A case of Vernet syndrome with varicella zoster virus infection

A 40-year-old man was admitted to our department, because of sudden onset of dysphagia, hoarseness, left neck pain and headache. There were no skin lesions. On neurological examination, there were paralysis of the left soft palate and constrictor muscles of the pharynx, weakness of the left sternocleidomastoid and left upper trapezius. In cerebrospinal fluid (CSF) examination, cell count and protein concentration were elevated. Antibody titer to varicella zoster virus (VZV) was elevated in both the serum and CSF. And VZV-DNA was detected by PCR from CSF. Gd enhanced MRI showed the nodular lesion at the left jugular foramen. The diagnosis of Vernet's syndrome (VS) associated with VZV infection was made. The patient's symptoms were immediately improved with 30 mg of prednisone and 3 g of varaciclovir daily for 14 days. Only a few cases of VS due to VZV have been reported previously. Our case is the first case that detected VZV-DNA in CSF by PCR.     

A single tube PCR assay for simultaneous amplification of HSV-1/-2, VZV, CMV, HHV-6A/-6B, and EBV DNAs in cerebrospinal fluid from patients with virus-related neurological diseases

Cerebrospinal fluid (CSF) specimens from 27 patients with encephalitis, meningitis, and other neurological diseases were studied for the presence of herpes simplex virus types 1 and 2 (HSV-1/-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesviruses 6A and 6B (HHV-6A/-6B) and Epstein-Barr virus (EBV) DNA using the polymerase chain reaction (PCR) method. The DNAs were amplified using two sets of consensus primer pairs in a single tube, bringing simultaneous amplification of the herpesviruses. The PCR products were analyzed by agarose gel electrophoresis, and Southern blot hybridization with virus-type specific probes, thus allowing discrimination between the different types of herpesviruses to be made. Each virus-specific probe was highly specific for identifying the PCR product. Thirty CSF specimens from 13 patients with encephalitis and 10 specimens from 10 patients with meningitis, respectively, were examined using this method. Eight patients with encephalitis and six with meningitis were positive for different herpesviruses, including patients with coinfections (HSV-1/-2 and VZV, VZV and CMV). Among four CSF specimens from four patients with other neurological disorders, dual amplification of CMV and EBV was present. Since identification of the types of herpesviruses in this system requires a very small amount of CSF, and is completed with one PCR, it is useful for routine diagnosis of herpesvirus infections in diagnostic laboratories. The viruses responsible for central nervous system infection are easily detected with various coinfection and serial patterns of herpesviruses, by this consensus primer-based PCR method. This may give an insight into the relationship between virus-related neurological diseases (VRNDS) and herpesvirus infections.     

Ungewöhnliche Manifestation eines Zoster sine herpete als unilaterales kaudales Hirnnervensyndrom

Multiple lower cranial nerve palsies are a rare complication following varicella zoster virus (VZV) reactivation, especially if typical herpetic eruptions are lacking. We report a case of a 45-year-old, immunocompetent male with unilateral involvement of the cranial nerves VIII, IX, X, and XI without skin lesions. Cerebrospinal fluid (CSF) studies revealed mononuclear pleocytosis with intrathecal antibody synthesis against VZV, while polymerase chain reaction (PCR) did not detect VZV or HSV (herpes simplex virus). The patient almost completely recovered after aciclovir administration. VZV reactivation without rash (zoster sine herpete) may lead to multiple cranial nerve palsies. PCR is a useful tool to detect VZV-DNA in CSF, but negative results do not exclude a reactivation. In case of multiple cranial nerve palsies of unknown etiology with mononuclear pleocytosis in CSF tumors of the skull base, meningitis tuberculosis, and meningeosis have to be excluded, and antiviral therapy should be discussed.     

Varicella zoster virus meningoencephalitis accompanied by rhabdomyolysis without skin eruption

We report a case of a 38-year-old man with a Varicella zoster virus (VZV) reactivation who manifested meningoencephalitis accompanied by rhabdomyolysis without a skin eruption. During the acute phase, VZV DNA was detected in serum and cerebrospinal fluid (CSF) by the polymerase chain reaction (PCR). After 16 days, all symptoms and signs resolved, and follow-up PCR studies revealed negative conversion of VZV in the serum and CSF. We discuss the possible underlying mechanism of VZV reactivation in our patient. This is the first case report of VZV reactivation meningoencephalitis accompanied by rhabdomyolysis without skin eruption demonstrated by viral DNA in the serum and CSF.     

Dramatic improvement of urinary retention and the left lower limb paresis with methylprednisolone in a case of regional encephalitis following varicella zoster infection]

We report a previously well 14-year-old male who developed left-sided hemiconvulsion, urinary retention and hemiplegia 1 months after varicella-zoster virus (VZV) infection. Brain T2-weighted MRI showed hyperintensity in medial fronto-parietal area including cyngulate gyrus, foot division of the motor cortex, para-central lobule and corpus callosum with right predominance, which corresponded to hyperperfusion area in SPECT study. MR angiography revealed no occlusion or narrowing of vessels. Cerebrospinal fluid (CSF) showed mononuclear pleocytosis. After methylprednisolone pulse tharapy under diagnosis of regional encephalitis, the patient recovered completely. Although polymerase chain reaction(PCR) could not detect VZV-DNA in CSF, antecedent VZV infection might be closely related to pathomechanism of the regional encephalitis. Dramatic response to steroid, rapid recovery on MRI and good prognosis supported that the underlying pathology was mainly vasogenic edema rather than cytotoxic edema.     

Subclinical reactivation of varicella zoster virus in all stages of HIV infection

Analysis of 200 paired serum and cerebrospinal fluid (CSF) samples from 180 HIV-positive individuals, 136 of whom had AIDS, revealed intrathecal synthesis of antibodies specific for varicella zoster virus (VZV) in 28 (16%) individuals, measles virus in 15 (8%), herpes simplex virus-1 (HSV-1) in 1 (0.6%), and HSV-2 in none. Of the 28 subjects with a positive VZV antibody specificity index, only 1 had zoster rash at the time of serum and CSF sampling; of the total 180 HIV-positive subjects, 146 (81%) had no history of zoster. Based on an estimated 33.4 million HIV-positive individuals worldwide, subclinical reactivation of VZV in even less than 16% of HIV-positive people suggests the possibility that millions of people have active VZV infection of the central nervous system. In cases of VZV vasculopathy, myelopathy and even zoster sine herpete, the CSF is often positive for anti-VZV antibody, but negative for VZV DNA. To rule out VZV infection of the nervous system, CSF must be tested for VZV DNA and anti-VZV IgG and IgM antibody.     

聚合酶链反应（PCR）对单纯疱疹病毒性脑炎的临床诊断价值

应用聚合酶链反应（ＰＣＲ）检测技术对１１８例颅内感染性疾病患者及３７例无神神经系统疾病患者脑脊液（ＣＳＦ）中的单纯疱疹病毒ＤＮＡ（ＨＳＶ－ＤＮＡ）进行了检测及分型。结果提示：“散发性脑炎”组的阳性率为３８．４６％（２０／５２），细菌、真菌性脑膜炎、其它病毒性脑炎组以及无神经系统疾病组均为阴性。作者认为：①本检测是目前单纯疹病毒性脑炎（ＨＳＥ）较为简便而准确的早期诊断方法之一；②ＨＳＶ分型检测，对病原诊断更具有全面性；③两型单纯疱疹病毒均可引起ＨＳＥ。     

Detection of virus in CSF from the cases with meningoencephalitis by next-generation sequencing

We screened for viral DNA in cerebrospinal fluid samples using next-generation sequencing (NGS) technology to diagnose CNS viral infections. We collected CSF samples from four cases with clinically suspected viral meningoencephalitis. DNA extracted from the samples was analyzed with NGS, and the results were further validated using PCR. Herpes simplex virus 1 (HSV-1) was detected in the CSF of two patients, HSV-2 and human herpes virus type 3 (HHV-3, VZV) in the CSF of two other patients separately. The number of unique reads of the identified viral genes ranged from 144 to 44205 (93.51 to 99.57 %). The coverage of identified viral genes ranged from 12 to 98 % with a depth value of 1.1 to 35, respectively. The results were further confirmed using PCR in three cases. The clinical presentation and outcomes of these four cases were consistent with the diagnostic results of NGS. NGS of CSF samples can be used as a diagnostic assay for CNS viral infection. Its further application for “pan-viral” or even “pan-microbial” screening of CSF might influence the diagnosis of CNS infectious diseases.     

巢式聚合酶链反应检测脑脊液中单纯疱疹病毒DNA

应用巢式聚合酶链反应(PCR)检测患者脑脊液(CSF)中单纯疱疹病毒1型(HSV-1)DNA。23例经鞘内HSV-1特异性IgG抗体检测阳性的“HSV-1型性脑炎(HSE)”中19例PCR阳性,4例阴性患者病程均超过1个月。22例IgG阴性的“散发性脑炎”中7例PCR阳性,此7例皆于发病1周内检查CSF,其中2例取材于发病当日。1周后复查7例患者,CSF PCR仍为阳性,IgG皆阴性,提示PCR适用于HSE的早期诊断。     

Localization of herpes simplex virus and varicella zoster virus DNA in human ganglia.

Human dorsal root ganglia from 14 randomly autopsied adults and 1 infant (all seropositive for both herpes simplex virus [HSV] and varicella zoster virus [VZV]) were examined for latent HSV-1 and VZV DNA by polymerase chain reaction. Thoracic ganglionic DNA from all subjects and trigeminal ganglionic DNA from 11 adults were analyzed. HSV-1 DNA was detected in trigeminal ganglia from 8 of 11 (73%) adults and in thoracic ganglia from 2 of 14 (14%) adults. VZV DNA was detected in trigeminal ganglia from 10 of 11 (91%) adults and in thoracic ganglia from 12 of 14 (86%) adults. None of the DNA samples were positive with primers specific for HSV-2. These findings indicate the presence of latent HSV-1 and VZV DNA in trigeminal ganglia and latent VZV DNA in thoracic ganglia of most seropositive adults. Furthermore, although HSV-1 latency most commonly develops in trigeminal ganglia, we also show for the first time the presence of HSV-1 latency in thoracic ganglia. Finally, both viruses can become latent in the same trigeminal ganglion.     

Detection of varicella-zoster virus DNA by polymerase chain reaction in cerebrospinal fluid of patients with herpes zoster meningitis

Summary In three of five patients with herpes zoster meningitis, varicella-zoster virus (VZV) DNA was detected by the polymerase chain reaction (PCR) in the initial samples of cerebrospinal fluid. DNA fragments of group A or B, following classification of VZV strains by the size of the variable region IV of VZV genome, were found at the 7th, 10th and 24th illness day in the three positive cases: one of these cases did not have skin lesions. These results suggest that the detection of VZV DNA by PCR is useful for the diagnosis of herpes zoster meningitis, as well as for its molecular epidemiology.     

Recurrent ascending myelitis: An unusual presentation of herpes simplex virus type 1 infection

We report on a healthy female with a unique relapsing transverse myelitis accompanied by herpes simplex virus type 1 (HSV-1) infection. Magnetic resonance imaging showed cord enlargement and increased signal intensity on T1-weighted image with gadolinium enhancement from T-4 to T-10 during the first attack and from C-1 to C-2 during the second episode. She was not diagnosed during the first attack. During the second episode, laboratory studies disclosed IgM and IgG antibodies to HSV at the outset with greater than fourfold increases in antibody levels in the serum and cerebrospinal fluid (CSF). Cells cultured from the CSF were positive for HSV-1 according to the immunofluoresecnce method. The presence of HVS-1 DNA in CSF was documented by polymerase chain reaction (PCR) technique. Acylovir was given with a partial recovery. We anticipate that PCR assay of CSF will assist early diagnosis of herpetic central nervous system disorders.     

Polymerase chain reaction analysis and oligoclonal antibody in the cerebrospinal fluid from 34 patients with varicella-zoster virus infection of the nervous system

Objective

To study cerebrospinal fluid (CSF) and serum samples from 34 consecutive patients suspected of having varicella‐zoster virus (VZV) infection of the central nervous system (CNS).

Population and methods

The patients were divided into three groups. The first group consisted of 27 patients with a rash in one to three dermatomes and clinical suspicion of meningitis and radiculitis; among them, three subgroups were distinguished according to the affected dermatome: ophthalmicus (n = 9), oticus (n = 11) and cervico‐thoraco‐lumbar zoster (n = 7). Four cases of zoster sine herpete (ZSH) were included in the second group: these patients presented with either radiculitis (n = 2) or meningoencephalitis (n = 2), without cutaneous eruption. The third group consisted of three patients with a generalised rash and encephalitis. A polymerase chain reaction (PCR) for VZV DNA and antigen‐driven immunoblots for oligoclonal anti‐VZV antibodies were carried out on all CSF samples.

Results

PCR of the CSF was positive in 44% of the patients from the first group, mainly within the first 7 days after eruption. In addition, intrathecal synthesis of anti‐VZV antibodies was detected in 37% of patients, always after an interval of 7 days (p<0.0001). Among the four patients with ZSH, a positive VZV PCR was detected in three patients and CSF‐specific oligoclonal anti‐VZV antibodies in two. PCR was also positive in the CSF of two of the three patients with generalised rash and encephalitis; local production of anti‐VZV antibodies was seen in a second CSF sample in one patient, and was also present in the third patient.

Conclusion

Amplification of VZV DNA by PCR in the CSF and antigen‐driven immunoblots have important diagnostic value in suspected VZV infection, although their presence depends on the timing of the CSF sampling. VZV is thought to be a causative agent in unexplained cases of meningitis associated with radiculitis or focal CNS symptoms, even in the absence of skin manifestations. In such patients, rapid diagnosis by this combined approach permits early antiviral treatment.Varicella‐zoster virus (VZV), an exclusively human herpesvirus, causes chickenpox (varicella), becomes latent in the cranial nerve and dorsal root ganglia, and may reactivate decades later in 10–20% of the population to produce shingles (zoster).¹ Shingles is characterised by unilateral radicular pain and a vesicular rash that is generally limited to one to three contiguous dermatomes. The annualised incidence of shingles is about 1.5–3 cases per 1000 people, but increases to 11 cases per 1000 in the population >60 years of age.² VZV can also cause neurological complications, very rarely during the primary infection (most often a varicella cerebellitis) and more often during the reactivation phase. The main complication is post‐herpetic neuralgia, a neuropathic pain syndrome that persists after the dermatomal rash has healed. Acute neurological complications may, however, occur, and affect either the peripheral nervous system (cranial neuropathies, motor radiculopathies of the arm or the leg, bladder and bowel dysfunction) or the central nervous system (CNS; meningitis, myelitis and vasculitic encephalitis). The same neurological complications may be observed in zoster sine herpete (ZSH), which is defined by a dermatomal pain without antecedent rash.³Cerebrospinal fluid (CSF) analysis is a key tool in the diagnosis of CNS infection with VZV. The amplification of VZV DNA by polymerase chain reaction (PCR) and the detection of intrathecal synthesis (ITS) of anti‐VZV‐specific antibodies are the most reliable ways of establishing a definite diagnosis of VZV CNS infection.⁴ We present a retrospective study on CSF samples collected from 34 consecutive patients suspected of harbouring CNS VZV infection. Our population included four cases with ZSH and three with disseminated rash with meningoencephalitis. We discuss correlations between the CSF results, the timing of CSF samples and the clinical picture.     

Bilateral middle cerebral artery infarctions following mild varicella infection: a case report

We report a two-year and one-month-old immunocompetent boy who developed aphasia and right hemiparesis eight months after mild varicella with only a few vesicles. Magnetic resonance images and angiography demonstrated mixed acute and old infarctions of the bilateral middle cerebral arteries. VZV-DNA was detected on polymerase chain reaction analysis of cerebral spinal fluid (CSF). He was treated with intravenous acyclovir and edaravone, and his speech and motor functions had almost recovered after two months. Cerebral lesions of the bilateral middle cerebral artery territories and virus DNA detection from CSF are rare in VZV-related vasculopathy and suggest incomplete immunoresponse to varicella in this patient.     

Varicella zoster virus is not a disease‐relevant antigen in multiple sclerosis

Herpesvirions and varicella zoster virus (VZV) DNA were recently reported in all 15 cerebrospinal fluid (CSF) samples from patients with relapsing‐remitting multiple sclerosis (MS) obtained within 1 week of exacerbation. Using identical electron microscopic and polymerase chain reaction techniques, including additional primer sets representing different regions of the VZV genome, we found no herpesvirions or VZV DNA in MS CSF or acute MS plaques. Although enzyme‐linked immunosorbent assay analysis demonstrated a higher titer of VZV antibody in MS CSF than in inflammatory control samples, recombinant antibodies prepared from clonally expanded MS CSF plasma cells did not bind to VZV. VZV is not a disease‐relevant antigen in MS. Ann Neurol 2009;65:474–479     

An Improved PCR Assay of Viral DNA in Cerebrospinal Fluid from Patients with Herpes Simplex Virus Type-1 Encephalitis

Abstract: Several investigators have attempted to establish a simple, sensitive and quantitative method for a PCR assay of viral DNA in the cerebrospinal fluid (CSF). However, the rate of a positive DNA test differs between laboratories using the same CSF samples from patients with herpes simplex virus type-1 (HSV-1) encephalitis because of differences in sensitivity of the detection. In the present study, we compared the sensitivity and quantity of nested PCR amplification from the pretreated CSF (nested PCR) with those of direct PCR that was performed by direct PCR amplification of the small amounts of CSF to the PCR "cocktail." We studied the advantages of the two different methods, "the direct and nested PCR," and established a two-step method as an improved PCR assay. HSV-1 DNA from the CSF samples obtained within 4 weeks after onset was detected in all seven cases.     

Herpesviruses in brains in Alzheimer's and Parkinson's diseases

We evaluated the association of HSV-1, HHV-6, and VZV with Alzheimer's disease (AD) and Parkinson's disease (PD). Brain specimens for viral DNA polymerase chain reaction represented 34 patients with AD, 40 with PD, and 40 controls. One AD patient (2.9%) was positive for HSV-1 DNA, 88.2% for HHV-6 DNA, and 26.5% for VZV DNA; 17.5% of PD patients were HSV-1 DNA-positive and 75% HHV-6-positive, whereas 40% had VZV DNA. Twenty-five percent of the controls were positive for HSV-1 DNA, 87.5% for HHV-6, and 27.5% for VZV. HSV-1, VZV, or HHV-6 DNA in brains was no additional risk factor for AD.     

Search for evidence of herpes simplex virus, type 1, or varicella-zoster virus infection in postmortem brain tissue from schizophrenic patients.

The highly sensitive polymerase chain reaction (PCR) was used to search for herpes simplex virus type 1 (HSV-I) or varicella-zoster virus (VZV) in the DNA extracted from postmortem temporal cortex samples of 8 schizophrenic subjects, 8 nonschizophrenic suicide victims and 8 normal controls. HSV-I or VZV-specific DNA amplification was not detected in any of the samples studied.     

A polymerase chain reaction assay of cerebrospinal fluid in patients with suspected herpes simplex encephalitis.

A polymerase chain reaction (PCR) was used to detect herpes simplex virus (HSV) deoxyribonucleic acid (DNA) in CSF of 109 patients with possible herpes simplex encephalitis. HSV DNA was found in 20/109 patients. In 14 of these patients the diagnosis was confirmed by a rise in CSF antibodies, isolation of HSV from the brain, or both. In 3 patients CSF antibodies did not rise and 3 patients did not have a follow up lumbar puncture or a brain biopsy. In 19/20 patients HSV DNA was present in the first CSF specimen. The virus was identified as HSV I in 15 patients and HSV II in 4; the virus was not typed in the other patient. A possible diagnosis of herpes simplex encephalitis was not confirmed in the 89 PCR-negative patients. HSV DNA was present in CSF of 3 patients who had meningitis with herpetic genital infections but it was not found in 24 patients with other neurological diseases. The results suggest that the detection of HSV DNA in CSF using a PCR assay will be an accurate method of early diagnosis of herpes simplex encephalitis.