Amyotrophic lateral sclerosis: Idiopathic and inherited

This chapter discusses the history, epidemiology, etiology and pathogenesis, and pathophysiology of amyotrophic lateral sclerosis (ALS). It is the most common form of adult motor neuron disease. Amyotrophy comes from the Greek word meaning "without muscle nourishment," and asymmetric muscle atrophy can be one of the most obvious signs of the disease. The term "lateral sclerosis" refers to the appearance of the lateral columns of the spinal cord in pathology specimens. Factors suggested as predictors of survival include age at onset, gender, clinical presentation (bulbar vs spinal), and rate of disease progression. Age at onset appears to be a powerful predictor of disease duration, with younger patients surviving longer. Also, progression to death is faster among patients with bulbar onset. Neuroepidemiological studies have analyzed toxic exposures, heavy metal exposure, occupation, physical activities, electrocution injuries, smoking, and alcohol use, among other mechanisms. Although ALS is categorized as a motor neuron disease, the lower motor neurons of the spinal cord are not the only ones affected (as occurs in polio). ALS is a neurodegenerative disorder of both the upper motor neurons of the motor cortex and the lower motor neurons in the anterior horn of the spinal cord. The chapter also describes the structural details and symptoms in relation to pathophysiology and natural history of ALS.