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Little is known about the genetic basis of amyotrophic lateral sclerosis (ALS) outside Europe and US. In this study, we investigated whether intermediate CAG expansions at ATXN1 were associated to ALS in the Brazilian population. To accomplish that, representative samples from 411 unrelated patients and 436 neurologically normal controls from 6 centers spread over the territory were genotyped to quantify ATXN1 expansions. We found that ATXN1 intermediate-length expansion (≥34 CAG repeats) are associated with the disease (odds ratio = 2.19, 95% CI = 1.081–4.441, p = .026). Most ATXN1-positive patients had classical phenotype, but some of them presented predominant lower motor neuron involvement. None of them had associated ataxia. Frontotemporal dementia was concomitantly found in 12.5% of patients carrying the intermediate ATXN1 expansion. Further studies are needed to validate these findings and to understand the pathophysiological mechanisms that connect ataxin-1 and ALS.

Introduction Skeletal muscle microRNAs (miRNAs) are potential candidate biomarkers for amyotrophic lateral sclerosis (ALS) that deserve further investigation. Objectives To identify miRNAs abnormally expressed in the skeletal muscle and plasma of patients with ALS, and to correlate them with parameters of disease progression. Methods Expression profile of miRNAs in muscle was evaluated using an array platform. Subsequently we assessed the plasmatic expression of candidate miRNAs in a set of 39 patients/39 controls. We employed generalized estimating equations to investigate correlations with clinical data. Results We identified 11 miRNAs differentially expressed in the muscle of ALS patients; of these, miR424, miR-214 and miR-206 were validated by qPCR in muscle samples. In plasma, we found only miR-424 and miR 206 to be overexpressed. Baseline expression of miR-424 and 206 correlated with clinical deterioration over time. Conclusion MiR-424 and miR-206 are potential prognostic markers for ALS.

WCN 2013 No: 886 Topic: 2—Movement Disorders Investigation of cortical brain damage in patients with Machado–Joseph disease T.J.R. Rezende, A. D'Abreu, R. Guimaraes, T.M. Lopes, I. Lopes-Cendes, G. Castellano, M.C. Franca Junior. Departament of Neurology, University of Campinas, Campinas, Brazil; Department of Cosmic Rays and Chronologic, University of Campinas, Campinas, Brazil; Department of Medical Genetics, Unicamp, Campinas, Brazil; Neurology, University of Campinas, Campinas, Brazil Background: Machado–Joseph disease (SCA3/MJD) is the most frequent spinocerebellar ataxia, and characterized by brainstem, basal ganglia and cerebellar damage. There are few MRI-based studies that investigate damage in the cerebral cortex. Objective: To investigate damage to cerebral cortex and subcortical structures in SCA3/MJD through MRI-based volumetry of high resolution images. Patients and methods: We included 44 patients with SCA3/MJD (mean age 49.0 ± 12.5, 22 men) and 44 healthy controls (mean age 48.7 ± 12.3, 22 men). Demographic/genetic data: CAG expansion (68.9 ± 5.1); SARA score (14.7 ± 7.2); Age at onset (40.5 ± 13.0); and disease duration (9.1 ± 4.0). All subjects underwent MRI scans in a 3T device, and 3D T1 images were used for volumetric analyses (slices of 1 mm, TE= 3.2 ms, TR= 7.1 ms, flip angle 8, isotropic voxels of 1 mm, FOV= 240 × 240). Measurement of cortical thickness and volume was performed using FreeSurfer software v.5.1. We performed ANCOVA using subject's age as a covariate to compare groups and performed a GLM regression to assess correlations. In all analyses, we used an uncorrected p = 0.001. Results: Group comparison showed reduction of cortical volume and thickness at left superior parietal, precentral and middle occipital gyri, as well as right paracentral sulcus and gyrus in SCA3/MJD. We also found volumetric reduction of cerebellar gray and white matter, thalamus, caudate, putamen, pallidum and ventral diencephalon. We then performed correlation analysis between clinical data and volume/thickness for those structures found to be atrophic in patients. Right pallidum volumes correlated with SARA scores (r =−0.512, p = 0.001). Conclusion: SCA3/MJD patients have extensive subcortical and cortical damage. Basal ganglia damage is related to disease severity. doi:10.1016/j.jns.2013.07.456 Abstract—WCN 2013 No: 674 Topic: 2—Movement Disorders Safety and efficacy of recombinant human platelet derived growth factor (Rhpdgf) in Parkinson's diseaseWCN 2013 No: 674 Topic: 2—Movement Disorders Safety and efficacy of recombinant human platelet derived growth factor (Rhpdgf) in Parkinson's disease G. Paul, O. Zachrisson, A. Varrone, P. Almqvist, M. Jerling, G. Lindh, S. Rehncrona, B. Linderoth, H. Bjartmarz, M. Svensson, K. Jansson Mercer, A. Forsberg, L.L. Shafer, A.M. Janson Lang, C. Halldin, P. Svenningsson, H. Widner, J. Frisen, S. Palhagen, A. Haegerstrand. Scania University Hospital, Lund, Sweden; Lund University, Lund, Sweden; NeuroNova AB, Sweden; Karolinska Institute, Sweden; Karolinska University Hospital, Stockholm, Sweden; Medtronic Inc., Minneapolis, MN, USA Objective: To evaluate safety, tolerability and exploratory efficacy of intracerebroventricular (ICV) administration of rhPDGF in patients with Parkinson's disease (PD). Background: ICV infusion of rhPDGF significantly and long-lastingly reduces PD-like behavior and increases dopamine-transporter (DAT) binding in PD models. This effect is dependent on rhPDGF-induced stem/progenitor cell proliferation in the lateral ventricular wall. These findings have prompted a clinical study in patients with moderate/ severe PD. Methods: 12 PD patients were implanted with a drug pump and investigational catheter (Medtronic Inc.) leading into the lateral ventricle. Three dose cohorts (0.2, 1.5 or 5 μg rhPDGF/day) received either rhPDGF or placebo (buffer, 1 patient/cohort) for 12 days, after which all received buffer. Follow-up time was 85 days. Objectives included safety and tolerability assessment, and UPDRS, MADRS, MMT, EQ5-D and DAT-binding (PET). Results: There were no unresolved adverse events related to the drug, infusion system or implant procedure. All patients improved in motor symptoms with no significant differences between dose cohorts. There were no significant therapeutic effects as assessed with MADRS, MMT or EQ5-D. Placebo patients displayed an expected reduction in DATbinding over time. Patients in the highest dose group showed not only stabilization, but an increase in DAT-binding in regions of dopaminergic denervation with a maximum in the putamen (P= 0.002). Conclusions: The ICV delivery of PDGF was safe and well tolerated and resulted in a significant dose-dependent positive effect on DAT-binding. The data support further clinical studies as PDGF may potentially slow down or reverse the nigrostriatal degeneration in PD. doi:10.1016/j.jns.2013.07.457 Abstract—WCN 2013 No: 858 Topic: 2—Movement Disorders Brief assessment of cognitive decline in the early stages of Parkinson s Disease—A two year longitudinal studyWCN 2013 No: 858 Topic: 2—Movement Disorders Brief assessment of cognitive decline in the early stages of Parkinson s Disease—A two year longitudinal study P. Bugalho, M. Viana-Baptista. Neurology, Hospital de Egas Moniz (CHLO), Portugal; Departamento de Neurologia, CEDOC, Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal Introduction: Cognitive decline influences the outcome of Parkinson's Disease. Our objectives were to perform a longitudinal assessment of cognitive dysfunction in early stage patients, with brief neuropsychological tests. Methods: Early stage, non-demented patients were assessed twice, over a 2 year interval, with the Frontal Assessment Battery (to detect frontal cognitive decline), the Mini-mental state examination (to detect global cognitive decline) and motor function scales. Dementia and hallucination were diagnosed according to DSM-IV criteria. We tested the relation between the clinical variables at baseline and the change in cognitive tests scores and the presence of dementia at follow-up. Results: Of an initial 75 patients cohort, 61 were reassessed. MiniMental State scores did not progress significantly. Frontal Assessment Battery lexical fluency score decreased significantly. Four patients presented with dementia at t1. Mini-Mental State Examination score bellow cut-off, higher gait dysfunction, speech, rigidity scores, the nontremor motor subtype and hallucinations were significantly related to dementia. Frontal dysfunction was related with a decrease in MMSE scores. Rigidity and speech dysfunction were related with a decrease in FAB scores. Conclusions: Decline in Mini-Mental State Examination and FAB scores is small and heterogeneous in the early stages of Parkinson's Disease. Scores bellow cut-off in the Mini-Mental State Examination Abstracts / Journal of the Neurological Sciences 333 (2013) e109–e151 e137