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

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 ons et of disseminated neurological symptoms. Macrophages and T lymphocytes dif fusely infiltrated smell vessel walls and the white matter mRNA for tumor n ecrosis factor alpha (TNF alpha) and inducible nitric oxide synthase (iNOS) was abundantly expressed Myelin sheaths were entirely Preserved. The secon d biopsy 76 days later showed confluent demyelinating lesions with a diffus e infiltration of macrophages that were positive for myelin debris, activat ion markers and TNF alpha end 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 demyel ination follows the migration of inflammatory cells from the circulation in to the white matter with subsequent inflammation and demyelination. inflamm ation alone may be sufficient to cause significant clinical deficits withou t demyelination. inflammatory mediators such as TNF alpha and NO ore involv ed at very early stages in the pathogenetic process. IVIG treatment may lea d to the deposition of immunoglobulins and to the activation of the complem ent cascade, but the clinical relevance of this particular finding remains uncertain.