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The juvenile myoclonic epilepsy mutant of the calcium channel β(4) subunit displays normal nuclear targeting in nerve and muscle cells.
Authors: Etemad S, Campiglio M, Obermair GJ, Flucher BE Abstract Voltage-gated calcium channels regulate gene expression by controlling calcium entry through the plasma membrane and by direct interactions of channel fragments and auxiliary β subunits with promoters and the epigenetic machinery in the nucleus. Mutations of the calcium channel β(4) subunit gene (CACNB4) cause juvenile myoclonic epilepsy in humans and ataxia and epileptic seizures in mice. Recently a model has been proposed according to which failed nuclear translocation of the truncated β(4) subunit R482X mutation resulted in altered transcription...
Source: Channels - December 21, 2014 Category: Molecular Biology Tags: Channels (Austin) Source Type: research

Esophoria or esotropia in adulthood: a sign of cerebellar dysfunction?
Abstract Convergent strabismus is a common diagnosis in early childhood, when it is mostly considered benign. If it develops later in life, strabismus can, however, be a sign of neurological disease. In these cases the underlying pathophysiological mechanisms are largely unknown. In this retrospective case–control study we analyzed the neuro-ophthalmological examination reports of 400 adult patients who presented at the German Center for Vertigo and Balance Disorders to determine an association between ocular misalignment and cerebellar dysfunction. Patients with cerebellar signs (i.e., cerebellar ataxia and/or ...
Source: Journal of Neurology - December 19, 2014 Category: Neurology Source Type: research

SC-III3, a novel scopoletin derivative, induces cytotoxicity in hepatocellular cancer cells through oxidative DNA damage and ataxia telangiectasia-mutated nuclear protein kinase activation
Conclusion: SC-III3 is able to efficiently inhibit the growth of hepatocellular carcinoma through inducing the generation of intracellular ROS, DNA damage and consequent S phase arrest, but lack of significant cytotoxicity against normal liver cells. This compound deserves further studies as a candidate of anticancer drugs. (Source: BMC Cancer)
Source: BMC Cancer - December 19, 2014 Category: Cancer & Oncology Authors: Peng ZhaoLi ChenLin-Hu LiZhi-Feng WeiBei TongYu-Gai JiaLing-Yi KongYue DaiYu-Feng Xia Source Type: research

Opsoclonus–myoclonus syndrome following rotavirus gastroenteritis
We describe the case of a 22‐month‐old girl with OMS following rotavirus gastroenteritis. Rotavirus should be considered in the differential diagnosis of OMS in children. (Source: Pediatrics International)
Source: Pediatrics International - December 18, 2014 Category: Pediatrics Authors: Esra Gurkas, Kivilcim Gucuyener, Unsal Yılmaz, Cengiz Havalı, Ercan Demir Tags: Patient Report Source Type: research

The Effects of Complete Vestibular Deafferentation on Spatial Memory and the Hippocampus in the Rat: The Dunedin Experience (Advance Article)
Source: Page Count 25Our studies conducted over the last 14 years have demonstrated that a complete bilateral vestibular deafferentation (BVD) in rats results in spatial memory deficits in a variety of behavioural tasks, such as the radial arm maze, the foraging task and the spatial T maze, as well as deficits in other tasks such as the five-choice serial reaction time task (5-CSRT task) and object recognition memory task. These deficits persist long after the BVD, and are not simply attributable to ataxia, anxiety, hearing loss or hyperactivity. In tasks such as the foraging task, the spatial memory deficits are evident i...
Source: Multisensory research - December 18, 2014 Category: Neuroscience Authors: Paul F. Smith, Cynthia L. Darlington and Yiwen Zheng Source Type: research

Pathological findings of anti-Yo cerebellar degeneration with Holmes tremor
Holmes tremor, also known as rubral tremor, is defined as the combination of rest, action and postural tremor in the upper extremities with the frequency around 4.5 Hz.1 Involvement of dentato-rubro-thalamic and/or nigrostriatal pathways have been considered contributory to the clinical manifestation,1 and the localisation of Holmes tremor was determined primarily based on the neuroimaging studies.2 To our knowledge, no detailed postmortem examinations were reported in Holmes tremor. Here, we present the pathology of a case with Holmes tremor associated with anti-Yo cerebellar degeneration. Case report A woman in her ...
Source: Journal of Neurology, Neurosurgery and Psychiatry - December 17, 2014 Category: Neurosurgery Authors: Rydz, D., Lin, C.-Y., Xie, T., Cortes, E., Vonsattel, J.-P., Kuo, S.-H. Tags: PostScript Source Type: research

The catalytic topoisomerase II inhibitor dexrazoxane induces DNA breaks, ATF3 and the DNA damage response in cancer cells
Conclusions and ImplicationsSimilar to TOP2A poisons, DRZ induces DNA double‐strand breaks followed by activation of DNA damage response. The DNA damage‐triggered ATF3 controls the level of p53 accumulation as well as double‐strand breaks generation and is proposed to serve as a switch between DNA damage and cell death following DRZ treatment. These findings suggest a mechanistic explanation for the diverse clinical observations associated with DRZ. (Source: British Journal of Pharmacology)
Source: British Journal of Pharmacology - December 17, 2014 Category: Drugs & Pharmacology Authors: Shiwei Deng, Tiandong Yan, Teodora Nikolova, Dominik Fuhrmann, Andrea Nemecek, Ute Gödtel‐Armbrust, Bernd Kaina, Leszek Wojnowski Tags: Research Paper Source Type: research

Deficiency of Ataxia Telangiectasia Mutated Kinase Delays Inflammatory Response in the Heart Following Myocardial Infarction [Heart Failure]
Conclusion ATM deficiency results in decreased dilative remodeling and delays inflammatory response acute post-MI. However, it associates with increased fibrosis and apoptosis. (Source: JAHA:Journal of the American Heart Association)
Source: JAHA:Journal of the American Heart Association - December 17, 2014 Category: Cardiology Authors: Daniel, L. L., Daniels, C. R., Harirforoosh, S., Foster, C. R., Singh, M., Singh, K. Tags: Heart Failure Source Type: research

Ataxia-Telangiectasia Mutated Kinase: A Potential New Target for Suppressing Inflammation in Heart Failure? [Editorials]
(Source: JAHA:Journal of the American Heart Association)
Source: JAHA:Journal of the American Heart Association - December 17, 2014 Category: Cardiology Authors: Kukreja, R. C. Tags: Editorials Source Type: research

Postinfectious Opsoclonus‐Myoclonus Syndrome in a 41‐Year‐Old Patient—Visualizing Hyperactivation in Deep Cerebellar Nuclei by Cerebral [18F]‐FDG‐ PET
ABSTRACT A 41‐year‐old woman presented with acute onset headache, vertigo, nausea, and gait disorder, initially interpreted as a common cold. Within 2 weeks, she developed a severe opsoclonus‐myoclonus syndrome with truncal ataxia. Cerebrospinal fluid examination and serological findings suggested a recent infection with Coxsackie B3 virus. [18F]‐FDG‐PET proved to be the only imaging tool to identify the underlying pathology depicting hyperactivation in the vestibulo‐ and spinocerebellum as well as hyperactivation of the ocular muscles. At the clinical follow‐up 4 months later, the patient's symptoms were con...
Source: Journal of Neuroimaging - December 16, 2014 Category: Radiology Authors: Mona Mustafa, Johannes Levin, Florian Schöberl, Axel Rominger Tags: Case Report Source Type: research

Induction of H2AX phosphorylation in tumor cells by gossypol acetic acid is mediated by phosphatidylinositol 3-kinase (PI3K) family
Conclusions: The member of PI3K family, DNA-PK, ATM and ATR are involved in the H2AX phosphorylation of MEC-1 cells. (Source: Cancer Cell International)
Source: Cancer Cell International - December 16, 2014 Category: Cancer & Oncology Authors: Zhong GuoJin ZhaoLei SongJian-Xiu MaChen-Jing WangShu-Yan PeiChao JiangShang-Biao Li Source Type: research

Differential increases of specific FMR1 mRNA isoforms in premutation carriers
Conclusions These findings suggest that RNA toxicity may arise from a relative increase of all FMR1 mRNA isoforms. Interestingly, the Iso10 and Iso10b mRNA isoforms, lacking the C-terminal functional sites for fragile X mental retardation protein function, are the most increased in premutation carriers relative to normal, suggesting a functional relevance in the pathology of FMR1-associated disorders. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 15, 2014 Category: Genetics & Stem Cells Authors: Pretto, D. I., Eid, J. S., Yrigollen, C. M., Tang, H.-T., Loomis, E. W., Raske, C., Durbin-Johnson, B., Hagerman, P. J., Tassone, F. Tags: Molecular genetics Functional genomics Source Type: research

WWOX-related encephalopathies: delineation of the phenotypical spectrum and emerging genotype-phenotype correlation
Conclusions Our results obtained by a combination of different molecular techniques undoubtedly incriminate WWOX as a gene for recessive IEE and illustrate the usefulness of high throughput data mining for the identification of genes for rare autosomal recessive disorders. The structure of the WWOX locus encompassing the FRA16D fragile site might explain why constitutive deletions are recurrently reported in genetic databases, suggesting that WWOX-related encephalopathies, although likely rare, may not be exceptional. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 15, 2014 Category: Genetics & Stem Cells Authors: Mignot, C., Lambert, L., Pasquier, L., Bienvenu, T., Delahaye-Duriez, A., Keren, B., Lefranc, J., Saunier, A., Allou, L., Roth, V., Valduga, M., Moustaine, A., Auvin, S., Barrey, C., Chantot-Bastaraud, S., Lebrun, N., Moutard, M.-L., Nougues, M.-C., Verme Tags: Eye Diseases, Genetic screening / counselling, Molecular genetics, Epilepsy and seizures Developmental defects Source Type: research

Massive CAG Repeat Expansion and Somatic Instability in Maternally Transmitted Infantile Spinocerebellar Ataxia Type 7
Conclusions and RelevanceWe document the first intertissue CAG instability reported to date in patients with SCA7, similar to SCA7 mouse models. Infantile SCA7, which is often paternally transmitted, can rarely arise by maternal transmission, which has implications for diagnosis and counseling among families of patients with SCA7. (Source: JAMA Neurology)
Source: JAMA Neurology - December 15, 2014 Category: Neurology Source Type: research

Identification of ATR-Chk1 Pathway Inhibitors
Resistance to DNA-damaging chemotherapy is a barrier to effective treatment that appears to be augmented by p53 functional deficiency in many cancers. In p53-deficient cells in which the G1–S checkpoint is compromised, cell viability after DNA damage relies upon intact intra-S and G2–M checkpoints mediated by the ATR (ataxia telangiectasia and Rad3 related) and Chk1 kinases. Thus, a logical rationale to sensitize p53-deficient cancers to DNA-damaging chemotherapy is through the use of ATP-competitive inhibitors of ATR or Chk1. To discover small molecules that may act on uncharacterized components of the ATR pathway, we...
Source: Cancer Research - December 14, 2014 Category: Cancer & Oncology Authors: Kawasumi, M., Bradner, J. E., Tolliday, N., Thibodeau, R., Sloan, H., Brummond, K. M., Nghiem, P. Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

Monitoring Cardiac Function During Idebenone Therapy in Friedreich's Ataxia.
Abstract Friedreich's ataxia (FA) is associated with progressive cardiac hypertrophy resulting from a genetic abnormality in the frataxin gene. Cardiac involvement is the most common cause of death (59%) in FA patients. Cardiac related death occurs at a significantly younger age than non-cardiac related death. Idebenone is a short-chain quinone analogue with a potent free-radical scavenger action. This drug has the potential to preserve and even improve mitochondrial function.Studies on Idebenone treatment showed rather conflicting results on FA cardiomyopathy. The present article reviews the clinical features of F...
Source: Current Pharmaceutical Design - December 13, 2014 Category: Drugs & Pharmacology Authors: Giovanni DS, Valeria P, Bahaa F, Majid AF Tags: Curr Pharm Des Source Type: research

66. Autonomic-sensory neuropathy onset in a patient with acute brainstem impairment – A case report
Here we report on a 64-year-old Caucasian man admitted to the Neurology department due to a history of severe hypoacusia, nausea, stipsis, cerebellar ataxia and progressing consciousness impairment, which raised up the clinical suspicion of acute cerebellitis and suggested the introduction of oral corticosteroids. At day 7, a mild improvement of cerebellar symptoms was followed by the onset of orthostatic hypotension, four limb sensory impairment and areflexia. The spinal tap displayed a mild protein increase (78mg/dl) and high-titer of anti-Hu (ANNA-1) antibodies in CSF. (Source: Clinical Neurophysiology)
Source: Clinical Neurophysiology - December 13, 2014 Category: Neuroscience Authors: S. Vigneri, V. Rispoli, C. Azzini, M.L. Caniatti, M.R. Tola, V. Simioni, J.G. Capone, E. Sette, V. Tugnoli Source Type: research

82. Prefrontal cortex as a compensatory functional substrate during ataxic overground gait: A correlation study between cortical activity and gait parameters
To investigate whether prefrontal cortex (PFC) activation is linked to compensatory mechanisms (time–distance parameters) or to gait features (kinematic parameters) specifically related to the functional role of the cerebellum in ataxic patients. We performed a correlation analysis between the PFC metabolic profile during gait and time–distance and kinematic parameters in a sample of 19 patients affected by neurodegenerative gait ataxia and 15 age/sex matched healthy subjects. PFC metabolism was evaluated by a 2-channel functional near-infrared imaging system while gait analysis was performed using a stereophotogrammet...
Source: Clinical Neurophysiology - December 13, 2014 Category: Neuroscience Authors: P. Caliandro, M. Serrao, L. Padua, G. Silvestri, C. Iacovelli, C. Simbolotti, S. Mari, G. Reale, C. Casali, P.M. Rossini Source Type: research

93. CANOMAD: Clinical and neurophysiological findings in two cases
The acronym CANOMAD (Chronic Ataxic Neuropathy, Ophthalmoplegia, IgM paraproteinemia, cold Agglutinin and Disialosyl antibodies) refers a rare immune-mediated peripheral neuropathy, whose clinical spectrum has still to be fully delineated. Herein we report the clinical and neurophysiological features of two CANOMAD patients.A 52-year-old man suffering from distal sensory symptoms and ataxia had received a first diagnosis of chronic inflammatory prominent-sensory polyneuropathy 11years ago. High-dose i.v. (Source: Clinical Neurophysiology)
Source: Clinical Neurophysiology - December 13, 2014 Category: Neuroscience Authors: E. Del Sordo, S. Casali, F. Ginanneschi, L. Insana, G. Capoccitti, C. Cardinali, D. Battista, A. Borgheresi, M. Cincotta, W. Borsini, F. Giannini Source Type: research

98. Early neurophysiological modifications in subacute polyneuropathy associated with meningeal carcinomatosis in linitis plastica
A 31-year-old woman came to Emergency Room in February 2014 for acute onset of cervical pain, vomiting and diplopia. Neurological examination showed right sixth nerve palsy, absent tendon reflexes and ataxia. General examination showed axillary skin lesions. Cerebrospinal fluid analysis showed low glucose and high total cell count; brain and spinal cord gadolinium-enhanced MRI was not conclusive. Neurophysiological evaluation (electroneurography, electromyography, blink reflex), was normal. Symptoms partially spontaneously resolved and she was discharged. (Source: Clinical Neurophysiology)
Source: Clinical Neurophysiology - December 13, 2014 Category: Neuroscience Authors: M. Zardoni, C. Bana, E. Capiluppi, P. Gambaro, L. Giani, C. Mariotti, M. Osio, C. Nascimbene, C. Lovati, C. Mariani Source Type: research

Helix-Coil Transition Induced by Metal Ion Interaction with a Grafted Iron-Binding Site of the CyaY Protein Family
Dalton Trans., 2014, Accepted ManuscriptDOI: 10.1039/C4DT02796E, PaperDiego Sebastian Vazquez, William Armando Agudelo, Angel Yone, Nora Vizioli, Martin Aran, Luis Gonzalez Flecha, Mariano Camilo Gonzalez Lebrero, Javier SantosIron-protein interactions are involved in electron transfer reactions. Alterations of these processes are present in a number of human pathologies; among then, in Friedreich's ataxia, in which a deficiency in...The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Dalton Trans. latest articles)
Source: RSC - Dalton Trans. latest articles - December 13, 2014 Category: Chemistry Authors: Diego Sebastian Vazquez Source Type: research

Systematic review of cardiac electrical disease in Kearns-Sayre syndrome and mitochondrial cytopathy
Kearns-Sayre syndrome (KSS) is a mitochondrial disorder characterised by onset before the age of 20years, progressive external ophthalmoplegia, pigmentary retinopathy, accompanied by either cardiac conduction defects, elevated cerebrospinal fluid protein or cerebellar ataxia. 50% of patients with KSS develop cardiac complications. The most common cardiac manifestation is conduction disease which may progress to complete atrioventricular block or bradycardia-related polymorphic ventricular tachycardia (PMVT). (Source: International Journal of Cardiology)
Source: International Journal of Cardiology - December 12, 2014 Category: Cardiology Authors: Peter Kabunga, Antony K. Lau, Kevin Phan, Rajesh Puranik, Christina Liang, Ryan L. Davis, Carolyn M. Sue, Raymond W. Sy Tags: Review Source Type: research

Coupling Transcriptional State to Large-Scale Repeat Expansions in Yeast
We present a model in which transcriptional state, linked to the nucleosomal density of a region, acts as a modulator of large-scale repeat expansions. Graphical abstract Teaser The molecular pathways of replication and transcription are implicated in the expansion of simple DNA repeats, but it has been difficult to distinguish their relative contributions. Shah et al. design and utilize genetic systems to investigate repeat instability in the absence of transcription, showing that transcriptional state rather than transcription through the repeat per se affects this process. The authors present a model linking transcript...
Source: Cell Reports - December 12, 2014 Category: Cytology Source Type: research

Activation of DNA Damage Response Signaling by Condensed Chromatin
Publication date: 11 December 2014 Source:Cell Reports, Volume 9, Issue 5 Author(s): Rebecca C. Burgess , Bharat Burman , Michael J. Kruhlak , Tom Misteli The DNA damage response (DDR) occurs in the context of chromatin, and architectural features of chromatin have been implicated in DNA damage signaling and repair. Whereas a role of chromatin decondensation in the DDR is well established, we show here that chromatin condensation is integral to DDR signaling. We find that, in response to DNA damage chromatin regions transiently expand before undergoing extensive compaction. Using a protein-chromatin-tethering system to...
Source: Cell Reports - December 12, 2014 Category: Cytology Source Type: research

Abstract IA08: PTEN and PI3K signaling in brain development and disease
Virtually all adult glioblastomas contain somatic mutations resulting in elevated activity of the receptor tyrosine kinase (RTK)/Ras/PI3K signaling axis, including common loss of function mutations in PTEN, activating mutations in PIK3CA encoding p110α, the catalytic subunit of PI3Kα, or mutations in PIK3R1, encoding p85α, the regulatory subunit of PI3K. Despite an important role in sporadic glioblastoma, germline PTEN mutations do not confer an increased genetic susceptibility to brain tumors. However, inherited mutation of PTEN is associated with macrocephaly and neurological abnormalities including seizures, ataxia, ...
Source: Cancer Research - December 12, 2014 Category: Cancer & Oncology Authors: Baker, S. J. Tags: Oral Presentations Source Type: research

Abstract IA12: Regulation of the RNF168-dependent response to DNA double-strand breaks
The chromatin-based response to DNA double-strand breaks (DSBs) is characterized by the accumulation of DNA repair factors and DNA damage signaling molecules within a large domain that surrounds the lesion. This response is largely dependent on ATM-dependent phosphorylation but also on chromatin ubiquitylation. Indeed, the RNF8 and RNF168 E3 ubiquitin ligases are necessary for the accumulation of proteins such as 53BP1, BRCA1 and RAD18 at sites of DNA damage. The critical importance of this pathway is manifested by the observation that biallelic mutations in the RNF168 gene results in an ataxia-telangiectasia-like syndrome...
Source: Cancer Research - December 12, 2014 Category: Cancer & Oncology Authors: Orthwein, A., Durocher, D. Tags: Oral Presentations Source Type: research

Abstract IA20: A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest
Telomere shortening and disruption of telomeric components are pathways that induce telomere deprotection. Here we describe another pathway, where prolonged mitotic arrest induces damage signals at telomeres in human cells. Exposure to microtubule drugs, kinesin inhibitors, proteasome inhibitors or the disruption of proper chromosome cohesion resulted in the formation of damage-foci at telomeres. Induction of mitotic telomere deprotection coincided with dissociation of TRF2 (Telomere Repeat binding Factor 2) from telomeres, telomeric 3′-overhang degradation and ATM (Ataxia Telangiectasia Mutated) activation, and could be...
Source: Cancer Research - December 12, 2014 Category: Cancer & Oncology Authors: Hayashi, M. T., Karlseder, J. Tags: Oral Presentations Source Type: research

Abstract 32: Suppression of medical radiation DNA damage in cancer susceptible and normal humans using a new aminothiol radioprotector
CT scan usage has greatly increased in the last two decades, with an estimated 85 million U.S. CT scans done in 2011. These exams are valuable and greatly enhance patient care. Certain CT scan and radiology procedures deliver ionizing radiation doses of 10-70 mSv. 30% of CT scan patients require three or more CT scans, some as many as nine. Recent studies reported significant correlations between CT radiation doses and subsequent tumors in children and adults. A 2012 report showed a radiation dose-dependent relationship between chest irradiation (mean dose = 14 mSv) in BRCA1/2-carrying women under age 30 and subsequent bre...
Source: Cancer Research - December 12, 2014 Category: Cancer & Oncology Authors: Fahl, W. E., Wuerzberger-Davis, S., Miyamoto, S. Tags: Poster Presentations Source Type: research

Metabotropic glutamate receptors as drug targets: what's new?
Abstract The question in the title: 'what's new?' has two facets. First, are 'clinical' expectations met with success? Second, is the number of CNS disorders targeted by mGlu drugs still increasing? The answer to the first question is 'no', because development program with promising drugs in the treatment of schizophrenia, Parkinson's disease, and Fragile X syndrome have been discontinued. Nonetheless, we continue to be optimistic because there is still the concrete hope that some of these drugs are beneficial in targeted subpopulations of patients. The answer to the second question is 'yes', because mGlu ligands a...
Source: Current Opinion in Pharmacology - December 12, 2014 Category: Drugs & Pharmacology Authors: Nicoletti F, Bruno V, Ngomba RT, Gradini R, Battaglia G Tags: Curr Opin Pharmacol Source Type: research

Importance of genetics in fetal alcohol effects: null mutation of the nNOS gene worsens alcohol-induced cerebellar neuronal losses and behavioral deficits.
Abstract The cerebellum is a major target of alcohol-induced damage in the developing brain. However, the cerebella of some children are much more seriously affected than others by prenatal alcohol exposure. As a consequence of in utero alcohol exposure, some children have substantial reductions in cerebellar volume and corresponding neurodevelopmental problems, including microencephaly, ataxia, and balance deficits, while other children who were exposed to similar alcohol quantities are spared. One factor that likely plays a key role in determining the impact of alcohol on the fetal cerebellum is genetics. However...
Source: Neurotoxicology - December 12, 2014 Category: Neurology Authors: Bonthius DJ, Winters Z, Karacay B, Bousquet SL, Bonthius DJ Tags: Neurotoxicology Source Type: research

Spinocerebellar ataxia type 6: a case report
O objetivo deste estudo foi verificar as alterações vestibulococleares observadas em um caso de ataxia espinocerebelar tipo 6. O caso foi encaminhado do Hospital de Clínicas para o Laboratório de Otoneurologia de uma Instituição de Ensino e foi submetido aos seguintes procedimentos: anamnese, inspeção otológica, avaliações audiológica e vestibular. O caso retrata uma paciente com diagnóstico genético de ataxia espinocerebelar tipo 6, do sexo feminino, com 57 anos de idade, que referiu desequilíbrio à marcha com tendência a queda para a esquerda, disartria e disfonia. Na avaliação audiológica apresentou ...
Source: Revista CEFAC - December 11, 2014 Category: Speech Therapy Source Type: research

Very Late-Onset Friedreich Ataxia with Laryngeal Dystonia
We report the case of a 64-year-old woman affected with VLOFA whose first symptoms (balance and gait disturbances) occurred at the age of 44 years. At the age of 62 years, she started complaining of a slowly progressive dysphonia showing the clinical aspects of laryngeal dystonia. Molecular analysis showed a 210- and 230-trinucleotide GAA repeat expansion in the two alleles of the FXN gene. Laryngeal dystonia has been reported only in very few cases of ataxia syndrome and never before in FRDA patients. It may represent a rare clinical manifestation of VLOFA thus confirming the high variability of the clinical spectrum of F...
Source: Case Reports in Neurology - December 11, 2014 Category: Neurology Source Type: research

Antibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in cerebellar ataxia
We report on a serum autoantibody associated with cerebellar ataxia. Immunohistochemical studies of sera from four patients referred for autoantibody testing revealed binding of high-titer (up to 1:5,000) IgG antibodies, mainly IgG1, to the molecular layer, Purkinje cell layer, and white matter on mouse, rat, porcine, and monkey cerebellum sections. The antibody bound to PC somata, dendrites, and axons, resulting in a binding pattern similar to that reported for anti-Ca/anti-ARHGAP26, but did not react with recombinant ARHGAP26. Extensive control studies were performed to rule out a broad panel of previously described para...
Source: Journal of Neuroinflammation - December 11, 2014 Category: Neurology Authors: Sven JariusMadeleine ScharfNora BegemannWinfried StöckerChristian ProbstIrina SeryshevaSigrun NagelFrancesc GrausDimitri PsimarasBrigitte WildemannLars Komorowski Source Type: research

Autopsy case of spinocerebellar ataxia type 31 with severe dementia at the terminal stage
Spinocerebellar ataxia type 31 (SCA31) is an autosomal dominant cerebellar ataxia commonly observed in Japan. However, few neuropathological examinations have been conducted. Here we report the case of a 76‐year‐old Japanese male SCA31 patient. He noticed dysarthria and difficulty walking at 65 years old. His symptoms subsequently deteriorated, although he could still walk with assistance at 70 years. At 73 years, when he could no longer walk, he was admitted to our hospital. He showed severe limb and truncal ataxia. His father and older brother had shown the same symptoms. Brain magnetic resonance imaging showed cereb...
Source: Neuropathology - December 11, 2014 Category: Neurology Authors: Tadashi Adachi, Michio Kitayama, Toshiya Nakano, Yoshiki Adachi, Shinsuke Kato, Kenji Nakashima Tags: CASE REPORT Source Type: research

Topography of Brain glucose Hypometabolism and Epileptic network in Glucose Transporter 1 Deficiency
Glucose transporter 1 deficiency syndrome (Glut1DS) is a genetically determined developmental encephalopathy resulting from insufficient transport of glucose into the brain (De Vivo et al., 1991). Cardinal clinical features include infantile-onset seizures, acquired microcephaly, ataxia, dysarthria, dystonia, intellectual disability, and motor retardation (Pearson et al., 2013). The majority of Glut1 DS patients present with seizures in infancy (Alter et al., 2014). However, seizure onset beyond the first year of life has been also described in the number of studies with normal intelligence and alteration in SLC2A1 gene (S...
Source: Epilepsy Research - December 11, 2014 Category: Neurology Authors: Cigdem Inan Akman, Frank Provenzano, Dong Wang, Kristin Engelstad, Veronica Hinton, Julia Yu, Ronald Tikofsky, Masonari Ichese, Darryl C. De Vivo Source Type: research

HDAC3 Regulates Brain Development [Developmental Biology]
The functional role of histone deacetylase 3 (HDAC3) in the developing brain has yet to be elucidated. We show that mice lacking HDAC3 in neurons and glia of the central nervous system, Nes-Cre/HDAC3 conditional KO mice, show major abnormalities in the cytoarchitecture of the neocortex and cerebellum and die within 24 h of birth. Later-born neurons do not localize properly in the cortex. A similar mislocalization is observed with cerebellar Purkinje neurons. Although the proportion of astrocytes is higher than normal, the numbers of oligodendrocytes are reduced. In contrast, conditional knockout of HDAC3 in neurons of the ...
Source: Journal of Biological Chemistry - December 11, 2014 Category: Chemistry Authors: Norwood, J., Franklin, J. M., Sharma, D., D'Mello, S. R. Tags: Neurobiology Source Type: research

Eight novel mutations in MLC1 from 18 Iranian patients with megalencephalic leukoencephalopathy with subcortical cysts.
This report shows that MLC is relatively common in Iranian population, as expected for rare diseases with high inbreeding, with a surprisingly high frequency of novel mutations. PMID: 25497041 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics)
Source: European Journal of Medical Genetics - December 11, 2014 Category: Genetics & Stem Cells Authors: Kariminejad A, Rajaee A, Ashrafi MR, Alizadeh H, Tonekaboni SH, Malamiri RA, Ghofrani M, Karimzadeh P, Mohammadi MM, Baghalshooshtari A, Bozorgmehr B, Kariminejad MH, Postma N, Abbink TE, van der Knaap MS Tags: Eur J Med Genet Source Type: research

Expanding the phenotype of PRPS1 syndromes in females: neuropathy, hearing loss and retinopathy
Conclusions: These results are in line with recent evidence of the existence of intermediate phenotypes in PRS-I deficiency syndromes and demonstrate that females can exhibit a disease phenotype as severe and complex as their male counterparts. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - December 10, 2014 Category: Internal Medicine Authors: Berta AlmogueraSijie HeMarta CortonPatricia Fernandez-San JoseFiona Blanco-KellyMaria López-MolinaBlanca García-SandovalJavier del ValYiran GuoLifeng TianXuanzhu LiuLiping GuanRosa TorresJuan PuigHakon HakonarsonXun XuBrendan KeatingCarmen Ayuso Source Type: research

Purkinje neuron Ca2+ influx reduction rescues ataxia in SCA28 model
Spinocerebellar ataxia type 28 (SCA28) is a neurodegenerative disease caused by mutations of the mitochondrial protease AFG3L2. The SCA28 mouse model, which is haploinsufficient for Afg3l2, exhibits a progressive decline in motor function and displays dark degeneration of Purkinje cells (PC-DCD) of mitochondrial origin. Here, we determined that mitochondria in cultured Afg3l2-deficient PCs ineffectively buffer evoked Ca2+ peaks, resulting in enhanced cytoplasmic Ca2+ concentrations, which subsequently triggers PC-DCD. This Ca2+-handling defect is the result of negative synergism between mitochondrial depolarization and alt...
Source: Journal of Clinical Investigation - December 9, 2014 Category: Biomedical Science Authors: Francesca Maltecca, Elisa Baseggio, Francesco Consolato, Davide Mazza, Paola Podini, Samuel M. Young Jr., Ilaria Drago, Ben A. Bahr, Aldamaria Puliti, Franca Codazzi, Angelo Quattrini, Giorgio Casari Source Type: research

Vitamin E supplementation in people with cystic fibrosis.
CONCLUSIONS: Vitamin E supplementation led to an improvement in vitamin E levels in people with cystic fibrosis, although the studies may have been at risk of bias. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy.In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal...
Source: Cochrane Database of Systematic Reviews - December 9, 2014 Category: Journals (General) Authors: Okebukola PO, Kansra S, Barrett J Tags: Cochrane Database Syst Rev Source Type: research

Oculoleptomeningeal Amyloidosis associated with transthyretin Leu12Pro in an African patient
Abstract Oculoleptomeningeal amyloidosis is a rare manifestation of hereditary transthyretin (TTR) amyloidosis. Here, we present the first case of leptomeningeal amyloidosis associated with the TTR variant Leu12Pro mutation in an African patient. A 43-year-old right-handed Nigerian man was referred to our centre with rapidly progressive neurological decline. He presented initially with weight loss, confusion, fatigue, and urinary and erectile dysfunction. He then suffered recurrent episodes of slurred speech with right-sided weakness. He went on to develop hearing difficulties and painless paraesthesia. Neurologic...
Source: Journal of Neurology - December 8, 2014 Category: Neurology Source Type: research

Small fiber neuropathy in a woman with fragile X-associated tremor/ataxia syndrome (FXTAS)
(Source: Journal of Neurology)
Source: Journal of Neurology - December 8, 2014 Category: Neurology Source Type: research

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) - A case report and review of literature.
We report 4-year follow-up of the patient since the beginning of the disease. PMID: 25440017 [PubMed - in process] (Source: Neurologia i Neurochirurgia Polska)
Source: Neurologia i Neurochirurgia Polska - December 8, 2014 Category: Neurology Authors: Figura M, Gaweł M, Kolasa A, Janik P Tags: Neurol Neurochir Pol Source Type: research

A Forward Genetic Screen in Mice Identifies Mutants with Abnormal Cortical Patterning
Formation of a 6-layered cortical plate and axon tract patterning are key features of cerebral cortex development. Abnormalities of these processes may be the underlying cause for a range of functional disabilities seen in human neurodevelopmental disorders. To identify mouse mutants with defects in cortical lamination or corticofugal axon guidance, N-ethyl-N-nitrosourea (ENU) mutagenesis was performed using mice expressing LacZ reporter genes in layers II/III and V of the cortex (Rgs4-lacZ) or in corticofugal axons (TAG1-tau-lacZ). Four lines with abnormal cortical lamination have been identified. One of these was a splic...
Source: Cerebral Cortex - December 8, 2014 Category: Neurology Authors: Ha, S., Stottmann, R. W., Furley, A. J., Beier, D. R. Tags: Articles Source Type: research

Co-occurrence of four nucleotide changes associated with an adult mitochondrial ataxia phenotype
Conclusions: Computational analysis of the PolG protein suggests that the p.K601E mutation is likely the most significant contributing factor to a pathogenic phenotype. However, the co-occurrence of multiple POLG alleles may be necessary in the development an adult-onset mitochondrial ataxia phenotype. (Source: BMC Research Notes)
Source: BMC Research Notes - December 8, 2014 Category: Research Authors: Ramón ZabalzaAnssi NurminenLaurie KaguniRafael GaresseM GallardoBelén Bornstein Source Type: research

Clinical Reasoning: A 28-year-old man with progressive gait disturbance and encephalopathy
A 28-year-old man with sickle cell disease presented with 7 months of difficulty walking. Initial examination 3 months prior to admission to our hospital was thought to be consistent with a polyneuropathy. He was areflexic, was unable to stand on toes or heels with decreased sensation on the left foot to light touch and vibration, had difficulty with heel to shin, and was unable to perform tandem gait. Laboratory tests revealed anemia (hemoglobin 7.2 g/dL) and elevated creatinine (1.49 g/dL). HIV, antinuclear antibodies, antineutrophil cytoplasmic antibodies, hepatitis serologies, rapid plasma reagin, thyroid-stimulating h...
Source: Neurology - December 8, 2014 Category: Neurology Authors: Massaro, A. M., Pruitt, A. Tags: Stroke in young adults, MRI, Gait disorders/ataxia, All Oncology RESIDENT AND FELLOW SECTION Source Type: research

Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability
Conclusion: Ile67Asn variant in SNAP25B is pathogenic because it inhibits synaptic vesicle exocytosis. We attribute the deleterious effects of the mutation to disruption of the hydrophobic α-helical coiled-coil structure of the SNARE complex by replacement of a highly hydrophobic isoleucine by a strongly hydrophilic asparagine. (Source: Neurology)
Source: Neurology - December 8, 2014 Category: Neurology Authors: Shen, X.-M., Selcen, D., Brengman, J., Engel, A. G. Tags: EMG ARTICLE Source Type: research

Management of levodopa-induced jig-like gait disorder with pallidal stimulation
Levodopa, a metabolic precursor of the neurotransmitter dopamine, is the most effective symptomatic therapy for Parkinson disease (PD); however, long-term treatment with levodopa is complicated by fluctuations in motor response ("wearing off") and medication-induced dyskinesias in the majority of patients. (Source: Nature Clinical Practice)
Source: Nature Clinical Practice - December 8, 2014 Category: Neurology Authors: Ferrara, J. M., Houghton, D. J., Knoop, C., Park, M. C. Tags: All Movement Disorders, Dystonia, Gait disorders/ataxia, Parkinson's disease/Parkinsonism, Surgery/Stimulation Cases Source Type: research

Risk of false positive genetic associations in complex traits with underlying population structure: A case study
This study demonstrates the risk of false positive associations when performing GWA studies on complex traits and underlying population structure when using 40–50,000 SNP markers and small sample size. (Source: The Veterinary Journal)
Source: The Veterinary Journal - December 7, 2014 Category: Veterinary Research Source Type: research

P001 MS-like presentations of HTLV-1 infection: Case-series and review of literature
Conclusion This article argues about similar presentations between HTLV-1 infection and MS, not mentioned before. Occasionally, HTLV-1 infection is misdiagnosed as MS and it should be considered in the differential diagnosis of patients supposed to have MS, especially in endemic areas. In other words, as MS is a diagnosis of exclusion, it is quite reasonable to do a routine HTLV-1 serological study (ELISA) for all suspected MS patients in endemic areas. (Source: Multiple Sclerosis and Related Disorders)
Source: Multiple Sclerosis and Related Disorders - December 7, 2014 Category: Neurology Source Type: research