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[Gorlin syndrome in the paediatric age].
CONCLUSIONS. In GS there is an increase in the likelihood of developing basal cell carcinomas and strict dermatological monitoring is necessary. A clinical neurological follow-up and also magnetic resonance imaging scans are needed for an early diagnosis of intracranial tumours, especially in the case of medulloblastomas. Odontogenic keratocysts, other skin disorders, and cardiac and ovarian fibromas are characteristic, as are skeletal abnormalities, which require regular clinical and neuroimaging controls and treatment if needed, but radiation must be avoided. GS is a rare disorder, but it must be suspected in the presenc...
Source: Revista de Neurologia - April 1, 2014 Category: Neurology Authors: Roncales-Samanes P, Pena-Segura JL, Fernando-Martinez R, Fuertes-Rodrigo C, Garcia-Oguiza A, Lopez-Pison J Tags: Rev Neurol Source Type: research

What Causes Ataxia?
Discussion Coordination and balance problems are caused by various problems affecting the central and peripheral nervous system. Normal development of a child or weakness of a child are commonly mistaken for true ataxia. Ataxia specifically refers to “…impairment of the coordination of movement without loss of muscle strength.” If it is purely due to abnormalities of the cerebellum then there should be no changes in mental status, sensation or weakness. Sometimes it is difficult to determine if there are abnormalities in other areas. For example, Guillian-Barre often presents with difficulty or clumsy wal...
Source: PediatricEducation.org - March 31, 2014 Category: Pediatrics Authors: pediatriceducationmin Tags: Uncategorized Source Type: news

Fixing frataxin: ‘ironing out’ the metabolic defect in Friedreich's ataxia
This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8 (Source: British Journal of Pharmacology)
Source: British Journal of Pharmacology - March 28, 2014 Category: Drugs & Pharmacology Authors: A Anzovino, D J R Lane, M L‐H Huang, D R Richardson Tags: Review Source Type: research

Evidence of dehydration and electrolyte disturbances in cases of perennial ryegrass toxicosis in Australian sheep
ConclusionWe speculate that changes in hydration status may be a contributory aetiological factor in those years in which high numbers of deaths are associated with PRGT outbreaks in Australia. (Source: Australian Veterinary Journal)
Source: Australian Veterinary Journal - March 26, 2014 Category: Veterinary Research Authors: MDA Combs, D Rendell, KFM Reed, WJ Mace, JC Quinn Tags: CASE SERIES AND CLINICAL REVIEW Source Type: research

Unravelling nerve-cell death in rare children's disease
(Sanford-Burnham Medical Research Institute) Researchers discover mutations in a protein that plays a role in the body's DNA repair system -- similar to what's observed in the rare children's disease ataxia-telangiectasia. The discovery provides an approach to identifying therapies that will resuscitate the broken DNA repair mechanism. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - March 25, 2014 Category: Global & Universal Source Type: news

Clinical Characteristics of Basilar‐Type Migraine in the Neurological Clinic of a University Hospital
ConclusionBasilar‐type migraine is an episodic disorder and occurred in 1.5% of patients with headache. More than one‐half of patients have their first attack in the second and third decade of life. Trigger factors were common, and patients should be educated to avoid trigger factors. (Source: Pain Medicine)
Source: Pain Medicine - March 25, 2014 Category: Anesthesiology Authors: Guomin Ying, Wen Fan, Nan Li, Jing Wang, Wangwen Li, Ge Tan, Jiying Zhou Tags: Original Article Source Type: research

A new intellectual disability syndrome caused by CTNNB1 haploinsufficiency
A girl patient born to healthy nonconsanguineous parents was referred at age 3 years and 2 months to our genetics department for testing due to developmental delay and postnatal microcephaly. Initial clinical evaluation revealed an overall developmental delay, mildly dysmorphic features, thin, sparse fair hair, and fair skin. Postnatal microcephaly and progressive ataxia and spasticity appeared later. Array CGH karyotyping showed a 333 kb de novo microdeletion on 3p22 covering the entire genomic sequence of a single gene, CTNNB1, which codes for β‐catenin. β‐catenin is a sub‐unit of a multiprotein complex, which ...
Source: American Journal of Medical Genetics Part A - March 25, 2014 Category: Genetics & Stem Cells Authors: Estelle Dubruc, Audrey Putoux, Audrey Labalme, Christelle Rougeot, Damien Sanlaville, Patrick Edery Tags: Clinical Report 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. (Source: Acta Paediatrica)
Source: Acta Paediatrica - March 24, 2014 Category: Pediatrics Authors: Kate Himmelmann, Paul Uvebrant Tags: Regular Article Source Type: research

Teaching NeuroImages: Snowball-like lesions with sudden hearing loss
A 53-year-old man presented with abrupt hearing loss, followed by a 4-week course of recurrent vertigo, headaches, and ataxia. Brain MRI revealed multiple punctate ischemic foci on corpus callosum (figure). Cerebral angiogram and echocardiogram were unremarkable. Susac syndrome was diagnosed following findings of branch retinal artery occlusion from fluorescein angiography (figure). (Source: Neurology)
Source: Neurology - March 24, 2014 Category: Neurology Authors: Oliveira, P., Mayeux, J. Tags: RESIDENT AND FELLOW SECTION Source Type: research

Aqueous extract of Glycyrrhiza inflata inhibits aggregation through upregulating PPARGC1A and NFE2L2-ARE pathways in cell models of spinocerebellar ataxia 3.
Abstract Spinocerebellar ataxia (SCAs) types 1, 2, 3, 6, 7, 17, and dentatorubropallidoluy-sianatrophy (DRPLA) as well as Huntington's disease (HD) are a group of neurodegenerative disorders caused by a CAG triplet repeat expansion encoding a long polyglutamine (polyQ) tract in the respective mutant proteins. The cytoplasmic and nuclear aggregate formation, pathological hallmark of polyQ diseases, is likely the initial process to trigger the subsequent pathological events. Compromised oxidative stress defense capacity and mitochondrial dysfunction have emerged as contributing factors to the pathogenesis of polyQ di...
Source: Free Radical Biology and Medicine - March 24, 2014 Category: Biology Authors: Chen CM, Weng YT, Chen WL, Lin TH, Chao CY, Lin CH, Chen IC, Lee LC, Lin HY, Wu YR, Chen YC, Chang KH, Tang HY, Cheng ML, Lee-Chen GJ, Lin JY Tags: Free Radic Biol Med Source Type: research

Checkpoint Kinase 2 (Chk2) supports sensitivity to platinum-based treatment in high grade serous ovarian cancer.
CONCLUSIONS: Chk2 is related to good response to platinum-based chemotherapy in advanced stage HGSOC patients. Chk2-depleted ovarian cancer cell lines have diminished platinum sensitivity, suggesting that Chk2 should not be considered a therapeutic target along with platinum-based treatment in HGSOC patients. PMID: 24657486 [PubMed - as supplied by publisher] (Source: Gynecologic Oncology)
Source: Gynecologic Oncology - March 20, 2014 Category: Cancer & Oncology Authors: Alkema NG, Tomar T, van der Zee AG, Everts M, Meersma GJ, Hollema H, de Jong S, van Vugt MA, Wisman GB Tags: Gynecol Oncol Source Type: research

FDA Grants Fast Track Designation To Edison Pharma's EPI-743
The U.S. Food and Drug Administration (FDA) has granted Fast Tack designation to Edison Pharmaceuticals’ lead drug EPI-743 for the treatment of Friedreich’s ataxia. (Source: Pharmaceutical Online News)
Source: Pharmaceutical Online News - March 19, 2014 Category: Pharmaceuticals Source Type: news

Episodic ataxia type 1: clinical characterization, quality of life and genotype-phenotype correlation
Episodic ataxia type 1 is considered a rare neuronal ion channel disorder characterized by brief attacks of unsteadiness and dizziness with persistent myokymia. To characterize the natural history, develop outcome measures for future clinical trials, and correlate genotype with phenotype, we undertook an international, prospective, cross-sectional study. Thirty-nine individuals (51% male) were enrolled: median age 37 years (range 15–65 years). We identified 10 different pathogenic point mutations in KCNA1 that accounted for the genetic basis of 85% of the cohort. Participants with KCNA1 mutations were more likely to ...
Source: Brain - March 19, 2014 Category: Neurology Authors: Graves, T. D., Cha, Y.-H., Hahn, A. F., Barohn, R., Salajegheh, M. K., Griggs, R. C., Bundy, B. N., Jen, J. C., Baloh, R. W., Hanna, M. G., on behalf of the CINCH Investigators Tags: Original Articles Source Type: research

Vestibular and cerebellar contribution to gaze optimality
Patients with chronic bilateral vestibular loss have large gaze variability and experience disturbing oscillopsia, which impacts physical and social functioning, and quality of life. Gaze variability and oscillopsia in these patients are attributed to a deficient vestibulo-ocular reflex, i.e. impaired online feedback motor control. Here, we assessed whether the lack of vestibular input also affects feed-forward motor learning, i.e. the ability to choose optimal movement parameters that minimize variability during active movements such as combined eye-head gaze shifts. A failure to learn from practice and reshape feed-forwa...
Source: Brain - March 19, 2014 Category: Neurology Authors: Sağlam, M., Glasauer, S., Lehnen, N. Tags: Original Articles Source Type: research

Impaired sensorimotor gating in Fmr1 knock out and Fragile X premutation model mice.
This study describes a novel phenotype in CGG KI mice that can be used in future therapeutic development targeting premutation associated symptoms. PMID: 24657592 [PubMed - as supplied by publisher] (Source: Behavioural Brain Research)
Source: Behavioural Brain Research - March 19, 2014 Category: Neurology Authors: Renoux AJ, Sala-Hamrick KJ, Carducci NM, Frazer M, Halsey KE, Sutton MA, Dolan DF, Murphy GG, Todd PK Tags: Behav Brain Res Source Type: research

Clinical and genetic analysis of Taiwanese patients with hereditary spastic paraplegia type 5
ConclusionsSpastic paraplegia type 5 is a common cause of AR and sporadic HSPs that has a higher frequency in Taiwanese than in other ethnic groups. It is associated with a CYP7B1 founder mutation and its phenotype is characterized by pronounced dorsal column sensory loss, with cerebellar ataxia in some patients. (Source: European Journal of Neurology)
Source: European Journal of Neurology - March 18, 2014 Category: Neurology Authors: M.‐Y. Lan, T.‐H. Yeh, Y.‐Y. Chang, H.‐C. Kuo, H. S. Sun, S.‐C. Lai, C.‐S. Lu Tags: Short Communication Source Type: research

Corrigendum
Most of the original conclusion section of the article “Evaluation of the Child With Acute Ataxia: A Systematic Review” by Whelan et al. in the July 2013 issue (2013;49:15-24; http://dx.doi.org/10.1016/j.pediatrneurol.2012.12.005) was copied from an article on the same topic by Dewesh Agrawal in UpToDate. The authors express extreme regret about the duplication and maintain that the error was inadvertent. The editor-in-chief has accepted their explanation and verified that no other portions of the paper contain duplicate material. The authors submitted the corrigendum that appears below, an approach that was approved ...
Source: Pediatric Neurology - March 18, 2014 Category: Neurology Tags: Corrigenda Source Type: research

Neurotropic T‐cell lymphocytosis : a cutaneous expression of CLIPPERS
Abstract Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disease of the central nervous system (CNS) that predominantly involves the pons and cerebellum and that improves with immunosuppressive treatment. Only recently described, the etiology is unknown, diagnosis is difficult and long‐term neurologic sequelae may occur without aggressive treatment. Herein, we describe a 59 year‐old woman who presented with subcutaneous nodules affecting her face, trunk, limbs and an indurated annular erythematous lesion on her forearm. This was associated with...
Source: Journal of Cutaneous Pathology - March 18, 2014 Category: Pathology Authors: Annika Smith, Yasmin Matthews, Steven Kossard, Jenny Turner, Michael E Buckland, John Parratt Tags: Case Report Source Type: research

A novel KCNA1 mutation causing episodic ataxia type I
We describe the phenotype of a novel KCNA1 mutation causing episodic ataxia. Patch‐clamp studies confirm the pathogenicity of the mutation in vitro and suggest that it is dominant with respect to wild type. Liver Transpl , 2014. © 2014 AASLD. (Source: Muscle and Nerve)
Source: Muscle and Nerve - March 18, 2014 Category: Internal Medicine Authors: Saskia Lassche, Sergio Lainez, Bastiaan R. Bloem, Bart P.C. Warrenburg, Jeannette Hofmeijer, Henny H. Lemmink, Joost G.J. Hoenderop, René J.M. Bindels, Gea Drost Tags: Short Report Source Type: research

FDA Awards Fast Track Status to Edison Pharmaceuticals' EPI-743 for Friedreich's Ataxia
EPI-743 in two phase 2 development studies for Friedreich's ataxia MOUNTAIN VIEW, Calif., March 17, 2014 -- (Healthcare Sales & Marketing Network) -- Edison Pharmaceuticals today announced that the United States Food and Drug Administration granted Fas... BiopharmaceuticalsEdison Pharmaceuticals, EPI-743, Friedreich's ataxia, Vincerinone (Source: HSMN NewsFeed)
Source: HSMN NewsFeed - March 17, 2014 Category: Pharmaceuticals Source Type: news

The expanding clinical and genetic spectrum of ATP1A3-related disorders
Conclusion: AHC and RDP constitute clinical prototypes in a continuous phenotypic spectrum of ATP1A3-related disorders. Intermediate phenotypes combining criteria of both conditions are increasingly recognized. Efficient stepwise mutation analysis of the ATP1A3 gene may prioritize those exons where current state of knowledge indicates mutational clusters. (Source: Neurology)
Source: Neurology - March 17, 2014 Category: Neurology Authors: Rosewich, H., Ohlenbusch, A., Huppke, P., Schlotawa, L., Baethmann, M., Carrilho, I., Fiori, S., Lourenco, C. M., Sawyer, S., Steinfeld, R., Gartner, J., Brockmann, K. Tags: Dystonia, Gait disorders/ataxia, Parkinson's disease/Parkinsonism ARTICLE Source Type: research

Peroxisomal D-bifunctional protein deficiency: Three adults diagnosed by whole-exome sequencing
Conclusion: Exome sequencing provides a powerful and elegant tool in the specific diagnosis of "mild" or "atypical" neurometabolic disorders. Given the broad differential diagnosis and the absence of detectable biochemical abnormalities in blood, molecular testing of HSD17B4 should be considered as a first-line investigation in patients with compatible features. (Source: Neurology)
Source: Neurology - March 17, 2014 Category: Neurology Authors: Lines, M. A., Jobling, R., Brady, L., Marshall, C. R., Scherer, S. W., Rodriguez, A. R., Lee, L., Lang, A. E., Mestre, T. A., Wanders, R. J. A., Ferdinandusse, S., Tarnopolsky, M. A., On behalf of the Canadian Pediatric Genetic Disorders Sequencing Consor Tags: Metabolic disease (inherited), Leukodystrophies, Peroxisomes, Cerebellum, All Genetics ARTICLE Source Type: research

Modeling Inherited Cardiac Disorders.
Abstract Advances in the understanding and treatment of cardiac disorders have been thwarted by the inability to study beating human cardiac cells in vitro. Induced pluripotent stem cells (iPSCs) bypass this hurdle by enabling the creation of patient-specific iPSC-derived cardiomyocytes (iPSC-CMs). These cells provide a unique platform to study cardiac diseases in vitro, especially hereditary cardiac conditions. To date, iPSC-CMs have been used to successfully model arrhythmic disorders, showing excellent recapitulation of cardiac channel function and electrophysiologic features of long QT syndrome types 1, 2, 3, a...
Source: Circulation Journal - March 17, 2014 Category: Cardiology Authors: Sallam K, Kodo K, Wu JC Tags: Circ J Source Type: research

Evaluation of monoclonal and oligoclonal gammopathies in a pediatric population in a major urban center.
Conclusions: The significance and presence of a monoclonal or oligoclonal gammopathy in pediatric and young adult populations is distinct from that seen in adults. PMID: 24619747 [PubMed - in process] (Source: American Journal of Clinical Pathology)
Source: American Journal of Clinical Pathology - March 14, 2014 Category: Pathology Authors: Karafin MS, Humphrey RL, Detrick B Tags: Am J Clin Pathol 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 - March 14, 2014 Category: Tropical Medicine Source Type: research

Continuous infusion of propofol or intermittent bolus of tiletamine‐zolazepam in squirrel monkeys (Saimiri sciureus)
Conclusions and clinical relevanceCardiopulmonary variables were similar between protocols, aside from the higher incidence of hypotension in PRO, indicating that further studies with a larger number of animals are required. Compared to tiletamine‐zolazepam, propofol anesthesia provided faster and superior anesthetic recovery in these animals. (Source: Veterinary Anaesthesia and Analgesia)
Source: Veterinary Anaesthesia and Analgesia - March 14, 2014 Category: Veterinary Research Authors: Rafaela Galante, José APC Muniz, Paulo HG Castro, Vanessa N Gris, Elizabeth R Carvalho, Dorli S Amora, Ricardo GD′OC Vilani Tags: Research Paper Source Type: research

ATDC in DNA Damage Response
Pancreatic ductal adenocarcinoma (PDAC) is characterized by therapeutic resistance for which the basis is poorly understood. Here, we report that the DNA and p53-binding protein ATDC/TRIM29, which is highly expressed in PDAC, plays a critical role in DNA damage signaling and radioresistance in pancreatic cancer cells. Ataxia-telangiectasia group D-associated gene (ATDC) mediated resistance to ionizing radiation in vitro and in vivo in mouse xenograft assays. ATDC was phosphorylated directly by MAPKAP kinase 2 (MK2) at Ser550 in an ATM-dependent manner. Phosphorylation at Ser-550 by MK2 was required for the radioprotective ...
Source: Cancer Research - March 13, 2014 Category: Cancer & Oncology Authors: Wang, L., Yang, H., Palmbos, P. L., Ney, G., Detzler, T. A., Coleman, D., Leflein, J., Davis, M., Zhang, M., Tang, W., Hicks, J. K., Helchowski, C. M., Prasad, J., Lawrence, T. S., Xu, L., Yu, X., Canman, C. E., Ljungman, M., Simeone, D. M. Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

Review: Iron metabolism and the role of iron in neurodegenerative disorders
Iron plays a role for the biogenesis of two important redox‐reactive prosthetic groups of enzymes, iron sulphur clusters (ISC) and heme. A part of these biosynthetic pathways takes plays in the mitochondria. While several important proteins of cellular iron uptake and storage and of mitochondrial iron metabolism are well‐characterized, limited knowledge exists regarding the mitochondrial iron importers (mitoferrins). A disturbed distribution of iron, hampered Fe‐dependent biosynthetic pathways and eventually oxidative stress resulting from an increased labile iron pool are suggested to play a role in several neurodeg...
Source: Neuropathology and Applied Neurobiology - March 13, 2014 Category: Neurology Authors: M. Hadzhieva, E. Kirches, C. Mawrin Tags: Review article Source Type: research

FUS colocalizes with polyglutamine, but not with TDP‐43 in neuronal intranuclear inclusions in spinocerebellar ataxia type 2
(Source: Neuropathology and Applied Neurobiology)
Source: Neuropathology and Applied Neurobiology - March 13, 2014 Category: Neurology Authors: F. Mori, Y. Toyoshima, K. Tanji, A. Kakita, H. Takahashi, K. Wakabayashi Tags: Scientific correspondence Source Type: research

An interesting case of metabolic dystonia: L-2 hydroxyglutaric aciduria
We report two siblings with dystonia diagnosed by classical neuroimaging findings with elevated urinary 2 hydroxyglutaric acid. Riboflavin therapy has shown promising results in a subset of cases, thus highlighting the importance of making the diagnosis in these patients. (Source: Annals of Indian Academy of Neurology)
Source: Annals of Indian Academy of Neurology - March 12, 2014 Category: Neurology Authors: Padma BalajiV ViswanathanAmarnath ChellathuraiDebasis Panigrahi Source Type: research

Atypical Wernicke's syndrome sans encephalopathy with acute bilateral vision loss due to post-chiasmatic optic tract edema
Soaham Dilip Desai, Diva Sidharth ShahAnnals of Indian Academy of Neurology 2014 17(1):103-105A middle aged male presented with acute bilateral vision loss, 4 weeks after undergoing gastric bypass surgery for gastric carcinoma. He had normal sensorium, fundoscopy, normal pupillary reaction to light, but had mild opthalmoparesis and nystagmus with ataxia. Magnetic resonance imaging of the brain revealed post-chiasmatic optic tract edema along with other classical features of Wernicke's syndrome. Thiamine supplementation leads to complete resolution of clinical as well as imaging findings. In appropriate clinical sett...
Source: Annals of Indian Academy of Neurology - March 12, 2014 Category: Neurology Authors: Soaham Dilip DesaiDiva Sidharth Shah Source Type: research

Clinical, hematological, and imaging observations in a 25-year-old woman with abetalipoproteinemia
In this report, we have described the phenotype of a young adult female who manifested with recurrent diarrheal illness in her first decade, followed by anemia, RP, and neurological involvement with progressive deafness, cerebellar and sensory ataxia, and subclinical neuropathy in her second decade of life. While RP and sensory ataxia due to vitamin E deficiency are well-recognized features of abetalipoproteinemia, deafness is rarely described. In addition, we have highlighted the abnormal posterior column signal changes in the cervical cord in this patient. Early recognition avoids unnecessary investigations and has a pot...
Source: Annals of Indian Academy of Neurology - March 12, 2014 Category: Neurology Authors: Madhu NagappaParayil S BinduSikandar AdwaniSangeeta K SeshagiriJitender SainiSanjib SinhaArun B Taly Source Type: research

Wernicke's encephalopathy following hyperemesis gravidarum
We report two cases of WE following HG, with two different outcomes. (Source: Indian Journal of Critical Care Medicine)
Source: Indian Journal of Critical Care Medicine - March 12, 2014 Category: Intensive Care Authors: Sandeep KantorSadanandan PrakashJuhi ChandwaniAntara GokhaleKalpana SarmaMaher J Albahrani Source Type: research

Olanzepine-induced neuroleptic malignant syndrome in a case of multiple sclerosis
Deepak Hanumanthaiah, Kumar RamanathanIndian Journal of Critical Care Medicine 2014 18(3):178-180Suspicion of neuroleptic malignant syndrome (NMS) is a frequent cause of emergent psychiatric consultation. Despite early recognition, NMS has remained a syndrome that causes high rates of morbidity and mortality. A 25-year-old male with multiple sclerosis presented to the accident and emergency department and E with ataxia. He was started on steroids. On the third day, he became tearful and anxious. A diagnosis of multiple sclerosis-induced psychosis was made and he was started on olanzepine 2.5 mg BD. On the sixth day the pat...
Source: Indian Journal of Critical Care Medicine - March 12, 2014 Category: Intensive Care Authors: Deepak HanumanthaiahKumar Ramanathan Source Type: research

A magic bullet to specifically eliminate mutated mitochondrial genomes from patients' cells
When mitochondrial diseases result from mutations found in the mitochondrial DNA, engineered mitochondrial‐targeted nucleases such as mitochondrial‐targeted zinc finger nucleases are shown to specifically eliminate the mutated molecules, leaving the wild‐type mitochondrial DNA intact to replicate and restore normal copy number. In this issue, Gammage and colleagues successfully apply this improved technology on patients' cells with two types of genetic alterations responsible for neuropathy ataxia and retinitis pigmentosa (NARP) syndrome and Kearns Sayre syndrome and progressive external ophthalmoplegia (PEO). In th...
Source: EMBO Molecular Medicine - March 12, 2014 Category: Molecular Biology Authors: Carlos T Moraes Tags: Closeup Source Type: research

Pregabalin add-on for drug-resistant partial epilepsy.
CONCLUSIONS: Pregabalin, when used as an add-on drug for treatment-resistant partial epilepsy, is significantly more effective than placebo at achieving a 50% or greater seizure reduction and significantly increasing seizure freedom. Results demonstrate efficacy for doses from 150 mg/day to 600 mg/day, with increasing effectiveness at 600 mg doses. The trials included in this review were of short duration and longer-term trials are needed to inform clinical decision making better. PMID: 24623260 [PubMed - as supplied by publisher] (Source: Cochrane Database of Systematic Reviews)
Source: Cochrane Database of Systematic Reviews - March 12, 2014 Category: Journals (General) Authors: Pulman J, Hemming K, Marson AG Tags: Cochrane Database Syst Rev Source Type: research

TDP1 deficiency sensitizes human cells to base damage via distinct topoisomerase I and PARP mechanisms with potential applications for cancer therapy
Base damage and topoisomerase I (Top1)-linked DNA breaks are abundant forms of endogenous DNA breakage, contributing to hereditary ataxia and underlying the cytotoxicity of a wide range of anti-cancer agents. Despite their frequency, the overlapping mechanisms that repair these forms of DNA breakage are largely unknown. Here, we report that depletion of Tyrosyl DNA phosphodiesterase 1 (TDP1) sensitizes human cells to alkylation damage and the additional depletion of apurinic/apyrimidinic endonuclease I (APE1) confers hypersensitivity above that observed for TDP1 or APE1 depletion alone. Quantification of DNA breaks and clo...
Source: Nucleic Acids Research - March 11, 2014 Category: Research Authors: Alagoz, M., Wells, O. S., El-Khamisy, S. F. Tags: Genome Integrity, Repair and Replication Source Type: research

Cystatin C is differentially involved in multiple system atrophy phenotypes
ConclusionsCysC changes are differentially present in the parkinsonian and cerebellar forms of MSA and may play an important role in the pathogenesis of this neurodegenerative condition. (Source: Neuropathology and Applied Neurobiology)
Source: Neuropathology and Applied Neurobiology - March 10, 2014 Category: Neurology Authors: Aintzane Urbizu, Julia Canet‐Pons, Ana M Munoz‐Marmol, Iban Aldecoa, Maria T Lopez, Yaroslau Compta, Ramiro Alvarez, Lourdes Ispierto, Eduardo Tolosa, Aurelio Ariza, Katrin Beyer Tags: Original Article Source Type: research

Use of the novel atypical opioid tapentadol in goats (Capra hircus): pharmacokinetics after intravenous, and intramuscular administration
The objective of the present study was to assess the pharmacokinetics of the novel atypical drug tapentadol (TAP) after intravenous (I.V.) and intramuscular (I.M.) injections in clinically healthy goats. A 2 × 2 cross‐over design study was carried out. Six local adult Nubian nonlactating, nonpregnant female goats, were given 5 mg/kg body weight of TAP by I.V. and I.M. routes. The concentrations of TAP in plasma were evaluated using a validated HPLC method. Transient adverse effects were noticed in some animals, especially after I.V. administration (tremors and ataxia). Three days after drug administration, severe hai...
Source: Journal of Veterinary Pharmacology and Therapeutics - March 10, 2014 Category: Veterinary Research Authors: E. Lavy, H.‐K. Lee, S.J. Mabjeesh, C. Sabastian, Y. Baker, M. Giorgi Tags: Short Communication Source Type: research

Infarct hemisphere and noninfarcted brain volumes affect locomotor performance following stroke
Conclusion: Individuals with chronic lesions within the right MCA territory, as compared to the left MCA territory, exhibit slower, more asymmetrical gait. For these individuals, larger GM volumes within regions outside of the infarcted vascular territory may help preserve locomotor control. (Source: Neurology)
Source: Neurology - March 10, 2014 Category: Neurology Authors: Chen, I.-H., Novak, V., Manor, B. Tags: MRI, Gait disorders/ataxia, Cerebellum, Basal ganglia, Infarction ARTICLE Source Type: research

Multicystic demyelinating myelopathy: Widening spectrum of pediatric aquaporin-4 autoimmunity
A 10-year-old girl presented with subacute lower limb weakness and gait ataxia. MRI revealed a large multicystic spinal cord lesion with patchy enhancement (figure 1, A–B) and 3 small (<6 mm) periventricular and deep white matter brain lesions. The presence of serum anti-aquaporin-4 immunoglobulin G (AQP4) (ELISA assay) and compatible neuropathologic features from neurosurgical specimens1 (figure 2) suggested the diagnosis of a neuromyelitis optica spectrum disorder.2 Targeted immunotherapy was started with partial lesion resolution (figure 1C). (Source: Neurology)
Source: Neurology - March 10, 2014 Category: Neurology Authors: Longoni, G., Bigi, S., Branson, H. M., Hawkins, C., Rutka, J. T., Filippi, M., Yeh, E. A. Tags: All Pediatric, All Spinal Cord, All Demyelinating disease (CNS), Devic's syndrome, Transverse myelitis NEUROIMAGES Source Type: research

Generalized Time-Dependent Model of Radiation-Induced Chromosomal Aberrations in Normal and Repair-Deficient Human Cells.
Abstract We have developed a model that can simulate the yield of radiation-induced chromosomal aberrations (CAs) and unrejoined chromosome breaks in normal and repair-deficient cells. The model predicts the kinetics of chromosomal aberration formation after exposure in the G0/G1 phase of the cell cycle to either low- or high-LET radiation. A previously formulated model based on a stochastic Monte Carlo approach was updated to consider the time dependence of DNA double-strand break (DSB) repair (proper or improper), and different cell types were assigned different kinetics of DSB repair. The distribution of the DSB...
Source: Radiation Research - March 10, 2014 Category: Physics Authors: Ponomarev AL, George K, Cucinotta FA Tags: Radiat Res Source Type: research

Kaleidoscopic protein-protein interactions in the life and death of ataxin-1: new strategies against protein aggregation.
Abstract Understanding how proteins protect themselves from aberrant aggregation is of primary interest for understanding basic biology, protein biochemistry, and human disease. We discuss the paradigmatic example of ataxin-1 (Atx1), the protein responsible for neurodegenerative spinocerebellar ataxia type 1 (SCA1). This disease is part of the increasing family of pathologies caused by protein aggregation and misfolding. We discuss the importance of protein-protein interactions not only in the nonpathological function of Atx1 but also in protecting the protein from aggregation and misfolding. The lessons learned fr...
Source: Trends in Neurosciences - March 10, 2014 Category: Neuroscience Authors: de Chiara C, Pastore A Tags: Trends Neurosci Source Type: research

Glionitrin A, a New Diketopiperazine Disulfide, Activates ATM-ATR-Chk1/2 via 53BP1 Phosphorylation in DU145 Cells and Shows Antitumor Effect in Xenograft Model.
Abstract In a recent study, we isolated the diketopiperazine disulfide glionitrin A from the co-culture broth of a mine drainage-derived fungus (Aspergillus fumigatus KMC901) and bacterium (Sphingomonas KMK001). Here, we investigated the antitumor activity of glionitrin A and its underlying molecular mechanisms in human prostate cancer DU145 cells. Glionitrin A showed significant cytotoxicity, promoting cell cycle arrest and apoptosis. Glionitrin A-treated cells exhibited elevated levels of phospho-histone 2AX (Ser139), a marker of DNA damage, and accumulated in both S phase and G2/M phase due to the activation of ...
Source: Biological and Pharmaceutical Bulletin - March 9, 2014 Category: Drugs & Pharmacology Authors: Kim YJ, Park HB, Yoo JH, Kwon HC, Kim J, Yang HO Tags: Biol Pharm Bull Source Type: research

A pharmacokinetic/clinical approach to postulate a local action of intra‐articular xylazine administration in the horse: a preliminary study
In conclusion, a systemic action of the drug after IA administration cannot be excluded. (Source: Journal of Veterinary Pharmacology and Therapeutics)
Source: Journal of Veterinary Pharmacology and Therapeutics - March 8, 2014 Category: Veterinary Research Authors: A. Di Salvo, G. Della Rocca, C. Bazzica, A. Giontella, P. Cagnardi, S. Nannarone Tags: Scientific Paper Source Type: research

Increased Catabolic State in Spinocerebellar Ataxia Type 1 Patients.
Abstract Autosomal dominant spinocerebellar ataxia type 1 (SCA1) is a genetic movement disorder with neuronal loss in the cerebellum, brainstem, and other cerebral regions. The course of SCA1 is accompanied with progressive weight loss and amyotrophia-the causes for that remain, however, unclear. We tested the hypothesis that an imbalance between energy intake and expenditure contributes to weight loss in SCA1 patients. Anthropometric measures, energy intake (food records), and resting (calorimetry) and free-living (accelerometry) energy expenditure were determined in 10 patients with genetically proven SCA1 and 10...
Source: Cerebellum - March 8, 2014 Category: Neuroscience Authors: Mähler A, Steiniger J, Endres M, Paul F, Boschmann M, Doss S Tags: Cerebellum Source Type: research

Neurophysiological Studies and Non-Motor Symptoms Prior to Ataxia in a Patient with Machado-Joseph Disease: Trying to Understand the Natural History of Brain Degeneration.
Abstract Spinocerebellar ataxia type 3 or Machado-Joseph disease is the most common spinocerebellar ataxia. In this neurological disease, anatomical, physiological, clinical, and functional neuroimaging demonstrate a degenerative process besides the cerebellum. We performed neurophysiological and neuroimaging studies-polysomnography, transcranial sonography, vestibular-evoked myogenic potential, single-photon emission computed tomography (SPECT) with (99m)Tc-TRODAT-1, and a formal neuropsychological evaluation in a patient with sleep complaints and positive testing for Machado-Joseph disease, without cerebellar atr...
Source: Cerebellum - March 8, 2014 Category: Neuroscience Authors: Pedroso JL, Bor-Seng-Shu E, Braga-Neto P, Ribeiro RS, Bezerra ML, do Prado LB, Batista IR, Alessi H, Teixeira MJ, Manzano GM, do Prado GF, Barsottini OG Tags: Cerebellum Source Type: research

Development of a Cell-Based, High-Throughput Screening Assay for ATM Kinase Inhibitors
The ATM (ataxia-telangiectasia, mutated) protein kinase is a major regulator of cellular responses to DNA double-strand breaks (DSBs), DNA lesions that can be caused by ionizing irradiation (IR), oxidative damage, or exposure to certain chemical agents. In response to DSBs, the ATM kinase is activated and subsequently phosphorylates numerous downstream substrates, including p53, Chk2, BRCA1, and KAP1, which affect processes such as cell cycle progression and DNA repair. Numerous studies have demonstrated that loss of ATM function results in enhanced sensitivity to ionizing irradiation in clinically relevant dose ranges, su...
Source: Journal of Biomolecular Screening - March 7, 2014 Category: Molecular Biology Authors: Guo, K., Shelat, A. A., Guy, R. K., Kastan, M. B. Tags: Original Research Source Type: research

CHOP, Penn get $3 million gift to establish center for rare disease
Children’s Hospital of Philadelphia and the University of Pennsylvania Health System have received a $3.25 million donation to establish the Penn Medicine/CHOP Friedreich’s Ataxia Center of Excellence. Funding for the center came from the Friedreich’s Ataxia Research Alliance (FARA) in a partnership with the Hamilton and Finneran families. The center is being created to expedite and support basic science and drug discovery findings for new treatments to help individuals living with Friedreich’s… (Source: bizjournals.com Health Care:Physician Practices headlines)
Source: bizjournals.com Health Care:Physician Practices headlines - March 6, 2014 Category: American Health Authors: John George Source Type: research

MicroRNA-223 Enhances Radiation Sensitivity of U87MG Cells In Vitro and In Vivo by Targeting Ataxia Telangiectasia Mutated
We examined the effect of microRNA-223 (miR-223), a regulator of ATM expression, on radiation sensitivity of cancer cells.Methods and Materials: Human embryonic kidney 293 T (293T) cells were infected with pLL3.7-miR-223 plasmid to generate the pLL3.7-miR-223 and -empty virus (EV) lentivirus (miR-223 and EV). A dual luciferase assay in which the reporter contained wild-type 3′ untranslated region (UTR) of ATM was performed. U87MG cells were infected with miR-223 or EV to establish the overexpressed stable cell lines (U87-223 or U87-EV, respectively). Cells were irradiated in vitro, and dose enhancement ratios at 2 Gy...
Source: International Journal of Radiation Oncology * Biology * Physics - March 6, 2014 Category: Radiology Authors: Liping Liang, Ji Zhu, Nicholas G. Zaorsky, Yun Deng, Xingzhong Wu, Yong Liu, Fangqi Liu, Guoxiang Cai, Weilie Gu, Lijun Shen, Zhen Zhang Tags: Biology Contributions Source Type: research