Varicella Zoster Virus Aseptic Meningitis: A Misleading Clinical and Laboratory Presentation: Three Cases Reports
Diana Khedr*, Shaimaa H Soliman and Sulaiman Alkhashan
Department of Neurology, Farwanya hospital, Kuwait
Submission: September 12, 2022; Published: September 27, 2022
*Corresponding author: Diana Khedr, Department of Neurology, Farwanya hospital, Kuwait
How to cite this article: Diana K, Shaimaa H S, Sulaiman A. Varicella Zoster Virus Aseptic Meningitis: A Misleading Clinical and Laboratory Presentation: 002 Three Cases Reports. Open Access J Neurol Neurosurg 2022; 17(3): 555965.DOI: 10.19080/OAJNN.2022.17.555965.
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Abstract
Background: A septic meningitis caused by varicella zoster virus (VZV) reactivation was less described in the literature, Varicella-zoster virus is a neurotropic virus that remain dormant in dorsal root ganglion after primary infection, usually manifested as chickenpox which gets reactivated in immunocompromized state presented usually with vesicular rash complicated with multi-organ affection such as central nervous system. Rarely this characteristic skin rash can be absent initially requiring high clinical suspicion for diagnosis. When no skin lesions are present, a high clinical suspicion is required to reach the diagnosis. In this report we described three clinical of varicella- zoster virus reactivation presented in atypical way in terms of clinical presentation and cerebrospinal fluid analysis.
Case presentation: Three patients otherwise healthy were admitted to the hospital with a chief complaint of headache, nausea, vomiting and symptoms suggestive of increased intracranial pressure (IIH). Resembling IIH but due to acute presentation and positive meningeal signs this was unlikely. The clinical examination did not show any neurological deficits or rash except lately in the first case. Lumbar puncture unexpectedly showed high opening pressure with markedly elevated CSF total and high total cell count with lymphocytic predominance which was misleading raising suspicion of tuberculous meningitis. Further CSF analysis, including polymerase chain reaction (PCR) and detection of intrathecal synthesis of antibodies, showed a VZV infection. Clinical follow-up examinations later on proved successful antiviral treatment.
Conclusion: In conclusion, absence of typical vesicular rash of varicella zoster initially as well as high opening CSF pressure with high CSF protein even young and previously healthy patients should not rule out consideration of varicella zoster meningitis.
Keywords: : Varicella zoster virus; Cerebrospinal fluid; IIH; Aseptic meningitis; Three cases report
Introduction
Infections with neurotropic herpes viruses (herpes simplex type 1 and 2, varicella zoster virus (VZV)) are frequent in humans. These viruses persist within cranial nerves, dorsal roots, and autonomic ganglia causing latent infections with the ability of reactivation [1]. Reactivation of VZV shows mainly a herpes zoster presenting with rash and pain affecting the entire dermatome and less frequently a zoster sine herpete [2-3]. VZV infection of the central nervous system (CNS) such as encephalitis, meningitis, myelitis, or angiitis occurs less frequently but is feared because of the numerous unfavourable outcomes [1,3,4]. Usually CNS infection with VZV comes along with dermal affection but can rarely develop without rash [1,3,5]. Acute infection or VZV reactivation affects predominantly older individuals and/or immunocompromised patients [1-3]. CNS infection with VZV in young healthy adults is rare and is unexpected and only very few cases have been described so far [5-7]. Here, we describe 3 cases of previously healthy young men with VZV meningitis who had only minimal symptoms.
Informed Consent
Written informed consent was obtained for all cases
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Cases Presentation
First Case
S.A 41 -year-old male patient, previously healthy with no significant medical or surgical, presented to our emergency department with acute onset of severe headache, photophobia, phonophobia and once vomiting. On examination, He had also severe neck pain with positive meningeal signs otherwise normal< neurological examination with normal fundus examination. Initial computed tomography on brain and angiography to rule out subarachnoid hemorrhage and dissection were unremarkable. A lumbar puncture showed high opening pressure of 26 cm H2O, high total cell count of 500 cell / mm3 with 97% lymphocytic predominance , high proteins of 1434 mg/dl ,negative TB PCR , negative culture and sensitivity and positive virology PCR for VZV (Table 1). Patient showed marked improvement of headache after lumbar puncture. Brain magnetic resonance imaging (MRI) with IV gadolinium was essentially normal. Human immunodeficiency antibodies (HIV) were negative, VZV aseptic meningitis diagnosis was considered, antiviral therapy with intravenous acyclovir 10 mg/kg/dose every 8 hrs for 14 days was given with marked improvement Interestingly on third day of antiviral therapy VZV eruption rash started to appear on his chest following dermatomal distribution.
tab 1Second Case
A.H 40-year-old male previously healthy, presented to our emergency department with acute onset of severe headache and photophobia associated with low grade fever with no skin rash. He had otherwise normal neurological examination with normal fundus examination with no meningeal signs. Initial computed tomography on brain and angiography to rule out subarachnoid hemorrhage and dissection were unremarkable. A lumbar puncture showed high opening pressure of 22 cm H2O, revealed high total cell count of 152 cell / mm3 with 60% lymphocytic predominance, high proteins of 1792 mg/dl, negative TB PCR, negative culture and sensitivity, and positive virology PCR for VZV (Table 1). Patient showed marked improvement of headache and photophobia after lumbar puncture. Brain magnetic resonance imaging (MRI) with IV gadolinium was essentially normal. Human immunodeficiency antibodies (HIV) were negative, VZV aseptic meningitis diagnosis was considered, antiviral therapy with intravenous acyclovir 10 mg/kg/dose every 8 hrs for 14 days was given with marked improvement back to his baseline status before discharge.
Third case:
A.S, 29 yrs. old male patient previously healthy, relatively obese with BMI of 35. He presented to our emergency department by five days history of low grade fever followed by sub- acute onsetb of severe headache of increased intracranial pressure character associated with nausea, vomiting, photophobia and increased on leaning forward. Few days later he started to have horizontal binocular diplopia. By examination, he had evident bilateral esotropia with positive cover uncover test suggesting bilateral six nerve palsy (false localizing sign). Fundus examination showed grade 2 bilateral papilledema. There were no meningeal signs but he had severe agonizing neck pain, otherwise normal neurological examination. MRI brain showed picture suggestive of idiopathic intracranial hypertension (IIH) with flattening of globe bilateral and empty sella turcica (). MRV was normal with no sinus thrombosis or stenosis. Lumbar puncture showed very high opening pressure above 40 cm H2O suggesting initial diagnosis of IIH which was supported by MRI brain picture but other CSF parameters were atypical which showed high cell count of 75 cells /mm3 with lymphocytic predominance of 90%, very high protein of 1235 mg /l and positive VZV PCR. HIV Abs were negative, other workup to rule out other secondary causes associated with IIH including vasculitic work up (APL, SLE, sarcoidosis) , hormonal profile were done and all were normal Finally, A diagnosis of VZV aseptic meningitis complicated or coexisting with IIH picture was considered, antiviral therapy with intravenous acyclovir 10 mg/ kg/dose every 8 hrs for 14 days was given with acetazolamide 500 mg TDS to control high CSF pressure with marked improvement of his symptoms before discharge.
Discussion
Reactivated VZV can cause wide varieties of neurologic disease [2,3]. The discovery of PCR increases the detection rate in diagnosis of viral meningitis due to varicella-zoster virus (VZV) [8]. Several studies conducted in patients with herpes zoster have demonstrated that subclinical meningeal irritation can occur in 40-50% of cases [9,10], but a careful review of the literature showed that VZV-related neurologic disease can occur without the classic herpes zoster exanthema, even in immunocompetent patients as described lately by (Susan et al. 2022) [11-13]. The present cases demonstrates the same atypical phenomenon with the initial CSF findings with high lymphocytic pleocytosis and elevated total CSF protein initially misleadingly suggested CNS tuberculosis. Interestingly, further CSF examinations detected a VZV infection, but in the third case there were increased intracranial pressure as a predominant clinical feature. The mechanism behind this increase remains poorly understood. However, this can be explained by one of the postulated theories according to Ibrahim et al. [14] where superimposed infection of baseline subclinical pseudotumor cerebri or caused primarily by the VZV meningitis [14-16]. Further explanation suggested the post-infectious allergic response to the causative virus and diffuse brain swelling [16]. The high opening pressure in our patient compared to previous reported cases may favor the first theory – subclinical pseudo-tumor cerebri with super-added infection. However, the dramatic response to antiviral medication suggests that aseptic meningitis was the direct cause of her symp- toms [10-12]. All patients received acyclovir intravenously for 1-2 weeks resulting in full recovery, suggesting that VZV meningitis tends to be of mild symptoms, good response to treatment and benign prognosis [17-19]. The difficulty in meningitis diagnosis is to distinguish whether it’s a viral or bacterial etiology, because this is crucial for treatment decisions. The treatment threshold is usually set low in clinical work, so that antibiotics, even antituberculosis treatment, are often prescribed in cases of doubt [18- 20].
Conclusion
We report here three cases of atypical VZV aseptic meningitis with clinical presentation that varies from very reassuring to atypical IIH presentation and also with misleading laboratory results which may suggest tuberculous meningitis early before PCR virology results. In conclusion, we highlight the importance of considering VZV as a possible cause for meningitis even in previously healthy young patients and the recommended diagnostic lumbar puncture. Detailed CSF diagnostic procedures including PCR and detection of intrathecal synthesis of antiviral antibodies (especially for VZV and HSV) should be considered even though CSF cell count and total protein seem to indicate a bacterial infection.
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