Epstein-Barr Virus Encephalitis Research Articles

Acute Epstein-Barr virus Encephalitis and hepatitis without mononucleosis syndrome: a case report

Acute Epstein-Barr virus Encephalitis and hepatitis without mononucleosis syndrome: a case report

Epstein-Barr Virus Encephalitis: A Review of Case Reports from the Last 25 Years.

Although uncommon, Epstein-Barr virus-related neurological disorders represent the seventh most frequent cause of infectious encephalitis in adults. The limited number of publications on EBV encephalitis mainly document isolated clinical cases. This study aimed to summarize published data on EBV encephalitis. A systematic literature search identified 97 EBV encephalitis cases. In the selected cases, EBV-related neurological disorders manifested as lymphocytic pleocytosis in the cerebrospinal fluid (CSF) with moderate hyperproteinorachia. The EBV PCR test was positive in 87% of the CSF samples, with wide-ranging viral loads. When encephalitis occurred in the context of past EBV infections, all of the EBV PCR tests on CSF samples were positive. On the contrary, negative EBV PCR tests on CSF samples occurred only in the context of primary infections. EBV PCR was rarely carried out on blood samples, contributing minimally to the diagnosis. For the treatment of EBV encephalitis, Aciclovir was used alone in 29% of cases, and in association with other drugs in 40% of cases. Ganciclovir (30%), corticoids (52%), and immunoglobulins (15%) were mainly used in association with other drugs. Cerebral imaging was abnormal in 69% of cases, mostly in the cerebellum and basal ganglia. This work highlights that the EBV PCR test on CSF samples is currently the main laboratory diagnostic test to diagnose EBV encephalitis. This diagnostic test is useful; however, it is imperfect. New complementary diagnostic tools, approved treatments, and standardized practices could improve patient management.

Epstein-Barr virus encephalitis presenting with brain mass lesions in a patient with human immunodeficiency virus infection

Epstein-Barr virus encephalitis presenting with brain mass lesions in a patient with human immunodeficiency virus infection

Overlapping Epstein-Barr virus encephalitis and autoimmune glial fibrillary acidic protein astrocytopathy

We describe three cases of overlapping Epstein-Barr virus (EBV) Encephalitis and Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy (GFAP-A). The three cases all presented with initial symptoms of fever, headache, coma, and posture tremor of the upper limbs, then followed by limb weakness and dysuria. All of the three cases were on ventilators. Case 1 and 2 improved dramatically after intravenous methylprednisoloneand immunoglobulin treatment. However, case 3 presented dyspneic, and died from gastrointestinal hemorrhage. The GFAP-A triggered by EBV intracranial infection could initially masquerade as EBV encephalitis only, and the detection of GFAP antibody is essential for differentiation.

Epstein–Barr virus encephalitis following unrelated peripheral blood stem cell transplantation in a child with AML

Epstein–Barr virus encephalitis following unrelated peripheral blood stem cell transplantation in a child with AML

Lessons from Epstein-Barr virus DNA detection in cerebrospinal fluid as a diagnostic tool for EBV-induced central nervous system dysfunction among HIV-positive patients.

Polymerase chain reaction (PCR) analysis of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid (CSF) remains vital for evaluating active EBV infection involving the central nervous system (CNS). CSF EBV DNA was often found in conjunction with other microbial infection affecting the CNS among patients infected with human immunodeficiency virus (HIV). Sometimes CSF EBV DNA is detectable in patients without neurological symptoms. This review focused on the clinical and laboratory features of CNS EBV infection among patients with HIV, and discussed various types of EBV-associated CNS infections, and predominant neoplasms involving CNS such as primary central nervous system lymphoma (PCNSL), CNS-non-Hodgkin's lymphoma, smooth muscle tumors and leiomyosarcomas, EBV encephalitis or myelitis, EBV meningitis and EBV coinfection with other causative agents were also included. Furthermore, the metagenomic next-generation sequencing technique with high sensitivity for the detection of pathogenic coinfection in the CSF were also reviewed. We concluded that CSF EBV-DNA detection with high sensitivity and specificity could be a useful diagnostic tool for CNS lymphoma among HIV patients; however, it is still unknown for other CNS diseases. We further summarized and conclude that positive CSF EBV-DNA detection combined with specific brain focal lesions could be a minimally invasive method to diagnose PCNSL. The occurrence of positive CSF EBV-DNA was influenced by PCR detection limit, PCR methods, immunocompromised status, the possible influence of anti-herpetic therapy and anti-HIV therapy, and the size and location of a tumor mass. Uniform PCR methods as vital diagnostic tools and optimal EBV-DNA load threshold need to be established.

MULTIFACTORIAL MENINGITIS IN A PATIENT WITH PREVIOUS EPSTEIN BARR VIRUS ENCEPHALITIS

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Gram negative bacillary meningitis is rare and mostly occurs in patients with recent neurosurgery. We present such a case of bacterial meningitis combined with other etiologies in a patient with previous Epstein Barr Virus (EBV) encephalitis. CASE PRESENTATION: 62-year-old male with history of diabetes, stroke and EBV encephalitis (1 month ago) presented with altered mentation. Lumbar puncture (LP) showed neutrophil predominant leukocytosis but cerebrospinal fluid (CSF) culture was negative. Brain imaging showed developing hydrocephalus. He was started on empiric meningitis coverage with antibacterial, antifungal and antitubercular regimen (due to basilar changes on imaging and mildly elevated adenosine deaminase in the CSF). He underwent right craniotomy with ventriculo-peritoneal (VP) shunt placement. Course complicated by worsening mentation requiring intubation for airway protection. Due to concern of hospital acquired pneumonia (HAP), piperacillin-tazobactam was added. Repeat LP showed improved leukocyte count but culture was again negative. He had persistent fevers after finishing piperacillin-tazobactam course; subsequent sputum culture and 3rd CSF culture now grew pseudomonas aeruginosa. He finished 21 days of systemic cefepime and 7 days of intrathecal tobramycin for pseudomonas; and 14 days of empiric amphotericin B (although fungal CSF culture was negative). He remains on empiric antitubercular regimen (isoniazid/rifampin/pyrazinamide/ethambutol) - culture negative. Mentation remains poor and family is currently deciding on aggressive care with tracheostomy or palliative care approach. DISCUSSION: In our case, meningitis on admission was likely some bacterial superinfection after viral encephalitis. After neurosurgery, 2nd CSF culture was negative likely due to ongoing antibiotics for HAP. 3rd CSF culture grew pseudomonas as patient was now off of piperacillin-tazobactam. Pseudomonas meningitis is rare and can occur as complication of neurosurgery, chronic cranial osteomyelitis, mastoiditis or trauma. The mortality rate ranges from 40 to 80%. Complications include hydrocephalus, brain abscesses, seizures, ventriculitis etc. The CSF gram stain is positive in 50% of cases with a positive culture result. Bacteremia is also present in about 50% of the cases. The usual empiric meningitis regimen does not cover pseudomonas and antipseudomonal agents can be added in patients with above risk factors. Cefepime/ceftazidime are empiric therapy and should be adjusted based on sensitivities. Dual therapy with intrathecal/intraventricular regimens can be started in resistant cases. Adjuvant steroids have shown no benefit. CONCLUSIONS: Timely recognition of risk factors for gram negative bacillary meningitis and starting empiric treatment regimen can improve the prognosis of such patients. REFERENCE #1: Berk SL, McCabe WR. Meningitis caused by gram-negative bacilli. Ann Intern Med. 1980;93(2):253. REFERENCE #2: Rahal JJ, Simberkoff MS. Host defense and antimicrobial therapy in adult gram-negative bacillary meningitis. Ann Intern Med. 1982;96(4):468. REFERENCE #3: S. Pai, L. Bedford et al. Pseudomonas aeruginosa meningitis/ventriculitis in a UK tertiary referral hospital. An International Journal of Medicine, Volume 109, Issue 2, February 2016, Pages 85–89, https://doi.org/10.1093/qjmed/hcv094 DISCLOSURES: No relevant relationships by Sahib Singh, source. Web Response no disclosure on file for Parth Jamindar

Post-infectious Akathisia in Epstein-Barr Virus Encephalitis with Bilateral Basal Ganglia Involvement and Clinical Improvement with Trihexyphenidyl (5068)

Post-infectious Akathisia in Epstein-Barr Virus Encephalitis with Bilateral Basal Ganglia Involvement and Clinical Improvement with Trihexyphenidyl (5068)

Bilateral symmetrical deep gray matter involvement and leptomeningeal enhancement in a child with MOG-IgG-associated encephalomyelitis

BackgroundCurrently, myelin oligodendrocyte glycoprotein (MOG)-IgG-associated encephalomyelitis (MOG-EM) is regarded as an independent inflammatory demyelinating disease. Magnetic resonance imaging (MRI) abnormalities occur in 44.4% of patients with MOG-EM. However, symmetrical deep gray matter involvement with leptomeningeal enhancement is rarely described in the literature.Case presentationA 3-year-old boy was admitted to our hospital because of acute onset fever, headache, vomiting and disturbance of consciousness. Neurological examination showed somnolence, neck stiffness and positive Kernig’s sign. Brain MRI demonstrated bilateral symmetrical lesions in the basal ganglia and thalamus as well as diffuse leptomeningeal enhancement along the sulci of bilateral hemisphere. Cerebrospinal fluid analysis demonstrated increased cell count (7 cells/mm3, mononuclear cells dominant) and protein (1.17 g/L) without glucose and chloride abnormality. Work-up for infectious and autoimmune causes, serum MOG IgG was positive by cell based assay. Therefore, a diagnosis of MOG-EM was established according to the international recommendatory criteria in 2018. He was administrated with intravenous methylprednisolone followed by oral corticosteroids and had recovered completely within 1 week.ConclusionsIn the setting of meningoencephalitis-like clinical presentation with bilateral symmetrical deep gray matter involvement, MOG-EM should be distinguished from other infectious and autoimmune disorders, such as Epstein-Barr virus (EBV) encephalitis, Japanese encephalitis and Anti-NMDA receptor (NMDAR) encephalitis. Besides, aseptic meningitis associated with leptomeningeal enhancement may be an atypical phenotype of MOG-EM.

Acute diffuse edematous-hemorrhagic Epstein–Barr virus meningoencephalitis

Introduction:In this study, we presented a rare case of Epstein–Barr virus (EBV) meningoencephalitis presented with meningoencephalitis-like symptoms and diffuse edematous hemorrhage.Patient concerns:A 77-year-old male patient was admitted to our hospital with fever, headache, confusion, and unconsciousness for 7 days. Physical examination revealed unconsciousness and stiffness of the neck.Diagnosis:The final diagnosis was EBV meningoencephalitis.Interventions:Ganciclovir (two times 350 mg/day, 21 days), methylprednisolone sodium succinate (120 mg, 5 days), and IV immunoglobulins (IV Ig) (0.4 g/kg, 5 days) were given to this patient.Outcomes:But the patient's clinical symptoms did not improve, and he was still in a coma. His family refused to be further diagnosed and discharged. After discharge for 2 months, the patient was in a coma. Four months later, the patient died of complications of pulmonary infection.Conclusion:The patient is an adult, and imaging was dominated by intracranial diffuse microhemorrhage and edema, which was different from the typical imaging characteristics of EBV encephalitis as previously reported. This specific imaging change may provide new clinical value for the diagnosis of EBV encephalitis.

A new therapy in Epstein-Barr virus-associated lymphoproliferative disease: a case report and a revision of the literature

BackgroundSystemic chronic active Epstein-Barr virus infection is an extremely rare childhood disease. Since chronic active Epstein-Barr virus infection can trigger the onset of Epstein-Barr virus-associated lymphoproliferative disease. The clinical manifestations of the disease vary according to the site of involvement; therefore, management may be challenging. Currently, there are no standardized guidelines for treating Chronic active Epstein-Barr virus infection effectively.Case presentationWe report a case of chronic active Epstein-Barr virus infection in a 5-year-old Chinese boy with intestinal, vascular, and neurological involvement. At age of 2 years and 7 months old, he had hepatomegaly and been diagnosed with Epstein-Barr virus infection. After treatment, he showed some clinical improvement. At age of 3 years and 3 months old, he presented with recurrent fever and diarrhea. Then he received methylprednisolone for 1 year and his symptoms ameliorated. At the age of 5 years, his symptoms recurred and had gastrointestinal hemorrhage and developed polyuria, frequent convulsions and hyponatremia. He was transferred to our hospital for further management. He was unconscious on admission and was diagnosised Epstein-Barr virus-lymphoproliferative disorder, based on the results in situ hybridization of EBV-encoded miRNA in sigmoid colon. Three-dimensional CT angiography demonstrated an aneurysm in the right internal carotid artery. Abdominal CT showed dilatation of vessels in part of the intestinal wall. He was also diagnosised Epstein-Barr virus encephalitis based on the elevated Epstein-Barr virus antibody titers and presence of Epstein-Barr virus DNA in the Cerebrospinal Fluid.A repeated duodenal artery embolization and symptomatic therapy could not control the hemorrhage after admission. He subsequently received treatment with ganciclovir, glucocorticoid, thalidomide, and propranolol. Hemorrhage was controlled in 5 days; his symptoms improved. The fever did not recur and the CSF pressure was also normalized. A follow-up CT at 3 months after admission showed regression of the aneurysm in the right internal carotid artery and the vascular lesion in the duodenum.Discussion and conclusionsA new treatment protocol including thalidomide and propranolol resulted in a marked improvement in his clinical symptoms, and shows promise as a novel and effective therapeutic approach for Chronic active Epstein-Barr virus infection-associated lymphoproliferative disorder.

Sodium oxybate (Xyrem) treatment in severely sleep-deprived child with Epstein–Barr virus encephalitis with lesion of sleep-wake regulation system: a case report

We present the effect of exogenous sodium oxybate (GHB) in a severely tormented boy unable to sleep and unable to be anesthetized due to a lesion in the sleep initiation system involving the tracks between the ventrolateral preoptic nucleus and the reticular system. We bypassed the system by using sodium oxybate's effect on the cortical GHB and GABAB receptors involved in the initiation and maintenance of sleep.

Epstein barr virus encephalitis in immune-competent children: An under recognized entity

Epstein barr virus encephalitis in immune-competent children: An under recognized entity

Clinical analysis of 7 patients with Epstein-Barr virus encephalitis after allogeneic hematopoietic stem cell transplantation

目的总结异基因造血干细胞移植（allo-HSCT）后合并EBV脑炎患者的发病特点、临床特征、治疗及转归。方法分析2012年1月至2015年12月在苏州大学附属第一医院行allo-HSCT后合并EBV脑炎的7例患者的临床资料。结果EBV脑炎总发生率为0.70%（998例中7例），中位发生时间为移植后第63（10~136）天，主要表现为发热伴精神神经症状，4例头颅磁共振成像（MRI）阳性。无关全相合移植2例，亲缘单倍体移植5例。预处理中7例均联合抗胸腺细胞球蛋白（ATG）预防移植物抗宿主病（GVHD），6例发生Ⅱ~Ⅳ度急性GVHD。经抗病毒联合利妥昔单抗治疗，所有患者EBV-DNA均转阴。至随访截止时间，共3例死亡，2例死于基础疾病复发，1例死于EBV脑炎进展。结论对于allo-HSCT后疑似EBV脑炎，尽早行脑脊液EBV-DNA及头颅MRI检查，以提高早期诊断率；联合利妥昔单抗治疗有效且耐受性良好。

Acute Epstein-Barr virus encephalitis in an immunocompetent adolescent patient

Universidade de Sao Paulo; Faculdade de Medicina de Ribeirao Preto; Hospital das Clinicas, Radiologia e Diagnostico por Imagem, Ribeirao Preto SP, Brasil.Correspondence: Rodolfo Mendes Queiroz; Rua Bernardino de Campos, 1426; 14015-130 Ribeirao Preto SP, Brasil; E-mail: rod_queiroz@hotmail.comConflict of interest: There is no conflict of interest to declare.Received 21 September 2016; Received in final form 24 March 2017; Accepted 15 April 2017.

Clinical characteristics of 73 children with Epstein-Barr virus encephalitis

Objective To summarize the clinical features of Epstein-Barr virus encephalitis(EBE), and to discuss the factors that could result in poor prognosis. Methods Seventy-three cases of EBE admitted to Beijing children′s Hospital, Capital Medical University from July 2006 to June 2016 were collected.The clinical features, laboratory tests and imaging results were analyzed, and the follow-up check-up by phone was conducted. Results EBE could occur at any time of the year, and more cases occurred in winter/spring than in summer/autumn.Ratio of male to female patients was 1.5∶1.0, and more cases occurred among the older children with their average age of 5 years and 6 months old.Specific types were: meningoencephalitis 56 cases(75.7%), demyelination 16 cases(21.9%), and acute cerebellar ataxia 1 case(1.4%). EBE included 24 cases (32.9%) of meningoencephalitis, 22 cases (30.1%) of encephalitis, 10 cases (14.0%) of meninges, 2 cases (2.7%) combined with myelitis, and 1 case (1.4%) combined with ophthalmoneuromyelitis.Only 2 cases were found with typical symptoms of infectious mononucleosis, 1 case was diagnosed as chronic Epstein-barr virus(EBV) infection, and 1 case was diagnosed as hemophagocytic histiocytosis.Clinical symptoms were: 70 cases (95.9%) of fever, 37 cases (50.7%) of convulsion, 34 cases (46.6%) of altered state of consciousness, 24 cases (32.9%) of vomit, and 21 cases (28.8%) of headache, which were found to be the primary symptoms, together with other symptoms, including 12 cases (16.4%) of hepatomegaly, 10 cases (13.7%) of rash, and 11 cases (15.0%) of other symptoms.There were 42 cases (57.5%) of central nervous system(CNS)infection positive and neck stiffness, 32 cases (43.8%) of Babinski′s sign positive, 10 cases (13.7%) of decreased muscle strength, 11 cases (15.1%) of atonia, 5 cases (6.8%) of hypermyotonia, 5 cases (6.8%) of coats disease positive, and 2 cases (2.7%) with Brudzinski signs.Twenty-two patients (30.1%) did not have CNS positive symptoms.There were 48 cases (45.8%) of magnetic resonance imaging (MRI) result showing abnormalities, with common symptoms including 9 cases (12.7%) of cytotoxic edema, 8 cases (11.3%) of demyelination, and 4 cases (5.6%) with encephalanalosis symptoms.Affected organs included 14 cases (19.7%) of frontal lobe, 11 cases (15.5%) of parietal lobe, 11 cases (15.5%) of temporal lobe, 8 cases (11.3%) of thalamus, 7 cases (9.9%) of basal ganglia, 6 cases (8.5%) of occipital, and 5 cases (7.0%) of corpus callosum etc.Follow-up check-up was conducted on 52 cases, with 21 cases lost contact, and 44 cases (84.6%) with good prognosis, 8 cases (15.4%) with poor prognosis and 3 death cases (5.8%). Serologic examinations found 20 cases (29.9%) of primary EBV infection [EBV-capsid antigen(CA)-IgM+ and core antigen(NA)-IgG-], 47 cases (70.1%) of existed EBV infection being activated (EBV-CA-IgM+ and NA-IgG+ ), and there was no statistically significant difference in terms of clinical characteristics and prognosis.Convulsion occurs more frequently in group of poor prognosis(P=0.03) after comparing the aspects of main clinical features, stage of EBV infection, underlying diseases and combined with other infections etc(P>0.001). Conclusions EBE can occur at various stage of EB infection.EBE can occur in various forms at clinic.CNS symptoms of meningoencephalitis, encephalitis, meninges, demyelination, and cerebellar ataxia etc.Patients’ brain parenchyma can be affected extensively, and most of the patients experienced good prognosis, the virus can cause lethal infection; while patients with symptoms of convulsion may experience poor prognosis. Key words: Epstein-Barr virus; Encephalitis; Child

Disseminated MAC: Broadening the Differential for Diarrhea in a Patient with Advanced AIDS

Diarrhea is a common problem in acquired immunodeficiency syndrome (AIDS). Aside from noninfectious causes, such as AIDS enteropathy and drug-induced diarrhea, the most common causes are opportunistic infections (OI). Disseminated Mycobacterium avium complex (MAC) is the most common OI with an incidence of 20% per year. There has been a dramatic decline in the incidence of disseminated MAC since the advent of highly active antiretroviral therapy (HAART). Clinicians must be familiar with the causes of diarrhea in AIDS to ensure timely institution of appropriate interventions. A fifty year old male with AIDS and CD4 count of three presented to the hospital with fever, encephalopathy, and failure to thrive. He was found to be septic with a urinary tract infection and bacteremia secondary to Escherichia coli, as well as Epstein-Barr virus (EBV) encephalitis. His hospital course was complicated by pancytopenia, and a bone marrow (BM) biopsy was performed due to concern for lymphoma in the setting of a positive EBV serology. Two weeks into hospitalization, he was resumed on his prior regimen of HAART, which included Ritonavir, Atazanavir, Emtricitabine and Tenofovir. One week later, he developed profuse, watery diarrhea. Stool studies were sent and while initially only positive for norovirus, two days later, acid-fast bacilli was also isolated. He began a regimen of Azithromycin, Isoniazid, Moxifloxacin, and Ethambutol to cover for both MAC and M. tuberculosis. His BM biopsy and blood cultures later resulted and were positive for MAC, confirming the diagnosis of disseminated MAC. Before HAART, diarrhea, which increases in frequency and severity as immune function declines, afflicted 40% to 80% of AIDS patients. With the initiation of HAART in a person with severe AIDS however, the risk of immune reconstitution inflammatory syndrome (IRIS) is significant and needs to be considered. Given the timing of this patient's diarrhea after resuming HAART, he most likely developed disseminated MAC secondary to IRIS. Although this patient initially tested positive for norovirus, which by itself would explain his diarrhea, comprehensive work-up led to the diagnosis of diarrhea secondary to disseminated MAC, and in turn, appropriate treatment. In an immunocompromised patient, multiple pathogens may be playing a role, and concomitant disease must always be considered.

Epstein-Barr Virus Encephalitis in an Immunocompetent Child: A Case Report and Management of Epstein-Barr Virus Encephalitis.

Epstein-Barr virus (EBV) usually causes mild, asymptomatic, and self-limited infections in children and adults; however, it may occasionally lead to severe conditions such as neurological diseases, malignant diseases, hepatic failure, and myocarditis. Epstein-Barr virus-related neurological disorders include meningitis, encephalitis, and cranial or peripheral neuritis, which are mostly seen in immunocompromised patients. The therapeutic modalities for EBV-related severe organ damage including central nervous system manifestations are still uncertain. Herein, we describe a seven-year-old boy with EBV encephalitis who presented with prolonged fever, exudative pharyngitis, reduced consciousness, and neck stiffness. Cranial magnetic resonance imaging showed contrast enhancement in the bilateral insular cortex and the right hypothalamus. The diagnosis was made by EBV-DNA amplification in both the blood and cerebrospinal fluid samples. He was discharged with acyclovir therapy without any sequelae.

Severe, life-threatening Epstein-Barr Virus encephalitis in an immunocompetent adolescent girl

A 14-year-old girl diagnosed with Epstein-Barr Virus encephalitis with generalized status epilepticus and cardiac arrest. The pathogenic role of Epstein-Barr Virus was identified by a polymerase chain reaction analysis of the patient's cere- brospinal fluid. Cranial computerized tomography and magnetic resonance imaging revealed no abnormalities. After being admitted to the intensive care unit, the patient exhibited progressive improvement until complete recovery from the disease. Despite the severity of the disease, the patient did not experience long-term sequelae.

Anterior opercular syndrome induced by Epstein–Barr virus encephalitis

We report a 19-year-old female presenting with fever, drooling, anarthria, and voluntary facial movement disruption, characteristic of anterior opercular syndrome (AOS). Serological examination revealed Epstein–Barr virus (EBV) infection following acute encephalitis with severe ataxia. A single-photon emission computerized tomography (SPECT) examination indicated hypoperfusion in the left perisylvian region, bilateral thalamus, occipital lobe, and cerebellum. This is the first report of AOS related to EBV encephalitis. SPECT was a useful method for detecting the damaged region of the operculum. In addition, AOS is a clinically distinct entity that may help us understand the mechanisms of language circuits within the operculum.