Severe aseptic leucoencephalopathy as immune reconstitution inflammatory syndrome in Caucasian and African patients

Objective: To assess if CNS Immune Reconstitution Inflammatory Syndrome (IRIS) may become manifest in form of aseptic inflammation presenting as severe leucoencephalopathy after highly active antiretroviral therapy (HAART) in HIV-1-positive patients.

Design: We describe a case series of immunocompromised HIV-1-positive patients who were started on HAART. All of them had clinical, laboratory follow-up tests and cerebral MRI in order to investigate the course and the underlying pathophysiology of an aseptic form of IRIS. One patient died and we performed a neuropathological examination.

Methods: HIV-1-positive patients on HAART were treated with corticosteroids after developing IRIS, although Methyl prednisolone has an additional immunosuppressive effect and represents the main therapy in this situation.

Results: No infectious agent was detected in all patients before and during HAART. Three of four immunocompromised patients were successfully treated with corticosteroids and survived up to now while HAART was never interrupted. One African patient died within two days despite intensive care due to cerebral edema.

Conclusion: In order to select the appropriate treatment, the above pathophysiological context should be considered in every HIV patient. It appears mandatory to clearly distinguish the infectious agent-driven type of IRIS from the type described here presenting as leucoencephalopathy due to aseptic vasculitis or cerebritis. Additionally, we hypothesize that there might be a difference in the course of IRIS and the outcome of the patients depending on the ethnic origin. But neither in the neuropathological findings nor in the cerebral imaging, had we found a conclusive reason for the different outcome of the Caucasian and African patients. The cases described here could contain a reference that cytotoxic immune response in HIV-1-positive patients can be directed against normal cerebral or perivascular parenchyma and must not necessarily be associated with infectious agents. Since the pathophysiology underlying IRIS in these cases appears to represent an aseptic, autoimmune mediated inflammation of the perivascular spaces and/or the cerebral parenchyma, this form of IRIS should reasonably be treated with corticosteroids.