title: Clinicopathological characteristics of patients with amyotrophic lateral sclerosis resulting in a totally locked-in state (communication Stage V).
abstract: In the present study, we performed a comprehensive analysis to clarify the clinicopathological characteristics of patients with amyotrophic lateral sclerosis (ALS) that had progressed to result in a totally locked-in state (communication Stage V), in which all voluntary movements are lost and communication is impossible. In 11 patients, six had phosphorylated TAR DNA-binding protein 43 (pTDP-43)-immunoreactive (ir) neuronal cytoplasmic inclusions (NCI), two had fused in sarcoma (FUS)-ir NCI, and three had copper/zinc superoxide dismutase (SOD1)-ir NCI. The time from ALS onset to the need for tracheostomy invasive ventilation was less than 24 months in ten patients. Regardless of accumulated protein, all the patients showed common lesions in the pallido-nigro-luysian system, brainstem reticular formation, and cerebellar efferent system, in addition to motor neurons. In patients with pTDP-43-ir NCI, patients with NCI in the hippocampal dentate granule neurons (DG) showed a neuronal loss in the cerebral cortex, and patients without NCI in DG showed a preserved cerebral cortex. By contrast, in patients with FUS-ir NCI, patients with NCI in DG showed a preserved cerebral cortex and patients without NCI in DG showed marked cerebral degeneration. The cerebral cortex of patients with SOD1-ir NCI was preserved. Together, these findings suggest that lesions of the cerebrum are probably not necessary for progression to Stage V. In conclusion, patients with ALS that had progressed to result in communication Stage V showed rapidly-progressed symptoms, and their common lesions could cause the manifestations of communication Stage V.
authors.affiliation: Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu-shi, Tokyo, 183-0042, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Pathology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu-shi, Tokyo, 183-0042, Japan. mochi@nihon-u.ne.jp.|Department of Neurology, Tokyo Metropolitan Kita Medical and Rehabilitation Center for the Disabled, 1-2-3 Jujodai, Kita-ku, Tokyo, 114-0033, Japan. mochi@nihon-u.ne.jp.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mochizuki
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8585, Japan.|Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata-shi, Niigata, 951-8585, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Takeuchi
authors.affiliation: Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu-shi, Tokyo, 183-0042, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu-shi, Tokyo, 183-0042, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagao
authors.affiliation: Department of Sensory and Motor System, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Watabe
authors.affiliation: Department of Laboratory Neuropathology, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Arai
authors.affiliation: Division of Neuropathology, Department of Brain Disease Research, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto-shi, Nagano, 390-8621, Japan.
authors.forename: Kiyomitsu
authors.initials: K
authors.lastname: Oyanagi
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8585, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
authors.affiliation: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata-shi, Niigata, 951-8585, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata-shi, Niigata, 951-8585, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.affiliation: Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu-shi, Tokyo, 183-0042, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Isozaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D001921:Brain / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011782:Quadriplegia / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
keywords: Amyotrophic lateral sclerosis; Brainstem reticular formation; Cerebral cortical degeneration; Communication Stage V; Pallido-nigro-luysian system; Totally locked-in state