New insights into immune reconstitution inflammatory syndrome of the central nervous system

Abstract

Purpose of review To highlight the importance of immune reconstitution inflammatory syndrome (IRIS) affecting the brain in HIV-infected individuals in the absence of opportunistic infections. To describe the varied clinical manifestations, unifying pathophysiological features and discuss the principles of management of this syndrome. Recent Findings IRIS within the brain is commonly seen in patients with HIV infection upon initiation of antiretroviral drugs. The fulminant forms occur in the face of opportunistic infections or uncontrolled viral replication within the brain. In this case the enhanced immune response is targeted against the microbial agent, and the brain suffers bystander damage. Treatment requires the combination of the antimicrobial agent, continued antiretrovirals and in some cases corticosteroids. It is increasingly being recognized that despite adequate control of viral replication in the brain some patients develop a chronic form of T cell encephalitis which appears to be driven by continued production of HIV-Tat protein. In others the immune response may be targeted against the host antigens in the brain. Summary In patients with CNS-IRIS the use of corticosteroids and strategies that prevent T cell migration into the brain may be needed. Extreme caution is necessary if viral eradication strategies are to employed that involve activation of viral reservoirs, since these patients may be at risk for developing CNS-IRIS.

Infectious encephalitis: mimics and chameleons

“…CNS immune reconstitution inflammatory syndrome is defined by a pathological inflammatory response to either a previously treated (paradoxical) or a previously undiagnosed (unmasked) opportunistic infection 39. Immune reconstitution inflammatory syndrome results from the restoration of a dysregulated immune response against pathogen-specific antigens.…”

“…In the setting of HIV, it is characterised by paradoxical clinical deterioration following initiation of cART. Although immune reconstitution inflammatory syndrome can occur in the setting of HIV alone, it more commonly occurs in response to an opportunistic organism such as Mycobacterium tuberculosis , Cryptococcus neoformans or JC virus (the agent responsible for progressive multifocal leukoencephalopathy) 39. Paradoxical worsening, manifesting altered consciousness, focal deficits, cranial neuropathies and seizures, occurs on average 3–5 weeks after starting treatment but can develop months after treatment 39.…”

Anti-N-Methyl-D-Aspartate Receptor Encephalitis in HIV Infection

“…Nevertheless, there is a recognized association between HIV infection and autoimmunity as patients with HIV infection managed with HAART may develop acute immune dysregulation collectively known as immune reconstitution inflammatory syndrome [9]. …”

Manifestaciones Neurológicas en Pacientes Ambulatorios con Diagnóstico de VIH Atendidos en el Hospital Carlos Andrade Marín.

“…La aparición de signos neurológicos o deterioro de los déficits previos son la forma de presentación más común del síndrome e reconstitución inmune y la mayoría de los casos de asocian a neuroinfecciones [39,40]. La distribución en el presente estudio fue similar al reporte de McCombe y colaboradores en Canadá, no existieron casos ambulatorios de síndrome de Guillain Barré ni de esclerosis lateral amiotrófica [41].…”