Page 109 - The Vasculitides Volumes 2

Childhood Vasculitic Stroke 85

infectious mechanisms may be more occult, the timelines less clear, and their associations
with stroke less definitive.

Although the association of large vessel cerebral arteriopathy in children with
inflammation is unclear, there are many similarities between large/medium cPACNS PVA.
An association was demonstrated between Varicella zoster virus (VZV) infection was
suggested in case-control [65] and cohort studies [66] of childhood AIS. Focal cerebral
arteriopathy associated with recent VZV infection has also been implied by case reports [67-
74]. Cerebrospinal fluid (CSF) pleocytosis [72, 73, 75] and VZV antigens [67, 70, 71, 73]
have occasionally been demonstrated in patients with stroke and recent VZV infection.
Herpes zoster ophthalmicus associated with arteriopathy and stroke has been described in
both adults [76-78] and children [79-81]. Tissue analysis from biopsy [82] and postmortem
studied patients with PVA [83] revealed vasculitis with lymphocytic infiltration and VZV-
positive immunohistochemistry with antigen deposition in the smooth muscle layer of the
vessel wall, suggested both direct infiltration and immune-mediated inflammation.

The clinical presentation, neuroimaging, and natural history of PVA are indistinguishable
from TCA except for the history of VZV infection within the preceding 12 months [42]. The
course is monophasic with subsequent stabilization or improvement of arteriopathy over
months [84]. Consistent with proximal MCA involvement, infarct patterns typically involve
lenticulostriate territories resulting primarily in deep basal ganglia infarcts [44, 45]. Proximal
segments of the ICA and ACA may also be involved as seen in TCA, FCA and cPACNS.
Therefore both direct and indirect parainfectious mechanisms may be responsible for some
vasculitis-associated strokes in children.

Other infectious agents are less commonly associated with arteriopathic stroke in children
(Table 1); and this list is illustrative rather than exhaustive. Fusiform aneurysms, focal
arteriopathy, and stroke occur in children with human immunodeficiency virus type 1(HIV1)
[85-87] and vasculitis has been shown on autopsy in children with the acquired immune
deficiency syndrome (AIDS) [88]. Isolated reports have associated neuroborreliosis, [89-91]
parvovirus B19, [92, 93], influenza A [94], Enterovirus [95], and Mycoplasma pneumoniae
[96-98] with focal cerebral arteriopathy and stroke in the pediatric population. It is important
to note that isolated case reports do not prove causation [25].

Rather than specific infectious pathogens, para- or post-infectious mechanisms in general
have been implicated in childhood cerebral arteriopathy pathogenesis and increased stroke
risk. Population-based studies have demonstrated associations between recent preceding
infections and arterial strokes in children [6]. The association between acute infections and
increased risk of vascular events is also recognized in the adult literature [99-101]. The
Vascular Effects of Infection in Pediatric Stroke (VIPS) study is an international research
endeavor designed to test the hypothesis that infection predisposes children to arteriopathy,
AIS, and stroke recurrence [102].

Diagnostic Work Up

The diagnostic work up of childhood stroke due to arteriopathy is summarized in Table 2.

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