1083 Analysis of dopamine transporter gene polymorphism in patients with Parkinson's disease

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Poster Abstracts

Wednesday, November 9, 2005

rest, and 6-7Hz with posture/action. No tremor was recorded in the right hand. Post alcohol, the tremor was significantly suppressed clinically and electrographically. Tremor frequency was unchanged from baseline. The mildly reduced left amt swing during gait and mild left hand bradykinesia was unchanged. The tremor has responded to a subsequent trial of propranolol. Conclusion: The clinical and electrographic findings fit with a classification of a Type II Parkinsonian Tremor Syndrome, as defined when the postural/kinetic tremor is 1.5Hz greater titan the rest tremor frequency. Electrophysiological studies objectively confirmed a significant response to alcohol, and clinically the tremor responds to propranolol. 1080 Asymptomafie autonoufic dysthnetion in Parkinson's Disease an dectr ophysiological study Nleenakshisundaram, Umaionlbahan, Valmurugendran, Uthamarayan. Sri Ramaehandra Medical College & Research Institute

(Deemed University), Chennai, India Background: Autonomic dysfunction in patients with Parkinson disease is generally believed to indicate a varied diagnosis and to exclude Parkinson disease. Although overt autonomic dysfunction is rare, asymptomatic autonomic dysfunction has been described in patients with Parkinson disease. Electrophysiologic evaluation of autonomic function in such asymptomatic patients has been rarely done. Methods: Fifty-four patients with Parkinson disease (diagnosed using standard criteria) were evaluated. Patients without any symptom of autonomic dysfunction were included in the study. Patients with other possible causes of autonomic dysfunction such as diabetes mellitus, drug intake and endocrine abnormalities were excluded from the study, as were patients who had significant postural hypotension on recording BP. The patients were subjected to electrophysiological evaluation with R-R interval (for parasympathetic system) and Sympathetic Skin Responses (SSR) (for sympathetic system). Results: A total of 16.66% of patients had absent SSR indicating sympathetic, dysfunction while 11.11%of patients had abnormalities of R - R interval indicating parasympathetic dysfunction. Conclusion: Electrophysiological evidence of autonomic dysfunction exists in a minority of patients with otherwise classical Parkinson disease who have no symptoms or signs of autonomic dysfunction clinically. It would be important to bear this fact in mind before classifying parkinsonian syndromes. 1081 A case of pergolide-imluced fibrosis with retroperitoneal, cardiac and pleural all, oration Villegas, E, Catfi, T, Guijarro, A, Valldeoriola, F, Ferrer-Ruscalleda, F. Hospital dos de maig, Hospital clinic i provirzeial Introduction: Pergolide is a dopaminergic agonist commonly used to treat Parkinson's disease (PD). Previous conmmnications had reported the association of this medication with retroperitoneal fibrosis. We present a woman diagnosed of P D in treatment with pergolide than developed a fibrosis in multiple localization, with good response to corticotherapy. Case report. An 85-year-old woman with P D began pergolide in 1999. In January 2005 the patient present a progressive general weakness, anorexia and attaemia. An computer tomography showed a plate-like mass in the pelvis enveloping right ureter with associated hydronephrosis, with a larger mass around aorta and pelvic, vessels, and pleural effusion. A cardiac, ultrasound detected engrossed aortic and tricuspid valves, with light insufficiency associated. The images highly suggested retroperitoneal and cardiac fibrosis. Pergolide was discontinued, and began treatment with prednisone 60 mg per day. The patient remained stable until disdmrge, and in posterior clinical and radiological controls

showed amelioration of general status and laboratory alterations, resolution of pleural effusion and partial disappearance of pelvic mass. Conclusions: Prolonged treatment with pergolide can provoke valvate and retroperitoneal fibrosis. Although tire disruption of treatment and corticotherapy can be effective, in patients with PD neurologist can attempt to replace pergolide by other dopanfinergic agonist without these effects, how mirapexin or ropinirole. 1082 Repetitive traaseralfial magnetic sthnulafion in patients with Parkiason's disease, Wflson's disease and essential tremor Wagner, An., Hermann, W, Gflnther, P, Wagner, A. Department of

Neurology, University of Leipzig, Leipzig, Germany Background: Repetitive transcranial magnetic stimulation (rTMS) is being increasingly used in the experimental treatment of neurological and psychiatric disorders. Although rTMS has been reported to be effective for Parkinson's disease, it has not yet been evaluated for Wilson's disease or essential tremor. Method: The therapeutic effectiveness of rTMS was examined in 15 patients suffering from Parkinson's disease (Hoehn & Yahr stage I and II), 15 patients with a neurological form of Wilson's disease, and 10 patients with essential tremor. A single subthreshold rTMS (5 Hz-rTMS) was carried out above the motor hand area of the primary motor cortex on both sides (190% of the active motor threshold, 2250 stimuli). Motor skills were tested using the Unified Parkinson's Disease Rating Scale (UPDRS, motor section) and a va'iting movement recorder system (CS-System) before and after treatment. Results: Patients with Parkinson's disease showed a significant improvement in the U P D R S (p -- 0.007) after rTMS, but not in the CS-System. However, neither the U P D R S (i~ -- 0.059) nor the CSSystem indicated any statistical significance in patients with Wilson's disease. Moreover, the patients with essential tremor did not show any significant improvement in either test (UPDRS, p - 0.063). Conclusion: The effectiveness of rTMS was confirmed in patients with Parkinson's disease. However, the movement disorders of patients with Wilson's disease and essential tremor were unaffected by rTMS. Given the different pathophysiology of the three diseases, our findings and those of other studies suggest that the positive therapeutic effects of rTMS are caused by changes in the dopaminergic system. 1083 Analysis of dopamine ~ansporter gene polymorphism in patients with Parkinson's disease Watanabe, NI ~, Nissato, S 1, Ohkoshi, N 1, Yoshizawa, T 1, Yoshizawa, K 2, Hayastfi, A s, Tamaoka, A 1. 1University of Tsulcuba,

Tsukuba, Japan; 2National ~fito Hospital, ~fito, Japan; 3Toride Ishikai Hospital, Toride, Japan Background: In patients who are on L-dopa and have had Parkinson's disease (PD) symptoms for more than 5 years, therapy is often complicated by development of abnormal involuntary movements (dyskinesia), psychiatric symptoms, and wearing-off phenomena. Individual genetic variations in the dopamine transporter gene (DAT) that controls the presynaptic uptake o f dopamine in the dopaminergic neurons of the nigrostriatal system may play a role in the therapeutic outcome o f PD. This transporter gene contains a a0-bp VNTR in the 3' untranslated region that affects the protein expression and is associated with PD. And the polymorphism was reported to associate with occurrence of psychosis and dyskinesia in Cocasian PD population. We investigated the polymorphism in Japanese patients with PD to clarify the possible association between the variation and L-dopa-induced adverse effects. Method: Subjects: 171 unrelated Japanese patients with PD were recruited from the Department of Neurology o f University Hospital of Tsukuba, National Mito Hospital, and Toride lstfikai Hospital.

Poster Abstracts Diagnosis was based on clinical symptoms according to the criteria of the U K Parkinson's Disease Brain Bank. Methods: High-molecalar-weight genomic D N A was prepared from venous blood using standard phenol/chloroform extraction. Genomic D N A segment containing V N T R polymovptfism o f the DATgene was amplified according to the previously published method (Persico AM, et al. 1995). Results: We detected four alleles in the locus that correspond to 10, 11, 9, and 7 repeat allele. Frequencies of the repeat variation were 0.86, 0.03, 0.06, and 0.05 respectively. Conclusion: The locus was also polylnorphic in Japanese PD population. 1084 Evaluation of liver-rdated adverse events with Tolcapone: a review of 7-Years of worldwide salary data

Watts, R 1, Krieorian, G 2. 1Department of Neurology, University of

Alabama at Birmingham, Birmingham, AL, USA.." 2Valeant Pharmaceuticals International, Costa Mesa, CA, USA Backgrouml: The COMT inhibitor tolcapone was approved as an adjunct to levodopa for use in Parkinson's Disease in 1997. Although very effective, post-marketing surveillance revealed 3 cases of fatal hepatotoxicity in patients who were not properly monitored, and new F D A guidelines for liver testing were established. Little information has since been published on the frequency o f liver-related adverse events (AEs) reported with this agent. Method: We conducted a review of the tolcapone global safety database in order to assess the incidence of liver-related AEs received by the manufacturer from February 1997 until December 2004. Results: About 100,000 patients received tolcapone worldwide between 2/97 and 5/99. A total of 156 hepatobiliary AEs were reported during this time period, and the majority of cases were isolated asymptomatic elevations in liver enzymes. Only 37 cases (0.04%) reported acute hepatitis or hepatic failure. New liver monitoring requirements were then introduced and an estimated 80,000 patients took the drug between 6/99 and 12/04. During this time, a total o f 63 cases of liverrelated AEs were reported, of which 6 cases (0.01%) were acute hepatitis (15 cases) or hepatic failure (1 case), and no deaths occurred due to liver failure. Conclusion: The overall incidence of liver-related adverse events with tolcapone was rare both before and after the new liver monitoring guidelines were implemented. The new guidelines have likely resulted in improved screening of patients and better monitoring of liver dysfunction while on tolcapone therapy.

1085 Parkinson's disease among Inuit in Greenland: mercury and lead as risk factors

Wermuth L, Koldkjur, OG, Bjerregaard P. 1Sonderborg Hospital,

Wednesday, November 9, 2005

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with the controls twice as high as the PD. Pb was neither elevated in controls (mean 0.60 Imaol/l; range 0.13-1.47; s.d. 0.3:1) nor in cases (mean 0.37; range 0.05-0.93; s.d. 0.24) but the controls had higher values than the cases. The differences were statistically significant (p < 0.001 for both Hg and Pb). Conclusion: The prevalence of PD in hmit is twice that found in the island o f Als, Den_mark. A lifelong exposure to Hg and other metals could alone or in combination with high concentrations of pesticides lead to a synergistic effect; probably in conjunction with genetic susceptibility. The reason for lower Hg and Pb values in the cases compared to the controls are most likely ascribed to partly replacement of marine food with a western style food at the time the PD stopped work. This and the reason for the high prevalence of PD require more investigations. 1086 The epideuliology of Parldnson's disease in the Faroe Islands

Wermuth, L l, Beth, S~, Skaalum, M ~, Joensen, P~, Weihe, P~, Grandjean, p3. 1Department of Neurology, Sonderborg Hospital,

University of Southern Denmark; 2The National Hospital, Torshavn, Faroe Islands," 3Department of Environmental Medicine, University of Southern Denmark Background: Epiderniological surveys on Parkinson's disease have shown great variation in prevalence depending on methods used. Crude levodopa use (LDU) in Denmark amounted to a level sirnilar to that of Sweden. However, in the Faroe Islands and Greenland the levels of L D U are twofold higher, adjusted for indicators of socioeconomic development. In 1995 a prevalence study in the Faroe Islands with a total population o f 43.703 inhabitants with case-finding methods was made. The crude prevalence of parkinsonism per July 1 1995 was 233,4 and of idiopathic Parkinson's disease 187.6 per 100.000 persons. In 1998 in Als (Dermmrk) a prevalence study with the same method used the crude prevalence of idiopathic Parkinson's disease was estimated to be 102.0 per 100 000 persons. Method: The same case-finding methods will be used: Collection of data from the pharmacies in the Faroe Islands. Registered patients with suspected PD in the National Hospital in Torshavn and information from all general practitioners. Patients will be examined, interviewed and blood samples taken. Results: In the smmner 2005 a new prevalence and incidence study is planned. In Denmark the LDU are 3.:1 DDD/1000 inhabitants per day, in the Faroe Islands the L D U are 4.69 DDD/1000 inhabitant per day and still higher than in Denmark. Conclusion: The case ascertainment and the diagnostic accuracy in tiffs study will be at the same high level as the last study. Data will be presented to the congress. 1087 Inhibitory control in Parldnson's disease

University of Southern Denmark, Dept. Of Clin. Biochernistry, Sonderborg, Denmark

Winograd-Gurvidl, C 1,z, Georgiou-Karistianis, N ~, Millist, L 2, White, 01"2. 2Monash University, Melbourne, Australia; 2The Mental

Objective: To investigate mercury (Hg) and lead (Pb) as possible risk factors for Parkinson's disease (PD) in an arctic population which has never been done before. Backgrouml: The arctic area has for decades been contaminated by heavy metals with accmnulation in the marine food. Inuit with their high consmnption of marine animals therefore bioaccunmlate the metals. Environmental factors, including metals, are believed to play an important role in PD. Method: Case-control study of Inuit in Greenland. Full-blood from 39 PD (mean age 68 yr) and 54 controls (mean age 63 yr) was analysed for Hg and Pb by atomic absorption spectrometry. Results: Hg was very high in both controls (mean 267 nmol/l; range 66935, s.d.197) and PD-cases (mean 134 rmlol/1); range 23-410; s.d. 86)

Parkinson's disease (PD) is a clinical syndrome characterized by a combination of tremor, rigidity and bradykinesia. The primary neuropathology is loss of dopaminergic neurons in nigrostriatal tracts. Failure in inhibitory control has recently become a focus of not only the cognitive functions related to PD, but also of the understanding of motor control. Eye movement paradigms provide a useful behavioural measure to precisely and non-nivasively investigate basic sensorimotor functions as well as higher order cognitive aspects of motor control, including the ability to inhibit and select (in)appropriate movements. This study investigated inlfibitory control in 13 individuals with mild-moderate PD and 13 age-matched healthy controls utilizing a number of saccadic eye movement

Health Research Institute, Melbourne, Australia