Long-Term Levodopa Use In Normal Substantia Nigra Cases (P3.081)

Objective: To determine the clinical and pathological profile of levodopa (LD) treated cases that have normal substantia nigra. Background: Parkinson disease (PD) is characterized by a combination of bradykinesia, rigidity, and tremor. Some of those also manifest in other disorders. Definite diagnosis of PD is only possible on pathological studies showing marked substantia nigra neuronal loss. Even in cases carefully selected for drug trials, Dopamine Transporter (DAT) imaging studies are normal in 4 to 15% of cases. While several neurological disorders are known to have normal DAT, most have predominant tremor and are assumed to have essential tremor (ET). There is no autopsy verification of underlying pathology in these cases. Design/Methods: Since 1968, all cases seen at Movement Disorder Clinics Saskatchewan have been offered autopsy at no cost to the family or estate; 491 cases have come to autopsy. Twenty-one individuals that had normal substantia nigra at autopsy and were treated with levodopa were identified. Results: Six cases received LD for 10 years. The drug was continued for life in 11 cases for subjective benefit or patient concern of symptomatic worsening. The most common adverse effects were nausea, vomiting, and “feeling sick” in five cases. No cases had objective motor symptom benefit, dyskinesia, or motor response fluctuations. In cases where LD was discontinued, there was no symptom worsening. The most common final diagnosis was ET with or without other pathology in 12 of 15 (80%) long-term treated case. Other diagnoses included ALS, Alzheimer’s disease, and vascular parkinsonism. Conclusions: Patients with normal substantia nigra had no objective symptomatic benefit on levodopa and no dyskinesia or motor response fluctuations. Levodopa is not toxic to substantia nigra. Disclosure: Dr. Rajput has nothing to disclose. Dr. Rajput has nothing to disclose. Dr. Robinson has nothing to disclose. Dr. Rajput has received personal compensation for activities with Teva Neuroscience and UCB Pharma as a speaker and/or consultant. Dr. Rajput has received research support from Merck Serono, Sanofi-Aventis Pharmaceuticals Inc., and Teva Neuroscience.