Varicella Zoster Virus Vasculopathy Research Articles

A Case of Varicella Zoster Virus Acute Retinal Necrosis, Vasculopathy, and Acute Ischemic Stroke in a Patient Newly Diagnosed with Systemic Sarcoidosis (P1-13.008)

A Case of Varicella Zoster Virus Acute Retinal Necrosis, Vasculopathy, and Acute Ischemic Stroke in a Patient Newly Diagnosed with Systemic Sarcoidosis (P1-13.008)

The Spectrum of Neurological Manifestations of Varicella-Zoster Virus Reactivation.

Varicella-Zoster virus (VZV) is a pathogenic human alpha herpes virus that causes varicella (chicken pox) as a primary infection and, following a variable period of latency in different ganglionic neurons, it reactivates to produce herpes zoster (shingles). The focus of this review is on the wide spectrum of the possible neurological manifestations of VZV reactivation. While the most frequent reactivation syndrome is herpes zoster, this may be followed by the serious and painful post-herpetic neuralgia (PHN) and by many other neurological conditions. Prominent among these conditions is a VZV vasculopathy, but the role of VZV in causing giant cell arteritis (GCA) is currently controversial. VZV reactivation can also cause segmental motor weakness, myelitis, cranial nerve syndromes, Guillain-Barre syndrome, meningoencephalitis, and zoster sine herpete, where a neurological syndrome occurs in the absence of the zoster rash. The field is complicated by the relatively few cases of neurological complications described and by the issue of causation when a neurological condition is not manifest at the same time as the zoster rash.

Increased human immunodeficiency virus viral load with cerebral infarction due to varicella zoster virus vasculopathy on treatment with bictegravir/emtricitabine/tenofovir alafenamide suspension: a case report and literature review

BackgroundVaricella-Zoster virus (VZV) vasculopathy occasionally occurs in immunocompromised patients and is difficult to treat. The risk factor and optimal therapy remain unclear. Patients with human immunodeficiency virus (HIV) and dysphagia or difficulty in oral intake receive antiretroviral therapy (ART) suspension. However, there remains little evidence regarding ART suspension.Case presentationWe experienced a case of a 55-year-old man diagnosed with HIV and severe multiple cerebral infarctions due to VZV vasculopathy. We started on bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) and acyclovir (ACV), and prednisone. He was started on BIC/TAF/FTC suspension because of deteriorated swallowing. The HIV viral load was increased; however, no drug-resistance genes were detected. We successfully treated him with doltegravir/abacavir/lamibudine suspension. We performed two literature reviews of the administration of BIC/TAF/3TC suspension and VZV vasculopathy in patients with HIV. Three cases of BIC/TAF/3TC suspension were considered treatment failures. Recent history of VZV infection and a CD4 count under 200 μL may be risk factors for VZV vasculopathy. The effective treatment may be using steroid and ACV; however, treatment duration could differ.ConclusionsBIC/TAF/FTC suspension administration may be unstable, and treating ACV and steroid may be optimal therapy for VZV vasculopathy; however, the evidence level is low.

Bilateral medial medullary infarction due to varicella‐zoster virus vasculopathy: A case report

AbstractBilateral medial medullary infarction (MMI) is a rare form of ischemic stroke, mainly caused by vertebral artery atherosclerosis or small penetrating artery disease. We report a case of bilateral MMI due to varicella‐zoster virus (VZV) vasculopathy. An 81‐year‐old man presented with altered consciousness and right hemiplegia during disseminated herpes zoster. Polymerase chain reaction analysis of his cerebrospinal fluid detected positive VZV‐DNA, and magnetic resonance imaging revealed ischemic infarction localized to the ventral part of the bilateral medial medulla and enhancement of the left vertebral artery. After initiating intravenous acyclovir administration, his consciousness, skin rashes, and general condition improved gradually, whereas pyramidal symptoms deteriorated into quadriplegia. This case demonstrates that VZV vasculopathy may cause bilateral MMI.

Unexplained Stroke and Multifocal Intracranial Stenosis due to Varicella Zoster Virus Vasculopathy

The classical prototype of Varicella Zoster Virus (VZV) associated vasculopathy is contralateral hemiplegia after herpes zoster ophthalmicus. We describe a 30-year-old patient with no vascular risk factors who presented with a lacunar stroke and was found to have focal intracranial stenosis. He presented again one and a half months later with new findings suggestive of progressive multifocal intracranial stenoses. Although vasculitis was suspected initially, varicella zoster virus reactivity raised the possibility of VZV associated vasculopathy. This case serves as a reminder to suspect this type of vasculopathy even in immunocompetent patients with no cutaneous manifestations. Intracranial stenosis affecting M1 of the middle cerebral artery and the distal portion of the internal carotid artery is common in VZV vasculopathy and should hint toward the diagnosis as shown in this case.

Varicella zoster virus Vasculopathy as a Rare Cause of Stroke.

Varicella zoster virus Vasculopathy as a Rare Cause of Stroke.

Vasculitis as a cause of stroke

The review considers the clinical picture, key aspects of the diagnosis and treatment of vasculitis that are the causes of strokes (giant cell arteritis, polyarteritis nodosa, varicella zoster virus vasculopathy, cerebrovascular pathology caused by herpes simplex virus types 1 and 2, primary CNS angiitis, adenosine deaminase-2 deficiency).

A case of varicella zoster virus vasculopathy with repeated cerebral infarction for which a FilmArray Meningitis/Encephalitis panel was useful for diagnosis

A case of varicella zoster virus vasculopathy with repeated cerebral infarction for which a FilmArray Meningitis/Encephalitis panel was useful for diagnosis

Repeated Vertebrobasilar Strokes Caused by Varicella Zoster Virus Vasculopathy.

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Varicella Zoster Virus Vasculopathy; an HIV Adult Presenting with Multiple Strokes

Varicella Zoster Virus Vasculopathy; an HIV Adult Presenting with Multiple Strokes

Targeted RNA Sequencing of VZV-Infected Brain Vascular Adventitial Fibroblasts Indicates That Amyloid May Be Involved in VZV Vasculopathy.

Background and ObjectivesCompared with stroke controls, patients with varicella zoster virus (VZV) vasculopathy have increased amyloid in CSF, along with increased amylin (islet amyloid polypeptide [IAPP]) and anti-VZV antibodies. Thus, we examined the gene expression profiles of VZV-infected primary human brain vascular adventitial fibroblasts (HBVAFs), one of the initial arterial cells infected in VZV vasculopathy, to determine whether they are a potential source of amyloid that can disrupt vasculature and potentiate inflammation.MethodsMock- and VZV-infected quiescent HBVAFs were harvested at 3 days postinfection. Targeted RNA sequencing of the whole-human transcriptome (BioSpyder Technologies, TempO-Seq) was conducted followed by gene set enrichment and pathway analysis. Selected pathways unique to VZV-infected cells were confirmed by enzyme-linked immunoassays, migration assays, and immunofluorescence analysis (IFA) that included antibodies against amylin and amyloid-beta, as well as amyloid staining by Thioflavin-T.ResultsCompared with mock, VZV-infected HBVAFs had significantly enriched gene expression pathways involved in vascular remodeling and vascular diseases; confirmatory studies showed secretion of matrix metalloproteinase-3 and -10, as well increased migration of infected cells and uninfected cells when exposed to conditioned media from VZV-infected cells. In addition, significantly enriched pathways involved in amyloid-associated diseases (diabetes mellitus, amyloidosis, and Alzheimer disease), tauopathy, and progressive neurologic disorder were identified; predicted upstream regulators included amyloid precursor protein, apolipoprotein E, microtubule-associated protein tau, presenilin 1, and IAPP. Confirmatory IFA showed that VZV-infected HBVAFs contained amyloidogenic peptides (amyloid-beta and amylin) and intracellular amyloid.DiscussionGene expression profiles and pathway enrichment analysis of VZV-infected HBVAFs, as well as phenotypic studies, reveal features of pathologic vascular remodeling (e.g., increased cell migration and changes in the extracellular matrix) that can contribute to cerebrovascular disease. Furthermore, the discovery of amyloid-associated transcriptional pathways and intracellular amyloid deposition in HBVAFs raise the possibility that VZV vasculopathy is an amyloid disease. Amyloid deposition may contribute to cell death and loss of vascular wall integrity, as well as potentiate chronic inflammation in VZV vasculopathy, with disease severity and recurrence determined by the host's ability to clear virus infection and amyloid deposition and by the coexistence of other amyloid-associated diseases (i.e., Alzheimer disease and diabetes mellitus).

Herpes-zoster-Update – was gibt es Neues?

AbstractShingles are triggered by the reactivation of an infection with the varicella zoster virus (VZV) and are characterized by specific vesicular skin lesions. Mostly, elderly patients are affected. Depending on the affected dermatome, some serious complications can be observed. The introduction of a vaccine against shingles in Germany offers a great potential for reducing the frequency and severity of this disease. There are both a live vaccine, which is no longer recommended, and an inactivated vaccine, which, however, is still not sufficiently recommended to the authorized patient groups and is also only available to a limited extent due to delivery bottlenecks. HZ neuralgia is a serious complication of the disease that requires rapid and effective therapy and should be handed over to experienced pain therapists rather too early than too late. Unfortunately, in everyday clinical practice only a few people are familiar with VZV vasculopathy, which is associated with a significantly increased risk of cerebral insults.

Multiple vascular events revealing varicella-zoster virus vasculopathy, the importance of the medical history: Case report

Varicella-zoster virus (VZV) usually causes localized zoster in adults. However, in immunocompromised patients, it can cause systemic manifestations. Early diagnosis and therapy are crucial for the prognosis of the patients. To raise awareness of the diagnosis of VZV vasculopathy and the importance of looking for signs of previous infection up to 12 months.

Recurrent stroke in varicella zoster associated vasculopathy

Varicella zoster virus (VZV) is well known for its neurotropism, primary infection and reactivation after variable latency periods. After reactivation from spinal or cranial nerve ganglia, viruses can affect the central nervous system and cranial vasculature via transaxonal migration followed by transmural spread from the adventitial layer to the intima. Stroke can occur following primary infection by VZV (varicella) or after reactivation (zoster). These infectious vasculitides by VZV can lead to unifocal or multifocal ischemic and hemorrhagic stroke either after cranial nerve or spinal dermatomal zoster. Usual difference between immunocompetent versus immunocompromised individuals is involvement of unifocal large vessel vasculopathy in the former while multifocal small vessel in later. This vasculopathy in some cases may be progressive leading to recurrent stroke even after antiviral treatment. Diagnosis becomes challenging and needs a high degree of suspicion in immunocompetent, younger individuals, in absence of rash and when there are comorbidities. We report a case of elderly immunocompetent women, who developed multifocal infarcts followed by ventricular and subarachnoid haemorrhage after thoracic varicella zoster. Diagnosis was confirmed by the presence of anti-VZV IgG antibodies in the cerebrospinal fluid. In view of the diverse clinic-radiological spectrum of VZV vasculopathy, early recognition of this clinical entity is warranted for improved outcome.

Amylin, Aβ42, and Amyloid in Varicella Zoster Virus Vasculopathy Cerebrospinal Fluid and Infected Vascular Cells

Varicella zoster virus (VZV) vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system infection produces amyloid. Aβ peptides, amylin, and amyloid were measured in cerebrospinal fluid (CSF) from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin's function during infection, amylin was knocked down with small interfering RNA and viral complementary DNA (cDNA) was quantitated. Compared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aβ40 was reduced and Aβ42 unchanged. Intracellular amylin, Aβ42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA. VZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin.

Central nervous system infections produced by varicella zoster virus.

Varicella zoster virus (VZV) causes varicella, establishes latency, then reactivates to produce herpes zoster. VZV reactivation can also cause central nervous system (CNS) disease with or without rash. Herein, we review these CNS diseases, pathogenesis, diagnosis, and treatment. The most common CNS manifestation of VZV infection is vasculopathy that presents as headache, cognitive decline, and/or focal neurological deficits. VZV vasculopathy has also been associated with cerebral amyloid angiopathy and moyamoya syndrome. Rarely, VZV will produce a meningitis, encephalitis, cerebellitis, and myelopathy. Pathogenic mechanisms include direct VZV infection of affected tissue, persistent inflammation, and/or virus-induced hypercoagulability. Diagnosis is confirmed by the temporal association of rash to disease onset, intrathecal synthesis of anti-VZV antibodies, and/or the presence of VZV DNA in CSF. Most cases respond to intravenous acyclovir with corticosteroids. VZV produces a wide spectrum of CNS disorders that may be missed as some cases do not have an associated rash or a CSF pleocytosis. Clinicians must be vigilant in including VZV in their differential diagnosis of CNS infections as VZV is a ubiquitous pathogen; importantly, VZV CNS infections are treatable with intravenous acyclovir therapy and corticosteroids.

Does Herpes Zoster Increase the Risk of Stroke and Myocardial Infarction? A Comprehensive Review.

Herpes zoster (HZ) caused by varicella zoster virus (VZV) reactivation is characterized as a vesicular rash of unilateral distribution that can also cause multiple complications; such as post-herpetic neuralgia; ophthalmic zoster; and other neurological issues. VZV can also increase incident hemorrhagic or ischemic complications by causing inflammatory vasculopathy. Thus; emerging epidemiological and clinical data recognizes an association between HZ and subsequent acute strokes or myocardial infarction (MI). This study reviewed published articles to elucidate the association between HZ and cerebrovascular and cardiac events. Individuals exposed to HZ or herpes zoster ophthalmicus had 1.3 to 4-fold increased risks of cerebrovascular events. Higher risks were noted among younger patients (age < 40 years) within one year after an HZ episode. The elevated risk of CV events diminished gradually according to age and length of time after an HZ episode. The putative mechanisms of VZV vasculopathy were also discussed. Several studies showed that the development of herpes zoster and herpes zoster ophthalmicus increased the risks of stroke; transient ischemic attack; and acute cardiac events. The association between VZV infection and cardiovascular events requires further studies to establish the optimal antiviral treatment and zoster vaccination to reduce zoster-associated vascular risk

Central nervous system varicella zoster vasculopathy in an immunocompromised patient.

Central nervous system (CNS) vasculopathy associated with Varicella Zoster Virus (VZV) infection, usually manifesting as stroke due to ischemic lesions by involvement of small arteries, is frequently misdiagnosed. Immunocompromised patients have a particularly higher risk of severe disease and also CNS involvement during or following VZV presentations. We report a case of an 84-year-old man, with myelodysplastic syndrome, who presented with herpes zoster ophthalmicus complicated with left periocular cellulitis and an abnormal neurological exam. Intravenous treatment with acyclovir and amoxicillin/clavulanic acid was began. VZV DNA was detected in the cerebrospinal fluid (CSF) and brain magnetic resonance imaging revealed three acute ischemic lesions in the left frontal and both cerebellar lobes. A VZV CNS multifocal vasculopathy was diagnosed and treatment with intravenous acyclovir continued for 21 days.Immunocompromised patients with VZV infection can have a more severe course of disease with disseminated involvement and multifocal vasculopathy. In these patients the CSF detection of anti-VZV IgG as well as VZV DNA can be helpful in the diagnosis of CNS VZV vasculopathy. The antiviral treatment can improve the outcome and should be adjusted taking in consideration the degree of immunosuppression. This clinical case and review of the literature highlights the challenges in the diagnosis and management of VZV CNS vasculopathy in immunocompromised patients.

Ischemic Stroke due to Virologically-Confirmed Varicella Zoster Virus Vasculopathy: A Case Series

Background: Limited data are available regarding the characteristics and prognosis of patients with stroke due to varicella zoster virus (VZV) vasculopathy. Methods: We studied 4 patients (2 men and 2 women; age, 38-63 years) from a single center who developed acute ischemic stroke due to VZV vasculopathy. The virological diagnosis was confirmed by detecting VZV DNA and/or the IgG antibody to VZV in the cerebrospinal fluid. Results: Three patients were taking immunosuppressive agents, including prednisolone and/or methotrexate, at baseline. Each patient had a characteristic skin rash prior to stroke, with the interval from rash to stroke onset ranging from 13 to 122 days. Two patients experienced antecedent cranial nerve palsies; one had the third, seventh, ninth, and 10th nerve palsies and the other had the fourth nerve palsy before stroke. Cerebral infarctions were located in the anterior circulation lesion (n = 1), in the posterior circulation lesion (n = 2), and in both lesions (n = 1). Intracranial arterial stenosis was only identified in one patient on magnetic resonance angiography. A high plasma d-dimer level was detected in 1 patient, whereas high β-thromboglobulin and platelet factor 4 levels were detected in 2 patients. As a result of combined therapies with acyclovir, steroid, and antithrombotic agents, neurological symptoms markedly improved in 3 patients, whereas 1 patient was left with moderate hemiplegia. Conclusions: Cranial nerve palsies may be prodromal symptoms of VZV-associated stroke. Increased levels of thrombotic markers may support the use of antithrombotic agents, although the benefit of combined treatment should be determined through larger studies.

Rehabilitation Outcomes of a Patient With Acute Pontine Infarction due to Varicella-zoster Virus Vasculopathy

Rehabilitation Outcomes of a Patient With Acute Pontine Infarction due to Varicella-zoster Virus Vasculopathy