Clinical and magnetic resonance analysis of varicella-zoster virus (VZV) transcranial nerve into brain-induced brainstem encephalitis

Background: In this study, we summarize the clinical and magnetic resonance characteristics of patients with varicella-zoster virus transcranial brain-induced brainstem encephalitis. Methods: The patient's baseline data meet the inclusion criteria were collected. All patients were admitted to the hospital for routine blood, urine, and stool, blood glucose, blood pressure, blood lipids, homocysteine, liver function, renal function, electrolytes, eight items before the operation, autoantibodies, 24-hour dynamic EEG. All patients underwent a head MRI scan, and the patients underwent lumbar puncture, perfecting routine cerebrospinal fluid, biochemical and cytological examinations, and high-throughput examination of cerebrospinal fluid pathogens. Result: Seven patients were enrolled in this study. All patients were associated with skin herpes in the area of cranial nerve distribution. Herpes is complicated with V-cranial nerve in 1 case, facial nerve (6 cases), vestibular nerve (5 cases), tongue pharynx, vagus nerve (1 case). The interval of central nervous system injury after 6 cases of skin herpes were 3-20 days. Laboratory and EEG examinations showed that all patients had no abnormalities in autoantibodies and preoperative eight items; low blood routines showed elevated white blood cells in 4 cases, elevated blood glucose in 4 cases, and abnormal liver function in 2 cases. Magnetic resonance imaging showed the disease involved 2 cases of the dorsolateral medulla, 6 cases with bridge arm, 1 case with multiple lesions, and 1 case without abnormal findings. Conclusion: CZV-induced cranial nerve palsy and encephalitis can leave serious sequelae, even life-threatening, early diagnosis and early treatment are essential. For VZV infections confined to the cranial nerve, MRI is necessary even without

3 evidence of brain stem injury, especially DWI sequences and 3D-CISS imaging can show extent of affected early cranial nerve.

Background
Varicella-zoster virus (VZV) is a member of the family Herpesviridae with the ability to establish latency in dorsal root-, autonomic-, cranial ganglia, and the infection can lead to the damaged of the cranial nerve [1][2][3]. Such as, the Ramsay Hunt syndrome (RHS), which characterized by peripheral facial nerve involvement, or encephalitis with the central nervous system (CNS) related signs and symptoms [4]. When the infected person getting older and immune function impaired, the virus may reactivate to produce herpes zoster. After herpes zoster has healed, many elderly patients develop postherpetic neuralgia. [5]. Thomas S et al. reviewed 282 patients with VZV reactivation, and they found that the trigeminal rash is the most common clinical manifestation, followed by a segmental rash, central nervous system infection, facial paralysis, post-herpetic neuralgia, and radiculitis. In addition, 1/4 patients with central nervous system infections and facial paralysis have no rash, and the infection can only be demonstrated by cerebrospinal fluid analysis. Although a small number of patients with a simple rash have mild inflammatory cerebrospinal fluid changes, the incidence of central nervous system infection and facial paralysis is significantly higher [6]. The study which coexistence of cranial nerve-damaged and VZV encephalitis is rare. VZV reaches the CNS by either retrograde axonal transport or through the bloodstream. Scattered 4 inflammatory infiltrates along the intrapontine facial nerve from its nuclear origin within the caudal and lateral pons to its nerve root exit zone at the lateral pons have been described histologically. However, there are more patients with cranial nerve injury after VZV infection, but the brain stem is rare, and it is mostly reported in cases. Due to the lack of systematic clinical and imaging features and unclear pathogenesis of the VZV, the rate of missed diagnosis and misdiagnosis is high [7,8].
Thus, this study trying to analysis the VZV transcranial brain-induced brainstem encephalitis in our department is as follows to understand the clinical features, magnetic resonance characteristics, treatment methods, and prognosis of VZV brainstem encephalitis. Through further research of VZV, we hope to promote cognition of the clinician's about this virus led to brainstem encephalitis and retrograde cranial brain stem encephalitis process and reduce the missed medical treatment process of patients.

. 1 B a s i c i n f o r m a t i o n a b o u t t h e p a t i e n t ' s
Seven patients with regional herpes from cranial nerve distribution from January  had a history of herpes in the area of cranial nerve distribution before onset, and more details show in Table 1.

Laboratory and EEG examination
Blood routine show white blood cells increased in four cases (57.14%), blood glucose increased in four cases (57.14%), liver function abnormalities in two cases (28.57%), all patients had no abnormalities in autoantibodies and preoperative eight items. One case of hyponatremia and hypochloremia. Two cases of abnormal EEG (28.57%), suggesting epilepsy discharge.

Magnetic resonance examination
All patients underwent MRI. Patient 1 showed left medulla, left bridge with patchy long T1 and long T2 signals, Flair showed high signal, and DWI showed high signal

Treatment and prognosis
The patients in this group were treated with standardized acyclovir antiviral therapy for ten days to 4 weeks after admission, supplemented with mannitol and symptomatic supportive care. Hormone (prednisone acetate 60 mg) was treated in three patients, and intravenous immunoglobulin was administered in one patient

Discussion
VZV is highly contagious and can be transmitted through respiratory droplets or direct contact with infected skin lesions [9][10][11]. VZV is neurotropic and which can be lurking in the neurons of the posterior root ganglia of the spinal cord for a long time after infection. When the infected people have lower resistance, tired, or reinfection, the virus can grow and reproduce and move along the nerve fibers to the skin [7]. When VZV causes to a rash, or alongside the nerve into the central nervous system and led to a retrograde infection which can cause complications such as brainstem encephalitis, meningitis, myelitis, and acute cerebrovascular disease. The elderly (greater than 65 years old) or immune dysfunction persons are common in VZV secondary infections [5,12]. Among the patients in this group, three were elderly patients, three patients with diabetes, and one patient had long-term oral hormones, which basically met the above-mentioned pathogenesis. Nerve VZV can be invaded into the skull through the nerve and can be invaded by meninges and brain parenchyma [13,14]. Two patients in this group were treated with disturbance of consciousness, two were positive for meningeal irritation, and six patients with MRI showed central nervous system injury, suggesting that both brain parenchyma and meninges were affected. Most patients often have a typical herpes-like rash several days before the onset of the disease. In this group, seven patients had rashes at different locations before the disease, mainly in the cranial nerve distribution area, and the time from herpes to central nervous system damage At present, there is no fixed pattern for the treatment of such diseases, but early administration of a sufficient amount of antiviral therapy, depending on the degree of damage and severity of the disease, the addition of hormones and intravenous injection of human immunoglobulin is necessary [7,21,22]. VZV invasion is different from vascular disease, because of the protective effect of the myelin sheath, early viral infection can't invade adjacent structures for a while, so the imaging performance is limited, but once the brain stem and brain parenchyma damage occur, the recovery period will be significantly prolonged [23,24].
According to a case report, these patients have an excellent long-term prognosis and are qualified for daily work. Although six patients in this group had residual or mild or severe neurological deficits at discharge, except for the intracranial spread of Patient 3VZV, most of the patients had no spread of VZV infection, and the clinical prognosis was relatively good. Unfortunately, the patients were not longterm prognosis evaluated accordingly.

Conclusion
The cranial nerve palsies and encephalitis caused by VZV can leave severe sequelae and even Threaten life, early diagnosis, early treatment is essential. VZV activation can be a cranial nerve distribution area herpes, such as RHS, perioral herpes, etc.
as the first performance, without any brain stem damage and symptoms and signs of encephalitis. VZV-induced brainstem encephalitis is susceptible to the bridge arm and the dorsolateral medulla, and MRI can be displayed. Therefore, for some VZV infections confined to the cranial nerve, MRI is necessary even without evidence of    Patient 5: The patient was admitted to the hospital due to walking left, and MRI showed that