Fibromuscular dysplasia and childhood stroke

Abstract

Arteriopathies are the leading cause of childhood stroke but mechanisms are poorly understood. Fibromuscular dysplasias are non-inflammatory arteriopathies classically described in adults with a cerebral-renal distribution and distinct 'string-of-beads' angiographic appearance. Diagnostic characteristics of paediatric fibromuscular dysplasia are uncharacterized. We aimed to compare pathologically proven versus clinically suspected paediatric fibromuscular dysplasia stroke cases to elucidate diagnostic features. Children in the Canadian Paediatric Ischaemic Stroke Registry, Calgary Paediatric Stroke Program, and published literature were screened for stroke associated with fibromuscular dysplasias or renal arteriopathy. Comparison variables included pathological classification, presentations, stroke types, imaging/angiography, treatments, and outcomes. We report 81 cases (15 new, 66 from the literature). For pathologically proven fibromuscular dysplasia (n = 27), intimal fibroplasia predominated (89%) and none had typical adult medial fibroplasia. Ischaemic strokes predominated (37% haemorrhagic) and were often multifocal (40%). Children often presented early (33% <12 months). Angiography demonstrated focal, stenotic arteriopathy (78%) rather than 'string-of-beads'. Renal arteriopathy (63%) with hypertension (92%) was common, with systemic arteriopathy in 72%, and moyamoya in 35%. Anti-inflammatory (29%) and anti-thrombotic (27%) therapies were inconsistently applied. Outcomes (mean 43 months) were poor in 63%, with stroke recurrence in 36%. Clinically suspected fibromuscular dysplasias (n = 31) were usually older, normotensive with string-of-beads angiography and good outcome. We conclude that fibromuscular dysplasia causes childhood stroke with distinctive clinic-radiological features including hypertension and systemic arteriopathy. Intimal fibroplasia predominates while 'string of beads' angiography is rare. Accurate clinical diagnosis is currently challenging.

Clinical and Imaging Characteristics of Arteriopathy Subtypes in Children with Arterial Ischemic Stroke: Results of the VIPS Study

“…We defined arteriopathy as “the imaging appearance of an in situ arterial abnormality (stenosis, irregularity, occlusion, banding, pseudoaneurysm, dissection flap) not attributable to an exogenous thrombus (e.g., cardioembolism) and not considered a normal developmental variant.” 13 The imaging finding of an isolated arterial occlusion could be classified as “no arteriopathy” (e.g., if the clinical history and/or the parenchymal imaging typified cardioembolism), “possible arteriopathy” (e.g., if the differential diagnosis included both cardioembolism and arterial dissection), or “definite arteriopathy” (e.g., if the imaging was definitive for moyamoya or dissection). The reviewers then classified the arteriopathies into subtypes (“secondary diagnosis”) using pre-established definitions for childhood arteriopathies 10,11 : arterial dissection, including unilateral focal cerebral arteriopathy-dissection type (FCA-d, further defined below); unilateral focal cerebral arteriopathy-inflammatory type (FCA-i), which includes transient cerebral arteriopathy (TCA); primary and secondary moyamoya (bilateral cerebral arteriopathy of childhood), genetic or syndromic arteriopathies such as PHACE syndrome, 16,17 primary and secondary diffuse/multifocal vasculitis, fibromuscular dysplasia, 18 iatrogenic, and others. The primary reviewers independently classified the secondary diagnosis; disagreements were resolved through consensus discussion by the full review team.…”

Focal Cerebral Arteriopathy: The Face With Many Names

“…Additional features such as beading have been described in transient cerebral arteriopathy, 6 reversible cerebral vasoconstriction syndrome, 9 and fibromuscular dysplasia. 10 In the setting of nonspecific angiography findings and the high likelihood of evolution of arterial abnormalities in the first 3 months, as seen in half of our patients, the use of appropriate imaging modalities is critical. Time-of-flight MRA is less specific in localizing and characterizing vessel abnormalities for accurate diagnosis; therefore, contrast studies with MRA, CT angiography, or digital subtraction angiography are particularly important in the setting of acute stroke to narrow the differential diagnosis before vessel remodeling occurs.…”

Arteriopathy Diagnosis in Childhood Arterial Ischemic Stroke

“…This includes TCA, a common arteriopathy among previously healthy children; the proximal middle cerebral artery banding seen in the very acute phase of this disease can be confused with fibromuscular dysplasia (FMD), an arteriopathy with a very different natural history (Figure 3). 28 Adding further to the challenge, the arteriopathies that are more common in adults are rarely seen in children. We made no diagnoses of atherosclerosis in VIPS, even among adolescents, and also no diagnoses of primary CNS vasculitis.…”