Fulminant tumefactive multiple sclerosis: Therapeutic implications of histopathology

Abstract

JO N 2 88 3 A 33-year-old Caucasian woman first presented with optic and sensory symptoms in September 2004. An optic neuritis in 2003 had not been evaluated neurologically. Family history was positive for MS, oligoclonal bands (OCB) were present in the CSF. Expanded disability status scale (EDSS) was 2.0, with a rapid remission of symptoms after intravenous methylprednisolone (IVMP) for 5 days. Cranial (c)MRI at time of diagnosis fulfilled MS criteria with about 20 disseminated T2-lesions [4]. No alternative diseases were found. All findings supported the diagnosis of MS according to Mc Donald criteria [5]. Since pregnancy was intended, no immunoprophylaxis was initiated. After two further exacerbations, a large left parietal lesion was externally suspected to be neoplastic in June 2005 (Fig.1A), however not biopsied as symptoms regressed after IVMP. Subcutaneous interferonbeta 1a (22 μg) was started and increased to 44 μg in spring 2006. Three distinct exacerbations occurred within 37 days between June 29 (EDSS 2.5) and August 5, 2006 (EDSS 5.0). Mitoxantrone was initiated with a cumulative dose of 17.5 mg per m2 body surface but no clinical benefit was achieved over three months. Intravenous immunoglobulins (IVIG) did not prevent new bouts either. After a single dose of natalizumab in December 2006 the patient was readmitted 10 days later with a focal status epilepticus and a subsequent stupor. Further serological diagnostics did not reveal new aspects, CSF-JCV testing and aquaporin antibodies were negative. A brain biopsy was performed. Histopathology revealed early active demyelination with little inflammation. Large numbers of macrophages with incorporated myelin fragments were demonstrated (Fig.2). Some macrophages labelled positive for the acute macMichael R. Haupts Sebastian K. Schimrigk Nils Brune Andrew Chan Guido Ahle Kerstin Hellwig Fatima B. Konig Uwe Schlegel Wolfgang Bruck Ralf Gold