A Case Report of Meningoencephalitis due to Varicella-zoster virus (VZV) in an HIV patient

Abstract

Meningoencephalitis due to Varicella-zoster virus (VZV) infection is an uncommon cause of meningoencephalitis in HIV patients. But the reactivation of VZV infection is more common in HIV patients and generally associated with an acute and severe meningoencephalitis. VZV can be diagnosed clinically if classical rash occurs but the diagnosis is challenging when typical rash is absent. CNS infections due to VZV are closely associated with morbidity and mortality in HIV-infected patients1. We reported a case of central nervous system CNS- VZV infection in an HIV-infected patient without typical VZV-related rash. A 64-year-old woman, a known case of positive HIV for 5 years, who was stable on ant- retroviral treatment (ART) presented with fever, headache and confusion. Meningism was detected and vital signs were stable. CT (brain) was normal. CD4 count was 374 and HIV viral load was undetectable. CSF examination revealed protein 345 mg/dl, total WBC 760 per cumm, Neutrophil 10%, Lymphocyte 80%, glucose 167 mg/dl, CSF gene Xpert MTB/RIF assay and cryptococcal Ag were negative. CSF PCR was positive for VZV and negative for other virus and bacteria. She was treated with IV acyclovir 15mg/kg 8 hrly for 14 days. After 3 weeks of hospitalization, she was discharged without neurological sequelae. VZV should be considered among the opportunistic pathogens that can involve CNS with meningoencephalitis in patients with HIV/AIDS disease.

Introduction

Varicella-zoster virus is a member of the herpes virus family that causes chicken pox (varicella) usually in childhood and may reactivate decades later to produce shingles (zoster). Neurological complications of VZV (varicella cerebellitis) are rarely seen during the primary infection and more often seen during the reactivation phase.² The pathogenic mechanisms of VZV reactivation in the CNS include neuronal and glial direct infection and immune mediated mechanism including vasculitis and demyelization.³ The most severe neurological complications can occur in immunocompromised patients and include aseptic meningitis, encephalitis with vasculitis, ventriculitis, severe necrotizing myelitis, post-herpetic neuralgia, and leukoencephalopathy.^4,5

Common causes of CNS diseases in HIV-infected patients are cryptococcal meningitis, tuberculosis meningitis, cerebral toxoplasmosis, cytomegalovirus encephalitis, progressive multifocal leukoencephalopathy and HIV-encephalopathy.^1,6 Therefore one of these CNS diseases may be considered first as initial diagnosis when an HIV-infected patient presents with neurological symptoms. VZV was not thought to be a common cause of CNS infection in HIV- infected patients.⁶ So when the patient is infected with rare pathogen like VZV or has unusual presentation, achieving a timely diagnosis may be difficult.

Case report

A 64-year-old woman, a know case of retroviral infection presented with fever, headache for three days and confusion of 1-day duration. Fever was high but not associated with chills, rigor, respiratory, cardiac, GI, UTI symptoms or skin rash. She also complained of headache which was more severe in the morning but denied fits or limb weakness and blurred vision. A day before admission, her family noticed sensorial changes and she was admitted into hospital. She had no history of head injury. She was diagnosed as retroviral infection 5 years ago and took ART (tenofovir, emtricitabine with efavirenz) but needed to change to another regime (abacavir, lamivudine, dolutegravir) because of increased liver enzymes. Her CD4 count on diagnosis was 234 which increased to 394 later on ART. Anti TB prophylaxis couldn’t give because of drug induced liver injury. She also has diabetes mellitus and hypertension which were fairly well-controlled. She had history of chicken pox 30 years ago.

On examination, GCS was 13/15. Vital signs were stable.

Meningism signs were detected. No skin rash or infection were noted.

Complete Blood Count revealed Hb 11, WBC 6.5, N 2.2, L 1.3, Platelet 279, CRP 5.1, normal liver and renal function tests.

Blood and urine culture were sterile. MP (ICT/film) and dengue serology were negative. CD4 count on admission was 374 and HIV viral load was not detected. CT brain was done with contrast and no abnormality was detected.

CSF examination revealed protein 345 (15-45) mg/dl, total WBC 760 (0-5) per cumm, neutrophil 10%, Lymphocyte 80%, glucose 167mg/dl which was 70% of blood glucose, CSF gene Xpert MTB/RIF assay and cryptococcal Ag were negative.

CSF PCR was positive for VZV and negative for HSV-1, HSV-2, HHV-6, EBV,

CMV, E coli, H influenza, listeria monocytogenes, Neisseria meningitidis, Strep agalactiae, Strep pneumoniae were negative.

CXR (PA) and USG (Abdo) were normal.

IV acyclovir 15mg/kg 8hrly was given for 14 days. CSF study was repeated again after 14 days and it showed significantly reduced cell count 97 per cumm and protein 53 mg/dl.

Serum IGRA was also done and turned out to be negative. Fever and headache improved dramatically during IV acyclovir treatment.

She was discharged three weeks after hospitalization without neurological sequelae.

Discussion

Reactivation of VZV infection in the CNS is more common in patients with AIDS than in the general population. Gray et al.¹⁰ reported VZV reactivation in CNS is more than 4% in AIDS patients. VZV associated meningoencephalitis is more frequent than myelitis.^2,5

Herpes zoster infection can occur in adults with HIV at any CD4 T lymphocyte count but the risk of disease is higher in CD4 counts less than 200 cells/mm3.^8,9,10 Corti et al¹¹ also studied 11 cases of neurological complications due to VZV in HIV patients. And they reported that all of them presented with signs and symptoms of meningoencephalitis and their median CD4 T cell count was 142 cells/µL. Six patients (54.5%) presented pleocytosis; they all had high CSF protein concentrations with a median of 2.1 g/dL. Overall survival was 63% (7 of 11 patients). The four patients who died had low cellular counts in CSF.11 In 2000, De La Blanchardiere and group also did study on 34 HIV patients who were infected with VZV. They reported that median CD4 count was 111cells/µL and encephalitis was most common presentation. They also stated that mortality was 18% and complete recovery was only 53%. They concluded that severe symptoms and a low CD4 cell count appeared to be associated with death or sequelae.¹² In comparison to those study, our case also presented with meningoencephalitis which was most common presentation of VZV reactivation and she has good prognosis likely due to good CD4 count, high CSF cell count and timely treatment.

In conclusion, reactivation of VZV in CNS is a severe and life-threatening complication in HIV/AIDS patients. Therefore, VZV should be considered as a one of the possible causes of meningoencephalitis in HIV-infected patients, either in the presence or absence of mucocutaneous lesions of VZV because timely antiviral treatment can result in a good prognosis.

Reference

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Author Information

Aye Mya Theingi-Win¹, Nyunt-Thein²

1. Consultant physician, Tropical and Infectious Diseases Department, Yangon General Hospital
2. Senior Consultant Physician, Former Head of Department of Medicine, Emeritus Professor of Medicine, University of Medicine (1), Yangon