Inferior long-term outcomes after surgery for lumbar disc herniation in patients with prior lumbar spine surgery.

BACKGROUND: Previous lumbar spine surgery is a frequent exclusion criterion for studies evaluating lumbar surgery outcomes. In real-life clinical settings, this patient population is important, as a notable proportion of patients evaluated for lumbar spine surgery have undergone prior lumbar surgery already previously. Knowledge about the long-term outcomes after microdiscectomy on patients with previous lumbar surgery and how they compare to those of first-time surgery is lacking. METHODS: The original patient cohort for screening included 615 consecutive patients who underwent surgery for lumbar disc herniation, with a median follow-up time of 18.1 years. Of these patients, 89 (19%) had undergone lumbar spine surgery prior to the index surgery. Propensity score matching (based on age, sex, and follow-up time) was utilized to match two patients without prior surgery with each patient with a previous surgery. The primary outcome measure was the need for further lumbar spine surgery during the follow-up period, and the secondary outcome measures consisted of present-time patient-reported outcome measures (Oswestry Disability Index, EuroQol-5D) and present-time ability to carry out employment. RESULTS: Patients who received previous lumbar surgeries had a higher need for further surgery (44% vs. 28%, p = 0.009) and had a shorter time to further surgery than the propensity score-matched cohort (mean Kaplan-Meier estimate, 15.7 years vs. 19.8 years, p = 0.008). Patients with prior surgery reported inferior Oswestry Disability Index scores (13.7 vs. 8.0, p = 0.036). and EQ-5D scores (0.77 vs. 0.86, p = 0.01). In addition, they had a higher frequency of receiving lumbar spine-related disability pensions than the other patients (12% vs. 1.9%, p = 0.01). CONCLUSIONS: Patients with previous lumbar surgery had inferior long-term outcomes compared to patients without prior surgery. However, the vast majority of these patients improved quickly after the index surgery. Furthermore, the difference in the patients' reported outcomes was small at the long-term follow-up, and they reported high satisfaction with the results of the study surgery. Hence, surgery for these patients should be considered if surgical indications are met, but special care needs must be accounted for when deliberating upon their indications for surgery.

The Finnish spine register (FinSpine): development, design, validation and utility.

PURPOSE: Our aim was to develop a nationwide, computer-based, Spine Register (FinSpine) for monitoring surgical activity, quality of surgery, long-term outcomes, and effectiveness of treatment. In this paper, we describe our experiences in the development and implementation of the register. METHODS: The register was developed by a steering group, consisting of orthopedic surgeons and neurosurgeons from the whole country. We strived to develop a register which would be in active use by spine surgeons and enable collection of Patient Reported Outcome and Experience Measures (PROMs and PREMs) automatically and prospectively. We are actively promoting the use of the register in order to gain a nationwide coverage and achieve high response-rates from both surgeons and patients. RESULTS: The use of FinSpine started in 2016 and it has been granted continuous funding from the Finnish Institute for Health and Welfare from the 1st of January 2023 onwards. Currently the register is used by 19/23 (83%) public hospitals and the use is expanding to private hospitals as well. The response-rate of surgeons is currently 80%. The response-rate of patients is on average 56% but reaches up to 90% in hospitals using register-coordinators. CONCLUSION: The use of FinSpine is increasing. By gaining a larger coverage and completeness, the data can be used for research purposes which we believe will influence decision making and ultimately improve the outcomes and quality of life of the patients. Comparison with other national spine registers is possible, since FinSpine includes similar baseline characteristics and outcome measures (e.g., ODI, EQ-5D, VAS).

Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease: A Randomized, Double-Blind, Multicenter Phase 1 Trial.

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 [18 F]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.

Incidence and prevalence of Hemifacial Spasm in Finland's largest hospital district.

BACKGROUND: Hemifacial spasm (HFS) is a movement disorder of facial muscles innervated by the facial nerve. This condition often demands regular utilization of healthcare resources. However, knowledge of the incidence and prevalence of this condition is based on scarce studies. This research aimed to identify the incidence and prevalence of HFS in Finland's largest hospital district. METHODS: This retrospective study was conducted in the largest hospital district in Finland (Helsinki and Uusimaa). The study included consecutive HFS patients who visited the departments of Neurology and Neurosurgery in the Hospital District of Helsinki and Uusimaa between 2014 and 2019. The demographics included sex, side of the spasm, treatment allocations, duration of symptoms before diagnosis, and age at the time of diagnosis. RESULTS: 279 patients were identified from the medical records. 62% of patients were women and had left-sided spasms. The crude mean incidence among women was almost double that of men (1.86 vs. 0.94). The highest crude mean annual incidence among men was in the age group 60-79 years, while among women, it peaked in the age group 80 years and over. The mean annual age-standardized incidence of HFS was 1.53, 1.94 in women, and 1.05 in men. The mean age-standardized yearly prevalence was 10.62, 11.62 among women, and 9.31 among men. The annual age-standardized prevalence of HFS increased steadily from 2014 to 2019. CONCLUSIONS: The incidence and prevalence of women outnumbered men. HFS is typically left-sided. The HFS incidence peaked after 80 years in women and men aged 60-79 years.

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

BACKGROUND: Lumbar 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. METHODS: A 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. RESULTS: The 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). CONCLUSION: Patients 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.

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

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 post-surgery). 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.

Long-Term Follow-Up After Cervical Laminectomy without Fusion for Cervical Spondylotic Myelopathy.

OBJECTIVE: The objectives were to study the effect of cervical laminectomy without fusion on the incidence of further cervical surgeries, the risk for cervical misalignment, and current functional status. METHODS: We retrospectively analyzed the clinical data of 340 patients who had undergone simple laminectomy for cervical spondylotic myelopathy (CSM) at Helsinki University Hospital between 2000 and 2011. RESULTS: Forty-one patients (12.1%) had later undergone another cervical surgery during the follow-up of a mean of 8.5 years (maximum, 17.5 years). The most common indication for further surgery was residual stenosis at adjacent or other cervical levels (34%). Five patients (1%) required further surgery for correction of a sagittal balance problem. The mean Neck Disability Index was 28% at a median of 9.0 years after laminectomy. The mean EQ-5D (EuroQol 5 Dimension 3 Level) index score was 58.8 for patients and 77.2 for age-matched and gender-matched general population controls (P = 0.000), indicating patients' reduced health-related quality of life. Worse preoperative condition in the Nurick score was related to a lower (i.e., worse) EQ-5D score. In an additional arm of the study with radiographic imaging (40 patients), the mean change in sagittal alignment was 4.0° toward lordotic, and a newly developed kyphosis was found in 7.5% of patients. CONCLUSIONS: Because CSM is a serious degenerative progressive condition resulting in decreased health-related quality of life even after surgical treatment, the low rate of corrective surgery needed for alignment issues per se indicates that simple laminectomy can be a viable treatment option in treating multilevel CSM.

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

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.

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

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.

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

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 (ie, discectomy only vs. 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 (<28 days from index surgery) were excluded. At 10 years postsurgery, the total reoperation rate was 16.8% and 12.8% with early reoperations excluded. The probability of surgery for adjacent level disease was 10.3% at 10 years and 16.8% for the duration of the entire follow-up, with the annual incidence rate of 1.1% for those with ASD requiring surgery. Statistically significant risk factors leading to the need for further cervical surgery included central spinal cord compression and smoking at the time of the index operation. After propensity score matching, there was no significant difference found between the outcomes of different types of surgery. A total of 443 patients were still able to be contacted 12-28 years after the surgery. Of the 281 patients responding to the questionnaires, 92% were still satisfied with the results. With respect to employment, 67% of patients were working, 7% were unemployed, and 7% were on disability due to cervical problems. The median NDI score was 12%, with 56% of patients having an NDI score lower than 15%; it has been suggested that this latter NDI score serves as a cut-off value for significant neck morbidity. The NDI scores were significantly higher among female patients, patients with spondylosis, and patients having undergone further cervical surgeries during the follow-up. CONCLUSIONS: Long-term satisfaction with the surgery was very high, and the employment rate among patients resembled that of the general population in Finland. Thus, the long-term prognosis after having ACDF surgery at a younger age seems to be good, even though nearly half of the patients experienced some persistent neck symptoms later in life.

Intraluminal cell transplantation prevents growth and rupture in a model of rupture-prone saccular aneurysms.

BACKGROUND AND PURPOSE: Aneurysm occlusion by intraluminal thrombus formation is the desired effect of all endovascular treatments. Intraluminal thrombus may, however, recanalize and be absorbed, unless it is infiltrated by cells that turn it into fibrous tissue (neointima). Because ruptured aneurysm walls are characterized by loss of smooth muscle cells, we assessed the impact of mural cell loss on wall remodeling of thrombosed aneurysms and investigated whether neointima formation could be enhanced by direct transplantation of cells into the thrombus. METHODS: Sidewall aneurysms were microsurgically created in rats (n=81). Certain aneurysms were decellularized. Thrombosis was induced using direct injection of a fibrin polymer into the aneurysm. CM-Dil-labeled smooth muscle cells were injected into 25 of 46 fibrin embolized aneurysms. Recanalization and aneurysm growth were monitored with magnetic resonance angiography. Endoscopy, optical projection tomography, histology, and immunohistochemistry were used to study the fate of transplanted cells, thrombus organization, and neointima formation. RESULTS: Decellularized embolized aneurysms demonstrated higher angiographic recurrence compared with decellularized embolized aneurysms with transplanted cells (P=0.037). Local cell replacement at the time of thrombosis resulted in better histological neointima formation than both nondecellularized embolized aneurysms (P<0.001) and decellularized embolized aneurysms (P=0.002). Aneurysm growth and rupture were observed exclusively in decellularized embolized aneurysms. CONCLUSIONS: Lack of smooth muscle cells in the aneurysm wall promotes wall degradation, aneurysm growth and rupture, even if the aneurysm is occluded by luminal thrombus. Transplantation of smooth muscle cells into the luminal thrombus can reduce this degenerative remodeling.

The Helsinki rat microsurgical sidewall aneurysm model.

Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced into clinical practice. Furthermore, experimental models are needed to elucidate the complex aneurysm biology leading to rupture of saccular aneurysms. Several different kinds of experimental models for saccular aneurysms have been established in different species. Many of them, however, require special skills, expensive equipment, or special environments, which limits their widespread use. A simple, robust, and inexpensive experimental model is needed as a standardized tool that can be used in a standardized manner in various institutions. The microsurgical rat abdominal aortic sidewall aneurysm model combines the possibility to study both novel endovascular treatment strategies and the molecular basis of aneurysm biology in a standardized and inexpensive manner. Standardized grafts by means of shape, size, and geometry are harvested from a donor rat's descending thoracic aorta and then transplanted to a syngenic recipient rat. The aneurysms are sutured end-to-side with continuous or interrupted 9-0 nylon sutures to the infrarenal abdominal aorta. We present step-by-step procedural instructions, information on necessary equipment, and discuss important anatomical and surgical details for successful microsurgical creation of an abdominal aortic sidewall aneurysm in the rat.

Loss of mural cells leads to wall degeneration, aneurysm growth, and eventual rupture in a rat aneurysm model.

BACKGROUND AND PURPOSE: The biological mechanisms predisposing intracranial saccular aneurysms to growth and rupture are not yet fully understood. Mural cell loss is a histological hallmark of ruptured cerebral aneurysms. It remains unclear whether mural cell loss predisposes to aneurysm growth and eventual rupture. METHODS: Sodium dodecyl sulfate decellularized and nondecellularized saccular aneurysm from syngeneic thoracic aortas were transplanted to the abdominal aorta of Wistar rats. Aneurysm patency and growth was followed up for 1 month with contrast-enhanced serial magnetic resonance angiographies. Endoscopy and histology of the aneurysms were used to assess the role of periadventitial environment, aneurysm wall, and thrombus remodeling. RESULTS: Nondecellularized aneurysms (n=12) showed a linear course of thrombosis and remained stable. Decellularized aneurysms (n=12) exhibited a heterogeneous pattern of thrombosis, thrombus recanalization, and growth. Three of the growing aneurysms (n=5) ruptured during the observation period. Growing and ruptured aneurysms demonstrated marked adventitial fibrosis and inflammation, complete wall disruption, and increased neutrophil accumulation in unorganized intraluminal thrombus. CONCLUSIONS: In the presented experimental setting, complete loss of mural cells acts as a driving force for aneurysm growth and rupture. The findings suggest that aneurysms missing mural cells are incapable to organize a luminal thrombus, leading to recanalization, increased inflammatory reaction, severe wall degeneration, and eventual rupture.

High-resolution TOF MR angiography at 4.7 Tesla for volumetric and morphologic evaluation of coiled aneurysm neck remnants in a rat model.

BACKGROUND: Detection of morphologic and volumetric changes in aneurysm necks is important when evaluating the effects of endovascular devices for aneurysm occlusion. PURPOSE: To optimize high-resolution 3D-TOF MRA at 4.7 T in order to achieve the best aneurysm-to-background contrast in experimental rat aneurysms, and to quantify the volume of the aneurysm neck by imaging. MATERIAL AND METHODS: Saccular aneurysms in the abdominal aorta of rats were coiled with platinum coils. Tissue relaxation times were measured, and used in a mathematical simulation. To optimize 3D-TOF angiography, imaging parameters were varied within the range obtained from the simulations. Tissue contrast and contrast-to-noise ratio were measured from MR images. TOF images were compared to conventional spin echo and gradient echo images and to endoscopic and histological analyses. RESULTS: Parameters yielding the best aneurysm-to-background contrast and contrast-to-noise ratio were determined. The agreement between the results from in vivo imaging and simulation was good. The optimized 3D-TOF MRA sequence (TR/TE/FA = 60 ms/6.6 ms/20°) had an isotropic voxel size of 117 µm, which enabled measurement of the aneurysm neck volume. CONCLUSION: High-resolution 3D-TOF angiography enables non-invasive quantification of changes in neck remnants of endovascularly coiled experimental aneurysms. In this model innovations like bioactive coils can be accurately tested for their efficacy for aneurysm occlusion.

Occlusion of neck remnant in experimental rat aneurysms after treatment with platinum- or polyglycolic-polylactic acid-coated coils.

BACKGROUND: Neck remnants and aneurysm recurrences are marked limitations of endovascular treatment of cerebral artery aneurysms. We compared the evolution of neck remnants of experimental arterial rat aneurysms after treatment with either platinum- or PGLA-coated coils. METHODS: We created 20 standard-size aneurysms in the abdominal aortas of male Wistar rats. Aneurysms were embolized with either PGLA-coated coils or platinum coils, with care taken to leave a neck remnant. Neck remnant size and shape was closely monitored to detect progressive enlargement or occlusion. Using a 4.7 T MR scanner, we acquired high-resolution MR images 6 times during the 4-week follow-up. For quantitative measurements, we used a high-resolution 3D-TOF angiography sequence. Results were verified by endoscopy and histology. RESULTS: Aneurysms treated with PGLA coils showed, on average, a 12.9% reduction of neck remnant size (P = .044) and significant disappearance of dog ears, the blood-filled spaces between coils and aneurysm wall. The aneurysms treated with platinum coils lacked these changes. In endoscopy, neointima was found to cover both PGLA and platinum coils but was more often incomplete or translucent in the platinum group. In histology, thrombus organization and inflammatory cell infiltration were higher with PGLA. CONCLUSION: Use of PGLA-coated coils was followed by a moderate progressive reduction of the neck remnant size and a better angiographic outcome, seen as disappearance of dog ears during follow-up. The rat model proved to be suitable for comparison of different coil types.

Association of fatal aneurysmal subarachnoid hemorrhage with human leukocyte antigens in the Finnish population.

Human leukocyte antigens (HLA) have been reported to associate with the risk of aneurysmal subarachnoid hemorrhage (SAH) and poor outcome after SAH. Our aim was to identify HLA antigens that associate with the risk of fatal SAH in the Finnish population. Medical records of 600 cadaveric organ donors were reviewed to find organ donors that succumbed to SAH (n = 232) or brain trauma (n = 151). HLA antigen frequencies in these groups were compared with HLA frequencies in a reference population of 10,000 bone marrow donors. Chi-Square test with Bonferroni correction and multiplicative logistic regression models were used and false positive result probabilities (FPRP) were calculated. Alpha-level was 0.01. HLA-A3 associated with fatal SAH (p = 0.0014, OR 1.3 and 95%CI 1.1-1.6) and HLA-DR7 inversely associated with fatal SAH (p = 0.0040, OR 0.3 and 95%CI 0.2-0.6). HLA-A3 but not HLA-DR7 showed also a positive trend in donors with brain trauma. FPRP was below 0.5 for HLA-A3, but clearly above 0.5 for HLA-DR7. HLA-A3 seems to associate with fatal SAH in the Finnish population. Further studies are needed to reveal the pathobiologic mechanisms for how HLA-A3 associates with the risk of fatal SAH in Finns.

Contribution of mural and bone marrow-derived neointimal cells to thrombus organization and wall remodeling in a microsurgical murine saccular aneurysm model.

OBJECTIVE: Endovascular occlusive therapy of human saccular cerebral artery aneurysms may fail because of thrombus recanalization and incomplete neointima formation. Bone marrow-derived progenitor cells may contribute to these processes, but their role in human saccular cerebral artery aneurysms and experimental aneurysm models remains unclear. METHODS: Experimental saccular aneurysms were constructed from syngeneic thoracic aortas transplanted end-to-side to the abdominal aorta of Wistar rats (n = 14), C57/B6 mice (n = 13), ApoE mice (n = 7), reporter gene expressing ROSA mice (n = 7), and mice with labeled bone marrow (ROSA [n = 12] or green fluorescent protein [n = 3]). Magnetic resonance imaging or angiography was used to monitor patency of the experimental aneurysms. Histology and immunohistochemistry were used to study thrombus organization and neointima formation and X-gal staining and confocal microscopy to study the origin of neointimal cells. RESULTS: Experimental aneurysms developed luminal pads of neointimal hyperplasia or organizing thrombosis that became thicker and occluded partly the lumen at later time points during the first week. Reporter gene mice (ROSA) revealed that 42 to 81% (median, 58%) of neointimal hyperplasia/organizing thrombosis was derived from the experimental aneurysm wall. Bone marrow-derived neointimal cells were found in only 5 of 15 mice (range, 11-73 per section; a median of 22 cells among a total of 2000-6000 wall cells). CONCLUSION: Thrombus organizing or neointimal cells were mostly derived from the experimental aneurysm wall, with only a minor contribution from the bone marrow. In human saccular cerebral artery aneurysms, the contribution of bone marrow-derived neointimal cells might be more important and should be compared with that found in other experimental models used to develop endovascular therapies.