Hanna Lehto

Natural History of Unruptured Intracranial Aneurysms: A Long-term Follow-up Study

Background and Purpose— Unruptured intracranial aneurysms are increasingly being detected and are a notable healthcare burden. We investigated the long-term natural history of unruptured intracranial aneurysms and risk factors predictive of subsequent rupture. Methods— A total of 142 patients with 181 unruptured intracranial aneurysms diagnosed between 1956 and 1978, when these were not treated, were followed up until death or subarachnoid hemorrhage, or until 2011 to 2012. Annual and cumulative incidences of aneurysm rupture and risk factors for rupture were studied using Kaplan–Meier survival analysis and Cox proportional hazards regression models. Results— The median follow-up time was 21.0 (range, 0.8–52.3) years. During 3064 person-years, there were 34 first episodes of aneurysm rupture, giving an average annual incidence of 1.1%. Eighteen patients died on account of an initial or recurrent aneurysm rupture. The cumulative rate of bleeding was 10.5% (95% confidence interval [CI], 5.2–15.8) at 10 years, 23.0% (95% CI, 15.4–30.6) at 20 years, and 30.1% (95% CI, 21.3–38.9) at 30 years. None of the index aneurysms bled after a follow-up of 25 years. Cigarette smoking (adjusted hazard ratio, 2.44; 95% CI, 1.02–5.88), location of the aneurysm in the anterior communicating artery (adjusted hazard ratio, 3.73; 95% CI, 1.23–11.36), patient age inversely (0.96 per year, 95% CI, 0.92–1.00) and aneurysm diameter ≥7 mm (adjusted hazard ratio, 2.60; 95% CI, 1.13–5.98) independently predicted subsequent aneurysm rupture, as did alcohol consumption (1.27 per 100 g/week; 95% CI, 1.05–1.53; P<0.05), but only in univariable analysis. Conclusions— Cigarette smoking, patient age inversely, and the size and location of the unruptured intracranial aneurysm seem to be risk factors for aneurysm rupture. The risk of bleeding decreases with a very long-term follow-up.

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.

Lifelong Rupture Risk of Intracranial Aneurysms Depends on Risk Factors A Prospective Finnish Cohort Study

Background and Purpose— Our aim was to define for the first time the lifelong natural course of unruptured intracranial aneurysms (UIAs) and identify high-risk and low-risk patients for the rupture. Methods— One hundred and eighteen patients (61 women) with UIAs were diagnosed between 1956 and 1978 and followed up until death or subarachnoid hemorrhage (SAH). The median age at the diagnosis was 43.5 years (range, 22.6–60.7 years). The median size of the UIA at the diagnosis was 4 mm (range, 2–25 mm). Analyzed risk factors for a rupture included sex, age, cigarette smoking, systolic blood pressure values, diagnosed hypertension, UIA size, and number of UIAs. Results— Thirty four (29%) out of 118 people had SAH during the lifelong follow-up. The median age at SAH was 51.3 years (range, 30.1–71.8 years). The annual rupture rate per patient was 1.6%. Female sex, current smoking, and aneurysm size of ≥7 mm in diameter were risk factors for a lifetime SAH. Depending on the risk factor burden, the lifetime risk of an aneurysmal SAH varied from 0% to 100%, and the annual rupture rate from 0% to 6.5%. Of the 96 patients with small (<7 mm) UIAs, 24 (25%) had an aneurysmal SAH during the follow-up. Conclusions— Almost 30% of all UIAs in people of working age ruptured during a lifelong follow-up. The risk varied substantially on the basis of risk factor burden. Because even small UIAs ruptured, treatment decisions of UIAs should perhaps be based on the risk factor status.

Anatomic risk factors for middle cerebral artery aneurysm rupture: computed tomography angiography study of 1009 consecutive patients.

BACKGROUND In a variety of surgical specialties, simulation-based technologies play an important role in resident training. The Congress of Neurological Surgeons (CNS) established an initiative to enhance neurosurgical training by developing a simulation-based curriculum to complement standard didactic and clinical learning. OBJECTIVE To enhance resident education in the management of traumatic brain injury by the use of simulation-based training. METHODS A course-based neurosurgical simulation curriculum was developed and offered at the 2012 CNS annual meeting. Within this curriculum, a trauma module was developed to teach skills necessary in the management of traumatic brain injury, including the performance of craniotomy for trauma. Didactic and simulator-based instruction were incorporated into the course. Written and practical pre- and posttests, as well as questionnaires, were used to assess the improvement in skill level and to validate the simulator as a teaching tool. RESULTS Fourteen trainees participated in the didactic section of the trauma module. Average performance improved significantly in written scores from pretest (75%) to posttest (87.5%, P < .05). Eight participants completed the trauma craniotomy simulator. Incision planning, burr hole placement (P < .02), and craniotomy size (P < .05) improved significantly. Junior residents (postgraduate years 1-3) demonstrated the most improvement during the course. CONCLUSION The CNS simulation trauma module provides a complementary method for residents to acquire necessary skills in the management of traumatic brain injury. Preliminary data indicate improvement in didactic and hands-on knowledge after training. Additional data are needed to confirm the validity of the simulator.BACKGROUND The middle cerebral artery (MCA) is the most frequent location for unruptured intracranial aneurysms. Controversy remains as to which unruptured MCA aneurysms should be treated prophylactically. OBJECTIVE To identify independent topographical and morphological variables that could predict increased rupture risk of MCA aneurysms. METHODS A retrospective analysis of computed tomography angiography data of 1009 consecutive patients with 1309 MCA aneurysms, referred between 2000 and 2009 to Helsinki University Hospital, was carried out. Morphological and topographical parameters examined for MCA aneurysms comprised aneurysm wall regularity, size, neck width, aspect ratio, bottleneck factor, height-width ratio, location along the MCA, side, distance from the internal carotid artery bifurcation, and dome projection in axial and coronal computed tomography angiography views. Univariate and multivariate logistic regression analyses were performed to determine independent risk factors for rupture. RESULTS Of the 1309 MCA aneurysms, 69% were unruptured and 31% were ruptured. Most unruptured MCA aneurysms were smaller than 7 mm (78%), with a smooth wall (80%) and a height-width ratio of 1 (47%) and were located at the main bifurcation (57%). Ruptured MCA aneurysms, mostly 7 to 14 mm in size (55%), had an irregular wall (78%) and a height-width ratio greater than 1 (72%) and were located at the main bifurcation (77%). Thirty-eight percent of MCA bifurcation aneurysms, 74% of large aneurysms, 64% of aneurysms with an irregular wall, and 49% of aneurysms with a height-width ratio greater than 1 were ruptured. CONCLUSION Location at the main MCA bifurcation, wall irregularity, and less spherical geometry were independently associated with rupture of MCA aneurysms with a correlation with aneurysm size. artery.

Microsurgical management of pineal region lesions: personal experience with 119 patients

BACKGROUND Lesions of the pineal region are histopathologically heterogeneous but often accompanied with severe progression of clinical signs. Surgical treatment remains challenging because of the close vicinity of the deep venous system and the mesencephalo-diencephalic structures in this region. We present the surgical approaches and techniques in a consecutive series of 119 patients treated by the senior author (J.H.) between 1980 and 2007 at 2 different neurosurgical university centers in Kuopio and Helsinki, Finland. METHODS Of the included patients, 107 (90%) presented with pineal region tumors and 12 (10%) with vascular malformations. The ITSC route was used for removal of the lesion in 111 (93%) patients and the OIH approach in 8 (7%) patients. All except one patient were operated on in a sitting position. RESULTS We reviewed all clinical data and radiographic images and analyzed all surgical videos. The pineal lesions were removed completely in most cases (88%). There was no surgical mortality. Twenty-two (18%) of the patients had complications in the postoperative period; these included 1 epidural hematoma, 9 transient Parinaud syndrome, 2 meningitis, 3 wound infections, 2 transient memory disturbances, 2 mild hemiparesis, 1 CSF fistula, and 2 cranial nerves palsies (IV and VI). During a 3.5-year follow-up, 12 patients with malignant lesions died; all patients with benign tumors survived. CONCLUSIONS The ITSC route is a safe and effective surgical approach, associated with low morbidity, complete lesion removal, and definitive histopathologic diagnosis. Considering risk vs benefit, we therefore believe that the surgical treatment can be offered in most cases as the first treatment option for pineal tumors.

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.

Long-term outcome of 114 children with cerebral aneurysms

OBJECT Population-based data on pediatric patients with aneurysms are limited. The aim of this study is to clarify the characteristics and long-term outcomes of pediatric patients with aneurysms. METHODS All pediatric patients (≤ 18 years old) with aneurysms among the 8996 aneurysm patients treated at the Department of Neurosurgery in Helsinki from 1937 to 2009 were followed from admission to the end of 2010. RESULTS There were 114 pediatric patients with 130 total aneurysms during the study period. The mean patient age was 14.5 years (range 3 months to 18 years). The male:female ratio was 3:2. Eighty-nine patients (78%) presented with subarachnoid hemorrhage. The majority of the aneurysms (116 [89%]) were in the anterior circulation, and the most common location was the internal carotid artery bifurcation (36 [28%]). The average aneurysm diameter was 11 mm (range 2-55 mm) with 16 giant aneurysms (12%). Eighty aneurysms (62%) were treated microsurgically, and 37 (28%) were treated conservatively due to poor medical and neurological status of the patient or due to technical reasons during the early years of the patient series. No connective tissue disorders common to pediatric aneurysm patients were diagnosed in this series, with the exception of 1 patient with tuberous sclerosis complex. The mean follow-up duration was 24.8 years (range 0-55.8 years). At the end of follow-up, 71 patients (62%) had a good outcome, 3 (3%) were dependent, and 40 (35%) had died. Twenty-seven deaths (68%) were assessed to be aneurysm-related. Factors correlating with a favorable long-term outcome were good neurological condition of the patient on admission, aneurysm location in the anterior circulation, complete aneurysm closure, and absence of vasospasm. Six patients developed symptomatic de novo aneurysms after a median of 25 years (range 11-37 years). Fourteen patients (12%) had a family history of aneurysms. There was no increased incidence for cardiovascular diseases in long-term follow-up. CONCLUSIONS Most aneurysms were ruptured and of medium size. Internal carotid artery bifurcation was the most frequent location of the aneurysms. There was a male predominance of pediatric patients with aneurysms. Most patients experienced good recovery, with 91% of the long-term survivors living at home independently without assistance and meaningfully employed. Altogether, almost a third of these patients finished high school and one-fifth had a college or university degree. Pediatric patients had a tendency to develop de novo aneurysms.

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

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.

De Novo and Recurrent Aneurysms in Pediatric Patients With Cerebral Aneurysms

Background and Purpose— Long-term angiographic follow-up studies on pediatric aneurysm patients are scarce. Methods— We gathered long-term clinical and angiographic follow-up data on all pediatric aneurysm patients (⩽18 years at diagnosis) treated at the Department of Neurosurgery, Helsinki University Central Hospital, between 1937 and 2009. Results— Fifty-nine patients with cerebral aneurysms in childhood had long-term clinical and radiological follow-up (median, 34 years; range, 4–56 years). Twenty-four patients (41%) were diagnosed with altogether 25 de novo and 11 recurrent aneurysms, with 9 (25%) of the aneurysms being symptomatic. New subarachnoid hemorrhage occurred in 7 patients; 4 of these patients died. Eight patients (33%) had multiple new aneurysms. The annual rate of hemorrhage was 0.4%, and the annual rate for the development of de novo or recurrent aneurysm was 1.9%. There were no de novo aneurysms in 7 patients with previously unruptured aneurysms. However, 1 recurrent aneurysm was diagnosed. Current and previous smoking (risk ratio, 2.44; 95% confidence interval, 1.07–5.55) was the only statistically significant risk factor for de novo and recurrent aneurysm formation in patients with previous subarachnoid hemorrhage, whereas hypertension, sex, or age at onset had no statistically significant effect. Smoking was also a statistically significant risk factor for new subarachnoid hemorrhage. Conclusions— Patients with ruptured intracranial aneurysms in childhood have a high risk for new aneurysms and new subarachnoid hemorrhage, especially if they start to smoke as adults. Life-long angiographic follow-up is mandatory.

Incidence of subarachnoid hemorrhage is decreasing together with decreasing smoking rates

Objective: To determine the nationwide incidence of subarachnoid hemorrhage (SAH) and report nationwide changes in smoking rates between 1998 and 2012 in Finland. Methods: In this register-based study, we utilized the nationwide Causes of Death Register and Hospital Discharge Register in identifying SAH events between 1998 and 2012. Population statistics in Finland, which were obtained through a database of Statistics Finland, were used to calculate crude annual incidence rates of SAH. For the direct age standardization of crude incidence rates, we used the European Standard Population (ESP) 2013. Data on changes in nationwide smoking rates between 1998 and 2012 were extracted from a database of the National Institute for Health and Welfare. Results: For the total of 79,083,579 cumulative person-years, we identified 6,885 people with SAH. Sudden deaths from SAH away from hospitals or in emergency rooms accounted for 1,771 (26%) of the events. Crude nationwide annual incidence rates varied between 6.2 and 10.0 per 100,000 persons, and increased by age particularly in women. Among 70- to 75-year-old women, the incidence of SAH was highest (22.5 per 100,000 persons). The 3-year average of ESP standardized incidence decreased 24% from 11.7 in 1998–2000 to 8.9 per 100,000 persons in 2010–2012. Daily smoking decreased 30% between 1998 and 2012. Conclusions: The incidence of SAH seems to be decreasing. This tendency may be coupled with changes in smoking rates. The incidence of SAH in Finland is similar to other Nordic countries.