Amyotrophic lateral sclerosis

© Springer-Verlag Berlin Heidelberg 2014. The core of the clinical syndrome of amyotrophic lateral sclerosis (ALS) is a progressive and typically rapid degeneration of a previously normally functioning motor system, comprising upper motor neurons (UMNs) of the primary motor cortex and corticospinal tract (CST), brainstem nuclei and the lower motor neurons (LMNs) arising from the anterior horns of the spinal cord. Weakness, with variable wasting, of the musculature of the limbs and of speech and swallowing ensues, with involvement of the diaphragm resulting in respiratory insuffi ciency and a median survival of 3 years. The marked clinical heterogeneity, frequent diagnostic delay and reliance of therapeutic trials on survival as the primary outcome measure make the discovery of biomarkers in ALS a research priority. Whilst the spinal anterior horns and corticospinal tract superfi cially appear to bear the brunt of histopathology in ALS, it has been clear for over half a century that degeneration extends to involve the extra-motor brain, preferentially involving areas of the frontal and temporal lobes having clinical and genetic overlap with some forms of frontotemporal dementia (FTD).