Measles virus and associated central nervous system sequelae

Worldwide, measles remains one of the most deadly vaccine-preventable diseases. In the United States, enrollment in the public schools requires that each child receives 2 doses of measles-containing vaccine before entry, essentially eliminating this once endemic disease. Recent outbreaks of measles in the United States have been associated with importation of measles virus from other countries and subsequent transmission to intentionally undervaccinated children. The central nervous system complications of measles can occur within days or years of acute infection and are often severe. These include primary measles encephalitis, acute postinfectious measles encephalomyelitis, measles inclusion body encephalitis, and subacute sclerosing panencephalitis. These measles-associated central nervous system diseases differ in their pathogenesis and pathologic effects. However, all involve complex brain-virus-immune system interactions, and all can lead to severe and permanent brain injury. Despite better understanding of the clinical presentations and pathogenesis of these illnesses, effective treatments remain elusive.     

Chlamydia pneumoniae infection of the central nervous system

Chlamydia pneumoniae is a common respiratory pathogen that is now being implicated in a number of chronic diseases. That the organism can infect vascular endothelium, macrophages and smooth muscle cells suggests that it may play a role in many systemic diseases. The present review focuses on the possibility that the central nervous system can also be a target of this agent. The tropism of C. pneumoniae to the neural tissue suggests it may play a role in diverse neurologic diseases, including Alzheimer's disease, multiple sclerosis and giant-cell arteritis.     

Pseudallescheria boydii infection of the central nervous system

Pseudallescheria boydii is a rare cause of central nervous system infection characteristically presenting as a neutrophilic meningitis or multiple brain abscesses. Factors predisposing to central nervous system infection with this fungus include immunosuppression and near drowning. The organism is infrequently cultured from fluid obtained by lumbar puncture, delaying clinical recognition and appropriate antifungal therapy. All untreated patients with P boydii infection of the central nervous system died. We describe a patient who developed a persistent neutrophilic meningitis with focal neurologic deficits due to P boydii 6 months after a freshwater aspiration pneumonia. We also review the characteristic clinical and pathologic features of previously reported cases and emphasize the importance of early detection and treatment in the management of this frequently intractable disease.     

The central nervous system and HIV infection

Human immunodeficiency virus (HIV) may be the cause of both primary and secondary brain diseases. In this review general features of HIV-associated neuropathology are discussed. Up to 90% of patients with AIDS have a variety of HIV-related brain diseases. Primary brain diseases including lymphocytic meningitis and HIV encephalitis are attributed directly to the effect of the virus on the brain. Secondary diseases including toxoplasmosis, cryptococcosis, primary leukoencephalopathies and lymphomas result from these patients' immunodeficiency status.     

Dengue infection presenting with central nervous system manifestation

The objective of this study was to investigate the possibility of dengue virus infection causing an abnormal neurologic presentation. Between 1996 and 1998, all pediatric patients with clinical manifestations of encephalitis-like illness who were admitted to the Department of Pediatrics, Siriraj Hospital were prospectively studied for any evidence of dengue virus infection. The diagnosis of dengue virus infection was based on mosquito viral isolation and serologic and polymerase chain reaction (PCR) evidence. Of 44 patients with the preliminary diagnosis of acute viral encephalitis, 8 were diagnosed with dengue infection. All of these 8 patients were diagnosed by serology. In addition to the serologic diagnosis, four also had positive PCR, one had positive viral isolation, and one had both positive PCR and viral isolation. Only two patients were diagnosed by serologic evidence alone. All except one had clinical courses and laboratory findings compatible with typical dengue infection. All had obvious encephalitic clinical manifestations with normal cerebrospinal fluid findings except one patient, who had mildly increased cerebrospinal fluid protein. All of these patients recovered completely and had benign clinical courses except one patient, who developed leakage symptoms. None had liver failure. Dengue virus can cause acute encephalopathy with fever. It can masquerade as other types of acute viral encephalitis. However, its clinical course and prognosis are usually favorable.     

Glucocorticoids in central nervous system bacterial infection.

OBJECTIVE: To evaluate evidence-based data on adjunctive glucocorticoid therapy in central nervous system bacterial infections. DESIGN: A literature review of studies, particularly controlled trials, that have evaluated dexamethasone therapy for acute bacterial meningitis and glucocorticoid therapy for tuberculous meningitis. MAIN OUTCOME MEASURES: Clinical outcomes were mortality and morbidity rates. Morbidity involved sensorineural hearing loss and other neurologic deficits (motor or behavioral disturbances, epilepsy, cranial nerve palsy, hydrocephalus, and psychomotor retardation). RESULTS: The evidence-based data support adjunctive dexamethasone therapy for children with Haemophilus influenzae meningitis. However, the optimal duration of therapy is not defined. Data are supportive but not conclusive that dexamethasone benefits meningitis caused by other bacterial agents and meningitis in adults. The evidence-based data are supportive but not conclusive that adjunctive glucocorticoid therapy benefits patients with tuberculous meningitis, particularly those with more severe infection. CONCLUSIONS: Although adjunctive glucocorticoid therapy may be beneficial in both acute bacterial meningitis and more severe tuberculous meningitis, there are conclusive data only for H influenzae meningitis in children. For acute bacterial meningitis, further studies are needed to clarify the optimal duration of dexamethasone therapy (2 vs 4 days), whether this therapy should be used routinely for adults with meningitis, and whether it should be used for pathogens other than H influenzae. For tuberculous meningitis, further studies are needed to provide conclusive evidence of benefit.     

儿童中枢神经系统新型隐球菌感染

对３例儿童中枢神经系统新型隐球菌感染患者临床特征和脑脊液结果的分析表明：（１）该菌可以感染多个脏器，而中枢神经系统最常受累。（２）病人的临床症状和体片与其他脑膜脑炎或脑膜炎相似。（３）如诊断不及时，则治疗效果不佳，预后极差。（４）为了提高治愈率，药物的应用和疗程必须严格遵守合理用药原则．     

Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis

Our identification of Chlamydia pneumoniae in the cerebrospinal fluid (CSF) of a patient with multiple sclerosis (MS) led us to examine the incidence of this organism in the CSF from 17 patients with relapsing–remitting MS, 20 patients with progressive MS, and 27 patients with other neurological diseases (OND). CSF samples were examined for C pneumoniae by culture, polymerase chain reaction assays, and CSF immunoglobulin (Ig) reactivity with C pneumoniae elementary body antigens. C pneumoniae was isolated from CSF in 64% of MS patients versus 11% of OND controls. Polymerase chain reaction assays demonstrated the presence of C pneumoniae MOMP gene in the CSF of 97% of MS patients versus 18% of OND controls. Finally, 86% of MS patients had increased CSF antibodies to C pneumoniae elementary body antigens as shown by enzyme-linked immunosorbent assay absorbance values that were 3 SD greater than those seen in OND controls. The specificity of this antibody response was confirmed by western blot assays of the CSF, using elementary body antigens. Moreover, CSF isoelectric focusing followed by western blot assays revealed cationic antibodies against C pneumoniae. Infection of the central nervous system with C pneumoniae is a frequent occurrence in MS patients. Although the organism could represent the pathogenetic agent of MS, it may simply represent a secondary infection of damaged central nervous system tissue. A therapeutic trial directed at eliminating C pneumoniae from the central nervous system may provide additional information on its role in MS. Ann Neurol 1999;46:6–14     

HIV infection of the central nervous system: clinical features and neuropathogenesis

Almost 65 million people worldwide have been infected with HIV since it was first identified in the early 1980s. Neurologic disorders associated with HIV type 1 affect between 40% and 70% of infected individuals. The most significant of these disorders include HIV-associated neurocognitive disorder, which comprises HIV-associated dementia, mild neurocognitive disorder, and asymptomatic neurocognitive impairment. Despite the availability of combination antiretroviral therapy, HIV-related central nervous system disorders continue to represent a substantial personal, economic, and societal burden. This review summarizes the clinical manifestations, diagnosis, treatment, and pathogenesis of the primary HIV-associated central nervous system disorders.     

Involvement of the central nervous system in patients with dengue virus infection

The findings of a neurological evaluation in 85 patients with confirmed, acute, dengue virus infection are described. Signs of central nervous system involvement were present in 18 patients (21.2%). The most frequent neurological symptom was mental confusion. The frequency of neurological involvement did not differ between patients with primary and secondary dengue infection, and the prevalence of central nervous system involvement in dengue fever and dengue hemorrhagic fever also did not differ significantly. The presence of CNS involvement did not influence the prognosis of dengue infection. Dengue viral CSF RNA was found in 7 of 13 patients submitted to a spinal tap, the CSF viral load being less than 1000 copies/ml. PCR was negative in serum samples obtained from three patients on the same day as the CSF samples, suggesting that the dengue virus actively enters the CNS and that the presence of the virus in the CNS does not result from passive crossing of the blood-brain barrier.     

Sex differences in susceptibility to viral infection of the central nervous system

We have characterized striking differences in recovery of male and female BALB/c and BALB/c-H-2^dm2 (dm2) mice from an experimental neurotropic viral infection of the central nervous system (CNS). Following intranasal inoculation of vesicular stomatitis virus (VSV), assays of tissue homogenates from female mice produced lower viral titers. There was also a significant reduction in the spread of virus from the rostral to caudal end of the brain in female mice. Enhanced recovery by female mice of both strains in response to this viral insult correlates with increased levels of Nitric Oxide Synthase (NOS) types I, II, and III expression, an increased prevalence of reactive astrocytes, earlier and enhanced levels of expression of Major Histocompatabilty Complex (MHC) class II molecules on astrocytes, endothelial and microglial cells, and increased T cell infiltration in the female BALB/c mouse. Taken together, these findings document sexual dimorphism in CNS immunity, and may provide an understanding of some of the mechanisms underlying many sex-biased diseases.     

Cerebrospinal fluid testing for the diagnosis of central nervous system infection.

The central nervous system (CNS) is susceptible to bacterial, viral, and fungal infections, and prion diseases. Examination of the cerebrospinal fluid (CSF) is crucial in diagnosing these infections. Cerebrospinal tests may directly identify an organism and its nucleic acid and surface constituents by culture, polymerase chain reaction (PCR), or antigen detection. Alternatively, antibody to an organism may be identified in CSF by enzyme-linked immunosorbent assay (ELISA), Western blot, or complement fixation assay. This article discusses how these CSF tests are performed and addresses the sensitivity and specificity of such tests for the diagnosis of selected CNS infections.     

Cerebrospinal fluid formula in patients with central nervous system infection

Knowledge of the CSF formula is clinically useful and at times critical in the analysis of a number of diagnostic problems presented by patients with CNS infections. The decision to withhold antimicrobial therapy in the patient with an acute meningitis syndrome, when viral etiology is suspected, is justified in the presence of a polymorphonuclear cellular reaction provided the CSF glucose is greater than 45 mg per dl and the protein less than 130 mg per dl. Patients who fail to improve clinically should be retapped in 8 to 12 hours. A persisting PMN reaction or the combination of a PMN pleocytosis and hypoglycorrachia virtually rules out viral infection and, in the face of negative routine cultures, requires a diligent search for focal parameningeal suppuration and consideration of CNS tuberculosis and fungal infection. Careful re-evaluation of the patient emphasizing factors such as duration of illness and potential sites of parameningeal suppuration will be useful in guiding further diagnostic studies. Head CT scanning including views of the sphenoid sinuses may be especially helpful in this regard.