MRI findings of recurrent herpes simplex encephalitis in an infant

We report the MRI findings of a 2-year-old boy with recurrent herpes simplex encephalitis (HSE). At the age of 14 months, the patient developed a high fever that lasted over 1 week and he did not receive appropriate treatment. At 6 months after the fever, MRI showed marked atrophic changes in both deep temporal lobes with hyperintensity in the hippocampi and parahippocampal gyri. Thirteen months after the first episode of the fever, the patient was diagnosed with recurrent HSE by polymerase chain reaction assay of the CSF; MRI at this time revealed diffuse cortical swelling. Hyperintensity on T2-weighted images was noted in the occipito-parietal cortex bilaterally, the left thalamus, the subcortical white matter and the splenium of the corpus callosum. Recurrence of HSE may be more common in infants than previously thought. It is important to consider the possibility of recurrent HSE and to understand that MRI findings in HSV1 encephalitis in infants and young children appear to differ from those observed in neonates, older children and adults.     

Vacuolating encephalitis in mice infected by human coronavirus OC43

Involvement of viruses in human neurodegenerative diseases and the underlying pathologic mechanisms remain generally unclear. Human respiratory coronaviruses (HCoV) can infect neural cells, persist in human brain, and activate myelin-reactive T cells. As a means of understanding the human infection, we characterized in vivo the neurotropic and neuroinvasive properties of HCoV-OC43 through the development of an experimental animal model. Virus inoculation of 21-day postnatal C57BL/6 and BALB/c mice led to a generalized infection of the whole CNS, demonstrating HCoV-OC43 neuroinvasiveness and neurovirulence. This acute infection targeted neurons, which underwent vacuolation and degeneration while infected regions presented strong microglial reactivity and inflammatory reactions. Damage to the CNS was not immunologically mediated and microglial reactivity was instead a consequence of direct virus-mediated neuronal injury. Although this acute encephalitis appears generally similar to that induced by murine coronaviruses, an important difference rests in the prominent spongiform-like degeneration that could trigger neuropathology in surviving animals.     

Rasmussen's syndrome and new-onset narcolepsy, cataplexy, and epilepsy in an adult

We report a case of new-onset seizures and narcolepsy in a previously healthy 40-year-old man. He developed severe daytime somnolence and cataplexy over the course of a few months. Brain MRI was normal, and polysomnography with multiple sleep latency testing confirmed a diagnosis of narcolepsy. His HLA haplotype is DQB1*0602 and cerebrospinal fluid analysis showed no detectable hypocretin. Approximately 18 months later, he developed complex partial seizures. Further MRI showed a progressively enlarging lesion involving the left frontotemporal and insular areas. Pathology from a partial resection was consistent with Rasmussen's syndrome. Evaluation for tumor, infectious, and paraneoplastic etiologies was negative. There was no further progression of the residual lesion on serial MRI. Although the pathophysiologic bases of narcolepsy and Rasmussen's syndrome are unknown, they may have an autoimmune basis. This unique case of both disorders in a single patient suggests the possibility of a common underlying disease process.     

The dual role of CD8+ T lymphocytes in the development of stress-induced herpes simplex encephalitis

Despite the generally restrictive nature of the blood–brain barrier (BBB), circulating lymphocytes can infiltrate into the central nervous system (CNS) during a variety of disease states. Although the contributions of these lymphocytes to CNS-associated disease have been identified in some viral models, the factors which govern this infiltration following herpes simplex virus (HSV) infection remain to be elucidated. We have developed a murine model of HSV encephalitis (HSE) to define the relationship among psychological stress, the recruitment of HSV-specific T cells into the CNS, and the development of HSE. Naive mice, as well as mice that had been vaccinated with a recombinant vaccinia virus (rVVESgB498–505) that elicits the generation of HSV-1 gB498–505-specific CD8⁺ T cells, were infected intranasally (i.n.) with HSV-1 McIntyre. Beginning one day prior to HSV-1 infection and continuing for a total of 9 days, naive and vaccinated mice were exposed to a well-established stressor, restraint stress. Naive, stressed mice exhibited increased symptoms of HSE and HSE-associated mortality as compared to non-stressed controls. A concomitant increase in CD4⁺ and CD8⁺ T cells in the brain was observed throughout the infection, with CD8⁺ T cells outnumbering CD4⁺ T cells. The development of HSE in these naive, stressed mice was accompanied by a delayed infiltration of gB498–505-specific CD8⁺ T cells after HSV spread into the brain. In contrast, both stressed and non-stressed rVVESgB498–505-vaccinated mice possessed gB498–505-specific CD8⁺ T cells prior to HSV challenge and were protected against HSE despite having detectable HSV-1 DNA in the brain. Together, these findings suggest that a delayed infiltration of CD8⁺ T cells into the brain may promote HSE in naive mice, while the presence of HSV-specific CD8⁺ T cells in the brain prior to HSV challenge is protective, possibly by limiting HSV replication and spread within the CNS.     

Anti-herpes simplex type 1 activity in IgG subclasses produced systemically and intrathecally in patients with herpes encephalitis

Summary The role of the humoral immune response in herpes simplex encephalitis (HSE) is largely unknown. The finding that herpes simplex virus type 1 (HSV 1) induced IgG Fc receptor binds to all IgG subclasses except IgG 3 prompted an investigation of anti-HSV activity in IgG subclasses from serum and cerebrospinal fluid (CSF) in ten patients with proven or highly probable HSE by means of a monoclonal antibody IgG subclass-specific solid-phase radioimmunoassay (SPRIA). In contrast to serum, CSF contained no or low anti-HSV IgG titres during the first 2 weeks of disease in five of seven patients tested. The IgG titres rose thereafter for at least 4 weeks after the start of illness and remained high in both serum and CSF up to 393 days. The anti-HSV IgG subclass distribution in serum was IgG 1 (ten of ten), IgG 2 (two of ten), IgG 3 (six of ten), and IgG 4 (six of ten). Two patients had a simultaneous anti-HSV IgG 3 and IgG 4 response. With the exception of one patient lacking anti-HSV IgG 4 and two patients lacking anti-HSV IgG 2, the subclass distribution in CSF was the same as in serum. The anti-HSV subclass distribution in sera from ten seropositive patients without evidence of recent herpes infection did not differ from that of the HSE patients, except that five of ten patients had simultaneous anti-HSV IgG 3 and IgG 4 responses. Thus we could not correlate the anti-HSV subclass response in patients with HSE with the subclass preference of the HSV-induced Fc receptor.     

Human immunodeficiency virus (HIV)-induced disease of the central nervous system: pathology and implications for pathogenesis

Summary Significant contributions from many different groups during the last 2 or 3 years have characterized relatively uniform neuropathological changes of the CNS in AIDS patients. They feature human immunodeficiency virus (HIV)-induced multinucleated giant cells as a histopathological hallmark and HIV demonstrable by electron microscopy, immunocytochemistry, and in situ hyridization. Unfortunately, a varying and confusing terminology is used to designate these changes which have been reported in surprisingly different incidences. Focal lesions have a microgranulomatous appearance and were designated as multifocal giant cell encephalitis or subacute encephalitis, which may be confused with the nodular encephalitis caused by cytomegalovirus. For some authors, the latter designation also covers characteristic diffuse white matter changes which have been termed progressive diffuse leukoencephalopathy by others, and which may overlap with focal lesions. Pathological features of these HIV-induced syndromes and other data do not support a major cytopathic effect of HIV on neural cells; rather, they suggest secondary pathogenetic events involving the predominant cell type in the lesion, the monocyte/macrophage/microglia. However, low-level, latent, and persisting HIV infections of neural cells cannot be excluded at present; the CNS may then serve as an early infected virus reservoir. A detailed correlation of clinical symptoms and stage of the infection to neuropathological changes is currently lacking but urgently needed. The presence of the HIV-receptor (CD4) molecule on brain cells is controversial; similarly, a putative cross-reaction of HIV proteins with trophic substances and transmitters needs to be substantiated.Supported in part by the Medical-Scientific Fund of the Lord Mayor of the Federal Capital of Vienna, Austria     

Cytomegalovirus (CMV) disease of the brain in AIDS and connatal infection: a comparative study by histology,immunocytochemistry and in situ DNA hybridization

Summary Brain tissues from 45 patients with AIDS and two brains with connatal cytomegalic inclusion body disease were investigated for a cytomegalovirus (CMV) etiology of encephalitic lesions. Nineteen brains showed evidence of CMV infection by histology, immunocytochemistry (ICC) using two different antibodies (mono- and polyclonal), and in situ hybridization (ISH). Fourteen cases with typical cytomegalic cells in conventional histology [eight with focally necrotizing encephalitis/ventriculitis including the two connatal infections and six with nodular encephalitis (NE)] revealed CMV with any method. In 5 of 15 AIDS cases of NE without cytomegalic cells, CMV infection was established by ISH, whereas ICC remained negative in these cases. Typical lesions of human immunodeficiency virus (HIV)-induced multifocal giant cell encephalitis (HIV encephalitis) in 13 brains were never labeled for CMV. In necrotizing encephalitis/ventriculitis, cell types which labeled for CMV, with and without cytomegalic change, comprised neurons, astrocytes, oligodendrocytes, ependyma, choroid plexus, endothelia, and cells in periand endoneurium, and in leptomeninges. Both ISH and ICC were able to detect widespread non-cytomegalic CMV-infected cells in normal parenchyma, well beyound the necrotizing lesions, in two AIDS cases. Labeling patterns of nuclei versus cytoplasms varied between the three methods for CMV detection. We conclude that in CNS tissues with cytomegalic cells, ICC and ISH are of comparable sensitivity; however, a diagnosis of CMV disease is possible in such cases by conventional histology. For an in situ diagnosis of CMV infection in NE without cytomegalic cells in AIDS, ISH is the method of choice. A selective vulnerability to CMV infection of any specific cell type of the human CNS is absent. With our detection methods, typical lesions of HIV encephalitis do not show local co-infection by CMV.Supported by The Lord Mayor's Medico-Scientific Fund Vienna, Austria     

Acute encephalitis with refractory,repetitive partial seizures

Acute encephalitis with refractory, repetitive partial seizures (AERRPS) represents a peculiar form of encephalitis mainly affecting children. They usually present abruptly with seizure or impaired consciousness as well as high-grade fever following antecedent infection. Seizures in AERRPS are almost exclusively of localized origin, whose semiology includes eye deviation, hemifacial twitching, hemiclonic convulsion, and autonomic manifestations. Partial seizures are brief, but repeat with increasing frequency and develop status epilepticus at nadir. They are extremely pharmaco-resistant and are only suppressed by intravenous administration of high-dose barbiturates. Although acute seizures are hardly controlled, patients gradually recover with decreasing seizure frequency and continuously evolve into post-encephalitic epilepsy without latent period. Residual cognitive impairment is common. Electroencephalograms in active stage demonstrate electrical seizure activities and interictal periodic discharges. Magnetic resonance imaging reveals late cerebral atrophy with limited signal abnormality. Persistent fever during active stage, cerebrospinal fluid (CSF) pleocytosis, and up-regulation of neopterin raise the hypothesis that inflammatory process is involved in this condition. Furthermore, early production of autoantibody against NMDA receptor 2B in serum and CSF, although its disease specificity is still in controversy, is suggestive of autoimmune etiology. Exploration for definite clinical marker is currently in progress.     

森林脑炎病毒RNA的提取及其性质

从森林脑炎病毒感染的鼠脑组织中直接抽提总核酸,然后经Sepharose4B柱层析将病毒RNA与细胞RNA分离,方法简便、分离的病毒RNA在260nm处有典型的紫外吸收光谱,260/280nm的比值近似2,对RNase敏感,有感染性。     

The treatment of subacute sclerosing panencephalitis with interferon: a case report

Summary A child with subacute sclerosing panencephalitis (SSPE) received intraventricular alpha interferon (IFN) as experimental treatment. The course was monitored by colleagues in pediatric neurology, neuro-opthalmology and clinical psychology, also by monthly EEGS and brain CT scans. Two courses of IFN were administered. During the first course, improvement occurred nearly to the premorbid level of function. About 1 month after this trial was stopped, a severe recrudescence rapidly produced a thalamic state. A second trial of IFN resulted in less improvement. When the brain CT showed severe degeneration, the second trial was stopped. Intraventricular administration of alpha IFN was well tolerated in both courses of therapy. Alpha IFN has promise in the treatment of SSPE but the optimal dosage and duration of treatment are undetermined.