Abstract and Introduction
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily affecting the upper and lower motor neurons. The lifetime risk of developing ALS is estimated at 1:350 for men and 1:500 for women, higher for those who have served in the military. The diagnosis remains clinical with electrodiagnostic support. Alternative diagnoses can usually be ruled out by the use of neuroimaging studies and laboratory evaluation. Perhaps because ALS is a diagnosis of exclusion, there is a substantial delay in diagnosis, upward of 12 months after the onset of symptoms, and most patients see three or more providers in the course of the diagnostic process. Once diagnosed, patients are best medically managed in a multidisciplinary care setting, an approach that has been shown to prolong survival and improve quality of life. Riluzole is the only disease-modifying therapy approved by the Food and Drug Administration, but numerous symptomatic therapies exist. In the past 20 years, ALS has become the focus of intense investigation by a worldwide community of basic scientists, and for clinical investigators the disease is an active area of research, with stem cell therapies, gene therapies, and a host of small molecule agents under investigation at various stages of clinical and preclinical development.
Introduction
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that is marked primarily by degeneration of upper motor neurons (UMNs) and lower motor neurons (LMNs). Degeneration of either UMNs or LMNs leads inexorably to weakness, the overriding symptom of the disease, which is associated with a variety of accompanying symptoms and signs. Lower motor neuron degeneration leads to muscle atrophy and fasciculations, while UMN degeneration leads to spasticity and increased reflex activity. For the clinician at the bedside, the presence of LMN and UMN findings in combination remains the clinical cornerstone of the diagnostic process.
Although motor neuron disease (MND) and ALS are diagnoses that are sometimes used interchangeably, MND is generally considered to denote a broad category of diseases affecting motor neurons including progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), flail arm syndrome (Vulpian-Bernhardt syndrome), flail leg syndrome (pseudopolyneuritic form), progressive bulbar palsy (PBP), and ALS with frontotemporal dementia (FTD); under the rubric of MND, ALS per se is the most common of these disorders.
The clinical diagnosis remains challenging and substantial diagnostic delays are typical. Although treatment options have expanded tremendously, riluzole remains the only proven therapy aimed at directly slowing disease progression. As a result, ALS is a field characterized by its pioneering research and focus on translation of scientific findings into clinical trials aimed at uncovering novel therapeutic strategies.
Semin Neurol. 2015;35(4):469-476. © 2015 Thieme Medical Publishers
