Purpose of Review: This article reviews the clinical features, diagnostic pathway, therapies, and current understanding of the pathophysiology of amyotrophic lateral sclerosis (ALS). The spectrum of motor neuron diseases is reviewed, and the clinical heterogeneity of ALS is described.

Recent Findings: ALS is increasingly recognized as a clinical spectrum disorder with pure upper and pure lower motor neuron presentations, supported by genetic links. The phenotypic variability is broad. Identification of ALS-related genes provides insights into disease mechanisms.

Summary: ALS is a progressive fatal multisystem neurodegenerative disease primarily affecting motor neurons. Clinical recognition of suspicious symptoms and the appropriate laboratory evaluation are essential to limit diagnostic delay and avoid unnecessary testing and procedures. ALS has broad genetic and hypothesized environmental causes and phenotypic variability. Recognizing related motor neuron diseases will prevent misdiagnosis while allowing proper disease counseling. Although ALS cannot be cured, implementation of appropriate symptomatic treatment is valuable.

Address correspondence to Dr Stephen Goutman, Department of Neurology, F2647 UH SOUTH, SPC 5223, 1500 E Medical Center Dr, Ann Arbor, MI 48109, [email protected].

Relationship Disclosure: Dr. Goutman has consulted for Cytokinetics, Inc, and has received research/grant support from the Agency for Toxic Substances and Disease Registry/Centers for Disease Control and Prevention; the ALS Association; the National Institutes of Health/National Institute of Environmental Health Sciences (K23ES027221); Neuralstem, Inc; and Target ALS.

Unlabeled Use of Products/Investigational Use Disclosure: Dr Goutman discusses the unlabeled/investigational use of amitriptyline, atropine, botulinium toxin, citalopram, and mexiletine for the symptomatic management of amyotrophic lateral sclerosis.