Amyotrophic lateral sclerosis: Clinical heterogeneity and approaches to classification

Abstract

Amyotrophic lateral sclerosis (ALS) is a clinically and pathogenically heterogenic disease. Clinical heterogeneity refers to the initial localization of the pathological process, the variability of the combination of signs of upper and lower motor neuronal damage, the age of the onset, the rate of progression, hereditary predisposition, and the presence of non-motor clinical manifestations. A large number of forms of the disease are described (primary lateral sclerosis, progressive muscular atrophy, progressive bulbar palsy, flail-arm syndrome, and others), which in some cases can be considered as independent diseases due to the localization of the pathological process, disease course and prognosis. In recent years, convincing evidences of the genetic and pathogenetic heterogeneity of ALS have also been obtained. Large heterogeneity makes it difficult to create a unified classification of ALS. Formal classifications used, for example, in the diagnostic criteria of El Escorial or the International Classification of Diseases of the 10th revision, do not take into account many of the important features of the disease. The article describes the clinical heterogeneity of ALS. The proposed classifications are compared. A new classification system that taking into account various features of the disease and can improves understanding of the diversity of ALS is described.

Keywords

• amyotrophic lateral sclerosis
• motor neuron disease
• primary lateral sclerosis
• progressive muscular atrophy
• progressive bulbar palsy
• clinical heterogeneity
• classification