Outcome of Lenalidomide Treatment for Cognitive Impairment Caused by Immune Reconstitution Inflammatory Syndrome in Patients with HIV-Related Cryptococcal Meningitis

Abstract

Purpose Cognitive impairment associated with human immunodeficiency virus (HIV)-related cryptococcal meningitis (HCM) in the context of immune reconstitution inflammatory syndrome is difficult to address. This study was a follow-up of lenalidomide treatment outcomes in patients with HCM and cognitive impairment after complete cryptococcal clearance. Patients and Methods Seven HCM patients with neuroinflammation and cognitive impairment after complete cryptococcal clearance were enrolled in this prospective study. Neurocognitive assessment, clinical examination and cerebrospinal fluid (CSF) assays were performed before and after lenalidomide treatment. Results After lenalidomide treatment, the Montreal Cognitive Assessment [week (W) 0 (median [interquartile range]: 23.0 (13.0–24.0) vs W24: 26.0 (24.0–28.00), P=0.018] and International HIV Dementia Scale scores [W0: 9.0 (2.5–10.5) vs W24: 11.0 (10.00–12.0), P=0.028] improved significantly, mainly in the domain of memory function. There was no significant difference in the Center for Epidemiological Research Depression scores for anxiety and depression before and after treatment. Further stratified analyses revealed that the patients with cognitive improvement group had higher levels of CSF white blood cells [94.0 (44.0–180.0) vs 0 (0–1.5), P=0.032], CSF protein [4.9 (3.0–6.6) vs 0.6 (0.5–0.7), P=0.034], CSF albumin [318.5 (190.9–346.5) vs 33.5 (30.4–46.2), P=0.034], and CSF IgG [160.5 (73.8–256. 0) vs 4.7 (4.3–7.4), P=0.034] but a lower CSF glucose level [2.4 (2.0–2.7) vs 2.8 (2.8–3.9), P=0.032] than the patients with cognitive non-improvement group before treatment. CSF inflammatory cytokines of the growth-related oncogene, interleukin [IL]-10, granulocyte-colony stimulating factor, IL-6, IL-8, complement factor H, tumor necrosis factor-α, and α-2 macroglobulin were obviously decreased in patients with cognitive improvement group after lenalidomide treatment. Conclusion Lenalidomide potentially reduces cognitive impairment caused by immune reconstitution inflammatory syndrome in patients with HCM after cryptococcal clearance by inhibiting intracranial inflammation.

Global trends in Cryptococcus and its interactions with the host immune system: a bibliometric analysis

“…Following the administration of ART, although there is a rapid restoration of cellular immunity in individuals with HIV/AIDS-associated Cryptococcus infection, there is a propensity for the emergence of immune reconstitution inflammatory syndrome (IRIS). This phenomenon is characterized by a pronounced inflammatory response within the central nervous system, correlated with a heightened mortality rate among affected individuals ( 49 , 50 ). Cryptococcal IRIS induces an aberrant inflammatory cascade that eventuates in host-mediated neuropathology ( 51 ).…”

The Managing Cancer and Living Meaningfully (CALM) Intervention Alleviates Chemotherapy-Related Cognitive Impairment in Patients with Breast Cancer by Modulating Pan-Immune-Inflammation Values

“… 16 Systemic inflammatory response markers and cytokines are important body inflammation indices, both of which have been explored for their correlation with cognitive function in many diseases. 17 A previous study noted that markers of systemic inflammation measures are correlated with circulating concentration of various cytokines, and the elevation of cytokines such as TNF- α, IL-1, and IL-6 may be earlier than the elevation of systemic inflammatory markers. 18 Therefore, it is important to analyze the correlation between CALM interventions to improve cognitive function and changes in the levels of systemic inflammatory markers.…”