Table 1 Differences in the pathogenesis and clinical manifestations of untreated CNS cryptococcosis and cryptococcal associated IRIS in patients with HIV/AIDS
From: Cryptococcal meningoencephalitis in HIV/AIDS: when to start antiretroviral therapy?
Features | HIV/AIDS associated central nervous system Cryptococcosis | Cryptococcal immune reconstitution syndrome |
|---|---|---|
Pathogenesis | Cryptococci crosses the microvascular endothelium of the blood brain barrier (BBB) of pial vessels and penetrating arterioles and capillaries via a transcellular pathway There is no disruption of the blood–brain-barrier Polysaccharide antigen and yeast accumulation in subarachnoid space affecting the reabsorption process of the CSF in arachnoid villi There is some evidence to suggest that the large number of yeasts residing in the perivascular spaces and brain parenchyma may affect the drainage of interstitial fluid into the perivascular spaces and therefore contributing to intracranial hypertension | Triggered by accumulation of cryptococcal polysaccharide in the subarachnoid space due to its decreased clearance producing rapid chemokine-mediated monocyte recruitment into the subarachnoid space leading to leptomeningitis This immunological response is dysregulated and causes inadequate cryptococcal killing and clearance of the fungus within the central nervous system |
Clinical spectrum of disease | Meningoencephalitis with symptoms predominantly caused by increased intracranial hypertension (headache, nausea, decreased hearing, decreased vision, and others) and less frequently of meningitis (fever and meningismus) Parenchymal forms (cryptococcomas) with symptoms of increased intracranial pressure and mass effect (i.e., seizures, brain herniation syndromes) Cerebrospinal fluid analysis with a paucity of white cells Cerebrospinal fluid culture with growth of Cryptococci | Meningitis manifesting in individuals receiving antifungal therapy and sudden onset of clinical neurologic deterioration after initiation of antiretroviral therapy (paradoxical IRIS) Meningitis with increased intracranial pressure among individuals with HIV and already receiving ARTs (unmasked IRIS) Cerebrospinal fluid analysis with a more inflammatory pattern (increased white cells) Cerebrospinal fluid culture with no growth |
Neuroimaging | Dilated Virchow Robin spaces in T2-weighted MRI imaging in basal ganglia and brain steam but in some cases also throughout cerebrum without evidence of leptomeningitis in most reported case series In parenchymal forms, the confluence of gelatinous pseudocysts may produce cryptococcomas | Leptomeningitis in MRI (T1-weighted images with contrast) |
Management | Antifungal therapy (induction, consolidation, suppression) and evacuation of CSF to reduce intracranial hypertension | Continuation of antifungal therapy CSF evacuation if indicated Corticosteroids |