Natural history and imaging prevalence of cavernous malformations in children and young adults

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>This study was undertaken to define the age-related prevalence of cavernous malformations (CMs) in children and young adults undergoing intracranial imaging. In addition, the authors aim to clarify the natural history of CMs in young people, especially in those with incidentally discovered lesions.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>To identify those patients with CMs, the authors retrospectively reviewed the electronic medical records of 14,936 consecutive patients 25 years of age or younger who had undergone brain MR imaging. In patients with a CM, clinical and imaging data were collected. Patients with untreated cavernomas who had more than 6 months of clinical and MR imaging follow-up were included in a natural history analysis. The natural history analysis included 110 CMs in 56 patients with a 3.5-year mean clinical follow-up interval (199 patient-years and 361 cavernoma-years).</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In 92 patients (0.6%), 164 CMs were identified. The imaging prevalence of cavernomas increased with advancing age (p = 0.002). Multiple CMs occurred in 28 patients (30%), and 8 patients (9%) had a family history of multiple CMs. Fifty patients (54%) presented with symptoms related to the cavernoma, of whom 30 presented with hemorrhage (33%). Of the 164 cavernomas identified, 103 (63%) were considered incidental, asymptomatic lesions. Larger size was associated with acute symptomatic presentation (p = 0.0001). During the follow-up interval, 6 patients with 8 cavernomas developed 11 symptomatic hemorrhages after initial identification. Five of the patients who had a hemorrhage during the follow-up interval had initially presented with hemorrhage, while only 1 had presented incidentally. The hemorrhage rate for all patients in the natural history group was 1.6% per patient-year and 0.9% per cavernoma-year. The hemorrhage rate was 8.0% per patient-year in the symptomatic group versus 0.2% in the incidental group. Symptomatic hemorrhage after long-term follow-up was associated with initial acute presentation (p = 0.02).</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The imaging prevalence of CM increases with advancing age during childhood. Patients presenting without hemorrhage have a significantly lower risk of bleeding compared with those who present with acute neurological symptoms. Comparing this series of children to prior analyses of CM natural history in adults, the authors' data do not suggest a higher bleeding risk in younger patients.</jats:p></jats:sec>

Peripheral Plasma Vitamin D and Non-HDL Cholesterol Reflect the Severity of Cerebral Cavernous Malformation Disease

“…Given the small numbers of cases with each disease aggressiveness feature, and the known correlation among the different features (i.e., patients with earlier symptom onset are more likely to experience greater lesion burden and multiple hemorrhages, patients with recent hemorrhage are more likely to experience recent lesional growth) [3], we subsequently considered the respective features of disease aggressiveness in chronic or acute domains for our primary hypothesis testing. Since CCM disease beginning in pediatric patients has been shown to be more severe than when disease onset is in adults [3,[5][6][7], we used symptoms beginning at or before 18 years of age as a feature of chronic disease aggressiveness. We also considered more than 25 SWI lesions, more than five T2-weighted lesions and more than one hemorrhage as features of chronic disease aggressiveness because these same thresholds correlated with cerebral vascular permeability in patients with CCM [1].…”

“…Clinical disease aggressiveness is portended by early age of onset [3,27], high lesion burden [3] and multiple clinical bleeds resulting in disability [4]. Acute disease aggressiveness is characterized by recent clinical hemorrhage, which predicts a higher likelihood of future bleeding [5][6][7]. Lesion genesis and asymptomatic hemorrhagic proliferation (lesion growth) have been considered as features of disease aggressiveness in preclinical studies [10,11,28] with potential clinical implications.…”

“…Some patients remain asymptomatic, while others are disabled from recurrent bleeds and/or high lesion burden [4]. Early age of lesion onset, multiple hemorrhages and increased lesion burden have been correlated in various studies with chronic disease severity [5][6][7][8][9]. Features of acute disease aggressiveness include clinically overt hemorrhage, CCM lesion growth and the genesis of new lesions [10,11].…”

Incidental Findings on Brain and Spine Imaging in Children

“…The annual risk of hemorrhage is lower as well; a recent report of a pediatric series estimated a 0.2% per lesion per year rate for incidental cavernomas. 62 Finally, in comparison with AVMs, the surgical management of cavernomas is relatively straightforward. Neurosurgeons are generally reluctant to operate on asymptomatic cavernomas, but exceptions may be made on the basis of such factors as interval enlargement, anatomic location, or family preference.…”

“…61 The imaging prevalence of incidental cavernomas in childhood has been estimated at 0.3%, and prevalence seems to increase with age. 62 Cavernomas become symptomatic either with seizures or from hemorrhage. They are distinct from AVMs in that hemorrhages are smaller, are less likely to cause disability depending on anatomic location, and are infrequently fatal.…”