5
continued for several weeks, this outbreak lasted for only 3 days and there were no secondary cases. Virology.-Adenovirus-like particles were found in fæces from four of the six children affected and from the nurse, but not from any of the other thirteen children. Salmonellse, shigellae, and enteropathic strains of E. coli were not found. Despite continuous efforts over several
NEW APPROACH TO MANAGEMENT OF INTRACRANIAL ANEURYSMS *
months in the Birmingham and Shrewsbury laboratories, and more recently in the Central Public Health Laboratory at Colindale, all attempts, using a wide variety of tissuecultures, failed to isolate the adenoviruses from the faeces. Feeble cytopathic effects were seen in some HEp2 cultures after 10-20 days’ incubation, but virus could not be subcultured from them. The adenoviruses in clarified faecal suspensions were much more strongly agglutinated by antisera to adenovirus type 7 than by antisera to other types. Luton6 found this method of typing to be reliable. The result was surprising because adenovirus type 7 was not regarded as a difficult virus to isolate, and we ourselves had never found it to be so.
Summary relieve the tension on intracranial aneurysms by temporarily clamping the internal carotid artery in the neck, so as to increase the expansibility of the artery. This approach was based on the concept (or "A principle ") that hæmorrhage is caused by the aneurysm having to bear the full force of systolic pulse pressure when atherosclerosis prevents this pressure being taken up by the normally expansile arterial wall. Follow-up has been fairly
Discussion In 50 to 60 % of cases of acute diarrhoea in young children, rotaviruses can be seen in the fæces 1—4 No rotaviruses were seen in our second outbreak; one child had previously had rotavirus diarrhoea in the first outbreak and was known to have antibodies to that virus. In the first outbreak rotaviruses were only seen in children with diarrhoea or " loose stools "; virus excretion did not continue after diarrhoea ceased. Carriers or sub-clinical cases were not found-in contrast to enteroviruses which commonly produce symptom-free infection. Electron microscopy of faeces enabled us to disthe adenoviruses quickly and to assign a provisional serotype to them, although we could not establish them in tissue-culture. cover
In the first outbreak one child seems to have the virus into the ward and transmitted it to others either directly or indirectly. The very similar virus of calf diarrhoea retains full infectivity in fasces kept for 7 months at room temperature.7 It is reasonable to expect that the human virus will also be stable, and that it may persist in the environment In the unless destroyed by careful disinfection. second outbreak, adenoviruses seem to have come from a common unknown source and to have affected several children at the same time.
brought
We thank Sister E. J. Greasley and Sister B. Sakuntanaga for their help in investigating these outbreaks; the Shrewsbury public-health laboratory staff and Mr R. E. Hadley for technical help; and Dr M. G. Pereira and Dr P. G. Higgins for their attempts to isolate the adenoviruses.
Requests for reprints should be addressed
to
T. H. F.
REFERENCES
Flewett, T. H., Bryden, A. S., Davies, H., Woode, G. N., Bridger, J. C., Derrick, J. M. Lancet, 1974, ii, 61. 2. Bishop, R. F., Davidson, G. P., Holmes, I. H., Ruck, B. J. ibid. 1974, i, 149. 3. Flewett, T. H., Davies, H., Bryden, A. S., Robertson, M. J. J. clin. Path. 1974, 27, 608. 4. Middleton, P. J., Szymanski, M. T., Abbott, G. D., Bortolussi, R., Hamilton, J. R. Lancet, 1974, i, 1241. 5 Bridger, J. C., Woode, G. N. Br. vet. J. (in the press). 6. Luton, P. J. clin. Path. 1973, 26, 914. 7. Woode, G. N., Bridger, J. C. Personal communication. 1.
W. J. ATKINSON Hurstwood Park
Hospital, Haywards Heath,
In six
cases an
attempt
was
Sussex
made to
short, but the preliminary findings in four of the six patients are encouraging. More attention must be paid in the future to the significance of atherosclerosis in the onset of bleeding from intracranial aneurysms and the incidence of postoperative problems. The argument that atherosclerosis permits the transmission of the systolic pulse directly to the aneurysm wall requires further investigation. The earlier pathological signs of atherosclerosis must receive greater attention, and post-mortem study of the walls of arteries in immediate juxtaposition to aneurysms with highpowered magnification is required. Introduction THE high mortality and morbidity which follow both conservative and surgical treatment of patients with intracranial aneurysms have led to attempts to take a new look at the problems of causation and therapy. One difficulty with the argument that intracranial aneurysms arise from congenital lesions is that the considerable majority " bleed " only after the age of 40. One explanation for this is the onset of atherosclerosis. In the early life of arteries, the systolic impulse in arterial walls is seen and felt as an expansion of the wall; the pulse has its systolic component. The pulse wave (i.e., the expansion of the wall) travels along the artery rather like the peristaltic wave in the oesophagus and gut but from a different cause, the heart in systole. When the artery is affected by atherosclerosis its wall becomes less elastic, so that when the systolic pulse wave travels to the periphery the blood-flow pressure is transmitted directly to the periphery and is not taken up by the expansion of the arterial wall. Because intracranial aneurysms lie at the fork junction of two branches of the artery, the blood-flow pressure in systole is transmitted more or less directly to the mouth of the aneurysm. Therefore, whereas previous to the onset of atherosclerosis each systolic wave of pressure was absorbed by the expansion of the arterial wall and the arterial bloodflow pressure at the periphery was less, now, with hardening of the arterial wall in atherosclerosis, each systolic wave of pressure is transmitted directly to the aneurysm, its contents, and wall. On this model (or " A principle ") atherosclerosis *
Based on a paper read at a meeting of the Academy of American Neurosurgeons and the Society of British Neurological Surgeons, held in Bermuda on Nov. 7, 1974.
6 SUMMARY OF CASES
A.c.c. = Anterior communicating artery. Int. car. Intracranial part of internal carotid artery. N=Normal. =
S
=
with subarachnoid haemorrhage. She had persistent headache for the next 5 months with weakness of right hand and foot. Arteriography (fig. 1) revealed a large aneurysm at junction of anterior communicating and left anterior cerebral arteries. Each anterior cerebral artery filled from its own side, but the right carotid arteriogram filled both anterior cerebral arteries. Patient right-handed. On April 25, 1972, the left internal carotid artery was clamped with two artery clamps for 1 hour under local anaesthesia and then released. The patient fully conscious, orientated, and without neurological symptoms throughout operation and subsequently. Now complains of occasional pain in right side of head and noise in head on left side. Personality, that of a fearful apprehensive woman, unchanged.
Case 2
Satisfactory.
D = Died.
leads to a more direct transmission of higher systolic pressure to the aneurysm, puts a greater strain on the wall, and leads to haemorrhage. Efforts to prevent the higher systolic pressure reaching the aneurysm might avert haemorrhage. This could be done by causing the arterial wall proximal (i.e., towards the heart) to the aneurysm to expand and so take up the systolic pressure. I have tried clamping the internal carotid artery in the neck in such a way as to contuse and break up the muscle and intimal layers of the arterial wall. Initially, when the clamps were released (slowly), there was a considerable expansion of the entire wall where it had been injured. I describe here the results with this surgical approach in six cases. The six cases are summarised in the table.
Aged 64. Acute subarachnoid haemorrhage 4 days before admission with confusion and drowsiness; disorientated;
Case-reports Case 7 -
Aged SO. This woman was first seen in November, 1971, with acute onset of headache and neck pain, but no loss of consciousness. Clinical diagnosis suggested aneurysm
2-Case 2 : anteroposterior arteriogram showing saccular aneurysm projecting upwards from bifurcation of left internal carotid artery.
Fig.
both
plantar responses extensor. Arteriography showed a saccular aneurysm arising vertically from junction of left internal carotid and middle cerebral arteries (fig. 2). On May 23, 1972, 12 days after onset of subarachnoid haemorrhage, left internal carotid artery was clamped for 1 hour under local anaesthetic and then released with no ill-effects. Steady recovery of ambulant state and retired life. When seen 2 years later, he had left-sided headache occasionally and angina pectoris but he leads similar life to pre-hæmorrhage state. Both superficial temporal pulses palpable. Bruit heard in left side of neck over carotid arteries. Case 3
Mt. l—Case
1: aneurysm in
anteroposterior arteriogram showing large region of left anterior cerebral artery.
Aged 44. Psychiatric observation for 8 years. Intracranial bruit noticed by patient for 20 years. Always stops when head turned to right and on pressing centre spot in left side of neck. Began suddenly, 20 years ago. No other neurological symptoms or signs apart from left deafness. Arteriography showed small sessile aneurysm 1 cm. below the bifurcation of the left internal carotid artery in the head. On Aug. 12, 1972, clamping of left internal carotid artery in the neck for 1 hour. No illeffects. Noise ceased. 1 year later noise returned in left
7 ear
similar
to
original symptom;
no
other
neurological
signs. Cas
Aged 51. Acute onset of subarachnoid haemorrhage 24 No loss of consciousness or hours before admission.
neurological symptoms except for meningism. Hypertensive, blood-pressure 180/120 mm. Hg. Arteriography showed that both anterior cerebral arteries filled from left side and revealed a large saccular aneurysm arising from the region of the anterior communicating artery. On July 18, 1972, 3 days after admission, left internal carotid artery clamped in the neck over a 2 cm. area with three artery clamps for 1 hour. No neurological symptoms or signs developed in that time and the clamps were released. The next day a mild right flaccid hemiparesis developed. This had disappeared by the time of his discharge home 3 weeks later. 1 year later, he complained of headaches at the back of his head. Had returned to work and was his former self in personality and work value. Bruit heard left side of neck. B.P. 220/120 mm. Hg despite hypotensive drugs and supervision by cardiologist.
Case 5
Aged 63. This patient had been followed up since March, 1968, when he had had an acute subarachnoid hemorrhage, loss of speech, and right hemiparesis, with subsequent complete recovery. He had then developed the ensuing years blindness of the left eye and finally loss of the right temporal half-vision. On one occasion, 6 months previous to this final stage, he had lost vision completely during an episode of headache and vomiting which had lasted for 2 days and been followed by recovery of right nasal vision only. Anxiety for his remaining vision prompted ophthalmologist and patient to seek further treatment of his intracranial aneurysm which had " initially been huge ", arising from the anterior communiover
Fig. 3-Case 5: oblique arteriogram showing aneurysm of left anterior cerebral artery (March, 1968).
artery (as seen in the left internal carotid arterioin 1968) (fig. 3). There was good cross-circulation gram from the right side in the right common carotid arteriogram. He was right-handed. In July, 1973, the left internal carotid artery was clamped in the neck for a period of 15 minutes under local 2 anaesthetic without onset of any neurological signs. days subsequent to this he developed dysphasia and right hemiparesis. These symptoms steadily improved over the ensuing 6 months, but he was left with poverty of fine finger movements of the right hand and slight hesitancy of speech. To date his vision remains unaltered with preservation of right nasal vision in the right eye only.
eating
Case 6
Aged 48. Subarachnoid hxmorrhage 1 day before admission without loss of consciousness or other neuro-
logical signs. B.P. on admission 160/86 mm. Hg. Right carotid arteriography showed that both anterior cerebral arteries filled from that side, and a lobular aneurysm arose from the anterior cerebral artery at the junction of the transverse and ascending part (fig. 4). On the left carotid arteriography the anterior cerebral artery did not fill at all on either side, but on crossed compression some contrast passed from the left to the right. On March 14, 1973, right common carotid artery clamped over a distance of 2 cm. for 15 minutes and then sheathed with ’Teflon ’ gauze. For the next 14 days she had a gradually improving left hemiplegia. In the period April 24-30, 1973, she was well, although drowsy. The drowsiness fluctuated for the next 3 days, and then, on May 3, having been well, she suddenly lost consciousness and died. Necropsy showed haemorrhage into the right frontal lobe and ventricular system from the region of the aneurysm of the right anterior cerebral artery. Seven weeks after crushing the common carotid artery and wrapping it with ’Dacron’ (teflon), the muscle coat and
Fig. 4-Case 6: carotid arteriogram showing aneurysm arising from junction of anterior communicating and anterior cerebral arteries (anteroposterior view).
8
removed while the tape around the common carotid artery was pulled to occlude the blood-flow. The tape was released slowly so that the contused arterial walls, which were at this stage adherent in the line of the clamps, re-expanded gradually. At this stage the patients complained of headache which abated in the course of 1-3 hours. The tape was finally removed and the platysma and skin layers were sutured.
were
Discussion The surgical approach tried here is based on the proposition that atherosclerosis is the main event lead-
haemorrhage from intracranial aneurysms and operation which leads to weakening and expansibility of the internal carotid arterial wall in
ing
that
to
an
the neck may prevent further haemorrhage from such aneurysms. The effect of atherosclerosis in taking away the original expansibility of the arterial wall is to impose greater strain of the aneurysmal wall. If Fig. 5--Case 6: low-power view of clamped section of common this effort can be nullified, then the aneurysmal wall carotid artery. will once more meet the systolic pulse pressure at a lower level. Direct surgical attack on the aneurysms of this series of six cases was not considered justifiable for various reasons, which included the size of the aneurysm, the age of the patient, the poor prospect of collateral circulation with both anterior cerebral artery supplies coming from one side only. Also, conservative treatment was considered unwise chiefly because there was strong evidence of risk of further complications to the patient. Accessible intracranial aneurysms will continue to be occluded surgically where the risk of physical and mental postoperative defect is likely to be slight. The site at the junction of the anterior cerebral arteries with the anterior communicating vessel is notoriously difficult of access, and it is impossible to predict the degree of mental deficit after operation. The incidence of infarction in the anterior cerebral artery territory is high when the proximal part of the anterior Fig. 6—Case 6: inner aspect of common carotid artery 7 weeks cerebral artery which supplies an aneurysm at this after clamping (minus sheath). site is occluded as a definitive form of treatment. The elastic lamina had disappeared as shown in fig. 5. Given that the atherosclerotic effect on the systolic vessel wall consists mainly of young, vascular connective pulse pressure is to inflict greater strain on the A marked giant-cell reaction was present in the tissue. wall at this site than occurs at an earlier aneurysmal 6 neighbourhood of where the dacron had been. Fig. non-atherosclerotic age, then it would seem that proshows the appearance of the right common carotid artery cedures designed to restore the expansibility of the post mortem without the dacron sheath. The total length of crushing at the time of the operation by the three proximal arterial wall are justified; this line of argu9 was mm. clamps ment is referred to as the " A principle ". To do so at the site of the proximal part of the anterior cerebral Operation artery would seem to promote an artificial aneurysmal Under local anaesthetic, injected superficially and problem beneath the frontal lobe-with all its own an difficulties. In the neck, it is anticipated that the incision the anterior border deeply, through along of the sternomastoid muscle, the carotid sheath was formation of a false aneurysm of the internal carotid dissected free to identify the bifurcation of the comartery would not be beyond the remedial powers of mon carotid artery, the common carotid artery itself, a vascular surgeon. It may well be that a stenosis, and its external and internal branches. A tape was and not a false aneurysm, arises slowly at the site of passed around the common carotid artery. Three clamping. This too would lower the systolic pulse artery clamps were placed on the internal carotid pressure on the aneurysm in the head and would also be amenable to vascular surgery if necessary. It is artery for 1 hour in the first three cases and 15 minutes in the later cases, except in case 6 where possible that the insertion of a living expansible graft into the internal carotid artery would produce better the common carotid artery only was clamped. During this time the patient was tested for speech and moveeffects than merely clamping that artery, but the Thereafter the clamps ments of the opposite limbs. reasoning behind the A principle will not be accepted
9
until it is shown by further study that it
can
be
validly
in
therapy. of hypotensive drugs would seem to be an essential corollary to the treatment of intracranial aneurysms if the A principle is accepted. In studying the use of these drugs by physicians in the treatment of arterial hypertension I have noticed that their routine administration does not necessarily lead to a persistent reduction of high systemic arterial blood-
applied The
use
pressure, and yet such treatment does lower the incidence of complications in the condition of arterial hypertension and atherosclerosis. Perhaps the antiadrenergic agents not only serve to reduce the arterial blood-pressure but also increase the expansibility of arterial walls by the reduction of the muscle tone in the arterial walls. If this is true then the use of these drugs must assist in the treatment of intracranial aneurysms because the reduction of muscle tone in arteries leading to the aneurysm will lead to greater expansibility of the arterial wall and so reduce the systolic pulse pressure at the site of the aneurysmso long as that vessel can still possess muscle tone and is not wholly atheromatous.
EFFECTS OF LONG-TERM PRACTOLOL THERAPY ON PLASMA-LIPIDS AFTER ACUTE MYOCARDIAL INFARCTION A. M. G. COCHRANE * D. DE BONO University of Cambridge and Addenbrooke’s Hospital, P. GHOSH
Cambridge In
Sum ary
double-blind controlled trial last12
months, long-term practolol significant effect on plasma-lipid concentrations in twenty patients who had had acute
therapy
ing
a
had
no
myocardial infarction.
Patients and Methods Patients included in this study had been admitted to Addenbrooke’s Hospital with myocardial infarction. The diagnosis was based on at least two of the following W.H.O. criteria: unequivocal electrocardiographic changes; typical history and clinical features of infarction; and raised levels of serum glutamic oxaloacetic transaminase and hydroxybutyrate dehydrogenase. Patients over the age of 70, and those in whom /3-blocking drugs were contraindicated, were excluded. All patients included in the trial had given their informed consent. Patients were allocated to control and treatment groups on the basis of coded numbers. The key to the code was not known to the investigators until after the study was completed. Treatment was usually initiated 14-21 days after infarction. Patients in the treatment group received 200 mg. of practolol twice daily (in some patients this was -later reduced to 100 mg. twice daily) and those in the placebo group received identical placebo tablets. The placebo group included sixteen males and three females and the praotolol group had nineteen males and The average age in the placebo group was 55 one female. years (range 40-68 years), and in the practolol group it was 52 years (range 34-67 years). The mean body-weights were 158 lb. (70-2 kg.) (range 133-192 lb.) and 161 lb. (71-5 kg.) (range 123-220 lb.), respectively. Patients were seen at 1, 3, 6, and 12 months after starting treatment. Venepuncture was done after a 12-hour fast, and the samples of plasma were analysed by semiautomated techniques for triglyceride6 and cholesterol7 concentrations. In addition, the lipoprotein pattern was
determined electrophoretically
on
cellulose
acetate
using
0-00238M Gelman high-resolution buffer (pH 8-8) and staining with Schiff’s reagent. Triglyceride concentrations of samples showing chylomicrons on lipoprotein electrophoresis were excluded from the final analysis. Two patients had to be withdrawn from the treatment group, and six from the control group, because of side-effects or because their medical condition had altered. The withdrawals in the practolol group were due to shortness of breath or persistent ventricular ectopic beats. No unusual cutaneous or ocular lesion 8 was seen in this small group during this particular period of study. .TABLE I-RESULTS OF PLASMA-TRIGLYCERIDE CONCENTRATION AFTER ACUTE MYOCARDIAL INFARCTION
Introduction DRUGS blocking adrenergic &bgr; receptors have been shown to inhibit catecholamine-induced lipolysis in vitro, and to block the increase in plasma-non-
esterified-fatty-acid which normally accompanies catecholamine infusion in vivo.23 Wegener et a1.4 claimed that propranolol could lower serum esterified fatty acid and cholesterol concentrations in patients with a "hyperkinetic cardiac syndrome"; however, their was not adequately controlled. Lloyd-Mostyn al.‘ were unable to repeat these results in a wellcontrolled cross-over trial, but the length of treatment (2 weeks) was relatively short. As yet there has been no long-term controlled study of the effect of a &bgr;-
study
et
plasma-lipid multicentre, double-blind trial to determine the efficacy of practoin preventing dysrhythmias after acute myocardial infarction provided us with an opportunity to investigate the effect of prolonged therapy with this &bgr; blocker on plasma-lipid concentrations. adrenergic-receptor-blocking drug concentrations. Our participation
* Present address:
on
in
a
King’s College Hospital, London SE5.
TABLE II-EFFECT OF PRACTOLOL ON PLASMA-CHOLESTEROL CONCENTRATION AFTER ACUTE MYOCARDIAL INFARCTION
continued for several weeks, this outbreak lasted for only 3 days and there were no secondary cases. Virology.-Adenovirus-like particles were found in fæces from four of the six children affected and from the nurse, but not from any of the other thirteen children. Salmonellse, shigellae, and enteropathic strains of E. coli were not found. Despite continuous efforts over several
NEW APPROACH TO MANAGEMENT OF INTRACRANIAL ANEURYSMS *
months in the Birmingham and Shrewsbury laboratories, and more recently in the Central Public Health Laboratory at Colindale, all attempts, using a wide variety of tissuecultures, failed to isolate the adenoviruses from the faeces. Feeble cytopathic effects were seen in some HEp2 cultures after 10-20 days’ incubation, but virus could not be subcultured from them. The adenoviruses in clarified faecal suspensions were much more strongly agglutinated by antisera to adenovirus type 7 than by antisera to other types. Luton6 found this method of typing to be reliable. The result was surprising because adenovirus type 7 was not regarded as a difficult virus to isolate, and we ourselves had never found it to be so.
Summary relieve the tension on intracranial aneurysms by temporarily clamping the internal carotid artery in the neck, so as to increase the expansibility of the artery. This approach was based on the concept (or "A principle ") that hæmorrhage is caused by the aneurysm having to bear the full force of systolic pulse pressure when atherosclerosis prevents this pressure being taken up by the normally expansile arterial wall. Follow-up has been fairly
Discussion In 50 to 60 % of cases of acute diarrhoea in young children, rotaviruses can be seen in the fæces 1—4 No rotaviruses were seen in our second outbreak; one child had previously had rotavirus diarrhoea in the first outbreak and was known to have antibodies to that virus. In the first outbreak rotaviruses were only seen in children with diarrhoea or " loose stools "; virus excretion did not continue after diarrhoea ceased. Carriers or sub-clinical cases were not found-in contrast to enteroviruses which commonly produce symptom-free infection. Electron microscopy of faeces enabled us to disthe adenoviruses quickly and to assign a provisional serotype to them, although we could not establish them in tissue-culture. cover
In the first outbreak one child seems to have the virus into the ward and transmitted it to others either directly or indirectly. The very similar virus of calf diarrhoea retains full infectivity in fasces kept for 7 months at room temperature.7 It is reasonable to expect that the human virus will also be stable, and that it may persist in the environment In the unless destroyed by careful disinfection. second outbreak, adenoviruses seem to have come from a common unknown source and to have affected several children at the same time.
brought
We thank Sister E. J. Greasley and Sister B. Sakuntanaga for their help in investigating these outbreaks; the Shrewsbury public-health laboratory staff and Mr R. E. Hadley for technical help; and Dr M. G. Pereira and Dr P. G. Higgins for their attempts to isolate the adenoviruses.
Requests for reprints should be addressed
to
T. H. F.
REFERENCES
Flewett, T. H., Bryden, A. S., Davies, H., Woode, G. N., Bridger, J. C., Derrick, J. M. Lancet, 1974, ii, 61. 2. Bishop, R. F., Davidson, G. P., Holmes, I. H., Ruck, B. J. ibid. 1974, i, 149. 3. Flewett, T. H., Davies, H., Bryden, A. S., Robertson, M. J. J. clin. Path. 1974, 27, 608. 4. Middleton, P. J., Szymanski, M. T., Abbott, G. D., Bortolussi, R., Hamilton, J. R. Lancet, 1974, i, 1241. 5 Bridger, J. C., Woode, G. N. Br. vet. J. (in the press). 6. Luton, P. J. clin. Path. 1973, 26, 914. 7. Woode, G. N., Bridger, J. C. Personal communication. 1.
W. J. ATKINSON Hurstwood Park
Hospital, Haywards Heath,
In six
cases an
attempt
was
Sussex
made to
short, but the preliminary findings in four of the six patients are encouraging. More attention must be paid in the future to the significance of atherosclerosis in the onset of bleeding from intracranial aneurysms and the incidence of postoperative problems. The argument that atherosclerosis permits the transmission of the systolic pulse directly to the aneurysm wall requires further investigation. The earlier pathological signs of atherosclerosis must receive greater attention, and post-mortem study of the walls of arteries in immediate juxtaposition to aneurysms with highpowered magnification is required. Introduction THE high mortality and morbidity which follow both conservative and surgical treatment of patients with intracranial aneurysms have led to attempts to take a new look at the problems of causation and therapy. One difficulty with the argument that intracranial aneurysms arise from congenital lesions is that the considerable majority " bleed " only after the age of 40. One explanation for this is the onset of atherosclerosis. In the early life of arteries, the systolic impulse in arterial walls is seen and felt as an expansion of the wall; the pulse has its systolic component. The pulse wave (i.e., the expansion of the wall) travels along the artery rather like the peristaltic wave in the oesophagus and gut but from a different cause, the heart in systole. When the artery is affected by atherosclerosis its wall becomes less elastic, so that when the systolic pulse wave travels to the periphery the blood-flow pressure is transmitted directly to the periphery and is not taken up by the expansion of the arterial wall. Because intracranial aneurysms lie at the fork junction of two branches of the artery, the blood-flow pressure in systole is transmitted more or less directly to the mouth of the aneurysm. Therefore, whereas previous to the onset of atherosclerosis each systolic wave of pressure was absorbed by the expansion of the arterial wall and the arterial bloodflow pressure at the periphery was less, now, with hardening of the arterial wall in atherosclerosis, each systolic wave of pressure is transmitted directly to the aneurysm, its contents, and wall. On this model (or " A principle ") atherosclerosis *
Based on a paper read at a meeting of the Academy of American Neurosurgeons and the Society of British Neurological Surgeons, held in Bermuda on Nov. 7, 1974.
6 SUMMARY OF CASES
A.c.c. = Anterior communicating artery. Int. car. Intracranial part of internal carotid artery. N=Normal. =
S
=
with subarachnoid haemorrhage. She had persistent headache for the next 5 months with weakness of right hand and foot. Arteriography (fig. 1) revealed a large aneurysm at junction of anterior communicating and left anterior cerebral arteries. Each anterior cerebral artery filled from its own side, but the right carotid arteriogram filled both anterior cerebral arteries. Patient right-handed. On April 25, 1972, the left internal carotid artery was clamped with two artery clamps for 1 hour under local anaesthesia and then released. The patient fully conscious, orientated, and without neurological symptoms throughout operation and subsequently. Now complains of occasional pain in right side of head and noise in head on left side. Personality, that of a fearful apprehensive woman, unchanged.
Case 2
Satisfactory.
D = Died.
leads to a more direct transmission of higher systolic pressure to the aneurysm, puts a greater strain on the wall, and leads to haemorrhage. Efforts to prevent the higher systolic pressure reaching the aneurysm might avert haemorrhage. This could be done by causing the arterial wall proximal (i.e., towards the heart) to the aneurysm to expand and so take up the systolic pressure. I have tried clamping the internal carotid artery in the neck in such a way as to contuse and break up the muscle and intimal layers of the arterial wall. Initially, when the clamps were released (slowly), there was a considerable expansion of the entire wall where it had been injured. I describe here the results with this surgical approach in six cases. The six cases are summarised in the table.
Aged 64. Acute subarachnoid haemorrhage 4 days before admission with confusion and drowsiness; disorientated;
Case-reports Case 7 -
Aged SO. This woman was first seen in November, 1971, with acute onset of headache and neck pain, but no loss of consciousness. Clinical diagnosis suggested aneurysm
2-Case 2 : anteroposterior arteriogram showing saccular aneurysm projecting upwards from bifurcation of left internal carotid artery.
Fig.
both
plantar responses extensor. Arteriography showed a saccular aneurysm arising vertically from junction of left internal carotid and middle cerebral arteries (fig. 2). On May 23, 1972, 12 days after onset of subarachnoid haemorrhage, left internal carotid artery was clamped for 1 hour under local anaesthetic and then released with no ill-effects. Steady recovery of ambulant state and retired life. When seen 2 years later, he had left-sided headache occasionally and angina pectoris but he leads similar life to pre-hæmorrhage state. Both superficial temporal pulses palpable. Bruit heard in left side of neck over carotid arteries. Case 3
Mt. l—Case
1: aneurysm in
anteroposterior arteriogram showing large region of left anterior cerebral artery.
Aged 44. Psychiatric observation for 8 years. Intracranial bruit noticed by patient for 20 years. Always stops when head turned to right and on pressing centre spot in left side of neck. Began suddenly, 20 years ago. No other neurological symptoms or signs apart from left deafness. Arteriography showed small sessile aneurysm 1 cm. below the bifurcation of the left internal carotid artery in the head. On Aug. 12, 1972, clamping of left internal carotid artery in the neck for 1 hour. No illeffects. Noise ceased. 1 year later noise returned in left
7 ear
similar
to
original symptom;
no
other
neurological
signs. Cas
Aged 51. Acute onset of subarachnoid haemorrhage 24 No loss of consciousness or hours before admission.
neurological symptoms except for meningism. Hypertensive, blood-pressure 180/120 mm. Hg. Arteriography showed that both anterior cerebral arteries filled from left side and revealed a large saccular aneurysm arising from the region of the anterior communicating artery. On July 18, 1972, 3 days after admission, left internal carotid artery clamped in the neck over a 2 cm. area with three artery clamps for 1 hour. No neurological symptoms or signs developed in that time and the clamps were released. The next day a mild right flaccid hemiparesis developed. This had disappeared by the time of his discharge home 3 weeks later. 1 year later, he complained of headaches at the back of his head. Had returned to work and was his former self in personality and work value. Bruit heard left side of neck. B.P. 220/120 mm. Hg despite hypotensive drugs and supervision by cardiologist.
Case 5
Aged 63. This patient had been followed up since March, 1968, when he had had an acute subarachnoid hemorrhage, loss of speech, and right hemiparesis, with subsequent complete recovery. He had then developed the ensuing years blindness of the left eye and finally loss of the right temporal half-vision. On one occasion, 6 months previous to this final stage, he had lost vision completely during an episode of headache and vomiting which had lasted for 2 days and been followed by recovery of right nasal vision only. Anxiety for his remaining vision prompted ophthalmologist and patient to seek further treatment of his intracranial aneurysm which had " initially been huge ", arising from the anterior communiover
Fig. 3-Case 5: oblique arteriogram showing aneurysm of left anterior cerebral artery (March, 1968).
artery (as seen in the left internal carotid arterioin 1968) (fig. 3). There was good cross-circulation gram from the right side in the right common carotid arteriogram. He was right-handed. In July, 1973, the left internal carotid artery was clamped in the neck for a period of 15 minutes under local 2 anaesthetic without onset of any neurological signs. days subsequent to this he developed dysphasia and right hemiparesis. These symptoms steadily improved over the ensuing 6 months, but he was left with poverty of fine finger movements of the right hand and slight hesitancy of speech. To date his vision remains unaltered with preservation of right nasal vision in the right eye only.
eating
Case 6
Aged 48. Subarachnoid hxmorrhage 1 day before admission without loss of consciousness or other neuro-
logical signs. B.P. on admission 160/86 mm. Hg. Right carotid arteriography showed that both anterior cerebral arteries filled from that side, and a lobular aneurysm arose from the anterior cerebral artery at the junction of the transverse and ascending part (fig. 4). On the left carotid arteriography the anterior cerebral artery did not fill at all on either side, but on crossed compression some contrast passed from the left to the right. On March 14, 1973, right common carotid artery clamped over a distance of 2 cm. for 15 minutes and then sheathed with ’Teflon ’ gauze. For the next 14 days she had a gradually improving left hemiplegia. In the period April 24-30, 1973, she was well, although drowsy. The drowsiness fluctuated for the next 3 days, and then, on May 3, having been well, she suddenly lost consciousness and died. Necropsy showed haemorrhage into the right frontal lobe and ventricular system from the region of the aneurysm of the right anterior cerebral artery. Seven weeks after crushing the common carotid artery and wrapping it with ’Dacron’ (teflon), the muscle coat and
Fig. 4-Case 6: carotid arteriogram showing aneurysm arising from junction of anterior communicating and anterior cerebral arteries (anteroposterior view).
8
removed while the tape around the common carotid artery was pulled to occlude the blood-flow. The tape was released slowly so that the contused arterial walls, which were at this stage adherent in the line of the clamps, re-expanded gradually. At this stage the patients complained of headache which abated in the course of 1-3 hours. The tape was finally removed and the platysma and skin layers were sutured.
were
Discussion The surgical approach tried here is based on the proposition that atherosclerosis is the main event lead-
haemorrhage from intracranial aneurysms and operation which leads to weakening and expansibility of the internal carotid arterial wall in
ing
that
to
an
the neck may prevent further haemorrhage from such aneurysms. The effect of atherosclerosis in taking away the original expansibility of the arterial wall is to impose greater strain of the aneurysmal wall. If Fig. 5--Case 6: low-power view of clamped section of common this effort can be nullified, then the aneurysmal wall carotid artery. will once more meet the systolic pulse pressure at a lower level. Direct surgical attack on the aneurysms of this series of six cases was not considered justifiable for various reasons, which included the size of the aneurysm, the age of the patient, the poor prospect of collateral circulation with both anterior cerebral artery supplies coming from one side only. Also, conservative treatment was considered unwise chiefly because there was strong evidence of risk of further complications to the patient. Accessible intracranial aneurysms will continue to be occluded surgically where the risk of physical and mental postoperative defect is likely to be slight. The site at the junction of the anterior cerebral arteries with the anterior communicating vessel is notoriously difficult of access, and it is impossible to predict the degree of mental deficit after operation. The incidence of infarction in the anterior cerebral artery territory is high when the proximal part of the anterior Fig. 6—Case 6: inner aspect of common carotid artery 7 weeks cerebral artery which supplies an aneurysm at this after clamping (minus sheath). site is occluded as a definitive form of treatment. The elastic lamina had disappeared as shown in fig. 5. Given that the atherosclerotic effect on the systolic vessel wall consists mainly of young, vascular connective pulse pressure is to inflict greater strain on the A marked giant-cell reaction was present in the tissue. wall at this site than occurs at an earlier aneurysmal 6 neighbourhood of where the dacron had been. Fig. non-atherosclerotic age, then it would seem that proshows the appearance of the right common carotid artery cedures designed to restore the expansibility of the post mortem without the dacron sheath. The total length of crushing at the time of the operation by the three proximal arterial wall are justified; this line of argu9 was mm. clamps ment is referred to as the " A principle ". To do so at the site of the proximal part of the anterior cerebral Operation artery would seem to promote an artificial aneurysmal Under local anaesthetic, injected superficially and problem beneath the frontal lobe-with all its own an difficulties. In the neck, it is anticipated that the incision the anterior border deeply, through along of the sternomastoid muscle, the carotid sheath was formation of a false aneurysm of the internal carotid dissected free to identify the bifurcation of the comartery would not be beyond the remedial powers of mon carotid artery, the common carotid artery itself, a vascular surgeon. It may well be that a stenosis, and its external and internal branches. A tape was and not a false aneurysm, arises slowly at the site of passed around the common carotid artery. Three clamping. This too would lower the systolic pulse artery clamps were placed on the internal carotid pressure on the aneurysm in the head and would also be amenable to vascular surgery if necessary. It is artery for 1 hour in the first three cases and 15 minutes in the later cases, except in case 6 where possible that the insertion of a living expansible graft into the internal carotid artery would produce better the common carotid artery only was clamped. During this time the patient was tested for speech and moveeffects than merely clamping that artery, but the Thereafter the clamps ments of the opposite limbs. reasoning behind the A principle will not be accepted
9
until it is shown by further study that it
can
be
validly
in
therapy. of hypotensive drugs would seem to be an essential corollary to the treatment of intracranial aneurysms if the A principle is accepted. In studying the use of these drugs by physicians in the treatment of arterial hypertension I have noticed that their routine administration does not necessarily lead to a persistent reduction of high systemic arterial blood-
applied The
use
pressure, and yet such treatment does lower the incidence of complications in the condition of arterial hypertension and atherosclerosis. Perhaps the antiadrenergic agents not only serve to reduce the arterial blood-pressure but also increase the expansibility of arterial walls by the reduction of the muscle tone in the arterial walls. If this is true then the use of these drugs must assist in the treatment of intracranial aneurysms because the reduction of muscle tone in arteries leading to the aneurysm will lead to greater expansibility of the arterial wall and so reduce the systolic pulse pressure at the site of the aneurysmso long as that vessel can still possess muscle tone and is not wholly atheromatous.
EFFECTS OF LONG-TERM PRACTOLOL THERAPY ON PLASMA-LIPIDS AFTER ACUTE MYOCARDIAL INFARCTION A. M. G. COCHRANE * D. DE BONO University of Cambridge and Addenbrooke’s Hospital, P. GHOSH
Cambridge In
Sum ary
double-blind controlled trial last12
months, long-term practolol significant effect on plasma-lipid concentrations in twenty patients who had had acute
therapy
ing
a
had
no
myocardial infarction.
Patients and Methods Patients included in this study had been admitted to Addenbrooke’s Hospital with myocardial infarction. The diagnosis was based on at least two of the following W.H.O. criteria: unequivocal electrocardiographic changes; typical history and clinical features of infarction; and raised levels of serum glutamic oxaloacetic transaminase and hydroxybutyrate dehydrogenase. Patients over the age of 70, and those in whom /3-blocking drugs were contraindicated, were excluded. All patients included in the trial had given their informed consent. Patients were allocated to control and treatment groups on the basis of coded numbers. The key to the code was not known to the investigators until after the study was completed. Treatment was usually initiated 14-21 days after infarction. Patients in the treatment group received 200 mg. of practolol twice daily (in some patients this was -later reduced to 100 mg. twice daily) and those in the placebo group received identical placebo tablets. The placebo group included sixteen males and three females and the praotolol group had nineteen males and The average age in the placebo group was 55 one female. years (range 40-68 years), and in the practolol group it was 52 years (range 34-67 years). The mean body-weights were 158 lb. (70-2 kg.) (range 133-192 lb.) and 161 lb. (71-5 kg.) (range 123-220 lb.), respectively. Patients were seen at 1, 3, 6, and 12 months after starting treatment. Venepuncture was done after a 12-hour fast, and the samples of plasma were analysed by semiautomated techniques for triglyceride6 and cholesterol7 concentrations. In addition, the lipoprotein pattern was
determined electrophoretically
on
cellulose
acetate
using
0-00238M Gelman high-resolution buffer (pH 8-8) and staining with Schiff’s reagent. Triglyceride concentrations of samples showing chylomicrons on lipoprotein electrophoresis were excluded from the final analysis. Two patients had to be withdrawn from the treatment group, and six from the control group, because of side-effects or because their medical condition had altered. The withdrawals in the practolol group were due to shortness of breath or persistent ventricular ectopic beats. No unusual cutaneous or ocular lesion 8 was seen in this small group during this particular period of study. .TABLE I-RESULTS OF PLASMA-TRIGLYCERIDE CONCENTRATION AFTER ACUTE MYOCARDIAL INFARCTION
Introduction DRUGS blocking adrenergic &bgr; receptors have been shown to inhibit catecholamine-induced lipolysis in vitro, and to block the increase in plasma-non-
esterified-fatty-acid which normally accompanies catecholamine infusion in vivo.23 Wegener et a1.4 claimed that propranolol could lower serum esterified fatty acid and cholesterol concentrations in patients with a "hyperkinetic cardiac syndrome"; however, their was not adequately controlled. Lloyd-Mostyn al.‘ were unable to repeat these results in a wellcontrolled cross-over trial, but the length of treatment (2 weeks) was relatively short. As yet there has been no long-term controlled study of the effect of a &bgr;-
study
et
plasma-lipid multicentre, double-blind trial to determine the efficacy of practoin preventing dysrhythmias after acute myocardial infarction provided us with an opportunity to investigate the effect of prolonged therapy with this &bgr; blocker on plasma-lipid concentrations. adrenergic-receptor-blocking drug concentrations. Our participation
* Present address:
on
in
a
King’s College Hospital, London SE5.
TABLE II-EFFECT OF PRACTOLOL ON PLASMA-CHOLESTEROL CONCENTRATION AFTER ACUTE MYOCARDIAL INFARCTION
