Varicella Zoster Virus Encephalitis Research Articles

Two Waves of Specific B Cell Memory Immunoreconstruction Observed in Anti-HHV1-3 IgG Kinetics after Hematopoietic Stem Cell Transplantation.

Humoral memory and specific antibody levels depend on the kind of antigen and individual immunofactors. The presence of IgM antibodies or a fourfold rise in specific IgG levels are generally accepted as diagnostic factors in the serology of acute viral infections. This basic model is not adequate for the herpes virome, especially after hematopoietic stem cell transplantation (HSCT), due to continuous, usually multifocal antigenic stimulation, various donor serostatuses, immunosuppression, and individual immunoreconstitution. A case-control study was conducted to identify active infection cases of human herpesvirus (HHV) (from 300 diagnosed immunocompromised patients) and to evaluate historically associated humoral factors to look at outcomes. We considered only the data of patients with meticulous differential diagnosis to exclude other causes, and thereby to observe pathways and temporal relationships, not the statistical ones usually collected in cohorts. Despite the small number, such data collection and analysis methods avoid a number of biases and indicate cause and effect. In this observational study, a retrospective analysis of data from 300 patients with clinical diagnosis of herpes simplex virus (HSV) and varicella zoster virus (VZV) reactivation showed a number of biases. Two well-differentiated cases (confirmed by a Tzanck test) with various diseases and conditioning evolutions of immune parameters showed an interesting pathway. Exponential decreases in specific IgGs after HSCT preceded virus replication were observed, with a cytopathic effect (shingles, VZV encephalitis and HSV-induced mucositis). The minima (lowest IgG levels) before herpesvirus reactivation were 234.23 mIU/mL and 94 RU/mL for VZV and HSV, respectively. This coincided with a low CD4 titer, but without other infectious processes. Other immune response parameters such as Treg, cytotoxic T cells, and complement and total IgG level were the same as they were before the transplant procedure. Interestingly, a second wave of immunoreconstitution with an anamnestic antibody response was not always observed. It coincided with prolonged herpes viral infection. A patient with lymphocyte depletion in conditioning showed an earlier second wave of immunoreconstitution (6th vs. 14th month). As is typical for infancy, the kinetics of the IgG level is unique after HSCT (the decline phase is first). Host microbiome factors (e.g., HHV1-3-serostatus) should be taken into account to predict risk of non-relapse mortality and survival after HSCT. The levels of specific antibodies help in predicting prognoses and improve disease management. A lack of differentiation and the confusing bias of the assessor (i.e., observer selection bias) are the main obstacles in statistical HHV1-3 research. Such time-lapse case studies may be the first to build evidence of a pathway and an association between immune parameters and HHV disease.

Characteristics, management and outcome of Herpes Simplex and Varicella-Zoster virus encephalitis: a multicentre prospective cohort study

ObjectiveTo characterize differences between Herpes Simplex virus encephalitis and Varicella-Zoster virus encephalitis (HSVE and VZVE) and other aetiologies of infectious encephalitis (IE), and to investigate the impact of time-to-aciclovir (ACV) start, ACV dose and duration on outcome. MethodsWe compared 132 HSVE, 65 VZVE and 297 other IE enrolled in a prospective cohort (ENCEIF). We estimated associations between time-to-ACV start, dose or duration and outcome through adjusted odds ratio (aOR) using logistic regression analysis. ResultsPrevalence of immunodepression differed among aetiologies: 15/65 (23%) for VZVE, 13/132 (10%) for HSVE and 30/297 (10%) for other IE (p <0.05), as was presence of seizure at admission: 27/132 (20%) for HSVE, 4/65 (6%) for VZVE and 43/297 (14%) for other IE (p <0.05). Poor outcome at hospital discharge (Glasgow outcome scale ≤3) differed among the three groups: 40/127 (31%) for HSVE, 12/65 (18%) for VZVE and 38/290 (13%) for other IE (p <0.05). Time-to-ACV start was associated with outcome in HSVE (aOR 3.61 [1.25–10.40]), but not in VZVE (aOR 0.84 [0.18–3.85]). Increased ACV dose was not associated with outcome among HSVE (aOR 1.25 [0.44–3.64]) nor VZVE (aOR 1.16 [0.24–5.73]). DiscussionHSVE and VZVE are distinct in clinical presentation, outcome and prognostic factors. The impact of early ACV initiation was more apparent for HSVE than for VZVE; however, this could be because of VZVE’s smaller sample size and lower outcome rate leading to low statistical power or because of potential distinct IE pathophysiology.

Nanopore targeted sequencing-based diagnosis of central nervous system infections in HIV-infected patients

BackgroundEarly and accurate etiological diagnosis is very important for improving the prognosis of central nervous system (CNS) infections in human immunodeficiency virus (HIV)-infected patients. The goal is not easily achieved by conventional microbiological tests. We developed a nanopore targeted sequencing (NTS) platform and evaluated the diagnostic performance for CNS infections in HIV-infected patients, with special focus on cryptococcal meningitis (CM). We compared the CM diagnostic performance of NTS with conventional methods and cryptococcal polymerase chain reaction (PCR).MethodsThis study included 57 hospitalized HIV-infected patients with suspected CNS infections from September 2018 to March 2022. The diagnosis established during hospitalization includes 27 cases of CM, 13 CNS tuberculosis, 5 toxoplasma encephalitis, 2 cytomegalovirus (CMV) encephalitis and 1 Varicella-zoster virus (VZV) encephalitis. The 2 cases of CMV encephalitis also have co-existing CM. Target-specific PCR amplification was used to enrich pathogen sequences before nanopore sequencing. NTS was performed on stored cerebrospinal fluid (CSF) samples and the results were compared with the diagnosis during hospitalization.Results53 (93.0%) of the patients were male. The median CD4 cell count was 25.0 (IQR: 14.0–63.0) cells/uL. The sensitivities of CSF culture, India ink staining, cryptococcal PCR and NTS for CM were 70.4% (95%CI: 51.5 − 84.1%), 76.0% (95%CI: 56.6 − 88.5%), 77.8% (59.2 − 89.4%) and 85.2% (95%CI: 67.5 − 94.1%), respectively. All those methods had 100% specificity for CM. Our NTS platform could identify Cryptococcus at species level. Moreover, NTS was also able to identify all the 5 cases of toxoplasma encephalitis, 2 cases of CMV encephalitis and 1 VZV encephalitis. However, only 1 of 13 CNS tuberculosis cases was diagnosed by NTS, and so did Xpert MTB/RIF assay.ConclusionsNTS has a good diagnostic performance for CM in HIV-infected patients and may have the ability of simultaneously detecting other pathogens, including mixed infections. With continuing improving of the NTS platform, it may be a promising alterative microbiological test for assisting with the diagnosis of CNS infections.

Don't rash it! The clinical significance of positive Varicella zoster virus PCR in cerebrospinal fluid of patients with neurological symptoms

BackgroundVaricella zoster virus (VZV) is among the leading pathogens causing meningitis and encephalitis. While VZV-PCR-positive CSF is considered a gold-standard for diagnosis, it is not-uncommon to detect VZV-DNA in CSF of patients with other acute or chronic illness. Our goal was to determine the clinical relevance of VZV-PCR-positive CSF when investigating patients with neurological symptoms. MethodsIn this retrospective cohort from the largest hospital in Israel, we collected demographic, clinical and laboratory data of patients with VZV-PCR-positive CSF, analyzing the significance of various parameters. ResultsDuring a 5-years study, 125 patient-unique VZV-PCR-positive CSFs were recorded, in which only 9 alternative diagnoses were noted. The commonest symptoms were headache (N = 104, 83 %) and rash (N = 96, 76 %). PCR-cycle-threshold (Ct), a surrogate of viral burden, did not significantly vary across the clinical manifestations; however, patients with rash and Ct<35 were prone to develop stroke in the following year (N = 6, 7 %). Empiric nucleoside-analogue treatment was not associated with a better outcome compared to treatment administered upon a positive-PCR result. DiscussionOur findings suggest that in patients with neurological symptoms, detection of VZV-DNA in CSF renders VZV the probable culprit. Nevertheless, a systematic evaluation of treatment and follow-up algorithms of patients with suspected or proved VZV meningitis and encephalitis is needed. The benefits of a prompt treatment should be weighed against the potential complications of nucleoside-analogue. Conversely, the propensity for stroke in patients with higher viral-burden, necessitates further studies assessing VZV causal role, directing additional workup, treatment and monitoring policy.

State of the Art: Acute Encephalitis.

Encephalitis is a devastating neurologic disease often complicated by prolonged neurologic deficits. Best practices for the management of adult patients include universal testing for a core group of etiologies, including herpes simplex virus (HSV)-1, varicella zoster virus (VZV), enteroviruses, West Nile virus, and anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody encephalitis. Empiric acyclovir therapy should be started at presentation and in selected cases continued until a second HSV-1 polymerase chain reaction test is negative. Acyclovir dose can be increased for VZV encephalitis. Supportive care is necessary for other viral etiologies. Patients in whom no cause for encephalitis is identified represent a particular challenge. Management includes repeat brain magnetic resonance imaging, imaging for occult malignancy, and empiric immunomodulatory treatment for autoimmune conditions. Next-generation sequencing (NGS) or brain biopsy should be considered. The rapid pace of discovery regarding autoimmune encephalitis and the development of advanced molecular tests such as NGS have improved diagnosis and outcomes. Research priorities include development of novel therapeutics.

Early Postoperative Varicella-Zoster Virus Encephalitis After Adult ABO-Incompatible Living Donor Liver Transplantation: A Case Report

There have never been any reports of adult varicella-zoster virus (VZV) encephalitis cases. Here, we report a case of VZV encephalitis after adult ABO-incompatible living donor liver transplantation (LDLT). A 38-year-old man with decompensated liver cirrhosis caused by the hepatitis C virus was referred to our hospital as an LDLT candidate. Rituximab was administered 3 weeks before the operation, and immunosuppression agents were administered 1 week before the LDLT. Plasma exchange was performed 3 times before the LDLT. The right lobe from his mother's liver was used for the ABO-incompatible LDLT. On postoperative day (POD) 9, vascular stenting for intraabdominal bleeding from the common hepatic artery was performed by interventional radiology and was followed by re-laparotomy for abdominal drainage of the hematoma. However, there were various degrees of continued bleeding thereafter. On POD 12, due to a convulsion seizure with loss of consciousness, the patient was started on anticonvulsant therapy. On POD 15, there was an increased frequency of convulsion attacks and a prolonged loss of consciousness. A lumbar puncture was performed on POD 20 due to the appearance of shingles. The positive polymerase chain reaction of the VZV-DNA from the cerebrospinal fluid was detected, and he was diagnosed with VZV encephalitis. He rapidly regained alertness, and there were no further observed convulsion attacks after administration of a steroid pulse and acyclovir. Brain magnetic resonance imaging performed on 2 subsequent postoperative months showed findings that matched with VZV encephalitis. He was discharged as he had recovered and was ambulatory 3 months after LDLT.

Can we forecast poor outcome in herpes simplex and varicella zoster encephalitis? A narrative review.

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are among the most commonly diagnosed infectious causes of sporadic encephalitis worldwide. Despite treatment, mortality and morbidity rates remain high, especially for HSV encephalitis. This review is intended to provide an overview of the existing scientific literature on this topic from the perspective of a clinician who is confronted with serious decisions about continuation or withdrawal of therapeutic interventions. We performed a literature review searching two databases and included 55 studies in the review. These studies documented or investigated specifically outcome and predictive parameters of outcome of HSV and/or VZV encephalitis. Two reviewers independently screened and reviewed full-text articles meeting the inclusion criteria. Key data were extracted and presented as a narrative summary. Both, HSV and VZV encephalitis have mortality rates between 5 and 20% and complete recovery rates range from 14 to 43% for HSV and 33 to 49% for VZV encephalitis. Prognostic factors for both VZV and HSV encephalitis are older age and comorbidity, as well as severity of disease and extent of magnetic resonance imaging (MRI) lesions on admission, and delay in treatment initiation for HSV encephalitis. Although numerous studies are available, the main limiting factors are the inconsistent patient selection and case definitions as well as the non-standardised outcome measures, which hampers the comparability of the studies. Therefore, larger and standardised observational studies applying validated case definitions and outcome measures including quality of life assessment are required to provide solid evidence to answer the research question.

Clinical manifestations of varicella zoster virus encephalitis in adults: A multifaceted presentation

The aim of this study is to investigate the clinical features and outcomes of adult Varicella Zoster Virus (VZV) encephalitis. The study analyzed the medical records, imaging results, electrophysiological findings, and prognosis of 9 patients diagnosed with VZV encephalitis.

Infectious Encephalitis in Adults: Characteristics, Outcome and Clinical Clues (S25.010)

<h3>Objective:</h3> Clinical characterization and comparison between the major causative agents of acute infectious encephalitis in adults. <h3>Background:</h3> The annual incidence of acute infectious encephalitis in adults is reported between 0.5–16 per 100,000 persons. West Nile virus (WNV) is among the most important causative agents of viral encephalitis. <h3>Design/Methods:</h3> We retrospectively characterize the clinical course of acute infectious encephalitis among adult patients admitted to the Tel-Aviv Medical Center between 2010 and 2020 (n=95), comparing major causative agents and focusing on WNV encephalitis (WNVE, n=31), varicella-zoster virus encephalitis (VZVE, n=30) and herpes simplex 1 virus encephalitis (HSV1E, n=13). <h3>Results:</h3> Patient groups differed in terms of age, with WNVE (median age 73) and VZVE (76) patients significantly older compared with HSV1E patients (51). CSF characteristics differed between groups, with VZVE patients having significant mononuclear white blood cell (WBC) predominance (99%) and HSV1E patients having lower CSF protein (57 mg/dL). Blood inflammation markers also differed significantly, with WBC higher in WNVE and C-reactive protein lower in HSV1E. Functional outcome was the worst in WNVE patients at discharge (median modified Rankin Scale [mRS] score 4) and last follow-up (median mRS score 4), reaching statistical significance when compared with VZVE patients. Differences in functional outcome prevailed when excluding patients with poor functional baseline (mRS score &gt; 2 before presentation). Logistic regression found age as an independent variable associated with worse functional outcome, and age, baseline mRS and WNVE (compared to VZVE) as associated with mortality. <h3>Conclusions:</h3> In odds with previous reports, WNVE and VZVE were far more common than HSV1E. Differences in laboratory characteristics could prove clinically useful early in the presentation of acute encephalitis. In some aspects, WNVE patients had a course resembling a bacterial, rather than viral, CNS infection. The detrimental outcome of WNVE emphasizes the need to promote solutions to WNV infection such as vaccinations and specific drugs. <b>Disclosure:</b> Dr. Maayan Eshed has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bionaut Labs Ltd. Dr. Levinson has nothing to disclose. Dr. Mina has nothing to disclose. Dr. Ashkenazi has nothing to disclose. Dr. Dekel has nothing to disclose. Dr. Cohen-Poradosu has nothing to disclose. Yifat Alcalay has nothing to disclose. Orna Aizenstein Lehavi has nothing to disclose. Yael Paran has nothing to disclose. Dr. Gadoth has received intellectual property interests from a discovery or technology relating to health care.

Structured Imaging Approach for Viral Encephalitis.

MR imaging is essential in diagnosing viral encephalitis. Clinical features, cerebrospinal fluid analysis and pathogen confirmation by polymerase chain reaction can be supported by assessing imaging features. MR imaging patterns with typical locations can identify pathogens such as temporal lobe for herpes simplex virus type 1; bilateral thalami for Japanese encephalitis and influenza virus ; and brainstem for enterovirus and rabies. In this article, we have reviewed representative viral encephalitis and its MR imaging patterns. In addition, we also presented acute viral encephalitis without typical MR imaging patterns, such as dengue and varicella-zoster virus encephalitis.

Two cases of Ramsay-Hunt syndrome following varicella zoster viral meningitis in young immunocompetent men: case reports

BackgroundRamsay-Hunt syndrome (RHS) due to varicella zoster virus (VZV) infection is commonly reported in individuals aged at least 50 years or immunocompromised individuals. VZV infection may invade the central nervous system (CNS) and cause meningitis or encephalitis, which are more likely to occur in patients with chronic diseases such as diabetes and chronic renal failure. However, cases with VZV-induced concurrent RHS and CNS infections are rare.Case presentationTwo young male patients, aged 32 and 43 years, with no underlying disease developed VZV meningitis, followed by RHS involving cranial nerves VII and VIII. Both patients presented with symptoms of peripheral facial palsy, and dizziness accompanied by tinnitus and hearing loss, which appeared several days after the onset of fever and headache. These symptoms were documented as facial neuropathy and sensorineural hearing loss in the electrophysiologic studies. Lymphocyte-dominant pleocytosis and VZV positivity were confirmed from cerebrospinal fluid examination and polymerase chain reaction, respectively. The patients were treated with intravenous acyclovir and oral steroids simultaneously. Following the treatment completion, both patients were relieved of their headaches and fever; however, facial palsy, dizziness, and tinnitus persisted. They were followed up at the outpatient clinic.ConclusionThese cases confirmed that RHS and CNS infections can co-exist even in young adults with normal immune function and more importantly, that CNS infection can precede RHS. Since early detection and treatment of RHS improve the prognosis, it is critical to closely monitor patients with VZV meningitis or encephalitis considering the possible superimposition of RHS.

Varicella-Zoster Virus Meningoencephalitis in a Lung Transplant Recipient

Introduction Solid organ transplant (SOT) recipients are susceptible to an array of infections and atypical clinical presentations. Varicella-zoster virus (VZV) becomes latent in dorsal root ganglia after the initial infection, and reinfection commonly presents with a painful rash. In SOT recipients, VZV can present as meningoencephalitis without an associated rash and is associated with high morbidity and mortality. We present a rare case of VZV meningoencephalitis in a lung transplant recipient. Case Report A 71-year-old woman with a history of bilateral lung transplant in 2014 and rheumatoid arthritis presented to an outside hospital with one week of fever and confusion. She was subsequently intubated after suffering a generalized tonic-clonic seizure. Upon transfer to our facility she had an unremarkable exam including skin exam. She was started on vancomycin, ceftriaxone, ampicillin, acyclovir, and fluconazole for presumed meningoencephalitis. Lumbar puncture revealed 100 WBC/mm3, with 93% lymphocytes. The cerebrospinal fluid (CSF) glucose was 125 mg/dL, protein was 233 mg/dL, cultures were negative but qualitative polymerase chain reaction (PCR) was positive for VZV. Electroencephalogram (EEG) revealed status epilepticus and magnetic resonance imaging (MRI) showed a T1 and T2 hypointensity in the right posterior periventricular white matter and scattered foci in bilateral cerebral white matter. Her status epilepticus was treated with antiepileptics and resolved by hospital day eight. She received 14 days of intravenous (IV) acyclovir 10mg/kg every 8 hours and was transitioned to oral valacyclovir for suppression for two months. On discharge her mental status had significantly improved but had not fully returned to her baseline. Summary Zoster is a common, benign disease caused by VZV and associated with painful cutaneous lesions. However, neurological manifestations without a rash are possible in SOT patients. Lumbar puncture and CSF analysis are crucial for diagnosis and typically shows lymphocytosis with viral culture, antibody, or PCR positive for VZV. Treatment of choice for VZV encephalitis is IV acyclovir for 7 days in the immunocompetent patient and 14 days in the immunosuppressed patient. This case demonstrates how prompt recognition and treatment of VZV meningoencephalitis can decrease mortality and neurologic disease in the immunocompromised patient. Solid organ transplant (SOT) recipients are susceptible to an array of infections and atypical clinical presentations. Varicella-zoster virus (VZV) becomes latent in dorsal root ganglia after the initial infection, and reinfection commonly presents with a painful rash. In SOT recipients, VZV can present as meningoencephalitis without an associated rash and is associated with high morbidity and mortality. We present a rare case of VZV meningoencephalitis in a lung transplant recipient. A 71-year-old woman with a history of bilateral lung transplant in 2014 and rheumatoid arthritis presented to an outside hospital with one week of fever and confusion. She was subsequently intubated after suffering a generalized tonic-clonic seizure. Upon transfer to our facility she had an unremarkable exam including skin exam. She was started on vancomycin, ceftriaxone, ampicillin, acyclovir, and fluconazole for presumed meningoencephalitis. Lumbar puncture revealed 100 WBC/mm3, with 93% lymphocytes. The cerebrospinal fluid (CSF) glucose was 125 mg/dL, protein was 233 mg/dL, cultures were negative but qualitative polymerase chain reaction (PCR) was positive for VZV. Electroencephalogram (EEG) revealed status epilepticus and magnetic resonance imaging (MRI) showed a T1 and T2 hypointensity in the right posterior periventricular white matter and scattered foci in bilateral cerebral white matter. Her status epilepticus was treated with antiepileptics and resolved by hospital day eight. She received 14 days of intravenous (IV) acyclovir 10mg/kg every 8 hours and was transitioned to oral valacyclovir for suppression for two months. On discharge her mental status had significantly improved but had not fully returned to her baseline. Zoster is a common, benign disease caused by VZV and associated with painful cutaneous lesions. However, neurological manifestations without a rash are possible in SOT patients. Lumbar puncture and CSF analysis are crucial for diagnosis and typically shows lymphocytosis with viral culture, antibody, or PCR positive for VZV. Treatment of choice for VZV encephalitis is IV acyclovir for 7 days in the immunocompetent patient and 14 days in the immunosuppressed patient. This case demonstrates how prompt recognition and treatment of VZV meningoencephalitis can decrease mortality and neurologic disease in the immunocompromised patient.

A Rare Case of Multiple Ring-Enhancing Lesions on Magnetic Resonance Imaging of the Brain in Varicella-Zoster Virus Encephalitis with Human Immunodeficiency Virus.

A Rare Case of Multiple Ring-Enhancing Lesions on Magnetic Resonance Imaging of the Brain in Varicella-Zoster Virus Encephalitis with Human Immunodeficiency Virus.

Cerebrovascular Complications After Adult-Onset Varicella-Zoster Virus Encephalitis in the Central Nervous System: A Literature Review.

BackgroundCerebrovascular complications after adult-onset varicella-zoster virus (VZV) encephalitis have been increasingly recognized. The aim of this study was to analyze clinical and neuroimaging findings, treatment and outcome of these patients.MethodsLiterature review from January 2000 to December 2019. We searched for studies published in PubMed, Embase and Chinese Biomedical Literature Database. Clinical symptoms, neuroimaging findings, treatment and outcome were evaluated.ResultsWe analyzed 31 articles with a total of adult-onset 34 cases, including 25 cases of ischemic stroke, 6 of intracerebral hemorrhage and 3 with venous sinus thrombosis. Ischemic stroke was the major complication after VZV encephalitis accounting of 73.35%. There were more males than females in ischemia or venous sinus thrombosis groups. The middle-aged was prone to cerebral infarction, the elderly was for cerebral hemorrhage, and the young was for venous sinus thrombosis. Cognitive impairment was the most common symptom either in the ischemic group or hemorrhagic group. The lesions of VZV-associated cerebral infarction or hemorrhage were multifocal and mostly involved in the parietal lobe, followed by frontal or temporal lobes. Venous sinus thrombosis was common in the transverse sinus. Multiple stenosis of the anterior and posterior circulation vessels was found. A 60.87% of the patients with antiviral treatment in the ischemic group had favorable prognosis. All patients with anticoagulant therapy in venous sinus thrombosis group improved well; however, 60% of the patients with intracerebral hemorrhage had a poor prognosis or died.ConclusionIschemic stroke was the majority of cerebrovascular complications after VZV encephalitis, which mainly occurred in middle-aged men. The lesions of VZV-associated cerebral infarction or hemorrhage were multifocal and did not accord with the characteristics of cerebrovascular diseases induced by atherosclerosis. The patients with venous sinus thrombosis had a relatively good prognosis. When the patient represents with some neurological symptoms about one month after VZV encephalitis, and multiple lesions probably induced by vasculitis are showed in neuroimaging, cerebrovascular complications related to VZV infection should be considered.

Varicella zoster virus encephalitis: a potentially serious complication during treatment with vedolizumab.

Vedolizumab is a monoclonal antibody that has demonstrated efficacy and a good safety profile in patients with inflammatory bowel disease. Varicella zoster virus encephalitis is a potentially serious complication not previously described with its use, highlighting the importance of vaccination, as well as early diagnosis and treatment of infections in this type of patients.

Concurrence of Chicken Pox and Varicella Zoster Virus Encephalitis in an Immunocompetent Female: A Case Report

Varicella-zoster virus (VZV) causes primary infection of chickenpox and when reactivated produces shingles along with the dermatomal distribution of the affected nerve. Immunocompromised and unvaccinated elderly people are at a higher risk of infection. Varicella can be prevented by vaccination. One of the potential complications of VZV infection is encephalitis. Our 44 years old immunocompetent patient development altered sensorium and seizures, five days after the onset of characteristic chickenpox lesions. CSF analysis was consistent with viral encephalitis. PCR of the CSF confirmed the diagnosis of VZV encephalitis. MRI reported bilateral periventricular small vessel ischemic changes. The patient was treated with injectable acyclovir for 14 days and prednisolone for 5 days with resulting dramatic clinical improvement. Anticonvulsants were given to control the seizures. The patient was discharged on the 15th day of admission with almost complete recovery without developing neurological sequelae.

Zebras Masquerading As Horses: A Case of Spinal Subarachnoid Haemorrhage

A previously independent 83-year-old lady presents with acute confusion, decreased mobility, urinary retention, and constipation, having recently received a course of oral acyclovir for shingles. The patient was noted to have extensive bruising to her upper limbs, and blood tests showed raised inflammatory markers with low platelet count, although this remained above 75 × 109/L. Her confusion on a background of shingles raised the differential diagnosis of varicella-zoster virus (VZV) encephalitis. CT head and MRI brain showed no acute intracranial abnormality. Lumbar puncture yielded frankly haemorrhagic cerebrospinal fluid (CSF), but viral polymerase chain reaction (PCR) testing was negative for the varicella-zoster virus. She later developed further right shoulder pain and right lower limb weakness three days post-initial lumbar puncture. Repeat CT head was unremarkable. MRI spine showed extensive spinal subarachnoid haemorrhage, with possible cervical arteriovenous malformation and L5/S1 spinal nerve compression. The patient was managed conservatively with dexamethasone and inpatient physiotherapy support. She was discharged after a long hospital stay at a new mobility baseline requiring hoist transfers.

Genetic Variants and Immune Responses in a Cohort of Patients With Varicella Zoster Virus Encephalitis.

Infection with varicella zoster virus (VZV) may involve different central nervous system (CNS) manifestations, including meningitis, encephalitis, and vasculitis. In cases in which otherwise healthy individuals are affected, an inborn error of immunity may underlie increased susceptibility or severity of infection. We collected a cohort of 17 adults who experienced VZV encephalitis and performed whole exome sequencing. Patient peripheral blood mononuclear cells were infected with VZV, and innate antiviral interferon (IFN) and cytokine responses as well as viral replication were evaluated. Data were analyzed by Mann-Whitney U test. We identified a total of 21 different potentially disease-causing variants in a total of 13 of the 17 patients included. These gene variants were within 2 major functional clusters: (1) innate viral sensors and immune pathways and (2) autophagy pathways. Antiviral IFN and cytokine responses were abnormal in the majority of patients, whereas viral replication was increased in only 2 of 17 patients. This study identifies a list of variants of pathogenic potential, which may serve as a platform for generating hypotheses for future studies addressing genetic and immunological factors associated with susceptibility to VZV encephalitis. These data, taken together, suggest that disturbances in innate sensing and autophagy pathways may predispose to VZV encephalitis.

Characteristics and outcome of varicella-zoster virus central nervous system infections in adults.

We conducted an observational retrospective study of all adults hospitalized for documented varicella-zoster virus (VZV) meningitis or encephalitis during years 2000-2015 in one referral centre. Thirty-six patients (21 males, 15 females) were included, with meningitis (n = 21), or meningoencephalitis (n = 15). Median age was 51 years [interquartile range, 35-76], and 6 patients (17%) were immunocompromised. Aciclovir was started in 32 patients (89%), with a median dose of 11 mg/kg/8 h [10-15]. No patient died, but 12 (33%) had neurological sequelae at discharge. Age was the only variable associated with adverse outcome (OR 1.98 [1.17-3.35] per 10-year increment, P = 0.011).

Cognitive impairment without altered levels of cerebrospinal fluid biomarkers in patients with encephalitis caused by varicella-zoster virus: a pilot study

Varicella-zoster virus (VZV) is one of the most common agents causing viral infections of the central nervous system (CNS). VZV encephalitis is associated with severe neurological sequelae, despite antiviral treatment. Cognitive impairment has been reported and VZV has been associated with dementia. Our aim was to investigate the cognitive impairment and cerebrospinal fluid biomarkers in a follow-up study of patients with VZV encephalitis. Thirteen patients with VZV encephalitis, diagnosed by detection of VZV DNA in cerebrospinal fluid (CSF) by PCR and concomitant symptoms of encephalitis, were included. Neuropsychological assessment in parallel with a lumbar puncture to obtain CSF was performed 1.5–7 years after acute disease. The CSF biomarkers neurofilament light chain (NFL), S100B, glial fibrillary acidic protein (GFAP), amyloid-β (Aβ) 40 and Aβ42, total tau (t-tau) and phosphorylated tau (p-tau) were analysed and compared to controls (n = 24). Cognitive impairment was shown in the domains of executive functions and speed/attention and to a minor degree in the domains of learning/memory and language, indicated by a significantly poorer performance on seven neuropsychological test variables. No convincing evidence of alterations in concentrations of biomarkers in the CSF were shown. Our results indicate that patients with VZV encephalitis suffer from cognitive impairment long time after acute disease. Importantly, these impairments do not seem to be accompanied by biomarker evidence of ongoing neuronal or astrocytic injury/activation or induction of dementia-related brain pathologies by the infection.