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.

Herpesvirus encephalitis diagnosed by polymerase chain reaction at the National Institute of Neurology of Mexico.

The frequency of central nervous system infections due to herpesvirus have been studied in various populations; however, studies in Mexican mestizo patients are scant. This paper documents the frequency of herpesvirus encephalitis in Mexican mestizo patients from the National Institute of Neurology and Neurosurgery (NINN) of Mexico. To study the frequency of herpetic viral encephalitis at the NINN in the period from 2004 to 2009. We reviewed clinical records from patients with clinically suspected encephalitis; polymerase chain reaction assays were done for detection of herpesviruses in cerebrospinal fluid (CSF) samples. The total number of patients studied was 502; in 59 (12%), the diagnosis of herpetic encephalitis was confirmed by PCR-based testing of CSF. Of them, 21 (36%) were positive for herpes simplex virus type 1, 15 (25%) for Epstein-Barr virus, 10 (17%) for varicella zoster virus, 8 (14%) for cytomegalovirus, 3 (5%) for human herpesvirus 6, and 2 (3%) for herpes simplex virus 2. Our results show a varied frequency of viral encephalitis in mestizo patients due to herpesviruses in a tertiary neurological center and point out the importance of modern molecular technology to reach the etiological diagnosis in cases of encephalitis.

Determinants of neurological syndromes caused by varicella zoster virus (VZV).

Varicella zoster virus (VZV) is a pathogenic human herpes virus which causes varicella as a primary infection, following which it becomes latent in peripheral autonomic, sensory, and cranial nerve ganglionic neurons from where it may reactivate after decades to cause herpes zoster. VZV reactivation may also cause a wide spectrum of neurological syndromes, in particular, acute encephalitis and vasculopathy. While there is potentially a large number of coding viral mutations that might predispose certain individuals to VZV infections, in practice, a variety of host factors are the main determinants of VZV infection, both disseminated and specifically affecting the nervous system. Host factors include increasing age with diminished cell-mediated immunity to VZV, several primary immunodeficiency syndromes, secondary immunodeficiency syndromes, and drug-induced immunosuppression. In some cases, the molecular immunological basis underlying the increased risk of VZV infections has been defined, in particular, the role of POL III mutations, but in other cases, the mechanisms have yet to be determined. The role of immunization in immunosuppressed individuals as well as its possible efficacy in preventing both generalized and CNS-specific infections will require further investigation to clarify in such patients.

Disseminated herpes zoster with acute encephalitis in an immunocompetent elderly man.

Varicella-zoster virus (VZV) encephalitis typically occurs in immunosuppressed populations such as in patients with HIV/AIDS, transplantation and autoimmune disease. However, it can also occur in healthy hosts. We present the case of an immunocompetent patient who presented with a clinical picture of VZV encephalitis with the sole precipitating factor of advanced age. We want to stress the importance of including VZV in the differential diagnosis for encephalitis in healthy elderly hosts. In patients with a clinical diagnosis of encephalitis, the presence of herpes zoster rash increases the likelihood of VZV encephalitis. However, the absence of a skin rash may not exclude the diagnosis. In general, there is an elevated risk of transient ischaemic attack and stroke associated with the diagnosis of herpes zoster infection. Early treatment is essential to prevent complications, including death.

[An autopsied case of severe varicella zoster virus-associated encephalomyelitis under immunosuppressant therapy].

The patient was a 40-year-old woman who was previously diagnosed with systemic lupus erythematosus and myasthenia gravis and had received prednisolone and tacrolimus for more than 7 years. In February 2017, she noticed pain in her lower back and weakness of the lower limbs, and was referred to our hospital on day 5. She had shingles in the right lower thoracic dermatomes and Brown-Séquard syndrome with right-sided dominant weakness in her lower limbs and left-sided superficial sensory disturbance below the L1 level. Varicella zoster virus (VZV)-associated myelopathy was suspected because of her symptoms and clinical findings. Despite the immediate administration of intravenous acyclovir after hospitalization, she lost consciousness and experienced a seizure related to cerebral hemorrhage in the left temporal lobe on the night of day 5. MRI showed enhanced lesions along the spinal cord and leptomeninges of the brainstem and temporal lobe. VZV-IgG and VZV-DNA were positive in the cerebrospinal fluid. Based on these clinical features and laboratory findings, she was diagnosed as VZV-associated vasculopathy and myelopathy. She subsequently had multiple cerebral infractions and hemorrhage, and developed sudden cardiopulmonary arrest on day 6, culminating in death on day 17. Autopsy showed that inflammatory mononuclear cells had infiltrated the vascular walls of the spinal cord. Immunohistochemistry revealed that some neurons and macrophages in the white matter of the spinal cord were positive for VZV. In addition, atrophic neurons, satellite cells surrounding these neurons, and infiltrating macrophages were immune-positive for VZV at the L2 dorsal root ganglia. These findings were consistent with VZV-associated vasculopathy and myelitis. Under immunosuppressive conditions, VZV can cause shingles and neuronal complications such as vasculopathy and myelitis, which are sometimes fatal despite the immediate administration of intravenous acyclovir. New treatment drugs or drugs to prevent VZV activation are desired.

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.

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.

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.

Detection of varicella-zoster virus from cerebrospinal fluid using advanced fragment analysis in a child with encephalitis: a case report.

BACKGROUND: Varicella zoster virus (VZV) encephalitis is an infectious inflammatory disease of brain that can cause irreversible mental damage without timely treatment. In fact, many viruses can cause encephalitis, and the viral loads in cerebrospinal fluid (CSF) in the early stage of the disease are usually too low to be detected. Here we report a case of VZV encephalitis diagnosed by advanced fragment analysis (AFA), which could potentially to contribute to early diagnosis of VZV central nervous system (CNS) infections with a small volume of CSF samples. CASE PRESENTATION: A 10-year-old boy was admitted to the hospital with obvious neurological symptoms of headache, dizziness and vomiting for one day. Physical examination showed left facial paralysis. Complete blood count (CBC) test only showed an unspecific inflammation, and the culture of cerebrospinal fluid and microscopic staining examination were all negative. AFA was performed to screen the common 18 encephalitis related pathogens in CSF. Obvious VZV DNA fragments were observed by capillary electrophoresis at 160 nt, suggesting the existence of VZV CNS infection in children. The results were consistence with real-time quantitative PCR and concomitant symptoms in the acute stage of the disease. CONCLUSIONS: We report a case of acute VZV encephalitis in a child without obvious skin manifestations, which was rapidly diagnosed by AFA. Overall, we would recommend the use of AFA analysis as the rapid screening system for the identification and differentiation of encephalitis pathogens in children.

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.

RNA Polymerase III as a Gatekeeper to Prevent Severe VZV Infections.

In most individuals, varicella zoster virus (VZV) causes varicella upon primary infection and zoster during reactivation. However, in a subset of individuals, VZV may cause severe disease, including encephalitis. Host genetics is believed to be the main determinant of exacerbated disease manifestations. Recent studies have demonstrated that defects in the DNA sensor RNA polymerase III (POL III) confer selective increased susceptibility to VZV infection, thus providing fundamental new insight into VZV immunity. Here we describe the roles of POL III in housekeeping and immune surveillance during VZV infection. We present the latest knowledge on the role of POL III in VZV infection and discuss outstanding questions related to the role of POL III in VZV immunity, and how this insight can be translated into clinical medicine.

High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid From Cases of Varicella Zoster Virus Encephalitis.

Background: Varicella zoster virus (VZV) may cause encephalitis, both with and without rash. Here we investigate whether viruses recovered from the central nervous system (CNS; encephalitis or meningitis) differ genetically from those recovered from non-CNS samples. Methods: Enrichment-based deep sequencing of 45 VZV genomes from cerebral spinal fluid (CSF), plasma, bronchoalveolar lavage (BAL), and vesicles was carried out with samples collected from 34 patients with and without VZV infection of the CNS. Results: Viral sequences from multiple sites in the same patient were identical at the consensus level. Virus from vesicle fluid and CSF in cases of meningitis showed low-level diversity. By contrast, plasma, BAL, and encephalitis had higher numbers of variant alleles. Two CSF-encephalitis samples had high genetic diversity, with variant frequency patterns typical of mixed infections with different clades. Conclusions: Low viral genetic diversity in vesicle fluid is compatible with previous observations that VZV skin lesions arise from single or low numbers of virions. A similar result was observed in VZV from cases of VZV meningitis, a generally self-limiting infection. CSF from cases of encephalitis had higher diversity with evidence for mixed clade infections in 2 cases. We hypothesize that reactivation from multiple neurons may contribute to the pathogenesis of VZV encephalitis.

Slowly progressing varicella zoster brainstem encephalitis complicating Ramsay Hunt syndrome in an immunocompetent patient: case report and review of the literature.

A 56-year-old immunocompetent male developed brainstem encephalitis complicating Ramsay Hunt syndrome. The disease had a slowly progressing course of months after the triggering infection, much longer than previously reported. Furthermore, magnetic resonance imaging, physical-chemical, and cell count analyses on cerebrospinal fluid were normal, whereas polymerase chain reaction for varicella zoster virus DNA was positive. The simultaneous negativity of both imaging and basic CSF exams is very rare, although possible event which confirms the irreplaceable role of viral screening on CSF. A systematic review of similar reports with highlights on the unusual aspects of our case is also presented.

Absent anti-N-methyl-D-aspartate receptor NR1a antibodies in herpes simplex virus encephalitis and varicella zoster virus infections.

PURPOSE: A 2012 report and subsequent case series described anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in patients during the acute phase and relapse of herpes simplex virus 1 (HSV1) encephalitis (HSV1E). However, the prevalence of this phenomenon is unknown and systematic studies on other viral infections of the nervous system are missing. MATERIALS AND METHODS: We retrospectively analyzed serial cerebrospinal fluid (CSF) and serum samples of consecutive patients treated for neurological HSV1, HSV2 and varicella zoster virus (VZV) infections in our tertiary care university hospital between 2003 and 2013 for the presence of antibodies directed against the NR1a subunit of the NMDAR using indirect immunofluorescence. RESULTS: In total, 88 patients with the following infections were identified through an electronic database search: HSV1 (24 with encephalitis), HSV2 (6 with meningitis, 3 with encephalitis and 1 with myelitis), or VZV (3 with meningitis, 33 with encephalitis, 17 with radiculitis and 1 with myelitis). Two patients with HSV1E and HSV2E, respectively, experienced a clinical relapse. Clinical follow-up was for up to 85 months, and repetitive serum and CSF analyses for up to 43 months. However, at no time did any of the 88 patients exhibit anti-NMDAR NR1a antibodies. CONCLUSIONS: In this study, we did not detect anti-NMDAR NR1a antibodies in serial CSF and serum samples of HSV1E patients or patients with other viral infections (HSV2 and VZV). However, the presence of antibodies directed against other epitopes of the NMDAR and other neuronal cell surface antigens cannot be excluded, necessitating further studies.

Varicella-zoster virus (VZV) DNA in serum of patients with VZV central nervous system infections.

OBJECTIVES: Varicella-zoster virus (VZV) is a common viral agent causing central nervous system (CNS) infections, normally diagnosed by detection of VZV DNA in cerebrospinal fluid (CSF). Our aim was to investigate trends in VZV DNAemia in VZV CNS infections, which could potentially contribute to diagnosis and secondly, correlate the amount of VZV DNA in serum to severity of disease. METHODS: Seventy-two patients with VZV CNS infections diagnosed by detection of VZV DNA in CSF and concomitant neurological symptoms were included. The amount of VZV DNA was measured by real-time PCR in paired serum and CSF samples and compared to a control group of herpes zoster (n = 36). RESULTS: An increased amount of VZV DNA was detected in serum in patients with encephalitis compared to patients with meningitis or Ramsay-Hunt syndrome, respectively (p = 0.003 and p = 0.024). A greater proportion of patients with VZV CNS infections and detectable VZV DNA in serum had ongoing rash compared to those without detectable VZV DNA in serum (p ≤ 0.001). The viral load in serum of patients with neurological symptoms was lower compared to in patients with herpes zoster without neurological symptoms (p ≤ 0.001) and only 32/72 of the patients with VZV CNS disease had VZV DNA detected in serum. CONCLUSION: Increased amount of VZV DNA in serum of patients with VZV CNS infections seems associated with encephalitis and ongoing rash. Additionally, viral DNA analysis by PCR in serum may be a helpful diagnostic tool although viral DNA analysis by PCR in CSF is the method of choice for diagnosis.