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

• Published in: Multiple sclerosis Vol. 5; no. 3; pp. 138 - 146
• Main Authors: Bitsch, A, Wegener, C, da Costa, C, Bunkowski, S, Reimers, C D, Prange, H W, Brück, W
• Format: Journal Article
• Language: English
• Published: Thousand Oaks, CA SAGE Publications 01-06-1999; Arnold
• Subjects: Acute Disease; Adult; Apoptosis; Biological and medical sciences; Biopsy; Brain - diagnostic imaging; Brain - pathology; Demyelinating Diseases - pathology; Humans; Immunohistochemistry; In Situ Hybridization; Inflammation - pathology; Magnetic Resonance Imaging; Male; Medical sciences; Multiple Sclerosis - classification; Multiple Sclerosis - diagnosis; Multiple Sclerosis - pathology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type II; RNA, Messenger - analysis; Stereotaxic Techniques; Time Factors; Tomography, X-Ray Computed; Tumor Necrosis Factor-alpha - genetics; pathogenesis; iNOS; IVIG; TNFa; demyelination; multiple sclerosis; Human; Immunohistochemistry; Nervous system diseases; Multiple sclerosis; Acute; Central nervous system; Exploration; Inflammatory disease; Case study; Pathology; Biopsy; Demyelination; Central nervous system disease; Brain (vertebrata)
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/135245859900500302

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.