Abstract Skeins or skein-like inclusions (SLIs) in motor neurons detected by ubiquitin immunohistochemistry are a characteristic finding of amyotrophic lateral sclerosis (ALS). Here we report ubiquitinated SLIs in the putamen and caudate nucleus from a case of ALS with dementia. A 48-year-old Japanese man developed apathy and amimia. Mental and neurological examinations revealed severe character change, muscle atrophy and fasciculation of the distal upper extremities and the tongue, and an exaggera- tion of the deep tendon reflex. He subsequently showed dysphagia and dysarthria. He died at the age of 51 years, after a total clinical course of about 2.5 years. By im- munohistochemistry, ubiquitin-immunoreactive intraneu- ronal inclusions were observed in the spinal anterior horn cells, the frontal, temporal and entorhinal cortices, dentate fascia of the hippocampus and the amygdala. In addition, ubiquitinated inclusions were also seen in the putamen and caudate nucleus, which appeared as aggregates of thread-like structures similar to SLIs in the spinal anterior horn neurons. They were not seen on hematoxylin-eosin staining, and they also did not show any argentophilia nor did they react with other antibodies, including antibody against tau protein. To our knowledge, this is the first re- port of the presence of SLIs in non-motor neurons. Our results thus support the notion that ALS is a multisystem disease, and not simply a disease of the motor neurons. Key words Amyotrophic lateral sclerosis · Ubiquitin · Inclusion body · Neostriatum · Immunohistochemistry Introduction A major recent advance in the pathology of amyotrophic lateral sclerosis (ALS) has been the finding of characteris- tic inclusion bodies present in the neurons detected by im- munohistochemical localization of ubiquitin. The most common form of ubiquitinated inclusion appears as ag- gregates of thread-like structures in the motor neurons, which have been called skeins or skein-like inclusions (SLIs) [9–12]. While most studies have concentrated on motor neurons, ubiquitin-immunoreactive inclusions have also been demonstrated in the non-motor cortex (frontal, temporal and entorhinal), dentate fascia of the hippocam- pus and the amygdala [1, 18, 19, 24]. However, these in- clusions form a crescent or circular pattern around the nu- clei, which are morphologically different from SLIs. There- fore, the presence of typical SLIs has not yet been re- ported in the non-motor neurons of ALS. We herein report the ubiquitinated SLIs in the neurons of the putamen and caudate nucleus from a case of ALS with dementia. Case report A 48-year-old Japanese male elite employee developed apathy and amimia. He could no longer carry out basic tasks, and he was thus eventually hospitalized at the age of 49 years. There was no previ- ous family history of any neurodegenerative diseases. Mental and neurological examinations revealed inappropriate verbal responses to the questions due to severe character change, muscle atrophy and fasciculation of the distal upper extremities and the tongue. He showed neither memory disturbance, gait disturbance nor parkin- sonism. A Japanese Wechsler adult intelligence scale-revised (WAIS-R) assessment yielded a verbal intelligence quotient (IQ) of 81, a performance IQ of 74 and a full scale IQ of 75. On the Mini-Mental State examination (MMSE) [2], he scored 25/30. The deep tendon reflex was exaggerated; however, bilateral Babinski’s signs were negative. An electromyogram and a nerve conduction study revealed a neurogenic pattern of muscle atrophy. A CT scan Toshiro Kawashima · Hitoshi Kikuchi · Masashi Takita · Katsumi Doh-ura · Koji Ogomori · Mariko Oda · Toru Iwaki Skein-like inclusions in the neostriatum from a case of amyotrophic lateral sclerosis with dementia Acta Neuropathol (1998) 96 : 541–545 © Springer-Verlag 1998 Received: 2 March 1998 / Revised, accepted: 13 May 1998 CASE REPORT T. Kawashima () · H. Kikuchi · K. Doh-ura · T. Iwaki Department of Neuropathology, Neurological Institute, Faculty of Medicine, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan e-mail: toshiro@np.med.kyushu-u.ac.jp, Tel.: +81-92-642-5539, Fax: +81-92-642-5540 T. Kawashima · K. Ogomori Department of Neuropsychiatry, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan M. Takita · M. Oda Department of Psychiatry, Imazu Red Cross Hospital, Fukuoka 819-0165, Japan