Journal ArticleDOI
Onset and spreading patterns of upper and lower motor neuron symptoms in amyotrophic lateral sclerosis.
Sonja Körner,Katja Kollewe,Marion Fahlbusch,Antonia Zapf,Reinhard Dengler,Klaus Krampfl,Susanne Petri +6 more
TLDR
The potential linkage between upper (UMN) and lower motor neuron (LMN) involvement in amyotrophic lateral sclerosis (ALS) has not yet been fully elucidated.Abstract:
Introduction
The potential linkage between upper (UMN) and lower motor neuron (LMN) involvement in amyotrophic lateral sclerosis (ALS) has not yet been fully elucidated. There is ongoing discussion as to whether ALS is primarily a disease of UMNs or LMNs.
Methods
We performed a retrospective analysis of 189 ALS patients from our ALS outpatient database to investigate the different spreading patterns of UMN and LMN affection in disease progression in relation to the onset region.
Results
The body region with the highest UMN involvement at onset in general also had the highest frequency of LMN signs and vice versa. This is in line with the hypothesis of a focal onset of disease, which then spreads to adjacent areas. However, there was a great variation between ALS phenotypes.
Discussion
These observations support the hypothesis of focal damage of a localized group of motor neurons, which then spreads to adjacent motor neurons. Muscle Nerve, 2011read more
Citations
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Journal ArticleDOI
Deciphering amyotrophic lateral sclerosis: what phenotype, neuropathology and genetics are telling us about pathogenesis.
John Ravits,Stanley H. Appel,Robert H. Baloh,Richard J. Barohn,Benjamin Rix Brooks,Lauren Elman,Mary Kay Floeter,Christopher E. Henderson,Catherine Lomen-Hoerth,Jeffrey D. Macklis,Leo McCluskey,Hiroshi Mitsumoto,Serge Przedborski,Jeffrey D. Rothstein,John Q. Trojanowski,Leonard H. van den Berg,Steven P. Ringel +16 more
TL;DR: If fundamental mechanisms could be identified and understood, ALS therapy could rationally target progression and stop the disease − a goal that seems increasingly achievable.
Journal ArticleDOI
Can regional spreading of amyotrophic lateral sclerosis motor symptoms be explained by prion-like propagation?
TL;DR: The concept of ‘propagation’ is dissected into contiguous and non-contiguous types, and this concept is expanded to the severity of the focal symptom as well as its regional spread which can be explained by cell to cell propagation in the local neuron pool.
Journal ArticleDOI
Non-human primate model of amyotrophic lateral sclerosis with cytoplasmic mislocalization of TDP-43.
Azusa Uchida,Hiroki Sasaguri,Nobuyuki Kimura,Mio Tajiri,Takuya Ohkubo,Fumiko Ono,Fumika Sakaue,Kazuaki Kanai,Takashi Hirai,Tatsuhiko Sano,Kazumoto Shibuya,Masaki Kobayashi,Mariko Yamamoto,Shigefumi Yokota,Takayuki Kubodera,Masaki Tomori,Kyohei Sakaki,Mitsuhiro Enomoto,Yukihiko Hirai,Jiro Kumagai,Yasuhiro Yasutomi,Hideki Mochizuki,Satoshi Kuwabara,Toshiki Uchihara,Hidehiro Mizusawa,Takanori Yokota +25 more
TL;DR: There is a species difference in transactive response deoxyribonucleic acid-binding protein 43 pathology, and the monkey model recapitulates amyotrophic lateral sclerosis pathology to a greater extent than rodent models, providing a valuable tool for studying the pathogenesis of sporadic amyotroph lateral sclerosis.
Journal ArticleDOI
Focality, stochasticity and neuroanatomic propagation in ALS pathogenesis.
TL;DR: Deconstructing these early in disease, before temporal-spatial summation induces complexity, shows that ALS begins focally at a seemingly random location and progresses contiguously, which suggests that focality and anatomic propagation of pathology are significant parts of pathogenesis-disease propagates over space as well as progresses over time.
Journal ArticleDOI
Disease origin and progression in amyotrophic lateral sclerosis: an immunology perspective
TL;DR: The modalities by which the immune system senses the core pathological process in motor neuron disorders are reviewed, focusing on tissue-specific immune responses in the neuromuscular junction and in the neuroaxis observed in affected individuals and in animal models of ALS.
References
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Journal ArticleDOI
El escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis
Journal ArticleDOI
Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man.
Lindsey R. Fischer,Deborah G. Culver,Philip Tennant,Albert A. Davis,Minsheng Wang,Amilcar A. Castellano-Sanchez,Jaffar M. Khan,Meraida Polak,Jonathan D. Glass +8 more
TL;DR: It is concluded that in this widely studied animal model of human ALS, and in this single human case, motor neuron pathology begins at the distal axon and proceeds in a "dying back" pattern.
Journal ArticleDOI
ALS motor phenotype heterogeneity, focality, and spread: Deconstructing motor neuron degeneration
John Ravits,Albert R. La Spada +1 more
TL;DR: Heterogeneity of motor phenotypes suggests motor neuron degeneration in ALS is in actuality a very orderly and actively propagating process and that fundamental molecular mechanisms may be uniform and their chief properties deduced.
Journal ArticleDOI
Focality of upper and lower motor neuron degeneration at the clinical onset of ALS
TL;DR: Motor neuron degeneration in ALS is a focal process at both upper and lower motor neuron levels of the motor system and then advances contiguously and separately to summate over time.
Journal ArticleDOI
Neuropathology with clinical correlations of sporadic amyotrophic lateral sclerosis: 102 autopsy cases examined between 1962 and 2000.
Yue-Shan Piao,Koichi Wakabayashi,Akiyoshi Kakita,Mitsunori Yamada,Shintaro Hayashi,Takashi Morita,Fusahiro Ikuta,Kiyomitsu Oyanagi,Hitoshi Takahashi +8 more
TL;DR: Neostriatal and temporal dystrophic neurites were associated with dementia and bulbar‐onset form through temporal lesions and temporal inclusions.
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