Vessel Wall Enhancement and Focal Cerebral Arteriopathy in a Pediatric Patient with Acute Infarct and COVID-19 Infection.

Herein, we report the findings of intracranial arterial wall enhancement, consistent with focal cerebral arteriopathy-inflammatory type, in a child presenting with acute infarct in the setting of coronavirus disease 2019 (COVID-19) infection. To our knowledge, this report provides the first description of vessel wall imaging findings in COVID-19-associated acute stroke.

Transient posterior cerebral arteriopathy: An unusual case enterovirus-related.

Transient Cerebral Arteriopathy (TCA) is one of the main causes of childhood stroke. Here we present an unusual case of Arterial Ischemic Stroke (AIS) caused by a TCA of posterior flow and originally located in the right thalamus. The detection of enterovirus in the cerebrospinal fluid allowed us to suppose a probable post infectious etiology. The course of symptoms was self-limited and the child had a complete clinical recovery after five days. A new ischemic lesion on the antero-inferior paravermian region of the left cerebellum was revealed by a following brain Magnetic Resonance Imaging (MRI) three months later and these findings were reported by further brain MRI control performed after 15 months. Comparing follow up Magnetic Resonance Angiography (MRA) with previous High Resolution Vessel Wall Magnetic Resonance Imaging (HRMI), we found a vessel narrowing at the level of the Posterior Inferior Cerebellar Artery that might explain the arteriopathy process. In conclusion, clinical and radiological course allow us to speculate that this multifocal cerebral arteriopathy might be a transient lesion due to enterovirus infection. To our knowledge, there are only three articles describing TCA enterovirus-related, and brain MRA was performed in only one case; in addition, no one with the involvement of the posterior circulation.

Issues in the Treatment of Neurological Conditions Caused by Reactivation of Varicella Zoster Virus (VZV).

Varicella zoster virus (VZV) is a ubiquitous neurotropic human herpesvirus. Primary infection usually causes varicella (chicken pox), after which virus becomes latent in ganglia along the entire neuraxis. Decades later, virus reactivates to produce herpes zoster (shingles), a painful dermatomally distributed vesicular eruption. Zoster may be further complicated by postherpetic neuralgia, VZV vasculopathy, myelitis, and segmental motor weakness. VZV reactivation has also been associated with giant cell arteritis. This overview discusses treatment of various conditions that often require both corticosteroids and antiviral drugs. Treatment for VZV-associated disease is often based on case reports and small studies rather than large-scale clinical trials. Issues that require resolution include the optimal duration of such combined therapy, more effective treatment for postherpetic neuralgia, whether some treatments should be given orally or intravenously, the widening spectrum of zoster sine herpete, and the role of antiviral therapy in giant cell arteritis.

Differential regulation of matrix metalloproteinases in varicella zoster virus-infected human brain vascular adventitial fibroblasts.

Upon reactivation, varicella zoster virus (VZV) spreads transaxonally, infects cerebral arteries and causes ischemic or hemorrhagic stroke, as well as aneurysms. The mechanism(s) of VZV-induced aneurysm formation is unknown. However, matrix metalloproteinases (MMPs), which digest extracellular structural proteins in the artery wall, play a role in cerebral and aortic artery aneurysm formation and rupture. Here, we examined the effect of VZV infection on expression of MMP-1, -2, -3, and -9 in primary human brain vascular adventitial fibroblasts (BRAFS). At 6 days post-infection, VZV- and mock-infected BRAFs were analyzed for mRNA levels of MMP-1, -2, -3 and -9 by RT-PCR and for corresponding total intra- and extracellular protein levels by multiplex ELISA. The activity of MMP-1 was also measured in a substrate cleavage assay. Compared to mock-infected BRAFs, MMP-1, MMP-3 and MMP-9 transcripts, cell lysate protein and conditioned supernatant protein were all increased in VZV-infected BRAFs, whereas MMP-2 transcripts, cell lysate protein and conditioned supernatant protein were decreased. MMP-1 from the conditioned supernatant of VZV-infected BRAFs showed increased cleavage activity on an MMP-1-specific substrate compared to mock-infected BRAFs. Differential regulation of MMPs in VZV-infected BRAFs may contribute to aneurysm formation in VZV vasculopathy.

Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis.

OBJECTIVE: Varicella-zoster virus (VZV) infection may trigger the inflammatory cascade that characterizes giant cell arteritis (GCA). METHODS: Formalin-fixed, paraffin-embedded GCA-positive temporal artery (TA) biopsies (50 sections/TA) including adjacent skeletal muscle and normal TAs obtained postmortem from subjects >50 years of age were examined by immunohistochemistry for presence and distribution of VZV antigen and by ultrastructural examination for virions. Adjacent regions were examined by hematoxylin & eosin staining. VZV antigen-positive slides were analyzed by PCR for VZV DNA. RESULTS: VZV antigen was found in 61/82 (74%) GCA-positive TAs compared with 1/13 (8%) normal TAs (p < 0.0001, relative risk 9.67, 95% confidence interval 1.46, 63.69). Most GCA-positive TAs contained viral antigen in skip areas. VZV antigen was present mostly in adventitia, followed by media and intima. VZV antigen was found in 12/32 (38%) skeletal muscles adjacent to VZV antigen-positive TAs. Despite formalin fixation, VZV DNA was detected in 18/45 (40%) GCA-positive VZV antigen-positive TAs, in 6/10 (60%) VZV antigen-positive skeletal muscles, and in one VZV antigen-positive normal TA. Varicella-zoster virions were found in a GCA-positive TA. In sections adjacent to those containing VZV, GCA pathology was seen in 89% of GCA-positive TAs but in none of 18 adjacent sections from normal TAs. CONCLUSIONS: Most GCA-positive TAs contained VZV in skip areas that correlated with adjacent GCA pathology, supporting the hypothesis that VZV triggers GCA immunopathology. Antiviral treatment may confer additional benefit to patients with GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.

[Current management of post-varicella stroke in children: a literature review]. / Prise en charge diagnostique et thérapeutique actuelle des accidents vasculaires cérébraux post-varicelleux chez l'enfant : revue de la littérature.

Among infectious factors, varicella-zoster virus (VZV) is a leading cause of central nervous system vasculopathy and stroke in childhood. Not only have viral markers been detected in the cerebrospinal fluid of affected patients, but also direct evidence of viral particles in the wall of cerebral arteries has been demonstrated in rare pathological specimens. This certainly reflects a localized infectious process likely associated with variable indirect inflammatory responses. Yet the usefulness in this setting of a lumbar puncture as well as of subsequent targeted antiviral and/or anti-inflammatory therapies is uncertain. Indeed, in the majority of cases, the so-called post-varicella angiopathy has a monophasic evolution with spontaneous resolution or stabilization, explaining diverging diagnostic and treatment approaches. In this paper, we have addressed this problematic area by reviewing 26 published cases from the year 2000 and three unpublished cases. Post-varicella stroke is typically associated with angiopathy most often involving the initial portion of the middle cerebral artery, causing a basal ganglia stroke. It tends to occur in young immunocompetent children. Thrombophilia work-up is in general negative. Lumbar puncture was performed in 17 out of 29 cases. Viral markers were examined in 14 cases, but were positive in only eight cases. Antiviral therapy was administrated in 11 children. In this small retrospective study, the treated children's vasculopathy did not progress more favorably nor was there a better outcome compared with untreated subjects.

A virulent vasculopathy.

Arteriopathy is an uncommon complication of primary varicella zoster virus (VZV) infection in the immunocompetent adult. We report a case of a 39-year-old woman known to be VZV negative prior to the event. She presented to the emergency department having experienced an episode of expressive aphasia and right upper limb paraesthesia lasting 15 min. The symptoms followed a 3-day period of general malaise, arthralgia and a generalised maculopapular itchy rash involving face and limbs. No immunocompromise was detected but an infectious contact was identified in the home. Imaging findings were consistent with a focal cerebritis/vasculopathy and VZV infection was confirmed with cerebrospinal fluid PCR analysis. Resolution of radiological signs occurred following prompt treatment with appropriate antivirals.

[Varicella, acute postinfectious arteriopathy and cerebral arterial thrombosis in childhood: a unique clinical and etiologic framework to be fully acknowledged]. / Varicelle, artériopathie aiguë post-infectieuse et infarctus cérébral artériel de l'enfant: un cadre clinique et étiologique à ne pas méconnaître.

Acute arteriopathies are the etiological factor of 25% of all the cerebral arterial thrombosis cases in childhood; they give way to ischemic strokes which have specific clinical and radiological features; varicella is the etiologic factor in 60% of the cases; favorable outcome is the rule; physiopathology and treatment remain under discussion.

Multifocal varicella-zoster virus vasculopathy without rash.

A 51-year-old woman with CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) developed stepwise progressive focal neurological deficits without zoster rash. Multifocal ischemic infarcts were seen on magnetic resonance imaging, and cerebral angiography revealed focal stenosis of arteries affecting the intracranial circulation. A brain biopsy was nondiagnostic. Virological etiology of the disease was verified by the detection of varicella-zoster virus antibody in cerebrospinal fluid and by reduced serum-cerebrospinal fluid varicella-zoster virus IgG ratios (compared with normally high ratios of total IgG and albumin). Treatment with intravenous acyclovir stabilized but did not significantly improve her neurological deficits.

Early and late onset manifestations of cerebral vasculitis related to varicella zoster.

Varicella-zoster associated cerebral vasculitis (VZCV) as a cause of cerebral infarction has hitherto been considered a rare condition. Ischemic stroke in previously healthy children has occurred during recovery from chickenpox or has been attributed to virus reactivation among immunosuppressed patients. The clinical, radiologic and immunologic findings in four children with VZCV will be reported. Clinical manifestations included sudden onset of hemiparesis, motor aphasia and disturbed consciousness in previously healthy children. Only one child had a history of chickenpox six weeks prior to the onset of stroke, whereas a latency period of up to four years between chickenpox and the onset of stroke was found in the other three children. Diagnosis of VZCV was confirmed repeatedly by demonstrating intrathecal production of varicella-zoster IgG antibodies in three children or a four-fold increase of varicella-zoster serum IgA-antibodies in one child. Intrathecal production of antibodies against other latent viruses and borreliosis could be excluded. PCR for varicella on CSF, performed in two patients, remained negative. No intrathecal production of varicella-zoster antibodies has been found in a control group of twenty clinically healthy children (age range from 2-18 years) with a previous varicella infection. During follow-up two children recovered completely whereas two children still suffer from serious neurological deficits. Immunological investigations, performed in three children, showed circulating immune-complexes with slightly lowered complement concentrations in two patients. In addition a lowered T-helper/T-suppressor cell ratio of unknown origin was found in three children. These immunological findings will be discussed in the light of the pathophysiology of VZCV.

Herpes zoster vasculitis: demonstration by MR angiography.

A patient presented with multiple cerebral infarcts in various vascular territories after having been treated for herpes zoster ophthalmicus. Magnetic resonance angiography demonstrated multiple focal stenoses involving the proximal intracranial vessels which corresponded to endarteritis at autopsy.