Partial recovery after PML

Staying alive: surviving PML IRIS or not? #MSBlog #MSResearch

"In keeping with the theme of natalizumab-associated PML this case study demonstrates a complication of washing-out natalizumab and letting a competent immune system access to the brain in someone with PML. The anti-viral lymphocytes that were being kept out of the brain by natalizumab flood back in and set-up a severe viral encephalitis. The resulting inflammation and swelling can be fatal, particularly if the PML load is large or is an area that can compromise vital brain functions, i.e. the brain stem. This is why this case needed to be treated with steroids. A confounding factor in PML IRIS could be MS rebound. The latter is the recurrence of MS disease activity that occurs 3-4 months after stopping natalizumab. In someone with PML we assume all the inflammation is due to PML-IRIS, but a substantial amount of it could be MS-related."

"I have been promoting MS-rebound post-natalizumab as the best model to study MS relapses. Understanding, why it occurs and in response to what may help us pin down the cause of MS. I think the rebound is in response to the virus that is causing MS; in other words MS-rebound is IRIS to another virus."

"IRIS TO ANOTHER VIRUS; rolls off the tongue like a line in a limerick."

"I proposed at meeting 18 months ago that we take volunteer MSers on natalizumab and  treat them with different lymphocyte depleting antibodies to see which cell is important in the evolution of relapses; i.e. anti-CD4, anti-CD8 and anti-CD20. I suspect the anti-CD8 and the anti-CD20 will prevent the rebound, but not the anti-CD4 therapy. If this was the case it would be a strong argument against MS being a CD4 T cell mediated autoimmune disease. Unfortunately, I would be surprised any ethics committee would allow you to perform this experiment."

PML IRIS

Calvi et al. Partial recovery after severe immune reconstitution inflammatory syndrome in a multiple sclerosispatient with progressive multifocal leukoencephalopathy. Immunotherapy. 20146(1):23-8. doi: 10.2217/imt.13.155.

Progressive multifocal leukoencephalopathy (PML) is a rare and severe complication of natalizumab therapy in MSers and it may be accompanied by immune reconstitution inflammatory syndrome (IRIS). Here, we describe a case of abnormally severe IRIS, which occurred 2 months after natalizumab-associated PML in a 38-year-old woman affected by multiple sclerosis. The patient was John Cunningham virus-positive and was treated for 21 months when she developed PML. The subsequent IRIS diffusely afflicted the brain, producing edema and signs of intracranial hypertension (increased pressure within the skull), with a clinically severe form compromising the state of consciousness, requiring intensive care and high-dosage steroid treatment. Nevertheless, she survived and partially recovered. There is still difficulty in differentiating PML progression from IRIS onset and there is not a clear description in the literature about different clinical forms of IRIS, prognostic factors and guidelines to properly treat this complication in order to reduce the residual disability of the patient surviving this treatment complication.

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