Neurological immune reconstitution inflammatory response: riding the tide of immune recovery

This manuscript reviews current reports about clinical aspects of immune reconstitution inflammatory syndrome (IRIS), with a particular emphasis on IRIS in the setting of progressive multifocal leukoencephalopathy (PML) and to a lesser extent on cryptococcal meningitis and HIV.

PML prognosis has been radically improved, as it has become possible to provide immune reconstitution, although some remaining morbidity and mortality results from excess inflammation. Similar pathologic responses are seen less often, but remain clinically important in cryptococcal meningitis, and HIV. Early diagnosis and active management of PML results in optimal outcomes with survival of 75% or higher in multiple recent series. These finding apply both to natalizumab and HIV-associated PML. Cryptococcal meningitis is frequently complicated by IRIS, and early treatment with antifungal therapy preceding HIV therapy provides optimal outcomes. HIV IRIS is reduced by early therapy, which is now recommended, but even on therapy, chronic dysregulated immune responses may play important roles in ongoing HIV-associated neurocognitive disease (HAND), which is common, as well as rare but more dramatic subacute encephalopathies.

The clinician must actively monitor and treat both opportunistic infection and the inflammatory response that is essential to recovery but may itself augment disease and injury.