PO19-WE-10 Apolipoprotein E polymorphism as a risk factor for Javanese with vascular dementia in Yogyakarta

19th World Congress of Neurology, Poster Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S155–S339

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PO19-WE-08 Clinical and electrophysiological features in Thai patients with Kennedy’s disease

PO19-WE-10 Apolipoprotein E polymorphism as a risk factor for Javanese with vascular dementia in Yogyakarta

N. Smitasin1 , K. Boonyapisit1 , T. Sangruji2 , C. Limwongse3 , M. Pithakpakorn3 , T. Poaim4 . 1 Division of Neurology, Department of Medicine, Siriraj Hospital, Bangkok, Thailand; 2 Department of Pathology, Siriraj Hospital, Bangkok, Thailand; 3 Department of Medicine, Siriraj Hospital, Bangkok, Thailand; 4 Siriraj Hospital, Bangkok, Thailand

A. Gofir1 , R. Susilowati2 , M.A. Zucha3 , M. Ar-Rochmah3 , E. Zulyadaini3 , A.Z. Hidayati3 . 1 Neurology Department, Faculty of Medicine Universitas Gadjah Mada, Yogyakarta, Indonesia; 2 Department of Biomolecular, Faculty of Medicine Universitas Gadjah Mada, Yogyakarta, Indonesia; 3 Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

Kennedy’s disease also known as x-linked spinal and bulbar muscular atrophy is an adult onset form of motor neuron disease, which is caused by an abnormality of the androgen receptor from CAG repeated expansion. The clinical is slowly progressive in nature with the age of onset of neurological symptoms typically from the age 30–50 years. We retrospectively reviewed the clinical, laboratories and electrodiagnosis form 20 patients (mean age of onset = 40 years, range 26–59 years) with Kennedy’s disease at Siriraj hospital. Tongue fasciculation was the most common clinical sign observed in these patients (90%) followed by facial fasciculation and peri-oral fasciculation. The creatinine phosphokinase was usually high (mean = 1368 U/L, range 102–2778 U/L) and number of CAG repeated was range from 46–56 repeats (mean 49.8 repeats). The electrodiagnosis revealed chronic neurogenic changes in all cases whereas fibrillation potentials are rarely found in limb muscles, the CMAPs and SNAPs were abnormal in half of the patients.

Purpose: Apolipoprotein E (ApoE) plays a key part in the development of dementia. Isoform ApoE is a major component of circulating lipoproteins. The regulatory role of apolipoprotein E in lipid transport and metabolism was utilized to investigate the allelic association between ApoE allele and vascular dementia in selected sample of Javanese with vascular dementia. Association between ApoE genotype and vascular dementia is still unknown. The purpose of this research is to observe that ApoE polymorphism is a risk factor of Javanese with vascular dementia in Yogyakarta. Method: We used case control study to twenty-nine patient who had history of stroke and cerebrovascular event were diagnosed with vascular dementia for first time based on DSM-IV and/or NIND-AIREN criteria. Cognitive function was assessed by using Mini Mental State Examination (MMSE). The diagnosis of vascular dementia is confirmed by Head CT-scan. DNA isolated from patients peripheral blood sample underwent ApoE genotype. Results: There were fifty-one subjects consist of twenty-nine cases and twenty-two controls. The baseline age between the case and control groups are the same, although they are different in numbers. Among the variants of these gene, alleles e 2, e 3, and e 4 constitute the common polymorphism found in most populations. Of these variants, apo e 3 is the most frequent (80.39%). Patients consist of e4 non carriers (n = 21), e2/e4 (n = 1) and e3/e4 (n = 7) carriers. Control consist of e4 non carriers (n = 19) and e3/e4 (n = 3) carriers. This research proves that ApoE e4 is not a significant risk factor for Javanese with vascular dementia (OR: 2.41, CI: 0.47–13.61, p: 0.31). Conclusion: Findings suggest that ApoE e4 allele is not a significant risk factor for Javanese with vascular dementia.

PO19-WE-09 The Charcot Marie Tooth disease (Connexin 32 CMTX): about a large family in Reunion Island Indian Ocean France D. Mignard1 , P. Latour2 , C. Moy de Lacroix-Mignard1 . 1 Neurology, Saint Pierre, Reunion; 2 Molecular Neurogenetics, Lyon Bron, France The CHARCOT-MARIE-TOOTH Disease is an inherited degenerative disorder of the peripheral nervous system, prevalence is evaluated to 1/2 500. All transmission modes are known. The dominant transmission is the most frequent in Europe. Three types of dominant CMT are described: the demyelinating type (CMT1), the neuronal type (CMT2) and the X-linked CMT (CMTX). Many mutations situated on the X chromosome are the cause of CMTX. Hemizygote men (XY) are often affected more severely than heterozygote women (XX). Case: We describe a large family: the number of patients affected by the mutation is high (35) and clinically, the high number of patients help us to study the male variability of the mutation in the family. Genetically, the mutation is peculiar: a heterozygote substitution G>A in exon 2 from GJB1gene (connexin 32 CMT X1) in 476 nucleotide (c476G>A). Method: We have studied 24 patients in this family: 8 hemizygote men and 15 heterozygote women with the same evaluation score (FDS, SHY). We report clinical, electrophysiological and genetic features. Few patients were not studied (dead or far away) (7 men and 5 women). They were described by their family and we estimated a FDS score only. We have studied the clinical and electrophysiological variability in male group and in female group. Conclusion: We showed high clinical heterogeneity in this family, in men and in women. We discuss two points: 1. Higher severity in hemizygote men. 2. Many asymptomatic diseases in heterozygote women.

PO19-WE-11 Engineering DRG-targeted helper-dependent adenoviruses for selective gene delivery T. Terashima1 , K. Oka2 , A.B. Kritz3 , H. Kojima4 , A.H. Baker3 , L. Chan5 . 1 Medicine, Neurology, Shiga University of Medical Science, Otsu, Japan; 2 Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States; 3 British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom; 4 Molecular Genetics in Medicine, Shiga University of Medical Science, Otsu, Japan; 5 Medicine, Baylor College of Medicine, Houston, United States Purpose: Developing a novel and safety strategy that targets therapeutic genes to dorsal root ganglion (DRG) neurons for the treatment of DRG neuronopathy, a common disorder for which there is no satisfactory treatment. Method: To generate DRG-targeting helper-dependent adenovirus vectors (HDAd), we inserted 3 different types of DRG homingpeptides into the fiber of helper virus, an adenovirus (Ad) that is detargeted for its native tropism (coxsackie and adenovirus receptor and heparan sulfate proteoglycan binding site). We injected the DRG-targeting HDAd into intrathecal lesion of mice and evaluated the transduction efficiency for two months. Moreover, we followed the several cytokine levels in cerebrospinal fluid and evaluated the toxicities for tissues. Results: Most effective HDAd produced a 100-fold higher transduction of DRG neurons and a markedly attenuated inflammatory response as compared to unmodified HDAd and first generation Ad. Three different kinds of DRG-targeting HDAd showed the different transduction patterns in the cell size distribution of DRG neurons.