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Seppo Juvela, Matti Porras and Kristiina Poussa

Object. The authors conducted a study to investigate the long-term natural history of unruptured intracranial aneurysms and the predictive risk factors determining subsequent rupture in a patient population in which surgical selection of cases was not performed.

Methods. One hundred forty-two patients with 181 unruptured aneurysms were followed from the 1950s until death or the occurrence of subarachnoid hemorrhage or until the years 1997 to 1998. The annual and cumulative incidence of aneurysm rupture as well as several potential risk factors predictive of rupture were studied using life-table analyses and Cox's proportional hazards regression models including time-dependent covariates.

The median follow-up time was 19.7 years (range 0.8–38.9 years). During 2575 person-years of follow up, there were 33 first-time episodes of hemorrhage from previously unruptured aneurysms, for an average annual incidence of 1.3%. In 17 patients, hemorrhage led to death. The cumulative rate of bleeding was 10.5% at 10 years, 23% at 20 years, and 30.3% at 30 years after diagnosis. The diameter of the unruptured aneurysm (relative risk [RR] 1.11 per mm in diameter, 95% confidence interval [CI] 1–1.23, p = 0.05) and patient age at diagnosis inversely (RR 0.97 per year, 95% CI 0.93–1, p = 0.05) were significant independent predictors for a subsequent aneurysm rupture after adjustment for sex, hypertension, and aneurysm group. Active smoking status at the time of diagnosis was a significant risk factor for aneurysm rupture (RR 1.46, 95% CI 1.04–2.06, p = 0.033) after adjustment for size of the aneurysm, patient age, sex, presence of hypertension, and aneurysm group. Active smoking status as a time-dependent covariate was an even more significant risk factor for aneurysm rupture (adjusted RR 3.04, 95% CI 1.21–7.66, p = 0.02).

Conclusions. Cigarette smoking, size of the unruptured intracranial aneurysm, and age, inversely, are important factors determining risk for subsequent aneurysm rupture. The authors conclude that such unruptured aneurysms should be surgically treated regardless of their size and of a patient's smoking status, especially in young and middle-aged adults, if this is technically possible and if the patient's concurrent diseases are not contraindications. Cessation of smoking may also be a good alternative to surgery in older patients with small-sized aneurysms.

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Seppo Juvela, Matti Porras and Kristiina Poussa

Object

The authors conducted a study to investigate the long-term natural history of unruptured intracranial aneurysms and the predictive risk factors determining subsequent rupture in a patient population in which surgical selection of cases was not performed.

Methods

One hundred forty-two patients with 181 unruptured aneurysms were followed from the 1950s until death or the occurrence of subarachnoid hemorrhage or until the years 1997 to 1998. The annual and cumulative incidence of aneurysm rupture as well as several potential risk factors predictive of rupture were studied using life-table analyses and Cox's proportional hazards regression models including time-dependent covariates.

The median follow-up time was 19.7 years (range 0.8–38.9 years). During 2575 person-years of follow up, there were 33 first-time episodes of hemorrhage from previously unruptured aneurysms, for an average annual incidence of 1.3%. In 17 patients, hemorrhage led to death. The cumulative rate of bleeding was 10.5% at 10 years, 23% at 20 years, and 30.3% at 30 years after diagnosis. The diameter of the unruptured aneurysm (relative risk [RR] 1.11 per mm in diameter, 95% confidence interval [CI] 1–1.23, p = 0.05) and patient age at diagnosis inversely (RR 0.97 per year, 95% CI 0.93–1, p = 0.05) were significant independent predictors for a subsequent aneurysm rupture after adjustment for sex, hypertension, and aneurysm group. Active smoking status at the time of diagnosis was a significant risk factor for aneurysm rupture (RR 1.46, 95% CI 1.04–2.06, p = 0.033) after adjustment for size of the aneurysm, patient age, sex, presence of hypertension, and aneurysm group. Active smoking status as a time-dependent covariate was an even more significant risk factor for aneurysm rupture (adjusted RR 3.04, 95% CI 1.21–7.66, p = 0.02).

Conclusions

Cigarette smoking, size of the unruptured intracranial aneurysm, and age, inversely, are important factors determining risk for subsequent aneurysm rupture. The authors conclude that such unruptured aneurysms should be surgically treated regardless of their size and of a patient's smoking status, especially in young and middle-aged adults, if this is technically possible and if the patient's concurrent diseases are not contraindications. Cessation of smoking may also be a good alternative to surgery in older patients with small-sized aneurysms.

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Seppo Juvela, Matti Porras and Olli Heiskanen

✓ To investigate the natural history of unruptured aneurysms and predictive risk factors determining subsequent rupture, the authors followed 142 patients with 181 unruptured aneurysms until death or subarachnoid hemorrhage intervened, or for at least 10 years after the unruptured aneurysm was diagnosed. Six patients had a symptomatic aneurysm, five had an incidentally discovered aneurysm, and 131 had multiple aneurysms, of which the ruptured lesion was clipped at the beginning of the follow-up study. The median follow-up time was 13.9 years (range 0.8 to 30.0 years). During 1944 patient-years of follow-up study there were 27 first episodes of hemorrhage from a previously unruptured aneurysm, giving an average annual rupture incidence of 1.4%. Fourteen of these bleeding episodes were fatal. The cumulative rate of bleeding was 10% at 10 years, 26% at 20 years, and 32% at 30 years after the diagnosis.

The only predictor for the rupture was the size of the aneurysm (p = 0.036). However, in patients with multiple aneurysms (the main subgroup) the only variable that tended to predict rupture was the age of the patient: risk of rupture was inversely associated with age (p = 0.080). The median diameter of the aneurysms was 4 mm at the beginning of the follow-up period, both in those with and those without a later hemorrhage. During the angiographic monitoring period, a ruptured aneurysm significantly (p < 0.001) increased in size in 17 patients with hemorrhage but aneurysms did not increase significantly in 14 patients without hemorrhage. In addition, a new aneurysm was found in six of 31 patients. The authors conclude that an unruptured aneurysm should be operated on, irrespective of its size, if it is technically possible and the patient's age and concurrent diseases are not contraindications to surgery.

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Seppo Juvela, Matti Porras and Kristiina Poussa

Object. The authors conducted a study to investigate the long-term natural history of unruptured intracranial aneurysms and the predictive risk factors determining subsequent rupture in a patient population in which surgical selection of cases was not performed.

Methods. One hundred forty-two patients with 181 unruptured aneurysms were followed from the 1950s until death or the occurrence of subarachnoid hemorrhage or until the years 1997 to 1998. The annual and cumulative incidence of aneurysm rupture as well as several potential risk factors predictive of rupture were studied using life-table analyses and Cox's proportional hazards regression models including time-dependent covariates.

The median follow-up time was 19.7 years (range 0.8–38.9 years). During 2575 person-years of follow up, there were 33 first-time episodes of hemorrhage from previously unruptured aneurysms, for an average annual incidence of 1.3%. In 17 patients, hemorrhage led to death. The cumulative rate of bleeding was 10.5% at 10 years, 23% at 20 years, and 30.3% at 30 years after diagnosis. The diameter of the unruptured aneurysm (relative risk [RR] 1.11 per mm in diameter, 95% confidence interval [CI] 1–1.23, p = 0.05) and patient age at diagnosis inversely (RR 0.97 per year, 95% CI 0.93–1, p = 0.05) were significant independent predictors for a subsequent aneurysm rupture after adjustment for sex, hypertension, and aneurysm group. Active smoking status at the time of diagnosis was a significant risk factor for aneurysm rupture (RR 1.46, 95% CI 1.04–2.06, p = 0.033) after adjustment for size of the aneurysm, patient age, sex, presence of hypertension, and aneurysm group. Active smoking status as a time-dependent covariate was an even more significant risk factor for aneurysm rupture (adjusted RR 3.04, 95% CI 1.21–7.66, p = 0.02).

Conclusions. Cigarette smoking, size of the unruptured intracranial aneurysm, and age, inversely, are important factors determining risk for subsequent aneurysm rupture. The authors conclude that such unruptured aneurysms should be surgically treated regardless of their size and of a patient's smoking status, especially in young and middle-aged adults, if this is technically possible and if the patient's concurrent diseases are not contraindications. Cessation of smoking may also be a good alternative to surgery in older patients with small-sized aneurysms.

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Seppo Juvela, Jari Siironen, Joona Varis, Kristiina Poussa and Matti Porras

Object. The aim of this study was to test whether enoxaparin treatment (40 mg subcutaneously once daily) reduces the risk of cerebral infarction after subarachnoid hemorrhage (SAH) and to investigate predictive risk factors for permanent ischemic lesions visible on follow-up computerized tomography (CT) scans obtained 3 months after SAH.

Methods. After undergoing surgery for a ruptured aneurysm, 170 patients were randomized in a prospective, double-blind, placebo-controlled trial to test the effect of enoxaparin on the occurrence of ischemic lesions, which were demonstrated on follow-up CT scans available for 156 patients. The presence of lesions correlated highly with an impaired outcome, as assessed using both the Glasgow Outcome and modified Rankin Scales (p < 0.01). Lesions occurred in 101 (65%) of the 156 patients. In half of the patients (51 patients) no lesion was visible on the CT scan obtained on the 1st postoperative day in 51 patients. On univariate analysis, the presence of lesions at 3 months post-SAH was not associated with enoxaparin treatment but did correlate with several clinical, radiological, and prehemorrhage variables. Significant independent risk factors for lesions consisted of an impaired initial clinical condition (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.03–6.73), amount of subarachnoid blood (OR 6.51, 95% CI 2.27–18.65), nocturnal occurrence of SAH (that is, between 12:01 a.m. and 8:00 a.m.; OR 4.32, 95% CI 1.28–14.52), fixed symptoms of delayed ischemia (OR 5.21, 95% CI 1.02–26.49), duration of temporary artery occlusion during surgery (OR 1.66 per minute, 95% CI 1.20–2.31), and body mass index (OR 1.13/kg/m2, 95% CI 1.01–1.28).

Conclusions The presence of ischemic lesions can be predicted by the severity of bleeding, delayed cerebral ischemia, excess weight, duration of temporary artery occlusion, and occurrence of nocturnal aneurysm rupture.

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Juri Kivelev, Christian N. Ramsey, Reza Dashti, Matti Porras, Olli Tyyninen and Juha Hernesniemi

✓Among cavernomas of the central nervous system, spinal ones are rare. The true incidence of spinal cavernomas is unclear, but with widespread use of magnetic resonance imaging the number of cases is increasing. Furthermore, cav-ernomas represent only 5–12% of all vascular anomalies of the spinal cord, with a mere 3% reported to be intradural and intramedullary in location. Cervical spine intradural extramedullary cavernomas are very seldom seen, and only 4 cases have been reported in world literature previously. In this report, a unique case of an intradural extramedullary spinal cavernoma was surgically treated in a patient who presented only with an intramedullary hemorrhage.

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Jari Siironen, Matti Porras, Joona Varis, Kristiina Poussa, Juha Hernesniemi and Seppo Juvela

Object

Identifying ischemic lesions after subarachnoid hemorrhage (SAH) is important because the appearance of these lesions on follow-up imaging correlates with a poor outcome. The effect of ischemic lesions seen on computed tomography (CT) scans during the first days of treatment remains unknown, however.

Methods

In 156 patients with SAH, clinical course and outcome, as well as the appearance of ischemic lesions on serial CT scans, were prospectively monitored for 3 months. At 3 months after SAH, magnetic resonance imaging was performed to detect permanent lesions that had not been visible on CT.

Results

Of the 53 patients with no lesions on any of the follow-up CT scans, four (8%) had a poor outcome. Of the 52 patients with a new hypodense lesion on the first postoperative day CT, 23 (44%) had a poor outcome. Among the remaining 51 patients with a lesion appearing later than the first postoperative morning, 10 (20%) had a poor outcome (p < 0.001). After adjusting for patient age; clinical condition on admission; amounts of subarachnoid, intracerebral, and intraventricular blood; and plasma glucose and D-dimer levels, a hypodense lesion on CT on the first postoperative morning was an independent predictor of poor outcome after SAH (odds ratio 7.27, 95% confidence interval 1.54–34.37, p < 0.05).

Conclusions

A new hypodense lesion on early postoperative CT seems to be an independent risk factor for poor outcome after SAH, and this early lesion development may be more detrimental to clinical outcome than a later lesion occurrence.

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Jari Siironen, Seppo Juvela, Joona Varis, Matti Porras, Kristiina Poussa, Sorella Ilveskero, Juha Hernesniemi and Riitta Lassila

Object. From the moment an intracranial aneurysm ruptures, cerebral blood flow is impaired, and this impairment mainly determines the outcome in patients who survive after the initial bleeding. The exact mechanism of impairment is unknown, but activation of coagulation and fibrinolysis correlate with clinical condition and outcome after aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to determine whether enoxaparin, a low-molecular-weight heparin, which is a well-known anticoagulating agent, has any effect on the outcome of aneurysmal SAH postoperatively.

Methods. In this randomized, double-blind, single-center clinical trial, 170 patients (85 per group) with aneurysmal SAH were randomly assigned to receive either enoxaparin (40 mg subcutaneously once daily) or a placebo, starting within 24 hours after occlusion of the aneurysm and continuing for 10 days. Analysis was done on an intention-to-treat basis. Outcome was assessed at 3 months on both the Glasgow Outcome and modified Rankin Scales. Patients were eligible for the study if surgery was performed within 48 hours post-SAH, and no intracerebral hemorrhage was larger than 20 mm in diameter on the first postoperative computerized tomography scan.

At 3 months, there were no significant differences in outcome by treatment group. Of the 170 patients, 11 (6%) died, and only 95 (56%) had a good outcome. Principal causes of unfavorable outcome were poor initial condition, delayed cerebral ischemia, and surgical complications. There were four patients with additional intracranial bleeding in the group receiving enoxaparin. The bleeding was not necessarily associated with the treatment itself, nor did it require treatment, and there were no such patients in the placebo group.

Conclusions. Enoxaparin seemed to have no effect on the outcome of aneurysmal SAH in patients who had already received routine nimodipine and who had received triple-H therapy when needed. Routine use of low-molecular-weight heparin should be avoided during the early postoperative period in patients with SAH, because this agent seems to increase intracranial bleeding complications slightly, with no beneficial effect on neurological outcome.