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Bradley A. Gross and Rose Du

OBJECTIVE

The aim of this paper is to define an overall cavernous malformation (CM) hemorrhage rate and risk factors for hemorrhage.

METHODS

The authors performed a systematic, pooled analysis via the PubMed database through October 2015 using the terms “cavernoma,” “cavernous malformation,” “natural history,” “bleeding,” and “hemorrhage.” English-language studies providing annual rates and/or risk factors for CM hemorrhage were included. Data extraction, performed independently by the authors, included demographic data, hemorrhage rates, and hemorrhage risk factors.

RESULTS

Across 12 natural history studies with 1610 patients, the mean age at presentation was 42.7 years old and 52% of patients (95% CI 49%–55%) were female. Presentation modality was seizure in 30% (95% CI 25%–35%), hemorrhage in 26% (95% CI 17%–37%), incidental in 17% (95% CI 9%–31%), and focal deficits only in 16% of cases (95% CI 11%–23%). CM location was lobar in 66% (95% CI 61%–70%), brainstem in 18% (95% CI 13%–24%), deep supratentorial in 8% (95% CI 6%–10%), and cerebellar in 8% (95% CI 5%–11%). Pooling 7 studies that did not assume CM presence since birth, the annual hemorrhage rate was 2.5% per patient-year over 5081.2 patient-years of follow-up (95% CI 1.3%–5.1%). Pooling hazard ratios across 5 studies that evaluated hemorrhage risk factors, prior CM hemorrhage was a significant risk factor for hemorrhage (HR 3.73, 95% CI 1.26–11.1; p = 0.02) while younger age, female sex, deep location, size, multiplicity, and associated developmental venous anomalies (DVAs) were not.

CONCLUSIONS

Although limited by the heterogeneity of incorporated reports and selection bias, this study found prior hemorrhage to be a significant risk factor for CM bleeding, while age, sex, CM location, size, multiplicity, and associated DVAs were not. Future natural history studies should compound annual hemorrhage rate with prospective seizure and nonhemorrhagic neurological deficit rates.

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Gabriel Zada, Rose Du and Edward R. Laws Jr.

Object

Endonasal approaches have become the gold standard intervention for many anterior and middle skull base tumors. The authors aimed to define some of the existing limitations of these approaches by reviewing their experience with complex sellar region tumors that were initially considered for both transsphenoidal and open skull base approaches and were thus deemed tumors at “the edge of the envelope.”

Methods

Between April 2008 and April 2010, 250 transsphenoidal operations were performed at Brigham and Women's Hospital. All cases were retrospectively reviewed to identify patients with complex sellar region tumors that were initially considered for, or soon thereafter required, an open craniotomy as the definitive treatment. The anatomical tumor characteristics that posed limitations to performing safe and effective endonasal skull base operations were reviewed.

Results

Thirteen cases exemplifying some of the existing limitations to achieving optimal surgical outcomes via transsphenoidal-based approaches are presented. The following 8 factors are separately discussed that repeatedly limited the extent of resection, increased the risk of the operation, and contributed to perioperative complications: significant suprasellar extension, lateral extension, retrosellar extension, brain invasion with edema, firm tumor consistency, involvement or vasospasm of the arteries of the circle of Willis, and encasement of the optic apparatus or invasion of the optic foramina.

Conclusions

Although the ability to approach and resect complex tumors using endonasal skull base techniques has evolved dramatically in recent years, several inherent tumor characteristics mandate extensive preoperative consideration. In selected cases these characteristics may lend support to selecting an open craniotomy as the initial operation.

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Alexander E. Ropper, Bradley A. Gross and Rose Du

Object

Type I spinal dural arteriovenous fistulas (SDAVFs) are low-flow vascular shunts fed by radicular arteries in patients who most often present with myelopathy. Although some fistulas are amenable to endovascular embolization, nearly all can be treated with direct microsurgical obliteration.

Methods

The authors reviewed their experience in treating 214 craniospinal arteriovenous malformations and/or fistulas over the last 8 years. Of these, 19 were spinal (9%), of which 15 (79%) were Type I SDAVFs. The authors reviewed the patients' epidemiological characteristics, presenting symptoms, and SDAVF angioarchitecture in all cases. They subsequently analyzed surgical obliteration rates and outcomes of all 11 patients who underwent fistula microsurgical obliteration.

Results

In all patients who underwent microsurgical treatment, complete angiographic obliteration of the fistula was achieved. At follow-up, 10 (91%) of 11 patients exhibited improvement, 1 patient (9%) was the same, and no patients were worse. Specifically, 8 (73%) of 11 patients had improvement in strength and sensation, 5 (71%) of 7 had improvement of bowel/bladder function, and 3 (60%) of 5 had improvement of preoperative paresthesias. There were no wound infections, CSF leaks, or permanent neurological deficits.

Conclusions

Microsurgical treatment of SDAVF provides direct access to the fistula point, allowing for high obliteration rates with excellent long-term improvement of preoperative deficits and limited periprocedural complications.

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Bradley A. Gross and Rose Du

Object

The purpose of this report was to provide overall arteriovenous malformation (AVM) hemorrhage rates and, with enhanced statistical power, to elucidate significant risk factors for hemorrhage.

Methods

The authors performed a meta-analysis via the PubMed database through January 2012 using the terms “AVM,” “arteriovenous malformation,” “natural history,” “bleed,” and “hemorrhage.” Additional studies were identified through reference searches in each reviewed article. English language studies providing annual hemorrhage rates for AVMs were included. Data extraction, performed independently by the authors, included demographic data, hemorrhage rates, and hazard ratios for hemorrhage risk factors. The analysis was performed using a random effects model.

Results

Nine natural history studies with 3923 patients and 18,423 patient-years of follow-up were identified for analysis. The overall annual hemorrhage rate was 3.0% (95% CI 2.7%–3.4%). The rate of hemorrhage was 2.2% (95% CI 1.7%–2.7%) for unruptured AVMs and 4.5% (95% CI 3.7%–5.5%) for ruptured AVMs. Prior hemorrhage (HR 3.2, 95% CI 2.1–4.3), deep AVM location (HR 2.4, 95% CI 1.4–3.4), exclusively deep venous drainage (HR 2.4, 95% CI 1.1–3.8), and associated aneurysms (HR 1.8, 95% CI 1.6–2.0) were statistically significant risk factors for hemorrhage. Any deep venous drainage (HR 1.3, 95% CI 0.9–1.75) and female sex (HR 1.4, 95% CI 0.6–2.1) demonstrated a trend toward an increased risk of hemorrhage that was not statistically significant. Small AVM size and older patient age were not significant risk factors for hemorrhage.

Conclusions

Arteriovenous malformations with prior hemorrhage, deep location, exclusively deep venous drainage, and associated aneurysms have greater annual hemorrhage rates than their counterparts, influencing surgical decision making and the selection of radiosurgery for these lesions.

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Bradley A. Gross and Rose Du

Object

Owing to their rarity, demographics, natural history, and treatment, results for spinal juvenile (Type III) extradural-intradural arteriovenous malformations (AVMs) are frequently only provided in case report format.

Methods

A pooled analysis was performed utilizing the PubMed database through April 2013. Individualized patient data were extracted to elucidate demographics, hemorrhage risk, and treatment result information.

Results

Twenty-nine studies describing 51 patients were included. The mean age at presentation was 15.0 ± 10.5 years with a slight male predilection (63%, 1.7:1 sex ratio). Presentation modality included progressive deficits in 35%, hemorrhage in 31%, acute deficits not attributed to hemorrhage in 22%, and asymptomatic/incidental in 12% of patients. The annual hemorrhage rate was 2.1%; statistically significant risk factors for hemorrhage included presentation age (HR 0.39 [95% CI 0.18–0.87]) and associated aneurysms (HR 8.74 [95% CI 1.76–43.31]). Seventy-seven percent of patients underwent treatment; after a mean follow-up of 2.6 ± 3.2 years, 73% were improved, 10% were the same, and 17% were worse neurologically. Of 25 cases with described angiographic results, 8 lesions were obliterated (32%). Of these 25 patients, 8 had AVMs with associated aneurysms, and the aneurysm was obliterated in all 8 patients. Over the course of 57.9 patient-years of follow-up, including 55.3 patient-years for partially treated AVMs, no hemorrhages were described, reflecting a trend toward protection from hemorrhage after treatment (p = 0.12, likelihood ratio test).

Conclusions

Spinal juvenile (Type III) extradural-intradural AVMs commonly present symptomatically. Associated arterial aneurysms increase their hemorrhage risk, and protection from hemorrhage may be achieved from partial obliteration of these lesions, particularly if targeted toward associated aneurysms.

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Bradley A. Gross, Alexander E. Ropper and Rose Du

Object

The association of aneurysms and cerebral arteriovenous malformations is well established in the literature. Aside from a small number of case reports and small patient series, this association has not been well explored with cerebral dural arteriovenous fistulas (DAVFs). This study was designed to elucidate this relationship in the authors' own patient cohort with DAVFs.

Methods

Cerebral angiograms of 56 patients with 70 DAVFs were reviewed for the presence of cerebral aneurysms. Background patient demographics, mode of presentation, and DAVF and aneurysm angiographic characteristics were noted.

Results

Twelve patients (21%) had aneurysms in addition to their DAVF. Three patients had multiple aneurysms. Of a total of 15 aneurysms, 5 (33%) occurred on DAVF feeding arteries and 10 (67%) were in remote locations. These patients more commonly presented with hemorrhage (58% vs 20% for those without aneurysms). Aneurysms were associated with DAVFs in any location (feeding artery or remote), but flow-related feeding artery aneurysms were more likely to be associated with Borden Type III DAVFs.

Conclusions

Twenty-one percent of patients with cerebral DAVFs also had aneurysms in this patient cohort. It is thus prudent to perform 6-vessel digital subtraction angiography on patients with DAVFs to rule out potential feeding artery and remote aneurysms. This association may be explained by flow-related phenomena, the initial inciting event leading to DAVF formation, as well as a potential genetic component or predisposition to develop these lesions.

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Giuseppe Lanzino

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Bradley A. Gross, Ning Lin, Rose Du and Arthur L. Day

Literature reports on the natural history of cerebral cavernous malformations (CMs) are numerous, with considerable variability in lesion epidemiology, hemorrhage rates, and risk factors for hemorrhage. In this review, the authors performed a meta-analysis of 11 natural history studies. The overall male-to-female ratio was 1:1, and the mean age at presentation was 30.6 years. Overall, 37% of patients presented with seizures, 36% with hemorrhage, 23% with headaches, 22% with focal neurological deficits, and 10% were asymptomatic. Some patients had more than one symptom. Seizure presentation was most prevalent among supratentorial CMs, while focal neurological deficits were common in patients with infratentorial CMs. By location, CMs were in the cerebral hemispheres (66%), brainstem (18%), basal ganglia or thalamus (8%), cerebellum (6%), and other (2.5% [combined supra- and infratentorial, callosal or insular]). Overall, 19% of patients harbored multiple intracranial CMs, and 9% had radiographically apparent associated developmental venous anomalies. An overall annual hemorrhage rate of 2.4% per patient-year (range 1.6%–3.1%) was identified across 3 studies. Prior hemorrhage and female sex were risk factors for bleeding, while CM size and multiplicity did not affect hemorrhage rates. Although not impacting the hemorrhage rate itself, deep location was a risk factor for increased clinical aggressiveness.

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Bradley A. Gross, Pui Man Rosalind Lai and Rose Du

Object

The rates and risk factors for external ventricular drain (EVD) placement and long-term shunt dependence in patients with ruptured arteriovenous malformations (AVMs) have not been systematically studied. In this study the authors evaluated the rates of EVD placement and shunt dependence, and risk factors for them, in a cohort of patients with ruptured AVMs.

Methods

The records of 87 consecutive patients with ruptured AVMs were reviewed for patient demographics, hemorrhage pattern, AVM angioarchitectural features, and surgical treatment. Univariate and multivariate logistic regression analyses were performed to evaluate risk factors for EVD placement, permanent shunt dependence, and long-term outcome (as measured by the modified Rankin Scale).

Results

Thirty-eight patients (44%) required EVD placement, and 16 (18%) required a permanent shunt. Statistically significant risk factors for EVD placement in the univariate analysis included initial Glasgow Coma Scale (GCS) score (p = 0.002), the presence of intraventricular hemorrhage (IVH; p < 0.001), AVM-associated aneurysms (p = 0.002), and early surgery (p = 0.01). Multivariate analysis revealed only AVM-associated aneurysms as statistically significant (p = 0.006). Risk factors for shunt placement included initial GCS score (p = 0.003), IVH (p = 0.01), deep supratentorial location (p = 0.034), and associated aneurysms (p = 0.03). Multivariate analysis revealed initial GCS score as a statistically significant risk factor (p = 0.041) as well as a strong trend for associated aneurysms (p = 0.06). Patient age, sex, associated subarachnoid hemorrhage, AVM grade, AVM size, and deep venous drainage were not associated with EVD placement or long-term shunt dependence.

Conclusions

Hydrocephalus from AVM rupture was associated with initial GCS score, IVH, and AVM-associated aneurysms. Arteriovenous malformations with associated aneurysms thus not only have a greater risk of hemorrhage but also a greater risk of hemorrhage-associated morbidity as a result of hydrocephalus.