Retroviruses and amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive, invariably fatal neurologic disorder resulting from upper and lower motor neuron degeneration, which typically develops during the sixth or seventh decade of life, and is diagnosed based on standard clinical criteria. Its underlying cause remains undetermined. The disease may occur with increased frequency within certain families, often in association with specific genomic mutations, while some sporadic cases have been linked to environmental toxins or trauma. Another possibility, first proposed in the 1970s, is that retroviruses play a role in pathogenesis. In this paper, we review the published literature for evidence that ALS is associated either with infection by an exogenous retrovirus or with the expression of human endogenous retroviral (HERV) sequences in cells of the central nervous system. A small percentage of persons infected with the human immunodeficiency virus-1 (HIV-1) or human T cell leukemia virus-1 (HTLV-1) develop ALS-like syndromes. While HTLV-1 associated ALS-like syndrome has several features that may distinguish it from classical ALS, HIV-infected patients may develop neurological manifestations that resemble classical ALS although it occurs at a younger age and they may show a dramatic improvement following the initiation of antiretroviral therapy. However, most patients with probable or definite ALS show no evidence of HIV-1 or HTLV-1 infection. In contrast, recent reports have shown a stronger association with HERV, as analysis of serum samples, and postmortem brain tissue from a number of patients with a classical ALS has revealed significantly increased expression of HERV-K, compared to controls. These findings suggest that endogenous retroviral elements are involved in the pathophysiology of ALS, but there is no evidence that they are the primary cause of the syndrome.

HIV-associated motor neuron disease

“…1 In the present case series, 3 patients showed improvement in symptoms after either initiation of or increased compliance of their ARV regimen. Two others showed prolonged survival although the symptoms continued to progress.…”

“…24 While the clinical presentation of HIV-associated MND is indistinguishable from sporadic ALS, the patients with HIV are typically younger, nearly all the cases are younger than 40 years of age at the time of onset of neurologic symptoms, and most of these patients are male. 1 Similarly, all the patients reported here are male. This likely reflects the epidemiology of HIV infection in the United States.…”

“…In a prior literature review, we had identified 29 cases. 1 Since then, one case of HIV infection and ALS-like disorder 22 and another 7 cases with a lower motor neuron disorder have been reported. 22,23 In one study of 1,700 patients with HIV infection, the prevalence of HIV-associated ALS was estimated as 3.5 cases/ 1,000 patients.…”

“…Of interest, the majority of these patients show variable degrees of response to antiretroviral (ARV) drugs with nearly complete reversal in some. [1][2][3][4][5][6][7] However, in these case reports, long-term follow-up is not available and the pathophysiology is unknown.…”

Teaching Neuro images : Snake eyes appearance in MRI in patient with ALS

“…The decision to subspecialize is a highly personal decision that may not be driven by patient demand. 2 This, in addition to the geographic distribution of neurologists demonstrated by Dall et al, could lead to an oversupply in a few subspecialties and a shortfall in others. All of this will be in the context of upcoming economic challenges described in the recent report by the American Academy of Neurology Workforce Task Force.…”