[Amyotrophic lateral sclerosis. Multisystem degeneration]

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.

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

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

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.

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.