Page 108 - The Vasculitides Volumes 2

84 Aleksandra Mineyko and Adam Kirton

applied to children [41, 51]. These include: (1) an acquired neurologic deficit that remains
unexplained after thorough evaluation, (2) either classic angiographic or histopathologic
features of angiitis within the CNS, and (3) no evidence of systemic vasculitis or any other
condition to which the angiographic or pathologic features could be attributed [46]. In the
face of less severely symptomatic children when angiography is negative and brain biopsy is
deferred, the clinical diagnoses of “probable” small vessel cPACNS may be considered.

Secondary Vasculitides

Connective Tissue Disorders

Neuropsychiatric manifestations in SLE may occur as a direct consequence of the
disease, such as antibody-mediated neuronal dysfunction, or its treatment. Vascular
mechanisms may also occur including complement activated vascular inflammation, Libman-
Sacks endocarditis, or thrombosis due to hypercoagulable states associated with high titers of
lupus anticoagulant and phospholipid antibodies [52]. The risk of AIS, CSVT, and
intracranial hemorrhage are all increased in SLE. Patients most commonly present with
angiogram-negative small vessel vasculitis or sinus venous thrombosis [52]. Of 185 pediatric
patients with SLE reviewed retrospectively, 64 (34.6%) had neuropsychiatric symptoms: 1
(0.5%) had transient ischemic attack (TIA), 18 (9.7%) had ischemic stroke, 4 (2.1%) had
venous thrombosis, and 2 (1.1%) had intracranial hemorrhage [53]. Another study found
cerebrovascular disease to be present in a total of 24% of their retrospective cohort [52].
Cardioembolic stroke secondary to Libman-Sacks, nonbacterial endocarditis has rarely been
reported in children [54]. Sjogren syndrome is an autoimmune disease rarely encountered in
children [55]. Case reports of adolescents with Sjogren syndrome and stroke have been
reported [56, 57], as did one presenting with Moyamoya syndrome. A study comparing
patients of all ages found cerebrovascular disease was less common in Sjogren syndrome
compared to SLE despite comparable incidence of neuropsychiatric symptoms [58].

Infection

An association of pediatric stroke with infection has long been suspected [59], and the
associated pathophysiology may be explained by direct infection of cerebral arteries or a
“triggering” effect leading to inflammatory cerebral arteriopathy that is para- or post-
infectious. The most direct evidence is described in children with stroke associated with
bacterial meningitis, in which the pathophysiology is presumed to result from inflammation
of perforating vessels in the subarachnoid space that traverse infected meninges [60, 61].
Large artery involvement has also been reported in association with bacterial meningitis [60,
61]. A late-onset, large vessel arteriopathy, beginning during the recovery phases of bacterial
meningitis is associated with poor outcome [62, 63]. The incidence of this infective
arteriopathy may be underestimated, reported in 37% of consecutive adults undergoing
conventional angiography after bacterial meningitis [64]. The diagnosis of meningitis-related
arteriopathy is relatively easy with clear evidence of bacterial meningitis. However, other

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