An autopsy case of amyotrophic lateral sclerosis with striatonigral and pallidoluysian degeneration and cat's‐eye‐shaped neuronal nuclear inclusions

We report the case of a Japanese woman with sporadic amyotrophic lateral sclerosis (ALS) of 28 months’ duration who died at the age of 66 years. Postmortem examination revealed moderate loss of neurons and phosphorylated TDP‐43 (p‐TDP‐43)‐immunoreactive neuronal and glial cytoplasmic inclusions in the upper and lower motor neurons. Additionally, marked neuronal loss was observed in the neostriatum, globus pallidum, subthalamic nucleus, and substantia nigra. p‐TDP‐43‐immunoreactive inclusions were frequently found in these areas. Neuronal loss and TDP‐43 pathology in the motor, striatonigral, and pallidoluysian systems were predominant on the right side. Moreover, p‐TDP‐43‐immunoreactive cat's‐eye‐shaped neuronal nuclear inclusions (NNIs) were observed in the affected lesions. NNIs in the striatonigral system were also positive for valosin‐containing protein (VCP). We diagnosed the patient as having ALS with striatonigral and pallidoluysian degeneration. Patients with ALS rarely experience pallido‐nigro‐luysian degeneration. To our best knowledge, only one case of ALS combined with striatonigral and pallidoluysian degeneration has been reported. Neuronal loss in the striatonigral and/or pallidoluysian systems has also been reported in patients with ALS with multisystem degeneration accompanied by long‐term use of an artificial respirator. Based on these findings, a possibility of an extremely rare subtype of ALS demonstrating selective loss of neurons in the striatonigral and pallidoluysian systems exists; another possibility is that this type could be an early stage or forme fruste of ALS with multisystem degeneration. Although VCP‐positive cat's‐eye‐shaped NNIs have been reported in spinocerebellar ataxia type‐2 cases, our case report presents VCP‐positive NNIs in a patient with ALS for the first time.