22 research outputs found

    Microsurgical Aneurysm Model in Rats and Mice : Development of Endovascular Treatment and Optimization of Magnetic Resonance Imaging

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    The rupture of a cerebral artery aneurysm causes a devastating subarachnoid hemorrhage (SAH), with a mortality of almost 50% during the first month. Each year, 8-11/100 000 people suffer from aneurysmal SAH in Western countries, but the number is twice as high in Finland and Japan. The disease is most common among those of working age, the mean age at rupture being 50-55 years. Unruptured cerebral aneurysms are found in 2-6% of the population, but knowledge about the true risk of rupture is limited. The vast majority of aneurysms should be considered rupture-prone, and treatment for these patients is warranted. Both unruptured and ruptured aneurysms can be treated by either microsurgical clipping or endovascular embolization. In a standard microsurgical procedure, the neck of the aneurysm is closed by a metal clip, sealing off the aneurysm from the circulation. Endovascular embolization is performed by packing the aneurysm from the inside of the vessel lumen with detachable platinum coils. Coiling is associated with slightly lower morbidity and mortality than microsurgery, but the long-term results of microsurgically treated aneurysms are better. Endovascular treatment methods are constantly being developed further in order to achieve better long-term results. New coils and novel embolic agents need to be tested in a variety of animal models before they can be used in humans. In this study, we developed an experimental rat aneurysm model and showed its suitability for testing endovascular devices. We optimized noninvasive MRI sequences at 4.7 Tesla for follow-up of coiled experimental aneurysms and for volumetric measurement of aneurysm neck remnants. We used this model to compare platinum coils with polyglycolic-polylactic acid (PGLA) -coated coils, and showed the benefits of the latter in this model. The experimental aneurysm model and the imaging methods also gave insight into the mechanisms involved in aneurysm formation, and the model can be used in the development of novel imaging techniques. This model is affordable, easily reproducible, reliable, and suitable for MRI follow-up. It is also suitable for endovascular treatment, and it evades spontaneous occlusion.Aivovaltimoaneurysman puhkeaminen aiheuttaa hengenvaarallisen lukinkalvonalaisen verenvuodon eli subaraknoidaalivuodon (SAVn). Suomessa SAVn insidenssi on yleisempi kuin muualla maailmassa, vuodon saa noin 1000 potilasta vuosittain. HeistÀ noin 50% menehtyy kuukauden sisÀllÀ vuodosta ja henkiinjÀÀneistÀ puolet vammautuu vakavasti. Tauti kohdistuu pÀÀasiallisesti työssÀkÀyvÀÀn vÀestöön, keski-ikÀ on 50-55 v. Vuotamaton aivovaltimoaneurysma löytyy 2-6% vÀestöstÀ. MenetelmÀÀ, jolla voisi ennakoida mitkÀ aneurysmat tulevat vuotamaan ja mitkÀ eivÀt, ei toistaiseksi ole. Valtaosaa vuotamattomista aneurysmista on pidettÀvÀ potentiaalisesti hengenvaarallisina, ja ne on pyrittÀvÀ sulkemaan joko mikrokirurgisella leikkauksella tai endovaskulaarisella (suonensisÀisellÀ) embolisaatiolla. Leikkauksessa aneurysman tyvi suljetaan mikrokirurgisesti metallisella klipsillÀ. Endovaskulaarisessa embolisaatiossa aneurysma tÀytetÀÀn röntgenlÀpivalaisuavusteisesti eri mittaisilla platinalanka-"koileilla". Koilaaminen on vÀhemmÀn kajoava toimenpide kuin mikrokirurginen leikkaus ja tÀten varteenotettava vaihtoehto. Kaikki aneurysmat eivÀt kuitenkaan sovellu koilattaviksi nykytekniikoilla, joko leveÀn kaulan, suuren koon tai hankalan sijainnin takia. Endovaskulaarisen hoidon jÀlkeen seuranta on vÀlttÀmÀtöntÀ, koska pitkÀaikaistulokset ovat leikkaukseen verrattuna heikommat. LisÀkoilaus voidaan tehdÀ mikÀli aneurysmaan tulee uudelleen verenvirtausta. Endovaskulaarisia hoitomenetelmiÀ on kehitettÀvÀ edelleen, jotta saavutettaisiin parempia pitkÀaikaistuloksia. Uusia menetelmiÀ on testattava koe-elÀinmalleilla ennen kuin niitÀ kÀytetÀÀn ihmisillÀ. TÀssÀ tutkimuksessa olemme pystyttÀneet ihmisen aivovaltimoaneurysmaa muistuttavan mikrokirurgisen aneurysmamallin rotassa, jolla pystymme tuottamaan vakiokokoisia aneurysmia, joita voidaan hoitaa endovaskulaarisesti. Seurantaa varten olemme optimoineet kuvanlaadun koe-elÀinmagneettikuvantamislaitteessa, jotta pystymme seuraamaan hoitojen jÀlkeisiÀ tapahtuvia muutoksia aneurysmissa. Olemme kÀyttÀneet rottamallia verrataksemme platinalankakoilia uudenlaiseen pinnoitettuun koiliin ja osoittaneet, ettÀ viimeksi mainitulla on hyödyllisiÀ ominaisuuksia. Rottamalli on aiempiin aneurysmamalleihin verrattuna halvempi. LisÀksi kokeelliset aneurysmat ovat vakiokokoisia, aukipysyviÀ ja magneettikuvausseurantaan soveltuvia

    Favorable long-term outcome in young adults undergoing surgery for lumbar disc herniation

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    Purpose The purpose of the study was to evaluate the long-term outcome after surgery for lumbar disc herniation in a young adult population. Methods A total of 526 consecutive patients between 18 and 40 years of age who underwent surgery for lumbar disc between 1990 and 2005 were included in the study. The primary outcomes were the need for new lumbar spine surgery during the follow-up and secondary outcomes were short-term subjective outcome, the Oswestry Disability Index (ODI) score, and the ability to carry out employment at the end of the long-term follow-up. Results A total of 96% of the patients had a reduction in their symptoms at the clinical follow-up (median of 50 days postsurgery). Twenty-one patients (4.0%) had a reoperation within 28 days. Excluding these early reoperations, 136 patients (26%) had additional lumbar spine surgery and 18 patients (3.4%) underwent lumbar fusion during the follow-up of median 18 years. The annual risk for new surgery was 1.4%. In total, 316 patients (60%) returned the ODI questionnaire, and their mean score was 8.1. Patients with a higher number of additional lumbar spine surgeries (p < 0.001) reported deteriorating ODI scores. Conclusion Patients showed excellent short-term recovery from their symptoms. In the long term, the mean ODI score for the patients was comparable to the normative population. However, a notable proportion of the patients required additional lumbar surgery during the follow-up period, and a higher number of lumbar surgeries was associated with poor ODI scores.Peer reviewe

    Spontaneous angiogram-negative subarachnoid hemorrhage : a retrospective single center cohort study

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    Background Spontaneous angiogram-negative subarachnoid hemorrhage (SAH) is considered a benign illness with little of the aneurysmal SAH-related complications. We describe the clinical course, SAH-related complications, and outcome of patients with angiogram-negative SAH. Methods We retrospectively reviewed all adult patients admitted to a neurosurgical intensive care unit during 2004-2018 due to spontaneous angiogram-negative SAH. Our primary outcome was a dichotomized Glasgow Outcome Scale (GOS) at 3 months. We assessed factors that associated with outcome using multivariable logistic regression analysis. Results Of the 108 patients included, 84% had a favorable outcome (GOS 4-5), and mortality was 5% within 1 year. The median age was 58 years, 51% were female, and 93% had a low-grade SAH (World Federation of Neurosurgical Societies grading I-III). The median number of angiograms performed per patient was two. Thirty percent of patients showed radiological signs of acute hydrocephalus, 28% were acutely treated with an external ventricular drain, 13% received active vasospasm treatment and 17% received a permanent shunt. In the multivariable logistic regression model, only acute hydrocephalus associated with unfavorable outcome (odds ratio = 4.05, 95% confidence interval = 1.05-15.73). Two patients had a new bleeding episode. Conclusion SAH-related complications such as hydrocephalus and vasospasm are common after angiogram-negative SAH. Still, most patients had a favorable outcome. Only acute hydrocephalus was associated with unfavorable outcome. The high rate of SAH-related complications highlights the need for neurosurgical care in these patients.Peer reviewe

    Spontaneous angiogram-negative subarachnoid hemorrhage : a retrospective single center cohort study

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    Background Spontaneous angiogram-negative subarachnoid hemorrhage (SAH) is considered a benign illness with little of the aneurysmal SAH-related complications. We describe the clinical course, SAH-related complications, and outcome of patients with angiogram-negative SAH. Methods We retrospectively reviewed all adult patients admitted to a neurosurgical intensive care unit during 2004-2018 due to spontaneous angiogram-negative SAH. Our primary outcome was a dichotomized Glasgow Outcome Scale (GOS) at 3 months. We assessed factors that associated with outcome using multivariable logistic regression analysis. Results Of the 108 patients included, 84% had a favorable outcome (GOS 4-5), and mortality was 5% within 1 year. The median age was 58 years, 51% were female, and 93% had a low-grade SAH (World Federation of Neurosurgical Societies grading I-III). The median number of angiograms performed per patient was two. Thirty percent of patients showed radiological signs of acute hydrocephalus, 28% were acutely treated with an external ventricular drain, 13% received active vasospasm treatment and 17% received a permanent shunt. In the multivariable logistic regression model, only acute hydrocephalus associated with unfavorable outcome (odds ratio = 4.05, 95% confidence interval = 1.05-15.73). Two patients had a new bleeding episode. Conclusion SAH-related complications such as hydrocephalus and vasospasm are common after angiogram-negative SAH. Still, most patients had a favorable outcome. Only acute hydrocephalus was associated with unfavorable outcome. The high rate of SAH-related complications highlights the need for neurosurgical care in these patients.Peer reviewe

    Anterior cervical discectomy and fusion in young adults leads to favorable outcome in long-term follow-up

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    Background Context Anterior cervical discectomy and fusion (ACDF) procedures is thought to lead to accelerated degeneration of the adjacent cervical discs and in some cases can be symptomatic (adjacent segment disease, or ASD). The occurrence of ASD is of particular interest when treating young individuals, as the cumulative disease burden may become increasingly significant during their expectedly long lifetime. However, the overall impact of a surgical intervention on the lifetime prognosis of ASD remains unclear. Purpose Our goal was to study the long-term outcomes of ACDF surgery among those members of the young adult population who have been operated on between the ages of 18 and 40. Study design Retrospective study. Patient Sample All patients between 18 and 40 years of age at the time of surgery who underwent ACDF due to degenerative cervical disorders at Helsinki University Hospital between the years of 1990 and 2005 (476 patients). Outcome Measures Cervical reoperation rate, satisfaction with the surgery, employment status, Neck Disability Index (NDI) Methods We retrospectively analyzed the medical records of all patients between 18 and 40 years of age at the time of surgery who underwent ACDF due to degenerative cervical disorders at Helsinki University Hospital between the years of 1990 and 2005. We sent questionnaires to all available patients at the end of the follow-up (median 17.5 years) to assess their current neck symptoms, general situations, and levels of satisfaction with the surgery. Furthermore, we compared the results for different types of ACDF surgeries (i.e., discectomy only versus synthetic cage or bone autograft implantation for fusion) in propensity-score-matched groups. Results Of the 476 patients who were included in the study, surgery was performed in 72% of the cases due to intervertebral disc herniation and in 28% due to spondylotic changes. The total reoperation rate during the entire follow-up (median 17.5 years) was 24%, and 19.5% if early reoperations (Peer reviewe

    Favorable long-term health-related quality of life after surgery for lumbar disc herniation in young adult patients

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    BackgroundLumbar disc herniation is often managed conservatively; nevertheless, surgical intervention can be required. Majority of patients experience a drastic relief of symptoms after surgery, but previous studies have reported that their health-related quality of life remains inferior compared to the general population for several years. There may be a major cumulative loss of health-related quality of life for young patients as they have long expected life ahead of them.MethodsA total of 526 eligible adult patients under the age of 40 underwent surgery for lumbar disc herniation from 1990 to 2005. Patients' baseline characteristics were acquired by chart review to confirm eligibility to the study. Follow-up quality of life data was acquired by sending patients EQ-5D questionnaire at median 18 years after index surgery, and those 316 patients responding to the questionnaire (60%) were included in the study. Propensity score matching was utilized to match every study patient with two general population sample participants from a large Finnish population health study. Primary objective was to compare the quality of life to that of the control population. Secondary objective was to explore which patient characteristics lead to inferior outcome.ResultsThe mean EQ-index for the patient cohort was 0.86, while it was 0.84 for the age and gender-matched general population sample (difference 0.02, 95% CI - 0.0004 to 0.049). Within the patient cohort, an increasing number of lifetime lumbar surgeries was associated with progressively deteriorating EQ-index scores (p = 0.049) and longer duration of symptoms prior to the surgery correlated with lower score (p = 0.013).ConclusionPatients who underwent surgery for lumbar disc herniation nearly two decades ago reported quality of life comparable to the age and gender-matched general population. However, patients who had undergone numerous lumbar surgeries had significantly worse outcome. Therefore, possible ways to prevent cumulation of lumbar surgeries could improve long-term health-related quality of life.Peer reviewe

    Young adults undergoing ACDF surgery exhibit decreased health-related quality of life in the long term in comparison to the general population

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    BACKGROUND CONTEXT: The leading surgical treatment of cervical radiculopathy is anterior cervical discectomy and fusion (ACDF). However, it has been suggested that ACDF procedures could lead to accelerated degeneration of the adjacent cervical discs (adjacent segment disease, or ASD) and the effect of ACDF surgery on neck symptoms and quality of life in the long term is not fully understood. Patients operated on at young ages generally have a long life expectancy and a long number of working years ahead of them. Thus, this patient group is of special interest when considering the accumulation of cervical problems due to possible ASD, the overall progressive nature of cervical degeneration in the long term, and their effects on related quality of life. PURPOSE: Our goal was to study the health-related quality of life in the long-term follow-up after ACDF surgery in the young adult population between the ages of 18 and 40. STUDY DESIGN: A retrospective cohort study with propensity matched controls. PATIENT SAMPLE: All patients between 18 and 40 years of age at the time of the surgery who underwent ACDF due to degenerative cervical disease at Helsinki University Hospital between the years 1990 and 2005 who had filled in the quality of life questionnaires 12 to 28 years after the surgery (281 patients), and a propensity matched control cohort of the general population selected based on age, sex, and smoking status. OUTCOME MEASURES: Quality of life measured by the EuroQol questionnaire (EQ-5D-3L and EQ-VAS). METHODS: The medical records of all patients who underwent ACDF due to degenerative cervical disease at the age of 18 to 40 years at Helsinki University Hospital between 1990 and 2005 were analyzed retrospectively. The EuroQol questionnaire was sent to all patients whose contact information could be obtained (443 patients) at the end of the follow-up (median 17.5 years) to assess their current quality of life. A total of 281 patients returned the questionnaires and were included in this study. Quality of life was compared to that in the general Finnish population using a similar sized control cohort selected through propensity matching. RESULTS: The patients who had undergone ACDF surgery reported significantly more problems than the general population cohort in three out of five dimensions that were assessed in the EQ-5D questionnaire, including mobility, usual activities, and pain/discomfort. Similarly, the overall EQ-5D-3L index calculated from the dimensional values was lower (0.74 vs. 0.83, p=.000), depicting a generally decreased health-related quality of life among patients. Spondylosis as a primary diagnosis, clinical myelopathy, and further cervical surgeries were associated with lower quality of life in the subgroup analyses of the patients. Similarly, in the EQ-VAS assessment, patient subgroups with spondylosis as a primary diagnosis, at least one reoperation, operation on more than one level, and clinical myelopathy were associated with lower scores and lower quality of life. The mean EQ-VAS score among patients was 73%. Regardless of the decreased health-related quality of life, there was no statistically significant difference in the concurrent employment status between the patient and control groups. CONCLUSIONS: The health-related life quality measured by the EQ-5D-3L was lower in the patient population than in the general population. Patients had more problems with mobility and usual activities and more pain/discomfort. However, satisfaction with the surgery was very high, and there was no significant difference in employment status between the patients and the control population. Patients with spondylosis as a primary diagnosis had lower quality of life compared to patients with disc herniation. Also, clinical myelopathy and further cervical surgeries during follow-up were associated with lower quality of life in the subgroup analyses of the patients. It must also be kept in mind that we do not know what the situation could have been without surgery and with conservative treatment only. (C) 2021 The Authors. Published by Elsevier Inc.Peer reviewe

    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

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    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∌8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

    Intraputamenal cerebral dopamine neurotrophic factor in Parkinson's disease: a randomized, double‐blind, multicenter phase 1 trial

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    Background: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD). Objective: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity. Methods: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone‐anchored transcutaneous port connected to four catheters. This phase 1 trial was divided into a placebo‐controlled, double‐blind, 6‐month main study followed by an active‐treatment 6‐month extension. Eligible patients, aged 35 to 75 years, had moderate idiopathic PD for 5 to 15 years and Hoehn and Yahr score ≀ 3 (off state). Seventeen patients were randomized to placebo (n = 6), 0.4 mg CDNF (n = 6), or 1.2 mg CDNF (n = 5). The primary endpoints were safety and tolerability of CDNF and DDS and catheter implantation accuracy. Secondary endpoints were measures of PD symptoms, including Unified Parkinson's Disease Rating Scale, and DDS patency and port stability. Exploratory endpoints included motor symptom assessment (PKG, Global Kinetics Pty Ltd, Melbourne, Australia) and positron emission tomography using dopamine transporter radioligand [18F]FE‐PE2I. Results: Drug‐related adverse events were mild to moderate with no difference between placebo and treatment groups. No severe adverse events were associated with the drug, and device delivery accuracy met specification. The severe adverse events recorded were associated with the infusion procedure and did not reoccur after procedural modification. There were no significant changes between placebo and CDNF treatment groups in secondary endpoints between baseline and the end of the main and extension studies. Conclusions: Intraputamenally administered CDNF was safe and well tolerated, and possible signs of biological response to the drug were observed in individual patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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