Here we report an atypical case of a 31-year-old immunocompetent patient with mild diabetes but no cutaneous lesions developed meningitis, encephalitis, and myelitis as a result of VZV reactivation. In the previous literature, CNS complications due to VZV infection usually manifesting as meningitis or encephalitis[5]. It was initially thought of as a mild disease that VZV is not routinely tested in CNS infections, although acute VZV CNS infections have been suggested to contribute to subsequent neurological impairment globally[6, 7]. Moreover, similar clinical presentations in viral CNS infections always leads to diagnostic and treatment delays, especially in immunocompetent patients without typical manifestations. Therefore, identifying the pathogen causing non-typical CNS infection in the early stage is crucial to achieve whole recovery and prevent complications.
VZV is a pathogenic human herpesvirus and spreads through airborne transmission, which causes varicella as a primary infection[8]. The virus then establishes latency in the spinal dorsal root and cranial sensory ganglia[9]. Cell-mediated immunity to VZV declines in the elderly or with low immunity, which triggers VZV reactivation and causes CNS infection manifesting as meningitis or encephalitis [10]. Viruses are now recognized as a common cause of CNS infections, and enterovirus is responsible for the largest number of meningoencephalitis cases especially during summer[11, 12]. However, VZV meningitis is more clinically common than previously regarded, and a Danish study reported that VZV infection accounted for 15% of all extra viral infections in 1066 cases with viral meningitis [13, 14]. The clinical manifestations of VZV meningitis were often diverse and complex and often varied widely among different patients[1]. Fever, headache, cranial nerve involvement, meningeal irritation, and RHS were the five most common symptoms at admission [1]. Our case primarily manifested fever, headache, and nuchal rigidity, while the brain imaging obtained was abnormal unlike previous reports and classical textbooks’ descriptions[6, 15]. The brain MRI showed mild hyperintense signal on bilateral T2WI and FlAIR sequences in the hippocampus. This abnormal neuroimaging was correlated with type of encephalitis and severity of complications.
Traditionally, the dermatomal rash and/or cutaneous lesions are considered characteristic findings for VZV infection [16]. However, several recent studies have confirmed the low sensitivity of this clinical sign, which is often absent in up to a third of cases with infection [17]. A Danish study of 162 patients with VZV meningitis reported approximately 40% of the patients developed without rash [13]. This condition has been described mainly in patients with low immunity for failing to generate sufficient immune responses [18]. Notably, our case with normal immunocompetence also presented no dermatomal rash throughout the course of the illness. This suggests that occurrence of vesicular rash involves more than just immune-mediated mechanisms. Furthermore, the patient acquired CNS infection during summer and symptoms are similar with common enterovirus cases, which makes diagnosing VZV infection challenging especially when the typical rash is absent. Therefore, further examination is still required to reveal the pathogen.
In most cases of VZV CNS infection, CSF analysis revealed an elevated protein level, leucocytosis with lymphocytic pleocytosis, and an average glucose level[7]. Our case is no exception in this regard, and hyperglycemia was directly associated with poor glycemic control. A high viral load was reflected by the WBC count and protein levels in the CSF, significantly correlated with the duration and severity of neurologic disease [14]. Thus, CSF analysis can help us initially assess the condition and subsequently give empirical antiviral therapy. Meanwhile, we used mNGS to detect a wide array of pathogen in CSF of this patient. Most commonly, mNGS can analysis any type of clinical samples, comprehensively analyze the sequence data of nucleic acids, align the outcome with the microorganism genome database, thereby rapidly identifying the pathogenic microorganisms [19, 20]. The pathogen-detection performance of mNGS for CNS infections showed notably higher sensitivity compared with conventional tests[21]. Therefore, mNGS has the potential to benefit patients with suspected severe CNS infections, and provide more accurate information to guide treatment plan in the early stage of illness.
On the treatment aspect, most patients with mild viral meningitis usually recover completely in 7 to 10 days without treatment. However, severe cases may require antiviral medications or hospitalization. The clinicians often start empirical acyclovir treatment, and the drug is stopped if CSF was negative for viruses. In this case, antiviral therapy with acyclovir was given to the patient on the 2nd day, and the physician adjusted the dose of acyclovir with 0.75 g IV q8h for ten days. During follow-up, the patient improved dramatically and became asymptomatic at the fifth day of hospitalization.