Pathogenesis and cell biology of amyotrophic lateral sclerosis (ALS)

Published on July 1, 2014   31 min

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My name is Pietro Fratta, and I'm a neurologist and a researcher at the UCL Institute of Neurology and at the National Hospital for Neurology and Neurosurgery in London. Today we'll be talking about the pathogenesis and cell biology of the neurodegenerative disorder Amyotrophic Lateral Sclerosis, ALS.
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The fundamental feature of ALS is that it's characterized by the degeneration of both upper and lower motor neurons. Upper motor neurons are in the brain, and lower motor neurons are in the brain stem and in the spinal cord. Other motor neuron diseases involve either upper motor neurons, such as progressive lateral sclerosis and hereditary spastic paraplegia, or the lower motor neurons, such as primary muscular atrophy, spinobulbar muscular atrophy, or spinal muscular atrophy. Clinically, the loss of both upper and lower motor neurons contributes to the progressive weakness. The loss of upper motor neurons instead specifically causes spasticity and brink reflexes, whilst the loss of the lower motor neurons causes fasciculations and muscle wasting.
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So clinically, ALS has an incidence of 2 in 200,000. And this is uniform across Western countries. There's a lifetime risk of 1 in 1,000. And the age of onset is typically between 55 and 65 years of age. Onset can occur even earlier, and 5% of cases occur before the age of 30 years. There's a prevalence of males, with a male to female ratio of 1.5 to 1. And 5% of cases have also positive family history. Inheritance in these cases is mostly autosomal dominant. The onset most frequently occurs in the limbs, but a bulbar onset can occur in a fourth to a third of patients. All muscles are affected, with the exception of the extraocular muscles, and this means that all major functions are impaired, such as walking, the use of the upper limbs, swallowing, and breathing. In 5% of cases, frontotemporal dementia can occur. And 50% percent of patients indeed show cognitive impairment, although this is mild. Death occurs typically three to five years after onset, mostly due to respiratory insufficiency.
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Pathogenesis and cell biology of amyotrophic lateral sclerosis (ALS)

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