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Ataxia

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Deferiprone in Friedreich ataxia: A 6‐Month randomized controlled trial
This study demonstrated an acceptable safety profile of deferiprone at 20mg/kg/day for the treatment of patients with FRDA. Subgroup analyses raise the possibility that, in patients with less severe disease, deferiprone 20mg/kg/day may reduce disease progression, whereas higher doses appear to worsen ataxia. Ann Neurol 2014 (Source: Annals of Neurology)
Source: Annals of Neurology - August 30, 2014 Category: Neurology Authors: Massimo Pandolfo, Javier Arpa, Martin B. Delatycki, Kim Hanh Le Quan Sang, Caterina Mariotti, Arnold Munnich, Irene Sanz‐Gallego, Geneieve Tai, Mark A. Tarnopolsky, Franco Taroni, Michael Spino, Fernando Tricta Tags: Research Article Source Type: research

TIN2-TPP1 Interaction Is Required for POT1 Function [DNA and Chromosomes]
The single-stranded DNA binding proteins in mouse shelterin, POT1a and POT1b, accumulate at telomeres as heterodimers with TPP1, which binds TIN2 and thus links the TPP1/POT1 dimers with TRF1 and TRF2/Rap1. When TPP1 is tethered to TIN2/TRF1/TRF2, POT1a is thought to block replication protein A binding to the single-stranded telomeric DNA and prevent ataxia telangiectasia and Rad3-related kinase activation. Similarly, TPP1/POT1b tethered to TIN2 can control the formation of the correct single-stranded telomeric overhang. Consistent with this view, the telomeric phenotypes following deletion of POT1a,b or TPP1 are phenocopi...
Source: Journal of Biological Chemistry - August 28, 2014 Category: Chemistry Authors: Frescas, D., de Lange, T. Tags: Cell Biology Source Type: research

Chk1 Interacts with MCMs [Signal Transduction]
Chk1 is an essential mediator of the DNA damage response and cell cycle checkpoint. However, how exactly Chk1 transduces the checkpoint signaling is not fully understood. Here we report the identification of the heterohexamic minichromosome maintenance (MCM) complex that interacts with Chk1 by mass spectrometry. The interaction between Chk1 and the MCM complex was reduced by DNA damage treatment. We show that the MCM complex, at least partially, contributes to the chromatin association of Chk1, allowing for immediate phosphorylation of Chk1 by ataxia telangiectasia mutated and Rad3-related (ATR) in the presence of DNA dama...
Source: Journal of Biological Chemistry - August 28, 2014 Category: Chemistry Authors: Han, X., Aslanian, A., Fu, K., Tsuji, T., Zhang, Y. Tags: DNA and Chromosomes Source Type: research

ATM-mediated Mad1 Serine 214 phosphorylation regulates Mad1 dimerization and the spindle assembly checkpoint
The spindle assembly checkpoint (SAC), which blocks anaphase onset until all chromosomes have bi-oriented, is one of the key self-monitoring systems of the eukaryotic cell cycle for genome stability. The mitotic arrest-deficient protein 1 (Mad1), a critical component of the SAC, is hyperphosphorylated in mitosis. However, the kinases responsible for Mad1 phosphorylation and its functional significance are not fully understood. Here we report that Mad1 is phosphorylated on Serine 214 by the Ataxia-Telangiectasia Mutated (ATM) kinase, a critical DNA damage response protein also activated in mitosis and required for the SAC. ...
Source: Carcinogenesis - August 27, 2014 Category: Cancer & Oncology Authors: Yang, C., Hao, J., Kong, D., Cui, X., Zhang, W., Wang, H., Guo, X., Ma, S., Liu, X., Pu, P., Xu, B. Tags: Original Manuscript Source Type: research

Epigenetic therapy for Friedreich's ataxia
Abstract Objective: To investigate whether a histone deacetylase inhibitor (HDACi) would be effective in an in vitro model for the neurodegenerative disease Friedreich's ataxia (FRDA) and to evaluate safety and surrogate markers of efficacy in a phase I clinical trial in patients. Methods: We used a human FRDA neuronal cell model, derived from patient induced pluripotent stem cells, to determine the efficacy of a 2‐aminobenzamide HDACi (109) as a modulator of FXN gene expression and chromatin histone modifications. FRDA patients were dosed in four cohorts, ranging from 30 mg/day to 240 mg/day of the formulated drug produ...
Source: Annals of Neurology - August 27, 2014 Category: Neurology Authors: Elisabetta Soragni, Wenyan Miao, Marco Iudicello, David Jacoby, Stefania Demercanti, Marinella Clerico, Filomena Longo, Antonio Piga, Sherman Ku, Erica Campau, Jintang Du, Pablo Penalver, Myriam Rai, Joseph C. Madara, Kristopher Nazor, Melinda O'Connor, A Tags: Research Article Source Type: research

Friedreich ataxia: New findings, new challenges
(Source: Annals of Neurology)
Source: Annals of Neurology - August 27, 2014 Category: Neurology Authors: David R. Lynch, Lauren Seyer Tags: Invited Commentary Source Type: research

Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks.
Abstract DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the process by which cells recover from the DNA damage checkpoint, a process called checkpoint recovery. Here, we show that Src family kinases promote inactivation of ataxia telangiectasia mutated (ATM)-dependent checkpoint signaling during recovery from DNA double-strand breaks. Inhibition of Src activity increased ATM-dependent phosphor...
Source: Biochemical and Biophysical Research communications - August 27, 2014 Category: Biochemistry Authors: Fukumoto Y, Kuki K, Morii M, Miura T, Honda T, Ishibashi K, Hasegawa H, Kubota S, Ide Y, Yamaguchi N, Nakayama Y, Yamaguchi N Tags: Biochem Biophys Res Commun Source Type: research

Corrigendum: EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia
Nature Neuroscience 17, 1286 (2014). doi:10.1038/nn0914-1286c Author: Jiali Li, Ronald P Hart, Elyse M Mallimo, Mavis R Swerdel, Alexander W Kusnecov & Karl Herrup (Source: Nature Neuroscience)
Source: Nature Neuroscience - August 26, 2014 Category: Neuroscience Authors: Jiali LiRonald P HartElyse M MallimoMavis R SwerdelAlexander W KusnecovKarl Herrup Tags: Corrigendum Source Type: research

Phenotypic overlap of alternating hemiplegia of childhood and CAPOS syndrome
We describe a 12-year-old boy with an unreported clinical presentation associated with a novel missense mutation of the ATP1A3 gene. (Source: Neurology)
Source: Neurology - August 25, 2014 Category: Neurology Authors: Rosewich, H., Weise, D., Ohlenbusch, A., Gartner, J., Brockmann, K. Tags: Dystonia, Gait disorders/ataxia, Parkinson's disease/Parkinsonism, Optic nerve, Audition CLINICAL/SCIENTIFIC NOTES Source Type: research

KCNC3(R420H), a K(+) channel mutation causative in spinocerebellar ataxia 13 displays aberrant intracellular trafficking.
Abstract Spinocerebellar ataxia 13 (SCA13) is an autosomal dominant disease resulting from mutations in KCNC3 (Kv3.3), a voltage-gated potassium channel. The KCNC3(R420H) mutation was first identified as causative for SCA13 in a four-generation Filipino kindred with over 20 affected individuals. Electrophysiological analyses in oocytes previously showed that this mutation did not lead to a functional channel and displayed a dominant negative phenotype. In an effort to identify the molecular basis of this allelic form of SCA13, we first determined that human KCNC3(WT) and KCNC3(R420H) display disparate post-translat...
Source: Neurobiology of Disease - August 22, 2014 Category: Neurology Authors: Gallego-Iradi C, Bickford JS, Khare S, Hall A, Nick JA, Salmasinia D, Wawrowsky K, Bannykh S, Huynh DP, Rincon-Limas DE, Pulst SM, Nick HS, Fernandez-Funez P, Waters MF Tags: Neurobiol Dis Source Type: research

Methoxetamine: a ketamine analog that is NOT bladder friendly
3.5 out of 5 stars Methoxetamine — a novel recreational drug with potent hallucinogenic properties. Zawilska JB. Toxicol Lett 2014 Aug 13. pii: S0378-4274(14)01298-3. doi: 10.1016/j.toxlet.2014.08.011. [Epub ahead of print] Abstract Methoxetamine (MXE) is a structural analog of ketamine, with effects that are similar but more intense and longer-lasting. Street names include: MXE Mexxy  M-ket MEX Kmax Special M MA “Legal ketamine” Minx Jipper Roflcoptr Since chronic exposure to ketamine is known to cause ulcerative cystitis, MXE is sometimes touted as “bladder friendly.” However, lack of clini...
Source: The Poison Review - August 20, 2014 Category: Toxicology Authors: Leon Tags: Medical bladder toxicity genitourinary toxicity ketamine methoxetamine MXE Source Type: news

The Development of Ataxia Telangiectasia Mutated Kinase Inhibitors.
Abstract Radiation and genotoxic drugs are two of the cornerstones of current cancer treatment strategy. However, this type of therapy often suffers from radio- or chemo-resistance caused by DNA repair mechanisms. With the aim of increasing the efficacy of these treatments, there has been great interest in studying DNA damage responses (DDR). Among the plethora of signal and effector proteins involved in DDR, three related kinases ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related) and DNA-PK (DNA-dependent protein kinase) play the main roles in initiation and regulation of signaling pathways in respons...
Source: Mini Reviews in Medicinal Chemistry - August 20, 2014 Category: Chemistry Authors: Andrsa M, Korabecny J, Nepovimova E, Jun D, Hodny Z, Moravcova S, Kuca K Tags: Mini Rev Med Chem Source Type: research

Understanding decreased fertility in women carriers of the FMR1 premutation: a possible mechanism for Fragile X-Associated Primary Ovarian Insufficiency (FXPOI)
Fragile X syndrome (FXS) and its associated disorders are caused by the expansion of the CGG repeat in the 5[prime] untranslated region of the fragile X mental retardation 1 gene (FMR1). The full mutation, defined as >200 cytosine-guanine-guanine (CGG) triplet repeats, causes FXS. Individuals with 55-199 CGG repeats, classified as premutation carriers, are affected by two distinct disorders depending on their premutation status. Disorders associated with premutation carriers include: Fragile X-associated Tremor Ataxia Syndrome (FXTAS) and Fragile X-associated Primary Ovarian Insufficiency (FXPOI). The molecular similaritie...
Source: BioMed Central - August 19, 2014 Category: Journals (General) Authors: Emmanuel Peprah Source Type: research

Behavioral and Neurochemical Changes Induced by Repetitive Combined Treatments of Ketamine and Amphetamine in Mice.
Abstract The combined abuse of recreational drugs such as ketamine (Ket) and amphetamine (Amph) should be seriously considered important social and health issues. Numerous studies have documented the behavioral and neurochemical changes associated with polydrug administration; however, most studies have only examined the acute effects. The consequences following chronic repetitive polydrug use are less studied. In the present study, intraperitoneal injections of saline, Amph (5 mg/kg), low dose Ket (LK, 10 mg/kg), high dose Ket (HK, 50 mg/kg), or Amph plus LK or HK (ALK or AHK) were conducted twice a day for thr...
Source: Neurochemical Research - August 19, 2014 Category: Neuroscience Authors: Lai CC, Lee LJ, Yin HS Tags: Neurochem Res Source Type: research

Genetic inactivation of midkine modulates behavioural responses to ethanol possibly by enhancing GABA(A) receptor sensitivity to GABA(A) acting drugs.
Abstract Midkine (MK) is a cytokine with important functions in dopaminergic neurons that is found upregulated in the prefrontal cortex of alcoholics. We have studied the behavioural effects of ethanol in MK genetically deficient (MK-/-) and wild type (MK+/+) mice. A low dose of ethanol (1.0g/kg), unable to cause conditioned place preference (CPP) in MK+/+ mice, induced a significant CPP in MK-/- mice, suggesting that MK prevents the rewarding effects of low doses of ethanol. However, this difference between genotypes is lost when a higher, rewarding, dose of ethanol (2.0g/kg) is used. Accordingly, the anxiolytic e...
Source: Behavioural Brain Research - August 19, 2014 Category: Neurology Authors: Vicente-Rodríguez M, Pérez-García C, Haro M, Ramos MP, Herradón G Tags: Behav Brain Res Source Type: research

Motoric cognitive risk syndrome: Multicountry prevalence and dementia risk
Conclusion: MCR is common in older adults, and is a strong and early risk factor for cognitive decline. This clinical approach can be easily applied to identify high-risk seniors in a wide variety of settings. (Source: Neurology)
Source: Neurology - August 18, 2014 Category: Neurology Authors: Verghese, J., Annweiler, C., Ayers, E., Barzilai, N., Beauchet, O., Bennett, D. A., Bridenbaugh, S. A., Buchman, A. S., Callisaya, M. L., Camicioli, R., Capistrant, B., Chatterji, S., De Cock, A.-M., Ferrucci, L., Giladi, N., Guralnik, J. M., Hausdorff, J Tags: Gait disorders/ataxia, Assessment of cognitive disorders/dementia, Cohort studies, Prevalence studies, Incidence studies ARTICLE Source Type: research

Mitochondrial EFTs defects in juvenile-onset Leigh disease, ataxia, neuropathy, and optic atrophy
Conclusions: We show that in addition to early-onset cardiomyopathy, TSFM mutations should be considered in childhood and juvenile encephalopathies with optic and/or peripheral neuropathy, ataxia, or Leigh disease. (Source: Neurology)
Source: Neurology - August 18, 2014 Category: Neurology Authors: Ahola, S., Isohanni, P., Euro, L., Brilhante, V., Palotie, A., Pihko, H., Lonnqvist, T., Lehtonen, T., Laine, J., Tyynismaa, H., Suomalainen, A. Tags: All Clinical Neurology, Mitochondrial disorders; see Genetics/Mitochondrial disorders, All Neuro-ophthalmology, All Pediatric, Cardiac ARTICLE Source Type: research

Neurophysiological evidence for generalized sensory neuronopathy in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS)
Discussion: We suggest that a sensory neuronopathy should be sought in cerebellar and/or vestibular ataxias, particularly where the degree of ataxia is out of proportion to the clinically identified cerebellar and/or vestibular dysfunction. © 2014 Wiley Periodicals, Inc. (Source: Muscle and Nerve)
Source: Muscle and Nerve - August 16, 2014 Category: Internal Medicine Authors: David J Szmulewicz, Linda Seiderer, G. Michael Halmagyi, Elsdon Storey, Leslie Roberts Tags: Research Article Source Type: research

Polyglutamine-expanded ataxin-3 impairs long-term depression in Purkinje neurons of SCA3 transgenic mouse by inhibiting HAT and impairing histone acetylation.
Abstract Our previous study using a transgenic mouse model of spinocerebellar ataxia type 3 (SCA3) reported that disease-causing ataxin-3-Q79 caused cerebellar malfunction by inducing transcriptional downregulation. Long-term depression (LTD) of parallel fiber-Purkinje neuron glutamatergic transmission is believed to be a cellular mechanism for motor learning and motor coordination in the cerebellum. Downregulated mRNA expression of calcineurin B, IP3-R1, myosin Va and PLC β4, which are required for the induction of cerebellar LTD, led to an impairment of LTD induction in Purkinje neurons of SCA3 transgenic mouse....
Source: Brain Research - August 16, 2014 Category: Neurology Authors: Chou AH, Chen YL, Hu SH, Chang YM, Wang HL Tags: Brain Res Source Type: research

The Ataxia Telangiectasia Mutated and Cyclin D3 Proteins Cooperate To Help Enforce TCRβ and IgH Allelic Exclusion.
Abstract Coordination of V rearrangements between loci on homologous chromosomes is critical for Ig and TCR allelic exclusion. The Ataxia Telangietasia mutated (ATM) protein kinase promotes DNA repair and activates checkpoints to suppress aberrant Ig and TCR rearrangements. In response to RAG cleavage of Igκ loci, ATM inhibits RAG expression and suppresses further Vκ-to-Jκ rearrangements to enforce Igκ allelic exclusion. Because V recombination between alleles is more strictly regulated for TCRβ and IgH loci, we evaluated the ability of ATM to restrict biallelic expression and V-to-DJ recombination of TCRβ an...
Source: Journal of Immunology - August 15, 2014 Category: Allergy & Immunology Authors: Steinel NC, Fisher MR, Yang-Iott KS, Bassing CH Tags: J Immunol Source Type: research

Chromosome End-specific DNA Damage Response in Mitosis [Cell Biology]
Chromosome ends contain nucleoprotein structures known as telomeres. Damage to chromosome ends during interphase elicits a DNA damage response (DDR) resulting in cell cycle arrest. However, little is known regarding the signaling from damaged chromosome ends (designated here as “TIPs”) during mitosis. In the present study, we investigated the consequences of DNA damage induced at a single TIP in mitosis. We used laser microirradiation to damage mitotic TIPs or chromosome arms (non-TIPs) in PtK2 kidney epithelial cells. We found that damage to a single TIP, but not a non-TIP, delays anaphase onset. This TIP-specific che...
Source: Journal of Biological Chemistry - August 14, 2014 Category: Chemistry Authors: Silva, B. A., Stambaugh, J. R., Yokomori, K., Shah, J. V., Berns, M. W. Tags: DNA and Chromosomes Source Type: research

Modulation of the age at onset in spinocerebellar ataxia by CAG tracts in various genes
Polyglutamine-coding (CAG)n repeat expansions in seven different genes cause spinocerebellar ataxias. Although the size of the expansion is negatively correlated with age at onset, it accounts for only 50–70% of its variability. To find other factors involved in this variability, we performed a regression analysis in 1255 affected individuals with identified expansions (spinocerebellar ataxia types 1, 2, 3, 6 and 7), recruited through the European Consortium on Spinocerebellar Ataxias, to determine whether age at onset is influenced by the size of the normal allele in eight causal (CAG)n-containing genes (ATXN1&ndash...
Source: Brain - August 13, 2014 Category: Neurology Authors: Tezenas du Montcel, S., Durr, A., Bauer, P., Figueroa, K. P., Ichikawa, Y., Brussino, A., Forlani, S., Rakowicz, M., Schols, L., Mariotti, C., van de Warrenburg, B. P. C., Orsi, L., Giunti, P., Filla, A., Szymanski, S., Klockgether, T., Berciano, J., Pand Tags: Original Articles Source Type: research

Neuroaxonal dystrophy in Merino‐Border Leicester × Polled Dorset lambs
ConclusionsThis is the first report of NAD in such crossbred lambs; the affected animals were much younger than in previously described cases of ovine NAD and myelin loss was of much greater magnitude than previously reported. (Source: Australian Veterinary Journal)
Source: Australian Veterinary Journal - August 13, 2014 Category: Veterinary Research Authors: JW Finnie, IV Jerrett, J Manavis, J Cave Tags: CASE REPORT Source Type: research

Multimodal evoked potentials in spinocerebellar ataxia types 1, 2, and 3
Conclusions: BAER was the most frequent abnormality in SCA types 1, 2, and 3; abnormalities of mSSEP were comparable in the three SCAs; whereas, abnormality of VEP was less often noted in SCA3. (Source: Annals of Indian Academy of Neurology)
Source: Annals of Indian Academy of Neurology - August 12, 2014 Category: Neurology Authors: Vijay ChandranKetan JhunjhunwalaMeera PurushottamSanjeev JainPramod Kumar Pal Source Type: research

A novel missense mutation in CCDC88C activates the JNK pathway and causes a dominant form of spinocerebellar ataxia
Conclusions This study expands our understanding of the cause of autosomal-dominant SCAs, a group of heterogeneous congenital neurological conditions in humans, and unveils a link between the JNK stress pathway and cerebellar atrophy. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - August 12, 2014 Category: Genetics & Stem Cells Authors: Tsoi, H., Yu, A. C. S., Chen, Z. S., Ng, N. K. N., Chan, A. Y. Y., Yuen, L. Y. P., Abrigo, J. M., Tsang, S. Y., Tsui, S. K. W., Tong, T. M. F., Lo, I. F. M., Lam, S. T. S., Mok, V. C. T., Wong, L. K. S., Ngo, J. C. K., Lau, K.-F., Chan, T.-F., Chan, H. Y. Tags: Open access Phenotypes Source Type: research

Correction
Sophie Tezenas du Montcel, Alexandra Durr, Maria Rakowicz, et al. Prediction of the age at onset in spinocerebellar ataxia type 1,2,3 and 6. J Med Genet 2014;51:479–86. doi:10.1136/jmedgenet-2013-102200. The author's name Béla Melegh has been corrected. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - August 12, 2014 Category: Genetics & Stem Cells Tags: Correction Source Type: research

Rapidly Progressive Ataxia During Rehabilitation and a Difficult Road to Diagnosis
(Source: Journal of the American Geriatrics Society)
Source: Journal of the American Geriatrics Society - August 12, 2014 Category: Geriatrics Authors: Yat‐Fung Shea, Tuen‐Ching Chan, Richard Shek‐Kwan Chang, Fong‐Kwong Sonny Hon, Joseph Shiu‐Kwong Kwan, Leung‐Wing Chu Tags: Letters to the Editor Source Type: research

Deferiprone in Friedreich’s Ataxia: A six‐month randomized controlled trial
This study demonstrated an acceptable safety profile of deferiprone at 20 mg/kg/day for the treatment of patients with FRDA. Subgroup analyses raise the possibility that, in patients with less severe disease, deferiprone 20 mg/kg/day may reduce disease progression, while higher doses appear to worsen ataxia. ANN NEUROL 2014. © 2014 American Neurological Association (Source: Annals of Neurology)
Source: Annals of Neurology - August 11, 2014 Category: Neurology Authors: Massimo Pandolfo, Javier Arpa, Martin B. Delatycki, Kim Hanh Le Quan Sang, Caterina Mariotti, Arnold Munnich, Irene Sanz‐Gallego, Geneieve Tai, Mark A. Tarnopolsky, Franco Taroni, Michael Spino, Fernando Tricta Tags: Research Article Source Type: research

Gait analysis and the cumulative gait index (CGI): Translational tools to assess impairments exhibited by rats with olivocerebellar ataxia.
This study characterizes gait alterations in laboratory rats rendered ataxic by destruction of the climbing fiber pathway innervating Purkinje cells and demonstrates that a single index can be used to describe overall gait impairments. PMID: 25116252 [PubMed - as supplied by publisher] (Source: Behavioural Brain Research)
Source: Behavioural Brain Research - August 10, 2014 Category: Neurology Authors: Lambert CS, Philpot RM, Engberg ME, Johns BE, Kim SH, Wecker L Tags: Behav Brain Res Source Type: research

[Comment] Nicotinamide in Friedreich's ataxia: useful or not?
Friedreich's ataxia is an autosomal recessive neurodegenerative disorder caused by mutations in the frataxin gene (FXN), leading to progressive ataxia, cardiomyopathy, scoliosis, and various other clinical features. Most patients have GAA repeat expansions in intron 1 of FXN, leading to decreased concentrations of frataxin protein and downstream mitochondrial dysfunction. The GAA repeats lead to gene silencing through heterochromatin formation, and decreased transcription of FXN mRNA. The coding region of the mRNA and the aminoacid sequence of the protein are normal, but the amount of protein produced is reduced; as a resu...
Source: LANCET - August 9, 2014 Category: Journals (General) Authors: David R Lynch, Kenneth H Fischbeck Tags: Comment Source Type: research

[Department of Error] Department of Error
Libri V, Yandim C, Athanasopoulos S, et al. Epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia: an exploratory, open-label, dose-escalation study. Lancet 2014; 384: 504–13—This Article should have been published under a Creative Commons CC BY open-access licence. The correction has been made to the online version as of May 8, 2014, and to the printed Article. (Source: LANCET)
Source: LANCET - August 9, 2014 Category: Journals (General) Authors: The Lancet Tags: Department of Error Source Type: research

[Department of Error] Department of Error
Lynch DR, Fischbeck KH. Nicotinamide in Friedreich's ataxia: useful or not? Lancet 2014; 384: 474–75—This Comment should have been published under a Creative Commons CC BY open-access licence. The correction has been made to the online version as of May 29, 2014, and to the printed Comment. (Source: LANCET)
Source: LANCET - August 9, 2014 Category: Journals (General) Authors: The Lancet Tags: Department of Error Source Type: research

[Articles] Epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia: an exploratory, open-label, dose-escalation study
Nicotinamide was associated with a sustained improvement in frataxin concentrations towards those seen in asymptomatic carriers during 8 weeks of daily dosing. Further investigation of the long-term clinical benefits of nicotinamide and its ability to ameliorate frataxin deficiency in Friedreich's ataxia is warranted. (Source: LANCET)
Source: LANCET - August 9, 2014 Category: Journals (General) Authors: Vincenzo Libri, Cihangir Yandim, Stavros Athanasopoulos, Naomi Loyse, Theona Natisvili, Pui Pik Law, Ping Kei Chan, Tariq Mohammad, Marta Mauri, Kin Tung Tam, James Leiper, Sophie Piper, Aravind Ramesh, Michael H Parkinson, Les Huson, Paola Giunti, Richar Tags: Articles Source Type: research

Training balance with opto-kinetic stimuli in the home: a randomized controlled feasibility study in people with pure cerebellar disease - Bunn LM, Marsden JF, Giunti P, Day BL.
OBJECTIVE: To investigate the feasibility of a randomized controlled trial of a home-based balance intervention for people with cerebellar ataxia. DESIGN: A randomized controlled trial design. SETTING: Intervention and assessment took place in the ... (Source: SafetyLit: All (Unduplicated))
Source: SafetyLit: All (Unduplicated) - August 8, 2014 Category: Global & Universal Tags: Economics of Injury and Safety, PTSD, Injury Outcomes Source Type: news

INCLEN Diagnostic Tool for Neuromotor Impairments (INDT-NMI) for Primary Care Physician: Development and Validation.
CONCLUSIONS: Graduate primary care physicians with a structured short training can administer the new tool and diagnose NMI in 2-9 year old children with high validity. INDT-NMI requires further evaluation in actual primary care settings. PMID: 25128993 [PubMed - as supplied by publisher] (Source: Indian Pediatrics)
Source: Indian Pediatrics - August 8, 2014 Category: Pediatrics Authors: Gulati S, Aneja S, Juneja M, Mukherjee S, Deshmukh V, Silberberg D, Bhutani VK, Pinto JM, Durkin M, Tudu P, Pandey RM, Nair MK, Arora NK, INCLEN Study Group, INCLEN Study Group Tags: Indian Pediatr Source Type: research

The first knockin mouse model of episodic ataxia type 2.
Abstract Episodic ataxia type 2 (EA2) is an autosomal dominant disorder associated with attacks of ataxia that are typically precipitated by stress, ethanol, caffeine or exercise. EA2 is caused by loss-of-function mutations in the CACNA1A gene, which encodes the α1A subunit of the CaV2.1 voltage-gated Ca(2+) channel. To better understand the pathomechanisms of this disorder in vivo, we created the first genetic animal model of EA2 by engineering a mouse line carrying the EA2-causing c.4486T>G (p.F1406C) missense mutation in the orthologous mouse Cacna1a gene. Mice homozygous for the mutated allele exhibit a ~70...
Source: Experimental Neurology - August 7, 2014 Category: Neurology Authors: Rose SJ, Kriener LH, Heinzer AK, Fan X, Raike RS, van den Maagdenberg AM, Hess EJ Tags: Exp Neurol Source Type: research

Speckle-type POZ protein, SPOP, is involved in the DNA damage response
Speckle-type POZ protein (SPOP) is an adaptor of the cullin 3-based ubiquitin ligase responsible for the degradation of oncoproteins frequently overexpressed in many tumor cells. Altered expression and somatic mutations of SPOP have been observed in various tumor types with chromosomal aberrations, indicating a role of SPOP in maintaining genome stability, although a detailed mechanism remains unclear. Here, we show that SPOP is a component of the DNA damage response (DDR). SPOP is recruited to DNA double-strand break sites and it forms nuclear foci after DNA damage. SPOP foci colocalize with -H2AX foci and are predominant...
Source: Carcinogenesis - August 6, 2014 Category: Cancer & Oncology Authors: Zhang, D., Wang, H., Sun, M., Yang, J., Zhang, W., Han, S., Xu, B. Tags: Original Manuscript Source Type: research

Deletion of UBE3A in brothers with Angelman syndrome at the breakpoint with an inversion at 15q11.2
This report describes a rare type of familial AS detected using the D15S10 FISH test. © 2014 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - August 6, 2014 Category: Genetics & Stem Cells Authors: Yukiko Kuroda, Ikuko Ohashi, Toshiyuki Saito, Jun‐Ichi Nagai, Kazumi Ida, Takuya Naruto, Takahito Wada, Kenji Kurosawa Tags: Clinical Report Source Type: research

Usefulness of frataxin immunoassays for the diagnosis of Friedreich ataxia
Conclusions Frataxin measurements from peripheral tissues can be used to identify FRDA patients and carriers. While multiple cell types and assays may be useful for diagnostic purposes, each assay and cell type used has its advantages and disadvantages depending on study design and scope. (Source: Journal of Neurology, Neurosurgery and Psychiatry)
Source: Journal of Neurology, Neurosurgery and Psychiatry - August 6, 2014 Category: Neurosurgery Authors: Deutsch, E. C., Oglesbee, D., Greeley, N. R., Lynch, D. R. Tags: Genetics, Immunology (including allergy), Brain stem / cerebellum, Drugs: CNS (not psychiatric), Spinal cord Movement disorders Source Type: research

Autosomal-recessive complicated spastic paraplegia with a novel lysosomal trafficking regulator gene mutation
Conclusions We diagnosed these patients as having adult CHS presenting spastic paraplegia with cerebellar ataxia and neuropathy. The clinical spectrum of CHS is broader than previously recognised. Adult CHS must be considered in the differential diagnosis of AR-HSP. (Source: Journal of Neurology, Neurosurgery and Psychiatry)
Source: Journal of Neurology, Neurosurgery and Psychiatry - August 6, 2014 Category: Neurosurgery Authors: Shimazaki, H., Honda, J., Naoi, T., Namekawa, M., Nakano, I., Yazaki, M., Nakamura, K., Yoshida, K., Ikeda, S.-i., Ishiura, H., Fukuda, Y., Takahashi, Y., Goto, J., Tsuji, S., Takiyama, Y. Tags: Genetics, Immunology (including allergy), Brain stem / cerebellum, Drugs: CNS (not psychiatric), Neuromuscular disease, Peripheral nerve disease Neurogenetics Source Type: research

Cortical susceptibility-weighted imaging hypointensity after stroke-like episode in MELAS
A 49-year-old woman with a known m.3243A>G tRNALeu(UUR) mutation (ie, the most frequent mutation in mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS)) diagnosed in the presence of migraine, diabetes mellitus, neurosensory hearing loss, short stature, cognitive deficit, ataxia and elevated lactate levels, presented with subacute aphasia and right hemiplegia. Brain MRI showed a typical stroke-like lesion in the left temporal and parietal lobe and prerolandic cortex. At this time, gradient-echo T2-weighted imaging showed hyperintensities in the involved regions (also visible on T2-weighted and ...
Source: Journal of Neurology, Neurosurgery and Psychiatry - August 6, 2014 Category: Neurosurgery Authors: Renard, D., Taieb, G. Tags: Immunology (including allergy), Headache (including migraine), Neuroimaging Neurological pictures Source Type: research

Genetics Home Reference: dilated cardiomyopathy with ataxia syndrome
http://ghr.nlm.nih.gov/condition/dilated-cardiomyopathy-with-ataxia-syndrome (Source: NLM General Announcements)
Source: NLM General Announcements - August 5, 2014 Category: Databases & Libraries Source Type: news

CAMTA controls Purkinje cell function and survival [Neuroscience]
Members of the calmodulin-binding transcription activator (CAMTA) family of proteins function as calcium-sensitive regulators of gene expression in multicellular organisms ranging from plants to humans. Here, we show that global or nervous system deletion of CAMTA1 in mice causes severe ataxia with Purkinje cell degeneration and cerebellar atrophy, partially resembling... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - August 5, 2014 Category: Science Authors: Long, C., Grueter, C. E., Song, K., Qin, S., Qi, X., Kong, Y. M., Shelton, J. M., Richardson, J. A., Zhang, C.-L., Bassel-Duby, R., Olson, E. N. Tags: Biological Sciences Source Type: research

What Is Ataxia and What Causes It?
Ataxia in common usage means unsteady gait. More ... (Source: About.com Bipolar Disorder)
Source: About.com Bipolar Disorder - August 5, 2014 Category: Psychiatry Authors: bipolar.guide at about.com Tags: health Source Type: news

Linkage analysis and whole-exome sequencing exclude extra mutations responsible for the parkinsonian phenotype of SCA2
CAG expansion within the exon 1 of ataxin-2 (ATXN2) gene responsible for spinocerebellar ataxia-2 (SCA2) has been reported to cause pure parkinsonism and other neurodegenerative disorders. However, it remains unclear whether CAG expansion is the only cause for SCA2 and its clinical alternatives, and whether extra mutations exist to modify the phenotypic diversity. To address this, we have conducted fine genetic mapping and exome sequencing for a large Chinese SCA2 pedigree predominantly manifesting parkinsonism (called SCA2-P). (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - August 2, 2014 Category: Neuroscience Authors: Chaodong Wang, Yanming Xu, Xiuli Feng, Jinghong Ma, Shu Xie, Yanli Zhang, Bei-Sha Tang, Piu Chan Source Type: research

Cerebrotendinous Xanthomatosis: The Effectiveness of High-Dose Piracetam for the Treatment of Cerebellar and Sensorial Ataxia.
PMID: 25084753 [PubMed - as supplied by publisher] (Source: Cerebellum)
Source: Cerebellum - August 2, 2014 Category: Neuroscience Authors: Uygunoglu U, Gunduz A, Menku SF, Yilmaz B, Hatipoglu E, Yalcinkaya C, Saip S, Apaydin H Tags: Cerebellum Source Type: research

Brain penetration of emodepside is increased in P‐glycoprotein‐deficient mice and leads to neurotoxicosis
In conclusion, P‐gp restricts brain penetration of EMO and prevents neurological toxicity of this drug in mice. (Source: Journal of Veterinary Pharmacology and Therapeutics)
Source: Journal of Veterinary Pharmacology and Therapeutics - August 1, 2014 Category: Veterinary Research Authors: S. Elmshäuser, L. C. Straehle, J. Kranz, R. Krebber, J. Geyer Tags: Scientific Paper Source Type: research

GLUTAMATE RECEPTOR ANTIBODIES IN NEUROLOGICAL DISEASES: Anti-AMPA-GluR3 antibodies, Anti-NMDA-NR1 antibodies, Anti-NMDA-NR2A/B antibodies, Anti-mGluR1 antibodies or Anti-mGluR5 antibodies are present in subpopulations of patients with either: Epilepsy, Encephalitis, Cerebellar Ataxia, Systemic Lupus Erythematosus (SLE) and Neuropsychiatric SLE, Sjogren's syndrome, Schizophrenia, Mania or Stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor's expression, impair glutamate-induced signaling and function, activate Blood Brain Barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and Ataxia in animal models, and can be removed or silenced in some patients by immunotherapy.
Abstract Glutamate is the major excitatory neurotransmitter of the Central Nervous System (CNS), and it is crucially needed for numerous key neuronal functions. Yet, excess glutamate causes massive neuronal death and brain damage by excitotoxicity-detrimental over activation of glutamate receptors. Glutamate-mediated excitotoxicity is the main pathological process taking place in many types of acute and chronic CNS diseases and injuries. In recent years, it became clear that not only excess glutamate can cause massive brain damage, but that several types of anti-glutamate receptor antibodies, that are present in t...
Source: Herpes - August 1, 2014 Category: Infectious Diseases Authors: Levite M Tags: J Neural Transm Source Type: research

Monitoring mood states in everyday life: A new device for patients with cerebellar ataxia
Thirty patients with cerebellar ataxia and 40 healthy volunteers underwent 7 days of mood monitoring using a new device requiring a low motor load. Its convergent validity and compliance were tested. The measurements resulted consistent with validated scale scores. Patients’ motor impairment did not affect the compliance. (Source: Psychiatry Research)
Source: Psychiatry Research - August 1, 2014 Category: Psychiatry Authors: Silvia Clausi, Fabio Aloise, Maria P. Contento, Luigi Pizzamiglio, Marco Molinari, Maria Leggio Source Type: research

Physical therapy for correcting postural and coordination deficits in patients with mild-to-moderate traumatic brain injury.
Abstract Abstract The purpose of this study was to test the effects of a conventional exercise program designed for correcting postural and coordination abnormalities in patients with mild-to-moderate traumatic brain injury (TBI). Using principles of motor learning applied to functional exercise training, exercises were performed while lying, sitting, standing and walking, with the goal of improving intra- and inter-limb coordination in the upper and lower extremities, postural stability and gait pattern. Twenty-two participants with TBI-related deficits received therapy in a supervised outpatient clinic. Therapy i...
Source: Physiotherapy Theory and Practice - August 1, 2014 Category: Physiotherapy Authors: Ustinova KI, Chernikova LA, Dull A, Perkins J Tags: Physiother Theory Pract Source Type: research