Clinical significance of Epstein-Barr virus in the cerebrospinal fluid of immunocompetent patients.

INTRODUCTION: Polymerase chain reaction (PCR)-based testing of cerebrospinal fluid (CSF) samples has greatly facilitated the diagnosis of central nervous system (CNS) infections. However, the clinical significance of Epstein-Barr virus (EBV) DNA in CSF of individuals with suspected CNS infection remains unclear. We wanted to gain a better understanding of EBV as an infectious agent in immunocompetent patients with CNS disorders. METHODS: We identified cases of EBV-associated CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with EBV PCR positivity in CSF who visited Pusan National University Hospital between 2010 and 2019. RESULTS: Of the 780 CSF samples examined during the 10-year study period, 42 (5.4 %) were positive for EBV DNA; 9 of the patients (21.4 %) were diagnosed with non-CNS infectious diseases, such as optic neuritis, Guillain-Barré syndrome, and idiopathic intracranial hypotension, and the other 33 cases were classified as CNS infections (22 as encephalitis and 11 as meningitis). Intensive care unit admission (13/33 patients, 39.3 %) and presence of severe neurological sequelae at discharge (8/33 patients, 24.2 %) were relatively frequent. In 10 patients (30.3 %), the following pathogens were detected in CSF in addition to EBV: varicella-zoster virus (n = 3), cytomegalovirus (n = 2), herpes simplex virus 1 (n = 1), herpes simplex virus 2 (n = 1), Streptococcus pneumomiae (n = 2), and Enterococcus faecalis (n = 1). The EBV-only group (n = 23) and the co-infection group (n = 10) did not differ in age, gender, laboratory data, results of brain imaging studies, clinical manifestations, or prognosis; however, the co-infected patients had higher CSF protein levels. CONCLUSION: EBV DNA in CSF is occasionally found in the immunocompetent population; the virus was commonly associated with encephalitis and poor prognosis, and frequently found together with other microbes in CSF.

Varicella Zoster Reactivation Causing Aseptic Meningitis in Healthy Adolescents: A Case Series And Review Of The Literature.

We describe 3 cases of adolescent varicella-zoster virus reactivation, complicated by aseptic meningitis, presenting to our institution in a 3-year period. These cases highlight varicella-zoster virus reactivation as an important cause of aseptic meningitis in the differential diagnosis of healthy adolescents, even in the absence of a characteristic exanthem. Evidence-based management recommendations are needed.

HIV vasculopathy versus VZV vasculitis in an HIV patient with multiple brain ischaemic infarcts.

We report the case of a 56-year-old man who presented to the emergency department with a 3-day onset of left limb weakness and feeling intoxicated with poor balance. Stroke hospitalisations in the USA decreased from 2000 to 2010, however the number of hospitalised patients with ischaemic stroke and HIV infection has increased significantly. Herein, we discuss the management of this unique case to highlight the importance of a broad differential diagnosis when approaching HIV/AIDS patients presenting with acute or subacute neurological focalisation. Given that HIV vasculopathy is a diagnosis of exclusion, it requires a thoughtful elimination of all possible aetiologies.

Acute disseminated encephalomyelitis following varicella-zoster virus infection: Case report of effective treated both in clinical symptom and neuroimaging.

INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is an idiopathic inflammatory demyelinating disorder of the central nervous system (CNS). Early treatment is the key for neurological recovery. METHODS: A case of ADEM associated with varicella-zoster virus infection was presented, in which magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) examinations were included. RESULTS: Magnetic resonance imaging of the brain revealed multiple hyperintense lesions at the subcortical level on fluid-attenuated inversion recovery (FLAIR), and MRI of the spinal cord revealed longitudinally segmented hyperintense lesions at the spinal cord on T2-weighted images. The patient was treated with methylprednisolone and gancyclovir, and had a favorable recovery. Subsequent MRI of the brain and cervical cord showed the previous abnormal hyperintensities had markedly disappeared. CONCLUSION: A rare case of ADEM with longitudinal segmented hyperintense lesions at the spinal cord on T2-weighted images was presented. Excellent response to ADEM treatment with high-dose steroids was reported resulting in a remarkable neurological recovery. A long-term follow-up is needed for prognosis.

Varicella-Zoster Virus in Cerebrospinal Fluid at Relapses of Multiple Sclerosis is Infective in Vitro.

BACKGROUND: We have reported the presence of varicella-zoster virus (VZV) DNA and viral particles in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients during exacerbation. It is not known whether these viruses are infective. AIM: To determine whether the VZV found in CSF of MS patients in exacerbation phase are infective. METHODS: VZV found in CSF of MS patients was quantified by qPCR. Vero E6 cell cultures were incubated with CSF of five MS cases positive for VZV DNA, containing herpes-like viral particles. Propagated virus harvested from these cultures were used to infect new VeroE6 cells. Localization of an immediate-early and a late structural VZV proteins was monitored by confocal microscopy after 72 h. CSF from five non-inflammatory neurological (NIN) patients were used as controls. RESULTS: A cytopathic effect was found in cultured cells inoculated with CSF from MS patients. Both, structural VZV glycoprotein (gB) and immediate-early VZV protein (IE62) were detected in Vero E6 cultures inoculated with samples from all five MS cases. CSF from control patients produced no effect on Vero E6 cells. CONCLUSION: When present in the CSF at relapses of MS, VZV is infective under in vitro conditions.

Varicella zoster lumbosacral plexopathy: a rare cause of lower limb weakness.

This is a rare case of Varicella zoster virus (VZV) lumbosacral plexopathy in an 84-year-old women presenting with lower limb weakness and rash. Contrast-enhanced MRI showed enhancement of the left L3-L5 descending nerves and left lumbosacral plexus consistent with inflammatory/infectious aetiology. Cerebrospinal fluid PCR confirmed VZV DNA and cerebrospinal fluid serological testing was positive for VZV immunoglobulin (Ig)M and IgG antibodies. The patient was treated with intravenous acyclovir but this was complicated by the development of acute renal failure attributed to acyclovir-induced nephropathy, requiring dose adjustment. After a prolonged course of oral acyclovir and inpatient rehabilitation, the patient made a partial neurological and functional recovery.

Varicella zoster virus infections in neurological patients: a clinical study.

BACKGROUND: Varicella zoster virus (VZV) reactivation is a common infectious disease in neurology and VZV the second most frequent virus detected in encephalitis. This study investigated characteristics of clinical and laboratory features in patients with VZV infection. METHODS: Two hundred eighty two patients with VZV reactivation that were hospitalized in the department of neurology in the time from 2005 to 2013 were retrospectively evaluated. Results from cerebrospinal fluid (CSF) analysis were available from 85 patients. RESULTS: Trigeminal rash was the most common clinical manifestation, followed by segmental rash, CNS infection, facial nerve palsy, postherpetic neuralgia, and radiculitis. MRI of the brain performed in 25/33 patients with encephalitis/meningitis did not show any signs of infection in the brain parenchyma. Only one patient showed contrast enhancement in the hypoglossal nerve. General signs of infection such as fever or elevated CRP values were found in only half of the patients. Furthermore, rash was absent in a quarter of patients with CNS infection and facial nerve palsy, and thus, infection could only be proven by CSF analysis. Although slight inflammatory CSF changes occurred in few patients with isolated rash, the frequency was clearly higher in patients with CNS infection and facial nerve palsy. CONCLUSION: Monosegmental herpes zoster is often uncomplicated and a diagnostic lumbar puncture is not essential. In contrast, CSF analysis is an essential diagnostic tool in patients with skin lesions and cranial nerve or CNS affection. In patients with neuro-psychiatric symptoms and inflammatory CSF changes analysis for VZV should be performed even in the absence of skin lesions.