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.