CNS non tumor
Motor neuron disorders
Amyotrophic lateral sclerosis (ALS)

Author: Margaret E. Flanagan, M.D. and Thomas J. Montine, M.D., Ph.D. (see Authors page)
Editor: Edward D. Plowey, M.D., Ph.D.

Revised: 2 October 2016, last major update September 2016

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Amyotrophic lateral sclerosis[title]
Cite this page: Amytrophic Lateral Sclerosis (ALS). PathologyOutlines.com website. http://pathologyoutlines.com/topic/cnsals.html. Accessed April 29th, 2017.
Definition / general
Essential features
  • Spinal cord and anterior spinal root atrophy
  • Upper and motor neuron loss with associated loss of myelinated axons
  • Neuronal inclusions:
    • Skein like inclusions
    • Hyaline (Lewy like) inclusions
    • Bunina bodies
Terminology
  • Popularly known as Lou Gehrig's disease
  • Progressive bulbar palsy (PBP) and progressive muscular atrophy (PMA) are generally considered to be variants of a single clinicopathologic syndrome (Ellison: Neuropathology, 3rd Edition, 2013)
    • PBP: syndrome of progressive dysarthria and dysphagia
      • ~25% of patients who develop other features of ALS initially present with PBP
    • PMA: condition where lower motor neuron signs correlating with loss of anterior horn cells occur in absence of upper motor neuron signs
      • Upper motor neurons are preserved
  • Primary lateral sclerosis (PLS) is usually regarded as a distinct entity because of the lack of lower motor neuron (LMN) involvement (Ellison: Neuropathology, 3rd Edition, 2013)
    • PLS: Upper motor neuron signs occur in the absence of lower neuron signs
      • Pathologic changes are confined to motor cortex and cortical spinal tracts
Epidemiology
Sites
  • Anterior spinal roots
  • Spinal cord
  • Hypoglossal nucleus
  • Primary motor cortex
  • Brain stem motor nuclei
Pathophysiology
Genetic Factors
  • 5 - 10% of patients with ALS have an autosomal dominant inherited form of the disease
  • Autosomal recessive and X linked forms of ALS have also been described.
  • Some gene variants act as risk factors for ALS (Ellison: Neuropathology, 3rd Edition, 2013):
    • Deletions within C terminal domain of NEFH gene coding for neurofilament heavy subunit have been found in several sporadic ALS patients
      • May be a susceptibility factor
    • Short expansions of glutamine forming a polyglutamine tract in the ataxin2 protein are associated with increased risk of ALS
Clinical features
Diagnosis
  • The diagnosis of ALS requires (Ellison: Neuropathology, 3rd Edition, 2013):
    • Presence of:
      • Evidence of lower motor neuron (LMN) degeneration by clinical, electrophysiological or neuropathological examination
      • Evidence of upper motor neuron (UMN) degeneration by clinical examination
      • Progression of the motor syndrome within a region or to other region, as determined by history or examination
    • Absence of:
      • Electrophysiological and pathological evidence of other disease processes that might explain the signs of LMN or UMN degeneration
      • Neuroimaging evidence of other disease processes that might explain the observed clinical and electrophysiological signs
Radiology description
Prognostic factors
Treatment
Gross description
Gross images

Images hosted on Pathout server:
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Contributed by Hannes Vogel, M.D.

Microscopic (histologic) description
Microscopic (histologic) images

Images hosted on Pathout server:
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Missing Image

Contributed by: Margaret E. Flanagan, M.D.

Positive stains
Negative stains
Differential diagnosis