Dennis R. Buis

Treatment of Brain Arteriovenous Malformations: A Systematic Review and Meta-analysis

CONTEXT Outcomes following treatment of brain arteriovenous malformations (AVMs) with microsurgery, embolization, stereotactic radiosurgery (SRS), or combinations vary greatly between studies. OBJECTIVES To assess rates of case fatality, long-term risk of hemorrhage, complications, and successful obliteration of brain AVMs after interventional treatment and to assess determinants of these outcomes. DATA SOURCES We searched PubMed and EMBASE to March 1, 2011, and hand-searched 6 journals from January 2000 until March 2011. STUDY SELECTION AND DATA EXTRACTION We identified studies fulfilling predefined inclusion criteria. We used Poisson regression analyses to explore associations of patient and study characteristics with case fatality, complications, long-term risk of hemorrhage, and successful brain AVM obliteration. DATA SYNTHESIS We identified 137 observational studies including 142 cohorts, totaling 13,698 patients and 46,314 patient-years of follow-up. Case fatality was 0.68 (95% CI, 0.61-0.76) per 100 person-years overall, 1.1 (95% CI, 0.87-1.3; n = 2549) after microsurgery, 0.50 (95% CI, 0.43-0.58; n = 9436) after SRS, and 0.96 (95% CI, 0.67-1.4; n = 1019) after embolization. Intracranial hemorrhage rates were 1.4 (95% CI, 1.3-1.5) per 100 person-years overall, 0.18 (95% CI, 0.10-0.30) after microsurgery, 1.7 (95% CI, 1.5-1.8) after SRS, and 1.7 (95% CI, 1.3-2.3) after embolization. More recent studies were associated with lower case-fatality rates (rate ratio [RR], 0.972; 95% CI, 0.955-0.989) but increased rates of hemorrhage (RR, 1.02; 95% CI, 1.00-1.03). Male sex (RR, 0.964; 95% CI, 0.945-0.984), small brain AVMs (RR, 0.988; 95% CI, 0.981-0.995), and those with strictly deep venous drainage (RR, 0.975; 95% CI, 0.960-0.990) were associated with lower case fatality. Lower hemorrhage rates were associated with male sex (RR, 0.976, 95% CI, 0.964-0.988), small brain AVMs (RR, 0.988, 95% CI, 0.980-0.996), and brain AVMs with deep venous drainage (0.982, 95% CI, 0.969-0.996). Complications leading to permanent neurological deficits or death occurred in a median 7.4% (range, 0%-40%) of patients after microsurgery, 5.1% (range, 0%-21%) after SRS, and 6.6% (range, 0%-28%) after embolization. Successful brain AVM obliteration was achieved in 96% (range, 0%-100%) of patients after microsurgery, 38% (range, 0%-75%) after SRS, and 13% (range, 0%-94%) after embolization. CONCLUSIONS Although case fatality after treatment has decreased over time, treatment of brain AVM remains associated with considerable risks and incomplete efficacy. Randomized controlled trials comparing different treatment modalities appear justified.

Repeated surgery for glioblastoma multiforme: only in combination with other salvage therapy.

BACKGROUND The purpose of the study was to evaluate the effects, frequency, and complications of repeated surgical resection for GBM relapse. METHODS A group of 32 patients with tumor recurrence, derived from a total of 126 consecutive patients with prior GBM, treated between 1999 and 2005 in the VU University Medical Center, Amsterdam, Netherlands, were retrospectively studied. Survival, functional status, morbidity, and mortality after starting salvage therapy for recurrent GBM were studied. Survival was analyzed using Kaplan-Meier survival curves, and log-rank statistics were used for group comparison. RESULTS Of the 32 patients with recurrent primary GBM, 20 received repeated surgery as salvage therapy. In 11 (55%) cases, repeated surgery was followed by CT or SRS. Nine (45%) patients receiving only repeated surgery showed significantly lower survival rates compared with the aforementioned 11 cases. The remaining 12 patients received only salvage CT or SRS and showed a significantly prolonged survival compared with the 9 cases receiving repeated surgery only. Surgical morbidity was 15%, and surgical mortality, 5%. CONCLUSION Despite inherent selection bias, this retrospective analysis suggests that repeated surgery for GBM relapse should only be considered in patients with severe symptoms and if additional salvage treatment can be administered postoperatively.

Higher complications and no improvement in mortality in the ACGME resident duty-hour restriction era: an analysis of more than 107,000 neurosurgical trauma patients in the Nationwide Inpatient Sample database.

BACKGROUND The Accreditation Council for Graduate Medical Education resident duty-hour restrictions were implemented in July 2003 based on the supposition that resident fatigue contributes to medical errors. OBJECTIVE To examine the effect of duty-hour restrictions on outcome in neurotrauma patients. METHODS The Nationwide Inpatient Sample database was analyzed for a time period with no restrictions (years 1999-2002) compared with a period with restrictions (years 2005-2008) for (1) mortality and (2) complications. We analyzed both teaching and nonteaching hospitals to account for potential differences attributed to non-resident-related factors. RESULTS There were 107,006 teaching hospital and 115,604 nonteaching hospital admissions for neurotrauma. Multivariate logistic regression demonstrated significantly more complications in the time period with restrictions in teaching hospitals. In nonteaching hospitals, there was no difference in complications. In both teaching and nonteaching hospitals, there was no difference in mortality between the 2 time periods. For teaching and nonteaching hospitals, there was no difference in hospital length of stay, but hospital charges were significantly higher in the period with restrictions. The occurrence of a complication was significantly associated with longer hospital length of stay and higher hospital charges in both time periods in both teaching and nonteaching hospitals. CONCLUSION The implementation of the Accreditation Council for Graduate Medical Education resident duty-hour restrictions was associated with increased complications and no change in mortality for neurotrauma patients in teaching hospitals. In nonteaching hospitals, there was no change in complications and mortality. The occurrence of a complication was associated with longer length of stay and higher hospital charges in both time periods in both teaching and nonteaching hospitals.

Radiosurgery of brain arteriovenous malformations in children

ObjectiveThe authors describe their experience in treating 22 children with a single brain arteriovenous malformation (bAVM) using a dedicated LINAC stereotactic radiosurgery unit.MethodsThe findings of 22 consecutive patients ≤ 18 years of age who underwent radiosurgery for a single bAVM and with at least 24 months of follow-up, or earlier proven obliteration,were reviewed. The median age at radiosurgery was 13.8 years,with a hemorrhagic presentation in 86%. Median bAVM-volume was 1.8 ml, with a median prescribed marginal dose of 19.0 Gy.ResultsThe crude complete obliteration-rate was 68% (n = 15) after a median follow-up of 24 months. The actuarial obliteration- rate was 45 % after two years and 64 % after three years. Patients with a radiosurgery-based AVM score ≤ 1 more frequently had an excellent outcome than patients with a bAVM score > 1 (71% vs. 20%, P = 0.12), as well as an increased obliteration rate (P = 0.03) One patient died from a bAVM-related hemorrhage 27 months after radiosurgery, representing a postradiosurgery hemorrhage rate of 1.3%/year for the complete followup interval. Overall outcome was good to excellent in 68% (n = 15). Radiation-induced changes on MR imaging were seen in 36% (n = 8) after a median interval of 12.5 months, resulting in deterioration of pre-existing neurological symptoms in one patient.ConclusionsRadiosurgery is a relatively effective, minimally invasive treatment for small bAVMs in children. The rebleeding rate is low, provided that known predilection places for bleeding had been endovascularly eliminated.Our overall results compare unfavourably to recent pediatric microsurgical series, although comparison between series remains imprecise. Nevertheless, when treatment is indicated in a child with a bAVM that is amenable to both microsurgery or radiosurgery, microsurgery should carefully be advocated over radiosurgery, because of its immediate risk reduction.

Spontaneous regression of brain arteriovenous malformations--a clinical study and a systematic review of the literature.

Objective and importanceComplete spontaneous obliteration of a brain arteriovenous malformation (AVM) is a rare event, with 67 angiographically proven cases in the world literature. We present a new case and a systematic literature review to determine possible mechanisms underlying this unusual phenomenon.Clinical presentationOne patient with a brain AVM was referred for radiosurgical treatment. Shortly before treatment however, complete spontaneous regression occurred. This patient had experienced a hemorrhage in the months before referral.ResultsWe found 38 articles in which 67 cases of complete and spontaneous regression of a brain AVM were presented. Male to female ratio was 1.2, with a mean age of 37 years (range 1–81). Regression occurred in 72% without new neurological events. Median size of the nidus was 2 cm (range 1–7). There was a single arterial feeder in 46 % and a single draining vein in 59%.ConclusionSpontaneous regression of a brain AVM is the result of multiple interacting factors. Intracranial hemorrhage and the presence of a single draining vein seem to play a major role in this process.

Color intensity projection of digitally subtracted angiography for the visualization of brain arteriovenous malformations.

OBJECTIVEReliable and rapid delineation of arteriovenous malformations enables the application of effective treatments such as stereotactic radiosurgery. We describe a new method to improve the speed and reliability of visualizing the flow of contrast images with digital subtraction angiography. METHODSIn line with current practices, digital subtraction angiography was used to produce a sequence of grayscale images. The new method combines the standard grayscale images produced by digital subtraction angiography into a single composite color image that encodes the contrast arrival time at each point of the brains circulatory system. The algorithm is simple, fast, and easy to implement. RESULTSThe technique allows the flow of contrast from a series of angiography images to be summarized in a single color image. CONCLUSIONThis visualization method promises to improve the speed of manual delineation of arteriovenous malformations. Further studies are required to evaluate the clinical value of the use of color intensity projection images, supplemented by grayscale images as necessary, in comparison with contouring on grayscale images only.

Clinical outcome after repeated radiosurgery for brain arteriovenous malformations

INTRODUCTION We assessed the clinical and radiological outcome after repeated radiosurgery for brain arteriovenous malformations (bAVMs) after failure of initial radiosurgery. MATERIALS AND METHODS Fifteen patients underwent repeated radiosurgery. The mean bAVM volume at first radiosurgery (S1) was 4.6 +/- 4.3 ml and that at second radiosurgery (S2) was 2.1 +/- 2.5 ml. The median marginal dose was 18 Gy at S1, and 21 Gy at S2. Modified Rankin Scale (MRS) score was determined in all patients at last follow-up (FU). RESULTS Complete obliteration was reached in nine patients (60%). Median time to obliteration was 50 months after S2. An excellent outcome (no new neurologic deficiencies, complete obliteration) was reached in seven patients (47%). Eleven patients (73%) showed a MRS1. Radiation-induced complications occurred in 20%, of which 13% occurred after S2. Radiological complications included cyst formation (n = 1), radiation-related edema (n = 4), and radiation necrosis (n = 1), resulting in an increasing mean MRS of 0.5 at S1, 0.6 at S2, to 0.8 at FU. No (re-)bleedings were encountered during 137-patient years at risk. DISCUSSION Repeated radiosurgery is a viable option for the treatment of small remnant bAVMs. We report 20% permanent radiation-induced complications. Such complications were mainly seen in relatively large, and therefore difficult to treat, bAVMs.

The Predictive Value of 3D Time-of-Flight MR Angiography in Assessment of Brain Arteriovenous Malformation Obliteration after Radiosurgery

This article addresses a common clinical problem: the MRA assessment of treatment effects on AVMs. The authors looked at the utility of T2 and time-of-flight MRA images in 120 pre- and postradiosurgery AVMs; 55 of these had been previously embolized. They compared the MRI findings with those from DSA and discovered that both MR sequences performed poorly when the residual nidus was less than 10 mm in size. Therefore, DSA is highly recommended to make the diagnosis of complete AVM obliteration. BACKGROUND AND PURPOSE: The purpose of radiosurgery of bAVMs is complete angiographic obliteration of its nidus. We assessed the diagnostic accuracy of 1.5T T2-weighted MR imaging and TOF-MRA images for detecting nidus obliteration after radiosurgery. MATERIALS AND METHODS: The pre- and postradiosurgery MR images and DSA images from 120 patients who were radiosurgically treated for a bAVM were re-evaluated by 2 observers for patency of the nidus (preradiosurgery) and obliteration (postradiosurgery: final follow-up MR imaging), by using a 3-point scale of confidence. Consensus reading of the DSA after radiosurgery was considered the criterion standard for obliteration. Sensitivity, specificity, PPVs, and NPVs, and overall diagnostic performance by using ROC were determined. RESULTS: Mean bAVM volume during radiosurgery was 3.4 mL (95% CI, 2.6–4.3 mL). Sixty-six patients (55%) had undergone previous endovascular embolization. The mean intervals between radiosurgery and follow-up MR imaging and for DSA, respectively, were 35.6 months (95% CI, 32.3–38.9 months) and 42.1 months (95% CI, 40.3–44.0 months). With ROC, an area under curve of 0.81–0.83 was found. PPVs and NPVs of final follow-up MR imaging for definitive obliteration varied between 0.85 and 0.95 and 0.55 and 0.62. An average false-positive rate, meaning overestimation of nidus obliteration, of 0.08 and an average false-negative rate, meaning underestimation of nidus obliteration of 0.48, were found. CONCLUSIONS: MRA is insufficient to diagnose obliteration in the follow-up of bAVMs after radiosurgery. A remaining nidus diameter <10 mm seems to be the major limiting factor for reliable assessment of obliteration. We highly recommend follow-up DSA for definitive diagnosis of complete obliteration.

Extensive White Matter Changes After Stereotactic Radiosurgery for Brain Arteriovenous Malformations: A Prognostic Sign for Obliteration?

OBJECTIVE Perinidal high-signal-intensity changes on T2-weighted magnetic resonance imaging can be seen surrounding radiosurgically treated brain arteriovenous malformations (AVM). Occasionally, these signal intensity changes develop far beyond the irradiated volume. A retrospective analysis of both the pre- and postradiosurgery magnetic resonance imaging and angiographic studies was performed to analyze the cause of these extensive perinidal white matter changes. METHODS The pre- and postradiosurgical magnetic resonance imaging and angiographic studies of 30 patients with T2 high-signal-intensity changes surrounding a brain AVM were analyzed retrospectively. Patients were divided into 2 groups on the basis of the extension of the signal intensity changes within or beyond the 10-Gy isodose area. The angiographic analysis was focused on the venous drainage pattern (deep versus superficial), venous stenosis, and the number of draining veins before and after radiosurgery. In addition, the obliteration rate was determined for the 2 subgroups. RESULTS Fourteen patients (47%) showed high-signal-intensity changes far beyond the 10-Gy isodose area. A single draining vein was more often present in these patients with extensive T2 hyperintensity signal changes than in the other group. Obliteration was achieved in 12 (88%) of 14 patients with extensive signal intensity changes, as opposed to 8 (50%) of 16 patients in the other group. CONCLUSION High-signal-intensity changes after radiosurgery for brain AVMs, far beyond the 10-Gy isodose area on T2-weighted images, are especially seen in brain AVMs draining through a single vein. The higher occlusion rate of brain AVMs under these circumstances is well appreciated.

Acquired encephaloceles and epilepsy in osteopetrosis

SummaryOsteopetrosis is a condition in which there is a defect in bone resorption by osteoclasts. With thickening of the skull and skull base, the cranial capacity becomes compromised and skull foramina gradually occlude, resulting in a wide range of neurological symptoms and signs. We present a case of autosomal dominant osteopetrosis with temporal lobe epilepsy and nasal obstruction due to acquired bifrontal encephaloceles associated with a decreased intracranial capacity. Neurosurgical reconstruction of the frontal skull base alleviated the symptoms of epilepsy and nasal obstruction.