Factors Contributing to Major Neurological Complications From Vein of Galen Malformation Embolization.

Importance: Major neurological complications from the embolization of vein of Galen malformations (VOGMs) are poorly understood. We provide a detailed analysis of contributors to periprocedural neurological complications and lessons learned. Objective: To assess the rate of major periprocedural neurological complications following VOGM embolization with major procedural and strategic contributors. Design, Setting, and Participants: This retrospective cohort study was conducted at a quarternary referral pediatric hospital (Hospital for Sick Children; Toronto, Ontario, Canada) from January 1999 to December 2018 with a mean clinical follow-up of 44.7 months; all children with VOGM diagnosed and/or treated were eligible (n = 48). Thirty-three patients who underwent endovascular treatment were included. Interventions: Endovascular staged transarterial embolization performed in 33 patients over 91 sessions. Main Outcomes and Measures: The primary outcome was the rate of periprocedural neurological complications (occurring within 1 week of embolization). The secondary outcomes were mortality, long-term neurological outcomes, and contributing anatomical and management factors to neurological complications. Results: Of 33 patients who underwent embolization (31 boys [64.6%]; 17 girls [35.4%]; median age at first embolization, 4 months [range, 0-29 months]), 10 patients (30.3%) developed major periprocedural neurological complications. Five of these patients died. Univariate logistic regression analyses identified internal cerebral vein drainage to the main venous sac of the VOGM and use of a microcatheter with a distal outer diameter of more than 2.0F as significant predictors of poor neurological outcomes. Lessons learned from our experience include the need to assess the internal cerebral vein drainage pattern on preprocedural magnetic resonance venography, avoidance of excessive embolization into the venous sac, treatment of more distal fistulae before proximal fistulae to avoid a sump effect, and preferably use of smaller (<2.0F outer diameter) microcatheters in neonatal embolization procedures. Conclusions and Relevance: In this cohort, 10 patients with VOGM treated with embolization (30.3%) experienced major periprocedural neurological complications, half of whom died. While these outcomes are superior to historic conservative and surgical treatment results, ongoing improvements in treatment and pretreatment diagnostic approaches are needed. Awareness of the lessons learned from our experience can help to avoid similar complications in the future for this vulnerable population.

Clinical course of untreated cerebral cavernous malformations: a meta-analysis of individual patient data.

BACKGROUND: Cerebral cavernous malformations (CCMs) can cause symptomatic intracranial haemorrhage (ICH), but the estimated risks are imprecise and predictors remain uncertain. We aimed to obtain precise estimates and predictors of the risk of ICH during untreated follow-up in an individual patient data meta-analysis. METHODS: We invited investigators of published cohorts of people aged at least 16 years, identified by a systematic review of Ovid MEDLINE and Embase from inception to April 30, 2015, to provide individual patient data on clinical course from CCM diagnosis until first CCM treatment or last available follow-up. We used survival analysis to estimate the 5-year risk of symptomatic ICH due to CCMs (primary outcome), multivariable Cox regression to identify baseline predictors of outcome, and random-effects models to pool estimates in a meta-analysis. FINDINGS: Among 1620 people in seven cohorts from six studies, 204 experienced ICH during 5197 person-years of follow-up (Kaplan-Meier estimated 5-year risk 15·8%, 95% CI 13·7-17·9). The primary outcome of ICH within 5 years of CCM diagnosis was associated with clinical presentation with ICH or new focal neurological deficit (FND) without brain imaging evidence of recent haemorrhage versus other modes of presentation (hazard ratio 5·6, 95% CI 3·2-9·7) and with brainstem CCM location versus other locations (4·4, 2·3-8·6), but age, sex, and CCM multiplicity did not add independent prognostic information. The 5-year estimated risk of ICH during untreated follow-up was 3·8% (95% CI 2·1-5·5) for 718 people with non-brainstem CCM presenting without ICH or FND, 8·0% (0·1-15·9) for 80 people with brainstem CCM presenting without ICH or FND, 18·4% (13·3-23·5) for 327 people with non-brainstem CCM presenting with ICH or FND, and 30·8% (26·3-35·2) for 495 people with brainstem CCM presenting with ICH or FND. INTERPRETATION: Mode of clinical presentation and CCM location are independently associated with ICH within 5 years of CCM diagnosis. These findings can inform decisions about CCM treatment. FUNDING: UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.

Challenges in the management of ruptured and unruptured brainstem arteriovenous malformations: outcome after conservative, single-modality, or multimodality treatments.

BACKGROUND: Brainstem arteriovenous malformations are challenging lesions, and benefits of treatment are uncertain. OBJECTIVE: To study the clinical course of Brainstem arteriovenous malformations and the influence of treatments on outcome. METHODS: We reviewed a prospective series of 31 brainstem arteriovenous malformations. Demographic, morphological, and clinical characteristics were recorded. Factors determining initial and final outcomes (modified Rankin Scale), results of treatments (cure rates, complications), and disease course were analyzed. RESULTS: Brainstem arteriovenous malformations were symptomatic and bled in 93% and 61% of cases, respectively. Examination was abnormal and initial modified Rankin Scale score was < 3 in 71% and 86% of patients, respectively. The average follow-up time was 6.2 years, and 26% of patients rebled (5.9 %/y). Treatment modalities included conservative, radiosurgical, endovascular, surgical, and multimodality treatment in 13%, 58%, 35%, 16%, and 26% of cases, respectively. The obliteration rate was 60% overall and 39% after radiosurgery, 40% after embolization, and 75% after microsurgery, with respective complication-free cure rates of 71%, 50%, and 0%. Overall procedural mortality and morbidity were 2.3% and 18.6%, respectively. Final modified Rankin Scale score was < 3 in 77% of cases. Neurological deterioration (35%) was related to treatment complications in 74% of cases with a negative impact of surgery (P = .04), palliative embolization (odds ratio = 16), and multimodality treatments (odds ratio = 24). Radiosurgery was inversely associated with worsening (odds ratio = 0.06). CONCLUSION: Brainstem arteriovenous malformations require individualized treatment decisions. Single-modality treatments with a reasonable chance of complete cure and low complication rate (such as radiosurgery) should be favored.

Microsurgical glue embolectomy of the middle cerebral artery following embolization of a maxillofacial arteriovenous malformation.

With increasing application of endovascular therapies worldwide, the management of procedure-related complications has become increasingly important. Of particular interest is the surgical management of complications refractory to endovascular recanalization. Here, we present the unique surgical management of an inadvertent intracranial glue embolus following urgent glue embolization of a maxillofacial arteriovenous malformation. This is the first report to document management of this complication. An arteriotomy was performed and the glue, despite being adhered to the vessel intima, was retrieved in its entirety from the middle cerebral artery (MCA). Following the procedure, the patient developed a new thrombus at the previous glue site, likely related to endothelial injury. With post-operative heparin therapy, the patient recovered to baseline neurological state. This report demonstrates that microsurgical arteriotomy and glue embolectomy of the MCA is feasible, safe and may be useful in the management of complications of inadvertent intracranial glue embolization.

Severely impaired cerebrovascular reserve in patients with cerebral proliferative angiopathy.

OBJECT: Cerebral proliferative angiopathy (CPA) has been morphologically distinguished from classically appearing brain arteriovenous malformations (AVMs) by exhibition of functional brain parenchyma that is intermingled with abnormal vascular channels. The presence of oligemia in this intralesional brain tissue may suggest ischemia, which is not detected in classic brain AVMs. The authors hypothesized that patients with CPA would exhibit a greater impairment of cerebrovascular reserve in neuronal tissue surrounding the true nidus compared with those with brain AVMs. METHODS: Four patients with CPA, 10 patients with brain AVMs and seizures, and 12 young healthy individuals were studied. The 4 patients with CPA underwent blood oxygen level-dependent MR imaging examinations while applying normoxic step changes in end-tidal CO(2) to obtain quantitative cerebrovascular reactivity measurements. RESULTS: Patients with a CPA lesion exhibited severely impaired perilesional cerebrovascular reserve in comparison with patients with brain AVMs and seizures (0.10 ± 0.03 vs 0.16 ± 0.03, respectively; p < 0.05), and young healthy individuals (0.10 ± 0.03 vs 0.21 ± 0.06, respectively; p < 0.01). CONCLUSIONS: This study demonstrated severely impaired cerebrovascular reserve in the perilesional brain tissue surrounding the abnormal vessels of patients with CPA. This finding may provide an additional means to distinguish CPA from classic brain AVMs.

Impact of individual intracranial arterial aneurysm morphology on initial obliteration and recurrence rates of endovascular treatments: a multivariate analysis.

OBJECT: The goal was to investigate whether morphological features of aneurysms can be identified that determine initial success and recurrence rates of coiled aneurysms of the basilar artery tip, the posterior communicating artery (PCoA), and the anterior communicating artery. METHODS: The authors evaluated 202 aneurysms in connection with their pretreatment morphological features including size, neck-to-dome ratio, angulation of the aneurysm in relation to the parent artery, orientation of the aneurysm dome, and associated anatomical variations. The mean follow-up was 19 months (range 6-96 months) after endovascular coil occlusion. Using multivariate logistic regression, probabilities for initial complete occlusion and long-term stability of the treatment were calculated. RESULTS: Recanalization occurred in 49 of 202 cases. Favorable factors for long-term stability included small aneurysms with small necks. However, additional factors related to local hemodynamic forces could be identified for the different aneurysm locations, which may influence initial success rates and long-term stability of aneurysm treatment with endovascular coiling. These factors were a medial dome orientation and a symmetrical disposition of both A(1) segments (for the anterior communicating artery), a posteroinferior dome orientation and a small-size PCoA (for the PCoA), and a cranial symmetrical fusion (for the basilar artery tip). CONCLUSIONS: A detailed pretreatment analysis of morphological features of aneurysms may help to determine those aneurysms that are more prone to recurrence, which could add to the treatment decision and the follow-up algorithm.

Malformations of the fetal dural sinuses.

BACKGROUND: Dural sinus malformation (DSM) is a term used to describe congenital vascular malformations characterized by massive dilation of one or more dural sinuses: these dilatations are typically associated with arteriovenous shunts. Such malformations can present antenatally but their early natural history and anatomy is poorly defined. METHODS: We reviewed five years of autopsy experience and retrieved three primary vascular malformations of the fetal dural sinuses with ultrasound, magnetic resonance imaging (MRI) and post-mortem correlation. RESULTS: Fetal ultrasound and MRI obtained between 19 and 23 weeks gestational age demonstrated in all cases dilation of the dural sinuses. In two cases vascular thromboses were present in either the dilated dural sinus (one of three) or the associated arteriovenous fistula (one of three). All cases were autopsied at 22-23 weeks gestational age. In one there was imaging and autopsy evidence of remodeling of the dural sinuses associated with a pial arteriovenous fistula. In two cases, no arteriovenous malformation was identified on initial imaging, but only became evident at autopsy. One case showed morphological overlap with vein of Galen aneurysmal malformation, with a midline arteriovenous shunt and vein of Galen ectasia. The other demonstrated a perisylvian dural arteriovenous fistula. CONCLUSION: In utero thrombosis of feeding vascular malformations or of the dural sinus malformation may be prominent. The early in utero developmental trajectory of dural sinus malformation (DSM) is poorly defined and deserves further study.

The natural history and predictive features of hemorrhage from brain arteriovenous malformations.

BACKGROUND AND PURPOSE: Patients harboring brain arteriovenous malformations (bAVMs) are at a lifelong risk for hemorrhagic strokes, but the natural history is poorly understood. We examined the impact of demographic and angiographic features on the likelihood of future hemorrhage. METHODS: A prospectively accrued database of bAVM patients maintained at the Toronto Western Hospital was analyzed; 678 consecutive, prospectively enrolled bAVM patients were followed for 1931.7 patient-years. The rate of hemorrhage over long-term follow-up was recorded. The impact of baseline clinical and radiographic features and partial treatment on time to hemorrhage were analyzed using survival analysis. Neurological outcome after hemorrhage was assessed using the Glasgow Outcome Score. RESULTS: Hemorrhage rates were 4.61% per year for the entire cohort (n=678), 7.48% per year for bAVMs with initial hemorrhagic presentation (n=258), 4.16% per year for initial seizure presentation (n=260), 3.99% per year for patients not harboring aneurysms (n=556), 6.93% per year for patients with associated aneurysms (n=122), and 5.42% per year for bAVMs with deep venous drainage (n=365). Hemorrhagic presentation was a significant independent predictor of future hemorrhage (HR, 2.15; P<0.01), whereas associated aneurysms (HR, 1.59; P=0.07) and deep venous drainage (HR, 1.59; P=0.07) showed a trend toward significance. Hemorrhage risk was unchanged in patients who underwent partial arteriovenous malformation embolization (n=211; HR, 0.875; P=0.32). CONCLUSIONS: Brain arteriovenous malformations presenting with hemorrhage, with deep venous drainage, or associated aneurysms have approximately 2-fold greater likelihood of a future hemorrhage. Partial treatment by embolization does not alter these risks. This natural history should be taken into account in the treatment strategy.

Wall enhancement, edema, and hydrocephalus after endovascular coil occlusion of intradural cerebral aneurysms.

OBJECT: Symptomatic local inflammation, aseptic meningitis, and hydrocephalus are reported in a group of patients treated with second generation/modified platinum coils. The purpose of this study was to define the frequency and determinants of magnetic resonance (MR) imaging findings of aneurysm wall enhancement, perianeurysmal edema, and hydrocephalus in a cohort of coil-embolized intradural cerebral aneurysms treated with bare platinum or modified platinum coils (Matrix or HydroCoils). METHODS: The authors retrospectively reviewed 359 Gd-enhanced MR follow-up studies of 181 treated aneurysms (125 ruptured) for mural enhancement. Univariate and multivariate logistic regression analyses were used to define mural enhancement associations with demographic, clinical, angiographic, treatment, and follow-up data. Embolization-related edema and hydrocephalus were defined in 95 MR imaging studies of 56 unruptured aneurysms. RESULTS: Asymptomatic wall enhancement was observed in lesions treated with all coil types, occurring in 21 (18.6%) of 113 bare platinum coil-treated aneurysms. Independent associations were HydroCoil treatment (odds ratio [OR] 9.75, 95% confidence interval [CI] 3.45-30.75) and increasing aneurysm size (OR 3.58, 95% CI 1.99-6.95). Five (8.9%) unruptured aneurysms had asymptomatic de novo edema, and 3 (5.3%) demonstrated hydrocephalus; all had been treated with HydroCoils. Hydrocephalus presentation was delayed (8-31 months) and symptomatic in 2 patients. CONCLUSIONS: Asymptomatic aneurysm wall enhancement occurred in 18.6% of embolizations performed with bare platinum coils, and probably represents a normal healing response. Perimural edema and hydrocephalus were observed only in patients treated with HydroCoils, but have been reported in patients treated with other modified platinum coils. These symptoms appear to represent an exaggerated inflammatory response during aneurysm healing. Increased vigilance for delayed hydrocephalus is required. Judicious clinical use of modified platinum coils is warranted until results of randomized trials are published.

Diagnostic characteristics and management of intracranial aneurysms in children.

Childhood aneurysms have special characteristics different from adults' aneurysms. Their features were found to significantly differ from aneurysms in adults especially in their gender prevalence, location, morphology and underlying etiology. Treatment options include both surgical and endovascular methods. Whenever possible, endovascular treatment for pediatric aneurysms is the recommended approach, since it offers both reconstructive and deconstructive techniques, durable results and better clinical outcome.

Arterial ischemic stroke in children.

Stroke in children is relatively rare. Advances in the clinical recognition and radiographic diagnosis of ischemic stroke have increased the frequency of the diagnosis in infants and children and have raised the need for immediate therapy. A vast amount of data has recently become available through basic research and neuroimaging techniques shedding new light on the chain of events that occur in ischemic stroke in animal models and in the adult population. Whether this new information can also be applied to the pediatric population remains to be seen, but it is likely that the active management of children with acute ischemic stroke in the near future will include brain protection, brain reperfusion, and prevention measures.

Cerebral sinovenous thrombosis in children.

Sinovenous thrombosis in children is rare, and the symptoms and signs are nonspecific especially in the neonatal population. MR imaging seems to be the most sensitive for accurate diagnosis of dural sinus thrombosis. General medical and neurologic supportive care is the mainstay of treatment. However, more active medical treatment such as anticoagulation, as well as an aggressive form of treatment such as retrograde transvenous fibrinolytic therapy, in children whose condition declines despite adequate anticoagulation therapy can be justified.

Analysis of cost related to clinical and angiographic outcomes of aneurysm patients enrolled in the international subarachnoid aneurysm trial in a North American setting.

OBJECTIVE: The goal of this study was to compare, in a North American setting, the cost-effectiveness of neurosurgical clipping versus endovascular coiling treatment of ruptured intracranial aneurysms. A secondary goal was to assess the clinical outcomes of patients enrolled into the International Subarachnoid Aneurysm Trial (ISAT) from the largest contributing North American center. METHODS: Of 230 patients with ruptured intracranial aneurysms, 62 were randomized into ISAT at our institution. Of these, 30 were randomized to endovascular coiling and 32 to neurosurgical clipping. For these, we evaluated the costs of treatment related to all aspects of the inpatient stay, the clinical outcomes at 2 months and at 1 year using the modified Rankin Scale, and the radiological outcomes at 6 months after Guglielmi detachable coiling. RESULTS: There were no significant differences in the total cost of treatment between the endovascular group and the neurosurgical clipping group. The benefits of apparent decrease in length of stay in the endovascular group were offset by higher procedure costs. There were no significant differences in clinical outcomes at 2 months and at 1 year. At 6 months after coiling, 15 (50%) of 30 aneurysms were completely obliterated, and 19 (63%) of 30 were angiographically stable. CONCLUSION: The high procedure costs of endovascular coiling tended to offset apparent reductions in length of stay. Long-term follow-up is indicated both for costs incurred after initial treatment and for clinical outcome in patients with incompletely obliterated aneurysms.

Separation of craniopagus twins in the era of modern neuroimaging, interventional neuroradiology, and frameless stereotaxy.

INTRODUCTION: Craniopagus twinning is a rare embryological event occurring in 1 in 2.5 million births. CASE REPORT: We present our recent experience with the separation of total vertical craniopagus twins in the modern era of neuroimaging and interventional neuroradiology. Three-dimensional CT images revealed the twins' heads were axially rotated 30 degrees. MRI showed deficient dura between the brains of the twins, and some sharing of parietal brain tissue. Cerebral angiography showed a dominant arterial circulation of one twin with unilateral middle cerebral artery (MCA) branches feeding the other twin. The twins shared a common superior sagittal sinus in its middle segment where a circular sinus was formed. Prior to surgery, endovascular separation of the twins' arterial and venous circulations was achieved in part using tantalum coils for the MCA feeders in one twin, and balloon occlusion of the anterior superior sagittal sinus of the other. Using the ISG wand intraoperatively, surgery proceeded stepwise and included the circumferential removal of bone and opening of the dura, separation of the twins' brains along leptomeningeal planes, and identification of the major draining veins from the superficial cerebral cortex. DISCUSSION: The separation of craniopagus twins demands a multidisciplinary team approach. Utilizing preoperative neuroendovascular techniques to occlude shared vascular anastomotic channels, complex total vertical craniopagus twins can now be successfully separated in a one-stage procedure.