Carlson Renee Donahue, Rolfes Melissa A, Birkenkamp Kate E, Nakasujja Noeline, Rajasingham Radha, Meya David B, Boulware David R
Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
Infectious Disease Institute, School of Medicine, Department of Medicine, Kampala, Uganda.
Metab Brain Dis. 2014 Jun;29(2):269-279. doi: 10.1007/s11011-013-9476-1. Epub 2014 Jan 9.
Cryptococcal meningitis is the most common cause of adult meningitis in Africa, yet neurocognitive outcomes are unknown. We investigated the incidence and predictors of neurologic impairment among cryptococcal survivors. HIV-infected, antiretroviral-naive Ugandans with cryptococcal meningitis underwent standardized neuropsychological testing at 1, 3, 6, and 12 months. A quantitative neurocognitive performance z-score (QNPZ) was calculated based on population z-scores from HIV-negative Ugandans (n = 100). Comparison was made with an HIV-infected, non-meningitis cohort (n = 110). Among 78 cryptococcal meningitis survivors with median CD4 count of 13 cells/μL (interquartile range: 6-44), decreased global cognitive function occurred through 12 months compared with the HIV-infected, non-cryptococcosis cohort (QNPZ-6 at 12 months, P = 0.036). Tests of performance in eight cognitive domains was impaired 1 month after cryptococcal diagnosis; however, cryptococcal meningitis survivors improved their global neurocognitive function over 12 months with residual impairment (mean z-scores < -1), only in domains of motor speed, gross motor and executive function at 12 months. There was no evidence that neurocognitive outcome was associated with initial demographics, HIV parameters, or meningitis severity. Paradoxically, persons with sterile CSF cultures after 14 days of induction amphotericin therapy had worse neurocognitive outcomes than those still culture-positive at 14 days (P = 0.002). Cryptococcal meningitis survivors have significant short-term neurocognitive impairment with marked improvement over the first 12 months. Few characteristics related to severity of cryptococcosis, including Cryptococcus burden, were associated with neurocognitive outcome.
隐球菌性脑膜炎是非洲成人脑膜炎最常见的病因，但神经认知结局尚不清楚。我们调查了隐球菌病幸存者中神经功能障碍的发生率及预测因素。患有隐球菌性脑膜炎、未接受过抗逆转录病毒治疗的HIV感染乌干达人在1、3、6和12个月时接受了标准化神经心理学测试。基于HIV阴性乌干达人（n = 100）的人群z评分计算定量神经认知表现z评分（QNPZ）。与HIV感染的非脑膜炎队列（n = 110）进行比较。在78例中位CD4细胞计数为13个/μL（四分位间距：6 - 44）的隐球菌性脑膜炎幸存者中，与HIV感染的非隐球菌病队列相比，至12个月时整体认知功能下降（12个月时QNPZ为 - 6，P = 0.036）。在隐球菌诊断后1个月，八个认知领域的表现测试受损；然而，隐球菌性脑膜炎幸存者在12个月内整体神经认知功能有所改善，但仍有残余损害（平均z评分＜ - 1），仅在12个月时运动速度、粗大运动和执行功能领域存在损害。没有证据表明神经认知结局与初始人口统计学特征、HIV参数或脑膜炎严重程度相关。矛盾的是，诱导使用两性霉素治疗14天后脑脊液培养无菌的患者，其神经认知结局比14天时仍培养阳性的患者更差（P = 0.002）。隐球菌性脑膜炎幸存者有明显的短期神经认知损害，在最初12个月内有显著改善。与隐球菌病严重程度相关的特征（包括隐球菌负荷）很少与神经认知结局相关。
