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significant impairment compared with the control group. The degree of impairment showed positive correlation with longer duration of the disease, older age at onset, severe motor disability, anxiety symptoms and positive psychotic symptoms. Most of the cognitive functions showed no significant differences between the patients receiving levodopa and those not receiving it. Conclusion: PD has a wide range of neuropsychiatric complications. Most of these complications are due to the disease process itself rather than levodopa. Higher levels of levodopa are associated with better cognitive performance but with some motor complicatiolas as dyskinesia.

1047 Accumulations of Phosphorylated alpha-Synudein and Tall in Nemcodegener ative Disease

Obi, O x, Moclffzuki, H ~, Iwatubo, T 2, Akiyama, H 3, Hasegawa, M 3, Mizuno, y1.2Dept" Neurology, duntendo University School of Medicine, Tokyo, Japan; :Dept. Pharmacy, Tokyo University School of Ivledieine, Tokyo, Japan; 3Dept. Psyehogeriatries, Tokyo Institute of Psychiatry, Tokyo, Japan

Background: Recent investigations have indicated that phosphoryla- tion of Ser 129 plays an important role for aggregation of alpha- synuclein. In tiffs study, we investigate relationship between Abeta, tau and phosphorylated alpha-synuclein in postnortem brain tissues. Method: Brains from 14 patients with AD and 13 with DLBD were studied immunoshisto-chemically. We used a monoclonal antibody, p-alpha#04, wlffch is specific to residues 124-134 of human alpha- synuclein containing phosphoserine at position 129. Results: Nearly half o f AD patients have alpha-synuclein positive Lewy pathology. Tau pathology fairly parallels the Abeta deposits in AD, while it is unproporfionably mild in many DLBD. However, total ( t a u + phosphorylated alpha-synuclein) neurite pathology of DLBD is comparable with that of AD. Conclusion: There is an overlap between AD and DLBD pathology. These diseases may share a pathological process of alpha-synuclein aggregation. A synergistical aggregation/accamulation pro cess between tau and phosphorylated alpha-synuclein has been suggested. We propose that in DLBD the cascade from Abeta to tau is shifted to that from Abeta to phosphorylated alpha-synuclein.

1048 Valvular Heart Disease in Parkinson's disease (PD) Patients: Comparative study of echocardiographic screening in PD and non-PD patients

Oeda, T ~, Masaki, M ~, Mizuta, E ~, Kitagawa, N ~, Sasaki, T ~, Ozawa, K 1, Kordstff, C 1, Kuno, S 2. ~Department Of Neurology Utano National Hospital & Clinical Research Centre; 2Department of Neurology Musashi Hospital National Center Of Neurology and Psychiatry

Background: Cardiac valvulopathy has been considered to be associated with the use of the ergot dopamine agonists in PD patients. However, the frequency of occurrence of tiffs side effect is uncertain. To clarify the risk of cardiac valvulopathy in PD patients on the clinical base, echocardiographic findings in PD patients were screened and compared with those in non-PD patients. Methods: 32 PD patients (mean 71.3y.o.) who were adnfftted to our hospital were examined by echocardiography on screening purpose from December 2003 to November 2004. The frequency of cardiac valvulopathy was compared with the results of 39 non-PD patients (mean 77.2y.o) who were admitted to the orthopedic department during the same period of time. All echocardiograms were evaluated by the same cardiologist. Results: The frequency of moderate or severe aortic regurgitations in the PD group (28.0°,5) was significantly higher than that in the non-PD group (17.7°,5). The frequency of mitral and tricuspid

regurgitations was also higher in the PD group (19.47,'o, 21.9%, respectively) than the non-PD group (0%, 5.17,'o, respectively) although these differences were insigtffficant. In the PD group, 15 patients took the ergot dopanffne agordst on the exanffnation and 9 of them (60.0%) were found to have valvular regurgitation. On the other hand, in 17 patients (153.1°,5) who did not take the ergot, only 3 patients (17.6%) were found to be abnormal. Conehision: These results suggest that the ergot dopamine agonists increase the risk of cardiac valvulopathy in PD patients.

1049 Inflammation regulates neuxogenesis in tile subventlicular zone of Parkinson's disease models

Oizumi Hideki

Background: Enhancement of neurogenesis could be an approach to upregulate dopaminergic neurons in Parkinson's disease (PD). To identify this hypothesis, we focused on the kinetics of the subven- tricular zone (SVZ), which leads young neurons into the core of the olfactory bulb through the rostral migratory stream (RMS) in PD models. We already reported that the inflammation reaction was one of important events in the pathogenesis of PD. Therefore, we also examined the relationship between neurogenesis and inflammation. Materials and methods: To identify the changes of neurogenesis, we measured the proliferation and differentiation of the NPCs in the SVZ by stereological analysis using MPTP treated mice as the PD models. Results and Conclusions: We found that there was a significant increase of EGFR positive cells and GFAP positive cells and decrease of PSA- NCAM positive cells in the SVZ after MPTP treatment. These indicated that MPTP treatment enhanced gliogenesis, inhibited the differentiation of neuronal precursors and inhibited neurogenesis of neuronal precursors in the SVZ. However, these responses were not identified in MPTP treated caspase-I 1 KO mice. The present results indicated that inflammation related to caspase-11 regulates neurogen- esis in the SVZ of PD models.

1050 Genetics of Parkinson's disease in Africa

Okubadejo, NU 1. 1Department of Medic&e, College of Medicine, University of Lagos, Lagos, Nigeria

Background: The post-genomic era has enabled characterization of genes associated with monogenic forms of Parkinson's disease (PD) and expanded understanding of mechanisms underlying sporadic. PD. Considering the genetic diversity of Africans, studies of genetics of PD in Africa may contribute to understanding the role of genetics in fanfflial and sporadic PD. Method: The databases of Medline ®, African Journals Online, and abstracts of relevant conferences were searched using the terms ~parkinson's disease, genetics and Africa'. Results: Five relevant articles were identified, and comprised < 1% of publications on genetics of PD worldwide. Four were from North Africa, one was from Zambia (Southern Africa), and all predomi- nantly focused on fanfflial PD. No studies on genetic susceptibility in sporadic PD were identified. Two described modes of inheritance of familial PD in Africans (autosomal dominant and autosomal recessive), and noted the clinical phenotype in comparison to non- Africans. Parkin mutations were demonstrated in a few fanfflies from North Africa with autosomal recessive juvenile parkinsordsm. LRRK2/PARK8 mutations were demonstrated in autosomal domi- nant PD in a few Nor th African families in one study, where the LRRK2 G2019S mutation was a commoner cause of ADPD in North Africa (141%) compared to Europe (2.8%). Conehision: Many opportunities for research in genetics of PD in Africa remain. In fanfflial PD, research will enable independent replication of genes, possible documentation of new mutations, and identification of new genes. For sporadic PD, genetic diversity,

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short length linkage disequilibrium, and reduced population admixture may all prefer an advantage for genetic, studies in Africa.

1051 Melanized nigral neurones in Caucasians and Atiicans

Olasode, B, Lees, A, Daniel, S, Subbakrishn, D, Muthane, U, Susarla, S, Chickabasaviah, Y, Henderson, J. lObafemi Awolowo University; 2Queen Square Brain Bank for Neurological Disorders, Institute of Neurology, London; 3NatPrince of Wales Medical Research Institute, Australia ional Institute of Mental Health and Neurosciences, Bangalore

Background: Debate on role of genetic and environment factors in etiopathogenesis o f Parkinson's Disease (PD) continues, as the prevalence of PD is higher amongst white than non-white populations yet it is 5-times lffgher in non-whites living in the US than in Nigeria. PD in Indians is low yet normal Indians reportedly have .~40% lower counts of melauized nigral neurons than the white from the UK. In this study we compare counts of melanized nigral neurons between neurologically normal Nigerians and British brains. Materials and Methods: Neuronal counts were estimated in an age- matched sample of 24 Nigerian and 7 British brains from neurologi- cally normal individuals. Two independent investigators blind to age and ethuicity performed counts of melanized neurons in a single 7~anl hemi-sections showing the substantia nigra pars compacta (SNipe). Results: No significant difference exits in the number of neurons between the Nigerians and U K (p -- 0.08, NS). Conclusion: Differences in melauized nigral neuronal numbers may not explain differences in the prevalence of PD between white and non- white populations. Tiffs suggests that factors other than neuronal numbers must also contribute to differential susceptibility of black vs. white races to PD.

1052 Huinoral hninutlity to oxidised a-synudein in Parkinson's disease

Ors, C ~ , Rowe, D a, Morel-Kopp, M 3, Ward, C 3, Russell, T ~, Ranola, M 1 and Halliday, G 2. 1Department of Neurology, Royal North Shore Hospital and the University of Sydney, Sydney, Australia; 2Prince of Wales Medical Research Institute and the University of New South Wales, Sydney, Australia; 3Northern Blood Research Centre, Department of Haematology, Royal North Shore Hospital and the University of Sydney, Sydney, Australia

Background: A humeral immune response to dopamine neurons is observed in Parkinson's disease (PD) nigra, and abnormalities in lymphocyte populations are observed in the peripheral blood of PD patients 1. The identity of the antigen triggering the humeral inmmne response to dopanffne neurons is unknown. Interactions between a-synuclein, dopanrine and oxidative stress produce abnormal cellular proteins, which may trigger the humeral immune reaction to dopamJne neurons. Method: We assessed the blood of 47 PD patients and controls for an antibody response to ~-s?muclein before and after oxidation with hydrogen peroxide and dopanffne, and also assessed the relationship between sermn antibody titre and peripheral blood 15anphocytes. Results: Antibodies to oxidative modifications of ~-synuclein did not distinguish patients with Parkinson's disease, although one third of PD patients had high antibody titres to dopanffne-oxidised ~-s?muclein. An interaction was observed between these higher antibody titres, a decrease in apoptotic markers and an increase in the nmnber of memory helper T cells, specifically CD4+ T lymphocytes. The numbers of cytotoxic memory T cells correlated with antibody titres to unmodified ~-synuclein in PD. Conclusion: Oxidised ~-synuclein is not likely to be the trigger for the humeral inmmne response to dopanffne neurons in PD. However, alterations in lymphocytic populations in PD relate to the oxidation state of a-synuclein.

1053 The mechanism and therapy of dropped head with Parkinsonism

Oyama, G 1, Hayashi, A a'2, Mizuno, y1. ~Department of Neurology, funtendo University, Tokyo, Japan; 2Department of Rehabilitation Medicine, funtendo University, Tokyo, Japan

Background: Dropped head with Parkinsonism is not high in frequency, but it is a symptom to lose activities of daily living (ADL) remarkably and it is hard to cure. We examined the mechanism of dropped head and the therapeutic effects of lidocaine, ethanol (nmscle afferent block; MAB), and botulinum toxin. Methods: Eight eases which had dropped head with Parknisonism, we examined muscle activities of neck on surface eleetromyography, and tried intramuscular injection of lidocaine, ethanol, and, botulinum toxin into sternocleidomastoideus nmscles (SCM). Results: In all cases, surface electromyography showed persistent nmscle contraction in dorsal neck nmscles at rest, but there are no activities on SCM. Elevating the head passively, the activities of dorsal neck muscles disappeared, and then activities on SCM developed. Injection of lidocaine improved the symptoms markedly. But the effect was temporal. BotulJnmn toxin injection was slightly effective and it took times till the effect appeared. The effect of MAB was same degree as lidocaine injection alone. Conclusion: The phenomenon of dropped head is a dystonic posture and supposed to be caused by dystonia of SCM including somewhat a factor of rigidity. Lidocaine was very effective but temporary, which is a good test for identification of target muscles.

1054 PARK2 inu|alions in patients with early-onset Parkinson's disease

Pchelina, S ~'2, Ivanova, 01, Hanina, N ~, Yakimovsky, A a, Schwarzman, A 2. 1St. Petersburg State Parley Medical University, S. Petersburg, Russia :Petersburg Nuclear Physics Institute, RAS, S. Petersburg, Russia

Parkinson's disease (PD) is a, progressive neurodegenerative disease of complex etiology. Mutations in the parkin gene (PARK2) have been identified as a common cause of autosomal recessive inherited PD associated with early disease manifestation. The aim of the present work was to identify nmtations in the PARK2 gene in St. Petersburg patients (ethnic Slavic) with early-onset parkinsonism and to study genotype-phenotype correlations. The following methods were applied: multiplex PCR, SSCP analysis, sequencing and quantitative real-time PCR with TaqMan probes. No exert deletions/duplications were found. Among 20 patients with early-onset parkinsonism two point mutations (R334C and S 167N) were found, respectively, in man with disease onset at 42 years and in woman disease onset at 50 years both in heterozygous state. In woman the disease progression was slow with good response to L-dopa treatment. Rigidity-akinetic symp- toms dominated. In man the disease progression was fast with weak response to L-dopa treatment.

1056 Ditl~renfial etti~ets of globus pallidus stimulation (GPS) on static and dynandc balance

Rodrigues, jp1, Edwards, DJ a, Walters, SE ~, Thickbroom, GW a, Stell, R a, Mastaglia, FL ~. 1Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Australia

Background: Postural instability is common in advanced PD and responds poorly to dopaminergic medications. We studied the effects of GPS on postural stability using quantitative posturography and clinical assessments. Method: Five PD patients (IF, age 54-69 yrs; mean duration 12 yrs.) with bilateral GPi stinmlators were studied off medication with and without GPS. Static sway was measured whilst standing on a force platform. Dynamic stability was assessed whilst patients leaned in