Abstract
OBJECTIVE—To understand the mechanisms causing neuronal death in amyotrophic lateral sclerosis (ALS), an electrophysiological technique of motor unit number estimation (MUNE) was used to examine the pattern of motor neuron loss in amyotrophic lateral sclerosis. The aim was to determine whether gradual lifelong loss of motor units precedes clinical disease or whether sudden, catastrophic loss of motor units occurs at the onset of the disease. METHOD—Using the statistical technique of motor unit number estimation, a cross sectional study was performed on a group of asymptomatic carriers of the Cu, Zn superoxide dimutase 1 (SOD1) gene. MUNE results were compared with those from age and sex matched family controls who did not carry the SOD1 mutation. A total of 87 subjects (45 men and 42 women) with an age range from 16-73 years of age were studied. RESULTS—There was no detectable difference in the number of motor units in SOD1 mutation carriers compared with SOD1 negative family controls or population controls. Symptomatic subjects showed a definite loss of motor units. The test-retest reproducibility of this technique yielded an average difference between MUNE results on separate occasions on the same subject of ±5%. CONCLUSION—The finding that presymptomatic SOD1 mutation carriers have a full complement of motor neurons indicates that mutation carriers must have normal survival of motor neurons until rapid and widespread cell death of these neurons occurs, coinciding with the onset of clinical features. This implies that symptomatic ALS is not the end result of a slow attrition of motor neurons.
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Selected References
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- Andersen P. M., Nilsson P., Keränen M. L., Forsgren L., Hägglund J., Karlsborg M., Ronnevi L. O., Gredal O., Marklund S. L. Phenotypic heterogeneity in motor neuron disease patients with CuZn-superoxide dismutase mutations in Scandinavia. Brain. 1997 Oct;120(Pt 10):1723–1737. doi: 10.1093/brain/120.10.1723. [DOI] [PubMed] [Google Scholar]
- Azzouz M., Leclerc N., Gurney M., Warter J. M., Poindron P., Borg J. Progressive motor neuron impairment in an animal model of familial amyotrophic lateral sclerosis. Muscle Nerve. 1997 Jan;20(1):45–51. doi: 10.1002/(sici)1097-4598(199701)20:1<45::aid-mus6>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
- Campbell M. J., McComas A. J., Petito F. Physiological changes in ageing muscles. J Neurol Neurosurg Psychiatry. 1973 Apr;36(2):174–182. doi: 10.1136/jnnp.36.2.174. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Daube J. R. Estimating the number of motor units in a muscle. J Clin Neurophysiol. 1995 Nov;12(6):585–594. doi: 10.1097/00004691-199511000-00005. [DOI] [PubMed] [Google Scholar]
- Felice K. J. A longitudinal study comparing thenar motor unit number estimates to other quantitative tests in patients with amyotrophic lateral sclerosis. Muscle Nerve. 1997 Feb;20(2):179–185. doi: 10.1002/(sici)1097-4598(199702)20:2<179::aid-mus7>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
- McComas A. J., Sica R. E., Campbell M. J., Upton A. R. Functional compensation in partially denervated muscles. J Neurol Neurosurg Psychiatry. 1971 Aug;34(4):453–460. doi: 10.1136/jnnp.34.4.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Olney R. K., Yuen E. C., Engstrom J. W. Statistical motor unit number estimation: reproducibility and sources of error in patients with amyotrophic lateral sclerosis. Muscle Nerve. 2000 Feb;23(2):193–197. doi: 10.1002/(sici)1097-4598(200002)23:2<193::aid-mus8>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
- Rosen D. R., Siddique T., Patterson D., Figlewicz D. A., Sapp P., Hentati A., Donaldson D., Goto J., O'Regan J. P., Deng H. X. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993 Mar 4;362(6415):59–62. doi: 10.1038/362059a0. [DOI] [PubMed] [Google Scholar]
- Sica R. E., McComas A. J., Upton A. R., Longmire D. Motor unit estimations in small muscles of the hand. J Neurol Neurosurg Psychiatry. 1974 Jan;37(1):55–67. doi: 10.1136/jnnp.37.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siddique T., Deng H. X. Genetics of amyotrophic lateral sclerosis. Hum Mol Genet. 1996;5(Spec No):1465–1470. doi: 10.1093/hmg/5.supplement_1.1465. [DOI] [PubMed] [Google Scholar]
- de Belleroche J., Orrell R., King A. Familial amyotrophic lateral sclerosis/motor neurone disease (FALS): a review of current developments. J Med Genet. 1995 Nov;32(11):841–847. doi: 10.1136/jmg.32.11.841. [DOI] [PMC free article] [PubMed] [Google Scholar]