Evaluation of and Controversies in Surgical Therapies Lindsay Symon This segment addresses the present situation in relation to surgery for cerebrovascular disease with particular reference to surgery for internal carotid stenosis, bypass surgery, and interventional neurosurgery for arteriovenous malformation or aneurysm.
Surgical Treatment for Occlusive Cerebrovascular Disease: Carotid and Vertebral Basilar Endarterectomy The extraordinary frequency of carotid endarterectomy in technically developed societies has led to great concern Carotid endarterectomy is a prophylactic operation performed with the single goal of preventing cerebral ischemia in the territory of the artery subjected to the procedure. The most common cause of ischemia IS atherosclerosis usually involving the internal carotid artery (lCA) at its origin and interfering with brain function by either obstructing the ICA and directly reducing its blood flow or by providing an irregular surface from which aggregates of platelets and thrombi pass into the carotid circulation and embohze the brain or the eye. Carotid endarterectomy has been the most common operation in relation to occlusive cerebrovascular disease. Great controversy existed as a result of which major clinical trials of randomly selected age-matched populations had been initiated in Europe and North America to evaluate the benefit of carotid endarterectomy in both symptomatic and asymptomatic patients. The American Heart Association has recently circulated to Fellows and Members of The Stroke Council of the American Heart Association a report from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, which has established clear evidence of the beneficial effect of endarterectomy for patients with recent hemispheric transient ischemic attacks or nondisabling strokes and ipsilateral high-grade 70-99% stenosis. The trial was conducted in 50 U.S. and Canadian services, all of which had documented surgical and neurological 56
J STROKECEREBROVASCDIS, VOL 2, NO
1, 1992
expertise. This has been defined as an institution in which the record of the performance of the procedure confirms a 30-day perioperative stroke morbidity and mortality of less than 6%. The trial was carefully designed to exclude a number of criteria such as diabetes mellitus, cancer with a low survival probability, serious cardiac disease, ischemic symptoms of unknown origin and other gross systemic disease. Outcome was assessed on medical, neurological, and functional grounds by participating neurologists for all patients 1 month after entry, every 3 months for the following year, then every 4 months for the remainder of the trial. Randomization of the high-grade stenosis group created a balanced treatment group of 295 medical and 300 surgical patients of a median age of 66 years (range, 35-80); one-third were women. The qualifying event was a nondisabling stroke in 32% of patients and one or more TIAs for the remainder of the group. There was an excellent compliance in the trial with a 5.4% crossover from medical to surgical; of the 300 patients randomized to surgery, all but one underwent carotid endarterectomy. There was a total perioperative stroke morbidity or mortality (up to 30 days postoperatively) of 5%, major stroke of 2%, and mortahty less than 1%. During a period of similar duration, just over 3% of the medical group had stroke morbidity or mortality. Including perioperative morbidity and mortahty, over 24% of medical patients but only 7% of surgical patients had fatal or nonfatal ipsilateral stroke at 18 months; an absolute risk reduction of 17% (p < 0.001). Conclusions cannot be drawn about possible benefits for symptomatic patients with moderate stenosis (30-69%) or for asymptomatic patients (asymptomatic arteries) trials underway. It is important that the findings of the specific carotid endarterectomy study described abo ve not be extrapolated to atherosclerotic carotid artery disease in general as yet. There are no good data to support the use of corrective surgery in the proximal or distal portions of the vertebral circulation. There has been recent interest in carotid endarter-
AIREN-NINDS1991 WORKSHOP
ectomy after anacute stroke (1). It was concluded that it was arbitrary to place a conventional 6-week lower limit following stroke after which surgery could be safely performed. Surgery performed less than 6 weeks after stroke carried no more risk than surgery performed later, provided that the patient's neurological condition was stable. Similar results were reported by Little et al. (2), who reviewed 302 operations, 27 of which were performed during the 30-day time period after completed cerebral infarction. They concluded that patients with minimal residual neurological deficit and normal findings on computed tomography (CT) were at low surgical risk, perhaps approaching that of patients with transient ischemic attacks. The question of whether these surgical patients did better than those with conservative management remains uncertain but might be answered by analysis of the extent of stenosis in the individual case, assuming that the general rules of the randomized cooperative study apply.
Bypass Surgery After an enormous burst of enthusiasm for extracranial to intracranial (EC/IC) bypass usually by superficial temporal and middle cerebral artery (MCA) anastomosis in the years following 1967, a multicenter randomized study was conducted. Included were those who had chmcal evidence of transient ischemic events or minor stroke in the territory of a stenosed or occluded MCA or a stenosed or occluded ICA not amenable or inaccessible to endarterectomy. Surgical patients survived stroke-free less often than did those in the nonsurgical group; no subgroup in the trial was shown to benefit compared With completely comparable control groups. Complex studies by Leblanc et al. (3) and Powers et al. (4) have failed to show that even patients with evidence of hemodynamically compromised circulation have evidence of specific benefit in terms of metabolism; however, in several studies, reduction of cerebral blood volume suggesting an improvement in regional perfusion pressure was recorded. The performance of the EC/IC bypass in relation to giant aneurysms has also been questioned in view of extensive work (5) on temporary vascular occlusion. It has been clearly shown that periods of up to 10 min of occlusion of the circulation With the prompt reestablishment of flow may be possible. Many giant aneurysms can be satisfactorily handled, therefore, without the necessity for bypass. The major utility seems to be as a prelude to the deliberate ligation of a major cerebral artery with an inoperable giant aneurysm or prior to extensive resect ion of the base of the
skull in relation to a vascular tumor such as the Fisch type C glomus tumor or masses involving the cavernous sinus.
Arteriovenous Malformations These lesions present usually with subarachnoid hemorrhage, fits, or advancing neurological disability. The generally accepted history of cerebral arteriovenous malformations (AVMs) with long-term follow-up includes an annual hemorrhage rate of 2-3% per year, except for the first year after hemorrhage when the rate is 6% (6). This gives an annual mortality and morbidity rate of 0.2-0.3% and 0.7-0.8%, respectively, with an approximate mortality of 10% and morbidity of 25% per hemorrhage. A recent excellent study by Ondra et al. (7), with a mean follow-up of 23 7 years followed 160 patients (96%) of the original population, which was practically every diagnosed unoperated AVM in the Finnish population The yearly hemorrhage rate was 4%, yearly neurological morbidity was 1.7%, and yearly mortality was 1%; in common with other studies (8), there was no reason to suppose that "bleeders" and "fitters" represented two separate populations. Seventy-one percent of the Finnish study presented with hemorrhage, 24% with seizures, and only 5% with other causes. At the end of 23 7 years, the morbidity and mortahty rates were 34% and 23%, respectively, rather than the previously expected figures of 17% and 7%. There is little doubt that some attempt to obliterate these lesions is important. The impact of surgery on the natural history was analyzed by Heros et al. (9). Successful surgical obliteration of AVMs in 153 patients showed that none had further hemorrhage during a mean follow-up of 3.8 years with 7.8% having limited morbidity. Of patients with preoperative seizures in this group, 53% had decreased seizure frequency, but 12.7% felt that the seizures were increased. Yeh et al. (10), using electrocorticographic mapping at the time of surgery, reported an excellent outcome in terms of seizure at 4 years in nearly 78% of cases, with improvement in 11%. The remaining 11% had fair or poor outcomes. Considerable controversy, however, still remains as to the relative place of surgery and endovascular obliterative techniques. However, a recent review by Purdy et al, (11) reviewing 51 patients who were embolized with polyvinylalcohol alone or with polyvinylalcohol with platinum microcoils (with one procedure aborted), gave an overall complication rate of 21% with 8% fixed neurological deficits or death. It is generally accepted that embolization by any tech-
JSTROKECEREBROVASCDIS, VOL 2, NO 1, 1992 57
AIREN-NINDS1991 WORKSHOP
nique is unlikely to obliterate completely an AVM. Its place in preoperative management remains uncertain. Radiation treatment for AVMs has advanced enormously. Steiner pioneered focused radiation with the gamma knife, which has also been used extensively in the United Kingdom. In Ogilvy's review (12) comparing results with conventional radiotherapy, focused stereotactic radiotherapy or linear accelerator treatment found the best results with the gamma knife: neurological deficits in 2-3%, mortality in 0 6%, and AVMobliteration at 2 years in 79-86%. Steiner et al.'s (13) views at present are that the gamma knife is effective for small lesions and carries occasionally greater risks and a lesser degree of satisfaction as multiple targets are placed in the larger AVM. Steiner has recently presented data to show that a second attempt by gamma knife irradiation may be made upon residual AVM at 2 years. This usually applies to larger lesions, in which several fields have been treated initially. The effects of partial obliteration are still uncertain, but partial obliteration by proton beam gave a recurrent hemorrhage rate of 20% at 8 years. The general neurosurgical experience has been that incomplete obliteration or removal of an AVM does not significantly change the postoperative risk of hemorrhage.
Cavernous Angioma A most interesting and controversial aspect of AVMs, however, is reflected in the recent interest in cavernous angiomas. These lesions were originally recognized as small AVMs in the wall of hematomas deep within the brainstem. In the past decade, increasing reports of the efficiency of removal of such lesions have appeared. Symon et al. (14) have reported the removal of cavernomas of the brainstem in nine cases with successful outcome. Fahlbusch et al. (15) have reported four cases, and there have been other reports from the United States (14,16,17) in which significant numbers of cases of cavernomas have been excised for recurrent or disastrous hemorrhage or for advancing neurological deficit. The same applies to lesions in the spinal cord, where the author has successfully removed three cavernomas from patients with advancing neurological deficit punctuated by episodic periods of hemorrhage. Magnetic resonance imaging (MRI) has become vital in the recognition of these lesions and their }Jreoperative planning, since arteriography is usually negative. These lesions are often co-existent with venous malformations, the significance of which remains obscure. Cerebral venous malformations have 58
/ STROKECEREBROVASCDIS, VOL 2, NO.1, 1992
been successfully treated by gamma knife or linear accelerator. Steiner et al. (13) does not recommend the use of the gamma knife for cavernomas.
Simple Aneurysms Controversies at the present time center on the use of endovascular techniques to obliterate cerebral aneurysms, the use of adjuncts to relieve vasospasm and possible protection of the brain during periods of ischemia associated with the vasospasm. The International Co-operative Study Group's findings recently published (18,19) revealed rather depressingly that only 58% of patients enrolled returned to their premorbid state at final assessment. Forty percent remained moderately or severely disabled, 2% were vegetative, and 26% had died. The most common causes of death and disability were vasospasm, the severity of the initial hemorrhage, rebleeding, or complications of surgery. In common with the initial surgical studies, there was a strong correlation between the level of consciousness at admission and eventual outcome: 72% of comatose patients died; only 11% made a good recovery. There were no differences in outcome for surgery performed early (0-3 days postsubarachnoid hemorrhage) or late (11-14 days), but the outcome appeared to be worse in general in patients operated on between 7 and 10 days after the hemorrhage. However, numerous units (including the author's own) have routinely operated between the 4th and the 8th day after subarachnoid hemorrhage with results comparable to the best reported, and it appears likely that the findings of the International Co-operative Study may not be absolute in this regard. The Co-operative Study, however, did suggest that the more alert the patient was, the better the results of early surgery were, and the more drowsy the patient was, the better the results with delay. Recent years have seen an increased acceptance of temporary occlusion (5) even by the use of intravascular balloons (20). These techniques are of particular value in the management of giant aneurysms (21).
Endovascular Treatment There has been an enormous increase in the interest of endovascular treatment for obliteration of aneurysms, but it has become clear that balloon occlusion of a recently ruptured aneurysm carries considerable risk. In our own series, morbidity statistics approach 50% in such cases . Aneurysms that have ruptured in the remote past and that contain little in the way of clot
AIREN-NINDS1991 WORKSHOP
(here again MRI is valuable), and aneurysms inaccessible in the cavernous sinus may perhaps be best treated by balloon occlusion, if suitable neurosurgical expertise is not available. The most extensive report comes from San Francisco (22) on 84 patients; indications for percutaneous balloon obliteration include failed previous surgery, anatomically difficult location, a fusiform aneurysm, inability to tolerate general anesthesia, or an aneurysm that was felt to be too large to clip. Treatment was delayed in stable patients if there was evidence of thrombus less than 6 weeks old (CT or MRI) and the mortality rate was 17.9%. There was a 10.7% stroke rate from a variety of causes. Fox and Drake (23) pointed out a 53% mortality in the subgroup of the San Francisco patients with incomplete obliteration. A partially treated aneurysm remains an untreated aneurysm. It is especially important that the matrix of survival produced by Alvord many years ago (24) be used to relate the efficacy of any aneurysm treatment taking into account the time from hemorrhage and the clinical grade of the patient. These have long been known as the main determinants of outcome in subarachnoid hemorrhage. The question of treatment of incidentally discovered aneurysms remains problematical. Despite the anecdotal publications relating to the successful obliterations of such lesions, and the general neurosurgical acceptance that, in a patient who has had a subarachnoid hemorrhage, complete treatment consists of the obliteration of all the available aneurysms, seriatim or at one time if they can be reached, there remains no clear evidence that the risks of surgery particularly in the posterior circulation of unruptured aneurysms are acceptable over the entire age range.
Other Methods of Treatment of Subarachnoid Hemorrhage A whole variety of drugs to treat vasospasm and to improve the ionic homeostasis of the brain have been tried. Thus, a trial with nimodipine was reported (25) from various centers in the United Kingdom. It claimed a significant difference in morbidity and mortality outcome in good grade cases of subarachnoid hemorrhage through operation by the use of intravenous nimodipine. A trial (26) comparing two doses (48 and 72 mg/day) found no significant difference in a 6month outcome. Despite the widespread use of nimodipine, patients still die or become severely disabled as a result of cerebral infarction after subarachnoid hemorrhage. Small studies with calcitonin-generelated-peptide (CGRP) by intra-arterial infusion (27) showed that this powerful vasodilator improved
neurological deficit during infusion, but the patients promptly relapsed after the infusion had stopped. Intraluminal mechanical vasodilation has been reported (28,29) to have increased improvement in a small number of cases with angiographic vasospasm in whom the artery was dilated forcibly by the inflation of an intraluminae balloon. This must be regarded as still controversial One of the most disappointing features of aneurysm surgery at the present time is the lack of scientific rigor as applied to the assessment of endovascular procedures by the International Co-operative Study Group. The reports of anecdotal selected series without controls add little in scientific value to the assessment of the procedures, but the difficulties of securing controlled trials of pathology traditionally, and perhaps acceptably managed by other means, clearly presents great difficulty.
References 1 PIOtrowski JJ, Bernhard VM, Rubin JR, et al 2. 3. 4
5. 6. 7.
8 9. 10. 11.
12. 13.
Timing of carotid endarterectomy after acute stroke I Vasc Surg 1990;11 :45-52. Little JR, Moufarrij NA, Furlan AJ Early carotid endarterectomy after cerebral infarction. Neurosurgery 1989;24'334-8 Leblanc R, Tyler JL, Mohr G, et al Hemodynamic and metabolic effects of cerebral revascularization J Neurosurg 1987,66'529-35. Powers WJ,Grubb RLJr, Raichie ME. Clmical results of extracranial-intracramal bypass surgery in patients with hemodynamic cerebrovascular disease. J Neurosurg 1989;70.61-7. [abre A, Symon L Temporary vascular occlusion during aneurysm surgery. Surg Neuro/1987;27 :47-63. Graf C], Perret GE, Tomer JC Bleeding from cerebral arteriovenous malformations as part of their natural history. J Neurosurg 1983,58'331-7. Ondra SL, Troupp H, George ED, et al The natural history of symptomatic arteriovenous malformattons of the brain: a 24-year follow-up assessment J Neurosurg 1990,73:387-91. Davis C, Symon L Management of arteriovenous malformations Acta Neuroclur 1985;74:4-11. Heros RC, Korosue K, Diebold PM Surgical excision of cerebral art eriovenous malformations- late results Neurosurgery 1990,26 57-8 Yeh DH, Kashiwagi S, Tew JM, et al. Surgical management of epilepsy associated With cerebral art eriovenous malformations. Neurosurgery 1990;72:216-23 Purdy PD, Samson D, Batjer HH, et ai. Preoperative embolization of cerebral arteriovenous malformations with polyvinyl alcohol particles: experience in 51 adults. AJNR 1990;11:501-10 Og ilvy CS, Radiation therapy for arteriovenous malformations. A review. Neurosurgery 1990;26'725-35. Steiner L, Lindquist CH, Steiner M. Radiosurgery. In: Advances and technical standards III neurosurgery New York- Springer, In press.
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59
AJREN-NlNDS1991 WORKSHOP 14. Symon L, Iakowski A, Bills D. Surgical treatment of pontomedullary cavernoma. In press. 15. Fahlbusch R, Strauss C, Huk W Surgical removal of pontomesencephahc cavernous hemangiomas Neurosurgery 1990;26:449-57. 16 Kashrwagi S, van Loveren HR, Tew JM Jr. DIagnosis and treatment of vascular brain-stem malformations J Neurosurg 1990,72:27-34 17. Heffez DS, Zinreich SJ, Long DM Surgical resection of intrinsic brain stem lesions: an overview Neurosurgery 1990,27:789-98. 18 Kassell NF, Torner JC, Clarke Haley E [r, et al The International Co-operative Study on the timing of aneurysm surgery. J Neurosurg 1990,73:37-47. 19 Kassell NF, Torner JC, Clark Haley E [r, et al The International Co-operative Study on the timing of aneurysm surgery. J Neurosurg 1990;73:18-36. 20 Shugart MA, Kwan ES, Heilman Be. Temporary balloon occlusion of a proximal vessel as an aid to chpping aneurysms of the basilar and parachnoid internal carotid arteries Technical note. Neurosurgery 1990;27:1169 21. Symon L,Vajda J. Surgical experiences with giant intracranial aneurysms J Neurosurg 1989,61'1009-28. 22 Higashida RT, Halbach VC, Barnwell SL, et al. Treatment of mtracramal aneurysms with preservation of parent vessel; results of percutaneous embolization in 84 patients A]NR 1990,11 633-40.
60
] STROKECEREBROVASCDIS, VOL 2, NO.1, 1992
23. Fox AJ, Drake CG. Endovascular therapy of intracranial aneurysms. A/NR 1990,11'641-2. 24. Alvord EC Jr, Loeser JD, Bailey WL, Copass MK Subarachnoid hemorrhage due to ruptured aneurysms: a simple method of estimating prognosis Arch Neurol 1972,27:273-4 25 Pickard JD, Murray GP, Illingworth RD, et al Effect of oral nimidopine on cerebral infarction after subarachnoid haemorrhage. British Aneurysm Nimidopine Tnal Br Med J 1989;298.636-42. 26 Gilsbach JM, Reulen HJ, Ljunggren B, et al. Earlyaneurysm surgery and preventive therapy WIth intravenously administered mmodipme. A multicentre double-blind dose-comparison study. Neurosurgery 1990,26458-64 27. Johnston FG, Bell BA, Robertson IJA, et al. Effect of calcitonin-gene-related peptide on post-operative neurological deficit after subarachnoid haemorrhage. Lancet 1990,1'869-72 28. Higashida RT, Halbach W, Cahan LD, et al Transluminal angioplasty for treatment of intracranial artenal vasospasm J Neurosurg 1989,71:648-53. 29. Newell DW, Eskridge JM, Mayberg MR, et al Angloplasty for the treatment of symptomatic vasospasm following subarachnoid haemorrhage. ] Neurosurg 1989;71:654-60.
Surgical Treatment for Occlusive Cerebrovascular Disease: Carotid and Vertebral Basilar Endarterectomy The extraordinary frequency of carotid endarterectomy in technically developed societies has led to great concern Carotid endarterectomy is a prophylactic operation performed with the single goal of preventing cerebral ischemia in the territory of the artery subjected to the procedure. The most common cause of ischemia IS atherosclerosis usually involving the internal carotid artery (lCA) at its origin and interfering with brain function by either obstructing the ICA and directly reducing its blood flow or by providing an irregular surface from which aggregates of platelets and thrombi pass into the carotid circulation and embohze the brain or the eye. Carotid endarterectomy has been the most common operation in relation to occlusive cerebrovascular disease. Great controversy existed as a result of which major clinical trials of randomly selected age-matched populations had been initiated in Europe and North America to evaluate the benefit of carotid endarterectomy in both symptomatic and asymptomatic patients. The American Heart Association has recently circulated to Fellows and Members of The Stroke Council of the American Heart Association a report from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, which has established clear evidence of the beneficial effect of endarterectomy for patients with recent hemispheric transient ischemic attacks or nondisabling strokes and ipsilateral high-grade 70-99% stenosis. The trial was conducted in 50 U.S. and Canadian services, all of which had documented surgical and neurological 56
J STROKECEREBROVASCDIS, VOL 2, NO
1, 1992
expertise. This has been defined as an institution in which the record of the performance of the procedure confirms a 30-day perioperative stroke morbidity and mortality of less than 6%. The trial was carefully designed to exclude a number of criteria such as diabetes mellitus, cancer with a low survival probability, serious cardiac disease, ischemic symptoms of unknown origin and other gross systemic disease. Outcome was assessed on medical, neurological, and functional grounds by participating neurologists for all patients 1 month after entry, every 3 months for the following year, then every 4 months for the remainder of the trial. Randomization of the high-grade stenosis group created a balanced treatment group of 295 medical and 300 surgical patients of a median age of 66 years (range, 35-80); one-third were women. The qualifying event was a nondisabling stroke in 32% of patients and one or more TIAs for the remainder of the group. There was an excellent compliance in the trial with a 5.4% crossover from medical to surgical; of the 300 patients randomized to surgery, all but one underwent carotid endarterectomy. There was a total perioperative stroke morbidity or mortality (up to 30 days postoperatively) of 5%, major stroke of 2%, and mortahty less than 1%. During a period of similar duration, just over 3% of the medical group had stroke morbidity or mortality. Including perioperative morbidity and mortahty, over 24% of medical patients but only 7% of surgical patients had fatal or nonfatal ipsilateral stroke at 18 months; an absolute risk reduction of 17% (p < 0.001). Conclusions cannot be drawn about possible benefits for symptomatic patients with moderate stenosis (30-69%) or for asymptomatic patients (asymptomatic arteries) trials underway. It is important that the findings of the specific carotid endarterectomy study described abo ve not be extrapolated to atherosclerotic carotid artery disease in general as yet. There are no good data to support the use of corrective surgery in the proximal or distal portions of the vertebral circulation. There has been recent interest in carotid endarter-
AIREN-NINDS1991 WORKSHOP
ectomy after anacute stroke (1). It was concluded that it was arbitrary to place a conventional 6-week lower limit following stroke after which surgery could be safely performed. Surgery performed less than 6 weeks after stroke carried no more risk than surgery performed later, provided that the patient's neurological condition was stable. Similar results were reported by Little et al. (2), who reviewed 302 operations, 27 of which were performed during the 30-day time period after completed cerebral infarction. They concluded that patients with minimal residual neurological deficit and normal findings on computed tomography (CT) were at low surgical risk, perhaps approaching that of patients with transient ischemic attacks. The question of whether these surgical patients did better than those with conservative management remains uncertain but might be answered by analysis of the extent of stenosis in the individual case, assuming that the general rules of the randomized cooperative study apply.
Bypass Surgery After an enormous burst of enthusiasm for extracranial to intracranial (EC/IC) bypass usually by superficial temporal and middle cerebral artery (MCA) anastomosis in the years following 1967, a multicenter randomized study was conducted. Included were those who had chmcal evidence of transient ischemic events or minor stroke in the territory of a stenosed or occluded MCA or a stenosed or occluded ICA not amenable or inaccessible to endarterectomy. Surgical patients survived stroke-free less often than did those in the nonsurgical group; no subgroup in the trial was shown to benefit compared With completely comparable control groups. Complex studies by Leblanc et al. (3) and Powers et al. (4) have failed to show that even patients with evidence of hemodynamically compromised circulation have evidence of specific benefit in terms of metabolism; however, in several studies, reduction of cerebral blood volume suggesting an improvement in regional perfusion pressure was recorded. The performance of the EC/IC bypass in relation to giant aneurysms has also been questioned in view of extensive work (5) on temporary vascular occlusion. It has been clearly shown that periods of up to 10 min of occlusion of the circulation With the prompt reestablishment of flow may be possible. Many giant aneurysms can be satisfactorily handled, therefore, without the necessity for bypass. The major utility seems to be as a prelude to the deliberate ligation of a major cerebral artery with an inoperable giant aneurysm or prior to extensive resect ion of the base of the
skull in relation to a vascular tumor such as the Fisch type C glomus tumor or masses involving the cavernous sinus.
Arteriovenous Malformations These lesions present usually with subarachnoid hemorrhage, fits, or advancing neurological disability. The generally accepted history of cerebral arteriovenous malformations (AVMs) with long-term follow-up includes an annual hemorrhage rate of 2-3% per year, except for the first year after hemorrhage when the rate is 6% (6). This gives an annual mortality and morbidity rate of 0.2-0.3% and 0.7-0.8%, respectively, with an approximate mortality of 10% and morbidity of 25% per hemorrhage. A recent excellent study by Ondra et al. (7), with a mean follow-up of 23 7 years followed 160 patients (96%) of the original population, which was practically every diagnosed unoperated AVM in the Finnish population The yearly hemorrhage rate was 4%, yearly neurological morbidity was 1.7%, and yearly mortality was 1%; in common with other studies (8), there was no reason to suppose that "bleeders" and "fitters" represented two separate populations. Seventy-one percent of the Finnish study presented with hemorrhage, 24% with seizures, and only 5% with other causes. At the end of 23 7 years, the morbidity and mortahty rates were 34% and 23%, respectively, rather than the previously expected figures of 17% and 7%. There is little doubt that some attempt to obliterate these lesions is important. The impact of surgery on the natural history was analyzed by Heros et al. (9). Successful surgical obliteration of AVMs in 153 patients showed that none had further hemorrhage during a mean follow-up of 3.8 years with 7.8% having limited morbidity. Of patients with preoperative seizures in this group, 53% had decreased seizure frequency, but 12.7% felt that the seizures were increased. Yeh et al. (10), using electrocorticographic mapping at the time of surgery, reported an excellent outcome in terms of seizure at 4 years in nearly 78% of cases, with improvement in 11%. The remaining 11% had fair or poor outcomes. Considerable controversy, however, still remains as to the relative place of surgery and endovascular obliterative techniques. However, a recent review by Purdy et al, (11) reviewing 51 patients who were embolized with polyvinylalcohol alone or with polyvinylalcohol with platinum microcoils (with one procedure aborted), gave an overall complication rate of 21% with 8% fixed neurological deficits or death. It is generally accepted that embolization by any tech-
JSTROKECEREBROVASCDIS, VOL 2, NO 1, 1992 57
AIREN-NINDS1991 WORKSHOP
nique is unlikely to obliterate completely an AVM. Its place in preoperative management remains uncertain. Radiation treatment for AVMs has advanced enormously. Steiner pioneered focused radiation with the gamma knife, which has also been used extensively in the United Kingdom. In Ogilvy's review (12) comparing results with conventional radiotherapy, focused stereotactic radiotherapy or linear accelerator treatment found the best results with the gamma knife: neurological deficits in 2-3%, mortality in 0 6%, and AVMobliteration at 2 years in 79-86%. Steiner et al.'s (13) views at present are that the gamma knife is effective for small lesions and carries occasionally greater risks and a lesser degree of satisfaction as multiple targets are placed in the larger AVM. Steiner has recently presented data to show that a second attempt by gamma knife irradiation may be made upon residual AVM at 2 years. This usually applies to larger lesions, in which several fields have been treated initially. The effects of partial obliteration are still uncertain, but partial obliteration by proton beam gave a recurrent hemorrhage rate of 20% at 8 years. The general neurosurgical experience has been that incomplete obliteration or removal of an AVM does not significantly change the postoperative risk of hemorrhage.
Cavernous Angioma A most interesting and controversial aspect of AVMs, however, is reflected in the recent interest in cavernous angiomas. These lesions were originally recognized as small AVMs in the wall of hematomas deep within the brainstem. In the past decade, increasing reports of the efficiency of removal of such lesions have appeared. Symon et al. (14) have reported the removal of cavernomas of the brainstem in nine cases with successful outcome. Fahlbusch et al. (15) have reported four cases, and there have been other reports from the United States (14,16,17) in which significant numbers of cases of cavernomas have been excised for recurrent or disastrous hemorrhage or for advancing neurological deficit. The same applies to lesions in the spinal cord, where the author has successfully removed three cavernomas from patients with advancing neurological deficit punctuated by episodic periods of hemorrhage. Magnetic resonance imaging (MRI) has become vital in the recognition of these lesions and their }Jreoperative planning, since arteriography is usually negative. These lesions are often co-existent with venous malformations, the significance of which remains obscure. Cerebral venous malformations have 58
/ STROKECEREBROVASCDIS, VOL 2, NO.1, 1992
been successfully treated by gamma knife or linear accelerator. Steiner et al. (13) does not recommend the use of the gamma knife for cavernomas.
Simple Aneurysms Controversies at the present time center on the use of endovascular techniques to obliterate cerebral aneurysms, the use of adjuncts to relieve vasospasm and possible protection of the brain during periods of ischemia associated with the vasospasm. The International Co-operative Study Group's findings recently published (18,19) revealed rather depressingly that only 58% of patients enrolled returned to their premorbid state at final assessment. Forty percent remained moderately or severely disabled, 2% were vegetative, and 26% had died. The most common causes of death and disability were vasospasm, the severity of the initial hemorrhage, rebleeding, or complications of surgery. In common with the initial surgical studies, there was a strong correlation between the level of consciousness at admission and eventual outcome: 72% of comatose patients died; only 11% made a good recovery. There were no differences in outcome for surgery performed early (0-3 days postsubarachnoid hemorrhage) or late (11-14 days), but the outcome appeared to be worse in general in patients operated on between 7 and 10 days after the hemorrhage. However, numerous units (including the author's own) have routinely operated between the 4th and the 8th day after subarachnoid hemorrhage with results comparable to the best reported, and it appears likely that the findings of the International Co-operative Study may not be absolute in this regard. The Co-operative Study, however, did suggest that the more alert the patient was, the better the results of early surgery were, and the more drowsy the patient was, the better the results with delay. Recent years have seen an increased acceptance of temporary occlusion (5) even by the use of intravascular balloons (20). These techniques are of particular value in the management of giant aneurysms (21).
Endovascular Treatment There has been an enormous increase in the interest of endovascular treatment for obliteration of aneurysms, but it has become clear that balloon occlusion of a recently ruptured aneurysm carries considerable risk. In our own series, morbidity statistics approach 50% in such cases . Aneurysms that have ruptured in the remote past and that contain little in the way of clot
AIREN-NINDS1991 WORKSHOP
(here again MRI is valuable), and aneurysms inaccessible in the cavernous sinus may perhaps be best treated by balloon occlusion, if suitable neurosurgical expertise is not available. The most extensive report comes from San Francisco (22) on 84 patients; indications for percutaneous balloon obliteration include failed previous surgery, anatomically difficult location, a fusiform aneurysm, inability to tolerate general anesthesia, or an aneurysm that was felt to be too large to clip. Treatment was delayed in stable patients if there was evidence of thrombus less than 6 weeks old (CT or MRI) and the mortality rate was 17.9%. There was a 10.7% stroke rate from a variety of causes. Fox and Drake (23) pointed out a 53% mortality in the subgroup of the San Francisco patients with incomplete obliteration. A partially treated aneurysm remains an untreated aneurysm. It is especially important that the matrix of survival produced by Alvord many years ago (24) be used to relate the efficacy of any aneurysm treatment taking into account the time from hemorrhage and the clinical grade of the patient. These have long been known as the main determinants of outcome in subarachnoid hemorrhage. The question of treatment of incidentally discovered aneurysms remains problematical. Despite the anecdotal publications relating to the successful obliterations of such lesions, and the general neurosurgical acceptance that, in a patient who has had a subarachnoid hemorrhage, complete treatment consists of the obliteration of all the available aneurysms, seriatim or at one time if they can be reached, there remains no clear evidence that the risks of surgery particularly in the posterior circulation of unruptured aneurysms are acceptable over the entire age range.
Other Methods of Treatment of Subarachnoid Hemorrhage A whole variety of drugs to treat vasospasm and to improve the ionic homeostasis of the brain have been tried. Thus, a trial with nimodipine was reported (25) from various centers in the United Kingdom. It claimed a significant difference in morbidity and mortality outcome in good grade cases of subarachnoid hemorrhage through operation by the use of intravenous nimodipine. A trial (26) comparing two doses (48 and 72 mg/day) found no significant difference in a 6month outcome. Despite the widespread use of nimodipine, patients still die or become severely disabled as a result of cerebral infarction after subarachnoid hemorrhage. Small studies with calcitonin-generelated-peptide (CGRP) by intra-arterial infusion (27) showed that this powerful vasodilator improved
neurological deficit during infusion, but the patients promptly relapsed after the infusion had stopped. Intraluminal mechanical vasodilation has been reported (28,29) to have increased improvement in a small number of cases with angiographic vasospasm in whom the artery was dilated forcibly by the inflation of an intraluminae balloon. This must be regarded as still controversial One of the most disappointing features of aneurysm surgery at the present time is the lack of scientific rigor as applied to the assessment of endovascular procedures by the International Co-operative Study Group. The reports of anecdotal selected series without controls add little in scientific value to the assessment of the procedures, but the difficulties of securing controlled trials of pathology traditionally, and perhaps acceptably managed by other means, clearly presents great difficulty.
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AJREN-NlNDS1991 WORKSHOP 14. Symon L, Iakowski A, Bills D. Surgical treatment of pontomedullary cavernoma. In press. 15. Fahlbusch R, Strauss C, Huk W Surgical removal of pontomesencephahc cavernous hemangiomas Neurosurgery 1990;26:449-57. 16 Kashrwagi S, van Loveren HR, Tew JM Jr. DIagnosis and treatment of vascular brain-stem malformations J Neurosurg 1990,72:27-34 17. Heffez DS, Zinreich SJ, Long DM Surgical resection of intrinsic brain stem lesions: an overview Neurosurgery 1990,27:789-98. 18 Kassell NF, Torner JC, Clarke Haley E [r, et al The International Co-operative Study on the timing of aneurysm surgery. J Neurosurg 1990,73:37-47. 19 Kassell NF, Torner JC, Clark Haley E [r, et al The International Co-operative Study on the timing of aneurysm surgery. J Neurosurg 1990;73:18-36. 20 Shugart MA, Kwan ES, Heilman Be. Temporary balloon occlusion of a proximal vessel as an aid to chpping aneurysms of the basilar and parachnoid internal carotid arteries Technical note. Neurosurgery 1990;27:1169 21. Symon L,Vajda J. Surgical experiences with giant intracranial aneurysms J Neurosurg 1989,61'1009-28. 22 Higashida RT, Halbach VC, Barnwell SL, et al. Treatment of mtracramal aneurysms with preservation of parent vessel; results of percutaneous embolization in 84 patients A]NR 1990,11 633-40.
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23. Fox AJ, Drake CG. Endovascular therapy of intracranial aneurysms. A/NR 1990,11'641-2. 24. Alvord EC Jr, Loeser JD, Bailey WL, Copass MK Subarachnoid hemorrhage due to ruptured aneurysms: a simple method of estimating prognosis Arch Neurol 1972,27:273-4 25 Pickard JD, Murray GP, Illingworth RD, et al Effect of oral nimidopine on cerebral infarction after subarachnoid haemorrhage. British Aneurysm Nimidopine Tnal Br Med J 1989;298.636-42. 26 Gilsbach JM, Reulen HJ, Ljunggren B, et al. Earlyaneurysm surgery and preventive therapy WIth intravenously administered mmodipme. A multicentre double-blind dose-comparison study. Neurosurgery 1990,26458-64 27. Johnston FG, Bell BA, Robertson IJA, et al. Effect of calcitonin-gene-related peptide on post-operative neurological deficit after subarachnoid haemorrhage. Lancet 1990,1'869-72 28. Higashida RT, Halbach W, Cahan LD, et al Transluminal angioplasty for treatment of intracranial artenal vasospasm J Neurosurg 1989,71:648-53. 29. Newell DW, Eskridge JM, Mayberg MR, et al Angloplasty for the treatment of symptomatic vasospasm following subarachnoid haemorrhage. ] Neurosurg 1989;71:654-60.
