Brain blood vessel abnormalities in Alagille usually stable over time

Children with MMA may require more monitoring, researchers say

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Blood vessel abnormalities in the brain, such as unusually narrow or bulging vessels, are common in children with Alagille syndrome and remain generally stable over time, according to a single-center study in the U.S.

The findings, based on data from up to 32 children with Alagille, suggest that routine monitoring of the abnormalities probably isn’t necessary for most patients. The exception would be for those with Moyamoya arteriopathy (MMA), a specific pattern of blood vessel abnormalities where some of the large arteries that carry blood to the brain are constricted.

The only child with MMA in this study showed rapid progression of this abnormality and needed surgery to address it, suggesting Alagille patients with MMA may need more intensive monitoring, the researchers said in “Evolution of cerebrovascular imaging and associated clinical findings in children with Alagille syndrome,” which was published in Neuroradiology.

Alagille syndrome is a genetic disorder that can cause a range of symptoms, including liver and heart problems. Some people with Alagille have abnormalities in the structure of brain blood vessels and there have been isolated reports of patients having serious problems like stroke that are presumably related to them.

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Frequency of brain blood vessel abnormalities in Alagille

Few reports have documented the “frequency and evolution of cerebrovascular [brain blood vessel] abnormalities specifically in children” with Alagille syndrome, however, leading scientists at The Children’s Hospital of Philadelphia to review data from patients who’d had brain imaging tests at their clinic.

“Describing these abnormalities in detail could help the multidisciplinary care team optimize management toward preventing potentially lethal or disabling outcomes,” the researchers wrote.

Of 55 Alagille children seen at their clinic, 32 (16 girls, 16 boys) who ranged in age from 8 months to 12 years at their first evaluation had suitable imaging data. More than half (56%) had cerebrovascular abnormalities, most often blood vessels that were abnormally narrowed, called stenosis, or bulging (aneurysm). Some children had more than one type.

The observed rate of cerebrovascular abnormalities may be overestimated relative to the total Alagille patient population, given that only children who had brain imaging as part of clinical care were included in the study, said researchers, who noted nevertheless that the data show that “in general, cerebral arteries in patients with [Alagille syndrome] are more frequently enlarged, elongated, or [twisted] than in the general population.”

Three patients showed signs of prior microhemorrhages, or small bleeds, in the brain “without associated visible cerebral aneurysms or stenosis.” All three had tetralogy of Fallot, a heart disorder that can occur in Alagille syndrome and can increase the risk of brain bleeding.

“We suggest that in these cases, the microhemorrhages were more likely related to the underlying [heart disease] rather than a complication of [cerebrovascular abnormalities],” the researchers wrote.

Thirteen children had more than one brain assessment, on average nearly five years apart. The data showed that cerebrovascular abnormalities were stable over time in all but one child. That child had MMA and was first seen with rapidly progressive vessel stenosis, which required surgery.

One child had a minor stroke with temporary blockage of blood flow to the brain, along with seizures and microhemorrhages, after four years of follow-up. Cerebrovascular anomalies in this patient were stable over time, but the patient had tetralogy of Fallot and multiple surgeries.

One child had a history of recurrent blood accumulation between the skull and the surface of the brain from an unknown cause. Another child also needed surgical management to prevent a brain aneurysm.

The data suggest “follow-up brain [imaging] scans might not be necessary in asymptomatic children with [Alagille syndrome] within [five] years,” the researchers wrote, noting patients whose imaging suggests MMA may be “exceptions to this recommendation” because the condition is linked to “cerebrovascular morbidity and mortality.”

The scientists emphasized that their results should be interpreted cautiously because their study was a retrospective assessment at a single center. Larger studies that follow patients regularly over a longer time “would contribute to a more accurate assessment of the natural history of ALGS and cerebrovascular event risks and determine new cost-benefit guidelines” for managing and monitoring patients, they said.