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1.
J Neuroradiol ; 51(4): 101184, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38387650

ABSTRACT

BACKGROUND AND PURPOSE: To evaluate the reliability and accuracy of nonaneurysmal perimesencephalic subarachnoid hemorrhage (NAPSAH) on Noncontrast Head CT (NCCT) between numerous raters. MATERIALS AND METHODS: 45 NCCT of adult patients with SAH who also had a catheter angiography (CA) were independently evaluated by 48 diverse raters; 45 raters performed a second assessment one month later. For each case, raters were asked: 1) whether they judged the bleeding pattern to be perimesencephalic; 2) whether there was blood anterior to brainstem; 3) complete filling of the anterior interhemispheric fissure (AIF); 4) extension to the lateral part of the sylvian fissure (LSF); 5) frank intraventricular hemorrhage; 6) whether in the hypothetical presence of a negative CT angiogram they would still recommend CA. An automatic NAPSAH diagnosis was also generated by combining responses to questions 2-5. Reliability was estimated using Gwet's AC1 (κG), and the relationship between the NCCT diagnosis of NAPSAH and the recommendation to perform CA using Cramer's V test. Multi-rater accuracy of NCCT in predicting negative CA was explored. RESULTS: Inter-rater reliability for the presence of NAPSAH was moderate (κG = 0.58; 95%CI: 0.47, 0.69), but improved to substantial when automatically generated (κG = 0.70; 95%CI: 0.59, 0.81). The most reliable criteria were the absence of AIF filling (κG = 0.79) and extension to LSF (κG = 0.79). Mean intra-rater reliability was substantial (κG = 0.65). NAPSAH weakly correlated with CA decision (V = 0.50). Mean sensitivity and specificity were 58% (95%CI: 44%, 71%) and 83 % (95%CI: 72 %, 94%), respectively. CONCLUSION: NAPSAH remains a diagnosis of exclusion. The NCCT diagnosis was moderately reliable and its impact on clinical decisions modest.


Subject(s)
Subarachnoid Hemorrhage , Tomography, X-Ray Computed , Humans , Subarachnoid Hemorrhage/diagnostic imaging , Reproducibility of Results , Female , Male , Middle Aged , Tomography, X-Ray Computed/methods , Aged , Adult , Observer Variation , Sensitivity and Specificity , Computed Tomography Angiography/methods , Cerebral Angiography/methods
2.
J Neurosurg Anesthesiol ; 34(1): 14-20, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-34116547

ABSTRACT

Following a brain insult, focal neurological deficits may develop. Despite resolution of these deficits with time, the subsequent administration of sedative medications and opioids may lead to recrudescence of previous neurological deficits. Therefore, the present systematic review aims to explore the role of different sedatives and opioid analgesics at reproducing focal neurological deficits in patients with previous brain insults undergoing surgery. Our PRISMA compliant systematic review covering the literature from 1990 to 2020 showed a consistent reoccurrence of neurological deficits following administration of benzodiazepines and opioids across 12 studies. It appears that in all studies, the manifestations were transient and affected mostly middle-aged patients (45 to 67 y of age). In addition, benzodiazepines and opioid antagonism by naloxone and flumazenil reverses the unmasking of prior neurological deficits. In contrast, it is not clear based on our study whether the unmasking or worsening of neurological deficits occurs following recent injuries or an older brain insult, although for most patients it appears to be the former. Future studies are needed to elucidate the mechanisms involved in unmasking prior deficits and/or extension of prior injuries by sedative and opioid analgesics. This review will aid in developing prospective studies on individual sedative medications and their effects on unmasking neurological deficits in patients with multiple brain pathologies.


Subject(s)
Analgesics, Opioid , Hypnotics and Sedatives , Aged , Analgesics, Opioid/adverse effects , Brain , Humans , Hypnotics and Sedatives/adverse effects , Middle Aged , Prospective Studies
3.
Can J Ophthalmol ; 55(5): 401-405, 2020 10.
Article in English | MEDLINE | ID: mdl-32589917

ABSTRACT

OBJECTIVE: Whether transverse venous sinus stenosis (TVSS) causes idiopathic intracranial hypertension (IIH) or is an effect of the increased intracranial pressures is controversial. The purpose of this study was to assess the feasibility of serial imaging in patients with IIH on medical management. DESIGN AND PARTICIPANTS: Patients found to have IIH and TVSS on contrast-enhanced magnetic resonance venography (CEMRV) were recruited in a prospective cohort study. Patients were medically managed and followed with a CEMRV immediately after lumbar puncture, 3-6 months after diagnosis with resolution of IIH symptoms, and 1 year after diagnosis. Ophthalmological data were collected at the time of diagnosis, 3-6 months after diagnosis, and 1 year after diagnosis. Feasibility data, including patient recruitment rate, barriers, and logistical issues, were recorded. RESULTS: Twenty patients with suspected IIH were screened, and 5 of 7 (71.4%; 95% confidence interval: 36.21-100) eligible patients were enrolled in 1 year, at completion. All recruited patients had clinical resolution of their IIH on medical therapy, and none of them had any obvious change in their TVSS. CONCLUSIONS: Prospective examination of TVSS with serial magnetic resonance imaging in patients with IIH is feasible. TVSS in patients with IIH did not show any change, despite clinical improvement on medical management in all participants.


Subject(s)
Intracranial Hypertension , Pseudotumor Cerebri , Transverse Sinuses , Constriction, Pathologic , Humans , Intracranial Hypertension/complications , Intracranial Hypertension/diagnosis , Pilot Projects , Prospective Studies , Pseudotumor Cerebri/complications , Pseudotumor Cerebri/diagnosis
4.
Can J Neurol Sci ; 47(1): 44-49, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31619298

ABSTRACT

BACKGROUND: Although the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke caused by intracranial anterior circulation large vessel occlusion (LVO) is proven, demonstration of local effectiveness is critical for health system planning and resource allocation because of the complexity and cost of this treatment. METHODS: Using our prospective registry, we identified all patients who underwent EVT for out-of-hospital LVO stroke from February 1, 2013 through January 31, 2017 (n = 44), and matched them 1:1 in a hierarchical fashion with control patients not treated with EVT based on age (±5 years), prehospital functional status, stroke syndrome, severity, and thrombolysis administration. Demographics, in-hospital mortality, discharge disposition from acute care, length of hospitalization, and functional status at discharge from acute care and at follow-up were compared between cases and controls. RESULTS: For EVT-treated patients (median age 66, 50% women), the median onset-to-recanalization interval was 247 min, and successful recanalization was achieved in 30/44 (91%). Alteplase was administered in 75% of cases and 57% of controls (p = 0.07). In-hospital mortality was 11% among the cases and 36% in the control group (p = 0.006); this survival benefit persisted during follow-up (p = 0.014). More EVT patients were discharged home from acute care (50% vs. 18%, p = 0.002). Among survivors, there were nonsignificant trends in favor of EVT for median length of hospitalization (14 vs. 41 days, p = 0.11) and functional independence at follow-up (51% vs. 32%, p = 0.079). CONCLUSION: EVT improved survival and decreased disability. This demonstration of single-center effectiveness may help facilitate expansion of EVT services in similar health-care jurisdictions.


Étude cas-témoin portant sur la thrombectomie endovasculaire dans un centre canadien de prise en charge des AVC. Contexte : Bien qu'on ait prouvé l'efficacité de la thrombectomie endovasculaire dans le cas d'accidents ischémiques cérébraux aigus causés par l'occlusion de grosses artères affectant la circulation antérieure intracrânienne, la démonstration de son efficacité sur le terrain est essentielle à la planification du réseau la santé et à l'allocation des ressources en raison de la complexité de ce traitement et des coûts qui y sont associés. Méthodes : À l'aide d'un registre prospectif, nous avons identifié tous les patients ayant bénéficié (n = 44), du 1er février 2013 au 31 janvier 2017, d'une thrombectomie endovasculaire à la suite d'un AVC survenu en dehors d'un établissement de la santé, AVC causé par l'occlusion de grosses artères. De manière hiérarchique, nous avons fait correspondre nos patients dans un rapport de 1 à 1 à nos témoins non traités par thrombectomie endovasculaire, et ce, en nous basant sur leur âge (± 5 ans), sur leur situation fonctionnelle avant d'être admis, sur les signes cliniques et la gravité de leur AVC, et sur l'administration d'un traitement thrombolytique. Nous avons également comparé leurs caractéristiques démographiques, leur taux de mortalité hospitalière, les modalités d'obtention d'un congé des soins intensifs, la durée de leur hospitalisation et leur situation fonctionnelle au moment de quitter les soins intensifs et à l'occasion d'un suivi. Résultats : Dans le cas de nos patients traités par thrombectomie endovasculaire (âge médian : 66 ans ; 50 % de femmes), l'intervalle médian entre les premiers signes d'un AVC et la recanalisation a été de 247 minutes. Fait à souligner, une recanalisation réussie a été accomplie dans 30 cas sur 44 (91 %). L'altéplase a été administré dans 75 % des cas et chez 57 % des témoins (p = 0,07). En ce qui concerne le taux de mortalité hospitalière, il a été de 11 % parmi tous nos cas et de 36 % chez nos témoins (p = 0,006) ; À noter que cet avantage en termes de survie a persisté au moment des suivis (p = 0,014). Plus de patients traités par thrombectomie endovasculaire ont obtenu leur congé des soins intensifs et sont revenus à la maison (50 % contre 18 % ; p = 0,002). Parmi les survivants à ces AVC, on a noté des tendances non significatives en faveur des patients traités par thrombectomie endovasculaire pour ce qui est de la durée médiane d'hospitalisation (14 jours contre 41 jours ; p = 0,11) et de l'autonomie fonctionnelle au moment des suivis (51 % contre 32 % ; p = 0,079). Conclusion : En somme, la thrombectomie endovasculaire a permis d'améliorer le taux de survie des patients ainsi que leur niveau d'autonomie fonctionnelle. Effectuée dans un seul établissement hospitalier, cette démonstration de l'efficacité de ce traitement pourrait contribuer à faciliter l'essor des traitements de thrombectomie endovasculaire dans d'autres systèmes de santé similaires.

5.
Can J Neurol Sci ; 47(1): 50-60, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31587672

ABSTRACT

OBJECTIVE: Endovascular thrombectomy (EVT) is efficacious for ischemic stroke caused by proximal intracranial large-vessel occlusion involving the anterior cerebral circulation. However, evidence of its cost-effectiveness, especially in a real-world setting, is limited. We assessed whether EVT ± tissue plasminogen activator (tPA) was cost-effective when compared with standard care ± tPA at our center. METHOD: We identified patients treated with EVT ± tPA after the Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing computed tomography to recanalization times trial from our prospective stroke registry from February 1, 2013 to January 31, 2017. Patients admitted before February 2013 and treated with standard care ± tPA constitute the controls. The sample size was 88. Cost-effectiveness was assessed using the net monetary benefit (NMB). Differences in average costs and quality-adjusted life years (QALYs) were estimated using the augmented inverse probability weighted estimator. We accounted for sampling and methodological uncertainty in sensitivity analyses. RESULTS: Patients treated with EVT ± tPA had a net gain of 2.89 [95% confidence interval (CI): 0.93-4.99] QALYs at an additional cost of $22,200 (95% CI: -28,902-78,244) per patient compared with the standard care ± tPA group. The NMB was $122,300 (95% CI: -4777-253,133) with a 0.85 probability of being cost-effective. The expected savings to the healthcare system would amount to $321,334 per year. CONCLUSION: EVT ± tPA had higher costs and higher QALYs compared with the control, and is likely to be cost-effective at a willingness-to-pay threshold of $50,000 per QALY.


Analyse coût-efficacité de la thrombectomie endovasculaire dans un contexte réel. Objectif : La thrombectomie endovasculaire (TE) est efficace dans le cas d'accidents ischémiques cérébraux (AIC) causés par une occlusion proximale de l'artère cérébrale antérieure. Toutefois, les preuves d'un bon rapport coût-efficacité, particulièrement dans le cadre d'une pratique réelle, demeurent limitées. Nous avons ainsi évalué au sein de notre établissement dans quelle mesure la thrombectomie endovasculaire jumelée à un traitement au moyen d'un activateur tissulaire du plasminogène (t-PA) étaient davantage rentables en comparaison avec des soins usuels également jumelés à un traitement de t-PA. Méthodes : En consultant nos registres prospectifs, nous avons identifié des patients traités par une thrombectomie endovasculaire jumelée à un traitement de t-PA après avoir subi, du 1er février 2013 au 31 janvier 2017, un traitement endovasculaire destiné à un petit AVC central et ischémique à occlusion proximale avec un accent mis sur la minimisation du temps de recanalisation par tomodensitométrie. Les patients hospitalisés avant février 2013 et auxquels des soins usuels avaient été prodigués de concert avec l'administration d'un t-PA ont fait partie de notre groupe témoin. Au total, notre échantillon était formé de 88 patients. Nous avons évalué le rapport coût-efficacité au moyen du concept d'avantage monétaire net (AMN). Nous avons également estimé les différences en ce qui concerne les coûts moyens et l'indicateur QALY (quality-adjusted life years) en faisant appel à un estimateur pondéré par l'inverse de la probabilité inverse (augmented inverse probability weighted estimator). Enfin, nous avons tenu compte de l'incertitude de notre échantillonnage et de nos choix méthodologiques dans nos analyses de sensibilité. Résultats : Les patients traités par thrombectomie endovasculaire et l'administration d'un t-PA ont donné à voir un gain net de 2,89 années selon l'indicateur QALY (IC 95 % : 0,93 ­ 4,99) pour un coût additionnel de 22 200 $ (IC 95 % : −28,902 ­ 78,244) par patient si on les compare à notre groupe témoin. L'AMN s'est quant à lui élevé à 122 300 $ (IC 95 % : −4 777 ­ 253 133), sa probabilité d'être rentable atteignant 0,85. À cet égard, les économies annuelles pour le système de soins de santé pourraient atteindre les 321 334 $. Conclusion : Il appert que la thrombectomie endovasculaire jumelée à un traitement de t-PA entraînent des coûts plus élevés et un meilleur indicateur QALY en comparaison avec notre groupe témoin. Il est probable qu'une telle approche soit rentable en vertu d'un seuil de disposition à payer (willingness-to-pay threshold) avoisinant les 50 000 $ par année selon le QALY.

6.
J Neurosurg Pediatr ; : 1-5, 2019 Sep 06.
Article in English | MEDLINE | ID: mdl-31491753

ABSTRACT

Transorbital penetration accounts for one-quarter of the penetrating head injuries (PHIs) in adults and half of those in children. Injuries that traverse (with complete penetration of) the brainstem are often fatal, with survivors rarely seen in clinical practice. Here, the authors describe the case of a 16-year-old male who suffered and recovered from an accidental transorbital PHI traversing the brainstem-the first case of complete neurological recovery following such injury. Neuroimaging captured the trajectory of the initial injury. A delayed-onset carotid cavernous fistula and the subsequent development of internal carotid artery pseudoaneurysms were managed by endovascular embolization.The authors also review the relevant literature. Sixteen cases of imaging-confirmed PHI traversing the brainstem have been reported, 14 involving the pons and 12 penetrating via the transorbital route. Management and outcome of PHI are informed by object velocity, material, entry point, trajectory, relationship to neurovascular structures, and the presence of a retained foreign body. Trauma resuscitation is followed by a careful neurological examination and appropriate neuroimaging. Ophthalmological examination is performed if transorbital penetration is suspected, as injuries may be occult; the potential for neurovascular complications highlights the value of angiography. The featured case shows that complete recovery is possible following injury that traverses the brainstem.

7.
J Neurointerv Surg ; 11(7): 690-693, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30514737

ABSTRACT

BACKGROUND: The efficacy of SILK flow diverters (SFD) in the management of cerebral aneurysms has been established. However, the risk of complications with parent artery occlusion (PAO) remains to be fully elucidated. The purpose of our study was to analyze intracranial aneurysms treated with SFDs and assess for occurrences and potential risk factors for PAO. MATERIALS AND METHODS: Between September 2010 and September 2017, 34 patients were treated for intracranial aneurysms using SFDs at a Canadian institution. This database was retrospectively analyzed for frequency of PAOs and statistical analysis performed for potential contributing factors. RESULTS: Following treatment with SFDs, average clinical and imaging follow-ups were 31 and 22 months, respectively. PAOs were identified in 21% (7/34) of patients and occurred between 8 days and 1.5 years from intervention but only in 11.8% in those compliant to anti-platelet medications. These were all associated with anterior circulation aneurysms (P=0.131) and had no associated neurological deficits. Of these, 57% (4/7) had a fusiform morphology compared with only 19% (5/27) in non-occluded patients (P=0.039). The presence of clinical symptoms at the time of initial SFD intervention was significantly associated with PAO (P=0.021). CONCLUSION: Delayed PAO is not an uncommon outcome of flow diverter deployment and could be seen up to 1.5 years after treatment with no associated neurological deficits. Anti-platelet non-adherence remains a risk factor for PAO. Fusiform morphology of the aneurysm and symptoms at the time of intervention were associated with subsequent occlusion.


Subject(s)
Cerebrovascular Disorders/diagnostic imaging , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Self Expandable Metallic Stents/trends , Adult , Aged , Canada/epidemiology , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/etiology , Databases, Factual/trends , Embolization, Therapeutic/methods , Embolization, Therapeutic/trends , Endovascular Procedures/methods , Endovascular Procedures/trends , Female , Follow-Up Studies , Humans , Intracranial Aneurysm/epidemiology , Male , Middle Aged , Retrospective Studies , Self Expandable Metallic Stents/adverse effects , Time Factors , Treatment Outcome
8.
Can J Neurol Sci ; 45(5): 522-526, 2018 09.
Article in English | MEDLINE | ID: mdl-30234469

ABSTRACT

BACKGROUND: In patients with subarachnoid haemorrhage (SAH) and a negative finding on CT angiography (CTA), further imaging with digital subtraction angiography (DSA) is commonly performed to identify the source of bleeding. The purpose of this study was to investigate whether negative findings on CTA can reliably exclude aneurysms in patients with acute SAH. METHODS: This retrospective study identified all DSAs performed between August 2010 and July 2014 within our institution. CT angiography was performed with a 64-section multidetector row CT scanner. Only DSAs from patients with confirmed SAH and a negative CTA result were included in the final analyses. A fellowship-trained neuroradiologist reviewed the imaging results. RESULTS: Of the 857 DSAs, 50 (5.83%) were performed in 35 patients with CTA-negative SAH. Of the 35 patients, three (8.57%) had positive findings on the DSA. In one patient, suspicious dissection of the extra- and intra-cranial segment of the right vertebral artery could not be confirmed even in retrospect. In the second patient, the suspicious finding of tiny protuberance from the left paraclinoid internal carotid artery (ICA) on DSA did not change on follow-up and did not change patient's management. The third patient had a posterior inferior cerebellar artery aneurysm, which was not seen on the initial CTA owing to the incomplete coverage of the head on the CTA. CONCLUSION: In patients with SAH, negative findings on a technically sound CTA are reliable in ruling out aneurysms in any pattern of SAH or no blood on CT. Our observations need to be confirmed with larger prospective studies.


Subject(s)
Angiography, Digital Subtraction/methods , Computed Tomography Angiography/methods , Subarachnoid Hemorrhage/diagnostic imaging , Adult , Aged , Female , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Retrospective Studies , Vertebral Artery/diagnostic imaging , Young Adult
9.
Can Assoc Radiol J ; 68(2): 154-160, 2017 May.
Article in English | MEDLINE | ID: mdl-28131334

ABSTRACT

Stroke is the second leading cause of mortality and the third leading cause of disability-adjusted life-years worldwide. For each minute of an ischemic stroke, an estimated 1.9 million brain cells die. The year 2015 saw the unprecedented publication of 5 multicentre, randomized, controlled trials. These studies showed that patients with acute ischemic stroke caused by large-vessel thrombus occlusion of the proximal anterior circulation had significantly reduced disability at 90 days when treated with endovascular thrombectomy and usual stroke care compared to usual stroke care alone. As a result, endovascular thrombectomy is now the new North American and European standard of care for suitable patients with acute ischemic stroke caused by large-vessel proximal anterior circulation occlusion. We review key take-home messages in this paradigm shift for radiologists, including the importance of time and workflow efficiency, what currently constitutes appropriate preimaging patient selection and imaging criteria, the use of newer generation thrombectomy devices, safety outcomes, as well as further areas still in need of elucidation.


Subject(s)
Endovascular Procedures , Magnetic Resonance Angiography , Stroke/diagnostic imaging , Stroke/surgery , Thrombectomy/methods , Tomography, X-Ray Computed , Age Factors , Angiography/methods , Brain Ischemia/complications , Humans , Patient Selection , Sex Factors , Stroke/etiology , Time Factors
10.
Can J Neurol Sci ; 42(3): 176-80, 2015 May.
Article in English | MEDLINE | ID: mdl-25857349

ABSTRACT

PURPOSE: To compare patient effective dose resulting from two alternative imaging protocols for pre-coiling assessment of intracranial aneurysms: a series of 2D Digital Subtraction Angiography (DSA) projections, and a 3D rotational angiography (RA) acquisition. METHODS: In a retrospective analysis, we investigated 44 patients who underwent endovascular coiling in our institution. Images were acquired on a biplane Image Intensifier system not equipped with dose-area product (DAP) meter. Conventional 2D DSA images were simulated with an anthropomorphic skull phantom. Entrance skin dose was measured with a 60 cc ion chamber, and the PCXMC Monte Carlo based software was used to calculate patient effective dose. For the RA protocol, a 16 cm computed tomography (CT) dosimetry phantom and a 100 mm pencil ion chamber were employed to measure the CT dose index. Patient effective dose was calculated with the ImPACT calculator. An unpaired two-tailed t-test was used to determine the significance of differences between patient doses in each group. RESULTS: Sixteen patients underwent the 2D DSA protocol with multiple projections; their mean number of cine runs was 5.1; the mean effective dose was 2.11 millisievert (mSv) (range 1.69-3.43 mSv). Twenty eight patients were assessed using the 3D RA protocol with the effective dose of 1.29 mSv. The difference between the means of two dose distributions was statistically significant (p=0.00028). CONCLUSION: Our study demonstrated that the patient effective dose was significantly lower from the 3D RA protocol than that from the 2D DSA protocol used in the planning of coiling of intracranial aneurysm.


Subject(s)
Angiography, Digital Subtraction/adverse effects , Endovascular Procedures/methods , Intracranial Aneurysm/diagnosis , Intracranial Aneurysm/surgery , Neurosurgical Procedures/methods , Adult , Humans , Imaging, Three-Dimensional , Middle Aged , Monte Carlo Method , Patient Care Planning , Phantoms, Imaging , Radiation Dosage , Retrospective Studies
12.
J Neurointerv Surg ; 6(1): 16-8, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23299106

ABSTRACT

PURPOSE: We present a series of cases featuring re-rupture of posterior communicating artery aneurysms in the immediate post-coiling period, where clots obscured the neck of the aneurysm during the procedure. We report on the incidence of re-rupture and discuss possible mechanisms behind this phenomenon. METHODS: This study included 462 aneurysms over a 10-year period which were treated with endovascular coiling. 137 of these were ruptured aneurysms. Radiographic and clinical information pertaining to the patients was collected. The immediate post-coiling period was defined as ≤3 days following the procedure. RESULTS: The incidence of re-rupture in the immediate post-coiling period was 1.4% (2/137). Of these two, one received recombinant tissue plasminogen activator and both received acetylsalicylic acid. One patient presented with adjacent hematoma on re-rupture. In both cases, clot obscured the aneurysm neck during the procedure. CONCLUSIONS: Re-rupture of intracranial aneurysms in the immediate post-coiling period is an exceedingly rare complication, and the events leading to it have not been discussed at length. Repeat treatment, follow-up imaging and close observation are merited in the setting of re-rupture of a posterior communicating artery aneurysm.


Subject(s)
Aneurysm, Ruptured/diagnosis , Endovascular Procedures/adverse effects , Intracranial Aneurysm/diagnosis , Intracranial Aneurysm/surgery , Aged , Aneurysm, Ruptured/etiology , Female , Humans , Middle Aged , Time Factors , Treatment Outcome
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