Amyotrophic Lateral Sclerosis Ali Nasim MD Fellow Neuroradiology

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 • T 2/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 T 2 signal in corticospinal tracts.

ALS: Imaging Findings Increased iron (low T 2 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 (SOD 1)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 Stone Stephen Hawking Jon

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. • stat. Dx. com • archives. org • athiestnexus. org • sabine. k 12. la. us • muppet. wikia. com