Pathologic heterogeneity persists in early active multiple sclerosis lesions

Imke Metz, Stephen D. Weigand, Bogdan F.G. Popescu, Josa M. Frischer, Joseph E. Parisi, Yong Guo, Hans Lassmann, Wolfgang Brück, Claudia F. Lucchinetti

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


Objective Multiple sclerosis (MS) lesions demonstrate immunopathological heterogeneity in patterns of demyelination. Previous cross-sectional studies reported immunopatterns of demyelination were identical among multiple active demyelinating lesions from the same individual, but differed between individuals, leading to the hypothesis of intraindividual pathological homogeneity and interindividual heterogeneity. Other groups suggested a time-dependent heterogeneity of lesions. The objective of our present study was to analyze tissue samples collected longitudinally to determine whether patterns of demyelination persist over time within a given patient. Methods Archival tissue samples derived from patients with pathologically confirmed central nervous system inflammatory demyelinating disease who had undergone either diagnostic serial biopsy or biopsy followed by autopsy were analyzed immunohistochemically. The inclusion criteria consisted of the presence of early active demyelinating lesions - required for immunopattern classification - obtained from the same patient at 2 or more time points. Results Among 1,321 surgical biopsies consistent with MS, 22 cases met the study inclusion criteria. Twenty-one patients (95%) showed a persistence of immunopathological patterns in tissue sampled from different time points. This persistence was demonstrated for all major patterns of demyelination. A single patient showed features suggestive of both pattern II and pattern III on biopsy, but only pattern II among all active lesions examined at autopsy. Interpretation These findings continue to support the concept of patient-dependent immunopathological heterogeneity in early MS and suggest that the mechanisms and targets of tissue injury may differ among patient subgroups. These observations have potentially significant implications for individualized therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)728-738
Number of pages11
JournalAnnals of neurology
Issue number5
StatePublished - May 2014

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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