VZV vasculopathy and postherpetic neuralgia: progress and perspective on antiviral therapy

Two serious complications of varicella-zoster virus (VZV) reactivation are vasculopathy and postherpetic neuralgia (PHN). Clinical-virologic analyses have proven that VZV vasculopathy is caused by chronic active virus infection in cerebral arteries. Conclusive evidence that PHN is caused by persistent or productive VZV infection is less compelling because human ganglia are not accessible during life for pathologic and virologic examination. However, the notion that PHN may reflect a smoldering VZV ganglionitis is supported by 1) the detection of VZV DNA and proteins in peripheral blood mononuclear cells of many patients with PHN; 2) studies of multiple patients with zoster sine herpete, which indicate a productive VZV ganglionitis; and 3) a favorable response of some patients with zoster sine herpete and PHN to antiviral treatment. Few studies have used antiviral therapy to manage PHN with conflicting results. Larger, double-blind studies, which give IV antiviral drug, are needed.     

The Pathophysiology of Essential Tremor and Parkinson’s Tremor

Varicella zoster virus (VZV) is an exclusively human neurotropic alphaherpesvirus. Primary infection causes varicella (chickenpox), after which the virus becomes latent in ganglionic neurons along the entire neuraxis. With advancing age or immunosuppression, cell-mediated immunity to VZV declines, and the virus reactivates to cause zoster (shingles), dermatomal distribution, pain, and rash. Zoster is often followed by chronic pain (postherpetic neuralgia), cranial nerve palsies, zoster paresis, vasculopathy, meningoencephalitis, and multiple ocular disorders. This review covers clinical, laboratory, and pathological features of neurological complications of VZV reactivation, including diagnostic testing to verify active VZV infection in the nervous system. Additional perspectives are provided by discussions of VZV latency, animal models to study varicella pathogenesis and immunity, and of the value of vaccination of elderly individuals to boost cell-mediated immunity to VZV and prevent VZV reactivation.     

Herpes zoster infection and postherpetic neuralgia

Varicella-zoster virus (VZV), the cause of chicken pox, establishes latent infection in sensory ganglia. Reactivation results in zoster (shingles), sometimes complicated by encephalitis (myelitis). Postherpetic neuralgia (PHN) is the major morbidity of zoster. PHN typically increases in frequency with age. The VZV vaccine, which was developed for children, may be effective in enhancing VZV immune reactivity and decreasing zoster in adults. Early antiviral treatment may be effective in decreasing PHN onset. Several other medications may be useful in treating established PHN. A recent report discussed intrathecal steroid use.     

疱疹后遗神经痛病人的神经损伤与水痘-带状疱疹病毒持续激活和复制的关系

目的　研究带状疱疹后遗神经痛 (PHN)患者的水痘 带状疱疹病毒 (VZV)持续激活、复制对感觉神经系统损伤的影响。方法　用感觉定量分析仪 (TSA 2 0 0 1)对 2 5例PHN患者和 38例带状疱疹患者的疼痛区及对侧镜像区进行感觉定量测量 ,同时用PCR和SouthernBlot方法对其外周血单核细胞 (PBMC)进行VZV检测。结果　带状疱疹急性期和PHN病人疼痛区的各感觉阈值均大于对侧镜像区 ,而愈后无PHN的带状疱疹病人两者间未见显著性差异 ;PHN病人的感觉缺失值大于带状疱疹急性期病人 ;PHN患者的VZV检出率为 32 % ,而在愈后无PHN患者却未检测到。结论　VZV在带状疱疹患者的背根神经节内长久复制和激活会引起神经系统严重的、甚至是不可逆的损伤 ,这对PHN的形成起着重要作用     

Chronic active VZV infection manifesting as zoster sine herpete,zoster paresis and myelopathy

After lumbar-distribution zoster, an HTLV-1-seropositive woman developed chronic radicular sacral-distribution pain (zoster sine herpete), cervical-distribution zoster paresis and thoracic-distribution myelopathy. Detection of anti-varicella zoster virus (VZV) IgM and VZV IgG antibody in cerebrospinal fluid (CSF), with reduced serum/CSF ratios of anti-VZV IgG compared to normal serum/CSF ratios for albumin and total IgG, proved that VZV caused the protracted neurological complications. Diagnosis by antibody testing led to aggressive antiviral treatment and a favorable outcome.     

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.     

Effect of Temporary Spinal Cord Stimulation on Postherpetic Neuralgia in the Thoracic Nerve Area

Objectives. The pain associated with herpes zoster can be classified as acute phase, persistent phase, or chronic phase, but if it is prolonged, it becomes resistant to treatment. It is clinically important to prevent transition to postherpetic neuralgia after the onset of herpes zoster, and the outcome depends on whether continuous and potent pain management can be achieved between the acute and persistent phases. We evaluated the effect of pain management leading to quick termination of pain using temporary spinal cord stimulation (SCS) which does not require implantation of a device. Materials and Methods. We performed continuous epidural blocks (CEB) on 52 patients with severe persistent pain of postherpetic neuralgia in the thoracic nerve area, and also inserted spinal stimulation leads in 14 who showed no improvement in the severe pain with concomitant pharmacotherapy. We expected to see the termination of pain with adequate analgesic effects mainly with SCS, and secondarily with the epidural analgesia as rescue therapy. Results. Severe pain accompanied by sensory dysfunction remained in 14 cases. By introducing SCS to the CEB, the visual analog scale baseline was rapidly reduced. Less epidural analgesia was required and the adverse reactions of lowered blood pressure in three cases and urinary retention in seven cases disappeared soon. The self‐rated satisfaction was higher with SCS than with CEB in all 14 cases, because it is highly controllable and has minimal activities of daily living–lowering effects. Conclusion. Temporary SCS, which does not require implantation of a device, may have a potent analgesic effect on severe pain in patients in the persistent phase after herpes zoster, and prevent transition to postherpetic neuralgia.     

Acute, chronic, and recurrent varicella zoster virus neuropathy without zoster rash

The authors report three patients with acute, chronic, and recurrent neuropathy associated with varicella zoster virus (VZV) infection but without zoster rash. CSF of all three patients contained VZV immunoglobulin G antibody, but not herpes simplex virus. In two patients, serum/CSF ratios of VZV immunoglobulin G were reduced compared to normal ratios for immunoglobulin G and albumin, and one patient also had VZV immunoglobulin M in CSF. All three patients received antiviral therapy and improved. The diagnosis of nervous system infection by VZV may be confirmed by the presence of antibody to VZV in CSF even without detectable VZV DNA.     

Postherpetic neuralgia

Following chicken pox infection, varicella-zoster virus stays as a latent infection in sensory root ganglia. After many years, the reactivation of this latent virus in sensory ganglia causes "herpes zoster". Herpes zoster (shingles) is an unilateral, dermatomal, localised, painful, vesicular, and contagious skin infection. In elderly and immunocompromised patients, shingles can cause complications such as postherpetic neuralgia (PHN) and direct central nervous system invasion. Early intervention with antiviral treatment, analgesic therapy and antidepressant therapy may reduce the risk of these complications. The treatment of PHN is same as for other neuropathic pain syndromes. The clinical importance of PHN is due to the severity and chronicity of pain which is usually not responsive to many treatments, and quality of life may be adversely affected by PHN.     

Acute herpetic and postherpetic neuralgia: clinical review and current management

The pain of acute herpes zoster (HZ) may be severe, but it is usually transitory. A minority of patients, with the elderly at particular risk, go on to develop persistent, severe, often disabling pain called postherpetic neuralgia. Though the clinical features of these conditions are well known, the pathology of PHN is poorly described and the pathogenesis of the pain in both remains conjectural. During the past 60 years, an extraordinary number of pharmacological, anesthetic, and surgical therapies have been applied in an attempt to ameliorate the symptoms of acute herpes zoster, enhance its healing, prevent its transition to postherpetic neuralgia, and treat the pain of those with this complication. Relatively few treatments have been studied in a controlled manner, and fully reliable, safe, and effective therapeutic approaches for preventing and treating postherpetic neuralgia have not yet been found. This review summarizes current information on the epidemiology, clinical features, and pathology of herpes zoster and postherpetic neuralgia, and critically examines the accumulated experience with the various treatments. Guidelines for management are suggested.     

168例带状疱疹及疱疹后遗神经痛临床分析

目的 了解带状疱疹的临床发病特点及相关因素.方法 回顾性分析168 例带状疱疹住院患者的临床资料.结果 发病以老年人较多(61.9%),发病部位以肋间神经区较多见(48.2%),伴发病占32.1%,误诊患者12.5%,后遗神经痛占21.4%.结论 带状疱疹老年患者、有伴发病、治疗延误者易出现后遗神经痛.     

The pathology of shingles: Head and Campbell's 1900 monograph.

Shingles (herpes zoster) and postherpetic neuralgia, a chronic neuropathic pain syndrome that can persist after the shingles lesions heal, were studied by eminent neurologists of the 19th century. Autopsy studies were used to establish sensory neural pathways in the peripheral and central nervous systems. More recently, zoster and postherpetic neuralgia have served as models for the study of the pathogenesis and treatment of neuropathic pain. Postherpetic neuralgia has the cardinal clinical features of all neuropathic pain syndromes, including sensory abnormalities, ongoing pain, and allodynia (touch-induced pain). Unlike most other neuropathic pain syndromes, such as trigeminal neuralgia or nerve root compressions, shingles has a well-defined pathogenesis and onset, as well as visible lesions, and is therefore uniquely suitable for study.     

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.     

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.     

Acyclovir responsive brain stem disease after the Ramsay Hunt syndrome

We report an immunocompetent patient with the Ramsay Hunt syndrome (RHS) followed days later by brainstem disease. Extensive virological studies proved that varicella zoster virus (VZV) was the causative agent. Treatment with intravenous acyclovir resulted in prompt resolution of all neurological deficits except peripheral facial palsy. This case demonstrates that after geniculate zoster, brainstem disease may develop even in an immunocompetent individual and effective antiviral therapy can be curative.     

S100β和NSE对带状疱疹后神经痛的监测与疗效评估

目的探讨血清S100β及NSE水平变化与带状疱疹后神经痛(PHN)的发生及治疗前后疗效的关联性。方法收集60例急性带状疱疹(HZ)住院患者,以及20例健康自愿者,运用酶联免疫分析法检测2组治疗前后血清S100β及NSE水平;统计带状疱疹后神经痛的发生率;检测并发带状疱疹后神经痛患者治疗前后血清S100β及NSE的水平变化。结果 60例HZ患者中带状疱疹后神经痛的发生率为13.3%;并发PHN的HZ患者治疗后血清S100β及NSE的水平(69.88±2.28,41.13±6.39)较未发生PHN的HZ患者血清S100β及NSE的水平(54.86±8.90,32.61±8.11)高,差异有统计学意义(P0.05);PHN患者发病前血清S100β及NSE水平(107.36±15.09,98.46±18.25)较治疗后(66.18±7.09,45.34±5.02)明显升高,差异有统计学意义(P0.05);S100β及NSE水平变化与PHN治疗疗效SF-MPQ评分存在正向关联性(P0.05)。结论血清S100β及NSE水平变化与带状疱疹后神经痛发生率及治疗前后疗效存在正向关联性,血清S100β及NSE水平监测可应用于对PHN发生的监测及PHN治疗效果的评估。     

带状疱疹神经系统并发症14例报告

目的 :报道带状疱疹神经系统并发症。方法 :对 14例病例的临床研究 ,阐述该病的临床特征 ,并结合文献 ,简述其发病机制和治疗。结果 :14例临床症状不同类型的患者包括单独疱疹后神经痛 4例 ,膝状神经节带状疱疹患者 6例 ,带状疱疹性感染性多发性神经炎患者 2例 ,带状疱疹脊随炎患者 1例 ,带状疱疹脑膜炎患者 1例。结论 :带状疱疹可引起多种神经系统并发症 ,治疗的目的是及时阻止或减轻感染向中枢神经系统等其他部位播散的危险性以及预防疱疹后神经痛。     

Neurovirulence of varicella and the live attenuated varicella vaccine virus

Varicella-zoster virus (VZV) is a neurotropic herpesvirus, which can cause a variety of complications during varicella infections. These range from meningoencephalitis to polyneuritis to retinitis. After primary VZV infection, VZV enters the dorsal root ganglia in a latent state. Reactivation from latency leads to zoster. The velocity of VZV is 13 cm per day, as the virus travels from ganglion to skin. The live attenuated varicella vaccine virus is markedly less neurovirulent than the wild-type virus. Nevertheless, a few cases of herpes zoster due to the vaccine virus have been documented. Usually, herpes zoster occurs in the same arm as the vaccination, often 3 or more years after vaccination. Thus, herpes zoster in a vaccinee often represents a reactivation of vaccine virus that was carried to the cervical dorsal root ganglia from a site of local replication in the arm. Finally, the role of autophagy during VZV infection is discussed. Autophagosome formation is a prominent feature in the skin vesicles during both varicella and herpes zoster. Therefore, autophagy is one of the innate immune mechanisms associated with VZV infection in humans.     

早期氦氖激光并红外线干预治疗对带状疱疹患者后遗神经痛的影响

目的 探讨早期氦氖激光并红外线干预治疗对带状疱疹患者后遗神经痛的效果.方法 66例带状疱疹伴严重神经痛患者分为治疗组和对照组,每组33例.治疗组在常规治疗的基础上早期加用氦氖激光并红外线治疗,对照组则待皮疹消退后才进行氦氖激光并红外线治疗,对两组的疗效进行比较. 结果 以视觉模拟评分法(VAS)评价治疗效果,治疗组的疗效优于对照组,两组比较差异有统计学意义(U=193.520,P=0.000).治疗组优良率为90.9%.有效率为100.0%,无后遗神经痛发生;对照组优良率为63.6%,有效率为81.8%,后遗神经痛发生3例,发生率为9.1%.结论 早期配合氦氖激光并红外线治疗带状疱疹,能较快地控制病情及缩短疗程,减少后遗神经痛发生.