Prevalence of pre-eclampsia in 265 patients with an intracranial aneurysm, 393 female relatives versus a control cohort: A case-control study.

BACKGROUND AND OBJECTIVES: There is emerging evidence on the connection between pre-eclampsia and saccular intracranial aneurysms (sIAs). Our aim was to study the prevalence of pre-eclampsia in sIA patients, their female relatives, and matched controls, and to examine familial sIA disease and familial pre-eclampsia in sIA patients' families. METHODS: We included all female sIA patients in the Kuopio Intracranial Aneurysm Patient and Family Database from 1995 to 2018. First, we identified the sIA patients, their female relatives, and matched population controls with the first birth in 1987 or later and studied the prevalence of pre-eclampsia. Second, all female sIA patients and all female relatives were analyzed for familial sIA disease and familial pre-eclampsia. Using the Finnish nationwide health registries, we obtained data on drug purchases, hospital diagnoses, and causes of death. RESULTS: In total, 265 sIA patients, 57 daughters, 167 sisters, 169 nieces, and 546 matched controls had the first birth in 1987 or later. Among them, 29 (11%) sIA patients, 5 (9%) daughters, 10 (6%) sisters, 10 (6%) nieces, and 32 (6%) controls had pre-eclampsia. Of all the 1895 female sIA patients and 12,141 female relatives, 68 sIA patients and 375 relatives had pre-eclampsia, including 32 families with familial pre-eclampsia. CONCLUSIONS: Pre-eclampsia was significantly more common in the sIA patients than in their matched controls. Familial sIA disease and familial pre-eclampsia co-occurred in seven families. Further studies of the mechanisms by which pre-eclampsia could affect the walls of brain arteries and increase the rupture risk in sIA disease are indicated.

Embolization techniques of spontaneous direct carotid-cavernous fistulae: a single-center experience.

PURPOSE: Spontaneous direct carotid-cavernous fistula (CCF) are usually caused by a ruptured carotid cavernous aneurysm. We studied treatment of spontaneous direct CCFs in a single-center cohort of a high-volume tertiary referral center, reporting anatomical details, technical approaches of treatment, and outcomes. METHODS: Adult patients with a spontaneous direct CCF treated between 2010-2022 with follow-up MRI and/or DSA imaging available were retrospectively analyzed. We studied age, sex, clinical presentation, angiographic findings, treatment techniques, outcomes, and complications. RESULTS: Out of 80 patients with CCFs, twelve patients were treated for a non-traumatic direct CCF (15%) in 13 sessions. Median age was 65 years. Two patients had an underlying connective tissue disorder. In 10 cases, the direct CCF was caused by a ruptured cavernous carotid aneurysm. The direct CCFs were treated by endovascular transarterial embolization (10 cases), transvenous embolization (1 case), or surgery (1 case). Selective closure of the shunt was possible in 10 patients. Two patients were treated with parent vessel occlusion (PVO; one endovascular; one surgical, with bypass). Complications occurred in 2 / 12 patients (17%), with permanent morbidity in two patients (17%): trigeminal neuralgia after PVO and new infarct after surgical PVO and bypass. Selective closure of CCF resulted in no morbidity. There was no mortality in our series. CONCLUSION: Spontaneous direct CCFs are caused by rupture of a cavernous carotid aneurysm in most cases. Selective closure of the shunt, usually feasible transarterially with coils, achieves good results. Reconstructive endovascular techniques are preferred to minimize treatment related neurological complications.

Pretreatment with a dual antiplatelet and anticoagulant (APAC) reduces ischemia-reperfusion injury in a mouse model of temporary middle cerebral artery occlusion-implications for neurovascular procedures.

BACKGROUND: Several neurovascular procedures require temporary occlusion of cerebral arteries, leading to ischemia of unpredictable length, occasionally causing brain infarction. Experimental models of cerebral ischemia-reperfusion injury have established that platelet adhesion and coagulation play detrimental roles in reperfusion injury following transient cerebral ischemia. Therefore, in a model of cerebral ischemia-reperfusion injury (IRI), we investigated the therapeutic potential of a dual antiplatelet and anticoagulant (APAC) heparin proteoglycan mimetic which is able to bind to vascular injury sites. METHODS: Brain ischemia was induced in mice by transient occlusion of the right middle cerebral artery for 60 min. APAC, unfractionated heparin (UFH) (both at heparin equivalent doses of 0.5 mg/kg), or vehicle was intravenously administered 10 min before or 60 min after the start of ischemia. At 24 h later, mice were scored for their neurological and motor behavior, and brain damage was quantified. RESULTS: Both APAC and UFH administered before the onset of ischemia reduced brain injury. APAC and UFH pretreated mice had better neurological and motor functions (p < 0.05 and p < 0.01, respectively) and had significantly reduced cerebral infarct sizes (p < 0.01 and p < 0.001, respectively) at 24 h after transient occlusion compared with vehicle-treated mice. Importantly, no macroscopic bleeding complications were observed in either APAC- or UFH-treated animals. However, when APAC or UFH was administered 60 min after the start of ischemia, the therapeutic effect was lost, but without hemorrhaging either. CONCLUSIONS: Pretreatment with APAC or UFH was safe and effective in reducing brain injury in a model of cerebral ischemia induced by transient middle cerebral artery occlusion. Further studies on the use of APAC to limit ischemic injury during temporary occlusion in neurovascular procedures are indicated.

Acute evacuation of 54 intracerebral hematomas (aICH) during the microsurgical clipping of a ruptured middle cerebral artery bifurcation aneurysm-illustration of the individual clinical courses and outcomes with a serial brain CT/MRI panel until 12 months.

PURPOSE: In aneurysmal intracerebral hemorrhage (aICH), our review showed the lack of the patient's individual (i) timeline panels and (ii) serial brain CT/MRI slice panels through the aICH evacuation and neurointensive care until the final brain tissue outcome. METHODS: Our retrospective cohort consists of 54 consecutive aICH patients from a defined population who acutely underwent the clipping of a middle cerebral artery bifurcation saccular aneurysm (Mbif sIA) with the aICH evacuation at Kuopio University Hospital (KUH) from 2010 to 2019. We constructed the patient's individual timeline panels since the emergency call and serial brain CT/MRI slice panels through the aICH evacuation and neurointensive care until the final brain tissue outcome. The patients were indicated by numbers (1.-54.) in the pseudonymized panels, tables, results, and discussion. RESULTS: The aICH volumes on KUH admission (median 46 cm3) plotted against the time from the emergency call to the evacuation (median 8 hours) associated significantly with the rebleeds (n=25) and the deaths (n=12). The serial CT/MRI slice panels illustrated the aICHs, intraventricular hemorrhages (aIVHs), residuals after the aICH evacuations, perihematomal edema (PHE), delayed cerebral injury (DCI), and in the 42 survivors, the clinical outcome (mRS) and the brain tissue outcome. CONCLUSIONS: Regarding aICH evacuations, serial brain CT/MRI panels present more information than words, figures, and graphs. Re-bleeds associated with larger aICH volumes and worse outcomes. Swift logistics until the sIA occlusion with aICH evacuation is required, also in duty hours and weekends. Intraoperative CT is needed to illustrate the degree of aICH evacuation. PHE may evoke uncontrollable intracranial pressure (ICP) in spite of the acute aICH volume reduction.

Should individual timeline and serial CT/MRI panels of all patients be presented in acute brain insult cohorts? A pilot study of 45 patients with decompressive craniectomy after aneurysmal subarachnoid hemorrhage.

PURPOSE: Our review of acute brain insult articles indicated that the patients' individual (i) timeline panels with the defined time points since the emergency call and (ii) serial brain CT/MRI slice panels through the neurointensive care until death or final brain tissue outcome at 12 months or later are not presented. METHODS: We retrospectively constructed such panels for the 45 aneurysmal subarachnoid hemorrhage (aSAH) patients with a secondary decompressive craniectomy (DC) after the acute admission to neurointensive care at Kuopio University Hospital (KUH) from a defined population from 2005 to 2018. The patients were indicated by numbers (1.-45.) in the pseudonymized panels, tables, results, and discussion. The timelines contained up to ten defined time points on a logarithmic time axis until death ([Formula: see text]; 56%) or 3 years ([Formula: see text]; 44%). The brain CT/MRI panels contained a representative slice from the following time points: SAH diagnosis, after aneurysm closure, after DC, at about 12 months (20 survivors). RESULTS: The timelines indicated re-bleeds and allowed to compare the times elapsed between any two time points, in terms of workflow swiftness. The serial CT/MRI slices illustrated the presence and course of intracerebral hemorrhage (ICH), perihematomal edema, intraventricular hemorrhage (IVH), hydrocephalus, delayed brain injury, and, in the 20 (44%) survivors, the brain tissue outcome. CONCLUSIONS: The pseudonymized timeline panels and serial brain imaging panels, indicating the patients by numbers, allowed the presentation and comparison of individual clinical courses. An obvious application would be the quality control in acute or elective medicine for timely and equal access to clinical care.

Number of Affected Relatives, Age, Smoking, and Hypertension Prediction Score for Intracranial Aneurysms in Persons With a Family History for Subarachnoid Hemorrhage.

BACKGROUND: Persons with a positive family history of aneurysmal subarachnoid hemorrhage are at increased risk of aneurysmal subarachnoid hemorrhage. Preventive screening for intracranial aneurysms (IAs) in these persons is cost-effective but not very efficient. We aimed to develop and externally validate a model for predicting the probability of an IA at first screening in persons with a positive family history of aneurysmal subarachnoid hemorrhage. METHODS: For model development, we studied results from initial screening for IA in 660 prospectively collected persons with ≥2 affected first-degree relatives screened at the University Medical Center Utrecht. For validation, we studied results from 258 prospectively collected persons screened in the University Hospital of Nantes. We assessed potential predictors of IA presence in multivariable logistic regression analysis. Predictive performance was assessed with the C statistic and a calibration plot and corrected for overfitting. RESULTS: IA were present in 79 (12%) persons in the development cohort. Predictors were number of affected relatives, age, smoking, and hypertension (NASH). The NASH score had a C statistic of 0.68 (95% CI, 0.62-0.74) and showed good calibration in the development data. Predicted probabilities of an IA at first screening varied from 5% in persons aged 20 to 30 years with two affected relatives, without hypertension who never smoked, up to 36% in persons aged 60 to 70 years with ≥3 affected relatives, who have hypertension and smoke(d). In the external validation data IA were present in 67 (26%) persons, the model had a C statistic of 0.64 (95% CI, 0.57-0.71) and slightly underestimated IAs risk. CONCLUSIONS: For persons with ≥2 affected first-degree relatives, the NASH score improves current predictions and provides risk estimates for an IA at first screening between 5% and 36% based on 4 easily retrievable predictors. With the information such persons can now make a better informed decision about whether or not to undergo preventive screening.

Sex Difference and Rupture Rate of Intracranial Aneurysms: An Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture. METHODS: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage. RESULTS: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58-0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (≥7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07-1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02-1.90). CONCLUSIONS: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.

Risk factor management matters more than pharmaceutical cyclooxygenase-2 inhibition in the prevention of de novo intracranial aneurysms.

BACKGROUND AND PURPOSE: Pathophysiological studies of saccular intracranial aneurysm (sIA) disease have shown that inflammation plays a crucial role in sIA development. Pharmaceutical inhibition of COX-2-PGE2-NF-κB signaling (COX-2, cyclooxygenase-2; PGE2, prostaglandin E2; NF-κB, nuclear factor κB) has been shown in animal models to inhibit sIA formation and progression suggesting that use of medication inhibiting COX-2 could reduce intracranial aneurysm formation also in patients. METHODS: The impact of COX-2 inhibition on de novo sIA formation was studied in two cohorts: in a previously described angiographically followed cohort of 1419 sIA patients and in a cohort of 117 sIA patients treated with stenting or stent-assisted embolization. Patients were identified from our population-based Kuopio Intracranial Aneurysm Database. Data on the use of anti-inflammatory medications and hospital diagnoses were obtained from national registries. Risk factors were identified by univariate and multivariate analyses. RESULTS: De novo sIA patients were younger and more often smokers. Use of COX-2 selective inhibitors or nonsteroidal anti-inflammatory drugs did not significantly reduce de novo sIA formation, but the percentage of patients with de novo sIA formation was smaller in patients with prescribed regular acetylsalicylic acid medication (1.1% vs. 3.6%). In the multivariate analysis, however, neither acetylsalicylic acid use nor other type of pharmaceutical inhibition of COX-2 reduced the formation of de novo sIAs. The risk was mostly affected by age, smoking history and irregular usage of antihypertensive medication regardless of used COX-2 inhibition level. CONCLUSION: For the prevention of de novo sIA formation, risk factor management with focus on cessation of smoking and treating hypertension adequately seems more important than pharmaceutical COX-2 inhibition.

Use of antihypertensive medication and formation of de novo intracranial aneurysms.

BACKGROUND AND PURPOSE: Hypertension is a risk factor for subarachnoid hemorrhage and is also considered a risk factor for saccular intracranial aneurysm (sIA) formation. However, there is little direct evidence that antihypertensive medication will reduce sIA formation. METHODS: The impact of antihypertensive medication on de novo sIA formation was studied in an angiographically followed cohort of 1419 patients. Patients were identified from our population-based Kuopio Intracranial Aneurysm Database, and data on the purchases of antihypertensive medication were obtained from a national registry. Univariate and multivariate analyses were used to investigate the risk factors. RESULTS: Of the 966 sIA patients who were prescribed with antihypertensive medication, 841 patients used the medication regularly; 20 of them had de novo sIA. One hundred and twenty-five patients used the medication irregularly and 12 of them developed de novo sIAs. Four hundred and fifty-three patients did not use antihypertensive medication even though 27 of them had a diagnosis of hypertension, and 10 of them developed de novo sIAs. In the multivariate analysis antihypertensive medication did not significantly reduce de novo sIA formation (hazard ratio [HR] 1.60, 95% confidence interval [CI] 0.84-3.06). Age at primary diagnosis (HR: 0.95, 95%: CI 0.93-0.98) and smoking history (HR: 5.53, 95% CI: 2.77-11.05) were significant risk factors for de novo sIA formation. Also, irregular usage of antihypertensive medication was a significant risk factor (HR: 3.84, 95% CI: 1.59-9.29) for de novo sIA formation. CONCLUSIONS: Antihypertensive agents were not associated with a reduction of de novo sIA formation, but irregular use of antihypertensive agents was associated with an increased risk of de novo sIA formation.

Pre-eclampsia, gestational diabetes and hypertensive disorders in patients with intracranial aneurysms: A case-control study.

BACKGROUND AND PURPOSE: The aim of this study was to define the prevalence of pre-eclampsia, gestational hypertension (HT), chronic HT, and gestational diabetes during pregnancy in a defined population of patients with saccular intracranial aneurysms (sIAs). METHODS: We included all patients with sIA, first admitted to the Neurosurgery Department of Kuopio University Hospital from its defined catchment population between 1990 and 2015, who had given birth for the first time in 1990 or later. The patients' medical records were reviewed, and clinical data were linked with prescription drug usage, hospital diagnoses and causes of death, obtained from nationwide registries. The prevalences of pre-eclampsia, other hypertensive disorders and gestational diabetes in patients were compared with a matched control population (n = 324). In addition, the characteristics of sIA disease in patients with pre-eclampsia were compared to those of sIA patients without pre-eclampsia. RESULTS: A total of 169 patients with sIA fulfilled the inclusion criteria. Of these, 22 (13%) had pre-eclampsia and 32 (19%) had other hypertensive disorders during pregnancy. In 324 matched controls who had given birth, the prevalence of pre-eclampsia was 5% (n = 15) and other hypertensive disorders were diagnosed in 10% (n = 34). There was no significant difference in prevalence of gestational diabetes (12% vs. 11%). Patients with sIA with pre-eclampsia more frequently had irregularly shaped aneurysms (p = 0·003). CONCLUSIONS: Pre-eclampsia was significantly more frequent in patients with sIA than in their population controls. Irregularly shaped aneurysms were more frequent in sIA patients with pre-eclampsia. Further studies are required to determine whether history of pre-eclampsia may indicate an elevated risk for sIA formation or rupture.

The outcomes of recurrent wide-necked intracranial aneurysms treated with the Woven EndoBridge (WEB): A retrospective bicenter study.

BACKGROUND: The Woven EndoBridge (WEB) is a device for the treatment of intracranial wide-necked bifurcation aneurysms. The safety and effectiveness of WEB for intracranial aneurysms have both been evaluated in previous trials. Our aim was to study the outcomes of recurrent intracranial aneurysms (IAs) treated with WEB. METHODS: Clinical and radiological outcomes of patients with a wide-necked aneurysm recurrence, which was treated with WEB device, were assessed. Imaging follow-up was performed with digital subtraction angiography and/or magnetic resonance angiography. Aneurysm occlusion was determined using by the Raymond-Roy Occlusion Classification (RROC). RROC 1 and RROC 2 were considered as adequate radiological outcome. RESULTS: Twenty-two patients with 23 recurrent IAs were treated with WEB. Of which, 17 of recurrent IAs (74%) previously treated by coiling, three (13%) by clipping and three (13%) by WEB. The most common location of the recurrent IA was the middle cerebral artery (n = 10, 43%). Endovascular treatment with WEB alone was suitable for 20 recurrent IAs (87%). Ancillary devices were also used: coils in two (9%), and a stent in one (4%). Radiological follow-up results available for all patients (range: 3-60 months; median 24 months). Adequate occlusion (RROC I and II) was achieved in 20 recurrent IAs (87%). A hemorrhagic complication occurred 2 weeks post treatment in one patient (5%). CONCLUSIONS: WEB could be an effective treatment with low rates of complications for challenging cases of recurrent wide-necked IAs.

Shunt performance in 349 patients with hydrocephalus after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Shunt-dependent hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH) is a common sequelae leading to poorer neurological outcomes and predisposing to various complications. METHODS: A total of 2191 consecutive patients with aSAH were acutely admitted to the Neurointensive Care at the Kuopio University Hospital between 1990 and 2018 from a defined population. A total of 349 (16%) aSAH patients received a ventriculoperitoneal shunt, 101 with an adjustable valve (2012-2018), 232 with a fixed pressure valve (1990-2011), and 16 a valveless shunt (2010-2013). Clinical timelines were reconstructed from the hospital records and nationwide registries until death (n = 120) or June 2019. RESULTS: Comparing the adjustable valves vs. the fixed pressure valves vs. the valveless shunts, intraventricular hemorrhage was present in 61%, 44% and 100%, respectively. The median times to the shunt were 7 days vs. 38 days vs. 10 days. The rates of the first revision were 25% vs. 32% vs. 69%. The causes included infection in 11% vs. 7% vs. 25% and overdrainage in 1% vs. 4% vs. 31%. The valveless shunt was the only independent risk factor (HR 2.9) for revision. After the first revision, more revisions were required in 48% vs. 52% vs. 45%. CONCLUSIONS: The protocol to shunt evolved over time to favor earlier shunt. In post-aSAH hydrocephalus, adjustable valve shunts, without anti-siphon device, can be installed at an early phase after aSAH, in spite of intraventricular blood, with a modest risk (25%) of revision. Valveless shunts are not recommendable due to high risk of revisions.

Clinical condition of 120 patients alive at 3 years after poor-grade aneurysmal subarachnoid hemorrhage.

BACKGROUND: To study the clinical condition of poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients alive at 3 years after neurointensive care. METHODS: Of the 769 consecutive aSAH patients from a defined population (2005-2015), 269 (35%) were in poor condition on admission: 145 (54%) with H&H 4 and 124 (46%) with H&H 5. Their clinical lifelines were re-constructed from the Kuopio Intracranial Aneurysm Database and Finnish nationwide registries. Of the 269 patients, 155 (58%) were alive at 14 days, 125 (46%) at 12 months, and 120 (45%) at 3 years. RESULTS: The 120 H&H 4-5 patients alive at 3 years form the final study population. On admission, 73% had H&H 4 but only 27% H&H 5, 59% intracerebral hematoma (ICH; median 22 cm3), and 26% intraventricular blood clot (IVH). The outcome was favorable (mRS 0-1) in 45% (54 patients: ICH 44%; IVH clot 31%; shunt 46%), moderate (mRS 2-3) in 30% (36 patients: ICH 64%; IVH clot 19%; shunt 42%), and unfavorable (mRS 4-5) in 25% (30 patients: ICH 80%; IVH clot 23%; shunt 50%). A total of 46% carried a ventriculoperitoneal shunt. ICH volume was a significant predictor of mRS at 3 years. CONCLUSIONS: Of poor-grade aSAH patients, 45% were alive at 3 years, even 27% of those extending to pain (H&H 5). Of the survivors, 75% were at least in moderate condition, while only 2.6% ended in hospice care. Consequently, we propose non-selected admission to neurointensive care (1) for a possibility of moderate outcome, and (2), in case of brain death, possibly improved organ donation rates.

Endovascular Intervention Versus Surgery in Ruptured Intracranial Aneurysms in Equipoise: A Systematic Review.

Background and Purpose- The benefits of endovascular intervention over surgery in the treatment of ruptured aneurysms of anterior circulation remains uncertain. Recently, published studies did not find superiority of endovascular intervention, challenging earlier evidence from a clinical trial. The earlier evidence also had a higher than average proportion of patients in good clinical status, leading to uncertainty about external validity of earlier trials. Methods- We performed a systematic review of studies after 2005 under a protocol published in the International Prospective Register of Systematic Reviews. Primary outcomes were posttreatment rebleeding and adverse events (procedural complications). Secondary outcomes were dependency at 3 to 6 and 12 months, delayed cerebral ischemia, and seizures. Results- Rebleeding was more frequent after endovascular intervention (Peto OR, 2.18 [95% CI, 1.29-3.70]; 3104 participants; 15 studies; I2=0%, Grading of Recommendations, Assessment, Development and Evaluation: very low certainty of evidence). Fewer adverse events were reported with the endovascular intervention (RR, 0.71 [95% CI, 0.53-0.95]; 1661 participants; 11 studies; I2=14%, Grading of Recommendations, Assessment, Development and Evaluation: low certainty of evidence). Three to six months dependency (RR, 0.82 [95% CI, 0.73-0.93]; 4081 participants; 18 studies; I2=15%, Grading of Recommendations, Assessment, Development and Evaluation: low certainty of evidence) and 12-month dependency (RR, 0.76 [95% CI, 0.66-0.86]; 1981 participants; 10 studies; I2=0%, Grading of Recommendations, Assessment, Development and Evaluation: low certainty of evidence) were lower after endovascular intervention. Conclusions- This study found consistent results between recent studies and the earlier evidence, in that endovascular intervention results in lower chance of dependency compared with surgery for repair of ruptured anterior circulation aneurysms. A lower proportion of patients in good clinical status in this review supports the application of the earlier evidence. Registration- URL: https://www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42018090396.

Periodontitis and gingival bleeding associate with intracranial aneurysms and risk of aneurysmal subarachnoid hemorrhage.

Oral bacteria DNA has been found in intracranial aneurysms (IA) and a high prevalence of periodontitis was reported in IA patients. We investigated whether periodontitis associates with IA formation and aneurysmal subarachnoid hemorrhage (aSAH). First, we compared in a case-control setting the prevalence of periodontal disease in IA patients (42 unruptured IA, 34 ruptured IA) and in age- and gender-matched controls (n = 70) from the same geographical area (Health 2000 Survey, BRIF8901). Next, we investigated whether periodontitis at baseline associated with aSAH in a 13-year follow-up study of 5170 Health 2000 Survey participants. Follow-up data was obtained from national hospital discharge and cause of death registries. Univariate analysis, logistic regression, and Cox-regression were used. Periodontitis (≥ 4mm gingival pocket) and severe periodontitis (≥ 6mm gingival pocket) were found in 92% and 49% of IA patients respectively and associated with IAs (OR 5.3, 95%CI 1.1-25.9, p < 0.000 and OR 6.3, 95%CI 1.3-31.4, p < 0.001, respectively). Gingival bleeding had an even stronger association, especially if detected in 4-6 teeth sextants (OR 34.4, 95%CI 4.2-281.3). Severe periodontitis in ≥ 3 teeth or gingival bleeding in 4-6 teeth sextants at baseline increased the risk of aSAH during follow-up (HR 22.5, 95%CI 3.6-139.5, p = 0.001 and HR 8.3, 95%CI 1.5-46.1, p = 0.015, respectively). Association of periodontitis and gingival bleeding with risk of IA development and aSAH was independent of gender, smoking status, hypertension, or alcohol abuse. Periodontitis and gingival bleeding associate with increased risk for IA formation and eventual aSAH. Further epidemiological and mechanistic studies are indicated.

Concordance in Aneurysm Size at Time of Rupture in Familial Intracranial Aneurysms.

Background and Purpose- Intracranial aneurysm (IA) size and location are important determinants of aneurysm rupture risk. In familial IAs there is concordance of location; however, if such concordance exists for size is unknown. We analyzed the concordance of aneurysm size at time of rupture in familial IAs. Methods- In pairs of affected relatives with aneurysmal subarachnoid hemorrhage, the ratio between the largest and the smallest aneurysm size at time of rupture was calculated. We also compared the proportion of families in which both IAs ruptured at a size < or ≥7 mm with the proportion of families in which one IA ruptured at <7 mm and another ≥7 mm. We calculated the repeatability with corresponding 95% CI for aneurysm size at time of rupture. Results- About 130 patients from 64 families were included. Of the 68 affected pairs 18 (26%) had a ratio ≤1.2, 38 (57%) had a ratio >1.2, and 12 (17%) had a ratio ≥3. We found no difference between the proportion of families (n=31; 49%) who both had IA at time of rupture <7 mm (n=20; 31%) or both ≥7 mm (n=11; 18%) and the proportion of those families with one patient with an IA <7 mm and another with an IA ≥7 mm (n=33; 51%; P=0.86). Overall, the repeatability in aneurysm size at rupture within familial IAs was 0.10 (95% CI, 0-0.35). Conclusions- There is no good concordance in aneurysm size at rupture within familial IAs. These data suggest that size of a ruptured IA in a family member should not significantly impact on the management of a familial unruptured IA in a relative.

Antipsychotic Use Among 1144 Patients After Aneurysmal Subarachnoid Hemorrhage.

Background and Purpose- At acute phase and neurointensive care, patients with aneurysmal subarachnoid hemorrhage (aSAH) may become agitated or delirious. We found no previous studies on psychotic disorders or antipsychotic drug (APD) use by long-term aSAH survivors. We defined the APD use and its risk factors among 12-month survivors of aSAH in an Eastern Finnish population-based cohort with long-term follow-up. Methods- We analyzed APD use in 1144 consecutive patients with aSAH alive at 12 months of the Kuopio intracranial aneurysm patient and family database and their age, sex, and birth municipality matched controls (3:1; n=3432) from 1995 to 2013 and median follow-up of 9 years. Using the Finish nationwide health registries, we obtained drug purchase and hospital discharge data. Results- In total, 140 (12%) of the 1144 patients started APD use first time after aSAH (index date), in contrast to 145 (4%) of the 3432 matched population controls. The cumulative rate of starting APD was 6% at 1 year and 9% at 5 years, in contrast to 1% and 2% in the controls, respectively. The rates at 1 and 5 years were only 1% and 2% in the 489 patients with a good condition (modified Rankin Scale score, 0 or 1 at 12 months; no shunt, intracerebral hemorrhage, or intraventricular hemorrhage). Instead, the highest rate of APD use, 23% at 5 years was among the 192 patients shunted for hydrocephalus after aSAH. Eighty-eight (63%) of the 140 aSAH patients with APD use had also concomitant antidepressant or antiepileptic drug use. Conclusions- The 12-month survivors of aSAH were significantly more likely to be started on APD after aSAH than their matched population controls. These patients often used antidepressant and antiepileptic drugs concomitantly. The use of APDs strongly correlated with signs of brain injury after aSAH, with low use if no signs of significant brain injury were present.

Saccular Intracranial Aneurysms in Children When Both Parents Are Sporadic or Familial Carriers of Saccular Intracranial Aneurysms.

BACKGROUND AND PURPOSE: To study the penetrance of saccular intracranial aneurysm (IA) disease in children when both parents carry the disease. PATIENTS AND METHODS: The Kuopio IA Patient and Family Database includes all 4,411 IA patients admitted to the Kuopio University Hospital from its defined Eastern Finnish catchment population since 1980. We fused IA database with hospital diagnoses for IA patients and their 46,021 relatives from a national registry to identify couples concordant for IA disease. Penetrance of IA disease and hypertension were studied in these families. RESULTS: A total of 3,659 IA patients had 1 or more children. In total, 18 couples concordant for the IA disease with a total of 48 children, all born healthy, were identified. Hypertension was diagnosed in 23 (64%) of the 36 parents, and 7 of the 12 sporadic-sporadic couples were concordant for hypertension. Six sporadic-sporadic couples were concordant for subarachnoid haemorrhage (SAH). None of the 24 children to the 12 sporadic-sporadic couples had been diagnosed with SAH or IA disease. Instead, 11 (46%) of the 24 children to the 6 familial-sporadic couples had a diagnosed with SAH or IA disease. CONCLUSIONS: Couples concordant for IA disease are uncommon but not exceedingly rare. Biparental sporadic exposure does not seem to increase the risk of a clinically diagnosed IA disease or SAH in the offspring. IAs were common in the children with biparental sporadic-familial exposure.

Endovascular coiling versus neurosurgical clipping for people with aneurysmal subarachnoid haemorrhage.

BACKGROUND: Around 30% of people who are admitted to hospital with aneurysmal subarachnoid haemorrhage (SAH) will rebleed in the initial month after the haemorrhage if the aneurysm is not treated. The two most commonly used methods to occlude the aneurysm for prevention of rebleeding are microsurgical clipping of the neck of the aneurysm and occlusion of the lumen of the aneurysm by means of endovascular coiling. This is an update of a systematic review that was previously published in 2005. OBJECTIVES: To compare the effects of endovascular coiling versus neurosurgical clipping in people with aneurysmal SAH on poor outcome, rebleeding, neurological deficit, and treatment complications. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (March 2018). In addition, we searched CENTRAL (2018, Issue 2), MEDLINE (1966 to March 2018), Embase (1980 to March 2018), US National Institutes of Health Ongoing Trials Register (March 2018), and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (last searched March 2018). We also contacted trialists. SELECTION CRITERIA: We included randomised trials comparing endovascular coiling with neurosurgical clipping in people with SAH from a ruptured aneurysm. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, and assessed trial quality and risk of bias using the GRADE approach. We contacted trialists to obtain missing information. We defined poor outcome as death or dependence in daily activities (modified Rankin scale 3 to 6 or Glasgow Outcome Scale (GOS) 1 to 3). In the special worst-case scenario analysis, we assumed all participants in the group with better outcome with missing follow-up information had a poor outcome and those in the other group with missing data a good outcome. MAIN RESULTS: We included four randomised trials involving 2458 participants (range per trial: 20 to 2143 participants). Evidence is mostly based on the largest trial. Most participants were in good clinical condition and had an aneurysm on the anterior circulation. None of the included trials was at low risk of bias in all domains. One trial was at unclear risk in one domain, two trials at unclear risk in three domains, and one trial at high risk in one domain.After one year of follow-up, 24% of participants randomised to endovascular treatment and 32% of participants randomised to the surgical treatment group had poor functional outcome. The risk ratio (RR) of poor outcome (death or dependency) for endovascular coiling versus neurosurgical clipping was 0.77 (95% confidence interval (CI) 0.67 to 0.87; 4 trials, 2429 participants, moderate-quality evidence), and the absolute risk reduction was 7% (95% CI 4% to 11%). In the worst-case scenario analysis for poor outcome, the RR for endovascular coiling versus neurosurgical clipping was 0.80 (95% CI 0.71 to 0.91), and the absolute risk reduction was 6% (95% CI 2% to 10%). The RR of death at 12 months was 0.80 (95% CI 0.63 to 1.02; 4 trials, 2429 participants, moderate-quality evidence). In a subgroup analysis of participants with an anterior circulation aneurysm, the RR of poor outcome was 0.78 (95% CI 0.68 to 0.90; 2 trials, 2157 participants, moderate-quality evidence), and the absolute risk decrease was 7% (95% CI 3% to 10%). In subgroup analysis of those with a posterior circulation aneurysm, the RR was 0.41 (95% CI 0.19 to 0.92; 2 trials, 69 participants, low-quality evidence), and the absolute decrease in risk was 27% (95% CI 6% to 48%). At five years, 28% of participants randomised to endovascular treatment and 32% of participants randomised to surgical treatment had poor functional outcome. The RR of poor outcome for endovascular coiling versus neurosurgical clipping was 0.87 (95% CI 0.75 to 1.01, 1 trial, 1724 participants, low-quality evidence). At 10 years, 35% participants allocated to endovascular and 43% participants allocated to surgical treatment had poor functional outcome. At 10 years RR of poor outcome for endovascular coiling versus neurosurgical clipping was 0.81 (95% CI 0.70 to 0.92; 1 trial, 1316 participants, low-quality evidence). The RR of delayed cerebral ischaemia at two to three months for endovascular coiling versus neurosurgical clipping was 0.84 (95% CI 0.74 to 0.96; 4 trials, 2450 participants, moderate-quality evidence). The RR of rebleeding for endovascular coiling versus neurosurgical clipping was 1.83 (95% CI 1.04 to 3.23; 4 trials, 2458 participants, high-quality evidence) at one year, and 2.69 (95% CI 1.50 to 4.81; 1 trial, 1323 participants, low-quality evidence) at 10 years. The RR of complications from intervention for endovascular coiling versus neurosurgical clipping was 1.05 (95% CI 0.44 to 2.53; 2 trials, 129 participants, low-quality evidence). AUTHORS' CONCLUSIONS: The evidence in this systematic review comes mainly from one large trial, and long-term follow-up is available only for a subgroup of participants within that trial. For people in good clinical condition with ruptured aneurysms of either the anterior or posterior circulation the data from randomised trials show that, if the aneurysm is considered suitable for both neurosurgical clipping and endovascular coiling, coiling is associated with a better outcome. There is no reliable trial evidence that can be used directly to guide treatment in people with a poor clinical condition.