Tag: Cerebral cavernous malformation (CCM)

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Atorvastatin Treatment of Cavernous Angiomas with Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial

Neurosurgery 2019 Dec 1;85(6):843-853

More than a million Americans harbor a cerebral cavernous angioma (CA), and those who suffer a prior symptomatic hemorrhage have an exceptionally high rebleeding risk. Preclinical studies show that atorvastatin blunts CA lesion development and hemorrhage through inhibiting RhoA kinase (ROCK), suggesting it may confer a therapeutic benefit.

OBJECTIVE: To evaluate whether atorvastatin produces a difference compared to placebo in lesional iron deposition as assessed by quantitative susceptibility mapping (QSM) on magnetic resonance imaging in CAs that have demonstrated a symptomatic hemorrhage in the prior year. Secondary aims shall assess effects on vascular permeability, ROCKactivity in peripheral leukocytes, signal effects on clinical outcomes, adverse events, and prespecified subgroups.

METHODS: The phase I/IIa placebo-controlled, double-blinded, single-site clinical trial aims to enroll 80 subjects randomized 1-1 to atorvastatin (starting dose 80 mg PO daily) or placebo. Dosing shall continue for 24-mo or until reaching a safety endpoint.

EXPECTED OUTCOMES: The trial is powered to detect an absolute difference of 20% in the mean percent change in lesional QSM per year (2-tailed, power 0.9, alpha 0.05). A decrease in QSM change would be a signal of potential benefit, and an increase would signal a safety concern with the drug.

DISCUSSION: With firm mechanistic rationale, rigorous preclinical discoveries, and biomarker validations, the trial shall explore a proof of concept effect of a widely used repurposed drug in stabilizing CAs after a symptomatic hemorrhage. This will be the first clinical trial of a drug aimed at altering rebleeding in CA.

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Which Cerebral Cavernous Malformations are Most Difficult to Dissect From Surrounding Eloquent Brain Tissue?

Neurosurgery 81:498–503, 2017

Cerebral cavernous malformations (CCM) may lead to repetitive intracerebral hemorrhage. In selected cases, a surgical resection is indicated.

OBJECTIVE: To identify magnetic resonance imaging (MRI) features of CCM that correlate with the difficulty of dissection and postoperative outcome.

METHODS: This study prospectively analyzed pre- and postoperative MRI features, intraoperative findings (surgical questionnaire), and postoperative outcome of 41 patients with eloquent CCM. Based on the results of the surgeon’s questionnaire and postoperative MRI findings, all surgical procedureswere dichotomized in a “difficult”(groupA) or “not difficult” (group B) lesion dissection. Based on the correlation of preoperative MRI features with groups A and B, a 3-tiered classification was established and tested for sensitivity and specificity.

RESULTS: In 22 patients, dissection of the lesion was rated difficult. This was significantly correlated with amount of postoperative diffusion restriction on MRI (P=.001) and postoperative outcome(P=.05). Various preoperative MRI featureswere tested for correlation and combined in a 3-tiered classification. Receiver operating characteristics revealed excellent and good results for predicting difficulty of dissection for the different classification types.

CONCLUSION: We provide a meticulous analysis and new classification of preoperative MRI features that seem to be involved in the microsurgical resection of CCM.

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