Epilepsy after operative treatment of ruptured cerebral aneurysms

Summary A retrospective analysis of 183 consecutive patients operated on for ruptured cerebral aneurysms and surviving at least one year revealed appearance of postoperative epilepsy in 14 cases (8 per cent) on an average of 10 months (range 0–23 months) after the operation. Factors associated with the development of secondary epilepsy were localization of the aneurysm on the middle cerebral artery, temporary clipping intraoperatively, wrapping technique to treat the aneurysm, and vasospasm seen on the postoperative control angiogram. Intraoperative and/or postoperative ischaemia seems to be the crucial phenomenon favouring the development of epilepsy. Identification of the risk factors may help to focus the anti-epileptic prophylaxis in cases prone to develop seizures.     

Immediate ultrastructural effects of endothelin-1 on rabbit basilar artery

Summary In this study intra-arterial Endothelin-1 was applied to rabbit basilar arteries and morphological findings were compared between two groups who were either perfusion fixed or immersion fixed. We planned to establish the quantitative dimension of the drug-induced morphological alterations, independent of the fixation technique's effect.There was an abundance of collagenous fibres deposited among the smooth muscle cells which was not observed in control arteries and after immersion fixation. These degenerative changes are similar to the finding following subarachnoid haemorrhage. The only fixation-related difference was the fact that lamina elastica interna was not corrugated in the perfusion fixation group.It is concluded that, the observed changes in the connective tissue of the arterial wall alter the passive elastic properties and so affect the degree of the response to the vasoactive messengers.     

血液动力学方法治疗犬脑血管痉挛的实验研究

采用不同的血液动力学方法，对犬网膜下腔出血后引起的症状性脑血管痉挛进行治疗，我们发现：（１）等容称释加胞二磷胆碱和多巴酚丁胺疗法与人工扩容疗法疗效相同，但与等容稀释加胞二磷胆碱疗法相比，疗效有显著性差异，前者尤其知于扩容稀释禁忌证的病人；（２）稀释剂中加入胞二磷胆碱，可使红细胞变形能力半加，改善脑微循环（３）大剂量应用多巴胺升压，部分病例可使ＣＶＳ加重，临床应慎用。     

The effects of an intracellular calcium antagonist HA 1077 on delayed cerebral vasospasm in dogs

Summary The effectiveness of calcium antagonists on a chronic cerebral vasospasm after an SAH is still under debate. Calcium channel blockers such as nimodipine, nefedipine etc. can dilate spastic arteries by intrathecal administration, but not by systemic (iv or po) use. HA 1077 is a novel and potent calcium antagonist vasodilator which is considered to act by employing different mechanisms from the usual calcium channel blockers since it inhibits 1. calcium ionophore A 23187 induced contraction in arterial strips and 2. phenylephrine induced contraction in calcium free media, suggesting that its site of action is in the intracellular space. HA 1077 is water soluble and relatively stable in light.In the present study, the efficacy of HA 1077 was evaluated on dogs by using the spiral arterial strips in vitro and by angiography in vivo. In the arterial strips from the control dogs, a 50% relaxation of KCl (15 mM) induced contraction was obtained by a 10^–6 M HA 1077 for the intracranial basilar and middle cerebral arteries, while a 10^–5 M was needed to obtain the same effect for the extracranial common carotid and vertebral arteries, indicating that HA 1077 is more effective for the intracranial arteries. A vasospasm was produced by the two haemorrhage model of Varsoset al. The average angiographic diameter of the basilar artery was reduced to 60% of the control on SAH day 7. Intravenous infusion of HA 1077 (0.5–3 mg/kg/30 min) significantly dilated the spastic basilar artery (up to 20–30%), for over 2 hours. A fall in the systemic BP remained less than 20% during this time. Such spasmolytic effects by intravenous administration could not have been obtained with the usual calcium channel blockers. HA 1077 may be suitable for the treatment of a vasospasm in humans as well.     

Subarachnoid haemorrhage of unknown aetiology

Summary The authors review the literature on subarachnoid haemorrhage of unknown aetiology (SAHUE) and analyze a personal series of 212 patients diagnosed as SAHUE. These patients represent 30% of all cases of primary SAH admitted over a 14.5 year period.The age, sex, antecedents and initial clinical presentation of patients with SAHUE were indistinguishable from those of patients with subarachnoid haemorrhage due to ruptured aneurysm (SAHRA). However, the present series of SAHUE compare favourably with both a personal and a previously reported series of SAHRA insofar as clinical grade on admission (94% of patients in grades I–II of Botterell), presence of blood on CT (51%), vasospasm (5%), ischaemic deficits (3.3%), persistent hydrocephalus (3.5%), rebleeding (6%) and fatal result (3.9%) are concerned.The amount of blood on CT scan in our patients with SAHUE was associated with a significantly higher incidence of brain ischaemia and hydrocephalus but did not correlate with the Botterell grade on admission or final outcome, which were good in the majority of cases regardless of the presence or not of visible cisternal haemorrhage. The results of the present series confirm that the final prognosis of patients with primary SAH showing normal four-vessel cerebral angiography is essentially favourable.     

Temporal profile of potassium channel dysfunction in cerebrovascular smooth muscle after experimental subarachnoid haemorrhage

The pathogenesis of cerebral vasospasm after subarachnoid haemorrhage (SAH) involves sustained contraction of arterial smooth muscle cells that is maximal 6–8 days after SAH. We reported that function of voltage-gated K⁺ (K_V) channels was significantly decreased during vasospasm 7 days after SAH in dogs. Since arterial constriction is regulated by membrane potential that in turn is determined predominately by K⁺ conductance, the compromised K⁺ channel dysfunction may cause vasospasm. Additional support for this hypothesis would be demonstration that K⁺ channel dysfunction is temporally coincident with vasospasm. To test this hypothesis, SAH was created using the double haemorrhage model in dogs and smooth muscle cells from the basilar artery, which develops vasospasm, were isolated 4 days (early vasospasm), 7 days (during vasospasm) and 21 days (after vasospasm) after SAH and studied using patch-clamp electrophysiology. We investigated the two main K⁺ channels (K_V and large-conductance voltage/Ca²⁺-activated (K_Ca) channels). Electrophysiologic function of K_Ca channels was preserved at all times after SAH. In contrast, function of K_V channels was significantly decreased at all times after SAH. The decrease in cell size and degree of K_V channel dysfunction was maximal 7 days after SAH. The results suggest that K_V channel dysfunction either only partially contributes to vasospasm after SAH or that compensatory mechanisms develop that lead to resolution of vasospasm before K_V channels recover their function.     

Overall results in 304 consecutive patients with acute spontaneous subarachnoid hemorrhage

The results obtained in 304 consecutive patients with spontaneous subarachnoid hemorrhage are described, the majority of whom (86%) were admitted while in acute condition. Only 46% of the patients in this series were in good condition at admission. The initial management was standardized for all patients, but the protocol of "delayed surgery" was applied to patients with subarachnoid hemorrhage from aneurysmal rupture. Two hundred and twenty-two patients (73%) had intracranial aneurysms. Of these, 20 (9%) were moribund and died shortly after admission; nine (4%) underwent emergency surgery due to the coexistence of a life-threatening cerebral hematoma; seven (3%) were operated upon within 3 days of admission; 78 (35%) died after rebleeding or after steady deterioration of the patient's condition due to vasospasm while awaiting surgery. Of the remaining 108 patients ready for delayed surgery, 12 (11%) (operation refused, elderly patients in poor general condition, spontaneous thrombosis of the aneurysm) were treated conservatively, and 96 (89%), who were in various clinical conditions, were actually operated on. Of these 96 patients, 79 (82%) exhibited excellent or good results, 5 (5%) were disabled, and 12 (12%) died. In the authors' experience, the overall management of intracranial aneurysms in unselected patients according to the protocol of delayed surgery results in significant loss of patients awaiting surgery, and good surgical results in the survivors.     

Prevention of cerebral vasospasm with OKY-046 an imidazole derivative and a thromboxane synthetase inhibitor. A preliminary co-operative clinical study

Summary The prevention of cerebral vasospasm with OKY-046, an imidazole derivative and a thromboxane synthetase inhibitor, was studied co-operatively at ten neurosurgical services. Intravenous administrations of 2, 5 or 10 /kg/minute of OKY-046 were given continuously from the earliest possible day to the 14th SAH-day to 82 pateints with ruptured cerebral aneurysm. Sixty-eight patients (83%) showed moderate to high high-density (SAH) in their initial CTs. Angiographic vasospasms were seen in 58 patients, representing 71% of all cases or 81% of the 72 cases for which angiograms were available; the vasospasms of 45 patients (55 or 63%) were moderate to severe. Symptomatic vasospasm occurred, however, only in 27 patients (33%); in 18 of those cases, moreover, the symptoms were mild or transient. The conditions of the patients at one month after the SAH were classified into 9 grades from 0 (normal) to 8 (deceased). Fifty-two patients (63%) were classified as 0 or 1, and 64 (78%) as better than 3 (possible daily life unaided). The administration of OKY-046 was proven to decrease TXB₂ in the blood.This paper emphasizes the effectiveness of the drug for symptomatic vasospasm, and supports our previous contention that cerebral microthrombosis may play an important role in the pathogenesis of cerebral vasospasm.     

Reversal of Cerebral Vasospasm by the Nitric Oxide Donor SNAP in an Experimental Model of Subarachnoid Haemorrhage

The constant release of nitric oxide (NO) is essential to maintain basal cerebrovascular tone. Oxyhaemoglobin, liberated by lysis of red blood cells after subarachnoid haemorrhage binds NO and prevents its entry into vascular smooth muscle cells. While endothelium-dependent vasoconstriction is preserved, decreased levels of NO inhibit endothelium-dependent relaxation and may cause vasospasm. S-nitrosothiols are potent vasodilators and precursors of NO. The authors' aim was to determine whether S-nitroso-N-acetylpenicillamine (SNAP), a stable S-nitrosothiol compound, could reverse vasospasm in an experimental vasospasm model in rabbit. Experimental subarachnoid haemorrhage (SAH) was induced in 37 New Zealand white rabbits. The animals were divided into four groups. Control (no SAH), SAH only, SAH plus saline and SAH plus SNAP. SNAP (15 micrograms/kg/min) or 0.09% saline (equal volume) was infused 46 hours after induction of SAH. All animals were killed by perfusion fixation 48 hours after SAH occurred. Basilar arteries were removed, sectioned and their cross sectional areas were evaluated in a blind manner, by light microscopy and by using computer assisted morphometry. Experimental SAH elicited vasospasm in all animals of SAH only and SAH plus saline group. In animals treated with SNAP, arterial narrowing was markedly attenuated without producing systemic hypotension. This widening achieved statistical significance when compared to the arteries of the SAH only and SAH plus saline group (p < 0.01). This study indicates that the NO donor SNAP is a potentially useful drug to reverse cerebral vasospasm due to SAH.     

Multiple intracranial aneurysms: A high risk condition

Summary There is still a relative silence in the literature on what policy should be followed in treating multiple aneurysms. The main risks are: bleeding of a formerly asymptomatic aneurysm during the haemodynamic tides of the peri-operative period; aneurysm(s) can be hidden on angiograms and tend to be overlooked easier in case of an already revealed aneursym; misjudgement of the ruptured one as a silent additional aneurysm, therefore left for second stage surgery.This paper, based on a material of 330 operations for multiple aneurysms, focuses on these problems. It advocates the one stage complete repair of all lesions using both options of bilateral pterional craniotomies or the contralateral approach. But it also describes those silent aneurysms which safely could be clipped later. Hazards and disadvantages concerning the more aggressive surgery proved to be less significant than the natural history of multiple aneurysms represents.Presented at the EANS Wintermeeting on High Risk Neurosurgery, Budapest, February 20–23, 1991.