Publications by authors named "Jaakko Rinne"

68 Publications

Occurrence, Risk Factors, and Time Trends for Late Reoperations due to Degenerative Cervical Spine Disease: A Finnish National Register Study of 19 377 Patients Operated on Between 1999 and 2015.

Neurosurgery 2021 02;88(3):558-573

National Institute for Health and Welfare, Centre for Health and Social economics, Helsinki, Finland.

Background: Surgery for degenerative cervical spine disease has escalated since the 1990s. Fusion has become the mainstay of surgery despite concerns regarding adjacent segment degeneration. The patient-specific trends in reoperations have not been studied previously.

Objective: To analyze the occurrence, risk factors, and trends in reoperations in a long-term follow-up of all the patients operated for degenerative cervical spine disease in Finland between 1999 and 2015.

Methods: The patients were retrospectively identified from the Hospital Discharge Registry. Reoperations were traced individually; only reoperations occurring >365 d after the primary operation were included. Time trends in reoperations and the risk factors were analyzed by regression analysis.

Results: Of the 19 377 identified patients, 9.2% underwent a late reoperation at a median of 3.6 yr after the primary operation. The annual risk of reoperation was 2.4% at 2 yr, 6.6% at 5 yr, 11.1% at 10 yr, and 14.2% at 15 yr. Seventy-five percent of the late reoperations occurred within 6.5 yr of the primary operation. Foraminal stenosis, the anterior cervical decompression and fusion (ACDF) technique, male gender, weak opiate use, and young age were the most important risk factors for reoperation. There was no increase in the risk of reoperations over the follow-up period.

Conclusion: The risk of reoperation was stable between 1999 and 2015. The reoperation risk was highest during the first 6 postoperative years and then declined. Patients with foraminal stenosis had the highest risk of reoperation, especially when ACDF was performed.
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http://dx.doi.org/10.1093/neuros/nyaa464DOI Listing
February 2021

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case-control comparison with family members.

Fluids Barriers CNS 2020 Sep 15;17(1):57. Epub 2020 Sep 15.

Department of Neurosurgery, Kuopio University Hospital, P.O.Box 100, 70029, Kuopio, KYS, Finland.

Background: The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families.

Methods: Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their ≥ 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher's exact test (two-tailed), the Mann-Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses.

Results: Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1-12.9, p = 0.030).

Conclusions: Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.
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http://dx.doi.org/10.1186/s12987-020-00217-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493374PMC
September 2020

A comprehensive p75 neurotrophin receptor gene network and pathway analyses identifying new target genes.

Sci Rep 2020 09 11;10(1):14984. Epub 2020 Sep 11.

Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital and University of Turku, Hämeentie 11, P.O. Box 52, 20521, Turku, Finland.

P75 neurotrophic receptor (p75NTR) is an important receptor for the role of neurotrophins in modulating brain plasticity and apoptosis. The current understanding of the role of p75NTR in cellular adaptation following pathological insults remains blurred, which makes p75NTR's related signaling networks an interesting and challenging initial point of investigation. We identified p75NTR and related genes through extensive data mining of a PubMed literature search including published works related to p75NTR from the past 20 years. Bioinformatic network and pathway analyses of identified genes (n = 235) were performed using ReactomeFIViz in Cytoscape based on the highly reliable Reactome functional interaction network algorithm. This approach merges interactions extracted from human curated pathways with predicted interactions from machine learning. Genome-wide pathway analysis showed total of 16 enriched hierarchical clusters. A total of 278 enriched single pathways were also identified (p < 0.05, false discovery rate corrected). Gene network analyses showed multiple known and new targets in the p75NTR gene network. This study provides a comprehensive analysis and investigation into the current knowledge of p75NTR signaling networks and pathways. These results also identify several genes and their respective protein products as involved in the p75NTR network, which have not previously been clearly studied in this pathway. These results can be used to generate novel hypotheses to gain a greater understanding of p75NTR in acute brain injuries, neurodegenerative diseases and general response to cellular damage.
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http://dx.doi.org/10.1038/s41598-020-72061-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486379PMC
September 2020

External Validation of the ELAPSS Score for Prediction of Unruptured Intracranial Aneurysm Growth Risk.

J Stroke 2019 09 30;21(3):340-346. Epub 2019 Sep 30.

Department of Neurology and Neurosurgery, University Medical Centre Utrecht, Utrecht, the Netherlands.

Background And Purpose: Prediction of intracranial aneurysm growth risk can assist physicians in planning of follow-up imaging of conservatively managed unruptured intracranial aneurysms. We therefore aimed to externally validate the ELAPSS (Earlier subarachnoid hemorrhage, aneurysm Location, Age, Population, aneurysm Size and Shape) score for prediction of the risk of unruptured intracranial aneurysm growth.

Methods: From 11 international cohorts of patients ≥18 years with ≥1 unruptured intracranial aneurysm and ≥6 months of radiological follow-up, we collected data on the predictors of the ELAPSS score, and calculated 3- and 5-year absolute growth risks according to the score. Model performance was assessed in terms of calibration (predicted versus observed risk) and discrimination (c-statistic).

Results: We included 1,072 patients with a total of 1,452 aneurysms. During 4,268 aneurysm-years of follow-up, 199 (14%) aneurysms enlarged. Calibration was comparable to that of the development cohort with the overall observed risks within the range of the expected risks. The c-statistic was 0.69 (95% confidence interval [CI], 0.64 to 0.73) at 3 years, compared to 0.72 (95% CI, 0.68 to 0.76) in the development cohort. At 5 years, the c-statistic was 0.68 (95% CI, 0.64 to 0.72), compared to 0.72 (95% CI, 0.68 to 0.75) in the development cohort.

Conclusion: s The ELAPSS score showed accurate calibration for 3- and 5-year risks of aneurysm growth and modest discrimination in our external validation cohort. This indicates that the score is externally valid and could assist patients and physicians in predicting growth of unruptured intracranial aneurysms and plan follow-up imaging accordingly.
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http://dx.doi.org/10.5853/jos.2019.01277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780020PMC
September 2019

Prevalence of thoracic aortic aneurysms and dilatations in patients with intracranial aneurysms.

J Vasc Surg 2019 12 18;70(6):1801-1808. Epub 2019 Jul 18.

Heart Center, Turku University Hospital and University of Turku, Turku, Finland.

Objective: The prevalence of intracranial aneurysms (IAs) is higher in patients with aortic aneurysms. However, there are lack of studies investigating prevalence of thoracic aortic aneurysms (TAAs) in patients with IAs. The objective of this study was to evaluate the prevalence and risk factors for thoracic aortic dilatations (TADs) and TAAs in patients with IAs.

Methods: We retrospectively reviewed data from 1777 patients with diagnosed IAs at our institution between 2006 and 2016. We included 411 patients with saccular IAs and available imaging studies (computed tomography or magnetic resonance imaging) of all thoracic aortic segments. TAD was defined according to age- and sex-matched normograms, and TAA as a diameter of greater than 4.0 cm.

Results: A total of 83 patients (20%) had TAD or TAA. The prevalence of TADs and TAAs were 18% (n = 74) and 8% (n = 31) without significant difference between unruptured and ruptured IAs (P = .7). Of the 74 patients with TAD, 22 (30%) had multiple TADs and 66% of the TADs located in the aortic arch. Older age (odds ratio [OR], 1.04; P = .006), rheumatic disease (OR, 4.73; P = .009) and alcohol abuse (OR, 4.77; P = .01) were significant risk factors for TAD/TAA.

Conclusions: The prevalence of TADs and TAAs is considerably greater in patients with IAs compared with reports from the general population, suggesting that IAs might be associated with aortopathy and might share a similar pathogenetic background with TADs/TAAs. Especially patients with IAs and a history of rheumatic disease and/or alcohol abuse are at high risk for TADs/TAAs.
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http://dx.doi.org/10.1016/j.jvs.2019.01.066DOI Listing
December 2019

Fatal traumatic brain injuries during 13 years of successive alcohol tax increases in Finland - a nationwide population-based registry study.

Sci Rep 2019 04 1;9(1):5419. Epub 2019 Apr 1.

Heart Center, Turku University Hospital, Turku, Finland.

We sought to investigate how increases in alcohol taxation and changes in alcohol consumption were associated with the incidence rate of fatal traumatic brain injuries (TBI) in Finland during the years 2004-2016. Nationwide, mandatory cause of death database covering all deaths in Finland was searched for all deaths related to TBIs (ICD-10: S06.X) in persons ≥16 years of age during 2004-2016. Study period included 28,657,870 person-years and 325,514 deaths of which 12,110 were TBI-related. Occurrence rates were standardized to European 2013 standard population. Data for alcohol consumption were obtained from the National Institute for Health and Welfare and for alcohol taxation from Ministry of Finance, Finland. Standardized incidence rate of TBI-related death was 22.0 (95% CI 21.61-22.38) per 100,000 person-years. Overall alcohol consumption decreased on average by 1.2% annually. Concurrently, the overall incidence rate of fatal TBIs decreased by 4.1% annually (by 4.3% in men and 2.4% in women). There was an association between overall alcohol consumption and TBI-related mortality rate (p < 0.001). Tax-rate increases of all beverage types were associated with decreased incidence rate of TBI-related death in men (p < 0.001), in women (p < 0.036) and overall (p < 0.001). In this population-based study, we report that during 13 years of successive alcohol tax increases, overall alcohol consumption has decreased in parallel with a reduction in the incidence rate of fatal TBIs in Finland.
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http://dx.doi.org/10.1038/s41598-019-41913-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443785PMC
April 2019

Unlikely association between Kawasaki disease and intracranial aneurysms: a prospective cohort study.

J Neurosurg Pediatr 2019 Feb 15:1-4. Epub 2019 Feb 15.

1Department of Neurosurgery, Division of Clinical Neurosciences.

OBJECTIVEKawasaki disease (KD) is a vasculitis that can cause aneurysm formation in coronary arteries and, more rarely, in peripheral arteries. A possible connection between KD and intracranial aneurysms is unclear. The purpose of this study was to determine if KD is associated with intracranial aneurysms.METHODSIn this prospective cohort study, all patients hospitalized and diagnosed with KD in the authors' hospital district area in the period from 1978 to 1995 were identified. Patients with a current age ≥ 25 years and a history of KD in childhood were included in the study, which was conducted between 2016 and 2017. Magnetic resonance angiography (MRA) of the brain was performed in all patients.RESULTSForty patients (25 males), whose mean age was 33.5 ± 3.9 years (mean ± standard deviation), were eligible for study inclusion. The mean age at KD diagnosis was 3.9 ± 3.1 years, and the mean follow-up was 29.5 ± 4.3 years. Six patients (15%) had coronary arterial lesions during the acute illness of KD. None of the patients (0%) had intracranial aneurysms on brain MRA, which is significantly under the prevalence of 10% (95% CI 0%-8.8%, p = 0.03) that is the recommended limit for intracranial aneurysm screening.CONCLUSIONSThe study results suggest that KD is not associated with an increased prevalence of intracranial aneurysms and that screening for intracranial aneurysms is not warranted in patients with a history of KD.
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http://dx.doi.org/10.3171/2018.11.PEDS18575DOI Listing
February 2019

[11C]PIB PET Is Associated with the Brain Biopsy Amyloid-β Load in Subjects Examined for Normal Pressure Hydrocephalus.

J Alzheimers Dis 2019 ;67(4):1343-1351

Institute of Clinical Medicine, Neurosurgery, University of Eastern Finland, Kuopio, Finland.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with concomitant amyloid-β (Aβ) pathology.

Objective: To compare the [11C]PIB PET uptake in the patients with suspected iNPH to Aβ and hyperphosphorylated-tau (HPτ) in the right frontal cortical biopsy, the cerebrospinal fluid (CSF) Aβ, the response to a CSF shunt, and the final clinical diagnosis of Alzheimer's disease (AD).

Methods: Patients (n = 21) from Kuopio NPH Registry (http://www.uef.fi/nph) with intraventricular pressure monitoring, immunostaining for Aβ and HPτ in the right frontal cortical biopsies, and a Mini-Mental State Examination and a Clinical Dementia Rating underwent [11C]PIB PET. Aβ, total tau, and Pτ181 were measured by ELISA from the ventricular (n = 15) and the lumbar (n = 9) CSF. Response to the shunt was seen in 13 out of the 15 shunted patients. AD was diagnosed in 8 patients during a median follow-up of 6 years (mean 7.3±2.4 years, range 3-1).

Results: [11C]PIB uptake in the right frontal cortex (ρ= 0.60, p < 0.01) and the combined neocortical [11C]PIB uptake score (ρ= 0.61, p < 0.01) were associated with a higher Aβ load in the right frontal cortical biopsy. Excluding one (1/15) outlier, [11C]PIB uptake was also associated with the ventricular CSF Aβ (ρ= -0.58, p = 0.03).

Conclusions: The findings show that [11C]PIB PET can reliably detect simultaneous amyloid pathology among the iNPH patients. Further studies will show whether amyloid PET could predict a clinical response to the shunt operation. In addition, the presence of Aβ pathology in the patients with iNPH might also warrant treatment with current AD drugs.
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http://dx.doi.org/10.3233/JAD-180645DOI Listing
May 2020

Risk Factors for Recurrent Hematoma After Surgery for Acute Traumatic Subdural Hematoma.

World Neurosurg 2019 Jan 10. Epub 2019 Jan 10.

Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital and University of Turku, Turku, Finland; Neurovascular Surgery Program, Section of Neurosurgery, University of Chicago Medicine and Biological Sciences, Chicago, Illinois, USA. Electronic address:

Objective: The development of postcraniotomy hematoma (PCH) after surgery for acute traumatic subdural hematoma (aSDH) has been associated with an increased risk of a poor outcome. The risk factors contributing to PCH remain poorly understood. Our aim was to study the potential risk factors for PCH in a consecutive series of surgically evacuated patients with aSDH.

Methods: A total of 132 patients with aSDH treated at Turku University Hospital (Turku, Finland) from 2008 to 2012 were enrolled in the present retrospective cohort study. The demographic, clinical, laboratory, and imaging data were collected from the medical records. A comprehensive analysis of the data using 6 different univariate methods, including machine learning and multivariate analyses, was conducted to identify the factors related to PCH.

Results: The incidence of PCH after primary surgery for traumatic aSDH was 10.6%. The patients experiencing PCH were younger (P = 0.04). No difference was found in the use of anticoagulant or antiplatelet medication for the patients with and without PCH. Multivariate analyses identified alcohol inebriation at the time of injury (odds ratio [OR], 12.67; P = 0.041) and hypocapnia (OR, 26.09; P = 0.003) as independent risk factors for PCH. The patients with PCH had had hyponatremia (OR, 0.08; P = 0.018) less often, and their maximal systolic blood pressure was lower (OR, 0.94; P = 0.009). The area under the curve for the multivariate model was 0.96 (P = 0.049), with a Youden index of 0.88.

Conclusions: The results suggest that alcohol inebriation at the time of injury and hypocapnia during hospitalization are risk factors for the development of PCH.
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http://dx.doi.org/10.1016/j.wneu.2018.12.155DOI Listing
January 2019

Copy number loss in is common among Finnish and Norwegian patients with iNPH.

Neurol Genet 2018 Dec 3;4(6):e291. Epub 2018 Dec 3.

Department of Neurosurgery (V.E.K., A. Jokinen, I.J., J.-M.L., A. Junkkari, J.E.J., V.L.), Kuopio University Hospital and University of Eastern Finland; Institute of Clinical Medicine-Neurology (S.H., M.H., H. Soininen, A.M.K.), University of Eastern Finland, Kuopio; Department of Neurosurgery (M.O., K.L.), University of Helsinki and Helsinki University Hospital; Clinical Neurosciences (C.A., A.K., J.F., J.R.), Department of Neurosurgery, University of Turku and Turku University Hospital; Department of Neurosurgery (A.R.), Tampere University Hospital; Unit of Clinical Neuroscience (M. Kauppinen, V.L.), Neurosurgery, University of Oulu and Medical Research Center, Oulu University Hospital; Institute of Biomedicine (M.H.), University of Eastern Finland, Kuopio; Analytical and Translational Genetics Unit (M. Kurki), Department of Medicine, Massachusetts General Hospital; Program in Medical and Population Genetics (M. Kurki), Broad Institute of MIT and Harvard; Stanley Center for Psychiatric Research (M. Kurki), Broad Institute for Harvard and MIT; Department of Neurology (H. Sato, T.K.), Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University Faculty of Medicine, Japan; Medical Research Center (A.M.R.), Oulu University Hospital, Finland; Unit of Clinical Neuroscience (A.M.R.), Neurology, University of Oulu, Finland; Department of Neurosurgery (P.K.E.), Oslo University Hospital-Rikshospitalet; and Institute of Clinical Medicine (P.K.E.), Faculty of Medicine, University of Oslo, Norway.

Objective: To evaluate the role of the copy number loss in in a Caucasian population.

Methods: Five hundred sixty-seven Finnish and 377 Norwegian patients with idiopathic normal pressure hydrocephalus (iNPH) were genotyped and compared with 508 Finnish elderly, neurologically healthy controls. The copy number loss in intron 2 of was determined using quantitative PCR.

Results: The copy number loss in intron 2 of was detected in 10% of Finnish (odds ratio [OR] = 1.9, = 0.0078) and in 21% of Norwegian (OR = 4.7, < 0.0001) patients with iNPH compared with 5.4% in Finnish controls. No copy number gains in were detected in patients with iNPH or healthy controls. The carrier status did not provide any prognostic value for the effect of shunt surgery in either population. Moreover, no difference was detected in the prevalence of hypertension or T2DM between copy number loss carriers and noncarriers.

Conclusions: This is the largest and the first multinational study reporting the increased prevalence of the copy number loss in intron 2 of among patients with iNPH, providing further evidence of its role in iNPH. The pathogenic role still remains unclear, requiring further study.
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http://dx.doi.org/10.1212/NXG.0000000000000291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283454PMC
December 2018

Single-center experience with six-month follow-up of FRED Jr® flow diverters for intracranial aneurysms in small arteries.

Acta Radiol 2019 Jul 25;60(7):917-924. Epub 2018 Oct 25.

2 Department of Neurosurgery, Turku University Hospital, Turku, Finland.

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http://dx.doi.org/10.1177/0284185118805266DOI Listing
July 2019

Acute Treatment of Ruptured Fusiform Posterior Circulation Posterior Cerebral, Superior Cerebellar, and Posterior Inferior Cerebellar Artery Aneurysms With FRED Flow Diverter: Report of 5 Cases.

Oper Neurosurg (Hagerstown) 2019 05;16(5):549-556

Department of Neurosurgery, Turku University Hospital, University of Turku, Turku, Finland.

Background: Flow diverter (FD) treatment of ruptured fusiform posterior cerebral artery (PCA), posterior inferior cerebellar artery (PICA), and superior cerebellar artery (SCA) aneurysms are limited to single reports.

Objective: To study the safety and efficacy of FD treatment for ruptured fusiform aneurysms of the PCA, SCA, and PICA.

Methods: Five patients with ruptured posterior circulation fusiform aneurysms and treated with a Flow-Redirection Endoluminal Device (FRED/FRED Jr; Microvention, Tustin, California) stent in the acute phase of subarachnoid hemorrhage between 2013 and 2016 were included and reviewed retrospectively.

Results: Two aneurysms located on the PICA, 2 on PCA, and 1 on the SCA. Mean treatment time with FD was 5.8 d (range, 0-11 d) from ictus. The technical success rate was 100%. On admission 2 patients were Hunt and Hess grade 1, 2 patients grade 3, and 1 patient grade 4. At discharge, 4 patients (80%) were independent (modified Ranking Scale (mRS) ≤2) and 1 patient had severe disability (mRS 4). None of the patients had aneurysmal rebleeding. All 5 aneurysms were completely occluded on angiographic follow-up (range, 3-22 mo). One patient had permanent intraprocedural in stent thrombosis and brain infarction. One patient had spontaneous nonaneurysmal intracerebral hemorrhage 1 mo after FD treatment. External ventricular drainage was inserted in 3 patients and ventriculoperitoneal shunt in 2 patients without hemorrhagic complications despite dual antiplatelet therapy.

Conclusion: FD could be considered as a treatment option for ruptured fusiform aneurysms located on PCA, PICA, or SCA when other treatment options are challenging.
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http://dx.doi.org/10.1093/ons/opy194DOI Listing
May 2019

Cranioplasty After Severe Traumatic Brain Injury: Effects of Trauma and Patient Recovery on Cranioplasty Outcome.

Front Neurol 2018 9;9:223. Epub 2018 Apr 9.

Department of Biomaterials Science and Turku Clinical Biomaterials Centre--TCBC, Institute of Dentistry, University of Turku, Turku, Finland.

Background: In patients with severe traumatic brain injury (sTBI) treated with decompressive craniectomy (DC), factors affecting the success of later cranioplasty are poorly known.

Objective: We sought to investigate if injury- and treatment-related factors, and state of recovery could predict the risk of major complications in cranioplasty requiring implant removal, and how these complications affect the outcome.

Methods: A retrospective cohort of 40 patients with DC following sTBI and subsequent cranioplasty was studied. Non-injury-related factors were compared with a reference population of 115 patients with DC due to other conditions.

Results: Outcome assessed 1 day before cranioplasty did not predict major complications leading to implant removal. Successful cranioplasty was associated with better outcome, whereas a major complication attenuates patient recovery: in patients with favorable outcome assessed 1 year after cranioplasty, major complication rate was 7%, while in patients with unfavorable outcome the rate was 42% ( = 0.003). Of patients with traumatic subarachnoid hemorrhage (tSAH) on admission imaging 30% developed a major complication, while none of patients without tSAH had a major complication ( = 0.014). Other imaging findings, age, admission Glasgow Coma Scale, extracranial injuries, length of stay at intensive care unit, cranioplasty materials, and timing of cranioplasty were not associated with major complications.

Conclusion: A successful cranioplasty after sTBI and DC predicts favorable outcome 1 year after cranioplasty, while stage of recovery before cranioplasty does not predict cranioplasty success or failure. tSAH on admission imaging is a major risk factor for a major complication leading to implant removal.
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http://dx.doi.org/10.3389/fneur.2018.00223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904383PMC
April 2018

Temporal Trends in Healthcare Costs and Outcome Following ICU Admission After Traumatic Brain Injury.

Crit Care Med 2018 04;46(4):e302-e309

Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Objective: To assess temporal trends in 1-year healthcare costs and outcome of intensive care for traumatic brain injury in Finland.

Design: Retrospective observational cohort study.

Setting: Multicenter study including four tertiary ICUs.

Patients: Three thousand fifty-one adult patients (≥ 18 yr) with significant traumatic brain injury treated in a tertiary ICU during 2003-2013.

Intervention: None.

Measurements And Main Results: Total 1-year healthcare costs included the index hospitalization costs, rehabilitation unit costs, and social security reimbursements. All costs are reported as 2013 U.S. dollars ($). Outcomes were 1-year mortality and permanent disability. Multivariate regression models, adjusting for case-mix, were used to assess temporal trends in costs and outcome in predefined Glasgow Coma Scale (3-8, 9-12, and 13-15) and age (18-40, 41-64, and ≥ 65 yr) subgroups. Overall 1-year survival was 76% (n = 2,304), and of 1-year survivors, 37% (n = 850) were permanently disabled. Mean unadjusted 1-year healthcare cost was $39,809 (95% CI, $38,144-$41,473) per patient. Adjusted healthcare costs decreased only in the Glasgow Coma Scale 13-15 and 65 years and older subgroups, due to lower rehabilitation costs. Adjusted 1-year mortality did not change in any subgroup (p < 0.05 for all subgroups). Adjusted risk of permanent disability decreased significantly in all subgroups (p < 0.05).

Conclusion: During the last decade, healthcare costs of ICU-admitted traumatic brain injury patients have remained largely the same in Finland. No change in mortality was noted, but the risk for permanent disability decreased significantly. Thus, our results suggest that cost-effectiveness of traumatic brain injury care has improved during the past decade in Finland.
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http://dx.doi.org/10.1097/CCM.0000000000002959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865506PMC
April 2018

Accuracy of 837 pedicle screw positions in degenerative lumbar spine with conventional open surgery evaluated by computed tomography.

Acta Neurochir (Wien) 2017 10 10;159(10):2011-2017. Epub 2017 Aug 10.

Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, Hämeentie 11, 20521, Turku, Finland.

Background: The spatial and directional accuracy of the positioning of pedicle screws in the lumbosacral spine with conventional open surgery assessed by computed tomography (CT) has been published in several studies, systematic reviews and meta-analyses with a short-term follow-up. Inaccurate pedicle screw insertion may cause neurologic symptoms and weakens the construct.

Methods: The data of 147 patients operated on with transpedicular screw fixation based on anatomical landmarks, supported by fluoroscopy, by a senior neurosurgeon in our clinic between 2000 and 2010 were analyzed retrospectively. The accuracy of the pedicle screw position was assessed by using postoperative CT images and graded in 2-mm increments up to 6 mm by two independent surgeons and partly by an independent radiologist.

Results: A total of 837 lumbosacral pedicle screws were inserted in 147 randomly selected patients by a senior neurosurgeon. A mean accuracy of 85.7% of the screws being inside the pedicles was identified by the surgeon observers, with 3.3% being perforated 4 mm or more outside the pedicles. Postoperative neurologic symptoms were observed on the side corresponding to the breach in an average of 25.9% of patients with pedicle perforations, and 89.2% of the misplaced screws were either medially or inferiorly inserted.

Conclusions: Screw application reached a mean accuracy of 85.7% based on anatomical landmarks supported by fluoroscopy, warranting computer-assisted navigation for increased accuracy. Our results of 24 patients (16.3%) with the breached screws indicate that the direction of the breach may be more important than the absolute deviation in causing new neurologic symptoms.
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http://dx.doi.org/10.1007/s00701-017-3289-7DOI Listing
October 2017

Traumatic brain injury patient volume and mortality in neurosurgical intensive care units: a Finnish nationwide study.

Scand J Trauma Resusc Emerg Med 2016 Nov 8;24(1):133. Epub 2016 Nov 8.

Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 4, PB-340, FI-00029 HUS, Helsinki, Finland.

Background: Differences in outcomes after traumatic brain injury (TBI) between neurosurgical centers exist, although the reasons for this are not clear. Thus, our aim was to assess the association between the annual volume of TBI patients and mortality in neurosurgical intensive care units (NICUs).

Methods: We collected data on all patients treated in the five Finnish university hospitals to examine all patients with TBI treated in NICUs in Finland from 2009 to 2012. We used a random effect logistic regression model to adjust for important prognostic factors to assess the independent effect of ICU volume on 6-month mortality. Subgroup analyses were performed for patients with severe TBI, moderate-to-severe TBI, and those who were undergoing mechanical ventilation or intracranial pressure monitoring.

Results: Altogether 2,328 TBI patients were treated during the study period in five NICUs. The annual TBI patient volume ranged from 61 to 206 patients between the NICUs. Univariate analysis, showed no association between the NICUs' annual TBI patient volume and 6-month mortality (p = 0.063). The random effect model showed no independent association between the NICUs' annual TBI patient volume and 6-month mortality (OR = 1.000, 95% CI = 0.996-1.004, p = 0.876). None of the pre-defined subgroup analyses indicated any association between NICU volume and patient mortality (p > 0.05 for all).

Discussion And Conclusion: We did not find any association between annual TBI patient volume and 6-month mortality in NICUs. These findings should be interpreted taking into account that we only included NICUs, which by international standards all treated high volumes of TBI patients, and that we were not able to study the effect of NICU volume on neurological outcome.
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http://dx.doi.org/10.1186/s13049-016-0320-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100100PMC
November 2016

Acute hormonal findings after aneurysmal subarachnoid hemorrhage - report from a single center.

Endocr Res 2017 May 18;42(2):125-131. Epub 2016 Oct 18.

e Department of Clinical Medicine, Biostatistics , University of Turku, and Turku University Hospital , Turku , Finland.

Purpose: The aim was to assess anterior pituitary hormone levels during the acute phase of aneurysmal subarachnoid hemorrhage (aSAH) and analyze the possible association with the clinical condition and outcome.

Material And Methods: Forty patients with aSAH whose aneurysm was secured by endovascular coiling were enrolled. Basal secretions of cortisol, testosterone, luteinizing hormone (LH), prolactin (PRL), and sex hormone binding globulin (SHBG) levels were measured up to 14 days after the incident.

Results: The main finding was that hypocortisolism was rare whereas testosterone deficiency was common in male patients. Furthermore, various other hormone deviations were frequent and there was wide interindividual variability. We found no association between delayed cerebral ischemia (DCI), outcome of the patients or aneurysm location, and hormone abnormalities, while both Hunt & Hess and Fisher grade were associated with low PRL levels. Hunt & Hess 5 was associated with low PRL concentration when compared to grades 1 (OR = 4.81, 95% CI 1.15-20.14, p = 0.03), 3 (OR 7.73, 95% CI 1.33-45.01, p = 0.02), and 4 (OR = 6.86 95% CI 1.28-26.83, p = 0.02). Fisher grade 4 was associated with low PRL concentration when compared to grades 3 (OR 3.37, 95% CI 1.06-10.73, p = 0.03) and 2 (OR 9.71, 95% CI 1.22-77.10, p = 0.04).

Conclusion: Deviations from normal and huge interindividual differences are common in hormone levels during the acute phase of aSAH. Routine assessment of anterior pituitary function in the acute phase of aSAH is not warranted. During the follow-up in the outpatient clinic, hormone concentrations were not measured, which would have brought a more long-term perspective into our findings.
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http://dx.doi.org/10.1080/07435800.2016.1242603DOI Listing
May 2017

Familial idiopathic normal pressure hydrocephalus.

J Neurol Sci 2016 Sep 25;368:11-8. Epub 2016 Jun 25.

Department of Neurosurgery, Kuopio University Hospital, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. Electronic address:

Idiopathic normal pressure hydrocephalus (iNPH) is a late-onset surgically alleviated, progressive disease. We characterize a potential familial subgroup of iNPH in a nation-wide Finnish cohort of 375 shunt-operated iNPH-patients. The patients were questionnaired and phone-interviewed, whether they have relatives with either diagnosed iNPH or disease-related symptomatology. Then pedigrees of all families with more than one iNPH-case were drawn. Eighteen patients (4.8%) from 12 separate pedigrees had at least one shunt-operated relative whereas 42 patients (11%) had relatives with two or more triad symptoms. According to multivariate logistic regression analysis, familial iNPH-patients had up to 3-fold risk of clinical dementia compared to sporadic iNPH patients. This risk was independent from diagnosed Alzheimer's disease and APOE ε4 genotype. This study describes a familial entity of iNPH offering a novel approach to discover the potential genetic characteristics of iNPH. Discovered pedigrees offer an intriguing opportunity to conduct longitudinal studies targeting potential preclinical signs of iNPH.
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http://dx.doi.org/10.1016/j.jns.2016.06.052DOI Listing
September 2016

The unruptured intracranial aneurysm treatment score: a multidisciplinary consensus.

Neurology 2015 Sep 14;85(10):881-9. Epub 2015 Aug 14.

Author affiliations are provided at the end of the article.

Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research.

Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement).

Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019-0.033).

Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.
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http://dx.doi.org/10.1212/WNL.0000000000001891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560059PMC
September 2015

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

Neurology 2015 Jun 6;84(22):2229-37. Epub 2015 May 6.

From Neurosurgery (J.H., M.I.K., M.v.u.z.F., T.K., J.E.J., A.I.) and Neurology (R.K.), NeuroCenter, Kuopio University Hospital, and Faculty of Health Sciences, School of Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio; Neurosurgery (A.R.), Tampere University Hospital; and Neurosurgery (J.R.), Turku University Hospital, Finland.

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.
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http://dx.doi.org/10.1212/WNL.0000000000001643DOI Listing
June 2015

Amyloid-β and Tau Dynamics in Human Brain Interstitial Fluid in Patients with Suspected Normal Pressure Hydrocephalus.

J Alzheimers Dis 2015 ;46(1):261-9

Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland and Neurosurgery, Institute of Clinical Medicine, University of Eastern Finland Kuopio, Finland.

Background: Amyloid-β (Aβ1 - 42), total tau (T-tau), and phosphorylated tau (P-tau181) in the cerebrospinal fluid (CSF) are the most promising biomarkers of Alzheimer's disease (AD). Still, little is known about the dynamics of these molecules in the living brain. In a transgenic mouse brain, soluble Aβ decreases with increasing age and advanced Aβ pathology as seen similarly in CSF.

Objective: To assess the relationship between AD-related pathological changes in human brain tissue, ventricular and lumbar CSF, and brain interstitial fluid (ISF).

Methods: Altogether 11 patients with suspected idiopathic normal pressure hydrocephalus underwent frontal cortical brain biopsy, 24-h intraventricular pressure monitoring, and a microdialysis procedure. AD-related biomarkers were analyzed from brain tissue, CSF, and ISF.

Results: ISF T-tau levels decreased strongly within the first 12 h, then plateauing until the end of the experiment. Aβ1 - 42 and P-tau181 remained stable during the experiment (n = 3). T-tau and P-tau were higher in the ISF than in ventricular or lumbar CSF, while Aβ1 - 42 levels were within similar range in both CSF and ISF samples. ISF P-tau correlated with the ventricular CSF T-tau (r = 0.70, p = 0.017) and P-tau181 (r = 0.64, p = 0.034). Five patients with amyloid pathology in the brain biopsy tended to reveal lower ISF Aβ1 - 42 levels than those six without amyloid pathology.

Conclusions: This is the first study to report ISF Aβ and tau levels in the human brain without significant brain injury. The set-up used enables sampling from the brain ISF for at least 24 h without causing adverse effects due to the microdialysis procedure to follow the dynamics of the key molecules in AD pathogenesis in the living brain at various stages of the disease.
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http://dx.doi.org/10.3233/JAD-142862DOI Listing
June 2016

Hypertension predisposes to the formation of saccular intracranial aneurysms in 467 unruptured and 1053 ruptured patients in Eastern Finland.

Ann Med 2014 May 3;46(3):169-76. Epub 2014 Mar 3.

Neurosurgery of NeuroCenter, Kuopio University Hospital , Kuopio , Finland.

Objective: Hypertension associates with subarachnoid hemorrhage from saccular intracranial aneurysm (sIA-SAH) when compared to matched controls or general population. Few series compare hypertension in unruptured sIA versus sIA-SAH, so its impact on the sIA disease remains uncertain.

Methods: Kuopio sIA Database ( www.uef.fi/ns ) contains all cases of unruptured and ruptured sIAs admitted to Kuopio University Hospital from its Eastern Finnish catchment population. We compared the age-adjusted incidence of drug-treated hypertension in 467 unruptured and 1053 ruptured sIA patients admitted to Kuopio University Hospital from 1995 to 2007, using the national registry of prescribed medicines.

Results: Antihypertensive medication was more frequent in the unruptured (73% versus 62%) with higher age-adjusted incidence. At sIA diagnosis, the sIA-SAH group had more often untreated hypertension (29% versus 23%). The size of unruptured sIAs increased with age at sIA diagnosis, independently of hypertension. Multiple sIAs, familial sIA, and sIA-SAH were not associated with hypertension in multivariate analysis. Results indicate that drug-treated hypertension associates with the formation of sIAs rather than their growth or rupture.

Conclusion: Hypertension is highly prevalent in the carriers of unruptured sIAs when compared to those with ruptured sIA. Hypertension may associate with the sIA formation, and may predispose to the rupture of sIA if untreated.
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http://dx.doi.org/10.3109/07853890.2014.883168DOI Listing
May 2014

High risk population isolate reveals low frequency variants predisposing to intracranial aneurysms.

PLoS Genet 2014 Jan 30;10(1):e1004134. Epub 2014 Jan 30.

Neurosurgery, NeuroCenter, Kuopio University Hospital, Kuopio, Finland ; Neurosurgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

3% of the population develops saccular intracranial aneurysms (sIAs), a complex trait, with a sporadic and a familial form. Subarachnoid hemorrhage from sIA (sIA-SAH) is a devastating form of stroke. Certain rare genetic variants are enriched in the Finns, a population isolate with a small founder population and bottleneck events. As the sIA-SAH incidence in Finland is >2× increased, such variants may associate with sIA in the Finnish population. We tested 9.4 million variants for association in 760 Finnish sIA patients (enriched for familial sIA), and in 2,513 matched controls with case-control status and with the number of sIAs. The most promising loci (p<5E-6) were replicated in 858 Finnish sIA patients and 4,048 controls. The frequencies and effect sizes of the replicated variants were compared to a continental European population using 717 Dutch cases and 3,004 controls. We discovered four new high-risk loci with low frequency lead variants. Three were associated with the case-control status: 2q23.3 (MAF 2.1%, OR 1.89, p 1.42×10-9); 5q31.3 (MAF 2.7%, OR 1.66, p 3.17×10-8); 6q24.2 (MAF 2.6%, OR 1.87, p 1.87×10-11) and one with the number of sIAs: 7p22.1 (MAF 3.3%, RR 1.59, p 6.08×-9). Two of the associations (5q31.3, 6q24.2) replicated in the Dutch sample. The 7p22.1 locus was strongly differentiated; the lead variant was more frequent in Finland (4.6%) than in the Netherlands (0.3%). Additionally, we replicated a previously inconclusive locus on 2q33.1 in all samples tested (OR 1.27, p 1.87×10-12). The five loci explain 2.1% of the sIA heritability in Finland, and may relate to, but not explain, the increased incidence of sIA-SAH in Finland. This study illustrates the utility of population isolates, familial enrichment, dense genotype imputation and alternate phenotyping in search for variants associated with complex diseases.
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http://dx.doi.org/10.1371/journal.pgen.1004134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907358PMC
January 2014

Stent-assisted embolization of recurrent or residual intracranial aneurysms.

Neuroradiology 2013 Oct 17;55(10):1221-31. Epub 2013 Jul 17.

Department of Clinical Radiology, Kuopio University Hospital and Kuopio University, P.O. Box 1777, 70211, Kuopio, Finland,

Introduction: Intracranial stents have theoretical advantages in the treatment of wide-necked intracranial aneurysms, but the usability of intracranial stents in the retreatment of recurrent intracranial aneurysms is relatively unknown. In this study, we aim to evaluate the safety and efficacy of stent-assisted embolization in the retreatment of recurrent or residual intracranial aneurysms.

Methods: Retrospective evaluation was carried out for 55 consecutive patients (17 men and 38 women; mean age 51.5 years), with 56 recurrent or residual intracranial aneurysms electively retreated with stent-assisted embolization.

Results: The technical success rate was 91% (50/55 patients). Procedural complications were encountered with six patients (11%). Angiographic and clinical follow-up data were available for 51 patients (93%), with a mean follow-up period of 28.1 months. No rebleedings were encountered during the study period. The clinical outcome was favorable in 50 patients (91%), with a Glasgow Outcome Score of 4 (N = 14) or 5 (N = 36) at the end of the study period. Poor clinical outcome correlated with very large (>2 cm) total aneurysm size (P = 0.002), large (>10 mm) recurrent aneurysm size (P = 0.011), and occurrence of periprocedural complications (P < 0.001).

Conclusion: Stent-assisted coil embolization is beneficial for the retreatment of wide-necked recurrent or residual intracranial aneurysms, but stability and permanent occlusion of the recurrent aneurysm is unlikely if the aneurysm exceeds 2 cm in diameter, the recurrent diameter of the aneurysm exceeds 10 mm, or if mass effect is present with the recurrent aneurysm.
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http://dx.doi.org/10.1007/s00234-013-1234-xDOI Listing
October 2013

Early and long-term excess mortality in 227 patients with intracranial dural arteriovenous fistulas.

J Neurosurg 2013 Jul 19;119(1):164-71. Epub 2013 Apr 19.

Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland.

Object: The aim of this study was to assess the early and long-term excess mortality in patients with intracranial dural arteriovenous fistula (DAVF) compared with a matched general Finnish population in an unselected, population-based series.

Methods: The authors identified 227 patients with DAVFs admitted to 2 of the 5 Departments of Neurosurgery in Finland--Helsinki and Kuopio University Hospitals--between 1944 and 2006. All patients were followed until death or the end of 2009. Long-term excess mortality was estimated using the relative survival ratio compared with the general Finnish population matched by age, sex, and calendar year.

Results: The median follow-up period was 10 years (range 0-44 years). Two-thirds (67%) of the DAVFs were located in the region of transverse and sigmoid sinuses. Cortical venous drainage (CVD) was present in 28% of the DAVFs (18% transverse and sigmoid sinus, 42% others). Of the 61 deaths counted, 11 (18%) were during the first 12 months and were mainly caused by treatment complications (5 of 11, 45%). The 1-year survivors presenting with hemorrhage experienced excess mortality until 7 years from admission. However, DAVFs with CVD were associated with significant, continuous excess mortality. There were more cerebrovascular and cardiovascular deaths in this group of patients than expected in the general Finnish population. Location other than transverse and sigmoid sinuses was also associated with excess mortality.

Conclusions: In the patients with DAVF there was excess mortality during the first 12 months, mainly due to treatment complications. Thereafter, their overall long-term survival became similar to that of the matched general population. However, DAVFs with CVD and those located in regions other than transverse and sigmoid sinuses were associated with marked long-term excess mortality after the first 12 months.
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http://dx.doi.org/10.3171/2013.3.JNS121547DOI Listing
July 2013

Type 2 diabetes and risk of rupture of saccular intracranial aneurysm in eastern Finland.

Diabetes Care 2013 Jul 27;36(7):2020-6. Epub 2013 Mar 27.

Neurosurgery, NeuroCenter, Kuopio University Hospital, Kuopio, Finland.

Objective: Type 2 diabetes is a risk factor for other forms of stroke, but its association with subarachnoid hemorrhage (SAH) from ruptured saccular intracranial aneurysm (sIA) has remained unclear.

Research Design And Methods: Kuopio Intracranial Aneurysm Database (www.uef.fi/ns) includes all ruptured and unruptured sIA cases from a defined catchment population in eastern Finland since 1980. We compared the age-adjusted incidences of type 2 diabetes in 1,058 ruptured and 484 unruptured sIA patients during 1994-2008, using the national registry of prescribed medicine purchases.

Results: Of the 1,058 ruptured sIA patients, 43% were males and 57% females, with a median age at rupture of 51 and 56 years, respectively. From 1994 to 2008 or until death, 9% had been prescribed antidiabetes medication (ADM) with a median starting age of 58 years for males and 66 years for females. Of the 484 unruptured sIA patients, 44% were males and 56% females, with a median age at the diagnosis of 53 and 55 years, respectively, and 9% had used ADM, with a median starting age of 61 years for males and 66 years for females. The incidence of type 2 diabetes was highest in the age-group 60-70 years, with no significant differences between the ruptured and unruptured sIA patients.

Conclusions: Our study suggests that type 2 diabetes does not increase the risk of rupture of sIA, which is by far the most frequent cause of nontraumatic SAH.
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http://dx.doi.org/10.2337/dc12-1048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687302PMC
July 2013

Characteristics and long-term outcome of 251 patients with dural arteriovenous fistulas in a defined population.

J Neurosurg 2013 May 21;118(5):923-34. Epub 2012 Dec 21.

Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland.

Object: Management of dural arteriovenous fistulas (DAVFs) has changed during the last decades due to increased knowledge of their pathophysiology and natural history as well as advances in treatment modalities. The authors describe the characteristics and long-term outcome of a large consecutive series of patients with DAVFs.

Methods: Altogether 251 patients with 261 DAVFs were treated in 2 of the 5 neurosurgery departments at Helsinki and Kuopio University Hospitals between 1944 and 2006. Clinical data and radiological examinations were reviewed to assess patients' overall long-term clinical outcome.

Results: The detection rate of DAVFs increased markedly in the 1970s and again in the 1990s when digital subtraction angiography was introduced. The incidence of DAVFs in a defined southern Finnish population was 0.51 per 100,000 individuals per year, which represents 32% of all the brain arteriovenous malformations. In the early part of the series, DAVFs were treated by proximal ligation of the feeding arteries. Later, most of the patients underwent preoperative embolization and subsequent craniotomy, and since 2000 stereotactic radiosurgery has been increasingly used in the treatment of DAVFs. Fifty-nine percent of the 261 fistulas were totally occluded. Treatment-related major complications were seen in 21 patients.

Conclusions: The advances in diagnostic methods (digital subtraction angiography, CT, and MRI) increased the detection rate of DAVFs, and as treatment modalities developed, the results of treatment and outcome of patients markedly improved with the introduction of endovascular techniques and stereotactic radiosurgery. Microsurgery is of limited use in DAVFs resistant to other treatment modalities.
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http://dx.doi.org/10.3171/2012.11.JNS111604DOI Listing
May 2013

Poor cognitive outcome in shunt-responsive idiopathic normal pressure hydrocephalus.

Neurosurgery 2013 Jan;72(1):1-8;discussion 8

Unit of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Background: Idiopathic normal pressure hydrocephalus (iNPH) causes cognitive decline that can be alleviated by shunting, but long-term outcome studies are scarce.

Objective: To elucidate the long-term cognitive condition of shunt-responsive iNPH patients.

Methods: The follow-up data (Kuopio University Hospital NPH Registry) of 146 patients diagnosed with iNPH by clinical and radiological examination, 24-hour intraventricular pressure monitoring, frontal cortical biopsy, and response to the shunt were analyzed for signs of dementia. The Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, and specified memory disorder criteria were used. Median follow-up was 4.8 years.

Results: At the end of follow-up, 117 (80%) of the 146 iNPH patients had cognitive decline and 67 (46%) had clinical dementia. The most common clinical diagnoses were Alzheimer disease and vascular dementia. In multivariate analysis of the 146 iNPH patients, memory deficit as a first symptom before shunt (odds ratio [OR] 18.3; 95% confidence interval [CI] 1.9-175), male sex (OR 3.29; 95% CI 1.11-9.73), age (OR 1.17 year; 95% CI 1.07-1.28), and follow-up time (OR 1.20 year; 95% CI 1.02-1.40) predicted dementia. Interestingly, 8 (5%) iNPH patients had dementia without any signs of other neurodegenerative diseases in clinical, neuroradiological, or brain biopsy evaluation. These patients initially presented a full triad of symptoms, with gait disturbance being the most frequent initial symptom followed by deterioration in cognition.

Conclusion: The novel findings were (a) a significant risk of dementia in iNPH initially responsive to cerebrospinal fluid shunt, (b) cognitive impairment most commonly due to iNPH-related dementia followed by concurrent degenerative brain disease, and (c) a subgroup with dementia related to iNPH without comorbidities.
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http://dx.doi.org/10.1227/NEU.0b013e31827414b3DOI Listing
January 2013

APOE4 predicts amyloid-β in cortical brain biopsy but not idiopathic normal pressure hydrocephalus.

J Neurol Neurosurg Psychiatry 2012 Nov 6;83(11):1119-24. Epub 2012 Sep 6.

Neurosurgery of NeuroCentre, Kuopio University Hospital, P.O. box 1777, 70211 Kuopio, Finland.

Objective: To investigate the association of apolipoprotein E (APOE) genotype, especially the APOE4 allele, to (1) idiopathic normal pressure hydrocephalus (iNPH) and (2) amyloid-β (Aβ) plaques in cortical brain biopsies of presumed NPH patients with and without a final clinical diagnosis of Alzheimer's disease (AD).

Methods: 202 patients with presumed NPH were evaluated by intraventricular pressure monitoring and frontal cortical biopsy immunostained against Aβ (134 semiquantified by Aβ plaques/mm2). The 202 patients and 687 cognitively healthy individuals were genotyped for APOE. The final clinical diagnoses in a median follow-up of 3.9 years were: 113 iNPH (94 shunt responsive, 16 shunt non-responsive, three not shunted); 36 AD (12 mixed iNPH + AD); 53 others.

Results: The APOE genotypes distributed similarly in the 94 shunt responsive and 16 non-responsive iNPH patients and healthy controls. In multivariate analysis, the APOE4 allele correlated independently with Aβ plaques in the cortical biopsies (OR 8.7, 95% CI 3.6 to 20, p<0.001). The APOE4 allele in presumed NPH predicted later AD as follows: sensitivity 61%; specificity 77%; positive predictive value 37%; negative predictive value 90%.

Conclusion: In presumed NPH patients, APOE4 associates independently with the presence of Aβ plaques in the frontal cortical biopsy. APOE4 is not a risk factor for iNPH and does not predict the response to shunt. Our data further support the view that the iNPH syndrome is a distinct dementing disease.

Trial Registration Number: Kuopio NPH Registry (http://www.uef.fi/nph).
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http://dx.doi.org/10.1136/jnnp-2011-303849DOI Listing
November 2012