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Amyotrophic Lateral Sclerosis (ALS)

Oculomotor Dysfunction in Amyotrophic Lateral Sclerosis: A Comprehensive Review

Although traditionally regarded as spared, a range of oculomotor dysfunction has been recorded in patients with amyotrophic lateral sclerosis. The apparent resistance to pathologic involvement of oculomotor control pathways in most patients with ALS has prompted comparative study to establish the key pathways that underlie motor neuronal vulnerability, with the hope of generating novel therapeutic strategies. Developments in the assessment of oculomotor function, including portable eye-tracking devices, have revealed more subtle impairments in ALS in relation to phenotype, which can now be better understood through parallel elucidation of the normal cerebral oculomotor control network. Given the clinicopathologic overlap between ALS and some types of frontotemporal dementia, the study of oculomotor function has particular value in probing the variable but consistent cognitive impairment seen in ALS and that reflects frontotemporal extramotor cerebral abnormalities. The study of oculomotor dysfunction holds significant promise as an additional source of much needed prognostic, monitoring, and mechanistic biomarkers for ALS. 

Eye movements are traditionally regarded as spared from involvement in most cases of amyotrophic lateral sclerosis, despite progressive weakness of limb, respiratory, and bulbar musculature. The pervasive nature of the networks that mediate oculomotor function, which lie outside the traditional regions that characterize ALS abnormalities, and the increased sophistication and practicality of eye-tracking equipment make this an attractive tool for the study of various aspects of ALS pathogenesis, particularly because it can be performed in patients unable to communicate. This review article explores what is known about normal oculomotor control, the nature of oculomotor dysfunction observed in ALS to date and how this might inform our understanding of regional pathologic abnormalities and current concepts of neuronal vulnerability, and the potential of eye tracking to generate biomarkers of extramotor cerebral involvement in ALS. Normal oculomotor pathways. This included all 3 patients with ophthalmoplegia but notably also 4 of 5 with dementia, demonstrating that oculomotor dysfunction might also serve as an independent marker of wider cerebral involvement and cognitive impairment in ALS. 

The finding of mutations of the SOD1 gene in approximately 20% of familial cases of ALS led to the development of SOD1 transgenic mouse models of ALS abnormalities. 27,28 Moreover, retrovirally induced expression of calbindin D conferred resistance to motor neurons exposed to sera from patients with ALS,29 and neurotransmitter release from motor neuron terminals in response to sera derived from patients with ALS was found to occur in spinal but not oculomotor motor neuron terminals. Oculomotor dysfunction was described as early as 1925 in a case of ALS said to have occurred with convergent strabismus that progressed to complete ophthalmoplegia. Slow vertical saccades were noted to be common in ALS-FTD,41 and another study42 suggested that oculomotor dysfunction in ALS might reflect the incidence of secondary abnormalities, such as parkinsonism. Hayashi H, Kato S. Total manifestations of amyotrophic lateral sclerosis: ALS in totally locked-in state. 

Keywords: [“ALS”,”oculomotor”,”patients”]
Source: https://jamanetwork.com/journals/jamaneurology/fullarticle/1107799

Formaldehyde Exposure May Pose Risk for Amyotrophic Lateral Sclerosis

CHICAGO- Preliminary results suggest that exposure to the chemical formaldehyde may increase the risk for amyotrophic lateral sclerosis, according to a report at the 60th Annual Meeting of the American Academy of Neurology. Researchers found that people with more than 10 years of exposure to formaldehyde had a 4.1 times increased risk for ALS, compared with those who had no exposure. Exposure to Chemicals and Risk for ALSPrior research has suggested that environmental toxins, including pesticides, may be associated with ALS. This notion has been backed by case-control and genetic studies implicating genes involved in pesticide detoxification, said Dr. Weisskopf. 

In the present investigation, Dr. Weisskopf’s group prospectively examined the relationship between regular exposure to 12 types of chemicals and ALS in 987,229 individuals who participated in the American Cancer Society-sponsored Cancer Prevention Study II. Participants were asked about their exposure to chemicals, including formaldehyde, in 1982, and they were then followed for approximately 15 years. The researchers also analyzed exposure to asbestos, acids/solvents, coal or stone dust, coal tar pitch/asphalt, diesel engine exhaust, dyes, gasoline exhaust, pesticides/herbicides, textile fibers/dust, wood dust, and x-ray/radioactive material. Regular formaldehyde exposure increased ALS risk by 34%. 

In addition, the longer the self-reported exposure to formaldehyde, the higher the risk for ALS. Thus, compared with those reporting no exposure, the adjusted relative risk for ALS was 1.5 in individuals who reported less than four years of exposure, 2.1 in those with four to 10 years of exposure, and 4.1 in those with more than 10 years of exposure. The study also found that an increased risk for ALS was seen with certain jobs. Individuals in these high-exposure jobs had a 28% greater risk for ALS. There are several possible mechanisms for formaldehyde neurotoxicity, said Dr. 

Weisskopf. Additional strengths of the study include its large size and uniform case ascertainment, as well as the fact that other factors that might contribute to ALS were controlled for, including sex, smoking status, military service, level of education, alcohol intake, occupation, vitamin E supplement use, and exposure to other chemicals. Possible limitations of the study include small numbers in some exposure categories, as well as self-assessment of exposure. Only mortality data were used to identify ALS cases. Dr. 

Weisskopf noted that because death certificates have been reported to accurately identify 70% to 80% of ALS-related deaths, they might be a reasonable surrogate for ALS incidence, due to the short survival time associated with the disease. 

Keywords: [“exposure”,”ALS”,”formaldehyde”]
Source: https://www.mdedge.com/neurology/article/73411/rare-diseases/formaldehyde-exposure-may-pose-risk-amyotrophic-lateral