Amyotrophic Lateral
Sclerosis
Ali Nasim MD
Fellow, Neuroradiology Division at UNC

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.

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

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

ALS: Clinical Findings
Types:
•
Classic - UMN and LMN
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Only UMN or only LMN
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Predominantly bulbar form - worse prognosis
•
Familial - 15-20%
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5600 cases per year in the US, 40-70 y/o, M:F 2:1

ALS: Clinical Findings
•
Progresses distal to proximal, with complete disability within 10 yrs
•
20% of patients survive >5 yrs
•
Familial and juvenile onset survive 20-30 yrs after diagnosis

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)
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Absence of electrophysiological, pathological or neuroimaging evidence of other disease processes.

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

ALS: Imaging Findings
Early unilateral (left) ALS involvement in a patient with associated callosal agenesis.

ALS: Imaging Findings
Curved MPR: Corticospinal Tract extension

ALS: Imaging Findings
Enhancement is atypical but occasionally seen.

ALS: Imaging Findings
Bilateral high T2 signal in corticospinal tracts.

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.

ALS: Imaging Findings
FLAIR images shows high signal in the cortico-spinal tracts due to Wallerian degeneration.

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

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

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

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

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.

ALS: Notable People
Affected
Lou Gehrig Stephen Hawking Jon
Stone

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

References
•
Kalra, S. et al, Neuroimaging in Amyotrophic Lateral Sclerosis. ALS and Other Motor Neuron Disorders.
2003:4 243-248.
•
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