{
  "abstract": "Introduction Alagille syndrome (ALGS) is a multisystem disorder caused by mutations in the JAG1-Notch signaling pathway, which plays a critical role in vascular smooth muscle cell differentiation and arterial wall integrity. Case reports have documented moyamoya disease, intracranial aneurysms, and spontaneous intracranial hemorrhage in ALGS patients. However, population-level data on cerebrovascular disease prevalence and spectrum are lacking. Patients with ALGS frequently require liver transplantation and cardiac surgery necessitating anticoagulation, making identification of occult cerebrovascular lesions clinically important. We characterized the prevalence and spectrum of cerebrovascular disease among hospitalized patients with Alagille syndrome using a national database.Methods We analyzed the National Inpatient Sample (NIS) from 2016-2023, identifying hospitalizations with Alagille syndrome using ICD-10-CM codes Q44.7 (2016-September 2023) and Q44.71 (October-December 2023). Cerebrovascular outcomes included structural vascular anomalies (unruptured cerebral aneurysm [I67.1], cerebral AVM [Q28.2], moyamoya disease [I67.5]), hemorrhagic events (subarachnoid hemorrhage [I60.x], intracerebral hemorrhage [I61.x]), and ischemic events (cerebral infarction [I63.x], TIA [G45.x]). Survey-weighted logistic regression models adjusted for age, sex, race (2016-2022), primary payer, hospital teaching status, and region were fit year-by-year and pooled via inverse-variance fixed-effects meta-analysis. Benjamini-Hochberg correction was applied for multiple comparisons.Results We identified 2,387 Alagille syndrome hospitalizations (weighted national estimate: 11,935). Median age was 2 years (IQR 0-32); 65.7% were pediatric (≤17 years); 49.1% were female. Cerebrovascular disease was present in 83 hospitalizations (3.5%), with adjusted odds ratio (aOR) of 1.70 (95% CI 1.33-2.17; P<.001) compared to the general NIS population. Structural vascular anomalies were markedly elevated: moyamoya disease was present in 0.7% (aOR 31.36; 95% CI 19.44-50.58; P<.001), unruptured cerebral aneurysm in 0.8% (aOR 12.28; 95% CI 7.79-19.36; P<.001), and the structural composite in 1.4% (aOR 11.28; 95% CI 8.02-15.88; P<.001). Hemorrhagic events (SAH/ICH) were present in 0.5% (aOR 2.92; 95% CI 1.61-5.31; P<.001). In contrast, ischemic stroke was not significantly elevated (0.7%; aOR 1.20; 95% CI 0.70-2.07; P=.498), nor was TIA or ischemic composite. Neurovascular procedures (coiling, clipping, thrombectomy) were performed in fewer than 11 hospitalizations across the 8-year period (exact count suppressed per HCUP requirements). Year-by-year estimates showed consistent direction of effect with low heterogeneity (I 2=7%). Cerebrovascular disease was more prevalent in adults (5.3%) than children (2.5%). In-hospital mortality was 5.4% overall versus 1.0% in the general population. Sensitivity analyses (phenotype-enriched cohort, COVID-period exclusion, 2023 exclusion) showed stable estimates.Conclusions Hospitalized patients with Alagille syndrome have significantly elevated cerebrovascular disease prevalence, predominantly driven by structural arteriopathies (moyamoya 31-fold, aneurysms 12-fold) and hemorrhagic events (3-fold) rather than ischemic stroke. The rarity of neurovascular interventions despite elevated aneurysm prevalence suggests potential underdiagnosis and undertreatment. These findings support consideration of systematic neurovascular screening in ALGS patients, particularly before liver transplantation or cardiac surgery requiring anticoagulation. Neurointerventionalists should be aware of the elevated aneurysm and moyamoya risk when evaluating patients with ALGS or JAG1 mutations.Disclosures M. Essibayi: None. H. Jamil: None.",
  "authors": [
    {
      "affiliations": [
        "Neurosurgery, Albert Einstein College of Medicine, Bronx, NY"
      ],
      "name": "M Essibayi"
    },
    {
      "affiliations": [
        "Neuroradiology, West Virginia University, Morgantown, WV"
      ],
      "name": "H Jamil"
    },
    {
      "affiliations": [
        "Neuroradiology, West Virginia University, Morgantown, WV"
      ],
      "name": "D Lakhani"
    }
  ],
  "title": "E-279 Cerebrovascular disease in alagille syndrome: elevated risk of structural arteriopathies and hemorrhagic events in a national cohort",
  "uid": "da656b53-af50-5c81-a65a-1274607c79c8"
}