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-

Spatial Assessment of the Association between Long-Term Exposure to Environmental Factors and the Occurrence of Amyotrophic Lateral Sclerosis in Catalonia, Spain: A Population-Based Nested Case-Control Study

“…However, only in some of them have environmental factors been suggested as a possible explanation for their occurrence [14, 48, 76-82]. This is particularly notable for exposure to metals [48, 77, 80, 81] and to agricultural chemicals [78-81], although exposure to industrial toxins [77] and to paper paste and water treatment plants [82] also appears. As early as 1977, Kilness and Hichberg [76] attributed selenium exposure over a period of 10 years to the small cluster (4 ALS cases that lived within 15 km of each other) that they identified in west-central South Dakota, USA.…”

“…As early as 1977, Kilness and Hichberg [76] attributed selenium exposure over a period of 10 years to the small cluster (4 ALS cases that lived within 15 km of each other) that they identified in west-central South Dakota, USA. Almost 30 years ago, Sienko et al [48] detected a cluster in a small fishing village next to Lake Michigan, USA, which is probably associated with a high intake of mercury. In addition to genetics, among the factors to which Sabel et al [80] attribute the existence of 2 significant clusters in south-eastern Finland (one at the time of death and other at the time of birth, of those who died between 1985 and 1995) and another in south-central Finland (at the time of death) is the exposure to heavy metals and agricultural chemicals.…”

“…Exposure to mercury may be linked to the aetiology of ALS [46, 47]. A case in point is the cluster located in a small fishing village next to Lake Michigan, the United States, where the fish had high levels of mercury [48]. The association of risk to ALS and the exposure to manganese is inconsistent.…”

Dietary ω-3 Polyunsaturated Fatty Acid Intake and Risk for Amyotrophic Lateral Sclerosis

“…All individuals with code 335.2 (motor neuron disease) listed as the underlying or contributing cause of death were considered to have had ALS. In a previous validation study, 17 it was found that ALS was the primary diagnosis listed on death certificates in the majority of instances where code 335.2 was listed as a cause or contributory cause of death. 17 …”

“…We requested permission to contact the treating neurologist and for release of relevant medical records from participants who reported a diagnosis of ALS on the open question on major illnesses or on the specific question. Because of the rapidly progressive nature of the disease (median survival 1.5 to 3 years), 15–17 many participants with ALS died before we could send the release request for medical records, so the request was sent to the closest family member. After obtaining permission, we asked the treating neurologists to complete a questionnaire to confirm the diagnosis of ALS and to rate the certainty of the diagnosis (definite, probable, or possible) and send medical records.…”