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

$368 Wednesday, November 9, 2005 Poster Abstracts

8 different directions for 1 second to displace their centre-of-pressure (COP) to match targets on a screen. Clinical measures comprised part III of the Unified Parkinson's Disease Rating Scale (UPDRS). Results: Static sway area was reduced to 66 ± 5% (SEM) of untreated values with GPS. Dynamic task reaction time improved to 87 d_ 14% of untreated values, while target hold achievement time and total task time remained unchanged. Target overshoot increased to 133 d- 14% and CoP wandering to 120 d- 22% of untreated values. Total UPDRS fell to 65 d- 9%, with reductions in rigidity and mxial subscores, however motor scores correlated poorly with static and dynamic balance measures. Conclusion: GPS has differential effects on static and dynamic postural control with improvement in static sway but not in dynamic stability. The effects of GPS on postural control appear to be independent of its other effects on limb and axial function.

1057 Synergetic efiect of ALflleiqler and Lewy-body changes on dementia

Saito, y~,2, Kanemaru, K 2, Arai, T 2, Sawabe, M ~, Murayama, S ~. 1Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.." :Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

Objeelive: In order to clarify the relationship between Alzheimer and Lewy-body type changes in dementia. Method: Serial 1395 autopsy cases from a geriatric hospital since 1995. The mean age was 80.6 with male to female ratio being 758:637. Parkinsonism and dementia were retrieved from the clinical records. Lewy body dementia (LBD) includes dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD), presenting with Lewy body-related neuronal degeneration involving the peripheral autonomic, the nigro-striatal and the limbic/neocortical systems. The diagnosis of Alzheimer disease (AD) was based on Braak's senile plaque (SP) Stage C and neurofibrillary tangle (NFT) stages equal to or above IV. Each case was classified into A D + L B D , A D + L B D + , AD LBD+ and AD LBD . Apolipoprotein E (Apo E) genotyping was detemfined in 1,114 from the 1,395 cases. Results: 120 cases ([8.6%)were categorized into A D + L B D - , 45 ([3.2%) A D - L B D + and 16 (1.1%) AD+LBD+. The series included 28 ([2.0%) PD cases, 16 (1.1%) of which showed dementia and was classified into one A D + L B D + and 15 AD LBD+ cases. The male to female ratio in A D + L BD , A D + L B D + and AD LBD+ was 0.53, 0.78 and 1.1, respectively. AD LBD+ with SP Stage C/NFT Stage 0-III covers 29% of all A D - L B D + , higher than 11% of A D - L B D - . The apoE z4 frequency in AD+LBD-, A D + L B D + , AD-LBD+ and AD-LBD- was 25%, 27%, 15% and 9.3%, respectively. Discussion and Conclusion: Our approach, avoiding confusion in tile nanffng of AD, DLB and PDD, confirms a mutual aggravating effect of AD and LBD changes causing dementia.

1058 Tumor Necrosis Factor-alpha blocking in a experimental model of parkinsonism

J. Salvalierra 1, R. DurAtl 1, Giner p .2 M. J. Ruiz-Magafia 1, B. Morales 1, F. Barrero 1, F. Alba 1, I. Prieto 3, M. Ramirez 3, F. Vires 1. llnstituto de Neuroeiozeias, Faeultad de Medieina, University of

2 Granada.." Unidad de Medieina bzterna, Antequera; 3Unit of Physiology, University of Jaen, Span

Background: Recent studies (Nagatsu et al., 2005) have found increased levels of proinflanmlatory cytokines, such as tmnor necrosis factor (TNF)-alpha and interleukin (IL)-I beta in the nigrostriatal region of postmortem brains of patients with sporadic Parkinson's disease (PD). Additionally, PD patients have increased serum levels of TNF-alpha that correlate with manifestations of neurological symp- toms (Gribova et al., 2003). Etanercept is a recombinant human TNF receptor fusion protein which blocks TNF-alpha, modulating inflam- matory processes. The objective of tiffs research was to assess if

etanercept, protects against experimental parkinsonism. We postulate that blood-brain barrier is altered in this animal model of parkinso- nism allowing subcutaneously given etanercept to reach therapeutic levels in the cerebrospinal fluid. Method: Thirty male Wistar rats were divided into five groups: (1) control group; (2) sham operated group, which received 4 pL of vehicle injection into striatum of both sides; (3) caudate-putamen (CP) lesion group, which received bilateral injections of 32 gg of 6-OHDA/ 4 pL into striatum; ([4) CP lesion group treated every 5 days with s.c. injections of 5 mg/kg body weight etanercept. After tile second injection, rats were lesion into CP and (5) substantia nigra (SN) lesioned group, which received bilateral administration of 6-OHDA into SN. Since one month before the lesion to one month post-lesion, motor activity of rats was measured by infrared beams, using a Motor Activity Monitor Letica LE8811. Student t test was used to statistical analysis. Results: Except during the six days post-lesion, there were no significant differences in the spontaneous motor activity among the groups. Conclusion: The subcutaneous administration of etanercept did not protect against experimental parkinsonism, probably because it can not cross the blood-brain barrier. Currently we are carrying out experiment adininistering intraventricalar etanercept to confirm our conclusions and assess therapeutic effects.

1059 Age at onset of Parldnson's disease in women is associated with age at menopause

Savettieri, G, Ragonese, P, D'Amelio, M, Callari, G, Morgante, L, Salenri, G, Epifanio, A, Morgante, L. University Of Palermo, Department Of Neurology, Oftabnology, Otolaringology, Psy University of Messina, Department of Neuroscience

Heading: Aim of this study was to verify if the age at onset of Parkinson's Disease (PD) is modified by factors modulating the estrogenic, stimulation during women's life. Background: EpidemJological and experimental studies suggest an association between factors reducing the estrogenic stimulation during women's life and PD risk. Methods: We included women affected by PD according to validated criteria, with a Mini Mental State Evaluation score > 24. Cumulative length of pregnancies, age at menarche, age and type of menopause were investigated through a structured questiommire. Linear and logistic regression analyses were used to estimate the association between the investigated variables and age at PD onset. Crude and adjusted OR, 95% CI and two-tailed p values were calculated. Results: We included 145 women affected by idiopathic. PD. Linear regression analyses showed a significant association between age at PD onset and age at menopause (adjusted r square -- 0.07; p - 0.002). A linear association approximating the statistical significance was also observed between PD age at onset and cumulative duration of preg- nancies (p - 0.05). At Logistic regression analyses age at PD onset, dichotomised according to the median of its distribution (61 years), was only associated with age at menopause ([OR 0.94; 95% CI 0.88- 1.00; p 0.06) approximating the statistical significance. Conclusions: These results further support the hypothesis regarding the role of endogenous estrogens in the development of PD. Our data also indicate an association between hormonal stimuli during fertile life and age at PD onset.

1060 Investigation on potential effects of continuous administration of rotigotine on sleep architecture in rats

ScheUer, D 1, Dummller, N 2, Porsolt, R 2. 1Sckwarz Biosciences, Monheim, Germany; 2Porsolt & Partners Pharmacology, Boulogne-Billancourt, France