Le Leah T, Spudich Serena S
Department of Neurology, Yale University, New Haven, Connecticut.
Semin Neurol. 2016 Aug;36(4):373-81. doi: 10.1055/s-0036-1585454. Epub 2016 Sep 19.
Since the advent of combination antiretroviral therapy (cART), HIV has transformed from a fatal disease to a chronic illness that often presents with milder central nervous system (CNS) symptoms laced with related confounders. The immune recovery associated with access to cART has led to a new spectrum of immune-mediated presentations of infection, phenotypically distinct from the conditions observed in advanced disease.HIV-associated neurocognitive disorder (HAND) entails a categorized continuum of disorders reflecting an array of clinical presentation, outcome, and increasing level of severity: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). HAND is defined through an assessment of neurocognitive abilities and functional performance. Progressive neurologic symptoms detected in patients on cART with detectable CSF viral load and a suppressed plasma viral load, or CSF viral load 1 log10 greater than low detectable plasma viral load, characterize a phenomenon termed symptomatic CSF "escape." CD8+ T-cell encephalitis, possibly a form of CNS immune reconstitution inflammatory syndrome, resembles CNS "escape" as it presents in patients despite viral suppression with cART. Cerebral toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy, are AIDS defining conditions with associated high mortality risk. Cerebral toxoplasmosis and cryptococcal meningitis typically manifest in immunosuppressed patients (<200 CD4+ T-cells/μL), while PML can occur in patients with higher CD4+ T-cell counts.Neurologic conditions are increasingly interconnected with chronic diseases, and classic opportunistic infections may have altered phenotypes in the cART era. However, there exist promising diagnostic methods and therapeutic approaches, as well as associated pitfalls in diagnosis and treatment.
自从联合抗逆转录病毒疗法(cART)问世以来,艾滋病病毒已从一种致命疾病转变为一种慢性病,常常表现为伴有相关混杂因素的较轻中枢神经系统(CNS)症状。获得cART治疗所带来的免疫恢复导致了一系列新的免疫介导的感染表现形式,其表型与晚期疾病中观察到的情况不同。与艾滋病病毒相关的神经认知障碍(HAND)包括一系列分类的疾病,反映了一系列临床表现、预后和严重程度不断增加的情况:无症状神经认知损害(ANI)、轻度神经认知障碍(MND)和艾滋病病毒相关痴呆(HAD)。HAND是通过对神经认知能力和功能表现的评估来定义的。在接受cART治疗且脑脊液病毒载量可检测且血浆病毒载量被抑制的患者中,或脑脊液病毒载量比低可检测血浆病毒载量高1 log10时检测到的进行性神经症状,是一种称为有症状脑脊液“逃逸”的现象的特征。CD8 + T细胞性脑炎可能是中枢神经系统免疫重建炎症综合征的一种形式,尽管接受cART治疗后病毒得到抑制,但它在患者中仍有表现,类似于中枢神经系统“逃逸”。脑弓形虫病、隐球菌性脑膜炎和进行性多灶性白质脑病是艾滋病的定义性疾病,具有较高的死亡风险。脑弓形虫病和隐球菌性脑膜炎通常在免疫抑制患者(<200个CD4 + T细胞/μL)中表现出来,而进行性多灶性白质脑病可发生在CD4 + T细胞计数较高的患者中。神经疾病与慢性疾病的联系日益紧密,在cART时代,经典的机会性感染可能具有改变的表型。然而,存在有前景的诊断方法和治疗方法,以及诊断和治疗中的相关陷阱。