Amyotrophic Lateral Sclerosis

Abstract

This chapter was originally intended to cover both amyotrophic lateral sclerosis (ALS) and multiple sclerosis, but we will concentrate on ALS. There are nonetheless several reports from the literature that ionotropic glutamate receptor antagonists have beneficial effects in animal models of multiple sclerosis (1,7,14,58,71,109) and this could develop into a very promising therapeutic area in the future. The interested reader is referred to the following review (59). However, the evidence for involvement of disturbances in the glutamatergic system in ALS is already convincing and has led to the use of the glutamate release inhibitor riluzole in the treatment of this disease. As such, we felt that a book on the therapeutic potential of ionotropic glutamate receptor antagonists and modulators would be incomplete without a chapter on this disease. RATIONALEALS, commonly called Lou Gehrig's disease, is a devastating neurological disorder characterized by selective upper and lower somatic, but not autonomic, motor neurone degeneration leading to paralysis and eventually death. The diagnosis of ALS requires the presence of both upper and lower motor neurone degeneration and progressive motor dysfunction. ALS occurs in 1 to 2.5 cases per 100,000 population, affects more men than women, and is most commonly diagnosed in middle age. Other functions such as intellectual abilities and sensory perception are preserved. At advanced stages patients become completely disabled, often requiring ventilatory support and feeding by gas-

Prevalence of Amyotrophic Lateral Sclerosis — United States, 2012–2013

“…The age groups 60-69 years and 70-79 years are the most common ages of diagnosis and those aged 18-39 years are the least. This finding is consistent with reported literature in the United States and abroad (1,6,(36)(37)(38)(39)(40)(41)(42)(43).…”

Prevalence of Amyotrophic Lateral Sclerosis — United States, 2012–2013

“…The age groups 60-69 years and 70-79 years are the most common ages of diagnosis and those aged 18-39 years are the least. This finding is consistent with reported literature in the United States and abroad (1,6,(36)(37)(38)(39)(40)(41)(42)(43).…”

A4T Mutation in the <i>SOD1</i> Gene Causing Familial Amyotrophic Lateral Sclerosis

“…In the review of Mitsumoto et al [10], only 37% of 1,746 ALS patients from 4 series had their initial symptoms in the legs, and this was the observation in the majority of our patients (11/13). Lower motor neuron signs have been predominant.…”

Time-course and characterization of orolingual motor deficits in B6SJL-Tg(SOD1-G93A)1Gur/J mice

“…When tongue motility and force were evaluated as a function of individual baseline performance, we found that the majority of these mice exhibited a tongue motility-only deficit. This differs from disease progression in ALS patients, in which tongue force deficits occur earlier and are more prevalent than motility deficits (DePaul et al, 1988;Mitsumoto et al, 1998;Langmore and Lehman, 1994). This difference may be explained by the lack of a tongue force challenge in this experiment.…”

Prevalence of Amyotrophic Lateral Sclerosis — United States, 2012–2013

“…The age groups 60-69 years and 70-79 years are the most common ages of diagnosis and those aged 18-39 years are the least. This finding is consistent with reported literature in the United States and abroad (1,6,(36)(37)(38)(39)(40)(41)(42)(43).…”

A4T Mutation in the <i>SOD1</i> Gene Causing Familial Amyotrophic Lateral Sclerosis

“…In the review of Mitsumoto et al [10], only 37% of 1,746 ALS patients from 4 series had their initial symptoms in the legs, and this was the observation in the majority of our patients (11/13). Lower motor neuron signs have been predominant.…”

Time-course and characterization of orolingual motor deficits in B6SJL-Tg(SOD1-G93A)1Gur/J mice

“…When tongue motility and force were evaluated as a function of individual baseline performance, we found that the majority of these mice exhibited a tongue motility-only deficit. This differs from disease progression in ALS patients, in which tongue force deficits occur earlier and are more prevalent than motility deficits (DePaul et al, 1988;Mitsumoto et al, 1998;Langmore and Lehman, 1994). This difference may be explained by the lack of a tongue force challenge in this experiment.…”

Prevalence of Amyotrophic Lateral Sclerosis — United States, 2012–2013

“…The age groups 60-69 years and 70-79 years are the most common ages of diagnosis and those aged 18-39 years are the least. This finding is consistent with reported literature in the United States and abroad (1,6,(36)(37)(38)(39)(40)(41)(42)(43).…”

A4T Mutation in the <i>SOD1</i> Gene Causing Familial Amyotrophic Lateral Sclerosis

“…In the review of Mitsumoto et al [10], only 37% of 1,746 ALS patients from 4 series had their initial symptoms in the legs, and this was the observation in the majority of our patients (11/13). Lower motor neuron signs have been predominant.…”

Time-course and characterization of orolingual motor deficits in B6SJL-Tg(SOD1-G93A)1Gur/J mice

“…When tongue motility and force were evaluated as a function of individual baseline performance, we found that the majority of these mice exhibited a tongue motility-only deficit. This differs from disease progression in ALS patients, in which tongue force deficits occur earlier and are more prevalent than motility deficits (DePaul et al, 1988;Mitsumoto et al, 1998;Langmore and Lehman, 1994). This difference may be explained by the lack of a tongue force challenge in this experiment.…”