1
Poster Abstracts Wednesday, November 9, 2005 $367 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 of 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 UK (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

1052 Humoral immunity to oxidised α-synuclein in Parkinson's disease

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Poster Abstracts Wednesday, November 9, 2005 $367

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