Brainstem and spinal cord motor neuron involvement with optineurin inclusions in proximal-dominant hereditary motor and sensory neuropathy

Proximal-dominant hereditary motor and sensory neuropathy (HMSN-P) is characterised by slowly progressive proximal-dominant atrophy and weakness with fasciculations, sensory disturbance and autosomal dominant inheritance.1 HMSN-P has been reported in Okinawa and Kansai, Japan, and the disease locus was mapped to 3q13.1.2 3 The clinical entity of HMSN-P remains controversial. Although this disease was originally described as a new HMSN, it has sometimes been referred to as a part of HMSN type 2 or axonal HMSN. On the other hand, some clinical features of HMSN-P are similar to those of familial amyotrophic lateral sclerosis (ALS).1 Here, we report an autopsy case of HMSN-P that exhibited prominent lower motor neuron (LMN) lesions in the spinal cord and in the brainstem nuclei. Furthermore, we demonstrated optineurin (OPTN)-positive inclusions, which are seen in sporadic and familial ALS,4 in the affected neurons of the present case. The patient is the index case of Kansai-type HMSN-P (IV:25 of pedigree 1).3 A 64-year-old man was admitted to a hospital because of gradually developing muscle atrophy and weakness with fasciculations. When he was 51 years old, he had difficulty in climbing up stairs. Five years after the onset, he needed support when walking. Two years later, he was unable to stand up by himself. In a few years, he became bed-ridden. When he was at 64 years of age, he had dysphagia and started tube-feeding after hospitalisation. Neurological examination on admission showed weakness in the facial, soft palate and sternocleidomastoid muscles and tongue atrophy (figure 1A); proximal-dominant weakness and prominent fasciculations were noted; deep …