Page 111 - The Vasculitides Volumes 2

Childhood Vasculitic Stroke 87

children [5, 103]. The importance of differentiating FCA from intracranial dissection was
recently highlighted by the description of four patients with classic FCA presentations but
pathologic and wall imaging evidence of intracranial dissection [104]. Additional well
defined, non-inflammatory childhood arteriopathies include Moyamoya disease or syndrome
[105], post-radiation vasculopathy [106], and other congenital arteriopathies [42]. Reversible
cerebral vasoconstriction syndrome (RCVS; Call-Fleming) has rarely been described in
children [107]. Fibromuscular dysplasia (FMD) is different in children from adult FMD, and
associated with arteriopathic stroke, systemic arteriopathy and hypertension [108].

Several conditions may also mimic small vessel vasculitis in children. Given the diverse
nature of both the clinical and imaging findings, broad categories must be considered
including demyelinating diseases such as acute disseminated encephalomyelitis, multiple
sclerosis, toxin exposures, inborn errors of metabolism, hypertensive crisis, neoplasia, notably
CNS lymphoma, and others. A difficult clinical distinction is made between small vessel
vasculitis and an increasing number of autoimmune encephalitides. Patients with autoimmune
encephalitis present with symptoms of headaches, personality changes, and other neurological
findings with non-specific lesions on imaging, as described in small vessel vasculitis,
however, the distinguishing features are normal cerebral angiography and different serum
biomarkers and/or brain biopsy pathology [109]. Skip lesions reported in primary
granulomatous angiitis of the CNS can further confound the diagnostic picture [110],
however full-thickness, lesional biopsies minimize the possibility of false-negative results
[43, 111].

Serologic Studies

Most children with cPACNS do not manifest systemic inflammatory markers as the
disease process is isolated to the CNS. Acute phase reactants such as ESR, CRP, and vWF are
often normal or only mildly elevated. Antinuclear antibody titers are also only variably
elevated [13, 15, 112]. One single-centre, retrospective study of 62 children with cPACNS
[41] found elevations in ESR in 51% of patients, CRP in 74%, IgG in 35%, anticardiolipin
antibodies in 44%, without ANCA. Elevations of inflammatory markers were not predictive
of outcome, progression, or disease type. Another single-centre cohort of patients with
cPACNS [113] found that 65% of 39 patients with both small and large-medium vessel
vasculitis had elevated vWF titers that correlated with disease activity. The findings of
elevated levels of tumor necrosis factor (TNF)-?, interleukin (IL)-2, IL-6, and IL-8 in
childhood AIS [114] suggests their potential usefulness in the laboratory evaluation of
cPACNS. Secondary CNS vasculitis is generally suggested after a detailed history and
physical examination. The presence of elevated non-specific inflammatory markers should
direct the laboratory investigation to serologically-specific disease markers, particularly those
that would dictate treatment such as SLE [52].

Cerebrospinal Fluid Analysis

CSF analysis is essential for excluding crucial considerations in the differential diagnosis
such as infection [115]. Although often normal [13, 15, 48, 116], elevated opening pressure,

Complimentary Contributor Copy