By Susan C. Pannullo, MD, and Swathi Chidambaram, MD
Dr. Pannullo is Associate Professor of Clinical Neurological Surgery, Weill Cornell Medical College; Adjunct Assistant Professor of Neurological Surgery, Columbia University College of Physicians and Surgeons; and Associate Attending Neurological Surgeon, NewYork-Presbyterian Hospital. Dr. Chidambaram is Fellow in Neurological Surgery, Weill Cornell Medical College.
Dr. Pannullo and Dr. Chidambaram report no financial relationships relevant to this field of study.
In this comprehensive review of studies comparing treatments for cerebral cavernous malformations, there were no randomized or blinded outcome trials, and the most effective treatment remains uncertain.
Poorthuis MHF, Rinkel LA, Lammy S, Al-Shahi Salman R. Stereotactic radiosurgery for cerebral cavernous malformations: A systematic review. Neurology 2019;93:e1971-e1979.
Cerebral cavernous malformations (CCMs) are intracranial vascular malformations found in 0.15-0.44% of the population. Often, CCMs are incidental findings on computed tomography (CT) and magnetic resonance imaging (MRI) scans. However, these lesions may present with seizures, neurological deficits, or intracerebral hemorrhages. The goal of treatment is to prevent these complications. Patients with CCM are managed conservatively with observation or treated with surgical excision or stereotactic radiosurgery (SRS). The role of SRS for CCM remains controversial, as randomized, controlled trials have not been performed, and no observational studies at low risk of bias have shown meaningful associations between treatment of CCM with SRS and better outcomes.
Poorthuis et al performed a systematic review of the literature to quantify clinical outcomes after SRS for CCM and compare them to microsurgical excision or conservative management to further explore the efficacy of SRS for treatment of CCMs. They searched Ovid Medline and Ovid EMBASE from inception until June 1, 2018, for peer-reviewed publications describing clinical outcomes after SRS for ≥ 10 people with CCM in cohorts with or without a comparison group treated with neurosurgical excision or conservative management. Two reviewers independently extracted data from the included studies to quantify cohort characteristics and the incidence of the primary outcome and secondary outcomes. The primary outcome was death attributed to CCM or its treatment. The secondary outcomes were incident nonfatal symptomatic intracranial hemorrhage (ICH), incident nonfatal and non-hemorrhagic persistent focal neurologic deficits (FND), a composite outcome (death attributed to CCM or its treatment or nonfatal ICH or nonfatal and non-hemorrhagic persistent FND), seizures, adverse radiation effects, and functional outcome.
From screening 361 references and excluding ineligible studies and smaller overlapping reports of included studies, 30 studies involving a total of 1,576 patients undergoing SRS for CCM were included. Of these, three studies compared SRS to neurosurgery, one study compared SRS to neurosurgery and conservative management, one study compared two cohorts receiving different types of SRS, and 25 cohort studies examined SRS alone. In general, included studies were at medium to high risk of bias. None of the studies were randomized, none concealed treatment allocation, and none used blinding of allocation or outcome assessment.
Four nonrandomized studies compared SRS to other treatment modalities, but did not demonstrate dramatic associations. The authors reported pooled estimates of the risks of SRS for CCM over approximately four years after treatment that they assert can be applied to clinical practice, especially for patients with CCM that have caused ICH. The risks after SRS appear similar to the untreated clinical course of CCM, by indirect comparison with the overall five-year risk of ICH found in a patient-level meta-analysis (15.8%; 95% confidence interval, 13.7-17.9). The authors concluded that it is not possible to be confident regarding the beneficial effects of SRS for CCM because of the shortage of comparative studies at low risk of bias, leaving reassurance only from indirect comparisons with untreated clinical course or neurosurgery. Outcomes did not differ by CCM location or type of SRS. The authors reported that after SRS for CCM, the annual incidences of death, ICH, and FND are < 5% and seem comparable to outcomes without SRS. They concluded that randomized trials of SRS for CCM are needed.
COMMENTARY
In this systematic review of SRS for CCM, the authors did not find any randomized trials, but included 30 observational studies involving a total of 1,576 patients (median sample size 34, age 40 years, 91% presented with ICH, 65% infratentorial CCM, and follow-up 48 months). This study reinforces the lack of clarity when choosing treatment options for CCMs. As the authors pointed out, randomized trials and higher-quality observational studies are needed to further investigate the role of SRS vs. surgery or observation in treating CCMs. In current clinical practice, SRS can be a reasonable option for CCMs in cases in which the patient is experiencing progressive neurological decline, intractable seizures, or multiple recurrent hemorrhages and simultaneously is not amenable to surgery. In such cases, a multidisciplinary team can guide the decision-making process regarding which management approach is optimal in any particular case.
