Recurrent Fulminant Tumefactive Demyelination With Marburg-Like Features and Atypical Presentation: Therapeutic Dilemmas and Review of Literature

Abstract

Atypical forms of demyelinating diseases with tumor-like lesions and aggressive course represent a diagnostic and therapeutic challenge for neurologists. Herein, we describe a 50-year-old woman presenting with subacute onset of left hemiparesis, memory difficulties and headache. Brain MRI revealed a tumefactive right frontal-parietal lesion with perilesional edema, mass effect and homogenous post-contrast enhancement, along with other small atypical lesions in the white-matter. Brain biopsy of cerebral lesion ruled out lymphoma or any other neoplastic process and patient placed on corticosteroids with complete clinical/radiological remission. Two years after disease initiation, there was disease exacerbation with reappearance of the tumor-like mass. The patient initially responded to high doses of corticosteroids but soon became resistant. Plasma-exchange sessions were not able to limit disease burden. Resistance to therapeutic efforts led to a second biopsy that showed perivascular demyelination, predominantly consisting of macrophages, with a small number of T and B lymphocytes, and the presence of reactive astrocytes, typical of Creutzfeldt-Peters cells. The patient received high doses of cyclophosphamide with substantial clinical/radiological response but relapsed after 7-intensive cycles. She received 4-weekly doses of rituximab with disease exacerbation and brainstem involvement. She eventually died with complicated pneumonia. We present a very rare case of recurrent tumefactive demyelinating lesions, with atypical tumor-like characteristics, with initial response to corticosteroids and cyclophosphamide, but subsequent development of drug-resistance and unexpected exacerbation upon rituximab administration. Our clinical case raises therapeutic dilemmas and points to the need for immediate and appropriate immunosuppression in difficult to treat tumefactive CNS lesions with Marburg-like features.

Marburg Multiple Sclerosis Variant: Complete Remission with Very Early Administration of Mitoxantrone—A Case Report

“…Moreover, CSF cytokines showed elevatedIL-10ands-IL2RwithoutelevationofIL-6 thatcouldsupportlymphomadiagnosis.Addedto the normal lymphocyte infiltrate, mainly com-poundedofT-lymphocytes,itcansuggestacrucial role of the Th1/Treg balance in Marburg's disease describedinMSforms [9].Becauseofitsscarcity,no randomized controlled trial is available to support treatment evidence in such fulminant cases. Most reported patients were treated using IV steroids or plasma exchange therapy without long-term efficacy [7][8][9][10][11][12]. Recent evidence does not support fingolimod and natalizumab to treat tumefactive MS, including Marburg's variant [13].…”

Clinico-radiologic features and therapeutic strategies in tumefactive demyelination: a retrospective analysis of 50 consecutive cases

“…One patient died after a disease course of 2 years due to the neurological consequences of the TDL (previously reported by our research team). 22 For the purposes of our study, we assigned an EDSS score of 10 to this patient. The mean EDSS score of the cohort at the TDL onset and at the end of the follow-up was 3.65 (SD ± 1.51) and 2.32 (SD ± 1.76), respectively.…”

“…Recurrent TDL represents a clinical/radiological syndrome that has not been thoroughly described before due to the limited numbers of cases. 18 , 22 , 27 – 30 It is unclear whether such cases belong to a separate subset of demyelinating diseases of the CNS or represent a variant of MS. Further clinical evidence on natural history and optimal treatment is warranted. Herein, we present for the first time in the literature 12 patients with recurrent TDL and try to identify any distinct features of this disease entity.…”

The Neuroimmunology of Multiple Sclerosis: Fictions and Facts

“…ISDs May Only Improve Long-Term Outcomes in a Small Subset of Patients Diagnosed With MS Using Current Criteria MS is a highly heterogeneous disease with respect to long-term outcomes. Some patients with severe MS can progress to bedbound existence or death within a few years of diagnosis (193) while classical MS plaques can be found in individuals who underwent autopsy after a long symptom-free life, a type of asymptomatic MS (194,195). Many biologic factors affect longterm outcomes, such as comorbidities and variable potential for CNS plasticity, neuronal repair, and remyelination.…”