Timo Koivisto

Outcomes of Early Endovascular Versus Surgical Treatment of Ruptured Cerebral Aneurysms A Prospective Randomized Study

Background and Purpose This prospective study was conducted to compare the outcomes of surgical clipping and endovascular treatment in acute (<72 hours) aneurysmal subarachnoid hemorrhage (SAH). Methods One hundred nine consecutive patients were randomly assigned to either surgical (n=57) or endovascular (n=52) treatment. Clinical and neuropsychological outcome was assessed at 3 and 12 months after treatment; MRI of the brain was performed at 12 months. Follow-up angiography was scheduled after clipping and 3 and 12 months after endovascular treatment. Results One year postoperatively, 43/41 (surgical/endovascular) patients had good or moderate recovery, 5/4 had severe disability or were in a vegetative state, and 9/7 had died (NS) according to intention to treat. Patients with good clinical recovery did not differ in their neuropsychological test scores. Symptomatic vasospasm (OR 2.47; 95% CI 1.45 to 4.19;P <0.001), poorer Hunt and Hess grade (OR 2.50; 95% CI 1.31 to 4.75;P =0.005), need for permanent shunt (OR 8.90; 95% CI 1.80 to 44.15;P =0.008), and larger size of the aneurysm (OR 1.22; 95% CI 1.02 to 1.45;P =0.032) independently predicted worsened clinical outcome regardless of the treatment modality. In MRI, superficial brain retraction deficits (P <0.001) and ischemic lesions in the territory of the ruptured aneurysm (P =0.025) were more frequent in the surgical group. Kaplan-Meier analysis (mean±SD follow-up 39±18 months) revealed equal survival in both treatment groups. No late rebleedings have occurred. Conclusions One-year clinical and neuropsychological outcomes seem comparable after early surgical and endovascular treatment of ruptured intracranial aneurysms. The long-term efficacy of endovascular treatment in preventing rebleeding remains open.

Susceptibility loci for intracranial aneurysm in European and Japanese populations

Stroke is the worlds third leading cause of death. One cause of stroke, intracranial aneurysm, affects ∼2% of the population and accounts for 500,000 hemorrhagic strokes annually in mid-life (median age 50), most often resulting in death or severe neurological impairment. The pathogenesis of intracranial aneurysm is unknown, and because catastrophic hemorrhage is commonly the first sign of disease, early identification is essential. We carried out a multistage genome-wide association study (GWAS) of Finnish, Dutch and Japanese cohorts including over 2,100 intracranial aneurysm cases and 8,000 controls. Genome-wide genotyping of the European cohorts and replication studies in the Japanese cohort identified common SNPs on chromosomes 2q, 8q and 9p that show significant association with intracranial aneurysm with odds ratios 1.24–1.36. The loci on 2q and 8q are new, whereas the 9p locus was previously found to be associated with arterial diseases, including intracranial aneurysm. Associated SNPs on 8q likely act via SOX17, which is required for formation and maintenance of endothelial cells, suggesting a role in development and repair of the vasculature; CDKN2A at 9p may have a similar role. These findings have implications for the pathophysiology, diagnosis and therapy of intracranial aneurysm.

Microneurosurgical management of anterior communicating artery aneurysms

BACKGROUND Anterior communicating artery complex is the most frequent site of intracranial aneurysms in most reported series. Anterior communicating artery aneurysms are the most complex aneurysms of the anterior circulation due to the angioarchitecture and flow dynamics of the ACoA region, frequent anatomical variations, deep interhemispheric location, and danger of severing the perforators with ensuing neurologic deficits. The authors review the practical microsurgical anatomy, importance of preoperative imaging in surgical planning, and microneurosurgical steps in dissection and clipping of ACoAAs. METHODS This review, and the whole series on intracranial aneurysms, are mainly based on the personal microneurosurgical experience of the senior author (JH) in 2 Finnish centers (Helsinki and Kuopio), which serve, without patient selection, the catchment area in Southern and Eastern Finland. RESULTS These 2 centers have treated more than 10000 patients with aneurysm since 1951. In the Kuopio Cerebral Aneurysm Database of 3005 patients with 4253 aneurysms, 1145 patients (38%) had altogether 1179 ACA aneurysms; of them, 898 patients harbored 921 (78%) ACoAAs. In this series, 715 patients (80%) presented with ruptured ACoAAs with the median diameter of 7 mm. Giant ACoAAs were present in 15 (2%), whereas only 3 (0.3%) were classified as fusiform. CONCLUSIONS Anterior communicating artery aneurysms present frequently with SAH at small size. Furthermore, unruptured ACoAAs may have increased risk of rupture regardless of size, also as an associated aneurysm, and require treatment. The aim in microneurosurgical management of an ACoAA is total occlusion of the aneurysm sac with preservation of flow in all branching and perforating arteries. This demanding task necessitates perfect surgical strategy based on review of the 3D angioarchitecture and abnormalities of the patients ACoA complex with its ACoAA and to orientate accordingly during the microsurgical dissection. The surgical trajectory should provide optimal visualization of the ACoA complex without massive brain retraction. Precise dissection in the 3D anatomy of the ACoA complex and perforators requires not only experience and skill but patience to work the dome and base under repeated protection of temporary clips and pilot clips. This is particularly important with the complex, large, and giant aneurysms.

The unruptured intracranial aneurysm treatment score A multidisciplinary consensus

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.

Saccular intracranial aneurysm disease: distribution of site, size, and age suggests different etiologies for aneurysm formation and rupture in 316 familial and 1454 sporadic eastern Finnish patients.

OBJECTIVEFinnish saccular intracranial aneurysm (sIA) disease associates to 2q33, 8q11, and 9p21 loci and links to 19q13, Xp22, and kallikrein cluster in sIA families. Detailed phenotyping of familial and sporadic sIA disease is required for fine mapping of the Finnish sIA disease. METHODSEastern Finland, which is particularly isolated genetically, is served by Kuopio University Hospitals Department of Neurosurgery. We studied the site and size distribution of unruptured and ruptured sIAs in correlation to age and sex in 316 familial and 1454 sporadic sIA patients on first admission from 1993 to 2007. RESULTSThe familial and sporadic aneurysmic subarachnoid hemorrhage patients had slightly different median ages (46 vs 51 years in men; 50 vs 57 years in women), different proportion of males (50% vs 42%), equal median diameter of ruptured sIAs (7 mm vs 7 mm) with no correlation to age, and equally unruptured sIAs (30% vs 28%). The unruptured sIAs were most frequent at the middle cerebral artery (MCA) bifurcation (44% vs 39%) and the anterior communicating artery (12% vs 13%), in contrast to the ruptured sIAs at the anterior communicating artery (37% vs 29%) and MCA bifurcation (29% vs 29%). The size of unruptured sIAs increased by age in the sporadic group. CONCLUSIONThe MCA bifurcation was most prone to develop unruptured sIAs, suggesting that MCA branching during the embryonic period might be involved. The different site distribution of ruptured and unruptured sIAs suggests different etiologies for sIA formation and rupture. The lack of correlation of size and age at rupture (exposure to risk factors) suggests that the size at rupture is more dependent on hemodynamic stress.

Distal anterior cerebral artery aneurysms: treatment and outcome analysis of 501 patients.

OBJECTIVEThis study presents the combined experience of two Finnish neurosurgical centers in the treatment of 501 consecutive patients with distal anterior cerebral artery (DACA) aneurysms. Our aim was to compare treatment outcomes of these lesions with intracranial aneurysms in general and to identify factors predicting the outcome. METHODSWe analyzed the clinical and radiological data of all 501 patients and focused on the 427 patients treated between 1980 and 2005, the era of microsurgery and computed tomographic imaging. No patients were lost to follow-up. We compared treatment and outcome of ruptured DACA aneurysms (n = 277) with all consecutive ruptured aneurysms from the Kuopio Cerebral Aneurysm Database (n = 2243) and used multivariate analysis to identify factors predicting 1-year outcome. RESULTSDACA aneurysms accounted for 6% of all intracranial aneurysms. They were smaller (median, 6 versus 8 mm), more frequently associated with multiple aneurysms (35 versus 18%), and presented more often with intracerebral hematomas (53 versus 26%) than ruptured aneurysms in general. Their microsurgical treatment showed the same complication rates (treatment morbidity, 15%; treatment mortality, 0.4%) as for other ruptured aneurysms. At 1 year after subarachnoid hemorrhage, they had similar favorable outcome (Glasgow Coma Scale score ≥4) as other ruptured aneurysms (74 versus 69%), but their mortality rate was lower (13 versus 24%). Factors predicting unfavorable outcome for ruptured DACA aneurysms were advanced age, Hunt and Hess grade greater than or equal to III, rebleeding before treatment, intracerebral hematoma, intraventricular hemorrhage, and severe preoperative hydrocephalus. CONCLUSIONDespite their specific features, with modern treatment methods, ruptured DACA aneurysms have the same favorable outcome and lower mortality at 1 year as ruptured aneurysms in general.

Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: proposal of an international research group.

Background and Purpose— To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. Methods— After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. Results— Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. Conclusions— Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

Atrophic Enlargement of CSF Volume after Subarachnoid Hemorrhage: Correlation with Neuropsychological Outcome

BACKGROUND AND PURPOSE: Ventricular dilation and sulcal enlargement are common sequelae after aSAH. Our aim was to quantify the late ventricular dilation and volumes of the CSF spaces after aSAH and to determine if they correlate with neurologic and cognitive impairments frequently detected in these patients. MATERIALS AND METHODS: 3D T1-weighted images needed for volumetry were available in 76 patients 1 year after aSAH, along with 75 neuropsychological assessments. Volumes of CSF segments and ICV were quantified by SPM in 76 patients and 30 control subjects to determine CSF/ICV ratios. The mCMI was calculated to roughly evaluate the ventricular dilation. The contributing factors for enlarged ventricles and CSF volumes were reviewed from radiologic, clinical, and neuropsychological perspectives. RESULTS: The mCMI was higher in patients with aSAH (0.23 ± 0.06) compared with control subjects (0.20 ± 0.04; P = .020). In line with these planimetric measurements, the SPM-based CSF/ICV ratios were higher in patients with aSAH (35.58 ± 7.0) than in control subjects (30.36 ± 6.25; P = .001). Preoperative hydrocephalus, higher HH and Fisher grades, and focal parenchymal lesions on brain MR imaging, but not the treatment technique, were associated with ventricular enlargement. The clinical outcome and presence of neuropsychological deficits correlated significantly with CSF enlargement. CONCLUSIONS: Ventricular and sulcal enlargement, together with reduced GM volumes, after aSAH may indicate general atrophy rather than hydrocephalus. Enlarged CSF spaces correlate with cognitive deficits after aSAH. A simple measure, mCMI proved to be a feasible tool to assess the diffuse atrophic brain damage after aSAH.

Brain atrophy and neuropsychological outcome after treatment of ruptured anterior cerebral artery aneurysms: a voxel-based morphometric study

IntroductionCognitive impairment after aneurysmal subarachnoid hemorrhage (aSAH) is frequently detected. Here, we describe the pattern of cerebral (gray matter) atrophy and its clinical relevance after treatment of aSAH caused by a ruptured anterior cerebral artery (ACA) aneurysm.MethodsThirty-seven aSAH patients with ACA aneurysm (17 surgical, 20 endovascular treatment) and a good or moderate clinical outcome (Glasgow Outcome Scale V or IV) and 30 controls underwent brain MRI. Voxel-based morphometric analysis was applied to compare the patients and controls. Patients also underwent a detailed neuropsychological assessment.ResultsThe comparisons between controls and either all patients (n = 37) or the subgroup of surgically treated patients (n = 17) revealed bilateral cortical atrophy in the frontal lobes, mainly in the basal areas. The brainstem, bilateral thalamic and hypothalamic areas, and ipsilateral caudate nucleus were also involved. Small areas of atrophy were detected in temporal lobes. The hippocampus and parahippocampal gyrus showed atrophy ipsilateral to the surgical approach. In the subgroup of endovascularly treated patients (n = 15), small areas of atrophy were detected in the bilateral orbitofrontal cortex and in the thalamic region. Twenty patients (54%) showed cognitive deficits in neuropsychological assessment.ConclusionGroup analysis after aSAH and treatment of the ruptured ACA aneurysm revealed gray matter atrophy, principally involving the frontobasal cortical areas and hippocampus ipsilateral to the surgical approach. Areas of reduced gray matter were more pronounced after surgical than endovascular treatment. Together with possible focal cortical infarctions and brain retraction deficits in individual patients, this finding may explain the neuropsychological disturbances commonly detected after treatment of ruptured ACA aneurysms.

Pituitary-adrenal function in patients with acute subarachnoid haemorrhage: a prospective cohort study

IntroductionSubarachnoid haemorrhage (SAH) may damage the hypothalamo-pituitary-adrenal gland (HPA) axis and disturb cortisol metabolism. There are no available data that relates to the response of the HPA axis in the acute phase of SAH. We aimed to characterise the behavior of serum adrenocorticotropic hormone (ACTH), total cortisol, stimulated total cortisol and free cortisol concentrations in acute aneurysmal SAH.MethodsA prospective cohort study was conducted of patients with acute aneurysmal SAH (n = 30) admitted to a tertiary university hospital. Patients admitted for elective aneurysmal surgery (n = 16) served as the control group. An ACTH stimulation test was performed twice during the first week and at three months. The main outcome measure was description of the ACTH-cortisol response by calculating serum free cortisol and measuring total cortisol and ACTH concentrations. A mixed models method was used for testing between the groups, allowing heterogeneity between the groups.ResultsPatients with SAH had higher initial serum total cortisol (mean +/- SD; 793 +/- 312 nmol/L) and free cortisol concentrations (83 +/- 55 nmol/L) than control patients (535 +/- 193 nmol/L, p = 0.001 and 33 +/- 18 nmol/L, p < 0.001, respectively). Thereafter, there were no differences in this respect. Serum free and total cortisol concentrations correlated but were unaffected by the severity of SAH. ACTH concentrations were comparable between SAH and control groups. Patients with Hunt-Hess grades IV to V had higher ACTH concentrations at day one (10.7 +/- 7.1 pmol/l/L) and day five (8.2 +/- 7.7 pmol/L) than patients with grade I-III (day one: 3.8 +/- 2.0 pmol/L, p = 0.002; day five: 4.7 +/- 1.8 pmol/L, p = 0.04).ConclusionsCalculation of serum free cortisol concentration was not helpful in identifying patients with potential hypocortisolism. SAH severity did not affect cortisol concentrations, possibly indicating relative pituitary-adrenal insufficiency in patients with more severe bleeding.Trial registrationClinicalTrials.gov Identifier NCT00614887.