BMJ 1994;308:1541-1543 (11 June)

Papers

Sequences specific for enterovirus detected in spinal cord from patients with motor neurone disease

C J Woodall, M H Riding, D I Graham, G B Clements 

Department of Veterinary Pathology, Royal (Dick) School of Veterinary Studies, Edinburgh EH9 1QH Scottish Serum Bank, Centre for Infection and Environmental Health, Ruchill Hospital, Glasgow G20 9NB Regional Virus Laboratory, Ruchill Hospital, Glasgow G20 9NB Department of Neuropathology, Institute Neurological Sciences, Southern General Hospital, Glasgow G51 4TF Correspondence to: Dr Clements.

Abstract

Objective : To investigate the association of enteroviruses with motor neurone disease, also known as amyotrophic lateral sclerosis.
Design : Analysis by enterovirus polymerase chain reaction of wax embedded material from spinal cords taken at necropsy from subjects with motor neurone disease and from age and sex matched controls. Setting - Specimens were collected in the west of Scotland and in London between 1982 and 1992.
Results : Sequences specific for a non-poliovirus type enterovirus were detected in spinal cord tissue from subjects with motor neurone disease. Amplification of a 414 base RNA target sequence in the conserved enterovirus 5' untranslated region from wax embedded tissue sections was successful in tissue from eight of 11 cases of sporadic motor neurone disease, one of two cases of familial motor neurone disease, and the one case of poliomyelitis, but not in the six matched controls or one case of antecedent poliomyelitis. In addition, sequences were detected in spinal cords from one monkey infected with wild type poliovirus and one monkey infected with polio vaccine. Comparison of sequences from cases of motor neurone disease with sequences of corresponding regions of the 5' untranslated regions of known picornaviruses showed them to be tightly grouped within the enterovirus genus closely related to coxsackievirus type B but not to polioviruses. Sequences derived from different parts of the spinal cord of the same subjects were identical, but sequences differed between individual subjects.
Conclusions : Conserved enteroviral sequences closely related to coxsackie B virus sequences were detectable in spinal cords from subjects with sporadic motor neurone disease and from one subject with possible familial motor neurone disease.

Clinical implications

  • Clinical implications

  • Indirect evidence has previously been available implicating enteroviruses in the aetiology of motor neurone disease

  • Nucleic acid sequences specific for enterovirus were detected in the spinal cords of eight of 11 cases of sporadic motor neurone disease and one of two cases of putative familial motor neurone disease

  • Sequences show a close relation to coxsackievirus B sequences

  • No sequences were detected in samples from six matched controls

  • Sequences derived from different parts of the spinal cord of the same subject were identical but they differ between individual subjects


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Relevant Article

Enterovirus hypothesis for motor neurone disease
N R Swanson, S A Fox, and F L Mastaglia
BMJ 1994 309: 743. [Extract] [Full Text]

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