LAUSR

Objective: To study the neuropathological features of SPG15 based on our cases. Background: Spastic paraplegia-15 (SPG15) is an autosomal recessive neurodegenerative disorder characterized by progressive spasticity primarily affecting the lower limbs. It is a complex form of spastic paraplegia, associated with other neurologic dysfunction, including variable mental retardation, hearing and visual defects, and thin corpus callosum. SPG15 is caused by homozygous or compound heterozygous mutation in the gene encoding spastizin (ZFYVE26) on chromosome 14q24.1, however, the pathomechanism of SPG15 is still unknown, nor the neuropathological feature of this disease has not been reported. Design/Methods: We examined three siblings of a family with SPG15 whose mutation is ZFYVE26 c.3928delT homo, p.S1310fs. Two of three patients have already died due to aspiration pneumonia and underwent autopsy. One younger sister is still alive and has been examined with MRI, Dopamine transporter SPECT imaging and metaiodobenzylguanidine (MIBG) scintigraphy. Results: The neuropathological study on two autopsy cases of this family revealed a severely atrophic brain with extreme thinning of the whole corpus callosum. Microscopically, neurodegeneration was found in the corticospinal tract, thalamus, cerebral white matter, substantia nigra and raphe nucleus, as well as in the anterior horn and posterior column of the spinal cord. The remaining neurons contained large amounts of lipofuscin. Lewy bodies nor melanophage were not found in nigra. Tyrosine hydroxylase-immunoreactive nerve fibers in the hearts had entirely disappeared. Dopamine transporter SPECT imaging of the live patient revealed severe loss of uptake in the striatum and MIBG scitigraphy showed completely loss of uptake on her heart, which is compatible with neuropathological features of her two siblings. Conclusions: SPG15 exhibits nigral degeneration and denervation of sympathetic neurons on heart, mimicking the pathology of Parkinson’s disease (PD). These observation suggests to us that there is a common pathomechanism of neurodegeneration among SPG15 and PD. Disclosure: Dr. Kowa has nothing to disclose. Dr. Miyawaki has nothing to disclose. Dr. Mitani has nothing to disclose. Dr. Futamura has nothing to disclose. Dr. Funakawa has nothing to disclose. Dr. Jinnai has nothing to disclose.