HIV-Negative Cryptococcal Meningoencephalitis Results in a Persistent Frontal-Subcortical Syndrome

Abstract

Twenty-seven previously healthy (of 36 consecutive eligible patients), HIV-negative cryptococcal meningoencephalitis (CM) patients underwent comprehensive neuropsychological evaluation during the late post-treatment period (1.3–4 years post diagnosis), assessing attention, language, learning, memory, visuospatial, executive function, information processing, psychomotor functioning, as well as mood symptoms. Seven of eight domains (all except attention) showed increased percentages of CM patients scoring in the less than 16th percentile range compared to standardized normative test averages, adjusted for education level and age. Comparison with a matched archival dataset of mild cognitive impairment/Alzheimer’s disease patients showed that CM patients exhibited relative deficits in psychomotor and executive function with fewer deficits in memory and learning, consistent with a frontal-subcortical syndrome. MRI evaluation at the time of testing demonstrated an association of lower neuropsychological functioning with ventriculomegaly. These studies suggest that CM should be included in the list of treatable causes of dementia in neurological work ups. Future studies are needed to identify diagnostic and treatment regimens that may enhance neurological function after therapy.

Divergent neuroimmune signatures in the cerebrospinal fluid predict differential gender-specific survival among patients with HIV-associated cryptococcal meningitis

“…Combining antifungal drugs with immunomodulatory interventions as new therapies could limit the fungal and immune assault on the CNS. Illustrated by high mortality among CMinfected subjects with more prominent brain lesions from magnetic resonance imaging and at autopsy who could benefit from combining antifungal drugs with immunomodulatory interventions (62)(63)(64)(65). As proposed by Casadevall and Pirofski (11,12), with appreciable control of fungal burden, immune responses may be a more prominent determinant of clinical outcomes.…”

“…Indeed, in CM, neutrophilia in the circulation was associated with poor survival outcome ( 80 ), brain hypoxia ( 15 , 81 , 82 ), subarachnoid blood vessel occlusion ( 83 ), brain tissue necrosis, and cerebellar infarction ( 64 ). Subsequently, survivors of CM suffered long-term CNS abnormalities associated with impaired faculty observed in sequelae among people without HIV infection ( 62 , 84 ). The persistent CNS abnormalities in sequelae noted in humans with fungal infections were similar to those observed among mouse models of Alzheimer’s disease ( 85 ).…”

Case Report: Paradoxical Inflammatory Response Syndrome in a Previously Healthy, HIV-Negative, Pediatric Patient With Cryptococcus gatii Meningitis

“…Little exists in the literature regarding the long-term outcomes of cryptococcal meningitis and the clinical course of PIIRS. In a study of previously healthy patients who developed cryptococcal meningoencephalitis, patients demonstrated psychomotor, and executive function deficiencies when neuropsychological testing was performed during the late posttreatment period ( 13 ). A follow-up of six cases of spinal arachnoiditis due to PIIRS showed a high rate of morbidity and mortality: one death, two patients who required walking assistance, one with residual wide-based gait, and two with normal ambulation ( 9 ).…”

Treatment recommendations for non-HIV associated cryptococcal meningoencephalitis including management of post-infectious inflammatory response syndrome

“…Gait abnormalities are also common and may be the result of an accompanying spinal arachnoiditis or hydrocephalus ( 25 ). Evidence of a subcortical dementia with reduced executive and psychomotor function on detailed neuropsychiatric exams may also suggest cryptococcal disease ( 26 ), as distinguished from the frontal dementias typical of Alzheimer's.…”