No abstract

OBJECTIVE Retrospective patient cohort studies have identified risk factors associated with recurrent focal neurological events in patients with symptomatic cerebral cavernous malformations (CCMs). Using a prospectively maintained database of patients with CCMs, this study identified key risk factors for recurrent neurological events in patients with symptomatic CCM. A simple scoring system and risk stratification calculator was then created to predict future neurological events in patients with symptomatic CCMs. METHODS This was a dual-center, prospectively acquired, retrospectively analyzed cohort study. Adult patients who presented with symptomatic CCMs causing focal neurological deficits or seizures were uniformly treated and clinically followed from the time of diagnosis onward. Baseline variables included age, sex, history of intracerebral hemorrhage, lesion multiplicity, location, eloquence, size, number of past neurological events, and duration since last event. Stepwise multivariable Cox regression was used to derive independent predictors of recurrent neurological events, and predictive accuracy was assessed. A scoring system based on the relative magnitude of each risk factor was devised, and Kaplan-Meier curve analysis was used to compare event-free survival among patients with different score values. Subsequently, 1-, 2-, and 5-year neurological event rates were calculated for every score value on the basis of the final model. RESULTS In total, 126 (47%) of 270 patients met the inclusion criteria. During the mean (interquartile range) follow-up of 54.4 (12–66) months, 55 patients (44%) experienced recurrent neurological events. Multivariable analysis yielded 4 risk factors: bleeding at presentation (HR 1.92, p = 0.048), large size ≥ 12 mm (HR 2.06, p = 0.016), eloquent location (HR 3.01, p = 0.013), and duration ≤ 1 year since last event (HR 9.28, p = 0.002). The model achieved an optimism-corrected c-statistic of 0.7209. All factors were assigned 1 point, except duration from last event which was assigned 2 points. The acronym BLED2 summarizes the scoring system. The 1-, 2-, and 5-year risks of a recurrent neurological event ranged from 0.6%, 1.2%, and 2.3%, respectively, for patients with a BLED2 score of 0, to 48%, 74%, and 93%, respectively, for patients with a BLED2 score of 5. CONCLUSIONS The BLED2 risk score predicts prospective neurological events in symptomatic CCM patients.

Background: Malignant atypical teratoid rhabdoid tumor (ATRT) usually develops in children. ATRTs are rare in adults, with only one case in the literature describing involvement of the anterior skull base. These primary intracranial tumors are characterized molecularly as SMARCB1 (INI1) deficient. Different types of such SMARCB1-deficient tumors exist in adulthood, usually in the form of extracranial tumors. Very few cases of such a new entity, named SMARCB1-deficient sinonasal carcinoma have been described with intracranial penetration and involvement of the anterior cranial fossa. Case Description: A 36-year-old male presented with acute cognitive deterioration. Over few hours, he developed a fulminant herniation syndrome. Imaging showed a tumor in the anterior cranial fossa surrounded by massive brain edema. The tumor has destroyed the frontal bone with involvement of the nasal cavities and paranasal sinuses. The patient underwent emergent decompressive craniectomy and tumor debulking but could not be saved. Pathological analysis revealed a highly cellular tumor without rhabdoid cells but with areas of necrosis. Further immunohistochemical stains revealed that neoplastic cells were diffusely and strongly positive for epithelial membrane antigen and P63 and negative for SMARCB1 (i.e., loss of expression), confirming the diagnosis of sinonasal carcinoma. Conclusion: To the best of our knowledge, this is the first report of a fulminant presentation of a SMARCB1- deficient tumor in young adult, involving the anterior cranial fossa and the paranasal sinuses. The main differential diagnosis of aggressive, primary, intracranial SMARCB1-deficient tumors in adults includes ATRT, SMARCB1- deficient sinonasal carcinoma, rhabdoid meningioma, and rhabdoid glioblastoma. Atypical tumors involving the anterior skull base without a clear histopathological pattern should therefore be checked for SMARCB1 expression.

INTRODUCTION: Studies using retrospective patient cohorts have identified risk factors associated with recurrent focal neurologic events in patients with symptomatic cerebral cavernous malformations (CCMs). METHODS: Adult patients presenting with symptomatic CCMs causing focal neurologic deficits or seizures were included. Baseline variables included age, gender, history of intracerebral hemorrhage, lesion multiplicity, location, eloquence, size, number of past neurologic events, and duration since last event. Stepwise multivariable Cox regression was used to derive independent predictors of recurrent neurologic events, and predictive accuracy was assessed. A scoring system based on the relative magnitude of the risk factors was devised, and Kaplan-Meier curve analysis compared event-free survival between different score values. Subsequently, 1-, 2-, and 5-year neurologic event rates were calculated for every score value based on the final model. RESULTS: 126 (47%) of 270 patients met inclusion criteria. During a mean follow-up of 4.5 years (54.4 months, range 12-66 months), 55 patients (44%) experienced recurrent neurologic events. Multivariable analysis yielded four risk factors: Bleeding at presentation (HR=1.92, p=0.048), Large size =12mm (HR=2.06, p=0.016), Eloquent location (HR=3.01, p=0.013), and Duration of =1 year since last event (HR=9.28, p=0.002). The model achieved an optimism-corrected c-statistic of 0.7209. All factors were assigned 1 point except duration from last event, which was assigned 2 points. The acronym, BLED2 summarizes the scoring system. The 1-, 2-, and 5-year risk of a recurrent neurologic event ranged from 0.6%, 1.2%, and 2.3%, respectively for patients with a BLED2 score of 0, to 48%, 74%, and 93%, respectively for patients with a BLED2 score of 5. CONCLUSION: The BLED2 risk score predicts prospective neurologic events in symptomatic CCM patients.