Evolution from viral encephalitis to autoimmune encephalitis to multiple sclerosis: a case report.

BACKGROUND: There are established associations between viral and autoimmune encephalitis as well as between autoimmune encephalitis and demyelinating central nervous system (CNS) diseases. Here, we report the evolution from varicella zoster virus (VZV) encephalitis to limbic autoimmune encephalitis (AIE) to multiple sclerosis (MS) in one patient. CASE REPORT: A woman in her mid-thirties presented with headache, aphasia, and a generalized tonic-clonic seizure. Cerebrospinal fluid (CSF) VZV polymerase chain reaction was positive and treatment with acyclovir was administered for VZV encephalitis. Five months later, the patient presented with cognitive deficits and MRI showed new bilateral hippocampal T2-hyperintensities. CSF analyses revealed pleocytosis and neuropil antibodies in tissue-staining. A diagnosis of limbic AIE was established and treatment with IV steroids and IV immunoglobulins initiated. One year later, the patient developed paresthesia of both legs and magnetic resonance imaging studies now showed new supratentorial and spinal demyelinating lesions. The patient was diagnosed with MS and treatment was changed to rituximab. CONCLUSIONS: This unique case report links three important neuroimmunological entities in characterizing the evolution from infectious to autoimmune encephalitis to multiple sclerosis in one patient. Identification of such rare clinical constellations is critical for correct treatment choice and provides important novel insights into the pathophysiology of neuroimmunological disorders including viral triggers and overlap manifestations of autoimmune CNS diseases.

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

OBJECTIVE: To 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. METHODS: We 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. RESULTS: Prevalence 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]). DISCUSSION: HSVE 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.

Varicella zoster encephalitis in an immunocompetent patient.

Encephalitis is inflammation of the brain parenchyma, most often caused by viruses. Historically, data have shown herpes simplex virus 1 and 2 to be the most common causes of viral encephalitis, with cases due to varicella zoster virus (VZV) more often seen in older age and immunocompromised states. However, emerging data show VZV as an increasingly common culprit of encephalitis in young, immunocompetent patients. PCR analysis of the cerebrospinal fluid is the most accurate diagnostic modality for viral encephalitis. Appropriate and complete treatment hinges on accurate identification of the cause of encephalitis, underscoring the need for comprehensive testing. We present a case of VZV encephalitis in an immunocompetent male patient in his 40s.

Varicella Zoster viral encephalitis without herpes: diagnosis by metagenomic next-generation sequencing of cerebrospinal fluid.

Acute Varicella Zoster viral encephalitis in immunocompetent adult patients without cutaneous herpes has rarely been reported. A 24-year-old female was hospitalized for a headache with a fever but without other obvious symptoms. Multiple routine examinations showed no abnormalities. Lumbar puncture indicated intracranial hypertension. The examination of cerebrospinal fluid by metagenomic next-generation sequencing demonstrated acute Varicella Zoster viral encephalitis. The patient's condition improved by treatment with acyclovir for antiviral therapy and mannitol dehydration to lower cranial pressure. Central Varicella Zoster viral infection should be emphasized as it is easily misdiagnosed and rare in clinical settings. Metagenomic next-generation sequencing of cerebrospinal fluid has significant advantages in the diagnosis of Varicella Zoster viral encephalitis.

Meningoencefalitis por virus Varicella-Zóster posterior a infección por SARS-CoV2: Reporte de dos casos / Meningoencephalitis caused by Varicella-Zoster virus after SARS-CoV2 infection: Two cases report

RESUMEN La meningoencefalitis por el VZV es una patología poco frecuente que se presenta con la reactivación del virus dentro del organismo. OBJETIVO: Describir la presentación clínica de dos pacientes con neuroinfección por VZV posteriormente a infección por SARS-CoV-2. REPORTE DEL CASO: El primer caso corresponde a un hombre de 59 años con antecedente de neumonía moderada por SARS-CoV-2 que después cursó con meningoencefalitis por VZV y, además, desarrolló un síndrome de Ramsay Hunt. El segundo caso es el de una mujer de 37 años con antecedente de infección leve por SARS CoV-2 con un cuadro de cefalea con signos de alarma, en quien se documentó neuroinfección por VZV

ABSTRACT Meningoencephalitis caused by varicella zoster virus is a rare pathology that presents due to the reactivation of the virus in the organism OBJECTIVE: To describe the clinical presentation of two patients with VZV neuroinfection presented after a SARS CoV-2 infection. CASE REPORT: The first case is a 59 year old male with previous moderate SARS CoV-2 infection who presented meningoencephalitis and was diagnosed with Ramsay Hunt's Syndrome. The second case is a 37 year old female with previous SARS CoV-2 infection who presented with an acute onset headache and was documented with VZV neuroinfection.

Neurological complications of varicella zoster virus reactivation: Prognosis, diagnosis, and treatment of 72 patients with positive PCR in the cerebrospinal fluid.

BACKGROUND: VZV infection can involve every level of the neurologic system: from the central nervous system (CNS) to the peripheral nervous system (PNS), including aseptic meningitis. Prognosis seems to differ between these neurological involvements. Prognostic factors remain unknown. METHODS: This is a retrospective multicenter study including all patients with a positive VZV polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) from eight centers in Paris (France) between 2011 and 2018. Unfavorable outcome was defined as mortality linked to VZV or incomplete recovery. Modified Rankin Scale (mRS) evaluated disability before and after the infection, with the difference designated as Rankin Delta. RESULTS: Seventy-two patients were included (53% male, median age 51 years, median mRS 0). Immunosuppression was reported in 42%. The clinical spectrum included 26 cases of meningitis, 27 instances of CNS involvement, 16 of PNS involvement, and 3 isolated replications (positive PCR but no criteria for neurological complications from VZV). Antiviral treatment was administered to 69 patients (96%). Sixty-two patients completed follow-up. Death linked to VZV occurred in eight cases. Unfavorable outcome (UO) occurred in 60% and was significantly associated with a higher prior mRS (Odd-ratio (OR) 3.1 [1.4-8.8] p = .012) and the presence of PNS or CNS manifestations (OR 22 [4-181] p = .001, OR 6.2 [1.3-33] p = .03, respectively, compared to meningitis). In the CSF, higher protein level (p < .0001) was also significantly associated with a higher Rankin Delta. CONCLUSIONS: Neurological complications of VZV with evidence of CSF viral replication are heterogeneous: aseptic meningitis has a good prognosis, whereas presence of CNS and PNS involvement is associated with a higher risk of mortality and of sequelae, respectively.

Advances and Perspectives in the Management of Varicella-Zoster Virus Infections.

Varicella-zoster virus (VZV), a common and ubiquitous human-restricted pathogen, causes a primary infection (varicella or chickenpox) followed by establishment of latency in sensory ganglia. The virus can reactivate, causing herpes zoster (HZ, shingles) and leading to significant morbidity but rarely mortality, although in immunocompromised hosts, VZV can cause severe disseminated and occasionally fatal disease. We discuss VZV diseases and the decrease in their incidence due to the introduction of live-attenuated vaccines to prevent varicella or HZ. We also focus on acyclovir, valacyclovir, and famciclovir (FDA approved drugs to treat VZV infections), brivudine (used in some European countries) and amenamevir (a helicase-primase inhibitor, approved in Japan) that augur the beginning of a new era of anti-VZV therapy. Valnivudine hydrochloride (FV-100) and valomaciclovir stearate (in advanced stage of development) and several new molecules potentially good as anti-VZV candidates described during the last year are examined. We reflect on the role of antiviral agents in the treatment of VZV-associated diseases, as a large percentage of the at-risk population is not immunized, and on the limitations of currently FDA-approved anti-VZV drugs. Their low efficacy in controlling HZ pain and post-herpetic neuralgia development, and the need of multiple dosing regimens requiring daily dose adaptation for patients with renal failure urges the development of novel anti-VZV drugs.

Varicella Zoster Virus Encephalitis in Denmark From 2015 to 2019-A Nationwide Prospective Cohort Study.

BACKGROUND: Knowledge of the epidemiology and clinical characteristics of varicella zoster virus (VZV) encephalitis remains limited. METHODS: Nationwide prospective cohort study of adults treated for microbiologically confirmed VZV encephalitis at Danish departments of infectious diseases from 2015 to 2019. Modified Poisson regression analysis was used to compute adjusted relative risks (RRs) of unfavorable outcome. RESULTS: We identified 92 adults (49% female) with VZV encephalitis, yielding an incidence of 5.3/1 000 000 per year (95% CI, 4.2-6.6). Median age was 75 years (IQR, 67-83) and immunocompromising conditions were frequent (39%). Predominant symptoms were confusion (76%), headache (56%), nausea (45%), gait disturbance (42%), and personality changes (41%). Cranial imaging showed cerebral vasculitis (including infarction and hemorrhage) in 14 (16%) patients and encephalitic abnormalities in 11 (13%) with predilection for the brainstem and deep brain structures. Intravenous acyclovir treatment was initiated a median (IQR) of 13.4 hours (5.2-46.3) since admission, while cranial imaging and lumbar puncture were performed after 6.3 hours (2.5-31.0) and 18.5 hours (4.9-42.0). In-hospital, 1-month, and 3-month mortalities were 4%, 9%, and 11%, respectively. Unfavorable outcome (Glasgow Outcome Score of 1-4) was found in 69% at discharge, with age (adjusted RR [aRR], 1.02; 95% CI, 1.01-1.03), vasculitis (aRR, 1.38; 95% CI, 1.02-1.86), and Glasgow Coma Scale (GCS) <15 (aRR, 1.32; 95% CI, 1.01-1.73) identified as independent risk factors. CONCLUSIONS: VZV encephalitis occurs primarily in elderly or immunocompromised patients with a higher incidence than previously estimated. The diagnosis is often delayed; risk factors for unfavorable outcome are age, cerebral vasculitis, and GCS <15.

Indolent varicella encephalitis with vasculopathy in an immunocompromised patient.

A 68-year-old female with B-cell non-Hodgkin's lymphoma presented to us with sequential blindness followed by hemiparesis. Four months earlier, the patient had developed chicken pox that was treated with intravenous acyclovir. An MRI brain showed multiple cerebral infarcts and beaded appearance of her intracranial vasculature. PET-CT showed hypermetabolism in the right frontal lobe and pons suggestive of encephalitis. Cerebral spinal fluid examination showed 15 cells and varicella zoster vasculopathy (VZVV) polymerase chain reaction was positive. A final diagnosis of indolent VZVV vasculopathy and encephalitis in an immunocompromised individual was made. This case highlights the slow and indolent progression of varicella central nervous system involvement.

An Autopsy Case of Varicella Zoster Virus Encephalitis with Multiple Brain Lesions.

Varicella-zoster virus (VZV) encephalitis in the absence of vasculopathy may rarely occur in association with herpes zoster. We herein report the case of a 67-year-old woman with non-Hodgkin's lymphoma undergoing chemotherapy who presented with an acute alteration in consciousness. Magnetic resonance imaging of the brain revealed multiple and nonspecific lesions of hyperintensity with mild edema in the cortex and subcortex. She was treated with intravenous acyclovir. However, two days after admission, the patient died and was diagnosed with VZV encephalitis. This case highlights the risk of VZV reactivation with severe neurological complications in patients undergoing immunosuppressive therapy.

Varicella zoster virus (VZV) oculomeningoencephalomyeloradiculitis: a previously undescribed constellation.

A 53-year-old immunocompromised woman developed acute left eye blindness and paraparesis suspected to be due to neuromyelitis optica (NMO). During treatment for NMO, right eye blindness and progressive multiple cranial neuropathies developed. Cerebrospinal fluid polymerase chain reaction (PCR) revealed Varicella zoster virus (VZV). This case emphasizes the importance of considering VZV in individuals, particularly the immunocompromised, presenting with a constellation of neurological signs and symptoms, even in the absence of rash.

Acute renal failure related to high doses of acyclovir (15 mg/kg/8 h) during treatment of varicella zoster virus encephalitis.

Varicella zoster virus (VZV) is less susceptible than herpes simplex virus to acyclovir. The optimal acyclovir regimen during VZV encephalitis remains unknown. We report two cases of acute renal failure after an increase in acyclovir dosage from 10 mg to 15 mg/kg/8 h during the treatment of VZV encephalitis according to French guidelines.

Case Report: Varicella-zoster Encephalitis with Acute Retinal Necrosis and Oculomotor Nerve Palsy.

SIGNIFICANCE: Varicella-zoster virus is a common cause of morbidity and vision loss in patients worldwide. It can affect any structure of the eye, from keratitis to acute retinal necrosis. Rapid diagnosis and treatment significantly improve clinical outcomes and quality of life. PURPOSE: The purpose of this study was to demonstrate a case where urgent referral to the emergency department was required to treat a patient with disseminated herpes zoster infection. CASE REPORT: This is a rare case of varicella-zoster virus encephalitis in a 70-year-old immunocompetent white man who initially presented to the eye clinic for vertical diplopia and floaters. He also had prior thoracic dermatomal rash, followed by new-onset headaches and cerebellar ataxia. Examination revealed a partial oculomotor nerve palsy in the right eye with bilateral optic disc edema and areas of retinitis consistent with acute retinal necrosis in both eyes. Polymerase chain reaction analysis of his aqueous humor and cerebrospinal fluid confirmed an active zoster infection. He received combination systemic and intravitreal antiviral medication until his retinitis resolved but required adjustments for recalcitrant disease and drug-induced nephrotoxicity. While on maintenance dosing of oral valacyclovir, he experienced reactivation in the form of bilateral vasculitis, which was successfully managed once restarting therapeutic oral dosing. CONCLUSIONS: This case describes a successful clinical course of acute retinal necrosis with strategies for its treatment in the setting of varicella-zoster encephalitis. Antiviral medication should be given as soon as possible, as prompt treatment has been shown to improve patient outcomes, although prognosis is typically poor in these cases. Multiple specialists are often needed to address different clinical challenges, including central nervous system involvement, viral strain resistance, disease reactivation, and drug toxicity.

Varicella zoster virus cerebral aneurysmal vasculopathy presenting in a newly-diagnosed HIV-positive patient.

We report the case of a newly-diagnosed HIV-positive patient with varicella zoster virus aneurysmal vasculopathy confirmed on intrathecal antibody testing, despite a negative Cerebrospinal fluid (CSF) Varicella Zoster Virus (VZV) Polymerase Chain Reaction (PCR). This highlights the importance of prompt treatment with antiviral and steroid therapy in the presence of clinical or radiological suspicion whilst awaiting further confirmatory testing.