Normal substantia nigra patients treated with levodopa – Clinical, therapeutic and pathological observations

Abstract Background Definite diagnosis of idiopathic Parkinson's disease is based on histological findings of marked substantia nigra neuronal loss and Lewy body inclusions. Almost all cases with clinical diagnosis of idiopathic Parkinson's disease are treated with levodopa. Because there is no biological marker for the diagnosis, erroneous clinical diagnosis and treatment of such cases with levodopa are well known. There is very limited literature on levodopa treated cases that had normal substantia nigra at autopsy. Methods Patients seen at Movement Disorders Clinic Saskatchewan are offered autopsy at no cost to the family/estate of the patient. Autopsy studies are performed by certified neuropathologists. Notation on the status of substantia nigra is made in every autopsied case. Results Between 1968 and 2014, 21 cases treated with levodopa had normal substantia nigra at autopsy. Eleven patients continued levodopa until death and 9 received the drug for four years or longer. No objective motor symptom benefit, dyskinesia or motor response fluctuations on levodopa were observed in any case. The most common final diagnosis was essential tremor. Conclusion Individuals with normal substantia nigra do not benefit from levodopa and do not manifest motor response fluctuations or dyskinesia. Long-term use of levodopa is not toxic to normal human substantia nigra.