Sleep disorders are long-term sequelae of both bacterial and viral meningitis

BACKGROUND: Many bacterial meningitis patients experience neurological or neuropsychological sequelae, predominantly deficits in short-term memory, learning, and attention. Neuropsychological symptoms after viral meningitis are observed less frequently. Sleep disturbance has been reported after both viral and bacterial meningitis. OBJECTIVES: To examine systematically the frequency and extent of sleep disturbance in meningitis patients. METHODS: Eighty six viral or bacterial meningitis (onset of acute disease at least 1 year previously) patients were examined using two standardised questionnaires (Schlaffragebogen B and the Pittsburgh Sleep Quality Index, PSQI) in conjunction with a standardised neurological examination, and compared to a control group of 42 healthy age-matched volunteers. RESULTS: Patients after both viral and bacterial meningitis described their sleep as reduced in quality and less restful than that of healthy control subjects; both patient groups had a pathological mean PSQI total score. Impaired sleep scores after meningitis were not correlated to either the Glasgow Coma Scale or the Glasgow Outcome Scale. Moreover, no relationship between residual neurological dysfunction or depressivity and sleep quality was observed. CONCLUSIONS: Impaired sleep is a long-term consequence of meningitis. Additional, so far undetermined, factors other than the severity of concomitant neurological deficits are responsible for the development of this sequela.     

Motor and somatosensory evoked potentials in tuberculous meningitis: a clinico-radiological correlation

OBJECTIVE: The sensory and motor functions in severe tuberculous meningitis (TBM) may be difficult to assess clinically and may be helped by evoked potential studies. Lack of motor and somatosensory evoked potential studies in TBM prompted the present study. METHODS: All the patients with TBM underwent detailed neurological evaluation and cranial CT scan study. Motor and somatosensory evoked potentials to both upper and lower limbs were carried out bilaterally. The outcome was defined on the basis of 3 month Barthel Index (BI) score into good (BI > 12) and poor (BI < 12). RESULTS: Forty-one highly probable patients with TBM whose ages ranged between 8 and 64 years and 14 of whom were females were included in this study. Twenty-three patients were in stage III (meningitis, neurological signs and altered sensorium), 12 in stage II (meningitis with neurological sign) and the remaining patients were in stage I (meningitis only). Cranial CT scan was carried out in all and MRI in 18 patients. On CT scan hydrocephalus was present in 21, infarction in 14 and tuberculoma in 4 patients. Motor evoked potential (MEP) was abnormal in 18 patients (36 limbs) and SEP in 9 patients (23 limbs). Upper limb central motor conduction time to abductor digiti minimi (CMCT-ADM) was abnormal in 15 and that to tibialis anterior (TA) in 21 limbs. CMCT abnormality was lateralized in 6 and only upper or lower limbs were involved in 11 patients. The SEP abnormalities were lateralized in 2 patients and only upper or lower limbs were involved in 3. The MEP changes correlated with stage of TBM and outcome whereas SEP with outcome only. CONCLUSION: Motor and somatosensory evoked potentials may be helpful in objective documentation of respective motor and sensory functions in TBM patients with altered sensorium.     

非HIV人群中结核性脑膜炎和隐球菌性脑膜炎鉴别诊断列线图模型的开发和验证

目的研究和开发针对非人类免疫缺陷病毒(HIV)人群中结核性脑膜炎和隐球菌性脑膜炎鉴别诊断的列线图模型,并对模型进行验证。方法回顾性收集西京医院神经内科收治的292名结核性脑膜和隐球菌性脑膜炎患者的临床资料,根据入院时间将240名患者纳入训练组,52名患者纳入验证组。对训练组患者进行单因素和多因素分析,筛选鉴别两种脑膜炎的差异因子。利用R软件构建鉴别诊断列线图模型,并对模型进行验证。在训练组和验证组中绘制ROC曲线和校准曲线对模型进行评价。结果单因素和多因素分析后发现,患者年龄、发热、自身免疫性疾病、脑脊液初压、脑脊液白细胞计数、脑脊液糖含量是鉴别结核性脑膜炎与隐球菌性脑膜炎的差异因子(P0.05)。模型灵敏度为80%,特异度为76.47%。列线图模型ROC曲线下面积在训练组和验证组中分别为0.853和0.897,模型区分度和校准度较好。结论在非HIV人群中结核性脑膜炎与隐球菌性脑膜炎的鉴别诊断列线图模型,对于基层医院进行脑膜炎的早期诊断和治疗具有一定的临床应用价值。[国际神经病学神经外科学杂志, 2021, 48(2):103-109]     

Blood-brain-barrier and intrathecal immunoglobulin changes in tuberculous meningitis and demyelinating disorders: a preliminary report from a South Indian hospital

Sixty-three paired serum and CSF samples (15 controls and 48 patients) were studied for CSF albumin quotient, IgG index and synthesis rate. Control values for albumin quotient and IgG index were less than 10.0 and less than 0.6 respectively. IgG synthesis rate/day was calculated according to the Tourtellotte formula and a value of greater than 3.0 mg/day is considered high. Our findings in patients with central demyelinations, subacute sclerosing panencephalitis, Guillain Barré Syndrome and cerebrovascular accidents are comparable to earlier studies. Fifteen tuberculous meningitis patients were studied and could be separated into 2 groups, 9 with elevated albumin quotients and 6 with normal albumin quotients. Three patients with elevated albumin quotients and 4 with normal albumin quotients showed increased intrathecal IgG synthesis.     

Antibody-induced neutrophil depletion prior to the onset of pneumococcal meningitis influences long-term neurological complications in mice

During pneumococcal meningitis, clearance of bacteria by recruited neutrophils is crucial for host protection. However, these innate immune mechanisms are often insufficient and treatment with antibiotics is necessary to prevent death. Despite this antibiotic treatment, approximately half of all survivors suffer lifelong neurological problems. There is growing evidence indicating the harmful effects of neutrophils on CNS integrity. Therefore, the present study investigated the roles of neutrophils in the acute inflammatory response and the resulting long-term neuropsychological effects in murine pneumococcal meningitis. Long-term behavioural and cognitive functions in mice were measured using an automated IntelliCage system. Neutrophil depletion with antibody 1A8 as adjunctive therapy was shown to remarkably impair survival in meningitic C57BL/6J mice despite antibiotic (ceftriaxone) treatment. This was accompanied by increased bacterial load in the cerebrospinal fluid (CSF) and an increase in IL-1β, but decrease in TNF, within the CSF at 20 h after bacterial inoculation. In the longer term, the surviving neutrophil-depleted post-meningitic (PM) mice displayed reduced diurnal hypolocomotion compared to PM mice treated with an isotype antibody. However, they showed nocturnal hyperactivity, and greater learning impairment in a patrolling task that is believed to depend upon an intact hippocampus. The data thus demonstrate two important mechanisms: 1. Neutrophil extravasation into the CNS during pneumococcal meningitis influences the pro-inflammatory response and is central to control of the bacterial load, an increase in which may lead to death. 2. Neutrophil-mediated changes in the acute inflammatory response modulate the neuropsychological sequelae in mice that survive pneumococcal meningitis.     

Rapid diagnosis of tuberculous meningitis by a dot-immunobinding assay

In this study, a dot-immunobinding assay (Dot-Iba) was standardized to measure circulating antimycobacterial antibodies in the cerebrospinal fluid (CSF) specimens for the rapid laboratory diagnosis of tuberculous meningitis (TBM). Specific CSF-IgG antibody to Mycobacterium tuberculosis from a culture proven patient with TBM was isolated and coupled with activated Cynogen bromide-Sepharose 4B. Using an immunoabsorbent affinity chromatography, 14 kDa antigen present in the culture filtrates of M. tuberculosis was isolated and this antigen was used in the Dot-Iba, to quantitate specific antimycobacterial antibodies in CSF specimens. The Dot-Iba gave positive results in all the 5 culture proven patients with TBM and gave no false positive results in CSFs from patients with partially treated pyogenic meningitis. Dot-Iba developed in our laboratory is a simple, rapid and specific method and more importantly suited for the routine application in laboratories with limited resources.     

结核性脑膜炎诊治的若干问题探讨（附44例报告）

本文总结了４４例结核性脑膜炎（结脑）的诊治经验。提出本病早期误诊，多因缺乏对本病的警惕性。人型ＰＰＤ试验阴性率高达４７．７％，故阴性者亦不能完全排除，滥用氨基糖甙类抗菌素及糖皮质激素，使病情隐蔽增加误诊机会。脑脊液的结核菌ＰＣＲ检查及反复多次进行胸部Ｘ线检查有利于确立诊断，头颅ＣＴ或ＭＲ检查有助于发现脑积水。对结脑的治疗除了控制结核感染外，还要注意防治并发症，对脑梗阻患者行侧脑室持续冲洗置换术治疗可收到良效。     

新型隐球菌脑膜炎30例临床分析

目的探讨30例新型隐球菌脑膜炎(CNM)的临床特征。方法回顾性分析2013—2016年入住中南大学湘雅医院神经内科的30例CNM患者的临床资料,结合文献对其进行讨论。结果 30例CNM患者,仅1例有明确鸽子接触史,6例合并有致免疫力低下的基础疾病,11例发病前为无基础疾病的健康人群。3例为急性起病,6例亚急性起病,21例慢性起病。临床表现为持续性或间歇性头痛,伴有发热、非喷射性呕吐。平均经2.1次腰穿确诊,发病至确诊天数平均为24.3天,21例曾被误诊为其他疾病。15例患者失访,15例有完整随访资料,其中仅3例使用(Am B或脂质体Am B+5-FC)-FCZ序贯治疗。完整随访的15例中,死亡2例,存活13例,生存率为87%。结论 CNM在正常人群和免疫力低下的人群中均可发生,由于临床表现、脑脊液化验结果不典型及确诊手段不敏感,导致发病至确诊周期过长,误诊率高。虽然临床实际应用的治疗方案差异较大,但总体生存率较高,积极治疗有助于CNM生存率提高。     

Long‐term outcomes of status epilepticus: A critical assessment

We reviewed 37 studies reporting long‐term outcomes after a status epilepticus (SE) episode in pediatric and adult populations. Study design, length of follow‐up, outcome measures, domains investigated (mortality, SE recurrence, subsequent epilepsy, cognitive outcome, functional outcome, or quality of life), and predictors of long‐term outcomes are summarized. Despite heterogeneity in the design of prior studies, overall risk of poor long‐term outcome after SE is high in both children and adults. Etiology is the main determinant of outcome, and the effect of age or SE duration is often difficult to distinguish from the underlying cause. The effect of the treatment on long‐term outcome after SE is still unknown.     

Clinical neurological trauma parameters as predictors for neuropsychological recovery and long-term outcome in paediatric closed head injury: a review of the literature

We present a review of recent prospective studies of long-term outcome in paediatric closed head injury. Special attention is given to the relationship between the neurological trauma parameters and neuropsychological outcome. First we discuss the most important methods of assessing the severity of the injury. We review the most prominent neurobehavioural and cognitive sequelae. Subsequently we address the question of prediction of residual sequelae in view of the early trauma parameters. The main problem when comparing different studies is the lack of procedural uniformity both in assessment of the severity of the injury as well as in measurement of neuropsychological outcome. Inconsistencies and discrepancies among various studies are pointed out. We summarise those results which are supported by many studies and hence are less controversial. In addition we present some recommendations for future investigations.     

The cortical neuroanatomy of neuropsychological deficits in mild cognitive impairment and Alzheimer's disease: a surface-based morphometric analysis

Patients with probable Alzheimer's disease (AD) and the amnesic form of mild cognitive impairment (aMCI) often demonstrate several types of neuropsychological deficits. These deficits are often related to cortical atrophy, induced by neuronal degradation. The purpose of this study is to investigate whether different anatomic patterns of cortical atrophy are associated with specific neuropsychological deficits. The participants were 170 patients with AD and 99 patients with aMCI. All participants underwent the Seoul Neuropsychological Screening Battery (SNSB), which includes tests that assess attention, language, visuospatial functions, verbal and visual memory, and frontal/executive functions. Cortical atrophy (thinning) was quantified by measuring the thickness of the cortical mantle across the entire brain using automated, three-dimensional magnetic resonance imaging. The relationship between cortical thickness and neuropsychological performance was analysed using stepwise multiple linear regression analyses. These analyses (corrected P < .001) showed that several specific brain regions with cortical thinning were associated with cognitive dysfunction including: digit span backward, verbal and picture recall, naming and fluency, drawing–copying, response inhibition and selective attention. Some of the other functions, however, were not associated with specific foci of cortical atrophy (digit span forward, the word reading portion of the Stroop test, word and picture recognition). Our study, involving a large sample of participants with aMCI and AD, provides support for the postulate that cortical thinning-atrophy in specific anatomic loci are pathological markers for specific forms of cognitive dysfunction.     

Utility of molecular and serodiagnostic tools in cerebral toxoplasmosis with and without tuberculous meningitis in AIDS patients: A study from South India

Background:

Antemortem diagnosis of cerebral toxoplasmosis, the second most common opportunistic infection (OI) in HIV-infected individuals in developing countries is a challenge.

Materials and Methods:

Toxoplasma gondii (T.gondii) -specific serology and nested polymerase chain reaction (nPCR) were evaluated in sera and ventricular/lumbar cerebrospinal fluid (CSF) of 22 autopsy confirmed cases of cerebral toxoplasmosis with HIV and 17 controls. Frequency of concomitant T.gondii infection was investigated in 17 cases of HIV-associated tuberculous meningitis (TBM).

Results:

The sensitivity, specificity, and positive and negative predictive values of T. gondii IgG on CSF (ventricular and lumbar) and sera was 100% in histology proven cerebral toxoplasmosis (concentrations: 258 ± 50, 231 ± 36, and 646 ± 243 IU/mL, respectively); majority (94%) being high avidity type, suggesting reactivation/reinfection. The sensitivity of B1 nPCR was 100% on ventricular CSF, whereas it was only 77% on lumbar CSF. Based on histology, nPCR, and IgG serology, T. gondii co-infection with TBM was observed in 65% (11/17) of cases.

Discussion and Conclusion:

CSF IgG serology and nPCR are tests with high sensitivity and specificity for the diagnosis of cerebral toxoplasmosis. TBM and cerebral toxoplasmosis can coexist and should be considered in the background of HIV infection in developing countries.     

Identifying functional imaging markers of mild cognitive impairment in early Alzheimer’s and Parkinson’s disease using multivariate analysis

Functional neuroimaging, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), provides a valuable technique for detecting regional changes in brain metabolic activity and blood flow associated with mild cognitive impairment (MCI) and dementia. Multivariate analysis techniques have recently received increasing attention. The results of multivariate analysis can be more easily interpreted as a signature of neuronal networks, which lend themselves to prospective application of results from the analysis of one dataset to entirely new datasets. They are well placed to provide information about mean differences and correlations with behavior with potentially greater statistical power and better reproducibility. This article will focus on investigating the baseline and progression of MCI using functional brain imaging techniques and multivariate analysis in order to understand the genesis and natural history of cognitive impairment in Alzheimer’s disease (AD) and Parkinson’s disease (PD), respectively.     

Determinants of intellectual outcome after surgical revascularization in pediatric moyamoya disease: a multivariate analysis

Objects The aim of this study was to clarify predictors for poor intellectual outcome in pediatric moyamoya disease.Methods Fifty-two pediatric patients were included. Clinical diagnosis was transient ischemic attacks (TIA) in 35 and completed stroke in 17. Ten patients underwent indirect synangiosis through small craniotomy, whereas the other 42 underwent superficial temporal artery (STA)–middle cerebral artery (MCA) anastomosis and indirect synangiosis through large craniotomy. Full-scale IQ (FSIQ) was measured using the Wechsler intelligence scale for children (WISC) after surgery. Multivariate logistic regression models were applied to test the effect of clinical factors on intellectual outcome.Results and conclusion Eight patients revealed mentally impaired status (FSIQ<70). Multivariate analysis revealed that completed stroke and small craniotomy surgery were significantly associated with poor intellectual outcome. Odds ratios of each factor were 33.4 (95% CI, 2.4–474) and 19.6 (95% CI, 1.8–215) respectively. Early diagnosis and the revascularization procedure over as wide an area as possible may be essential to improve their intellectual outcome.     

Striatal dopamine transporter binding for predicting the development of delayed neuropsychological sequelae in suicide attempters by carbon monoxide poisoning: A SPECT study

Carbon monoxide poisoning (COP) after charcoal burning results in delayed neuropsychological sequelae (DNS), which show clinical resemblance to Parkinson's disease, without adequate predictors at present. This study examined the role of dopamine transporter (DAT) binding for the prediction of DNS. Twenty-seven suicide attempters with COP were recruited. Seven of them developed DNS, while the remainder did not. The striatal DAT binding was measured by single photon emission computed tomography with ^99mTc-TRODAT. The specific uptake ratio was derived based on a ratio equilibrium model. Using a logistic regression model, multiple clinical variables were examined as potential predictors for DNS. COP patients with DNS had a lower binding on left striatal DAT binding than patients without DNS. Logistic regression analysis showed that a combination of initial loss of consciousness and lower left striatal DAT binding predicted the development of DNS. Our data indicate that the left striatal DAT binding could help to predict the development of DNS. This finding not only demonstrates the feasibility of brain imaging techniques for predicting the development of DNS but will also help clinicians to improve the quality of care for COP patients.