Common Features Between Stroke Following Varicella in Children and Stroke Following Herpes Zoster in Adults

Abstract

The cerebral arteries are innervated by afferent fibers from the trigeminal ganglia. Varicella-zoster virus (VZV) frequently resides in the trigeminal ganglion. Reports of arterial ischemic stroke due to VZV cerebral vasculopathy in adults after herpes zoster have been described for decades. Reports of arterial ischemic stroke due to post-varicella cerebral arteriopathy in children have also been described for decades. One rationale for this review has been post-licensure studies that have shown an apparent protective effect from stroke in both adults who have received live zoster vaccine and children who have received live varicella vaccine. In this review, we define common features between stroke following varicella in children and stroke following herpes zoster in adults. The trigeminal ganglion and to a lesser extent the superior cervical ganglion are central to the stroke pathogenesis pathway because afferent fibers from these two ganglia provide the circuitry by which the virus can travel to the anterior and posterior circulations of the brain. Based on studies in pseudorabies virus (PRV) models, it is likely that VZV is carried to the cerebral arteries on a kinesin motor via gE, gI and the homolog of PRV US9. The gE product is an essential VZV protein.

Inflammatory Type Focal Cerebral Arteriopathy of the Posterior Circulation in Children: A Comparative Cohort Study

“…The reason why arteriopathy occurs in the proximal segments of the circle of Willis remains unclear. It has been hypothesized that when VZV reactivates in ganglia, 38 the viral capsid may migrate by axonal retrograde transport (sensory nerve fibers) to the vessel wall of these vessels and replicate and induce a local inflammatory response after transmural spread. This is supported by a report that showed VZV in the vessel wall of the MCA in a child who died of a stroke.…”

Inflammatory Type Focal Cerebral Arteriopathy of the Posterior Circulation in Children: a comparative cohort study

“…21 The association of VZV infection with FCA-i in the AC was not stronger than in PC. It is hypothesized that upon reactivation of VZV ganglia, 37 the viral capsid might migrate through P a g e 14 of 32 axonal retrograde transport (sensory nerve fibers) to the vessel wall of proximal segments of the circle of Willis, replicate and induce a local inflammatory response after transmural spreading. Experimental studies in monkeys demonstrated that intracerebral arteries receive afferent fibers from trigeminal and superior cervical ganglia (harboring latent varicella infection), not only to the carotid T-junction but to a lesser extent also to the posterior, rostral BA, PCA and SCA 38 A study in rats demonstrated that the first and second spinal ganglion reach intracranial parts of the ipsilateral parts of the ipsilateral vertebral artery as well as the BA (as represented in Figure 2).…”

Evidence of varicella zoster virus (VZV) reactivation in children with arterial ischemic stroke: Results of the VIPS II Study

“…8 Because VZV remains latent in the trigeminal ganglion, and the trigeminal nerve innervates the cerebral arteries affected in FCA, VZV latent in trigeminal nerve is hypothesized to reactivate, travel antegrade along nerve branches to cerebral arteries, and result in a unilateral focal inflammatory arteriopathy. 9,10 However, the VZV landscape has changed in recent decades with most children in North America and Australia now receiving VZV vaccination in early childhood and chicken pox thus occurring infrequently. In addition, an alternate hypothesis exists for the relationship between VZV and stroke: rather than VZV triggering stroke, stroke may trigger VZV reactivation during the period of post-stroke down-regulation of immunity.…”

“…6, 7 FCA after chicken pox is also known as “post-varicella arteriopathy.” 8 Because VZV remains latent in the trigeminal ganglion, and the trigeminal nerve innervates the cerebral arteries affected in FCA, VZV latent in trigeminal nerve is hypothesized to reactivate, travel antegrade along nerve branches to cerebral arteries, and result in a unilateral focal inflammatory arteriopathy. 9, 10…”