AMYOTROPHIC LATERAL SCLEROSIS

AMYOTROPHIC LATERAL SCLEROSIS - Colin R.Bamford,MD
BASICS
DESCRIPTION
A degenerative disease (or group of diseases), that affects the upper and lower motor neurons
• Amyotrophic lateral sclerosis is the term applied to the sporadic and most common form of the disease. It includes a number of overlapping syndromes, such as pseudobulbar palsy, progressive bulbar palsy, progressive muscular atrophy, and primary lateral sclerosis.
• Familial ALS is an autosomal dominant or recessive disease, which is clinically similar to sporadic ALS but probably represents a distinct entity pathologically and biochemically.
• ALS-Parkinson-dementia complex of Guam is an ALS-like syndrome, often, but not always, associated with Parkinson syndrome and dementia, which is prevalent among the Chamorro Indians of Guam and very rare in the United States.
• System(s) Affected: Nervous
• Synonym(s): Motor neuron disease; Lou Gehrig disease; ALS
ALERT
Pediatric Considerations
• Infantile and juvenile spinal muscular atrophies are conditions that are distinct from amyotrophic lateral sclerosis both clinically and pathologically.
• Symptoms of ALS may inappropriately be attributed to age.
Pregnancy Considerations
• Uncommon among affected individuals
• Pregnancy would be unwise in any individual suffering from a disease with so poor a prognosis.
• If pregnancy did occur, the only foreseeable difficulties would be related to weakness.
EPIDEMIOLOGY
Incidence
0.4-2.0/100,000
Prevalence
• 5.0-8.0/100,000
• Predominant age: Uncommon before age 40
• Predominant sex: Male > Female
RISK FACTORS
Age > 40
Genetics
Familial ALS
ETIOLOGY
• Sporadic ALS: Degeneration of the upper and lower motor neurons with their respective axons
- Cause is unknown, but elevated levels of glutamate have been found in serum and cerebrospiral fluid (CSF)
- High levels of glutamate are toxic; 90-95% of the cases of ALS are sporadic.
• Familial ALS: A genetically transmitted degenerative disease
- Gene locus has been localized to the long arm of chromosome 21 and encodes the enzyme superoxide dismutase in 20% of familial ALS cases. 5-10% of the ALS cases are familial.
• ALS-Parkinson-dementia complex of Guam: Possible relationship to ingestion of the cycad nut or to some other environmental toxin

DIAGNOSIS
SIGNS AND SYMPTOMS
Physical Exam
Variable combinations of
• Unexplained weight loss
• Focal wasting of muscle groups
• Limb weakness with variable symmetry and distribution
• Difficulty walking
• Difficulty swallowing
• Slurring of speech
• Inability to control affect
• Atrophy of muscle groups, initially in a myotomal distribution
• Fasciculations (other than calves)
• Hyperactive deep tendon reflexes (including jaw jerk)
• Spares cognitive, oculomotor, sensory, and autonomic functions
TESTS
Lab
• Elevated levels of glutamate in CSF and serum
• Anti-monosialoganglioside autoantibodies in low titer commonly found (of unclear significance)
• Possibly reduced levels of nerve growth factor
• There is no simple reliable laboratory test available that confirms the diagnosis of ALS.
Diagnostic Procedures/Surgery
• Electromyography: Denervation potentials (fibrillations, positive sharp waves) and often doublets are associated with prominent fasciculations, which suggest anterior horn cell dysfunction. Voluntary motor unit potentials have increased amplitude, long duration, and/or polyphasic pattern. The recruitment pattern is reduced for the force generated, and individual motor units have a high rate of discharge.
• Muscle biopsy: The biopsy will show groups of shrunken angulated muscle fibers (grouped atrophy) amid other groups of fibers with a uniform fiber type (fiber type grouping).
Pathological Findings
• Loss of Betz cells in the motor cortex
• Atrophic or absent anterior horn cells of spinal cord
• Atrophic or absent neurons within the motor nuclei of the medulla and pons
• Degeneration of the lateral columns of the spinal cord
• Atrophy of the ventral roots
• Grouped atrophy of muscle (motor units)
DIFFERENTIAL DIAGNOSIS
• Focal motor neuropathy
• Cervical spondylosis
• Lead intoxication
• Spinal muscular atrophy (adult form)
• Primary lateral sclerosis
• Familial spastic paraparesis
• Spinal multiple sclerosis
• Tropical spastic paraparesis
TREATMENT
GENERAL MEASURES
• Outpatient initially, may ultimately need nursing home placement and/or hospice
• Supportive care is necessary for complicating emergencies (aspiration, respiratory failure). Use of a respirator is a major ethical dilemma. Consideration should be given to those with selective respiratory dysfunction.
• Discussion of advance directive, focusing on patient's specific values about which interventions to be used, is critical to meeting the patients needs.
• Prosthetic devices (e.g., wheelchair)
Diet
Modify as tolerated; tube feedings may be necessary
Activity
As tolerated
SPECIAL THERAPY
Therapeutic trials of the efficacy of antioxidants (vitamins E and C and beta-carotene), nerve growth factor, gabapentin, myotrophin, and thyrotropin-releasing hormone have been undertaken. Reports are not encouraging.
MEDICATION (DRUGS)
Riluzole produces a slight prolongation in life expectancy by decreasing the release of glutamate.
FOLLOW-UP
PROGNOSIS
• ALS usually results in death within 5 years.
• Patients who predominantly manifest progressive muscular atrophy have a better prognosis.
• There have been reports of spontaneous arrest of the disease.
COMPLICATIONS
• Aspiration pneumonia
• Decubitus ulcers
• Pulmonary embolism
• Nutritional deficiency
PATIENT MONITORING
• Initially every 3 months, frequency to be increased as needed for symptomatic therapy
• Patients with a presumed diagnosis of ALS should have imaging of the cervical spine and electrodiagnostic studies.
REFERENCES
1. Brown WF, Botton CF. Clinical Electromyography. 2nd ed. Boston, MA: Butterworth-Heinemann; 1993.
2. Rowland LD, ed. Merritt's Textbook of Neurology. 9th ed. Philadelphia, PA: Williams  Wilkins; 1995.
MISCELLANEOUS
Also referred to as Mill's variant (unilateral involvement)