Heterogeneity of cerebral perfusion 1 week after haemorrhage is an independent predictor of clinical outcome in patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid haemorrhage (aSAH) can be associated with acute global and regional decrease in cerebral perfusion. Furthermore, cerebral vasospasm may lead to development of delayed ischaemic deficits. The aim of the study was to find out whether cerebral perfusion heterogeneity, an indicator of cerebral microvascular function and autoregulation, measured by single-photon emission tomography (SPET), is able to predict the long-term clinical outcome of aSAH. METHODS: The perfusion SPET data of 55 patients with aSAH were analysed by dividing the brain into 384 regions of interest. Spatial perfusion heterogeneity was assessed by calculating the relative dispersions (RD, coefficient of variation) from the SPETs performed before treatment (RD1) and 1 week after early surgical or endovascular treatment of the ruptured aneurysm (RD2). Both RDs were compared to the clinical outcome (Glasgow Outcome Scale, GOS), neuropsychological test scores and late ischaemic findings in MRI 1 year after SAH. RESULTS: High RD2 (OR 1.96; 95% CI 1.18-3.26; p = 0.009) and poor clinical condition (Hunt and Hess grade) on admission (OR 6.60; 95% CI 1.78-24.52; p = 0.005) proved to be independent predictors of poor or moderate clinical outcome (GOS 1-4). RD2 was higher in patients with ischaemic findings in 12-month MRI than in those without ischaemic findings (p = 0.008). RD2 also correlated with neuropsychological outcome 1 year after aSAH. CONCLUSIONS: Perfusion heterogeneity is an independent predictor of the clinical outcome of aSAH and may thus be a valuable measure in the assessment of the disease.

Beta-galactosidase gene transfer to human malignant glioma in vivo using replication-deficient retroviruses and adenoviruses.

Both retro- and adenovirus-mediated gene therapy have been suggested as a novel approach to the treatment of malignant brain tumors. However, little information is available about the gene transfer efficiency in human malignant glioma in vivo. We compared the feasibility and safety of retrovirus- and adenovirus-mediated beta-galactosidase gene transfer in human malignant glioma. Beta-galactosidase gene was transferred to 10 patients with malignant glioma via a catheter inserted into the tumor. The catheter was left in place until the tumor resection. To maximize gene transfer efficiency, gene transfer vectors (BAG retroviruses, titer, 6 x 10(5) CFU; and adenoviruses, titer from 3 x 10(8) to 3 x 10(10) PFU) were injected into the tumor via the catheter once a day for three consecutive days, followed by tumor resection 1-2 days later. Tumor was resected in such a way that the catheter was still in place inside the tumor, which permitted accurate histological analysis of the transduced tumors. X-Gal staining for beta-galactosidase activity was used to study gene transfer efficiency and distribution of the marker gene. Beta-galactosidase gene transfer was well tolerated with both vectors. Except for two patients with clear increases in serum adenovirus antibody titers, no adverse tissue responses or systemic complications were noticed in any of the patients. Gene transfer was successful in all patients. Gene transfer efficiency varied between <0.01 and 4% with retroviruses and between <0.01 and 11% with adenoviruses. However, the transgene activity was not evenly distributed in the tumors. Both glioma cells and endothelium in the tumor blood vessels were transduced with retro- and adenovirus vectors. In conclusion, the safety and feasibility of in vivo gene transfer to human malignant glioma was established with retro- and adenovirus vectors. Adenoviruses were more efficient than retroviruses in achieving in vivo gene transfer. Transduction of endothelial cells may have important consequences for the proposed treatment strategies and selection of treatment genes. The results justify clinical gene therapy trials for malignant glioma.

Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses.

Herpes simplex virus thymidine kinase (HSV tk) gene therapy combined with ganciclovir (GCV) medication is a potential new method for the treatment of malignant glioma. We have used both retrovirus-packaging cells (PA317/tk) and adenoviruses (Adv/tk) for gene therapy for malignant glioma. Retrovirus-packaging cells were used for eight tumors in seven patients and adenoviruses were used for seven tumors in seven patients. As a control group, seven tumors in seven patients were transduced with lacZ marker gene 4-5 days before tumor resection. Safety and efficacy of the gene therapy were studied with clinical evaluation, blood and urine samples, MRI follow-up, and survival of the patients. Four patients with adenovirus injections had a significant increase in anti-adenovirus antibodies and two of them had a short-term fever reaction. Frequency of epileptic seizures increased in two patients. No other adverse events possibly related to gene therapy were detected. In the retrovirus group, all treated gliomas showed progression by MRI at the 3-month time point, whereas three of the seven patients treated with Adv/tk remained stable (p < 0.05). Mean survival times for retrovirus, adenovirus, and control groups were 7.4, 15.0, and 8. 3 months, respectively. The difference in the survival times between the adenovirus and retrovirus groups was significant (p < 0.012). It is concluded that HSV tk gene therapy is safe and well tolerated. On the basis of these results further trials are justified, especially with adenovirus vectors.

Evidence for excess long-term mortality after treated subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The purpose of this study was to examine the long-term mortality rate of patients with aneurysmal subarachnoid hemorrhage (SAH) compared with that of the general population. METHODS: Aneurysmal SAH patients who were treated for ruptured aneurysm from 1977 through 1998 in a tertiary referral center (n=1537) were followed up for a median of 7.5 years. Dates and causes of death were determined. Standardized mortality ratios (observed/expected deaths) according to age, sex, and Glasgow Outcome Scale at 12 months after surgery were calculated. RESULTS: The mortality rate among patients with good recovery at 12 months was twice that of the general population. The excess mortality appeared to be most evident in younger age groups. Cerebrovascular and cardiovascular diseases were the principal causes of premature death. The result was similar among patients without preexisting cardiovascular diseases at the time of SAH. CONCLUSIONS: Aneurysmal SAH patients have an excess mortality rate even after successful treatment of ruptured aneurysms. Therefore, aneurysmal SAH should be viewed more as one aspect of a chronic general vascular disease, and more attention should be given to treatment of risk factors and long-term follow-up of these patients.

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.

[18F]FDG-PET reveals temporal hypometabolism in patients with temporal lobe epilepsy even when quantitative MRI and histopathological analysis show only mild hippocampal damage.

BACKGROUND: The relationship between reduced glucose metabolism in positron emission tomography with fludeoxyglucose F 18 ([(18)F]FDG-PET) and hippocampal damage (HD) in patients with temporal lobe epilepsy is still unclear. OBJECTIVE: To determine whether the presence and severity of HD verified by quantitative magnetic resonance imaging (QMRI) and histopathological analysis affect the degree of hypometabolism. PATIENTS AND METHODS: Sixteen patients with drug-resistant temporal lobe epilepsy underwent [(18)F]FDG-PET and QMRI (hippocampal volumetry and T2 relaxometry) before surgery. Histopathological analysis of the hippocampus included measurements of neuronal loss, proliferation of glial cells, and mossy fiber sprouting. The asymmetry in glucose metabolism described the degree of hypometabolism. RESULTS: Temporal hypometabolism was not related to severity of HD as measured by QMRI or histopathological analysis. The degree of hypometabolism did not differ in patients with mild, moderate, or severe HD. In addition, [(18)F]FDG-PET revealed significant temporal hypometabolism even though hippocampal QMRI findings were normal or showed only mild HD. Thus, glucose consumption was reduced over and above the histopathological changes. CONCLUSIONS: [(18)F]FDG-PET is sensitive for localizing the epileptogenic region in patients with temporal lobe epilepsy. However, it is insensitive to reflect the severity of HD.

Herpes simplex virus thymidine kinase gene therapy in experimental rat BT4C glioma model: effect of the percentage of thymidine kinase-positive glioma cells on treatment effect, survival time, and tissue reactions.

Herpes simplex virus thymidine kinase (HSV-tk) gene transfer and ganciclovir (GCV) administration have been suggested for the treatment of malignant gliomas. To understand tissue responses and possible ways to improve the treatment effect, we studied tumor growth, tissue reactions, and survival time after HSV-tk/GCV treatment in a syngeneic BT4C rat glioma model by mixing various ratios of stably transfected HSV-tk-expressing BT4C-tk glioma cells with wild-type BT4C glioma cells (percentage of BT4C-tk cells: 0%, 1%, 10%, 30%, 50%, and 100%), followed by injection into BDIX rat brains (n = 79). With the exception of some animals with end-stage tumors, very little astroglia or microglia reactivity was detected in the wild-type tumors as analyzed by immunocytochemistry using glial fibrillary acid protein (GFAP)-, vimentin-, human histocompatibility leukocyte antigen-DR-, OX-42-, and CD68-specific monoclonal antibodies. After 14 days of GCV treatment, tumors induced with > or = 10% BT4C-tk cells showed a significant reduction in tumor size (P < .05) and prolonged survival time (P < .01). Astrogliosis, as indicated by a strong GFAP and vimentin immunoreactivity, was seen in the tumor scar area. GFAP and vimentin reactivity was already present after the GCV treatment in tumors induced with 1% BT4C-tk cells. Much less human histocompatibility leukocyte antigen-DR-positive microglia was seen in the treated animals, indicating low microglia reactivity and immunoactivation against the tumor. However, GCV-treated tumors were positive for apoptosis, indicating that apoptosis is an important mechanism for cell death in the BT4C-tk glioma model. Our results suggest that > or = 10% transfection efficiency is required for a successful reduction in BT4C glioma tumor size with HSV-tk/GCV treatment in vivo. Tissue reactions after 14 days of GCV treatment are characterized by astrogliosis and apoptosis, whereas microglia response and immunoactivation of the brain cells appear to play a minor role. Stimulation of the microglia response by gene transfer or other means might improve the efficacy of the HSV-tk/GCV treatment in vivo.

[11 C]Flumazenil binding in the medial temporal lobe in patients with temporal lobe epilepsy: correlation with hippocampal MR volumetry, T2 relaxometry, and neuropathology.

OBJECTIVE: To detect reduced [11C]flumazenil in patients with temporal lobe epilepsy (TLE) and to relate binding to histopathology. METHODS: The authors studied 16 patients who underwent epilepsy surgery because of drug-resistant TLE using [11C]flumazenil PET and quantitative MRI. In 12 patients, resected hippocampus was available for histologic analysis. [11C]Flumazenil binding potential (fitted BP) was assessed with the simplified reference tissue model. RESULTS: [11C]Flumazenil fitted BP in the medial temporal lobe was reduced in all patients with abnormal hippocampal volumetry or T2 relaxometry on MRI. Fitted BP was also reduced in 46% of the patients with hippocampal volume within the normal range and in 38% of patients with less than 2 SD T2 prolongation. In all MRI-negative/PET-positive patients, the histologic analysis verified hippocampal damage. Also, [11C]flumazenil fitted BP correlated with the severity of reduced hippocampal volume, T2 prolongation, and histologically assessed neuronal loss and astrogliosis. CONCLUSION: [11C]Flumazenil PET provides a useful tool for investigating the hippocampal damage in vivo even in patients with no remarkable hippocampal abnormalities on quantitative MRI.

Gastric tonometry after subarachnoid hemorrhage.

OBJECTIVE: To evaluate splanchnic tissue perfusion, assessed by gastric tonometry, in patients with subarachnoid hemorrhage (SAH) and to study the effect of treatment, either surgical or endovascular, and the severity of initial SAH on splanchnic tissue perfusion. DESIGN: Prospective observational substudy, part of a randomised controlled trial of early treatment of ruptured intracranial aneurysms. SETTING: Intensive care unit (ICU) of a university hospital. PATIENTS: A consecutive sample of 26 patients [13 surgical (7/6 Hunt & Hess Grade I-II/H & H Gr IV-V) and 13 endovascular (3/10 H & H Gr I-II/H & H Gr IV-V)] out of 56 SAH patients randomly assigned to either endovascular or surgical treatment during the substudy period between 1 May 1995 and 31 August 1996. All patients were treated within 72 h after SAH. MEASUREMENTS AND RESULTS: After treatment of a ruptured aneurysm, hemodynamics and gastric intramucosal pCO2 were measured during the first 4 h and between 6 h and 12 h after aneurysm treatment. In the whole sample, neither the gastric intramucosal-arterial pCO2 difference (pCO2 gap) (1.5+/-1.9 kPa and 1.7+/-1.2 kPa, NS) nor gastric intramucosal pH (7.28+/-0.12 and 7.29+/-0.08, NS) changed during the study. There were no differences in pCO2 gap or gastric intramucosal pH between treatment groups or Hunt & Hess grade groups during the study period. CONCLUSIONS: Splanchnic tissue perfusion may be insufficient even though there is no systemic hemodynamic disturbance in patients after SAH. Neither the therapeutic treatment nor pre-treatment Hunt & Hess grade is associated with a specific pattern of pCO2 gap.

Contribution of non-neurologic disturbances in acute physiology to the prediction of intensive care outcome after head injury or non-traumatic intracranial haemorrhage.

OBJECTIVE: To study the additional contribution of non-neurologic disturbances in acute physiology and chronic health to the prediction of intensive care outcome in patients with head injury or non-traumatic intracranial haemorrhage. DESIGN: A nationwide study in Finland with prospectively collected data on all adult patients admitted to intensive care after head trauma or non-traumatic intracranial haemorrhage during a 14-month period. Two-thirds of the patients were randomly selected to derive predictive models, and the remaining one third constituted the validation sample. SETTING: A total of 25 medical and surgical ICUs in Finland (13 in tertiary referral centers). PATIENTS: 901 consecutive adult patients with head injury or non-traumatic intracranial haemorrhage. MEASUREMENTS AND RESULTS: Variables of the APACHE II including Glasgow Coma Score were collected at the time of ICU admission. Two predictive models were created to explain hospital mortality. The addition of variables describing acute physiology to a predictive model consisting of Glasgow Coma Score, age, diagnosis of head injury and the type of ICU admission did not increase its performance in discriminating between survivors and nonsurvivors, but the calibration accuracy of the predictive model especially at the high ranges of risk was improved. CONCLUSIONS: The non-neurologic disturbances in acute physiology have prognostic significance in the prediction of intensive care outcome in patients with head injury or non-traumatic intracerebral haemorrhage. The created predictive model may supplement clinical judgement of this patient group.

Reduced N-acetylaspartate concentration in temporal lobe epilepsy by quantitative 1H MRS in vivo.

We used proton magnetic resonance spectroscopy (1H MRS) to determine concentrations of N-acetylaspartate (NAA), creatine and choline in vivo (63 MHz) and in vitro (400 MHz) in seven patients undergoing surgical treatment of intractable temporal lobe epilepsy (TLE). Nine healthy volunteers were used as controls for in vivo MRS. NAA concentrations in vivo on the ipsilateral and contralateral sides were 6.5 +/- 1.3 (s.d.) and 7.9 (+/- 2.1) mmol l-1, respectively and 8.6 (+/- 0.8) mmol l-1 in the volunteers. NAA concentration in vitro was 3.2 (+/- 0.9) mumol g-1 wet weight (ww) and the corresponding concentration from the macroscopically intact brain tissue was 4.7 (+/- 1.0) mumol g-1 ww. Thus, in vivo quantitative 1H MRS identified the size of seizure focus in patients with temporal lobe epilepsy.

Auditory event-related potentials differentiate patients with normal pressure hydrocephalus and patients with concomitant Alzheimer's disease verified by brain biopsy.

We studied 51 patients with clinical symptoms and CT findings suggesting normal pressure hydrocephalus (NPH). Tests included head MRI, auditory event-related potentials (ERPs), thorough neuropsychological testing and intraventricular intracranial 24 h pressure recording and infusion testing. A brain biopsy was also obtained to verify a concomitant dementing process (Alzheimer's disease; AD). Patients were divided into subgroups according to the need of shunt and the biopsy findings, and their ERPs were analysed blindly. The present results suggest that non-invasive ERPs aid in the differentiation of pure NPH from NPH with concomitant AD.

MR volumetry of the entorhinal, perirhinal, and temporopolar cortices in drug-refractory temporal lobe epilepsy.

BACKGROUND AND PURPOSE: The occurrence of damage in the entorhinal, perirhinal, and temporopolar cortices in unilateral drug-refractory temporal lobe epilepsy (TLE) was investigated with quantitative MR imaging. METHODS: Volumes of the entorhinal, perirhinal, and temporopolar cortices were measured in 27 patients with unilateral drug-refractory TLE, 10 patients with extratemporal partial epilepsy, and 20 healthy control subjects. All patients with TLE were evaluated for epilepsy surgery and underwent operations. RESULTS: In left TLE, the mean volume of the ipsilateral entorhinal cortex was reduced by 17% (P <.001 compared with control subjects) and that of the ipsilateral temporopolar cortex by 17% (P <.05). In right TLE, the mean ipsilateral entorhinal volume was reduced by 13% (P < or =.01), but only in patients with hippocampal atrophy. Asymmetry ratios also indicated ipsilateral cortical atrophy. When each patient was analyzed individually, the volume of the ipsilateral hippocampus was reduced (> or = 2 SD from the mean of controls) in 63% and that of the entorhinal cortex in 52% of patients with TLE. Furthermore, ipsilateral entorhinal (left: r = 0.625, P <.001; right: r = 0.524, P < or =.01), perirhinal (left: r = 0.471, P <.05), and temporopolar (right: r = 0.556, P <.01) volumes correlated with ipsilateral hippocampal volumes. There was no association, however, with clinically or pathologically identified causes of epilepsy, duration of epilepsy, or age at onset of epilepsy. Mean cortical volumes were unaffected in extratemporal partial epilepsy. CONCLUSION: Subpopulations of patients with unilateral TLE have ipsilateral damage in the entorhinal and temporopolar cortices. The damage is associated with hippocampal damage.

MR imaging of the hippocampus in normal pressure hydrocephalus: correlations with cortical Alzheimer's disease confirmed by pathologic analysis.

BACKGROUND AND PURPOSE: MR studies have shown hippocampal atrophy to be a sensitive diagnostic feature of Alzheimer's disease (AD). In this study, we measured the hippocampal volumes of patients with a clinical diagnosis of normal pressure hydrocephalus (NPH), a potentially reversible cause of dementia when shunted. Further, we examined the relationship between the hippocampal volumes and cortical AD pathologic findings, intracranial pressure, and clinical outcomes in cases of NPH. METHODS: We measured hippocampal volumes from 37 patients with a clinical diagnosis of NPH (27 control volunteers and 24 patients with AD). The patients with NPH underwent biopsy, and their clinical outcomes were followed for a year. RESULTS: Compared with those for control volunteers, the findings for patients with NPH included a minor left-side decrease in the hippocampal volumes (P < .05). Compared with those for patients with AD, the findings for patients with NPH included significantly larger hippocampi on both sides. Although not statistically significant, trends toward larger volumes were observed in patients with NPH who had elevated intracranial pressure, who benefited from shunting, and who did not display cortical AD pathologic findings. CONCLUSIONS: Measurements of hippocampal volumes among patients with a clinical diagnosis of NPH have clear clinical implications, providing diagnostic discrimination from AD and possibly prediction of clinical outcome after shunting.

Management outcome for vertebrobasilar artery aneurysms by early surgery.

Treatment of vertebrobasilar artery aneurysms remains fraught with complications, even in the present era of microneurosurgery. In a series of 1150 consecutive patients with cerebral aneurysms from a defined catchment area with 870,000 inhabitants, 93 with vertebrobasilar artery aneurysms were treated by two surgeons during a 14-year period. Sixty-three patients had surgery, 36 during the first week after bleeding. There was no surgical mortality among 33 good grade patients. Nine (14%) of the 63 surgical cases had died at 1 year. Forty-nine (53%) of the total group of 93 patients were functioning independently at 1 year. Overall management mortality was 37%. All 11 patients admitted in Grade V died. In spite of improvements in surgical techniques, we are far from achieving ideal results. Early diagnosis and surgery before rupture are urgently needed. Arteriosclerotic giant aneurysms remain untreatable.

Management outcome for multiple intracranial aneurysms.

The management outcome of 302 patients with multiple intracranial aneurysms (MIA) from a series of 1314 patients with cerebral aneurysms was assessed using the Glasgow Outcome Scale 1 year after diagnosis and/or treatment. The outcome was significantly poorer for patients with MIA than for those with single intracranial aneurysms (SIA). The difference in the frequencies of poor outcome (Glasgow Outcome Scale Grades 3-5) was most evident in patients with Hunt and Hess Grades 2 or 3 (MIA, 29%; SIA, 19%). The management mortality in all grades attributable to all causes was 24% in patients with MIA and 20% in those with SIA and 16 and 11%, respectively, after surgery. At the 1-year follow-up point, 66% of the patients with MIA were independent (SIA, 72%); after surgery, 74% (SIA, 81%); after subarachnoid hemorrhage, 65% (SIA, 71%); and after subarachnoid hemorrhage and surgery, 73% (SIA, 80%). Patients with aneurysms at the vertebrobasilar arteries fared badly; otherwise, the sites of the aneurysms and their different combinations had no effect on outcome, nor did the timing of surgery. In this study, again, only two-thirds of the detected aneurysms could be secured. The aneurysms left without treatment were mostly in patients with very poor grade (n, 55) and/or old (n, 23) patients or were intracavernous (n, 26). The results seemed to be more unsatisfactory as the number of aneurysms increased. In multivariate analysis, delayed neurological deficit had the most significant independent contribution to outcome in patients with MIA, far more than in patients with SIA. This can be explained by the increased manipulation of cerebral arteries during multiple aneurysm surgery.

Analysis of 561 patients with 690 middle cerebral artery aneurysms: anatomic and clinical features as correlated to management outcome.

In a series of 1314 consecutive patients with cerebral aneurysms from a defined catchment area in eastern Finland (870,000 inhabitants), 561 patients (43%) had middle cerebral artery aneurysms (MCAAs). One or more associated aneurysms were common; 221 patients with MCAAs (39%) had multiple intracranial aneurysms (MIA). In other words, three-fourths (73%) of all patients with MIA had at least one MCAA. Multiple MCAAs, found in 111 patients (20%), were common in this Finnish population. One hundred of these patients had bilateral MCAAs, of whom 63 had mirror aneurysms, that is, aneurysms at the same site but on different sides. Thirty-five patients had "pure" mirror aneurysms, that is, they did not have any other aneurysms. Most MCAAs (81%) were located at the bifurcation. Three-fourths (72%) of the proximal MCAAs were associated with MIA. Giant aneurysms were significantly more common as single MCAAs than as any other single aneurysm. The frequency of intracerebral hematomas (42%) was by far higher in patients with MCAAs than in patients with ruptured aneurysms at other sites. Most of the intracerebral hematomas occurred in patients with bifurcation MCAAs that pointed laterally. Patients with MCAAs had surprisingly bad management outcomes despite good surgical results in patients with good Hunt and Hess grades. There were significantly more poor outcomes (Glasgow Outcome Scale score, 3-5) among patients with ruptured MCAAs than among those with any other anterior circulation aneurysms (32 and 25%, respectively). Also, the multiplicity of aneurysms increased the risk for poor outcome, which occurred in 39% of the patients who had MIA with one MCAA and 37% of those who had multiple MCAAs. Epilepsy, severe hemiparesis, and visual field deficits were the most common disabilities in long-term survivors, associated far more frequently with MCAAs than with aneurysm at other sites.

Late epilepsy after aneurysm operations.

The risk of late epilepsy was analyzed in a consecutive series of 177 patients operated on for supratentorial aneurysms. Late seizures occurred in 25 patients (14%); the seizures were recurrent in 21 patients (12%). Most seizures were partial, secondary generalized, or generalized tonic-clonic (72%). The mean latency between the operation and seizures was 8.4 months (range, 1 to 24 months), and in only 2 patients was the interval more than 12 months. The most important risk factors were preoperative and postoperative complications. Only 2.5% of the 81 Grade I patients developed epilepsy, compared to 33% of the 42 Grade III-IV patients. Other risk factors were location of the aneurysm in the middle cerebral artery, the presence of a large intracerebral hematoma, postoperative spasm with late ischemic infarction, and shunt-dependent hydrocephalus. The timing of operation or intraventricular intracranial pressure monitoring did not change the risk of late epilepsy. The fact that only 2 patients had early epilepsy may have been due to routine treatment with prophylactic anticonvulsants. The value of prophylaxis in late epilepsy is unproven, but prophylactic treatment could be useful in patients with a high risk of epileptic seizures.

Saccular aneurysms of the distal anterior cerebral artery and its branches.

We report a series of 84 consecutive patients (41 women) with 92 distal anterior cerebral artery aneurysms (DACAA). All aneurysms were saccular. Four different locations of DACAAs were found: proximal, 5 aneurysms; frontobasal, 8; genu corporis callosi, 72; and distal, 7. Sixty-five patients presented with subarachnoid hemorrhage (SAH), the rest were incidental findings in patients with multiple aneurysms. Forty-five patients had single DACAAs. Multiple aneurysms (a total of 117) were found in 39 patients (46.4%), and DACAAs were responsible for SAH in 20 patients. Of the 65 patients with SAH, 54 underwent mainly early direct surgery, and 46 (85%) of these had good outcomes 1 year after surgery. Three patients remained severely disabled, and five patients (9%) died. All of the poor surgical results were obtained in patients with severe preoperative deficits. Exact measurements of DACAA sizes and necks were smaller than those of cerebral aneurysms in other locations. Aside from localization, microsurgery of these aneurysms presented no special difficulties, as compared with surgery of aneurysms in other locations.

Early aneurysm operation and outcome in two remote Scandinavian populations.

The Kuopio University Clinic is the neurosurgical referral center for a population of 930,000 inhabitants in central Finland while the Lund University Clinic is the neurosurgical referral center for a population of 1.46 million inhabitants in southern Sweden. The incidence of aneurysmal subarachnoid hemorrhage (SAH) is approximately 19/100,000/year in central Finland and approximately five/100,000/year in southern Sweden. During the calendar year 1982, 69 patients with a ruptured supratentorial aneurysm were admitted in Lund, and 71 such patients were admitted in Kuopio. Thirty-nine patients in neurological Grades I to III (according to Hunt and Hess) underwent early aneurysm operation in Lund, and 46 such patients were operated on within a week after SAH in Kuopio. In the combined series of 85 Grade I to III patients with aneurysm operation within a week after rupture, 78% made a good recovery; the morbidity rate was 14%, and the mortality rate was 8%.