Fibromuscular Dysplasia and Childhood Stroke
By Sotirios Keros, MD, PhD, Instructor, Department of Pediatrics, Division of Pediatric Neurology, Weill Cornell Medical College. Dr. Keros reports no financial relationships relevant to this field of study.
Synopsis: Childhood fibromuscular dysplasia is a fairly distinct entity from the typical adult form, and the "string of beads" finding on angiography is relatively uncommon.
Source: Kirton A, et al. Fibromuscular dysplasia and childhood stroke. Brain 2013;136(Pt 6):1846-1856.
Arteriopathies are a major cause of stroke in child-hood and typically are associated with poor outcomes. Fibromuscular dysplasias (FMD) represent a distinct group of arteriopathy, with the classic medial fibroplasia form typified by refractory hypertension, renal artery involvement, and stroke with a "string of beads" appearance on angiography. Diagnosis of childhood FMD, however, is difficult due to many non-classic presentations.
In this retrospective case study, the authors searched for cases from two Canadian stroke registries, as well from a PubMed search. Inclusion criteria were children (newborns to age 18) who had an arterial stroke associated with either pathologic or radiographic evidence of FMD or renal arteriopathy. Eighty-one cases were discovered, with most strokes classified as arterial ischemic strokes or transient ischemic attack (81%), hemorrhagic stroke (16%), or both (2.5%). Of these 81 cases, 27 represented pathologically proven FMD, primarily identified by either autopsy or by biopsies of the renal or temporal arteries. Nineteen of these proven cases had sufficient detail to identify a specific pathological subtype, with 17 classified as intimal fibroplasia and two as medial hyperplasia. The remaining eight cases had pathological changes throughout all three layers of the arterial wall and were unclassifiable. The median age at onset of symptoms was 7 years (range 2 months to 16 years), with one-third presenting during the first year of life. Seventy percent of the cases presented with neurologic complaints, primarily motor deficits (65%) or seizures (33%). While 82% of the pathologically proven cases were found to have a confirmed stroke, 19% had a transient ischemic attack as their only clinical neurologic finding at presentation.
The results of cerebrovascular imaging were available in 19 children in the pathologically proven group, with only six (31%) of those cases reporting a string of beads type appearance. In these six cases, five had an unclassifiable pathology while the remaining child had intimal fibroplasia. Of the 13 cases without a string of beads appearance, nine (64%) were described as showing focal stenosis, segmental stenosis, or occlusion. Seven of these nine had intimal fibroplasia. Moyamoya syndrome was diagnosed in 33% in the pathologically proven group. Renal arteriopathy was present in 15 (56%) cases and all had documented hypertension, with 88% of these cases reporting abnormal renin or aldosterone levels. Twenty-one of the 27 had investigations for systemic arteriopathy, and 16 of these reported abnormalities in noncerebral or renal arteries such as the aortic (50%), celiac/mesenteric (43%), coronary (43%), peripheral (21%), pulmonary (14%), splenic (14%), external carotid (8%), and hepatic/pancreatic (8%) arteries.
Various medical and surgical treatments were reported in these patients, including corticosteroids, antithrombotic or antiplatelet therapies, renal angioplasty, nephrectomy, and cerebral revascularization. Overall, treatment reporting was limited, and did not allow for outcomes comparisons. In all cases with outcome data, 37% were classified by the authors as "good" with the remaining 63% classified as "poor." Nine of 27 patients had a recurrence of ischemic stroke at a median interval of 29 months. There were 12 deaths (44%).
The 27 cases in the pathologically proven group were compared to 31 cases of clinically diagnosed FMD. Among the statistically significant findings, the children in the clinically diagnosed group were less likely to present in the first year of life (9% vs 33%). They were more likely to present with neurologic symptoms (95% vs 70%), have a string of beads appearance on angiography (74% vs 22%), and have unilateral disease (86% vs 19%). The clinically diagnosed group was less likely to have a poor outcome (32% vs 63%), have recurrence (8% vs 36%), or to die (4% vs 44%). There were no cases of hemorrhagic stroke in this group. In a subset analysis of all 15 postpubertal cases, no differences were found in the variables that are associated with the typical adult FMD.
There are obvious limitations inherent in any analysis of retrospective cases taken from multiple registries and literature reviews. Despite this, the authors find many important, novel differences between pathologically proven FMD and the suspected cases. It is clear that the absence of the typical string of beads finding does not rule out FMD in children and that pathologic confirmation is necessary for diagnosis. In addition, a string of beads type finding is present in other relatively common childhood arteriopathies, such as transient cerebral arteriopathy, whose clinical characteristics overlap closely with the suspected FMD group, suggesting that FMD may not be the correct diagnosis for many of those cases. The authors suggest that the best available angiography be performed in all unexplained cases of childhood stroke, including renal and other systemic arteries. Intimal fibroplasia and ischemic stroke with recurrence were common in the childhood FMD, all of which are rare in adult disease. This suggests that prepubertal FMD is a fairly distinct entity. Given the high incidence of ischemic stroke and recurrence, primary and secondary prevention, such as antiplatelet therapy, should be strongly considered.