Jukka Huttunen

Positron emission tomography with [18F]flutemetamol and [11C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients

This study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [18F]flutemetamol and amyloid‐β measured by immunohistochemical and histochemical staining in a frontal cortical biopsy.

Epilepsy after aneurysmal subarachnoid hemorrhage A population-based, long-term follow-up study

Objective: The aim was to elucidate the incidence and risk factors of epilepsy after subarachnoid hemorrhage (SAH) from saccular intracranial aneurysm (sIA) in a population-based cohort. Methods: The Kuopio sIA Database (www.uef.fi/ns) includes all unruptured and ruptured sIA cases admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland. The use of prescribed medicines, including reimbursable antiepileptic drugs, has been entered from the Finnish national registries. The cumulative incidence and independent risk factors of epilepsy and death were analyzed in 876 patients with sIA-SAH admitted from 1995 to 2007. The competing risks analysis was used to correctly estimate the probability of epilepsy, because epilepsy and death after sIA-SAH may share risk factors. Results: The follow-up ended at death (n = 200) or December 31, 2008; median follow-up time was 76 months. Epilepsy was diagnosed in 113 patients in a median of 8 months after sIA-SAH. Cumulative incidence of epilepsy after sIA-SAH was 8% at 1 year and 12% at 5 years. Thirty-three percent of patients with intracerebral hemorrhage (ICH) >15 cm3 developed epilepsy. In the 876 patients with sIA-SAH, the independent risk factors for epilepsy were ICH >15 cm3, Hunt and Hess grade III–V, and acute seizures. Conclusions: Cumulative incidence of epilepsy is 12% at 5 years. Epilepsy and 12-month mortality after sIA-SAH share poor Hunt and Hess grading as an independent risk factor. Epilepsy in the 2-week survivors of sIA-SAH is predicted by signs of primary injury in the brain tissue, most notably ICH.OBJECTIVE The aim was to elucidate the incidence and risk factors of epilepsy after subarachnoid hemorrhage (SAH) from saccular intracranial aneurysm (sIA) in a population-based cohort. METHODS The Kuopio sIA Database (www.uef.fi/ns) includes all unruptured and ruptured sIA cases admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland. The use of prescribed medicines, including reimbursable antiepileptic drugs, has been entered from the Finnish national registries. The cumulative incidence and independent risk factors of epilepsy and death were analyzed in 876 patients with sIA-SAH admitted from 1995 to 2007. The competing risks analysis was used to correctly estimate the probability of epilepsy, because epilepsy and death after sIA-SAH may share risk factors. RESULTS The follow-up ended at death (n = 200) or December 31, 2008; median follow-up time was 76 months. Epilepsy was diagnosed in 113 patients in a median of 8 months after sIA-SAH. Cumulative incidence of epilepsy after sIA-SAH was 8% at 1 year and 12% at 5 years. Thirty-three percent of patients with intracerebral hemorrhage (ICH) >15 cm(3) developed epilepsy. In the 876 patients with sIA-SAH, the independent risk factors for epilepsy were ICH >15 cm(3), Hunt and Hess grade III-V, and acute seizures. CONCLUSIONS Cumulative incidence of epilepsy is 12% at 5 years. Epilepsy and 12-month mortality after sIA-SAH share poor Hunt and Hess grading as an independent risk factor. Epilepsy in the 2-week survivors of sIA-SAH is predicted by signs of primary injury in the brain tissue, most notably ICH.

Risk of Shunting After Aneurysmal Subarachnoid Hemorrhage: A Collaborative Study and Initiation of a Consortium.

Background and Purpose— Shunt dependent hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH) is a common sequela that may lead to poor neurological outcome and predisposes to various interventions, admissions, and complications. We reviewed post-aSAH shunt dependency in a population-based sample and tested the feasibility of a clinical risk score to identify subgroups of aSAH patients with increasing risk of shunting for hydrocephalus. Methods— A total of 1533 aSAH patients from the population-based Eastern Finland Saccular Intracranial Aneurysm Database (Kuopio, Finland) were used in a recursive partitioning analysis to identify risk factors for shunting after aSAH. The risk model was built and internally validated in random split cohorts. External validation was conducted on 946 aSAH patients from the Southwestern Tertiary Aneurysm Registry (Dallas, TX) and tested using receiver-operating characteristic curves. Results— Of all patients alive ≥14 days, 17.7% required permanent cerebrospinal fluid diversion. The recursive partitioning analysis defined 6 groups with successively increased risk for shunting. These groups also successively risk stratified functional outcome at 12 months, shunt complications, and time-to-shunt rates. The area under the curve–receiver-operating characteristic curve for the exploratory sample and internal validation sample was 0.82 and 0.78, respectively, with an external validation of 0.68. Conclusions— Shunt dependency after aSAH is associated with higher morbidity and mortality, and prediction modeling of shunt dependency is feasible with clinically useful yields. It is important to identify and understand the factors that increase risk for shunting and to eliminate or mitigate the reversible factors. The aSAH-PARAS Consortium (Aneurysmal Subarachnoid Hemorrhage Patients’ Risk Assessment for Shunting) has been initiated to pool the collective insights and resources to address key questions in post-aSAH shunt dependency to inform future aSAH treatment guidelines.

De Novo Aneurysm Formation in Carriers of Saccular Intracranial Aneurysm Disease in Eastern Finland

Background and Purpose— Formation of new (de novo) aneurysms in patients carrying saccular intracranial aneurysm (sIA) disease has been published, but data from population-based cohorts are scarce. Methods— Kuopio sIA database (http://www.uef.fi/ns) contains all unruptured and ruptured sIA patients admitted to Kuopio University Hospital from its Eastern Finnish catchment population. We studied the incidence and risk factors for de novo sIA formation in 1419 sIA patients with ≥5 years of angiographic follow-up, a total follow-up of 18 526 patient-years. Results— There were 42 patients with a total of 56 de novo sIAs, diagnosed in a median of 11.7 years after the first sIA diagnosis. The cumulative incidence of de novo sIAs was 0.23% per patient-year and that of subarachnoid hemorrhage from a ruptured de novo sIA 0.05% per patient-year. The risk of de novo sIA discovery per patient-year increased with younger age at the first sIA diagnosis: 2.2% in the patients aged <20 years and 0.46% in the patients aged between 20 and 39 years. In Cox regression analysis, smoking history and younger age at the first sIA diagnosis significantly associated with de novo sIA formation, but female sex, multiple sIAs, and sIA family did not. Conclusions— Patients aged < 40 years at the first sIA diagnosis are in a significant risk of developing de novo sIAs, and they should be scheduled for long-term angiographic follow-up. Smoking increases the risk of de novo sIA formation, suggesting long-term follow-up for smokers. Antismoking efforts are highly recommended for sIA patients.

Antidepressant Use After Aneurysmal Subarachnoid Hemorrhage: A Population-Based Case–Control Study

Background and Purpose— To elucidate the predictors of antidepressant use after subarachnoid hemorrhage from saccular intracranial aneurysm (sIA-SAH) in a population-based cohort with matched controls. Methods— The Kuopio sIA database includes all unruptured and ruptured sIA cases admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland, with 3 matched controls for each patient. The use of all prescribed medicines has been fused from the Finnish national registry of prescribed medicines. In the present study, 2 or more purchases of antidepressant medication indicated antidepressant use. The risk factors of the antidepressant use were analyzed in 940 patients alive 12 months after sIA-SAH, and the classification tree analysis was used to create a predicting model for antidepressant use after sIA-SAH. Results— The 940 12-month survivors of sIA-SAH had significantly more antidepressant use (odds ratio, 2.6; 95% confidence interval, 2.2–3.1) than their 2676 matched controls (29% versus 14%). Classification tree analysis, based on independent risk factors, was used for the best prediction model of antidepressant use after sIA-SAH. Modified Rankin Scale until 12 months was the most potent predictor, followed by condition (Hunt and Hess Scale) and age on admission for sIA-SAH. Conclusions— The sIA-SAH survivors use significantly more often antidepressants, indicative of depression, than their matched population controls. Even with a seemingly good recovery (modified Rankin Scale score, 0) at 12 months after sIA-SAH, there is a significant risk of depression requiring antidepressant medication.

Irregular Shape Identifies Ruptured Intracranial Aneurysm in Subarachnoid Hemorrhage Patients With Multiple Aneurysms

Background and Purpose— We investigated which aneurysm-related risk factors for rupture best discriminate ruptured versus unruptured saccular intracranial aneurysms (sIAs) in subarachnoid hemorrhage patients with multiple sIAs. Methods— We included 264 subarachnoid hemorrhage patients with a ruptured sIA and at least one additional unruptured sIA, from the Kuopio Intracranial Aneurysm database from 2003 to 2015. These patients had 268 ruptured and 445 unruptured sIAs. Angiograms of the 713 sIAs were reevaluated for multiple variables describing aneurysm shape. Multivariate generalized linear mixed models were used to calculate odds ratios with corresponding 95% confidence intervals for the independent risk factors for aneurysm rupture. Results— In the multivariate analysis, only sIA size (P<0.004) and irregular shape (P<0.000) independently associated with sIA rupture. As an independent risk factor, irregular shape showed the strongest association with rupture (odds ratio 90.3; 95% confidence interval, 47.0–173.5). The sIA location, flow angles, bottleneck factor, or aspect ratio were not significantly associated with rupture. Conclusions— Irregular shape may identify the ruptured sIA better than size in patients presenting with aSAH and multiple sIAs.

Epilepsy-associated long-term mortality after aneurysmal subarachnoid hemorrhage

Objective: To elucidate the epilepsy-associated causes of death and subsequent excess long-term mortality among 12-month survivors of subarachnoid hemorrhage from saccular intracranial aneurysm (SIA-SAH). Methods: The Kuopio SIA Database (kuopioneurosurgery.fi) includes all SIA-SAH patients admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland. The study cohort consists of 779 patients, admitted from 1995 to 2007, who were alive at 12 months after SIA-SAH. Their use of reimbursable antiepileptic drugs and the causes of death (ICD-10) were fused from the Finnish national registries from 1994 to 2014. Results: The 779 12-month survivors were followed up until death (n = 197) or December 31, 2014, a median of 12.0 years after SIA-SAH. Epilepsy had been diagnosed in 121 (15%) patients after SIA-SAH, and 34/121 (28%) had died at the end of follow-up, with epilepsy as the immediate cause of death in 7/34 (21%). In the 779 patients alive at 12 months after SIA-SAH, epilepsy was an independent risk factor for mortality (hazard ratio 1.8, 95% confidence interval 1.1–3.0). Conclusions: Comorbid epilepsy in 12-month survivors of SIA-SAH is associated with increased risk of death in long-term follow-up. Survivors of SIA-SAH require long-term dedicated follow-up, including identification and effective treatment of comorbid epilepsy to prevent avoidable deaths.

Polycystic kidney disease among 4,436 intracranial aneurysm patients from a defined population

Objective: To define the association of autosomal dominant polycystic kidney disease (ADPKD) with the characteristics of aneurysmal subarachnoid hemorrhage (aSAH) and unruptured intracranial aneurysm (IA) disease. Methods: We fused data from the Kuopio Intracranial Aneurysm database (n = 4,436 IA patients) and Finnish nationwide registries into a population-based series of 53 IA patients with ADPKD to compare the aneurysm- and patient-specific characteristics of IA disease in ADPKD and in the general IA population, and to identify risks for de novo IA formation. Results: In total, there were 33 patients with ADPKD with aSAH and 20 patients with ADPKD with unruptured IAs. The median size of ruptured IAs in ADPKD was significantly smaller than in the general population (6.00 vs 8.00 mm) and the proportion of small ruptured IAs was significantly higher (31% vs 18%). Median age at aSAH was 42.8 years, 10 years younger than in the general IA population. Multiple IAs were present in 45% of patients with ADPKD compared to 28% in the general IA population. Cumulative risk of de novo IA formation was 1.3% per patient-year (vs 0.2% in the general IA population). Hazard for de novo aneurysm formation was significantly elevated in patients with ADPKD (Cox regression hazard ratio 7.7, 95% confidence interval 2.8–20; p < 0.0005). Conclusions: Subarachnoid hemorrhage occurs at younger age and from smaller IAs in patients with ADPKD and risk for de novo IAs is higher than in the general Eastern Finnish population. ADPKD should be considered as an indicator for long-term angiographic follow-up in patients with diagnosed IAs.

Impact of Young Age on the Presentation of Saccular Intracranial Aneurysms: Population-Based Analysis of 4082 Patients

BACKGROUND Formation and rupture of saccular intracranial aneurysms (sIAs) may have different pathobiologies in patients with younger age at first diagnosis of sIA disease. OBJECTIVE To study the phenotype of sIA disease and formation of new (de novo) sIAs in patients below 40 yr. METHODS A population‐based cohort study was conducted in 613 young (<40 yr) sIA patients with first diagnosis between 1980 and 2014 and total angiographic follow‐up of 3768 yr. RESULTS Of the 613 sIA patients <40 yr, 508 had aneurysmal subarachnoid hemorrhage (sIA‐SAH) and 105 unruptured sIA(s) at first sIA diagnosis. Hypertension was 2 times less common among <40 than >40‐yr‐old patients (unruptured and ruptured). Smoking was very prevalent in <40‐yr‐old patients (33% in SAH, 68% unruptured). SAH patients <40 yr more often had family history of sIA, and lower PHASES scores (age omitted, P < .001). Ruptured sIAs were small (<7 mm) in 33% of 39 to 30 yr patients, in 44% of 29 to 20 yr patients, and 57% of <19 yr patients. Their shape was irregular in 90% 94% and 95% respectively. Smoking history (hazard ratio [HR] 2.8, 95% confidence interval [CI] 1.2‐7.0) family history for sIAs (HR 3.1, 95% CI 1.3‐7.7) and age at presentation (HR .91 per year, 95% CI .85‐.98) were risk factors for de novo sIA formation, diagnosed in 4% even after 20 yr (median 11.8 yr). CONCLUSION Smoking and family history are risk factors for sIA formation and aneurysmal SAH at young age. Young aneurysmal SAH patients had lower PHASES scores and often rupture from a small sIA, suggesting need for more aggressive management.

Neurofibromatosis type 1 is not associated with subarachnoid haemorrhage

Background The prevalence of intracranial aneurysms (IAs) has been proposed to be elevated in the patients with neurofibromatosis type 1 (NF1). Our aims were to determine the prevalence of NF1 in a large Finnish population based cohort of IA patients and, on the other hand, the occurrences of subarachnoid haemorrhage and unruptured intracranial aneurysms in a nationwide population-based cohort of NF1 patients and its matched ten-fold control cohort. Methods The Kuopio IA Database (www.kuopioneurosurgery.fi) includes all ruptured and unruptured IA cases admitted to the Kuopio University Hospital (KUH) from its defined Eastern Finnish catchment population since 1980. In this registry-based study, we cross-linked the Kuopio IA database with the Finnish national registry covering all hospital diagnoses. The NF1 diagnoses of the 4543 patients with either saccular of fusiform IA were identified from 1969 to 2015 and verified from patient records. Our second approach was to analyze the occurrence of aneurysmal subarachnoid haemorrhage (aSAH) and unruptured IAs in a nationwide population-based database of 1410 NF1 patients and its ten-fold matched control cohort (n = 14030) using national registry of hospital diagnoses between 1987 and 2014. Results One NF1 patient was identified among the 4543 IA patients. Three verified IA cases (one unruptured IA and two aSAH cases) were identified in the cohort of 1410 NF1 patients, with similar occurrences in the control cohort. Conclusions We found no evidence in our population-based cohorts to support the conception that NF1 is associated with IAs. Our results indicate that the incidence of aSAH is not elevated in patients with NF1. Further studies are required to confirm that there is no association between NF1 and unruptured IAs.