Meningitis in a community with a high prevalence of tuberculosis and HIV infection

OBJECTIVES: To evaluate the spectrum of aetiologies, and distinguishing clinical and laboratory features, of meningeal infection in a community with a high prevalence of tuberculosis (TB) and HIV infection. SETTING: A hospital serving mineworkers, originating from rural areas of Southern Africa. DESIGN: Prospective cohort of 60 consecutive lumbar punctures (LPs), performed for suspected meningitis. MEASUREMENTS: Clinical history and examination; concurrent cerebrospinal fluid (CSF) and blood samples; mortality status six months after entry to study. RESULTS: 38 of 57 patients (66.7%) were HIV-1 positive, 59.5% of whom had a CD4 count <200 cells/mm3. Nine patients had tuberculous meningitis (TBM) and two had tuberculomas; four developed disease while on TB therapy. There was one case of multidrug, and two of isoniazid-resistant TBM. There were nine episodes of cryptococcal meningitis (seven patients), nine of aseptic meningitis, two of neurosyphilis and 20 normal LPs, including four with AIDS dementia complex (ADC). Ten patients with meningococcal infection, part of a larger outbreak, were significantly younger (p=0.004). All patients with tuberculous, cryptococcal (most immune-suppressed p<0.001) and aseptic meningitis were HIV-1 positive. Within six months, 19 patients had died. Death was associated with HIV positivity (p=0.004), low CD4 count (p<0.001) and a diagnosis of cryptococcal meningitis, CNS TB or ADC. CONCLUSION: HIV has a major impact on the burden of disease and mortality, with a predominance of opportunistic chronic meningitides, despite a meningococcal outbreak, in this community. Of concern is the development of TBM despite therapy, and the emergence of drug-resistant strains.     

Chronic meningitis in Thailand. Clinical characteristics, laboratory data and outcome in patients with specific reference to tuberculosis and cryptococcosis

The charts of 114 consecutive patients with chronic meningitis admitted to a general hospital in Bangkok, Thailand, between 1993 and 1999 were retrospectively reviewed. The most common causative agents were Cryptococcus neoformans (54%) and Mycobacterium tuberculosis (37%). HIV and other underlying diseases had a major impact on the presentation of chronic cryptococcal meningitis patients. Compared to HIV-negative cryptococcal meningitis patients (21%), HIV-positives (79%) had a significantly lower incidence of focal signs (p = 0.02), hydrocephalus (p = 0.03) and seizures (p = 0.001) during hospital stay, furthermore, a lower leucocyte level, a significantly higher glucose level (p = 0.02) and a lower protein level (p = 0.03) in the first cerebrospinal fluid examination. Of the 43 patients with chronic tuberculous meningitis, only 3 were HIV positive. Focal neurologic deficits were found more frequently in tuberculous meningitis patients (p = 0.001) when compared to cryptococcal meningitis patients without HIV. Cerebral infarction on cerebral CT was indicative of tuberculous meningitis. Cryptococcal meningitis patients with HIV infection had a worse outcome compared to non-AIDS patients. Advanced stage of the disease on admission, decreased level of consciousness prior to and on the admission day and raised intracranial pressure above 40 cm H(2)O at any given time were predictive of a poor outcome in tuberculous meningitis patients.     

The role of an Ommaya reservoir in the management of children with cryptococcal meningitis

Cryptococcal meningitis is the most common life-threatening fungal infection and is associated with high mortality in children. Amphotericin B plus flucytosine and fluconazole is the optimal current therapy. Implantation of an Ommaya reservoir for intraventricular infusion of medication and aspiration of cerebrospinal fluid (CSF) for the treatment of increased intracranial pressure (ICP) has been reported. Intraventricular injection of amphotericin B through an Ommaya reservoir in children with cryptococcal meningitis has not been reported previously. We report two children who had cryptococcal meningitis and associated increased intracranial pressure, and were treated with an Ommaya reservoir. Both patients experienced rapid reversal of symptoms. At the time of discharge both patients had recovered and have remained asymptomatic.     

The prognosis of hearing impairment complicating HIV-negative cryptococcal meningitis

Eight patients who had sensorineural hearing loss (SNHL) associated with cryptococcal meningitis were studied. After a minimum 3-year follow-up, one had died. Among the seven survivors, three had improved, two stabilized, and two progressed. Predictive factors included visual disturbance, meningeal enhancements on MRI, and a CSF cryptococcal antigen titer of >1:1,024. SNHL accounted for 30.8% (8/26) of cryptococcal meningitis patients in our study.     

基于单中心的中枢神经系统感染的疾病谱及预后分析

目的 探究中枢神经系统感染(central nervous system infection,CNSI)的疾病谱及预后分析.方法 回顾性分析河南科技大学第一附属医院神经内科2019年5月至2020年12月收治的102例CNSI患者的病例资料,分析临床基线资料,统计CNSI患者的发病率、病死率.结果 102例CNSI患者...     

肾脏病患者糖皮质激素和免疫抑制剂治疗并发隐球菌脑膜炎的诊断和治疗

目的肾脏病患者并发隐球菌脑膜炎的临床表现和诊治。方法分析4例糖皮质激素和免疫抑制剂治疗过程中并发隐球菌脑膜炎的临床表现、误诊原因、治疗特殊性和转归。结果例1为原发性小血管炎、Ⅲ型新月体肾炎患者;隐球菌败血症用氟康唑治疗过程中并发隐球菌脑膜炎和葡萄球菌败血症。例2、3、4均为系统性红斑狼疮患者,狼疮性肾炎(LN)维持治疗期出现发热,头痛,例1和例4继发癫痫,例2复视。例2和例3分别误诊3和5个月。4例均无家鸽接触史,有多种抗生素应用史,脑脊液均发现隐球菌。抗真菌治疗5～9天后体温正常。例1:氟康唑治疗22个月,大蒜素(120～60mg)7个月,痊愈。例2两性霉素B(总量2837mg)和氟康唑17个月。例3尿毒症行腹膜透析,伏立康唑静脉输注,1月后死亡。例4两性霉素B脂质体静脉输注并伏立康唑口服。例2和例4仍在抗真菌治疗中。结论肾脏病患者激素和免疫抑制剂治疗过程中如出现不明原因的发热、头痛尤其是癫痫、复视者,警惕隐球菌脑膜炎;有效长程抗真菌治疗外,加强支持治疗和并存的其他感染治疗尤为重要。     

Spectrum of fungal infection in a neurology tertiary care center in India

There is a paucity of studies on spectrum of fungal infections in neurology care. This study reports clinical, MRI and outcome of patients with central nervous system (CNS) fungal infections. 39 patients with CNS fungal infections treated in neurology service during the last 3?years were included and a detailed medical history and clinical examination were undertaken. Cranial MRI including paranasal sinuses were carried out and the location and nature of abnormalities were noted. Fungal infection was confirmed by CSF examination or histopathology. Death during hospital stay was noted. The median age was 37 (8–72)?years and 8 were females. The clinical features included altered sensorium in 31, focal motor deficits in 13, visual loss in 12, seizures in 10, diplopia in 7, and papilledema in 9 patients. 28 patients had the following predisposing conditions: HIV in 15, diabetes in 8, corticosteroid in 2 and alcohol, immunosuppression, neutropenia and analgesic abuse in 1 patient each. On CT or MRI scan, 5 patients had meningeal enhancement, 7 sinusitis, 10 each granuloma and infarction, 4 hydrocephalous and 1 cerebral venous sinus thrombosis. 28 patients had cryptococcal meningitis, 7 zygomycosis, 2 aspergillosis and 1 each candida and phaeohyphomycosis. Death was related to the type of fungal infection; all patients with zygomycosis and candida infection died. Rhinocerebral form of fungal infection due to zygomycetes has poorer survival compared to meningitis group which was mainly due to cryptococcal infection.     

脑脊液细胞学迈－格－姬染色在隐球菌脑膜炎诊断中的价值

目的 探讨脑脊液细胞学迈-格-姬(MGG)染色在隐球菌脑膜炎诊断中的价值.方法 对笔者所在医院诊治的48例隐球菌脑膜炎患者脑脊液涂片墨汁染色、细胞学MGG染色检查结果及诊断进行分析.结果 48例隐脑患者首次脑脊液常规墨汁染色发现隐球菌33例,首次检出率为68.8％;MGG染色发现46例,首次检出率为95.8％.MGG染色诊断隐球菌脑膜炎的敏感度高于墨汁染色,差别有统计学意义(P＜0.05).结论 脑脊液MGG染色检查对隐球菌的检出率可达95.8％,且可在脑脊液细胞学检查时一次完成,无需特殊染色,可作为中枢神经系统感染患者常规脑脊液细胞学检查.     

Intracerebral mass lesion diagnosed as cryptococcoma in a patient with sarcoidosis, a rare opportunistic manifestation induced by immunosuppression with corticosteroids

Cryptococcal infection of the central nervous system (CNS) typically affects patients with HIV infection. In addition, opportunistic infections can also occur during immunosuppressive therapies. Some patients develop cryptococcal meningitis. Cryptococcomas, however, are rarely observed. A 42-year-old patient with sarcoidosis known for 2??years presented with a cerebral mass lesion primarily thought to be CNS sarcoidosis. Stereotactic biopsy and extensive micro- and macrobiological investigations revealed a cryptococcoma which had emerged from cryptococcal meningitis despite 3 months of treatment. Differential diagnosis of cerebral cryptococcoma is difficult due to the unspecific findings in the CSF analysis if C. neoformans fails to be detected using Indian ink staining or PCR studies. In this case, stereotactic biopsy and pathohistological examination revealed C. neoformans causing intracerebral mass lesion. Intensive treatment with antifungal drugs was followed by remission of all symptoms. In conclusion, cryptococcoma of the CNS represents a very important indication of mass lesions in patients suffering from sarcoidosis and treated with corticosteroids.     

Rapid diagnosis of cryptococcal meningitis by microscopic examination of centrifuged cerebrospinal fluid sediment.

The classic India ink test is positive in only half of cryptococcal meningitis cases, and reliable, rapid cryptococcal antigen (CRAG) testing requires technical expertise and facilities not always available. We therefore examined cerebrospinal fluid (CSF) sediment using May-Giemsa, periodic acid-Schiff, and Gram stains in 16 patients with cryptococcal meningitis. The India ink test was positive in seven patients (44%), while microscopic examination of sediment revealed cryptococci in 13 (81%); in six of these 13 the India ink test was negative. Both methods failed to detect the pathogen in the remaining three patients. CRAG testing in CSF was negative in two patients (one with acquired immunodeficiency syndrome, one with diabetes mellitus) whose India ink test also was negative while cryptococci were identified in their CSF sediment. No false positives occurred with CSF May-Giemsa staining in 27 cases of aseptic meningitis with negative cultures for Cryptococcus. In all, microscopic examination of centrifuged and stained CSF sediment proved more sensitive for rapid diagnosis of cryptococcal meningitis than the India ink method, and in two of our patients cryptococci were seen in centrifuged CSF sediment despite negative CRAG and India ink tests.     

Seizures in human immunodeficiency virus infection

Among 630 patients with human immunodeficiency virus infection, 70 patients with new-onset seizures were studied. Generalized seizures occurred in 66 patients (94%): they occurred as the initial seizure in 56 patients (80%) and during follow-up in another 10 patients (14%). Partial seizures (18 patients), status epilepticus (10 patients), and recurrent seizures (38 patients) were also noted. Identified processes included cerebral toxoplasmosis in 11 patients, cerebral lymphoma in 8, metabolic derangement in 8, cryptococcal meningitis in 7, and vascular infarction in 4. In 32 patients (46%) seizures were not associated with identifiable brain lesions and were believed to result from human immunodeficiency virus cerebral infection. Phenytoin treatment was associated with adverse drug reactions in 16 of 62 patients who received it. Our results suggest that the majority of patients with human immunodeficiency virus and seizures do not have secondary focal brain lesions as the cause of the seizures and that human immunodeficiency virus infection alone can, and often does, cause seizures.     

Cryptococcal meningitis: clinical, diagnostic and therapeutic overviews

Cryptococcal meningitis has emerged as a leading cause of infectious morbidity and mortality in patients with AIDS. Among the human immunodeficiency virus (HIV)-seropositive subjects, cryptococcal meningitis is the second most common cause of opportunistic neuro-infection. Current trends are changing due to the marked improvement of quality and length of life produced by highly active antiretroviral therapy (HAART). The introduction of generic HAART in India has resulted in an increase in the number of individuals getting treatment for HIV infection, as the cost of highly active antiretroviral therapy (HAART) has decreased 20- fold. Cryptococcal meningitis occurs in non-HIV patients who are immunodeficient due to diabetes, cancer, solid organ transplants, chemotherapeutic drugs, hematological malignancies etc and rarely in healthy individuals with no obvious predisposing factors. Diagnosis of cryptococcal meningitis is fairly straightforward once the diagnosis is considered in the differential diagnosis of chronic meningitis. Treatment of a patient with cryptococcal infection is a challenge for both the physician and the patient, but rewarding, as many would recover with timely and adequate antifungal therapy.     

Neurological complications in AIDS patients: the 1-year retrospective study in Chiang Mai University, Thailand

The first case of AIDS patient in the northern part of Thailand was reported in 1987 (Vithayasai et al., 1996), marking the outbreak of an epidemic. In our experience, the neurological involvement in AIDS patients seems to have changed in pattern and incidence during the last 8 years. We have conducted a retrospective study to review the incidence of AIDS-defining diseases in the patients admitted to Chiang Mai University Hospital, Thailand during the period September 2001 to August 2002. There were 155 AIDS patients admitted during this specified period, 118 of which were male and 37 female, aged between 16 and 60. The incidence of neurological complications was 50.3 per 100 person-years, in which central nervous system involvement account for 46.5 per 100 person-years and peripheral nervous system involvement account for 3.8 per 100 person-years. The incidence of cryptococcal meningitis appeared to be decreasing since 1994 whereas the incidence of cerebral toxoplasmosis appeared to be increasing. The incidence of cryptococcal meningitis, cerebral toxoplasmosis and cytomegalovirus (CMV) infection was 18.0, 14.8 and 7.0 per 100 person-years, respectively. Other common non-neurological AIDS-defining illnesses in northern Thailand include pulmonary tuberculosis (15.4 per 100 person-years), extra-pulmonary tuberculosis (9.6 per 100 person-years), and disseminated penicilliosis (12.2 per 100 person-years). In this way and summarizing, in northern Thailand, the three most common neurological involvements before the era of highly active anti-retroviral therapy are cryptococcal meningitis, cerebral toxoplasmosis and CMV infection. The incidence of cryptococcal meningitis appeared to be decreasing whereas the incidence of cerebral toxoplasmosis seemed to be increasing.     

基本临床及实验室资料在成人结核性脑膜炎中的诊断价值

目的 以基本的临床及实验室资料为基础寻找成人结核性脑膜炎和新型隐球菌性脑膜炎的鉴别点,并建立相应诊断规则.方法 实验对象为中山大学附属第三医院2000年～2008连续住院的成人患者,包括100例结核性脑膜炎患者及119例新型隐球菌性脑膜炎患者,并分析其基本的临床及实验室资料.运用logistic回归分析寻找可独立预测结核性脑膜炎的危险因素,并建立相应的诊断规则.结果 Logistic回归分析得出六项可独立预测结核性脑膜炎的危险因素:性别、神志改变、视听损害、脑脊液蛋白、脑脊液白细胞数及合并颅外结核.利用上述因素建立的诊断规则其诊断结核性脑膜炎的灵敏度为78.0%,特异度为95.2%,阳性预测价值92.9%,阴性预测价值84.4%.结论 基本的临床及实验室资料有助于帮助鉴别结核性脑膜炎和新型隐球菌性脑膜炎,可在实验室条件不够完善的广大基层医院应用.     

Intracranial hypertension causing visual failure in cryptococcus meningitis.

Thirty four patients with cryptococcal meningitis seen in the University of Malaya medical centre since 1980 were reviewed. Eleven patients had bilateral papilloedema and visual impairment but eventually survived. Seven patients had intensive aggressive measures, including shunting to reduce intracranial hypertension irrespective of ventricular size shown in CT scan, and showed substantial improvement in vision. It is concluded that papilloedema and visual failure in cryptococcal meningitis reflects raised intracranial pressure and that this should be treated vigorously.     

Raised ICP in a child with cryptococcal meningitis: CT evidence of a distal CSF block

Raised intracranial pressure (ICP) often complicates the course of cryptococcal meningitis. The pathogenesis of the severely raised cerebrospinal fluid (CSF) pressure commonly associated with this condition is largely unexplained, because the majority of patients have normal cranial computed tomographic (CT) findings when diagnosed. We report a case of cryptococcal meningitis in a child who had severely raised CSF pressure on admission, and in whom repeated CT scanning showed progressive enlargement of the subarachnoid space and ventricular system during the course of treatment. The normalization of these spaces after ventriculoperitoneal (VP) shunting suggests a distal CSF block as the cause of the raised ICP in this patient. The CSF pressure was monitored and treatment with oral acetazolamide and furosemide resulted in a definite, but slow and incomplete lowering of ICP. Intrathecal therapy with hyaluronidase had no beneficial effect on either ICP or the degree of visual loss.     

获得性免疫缺陷综合征神经系统损害临床分析

目的 提高对获得性免疫缺陷综合征(艾滋病)合并神经系统损害临床特点的认识,以减少漏诊.方法 对28例人类获得性免疫缺陷病毒(HIV)感染和(或)艾滋病患者中的12例合并神经系统损害患者的临床资料和机会感染性疾病情况进行回顾,并结合文献分析总结.结果 12例患者分别诊断为艾滋病脑病(5例)、慢性脑膜炎(3例)、周围神经病...     

Acute polyradiculopathies in HIV-infected patients

We studied 17 consecutive cases of acute polyradiculopathy (PR) diagnosed in HIV-infected patients to investigate the possible causes of this syndrome in our milieu. Sixteen patients presented with lumbosacral PR and one patient had predominantly cervical PR. Electrophysiological study showed a predominantly motor axonal neuropathy in all patients examined. Six patients had a laboratory-confirmed aetiology for the PR: cytomegalovirus (CMV) was isolated from cerebrospinal fluid (CSF) in three cases, meningeal lymphomatosis was diagnosed by CSF cytology in two cases, and one patient had cryptococcal meningitis. Another patient was thought to have acute axonal polyradiculoneuritis associated with HIV infection. CMV and Mycobacterium tuberculosis were the probable agents in four and three patients, respectively. Finally, in three patients a cause could not be established. Both ganciclovir and foscarnet were effective in the treatment of definite or probable CMV PR. The present study confirms that acute lumbosacral PR in HIV-infected patients must be considered a syndrome with different causes. CMV and M. tuberculosis infections were the most frequent causative agents in our series (41% and 18% of the cases, respectively). Early empirical therapy is often necessary as definite diagnosis may be delayed or never achieved. Our experience suggests that, at least in our milieu, antituberculous drugs should be considered in some cases together with ganciclovir or foscarnet in the empirical therapy for PR in HIV-infected patients. Received: 14 April 1997 / Accepted: 6 June 1997     

系统性红斑狼疮合并中枢神经系统感染34例临床分析

目的研究分析系统性红斑狼疮(SLE)合并中枢神经系统感染的临床表现。方法回顾性分析2001年1月至2011年12月石家庄平安医院34例SLE合并中枢神经系统感染患者临床资料,提出临床特征及其相关危险因素。结果 34例SLE合并中枢神经系统感染,发生率为1.44%;其中结核性脑膜炎25例(73.53%),新型隐球菌脑膜炎7例(20.59%),病毒性脑膜炎2例(5.88%)。给予内科常规治疗,25例结核性脑膜炎痊愈21例,死亡4例;7例隐球菌脑膜炎痊愈3例,死亡4例。病毒性脑膜炎痊愈1例,死亡1例。本文SLE合并中枢神经系统感染34例中总共死亡9例(26.47%)。全部患者在诊断前均经过糖皮质激素治疗,28例患者应用较大剂量激素治疗,18例患者联合免疫抑制剂治疗。SLE合并中枢神经系统感染的临床特点主要为高热、头痛及意识障碍;狼疮活动度评分(SLEDAI)平均9±3分。脑脊液检查发现糖和氯化物降低明显。结论①系统性红斑狼疮合并中枢神经系统感染以结核性脑膜炎最常见;②肾上腺皮质激素、免疫抑制剂的应用是SLE合并感染的危险因素;③SLE合并中枢神经系统感染与狼疮活动度无关,而神经精神狼疮多发生于狼疮高度活动期,SLEDAI评分对二者鉴别诊断有意义;④狼疮合并中枢神经系统感染以高热、头痛及颅内压增高为主要表现,反复腰穿脑脊液检查对SLE合并中枢神经系统感染的诊断和判断预后有重要价值。