Recollections in Aneurysm Surgery
Fig. 1. The inspiration.
In the very early sixties, a chance encounter with an epileptic patient who had one large pupil and a slightly drooped eyelid set off a lifetime of interest in the endovascular approach to hemorrhagic neurovascular disease. Twenty-three years earlier this woman had a typical subarachnoid hemorrhage with a complete third nerve palsy. Her diplopia slowly resolved over a period of several months. Radiographically she had a clearly calcified ring juxtaposed to her normal carotid artery, in the exact position of a typical aneurysm. The thought occurred that if she could repair her aneurysm spontaneously by endothrombosis, perhaps induced endothrombosis might have a role. As is the rule this was not a new idea. A French worker (whose name is now lost) made some comment upon the effect of an electric current upon blood clotting in the middle of the last century. The legendary Macewen of Glasgow, before the end of that century, had distinguished between red clots which disappear and white clots (organized clots) which maintained occlusion. Sawyer in the fifties had identified the thrombogenic role of the positive current and the clot inhibitory role of the negative. Blakemore and others in the thirties had induced thrombosis within aortic aneurysms by threading wire into them and in 1939 Werner and Blakemore had actually thrombosed an intracranial aneurysm by passing wire into it through the eye socket of an amblyopic eye. Bill Adams, Chief of Surgery at the University of Chicago in the fifties, confided that copper was the most effective wire for abdominal aneurysms.|
We constructed aneurysms on the femoral artery of the dog, found out that they were either difficult to keep patent, or too easy to thrombose. We then went on to use the intact femoral artery as the experimental vessel testing external and internal electrodes, the surface area of electrodes, and the time and range of current. With as little as 250 microvolts a good clot could be produced. By switching polarity, it could be dispersed or built up at will. Steel needles electroplated out and disintegrated. Platinum did not. All of this was reported in 1964. The same year, a giant hemangioma of the scalp was eliminated by a sustained DC current and was similarly reported. A subsequent (brilliant?) laboratory study of 22 different implanted metals and alloys and another series of vapor deposited rare earths was made without use of a current. Metals which undergo a slow surface chemical charge (as occurs when a copper roof turns green) generate a low battery effect. It turned out as Adams had predicted that copper and it alloys (which had advantages in terms of hardness and springiness) were the best thrombogenic materials. Platinum came close to zero. The "Journal of Neurosurgery" rejected the study which remains unpublished, (which may be why current interventionists have so much trouble sealing the neck of their aneurysm).
In the first clinical efforts, the aneurysm, exposed by craniotomy, had a DC current passed across its base. It was known, however, that an aneurysm does not bleed when pierced by a small needle, only upon its withdrawal. Effective thrombosis was then achieved by aneurysm puncture. The steel needle (31 gauge) electroplated itself into the aneurysm wall and disappeared. Later, copper clad steel needles were electrically detached using the same principle as is used by current aneurysm interventionists. Later, mechanically detached needles and a special stereotactic machine, which placed a line of needles across the necks of larger aneurysms (like a sewing machine) were devised. Since the beginning, right through to the present, intraoperative angiography has been an essential component of our work.
Branches which overlay the neck, thus preventing adequate access to it, resulted in incomplete occlusion in some, The major problem was not technical, but spasm which remained uncontrolled. It was thought, at that time, that craniotomy was a major factor in the genesis of spasm and it was thus a major disappointment that the virtually trauma-free procedure did not eliminate it. In 1974, ten years after the study was commenced, the total of 16 patients were reviewed. It was concluded that, though effective technically, the method did not offer enough advantage over simple clipping of the smaller aneurysm to make the greater technical difficulty. Thrombosis of those giant aneurysms, for which there was not good clipping solution, continued until clipping techniques improved and percutaneous intervention arrived.
The Medical Management
This began with an attempt to concentrate a therapeutic radioisotope of iodine in the immediate vicinity of the tumor by inhibiting fibrin clearance from the transudated fluid. The project fizzled, but a knowledge of clotting mechanisms and of antifibrinolytic drugs grew. The duration of our now standard DC induced experimental clot in the dog was studied with and without an antifibrinolytic drug. At the end of a week, most untreated clots had disappeared and most treated clots persisted, but they all eventually disappeared. In our clinical trial published in 1968, it was confirmed that epsilon amino caproic acid effectively reduced the rate of rebleeding. Most subsequent studies, mostly in Europe, used a different, though similar, drug. The final conclusion of all those was that, yes indeed, the antifibrinolytic drugs did reduce rebleeding but enhanced the late effects of spasm, so that the overall clinical results were not improved. The original idea had never been to substitute antifibrinolysis for surgery, merely to delay it. This concept was never perfectly tested. Further efforts were made to add hypotension to the presurgical management. As the natural history of the spasm became better understood, it was clear that, at any time over the first three days, hypotension could be safely applied to the awake patient, thereby protecting him up to the moment of surgery. Though the peak rebleeding period has now been recognized to occur on the first day instead of at the end of the first week, there is no evidence that many surgeons take advantage of the early protection that careful hypotension offers in the immediate preoperative hours.
In 1978, we reviewed our combined medical/surgical management of aneurysms and were able to report, for the first time, a series of 100 consecutive patients operated on without surgical mortality. The above 100 cases were selected out from a group of 130 patients with a 15% total subarachnoid hemorrhage mortality rate from rebleeding and deterioration. Subsequent to these studies, the pendulum has swung to early operation once more.
As intervention techinques continue to improve, it seems inevitable that at the time of the first arteriogram, the aneurysm might be simultaneously sealed. Perhaps the aim to completely and permanently occlude the aneurysm by this means is not necessary. If the immediate risk of hemorrhage could be eliminated, then elective definitive clipping of the aneurysm neck by surgery might be the best solution. We learned over the course of time that copper was a better material than platinum and that mechanical detachment was better than electrical detachment. We suspect that such modifications might improve the interventionist's results.
Central Blood Flow Issues
Laboratory studies were carried out over the 73-83 decade in collaboration with a series of colleagues, de la Torre, Brown, Afar, and Crockard. They documented the role of mannitol and dimethyl sulfoxide in increasing blood flow in the laboratory and in the clinical setting. Subsequently, we used mannitol extensively to boost perfusion (rather than to control intracranial pressure) during the time of spasm. Dimethyl sulfoxide was a more powerful medication, but the clinical cloud that lay over its intemperate use in other clinical situations prevented a clinical trail in subarachnoid hemorrhage.
Osaki, Cheung, and McIlhany studied the spasmogenic effects of disintegrating blood cells and identified a breakdown product of hemoglobin with a molecular weight of 40-45,000 as the main component.
Historically, aneurysm treatment has oscillated. There was a swing from medical management to surgery in the early fifties then a hesitation, then again a renewal in the sixties. Perhaps there is a new impending retreat as intervention gets better.
There was a swing from the late operation of Norlen in 1952, to the early operation of many of his contemporaries to late again, and now once more early, though the evidence of the international study that brought about this most recent swing has not been overwhelming. Endovascular occlusion came and went and came again. Will it go? Perhaps one more swing is over the horizon. If the interventionist succeeds in early closure, the problem of spasm will remain. Perhaps spinal fluid drainage, the only treatment available when I was a medical student in the forties, will make a comeback.
Ausman, J.I., Diaz, KG., Mullan, S., et al: Posterior inferior to posterior inferior cerebellar artery anastomosis combined with trapping for vertebral artery aneurysm. Case report. J Neurosurg 73:462-465, 1990.
Brown, ED., Crockard, H.A., Johns, L.M. and Mullan, S.: The effects of sodium nitroprusside and trimedhaphan camsylate on cerebral blood flow in Rhesus monkeys. Neurosurg. 2:31-34, 1978.
Brown, ED., Hanlon, K, and Mullan, S.: Treatment of aneurysmal hemiplegia widh dopamine and mannitol. . Neurosurg 49:525-529, 1978.
Brown, J.A., Wollmann, R.L., and Mullan, S.: Myopadhy induced by epsilon-aminocaproic acid. Case report. J Neurosurg 57:130- 134, 1982.
Cheung, S.T., McIlhaney, M.R, Lim, R., and Mullan, S.: Preliminary characterization of vasocontractile activities in erythroc,vtes. J Neurosurg 53 :37-43, 1980.
delaTorre,J.D., Kawanaga,H.M., end Mullen, S.: Treatment of experimental middle cerebralartery occlusion. Neurology 25:383-384, 1975.
Dobben, G.E., Mullan, S. and Moseley, R.D.: A new biplane neuroradiologic localizing instrument. Radiology, 89:329, 1967.
Jafar, JJ., Johns, L.M., and Mullan, S.: The effect of mannitol on cerebral blood flow. J Neurosurg 64:754-759, 1986.
McIlhany, M.R, Cheung, S.T., Osaki, N., Lim, R., and Mullan, S.: Carotid Spasm. R.H. Wilkins (ed). Williams & Wilkins, p. 184. 1980.
McIlhany, M.R, Johns, L.M., Leipzig, TJ., Patronas, N.G., Brown, ED., and Mullan, S.: In Vivo characterization of vasocontractile activities in erythrocytes. J Neurosurg 53:356-361, 1983.
Mullan, S. and Dawley, J.: Antifibrinolytic Therapy for intracranial aneurysms. J Neurosurg 28:2 1, 1968.
Mullan, S. and Suwanwela, C.: The effect of hypodhermiaon acute experimental subarachnoid hemorrhage in dogs. Surg. Forum 9:708, 1959.
Mullan, S., Beckman, E, end Vailati, G.: Simplified dhrombosis of a large, hypertrophichemangioma of dhe scalp.J. Neurosurg. 21:68, 1964.
Mullan, S., Beckman, E, Vailati, G., Karasick,J., and Dobben, G.: An experimental approach to dhe problem of cerebral aneurysm.J. Neurosurg. 21:838, 1964.
Mullan, S., Dobben, G. Vailati, G., et al: Copper electric dhrombosis of intracranial aneurysms. In deVet AC (ed): Proceedings 3rd International Congress Neurosurgery, Copenhagen, 1965. Amsterdam, Excerpta Medica Foundation, 1966, pp 655-661.
Mullan, S., Duda, E.E. and Patronas, NJ.: Some examples of balloon technology in neurosurgery. J Neurosurg 52:321-329, 1980.
Mullan, S., Hanlon, K., and Brown, ED.: Management of 136 consecutive supratentorial berry aneurysms. J. Neurosurg. 49:794-804, 1978.
Mullan, S., Jafar, J., Hanlon, K. and Brown ED.: Dimedhyl sulfoxide in dhe management of postoperative hemiplegia. Read at the Second International Workshop on Cerebral Vasospasm, Amsterdam, July 1979.
Mullan, S., Jafar, JJ., Hanlon, K., and Brown, ED.: Dimethyl Sulfoxide in the management of post-operative hemiplegia: Cerebral Arterial Spasm. R.H. W~lkins (ed), Wflliams & Wiikins: pp 646-653, 1980.
Mullan, S., Raimondi, AJ., Dobben, G., Vailati, G., and Hekmatpanah,J.: Electrically induced dhrombosis in intracranial aneurysms.J. Neurosurg. 22:539547, 1965.
Mullan, S., Reyes, C., Dawley, J., and Dobben, G.: Stereotactic copper electric thrombosis of intracranial aneurysms. Progr. Neurol. Surg. 3, Karger, Basel/New York, 1967.
Mullan, S., Reyes, C., Dawley, J., and Dobben, G.: Stereotactic copper electric thrombosis of intracranial aneurysms: Progr. Neurol. Surg., Vol. 3, Karger, Basel end Year Book,pp. 193-211, 1969.
Mullan, S.,: New technics in neurosurgery. Postgrad. Med., 34:636, 1965.
Mullan, S.: Conservative management of dhe recendy ruptured aneurysm. Surg. Neurol., 3:27-32,1975.
Mullan, S.: Experiences widh surgical dhrombosis of intracranial berry aneurysms and carotid cavernous fistulas.J. Neurosurg. 41:657-670, 1974.Mullan, S.: Operative thrombosis of aneurysms and fistulae. In Advances in Surgery for Cerebral Stroke. The Proceedings, Springer-Verlag, June 1988.
Mullan, S.: Stereotactic dhrombosis of intracranial aneurysms. Confin. Neurol. 31 :94, 1969.
Mullan, S.: The initial medical management of ruptured intracranial aneurysms. In Current Controversies in Neurosurgery. T.R Morley (ed)., W.B. Saunders Co., Philadelphia, pp 259-269, 1976.
Osaki, N. end Mullen, S.: Possible role of the erythrocyte in causing prolonged cerebralvasospasm.J. Neurosurg. 51:733-778, 1979.