1. Amyotrophic Lateral Sclerosis
Ali Nasim MD
Fellow, Neuroradiology Division at UNC

2. 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.

3. History of ALS
First described in publication by Dr. Jean-Martin Charcot, in Paris.
Lectures translated into English

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

5. ALS: Clinical Findings
Types:
Classic - UMN and LMN
Only UMN or only LMN
Predominantly bulbar form - worse prognosis
Familial %
5600 cases per year in the US, y/o, M:F 2:1

6. ALS: Clinical Findings
Progresses distal to proximal, with complete disability within 10 yrs
20% of patients survive >5 yrs
Familial and juvenile onset survive yrs after diagnosis

7. 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.

8. 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

9. ALS: Imaging Findings
Early unilateral (left) ALS involvement in a patient with associated callosal agenesis.

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

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

12. Bilateral high T2 signal in corticospinal tracts.
ALS: Imaging Findings
Bilateral high T2 signal in corticospinal tracts.

13. 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.

14. ALS: Imaging Findings
FLAIR images shows high signal in the cortico-spinal tracts due to Wallerian degeneration.

15. ALS: Imaging Findings MR Spectroscopy: Decreased NAA/Cr ratio
Increased choline and myoinositol
Decreased glutamate in the precentral gyrus and peri-rolandi white matter

16. ALS: Pathology Loss of cortical pyramidal motor neurons and gliosis
Corticospinal tracts with variable patterns of degeneration
Precentral gyrus atrophy

17. ALS: Pathophyiology Cause of Spontaneous ALS unknown
Single gene mutations can lead to selective motor neuron loss
Glutamate excitotoxicity (etiology unknown)

18. ALS: Pathophyiology Familial ALS:
Copper/Zinc Superoxide dismutase (SOD1)gene mutation found to be associated with 20% of familial ALS
Gain of function mutation

19. ALS: Interesting Info
Reports of populations with increased incidence, most notably the Chamarro people of Guam (ALS-PCD)
Incidence ranging cases / 100,000 (nml cases/ 100,00)
Recent theory is that this was due to bat consumption and exposure to BMMA excitotoxins.

20. ALS: Notable People Affected
Lou Gehrig Stephen Hawking Jon Stone

21. ALS: Treatment Riluzole - glutamate release inhibitor
-Has been shown to increase NAA/Cr ratio
Symptom treatment - ventilation, anti-spastic medications

22. References
Kalra, S. et al, Neuroimaging in Amyotrophic Lateral Sclerosis. ALS and Other Motor Neuron Disorders :
Kalra, S. et al, Gabapentin Therapy for Amyotrophic Lateral Sclerosis: Lack of Improvement in Neuronal Integrity Shown by MR Spectroscopy AJNR, Mar 2003; 24:
Bowen, B. , MR Imaging and Localized Proton Spectroscopy of the Precentral Gyrus in Amyotrophic Lateral Sclerosis AJNR, Apr 2000; 21:
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