HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Podcast Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Ravits, J. M. Articles by La Spada, A. R. PubMed PubMed Citation Articles by Ravits, J. M. Articles by La Spada, A. R. Related Collections All Clinical Neurology Anterior nerve cell disease Amyotrophic lateral sclerosis

ALS motor phenotype heterogeneity, focality, and spread

Deconstructing motor neuron degeneration

From the Section of Neurology, Virginia Mason Medical Center, and the Translational Research Program, Benaroya Research Institute at Virginia Mason (J.M.R.), Seattle, WA; and Departments of Laboratory Medicine, Neurology, and Medicine, & Center for Neurogenetics & Neurotherapeutics (A.R.L.), University of Washington, Seattle.

Address correspondence and reprint requests to Dr. John Ravits, Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, WA 98101 jravits{at}benaroyaresearch.org

Heterogeneity of motor phenotypes is a clinically well-recognized fundamental aspect of amyotrophic lateral sclerosis (ALS) and is determined by variability of 3 independent primary attributes: body region of onset; relative mix of upper motor neuron (UMN) and lower motor neuron (LMN) deficits; and rate of progression. Motor phenotypes are determined by the anatomy of the underlying neuropathology and the common defining elements underlying their heterogeneity are that motor neuron degeneration is fundamentally a focal process and that it spreads contiguously through the 3-dimensional anatomy of the UMN and LMN levels, thus causing seemingly complex and varied clinical manifestations. This 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. This also suggests opportunities for translational research to seek pathobiology directly in the less affected regions of the nervous system.

Abbreviations: ALS = amyotrophic lateral sclerosis; FTD = frontotemporal dementia; LMN = lower motor neuron; UMN = upper motor neuron.

Disclosure: Author disclosures are provided at the end of the article.

Received January 28, 2009. Accepted in final form May 29, 2009.

This article has been cited by other articles:

				S. J. Rabin, J. M. H. Kim, M. Baughn, R. T. Libby, Y. J. Kim, Y. Fan, R. T. Libby, A. La Spada, B. Stone, and J. Ravits Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology Hum. Mol. Genet., November 13, 2009; (2009) ddp498v2. [Abstract] [Full Text] [PDF]