More MS news articles for July 2000

Heterogeneity of Multiple Sclerosis Lesions: Implications for the Pathogenesis of Demyelination

From
Annals of Neurology
June 2000 (Volume 47, Number 6)
Lucchinetti C, Brück W, Parisi J, et al
Ann Neurol. 2000;47:707-717.

Multiple Sclerosis (MS) is an idiopathic demyelinating disease that affects the central nervous system (CNS). It commonly causes disability in young adults and the clinical course is unpredictable. The variation of the disease within individuals and among groups affected with MS has led some to suggest a multifactorial etiology rather than a solitary cause. Lucchinetti and colleagues conducted a pathological analysis of actively demyelinating lesions from patients with MS to determine the patterns of demyelination.

The samples were collected from 3 international centers and comprised 51 biopsies and 32 autopsies. All of the cases met the neuropathological diagnostic criteria of inflammatory demyelinating disease compatible with MS. The mean duration of the clinical course before the autopsy was 39 months and the mean interval between the first symptom and biopsy was 9 months. The total follow-up period for the biopsy cases was 37 months.

Four different patterns of demyelination were detected. Although all of the lesions had evidence of inflammatory infiltration by macrophages and T lymphocytes, different distinct patterns were discovered on the basis of myelin protein loss, immunopathologic evidence of complement activation, plaque distribution and patterns of oligodendrocyte destruction. Patterns I and II shared similar characteristics. The active demyelination occurred in association with a T-lymphocyte and macrophage-dominated inflammatory pattern. Pattern II was distinguished from pattern I by the prominent deposition of immunoglubulins (mainly IgG) and complement C9neo antigen at the active site of myelin destruction. The demyelinated plaques of patterns I and II were typically centered on small venules and veins and had sharply demarcated edges with perivenous extensions. Patterns III and IV displayed a prominent loss of oligodendrocytes at the active plaque borders. The pattern of demyelination suggested a viral or toxin-induced etiology rather than an autoimmune process. The patterns identified were homogenous within patient specimens, but heterogeneous between different samples (patients). No evidence was found for heterogeneity within the autopsy of an individual specimen.

The most frequent pattern identified in the series was pattern II, followed by patterns III, I, and IV. Follow-up information was available on 43 of the patients who had biopsies. Thirty-three developed clinically definite MS (Poser criteria) and 6 displayed a monophasic illness with recovery and no further events up until the last follow-up (up to 36 months after disease onset). Four of the 43 patients died in the acute phase of the disease process.

Although 4 fundamentally different patterns of demyelination were found, there was no direct link to specific pathogenetic mechanisms. Despite the absence of a direct connection to the cause of multiple sclerosis, the heterogeneity found in MS lesions may provide further understanding of the disease process and lead to potent therapeutic treatments.