Disease course and outcome of 15 monocentrically treated natalizumab-associated progressive multifocal leukoencephalopathy patients

Abstract

ObjectiveAlthough the prognosis of natalizumab-associated progressive multifocal leukoencephalopathy (PML) seems to be better than HIV-associated PML, little is known about the long-term functional outcome in multiple sclerosis (MS) patients and the subsequent return of MS disease activity. We evaluated retrospectively 15 patients with natalizumab-associated PML treated at our centre.Patients and methodsFifteen MS-PML patients (nine women, six men) were referred to us from adjacent local centres. The patients had a median natalizumab exposure of 34 months at PML diagnosis. They received standardised treatment as described in previous work. Expanded Disability Status Scale (EDSS) and Karnofsky score in the year pre-PML, at PML-diagnosis (pre-immune reconstitution inflammatory syndrome (IRIS)) and post-PML were determined in 3–6 monthly intervals.ResultsThe median follow-up of these 15 patients was 21.5 months. None of the 15 patients died. Three patients had a Karnofsky score of 80 or higher, nine patients between 50–70 and three patients of 40 or lower at latest examination. Eight of the 15 patients developed seizures during acute PML phase. Fifty percent of those patients were not seizure-free one year post PML, despite continuation of antiepileptic treatment. The median EDSS in the year pre-PML was 2.5, 4.5 at PML diagnosis, 6.5 post-IRIS and 5.5 at latest examination. CSF became virus-free in eight of the 15 patients after a median time of 4.5 months. In nine patients, disease reappeared after a median time of seven months from PML diagnosis.ConclusionsAlthough the clinical outcome of natalizumab-treated PML patients is much better than in patients with HIV-associated PML, this may be further improved by treatment at reference centres using standardised therapy regimens and transient intensive care if needed. Systematic studies of appropriate MS immunotherapies after PML are critically needed.

Progressive multifocal leukoencephalopathy: new concepts

“…Most of the reported patients who developed IRIS received high-dose glucocorticoids (dexamethasone or methylprednisolone) followed by a slow tapering in order to lessen the immune reconstitution and avoid additional damage 18 . There is evidence of a better survival in PML associated with Natalizumab use (70%) compared to other conditions, but survivors may have a higher degree of disability 20 .…”

Natalizumab Associated Progressive Multifocal Leukoencephalopathy-Immune Reconstitution Inflammatory Syndrome in a Patient with Multiple Sclerosis: Case Report

“…2,6,8 On MRI scans, new lesions are generally seen in areas mainly within subcortical white matter, not previously affected by MS. Gadolinium enhancement is usually minimum or absent. 2 The diagnosis of PML can be established by clinical history and evaluation, brain MRI scans, and detection of JC virus DNA in the CSF or by immunohistochemistry on brain tissue following biopsy.…”

Monoclonal Antibody for Multiple Sclerosis Treatment

“…Несмотря на столь благоприятный спектр указанных выше возможных побочных эффектов, не стоит забы-вать, что к настоящему времени зарегистрировано уже более 300 случаев прогрессирующей мультифокальной лейкоэнцефалопатии (ПМЛ) [4]. ПМЛ -это быстро про-грессирующее демиелинизирующее инфекционное забо-левание ЦНС с асимметричным поражением вещества головного мозга, вызывающееся активацией полиома-вируса человека -2 (JCV), носителем которого является около 80% населения.…”