Matti Vapalahti

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.

Quantitative metabolite patterns of human brain tumors: detection by 1H NMR spectroscopy in vivo and in vitro.

Objective The aim of the present study was to investigate quantitative metabolite patterns in human brain tumors by 1H nuclear MR spectroscopy (1H MRS). Materials and Methods Single voxel 1H MRS was used in studying metabolites in 23 primary brain tumors in vivo. The T2 relaxation times and saturation factors were determined for N-acetylaspartate (NAA), total creatine (Cr), choline-containing compounds (Cho), and water, which was used as an internal standard in computations of metabolite concentrations in vivo. Metabolites in biopsy specimens from 75 tumors were quantified by means of 1H MRS in vitro. Results The NAA concentrations were lower in brain tumors than in normal tissue in vitro and in vivo, irrespective of the histological type. The NAA was some threefold higher in vivo than in vitro, which could be due to partial volume effect and/or contributions from other metabolites to the peak at 2.02 ppm in vivo. Ratios of Cho to Cr concentrations were elevated in tumors relative to normal brain in vivo. Absolute Cho was some 50% higher in both benign astrocytomas and oligodendrogliomas in vivo than in normal brain. However, Cho concentration in vitro was significantly higher only in pituitary adenomas than in healthy white matter. Total creatine was ∼50% lower in malignant astrocytomas and meningiomas than in normal brain. Conclusion It is concluded that absolute concentrations of metabolites in vivo yield a different picture of tumor metabolites than that derived from uncorrected metabolite ratios.

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.

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 surgery improves the cure of aneurysm-induced oculomotor palsy

BACKGROUND Aneurysm of the internal carotid-posterior communicating artery (ICA-PCoA) is the most frequent cause of sudden unilateral oculomotor palsy. Timely surgery for the aneurysm is the most important factor for third nerve recovery. METHODS We scrutinized the world literature with nearly one thousand cases of isolated unilateral oculomotor palsy caused by intracranial aneurysms and treated with surgery. Only those reports (one-third of all) in which the time interval between onset of oculomotor palsy and surgery could be determined were included. We treated 1314 patients with cerebral aneurysms (183 = 14% with ICA-PCoA aneurysms) from our catchment area in Eastern Finland during years 1977-1992. Twenty-eight patients having oculomotor palsy caused by ICA-PCoA aneurysm had surgery as soon as the diagnosis was made. RESULTS Eight of 9 patients operated within three days (0-3) and 4 of 6 patients operated on within 4 to 6 days the onset of oculomotor palsy had complete recovery of their third nerve function, in contrast to only 4 of 13 patients operated on later. Especially those operated on more than four weeks later had a dismal outcome: only 1 of 6 had complete recovery. CONCLUSIONS We recommend immediate admission and acute or early surgery for aneurysm-induced third nerve palsy, preferably within 3 days, to avoid functionally and cosmetically invalidizing disability.

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.

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.

Association Between the Density of Mossy Fiber Sprouting and Seizure Frequency in Experimental and Human Temporal Lobe Epilepsy

Summary: Purpose: If the sprouting of granule cell axons or mossy fibers in the dentate gyrus is critical for the generation of spontaneous seizures in temporal lobe epilepsy (TLE), one could hypothesize that epileptic animals or humans with increased sprouting would have more frequent seizures. This hypothesis was tested by analyzing the data gathered from experimental and human epilepsy.

Adenovirus-mediated herpes simplex virus thymidine kinase gene therapy in BT4C rat glioma model.

Adenovirus (Adv)-mediated herpes simplex virus thymidine kinase (adv/tk) gene therapy combined with ganciclovir (GCV) medication is a promising approach for the treatment of malignant glioma. However, optimal administration and the effect of possible adjuvant treatments have not been fully examined. In the present study, we examined the efficacy of adv/tk/GCV gene therapy in a syngeneic BT4C rat malignant glioma model, either as a single administration or given as three injections during three consecutive days. The effect of combined adv-mediated macrophage colony-stimulating factor (MCSF) and adv/tk gene transfer was also studied. BT4C malignant glioma cells were injected into the right corpus callosum of BDIX rats (n=112). Before gene therapy, the presence of tumors was verified by MRI. The rats were divided into eight groups as follows: group I (n=20) received a single adv/tk gene transfer (total dose 4×108 pfu) and GCV treatment for 14 days; group II (n=5) received the same gene transfer without GCV; group III (n=28) received three adv/tk injections (total dose 4×108 pfu) on three consecutive days and GCV for 14 days; group IV (n=5) received three similar adv/tk injections without GCV medication; group V (n=13) received three adv/MCSF injections (total dose 2×108 pfu) on three consecutive days and GCV medication; group VI (n=12) received three adv/tk and adv/MCSF (total dose 6×108 pfu) injections on three consecutive days followed by GCV medication; and group VII (n=12) the same treatment without GCV. Group VIII (n=17) consisted of wild-type BT4C malignant glioma tumors without any treatment. Treatment effect and tissue responses were characterized by general histology, immunohistochemistry, MRI, and survival of the study groups. The best treatment effect and survival was found in rats treated with adv/tk gene transfer once a day for three consecutive days (P<.05). No improvement of the treatment effect was seen after the combined adv/tk and adv/MCSF gene transfer compared with the repeated adv/tk gene transfer. The results show that 20% of the rats can be cured (survival >6 months) after optimized adv/tk gene therapy. It is concluded that repeated intratumoral administration of adv/tk is a promising approach for the treatment of malignant glioma tumors in vivo.

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.