Two surgical strategies (early carotid reperfusion vs. Central aortic repair-first) of acute type a aortic dissection complicated with cerebral malperfusion syndrome: a meta-analysis and systematic review.

OBJECTIVE: Cerebral malperfusion (CM) is a common comorbidity in acute type A aortic dissection (ATAAD), which is associated with high mortality and poor neurological prognosis. This meta-analysis investigated the surgical strategy of ATAAD patients with CM, aiming to compare the difference in therapeutic effectiveness between the central repair-first and the early reperfusion-first according to clinical outcomes. METHODS: The meta-analysis and systematic review was conducted based on studies sourced from the PubMed, Embase, and Cochrane literature database, in which cases of ATAAD with CM underwent surgical repair were included. Data for baseline characteristics, mortality, survival were extracted, and risk ratio (RR) values and the pooled mortality were calculated. RESULTS: A total of 17 retrospective studies were analyzed, including 1010 cases of ATAAD with CM underwent surgical repair. The pooled early mortality in early reperfusion group was lower (8.1%; CI, 0.02 to 0.168) than that in the central repair group (16.2%; CI, 0.115 to 0.216). The pooled long-term mortality was 7.9% in the early reperfusion cohort and 17.4% the central repair-first cohort, without a statistically significant heterogeneity (I [2] = 51.271%; p = 0.056). The mean time of symptom-onset-to-the-operation-room in all the reports was 8.87 ± 12.3 h. CONCLUSION: This meta-analysis suggested that early reperfusion-first may achieved better outcomes compared to central repair-first in ATAAD patients complicated with CM to some extent. Early operation and early restoration of cerebral perfusion may reduce the occurrence of some neurological complications. TRIAL REGISTRATION: The meta-analysis was registered in the International Prospective Register of Systematic Reviews database (No. CRD CRD42023475629) on Nov. 8th, 2023.

The Epidemiological Burden of Neurovascular Pathology in Nigeria: A Systematic Review and Pooled Patient-Level Analysis.

OBJECTIVE: Vascular neurosurgery has developed significantly in Nigeria, but its burden and challenges remain unclear. This study systematically reviewed vascular neurosurgical literature from Nigeria. METHODS: Four research databases and gray literature sources were searched from 1962-2021. ROBINS-I tool was used to assess risk of bias. Descriptive, narrative, and statistical analyses were conducted on all variables. Where appropriate, paired t-tests and Chi-squared independence tests were used (α = 0.05). RESULTS: 56 articles were included and 3203 patients pooled for analysis. Risk of bias was moderate-high. Most articles were published over the last 20 years with retrospective cohort studies and case reports being the most common study designs. The cohort had a relatively even gender split and an average age of 49 years (±22). Cerebrovascular accidents accounted for over 85% of diagnoses, with most etiologies being traumatic. Headache and motor deficit were the most prevalent clinical features. X-ray and carotid angiography were the most commonly reported imaging modalities, closely followed by computed tomography (CT) and CT angiography. The top two radiological diagnoses were ischemic cerebrovascular disease and intracerebral hematoma. Aneurysmal clipping and hematoma evacuation were the most commonly reported treatment modalities. Outcome at last follow-up was favorable in 48%. The mortality rate was 6%. Post-treatment complications included chest infection and rebleeding. CONCLUSIONS: This study illustrates the epidemiological burden of neurovascular pathology (based on the available data in published literature) in Nigeria, and raises awareness amongst service providers and researchers of the attendant challenges and epochal trends seen within vascular neurosurgery in Nigeria.

Advances in the Endovascular Management of Cerebrovascular Disease.

The field of endovascular neurosurgery has experienced remarkable progress over the last few decades. Endovascular treatments have continued to gain traction as the advancement of technology, technique, and procedural safety has allowed for the expansion of treatment indications of various cerebrovascular pathologies. Interventions such as the coiling of intracranial aneurysms, carotid artery stenting, mechanical thrombectomy in the setting of ischemic stroke, and endovascular embolization of arteriovenous malformations have all seen transformations in their safety and efficacy, expanding the scope of endovascularly treatable conditions and offering new hope to patients who may have otherwise not been candidates for surgical intervention. Despite this notable progress, challenges persist, including complications associated with device deployment and questions regarding long-term outcomes. This article explores the advancements in endovascular neurosurgical techniques, highlighting the impact on patient care, outcomes, and the evolution of traditional surgical methods.

Vertebral Artery to Middle Cerebral Artery Bypass for Flow Augmentation.

BACKGROUND AND IMPORTANCE: Extracranial-intracranial bypass remains an enduring procedure for a select group of patients suffering from steno-occlusive cerebrovascular disease. Although the superficial temporal artery (STA) to middle cerebral artery (MCA) bypass is most familiar among neurosurgeons, particular circumstances preclude the use of an STA donor. In such cases, alternative revascularization strategies must be pursued. CLINICAL PRESENTATION: A 63-year-old female presented with symptoms of hemodynamic insufficiency and was found to have left common carotid artery occlusion at the origin. She experienced progressive watershed ischemia and pressure-dependent fluctuations in her neurological examination despite maximum medical therapy. The ipsilateral STA was unsuitable for use as a donor vessel. We performed an extracranial vertebral artery (VA) to MCA bypass with a radial artery interposition graft. CONCLUSION: This technical case description and accompanying surgical video review the relevant anatomy and surgical technique for a VA-MCA bypass. The patient was ultimately discharged home at her preoperative neurological baseline with patency of the bypass. The VA can serve as a useful donor vessel for cerebral revascularization procedures in pathologies ranging from malignancies of the head and neck to cerebral aneurysms and cerebrovascular steno-occlusive disease.

Factors Affecting the Prognosis of Patients with Acute Cerebrovascular Occlusion with High National Institutes of Health Stroke Scale Scores Treated with SWIM Technology.

Objective: We aimed to explore the factors affecting the prognosis of patients with acute cerebrovascular occlusion with high National Institutes of Health Stroke Scale (NIHSS) scores treated with the SWIM (Solitaire™ stent retriever-assisted thrombectomy with immediate mechanical aspiration) technique using an intracranial support catheter. Methods: A retrospective analysis was conducted in 72 patients with acute cerebrovascular occlusion who underwent SWIM surgery in the Affiliated Hospital of Chengde Medical University in China between January 2020 and June 2022. The patients were divided into a good prognosis group (Modified Rankin Score [mRS] 0 to 2; n = 30) and a poor prognosis group (mRS score 3 to 6; n = 42) on their mRS scores 3 months after surgery. The THRIVE (TICI, hemorrhage, reocclusion, infarction, vessel, and embolism) score at different time points before and after the SWIM procedure and the postoperative revascularization rate were compared in the 2 NIHSS score groups. Univariate and logistic regression analyses were performed to identify the risk factors that affected the prognosis of patients with acute cerebrovascular occlusion treated with the SWIM procedure. Results: The NIHSS score difference at various time points after SWIM surgery in patients with low to moderate NIHSS scores was significantly higher than in patients with high NIHSS scores (P < .05). The postoperative revascularization rate in patients with high NIHSS scores was 74.36%, which was not significantly different from that in patients with low to moderate scores (84.85%; P > .05). The poor prognosis in patients with acute cerebrovascular occlusion after SWIM surgery was related to age, hypertension, NIHSS score, Glasgow Coma Scale (GCS) score, Essen Stroke Risk Score (ESRS), onset-to-treatment time (OTT) and Alberta Collateral Grading Scale (ACGS) score (P < .05). Logistic regression analysis showed that age, admission NIHSS score and ACGS score were independent risk factors that affected the prognosis in patients with acute cerebrovascular occlusion treated with the SWIM procedure (P < .05). Conclusion: The prognosis in patients with acute cerebrovascular occlusion with high NIHSS scores after SWIM surgery was poor. Advanced age, high NIHSS score and ACGS score were independent risk factors that affected the prognosis in patients with acute cerebrovascular occlusion treated with the SWIM procedure. Overall, incorporating these findings into clinical practice promotes personalized approaches, interdisciplinary collaboration and timely interventions to optimize outcomes in patients undergoing the SWIM procedure for acute cerebrovascular occlusion.

[Monitoring during Cerebrovascular Surgery].

Intraoperative monitoring of cerebrovascular disease is performed in direct surgery and endovascular treatment to prevent complications due to blood flow disturbance. Typical surgeries in which monitoring is useful are revascularization surgeries, such as bypass, carotid endarterectomy, and aneurysm clipping surgery. Revascularization is performed to normalize intracranial and extracranial blood flow but requires interruption of blood flow to the brain, even for a short time. Changes in cerebral circulation and function when blood flow is blocked cannot be generalized because they are affected by collateral circulation and differ among cases. Monitoring is important to understand these changes during surgery. It is also used in revascularization procedures to check if the reestablished cerebral blood flow is adequate. Changes in monitoring waveforms can detect the emergence of neurological dysfunction, but in some cases, clipping surgery can end with missing waveforms, leading to dysfunction. Even in such cases, it can help identify which surgery caused the malfunction and improve the outcome of subsequent surgeries.

[Chinese expert consensus on intraoperative neurophysiological monitoring of intracranial aneurysms (2023 edition)].

Intracranial aneurysm is a common disease in neurosurgery, and intraoperative vascular injury causes postoperative ischemic complications that seriously influence patient prognosis. Intraoperative neurophysiological monitoring (IONM) enables effective identification of early intraoperative ischemia and thus reduces related complications. The Clinical Neurophysiology Committee of the Chinese Research Hospital Association and the Neurosurgeons Branch of the Chinese Medical Doctor Association organized national experts in neurophysiology and cerebrovascular disease to develop this expert consensus based on a review of published guidelines, consensuses and clinical evidence both at home and abroad, and after Delphi expert consultation. A consensus was formed on four aspects, including commonly used IONM techniques and parameter settings, perioperative preparation and interpretation of results, the value of intraoperative electrophysiological monitoring of aneurysms at different sites, and electrophysiological monitoring in special cases. Moreover, according to level of evidence recommended by GRADE criteria, nine recommendations were put forward from the above four aspects to provide a reference for clinical intracranial aneurysm intraoperative neurophysiological monitoring practice.

[Considerations when handling common acute intracranial vascular anomalies]. / Akuta vaskulära neurokirurgiska tillstånd kräver snabb hantering.

Conditions involving intracranial vascular anomalies are increasingly diagnosed, not least incidentally, with the increasing availability of neuroradiological investigations. Acute deterioration and development of symptoms due to a vascular condition could require neurosurgical intervention depending on the nature of the condition and status of the patient. On the other hand, asymptomatic patients with incidental findings require careful consideration and risk assessment when deciding on whether or not to treat the condition, and if so, how. In this review article we provide a summary of some of the most common neurosurgical vascular conditions and outline management considerations in both the acute and elective setting.

The value of intraoperative indocyanine green angiography in microvascular decompression for hemifacial spasm to avoid brainstem ischemia.

PURPOSE: Despite being rarely reported, ischemic insults resulting from compromising small brainstem perforators following microvascular decompression (MVD) remain a potential devastating complication. To avoid this complication, we have been using indocyanine green (ICG) angiography intraoperatively to check the flow within the small brainstem perforators. We aim to evaluate the safety and usefulness of ICG videoangiography in MVD. METHODS: We extracted retrospective data of patients who received ICG videoangiography from our prospectively maintained database for microvascular decompression. We noted relevant data including demographics, offending vessels, operative technique, outcome, and complications. RESULTS: Out of the 438 patients, 15 patients with a mean age (SD) of 53 ± 10.5 years underwent intraoperative ICG angiography. Male:female was 1:1.14. The mean disease duration prior to surgery was 7.7 ± 5.3 years. The mean follow-up (SD) was 50.7 ± 42.0 months. In 14 patients, the offending vessel was an artery, and in one patient, a vein. Intraoperative readjustment of the Teflon pledget or sling was required in 20% (3/15) of the cases. No patient had any sort of brainstem ischemia. Eighty percent of the patients (12/15) experienced complete resolution of the spasms. 86.7% (13/15) of the patients reported a satisfactory outcome with marked improvement of the spasms. Three patients experienced slight hearing affection after surgery, which improved in two patients later. There was no facial or lower cranial nerve affection. CONCLUSION: Intraoperative ICG is a safe tool for evaluating the flow within the brain stem perforators and avoiding brainstem ischemia in MVD for hemifacial spasm.

Rethinking Cerebral Bypass Surgery.

Despite the evolution of indications, cerebral bypass remains an important treatment for selected patients with moyamoya disease, steno-occlusive cerebrovascular disease, complex aneurysms, and tumors. Ongoing advancements in patient selection and recent strategic, technical, and technological innovations are facilitating more tailored constructs with lower complication rates and continue to reshape the field. The consolidation of cerebral bypass to specialized centers will likely continue as the complexity of both the pathologies requiring treatment and the revascularization constructs performed increases.

Analysis of Perioperative Nursing Intervention Effect of Cerebrovascular Intervention Patients Based on Intelligent Internet of Things.

The postoperative results of cerebrovascular surgery patients have been successfully used in medical practice using the Internet. The results obtained through data analysis were used in the study. So far, 120 patients who underwent cerebrovascular surgery from February 2018 to December 2018 have been enrolled. The selected class was divided into two groups: 60 psychiatric patients, a control group and an observation group. The former is medical treatment and the latter is postoperative treatment. Results: The results showed that the blood pressure of control group was lower than that of control group, and the incidence of adverse events was lower than that of control group (P < 0.05). Meanwhile, the average hospitalization rate of cerebrovascular disease patients in control group was lower than that in control group (P < 0.05). Conclusion: For patients with cerebrovascular disease, postoperative nursing can reduce the incidence of postoperative complications, reduce the risk of surgery, and improve the effect of surgery. Acute ischemic stroke refers to a kind of clinical syndrome caused by abnormal blood supply in the brain, resulting in ischemia, hypoxic brain tissue necrosis, and focal or comprehensive neurological deficiency. Among them, progressive cerebral infarction accounted for about 20~35%, and most occurred in the early stage of the disease (48~72)h.

A Proposed Algorithm for Managing Cerebral Proliferative Angiopathy.

OBJECTIVE: Cerebral proliferative angiopathy (CPA) is a rare disease, characterized by a large vascular nidus, diffuse angiogenesis, and intermingled normal brain tissue. Conservative treatment, endovascular intervention, indirect revascularization, and radiotherapy have been applied to treat this disease. However, some cases deteriorate even after non-conservative treatment, and there has been no standard of treatment for this disease so far. In order to build a better treatment strategy, we review literature, present our case and propose an algorithm for managing CPA. METHODS: Following the PRISMA principle, we systemically reviewed literature discussing CPA. A case successfully managed with multi-modal treatment is also illustrated. RESULTS: A total of 23 articles with 74 cases of CPA were found. Thirty-three patients received single-modal management. These 33 cases include 24 receiving endovascular intervention, 7 receiving indirect revascularization, and 2 receiving radiotherapy. Three of the 33 patients deteriorated clinically, and 1 expired. We present a 6-year-old boy with left hemispheric CPA receiving indirect revascularization, followed by 2 consecutive courses of stereotactic radiosurgery targeting arteriovenous shunts in the left basal ganglia and arteriovenous shunts around the olfactory groove. In the follow-up period of more than 4 years, good collateral formation, improved perilesional perfusion, CPA shrinkage, and symptom relief were all achieved. CONCLUSIONS: Based on our literature review and case, we propose an algorithm for the management of CPA and emphasize that multi-modal treatment is necessary for most CPA cases.

Risk of cardiovascular intervention after androgen deprivation therapy in prostate cancer patients with a prior history of ischemic cardiovascular and cerebrovascular disease: A nationwide population-based cohort study.

BACKGROUND: Androgen deprivation therapy for prostate cancer is known to increase the risk of cardiovascular disease, but there is controversy regarding the cardiovascular risk in patients with preexisting cardiovascular disease. This study assessed the risk of cardiovascular intervention after androgen deprivation therapy in patients with a history of cardiovascular disease, cerebrovascular disease, and cardiovascular intervention. MATERIALS AND METHODS: Between 2008 and 2017, 195,308 men with newly diagnosed prostate cancer were identified from the nationwide claims database in South Korea. Among them, 49,090 men with a history of ischemic cardiovascular and cerebrovascular diseases were analyzed. The patients were divided into the androgen deprivation therapy (n = 14,092) and non-androgen deprivation therapy (n = 34,988) groups. The primary outcome was cardiovascular interventions (percutaneous transluminal angioplasty and coronary bypass surgery). Cox proportional hazard regression models were used to estimate the adjusted hazard ratios and 95% confidence intervals of the events. RESULTS: After balancing the covariates with 1:1 exact matching, the two groups had 10,514 subjects each. Multivariable analysis demonstrated that androgen deprivation therapy was not significantly associated with an increased risk of cardiovascular interventions (hazard ratio, 1.060; 95% confidence interval, 0.923-1.217; P = 0.4104), regardless of the duration of therapy. A history of cardiovascular intervention, diabetes mellitus, antithrombotic medication use, and cardiovascular events significantly increased the risk of cardiovascular intervention. CONCLUSIONS: Androgen deprivation therapy was not associated with cardiovascular intervention in patients with a previous history of cardiovascular disease, regardless of the duration of therapy. Therefore, the cardiovascular risk of androgen deprivation therapy should be reassessed in this population.

Thrombectomy Complications in Large Vessel Occlusions: Incidence, Predictors, and Clinical Impact in the ETIS Registry.

BACKGROUND AND PURPOSE: Procedural complications in thrombectomy for large vessel occlusions of the anterior circulation are not well described. We investigated the incidence, risk factors, and clinical implications of thrombectomy complications in daily clinical practice. METHODS: We used data from the ongoing prospective multicenter observational Endovascular Treatment in Ischemic Stroke Registry in France. The present study is a retrospective analysis of 4029 stroke patients with anterior large vessel occlusions treated with thrombectomy between January 2015 and May 2020 in 18 centers. We systematically collected procedural data, incidence of embolic complications, perforations and dissections, clinical outcome at 90 days, and hemorrhagic complications. RESULTS: Procedural complications occurred in 7.99% (95% CI, 7.17%-8.87%), and embolus to a new territory (ENT) was the most frequent (5.2%). Predictors of ENTs were terminal carotid/tandem occlusion (odds ratio [OR], 5 [95% CI, 2.03-12.31]; P<0.001) and an increased total number of passes (OR, 1.22 [95% CI, 1.05-1.41]; P=0.006). ENTs were associated to worse clinical outcomes (90-day modified Rankin Scale score, 0-2; adjusted OR, 0.4 [95% CI, 0.25-0.63]; P<0.001), increased mortality (adjusted OR, 1.74 [95% CI, 1.2-2.53]; P<0.001), and symptomatic intracerebral hemorrhage (adjusted OR, 1.87 [95% CI, 1.15-3.03]; P=0.011). Perforations occurred in 1.69% (95% CI, 1.31%-2.13%). Predictors of perforations were terminal carotid/tandem occlusions (39.7% versus 27.6%; P=0.028). 40.7% of patients died at 90 days, and the overall rate of poor outcome was 74.6% in case of perforation. Dissections occurred in 1.46% (95% CI, 1.11%-1.88%) and were more common in younger patients (median age, 64.2 versus 70.2 years; P=0.002). Dissections did not affect the clinical outcome at 90 days. Besides dissection, complications were independent of the thrombectomy technique. CONCLUSIONS: Thrombectomy complication rate is not negligible, and ENTs were the most frequent. ENTs and perforations were associated with disability and mortality, and terminal carotid/tandem occlusions were a risk factor. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03776877.

Combined medical therapy and neurosurgical revascularization preventing stroke in post-varicella angiopathy: Case report and review of literature.

BACKGROUND: Post varicella angiopathy (PVA) is an underdiagnosed but potentially severe disease in both pediatric and adult settings. No guidelines are available for the medical and neurosurgical management of this condition. We report the first pediatric case with headache and PVA who was treated with surgical revascularization before the onset of ischemic events. METHODS: This case report was conducted via retrospective chart review. A literature review was also completed, in order to identify previously described PVA undergone to revascularization. RESULTS: We report on a 9-year-old boy presenting with a long history of headache and PVA involving the distal left middle cerebral artery. The arterial lesion rapidly worsened over a 10 months' period with formation of focal moyamoya-like collaterals, despite an adequate intravenous antiviral treatment. The pattern of headaches significantly changed with a clear left-side lateralization and a "re-build-up" phenomenon on EEG. The patient was treated with left superficial temporal artery - middle cerebral artery (STA-MCA) bypass and encephalo-duro-arterio-myo-pericranial-synangiosis. This combined treatment resulted in an immediate and persistent improvement of brain perfusion, accompanied by prompt resolution of neurological symptoms. Two cases who presented with Suzuki stage III (unilateral or bilateral) moyamoya PVA and recurrent strokes or transient ischemic attacks despite adequate pharmacological prophylaxis have been surgically treated using both indirect and direct revascularization technique. The outcome was good in both cases. CONCLUSION: Surgical revascularization may have a role in the treatment of PVA and may prevent stroke. Given the lack of standardized treatment algorithms, individualized regimens should be formulated on a case-specific basis.

Predicting hemorrhagic transformation after large vessel occlusion stroke in the era of mechanical thrombectomy.

Serum biomarkers are associated with hemorrhagic transformation and brain edema after cerebral infarction. However, whether serum biomarkers predict hemorrhagic transformation in large vessel occlusion stroke even after mechanical thrombectomy, which has become widely used, remains uncertain. In this prospective study, we enrolled patients with large vessel occlusion stroke in the anterior circulation. We analyzed 91 patients with serum samples obtained on admission. The levels of matrix metalloproteinase-9 (MMP-9), amyloid precursor protein (APP) 770, endothelin-1, S100B, and claudin-5 were measured. We examined the association between serum biomarkers and hemorrhagic transformation within one week. Fifty-four patients underwent mechanical thrombectomy, and 17 patients developed relevant hemorrhagic transformation (rHT, defined as hemorrhagic changes ≥ hemorrhagic infarction type 2). Neither MMP-9 (no rHT: 46 ± 48 vs. rHT: 15 ± 4 ng/mL, P = 0.30), APP770 (80 ± 31 vs. 85 ± 8 ng/mL, P = 0.53), endothelin-1 (7.0 ± 25.7 vs. 2.0 ± 2.1 pg/mL, P = 0.42), S100B (13 ± 42 vs. 12 ± 15 pg/mL, P = 0.97), nor claudin-5 (1.7 ± 2.3 vs. 1.9 ± 1.5 ng/mL, P = 0.68) levels on admission were associated with subsequent rHT. When limited to patients who underwent mechanical thrombectomy, the level of claudin-5 was higher in patients with rHT than in those without (1.2 ± 1.0 vs. 2.1 ± 1.7 ng/mL, P = 0.0181). APP770 levels were marginally higher in patients with a midline shift ≥ 5 mm than in those without (79 ± 29 vs. 97 ± 41 ng/mL, P = 0.084). The predictive role of serum biomarkers has to be reexamined in the mechanical thrombectomy era because some previously reported serum biomarkers may not predict hemorrhagic transformation, whereas the level of APP770 may be useful for predicting brain edema.

Systemic Inflammation Response Index and Systemic Immune-Inflammation Index Are Associated with Clinical Outcomes in Patients Treated with Mechanical Thrombectomy for Large Artery Occlusion.

BACKGROUND: Inflammation plays a pivotal role in acute ischemic stroke, and various inflammatory markers are known to predict prognosis of acute ischemic stroke. This study aimed to evaluate the prognostic value of systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII) after mechanical thrombectomy (MT) for acute ischemic stroke caused by large artery occlusion. METHODS: The study enrolled 440 patients who underwent MT for large artery occlusion. SIRI and SII were calculated using laboratory data on admission. Prognosis was estimated with modified Rankin Scale at 3 months, and favorable clinical outcome was defined by a modified Rankin Scale score of 0-2. Receiver operating characteristic analysis was used to calculate the optimal cutoff values of SIRI and SII for predicting clinical outcome. Multivariate analysis was used to assess the relationship of SIRI and SII with clinical outcome. RESULTS: In receiver operating characteristic analysis, the optimal cutoff values for SIRI and SII were 2.9 and 853, respectively (area under the curve 0.799, 95% confidence interval [CI] 0.756-0.843, P < 0.001 and area under the curve 0.679, 95% CI 0.643-0.745, P < 0.001, respectively). Multivariate analysis revealed that SIRI <2.9 (odds ratio 2.27, 95% CI 1.29-5.17, P = 0.019) and SII <853 (OR 1.82, 95% CI 1.16-3.10, P = 0.031) were independent predictors of favorable clinical outcome after MT. CONCLUSIONS: Decreased SIRI and SII were associated with favorable clinical outcome after MT. SIRI and SII represent potential prognostic factors in patients undergoing MT for large artery occlusion.