Current status of the search for virus in amyotrophic lateral sclerosis (ALS)

Clinicians have noted resemblance between ALS with predominantly lower motor involvement and a chronic type of poliomyelitis. Occasional cases of ALS show lymphocytic infiltrations in the neuropathology. Cytoplasmic inclusion bodies as well as possible transmission of ALS to the monkey, were noted by Soviet investigators. Major questions about the latter remain, but inclusion bodies have been seen in cases outside the USSR, and search for a virus has been pursued. So far, efforts at culture, including the technique of co-cultivation, have not been successful in 3 different laboratories using material from ALS autopsied within 2 hours of death. Nor has such material and specimens from other cases produced transmissible disease in animals of laboratories where kuru, Jakob's disease and SSPE have been transmitted. Study of serum antibodies has also been negative. These negative culture, transmission and antibody studies do not exclude a viral etiology: in kuru, for example, many years passed before transmission was demonstrated, which remains the only evidence of kuru's infectivity. Evidence of an immunologic disorder in ALS has been obtained from kidney biopsies, the lack of any clinical benefit from immunosuppression may indicate that the kidney finding reveals a response to infection, though whether viral or even relevant is unknown. Two recent ALS cases will be illustrated in which virus-like particles were demonstrated post mortem by electronmicroscopy. In one, myxovirus-like tubules were seen mainly in motor neurons; in the other, picorna-virus-like crystals were found in skeletal muscles. Different viruses can cause identical disease, but 2 different viruses in different sites in ALS also suggest that at least one type of particle is an adventitious finding of no general significance. An additional impetus to continue the search is the slowly progressive type C-virus myelitis in wild mice. This disease has many dissimilarities to ALS, including different morphology of the virus, but may provide a model for slow-virus amyotrophy.