Feasibility of minocycline and doxycycline use as potential vasculostatic therapy for brain vascular malformations: pilot study of adverse events and tolerance.

BACKGROUND: Tetracyclines may be useful in preventing pathological vascular remodeling, thus decreasing the risk of spontaneous hemorrhage from brain vascular malformations. METHODS: Arteriovenous malformation (AVM) and intracranial aneurysm patients undergoing noninvasive management were treated with minocycline or doxycycline (200 mg/day) up to 2 years in a prospective open-label safety pilot trial. The primary outcome was to compare dose-limiting intolerance, defined as treatment-related dose reduction or withdrawal between the agents. RESULTS: Twenty-six patients with AVMs (n = 12) or aneurysms (n = 14) were recruited. Adverse event rates were similar to other reported trials of these agents; 4 of 13 (31%) minocycline and 3 of 13 (23%) doxycycline patients had dose-limiting intolerance (hazard ratio = 3.1, 95% CI = 0.52-18.11, log rank p = 0.70). CONCLUSIONS: It is feasible to propose a long-term trial to assess the potential benefit of tetracycline therapy to decrease hemorrhagic risk in brain vascular malformations.

Effect of presenting hemorrhage on outcome after microsurgical resection of brain arteriovenous malformations.

OBJECTIVE: We hypothesized that patients with unruptured arteriovenous malformations (AVMs) at presentation have an increased risk of deterioration compared with patients with ruptured AVMs. METHODS: A consecutive series of 224 patients treated microsurgically by a single neurosurgeon during a period of 6.4 years was analyzed. Initial hemorrhagic presentation was the primary predictor variable. Neurological outcomes were assessed by use of the Modified Rankin Scale (MRS) and Glasgow Outcome Scale (GOS), and logistic regression identified predictors of deterioration at follow-up (mean duration, 1.3 yr) relative to baseline before any intervention. RESULTS: Overall, 120 patients (54%) presented with hemorrhage, and all 224 patients underwent microsurgical resection. Complete resection was achieved in 220 patients (98%). According to GOS score, 13 patients (5.8%) deteriorated; according to MRS score, 45 patients (20.1%) deteriorated. Fifteen patients (6.7%) died. Hemorrhagic presentation was associated with improved outcomes, with a mean change in MRS score of +0.89 in patients with ruptured AVMs and -0.38 in patients with unruptured AVMs (P < 0.001). The final mean MRS scores in patients with unruptured AVMs were better than those in patients with ruptured AVMs (1.44 versus 1.90; P = 0.048). Presentation with an unruptured AVM was a predictor of worsening MRS score (odds ratio, 2.33; 95% confidence interval, 1.3-4.3; P = 0.006) but not of worsening GOS score. CONCLUSION: Presentation with AVM hemorrhage is an underappreciated predictor of outcome after therapy that includes microsurgical resection. Patients with ruptured AVMs tended to have deficits at presentation and generally improved after surgery, whereas patients with unruptured AVMs tended to have normal or nearly normal neurological function at presentation and were susceptible to worsening, albeit slight, as measured by MRS scores. Sensitive outcome measures such as MRS detect subtle symptoms and impairments missed by coarser measures such as GOS. Patients should be counseled that the risks associated with elective resection of unruptured AVMs may be higher than recognized previously. Hemorrhagic brain injury and its secondary effects may mask this surgical morbidity.