Motor neuron disease: the bare essentials.

The existence of a large number of neurological diseases in which the motor neuron is the principal site of pathology suggests that these cells and their neuronal networks have a specific set of vulnerabilities. Recent research, largely based on relatively rare genetic forms of motor neuron disease, indicates that these cells are vulnerable to defects in excitotoxicity, RNA transport and splicing, axonal protein transport, mitochondrial function, protein misfolding and oxidative stress. The most important motor neuron disease is a largely sporadic, late onset, degenerative condition, known simply as motor neuron disease (MND) or more widely as amyotrophic lateral sclerosis (ALS), which currently remains untreatable and uniformly fatal. In essence, MND is a progressive motor syndrome with clinical evidence of upper motor neuron dysfunction (spasticity, brisk reflexes, extensor plantar responses) and denervation (muscle wasting, weakness and fasciculation). It is typically asymmetrical in onset and progresses in a non-random pattern suggesting a pathological process with a focal onset and anatomically contiguous spread. Although predominantly a motor disorder, there is evidence of multisystem involvement (especially cognitive, but occasionally sensory or autonomic). The diagnosis is clinical, although imaging is usually necessary to exclude structural pathology mimicking MND. Neurophysiology should not be considered to be a diagnostic test but can provide support for the presence of denervation and exclude other conditions such as pure motor inflammatory demyelinating neuropathies.