Amyotrophic lateral sclerosis (ALS) is a motor neuron disease, which involves both upper and lower motor neurons. It includes a sporadic presentation in addition to >20 types of familial conditions. Familial ALS occurs in 5–10% of patients, including those with mutations in the C9ORF72, SOD1, and other genes. Other systems may be affected in addition to motor neurons in some patients with sporadic, as well as familial ALS. For example, patients with C9ORF72 mutation may present with frontotemporal dementia. These findings strongly suggest that ALS is not a single disease entity but represents a group of disorders that share features of motor neuron involvement.
Considering the background presented earlier, it is reasonable to conclude that muscle pathology is not homogeneous but invariably shows features of neurogenic atrophy. A pattern of small scattered groups of angulated muscle fibers is commonly observed in biopsy specimens obtained in the early stages of the disease. Architectural changes such as target/targetoid fibers, internal nuclei, and split fibers may be observed, although they are uncommon. A mild degree of inflammatory cell infiltration and small numbers of necrotic fibers are identified in a small percentage of patients during the progressive stage of the disease. Extensive fiber-type grouping is not usually observed.