Autopsy-Proven Amyotrophic Lateral Sclerosis Coexisted With Parkinson Disease: A Novel Association Of TDP-43 Proteinopathy And α-Synucleinopathy (P1.056)

OBJECTIVE: We present the clinicopathological characteristics of patients with amyotrophic lateral sclerosis (ALS) who experienced precedent parkinsonism. BACKGROUND: ALS is characterized by TAR DNA-binding protein 43 kD (TDP-43) proteinopathy and Parkinson disease (PD) by α-synucleinopathy. However, the coexistence of the two proteinopathy has not been demonstrated. DESIGN/METHODS: Among 180 patients with ALS resistered from July 2007 to September 2013, 3 patients (1.6%) presented with parkinsonism before developing ALS-related symptoms. All the patients underwent thorough neurological examination as well as brain MRI, SPECT, and MIBG myocardial scintigraphy. Two of the patients underwent autopsy. RESULTS: All the three patients were women without family history of neurodegenerative disorders. Average ages at onset of parkinsonism and ALS were 65 and 68 years old. All the patients demonstrated no signs of cognitive decline. Cardiac uptake of MIGB was decreased in all the patients. Respiratory support was needed in an average of 11.7 months after onset of ALS. Two of the patients died of respiratory failure and they underwent autopsy, which revealed the shared neuropathological findings consistent with ALS and PD: Lewy bodies were abundant in the anterior wall of left ventricle, the esophagus, the spinal cord, the brainstem, the limbic system, and the neocortex. Pathological findings indicative of multiple system atrophy were not observed. The corticospinal tracts exhibited bilateral degeneration. Loss of spinal anterior horn cells and gliosis were observed, whereas posterior columns, Clarke’s columns, intermediate lateral columns, and the Onuf’s nucleus were spared. Bunina bodies were identified in the lower motor neurons. TDP-43-positive neuronal and glial cytoplasmic inclusions were observed throughout the central nervous system. CONCLUSIONS: We described 3 patients with ALS who experienced precedent parkinsonism. Coexistence of the TDP-43 proteinopathy and the α-synucleinopathy was proved in two autopsy cases. Study Supported by: Grants-in-Aid from the Research Committee of CNS Degenerative Diseases, the Ministry of Health, Labour and Welfare of Japan, from the Japan Society for the Promotion of Science Disclosure: Dr. Izumi has nothing to disclose. Dr. Sumikura has nothing to disclose. Dr. Fujita has nothing to disclose. Dr. Kamada has nothing to disclose. Dr. Shimatani has nothing to disclose. Dr. Miyamoto has nothing to disclose. Dr. Koizumi has nothing to disclose. Dr. Miyazaki has nothing to disclose. Dr. Hatsuta has nothing to disclose. Dr. Nodera has nothing to disclose. Dr. Nishida has nothing to disclose. Dr. Murayama has nothing to disclose. Dr. Kaji has received personal compensation for activities with GlaxoSmithKline, Inc. as a consultant. Dr. Kaji has received research support from GlaxoSmithKline, Inc.