Ubiquitinated neuronal inclusions in the neostriatum in patients with amyotrophic lateral sclerosis with and without dementia - A study of 60 patients 31 to 87 years of age

Objective and methods: Neuronal degeneration in amyotrophic lateral scleros is (ALS) is associated with ubiquitinated cytoskeletal alterations in the m otor neuron system. Ubiquitin-positive inclusions are also seen in the limb ic system in ALS with dementia (ALS-D). Recently, similar inclusions were r eported to occur in the neostriatum in a case of ALS-D. We, therefore, immu nohistochemically examined the neostriatum from 60 patients with ALS and 60 control subjects. Results: Two forms of ubiquitin-positive inclusions were found in the ALS neostriatum: rod-like inclusions in the large neurons and crescent-shaped inclusions in the small neurons. The former were found in 14 ALS and Is control subjects, whereas the latter were specific to ALS, th e crescent-shaped inclusions in small neurons were found in 27 ALS patients , and the immunohistochemical and ultrastructural features were identical t o those of the extra-motor inclusions of ALS. Moreover. characteristic temp oral lesions consistent with those seen in ALS-D were found in 8 patients, of whom 2 had shown dementia. Conclusion: The present findings strongly sug gest that neostriatal small neurons are also involved in the disease proces s in ALS.