An autopsy case of spinal bulbar muscular atrophy concomitant with multiple system atrophy pathology

We describe an autopsy case of spinal bulbar muscular atrophy (SBMA) concomitant with multiple system atrophy (MSA). A Japanese male patient developed gait disturbance in his twenties. His brother and niece also presented with similar clinical symptoms. His condition gradually worsened, and he became immobile at the age of 50 years. Genetic analysis revealed the expansion of CAG repeats of the SBMA gene. At 63 years of age, cerebellar ataxia symptoms emerged. Magnetic resonance images of the head showed a "hot cross bun sign" at the pontine basis and bilateral atrophy of the middle cerebellar peduncles and cerebellar hemispheres, suggesting MSA. He died of pneumonia at the age of 65 years, with a clinical illness of approximately 40 years. The neuropathological diagnosis was consistent with both SBMA and MSA. Neurons of the spinal anterior horn and brainstem motor nuclei were diminished. 1C2 (polyglutamine) immunoreactive intranuclear and intracytoplasmic inclusions were observed in the neurons in the substantia nigra, brainstem tegmentum, pontine nuclei, spinal anterior horn cells and Onuf's nucleus. These findings were suggestive of SBMA. Meanwhile, neurons of the inferior olivary nuclei, pontine nuclei, and Purkinje cells were nearly completely lost. The cerebellar white matter, pontine basis, and middle cerebellar peduncles showed a prominent loss of fibers. α-synuclein positive glial cytoplasmic inclusions were observed in widespread areas. These findings were suggestive of MSA. To the best of our knowledge, another case of SBMA accompanying MSA, similar to the present case, have been reported to date. Moreover, several cases of pathologically proven amyotrophic lateral sclerosis and MSA have been reported. The development of molecular biological techniques and accumulation of pathologically diagnosed patients may reveal common pathological mechanisms in SBMA and MSA.