Monofocal Posterior Fossa Natalizumab-Associated PML-IRIS

Background:

Progressive multifocal leucoencephalopathy [PML] has emerged as a potentially fatal opportunistic infection with limited, if any treatment options, complicating natalizumab [NTZ] treatment for people with multiple sclerosis [MS]¹. Mainstream management is to restore immune competence by suspending NTZ and plasmapheresis [PLEX] can speed drug elimination¹. However, this can be further complicated by immune reconstitution inflammatory syndrome [IRIS]².

Objectives:

We report a rare case of PML-IRIS.

Methods:

A 36 year old woman responded to NTZ every 4 weeks for relapsing MS since 2007 after failing interferon-beta, with no prior immunosuppression. Serum JC virus antibody was known positive since 2011 but she continued treatment due to sustained NTZ high efficacy, monitored clinically and on MRI every 4 to 6 months.

Results:

In September 2016 she noticed subtle worsening of speech and balance, and emotional lability; physical examination confirmed a cerebellar syndrome and MRI revealed an ill-defined area of increased T2 signal within the right cerebellum and brachium pontis, T1 hypointensity in the pons with patchy and nodular gadolinium enhancement. Ultra-sensitive cerebrospinal fluid tested positive for JCV DNA, with a low but inconclusive viral count. She underwent 5 courses of PLEX uneventfully and initiated Mefloquine+Mirtazapine but a week later she worsened again. MRI showed patchy enhancing white matter lesions in the bilateral pons, cerebellar hemispheres and peduncles suggestive of IRIS.  After 14 days of IV 1g/d steroids, she gradually showed sustained improvement both clinically and on MRI. However challenging, early PML diagnosis when MRI shows only monofocal abnormality is associated with better outcomes^{3 4,5}. Cerebral hemispheres are the most common locations⁶, but our patient presented with isolated posterior fossa lesions, a topography seen in less than 10% of known cases⁴. Though JCV classically infects oligodendrocytes, it is proven that the virus can also affect the cerebellar granular cells causing cerebellar atrophy, without evidence of cerebral hemispheres affection⁷.

Conclusions:

clinical and MRI vigilance in NTZ treatment for MS is paramount. Early PML diagnosis and aggressive IRIS management increase the odds for a better outcome. Remarkably this case showed T1 hypointensity “across” the pons on MRI, rarely described in HIV-PML but never published yet in MS^8,9,10.