Brain thermo-pooling is the major problem in pediatric influenza encephalitis

The prognosis of pediatric encephalitides, such as infantile influenza encephalitis, is still poor because of the rapid progression, severe brain edema, selective bilateral basal ganglia necrosis, and a poor immune function, the mechanism of which is still unknown. Especially, little is known about virus es in CSF and brain tissue with influenza encephalitis, which hampers successful treatment of this condition. Recently, hypothermia treatment has attracted attention as the management of infantile influenza encephalitis to prevent severe brain edema. Recent clinical studies have revealed brain thermo-pooling (elevation of brain tissue temperature) with damage of blood-brain barrier (BBB). We then studied brain injury mechanism after severe brain injuries, cerebral strokes, reperfusion after shock, and high fever with lower cerebral perfusion pressure in our ICU. The brain thermo-pooling phenomenon results from body temperature higher than 38 degrees C, systolic blood temperature lower than 90-100 mmHg, and cerebral perfusion pressure (CPP) lower than 70 mmHg that hinders washout of brain tissue temperature by cerebral blood flow. We have recorded of brain tissue temperature of 40-44 degrees C in various brain injured patients. Some pathophysiological changes in infantile influenza encephalitis may be explained on the basis of this brain thermo-pooling phenomenon. In systemic infection, it causes severe brain edema by activation of cytokines and destruction of BBB, bilateral basal ganglia necrosis by acute severe brain hypoxia, resulting in poor prognosis without control of brain temperature. In other words, brain thermo-pooling, is the major target of treatment for infantile influenza encephalitis. In this paper, new concepts of the brain injury mechanism and methods of brain hypothermia treatment of pediatric influenza encephalitis are presented.     

Hepatitis C virus (HCV) infection as a risk factor for spontaneous intracerebral hemorrhage: hospital based case-control study.

Hepatitis C Virus (HCV) infection was investigated as a risk factor for intracerebral hemorrhage (ICH) by HCV antibody screening in 462 patients with ICH and 462 control patients with cerebral infarction matched by age and sex. Laboratory examinations of hemostatic parameters and cholesterol level were also performed in patients with ICH. HCV infection was significantly more frequent in patients with ICH than controls (8.7% vs 3.5%, P< 0.01). ICH patients with HCV infection had significantly higher L-alanine:2-oxoglutarate aminotransferase level (P< 0.001), lower cholesterol level (P< 0.05), lower platelet count (P< 0.05), and longer prothrombin time (P< 0.01) than ICH patients without HCV infection, although most of these values were within the normal range. These results demonstrate that HCV infection is a risk factor for spontaneous ICH. Subclinical clotting disorder and/or vessel wall friability resulting from hypocholesteremia may be associated with ICH in patients with HCV infection.     

^18F-FDG PETCT在抗NMDA受体脑炎及病毒性脑炎诊断中的价值

抗N-甲基-D-天冬氨酸(NMDA)受体脑炎及病毒性脑炎的临床表现相似但治疗方法及预后不同,故早期鉴别至关重要。抗体检测及病原学检测存在延时、假阴性等不足,常规辅助检查缺乏特异性,鉴别价值有限。^18F脱氧葡萄糖(FDG)标记的正电子发射计算机断层显像(PETCT)检查对于抗NMDA受体脑炎早期代谢异常敏感性高,存在特征性的枕叶低代谢和额颞叶高代谢。病毒性脑炎行^18F-FDG PETCT检查研究病例数较少,不同病毒性脑炎的脑代谢表现不同,但均无特征性的枕叶代谢减退。本文现围绕NMDA受体脑炎及病毒性脑炎行^18F-FDG PETCT检查时的脑代谢特点综述如下。     

Hepatitis C virus (HCV) interaction with astrocytes: nonproductive infection and induction of IL-18

Hepatitis C virus (HCV) infection causes the central nervous system (CNS) abnormalities in more than 50 % of chronically infected subjects. However, the underlying mechanisms are largely unknown. In this study, we characterized the HCV interactions with astrocytes, one of the putative HCV target cells in the brain. We demonstrated that primary human astrocytes (PHA) were very inefficiently infected by HCV, either in the cell-free form or through cell–cell contact. We then determined the potential restriction steps of HCV infection and replication in these cells. PHA expressed all known HCV receptors but failed to support HCV entry. HCV IRES-mediated RNA translation was functional in PHA and further enhanced by miR122 expression. Nevertheless, PHA did not support HCV replication regardless of miR122 expression. To our great surprise, we found that HCV exposure induced robust IL-18 expression in PHA and exhibited direct neurotoxicity. Taken together, these results showed that astrocytes did not support productive HCV infection and replication, but HCV interactions with astrocytes and neurons alone might be sufficient to cause CNS dysfunction.     

Diffuse white matter lesions associated with herpes simplex encephalitis as observed on magnetic resonance imaging

A 2-year-old boy with herpes simplex encephalitis developed diffuse brain lesions involving the white matter of both cerebral hemispheres. These lesions in the white matter were clearly observed on magnetic resonance imaging (MRI) with the T2-weighted sequence, and were found to have spontaneously disappeared on subsequent MRI performed 7 weeks later. Brain lesions associated with herpes simplex encephalitis in the literature are reviewed and the pathogenesis in the present case is discussed.     

Regulation of microglial cell responses in murine Toxoplasma encephalitis by CD200/CD200 receptor interaction

Under autoimmune inflammatory conditions within the brain, evidence suggests that neurons downregulate microglial activation through CD200/CD200R interaction, which reduces disease severity. To gain insight into the regulation of intracerebral immune reactions by resident brain cells in chronic cerebral infections, the expression of the CD200 antigen and the CD200R as well as the functional role of CD200/CD200R interactions were characterized in murine Toxoplasma encephalitis. In the normal brain of C57BL/6 wild type mice, CD200 was ubiquitously expressed on neurons, their axons, cerebral endothelial cells, and plexus macrophages. CD200R was expressed at very low levels on cerebral macrophages and microglia without differences between CD200^−/− and wild type mice. Infection of C57BL/6 mice with Toxoplasma gondii induced an upregulation of CD200R on microglia and of CD200 on blood vessel endothelial cells. In Toxoplasma encephalitis of CD200^−/− mice, microglial cell numbers strongly increased due to an enhanced proliferation indicated by increased Ki-67 immunoreactivity. In addition, microglial activation was increased in CD200^−/− mice as evidenced by a further upregulation of already high MHC class II levels as well as an increased expression of the anti-parasitic effector molecules, TNF and iNOS. The increased microglial cell activation resulted in a reduced intracerebral parasite burden and an increased survival rate. Thus, in Toxoplasma encephalitis, microglial activity was regulated via CD200/CD200R-mediated interaction further pointing to an intrinsic regulation of brain resident cells under inflammatory CNS conditions.     

Neuronal apoptosis mediated by IL-1 beta expression in viral encephalitis caused by a neuroadapted strain of the mumps virus (Kilham Strain) in hamsters.

The neuroadapted Kilham strain of the mumps virus produces lethal encephalitis in newborn hamsters after intracerebral inoculation. The pathogenesis of this encephalitis is not fully understood, but recently, apoptosis and associated cytokine production have been recognized to be major pathologic mechanisms by which viruses cause injury to neuronal host cells. To analyze the main factors producing brain injury in this viral encephalitis, the following questions were investigated: (1) does the virus induce neuronal apoptosis and (2) does expression of cytokines regulate the induction of neuronal apoptosis? Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was used as a marker of neuronal apoptosis and TUNEL-positive neurons were widespread in the infected cerebral cortex. DNA fragmentation yielding DNA ladders characteristic of apoptosis was also observed in infected hamster brain tissue. Apoptotic cells in infected brains were observed after the appearance of inflammatory changes. Overexpression of IL-1 beta, but not TNF-alpha or Fas-L, was clearly detected in infected brains, as determined by Western blot and RT-PCR. Immunohistochemistry revealed a striking correlation between IL-1 beta expression and neuronal apoptosis. Injection of recombinant IL-1 beta into normal hamster brain resulted in neuronal apoptosis in cerebral cortex. On the other hand, neutralizing IL-1 beta antibodies decreased the number of cells undergoing apoptosis in infected hamster brains and subsequent death. We conclude that the fatal encephalitis induced by the Kilham strain of the mumps virus is mediated by immunopathological processes and that overexpression of IL-1 beta, which mediates the induction of neuronal apoptosis, may play a major role in these processes.     

Clinical contributors to cerebral white matter integrity in HIV-infected individuals

HIV-infected people frequently exhibit brain dysfunction characterized by preferential damage to the cerebral white matter. Despite suppressed viral load and reconstituted immune function afforded by combination antiretroviral therapy (CART), brain dysfunction continues to be observed even in medically stable individuals. To provide insight into the etiology of HIV-associated brain dysfunction in the CART era, we examined the effects of HIV disease markers, antiretroviral treatment, hepatitis C (HCV) coinfection, and age on DTI measures of white matter integrity in a cohort of 85 individuals aged 23 to 65 years with chronic HIV infection. Fractional anisotropy and mean diffusivity were derived from 29 cerebral white matter regions, which were segmented on each individual brain using a high-resolution T1-weighted image and registered to diffusion images. Significant effects of clinical variables were found on white matter abnormalities in nearly all brain regions examined. Most notably, HCV coinfection and older age were associated with decreased anisotropy or increased diffusivity in the majority of brain regions. Individuals with higher current CD4 levels exhibited higher anisotropy in parietal lobe regions, while those undergoing antiretroviral treatment exhibited higher anisotropy in temporal lobe regions. The observed diffuse pattern of white matter injury suggests that future neuroimaging studies should employ methodologies that are not limited to circumscribed regions of interest. The current findings underline the multifactorial nature of HIV-associated brain dysfunction in the CART era, and the importance of examining the effects of HIV disease in the context of other comorbidities, in particular HCV coinfection and aging.     

A medical overview of encephalitis

Encephalitis is uncommon but is a neurological emergency which must be considered in a patient presenting with altered consciousness. Encephalitis is a diffuse inflammatory process of the brain parenchyma associated with evidence of brain dysfunction. The presentation of encephalitis can be acute or chronic. The aetiology of encephalitis can be broadly divided into two major subtypes. (1) Infection-related encephalitis which is a direct consequence of pathogenic viral, bacterial or parasitic agents. Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are the most common cause of acute infectious encephalitis. (2) Autoimmune-mediated encephalitis which is mediated by an aberrant immune response. This can be triggered by a recent viral infection or vaccination. An example of this would be acute disseminated encephalitis (ADEM). This article will focus on the medical management of acute encephalitis. This will involve an extensive overview of the literature reviewing the diagnosis, investigation and treatment of acute viral encephalitis, ADEM and acute haemorrhagic leukoencephalopathy (AHLE). Encephalitis can also present chronically, and some of the different types of chronic encephalitis will be discussed.     

Neuropsychiatric interpretations of postencephalitic movement disorders.

This study reviews the impact of encephalitis lethargica (EL) on concepts of behaviour and movement during the 1920s and 1930s. Clinicopathological correlations were imprecise but supported the role of subcortical structures in complex patterns of motor behaviour. This possibility challenged the widely assumed hegemony of the cerebral cortex. There was a perceived link between involuntary movements and reduced impulse control and also between parkinsonism and a defect in volition. Contemporary observers interpreted postencephalitic phenomena such as oculogyria in psychodynamic as well as in neurophysiological terms. EL also gave some support to the idea that neuroses such as obsessional neurosis and hysteria might have an organic basis. These speculations recently have acquired more credibility. The large amount of literature on EL and its sequelae could perhaps make further contributions to understanding the pathology of voluntary movement and action.     

Toxoplasma encephalitis in a HIV patient: unusual involvement of the corpus callosum

In patients with acquired immuno-deficiency syndrome, the differential diagnosis between primary brain lymphoma and toxoplasma encephalitis is not radiologically always straightforward, especially in the presence of a solitary cerebral lesion. In this context, involvement of the corpus callosum is almost exclusively associated with primary brain lymphoma. We describe here an HIV-infected patient who presented with a single and large cerebral lesion affecting the corpus callosum, suggestive of primary brain lymphoma on MRI-scan but who nonetheless responded clinically and radiologically to an anti-toxoplasma drug trial confirming the diagnosis of toxoplasma encephalitis.     

Comparisons of HIV-1 viral sequences in brain, choroid plexus and spleen: potential role of choroid plexus in the pathogenesis of HIV encephalitis

Possible mechanisms of HIV transmission to the brain include direct viral infection of cerebral endothelium and hematogeneous dissemination of viral-infected lymphocytes and monocytes. Cerebrospinal fluid dissemination from a primary infection of choroid plexus (CPx) is an alternative mechanism supported by recent studies in our laboratory. We showed that HIV-infected asymptomatic patients as well as AIDS patients have HIV infection of the CPx; the cell types so infected included stromal monocytes and dendritic cells. To further explore the potential role of CPx in the pathogenesis of HIV encephalitis, we analyzed HIV sequences from brain, CPx, and spleen of four AIDS patients by extracting DNA from paraffin sections and amplifying the V3 region of the HIV env gene by PCR. Several different clones from each tissue were characterized. We found that viruses from the brain and spleen grouped into two distinct clusters, while viruses of the CPx contained viral strains that were a mixture of those found in the brain or spleen. Net charge analysis of the V3 tip region showed that the brain viral sequences had fewer positive charges than blood viral sequences. Our results support the hypothesis that CPx may be one of the sites where HIV-1 gains access to the brain from the blood and therefore contains viruses that are of both genotypes.     

Japanese encephalitis presenting with left hemiplegia and thalamic neglect--a case report]

This report concerns a 51-year-old right-handed man with Japanese encephalitis, showing left hemiplegia and left hemispatial neglect. On admission, he had a slight fever, mild consciousness disturbance, left hemiplegia, and left hemispatial neglect but no neck stiffness, headache nor nausea. He was treated on the basis of cerebral infarction, but his fever and consciousness disturbance worsened. We found pleocytosis (145/mm3) in the cerebrospinal fluid (CSF) and right thalamic edema on a brain CT scan obtained 4 days later. He was finally diagnosed as having Japanese encephalitis on the basis of an increase in anti-viral antibodies observed in paired CSF and serum samples. In the exacerbation phase, 123I-IMP single photon emission CT (SPECT) demonstrated a marked decrease in cerebral perfusion in the right hemisphere, while a brain MRI revealed irregular lesions localized the right thalamus (mainly posterior and medial parts), showing low intensity on T1-weighted and high intensity on T2-weighted images. In the recovery phase, asymmetrical perfusion was no longer observed on SPECT and the symptoms including the left hemispatial neglect had improved. These findings suggest that the left hemispatial neglect in this patient might been caused by the right thalamic lesion resulting in damage to the activating system of the right hemisphere. This case thus shows that acute onset of hemispatial neglect could be caused by cerebral encephalitis.     

Ondine''s curse in listeria monocytogenes brain stem encephalitis

A case of necrotizing brain stem encephalitis due to listeria monocytogenes is described in a 48-year-old man who had brain stem encephalitis of complicated course and with selective destruction of the vasomotoric and respiratory centers. He developed that very rare Ondine's curse syndrome, being only able to breathe when awake. The literature on Ondine's curse and brain stem encephalitis due to LM is reviewed. Brain stem encephalitis has a mortality near 100%. The only treatment for Ondine's curse is lifelong artificial ventilation.     

Focal Status Epilepticus and Epilepsia Partialis Continua in Adults and Children

Summary: Focal status epilepticus and epilepsia partialis continua (FSE-EPC) are most frequently seen with chronic focal progressive encephalitis of Rasmussen and Russian spring-summer encephalitis. FSE-EPC may be the presenting feature of nonketotic hyperglycemic diabetes mellitus but is more often noted as a late complication especially if there is a coexistent cerebral lesion such as cerebral infarction. FSE-EPC may be related to multiple sclerosis, primary or metastatic brain tumors, the MERRF-MELAS syndrome, benign epilepsy of childhood with rolandic spikes, and in some adults with acquired aphasia. The physiological origin of the myoclonic jerks seen in EPC is cortical and may be either spontaneous or provoked by the joint position of the affected limb. The treatment of FSE-EPC is influenced by the underlying disorder.     

Herpes simplex virus encephalitis complicated by intracerebral hematoma

Herpes simplex virus (HSV) encephalitis complicated by cerebral hematoma is extremely rare. We report a 54-year-old man with hepes simplex encephalitis complicated by intracerebral hematoma and review the literature and describe the characteristics of HSV encephalitis complicated by intracerebral hematoma.     

复方阿胶冲剂治疗乙脑脑水肿的疗效观察

以复方阿胶冲剂为主，治疗流行性乙型脑炎脑肿３４例，用西医传统治疗３４例作对照，经五项指标观察对比，结果表明前组病程缩短、恢复期症状的后遗症明显减少，配用的甘露醇用量亦显著减少，且不用血制品，是一种值得推广的中西医结合治疗脑水肿的有效措施。     

The presentation of small-cell lung cancer with metastatic carcinomatous encephalitis in a non-Hodgkin's lymphoma patient

BACKGROUND: Carcinomatous encephalitis or milary cerebral metastases characterized by signs of diffuse encephalopathy is a rare form of brain metastases. Tiny tumor nodules are seen throughout the cortical and subcortical gray matter. OBSERVATION: We report the case of a patient with a history of non-Hodgkin lymphoma who developed carcinomatous encephalitis probably secondary to small-cell lung cancer. This case is discussed in light of findings of 16 cases of carcinomatous encephalitis reported in the literature. We discuss clinical, radiological, histological, pathophysiological characteristics and the survival of this form. CONCLUSION: The frequency of carcinomatous encephalitis is underestimated because clinical expression is non specific. Brain magnetic resonance imaging must be performed in all patients presenting encephalopathy without an obvious cause.     

Acute diffuse lymphocytic meningoencephalitis: a clinico-pathological report of a case

A clinicopathologic case of acute diffuse lymphocytic meningoencephalitis in a 8-year-old child is reported. Clinical picture started 7 days prior to death and was characterized by fever and occipital cephalea followed by worsening of general conditions, vomiting and generalized convulsive crisis together with cardiopulmonary arrest and coma. The pathologic examination showed alterations only in the brain, namely pronounced cerebral edema and inflammatory infiltrate, predominantly lymphocytic, perivascular, particularly in the white matter, in all regions analyzed. This case is compared to the ones described in the literature and the etiopathogenesis of acute diffuse lymphocytic meningoencephalitis is discussed. The necessity of making public cases of non-bacterial acute encephalitis is emphasized, due to the fact that most of them remain with undetermined etiology.