Neuro-psychological sequelae in HIV-negative cryptococcal meningitis after complete anti-fungal treatment

Purposes: The cognitive sequelae and influence of depression in patients with cryptococcal meningitis (CM) after complete anti-fungal treatment has not been completely surveyed in literature. Methods: Seventeen HIV-negative CM patients and 26 healthy controls were enrolled in this prospective study. Neuro-psychological evaluation was performed to assess the attention, execution, speech and language, semantic and visuo-construction function, and depression. These were correlated with longitudinal magnetic resonance imaging (MRI) through the following checklists: dilated Virchow-Robin spaces, pseudo-cysts, intra-cerebral nodule or mass, meningeal enhancement, hydrocephalus, and hyper-intensity of white matter. For cognitive outcome measurement, initial clinical and biochemical markers were collected and analyzed. Results: The mean follow-up duration in CM patients was 69.6 months. They had impairments in attention, execution, speech and language, and visuo-construction function, while six (35%) patients fulfilled the depression criteria. Initial cryptococcal antigen titer was inversely correlated with block design score (ρ = -0.54, p< 0.05), after adjustment for depression. Patients with two or more CM-related lesions had higher CSF lactate (mean, 43.4; SD, 19.5) at baseline than those with less than two CM-related lesions (mean, 19.2; SD, 12.6) (p=0.04). CM with depression is highly associated with poor cognitive performance and higher likelihood of two or more lesions in MRI (likelihood ratio=6.012, p=0.014). Conclusion: Cognitive deficits persist in CM patients even after complete treatment. The number of lesions plays an important role in cognitive performance and depression. Extensive involvement of the cognitive domains with wide radiographic presentations suggests a disseminated nature of cryptococcus.