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.
 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.

• statDx.com
• archives.org

• athiestnexus.org

• sabine.k12.la.us

• muppet.wikia.com