Amyotrophic Lateral Sclerosis

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Amyotrophic Lateral Sclerosis

• Ali Nasim MD
• Fellow, Neuroradiology Division at UNC

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What is ALS?

• A-myo-trophic no-muscle-nourishment
• Lateral Sclerosis refers to involvement of the
  lateral corticospinal tracts.
• ALS is a degeneration of somatic motor neurons
  extending from upper motor cortical pyramidal
  neurons to lower motor neurons of the brainstem
  and cord.

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History of ALS

• 1869 - First described in publication by Dr.
  Jean-Martin Charcot, in Paris.
• 1881 - Lectures translated into English

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ALS Clinical Findings

• Symptoms
• Upper motor - Babinski, spasticity,
  hyperreflexia.
• Lower motor - asymmetric muscle weakness,
  atrophy, fasciculations
• Bulbar signs - dysphagia, slurred speech

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ALS Clinical Findings

• Types
• Classic - UMN and LMN
• Only UMN or only LMN
• Predominantly bulbar form - worse prognosis
• Familial - 15-20
• 5600 cases per year in the US, 40-70 y/o, MF
  21

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ALS Clinical Findings

• Progresses distal to proximal, with complete
  disability within 10 yrs
• 20 of patients survive gt5 yrs
• Familial and juvenile onset survive 20-30 yrs
  after diagnosis

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ALS Clinical Findings

• Revised El Escorial World Federation of
  Neurology criteria
• Evidence of LMN degeneration by clinical,
  electrophysiological, or neuropathological
  examination
• Evidence of UMN degeneration by clinical
  examination
• Progressive spread of symptoms or signs within a
  region or to other regions (The body is divided
  into four regions cranial, cervical, thoracic
  and lumbosacral)
• Absence of electrophysiological, pathological or
  neuroimaging evidence of other disease processes.

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ALS Imaging Findings

• Can have normal imaging
• Focal atrophy in chronic cases
• T2/FLAIR hyperintensity extending along the
  corticospinal tract from corona radiata to the
  brainstem
• Contrast enhancement - ?
• Deposition of iron in affected cortex

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ALS Imaging Findings
Early unilateral (left) ALS involvement in a
patient with associated callosal agenesis.
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ALS Imaging Findings
Curved MPR Corticospinal Tract extension
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ALS Imaging Findings
Enhancement is atypical but occasionally seen.
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ALS Imaging Findings
Bilateral high T2 signal in corticospinal tracts.
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ALS Imaging Findings
Increased iron (low T2 signal) deposition in the
gray matter of the peri-Rolandic regions which
underlying high signal in the white matte and
dilatation of the adjacent cortical sulci.
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ALS Imaging Findings
FLAIR images shows high signal in the
cortico-spinal tracts due to Wallerian
degeneration.
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ALS Imaging Findings

• MR Spectroscopy
• Decreased NAA/Cr ratio
• Increased choline and myoinositol
• Decreased glutamate in the precentral gyrus and
  peri-rolandi white matter

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ALS Pathology

• Loss of cortical pyramidal motor neurons and
  gliosis
• Corticospinal tracts with variable patterns of
  degeneration
• Precentral gyrus atrophy

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ALS Pathophyiology

• Cause of Spontaneous ALS unknown
• Single gene mutations can lead to selective
  motor neuron loss
• Glutamate excitotoxicity (etiology unknown)

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ALS Pathophyiology

• Familial ALS
• Copper/Zinc Superoxide dismutase (SOD1)gene
  mutation found to be associated with 20 of
  familial ALS
• Gain of function mutation

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ALS Interesting Info

• Reports of populations with increased incidence,
  most notably the Chamarro people of Guam
  (ALS-PCD)
• Incidence ranging 140-400 cases / 100,000 (nml
  0.5-2 cases/ 100,00)
• Recent theory is that this was due to bat
  consumption and exposure to BMMA excitotoxins.

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ALS Notable People Affected
Lou Gehrig Stephen Hawking Jon
Stone
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ALS Treatment

• Riluzole - glutamate release inhibitor
• -Has been shown to increase NAA/Cr ratio
• Symptom treatment - ventilation, anti-spastic
  medications

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References

• Kalra, S. et al, Neuroimaging in Amyotrophic
  Lateral Sclerosis. ALS and Other Motor Neuron
  Disorders. 20034 243-248.
• Kalra, S. et al, Gabapentin Therapy for
  Amyotrophic Lateral Sclerosis Lack of
  Improvement in Neuronal Integrity Shown by MR
  Spectroscopy AJNR, Mar 2003 24 476 - 480.
• Bowen, B. , MR Imaging and Localized Proton
  Spectroscopy of the Precentral Gyrus in
  Amyotrophic Lateral Sclerosis AJNR, Apr 2000
  21 647 - 658.
• statDx.com
• archives.org
• athiestnexus.org
• sabine.k12.la.us
• muppet.wikia.com