**5. Encephalitis and cerebral infarction associated with granulomatous vasculitis**

The symptoms of encephalitis include acute disturbance of consciousness, headache, fever, and convulsions. Neurological findings of encephalitis include meningeal irritation symptoms, such as nuchal rigidity; however, patients with encephalitis sometimes present with motor paralysis and sensory disturbance due to parenchymal brain damage.

Among the pathogens that cause viral encephalitis, VZV is the second most common cause following HSV, accounting for 5% of the total encephalitis cases [14]. According to a recent analysis that used PCR, though, the risk of VZV encephalitis increases in elderly individuals, those with herpes zoster ophthalmicus, and those with disseminated herpes zoster, and this result indicates that the incidence of VZV encephalitis might have increased [15].

The clinical manifestations of VZV encephalitis include meningoencephalitis and vasculopathy [16]. The meningoencephalitis form shows no detectable lesions on MRI. In contrast, the vasculopathy form is characterized by non-specific ischemia, hemorrhagic lesions, and multiple white matter lesions on MRI [16]. Pathological studies suggested that VZV encephalitis develops based on vasculopathy in the large and small vessels. Therefore, MRI typically demonstrates ischemic or hemorrhagic infarction in both gray and white matter and particularly at graywhite matter junctions as characteristic imaging findings of VZV encephalitis [16]. In VZV encephalitis, lesions in the temporal lobe and limbic system, which are often observed in patients with herpes simplex encephalitis, are rare. Moreover, hemorrhagic lesions and necrosis, which are characteristics of herpes simplex encephalitis, are not commonly observed. Because VZV DNA is generally detected in the CSF of adult patients with VZV encephalitis, direct viral invasion to the CNS is believed to be the pathology of VZV encephalitis. In contrast, in varicella encephalitis in children who develop acute cerebellar ataxia associated with varicella infection, VZV is not detected in the CSF. Therefore, a secondary immunological allergic mechanism is considered as the pathology of varicella encephalitis.

Cerebral infarction caused by granulomatous vasculitis is a complication of herpes zoster infection [1, 17]. A typical patient presents with herpes zoster ophthalmicus, followed by postherpetic contralateral hemiplegia, and develops cerebral infarction between the eighth day and sixth month after herpes zoster infection

(average of 7 weeks) [18, 19]. Patients with cerebral infarction often present with stenosis or obstruction in the anterior cerebral artery or middle cerebral artery. Because VZV DNA and antigens are detected in the walls of cerebral arteries, this evidence should provide an anatomic pathway for transaxonal spread of VZV after reactivation from trigeminal ganglia as a mechanism of intracerebral VZV vasculopathy [20–22]. The incidence of stroke increases 6 months after the onset of herpes zoster infection [23], and VZV vaccine and antiviral drug therapy may help reduce the risk of stroke after herpes zoster infection [24]. Cerebral infarction can also develop after varicella infection in children [25]. Although it is rare, it occurs within 6 months after varicella infection, and a similar mechanism as cerebral infarction after varicella zoster infection is considered [25]. In these conditions, VZV, which causes latent infection in the trigeminal ganglion after varicella infection, reactivates and directly invades the vessels in the CNS.
