Aneurysmal subarachnoid haemorrhage in pregnancy

European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 131–143

Review

Aneurysmal subarachnoid haemorrhage in pregnancy Daniel O. Selo-Ojemea,*, Laurence A.G. Marshmanb, Amaju Ikomia, Dale Ojutikua, Robert A. Aspoasb, Sanjiv J. Chawdac, Gursharan P.S. Bawad, Manjit S. Raie a

Directorate of Obstetrics, Gynaecology and Paediatrics, Basildon and Thurrock University Hospitals NHS Trust, Nethermayne, Basildon, Essex SS16 5NL, UK b Department of Neurovascular Surgery, Oldchurch Hospital, Romford, Essex RM7, UK c Department of Neuroradiology, Oldchurch Hospital, Romford, Essex RM7, UK d Department of Anaesthesia, Oldchurch Hospital, Romford, Essex RM7, UK e Department of Medical Physics, Oldchurch Hospital, Romford, Essex RM7, UK Received 7 December 2003; received in revised form 23 February 2004; accepted 5 April 2004

Abstract Although uncommon, aneurysmal subarachnoid haemorrhage (SAH) in pregnancy can be devastating for both mother and baby. It is the leading cause of other indirect maternal death in England and Wales accounting for 60 deaths in the decade 1988–1999. No single obstetric or neurosurgical unit has sufficiently large database or experience in managing this condition in pregnancy. With significant improvements in antenatal care and management of deliveries, non-obstetric causes of maternal death such as aneurysmal subarachnoid haemorrhage are likely to become increasingly significant. The clinical features of aneurysmal subarachnoid haemorrhage closely resemble those of other commoner conditions seen in pregnancy. It is therefore imperative that awareness by obstetricians and other frontline staff is increased so that a high index of suspicion is maintained when pregnant women present with unique headaches. Prompt neurosurgical referral is vital and early involvement of an experienced neuroradiologist essential. It is only when an early diagnosis is made and an aggressive treatment instituted that the bleak case-fatality figure associated with aneurysmal subarachnoid haemorrhage in pregnancy can be improved. This review, by a multidisciplinary and multicenter team, provides a comprehensive update on the epidemiology, aetiology, clinical presentation, diagnosis and the complexities of the multidisciplinary management of this serious and potentially fatal condition when it occurs in pregnancy. # 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Subarachnoid haemorrhage; Pregnancy; Aneurysm

Contents 1. Introduction . . . . . . . . . . 2. Methodology . . . . . . . . . . 3. Epidemiology . . . . . . . . . 4. Aetiology . . . . . . . . . . . . 4.1. Pregnancy . . . . . . . 4.2. Genetic factors. . . . 4.3. Other factors . . . . . 5. Clinical features . . . . . . . 5.1. Symptoms . . . . . . . 5.2. Warning headache . 5.3. Signs . . . . . . . . . . 6. Complications . . . . . . . . . 6.1. Re-bleeding . . . . . . 6.2. Cerebral vasospasm

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

* Corresponding author. Fax: þ44-1277-229238. E-mail address: [email protected] (D.O. Selo-Ojeme).

0301-2115/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2004.04.016

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

. . . . . . . . . . . . . .

132 132 132 133 133 133 133 134 134 134 134 135 135 135

132

D.O. Selo-Ojeme et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 131–143

6.3. Death . . . . . . . . . . . . . . . . . . . . 6.4. Other complications . . . . . . . . . . 7. Diagnosis . . . . . . . . . . . . . . . . . . . . . . 7.1. Computed tomographic (CT) scan 7.2. Angiography . . . . . . . . . . . . . . . 8. Management . . . . . . . . . . . . . . . . . . . . 8.1. Unruptured aneurysm . . . . . . . . . 8.2. Ruptured aneurysm. . . . . . . . . . . 8.2.1. Endovascular embolisation. . . . . 8.2.2. Surgery . . . . . . . . . . . . . . . . . . 8.2.3. Medical management (Table 6) . 8.2.4. Anaesthesia . . . . . . . . . . . . . . . 8.2.5. Obstetric management . . . . . . . . 9. Conclusion . . . . . . . . . . . . . . . . . . . . . 10. Key points . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . .

135 135 135 136 136 136 136 137 137 138 139 140 140 140 141 141

1. Introduction

2. Methodology

Although aneurysmal subarachnoid haemorrhage (SAH) is an uncommon event in pregnancy, its consequences can be devastating for both mother and baby as it is associated with significant mortality and serious maternal morbidity [1]. In the UK, aneurysmal SAH is the leading cause of other indirect maternal death [2]. During the period from 1988 to 1999, there were 60 maternal deaths from aneurysmal SAH in England and Wales [2–5]. In 1990, Dias and Sekhar [1] found that of 154 pregnant patients with a verified intracranial haemorrhage, 77% were caused by a ruptured intracranial aneurysm. In general, despite considerable advances in the diagnosis and treatment of SAH, the case fatality rate continues to be grave [6,7]. Furthermore, SAH continues to be associated with a high incidence of misdiagnosis [8]. While about 12% of patients die before receiving medical attention [9], 40% of those hospitalised die within 1 month of the event, and of those who survive, more than one-third develop major neurologic deficits [10]. Since it is uncommon, not many obstetric and neurosurgical units have significant experience in the management of pregnancy-related SAH. Indeed, the literature on the subject is sparse, and consists mostly of small case series and isolated case reports [11–21]. Nevertheless, as we continue to make significant improvements in antenatal care and management of deliveries, non-obstetric causes of maternal death such as aneurysmal SAH are likely to become increasingly significant causes of maternal mortality and morbidity. Thus, it becomes imperative that obstetricians and other frontline staff have a high index of suspicion so that the bleak case-fatality figures of aneurysmal SAH in pregnancy might be potentially ameliorated, through early diagnosis and timely intervention. This article, by a multidisciplinary and multicenter team, aims to provide an up to date review of the aetiology, clinical features, diagnosis and the intricacies of the multidisciplinary management of aneurysmal SAH in pregnancy.

A MEDLINE search via PubMed from 1 January 1966 to July 2003 using the search terms ‘pregnancy’, ‘subarachnoid haemorrhage’, ‘aneurysm’, non-traumatic/atraumatic, ‘endovascular embolisation’, and ‘anaesthesia’ was performed. Only articles in the English language were considered. All published case reports and case series on pregnancy related SAH, review articles on SAH as well as cerebral haemorrhages in pregnancy along with other articles that illuminate the subject in general were considered relevant and selected for review. Additional material was obtained from the reference list of selected articles.

3. Epidemiology In general, there is a wide variation in the incidence of SAH reported in different countries. For example, it is high in the United States, Finland and Japan [6] but low in New Zealand and the Middle East. Typically, the incidence varies with age and race, being more common in African Americans than in white Americans [22]. A review of 13 epidemiological studies has suggested an approximate incidence of 10 per 100,000 population (with a range of 6.5–26.4 per 100,000). SAH is consistently more frequent in women. Although no reliable data exist, the incidence of SAH is thought to be increased during pregnancy [1,23] complicating as many as 20 per 100,000 deliveries [23–26]. Furthermore, there is some tendency towards an increased incidence with increasing maternal age and parity [10]. Generally, increased plasma volumes associated with pregnancy, along with higher rates of pregnancy-induced hypertension within certain sub-groups, would constitute plausible factors in explaining such increased risk [1]. Indeed, some have found the risk of rupture to parallel the haemodynamic changes associated with pregnancy, reaching an apex in the third trimester [1,27].

D.O. Selo-Ojeme et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 131–143

The anatomical distribution of intracranial berry aneurysms during pregnancy is similar to that found in the general population. Typically found at the bifurcations of major vessels associated with the circle of Willis, Berry aneurysms are multiple in up to 33% of SAH [28], and familial in 5– 10% [29]. The gross haemodynamic fluctuations associated with labour and delivery, particularly in association with ‘bearing down’ efforts, might be expected to be associated with increased rates of aneurysmal rupture. This notion, however, had been previously questioned. For example, in a retrospective review of 118 patients with verified ruptured arterial aneurysms, Dias and Sekhar [1] found that 90% of ruptures occurred during pregnancy, 8% during the puerperium and 2% during labour and delivery. Nevertheless, assuming durations for pregnancy, labour and delivery, and early puerperium of 6720, 12 and 240 h, respectively, the above figures would translate to rates of 1:58  102 , 1:67  101 and 4:17  102 h—that is, considerably more aneurysmal SAH during labour and delivery. This fact is well illustrated graphically by Stoodley et al [30].

4. Aetiology Whilst the most frequent cause of SAH is a ruptured cerebral aneurysm (and the only cause discussed in this review) it is important to note that numerous other causes abound, as listed in Table 1. The underlying pathology in Table 1 The causes of SAH Common Berry aneurysm Arterio-venous malformation Unknown Rare Non-saccular (fusiform) aneurysms Atherosclerotic aneurysms Mycotic aneurysms Oncotic aneurysms Dissecting aneurysms Traumatic aneurysms Blood dyscrasias Coagulopathy Disseminated intravascular coagulopathy Anticoagulants Myeloproliferative disorders Vasculopathies Connective tissue disorder Heno¨ ch Scho¨ nlein purpura Rheumatic fever Moya Moya Drugs Amphetamines Anabolic steroids Eclampsia

133

intracranial aneurysmal formation and rupture is a weakness of the vessel wall. It has been noted that aneurysms arising from intracranial arteries are considerably more common than those arising from extracranial arteries of similar size. This fact probably relates to the frequency of defects within the tunica media (particularly at points of bifurcation) of cerebral vessels, combined with their singular lack of an external elastic lamina [27–31]. However, certain other factors have also been implicated in the predisposition of intracranial arteries to aneurysm formation and rupture. 4.1. Pregnancy There may, potentially, be up to a five-fold increased risk of an intracranial haemorrhage during pregnancy [32,33]. The physiological hormonal and haemodynamic changes of pregnancy are thought induce specific alterations on the arterial and venous intima in addition to changes in the organisation and content of the media [25,34]. In general, some of the effects of pregnancy on arterial integrity include the formation intimal hyperplasia, and, changes in the arterial media along with fragmentation of reticulum fibres, decrease in acid mucopolysaccharides and loss of the normal corrugation of elastic fibres [25]. These changes, mediated by increased levels of oestrogen, progesterone, human chorionic gonadotrophin and more importantly, relaxin, potentially predispose to aneurysm formation, enlargement and rupture [35] and thus may be reflected in increased rupture rates as pregnancy progresses [1,27]. Indeed, as observed by some authors [25,30], one-half of all ruptured arterial aneurysms (including those of visceral and renal arteries) in women under the age of 40 years are pregnancy related. 4.2. Genetic factors There is a growing body of evidence that implicates genetic factors in the pathogenesis of intracranial aneurysms [36]. It is known that intracranial aneurysms are strongly associated with heritable connective-tissue disorders such as the autosomal dominant polycystic kidney disease [37]. Furthermore, a familial occurrence has been noted with the risk of intracranial aneurysm among first-degree relatives of patients with aneurysmal SAH being four times higher than the risk in the general population [37]. This was recently confirmed by a Danish study which found that first degree relatives of patients with SAH have a three- to five-fold increased risk of SAH when compared with the general population [38]. 4.3. Other factors Cigarette smoking has consistently been identified in population studies as a predisposing factor to aneurysmal SAH and the risk is increased 3–10-fold [39–41]. A moderate to high level of alcohol consumption is also an identified risk factor [41].

134

D.O. Selo-Ojeme et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 131–143

Table 2 Factors associated with aneurysmal dilatation and rupture Meningeal infections Blood dyscrasias Inherited vascular diseases Trauma

Tumours Congenital abnormalities Inflammatory processes Connective tissue disorders

Hypertension has been shown to be associated with an increased risk of aneurysmal SAH [40] but it is thought that the risk posed is not as high as that associated with smoking. In pregnancy however, hypertension is associated with 10– 20% of SAH [25,34,42,43] and is a factor in a third of those that are fatal. For example, eclampsia or pre-eclampsia is present in 14–40% of intracranial haemorrhages associated with pregnancy [33,44]. Other factors [45] leading to arterial aneurysmal formation and rupture are listed in Table 2. It is noteworthy that in 5–10% of cases of spontaneous SAH, no causative lesion or predisposing trigger can be identified [46]. In one series of 500 non-pregnant patients, 34% of SAHs developed during non-strenuous activities and 12% during sleep [8,47].

5. Clinical features The clinical features of an aneurysmal SAH in pregnancy do not differ from those in the general population. The initial haemorrhage may be fatal, result in devastating neurological outcomes, or may produce relatively minor symptoms. 5.1. Symptoms The characteristic symptom of an aneurysmal SAH is a unique headache that is severe and of sudden onset. It is variously described as ‘‘an explosion within the head’’, ‘‘the worst headache of my life’’, ‘‘as if some one hit me on the head with a bat’’ or ‘‘as if something burst inside my head’’ [8,17,19,48]. The headache, which is usually suboccipital or frontal, may be associated with nausea and vomiting [20]. There may be blurring of vision, neck stiffness and photophobia. In some cases, focal neurological disorders (suggesting intracerebral haematomas) and coma may be present from the outset. Headache is a common symptom in the pregnant and nonpregnant population. In the latter, 1–4% of all patients with headaches that are serious enough to necessitate presentation at an emergency department have a subarachnoid haemorrhage [49,50]. When the presentation is ‘‘the worst headache ever’’, the incidence of SAH rises to 12% [51] increasing to 25% if this symptom is associated with clinical signs [52]. Thus, a high index of suspicion must be maintained when a pregnant woman presents with a uniquely severe headache.

Occasionally, the headache begins less dramatically, raising other diagnostic possibilities such as pre-eclampsia, migraine, cerebral venous thrombosis and meningitis. 5.2. Warning headache When the typical headache precedes aneurysmal rupture by several days or weeks, it is referred to as a warning headache. This phenomenon occurs in about 20–50% of patients with documented SAH [53–55]. The headache, which may be localised or generalised, can be mild and either resolve spontaneously or be relieved by non-narcotic analgesic [56]. This less severe headache, which also develops abruptly and has a distinctive quality, may be due to minor leakage of blood into the aneurysm wall or subarachnoid space [57]: the so called ‘‘warning leak’’ or ‘‘sentinel leak’’ [53]. However, similar symptoms with equally grave import may also emanate from either acute aneurysmal distention (i.e. a ‘symptomatic’ unruptured aneurysm) or, even, de novo aneurysm formation. 5.3. Signs Once aneurysmal SAH is suspected, the specific clinical signs of meningism and/or intra-ocular haemorrhage must be sought. A clinical diagnosis of an SAH can be firmly established if these are demonstrated. Meningeal irritation, which manifests as neck stiffness, occurs as a result of the breakdown of blood products within the subarachnoid space eliciting an aseptic meningitis [58,59]. It is present in about 90% cases [60] but may not develop until several hours following SAH. Intra-ocular bleeding, seen as unilateral or bilateral subhayloid haemorrhages on ophthalmoscopy, is also present in approximately 25% of patients [14]. In some cases (15%), SAH presents as seizures [14] and in about a third of cases focal neurological deficits are demonstrable. When there is coma, the associated maternal mortality may be as high as 45–75% [42]. The patient’s clinical condition on arrival at the hospital is an important guide to prognosis. Various grading systems have been formulated in an attempt to predict clinical outcome [61]. Although no grading instrument has consistently outperformed any other [61], one system that has gained universal acceptance and is currently widely used is that developed by the World Federation of Neurological Surgeons (WFNS) [62] (Table 3). The higher the WFNS grade, the worse the prognosis. Table 3 World Federation of Neurological Surgeons (WFNS) grading scale WFNS grade

Glasgow coma score

Motor deficit

I II III IV V

15 14–13 14–13 12–7 6–3

Absent Absent Present Present or absent Present or absent

D.O. Selo-Ojeme et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 131–143

135

6. Complications

7. Diagnosis

6.1. Re-bleeding

It is important that an accurate early diagnosis of an SAH is made as early definitive treatment reduces short-term complication and improves clinical outcome. However, it is occasionally difficult to distinguish SAH from either severe pre-eclampsia, or from eclampsia [14]. There may be transient hypertension following aneurysm rupture due to raised intracranial pressure or an increase in catecholamine release. Proteinuria may be detected in up to 30% of cases. The manifestations of pre-eclampsia, eclampsia and SAH may be similar, but the consequences and management are entirely different. The principles of investigation of the pregnant patient with a suspected aneurysmal SAH do not differ from those of a non-pregnant patient. In a manner similar to other severe and potentially fatal conditions such as eclampsia, immediate efforts are directed to reducing the risk of complications to the pregnant woman with an aneurysmal rupture. Thus, radiological and surgical procedures should not be delayed or avoided because of fear of harming the foetus [48]. Nevertheless, the risk of foetal abnormalities resulting from radiation exposure is often a source of concern. The effects of radiation on the foetus are highly dependent on the radiation dose and the stage of foetal development at the time of exposure; and the probability of radiation damage increase with increasing absorbed dose [72]. In the first 2 weeks of development, radiation damage is most likely to cause embryonic death, whereas in the sixth to the tenth week (where cellular sub-specialisation, i.e. organogenesis has already commenced) congenital abnormalities in the surviving foetus are more likely. In the period from 8 weeks until birth, the risks associated with radiation include growth retardation with microcephaly, retardation due to neuron depletion, and the later development of childhood cancer. Foetal neuron depletion as a result of radiation is often manifested as severe mental retardation (SMR). The risk of inducing SMR between 8 and 15 weeks has been assessed at 40% per Gy absorbed, and there is a loss of 3 IQ points for each 100 mGy absorbed [73,74]. However, current evidence suggests that there is no increased foetal risk of malformations, growth restriction, or abortions from a radiation dose less than 50 mGy [75]. The association between in utero diagnostic radiation exposure and an increased risk of childhood cancers has been questioned. According to the National Radiological Protection Board of the United Kingdom [76], this risk barely exceeds the threshold for diagnostic studies. The American College of Radiology [77], states that no single diagnostic procedure results in a radiation dose significant enough to threaten the well being of the developing embryo and foetus. Indeed, the ionisation produced by the newer CT scanners is focal with almost no scattering [78]. Thus, foetal exposure to a single diagnostic X-ray procedure should not be an indication for therapeutic abortion [75]. At exposure levels below 10 mGy, the statistical probability of a detectable radiation effect on the foetus is so

The primary goal in the management of aneurysmal SAH is the prevention of re-bleeding which is the most fatal complication with a mortality rate in the region of 50–70% [63,64]. The risk of re-bleeding is 4% over the first 24 h following aneurysmal haemorrhage and rises to 10–20% in the first month [65,66], and, mortality is progressively increased with each successive re-rupture. Re-bleeding occurs in 33–50% of untreated ruptured intracranial aneurysms within 4–6 weeks [64–67]. 6.2. Cerebral vasospasm Ecker and Riemenschneider [68] first documented angiographic arterial vasospasm (VSM) following aneurysmal SAH in 1951. With a distribution largely restricted to the parent artery of aneurysm rupture, but with an additional distribution related to the bulk of the associated clot released (this probably reflecting the action of various blood-derived agents, such as oxyhaemoglobin and platelet-derived serotonin), VSM can eventually cause delayed cerebral ischaemia (DCI) by an essentially unknown mechanism [64]. In an overview of 10,445 cases amongst 297 studies, DCI occurred in 33% of patients [69]. Its onset varied from 2–4 days to over 14 days after SAH, with a mean onset at around 8 days. Once started, DCI steadily attained a zenith over 1–4 days and in general, should the patient have survived, some degree of recovery was the rule. Nevertheless, once established, DCI possesses the same natural history as that associated with any other stroke: thus, death occurs in 30%, permanent neurological deficit occurs in a further 34%, whilst 36% ultimately achieve a good outcome. 6.3. Death Although aneurysmal SAH is more frequent in females than males, the case fatality rate is similar (males 48%, females 46%) [70]. In general, when there is an aneurysmal rupture, death is instant in 10–15% of cases and without treatment, 65% are dead in 1 year [30]. The mortality and morbidity rates associated with aneurysmal subarachnoid haemorrhage in pregnancy are high. Estimates of maternal mortality rates ranges from 13 to 85% [1,24, 42]. 6.4. Other complications In a recent series, pulmonary complications were documented in about 22% cases [71] and hyponatremia occurred in 10–34% of patients several days after an SAH [63]. It usually responds to careful salt replacement with normal saline.

136

D.O. Selo-Ojeme et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 131–143

small that it is outweighed by the medical benefits of the procedure to the mother and, therefore, indirectly to the foetus. Nevertheless, it is important to take precautions to limit radiation exposure to mother and foetus. The use of foetal shielding certainly reduces the risk of ionising radiation [18,19]. 7.1. Computed tomographic (CT) scan A computed tomographic (CT) scan, the first diagnostic study of choice with SAH in general, should be performed as soon as possible to confirm the presence of subarachnoid blood and to detect any associated intracerebral or intraventricular haemorrhage (with potentially associated hydrocephalus) [63,79]. As aforementioned, CT scan is relatively safe for both mother and foetus: however, some have argued that magnetic resonance imaging (MRI) should be used in preference, to delimit the perceived potential risk of ionising radiation [11]. In addition, MRI may also help to differentiate eclampsia from aneurysmal SAH [11]. Notwithstanding, MRI is a notoriously scarce resource—rarely as available as CT (particularly in the acute situation) [80]. Indeed, many district general hospitals do not possess MRI and, of those that do, expertise in diagnosing SAH may be limited (especially where only routine imaging is obtained, since only fluid attenuated inversion recovery (FLAIR) is equivalent to CT in detecting SAH [81]). Furthermore, given that many patients are agitated and confused after SAH, along with the fact that MRI scanning times are much longer than with CT, CT is altogether the more pragmatic investigation currently available for diagnosing SAH [82]. Because, however, the ability to correctly identify SAH radiologically varies widely among different disciplines [83], all CTs (or, where performed, MRI) should be urgently reviewed by an expert service: for example the regional oncall Neurosurgical service in the UK (preferably via computer-link). Due to the rapid clearing of blood from the subarachnoid space, the sensitivity of CT or MRI at detecting haemorrhage decreases over time. For example, with the older CT scanners used by the International Cooperative Study of the Timing of Aneurysm Surgery, the sensitivity decreased from 92% on the day of rupture through 86% 1 day later, 80% at 3 days to 70% at 5 days [84–86] With modern third generation CT scanners, sensitivity is 98% in first 12 h and 93% in first 24 h [51]. It is important to note that both CT and MRI are truly negative in detecting SAH in a variable proportion of cases [80]. In these situations, where the clinical presentation is highly suggestive of an SAH, but where both CT and MRI are negative, equivocal, or technically inadequate, lumbar puncture should be performed [80]. In all such cases, persistent blood staining of CSF throughout a three-bottle collection should be noted. Also important is an abnormal white: red blood cell ratio (commensurate with meningism and aseptic meningitis) [58,59] and a supernatant that is

frankly xanthochromatous. The latter relates to the fact that, as erythrocytes rapidly disseminate throughout the subarachnoid space (where they may persist for days or weeks), their progressive lysis liberates haemoglobin which is subsequently metabolised first to oxyhaemoglobin (reddish pink) and, then, eventually to bilirubin (yellow). Although the formation of bilirubin is diagnostically more reliable, it is an enzyme-dependent process that can take up to 12 h [87]. Therefore, timing is important in the interpretation of lumbar puncture results. While some authors recommend waiting 12 h after onset of headache [78,84,88], others argue against delayed lumbar puncture in patients with negative CT scans and suggest that where clinical suspicion is high, patients with persistently bloody CSF without xanthochromia should undergo vascular imaging [8]. LP is safe to perform in the absence of intracranial mass lesions (as detectable by CT or MRI), whilst the theoretical risk of re-rupture (by virtue of increased trans-mural pressure difference consequent upon cerebrospinal fluid (CSF) removal) is rarely encountered in practice. 7.2. Angiography Once a CT scan confirms haemorrhage, intra-arterial digital subtraction angiography (DSA) is currently undertaken to define vascular anatomy and identify the source of bleeding. It is, however, likely that spiral CT-angiography will supersede this modality in the near future. Where CT or MRI has identified a potential site for the aneurysm, DSA is commenced using the parent vessel of the likely source: however, since aneurysms are multiple in 25% [29], four vessel DSA is routinely undertaken in diagnosis. Indeed, where CT or MRI has suggested an aneurysmal source suitable for endovascular coiling (such as, for example, a basilar tip aneurysm) DSA may proceed to complete treatment under the same anaesthetic. In general, the risk of stroke or transient neurological deficit with DSA is approximately 1% [89]. DSA may require to be repeated after an interval of several days since VSM following a bleed occasionally obscures aneurysm visualisation by limiting blood flow (and consequently, contrast delivery) [17]. DSA should be delayed in patients with profound alteration of consciousness, with or without focal neurologic deficits, because of the associated poor prognosis and high operative mortality [48]. Whilst magnetic resonance angiography (MRA) may also be used to detect cerebral aneurysms, its specificity is inferior to that of DSA (particularly for small aneurysms).

8. Management 8.1. Unruptured aneurysm The management of unruptured cerebral aneurysms is currently marred by controversy. The results of the Inter-

D.O. Selo-Ojeme et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 131–143

national Study of Unruptured Aneurysms (ISUA) [29] suggested that all aneurysms smaller than 10 mm in size in patients without a prior SAH ought to be managed conservatively, since the risk of rupture was estimated at only 0.05% per year. However, various biases (in particular, selection biases) undermined this study, questioning its general applicability [90]. Notwithstanding, the more recent [91] (and less methodologically flawed [92]) prospective data from ISUIA have yielded similar findings: and have endorsed the view that small aneurysms should merely be observed. Given ISUIA findings, however, it is interesting to note that most aneurysms that do eventually rupture are, nevertheless, smaller than 10 mm. This paradoxical may be potentially explained by hypothesising either that most ruptures occur in aneurysms that have spontaneously arisen de novo shortly before they subsequently rupture; or, instead, that aneurysm size decreases following SAH (either by some form of contraction, or by artefact of external clot pressure) [89]. In either case, the findings of ISUIA remain applicable, and represent the best evidence-base currently available to manage incidental unruptured aneurysms on a serial basis, because ISUIA reflects the natural history of more ‘stable’ aneurysms of all sizes [89]. The general consensus is that all ‘symptomatic’ unruptured aneurysms (i.e. those associated with acute headache and/or cranial nerve paresis indicative of acute distention [35]) that are lobulated, associated with a prior aneurysm rupture elsewhere, greater than 10 mm in size or, instead, of any initial size but with evidence of serial growth ought to be definitively treated. However, given that both aneurysm growth—as well as aneurysm rupture—might be more likely as pregnancy advances [1,27], pregnant women harbouring incidental aneurysms might instead choose to ignore ISUIA data regarding small aneurysms (which, therefore, might not apply to pregnancy); and, in consequence, opt for elective aneurysm obliteration prior to attempting to conceive. 8.2. Ruptured aneurysm It is universally accepted that pregnant patients with ruptured intracranial aneurysms should be treated in the same way as patients who are not pregnant. Therefore, neurosurgical considerations take precedence over obstetric considerations. It is thus vital to obtain prompt neurosurgical consultation once an SAH is suspected. Where adequate local neurosurgical support is lacking, urgent transfer to a centre with combined neurosurgical and neuroradiological expertise should be actioned, with due consideration given to immediate resuscitation or medical stabilisation. A multidisciplinary approach to management is essential which should involve a neurosurgeon, an interventional neuroradiologist, a neuroanaesthetist and a neonatologist (if the foetus is preterm). Immediate consideration is given for treatment—with or without delivery of the baby—in order

137

to obviate the risk of recurrent and, increasingly devastating, secondary haemorrhage [1,23,35,48]. 8.2.1. Endovascular embolisation In 1990, a detachable platinum coil device, the Guglielmi detachable coil (GDC; Boston Scientific/Target Therapeutics, Freemont, CA, USA) [93] was introduced into clinical practice in order to exclude the aneurysm from the parent vessel by exciting thrombosis within the sac. The supreme advantage of this technique was that it permitted aneurysm exclusion endovascularly via the same route as that used for diagnostic DSA. Even soon after its introduction, GDC became the treatment-of-choice for obliterating technically difficult posterior circulation and cavernous segment aneurysms. However, after 1995 GDC became so widely used— both in anterior and posterior circulation aneurysms, as well as in ruptured and unruptured aneurysms [94]—that the primary place of surgical clipping as the standard treatment strategy for all aneurysms became seriously challenged. In consequence, the International Subarachnoid Aneurysm Trial (ISAT) study, was set up to formally determine whether GDC or clipping could reduce death and dependency (as defined by modified Rankin scale 3–6) by 25% at 1 year. In addition, further differences between GDC and clipping (such as the prevention of re-bleeding, quality of life at 1 year, frequency of epilepsy, cost-effectiveness as well as neuropsychological outcomes) would also be sought. Patients were considered eligible for randomisation if SAH could be proven by CT or LP within 28 days, if an aneurysm—feasibly responsible for SAH—could be demonstrated on DSA or CT-angiography, if the patient was in a clinical state that could justify treatment by either arm, if the aneurysm demonstrated was suitable for treatment by either arm, if uncertainty existed over which arm should be used, and finally if appropriate consent could be obtained. Initially commenced as a pilot study in 1994, but with full study implementation occurring by 1997, ISAT was subsequently curtailed prematurely by virtue of clear results demonstrating significantly less death and dependency at 1 year in those randomised to GDC [95]. Furthermore, a recent clinical comparison has also demonstrated that patients in good clinical grade on admission (i.e. WFNS Grades I–III) were less likely to suffer VSM or DCI when treated by GDC as compared to surgical clipping [96]. In consequence, current UK and European practice has now shifted toward GDC as the primary treatment modality in all SAH patients who would otherwise have met ISAT criteria [97]. Unfortunately, however, not all aneurysms are suitable for GDC. In particular, many middle cerebral artery (MCA) aneurysms, where terminal branches frequently arise from the sac itself, are not suitable. In this context, it is of note that MCA aneurysms were grossly under-represented in ISAT – this almost certainly reflecting the fact that ‘‘uncertainty regarding suitability for either treatment’’ (a methodological requirement for ISAT enrolment) could not be sustained in

138

D.O. Selo-Ojeme et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 131–143

such cases. In addition, excessive VSM potentially obstructs endovascular access; whilst all aneurysms with excessive neck/fundus ratios risk GDC prolapse back into the parent lumen (although, increasingly, balloon and stenting techniques—along with the use of onyx—will gradually reduce this number). Perhaps more pertinently still, an increasing number of potential flaws have been highlighted with ISAT [98]. In particular, of the 9559 SAH patients initially approached, only 2143 subsequently underwent randomisation: thus rendering ISAT potentially under-representative. Furthermore, even limited follow-up DSA (such as that contained within ISAT data at 1 year) has demonstrated significantly increased obliteration-failure with GDC as compared to surgical clipping [95,98]. In consequence, all decisions should be currently taken by a dedicated neurovascular service: able to combine both neurosurgical and endovascular intervention, along with full counselling for each and every patient. There may also be concerns regarding the ‘swing’ toward GDC as the primary treatment modality with regard to pregnancy in view of the prolonged radiation exposure implied with DSA screening during embolisation. To assess this, a phantom (consisting of ‘solid water’, perspex and ‘bolus’ with an AP thickness of 24.5 cm) was simulated in the neurosurgical author’s DSA suite. In this study, the scattered ‘uterine’ dose absorbed was found to be 11 mGy/min, whilst the direct ‘uterine’ dose was 4.6 mGy/min. Assuming screening duration ranges for ‘groin’ of 0–30 s and 15–45 min for ‘head’, the absorbed foetal radiation dose therefore ranged from 0.17 to 2.8 mGy. Such a dose range suggests a foetal risk of between 1:247,000 and 1:15,000 for a hereditary disease at birth (risk coefficient: 2:4  105 mGy1), or between 1:194,000 to 1:11,000 for a fatal cancer by age 15 years (risk coefficient: 3:0  105 mGy1) [72,73]. Given the natural frequency of a heritable disease manifesting at birth of between 1 and 6%, or a natural cumulative risk of fatal childhood cancer by age 15 years of approximately 1:1300 [99], the risks associated with even relatively prolonged GDC appear

in orders of magnitude below that which naturally prevails. Such figures may therefore be used to provide reassurance to expectant mothers during counselling for aneurysmal obliteration. Other issues regarding GDC counselling, however, relate to the practicalities of the procedure itself, which, in fact, may pose potentially more pressing problems. For example, GDC must be carried out under general anaesthesia within the confines of a DSA suite, whilst full systemic heparinisation must be used throughout. The former is required to stop patient movement during aneurysmal microcatheterisation, whilst the latter helps prevent thrombo-embolic complications during embolisation (heparin usually being discontinued 12 h following the procedure) [18]. A particularly serious problem here relates to the need for foetal monitoring within the unfamiliar environment of a DSA suite: especially in cases where foetal distress might become apparent. A similarly fraught situation is that of SAH during labour and delivery. In both of these situations, many might prefer surgical clipping to GDC: especially in the latter scenario, where simultaneous aneurysm exclusion is advantageous, but where systemic heparinization—as required for GDC—is decidedly disadvantageous. Notwithstanding, to date four case series (involving nine patients, all under 40year-old) have been reported in the literature of successful endovascular embolisation in pregnancy and immediately postpartum (Table 4). Successful vaginal deliveries were achieved following endovascular treatment in the second and third trimesters [11,18,19]. GDC have also been performed successfully shortly after caesarean deliveries [19,100]. 8.2.2. Surgery In contrast to GDC, the surgical management of a ruptured or unruptured intracranial aneurysm aims to exclude the sac from the circulation by obliterating it extravascularly, using a clip at the site of the neck flush with the arterial wall. This, therefore, requires an open craniotomy. Prior to ISAT, surgical clipping was the mainstay of aneurysm exclusion in

Table 4 Use of GDC in the management of aneurysms during pregnancy: documented cases Author

Year

Patient’s age (years)

Gestational age at treatment (weeks)

Pregnancy outcome

Meyers et al. [19]

2000

34 36 36

30 Midtrimester Late 3rd trimester

SVD at term Live birth 37 days later CS for twinsa

Piotin et al. [18]

2001

25 31

32 22

CS SVD at 40 weeks

Shahabi et al. [100]

2001

36

38

CSa

Kizilkilic et al. [11]

2003

25 39 26

10 18 28

Elective TOP SVD at 34 weeks SVD at 38 weeks

SVD: spontaneous vaginal delivery; CS: caesarean section; TOP: termination of pregnancy. a Endovascular embolisation was performed after the caesarean section.

D.O. Selo-Ojeme et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 131–143

the vast majority of cases, and boasted a long-term exclusion efficacy [1]. Indeed, surgical clipping still affords significant advantages over GDC in several key areas. For example, craniotomy permits aneurysm exclusion under direct vision: an important and distinct advantage over GDC wherever intra-procedural rupture occasionally occurs (potentially 20% of cases) [98]. In addition, craniotomy permits concurrent treatment of an associated but separate neurosurgical condition: such as obstructive hydrocephalus or intracerebral haematoma. Furthermore, clipping has an established record for long-term efficacy [1] in contrast to the short-term results so far obtained with GDC [95,98]. However, perhaps the most pertinent indication for surgery over GDC in the context of pregnancy is where aneurysm rupture occurs during labour: in this situation, simultaneous delivery and aneurysm exclusion might be considered desirable. One area of controversy, however, is in the timing of aneurysm surgery: in particular, whether this should be early or delayed. In 1990, the International Cooperative Study on the Timing of Aneurysm Surgery found no significant difference in outcome between early (days 0–3) or late surgery (days 11–14) [84,85]. Although a later analysis of the North American data contained within the study suggested a better outcome with earlier surgery [101], these results could have reflected an artefact of early and more aggressive treatment of VSM as subsequently permitted by early aneurysm exclusion. Notwithstanding, most neurosurgeons would currently recommend early aneurysmal repair in patients who are in good clinical grade [102]. There are no formal studies to guide the optimal mode of obstetric management of patients with ruptured SAH in pregnancy. For gestational ages less than 24 weeks, it is reasonable for aneurysm exclusion measures to proceed as best for the mother. If the surgery is successful, and the pregnancy continues to term, vaginal delivery should be the goal. For gestational ages beyond 34 weeks, optimal anaesthesia should be established and a caesarean section performed. Thereafter, anaesthesia is adjusted for aneurysm exclusion [17,18,76,103–105]. Between 26 and 34 weeks, aneurysm exclusion should proceed and, if the foetus is stable, pregnancy is allowed to continue. During aneurysm exclusion, the foetal heart rate must be monitored continuously so that any foetal distress can be detected. This may require an emergency caesarean section with interval suspension of aneurysm treatment [19,104]. Adequate preparation must therefore be made to deal with acute foetal distress at any time during exclusion, and the neonatal team must be prepared to deal with the ‘co-anaesthetized’ baby delivered at an unexpected time [104]. This is particularly pertinent with GDC within the DSA suite and the logistics of this should have been fully related to the mother well in advance during counselling. If aneurysmal rupture occurs during labour, simultaneous caesarean section and aneurysm exclusion should be performed with swift delivery of the baby performed first in order to limit anaesthetic exposure to the foetus and allow management efforts to be concentrated on

139

Table 5 Relative advantages and disadvantages of deploying GDC vs. surgical clipping in the management of intracranial aneurysms GDC

Clipping

Anterior or posterior circulation possible (but MCAs difficult)

Anterior circulation mainly (posterior circulation and infraclinoid segment aneurysms difficult) All neck:fundus ratios potentially treatable Severe VSM not preclusive Pre-operative rupture controlled Treatment of associated condition (e.g. intracerebral hematoma) simultaneous

Wide neck:fundus ratios difficult Severe VSM preclusive Per-operative rupture uncontrolled Treatment of associated condition (e.g. intracerebral hematoma) deferred

the mother [17]. Such a scenario might lead some to prefer surgical clipping to GDC, despite the current trend advocated by ISAT. When rupture occurs postpartum, the patient is treated as if she were not pregnant. Table 5 summarises the pros and cons of GDC versus surgery. 8.2.3. Medical management (Table 6) The medical management of aneurysmal SAH in pregnancy is also potentially problematic. The standard regimen to combat VSM and DCI (particularly following aneurysm exclusion) is hypertensive, hypervolaemic, haemodilution (i.e. ‘triple-H therapy’). Clearly this might have some implications for the mother in whom the circulating volume is already increased (although some have suggested that DCI might be naturally offset by such physiological changes). In addition, prophylactic nimodipine (a calcium channel blocker) is instituted from the onset of SAH for a period of 21 days. Initially developed to combat VSM (nimodipine specifically dilates cerebral vessels), nimodipine’s probable mode of action is as a neuroprotective agent: offsetting DCI by increasing neuronal ischaemic tolerance. Nimodipine has been shown to be potentially teratogenic and embryotoxic in animals: nevertheless, its direct effect on human foetuses remains unknown. It has potential anti-hypertensive side effects and may cause maternal hypotension and consequent foetal hypoxia (Table 6).

Table 6 Medical management of SAH and VSM Common Nimodipine: oral prophylactic use for 21 days Hypertensive, hypervolaemic haemodilution (i.e. ‘triple H’) therapy Inotropes (noradrenaline, dopamine, dobutamine) Rare Papaverine (intra-arterial during DSA, or topically at surgery) Intra-arterial nimodipine during DSA Vasopressin Mannitol Sodium nitroprusside Corticosteroids

140

D.O. Selo-Ojeme et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 131–143

Whilst trans-luminal angioplasty may occasionally be used to directly treat VSM, agents such as papaverine (or even intra-arterial nimodipine) are also often required to permit micro-catheterization in such cases: indeed, papaverine may be locally-applied during DSA as a specific treatment modality for VSM in itself. It is unknown, however, what effects papaverine has on the foetus. Agents used to induce hypertension, such as dopamine and vasopressin must be used with caution: in particular, in patients diagnosed with pregnancy-induced hypertension [64]. Aminocaproic acid, an agent formerly used to offset rebleeding prior to aneurysm exclusion, is singularly inappropriate in pregnancy because of the existing hypercoagulable status. Anti-convulsants are indicated in patients with seizures or, potentially, in those of poor clinical grade. They are associated with teratogenicity (craniofacial anomalies, growth and mental retardation) and maternal folate deficiency. They may also contribute to neonatal coagulopathy, neonatal depression and drug withdrawal syndromes. The use of diuretics can be problematic as they may cause maternal dehydration and subsequent hypotension, uterine hypoperfusion and foetal injury. Mannitol crosses the placenta to a variable extent and may accumulate disproportionately in the foetus increasing foetal plasma osmolarity and consequent foetal dehydration due to net flow of water from foetus to mother [106]. High doses of steroids have not been shown to have any deleterious effects on the foetus. However, because of their widespread metabolic effects, they should be used with caution. Long-term use particularly in the last trimester may result in foetal adrenal suppression and neonatal hypoadrenalism. Nonetheless, their use in SAH is rarely indicated [64]. In the light of these limitations, due consideration must be giving to maintaining a fine balance between maternal wellbeing and foetal safety when pharmacological agents are used in the treatment of aneurysmal SAH. 8.2.4. Anaesthesia The occasional need for a hypotensive state during surgical clipping makes neuro-anaesthesia challenging in pregnancy: however, the current trend toward endovascular obliteration clearly obviates this requirement. The participation of a perinatal anesthesiologist with experience in obstetric anaesthesia is therefore necessary [78,103]. It is important to maintain uterine blood flow and transplacental oxygenation of the foetus at all times. Neuro-anaesthesia must be carefully planned, as appropriate timing or sequencing of procedures potentially minimises or eliminates foetal exposure to the various anaesthetic agents and avoids surges of hypotension, hypertension, hypoxia and hypercarbia. Adjuncts that have been utilised include hypothermia, drug-induced hypotension and barbiturate infusion during the temporary clipping that is sometimes required during aneurysm isolation at surgery [105]. However, there have

been no reports of teratogenicity associated with neuroanaesthesia [107]. 8.2.5. Obstetric management There is no neurosurgical contraindication to vaginal delivery following aneurysm exclusion provided that the patient is of good WFNS grade. Both caesarean section and vaginal delivery have been associated with equivalent mortality rates for both mother and foetus in advanced gestations [1,108]. Pregnancy should therefore be allowed to progress to term following aneurysm exclusion. A consultant neuro-anaesthetist should evaluate the patient antenatally in order to formulate a management plan for labour. Oxytocic agents and amniotomy can safely be used to induce labour. In the past, elevated intravascular pressure resulting from straining during active labour was thought to increase the risk of intracranial haemorrhage—particularly in those habouring berry aneurysms. However, current evidence suggests that the risk of intracranial haemorrhage in the presence of an untreated cerebrovascular lesion does not significantly differ between vaginal delivery and caesarean section [1,19,64]. Nevertheless, it would seem sensible to advise against maternal bearing-down efforts during labour in women with unruptured aneurysms since, whilst the concordant CSF pressure elevation limits the pressure differential across the aneurysm wall during the Valsalva maneuver, the CSF pressure-surge appears to fall faster than the arterial pressure-surge, thereby temporarily risking rupture at the end of the maneuver [25]. In consequence, strategies such as shortening the second stage, the use of epidural analgesia and, if necessary, the employment of an instrumental delivery potentially decreases the risk of rupture during vaginal delivery [1]. If labour begins or is likely to begin shortly after aneurysm exclusion, then caesarean section should be considered to avoid an unnecessarily prolonged labour. Caesarean section is also recommended if there is doubt about the adequacy of occlusion (particularly prevalent with GDC [95,98]), if an incidental unruptured aneurysm suddenly becomes symptomatic, or if rupture occurs in the third trimester. Systemic heparinisation must, of course, be rapidly and completely reversed after GDC whenever caesarean section is indicated in this way.

9. Conclusion A reduction in the high maternal mortality and morbidity associated with aneurysmal SAH can only be achieved through early diagnosis and timely neurosurgical intervention. It is therefore imperative that frontline obstetric staffs maintain a high index of suspicion when a pregnant woman presents with an unusual headache so that prompt neurosurgical consultation can be made. This will reduce the incidence of misdiagnosis with its associated severe consequences.

D.O. Selo-Ojeme et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 131–143

10. Key points  Ruptured SAH was responsible for 60 maternal deaths in England and Wales between 1988 and 1999.  Predominant presenting symptom is a uniquely severe headache.  Urgent neurovascular consultation is vital once suspected.  The principles of management are similar to those in a non-pregnant woman.  Endovascular embolisation is a useful alternative to clipping.  There is no contraindication to vaginal delivery following successful treatment remote from term.

References [1] Dias MS, Sekhar LN. Intracranial haemorrhage from aneurysms and arteriovenous malformations during pregnancy and the puerperium. Neurosurgery 1990;7:855–66. [2] De Swiet M. Other indirect deaths. In: Gwyneth L, editor. Why mothers die. Report on confidential enquiries into maternal deaths in the United Kingdom 1997–1999. London: RCOG Press; 2001. [3] Hibbard BM, editor. Report on confidential enquiries into maternal deaths in the United Kingdom 1988–1990. London: HMSO; 1993. [4] Hibbard BM, editor. Report on confidential enquiries into maternal deaths in the United Kingdom 1991–1993. London: HMSO; 1996. [5] Gwyneth L, editor. Why mothers die. Report on confidential enquiries into maternal deaths in the United Kingdom 1994–1996. London: TSO; 1999. [6] Inagawa T, Tokuda Y, Ohbayashi N, Takaya M, Moritake K. Study of aneurysmal subarachnoid haemorrhage in Izumo City, Japan. Stroke 1995;26:761–6. [7] Schievink WI, Wijdicks EFM, Piepgras DG, Chu C-P, O’Fallon WM, Whisnant JP. The poor prognosis of ruptured intracranial aneurysms of the posterior circulation. J Neurosurg 1995;82:791–5. [8] Edlow JA, Caplan LR. Avoiding pitfalls in the diagnosis of subarachnoid haemorrhage. N Engl J Med 2000;342:29–36. [9] Schievink WI, Wijdicks EFM, Parisi JE, Piepgrass DG, Whisnant JP. Sudden death from aneurysmal subarachnoid haemorrhage. Neurology 1995a;45:871–4. [10] Longstreth Jr. WT, Nelson LM, Koepsell TD, van Belle G. Clinical course of spontaneous subarachnoid haemorrhage: a populationbased study in King County, Washington. Neurology 1993;43:712– 8. [11] Kizilkilic O, Albayram S, Adaletli I, kantarci F, Uzma O, Islak C, et al. Endovascular treatment of ruptured intracranial aneurysms during pregnancy: report of three cases. Arch Gynecol Obstet 2003;268:325–8. [12] Basama FMS, Clarke JFB. Subarachnoid haemorrhage from ruptured aneurysm during pregnancy. J Obstet Gynaecol 2000;20: 635–6. [13] Catanzarite VA, Ferguson 2nd JE, Hensleigh P, Wienstein C, Cortina P. Management of pregnancy subsequent to rupture of an intracranial aneurysm. Am J Perinatol 1984;1:174–6. [14] Giannotta SL, Daniels U, Zelman V, Boyat A. Ruptured intracranial aneurysms during pregnancy: a report of four cases. J Reprod Med 1986;31:139–47. [15] Gill TE, Mani S, Dessables DR. Anaesthetic management of cerebral aneurysm clipping during pregnancy: a case report. AANA J 1993;61:282–6. [16] Hubert P. Acute subdural haematoma of the convexity caused by rupture of an aneurysm in the anterior communicating artery.

[17]

[18]

[19]

[20]

[21]

[22]

[23] [24] [25] [26]

[27] [28] [29]

[30] [31]

[32] [33] [34]

[35] [36] [37]

[38]

[39]

[40]

141

A propos of a case in a pregnant woman. Neurochirurgie 1994;40:363–8. Kriplani A, Relan S, Misra NK, Mehta VS, Takkar D. Ruptured intracranial aneurysm complicating pregnancy. Int J Gynecol Obstet 1995;48:201–6. Piotin M, Filho CBA, Kothimbakam R, Moret J. Endovascular treatment of acutely ruptured intracranial aneurysm in pregnancy. Am J Obstet Gynecol 2001;185:1261–2. Meyers PM, Halbach VV, Malek AM, Phatouros CC, Doed CF, Lawton MT, et al. Endovascular treatment of cerebral artery aneurysms during pregnancy: report of three cases. Am J Neuroradiol 2000;21:1306–11. Georgantopoulou C, Jha R. Intracranial aneurysm in pregnancy presenting as hyperemesis gravidarum. J Obstet Gynecol 2003;23:74–5. Nedd KJ, Kent M, Powell Jr. V. Subarachnoid haemorrhage during pregnancy and puerperium: report of 3 cases and review of the literature. J Am Osteopath Assoc 1986;86:183–8. Broderick JP, Brott T, Tomsick T, Huster G, Miller R. The risk of subarachnoid haemorrhage and intracerebral haemorrhages in blacks as compared with whites. N Engl J Med 1992;326:733–6. Mas JL, Lamy C. Stroke in pregnancy and the puerperium. J Neurol 1998;245:305–15. Miller HJ, Hinkley CM. Berry aneurysms in pregnancy: a 10-year report. S Med J 1970;63:279–85. Barrett JM, Van Hooydonk JE, Boem FH. Pregnancy-related rupture of arterial aneurysms. Obstet Gynecol Surv 1982;37:557–66. Siwolke GA, Cox SM, Cunningham GG. Cerebrovascular accidents complicating pregnancy and the puerperium. Obstet Gynecol 1991;78:37–42. Stehbens WE. Aetiology of cerebral aneurysms. Lancet 1981;2:524–5. Yas¸argil MG. Clinical considerations, surgery of the intracranial aneurysms and results. Stuttgart: Georg Thieme Verlag; 1984. Wiebers DO. Unruptured intracranial aneurysms: risk of rupture and risks of surgical intervention. The international study of unruptured intracranial aneurysms investigators. N Engl J Med 1998;339(24):1725–33. Stoodley MA, Macdonald RL, Weir BK. Pregnancy and intracranial aneurysms. Neurosurg Clin N Am 1998;9:549–56. Austin G, Fisher S, Dickson D, Anderson D, Richardson S. The significance of the extracellular matrix in intracranial aneurysms. Ann Clin Lab Sci 1993;23:97–105. Wong MC, Giuliani MJ, Haley Jr. EC. Cerebrovascular disease and stroke in women. Cardiology 1990;77(Suppl 2):80–90. Kittner SJ, Stern BJ, Feeser BR, et al. Pregnancy and the risk of stroke. N Engl J Med 1996;335:768–74. de la Monty SM, Moore GW, Monk MA, Hutchins GM. Risk factors for the development and rupture of intracranial berry aneurysms. Am J Med 1985;78:957–64. Weir BK, Drake CG. Rapid growth of residual aneurysmal neck during pregnancy: a case report. J Neurosurg 1991;75:780–2. Schievink WI. Genetics and aneurysmal formation. Neurosurg Clin N Am 1998;9:485–95. Schievink WI, Michels VV, Piepgras DG. Neurovascular manifestations of heritable connective tissue disorders: a review. Stroke 1994a;25:889–903. Gaist D, Vaeth M, Tsiropoulos I, Christensen K, Corder E, Olsen J, et al. Risk of subarachnoid haemorrhage in first-degree relatives of patients with subarachnoid haemorrhage: follow up study based on national registries in Denmark. BMJ 2000;320:141–6. Petitti DB, Wingerd J. Use of oral contraceptives, cigarette smoking, and risk of subarachnoid haemorrhage. Lancet 1978;2:234–5. Knekt P, Reunanen A, Aho K, et al. Risk factors for subarachnoid haemorrhage in a longitudinal population study. J Clin Epidemiol 1991;44:933–5.

142

D.O. Selo-Ojeme et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 131–143

[41] Juvela S, Hillbom M, Numminen H, Kosinen P. Cigarette smoking and alcohol consumption as risk factors for aneurysmal subarachnoid haemorrhage. Stroke 1993;24:639–46. [42] Amias AG. Cerebral vascular disease in pregnancy. 1. Haemorrhage. J Obstet Gynecol Br Commonwealth 1970;77:100–2. [43] Maymon R, Fejgin M. Intracranial haemorrhage during pregnancy and puerperium. Obstet Gynaecol Surv 1990;45:157–9. [44] Sharshar T, Lamy C, Mas JL. Incidence and causes of strokes associated with pregnancy and puerperium: a study in public hospitals of Ile de France. Stroke 1994;26:930–6. [45] Young BJ, Seigerman MH, Hurst RW. Subarachnoid haemorrhage and aneurysms. Semin Ultrasound CT MR 1996;17:265–77. [46] Doung H, Melancon D, Tampieri D, Ethier R. The negative angiograms in subarachnoid haemorrhage. Neuroradiology 1996;38:15–9. [47] Schievink WI, Karemaker JM, Hageman LM, van der Werf DJM. Circumstances surrounding aneurysmal subarachnoid haemorrhage. Surg Neurol 1989;32:266–72. [48] Wiebers DO. Subarachnoid haemorrhage in pregnancy. Semin Neurol 1988;8:226–9. [49] Leicht MJ. Non-traumatic headache in the emergency department. Ann Emerg Med 1980;9:404–9. [50] Ramirez-Lassepas M, Espinosa CE, Cicero JJ, Johnston KL, Cipolle RJ, Barber DL. Predictors of intracranial pathologic findings in patients who seek emergency care because of headache. Arch Neurol 1997;54:1506–9. [51] Morgenstern LB, Luna-Gonzales H, Huber Jr. JC, et al. Worst headache and subarachnoid haemorrhage: prospective modern computed tomography and spinal fluid analysis. Ann Emerg Med 1998;32:297–304. [52] Linn FH, Wijdicks EF, van de Graff Y, Weerdesteyn-van Vliet FA, Bar-Telds AI, van Gijn J. Prospective study of sentinel haemorrhage in aneurysmal subarachnoid haemorrhage. Lancet 1994;344:590–3. [53] Duffy GP. The ‘warning leak’ in spontaneous subarachnoid haemorrhage. Med J Aust 1983;1:514–6. [54] Juvela S. Minor leak before rupture of an intracranial aneurysm and subarachnoid haemorrhage of unknown aetiology. Neurosurgery 1992;30:7–11. [55] Jakobson KE, Saveland H, Hillman J, et al. Warning leak and management outcome in aneurysmal subarachnoid haemorrhage. J Neurosurg 1996;85:995–9. [56] Seymour JJ, Moscati RM, Jehle DV. Response of headaches to nonnarcotic analgesics resulting in missed intracranial haemorrhage. Am J Emerg Med 1995;13:43–5. [57] 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;1:33–45. [58] Hammmes EM. Reaction of the meninges to blood. Arch Neurol Psychiatr 1994;52:505–14. [59] Jackson IJ. Aseptic haemogenic meningitis: an experimental study of aseptic meningeal reactions due to blood and its breakdown products. Arch Neurol Psychiatr 1949;65:572–89. [60] El Gawly RM. Ruptured intracranial aneurysm in pregnancy: a case report and review of the literature. Eur J Obstet Gynaecol 1992;46:150–3. [61] Cavanagh SJ, Gordon VL. Grading scales used in the management of aneurysmal subarachnoid haemorrhage: a critical review. J Neurosci Nurs 2002;34:288–95. [62] Report of World Federation of Neurological Surgeons Committee on a universal subarachnoid haemorrhage grading scale. J Neurosurg 1988;68:985–6. [63] Mayberg MR, Batjer HH, Dacey R, et al. Guidelines for the management of subarachnoid haemorrhage. Circulation 1994;90:2592–605. [64] Dias MS. Neurovascular emergencies in pregnancy. Clin Obstet Gynecol 1994;37:337–54.

[65] Barrow DL, Reisner A. Natural history of intracranial aneurysms and vascular malformations. Clin Neurosurg 1993;40:3–39. [66] Kassell NF, Torner JC. Aneurysmal re-bleeding: a preliminary report from the cooperative aneurysm study. Neurosurgery 1983;13:479–81. [67] Pool JL. Treatment of intracranial aneurysms during pregnancy. JAMA 1963;192:209–14. [68] Ecker A, Riemenschneider PA. Arteriographic demonstration of spasm of the intracranial arteries with special reference to saccular arterial aneurysms. J Neurosurg 1951;8:660–7. [69] Dorsch NWC, King MT. A Review of cerebral vasospasm in aneurysmal subarachnoid haemorrhage. J Clin Neurosci 1994;1:19– 26. [70] Huang J, van Gelder JM. The probability of sudden death from rupture of intracranial aneurysms. Neurosurgery 2002;51(5):1101– 7. [71] Friedman JA, Pichelmann MA, Piepgras DG, McIver JI, Toussaint 3rd. LG, McClelland RL, et al. Pulmonary complications of aneurysmal subarachnoid haemorrhage. Neurosurgery 2003;52:1025–31. [72] Committee on Biological Effects of Ionizing Radiation, National Research Council. Other somatic and foetal effects. In: Beir V, editor. Effects of exposure to low levels of ionizing radiation. Washington: National Academy Press; 1990. [73] Recommendations of the International Commission on radiological protection. ICRP publication 60. ISBN 0 08 041144 4. [74] Advice on exposure to ionizing radiation during pregnancy. National Radiological Protection Board 1998. ISBN 0 85951 420X. [75] Brent RL. Utilization of developmental basic science principles in the evaluation of reproductive risks from pre- and post conception environmental radiation exposures. Teratology 1999;59:182. [76] National Radiological Protection Board. Board statement on diagnostic medical exposures to ionizing radiation during pregnancy. Documents of the NRPB 4(4). London: HMSO; 1993. [77] Hall EJ. Scientific view of low-level radiation risks. Radiographics 1991;11:509. [78] D’Haese J, Christiaens F, D’Haens J, Camu F. Combined caesarean section and clipping of a ruptured cerebral aneurysm: a case report. J Neurosurg Anesthesiol 1997;9:341–5. [79] Findlay JM. Current management of aneurysmal subarachnoid haemorrhage guidelines from the Canadian Neurological Society. Can J Neurol Sci 1997;24:161–70. [80] van Gijn J, Rinkel GJE. Subarachnoid haemorrhage: diagnosis, causes and management. Brain 2001;124:249–78. [81] Noguchi K, Ogawa T, Inugami A, Toyoshima H, Sugawara S, Hatazawa J, et al. Acute subarachnoid haemorrhage: MR imaging with fluid-attenuated inversion recovery pulse sequences. Radiology 1995;196:773–7. [82] Ferrio MF, Daniele D, Bradac GB. Computed tomography in the diagnosis of subarachnoid haemorrhage. Rivista di Neuroradiol 2002;15:513–21. [83] Schriger D, Kalafut M, Starkman S, Krueger M, Saver J. Cranial computed tomography interpretation in acute stroke: physician accuracy in determining eligibility for thrombolytic therapy. JAMA 1998;279:1293–7. [84] van Gijn J, van Dongen KJ. The time course of aneurysmal haemorrhage on computed tomograms. Neuroradiology 1982;23:153–6. [85] Kassell NF, Torner JC, Haley Jr. EC, Jane JAA, Adams HP, Kongable GL. The international cooperative study on the timing of aneurysmal surgery. 1. Overall management results. J Neurosurg 1990a;73:18–36. [86] Kassell NF, Torner JC, Jane JA, Haley EC, Adams HP. The international cooperative study on the timing of aneurysmal surgery. 11. Surgical results. J Neurosurg 1990;73:37–47. [87] Roost KT, Pimstone NR, Diamond I, Schmid R. The formation of cerebrospinal fluid xanthochromia after subarachnoid haemorrhage:

D.O. Selo-Ojeme et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 116 (2004) 131–143

[88]

[89]

[90] [91]

[92] [93]

[94]

[95]

[96]

enzymatic conversion of haemoglobin to bilirubin by arachnoid and choroid plexus. Neurology 1972;22:973–7. Schull MJ. Lumbar puncture first: an alternative model for the investigation of lone acute sudden headache. Acad Emerg Med 1999;6:131–6. Bederson JB, Awad IA, Wiebers DO, Piepgras D, Haley EC, Brott T, et al. Recommendations for the management of patients with unruptured intracranial aneurysms. A statement for healthcare professionals from the stroke council of the American Heart Association. Circulation 2000;102:2300–8. Weir BK. Unruptured intracranial aneurysms: a review. J Neurosurg 2002;96(1):3–42. Wiebers DO. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003;362:103–10. White PM, Wardlaw J. Unruptured intracranial aneurysms: prospective data have arrived. Commentary. Lancet 2003;362:90–1. Guglielmi G, Vinuela F, Dion J, Duckwiler G. Electrothrombosis of saccular aneurysms via endovascular approach. Part 2. Preliminary clinical experience. J Neurosurg 1991;75:8–14. Brilstra EH, Rinkel GJE, van der Graaf Y, van Rooij WJJ, Algra A. Treatment of intracranial aneurysms by embolisation with coils: a systematic review. Stroke 1999;30:470–6. Molyneux A. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 2002;360:1267–74. Rabinstein AA, Pichelmann MA, Friedman JA, Piepgrass DG, Nichols DA, McIver JI, et al. Symptomatic vasospasm and outcomes following aneurysmal subarachnoid haemorrhage: a comparison between surgical repair and endovascular coil occlusion. J Neurosurg 2003;98:319–25.

143

[97] Nichols DA, Brown Jr. RD, Meyer FB. Coils or clips in subarachnoid haemorrhage? Lancet 2002;360:1262. [98] Ausman JI. ISAT study: is coiling better than clipping? Surg Neurol 2003;59:162–75. [99] Doll R, Wakeford R. Review article. Risk of childhood cancer from foetal irradiation. Br J Radiol 1997;70:130–9. [100] Shahabi S, Tecco L, Jani J, Pirotte B, Rodesch G, Baurain M, et al. Management of a ruptured basilar artery aneurysm during pregnancy. Acta Chir Belg 2001;101:193–5. [101] Haley EC, Kassell NF, Torner JC. The international cooperative study on the timing of aneurysmal surgery. The North American experience. Stroke 1992;23:205–14. [102] Whitfield PC, Kirkpatrick PJ. Timing of surgery for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2001;(2):CD001697. [103] Whitburn RH, Laishley RS, Jewkes DA. Anaesthesia for simultaneous caesarean section and clipping of intracerebral aneurysm. Br J Anaesth 1990;64:642–5. [104] Jaeger K, Ruschulte H, Muhlhaus K, Tatagiba M. Combined emergency caesarean section and intracerebral aneurysm clipping. Anaesthesia 2000;55:1138–40. [105] Reichman OH, Karlman RL. Berry aneurysm. Surgery in the pregnant patient. Surg Clin N Am 1995;75:115–21. [106] Bruns PD, Linder RO, Drose VE, Bataglia F. The placental transfer of water from foetus to mother following intravenous infusion of hypertonic mannitol to maternal rabbit. Am J Obstet Gynecol 1963;86:160–6. [107] Mazze RI, Kallen B. Reproductive outcome after anaesthesia and operation during pregnancy: a registry of 5405 cases. Am J Obstet Gynecol 1989;161:1178. [108] Cannell DC, Botterell EH. Subarachnoid haemorrhage and pregnancy. Am J Obstet Gynecol 1956;2:844–55.