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

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, 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) 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.

Curved MPR: Corticospinal Tract extension ALS: Imaging Findings Curved MPR: Corticospinal Tract extension

Enhancement is atypical but occasionally seen. ALS: Imaging Findings Enhancement is atypical but occasionally seen.

Bilateral high T2 signal in corticospinal tracts. 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. statDx.com archives.org athiestnexus.org sabine.k12.la.us muppet.wikia.com