Clinical Features Neuropathology

With a worldwide prevalence of ~5 per 100,000, amyotropic lateral sclerosis (ALS) usually occurs in mid to late life and is manifest as progressive muscle weakness accompanied by hyperreflexia and spasticity associated with fibrillations, fasciculations, and giant polyphasic potentials. Muscle biopsies demonstrate denervation and muscle atrophy, and patients usually die of intercurrent illnesses. Muscle atrophy and weakness reflect selective degeneration of large motor neurons of the brain stem and spinal cord; spasticity, hyperreflexia, and extensor plantar signs are attributable to lesions of upper motor neurons.

Lower motor neurons show several abnormalities: the presence of phosphorylated neurofilament and ubiquitin immunoreactivities in inclusions within cell bodies, Lewy body-like intracytoplasmic inclusions, NF swellings of proximal axons, fragmentation of the Golgi, and attenuation of dendrites. In some cases of superoxide dismutase-1 (SOD1)-linked familial ALS (FALS), intracytoplasmic inclusions contain SOD1, ubiquitin, and neurofilament immunoreactivities, and neurofilaments accumulate in cell bodies and neuronal processes, particularly proximal axons. The roles of these inclusions are unclear. The presence of ubiquitin immunoreactivity suggests that these inclusions contain proteins destined for degradation, presumably in part via the proteosome. Whether components within these aggregates sequester essential molecules needed for the biology of motor neurons or whether the

Encyclopedia of the Human Brain Volume 3

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malfolded protein can perform aberrant catalytic reactions is unknown.

Motor nerves show axonal atrophy and Wallerian degeneration. Eventually, the numbers of motor neurons in brain stem nuclei and spinal cord are reduced and there is a loss of large pyramidal neurons in motor cortex. These lesions are accompanied by degeneration of axons in peripheral motor nerves and corticospinal tracts, respectively, and denervation of target fields of these axons. Although the mechanisms of neuronal death in ALS are poorly characterized, recent studies have documented that motor neuron degeneration structurally resembles the process of apoptosis. In ALS motor cortex and spinal cord anterior horn, there is evidence of DNA fragmentation, caspase-3 activation, and redistribution of cell death proteins such as Bcl-2, Bax, and Bak.

A variety of mechanisms, including excitotoxicity, copper toxicity, oxidation/nitration-mediated damage, protein misfolding, aggregation of critical components, apoptosis, calcium-mediated processes, and alterations in the biology of neurofilaments are among the processes that have been suggested to play roles in ALS and FALS.

Understanding And Treating Autism

Understanding And Treating Autism

Whenever a doctor informs the parents that their child is suffering with Autism, the first & foremost question that is thrown over him is - How did it happen? How did my child get this disease? Well, there is no definite answer to what are the exact causes of Autism.

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