A shift from open to endovascular repair in the treatment of ruptured middle cerebral artery aneurysms: a single institution experience.

PURPOSE: Middle cerebral aneurysms were underrepresented in the two largest trials (BRAT and ISAT) for the treatment of ruptured intracranial aneurysms. Recent institutional series addressing the choice between endovascular or open repair for this subset of aneurysms are few and have not yielded a definitive conclusion. We compare clinical outcomes of patients presenting with acute subarachnoid hemorrhage from ruptured middle cerebral artery aneurysms undergoing either open or endovascular repair. METHODS: We conducted a retrospective review of 138 consecutive patients with ruptured middle cerebral artery aneurysms admitted into our institution from January 2008 to March 2019 to compare endovascular and open surgical outcomes. RESULTS: Of the ruptured middle cerebral artery aneurysms, 57 underwent endovascular repair while 81 were treated with open surgery. Over the study period, there was a notable shift in practice toward more frequent endovascular treatment of ruptured MCA aneurysms (31% in 2008 vs. 91% in 2018). At discharge (49.1% vs 29.6%; p = .002) and at 6 months (84.3% vs 58.6%; p = 0.003), patients who underwent endovascular repair had a higher proportion of patients with good clinical outcomes (mRS 0-2) compared to those undergoing open surgery. Long-term follow-up data (endovascular 54.9 ± 37.9 months vs clipping 18.6 ± 13.4 months) showed no difference in rebleeding (1.8% vs 3.7%, p = 0.642) and retreatment (5.3% vs 3.7%, p = 0.691) in both groups. CONCLUSION: Our series suggests equipoise in the treatment of ruptured middle cerebral artery aneurysms and demonstrates endovascular repair as a potentially feasible treatment strategy. Future randomized trials could clarify the roles of these treatment modalities.

The proximal balloon occlusion together with direct thrombus aspiration (protect plus) technique: Experience at a tertiary comprehensive stroke center.

BACKGROUND: Timely restoration of cerebral blood flow using reperfusion therapy is the most effective maneuver for salvaging penumbra. We re-evaluated the previously described PROTECT (PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration during stent retriever thrombectomy) Plus technique at a tertiary comprehensive stroke center. METHODS: We retrospectively analyzed all patients who underwent mechanical thrombectomy with stentrievers between May 2011 and April 2020. Patients were divided between those who underwent PROTECT Plus and those who did not (proximal balloon occlusion with stent retriever only). We compared the groups in terms of reperfusion, groin to reperfusion time, symptomatic intracranial hemorrhage (sICH), modified Rankin Scale (mRS) score at discharge. RESULTS: Within the study period, 167 (71.4%) PROTECT Plus and 67 (28.6%) non-PROTECT patients which met our inclusion criteria. There was no statistically significant difference in the number of patients with successful reperfusion (mTICI >2b) between the techniques (85.0% vs 82.1%; p = 0.58). The PROTECT Plus group had lower rates of mRS ≤2 at discharge (40.1% vs 57.6%; p = 0.016). The rate of sICH was comparable (p = 0.35) between the PROTECT Plus group (7.2%) and the non-PROTECT group (3.0%). CONCLUSION: The PROTECT Plus technique using a BGC, a distal reperfusion catheter and stent retriever is feasible for recanalization of large vessel occlusions. Successful recanalization, first-pass recanalization and complication rates are similar between PROTECT Plus and non-PROTECT stent retriever techniques. This study adds to an existing body of literature detailing techniques that use both a stent retriever and a distal reperfusion catheter to maximize recanalization for patients with large vessel occlusions.

Inflammatory Biomarkers and Intracranial Hemorrhage after Endovascular Thrombectomy.

BACKGROUND: Intracranial hemorrhage after endovascular thrombectomy is associated with poorer prognosis compared with those who do not develop the complication. Our study aims to determine predictors of post-EVT hemorrhage - more specifically, inflammatory biomarkers present in baseline serology. METHODS: We performed a retrospective review of consecutive patients treated with EVT for acute large vessel ischemic stroke. The primary outcome of the study is the presence of ICH on the post-EVT scan. We used four definitions: the SITS-MOST criteria, the NINDS criteria, asymptomatic hemorrhage, and overall hemorrhage. We identified nonredundant predictors of outcome using backward elimination based on Akaike Information Criteria. We then assessed prediction accuracy using area under the receiver operating curve. Then we implemented variable importance ranking from logistic regression models using the drop in Naegelkerke R2 with the exclusion of each predictor. RESULTS: Our study demonstrates a 6.3% SITS (16/252) and 10.0% NINDS (25/252) sICH rate, as well as a 19.4% asymptomatic (49/252) and 29.4% (74/252) overall hemorrhage rate. Serologic markers that demonstrated association with post-EVT hemorrhage were: low lymphocyte count (SITS), high neutrophil count (NINDS, overall hemorrhage), low platelet to lymphocyte ratio (NINDS), and low total WBC (NINDS, asymptomatic hemorrhage). CONCLUSION: Higher neutrophil counts, low WBC counts, low lymphocyte counts, and low platelet to lymphoycyte ratio were baseline serology biomarkers that were associated with post-EVT hemorrhage. Our findings, particularly the association of diabetes mellitus and high neutrophil, support experimental data on the role of thromboinflammation in hemorrhagic transformation of large vessel occlusions.

Endovascular treatment of cavernous carotid artery aneurysms: A 10-year, single-center experience.

BACKGROUND: Cavernous carotid artery aneurysms can be treated by several endovascular techniques including flow diversion (FD) and parent vessel occlusion (PVO). We reviewed our institution's consecutive series of endovascularly treated cavernous carotid artery aneurysms to compare these two modalities and their associated clinical and radiographic outcomes. METHODS: All patients harboring a cavernous carotid artery aneurysm treated by FD or PVO from January 2008 to December 2018 were enrolled. Data were collected retrospectively and analyzed on patient presentation, aneurysm dimensions, treatments and related complications, rate of aneurysm occlusion, sac regression, and outcomes. RESULTS: Fourteen patients were treated with FD and 12 underwent PVO subsequent to passing a balloon test occlusion. There was no significant difference between treatment modalities in aneurysmal occlusion (97.0 ± 8.4% (FD) vs. 100% (PVO), p = 0.23), degree of sac regression (62.5 ± 16.7% (FD) vs. 56.8 ± 24.3% (PVO), p = 0.49), or near-complete to complete symptom improvement (66.7% (FD) vs. 81.8% (PVO), p = 0.62). Major complications included subarachnoid hemorrhage from aneurysmal rupture in 1 (7.1%) patient post-FD and 2 (16.7%) ischemic strokes following PVO. CONCLUSIONS: Endovascular treatment of cavernous carotid artery aneurysms by FD or PVO are both effective and safe. There is insufficient evidence to recommend one technique over the other and decision making should be individualized to the patient, their aneurysm morphology, and operator experience.

Changes in Cerebral Perfusion with Induced Hypertension in Aneurysmal Subarachnoid Hemorrhage: A Pilot and Feasibility Study.

BACKGROUND: The effects of induced hypertension (IH) on cerebral perfusion after subarachnoid hemorrhage (SAH) are unclear. The objectives of this investigation are to: (1) determine whether there are differences in cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) measured with computed tomography perfusion (CTP) before and after IH; (2) evaluate differences in the presence of infarction and clinical outcome between patients with and without IH. METHODS: We performed a retrospective cohort analysis of 25 aneurysmal SAH patients. IH was initiated as per the standard institutional protocol when patients showed clinical symptoms of delayed cerebral ischemia (DCI). Differences in CBF, CBV, and MTT between early (<72 h after aneurysm rupture) and late (7-10 days after aneurysm rupture) CTP were quantified in patients with (n = 13) and without IH (n = 12). Outcome measures included cerebral infarction and clinical outcome at 3 months. RESULTS: Early MTT was significantly greater in the IH group compared to the no-IH group. There was no difference in early or late CBV or CBF between the two groups. In patients that received IH, there was a significant decrease in MTT between the early (7.0 ± 1.2 s) and late scans (5.8 ± 1.6 s; p = 0.005). There was no difference in the incidence of infarction (5/13 vs. 2/11) or poor outcome (3/11 vs. 6/13) between the IH and no-IH groups, respectively (p > 0.05). CONCLUSIONS: Elevated MTT is a significant factor for the development of DCI in patients eventually requiring IH therapy and is improved by IH treatment. Therapies to prevent DCI and improve clinical outcome may need to be initiated earlier, when cerebral perfusion abnormalities are first identified.

Association Between MRI Exposure During Pregnancy and Fetal and Childhood Outcomes.

IMPORTANCE: Fetal safety of magnetic resonance imaging (MRI) during the first trimester of pregnancy or with gadolinium enhancement at any time of pregnancy is unknown. OBJECTIVE: To evaluate the long-term safety after exposure to MRI in the first trimester of pregnancy or to gadolinium at any time during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Universal health care databases in the province of Ontario, Canada, were used to identify all births of more than 20 weeks, from 2003-2015. EXPOSURES: Magnetic resonance imaging exposure in the first trimester of pregnancy, or gadolinium MRI exposure at any time in pregnancy. MAIN OUTCOMES AND MEASURES: For first-trimester MRI exposure, the risk of stillbirth or neonatal death within 28 days of birth and any congenital anomaly, neoplasm, and hearing or vision loss was evaluated from birth to age 4 years. For gadolinium-enhanced MRI in pregnancy, connective tissue or skin disease resembling nephrogenic systemic fibrosis (NSF-like) and a broader set of rheumatological, inflammatory, or infiltrative skin conditions from birth were identified. RESULTS: Of 1 424 105 deliveries (48% girls; mean gestational age, 39 weeks), the overall rate of MRI was 3.97 per 1000 pregnancies. Comparing first-trimester MRI (n = 1737) to no MRI (n = 1 418 451), there were 19 stillbirths or deaths vs 9844 in the unexposed cohort (adjusted relative risk [RR], 1.68; 95% CI, 0.97 to 2.90) for an adjusted risk difference of 4.7 per 1000 person-years (95% CI, -1.6 to 11.0). The risk was also not significantly higher for congenital anomalies, neoplasm, or vision or hearing loss. Comparing gadolinium MRI (n = 397) with no MRI (n = 1 418 451), the hazard ratio for NSF-like outcomes was not statistically significant. The broader outcome of any rheumatological, inflammatory, or infiltrative skin condition occurred in 123 vs 384 180 births (adjusted HR, 1.36; 95% CI, 1.09 to 1.69) for an adjusted risk difference of 45.3 per 1000 person-years (95% CI, 11.3 to 86.8). Stillbirths and neonatal deaths occurred among 7 MRI-exposed vs 9844 unexposed pregnancies (adjusted RR, 3.70; 95% CI, 1.55 to 8.85) for an adjusted risk difference of 47.5 per 1000 pregnancies (95% CI, 9.7 to 138.2). CONCLUSIONS AND RELEVANCE: Exposure to MRI during the first trimester of pregnancy compared with nonexposure was not associated with increased risk of harm to the fetus or in early childhood. Gadolinium MRI at any time during pregnancy was associated with an increased risk of a broad set of rheumatological, inflammatory, or infiltrative skin conditions and for stillbirth or neonatal death. The study may not have been able to detect rare adverse outcomes.

Intra-Arterial Therapy and Post-Treatment Infarct Volumes: Insights From the ESCAPE Randomized Controlled Trial.

BACKGROUND AND PURPOSE: The goal of reperfusion therapy in acute ischemic stroke is to limit brain infarction. The objective of this study was to investigate whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in post-treatment infarct volume. METHODS: The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 315 enrolled subjects (endovascular treatment n=165; control n=150), 314 subject's infarct volumes at 24 to 48 hours on magnetic resonance imaging (n=254) or computed tomography (n=60) were measured. Post-treatment infarct volumes were compared by treatment assignment and recanalization/reperfusion status. Appropriate statistical models were used to assess relationship between baseline clinical and imaging variables, post-treatment infarct volume, and functional status at 90 days (modified Rankin Scale). RESULTS: Median post-treatment infarct volume in all subjects was 21 mL (interquartile range =65 mL), in the intervention arm, 15.5 mL (interquartile range =41.5 mL), and in the control arm, 33.5 mL (interquartile range =84 mL; P<0.01). Baseline National Institute of Health Stroke Scale (P<0.01), site of occlusion (P<0.01), baseline noncontrast computed tomographic scan Alberta Stroke Program Early CT score (ASPECTS) (P<0.01), and recanalization (P<0.01) were independently associated with post-treatment infarct volume, whereas age, sex, treatment type, intravenous alteplase, and time from onset to randomization were not (P>0.05). Post-treatment infarct volume (P<0.01) and delta National Institute of Health Stroke Scale (P<0.01) were independently associated with 90-day modified Rankin Scale, whereas laterality (left versus right) was not. CONCLUSIONS: These results support the primary results of the ESCAPE trial and show that the biological underpinning of the success of endovascular therapy is a reduction in infarct volume. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

The future of endovascular treatment: Insights from the ESCAPE investigators.

The ESCAPE trial demonstrated strong morbidity benefit and mortality reduction for endovascular stroke treatment. Following the release of the main results, the ESCAPE trial investigators convened at a 2-day close-out meeting in March 2015 in Banff, Alberta, Canada. Meeting discussions focused on system implications, procedural characteristics, and future directions. We report the proceedings of the meeting, which provide insights from the trialists into the issues of generalizability, treatment limitations, as well as future directions and opportunities in stroke care optimization.

Magnetic resonance susceptibility weighted imaging in neurosurgery: current applications and future perspectives.

Susceptibility weighted imaging (SWI) is a relatively new imaging technique. Its high sensitivity to hemorrhagic components and ability to depict microvasculature by means of susceptibility effects within the veins allow for the accurate detection, grading, and monitoring of brain tumors. This imaging modality can also detect changes in blood flow to monitor stroke recovery and reveal specific subtypes of vascular malformations. In addition, small punctate lesions can be demonstrated with SWI, suggesting diffuse axonal injury, and the location of these lesions can help predict neurological outcome in patients. This imaging technique is also beneficial for applications in functional neurosurgery given its ability to clearly depict and differentiate deep midbrain nuclei and close submillimeter veins, both of which are necessary for presurgical planning of deep brain stimulation. By exploiting the magnetic susceptibilities of substances within the body, such as deoxyhemoglobin, calcium, and iron, SWI can clearly visualize the vasculature and hemorrhagic components even without the use of contrast agents. The high sensitivity of SWI relative to other imaging techniques in showing tumor vasculature and microhemorrhages suggests that it is an effective imaging modality that provides additional information not shown using conventional MRI. Despite SWI's clinical advantages, its implementation in MRI protocols is still far from consistent in clinical usage. To develop a deeper appreciation for SWI, the authors here review the clinical applications in 4 major fields of neurosurgery: neurooncology, vascular neurosurgery, neurotraumatology, and functional neurosurgery. Finally, they address the limitations of and future perspectives on SWI in neurosurgery.

Randomized assessment of rapid endovascular treatment of ischemic stroke.

BACKGROUND: Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation. METHODS: We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group). Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. Workflow times were measured against predetermined targets. The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care (shift analysis). RESULTS: The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P<0.001). The primary outcome favored the intervention (common odds ratio, 2.6; 95% confidence interval, 1.7 to 3.8; P<0.001), and the intervention was associated with reduced mortality (10.4%, vs. 19.0% in the control group; P=0.04). Symptomatic intracerebral hemorrhage occurred in 3.6% of participants in intervention group and 2.7% of participants in control group (P=0.75). CONCLUSIONS: Among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment improved functional outcomes and reduced mortality. (Funded by Covidien and others; ESCAPE ClinicalTrials.gov number, NCT01778335.).

Evolving role of MRI in optimizing the treatment of multiple sclerosis: Canadian Consensus recommendations.

BACKGROUND: Magnetic resonance imaging (MRI) is increasingly important for the early detection of suboptimal responders to disease-modifying therapy for relapsing-remitting multiple sclerosis. Treatment response criteria are becoming more stringent with the use of composite measures, such as no evidence of disease activity (NEDA), which combines clinical and radiological measures, and NEDA-4, which includes the evaluation of brain atrophy. METHODS: The Canadian MRI Working Group of neurologists and radiologists convened to discuss the use of brain and spinal cord imaging in the assessment of relapsing-remitting multiple sclerosis patients during the treatment course. RESULTS: Nine key recommendations were developed based on published sources and expert opinion. Recommendations addressed image acquisition, use of gadolinium, MRI requisitioning by clinicians, and reporting of lesions and brain atrophy by radiologists. Routine MRI follow-ups are recommended beginning at three to six months after treatment initiation, at six to 12 months after the reference scan, and annually thereafter. The interval between scans may be altered according to clinical circumstances. CONCLUSIONS: The Canadian recommendations update the 2006 Consortium of MS Centers Consensus revised guidelines to assist physicians in their management of MS patients and to aid in treatment decision making.

Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times (ESCAPE) trial: methodology.

ESCAPE is a prospective, multicenter, randomized clinical trial that will enroll subjects with the following main inclusion criteria: less than 12 h from symptom onset, age > 18, baseline NIHSS >5, ASPECTS score of >5 and CTA evidence of carotid T/L or M1 segment MCA occlusion, and at least moderate collaterals by CTA. The trial will determine if endovascular treatment will result in higher rates of favorable outcome compared with standard medical therapy alone. Patient populations that are eligible include those receiving IV tPA, tPA ineligible and unwitnessed onset or wake up strokes with 12 h of last seen normal. The primary end-point, based on intention-to-treat criteria is the distribution of modified Rankin Scale scores at 90 days assessed using a proportional odds model. The projected maximum sample size is 500 subjects. Randomization is stratified under a minimization process using age, gender, baseline NIHSS, baseline ASPECTS (8-10 vs. 6-7), IV tPA treatment and occlusion location (ICA vs. MCA) as covariates. The study will have one formal interim analysis after 300 subjects have been accrued. Secondary end-points at 90 days include the following: mRS 0-1; mRS 0-2; Barthel 95-100, EuroQOL and a cognitive battery. Safety outcomes are symptomatic ICH, major bleeding, contrast nephropathy, total radiation dose, malignant MCA infarction, hemicraniectomy and mortality at 90 days.

Aneurysmal subarachnoid haemorrhage from a neuroimaging perspective.

Neuroimaging is a key element in the management of patients suffering from subarachnoid haemorrhage (SAH). In this article, we review the current literature to provide a summary of the existing neuroimaging methods available in clinical practice. Noncontrast computed tomography is highly sensitive in detecting subarachnoid blood, especially within 6 hours of haemorrhage. However, lumbar puncture should follow a negative noncontrast computed tomography scan in patients with symptoms suspicious of SAH. Computed tomography angiography is slowly replacing digital subtraction angiography as the first-line technique for the diagnosis and treatment planning of cerebral aneurysms, but digital subtraction angiography is still required in patients with diffuse SAH and negative initial computed tomography angiography. Delayed cerebral ischaemia is a common and serious complication after SAH. The modern concept of delayed cerebral ischaemia monitoring is shifting from modalities that measure vessel diameter to techniques focusing on brain perfusion. Lastly, evolving modalities applied to assess cerebral physiological, functional and cognitive sequelae after SAH, such as functional magnetic resonance imaging or positron emission tomography, are discussed. These new techniques may have the advantage over structural modalities due to their ability to assess brain physiology and function in real time. However, their use remains mainly experimental and the literature supporting their practice is still scarce.

Hemorrhagic epidermoid cyst in a patient with generalized tonic clonic seizure.

Epidermoid cysts account for approximately 1% of all intracranial tumors. Hemorrhage into an epidermoid cyst is extremely rare, and has only been reported a few times. To our knowledge, there are no reports of a hemorrhagic epidermoid cyst presenting with a first generalized tonic clonic seizure. We present a 68-year old female with an epidermoid cyst with intracystic hemorrhage who presented with a first time generalized tonic clonic seizure. When complicated with hemorrhage, the diagnosis of an epidermoid cyst is challenging and there is a potential for misdiagnosis.

Highly proliferative sellar chordoma with unusually rapid recurrence.

Chordomas are tumors of notochordal differentiation of low to intermediate grade malignancy. These tumors are typically slow growing, with an indolent but progressive clinical course. We present a case of a highly proliferative chordoma arising in a 73-year-old woman with unusually rapid clinical growth and aggressive histologic and immunohistochemical features. This patient had an unusually brief preclinical course and within 1 month of developing headaches presented to medical attention with diplopia. The resected chordoma showed uncommonly elevated mitotic activity, without the histologic hallmarks of de-differentiation. This proliferative activity correlated with elevated Ki67 staining (60%), B-cell leukemia/lymphoma1 (BCL1) expression (100%), and topoisomerase IIα staining (>95%). E-cadherin expression was also lost throughout the majority of the tumor. Other markers of epithelial mesenchymal transition (EMT) including vimentin, N-cadherin, Slug and Twist, were also strongly expressed in this aggressive tumor. The sellar component of the tumor recurred within a 2-month interval. The evaluation of the additional biomarkers, including makers of EMT studied in this, case may allow for identification of aggressive chordomas in which the tempo of disease is significantly more rapid than in typical cases of chordoma.