Abstract
Subclinical demyelinating lesions may occur in the brains of asymptomatic individuals, and the first-degree relatives of multiple sclerosis (MS) patients are at particular risk. Clinical and MRI examinations were performed in nine sibships from families with two or more cases of MS. These included 14 patients with clinically definite MS, three patients with clinically probable MS, and 27 asymptomatic siblings. Systematic criteria were applied to MRI interpretations to increase their specificity for MS. Thirteen (76%) of the 17 patients with MS showed lesions suggesting MS. Lesions were also found in six (38%) of the 16 asymptomatic siblings under age 50 and in eight (73%) of the 11 over age 50. Judged by stringent criteria, the lesions of only three (11%) of the 27 asymptomatic siblings were considered to be due to demyelination. The results demonstrate the occurrence of subclinical demyelination in asymptomatic siblings of MS patients and stress the importance of clinical follow up and MRI studies of the first-degree relatives when classifying them as healthy in family studies.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Cutler J. R., Aminoff M. J., Brant-Zawadzki M. Evaluation of patients with multiple sclerosis by evoked potentials and magnetic resonance imaging: a comparative study. Ann Neurol. 1986 Nov;20(5):645–648. doi: 10.1002/ana.410200518. [DOI] [PubMed] [Google Scholar]
- Dalakas M. C., Rose J. W., Paul J., Engel W. K., McClure J. E., Goldstein A. L. Increased circulation of T lymphocytes bearing surface thymosin alpha 1 in patients with myasthenia gravis: effect of thymectomy. Neurology. 1983 Feb;33(2):144–149. doi: 10.1212/wnl.33.2.144. [DOI] [PubMed] [Google Scholar]
- Duquette P., Charest L. Cerebrospinal fluid findings in healthy siblings of multiple sclerosis patients. Neurology. 1986 May;36(5):727–729. doi: 10.1212/wnl.36.5.727. [DOI] [PubMed] [Google Scholar]
- Fazekas F., Offenbacher H., Fuchs S., Schmidt R., Niederkorn K., Horner S., Lechner H. Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis. Neurology. 1988 Dec;38(12):1822–1825. doi: 10.1212/wnl.38.12.1822. [DOI] [PubMed] [Google Scholar]
- Gebarski S. S., Gabrielsen T. O., Gilman S., Knake J. E., Latack J. T., Aisen A. M. The initial diagnosis of multiple sclerosis: clinical impact of magnetic resonance imaging. Ann Neurol. 1985 May;17(5):469–474. doi: 10.1002/ana.410170509. [DOI] [PubMed] [Google Scholar]
- Giesser B. S., Kurtzberg D., Vaughan H. G., Jr, Arezzo J. C., Aisen M. L., Smith C. R., LaRocca N. G., Scheinberg L. C. Trimodal evoked potentials compared with magnetic resonance imaging in the diagnosis of multiple sclerosis. Arch Neurol. 1987 Mar;44(3):281–284. doi: 10.1001/archneur.1987.00520150035017. [DOI] [PubMed] [Google Scholar]
- Gilbert J. J., Sadler M. Unsuspected multiple sclerosis. Arch Neurol. 1983 Sep;40(9):533–536. doi: 10.1001/archneur.1983.04050080033003. [DOI] [PubMed] [Google Scholar]
- Goodkin D. E., Doolittle T. H., Hauser S. S., Ransohoff R. M., Roses A. D., Rudick R. A. Diagnostic criteria for multiple sclerosis research involving multiply affected families. Arch Neurol. 1991 Aug;48(8):805–807. doi: 10.1001/archneur.1991.00530200041016. [DOI] [PubMed] [Google Scholar]
- Hendrie H. C., Farlow M. R., Austrom M. G., Edwards M. K., Williams M. A. Foci of increased T2 signal intensity on brain MR scans of healthy elderly subjects. AJNR Am J Neuroradiol. 1989 Jul-Aug;10(4):703–707. [PMC free article] [PubMed] [Google Scholar]
- Hunt A. L., Orrison W. W., Yeo R. A., Haaland K. Y., Rhyne R. L., Garry P. J., Rosenberg G. A. Clinical significance of MRI white matter lesions in the elderly. Neurology. 1989 Nov;39(11):1470–1474. doi: 10.1212/wnl.39.11.1470. [DOI] [PubMed] [Google Scholar]
- Jacobs L., Kinkel W. R., Polachini I., Kinkel R. P. Correlations of nuclear magnetic resonance imaging, computerized tomography, and clinical profiles in multiple sclerosis. Neurology. 1986 Jan;36(1):27–34. doi: 10.1212/wnl.36.1.27. [DOI] [PubMed] [Google Scholar]
- Kinnunen E., Wikström J., Porras J., Palo J. The epidemiology of multiple sclerosis in Finland: increase of prevalence and stability of foci in high-risk areas. Acta Neurol Scand. 1983 May;67(5):255–262. doi: 10.1111/j.1600-0404.1983.tb04574.x. [DOI] [PubMed] [Google Scholar]
- Lechner H., Schmidt R., Bertha G., Justich E., Offenbacher H., Schneider G. Nuclear magnetic resonance image white matter lesions and risk factors for stroke in normal individuals. Stroke. 1988 Feb;19(2):263–265. doi: 10.1161/01.str.19.2.263. [DOI] [PubMed] [Google Scholar]
- Lynch S. G., Rose J. W., Smoker W., Petajan J. H. MRI in familial multiple sclerosis. Neurology. 1990 Jun;40(6):900–903. doi: 10.1212/wnl.40.6.900. [DOI] [PubMed] [Google Scholar]
- Mackay R. P., Myrianthopoulos N. C. Multiple sclerosis in twins and their relatives. Arch Neurol. 1966 Nov;15(5):449–462. doi: 10.1001/archneur.1966.00470170003001. [DOI] [PubMed] [Google Scholar]
- McDonald W. I. Diagnosis of multiple sclerosis. BMJ. 1989 Sep 9;299(6700):635–637. doi: 10.1136/bmj.299.6700.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nuwer M. R., Visscher B. R., Packwood J. W., Namerow N. S. Evoked potential testing in relatives of multiple sclerosis patients. Ann Neurol. 1985 Jul;18(1):30–34. doi: 10.1002/ana.410180106. [DOI] [PubMed] [Google Scholar]
- Ormerod I. E., Roberts R. C., du Boulay E. P., McDonald W. I., Callanan M. M., Halliday A. M., Johnson G., Kendall B. E., Logsdail S. J., Macmanus D. G. NMR in multiple sclerosis and cerebral vascular disease. Lancet. 1984 Dec 8;2(8415):1334–1335. doi: 10.1016/s0140-6736(84)90836-5. [DOI] [PubMed] [Google Scholar]
- PRATT R. T. C., COMPSTON N. D., McALPINE D. The familial incidence of disseminated sclerosis and its significance. Brain. 1951;74(2):191–232. doi: 10.1093/brain/74.2.191. [DOI] [PubMed] [Google Scholar]
- Palo J., Ketonen L., Wikström J. A follow-up study of very low field MRI findings and clinical course in multiple sclerosis. J Neurol Sci. 1988 Apr;84(2-3):177–187. doi: 10.1016/0022-510x(88)90123-2. [DOI] [PubMed] [Google Scholar]
- Paty D. W., Oger J. J., Kastrukoff L. F., Hashimoto S. A., Hooge J. P., Eisen A. A., Eisen K. A., Purves S. J., Low M. D., Brandejs V. MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT. Neurology. 1988 Feb;38(2):180–185. doi: 10.1212/wnl.38.2.180. [DOI] [PubMed] [Google Scholar]
- Phadke J. G., Best P. V. Atypical and clinically silent multiple sclerosis: a report of 12 cases discovered unexpectedly at necropsy. J Neurol Neurosurg Psychiatry. 1983 May;46(5):414–420. doi: 10.1136/jnnp.46.5.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SCHAPIRA K., POSKANZER D. C., MILLER H. Familial and conjugal multiple sclerosis. Brain. 1963 Jun;86:315–332. doi: 10.1093/brain/86.2.315. [DOI] [PubMed] [Google Scholar]
- Sadovnick A. D., Baird P. A., Ward R. H. Multiple sclerosis: updated risks for relatives. Am J Med Genet. 1988 Mar;29(3):533–541. doi: 10.1002/ajmg.1320290310. [DOI] [PubMed] [Google Scholar]
- Sola P., Scarpa M., Faglioni P., Sorgato P., Merelli E. Diagnostic investigations in MS: which is the most sensitive? Acta Neurol Scand. 1989 Nov;80(5):394–399. doi: 10.1111/j.1600-0404.1989.tb03900.x. [DOI] [PubMed] [Google Scholar]
- Uitdehaag B. M., Polman C. H., Valk J., Koetsier J. C., Lucas C. J. Magnetic resonance imaging studies in multiple sclerosis twins. J Neurol Neurosurg Psychiatry. 1989 Dec;52(12):1417–1419. doi: 10.1136/jnnp.52.12.1417. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wikström J., Palo J. Studies on the clustering of multiple sclerosis in Finland I: Comparison between the domiciles and places of birth in selected subpopulations. Acta Neurol Scand. 1975 Feb;51(2):85–98. doi: 10.1111/j.1600-0404.1975.tb01362.x. [DOI] [PubMed] [Google Scholar]
- Williams A., Eldridge R., McFarland H., Houff S., Krebs H., McFarlin D. Multiple sclerosis in twins. Neurology. 1980 Nov;30(11):1139–1147. doi: 10.1212/wnl.30.11.1139. [DOI] [PubMed] [Google Scholar]
- Yetkin F. Z., Haughton V. M., Papke R. A., Fischer M. E., Rao S. M. Multiple sclerosis: specificity of MR for diagnosis. Radiology. 1991 Feb;178(2):447–451. doi: 10.1148/radiology.178.2.1987607. [DOI] [PubMed] [Google Scholar]