Amyotrophic Lateral Sclerosis

Ali Nasim MDFellow, 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 FindingsSymptoms:

•Upper motor - Babinski, spasticity, hyperreflexia.

•Lower motor - asymmetric muscle weakness, atrophy, fasciculations

•Bulbar signs - dysphagia, slurred speech

ALS: Clinical FindingsTypes:

•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, 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 Revised El Escorial World Federation of Neurology criteria:Neurology criteria:

• Evidence of LMN degeneration by clinical, Evidence of LMN degeneration by clinical, electrophysiological, or neuropathological electrophysiological, or neuropathological examination 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.

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

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:

• Decreased NAA/Cr ratio

• Increased choline and myoinositol

• Decreased glutamate in the precentral gyrus and peri-rolandi white matter

ALS: Pathology

• Loss of cortical pyramidal motor neurons and gliosis

• Corticospinal tracts with variable patterns of degeneration

• Precentral gyrus atrophy

ALS: Pathophyiology

• Cause of Spontaneous ALS unknown

• Single gene mutations can lead to selective motor neuron loss

• 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.

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