[Amyotrophic lateral sclerosis. Multisystem degeneration]

Abstract

Background: There is increasing evidence that amyotrophic lateral sclerosis (ALS) has to be regarded as multisystem degeneration rather than as purely a motor neuron disease, as it also includes various dnonmotor symptoms. This modern view has been confirmed by neuropathological and imaging findings.

Objectives: To review recent findings supporting the idea of multisystem degeneration and to describe the implications for diagnostics and therapy.

Methods: A discussion of recent clinical, imaging, and neuropathological findings is presented.

Results: Symptoms of ALS include not only motor symptoms but also cognitive impairment, oculomotor abnormalities, and extrapyramidal and sensory symptoms. As a neuropathological correlate, a systematic spreading of "transactive response DNA binding protein 43 kDa" (TDP-43) over functionally connected cortical structures has been described.

Conclusions: Nonmotor symptoms are regularly seen in ALS, although they usually do not dominate the clinical picture. Recent neuropathological findings offer new perspectives for diagnostics and therapy in ALS.

Keywords: Amyotrophic lateral sclerosis; DNA-binding proteins; Motor neuron disease; Nervous system diseases; Protein TDP-43.