Trial of immunosuppression in amyotrophic lateral sclerosis using total lymphoid irradiation

Daniel B. Drachman, Vinay Chaudhry, David Cornblath, Ralph W. Kuncl, Alan Pestronk, Lora Clawson, E. David Mellits, Shirley Quaskey, Thomas Quinn, Allison Calkins, Stanley Order

Research output: Contribution to journalArticlepeer-review


Although the cause of amyotrophic lateral sclerosis (ALS) remains unknown, recent studies have suggested an autoimmune mechanism of pathogenesis. Previous trials of immunosuppressive treatment have yielded inconclusive results. Our study was designed to determine whether more powerful and prolonged immunosuppression, produced by total lymphoid irradiation (TLI), would alter the course of ALS. In a double‐blind, randomized, placebo‐controlled study, 30 patients with classic ALS were treated with TLI, and 31 were given sham radiation. Quantitative measurements of muscle strength, functional motor activity, and humoral and cellular immune status were followed for 2 years, or until death or respirator dependence. Motor function in the TLI‐treated and control groups showed no significant differences throughout the study. Overall survival was not significantly different in the TLI‐treated and control groups. TLI effectively suppressed cellular and humoral immune function throughout the 2‐year study period. Analysis of the relationship between immunosuppression and motor functions showed no consistent effect of treatment. We conclude that powerful and prolonged immunosuppression produced by TLI did not benefit patients with ALS. This fails to support the concept of an autoimmune mechanism of pathogenesis of ALS.

Original languageEnglish (US)
Pages (from-to)142-150
Number of pages9
JournalAnnals of neurology
Issue number2
StatePublished - Feb 1994

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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