Cavernous malformations (CMs) affecting the central nervous system occur in approximately 0.16% to 0.4% of the general population. The majority (85%) of the CMs are in a sporadic form, but the genetic background of sporadic CMs remains enigmatic. Of the 81 patients, 73 (90.1%) patients were detected carrying somatic missense variants in 2 genes: MAP3K3 and PIK3CA by whole-exome sequencing (WES). The mutation spectrum correlated with lesion size (P = 0.001), anatomical distribution (P < 0.001), MRI appearance (P = 0.004) and haemorrhage events (P = 0.006). PIK3CA mutation was a significant predictor of overt haemorrhage events (P = 0.003, OR = 11.252, 95% CI = 2.275-55.648). Enrichment of endothelial cell (EC) population was associated with a higher fractional abundance of the somatic mutations. Overexpression of the MAP3K3 mutation perturbed angiogenesis of EC models in vitro and zebrafish embryos in vivo. Distinct transcriptional signatures between different genetic subgroups of sporadic CMs were identified by single-cell RNA-sequencing (scRNA-seq) and verified by pathological staining. Significant apoptosis in MAP3K3 mutation carriers and overexpression of GDF15 and SERPINA5 in PIK3CA mutation carriers contributed to their phenotype. We identified activating MAP3K3 and PIK3CA somatic mutations in the majority (90.1%) of sporadic CMs and PIK3CA mutations could confer a higher risk for overt haemorrhage. Our data provide insights into genomic landscapes, propose a mechanistic explanation and underscore the possibility of a molecular classification for sporadic CMs.

Pediatric intracranial aneurysms differ in many ways from those in adults: male predominance; high incidence of giant, dissecting, and fusiform aneurysms; high incidence of aneurysms in the posterior circulation; high incidence of spontaneous thrombosis; better Hunt-Hess grades at presentation; and better therapeutic outcome. For children with intracranial aneurysms, both microsurgical approaches and endovascular treatment were effective. For many complex aneurysms, endovascular therapy was the best choice.

Object The authors conducted a study to assess the clinical pattern, radiological features, therapeutic strategies, and long-term outcomes in patients with intramedullary spinal cord cavernomas (ISCCs) based on a large case series. Methods This retrospective study identified 96 patients (60 males, 36 females) surgically (81 cases) or conservatively (15 cases) treated for ISCCs between May 1993 and November 2007. Each diagnosis was based on MR imaging and spinal angiography evidence. For all surgically treated patients, the diagnosis was verified pathologically. The neurological outcomes pre- and postoperatively, as well as long-term follow-up, were assessed using the Aminoff-Logue Disability Scale. Results The mean age at the onset of symptoms was 34.5 years (range 9–80 years). Of the lesions, 68 (71%) were located in the thoracic spine, 25 (26%) in the cervical spine, and only 3 (3%) in the lumbar spine. The median symptom duration was 19.7 months. The clinical behavior of the lesion was a slow progression in 73 cases and an acute decline in 23 cases. Long-term follow-up data (mean 45.8 months, range 10–183 months) were available for 75 patients (64 surgical cases and 11 conservative cases). In the surgical group, a complete resection was achieved in 60 patients, and incomplete resection was detected in 4 patients after operation. At the end of the follow-up period in the operative group, 23 patients (36%) improved, 35 (55%) remained unchanged, and 6 (9%) worsened. In the nonoperative group, 5 patients improved, 6 patients remained unchanged, and none worsened. Conclusions For differential diagnosis, spinal angiography was necessary in some cases. For most symptomatic lesions, complete microsurgical resection of the symptomatic ISCC is safe and prevents rebleeding and further neurological deterioration. However, in patients whose lesions were small and located ventrally in the spinal cord, one can also opt for a rigorous follow-up, considering the high surgical risk.

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