May is amyotrophic lateral sclerosis (ALS) awareness month.  ALS is the most common progressive neurodegenerative disease.  It is predicted that over 300,000 individuals in the current population of the United States will die due to ALS.  It has an incidence of 1-3/100,000 individuals and a prevalence of 3-5/100,000 individuals.  ALS is rapidly progressive, having a median survival of only 3-5 years, highlighting the need for advances in treatments.

The average onset of ALS occurs between 55-75 years of age for sporadic cases and 45-50 years of age for familial cases. Most cases of ALS are sporadic, with only 10% of cases being familial. The disease has a 1.5:1 predominance for males.  

ALS leads to death of both upper and lower motor neurons, leading to progressive loss of neurologic function.  Initial presentations vary due to differences in the predominance of upper and lower motor neuron findings.  Patients that initially manifest with upper or lower motor neuron loss may present with asymmetric distal limb weakness, leading to progressive muscles atrophy.  The disease progresses until virtually all muscles are involved.  Patients may also exhibit muscle twitching, fasciculations, spasticity, and hyperreflexia.  Patients that initially present with bulbar involvement may exhibit dysphagia and difficulty moving the facial muscles.  As patients experience degeneration of the corticobulbar projections innervating the brainstem, they may develop dysarthria.  They may also exhibit a pseudobulbar affect.  Patients with ALS typically demonstrate intact sphincter tone and well as bowel and bladder continence. The respiratory muscles are typically involved late in the disease process, with respiratory failure being the leading cause of death in patients with ALS.

ALS is diagnosed by clinical findings and data obtained from electrophysiology testing.  A muscle biopsy is not required for diagnosis.  The diagnosis of ALS requires signs of both upper and lower motor neuron degeneration.

Treatments for ALS are limited.  Riluzole is a glutamate inhibitor that may slow the progression of ALS.  Edaravone is a free radical and peroxynitrite scavenger approved by the FDA that may help reduce the disability associated with ALS, but impacts on survival were not included as an end-point by the studies performed. All other treatments aim to control the symptoms associated with progressive muscle weakness.   A select group of patients that demonstrate gammopathy may benefit from plasmapheresis and immunosuppression.

Read more:

Adams and Victor's Principles of Neurology, 11e: Chapter 38: Degenerative Diseases of the Nervous System

Harrison's Principles of Internal Medicine, 20e: Chapter 429: Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases

Quick Medical Diagnosis & Treatment 2019: Motor Neuron Disease, Degenerative