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Lesion development in Marburg's type of acute multiple sclerosis: from inflammation to demyelination

Department of Neurology, Georg-August-University, Robert-Koch-Straûe 40, 37075 Göttingen, Germany

C Wegener

Department of Neuropathology, Georg-August-University, Robert-Koch-Straûe 40, 37075 Göttingen, Germany

C da Costa

Department of Neuropathology, Georg-August-University, Robert-Koch-Straûe 40, 37075 Göttingen, Germany

S Bunkowski

Department of Neuropathology, Georg-August-University, Robert-Koch-Straûe 40, 37075 Göttingen, Germany

C D Reimers

Department of Clinical Neurophysiology, Georg-August-University, Robert-Koch-Straße 40, 37075 Göttingen, Germany

H W Prange

Department of Neurology, Georg-August-University, Robert-Koch-Straûe 40, 37075 Göttingen, Germany

W Brück

Department of Neuropathology, Georg-August-University, Robert-Koch-Straûe 40, 37075 Göttingen, Germany

We report a patient who suffered from acute inflammatory CNS demyelination and underwent two consecutive diagnostic stereotactic brain biopsies during the early disease course. The first lesion was drawn 33 days after the onset of disseminated neurological symptoms. Macrophages and T lymphocytes diffusely infiltrated small vessel walls and the white matter. mRNA for tumor necrosis factor alpha (TNFa) and inducible nitric oxide synthase (iNOS) was abundantly expressed. Myelin sheaths were entirely preserved. The second biopsy 76 days later showed confluent demyelinating lesions with a diffuse infiltration of macrophages that were positive for myelin debris, activation markers and TNFa and iNOS mRNA. IgG and C9neo deposits were found along myelin sheaths. The patient had received intravenous immunoglobulins (IVIG) prior to biopsy. Findings from this single patient affirm that demyelination follows the migration of inflammatory cells from the circulation into the white matter with subsequent inflammation and demyelination. Inflammation alone may be sufficient to cause significant clinical deficits without demyelination. Inflammatory mediators such as TNFa and NO are involved at very early stages in the pathogenetic process. IVIG treatment may lead to the deposition of immunoglobulins and to the activation of the complement cascade, but the clinical relevance of this particular finding remains uncertain.

Key Words: demyelination • iNOS • IVIG • multiple sclerosis • pathogenesis • TNFa

Multiple Sclerosis, Vol. 5, No. 3, 138-146 (1999)
DOI: 10.1177/135245859900500302


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