Toxoplasmic encephalitis in AIDS.

Involvement of the central nervous system (CNS) is common in patients with advanced disease due to human immunodeficiency virus (HIV). Symptoms range from lethargy and apathy to coma, incoordination and ataxia to hemiparesis, loss of memory to severe dementia, and focal to major motor seizures. Involvement may be closely associated with HIV infection per se, as in the AIDS dementia complex, but is frequently caused by opportunistic pathogens such as Toxoplasma gondii and Cryptococcus neoformans or malignancies such as primary lymphoma of the CNS. The clinical presentations of attendant and direct CNS involvement are remarkably non-specific and overlapping, yet a correct diagnosis is critical to successful intervention. Toxoplasmic encephalitis is one of the most common and most treatable causes of AIDS-associated pathology of the CNS. A great deal has been learned in the last 10 years about its unique presentation in the HIV-infected patient with advanced disease. Drs. Benjamin J. Luft of the State University of New York at Stony Brook and Jack S. Remington of the Stanford University School of Medicine and Palo Alto Medical Foundation's Research Institute have studied T. gondii for many years and are two of the leading experts in the field. This commentary comprises an update of their initial review (J Infect Dis 1988;157:1-6) and a presentation of the current approaches to diagnosing and managing toxoplasmic encephalitis in HIV-infected patients.     

Toxoplasmic encephalitis in patients with AIDS

Toxoplasmic encephalitis has been recognized as a major CNS complication in patients with AIDS and is the most frequent cause of focal intracerebral lesions in these patients. This complication of AIDS is almost always observed in patients who have a chronic (latent) infection with Toxoplasma gondii. Therefore, patients who from the outset of their HIV infection or AIDS are known to have antibodies to T. gondii should be considered at risk for development of toxoplasmic encephalitis. Although serologic tests cannot distinguish active from latent infection, a patient who is seronegative for Toxoplasma antibodies is unlikely to have toxoplasmic encephalitis. Neuroradiologic studies may be highly suggestive of toxoplasmic encephalitis, but, at present, the definitive diagnosis can be made only by demonstration of Toxoplasma in brain tissue. The unique pathogenesis of toxoplasmic encephalitis in patients with AIDS makes intensive primary therapy followed by a lifelong suppressive regimen necessary. We recommend 6 weeks of high doses of pyrimethamine and sulfadiazine (or trisulfapyrimidines) as primary therapy for the acute disease followed by daily administration of reduced doses of these drugs. The use of clindamycin as an alternative drug for primary therapy, at least at present, must be regarded as investigational and should be reserved for patients who suffer severe reactions to the sulfonamides. As most patients will respond to their primary therapy, those who fail to improve clinically and radiologically to therapy within 10 days should be evaluated for additional or alternative causes of their intracerebral pathology. This will often necessitate brain biopsy.     

艾滋病相关性弓形虫脑炎的影像学诊断

目的 评估艾滋病脑弓形虫脑炎的影像表现的诊断价值. 方法 回顾分析17例艾滋病脑弓形虫脑炎患者的影像表现. 结果 病变多为双侧多发,可少发;侵犯基底核12例,丘脑3例,皮髓质连接区1例;累及小脑及脑干1例;CT呈低密度,MRI呈长T1、长T2信号;周围水肿效应明显;增强扫描,小环状、螺旋状或靶形增强12例;巨大环形增强1例;多发病灶15例,单发2例. 结论 位于基底节区的多发小环状、螺旋状或靶形增强,高度提示脑弓形虫脑炎.CT和MRI对弓形虫脑炎是有效的诊断方法.MRI对病灶检出率明显高于CT.     

Sulfadiazine-induced crystalluria in AIDS patients with toxoplasma encephalitis

Toxoplasma encephalitis is the most common opportunistic infection of the central nervous system in patients with AIDS. The treatment of choice is a combination of sulfadiazine and pyrimethamine. We present here four patients with AIDS treated for toxoplasmic encephalitis who developed sulfadiazine-induced crystalluria. This complication was rapidly reversible with rehydration and urine alkalinization. Patients with AIDS treated with high doses of sulfadiazine should be adequately hydrated, and their urinary pH maintained above 7.5 to prevent sulfadiazine-induced crystalluria.     

AIDS合并巨细胞病毒脑炎临床分析

目的探讨艾滋病（AIDS）合并巨细胞病毒脑炎（CMVE）的临床特点及治疗转归。方法回顾性地收集北京地坛医院2011年3月-2013年2月收治的8名合并CMVE的AIDS病人的临床资料,分析其症状和体征、辅助检查、病毒学检查及治疗转归情况。结果 8例病人脑脊液CMV脱氧核糖核酸（DNA）或CMV-IgM抗体阳性,但血清中CMV DNA可阴性。7例CD4＋淋巴细胞计数均〈30/μL,轻症、早期病人可不伴随神经精神症状,头颅核磁共振（MRI）检查可无异常,7例患者经抗CMV及高效抗反转录病毒治疗（HAART）后均获得临床好转。结论合并CMVE易出现在CD4＋淋巴细胞计数低的AIDS病人中,及时对可疑病人进行脑脊液CMV DNA或CMV-IgM抗体检查,有利于早期诊断和治疗。     

Dementia in AIDS patients in Oslo; the role of HIV encephalitis and CMV encephalitis.

In a well-defined population of adult AIDS patients from Oslo, we studied the correlation between clinical dementia and autopsy results. The study included 91% of all adult AIDS patients from Oslo who died between 1983 and 1996. The autopsy rate was 73% (167/229). Twenty-three percent of patients had definite dementia and 24% possible dementia. In more than half of the patients with definite dementia multinucleated giant cells were present in the brain tissue, suggesting that the dementia was due to HIV encephalitis. Diffuse damage of white matter also showed a significant association with clinical dementia. When found alone it tended to occur in symptomatic patients with a short survival time from onset of dementia until death. This indicates that diffuse damage of white matter may be an early stage of HIV encephalitis. CMV encephalitis was found in 28 cases (17%). Of these, 20 were classified as definitely or possibly demented. In 14 of these 20 cases we detected no multinucleated giant cells, suggesting that CMV caused or contributed to the dementia. Multiple logistic regression supported an association between CMV and conditions clinically classified as HIV dementia. We conclude that HIV encephalitis is the major cause of dementia in AIDS patients, but that CMV encephalitis as a cause of dementia has been underestimated.     

20例AIDS合并巨细胞病毒脑炎的临床分析

目的探讨AIDS并发巨细胞病毒脑炎的临床特点、诊治及转归。方法回顾性分析北京地坛医院2012年1月—2015年1月明确诊断为AIDS并发巨细胞病毒脑炎的20例患者临床资料,分析其临床表现特点、脑脊液检测结果及诊治过程。结果 20例患者均处于AIDS晚期的严重免疫缺陷状态,临床表现不典型,多有智力下降、头痛、意识障碍以及神经功能受损表现,影像学检查无显著特异性,疗效较差。结论巨细胞病毒脑炎临床表现缺乏特异性,须尽早确诊治疗以降低病死率。     

Diagnosis and quantitative detection of HSV DNA in samples from patients with suspected herpes simplex encephalitis

Diagnosis of herpes simplex encephalitis (HSE) is based on the detection of herpes simplex virus (HSV) DNA in patients’ CSF samples. HSV DNA quantitation has the potential for estimating the effects of antiviral therapy. The aim of this study was to diagnose HSV DNA in HSE suspected patients and the quantitative analysis of its genome using real-time PCR to assess the value of the viral load in the course of antiviral treatment. The CSF samples were collected from 236 consecutive HSE suspected patients from November 2004 to May 2008. Upon DNA extraction, the samples were analyzed by Real-Time PCR assay. A set of primers amplified a common sequence of HSV glycoprotein B gene. The copy numbers of unknown samples were expressed via a standard curve drawn with a known amount of amplified cloned plasmid. Of the 236 samples, 137 (58%) came from males and 99 (42%) from females. The HSV genome was detected in 22 (9.3%) patients by PCR, 13 males/9 females. Serial CSF samples were available from 10 of the 22 patients. The range of the HSV DNA copy numbers in the clinical samples ranged from 2.5 × 10² to 1.7 × 10⁶ copies/mL of CSF. Quantitative PCR results can be helpful in evaluating the efficacy of antiviral therapy in the above-mentioned patients. There is an association between the initial viral load and the duration of treatment course.     

Low-dose trimethoprim-sulfamethoxazole prophylaxis for toxoplasmic encephalitis in patients with AIDS.

OBJECTIVE: To determine the efficacy of low-dose trimethoprim-sulfamethoxazole (trimethoprim, 160 mg plus sulfamethoxazole, 800 mg; one tablet twice daily, 2 days per week) as primary prophylaxis against toxoplasmic encephalitis in patients with human immunodeficiency virus (HIV) infection and previous Pneumocystis carinii pneumonia. DESIGN: A retrospective study. SETTING: Tertiary referral teaching hospital. PATIENTS: During a 3-year period after primary episodes of P. carinii pneumonia, 60 patients received trimethoprim-sulfamethoxazole, and 95 patients received pentamidine (aerosolized in 78 patients and intravenous in 17 patients) as secondary prophylaxis. RESULTS: No patient in the trimethoprim-sulfamethoxazole group and no patient seronegative for Toxoplasma gondii developed toxoplasmic encephalitis, compared with 12 of 36 (33%; 95% Cl, 19% to 51%) seropositive patients in the pentamidine group (trimethoprim-sulfamethoxazole compared with pentamidine, P = 0.008). A significant difference was seen in the time to development of toxoplasmic encephalitis between the trimethoprim-sulfamethoxazole group (no case at 1153 days) and the pentamidine group (median time, 460 days) (P = 0.004). Neither the CD4+ lymphocyte count at the start of prophylaxis nor zidovudine therapy during the period of prophylaxis influenced the rate of toxoplasmic encephalitis in any group. CONCLUSIONS: Low-dose trimethoprim-sulfamethoxazole (four tablets per week) appears to be effective prophylaxis against toxoplasmic encephalitis in HIV-infected patients with previous P. carinii pneumonia. A prospective, randomized, controlled study is needed to further evaluate these findings.     

Cytomegalovirus encephalitis in two patients with AIDS receiving ganciclovir for cytomegalovirus retinitis

Cytomegalovirus (CMV) encephalitis has been reported with increasing frequency in patients with AIDS. Nevertheless, the management of CMV-related encephalitis appears to be problematic and data in the literature on the clinical efficacy of ganciclovir therapy is sparse and controversial. We describe two patients with AIDS who developed CMV encephalitis while receiving ganciclovir maintenance therapy for CMV retinitis. Moreover, there was no improvement in neurological status or virological and radiological response during a further induction course of ganciclovir. These observations suggest that the currently recommended therapeutic protocols with ganciclovir are not effective in the prevention and treatment of CMV encephalitis in patients with AIDS.     

Motor recovery following acute stroke

There is little information available from which normal patterns of recovery from acute stroke can be ascertained. Most attention has been directed towards functional recovery in stroke patients but the neurological basis on which this occurs needs to be documented in a large cohort of patients. One hundred and fifty-seven patients admitted to hospital with a clinical diagnosis of acute stroke were examined daily for up to 28 days to determine the patterns of recovery of limb tone, power and reflexes. Changes in these variables during the first 28 days after stroke are described.