Neuropsychiatric sequelae of Nipah virus encephalitis

The authors followed nine patients with Nipah virus encephalitis over the course of 24 months. Eight of the nine developed psychiatric features assigned to the encephalitis. Three patients developed major depressive disorder immediately after recovering from the encephalitis, and two developed depression approximately 1 year after the outbreak. Two patients developed personality changes, and two suffered chronic fatigue syndrome. Neuropsychological testing was accomplished in eight of the nine patients. Deficits in attention, verbal, and/or visual memory were substantial in seven of the eight patients tested. Verbal memory was more impaired than visual memory in these patients. Comparison between psychiatric and cognitive impairment and total number of brain lesions showed no discernible trends.     

High apolipoprotein E in cerebrospinal fluid of patients with Lewy body disorders is associated with dementia

Apolipoprotein E ε4 allele (APOE ε4) increases the apolipoprotein E (apoE) protein levels in Alzheimer’s disease (AD) cerebrospinal fluid (CSF). Thus, we hypothesized that apoE levels were also associated with the APOE genotype, and amyloid-β (Aβ)-associated clinical, functional, and imaging parameters in patients with Lewy body-associated disorders (LBD). Indeed, similar to AD, patients with LBD displayed high CSF apoE levels (greatest in patients with dementia with LBD), and this was linked to APOE ε4. High CSF apoE protein correlated positively with CSF soluble amyloid precursor protein, total tau, and cortical and striatal Pittsburgh compound B retention; and correlated negatively with CSF Aβ₄₂, cognitive tests scores, and glucose uptake ratio in the temporal and parietal cortices. APOE ε4-triggered accumulation of apoE in CSF is related to Aβ-associated clinical and functional imaging parameters in LBD. Accordingly, therapeutic strategies aimed at reducing apoE levels in the brain should be explored not only in AD but also in LBD, particularly when accompanied with dementia.     

Chronic mumps virus encephalitis. Mumps antibody levels in cerebrospinal fluid

To study the outcome of mumps virus encephalitis 47 patients were contacted 1-15 years after the acute encephalitis associated with mumps virus infection. Twenty-three patients experienced clinical sequelae such as difficulties in memory and learning, focal motor or sensory signs, and loss of hearing and visual acuity. Lumbar puncture was performed on 8 patients. Antibodies to mumps virus were detected in 6 cerebrospinal fluid (CSF) specimens using enzyme immunoassay and in 3 patients an abnormal serum/CSF antibody ratio was observed 11, 26 and 58 (controls greater than 85); 14.3, 1.4 and 6.1 years after the acute encephalitis, respectively. Antibodies to other microbes were either undetectable in the CSF or the serum/CSF ratios were normal. The clinical sequelae in about half of the patients and the signs of intrathecal mumps antibody production are suggestive of a chronic process in the central nervous system after encephalitis associated with mumps virus infection.     

Diagnostic value of cerebrospinal fluid antibodies in herpes simplex virus encephalitis.

Antibodies to different viruses and bacteria were measured in the cerebrospinal fluid (CSF) of six patients with herpes simplex virus encephalitis proven by brain biopsy and in five others with a presumptive diagnosis. Antibodies to herpes simplex virus but not to other organisms appeared in the CSF of all patients after the first weeks of the illness. Herpes simplex virus antibodies were not found in control CSF. The antibodies persisted in the CSF and the serum/CSF antibody ratio remained altered, 32:1 to less than 1:1, in all cases during the follow-up to 29 months or until death. The CSF albumin level was normal and the IgG index (formula: see text) elevated in four proven and three presumptive cases indicating a local antibody production; in four patients the findings were inconsistent. These results suggest that prolonged antigen stimulation is present in the central nervous system after acute herpes simplex encephalitis and that serological measurements combined with immunoglobulin and albumin determinations may provide a tentative but not definite diagnosis in some cases after the acute phase of encephalitis together with a method for follow-up of patients.     

Limited value of cerebrospinal fluid for direct detection ofToxoplasma gondii in toxoplasmic encephalitis associated with AIDS

The diagnosis of acquired immunodeficiency syndrome-associated toxoplasmic encephalitis (TE), a typically focal disease resulting from reactivation of tissue cysts, relies mainly on indirect diagnostic methods. In a prospective study, we investigated the value of detection ofToxoplasma gondii in cerebrospinal fluid (CSF) by using the polymerase chain reaction and the mouse inoculation test. Twenty-four patients with 26 episodes of TE, 2 HIV-infected patients with primary acuteToxoplasma infection, and 38 HIV-infected control patients with latentToxoplasma infection were investigated. Detection ofT. gondii in CSF by both methods was possible in only 3 of the TE patients (11.5%), the remaining patients being negative with either of the methods. In contrast,T. gondii DNA was detected in both of the acutely infected patients, indicating that in primary acute toxoplasmosis parasites may easily be found in the CSF, whereas in the majority of TE cases in immunocompromised patients,T. gondii parasites do not gain access to the CSF drawn by lumbar puncture.     

Nipah virus: An emergent paramyxovirus causing severe encephalitis in humans

Nipah virus is a recently emergent paramyxovirus that is capable of causing severe disease in both humans and animals. The first outbreak of Nipah virus occurred in Malaysia and Singapore in 1999 and, more recently, outbreaks were detected in Bangladesh. In humans, Nipah virus causes febrile encephalitis with respiratory syndrome that has a high mortality rate. The reservoir for Nipah virus is believed to be fruit bats, and humans are infected by contact with infected bats or by contact with an intermediate animal host such as pigs. Person to person spread of the virus has also been described. Nipah virus retains many of the genetic and biologic properties found in other paramyxoviruses, though it also has several unique characteristics. However, the virologic characteristics that allow the virus to cause severe disease over a broad host range, and the epidemiologic, environmental and virologic features that favor transmission to humans are unknown. This review summarizes what is known about the virology, epidemiology, pathology, diagnosis and control of this novel pathogen.     

AIDS myelopathy is not associated with elevated HIV viral load in cerebrospinal fluid

ARTICLE ABSTRACT: The pathogenesis of AIDS-associated myelopathy is unknown. Elevated HIV-1 viral load in CSF has been associated with cognitive impairment. The authors investigated if a similar association exists in patients with myelopathy. The authors evaluated levels of HIV-1 RNA in the CSF of 16 individuals with AIDS myelopathy and in 16 nonmyelopathic HIV-infected control subjects. There was no correlation between levels of HIV-1 RNA and the presence or severity of myelopathy.     

Amyloid beta 1-42 in cerebrospinal fluid is associated with cognitive plasticity

Cerebrospinal fluid (CSF) total tau-protein (t-tau) and amyloid-beta 1-42 (Abeta^1-42) have been increasingly included in the diagnostic process of Alzheimer's disease (AD). We aimed to analyze whether these CSF biomarkers correlate with cognitive plasticity as measured by a dynamic recognition test strategy. We assessed 29 elderly individuals (15 with incipient and 14 without AD) from an outpatient memory clinic at a university hospital by a Testing-the-Limits (TtL) based recognition paradigm consisting of a pre-test (baseline) and two post-test conditions with an interposed encoding instruction. We identified a negative association between Abeta^1-42 and the two post-test failure rates, but not with that of the pre-test. Also, none of the standard tests correlates with Abeta 42-1 level. T-tau does not correlate with recognition performance. Our results suggest that Abeta^1-42 could be useful as a state marker for cognitive plasticity.     

Treatment of acute Nipah encephalitis with ribavirin.

Nipah virus, a newly identified paramyxovirus caused a severe outbreak of encephalitis in Malaysia with high fatalities. We report an open-label trial of ribavirin in 140 patients, with 54 patients who were managed prior to the availability of ribavirin or refused treatment as control. There were 45 deaths (32%) in the ribavirin arm; 29 deaths (54%) occurred in the control arm. This represents a 36% reduction in mortality (p = 0.011). There was no associated serious side effect. This study suggests that ribavirin is able to reduce the mortality of acute Nipah encephalitis.     

Interferon gamma concentration in the cerebrospinal fluid of patients with tick-borne encephalitis

BACKGROUND AND PURPOSE: The purpose of this work was to evaluate interferon gamma (IFN-g) concentration in the cerebrospinal fluid of patients with diagnosed tick-borne encephalitis (TBE) early in the course of the disease and after the treatment. MATERIAL AND METHODS: The cerebrospinal fluid of 40 patients with TBE was examined. Patients were divided into 4 groups: group 1 consisted of 13 patients with mild clinical course, group 2 included 12 patients with prolonged TBE showing the presence of inflammatory markers after the treatment, group 3 comprised 9 patients with severe TBE presenting with disorders of consciousness and group 4 consisted of 6 patients with a simultaneous B. burgdorferi infection. The cerebrospinal fluid was examined twice--during TBE diagnosing and after the treatment. IFN-g was detected by the ELISA method. RESULTS: The concentration of IFN-g in the cerebrospinal fluid in the first examination was significantly higher in all four groups of patients in comparison with controls. After the treatment, concentration of IFN-g decreased significantly in all studied groups. The highest concentration of IFN-g at the first examination was found in group 3. The concentration of IFN-g at the second examination was similar among 4 groups of patients and in controls. CONCLUSIONS: We found the correlation between IFN-g concentration in the cerebrospinal fluid of patients at the early stage of TBE and inflammation activity. We did not find any association between IFN-g concentration and a persistent increase of the cerebrospinal fluid parameters.     

Core cerebrospinal fluid biomarker profile in anti-LGI1 encephalitis

Journal of Neurology - To compare CSF biomarkers’ levels in patients suffering from anti-Leucine-rich Glioma-Inactivated 1 (LGI1) encephalitis to neurodegenerative [Alzheimer’s disease...     

病毒性脑炎患者血液和脑脊液博尔纳病病毒p24的检测

目的探讨博尔纳病病毒（BDV）与病毒性脑炎（VE）的关系。方法采用巢式逆转录聚合酶链反应（RT-PCR）结合荧光定量（FQ）PCR检测了52例VE患者和32例外科手术患者外周血液（PBMC）和脑脊液有核细胞（CSFMC）中的BDV p24基因片段，对阳性产物进行了基因序列测定、同源性和氨基酸顺序分析。结果VE患者PBMC和CSFMC中BDV p24基因片段阳性率（分别为9．6％和11．5％）明显高于对照组（0，P〈0．05）；PBMC和CSFMC中BDV p24基因片段拷贝数的对数值呈显著正相关（r=0．653，P〈0．05）；CSFMC所含目的基因片段阳性产物测序后，与BDV标准病毒株V核苷酸序列比较同源性为96．5％，在3个位点出现突变（nt1649T→C，nt1670C→T，nt1673C→T），突变率为3．5％。从系统发生树图形可以看出，该目的基因片段与澳大利亚马脑组织分离的S88和德国绵羊血液分离的H544病毒株亲缘关系最近。结论宁夏及其周边地区部分VE患者中可能存在BDV感染。     

The neurological manifestations of Nipah virus encephalitis, a novel paramyxovirus.

A novel Hendra-like paramyxovirus named Nipah virus (NiV) was the cause of an outbreak among workers from one abattoir who had contact with pigs. Two patients had only respiratory symptoms, while 9 patients had encephalitis, 7 of whom are described in this report. Neurological involvement was diverse and multifocal, including aseptic meningitis, diffuse encephalitis, and focal brainstem involvement. Cerebellar signs were relatively common. Magnetic resonance imaging scans of the brain showed scattered lesions. IgM antibodies against Hendra virus (HeV) were present in the serum of all patients. Two patients recovered completely. Five had residual deficits 8 weeks later.     

Increased intracranial pressure is associated with elevated cerebrospinal fluid ADH levels in closed-head injury

Abstract

Objectives: Head injury frequently results in increased intracranial pressure and brain edema. Investigators have demonstrated that ischemic injury causes an increase in cerebrospinal fluid (CSF) levels of antidiuretic hormone (ADH); increased CSF ADH levels exacerbate cerebral edema, and inhibition of the ADH system with specific ADH antagonists reduces cerebral edema. The current study was designed to test the hypothesis that elevated levels of ADH are present in the CSF of subjects with head injury.

Methods: Ventricular CSF and blood samples were taken from 11 subjects with head injury and 12 subjects with no known head trauma or injury. ADH levels were analyzed using radioimmunoassay. Severity of increased intracranial pressure (ICP) was rated in head-injured subjects using a four-point ordinal scale, based on which treatments were necessary to reduce ICP.

Results: Subjects with head injury had higher CSF (3.2 versus 1.2 pg/ml; P<0.02) and plasma (4.1 versus 1.4 pg/ml; P<0.02) levels of ADH than did control subjects. In head-injured subjects, CSF ADH levels positively correlated with severity of ICP.

Discussion: The results of this study suggest that ADH plays a role in brain edema associated with closed head injury.     

Spread of herpes simplex virus to the cerebrospinal fluid and the meninges in experimental mouse encephalitis

Summary The development of the inflammatory response within the brain, meninges and cerebrospinal fluid (CSF) compartment has been studied for the first time simultaneously in experimental herpes simplex virus (HSV) encephalitis after inoculation via the cornea. Two major viral pathways were found from the eye to the brain: one through the trigeminal nerve to the brain stem and one through the nasolacrimal duct to the olfactory system. Viral antigen was found to be present in the CNS before there were clinical signs or cellular infiltration of brain tissue. Subsequently, the virus spread to all parts of the trigeminal brain stem complex. This phenomenon was accompanied by severe inflammation of the meninges covering the trigeminal root near its entry into the brain stem. The meninges near the entry of the olfactory fila also contained antigen. However, HSV-1 did not spread along meningeal rami of the trigeminal nerve and, consequently, is — at least in this experimental model — not a route to reach the inferior frontal and temporal lobes. The development of CSF changes followed the histopathological development of meningitis and encephalitis closely. HSV-DNA could be detected in the CSF from day 4 post inoculation (p.i.) and HSV-1-specific immunofluorescence in CSF cells was convincingly present on day 5 p.i.; on the same days (4 and 5 p.i.) inflammatory cells were found in apposition to infected cells in the brain. We postulate that HSV is carried to the CSF by infected leukocytes rather than a direct spread to the CSF by simple extension of the encephalitic process to the meningeal surface. Consequently, the chances of detection of viral antigen in CSF cells or HSV-DNA by polymerase chain reaction in CSF at an early, pre-encephalitic stage of disease are slight. The relevance of the findings to the pathogenesis and diagnosis of human herpes simplex encephalitis is discussed.Supported in part by the Stichting Prof. AAH Kassenaar Fonds, Faculty of Medicine, University of Leiden     

Elevated cerebrospinal fluid IgA in humans and rats is not associated with secretory component

Immunoglobulin A (IgA) is transported across mucosal tissue membranes covalently bound to secretory component (SC). To determine if this receptor-mediated process also occurs at central nevous system (CNS) boundaries, cerebrospinal fluid (CSF) and serum from patients with CNS neuroinflammatory disease were analyzed for IgA and SC. Excess CSF IgA was detected in six of 24 patients, but no significant CSF SC was detected. In a parallel study using a rat model with normal brain barriers, inactivated lymphocytic choriomeningitis virus was microinfused into CSF. Elevated CSF IgA was detected in four of six rats, yet the proportion of secretory IgA was again insignificant compared to normal exocrine fluids (bile, semen). There does not appear to be a secretory IgA immune system at CNS boundaries and elevated CSF IgA is attributed to intrathecal synthesis.