surgical and medical approach seems to offer no advantage in mild disease, although it is the method most favoured in advanced cases.' 17 Where in vitro fertilisation is available as an option, results often compare unfavourably with its use for uncomplicated tubal block.27 The debate about management continues, awaiting the publication of large scale randomised controlled trials. In the meantime the choice of treatment is usually based on anecdotal experience and local preferences. Extensive disease remains a cause of considerable morbidity, for which the only definitive treatment is surgical castration. A greater understanding of the aetiology, pathogenesis, and natural course of the condition is long overdue. C P WEST
Consultant Gynaecologist, University of Edinburgh Centre for Reproductive Biology, Edinburgh EH3 9EW
I Te Linde RW. Endometriosis. In: Te Linde RW, ed. Operative gynaecology. London: Pitman, 1962: 505-31. 2 Simpson JL, Elias S, Mlalinak LR, Buttram VC. Heritable aspects of endometriosis. I. Genetic studies. Amj Obstet GsNiecol 1980;137:327-3 1. 3 Strathy JH, Molgaard CA. Coulam CB, Melton LJ. Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women. Fertil Steril 1982;38:667-72. 4 Jones HW. Rock JA. Other factors associated with infertility. In: Pepperell RJ, Hudson B, Wood C, eds. The inifertile couple. Edinburgh: Churchill Lisingstone, 1987: 181-207. 5 Templeton AA, Kerr MG. An assessment of laparoscopy as the primarv investigation in the subfertile female. Br] Obstet Gx'naecol 1977;84:760-2.
6 Hull MGR, Glazner CMA, Kelly NJ. et al. Population study of causes. treatment, and outcome of infertility. BrMedJ 1985;291:1693-7. 7 Cates WX, Farley TMM, Rowe PJ. Worldwide patterns of infertility: is Africa different? Lancet
8 Muse KN, Wilson EA. How does mild endometriosis cause infertility? FertilSteril 1982;38:145-52. 9 Bancroft K, Vaughan Williams CA, Elstein M. Minimal/mild endometriosis and infertility. A review. BrJ Obstet Gynaecol 1989;96:454-60. 10 Schmidt CL. Endometriosis: a reappraisal of pathogenesis and treatment. Fertil Steril 1985;44: 157-73. 11 Seibel MM, Berger MJ, Weinstein FG, Taymor ML. The effectiveness of danazol on subsequent fertilitv in minimal endometriosis. Fertil Steril 1982;38:534-7. 12 Thomas EJ, Cooke ID. Successful treatment of endometriosis: Does it benefit infertile women? Br
Medj 1987;294:1117-9. 13 Telimaa S. Danazol and medroxyprogesterone acetate inefficacious in the treatment of infertility in endometriosis. Fertil Steril 1988;50:872-5. 14 Schenken RS, Malinak LR. Conservative surgery versus expectant management for the infertile patient with mild endometriosis. Fertil Steril 1982;37:183-6. 15 Hull ME, Moghissi KS, Magyar DF, Hayes MF. Comparison of different treatment modalities of endometriosis in infertile women. FertilSteril 1987;47:40-4. 16 Thomas EJ, Cooke ID. Impact of gestrinone on the course of asymptomatic endometriosis. BrMedJ 1987;294:272-4. 17 Olive DL, Haney AF. Endometriosis-associated infertility: a critical review of therapeutic approaches. Obstet Gynecol Surv 1986;41:538-55. 18 American Fertility Society. Revised American Fertility Society classification of endometriosis. FertilSteril 1985;43:351-2. 19 Evers JLH. The second-look laparoscopy for evaluation of the results of medical treatment of endometriosis should not be performed during ovarian suppression. Fertil Steril 1987;47:502-4. 20 Pittaway DE, Fayez JA. The use of CA-125 in the diagnosis and management of endometriosis. FertilSternl 1986;46:790-5. 21 Shaw RW. LHRH analogues in the treatment of endometriosis-comparative results with other treatments. Bailliere's Clin Obstet Gynaecol 1988;2:659-75. 22 Allen JK, Fraser IS. Cholesterol, high density lipoprotein and danazol. j Clin Endocrinol Metab 198 1;53:149-52. 23 Murphy AA. Operative laparoscopy. Fertil Steril 1987;47:1-18. 24 Sutton C, Hill D. Laser laparoscopy in the treatment of endometriosis. A 5-year study. BrJ Obstet Gynaecol 1990;97:181-5. 25 Jansen R, Russell P. Nonpigmented endometriosis: clinical, laparoscopic and pathological definition. -AmJ Obstet Gynecol 1986;155:1154-9. 26 Cheng VS. Ureteral injury resulting from laparoscopic fulgation of endometriosis implants. AmJ Obstet Gvnecol 1976;126:1045-7. 27 Matson PL, Yovich JL. The treatment of infertility associated with endometriosis by in vitro fertilisation. Fertil Steril 1986;46:432-4.
Warning leak in subarachnoid haemorrhage All too often the diagnostic importance of a warning headache is missed The diagnosis of aneurysmal subarachnoid haemorrhage is easy when the presentation follows the classic pattern: a very severe headache associated with stiff neck, photophobia, and nausea and vomiting, often with loss of consciousness. Neurosurgeons, who have the benefit of hindsight, are aware that about half of the patients they see with aneurysms have experienced minor bleeding episodes days to several months before their major haemorrhage.'6 The recognition of these "warning leaks" probably offers the best opportunity for altering the otherwise serious prognosis of aneurysmal subarachnoid haemorrhage,/ but they often are misinterpreted.4-6 The most common symptom of a warning leak is headache. It is often accompanied by transient nausea, vomiting, and neck pain and is often so unusual in severity and location that medical advice is sought.46 The site of the headache seems to be a poor localising symptom for the aneurysm-with the exception of internal carotid-posterior communicating aneurysms, in which the headache often is ipsilateral and retro-orbital.3 46 The warning headache usually subsides over one or two days,4 but in some cases it is unremitting for as long as two weeks or until a subsequent major haemorrhage occurs. 6
About two thirds of the patients with a warning headache have associated signs and symptoms such as nausea and vomiting, meningism, neck pain, visual disturbances, and motor or sensory disturbances.36 Nausea or vomiting, or both, seem to be characteristic in patients with anterior communicating aneurysms and anterior cerebral aneurysms, whereas motor weakness and speech disturbances often reflect an aneurysm of the middle cerebral artery.3 Another characteristic warning feature in patients with an aneurysm of 190
the internal carotid artery is impairment of the extraocular muscles due to third nerve palsy. Waga et al in a retrospective study found this symptom in one patient in four with a warning leak and an aneurysm of the internal carotid artery.3 The five largest series of patients with warning signs and intracranial aneurysms comprise a total of 629 patients, and the data show that about 50% (range 28-60%) of patients with a bleeding saccular aneurysm admitted to a neurosurgical department will have had a premonitory warning leak.2 6 In series of patients with aneurysms that include those who die before receiving medical attention the proportion has been estimated at 15-20%.9 Possibly, as many as 60% of all patients with aneurysms who eventually have a major haemorrhage will have had one or more warning signs weeks or months before the event. The incidence may be slightly higher in women than in men.2 3 Pathological examination of aneurysms from patients who had had warning signs often shows minor haemorrhages in the wall of the aneurysm and adherence of the aneurysm to the contiguous brain through reactive changes.'" I This evidence suggests that warning signs are due to a minor leakage of blood into the subarachnoid space, hence the term "warning leak."2 6 1' Other explanations that have been proposed for the forewarnings of major subarachnoid haemorrhage include a sudden expansion of the aneurysm and ischaemia due to cerebral vasospasm.2 12 In the large series of patients recorded as having features suggesting warning leaks, around half complained of their symptoms less than one week before the occurrence of the major haemorrhage.' 36In most of the remainder the major bleed occurred within a month, but in some patients the interval was years. There may be more than one warning BMJ
leak.2 3 The combination of a sudden onset of headache and pain in the neck and back seems to be the most urgent picture, but more extensive studies are necessary to evaluate the implications of the different warning signs. The overall outcome of treatment for ruptured cerebral aneurysms depends on a multiplicity of both medical and organisational factors. 13 Unfortunately, in patients with saccular aneurysms morbidity and mortality figures have not changed in recent decades -primarily because the diagnosis is still usually established only after rupture." II The second great problem is the lack of any explanation of vasospasm, which is the principal cause of death and disability among patients with aneurysms who reach hospital. One of the more important factors determining the ultimate outcome in a patient with a ruptured aneurysm is his or her clinical condition on admission. 16 Leblanc's prospective study of 87 patients consecutively admitted with subarachnoid haemorrhage from a cerebral aneurysm showed that 25 patients had had a minor leak followed by a major rupture, and of these only 10 (40%) were in good clinical condition on admission (Hunt and Hess stage- I-II'7), in contrast with 89% of those patients who had had only one bleeding episode.6 Not surprisingly, the mortality in those who had had a major rupture was three times higher than in those who had had only one bleed. The clinical benefit of recognising and treating the patient with an aneurysm before a major rupture occurs has been well documented by others.25 Indeed, the adverse prognostic effect of a missed warning leak is as severe as the effect of a clear cut sequence of rebleeding episodes, both when the rebleed complicates the hospital course'8-20 or when it occurs several years later.2' 22 Yet while the importance of recognising the minor leak seems obvious, no study has so far explained why it has such an adverse effect of prognosis. One explanation might be that the subarachnoid haemorrhage is more severe after a warning leak, but there is no evidence to support this. Recent observations have suggested that immunological processes may be concerned in the pathogenesis of cerebral
vasospasm,72326 in which case missed episodes of minor bleeding might predispose to its development and in this way affect the prognosis. The warning headache is often so unusual in severity and location that patients seek medical advice. In Leblanc's study this was true of four out of every 10 patients, but in no case was the correct diagnosis made.6 The warning leaks were all misinterpreted as attacks of migraine, tension headache, the flu, sinusitis, or a "sprained neck." Similarly, in Duffy's series eight of 13 patients with a warning symptom had consulted their general practitioners at the time of the warning leak.5 Five were admitted to hospital-but all were discharged without undergoing appropriate investigations for a possible intracranial haemorrhage. The tentative diagnoses made at consultation were tension headache, neck pain, gastroenteritis, hypertension, migraine, viral illness, temporal arteritis, and eye strain. What can we conclude? A minor leak should be suspected in those patients without a history of severe headaches who present with severe, unremitting, unusual pain in the head or face, particularly if it is hemicranial, hemifacial, or periorbital. Other signs of an aneurysm such as a third nerve palsy may also occur. Vomiting and photophobia certainly strengthen the case, and meningism does so even more; patients with these symptoms require urgent referral and need further investigation. Duffy has shown that computed tomography may be unreliable in showing the subarachnoid blood produced by a minor leak, and lumbar puncture is the examination of choice once computed tomography has ruled out an intracranial mass lesion or intracranial hypertension.' If xanthochromic staining of the cerebrospinal fluid is seen or if the cerebrospinal fluid is bloody after an atraumatic puncture then angiography should be performed promptly.
1 Gillingham FJ. The management of ruptured intracranial aneurysms. Scott Med J 1967;12: 377-83. 2 Okawara S-H. Warning signs prior to rupture of an intracranial aneurysm. J Neurosurg 1973; 38:575-80. 3 Waga S, Ohtsubo K, Handa H. Warning signs in intracranial aneurysms. Surg Neurol 1973;3: 15-20. 4 King RB, Saba MI. Forewarnings of major subarachnoid hemorrhage due to congenital berry aneurysm. NY State)' Med 1974;74:638-9. 5 Duffy GP. The warning leak in spontaneous subarachnoid haemorrhage. Med J Aust 1983;i:514-6. 6 Leblanc R. The minor leak preceding subarachnoid hemorrhage.J Neurosurg 1987;66:35-9. 7 Ostergaard JR. Risk factors in intracranial saccular aneurysms. Aspects on the formation and rupture of aneurysms, and development of cerebral vasospasm. Acta Neurol Scand 1989;80: 81-98. 8 Bonita R, Thomson S. Subarachnoid hemorrhage: epidemiology, diagnosis, management, and outcome. Stroke 1985;16:591-4. 9 Ljunggren B, Saveland H, Brandt L, Zygmunt S. Early operation and overall outcome in aneurysmal subarachnoid hemorrhage. J7 Neurosurg 1985;62:547-5 1. 10 Gillingham FJ. The management of ruptured intracranial aneurysm. Ann R Coll Surg Engl 1958;23:89-1 17. 11 Ball MJ. Pathogenesis of the "sentinel headache" preceding berry aneurysm rupture. Can Med AssocJ 1975;112:78-9. 12 Day JW, Raskin NH. Thunderclap headache: symptoms of unruptured cerebral aneurysm. Lancet 1986;ii: 1247-8. 13 Kassel NF, Drake CG. Timing of aneurysm surgery. Neurosurgery 1982;10:514-9. 14 Phillips LH, Whisnant JP, O'Fallon WM, Sundt TM. The unchanging pattern of subarachnoid hemorrhage in a conmmunity. Neurology 1980;30:1034-40. 15 Rosenorn J, Eskesen V, Schmidt K, et al. Clinical features and outcome in 1076 patients with
ruptured intracranial saccular aneurysms: a prospective consecutive study. Br J Neurosurg 1987;1:33-46. Disney L, Weir B, Grace M, and the Canadian Nimodipine Study Group. Factors influencing the outcome of aneurysm rupture in poor grade patients: a prospective series. Neurosurgery 1988;23: 1-9. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysm. J Neurosurg 1968;28:14-20. Locksley HB. Report on the cooperative study of intracranial aneurysms and subarachnoid hemorrhage. Section V, part I. Natural history of subarachnoid hemorrhage, intracranial aneurysms, and arteriovenous malformations. J Neurosurg 1966;25: 219-39. Drake CG. Management of cerebral aneurysm. Stroke 1981;12:273-83. Torner JC, Kassell NF, Wallace RB, Adams HP. Preoperative prognostic factors for rebleeding and survival in aneurysm patients receiving antifibrinolytic therapy: report on the cooperative study. Neurosurgery 1981;9:506-13. Winn HR, Almaani WS, Berga SL, Jane JA, Richardson AE. The long-term outcome in patients with multiple aneurysms. Incidence of late haemorrhage and implications for treatment of incidental aneurysms. J Neurosurg 1983;59:642-5 1. Nishioka H, Torner JC, Graf CJ, Kassels NF, Sahs AL, Goettler LC. Cooperative study of intracranial aneurysms and subarachnoid hemorrhage: a long-term prognostic study. II. Ruptured intracranial aneurysms managed conservatively. Arch Neurol 1984;41:1142-6. Pellettieri L, Carlson CA, Lindholm L. Is the vasospasm following subarachnoid hemorrhage an immunoreactive disease? Experientia 1981;37:1170-1. Hoshi T, Shimizu T, Kito K, et al. Immunological study of late cerebral vasospasm in subarachnoid hemorrhage: detection of immunoglobulin, C3, and fibrinogen in cerebral arterial walls by immunofluorescence method. Neurol Med Chir (Tokyo) 1984;24:647-54. Pellettieri L, Nilsson B, Carlson CA, Nilsson U. Serum immunocomplexes in patients with subarachnoid hemorrhage. Neurosurgery 1986;19:767-71. Ostergaard JR, Kristensen BO, Svehag S-E, Teisner B, Miletic T. Immune complexes and complement activation following rupture of intracranial saccular aneurysms. J Neurosurg 1987;66:891-7.
JOHN R 0STERGAARD Senior Registrar, Department of Paediatrics A, University Hospital of Aarhus, DK-8000 Aarhus C, Denmark
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