Amyotrophic Lateral SclerosisAli 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 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 FindingsCan 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 FindingsEarly unilateral (left) ALS involvement in a patient with associated callosal agenesis.

ALS: Imaging FindingsCurved MPR: Corticospinal Tract extension

ALS: Imaging FindingsEnhancement is atypical but occasionally seen.

ALS: Imaging FindingsBilateral high T2 signal in corticospinal tracts.

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

ALS: Imaging FindingsMR 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 AffectedLou Gehrig Stephen Hawking Jon Stone

ALS: TreatmentRiluzole - 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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