Takahiro Takeda1, Sayuri Kokubun2, Yumiko Saito2, Atsuko Tsuneyama2, Ai Ishikawa2, Sagiri Isose2, Kimiko Ito2, Kimihito Arai2, Akihiro Koreki3, Atsuhiko Sugiyama4, Satoshi Kuwabara4, Kazuhiro Honda2. 1. Department of Neurology, National Hospital Organization Chibahigashi National Hospital, 673 Nitona-cho, Chuo-ku, Chiba-shi, Chiba, 260-8712, Japan. takahirotakeda58@yahoo.co.jp. 2. Department of Neurology, National Hospital Organization Chibahigashi National Hospital, 673 Nitona-cho, Chuo-ku, Chiba-shi, Chiba, 260-8712, Japan. 3. Department of Psychiatry, National Hospital Organisation Shimofusa Psychiatric Medical Center, Chiba, Japan. 4. Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Abstract
OBJECTIVE: This study aimed to clarify the relationship between progressive medial temporal atrophy and onset subtype in patients with amyotrophic lateral sclerosis (ALS). METHODS: Medial temporal atrophy, ALS functional rating scale (ALSFRS), and cognitive function were assessed in 119 patients who were grouped into three ALS subtypes: bulbar, upper limb, and lower limb onset. Medial temporal atrophy, represented by a Z-score, was determined using an analysis software of magnetic resonance images known as the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD). Among 119 patients, 60 underwent follow-up VSRAD, ALSFRS, and cognitive testing. The sequential data were compared among onset subtypes. Furthermore, TDP-43 pathology was assessed in 20 autopsied patients (including seven who underwent VSRAD before death) to examine the relationships among medial temporal atrophy, onset subtypes, and severity of the hippocampal TDP-43 pathology. RESULTS: Multiple regression analysis revealed that the Z-score at baseline was associated with the age of onset and duration of illness. A high Z-score at baseline and the bulbar/upper limb subtypes affected the progression rate of Z-score. Pathological examination revealed increased hippocampal TDP-43 pathology score associated with bulbar and upper limb subtypes. Moreover, the Z-score before death correlated with the hippocampal TDP-43 pathology score. CONCLUSION: Medial temporal atrophy in ALS is associated with bulbar and upper limb onset subtypes. This progression may be related to the extent of TDP-43 pathology.
OBJECTIVE: This study aimed to clarify the relationship between progressive medial temporal atrophy and onset subtype in patients with amyotrophic lateral sclerosis (ALS). METHODS: Medial temporal atrophy, ALS functional rating scale (ALSFRS), and cognitive function were assessed in 119 patients who were grouped into three ALS subtypes: bulbar, upper limb, and lower limb onset. Medial temporal atrophy, represented by a Z-score, was determined using an analysis software of magnetic resonance images known as the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD). Among 119 patients, 60 underwent follow-up VSRAD, ALSFRS, and cognitive testing. The sequential data were compared among onset subtypes. Furthermore, TDP-43 pathology was assessed in 20 autopsied patients (including seven who underwent VSRAD before death) to examine the relationships among medial temporal atrophy, onset subtypes, and severity of the hippocampal TDP-43 pathology. RESULTS: Multiple regression analysis revealed that the Z-score at baseline was associated with the age of onset and duration of illness. A high Z-score at baseline and the bulbar/upper limb subtypes affected the progression rate of Z-score. Pathological examination revealed increased hippocampal TDP-43 pathology score associated with bulbar and upper limb subtypes. Moreover, the Z-score before death correlated with the hippocampal TDP-43 pathology score. CONCLUSION: Medial temporal atrophy in ALS is associated with bulbar and upper limb onset subtypes. This progression may be related to the extent of TDP-43 pathology.
Authors: Johannes Brettschneider; Kelly Del Tredici; Jon B Toledo; John L Robinson; David J Irwin; Murray Grossman; EunRan Suh; Vivianna M Van Deerlin; Elisabeth M Wood; Young Baek; Linda Kwong; Edward B Lee; Lauren Elman; Leo McCluskey; Lubin Fang; Simone Feldengut; Albert C Ludolph; Virginia M-Y Lee; Heiko Braak; John Q Trojanowski Journal: Ann Neurol Date: 2013-06-19 Impact factor: 10.422
Authors: Manuela Neumann; Deepak M Sampathu; Linda K Kwong; Adam C Truax; Matthew C Micsenyi; Thomas T Chou; Jennifer Bruce; Theresa Schuck; Murray Grossman; Christopher M Clark; Leo F McCluskey; Bruce L Miller; Eliezer Masliah; Ian R Mackenzie; Howard Feldman; Wolfgang Feiden; Hans A Kretzschmar; John Q Trojanowski; Virginia M-Y Lee Journal: Science Date: 2006-10-06 Impact factor: 47.728