Cavernous malformations are congenital abnormalities of the cerebral vessels that affect 0.5% to 0.7% of the population. They occur in two forms: a sporadic form characterized by isolated lesions, and a familial form characterized by multiple lesions with an autosomal dominant mode of inheritance. The management of patients with cavernous malformations, particularly those with the familial form of the disease, remains a challenge because little is known regarding the natural history. The authors report the results of an ongoing study in which six families afflicted by familial cavernous malformations have been prospectively followed with serial interviews, physical examinations, and magnetic resonance (MR) imaging at 6- to 12-month intervals. A total of 59 members of these six families were screened for protocol enrollment; 31 (53%) had MR evidence of familial cavernous malformations. Nineteen (61%) of these 31 patients were symptomatic, with seizures in 12 (39%), recurrent headaches in 16 (52%), focal sensory/motor deficits in three (10%), and visual field deficits in two (6%). Twenty-one of these 31 patients underwent at least two serial clinical and MR imaging examinations. A total of 128 individual cavernous malformations (mean 6.5 +/- 3.8 lesions/patient) were identified and followed radiographically. During a mean follow-up period of 2.2 years (range 1 to 5.5 years), serial MR images demonstrated 17 new lesions in six (29%) of the 21 patients; 13 lesions (10%) showed changes in signal characteristics, and five lesions (3.9%) changed significantly in size. The incidence of symptomatic hemorrhage was 1.1% per lesion per year. The results of this study demonstrate that the familial form of cavernous malformations is a dynamic disease; serial MR images revealed changes in the number, size, and imaging characteristics of lesions consistent with acute or resolving hemorrhage. It is believed that the de novo development of new lesions in this disease has not been previously reported. These findings suggest that patients with familial cavernous malformations require careful follow-up monitoring, and that significant changes in neurological symptoms warrant repeat MR imaging. Surgery should be considered only for lesions that produce repetitive or progressive symptoms. Prophylactic resection of asymptomatic lesions does not appear to be indicated.

Oncogenic TACC-tics Human cancers exhibit many types of genomic rearrangements—including some that juxtapose sequences from two unrelated genes—thereby creating fusion proteins with oncogenic activity. Functional analysis of these fusion genes can provide mechanistic insights into tumorigenesis and potentially lead to effective drugs, as famously illustrated by the BCR-ABL gene in chronic myelogenous leukemia. Singh et al. (p. 1231 , published online 26 July) identify and characterize a fusion gene present in 3% of human glioblastomas, a deadly brain cancer. In the resultant fusion protein, the tyrosine kinase region of the fibroblast growth factor receptor (FGFR) is joined to a domain from a transforming acidic coiled-coil (TACC) protein. The TACC-FGFR protein is oncogenic, shows unregulated kinase activity, localizes to the mitotic spindle, and disrupts chromosome segregation. In mice, FGFR inhibitors slowed the growth of tumors driven by the TACC-FGFR gene, suggesting that a subset of glioblastoma patients may benefit from these types of drugs.

Dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging can be used to predict median time to progression in patients with gliomas, independent of pathologic findings. Patients who have HGGs and LGGs with a high relative CBV (>1.75) have a significantly more rapid time to progression than do patients who have gliomas with a low relative CBV.

Echo-planar perfusion imaging is useful in the preoperative assessment of tumor grade and in providing diagnostic information not available with conventional MR imaging. The areas of perfusion abnormality are invaluable in the precise targeting of the stereotactic biopsy.

Convergent evidence supports a role for anterior prefrontal cortex (PFC) in metacognition—the capacity to evaluate cognitive processes—but whether metacognition relies on global or domain-specific substrates is unknown. Fleming et al. report that patients with anterior PFC lesions show impaired perceptual metacognition despite intact memory metacognition, supporting a domain-specific account.