Tremor/Ataxia Syndrome, a late‐onset neurodegenerative disorder with diffuse white matter neuropathology. Here, we conducted first‐ever graph theoretical network analyses in fXPCs using 30‐direction diffusion‐weighted magnetic resonance images acquired from 42 healthy controls aged 18–44 years (HC; 22 male and 20 female) and 46 fXPCs (16 male and 30 female). Globally, we found n...
Source: Human Brain Mapping - February 27, 2014 Category: Neurology Authors: Alex Leow, Danielle Harvey, Naomi J. Goodrich‐Hunsaker, Johnson Gadelkarim, Anand Kumar, Liang Zhan, Susan M. Rivera, Tony J. Simon Tags: Research Article Source Type: research
The panorama of cerebral palsy in Sweden. XI. Changing patterns in the birth‐year period 2003‐2006
ConclusionThe overall prevalence of CP in western Sweden was stable. However, the distribution of CP types changed and the term hemiplegia increased significantly. Among children with CP born extremely preterm, the percentage born before 26 weeks of gestation had increased.This article is protected by copyright. All rights reserved. (Source: Acta Paediatrica)
Source: Acta Paediatrica - February 27, 2014 Category: Pediatrics Authors: K. Himmelmann, P. Uvebrant Tags: Regular Article Source Type: research
Mimosine Blocks S Phase Entry through ATM Activation [Cell Biology]
Mimosine is an effective cell synchronization reagent used for arresting cells in late G1 phase. However, the mechanism underlying mimosine-induced G1 cell cycle arrest remains unclear. Using highly synchronous cell populations, we show here that mimosine blocks S phase entry through ATM activation. HeLa S3 cells are exposed to thymidine for 15 h, released for 9 h by washing out the thymidine, and subsequently treated with 1 mm mimosine for a further 15 h (thymidine → mimosine). In contrast to thymidine-induced S phase arrest, mimosine treatment synchronizes >90% of cells at the G1-S phase boundary by inhibiting the tran...
Source: Journal of Biological Chemistry - February 27, 2014 Category: Chemistry Authors: Kubota, S., Fukumoto, Y., Ishibashi, K., Soeda, S., , Yuki, R., Nakayama, Y., Aoyama, K., Yamaguchi, N., Tags: Cell Biology Source Type: research
Distinct Phenotype Clusters in Childhood Inflammatory Brain Diseases: Implications for Diagnostic Evaluation
ConclusionChildren with inflammatory brain diseases presented with distinct phenotypical patterns that are associated with specific diagnoses. This information may inform the development of a diagnostic classification of childhood inflammatory brain diseases and suggest that specific pathways of diagnostic evaluation are warranted. (Source: Arthritis and Rheumatism)
Source: Arthritis and Rheumatism - February 25, 2014 Category: Rheumatology Authors: Tania Cellucci, Pascal N. Tyrrell, Marinka Twilt, Shehla Sheikh, Susanne M. Benseler Tags: Vasculitis Source Type: research
Genetic Relationship Between Predisposition for Binge Alcohol Consumption and Blunted Sensitivity to Adverse Effects of Alcohol in Mice
ConclusionsThese results suggest that HDID‐1 mice exhibit aspects of blunted ataxic and hypnotic sensitivity to EtOH which may influence their high EtOH intake via DID, but do not display widely different development of AFT. These findings differ from previous findings with the high alcohol‐preferring (HAP) selected mouse lines, suggesting that genetic predisposition for binge, versus other forms of excessive alcohol consumption, is associated with unique responses to EtOH‐induced motor incoordination. (Source: Alcoholism: Clinical and Experimental Research)
Source: Alcoholism: Clinical and Experimental Research - February 25, 2014 Category: Addiction Authors: Brandon M. Fritz, Kristy A. Cordero, Amanda M. Barkley‐Levenson, Pamela Metten, John C. Crabbe, Stephen L. Boehm Tags: Original Article Source Type: research
Clinical assessment of the sensory ataxias; diagnostic algorithm with illustrative cases.
Abstract Ataxia is a common neurological syndrome resulting from cerebellar, vestibular or sensory disorders. The recognition and characterisation of sensory ataxia remains a challenge. Cerebellar ataxia is the more common and easier to identify; sensory ataxia is often mistaken for cerebellar ataxia, leading to diagnostic errors and delays. A coherent aetiological work-up is only possible if clinicians initially recognise sensory ataxia. We discuss ways to separate sensory from cerebellar ataxia, the causes of sensory ataxia and the clinico-neurophysiological syndromes causing the sensory ataxia syndromes. We summ...
Source: Practical Neurology - February 25, 2014 Category: Neurology Authors: Chhetri SK, Gow D, Shaunak S, Varma A Tags: Pract Neurol Source Type: research
Topiramate add-on for drug-resistant partial epilepsy.
CONCLUSIONS: Topiramate has efficacy as an add-on treatment for drug-resistant partial epilepsy in that it is three times more effective compared to a placebo in reducing seizures. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of topiramate. In the short term topiramate as an add-on has been shown to be associated with several adverse events. The results of this review cannot be extrapolated to monotherapy or treatment of other epilepsy types and future research should consider examining the effect of dose. PMID: 24570033 [PubMed - as supplied by publi...
Source: Cochrane Database of Systematic Reviews - February 25, 2014 Category: Journals (General) Authors: Pulman J, Jette N, Dykeman J, Hemming K, Hutton JL, Marson AG Tags: Cochrane Database Syst Rev Source Type: research
Familial Alzheimer’s disease–associated presenilin-1 alters cerebellar activity and calcium homeostasis
Familial Alzheimer’s disease (FAD) is characterized by autosomal dominant heritability and early disease onset. Mutations in the gene encoding presenilin-1 (PS1) are found in approximately 80% of cases of FAD, with some of these patients presenting cerebellar damage with amyloid plaques and ataxia with unclear pathophysiology. A Colombian kindred carrying the PS1-E280A mutation is the largest known cohort of PS1-FAD patients. Here, we investigated PS1-E280A–associated cerebellar dysfunction and found that it occurs early in PS1-E208A carriers, while cerebellar signs are highly prevalent in patients with dementia. Postm...
Source: Journal of Clinical Investigation - February 24, 2014 Category: Biomedical Science Authors: Diego Sepulveda-Falla, Alvaro Barrera-Ocampo, Christian Hagel, Anne Korwitz, Maria Fernanda Vinueza-Veloz, Kuikui Zhou, Martijn Schonewille, Haibo Zhou, Luis Velazquez-Perez, Roberto Rodriguez-Labrada, Andres Villegas, Isidro Ferrer, Francisco Lopera, Tho Source Type: research
cAMP signaling inhibits radiation-induced ATM phosphorylation leading to the augmentation of apoptosis in human lung cancer cells
Conclusions: cAMP signaling inhibits radiation-induced ATM activation by PKA-dependent activation of PP2A, and this signaling mechanism augments radiation-induced apoptosis by reducing ATM-dependent activation of NF-kappaB in lung cancer cells. (Source: Molecular Cancer)
Source: Molecular Cancer - February 24, 2014 Category: Cancer & Oncology Authors: Eun-Ah ChoEui-Jun KimSahng-June KwakYong-Sung Juhnn Source Type: research
Rater Agreement on Gait Assessment during Neurologic Examination of Horses
Conclusion and Clinical ImportanceClinicians should be aware of poor agreement even between skilled observers of equine gait abnormalities, especially when the clinical signs are subtle. (Source: Journal of Veterinary Internal Medicine)
Source: Journal of Veterinary Internal Medicine - February 24, 2014 Category: Veterinary Research Authors: E. Olsen, B. Dunkel, W.H.J. Barker, E.J.T. Finding, J.D. Perkins, T.H. Witte, L.J. Yates, P.H. Andersen, K. Baiker, R.J. Piercy Tags: Original Article Source Type: research
Multiple system atrophy of the cerebellar type: Clinical state of the art
ABSTRACT Multiple system atrophy (MSA) is a late‐onset, sporadic neurodegenerative disorder clinically characterized by autonomic failure and either poorly levodopa‐responsive parkinsonism or cerebellar ataxia. It is neuropathologically defined by widespread and abundant central nervous system α‐synuclein–positive glial cytoplasmic inclusions and striatonigral and/or olivopontocerebellar neurodegeneration. There are two clinical subtypes of MSA distinguished by the predominant motor features: the parkinsonian variant (MSA‐P) and the cerebellar variant (MSA‐C). Despite recent progress in understanding the patho...
Source: Movement Disorders - February 24, 2014 Category: Neurology Authors: David J. Lin, Katherine L. Hermann, Jeremy D. Schmahmann Tags: Review Source Type: research
A Curative Treatment Option for Complex Regional Pain Syndrome (CRPS) Type I: Dorsal Root Entry Zone Operation (Report of Two Cases).
Abstract Complex Regional Pain Syndrome Type I (CRPS-I) is a debated health problem concerning its pathophysiology and treatment strategies. A 12-year-old boy and a 35-year-old woman were diagnosed with CRPS-I at different times. They had previously undergone various types of interventions with no success. After one year of follow-up and observation, DREZ lesioning operation was performed. Afterwards, both cases had transient lower extremity ataxia. The first case was followed for 60 months with no recurrence and total cure. The second case was pain-free until the 6th month, when she required psychological support;...
Source: Turkish Neurosurgery - February 21, 2014 Category: Neurosurgery Authors: Kanpolat Y, Al-Beyati E, Ugur HC, Akpinar G, Kahilogullari G, Bozkurt M Tags: Turk Neurosurg Source Type: research
Posterior inferior cerebellar artery aneurysms: operative strategies based on a surgical series of 27 patients.
CONCLUSION: PICA aneurysms, by virtue of their rarity and strategic location pose a unique technical challenge. Depending on the PICA segment affected, variations in the surgical corridor and clipping strategy were major contributors to good outcomes. PMID: 24535788 [PubMed - in process] (Source: Turkish Neurosurgery)
Source: Turkish Neurosurgery - February 21, 2014 Category: Neurosurgery Authors: Viswanathan GC, Menon G, Nair S, Abraham M Tags: Turk Neurosurg Source Type: research
74 Year‐Old Woman with Systemic Lupus Erythematosis and Recent Onset Ataxia
(Source: Brain Pathology)
Source: Brain Pathology - February 18, 2014 Category: Neurology Authors: Pasquale Donnarumma, Angelo Pichierri, Roberto Tarantino, Andrea Gennaro Ruggeri, Manila Antonelli, Roberto Delfini Tags: Case of Month November 2013 Source Type: research
CDK5 protects from caspase‐induced Ataxin‐3 cleavage and neurodegeneration
This article is protected by copyright. All rights reserved. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - February 18, 2014 Category: Neurology Authors: Jan Liman, Sebastian Deeg, Aaron Voigt, Hannes Voßfeldt, Christoph P. Dohm, André Karch, Jochen Weishaupt, Jörg B. Schulz, Mathias Bähr, Pawel Kermer Tags: Original Article Source Type: research
Genistein inhibits DNA methylation and increases expression of tumor suppressor genes in human breast cancer cells
In this study, we investigated whether genistein could modulate the DNA methylation status and expression of cancer‐related genes in breast cancer cells. We treated MCF‐7 and MDA‐MB‐231 human breast cancer cells with genistein in vitro. We found that genistein decreased the levels of global DNA methylation, DNA methyltransferase (DNMT) activity and expression of DNMT1. Yet, the expression of DNMT3A and DNMT3B showed no significant change. Using molecular modeling, we observed that genistein might directly interact with the catalytic domain of DNMT1, thus competitively inhibiting the binding of hemimethylated DNA to...
Source: Genes, Chromosomes and Cancer - February 16, 2014 Category: Cancer & Oncology Authors: Qi Xie, Qian Bai, Ling‐Yun Zou, Qian‐Yong Zhang, Yong Zhou, Hui Chang, Long Yi, Jun‐Dong Zhu, Man‐Tian Mi Tags: Research Article Source Type: research
MicroRNA-181a Functions as an Oncomir in Gastric Cancer by Targeting the Tumour Suppressor Gene ATM.
Abstract Based on our previous experiments, this study is to further investigate the functional significance of miR-181a and its target gene in gastric cancer. Expression of miR-181a was detected by qRT-PCR in three normal gastric tissues and three human gastric cancer cell lines (SGC-7901, MGC-803, and BGC-823 cells). After transfection with miR-181a inhibitor, proliferation, apoptosis, migration, and invasion of the SGC-7901 cells were evaluated. Ataxia-telangiectasia mutation (ATM) was predicted as a target gene of miR-181a with bioinformatics analysis, and was verified by lucifersae reporter assay. Expression o...
Source: Pathology Oncology Research - February 16, 2014 Category: Pathology Authors: Zhang X, Nie Y, Li X, Wu G, Huang Q, Cao J, Du Y, Li J, Deng R, Huang D, Chen B, Li S, Wei B Tags: Pathol Oncol Res Source Type: research
Posterior Subthalamic Area Deep Brain Stimulation for Fragile X–Associated Tremor/Ataxia Syndrome
Source: Neuromodulation - February 14, 2014 Category: Neurology Authors: Genko Oyama, Atsushi Umemura, Yasushi Shimo, Natsuko Nishikawa, Asuka Nakajima, Takayuki Jo, Madoka Nakajima, Hisato Ishii, Daisuke Yamada, Masashi Takanashi, Hajime Arai, Eiji Nanba, Nobutaka Hattori Tags: Letter to the Editor Source Type: research
Inactivation of mTor arrests bovine oocytes in the metaphase‐I stage, despite reversible inhibition of 4E‐BP1 phosphorylation
In conclusion, Torin2 enables an effective and specific inhibition of 4E‐BP1 phosphorylation, which may be valuable to investigate maturation specific protein synthesis in more detail. Mol. Reprod. Dev. 2014. © 2014 Wiley Periodicals, Inc. (Source: Molecular Reproduction and Development)
Source: Molecular Reproduction and Development - February 14, 2014 Category: Reproduction Medicine Authors: Sophia Mayer, Christine Wrenzycki, Wolfgang Tomek Tags: Research Article Source Type: research
Effects of acute phencyclidine administration on arginine metabolism in the hippocampus and prefrontal cortex in rats.
Abstract Phencyclidine (PCP), a non-competitive N-methyl-D-aspartate glutamate receptor antagonist, induces schizophrenic symptoms in healthy individuals, and altered arginine metabolism has been implicated in schizophrenia. The present study investigated the effects of a single subcutaneous injection of PCP (2, 5 or 10 mg/kg) on arginine metabolism in the sub-regions of the hippocampus and prefrontal cortex in male young adult Sprague-Dawley rats. Animals' general behavior was assessed in the open field apparatus 30 min after the treatment, and the brain tissues were collected at the time point of 60 min post-trea...
Source: Neuropharmacology - February 14, 2014 Category: Drugs & Pharmacology Authors: Knox LT, Yu J, Collie ND, Zhang H, Liu P Tags: Neuropharmacology Source Type: research
Autosomal dominant cerebellar ataxias: a systematic review of clinical features
ConclusionsAutosomal dominant cerebellar ataxias encompass a broad spectrum of clinical features with high prevalence of non‐ataxia symptoms. Certain features distinguish different genetic subtypes. A new algorithm for ADCA classification at disease onset is proposed. (Source: European Journal of Neurology)
Source: European Journal of Neurology - February 12, 2014 Category: Neurology Authors: M. Rossi, S. Perez‐Lloret, L. Doldan, D. Cerquetti, J. Balej, P. Millar Vernetti, M. Hawkes, A. Cammarota, M. Merello Tags: Original Article Source Type: research
Impact of copper deficiency in humans
Humans consume about 1 mg of copper daily, an amount thought adequate for most needs. Genetic, environmental, or physiological alterations can impose a higher copper set point, increasing risk for copper‐limited pathophysiology. Humans express about a dozen proteins that require copper for function (cuproenzymes). Limitation in the activity of cuproenzymes can explain the pleiotropic effect of copper deficiency. However, for most of the salient features of human copper deficiency, the precise molecular mechanisms are unknown. This is true for the two most common clinical features, hypochromic anemia and adult onset perip...
Source: Annals of the New York Academy of Sciences - February 12, 2014 Category: Science Authors: Joseph R. Prohaska Tags: Original Article Source Type: research
Ophthalmic features of PLA2G6-related paediatric neurodegeneration with brain iron accumulation.
CONCLUSIONS: Upgaze palsy, although not a previously reported finding, was confirmed in all patients (except in one for whom assessment could not be performed) and thus can be considered part of the phenotype in children and young adults. Other frequent findings not previously highlighted were abnormal convergence, saccadic pursuit, and saccadic intrusions. Optic nerve head pallor and strabismus, previously reported findings in the disease, were found in 100% and 50% of our cohort, respectively, and the strabismus in our series was always exotropia. Taken together, these clinical findings may be helpful in distinguishing P...
Source: The British Journal of Ophthalmology - February 12, 2014 Category: Opthalmology Authors: Khan AO, Aldrees A, Elmalik SA, Hassan HH, Koenig M, Stevanin G, Azzedine H, Salih MA Tags: Br J Ophthalmol Source Type: research
FDA Grants Orphan Drug Status To Edison Pharmaceutical's EPI-743
Friedreich's Ataxia Research Alliance (FARA) has announced in a press release that the FDA has granted orphan drug status to Edison Pharmaceutical’s EPI-743 (vatiquinone). The drug treats Friedreich’s ataxia, a rare nervous system disorder. (Source: Pharmaceutical Online News)
Source: Pharmaceutical Online News - February 11, 2014 Category: Pharmaceuticals Source Type: news
Safety and tolerability of carbamylated erythropoietin in Friedreich's ataxia
ConclusionCEPO was safe and well tolerated in a 2‐week treatment phase. Secondary outcome measures remained without apparent difference between CEPO and placebo. © 2014 International Parkinson and Movement Disorder Society (Source: Movement Disorders)
Source: Movement Disorders - February 11, 2014 Category: Neurology Authors: Sylvia Boesch, Wolfgang Nachbauer, Caterina Mariotti, Francesco Sacca, Alessandro Filla, Thomas Klockgether, Thomas Klopstock, Ludger Schöls, Heike Jacobi, Boriana Büchner, Jennifer Müller Hagen, Lorenzo Nanetti, Karen Manicom Tags: Brief Report Source Type: research
Synergistic enhancement of NK cell-mediated cytotoxicity by combination of histone deacetylase inhibitor and ionizing radiation
Conclusions: This study suggests that the expressions of NKG2D ligands are regulated in a complex manner at the multilevel of gene expression, and that their expressions can be induced by combinatorial treatments in lung cancer cells. (Source: Radiation Oncology)
Source: Radiation Oncology - February 10, 2014 Category: Cancer & Oncology Authors: Cheol-Hun SonJin-Hee KeumKwangmo YangJiho NamMi-Ju KimSun-Hee KimChi-Dug KangSae-Ock OhChi-Dae KimYou-Soo ParkJaeho Bae Source Type: research
Protein found to be associated with canine hereditary ataxia
Researchers have found a link between a mutation in a gene called RAB 24 and an inherited neurodegenerative disease in Old English sheepdogs and Gordon setters. The findings may help further understanding of neurodegenerative diseases and identify new treatments for both canine and human sufferers. (Source: ScienceDaily Headlines)
Source: ScienceDaily Headlines - February 7, 2014 Category: Science Source Type: news
Revisiting p53 for cancer-specific chemo- and radiotherapy: Ten years after.
Abstract Despite intense studies, highly effective therapeutic strategies against cancer have not yet been fully exploited, because few true cancer-specific targets have been identified. Most modalities, perhaps with the exception of radiation therapy, target proliferating cells, which are also abundant in normal tissues. Thus, most current cancer treatments have significant side effects. More than 10 years ago, the tumor suppressor p53 was first explored as a cancer-specific target. At the time, the approach was to introduce a normal p53 gene into mutant p53 (mp53) tumor cells to induce cell cycle arrest and apopt...
Source: Cell Cycle - February 7, 2014 Category: Cytology Authors: Beckta JM, Ahmad SF, Yang H, Valerie K Tags: Cell Cycle Source Type: research
Canine Hereditary Ataxia in Old English Sheepdogs and Gordon Setters Is Associated with a Defect in the Autophagy Gene Encoding RAB24
by Caryline Agler, Dahlia M. Nielsen, Ganokon Urkasemsin, Andrew Singleton, Noriko Tonomura, Snaevar Sigurdsson, Ruqi Tang, Keith Linder, Sampath Arepalli, Dena Hernandez, Kerstin Lindblad-Toh, Joyce van de Leemput, Alison Motsinger-Reif, Dennis P. O'Brien, Jerold Bell, Tonya Harris, Steven Steinberg, Natasha J. Olby Old English Sheepdogs and Gordon Setters suffer from a juvenile onset, autosomal recessive form of canine hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex. The clinical and histological characteristics are analogous to hereditary ataxias in humans. Linkage and genome-wide ass...
Source: PLoS Genetics - February 6, 2014 Category: Genetics & Stem Cells Authors: Caryline Agler et al. Source Type: research
Pharyngeal-cervical-brachial variant of Guillain-Barre syndrome
The pharyngeal-cervical-brachial (PCB) variant of Guillain–Barré syndrome is defined by rapidly progressive oropharyngeal and cervicobrachial weakness associated with areflexia in the upper limbs. Serial nerve conduction studies suggest that PCB represents a localised subtype of Guillain–Barré syndrome characterised by axonal rather than demyelinating neuropathy. Many neurologists are unfamiliar with PCB, which is often misdiagnosed as brainstem stroke, myasthenia gravis or botulism. The presence of additional ophthalmoplegia and ataxia indicates overlap with Fisher syndrome. Half of patients with...
Source: Journal of Neurology, Neurosurgery and Psychiatry - February 6, 2014 Category: Neurosurgery Authors: Wakerley, B. R., Yuki, N. Tags: Editor's choice, Immunology (including allergy), Cranial nerves, Drugs: CNS (not psychiatric), Neuromuscular disease, Stroke, Ophthalmology Source Type: research
Neuronal intranuclear inclusion disease cases with leukoencephalopathy diagnosed via skin biopsy
In this study, we identified... (Source: Journal of Neurology, Neurosurgery and Psychiatry)
Source: Journal of Neurology, Neurosurgery and Psychiatry - February 6, 2014 Category: Neurosurgery Authors: Sone, J., Kitagawa, N., Sugawara, E., Iguchi, M., Nakamura, R., Koike, H., Iwasaki, Y., Yoshida, M., Takahashi, T., Chiba, S., Katsuno, M., Tanaka, F., Sobue, G. Tags: PostScript Source Type: research
Molecular, clinical and peripheral neuropathy study of Tunisian patients with ataxia with vitamin E deficiency
We examined the clinical and molecular features of a large cohort of 132 Tunisian patients affected with ataxia with vitamin E deficiency. Of these patients, nerve conduction studies were performed on 45, and nerve biopsy was performed on 13. Serum vitamin E was dramatically reduced for 105 of the patients analysed. Molecular analysis revealed that 91.7% of the patients (n = 121) were homozygous for the 744delA mutation. Three other mutations were detected among the remaining patients (8.3%, n = 11) in the homozygous state. Two were previously reported (400C>T and 205-1G>T), and one was novel (553+1T>A). Age of on...
Source: Brain - February 5, 2014 Category: Neurology Authors: Euch-Fayache, G. E., Bouhlal, Y., Amouri, R., Feki, M., Hentati, F. Tags: Original Articles Source Type: research
The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation
We previously localized a new form of recessive ataxia with generalized tonic-clonic epilepsy and mental retardation to a 19 Mb interval in 16q21-q23 by homozygosity mapping of a large consanguineous Saudi Arabian family. We now report the identification by whole exome sequencing of the missense mutation changing proline 47 into threonine in the first WW domain of the WW domain containing oxidoreductase gene, WWOX, located in the linkage interval. Proline 47 is a highly conserved residue that is part of the WW motif consensus sequence and is part of the hydrophobic core that stabilizes the WW fold. We demonstrate that prol...
Source: Brain - February 5, 2014 Category: Neurology Authors: Mallaret, M., Synofzik, M., Lee, J., Sagum, C. A., Mahajnah, M., Sharkia, R., Drouot, N., Renaud, M., Klein, F. A. C., Anheim, M., Tranchant, C., Mignot, C., Mandel, J.-L., Bedford, M., Bauer, P., Salih, M. A., Schule, R., Schols, L., Aldaz, C. M., Koenig Tags: Original Articles Source Type: research
Drosophila Nesprin-1 controls glutamate receptor density at neuromuscular junctions.
Abstract Nesprin-1 is a core component of a protein complex connecting nuclei to cytoskeleton termed LINC (linker of nucleoskeleton and cytoskeleton). Nesprin-1 is anchored to the nuclear envelope by its C-terminal KASH domain, the disruption of which has been associated with neuronal and neuromuscular pathologies, including autosomal recessive cerebellar ataxia and Emery-Dreifuss muscular dystrophy. Here, we describe a new and unexpected role of Drosophila Nesprin-1, Msp-300, in neuromuscular junction. We show that larvae carrying a deletion of Msp-300 KASH domain (Msp-300 (∆KASH) ) present a locomotion defect s...
Source: Cellular and Molecular Life Sciences : CMLS - February 4, 2014 Category: Cytology Authors: Morel V, Lepicard S, N Rey A, Parmentier ML, Schaeffer L Tags: Cell Mol Life Sci Source Type: research
Urinary Symptoms and Urodynamics Findings in Patients with Friedreich's Ataxia
Conclusions LUTS was found in a large percentage of patients with FA, but only a few related it to their quality of life impairment. Although creatinine levels was normal in this sample, some patients may show upper urinary tract abnormalities, with deserves close observation and proper care. (Source: International Braz J Urol)
Source: International Braz J Urol - February 3, 2014 Category: Urology & Nephrology Source Type: research
Progressive myoclonic epilepsies: It takes a village to make a diagnosis
The progressive myoclonus epilepsies (PMEs) are a devastating group of rare disorders1 that manifest with increasing action myoclonus, which is also present at rest but activates with stimuli such as noise, light, or touch. Ultimately, patients become wheelchair-bound and experience early death. Neurologic signs that frequently but not reliably coexist include other seizure types (particularly generalized tonic-clonic), progressive ataxia, and dementia. Typically, presentation is in late childhood or adolescence; however, all ages may be affected. Although distinction from more common forms of genetic generalized epilepsy,...
Source: Neurology - February 3, 2014 Category: Neurology Authors: Knupp, K., Wirrell, E. Tags: Myoclonus; see Movement Disorders/myoclonus, Epilepsy semiology, Generalized seizures EDITORIALS Source Type: research
Fruit flies reveal normal function of gene mutated in spinocerebellar ataxia type 7
Disruptive clumps of mutated protein are often blamed for clogging cells and interfering with brain function in patients with the neurodegenerative diseases known as spinocerebellar ataxias. But a new study in fruit flies suggests that for at least one of these diseases, the defective proteins may not need to form clumps to do harm. (Source: ScienceDaily Headlines)
Source: ScienceDaily Headlines - February 1, 2014 Category: Science Source Type: news
Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large‐scale deletions or point mutations
This study constitutes proof‐of‐principle that, through heteroplasmy manipulation, delivery of site‐specific nuclease activity to mitochondria can alleviate a severe biochemical phenotype in primary mitochondrial disease arising from deleted mtDNA species. Mutations and rearrangements of mitochondrial DNA (mtDNA) are a common cause of human disease, where they often co‐exist with wild‐type mtDNA within a single cell. Mitochondrially targeted engineered zinc finger nucleases (mtZFNs) can phenotypically rescue a severe mtDNA‐mediated dysfunction and show future therapeutic potential. (Source: EMBO Molecular Medicine)
Source: EMBO Molecular Medicine - February 1, 2014 Category: Molecular Biology Authors: Payam A Gammage, Joanna Rorbach, Anna I Vincent, Edward J Rebar, Michal Minczuk Tags: Report Source Type: research
Intermittent Maple Syrup Urine Disease: Two Case Reports
The presenting symptoms and clinical course of 2 cases of intermittent maple syrup urine disease (MSUD) are described. Intermittent MSUD is a potentially life-threatening metabolic disorder caused by a deficiency of branched-chain α-keto acid dehydrogenase, the enzyme complex that decarboxylates the 3 branched-chain amino acids. In contrast to classic MSUD, children with the intermittent form show normal development with normal intelligence and, when asymptomatic, normal levels of branched-chain amino acids. Symptoms usually appear between 5 months and 2 years of age, when a trivial infection such as otitis media or ...
Source: PEDIATRICS - January 31, 2014 Category: Pediatrics Authors: Axler, O., Holmquist, P. Tags: Case Report Source Type: research
Preliminary pharmacokinetics of morphine and its major metabolites following intravenous administration of four doses to horses
This study extends previous studies and is the first report describing the metabolites of morphine in the horse. Plasma concentrations of morphine‐3‐glucuronide, a metabolite with demonstrated neuro‐excitatory activity in mice, far exceeded that of morphine‐6‐glucuronide. Further study is warranted to assess whether the high levels of the morphine‐3‐glucuronide contribute to the dose‐dependent excitation observed at high morphine doses. (Source: Journal of Veterinary Pharmacology and Therapeutics)
Source: Journal of Veterinary Pharmacology and Therapeutics - January 31, 2014 Category: Veterinary Research Authors: H. K. Knych, E. P. Steffey, D. S. McKemie Tags: Scientific Paper Source Type: research
Effects of Carbonic Anhydrase-Related Protein VIII on Human Cells Harboring A8344G Mitochondrial DNA Mutation
In this study, we show that there is a significant decrease of CA8 (carbonic anhydrase-related protein VIII) in cybrids harboring MERRF A8344G mutation. CA8 deficiency and mutations were found to be associated with a distinctive lifelong gait disorder in wdl (Waddles) mice and novel syndromes characterized by cerebellar ataxia and mental retardation in the human. Our results showed that overexpression of CA8 in MERRF cybrids significantly decreased cell death induced by (STS) staurosporine treatment, suggesting a protective function of CA8 in cells harboring the A8344G mutation of mtDNA.Interestingly, an increase in the fo...
Source: BJ Cell - January 30, 2014 Category: Biochemistry Authors: T Wang, C Cheng, T Chi, Y Ma, S Wu, Y Wei, M Hsieh Tags: BJ Disease Source Type: research
Aqueous extract of Gardenia jasminoides targeting oxidative stress to reduce polyQ aggregation in cell models of spinocerebellar ataxia 3.
Abstract Spinocerebellar ataxias (SCAs), caused by expanded CAG repeats encoding a long polyglutamine (polyQ) tract in the respective proteins, are characterized by the accumulation of intranuclear and cytoplasmic misfolded polyQ aggregation that leads to cell death. Suppression of aggregate formation can inhibit a wide range of downstream pathogenic events and is expected to be a therapeutic strategy for SCAs. Here we show the anti-aggregation potential of Gardenia jasminoides (G. jasminoides) and its components/metabolite geniposide, crocin, and genipin, in ATXN3/Q75-GFP 293 cells, a putative SCA3 cell model. We ...
Source: Neuropharmacology - January 30, 2014 Category: Drugs & Pharmacology Authors: Chang KH, Chen WL, Wu YR, Lin TH, Wu YC, Chao CY, Lin JY, Lee LC, Chen YC, Lee-Chen GJ, Chen CM Tags: Neuropharmacology Source Type: research
Clinical characterization and identification of duplication breakpoints in a Japanese family with Xq28 duplication syndrome including MECP2
Xq28 duplication syndrome including MECP2 is a neurodevelopmental disorder characterized by axial hypotonia at infancy, severe intellectual disability, developmental delay, mild characteristic facial appearance, epilepsy, regression, and recurrent infections in males. We identified a Japanese family of Xq28 duplications, in which the patients presented with cerebellar ataxia, severe constipation, and small feet, in addition to the common clinical features. The 488‐kb duplication spanned from L1CAM to EMD and contained 17 genes, two pseudo genes, and three microRNA‐coding genes. FISH and nucleotide sequence analyses dem...
Source: American Journal of Medical Genetics Part A - January 29, 2014 Category: Genetics & Stem Cells Authors: Daisuke Fukushi, Kenichiro Yamada, Noriko Nomura, Misako Naiki, Reiko Kimura, Yasukazu Yamada, Toshiyuki Kumagai, Kumiko Yamaguchi, Yoshishige Miyake, Nobuaki Wakamatsu Tags: Research Article Source Type: research
A novel recurrent mutation in ATP1A3 causes CAPOS syndrome
Conclusion: Other mutations in ATP1A3 have previously been demonstrated to cause rapid-onset dystonia-parkinsonism (also called dystonia-12) or alternating hemiplegia of childhood. This study shows that an allelic mutation in ATP1A3 produces CAPOS syndrome. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - January 28, 2014 Category: Internal Medicine Authors: Michelle DemosClara van KarnebeekColin RossShelin AdamYaoqing ShenShing ZhanCasper ShyrGabriella HorvathMohnish SuriAlan FryerSteven JonesJan Friedman Source Type: research
International patient alliance to fund Spanish Friedreich's ataxia gene-therapy project
(Institute for Research in Biomedicine (IRB Barcelona)) The gene therapy-based research project to tackle Friedreich's ataxia launched in November in labs at the Institute for Research in Biomedicine, in Barcelona, and the "Centro de Biología Molecular Severo Ochoa", in Madrid, has received 100,000 US$ per year for two years from the Friedreich's Ataxia Research Alliance. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - January 28, 2014 Category: Biology Source Type: news
Loss of GABAergic cortical neurons underlies the neuropathology of Lafora disease
Conclusions: Here, we concluded that there is impairment in GABAergic neurons neurodevelopment in the cerebral cortex, which occurs prior to the formation of Lafora bodies in the cytoplasm. The dysregulation of cerebral cortex development may contribute to Lafora disease pathogenesis. (Source: Molecular Brain)
Source: Molecular Brain - January 28, 2014 Category: Neuroscience Authors: Saida OrtolanoIrene VieitezRoberto Agis-BalboaCarlos Spuch Source Type: research
A novel missense mutation in CACNA1A evaluated by in silico protein modeling is associated with non-episodic spinocerebellar ataxia with slow progression.
Abstract Spinocerebellar ataxia type 6 (SCA6), episodic ataxia type 2 (EA2) and familial hemiplegic migraine type 1 (FHM1) are allelic disorders of the gene CACNA1A encoding the P/Q subunit of a voltage gated calcium channel. While SCA6 is related to repeat expansions affecting the C-terminal part of the protein, EA2 and FHM phenotypes are usually associated with nonsense and missense mutations leading to impaired channel properties. In three unrelated families with dominant cerebellar ataxia, symptoms cosegregated with CACNA1A missense mutations of evolutionary highly conserved amino acids (exchanges p.E668K, p.R5...
Source: European Journal of Medical Genetics - January 28, 2014 Category: Genetics & Stem Cells Authors: Bürk K, Kaiser FJ, Tennstedt S, Schöls L, Kreuz FR, Wieland T, Strom TM, Büttner T, Hollstein R, Braunholz D, Plaschke J, Gillessen-Kaesbach G, Zühlke C Tags: Eur J Med Genet Source Type: research
Carbonic Anhydrase‐Related Protein VIII antibodies and paraneoplastic cerebellar degeneration
Paraneoplastic cerebellar degeneration (PCD) is a common cause of subacute cerebellar ataxia caused by widespread loss of the Purkinje cells of the cerebellum. PCD diagnosis can be confirmed by detection of onconeural antibodies that may also indicate the underlying tumor type . Most onconeural antibodies associated with PCD recognize intracellular antigens in Purkinje cells . These antigens are supposed to induce, besides the antibody synthesis, an antigen‐specific cytotoxic T‐cell attack that probably is responsible of the Purkinje cell death and limited response to treatment [3,4]. The most common onconeural a...
Source: Neuropathology and Applied Neurobiology - January 22, 2014 Category: Neurology Authors: Romana Höftberger, Lidia Sabater, Fernando Velasco, Robert Ciordia, Josep Dalmau, Francesc Graus Tags: Scientific Correspondence Source Type: research
Nystagmus as an early ocular alteration in Machado-Joseph disease (MJD/SCA3)
Conclusions: The frequency of nystagmus in asymptomatic carriers and its absence in non-carriers of the mutation, suggests that nystagmus may appear before gait disturbance and can thus be considered an early sign of MJD. (Source: BMC Neurology)
Source: BMC Neurology - January 22, 2014 Category: Neurology Authors: Mafalda RaposoJoão VasconcelosConceição BettencourtTeresa KayPaula CoutinhoManuela Lima Source Type: research