[Motor neuron diseases. Present]

Recent progress in our understanding of motor neuron diseases, particularly those of degenerative pathogenesis such as spinal muscular atrophies (SMA) and amyotrophic lateral sclerosis (ALS), have to be described as historic. They are essentially of three types: 1) In first place are advances afforded by molecular genetics both in SMA (with the discovery of survival motor neurons and neuronal apoptosis inhibitor protein, which are markers of the disease and their pathogenetic mechanism) and in ALS (with the discovery of the super oxide dismutase [SOD1] gene, involved in the genesis of familial forms of ALS and other types of SMA such as certain forms of familial juvenile ALS, bulbar-spinal atrophy with gynecomasty and others). 2) In second place are biological data detailing the mechanisms of neuron death, whether programed or not, and emphasizing the importance of the so-called trophic or neurotrophin factors-whether nerve growth factor, brain-derived-neurotrophic factor, neurotrophin-3 or others whose effect of preventing neuron death has been demonstrated in vitro-as well as that of other substances such as Ca(2+)-activated neutral protease, which stabilizes synapses during development. It is assumed that one or another of these data will lead to therapeutic strategies for blocking the cascade of events that lead to neuron degeneration. 3) Finally, the strong impact of neuroimmunology in the field of neuromuscular pathology has been of interest mainly in neurogenic diseases marked purely and essentially be motor expression. As markers and pathogens, antiganglioside antibodies must necessarily be determined at this time in such entities as multifocal motor neuropathy, Guillain-Barré syndrome, acute axon motor neuropathy, Miller-Fisher syndrome and others, as their presence can inform therapeutic approaches. These three aspects and others currently under discussion will be treated in this course. At the same time the basic diagnostic aspects of motor neuron diseases will be emphasized: electrophysiologic assessment, on the one hand, and clinical features on the other. Establishing an exhaustive classification of SMA, from the earliest forms of infancy to adult types, is of great priority, as is exposing the full range of SMA according to whether distal or proximal predominance of atrophy is present. Our current understanding of the field is summarized in ten chapters on degenerative motor neuron diseases.