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Ataxia

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Effects of miglustat treatment in a patient affected by an atypical form of Tangier Disease
Conclusions: These results suggest miglustat as a possible therapeutic approach in this untreatable disease. The mechanisms by which miglustat ameliorates at least some clinical manifestations of TD needs to be further investigated. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - September 18, 2014 Category: Internal Medicine Authors: Annalisa SechiAndrea DardisStefania ZampieriClaudio RabacchiPaolo ZanoniSebastiano CalandraGiovanna De MaglioStefano PizzolittoValerio MaruottiAntonio Di MuzioFrances PlattBruno Bembi Source Type: research

A Case of Cerebellar Ataxia Associated with HIV Infection
Cerebellar complications of HIV infection primarily manifested in ataxia, usually arise as the result of cerebellar lesions due to opportunistic infections, vasculitis or neoplastic processes. A 28 year old female known to have HIV infection for last four years, presented to our hospital with progressive unsteadiness in walking, slurring of speech and intention tremors for the last two months. There was no family history of similar complaints, and she was on Anti retroviral treatment for last one and a half years. The results of examination were notable for severe dysarthria, slow saccades, a conspicuous dysmetria and dysd...
Source: Journal of the International Association of Physicians in AIDS Care (JIAPAC) - September 17, 2014 Category: Infectious Diseases Authors: Anand, K. S., Wadhwa, A., Garg, J. Tags: Case Reports Source Type: research

Epigenetic therapy for Friedreich ataxia
ObjectiveTo investigate whether a histone deacetylase inhibitor (HDACi) would be effective in an in vitro model for the neurodegenerative disease Friedreich ataxia (FRDA) and to evaluate safety and surrogate markers of efficacy in a phase I clinical trial in patients. MethodsWe 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 4 cohorts, ranging from 30mg/day to 240mg/day of the formulated drug product of HDACi 109, RG2...
Source: Annals of Neurology - September 16, 2014 Category: Neurology Authors: Elisabetta Soragni, Wenyan Miao, Marco Iudicello, David Jacoby, Stefania De Mercanti, Marinella Clerico, Filomena Longo, Antonio Piga, Sherman Ku, Erica Campau, Jintang Du, Pablo Penalver, Myriam Rai, Joseph C. Madara, Kristopher Nazor, Melinda O'Connor, Tags: Research Article Source Type: research

Processing of double-R-loops in (CAG){middle dot}(CTG) and C9orf72 (GGGGCC){middle dot}(GGCCCC) repeats causes instability
R-loops, transcriptionally-induced RNA:DNA hybrids, occurring at repeat tracts (CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n, are associated with diseases including myotonic dystrophy, Huntington's disease, fragile X and Friedreich's ataxia. Many of these repeats are bidirectionally transcribed, allowing for single- and double-R-loop configurations, where either or both DNA strands may be RNA-bound. R-loops can trigger repeat instability at (CTG)·(CAG) repeats, but the mechanism of this is unclear. We demonstrate R-loop-mediated instability through processing of R-loops by HeLa and human neuron-like cell extracts. Doubl...
Source: Nucleic Acids Research - September 16, 2014 Category: Research Authors: Reddy, K., Schmidt, M. H. M., Geist, J. M., Thakkar, N. P., Panigrahi, G. B., Wang, Y.-H., Pearson, C. E. Tags: Genome integrity, repair and replication Source Type: research

The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia
Conclusion: There is great variability of phenotype and severity in A-T, including a wide spectrum of movement disorders. Karyotype and repeated AFP level assessments should be performed in adults with unexplained movement disorders as valuable clues towards the diagnosis. In case of a compatible phenotype, A-T should be considered even if age at onset is late and progression is slow. (Source: Neurology)
Source: Neurology - September 15, 2014 Category: Neurology Authors: Meneret, A., Ahmar-Beaugendre, Y., Rieunier, G., Mahlaoui, N., Gaymard, B., Apartis, E., Tranchant, C., Rivaud-Pechoux, S., Degos, B., Benyahia, B., Suarez, F., Maisonobe, T., Koenig, M., Durr, A., Stern, M.-H., Dubois d'Enghien, C., Fischer, A., Vidailhe Tags: All Clinical Neurology, All Movement Disorders, Dystonia, Gait disorders/ataxia, Myoclonus ARTICLE Source Type: research

Primary intracranial plasma cell granuloma responsive to rituximab
Plasma cell granuloma (PCG) is a sporadically occurring tumor-like mass that is histologically characterized by a non-neoplastic proliferation of inflammatory cells. The predominant cell types in PCG are polyclonal plasma cells and their precursors, including a substantial amount of mature B cells. (Source: Neurology)
Source: Neurology - September 15, 2014 Category: Neurology Authors: Schneider, C., Henning, T. D., Fink, G. R., Schroeter, M., Lehmann, H. C. Tags: MRI, Gait disorders/ataxia, Visual fields, Primary brain tumor CLINICAL/SCIENTIFIC NOTES Source Type: research

Autonomic dysfunction is a major feature of cerebellar ataxia, neuropathy, vestibular areflexia 'CANVAS' syndrome
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a recently recognized neurodegenerative ganglionopathy. Prompted by the presence of symptomatic postural hypotension in two patients with CANVAS, we hypothesized that autonomic dysfunction may be an associated feature of the syndrome. We assessed symptoms of autonomic dysfunction and performed autonomic nervous system testing among 26 patients from New Zealand. After excluding three patients with diabetes mellitus, 83% had evidence of autonomic dysfunction; all patients had at least one autonomic symptom and 91% had more than two symptoms. We also ...
Source: Brain - September 13, 2014 Category: Neurology Authors: Wu, T. Y., Taylor, J. M., Kilfoyle, D. H., Smith, A. D., McGuinness, B. J., Simpson, M. P., Walker, E. B., Bergin, P. S., Cleland, J. C., Hutchinson, D. O., Anderson, N. E., Snow, B. J., Anderson, T. J., Paermentier, L. A. F., Cutfield, N. J., Chancellor, Tags: Reports Source Type: research

TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment
Autosomal dominant cerebellar ataxia corresponds to a clinically and genetically heterogeneous group of neurodegenerative disorders that primarily affect the cerebellum. Here, we report the identification of the causative gene in spinocerebellar ataxia 21, an autosomal-dominant disorder previously mapped to chromosome 7p21.3-p15.1. This ataxia was firstly characterized in a large French family with slowly progressive cerebellar ataxia, accompanied by severe cognitive impairment and mental retardation in two young children. Following the recruitment of 12 additional young family members, linkage analysis enabled us to defin...
Source: Brain - September 13, 2014 Category: Neurology Authors: Delplanque, J., Devos, D., Huin, V., Genet, A., Sand, O., Moreau, C., Goizet, C., Charles, P., Anheim, M., Monin, M. L., Buee, L., Destee, A., Grolez, G., Delmaire, C., Dujardin, K., Dellacherie, D., Brice, A., Stevanin, G., Strubi-Vuillaume, I., Durr, A. Tags: Reports Source Type: research

Aggressive pituitary lesion with a remarkably high Ki-67
The uncommon aggressive pituitary tumors are named carcinomas when metastases are detected, either in the central nervous system and/or systemically. Some cases are associated with hormonal overproduction, but most are diagnosed because of local symptoms. These neoplasias are generally refractory to current treatments. A 51 year-old woman presented sudden onset of headache, left arm paresis and left facial hypoesthesia. Computed tomography scan and magnetic resonance imaging revealed a pituitary tumor invading the left sphenoidal and cavernous sinuses. Laboratory data excluded hormonal hypersecretion. The patient underwent...
Source: Arquivos Brasileiros de Endocrinologia e Metabologia - September 10, 2014 Category: Endocrinology Source Type: research

Nasality in Friedreich ataxia.
Abstract Abstract Perceptual speech research in Friedreich ataxia (FRDA) has identified altered nasality as a key component of the dysarthria profile, however the incidence and severity of abnormal nasality remains unknown. Utilizing objective and perceptual methods, data on the relationship between resonance, disease duration, severity, age of onset and genetic profiles were collated. Thirty-seven participants with FRDA and 24 healthy controls provided contemporaneous speech samples for perceptual analysis, and single word samples for acoustic analysis. A subset of participants (eight participants with FRDA and ei...
Source: Clinical Linguistics and Phonetics - September 10, 2014 Category: Speech Therapy Authors: Poole ML, Wee JS, Folker JE, Corben LA, Delatycki MB, Vogel AP Tags: Clin Linguist Phon Source Type: research

The multidisciplinary adult ataxia telangiectasia service
Conclusion In a rare degenerative neurological condition re-evaluation by a specialist MDT, whilst not affecting disease progression, leads to novel interventions to improve patient care. (Source: Journal of Neurology, Neurosurgery and Psychiatry)
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Stavrou, M., Bull, T., Thaivalappil, F., Oscroft, N. Tags: Abstracts Source Type: research

Steroid responsive cerebral amyloid angiopathy
Cerebral amyloid angiopathy (CAA) can occasionally present with encephalopathy, unsteadiness and seizures, as a result of an inflammatory response to the deposition of beta–amyloid within the cerebral blood vessels and leptomeninges. In this case report, we describe a patient who has responded very favourably to immunosuppression. A previously fully independent 67 year old lady presented with a short history of confusion, worsening unsteadiness and self neglect. Neurologically, she was disorientated, dyspraxic with limb weakness and ataxia. MRI showed extensive bilateral white matter change and oedema throughout both...
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Joe, D., Holmes, P. Tags: Abstracts Source Type: research

IDIOPATHIC AXONAL NEUROPATHY AND PRIMARY SJoGREN'S SYNDROME
Conclusions PSS is a common association in otherwise undiagnosed sensory axonal neuropathy. Salivary gland biopsy should be considered in all patients with an unidentified cause for sensory neuropathy and sicca symptoms. (Source: Journal of Neurology, Neurosurgery and Psychiatry)
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Laverse, E., Samaraweera, A., Ng, W.-F., Miller, J. Tags: Abstracts Source Type: research

A case of recurrent miller fisher syndrome
Conclusion The risk of recurrence of GBS is reported between 1–6% (2) but recurrent MFS is extremely rare, with only 21 cases in the literature. In this case, the typical clinical presentation of MFS coupled with previous episodes may suggest an underlying predisposition, or even a pathogenic role for anti-gq1b antibody. (Source: Journal of Neurology, Neurosurgery and Psychiatry)
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Thomas, J., Smith, P., Johnston, A. Tags: Abstracts Source Type: research

Ondine's curse
Ondine was cursed and had to remember to breath. Acquired central hypoventilation is rare but potentially treatable. A 60 year old woman was admitted to intensive care with increasing drowsiness and hypoventilation. She had initially noticed a dry mouth and slurred speech 7 weeks earlier, and subsequently developed postural hypotension followed by progressing incoordination and left sided deafness. On examination she was ventilated, and now fully aware, with upbeat nystagmus, a left 6th nerve palsy, with loss of lower limb reflexes and left sided ataxia. Extensive blood tests and MRI brain were normal. CSF was acellular wi...
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Sarkar, P., Fuller, G. Tags: Abstracts Source Type: research

The clinical and genetic spectrum of hemiplegic migraine
Conclusions CACNA1A is a major disease gene but HM shows significant clinical and, genetic heterogeneity. The paroxysmal disorders gene panel will be an important diagnostic tool in investigating HM, related disorders and the role of ion channels. Whole-exome sequencing is underway for unresolved cases. (Source: Journal of Neurology, Neurosurgery and Psychiatry)
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Jaffer, F., Gardiner, A., Polke, J., Pittman, A., Prabhakar, P., Kurian, M., Sweeney, M., Hanna, M. G., Houlden, H. Tags: Abstracts Source Type: research

An occult disease... and one that changed my practise
Neuromyelitis optica (NMO) and NMO spectrum disorder are well characterized demyelinating neurological conditions with established but evolving diagnostic criteria. Antibody mediated inflammation underpins their aetiology, in particular relating to antibodies to the aquaporin-4 transmembrane channel. NMO forms an important differential diagnosis to multiple sclerosis, requires a different treatment strategy and is therefore important to discriminate. A middle-aged woman presented with an acute inflammatory encephalopathy with subsequent brainstem relapse. Aquaporin-4 antibodies were positive. Following routine examination,...
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Shatti, D., Price, C., Luppe, S., Scolding, N. Tags: Abstracts Source Type: research

An unusual diagnosis of pinpoint tonic pupils
A 65 year old female presented following 2 weeks of coryzal symptoms with subacute diplopia and ataxia limiting her mobility. She noticed left hand paraesthesia, spreading over 2 days to both upper limbs and face. Examination revealed bilateral ptosis (no evidence of fatigability), miotic tonic pupils with complete ophthalmoplegia, total areflexia and patchy loss of vibration sense in both upper and lower limbs. Power was normal throughout. Proprioception and sensation to light touch were intact. In the peripheral hospital MRI brain and CSF examination were unremarkable. Tensilon test was negative. She was started on intra...
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Mihalova, T., Jackson, S., Verghese, P. Tags: Abstracts Source Type: research

Status epilepticus secondary to unusual encephalopathy
An 18-year-old girl presented urgently with recurrent focal seizures. The seizures start with myoclonic jerking of the left leg, spreading to the left arm and head. She had complained of mild migraine like headaches for the last 4 weeks and had had formal visual hallucinations. She had no past medical history. She was apyrexial, with continuous myoclonic activity of the left leg, arm and head, left homonymous hemianopia and left sided ataxia. Routine blood tests were normal or negative, HIV test was negative, MRI brain showed right parieto-occipital gyral swelling, CSF examination was normal with normal CSF lactate. Geneti...
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Ali, K., Flower, M., Lawthom, C. Tags: Abstracts Source Type: research

Symptoms of mitochondrial disease falling on deaf ears
We present a 37-year-old woman referred to our neurology clinic after an incidental finding of bilateral caudate, lentiform and pulvinar calcification during workup for cochlear implant surgery. She was born at 30 weeks' gestation with her identical twin sister and was found to have progressive sensorineural hearing loss from eight years of age. She had had no seizures, ataxia, weakness, psychosis or involuntary movements. Her mother had diabetes mellitus. On examination, she was areflexic but otherwise normal. Neurophysiology showed a mild sensory neuropathy. Mitochondrial gene testing showed heteroplasmy for m.3243A>G...
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Chinthapalli, V. K., Warner, G. Tags: Abstracts Source Type: research

Two cases with an important reminder
We describe two patients presented neurologically, the delay in recognising HIV led to clinical deterioration and unnecessary investigations. A 45-year-old woman, presented with right hemiparesis, initial assessment suggested cerebrovascular event. 5 weeks later, she represented with coma and seizures. MRI brain showed large ring enhancing lesion with multiple peripheral lesions, this was thought to represent metastaic disease. Brain biopsy revealed toxoplasmosis, HIV test was positive. She was treated with antiretroviral and anti-toxoplasmosis therapy. She was left with significant neurological impairment. A 47-year-old m...
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Ali, K., Lowman, A., Powell, R. Tags: Abstracts Source Type: research

From ataxia to bilateral facial palsy due to one virus
Discussion Neurological complications occur in up to 8% of patients with EBV infection. Although viral meningitis is the commonest presentation, it may result in encephalitis, cerebellitis, cranial nerve palsies, myelitis and neuropathies. Cerebrospinal fluid viral DNA testing is often negative and the diagnosis requires careful history-taking for preceding systemic symptoms. (Source: Journal of Neurology, Neurosurgery and Psychiatry)
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Chinthapalli, V. K., Chinthapalli, S., Trend, P. Tags: Abstracts Source Type: research

Immunocompetent pml--an immunological scotoma?
We describe two cases of progressive multifocal leucoencephalopathy (PML) presenting as stroke in the immunocompetent. A 73-year-old man with a background of treated prostate carcinoma presented in October 2013 with a right hemiplegia; a diagnosis of lacunar infarction was made following CT. However, he progressed with increasing pyramidal weakness, ataxia, dysphasia and dysarthria. MRI in December revealed confluent T2 and FLAIR hyperintense white matter change with normal DWI. Extensive infective, vasculitic and malignancy screen were unremarkable; PCR in serum and CSF demonstrated JC virus DNA. Unfortunately the patient...
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Cooper, R., Doshi, A., Harris, P., Sivagnanasundaram, J., Wells, G., Barritt, A., Aram, J., Giovannoni, G., Gnanapavan, S., Dobson, R. Tags: Abstracts Source Type: research

Listeria rhombencephalitis--an evolving brainstem syndrome
A 59-year-old man presented with gradual onset left sided facial numbness and vomiting. Over the following 7 days he developed stepwise brainstem deficits including left sided facial weakness, ataxia, nystagmus and bulbar weakness with absent gag reflex. The patient subsequently suffered respiratory arrest and was intubated. CT head was normal and lumbar puncture revealed CSF lymphocytosis with a mildly raised protein. Initial treatment included acyclovir and methylprednisolone. MRI head showed bilateral nodular ring enhancing lesions in the brainstem. The diagnosis of Listeria monocytogenes rhombencephalitis was made foll...
Source: Journal of Neurology, Neurosurgery and Psychiatry - September 9, 2014 Category: Neurosurgery Authors: Hrastelj, J., Willis, M., Dawson, K. Tags: Abstracts Source Type: research

A Home Balance Exercise Program Improves Walking in People With Cerebellar Ataxia
Conclusions. Improvement in locomotor performance in people with cerebellar ataxia was observable after a 6-week home balance exercise program. The exercise program must be designed to provide a significant challenge to the person’s balance. (Source: Neurorehabilitation and Neural Repair)
Source: Neurorehabilitation and Neural Repair - September 8, 2014 Category: Neurology Authors: Keller, J. L., Bastian, A. J. Tags: Clinical Research Articles Source Type: research

New tricks for an old fox: Impact of TGFβ on the DNA damage response and genomic stability.
Abstract Transforming growth factor-β (TGFβ) is a well-known master regulator of cellular proliferation and is a critical factor in the maintenance of tissue homeostasis. TGFβ is classically defined as a tumor suppressor that functions in the early stages of carcinogenesis, yet paradoxically it functions as a tumor promoter in established cancers. Less well studied is its role in maintaining genomic stability through its participation in the DNA damage response (DDR). Deletion of Tgfb1 in murine epithelium increases genomic instability (GIN) as measured by gene amplification, aneuploidy, and centrosome aberratio...
Source: Science Signaling - September 6, 2014 Category: Biomedical Science Authors: Barcellos-Hoff MH, Cucinotta FA Tags: Sci Signal Source Type: research

Oxidative DNA damage induces the ATM-mediated transcriptional suppression of the Wnt inhibitor WIF-1 in systemic sclerosis and fibrosis.
Abstract Systemic sclerosis (SSc) is an autoimmune disease characterized by extensive visceral organ and skin fibrosis. SSc patients have increased production of autoreactive antibodies and Wnt signaling activity. We found that expression of the gene encoding Wnt inhibitor factor 1 (WIF-1) was decreased in fibroblasts from SSc patient biopsies. WIF-1 deficiency in SSc patient cells correlated with increased abundance of the Wnt effector β-catenin and the production of collagen. Knocking down WIF-1 in normal fibroblasts increased Wnt signaling and collagen production. WIF-1 loss and DNA damage were induced in norma...
Source: Science Signaling - September 6, 2014 Category: Biomedical Science Authors: Svegliati S, Marrone G, Pezone A, Spadoni T, Grieco A, Moroncini G, Grieco D, Vinciguerra M, Agnese S, Jüngel A, Distler O, Musti AM, Gabrielli A, Avvedimento EV Tags: Sci Signal Source Type: research

[Familial paroxysmal kinesigenic dyskinesia. A case description.]
Abstract Paroxysmal dyskinesias are movement disorders characterized by sudden episodes of involuntary movements. They are divided into kinesigenic, non-kinesigenic, and exercise-induced dyskinesias. Emphasis is made on the importance of the clinical history and fully describing the episodes in the differential diagnosis. The case is presented of a twelve year-old female with paroxysmal episodes of tongue torsion and dystonic postures of the upper limbs when start running or descending stairs and in the beginning of physical exercise, which ceased spontaneously seconds later. Some episodes were triggered by stress....
Source: Anales de Pediatria - September 6, 2014 Category: Pediatrics Authors: Extreia J, Monteiro I, Ferreira A, Rocha S Tags: An Pediatr (Barc) Source Type: research

T.P.34: A family with epilepsy, movement disorders, mental retardation and exercise-induced myoglobinuria: A complex phenotype caused by two different rare disorders
We report a 44-years-old man, who presented, since the age of 20, recurrent episodes of rhabdomyolysis after exercise or prolonged fasting; he also showed a mild mental retardation and sporadic choreo-athetoid movements. His 14-years-old son had a psychomotor developmental delay with episodes of drowsiness and head drops, occurring mainly at fasting, and exercise-induced choreo-athetoid movements but no history of pigmenturia. Neurological examination revealed microcephaly, mild spastic ataxia and mental retardation. EEG was normal in the proband but in the son showed, during fasting, diffuse spike-wave discharges disappea...
Source: Neuromuscular Disorders - September 4, 2014 Category: Neurology Authors: A. Toscano, E. Ferlazzo, S. Romeo, F. Montagnese, U. Aguglia, C. Rodolico, O. Musumeci Source Type: research

T.P.32: Sensory neuropathy as a major clinical feature of LCHAD deficiency
We report two patients with LCHAD deficiency presenting with a sensory neuronopathy (“ganglionopathy”). Patient 1: A 47year-old woman experimented recurrent rhabdomyolysis attacks since the age of 4. She also complained of neuropathic pain and paresthesias in extremities. She had severe proprioceptive ataxia, bilateral pes cavus, and moderate distal hypoesthesia. Deep tendon reflexes were absent. Nerve conduction studies (NCS) revealed markedly asymmetric decreased amplitudes and low velocity conduction in median nerves, complete abolition of others sensitive potentials, and normal motor conduction. EMG showed moderate...
Source: Neuromuscular Disorders - September 4, 2014 Category: Neurology Authors: S. Souvannanorath, T. Maisonobe, V. Valayannopoulos, Y. Nadjar, F. Mochel, A. Boutron-Corriat, M. Brivet, P. Laforêt Source Type: research

G.P.193: Ataxia, core myopathy, beta-ketothiolase deficiency, dentate nuclear abnormalities and learning difficulties in a pair of consanguineous siblings. A new association or double trouble?
We describe a sibling pair, (female aged 14years and male aged 10years) with profound ataxia, moderate learning difficulties and proximal muscle weakness. The parents were first cousins and healthy with no other family history of any disorders. The family were of Pakistani origin. Both siblings were found to have a core myopathy on muscle biopsy. Further genetic investigations for causes of core myopathy (RYR1 and SEPN1) did not reveal any mutations. In addition to the myopathy, the older sibling was found to have a urine organic acid profile consistent with beta-ketothiolase deficiency. This was confirmed by finding absen...
Source: Neuromuscular Disorders - September 4, 2014 Category: Neurology Authors: A. Majumdar, G. Pierre, A. Bowron, S. Love, K. Kurian Source Type: research

G.P.190: Multiple deletions in mitochondrial DNA in myofibrillar myopathy and centronuclear myopathy
Multiple deletions in mitochondrial DNA (mtDNA) are associated with mutations in nuclear genes which encode proteins either directly or indirectly involved in the replication or maintenance of mtDNA. To date, mutations in twelve nuclear genes, POLG, POLG2, C10orf2, SLC25A4, RRM2B, TK2, MPV17, DGUOK, OPA1, MFN2, MGME1, and DNA2 have been identified in patients with multiple deletions in mtDNA, yet the genetic cause of multiple mtDNA deletions still remains undefined in a large number of patients. In addition to patients with a classic mitochondrial myopathy, multiple mtDNA deletions are also found in patients with myopathie...
Source: Neuromuscular Disorders - September 4, 2014 Category: Neurology Authors: J. Schaefer, U. Reuner, H. Reichmann, M. Meinhardt, S. Jackson Source Type: research

G.P.186: Gene expression profile of cybrid cells harbouring a mitochondrial DNA mutation in the MT-ATP6 gene reveals new pathogenic pathway
Mutations in the human mitochondrial MT-ATP6 gene, encoding ATP synthase subunit a, are causing different neurological disorders such as Neurogenic Ataxia and Retinitis Pigmentosa (NARP), Leigh’s syndrome, Charcot-Marie-Tooth neuropathy, and more recently paralysis episodes. The deleterious consequences of these MT-ATP6 mutations are still the matter of debate with respect to their cellular impact and influence of the nuclear background. To investigate the primary molecular mechanisms independently from the impact of nuclear genome, we constructed cybrids with homoplasmic levels of the MT-ATP6 m.9185T>C mutation previous...
Source: Neuromuscular Disorders - September 4, 2014 Category: Neurology Authors: G. Fayet, K. Aure, P. Lesimple, C. L’Hermitte-Stead, C. Chevalier, A. Magot, R. Houlgatte, Y. Pereon, A. Lombes, F. Savagner Source Type: research

G.P.157: Clinical and pathological features associated with mutations in MICU1
We present the clinical/pathological features in a cohort of 18 patients. Patients presented between birth and 8years with a mild, relatively static, proximal myopathy associated with high Creatinine Kinase (2000–10,000iu/L), learning difficulties and frequent microcephaly. At follow up (5–28yrs), all remained ambulant but variable extrapyramidal symptoms had developed in the majority by the end of the 1st decade. Other features suggestive of mitochondrial dysfunction included peripheral neuropathy, icthyosis, stroke like episodes, episodic weakness, ataxia and cataracts. Cardiomyopathy was not seen. Serum and CSF lact...
Source: Neuromuscular Disorders - September 4, 2014 Category: Neurology Authors: A.M. Childs, K. Pysden, H. Roper, G. Chow, E.H. Niks, M. Kriek, P.F. Chinnery, D. Lewis-Smith, M. Duchen, G. Szabadkai, C. Logan, E. Sheridan, C. Sewry, F. Muntoni Source Type: research

G.P.59: Muscle pathology as a diagnostic clue to Allgrove syndrome
Allgrove or triple A syndrome is an autosomal-recessive disorder caused by mutations in the AAAS gene, coding for the nucleoporin ALADIN. While the eponymous combination of Achalasia, Addisonianism and Alacrimia seems hard to miss, these cases are a diagnostic challenge when this trias is incomplete and other neurological signs from a broad range of associated symptoms predominate. This was the case with a 15year old boy from a consanguineous family suffering from progressive distal limb muscle weakness and atrophy as well as mild learning disability, whose muscle and sural nerve biopsy samples we received. No abnormalitie...
Source: Neuromuscular Disorders - September 4, 2014 Category: Neurology Authors: J. Reimann, N. Kohlschmidt, K. Kappes-Horn, M. Stepien-Mehring, K. Tolksdorf, K. Kuchelmeister Source Type: research

Oral epithelial dysplasia: the role of ATR-Fanconi anaemia pathway in malignant transformation
Background: The Fanconi Anaemia (FA) pathway is responsible for homologous recombination repair of DNA interstrand crosslink damage. This checkpoint in S-phase of the cell cycle is mediated by ATR (Ataxia Telangiectasia Rad-3) and BRCA-1. The role of this tumour suppressor pathway in early oncogenesis is evaluated in oral dysplasia (OED) which transformed into oral squamous cell carcinoma (OSCC) by evaluating expression of FANC-D2 protein. (Source: The British Journal of Oral and Maxillofacial Surgery)
Source: The British Journal of Oral and Maxillofacial Surgery - September 4, 2014 Category: ENT & OMF Authors: Michael Ho, A. Triantafyllou, J.M. Risk, R.J. Shaw, J.B. Wilson Tags: Abstracts Source Type: research

Event Gathers World-Renowned Researchers and Community Leaders to Find...
Scientists, physicians, patients, families, and community leaders from around the world will join together in Tampa Bay from September 4-6 for the Friedreich’s Ataxia Research Alliance’s (FARA) sixth...(PRWeb September 02, 2014)Read the full story at http://www.prweb.com/releases/2014/09/prweb12139752.htm (Source: PRWeb: Medical Pharmaceuticals)
Source: PRWeb: Medical Pharmaceuticals - September 4, 2014 Category: Pharmaceuticals Source Type: news

Multiple carboxylase deficiency (late onset) due to deficiency of biotinidase
Debadatta Mukhopadhyay, Manoj Kumar Das, Sandipan Dhar, Maya MukhopadhyayIndian Journal of Dermatology 2014 59(5):502-504Biotinidase is a ubiquitous mammalian cell enzyme occurring in liver, serum and kidney. It cleaves biotin from biocytin, which is a cofactor for biotin dependent enzymes, namely the human carboxylases. Biotinidase deficiency is associated with a wide spectrum of neurological, dermatological, immunological and ophthalmological abnormalities. This is a case of a 3-year-old boy presenting with delayed developmental milestones, tachypnea, progressively increasing ataxia, alopecia and dermatitis, all which dr...
Source: Indian Journal of Dermatology - September 1, 2014 Category: Dermatology Authors: Debadatta MukhopadhyayManoj Kumar DasSandipan DharMaya Mukhopadhyay Source Type: research

Sensory ganglionopathy with livedoid vasculopathy controlled by immunotherapy
Conclusion: Sensory ganglionopathies associated with autoimmune and inflammatory conditions may be characterized by a sub‐population of “sick” dorsal root ganglia that can be rescued with aggressive immunotherapy. © 2014 Wiley Periodicals, Inc. (Source: Muscle and Nerve)
Source: Muscle and Nerve - September 1, 2014 Category: Internal Medicine Authors: James J.P. Alix, Marios Hadjivassiliou, Rokiahmah Ali, David Slater, Andrew G. Messenger, D. Ganesh Rao Tags: Case of the Month Source Type: research

Executive deficit in spinocerebellar ataxia type 2 is related to expanded CAG repeats: Evidence from antisaccadic eye movements.
In conclusion, antisaccadic eye movement abnormalities are a newly recognized association with the genetic abnormality in SCA2 and correlate with executive dysfunction in SCA2. Antisaccade parameters are a promising source of cognitive biomarkers for exploring the disease pathophysiology, and assessing the efficacy of therapeutic options. PMID: 25189938 [PubMed - as supplied by publisher] (Source: Brain and Cognition)
Source: Brain and Cognition - September 1, 2014 Category: Neurology Authors: Rodríguez-Labrada R, Velázquez-Pérez L, Aguilera-Rodríguez R, Seifried-Oberschmidt C, Peña-Acosta A, Canales-Ochoa N, Medrano-Montero J, Estupiñan-Rodríguez A, Vázquez-Mojena Y, González-Zaldivar Y, Laffita Mesa JM Tags: Brain Cogn Source Type: research

Targeted disruption of Ataxia-telangiectasia mutated gene in miniature pigs by somatic cell nuclear transfer.
Abstract Ataxia telangiectasia (A-T) is a recessive autosomal disorder associated with pleiotropic phenotypes, including progressive cerebellar degeneration, gonad atrophy, and growth retardation. Even though A-T is known to be caused by the mutations in the Ataxia telangiectasia mutated (ATM) gene, the correlation between abnormal cellular physiology caused by ATM mutations and the multiple symptoms of A-T disease has not been clearly determined. None of the existing ATM mouse models properly reflects the extent to which neurological degeneration occurs in human. In an attempt to provide a large animal model for A...
Source: Biochemical and Biophysical Research communications - September 1, 2014 Category: Biochemistry Authors: Kim YJ, Ahn KS, Kim M, Kim MJ, Park SM, Ryu J, Ahn JS, Heo SY, Kang JH, Choi YJ, Choi SJ, Shim H Tags: Biochem Biophys Res Commun Source Type: research

The Shepherd's Crook Sign: A New Neuroimaging Pareidolia in Joubert Syndrome
CONCLUSIONSNeuroimaging diagnosis of JS, which already involves the pareidolical recognition of specific patterns indicative of the disease, can be improved by recognition of the shepherd's crook sign on MRI, CT, and cranial ultrasound. (Source: Journal of Neuroimaging)
Source: Journal of Neuroimaging - September 1, 2014 Category: Radiology Authors: Andrew T. Manley, Paul M. Maertens Tags: Case Report Source Type: research

Healing of Granulomatous Skin Changes in Ataxia‐Telangiectasia After Treatment with Intravenous Immunoglobulin and Topical Mometasone 0.1% Ointment
This report demonstrates the first reported case in which the granulomatous skin lesions of AT healed after aggressive application of topical steroids with concurrent IVIG therapy, without oral steroids. A brief review of cutaneous granulomas in the setting of immunodeficiency is also presented. (Source: Pediatric Dermatology)
Source: Pediatric Dermatology - September 1, 2014 Category: Dermatology Authors: Emily D. Privette, Gita Ram, James R. Treat, Albert C. Yan, Jennifer R. Heimall Tags: Case Report Source Type: research

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

Late onset Lafora disease and novel EPM2A mutations: Breaking paradigms
Lafora type progressive myoclonic epilepsy (LD, OMIN 254780) is an autosomal recessive neurodegenerative disorder characterized by intractable stimuli-sensitive tonic-clonic, myoclonic and occipital seizures. Myoclonus start at 10 to 12 years of age followed by cerebellar ataxia, dysartria and cognitive decline, psychosis, amaurosis, mutism, muscle wasting, rapidly progressive dementia and respiratory failure. The onset in late childhood or adolescence with rapid deterioration and death between 17 and 24 years of age has been considered a characteristic feature of LD due to EPM2A mutations (Delgado-Escueta et al., 2007; Ba...
Source: Epilepsy Research - August 30, 2014 Category: Neurology Authors: Aurelio Jara-Prado, Adriana Ochoa, María Elisa Alonso, Gabriel A. Lima Villeda, Francisca Fernández-Valverde, Luis Ruano-Calderón, Steven Vargas-Cañas, Reyna M. Durón, Antonio V. Delgado-Escueta, Iris E. Martínez-Juárez 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

Pancreatic ductal adenocarcinoma: Risk factors, screening, and early detection.
Abstract Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome...
Source: World Journal of Gastroenterology : WJG - August 28, 2014 Category: Gastroenterology Authors: Becker AE, Hernandez YG, Frucht H, Lucas AL Tags: World J Gastroenterol 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