The protean manifestations of varicella-zoster virus vasculopathy

Varicella-zoster virus (VZV) vasculopathy in the central nervous system (CNS) affects large and small cerebral vessels. Large-vessel disease is most common in immunocompetent individuals, whereas small-vessel disease usually develops in immunocompromised patients. In some patients, both large and small vessels are involved. Neurological features are protean. Neurological disease often occurs months after zoster and sometimes without any history of zoster rash. Magnetic resonance imaging (MRI) scanning, cerebral angiography, and examination of cerebrospinal fluid (CSF) with virological analysis are needed to confirm the diagnosis. VZV vasculopathy patients do not always have VZV DNA in CSF, but diagnosis can be confirmed by finding anti-VZV antibody in CSF, along with reduced serum/CSF ratios of VZV immunoglobulin G (IgG) compared to albumin or total IgG. When VZV vasculopathy develops months after zoster, antiviral treatment is often effective.     

Neurologic manifestations of varicella zoster virus infections

Varicella zoster virus (VZV) causes acute viral exanthema in childhood, becomes latent, and can reactivate years later to produce neurologic disease. Primary VZV infection is associated with acute cerebellitis and stroke, particularly in childhood. VZV reactivation may result in neuropathy, myelitis, stroke, and encephalitis, the latter two syndromes the result of small and large vessel vasculopathy. Prompt diagnosis and treatment are critical to minimize morbidity in herpes zoster as well as morbidity and death in VZV vasculitis and encephalitis. Detection of anti-VZV antibodies in cerebrospinal fluid is the most sensitive method of diagnosing varicella infection of the nervous system. Despite the advent of the VZV vaccine, varicella remains a significant cause of neurologic morbidity.     

Bihemisphere Ischemia Due to a Unilateral Lesion: A Case Report

Bihemispheric ischemic strokes secondary to unilateral vessel disease are uncommon. We present the case of a 70-year-old man with multiple acute/subacute bilateral infarcts. The patient was found to have stenosis of the left internal carotid artery secondary to herpes zoster ophthalmicus vasculopathy, with involvement of the left proximal middle and anterior cerebral arteries. Angiographic studies also revealed A1 segment aplasia of the right anterior cerebral artery (ACA), thus indicating dependence on the left-sided circulation for perfusion of the bilateral ACA vascular territory. This case illustrates how A1 segment aplasia, an anatomic variant of the circle of Willis detected by angiographic studies, can contribute to bilateral infarction in the ACA vascular territory.     

Oligoclonal immunoglobulins in cerebrospinal fluid during varicella zoster virus (VZV) vasculopathy are directed against VZV

Limited analyses of cerebrospinal fluid from patients with central nervous system infections have shown that the oligoclonal IgG is antibody directed against the agent that causes disease. Using a new method involving binding of IgG to beads coated with lysates prepared from candidate infectious antigens, we showed that the oligoclonal IgG in cerebrospinal fluid of a patient with chronic varicella zoster virus vasculopathy is directed against the causative virus. This approach holds promise in identifying and purifying the relevant oligoclonal IgGs in inflammatory central nervous system diseases of unknown cause.     

A case of delayed cerebral infarction occurring in puerperium preceded by herpes zoster ophthalmicus in late pregnancy]

Delayed central neurological symptoms following herpes zoster ophthalmicus (HZO) such as "herpes zoster ophthalmicus and delayed contralateral hemiparesis" are considered to be due to ipsilateral intracranial vasculopathy. We experienced a rare case with cerebral infarction occurred in puerperium following HZO in late pregnancy. A healthy 30-year-old woman had left HZO at weeks 35 of gestation. She was given acyclovir (ACV) for external use and improved with small pigmentation on the left eye-lid. Seven weeks after the onset of HZO, she suddenly developed aphasia and right hemiparesis. Cerebral angiogram showed narrowing on M 1 segment of the ipsilateral middle cerebral artery. The occlusion was seen on peripheral portion of the angular artery on the same side. In cerebrospinal fluid (CSF), cell count was slightly elevated, but concentration of protein and sugar were normal. Varicella-zoster titer was increased in both serum and CSF. She was treated with intravenous ACV (1500 mg/day) for 10 days. On the next day after the treatment, the cell count was normalized and on 18th day, varicella-zoster titer was decreased in CSF. Higher brain function improved and no relapses occurred. This is a first case of delayed cerebral infarction occurring in puerperium preceded by herpes zoster ophthalmicus in late pregnancy, as far as we searched. We should treat carefully pregnant or lactating patients with HZO, considering delayed cerebral infarction.     

Ischemic cerebral vascular accident and zoster infection

Herpes zoster is uncommonly followed by cerebral infarction. The pathophysiological mechanism remains uncertain. Outcome is favorable after early specific treatment. We report the case of a 70-year-old woman who developed right hemiparesis with aphasia 15 days after thoracic herpes zoster. The herpes zoster induced cerebral vasculitis was hypothesized as no other etiology could be identified after detailed assessment of the cerebral infarction including brain MRI and cerebrospinal fluid study, and as the clinical course responded to antiviral therapy.     

Infectious Vasculopathy of Intracranial Large- and Medium-Sized Vessels in Neurological Intensive Care Unit: A Clinico-Radiological Study

Background  

Infections are a well-known cause of cerebral vasculopathy and vasculitis. We aimed to analyze the frequency of intracranial vasculopathy attributable to infection, the spectrum of causative microorganisms, imaging, and cerebrospinal fluid (CSF) characteristics as well as clinical course and outcome.     

Varicella with delayed hemiplegia

We report 4 children who developed acute hemiplegia 7 weeks to 4 months after varicella infection. In 2 patients, carotid angiography demonstrated segmental narrowing and occlusion of the middle cerebral artery. Their clinical and angiographic features were similar to those associated with contralateral hemiplegia after herpes zoster ophthalmicus, the pathogenesis of which comprises cerebral angiitis due to varicella zoster viral infection. We believe that our patients had the same pathogenesis. In a survey of infectious diseases in our region, the frequency of varicella with delayed hemiparesis was roughly 1:6,500 varicella patients.     

脑梗死患者血液和脑脊液NSE质量浓度测定及其临床意义的相关性研究

目的　观察急性期和恢复期脑梗死患者血液和脑脊液的神经元特异性烯醇化酶 (neuron-specific enolase,NSE)质量浓度变化 ,探讨其与神经功能缺损程度、脑梗死体积、颅内压以及患者年龄等方面的相关性。方法　该实验采用酶联免疫吸附法 (enzyme-linked immunosorbent assay,ELISA) ,检测观察组 (4 6例 )、对照组 (2 5例 )血液及脑脊液 NSE质量浓度 ,并应用 SPSS1 0 .0统计软件包进行统计学分析。结果　急性脑梗死 (acute cere-bralinfarction,ACI)患者血液和脑脊液 NSE质量浓度显著高于恢复期患者和对照组 (P <0 .0 1 ) ;ACI患者脑脊液 NSE质量浓度显著高于血液 (P <0 .0 1 ) ;血液和脑脊液 NSE质量浓度与梗死体积均呈显著正相关 (P <0 .0 1 ) ,与出院时神经功能缺损程度呈显著正相关 (P <0 .0 1 )。结论　脑脊液或血清中的 NSE质量浓度是脑组织破坏后较合适的生化标记物 ,有助于判断脑梗死患者梗死范围、监测病情变化及疗效观察。     

Fatal varicella-zoster virus vasculopathy associated with adalimumab therapy

OBJECTIVE To describe the case of a patient who had been receiving adalimumab for rheumatoid arthritis and died of varicella-zoster virus vasculopathy with multifocal cerebral hemorrhage. DESIGN Case report. SETTING Hanyang University Hospital, Seoul, Republic of Korea. PATIENT A 66-year-old woman with adalimumab therapy for rheumatoid arthritis followed by stuporous mental changes. RESULTS Magnetic resonance imaging scans showed multifocal parenchymal lesions and hemorrhage in the brainstem and supratentorial areas. Polymerase chain reaction analysis of the cerebrospinal fluid was positive for varicella-zoster virus. The patient died of multifocal vasculopathy despite intensive antiviral and antibacterial medication. CONCLUSIONS Varicella-zoster virus multifocal vasculopathy with encephalitis may be associated with adalimumab therapy. Clinicians should be aware of the possibility of fatal varicella-zoster virus vasculopathy with encephalitis in patients undergoing adalimumab therapy for rheumatoid arthritis.     

急性脑梗死患者脑脊液及血浆D-二聚体含量的测定和意义

目的　对急性动脉硬化脑梗死 (简称急性脑梗死 )患者脑脊液及血浆D -二聚体的含量进行了检测并探讨其临床意义。方法　采用酶联免疫吸附试验 (ELISA)双抗体夹心法检测急性脑梗死患者脑脊液及血浆D -二聚体的含量 ,并与对照组比较。结果　急性脑梗死患者脑脊液及血浆D -二聚体水平明显增高 ,与对照组比较有显著性差异 (P <0 .0 1)。结论　急性脑梗死后脑脊液和血浆中的纤溶活性增高     

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.     

Optic neuritis heralding varicella zoster virus retinitis in a patient with acquired immunodeficiency syndrome

We report on a 29-year-old severely compromised acquired immunodeficiency syndrome patient who developed retrobulbar optic neuritis 5 weeks after an episode of cutaneous herpes zoster infection. During the optic neuritis, varicella zoster virus could be demonstrated in the cerebrospinal fluid. The neuritis responded well to treatment with foscarnet, but, 3 weeks into therapy, varicella zoster retinitis developed. Additional treatment with intravenous acyclovir stopped progression of the retinitis and resulted in healing of the retinal lesions. This case suggests that retrobulbar optic neuritis can be regarded as a prodrome of imminent acute retinal necrosis. Early recognition and prompt therapy with combined antivirals may prevent the development of this devastating ocular complication of varicella zoster infection.     

Thrombotic cerebral vasculopathy associated with herpes zoster

We describe the clinical, radiographic, and pathological findings in 3 patients with large-vessel cerebral vasculopathy following herpes zoster. Two of the patients were studied at postmortem examination, and a brain biopsy was performed in the third. Each of the 3 patients suffered thrombotic occlusions of large vessels without notable inflammatory or granulomatous changes following trigeminal or segmental herpes zoster infection. In the 2 autopsied patients, varicella-zoster virus (VZV) antigens were detected by immunoperoxidase staining within the media of the affected cerebral arteries. Little or no inflammation was associated with the foci of the VZV antigens. These studies provide evidence that the vasculopathy following herpes zoster may result from direct VZV infection of the artery and the in situ thrombosis can develop within the infected vessels in the absence of clear inflammatory vasculitis.     

Soluble IL-2 receptors in acute and subacute encephalitis

Elevated levels of soluble interleukin-2 receptors were present in the serum from patients with acute primary and postinfectious encephalitis and subacute sclerosing panencephalitis. In addition, soluble interleukin-2 receptors were detected in the cerebrospinal fluid from patients with acute primary encephalitis. Their presence in the cerebrospinal fluid was not explained by damage to the blood-brain barrier and our data attest to their local origin. This suggests that it may be possible in certain neurological diseases to detect cerebral T-lymphocyte activation through a specific marker in the cerebrospinal fluid.     

急性脑血管病患者血清和脑脊液中胰岛素样生长因子-1的测定及其临床意义

目的　探讨急性脑血管病患者血清及脑脊液中胰岛素样生长因子 - 1(IGF - 1)浓度的变化及其临床意义。方法　观察 40例脑血管病患者和 2 0例正常人血清及脑脊液IGF - 1浓度。病例组 :脑梗死组2 0例 ,脑出血组 2 0例 ,所有患者均在发病后第 3天抽取静脉血 2ml,其中脑梗死组在抽血当天作腰穿抽取脑脊液 2ml。IGF - 1采用酶联免疫分析方法测定。应用SPSS统计软件包进行统计分析 ,组间比较采用t检验。结果　病例组与对照组血清中IGF - 1浓度有明显统计学差异 (P <0 .0 1) ,脑梗死组与脑出血组血清中IGF - 1浓度无统计学差异 (P >0 .0 5 )。脑梗死组与对照组脑脊液中IGF - 1浓度有明显统计学差异 (P <0 .0 1)。结论　脑梗死和脑出血患者急性期血清IGF - 1浓度明显降低 ,脑梗死组患者急性期脑脊液IGF - 1浓度明显增高。     

Cerebrospinal fluid analysis in the diagnosis and treatment of arterial ischemic stroke

With the advent of magnetic resonance imaging as a rapid and accurate way to diagnose arterial ischemic stroke, cerebrospinal fluid assessment is rarely performed, unless infectious or inflammatory processes are obvious. Recent advances in the understanding of the pathophysiology of childhood stroke have implicated a growing list of discrete or occult infectious and inflammatory conditions which may involve intracranial arteries and neighboring structures. Cerebrospinal-fluid assessment may allow the detection of markers identifying processes (including infectious, inflammatory, metabolic, and traumatic) potentially involved in cerebral vasculopathy and stroke. The analysis of cerebrospinal fluid in arterial ischemic strokes, including apparently idiopathic strokes, may yield essential information on pathophysiology, allowing for optimal therapeutic decisions and prognostic considerations.     

Neuroimaging of Acute Cerebellitis

Acute cerebellitis is one of the main causes of acute cerebellar dysfunction in childhood and may be infectious, postinfectious, or postvaccination. The etiology of acute cerebellitis is usually viral. Varicella zoster, Epsten-Barr, rubeola, pertussis, diphtheria, and coxsackie viruses are the most frequently involved agents. Diagnosing of acute cerebellitis can sometimes be difficult because the patient may present only mild cerebellar signs and the examination of cerebrospinal fluid may be normal. The authors present the clinical and neuroimaging findings of 2 patients presenting with acute cerebellitis. Their magnetic resonance imaging showed hyperintense signal of cerebellar gray matter in T2-weighted sequences, which is a strong indication of a diagnosis of acute cerebellitis.     

Case of zoster sine herpete presenting with dysphagia diagnosed by PCR analysis of VZV DNA in auricular skin exudates]

A 66-year-old woman was admitted to our hospital because of hoarseness and dysphagia after right earache and pharyngalgia. She showed right glossopharyngeal nerve and vagus nerve palsies, but no other neurological deficits. There was no skin rash within the regions of her ear, oral cavity, pharynx and larynx. Slight increase of mononuclear cells was noted in the cerebrospinal fluid. MR brain imaging was normal. We diagnosed her as zoster sine herpete (ZSH) and treated her with acyclovir, after which she almost completely recovered. The examination of antibodies and DNA of varicella zoster virus (VZV) in the serum and cerebrospinal fluid revealed a pattern of previous zoster infection without evidences of reactivation. However, VZV DNA was detected in auricular skin exudates with PCR. We conclude that PCR analysis of VZV DNA in auricular skin exudates can be a useful diagnostic tool for the diagnosis of zoster sine herpete presenting with painful glossopharyngeal nerve and vagus nerve palsies.     

Intrathecal humoral immune reaction in zoster infections

Intrathecal humoral immune reaction in 26 patients with a reactivation of varicella-zoster virus was analyzed. 11 suffered from ganglionitis, in 7 cases an additional affection of the lower motor neuron was demonstrable. In 8 patients, meningitis, myelitis or cerebral infarctions by zoster angiitis were diagnosed. Intrathecal immune reaction in ganglionitis was weak whereas an intense IgG synthesis became demonstrable in all meningomyelitis/cerebral infarction cases. As demonstrated by immunoblotting, in early stages of the disease immune reaction in serum and cerebrospinal fluid differed only quantitatively. In the further course, most intrathecally synthesized antibodies were directed against low molecular antigens whereas serum pattern did not change. In some patients, additional antibodies not detectable in serum were demonstrable. Though intensity markedly differed, no qualitative differences between the immune response in ganglionitis and more widespread zoster infections of the CNS were detectable.