Surg Neurol 305 1990 ;33 :305-13 Vascular Malformations and Pregnancy Balaji Sadasivan, M .B .B .S ., F.R.C.S ., Ghaus M . Malik, M .D., Chang Lee, M.D., and James 1. Ausman, M.D ., Ph.D. Henry Ford Neurosurgical Institute, Department of Neurological Surgery, Henry Ford Hospital Division, and Department of Gynecology & Obstetrics, Henry Ford Hospital, Detroit, Michigan Sadasivan B, Malik GM, Lee C, Austrian JI. Vascular malformations and pregnancy . Surg Neurol 1990 ;33 :305-13 . Between January 1975 and June 1989, 240 patients with cerebral vascular malformations were treated at Henry Ford Hospital . In 16 of the patients, the treatment was influenced by pregnancy. Eleven of the patients presented with hemorrhage, four with seizures, and one with hydrocephalus . There were no maternal or fetal deaths in the patients presenting with seizure or hydrocephalus . There were two maternal deaths and one fetal death among the cases presenting with hemorrhage . In the patients with seizure or hydrocephalus, the pregnancy was brought to term and obstetric indications used to determine the time and method of delivery . Hydrocephalus was treated by shunting, and seizures with medication . Antiepileptic drug levels fluctuate in pregnancy and hence were closely monitored to ensure therapeutic levels . Vascular malformations are the most common cause of subarachnoid hemorrhage in pregnancy . The risk of rebleed in the same pregnancy is about 27% . If an arteriovenous malformation ruptures during pregnancy and the patient's condition deteriorates, appropriate emergency surgery should be done . In stable patients, our policy has been to bring the pregnancy to term and then electively perform a craniotomy to excise the arteriovenous malformation. KEY WORDS : Arteriovenous malformation ; Hydrocephalus ; Pregnancy ; Seizures ; Subarachnoid hemorrhage Introduction Spontaneous subarachnoid hemorrhage (SAH) due to ruptured aneurysm or arteriovenous malformation (AVM) accounts for about 4 .4% of all maternal deaths [2] . It is the third most frequent nonobstetric cause for maternal death [2] . About half the patients who present with SAH during pregnancy have a ruptured AVM Address reprint requests to : Ghaus M . Malik, M .D ., Henry Ford Neurosurgical Institute, Department of Neurological Surgery, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, Michigan 48202 . Received October 20, 1989 ; accepted December 19, 1989 . 0 1990 by Elsevier Science Publishing Co., Inc. [22,23}. The presence of an AVM, ruptured or unruptured, complicates the management of pregnancy . Pregnancy also affects the natural history of an AVM, making it more likely to hemorrhage . We present our experience in the management of 16 patients with vascular malformations complicated by pregnancy . We also discuss some of the problems in the management of vascular malformations during pregnancy . Clinical Material and Methods Between January 1975 and June 1989, 240 patients with cerebral vascular malformations were treated at Henry Ford Hospital . In 16 of the patients, the management was complicated by pregnancy . Eleven patients had a history of hemorrhage . The unruptured AVMs were diagnosed because of seizures in four patients and hydrocephalus in one patient . Results Ruptured Arteriovenous Malformation The clinical findings, management, and outcome of each case are summarized in Table 1 . One case of hemorrhage occurred in the first trimester, three cases in the second trimester, four cases in the third trimester, and three cases in the puerperium. There were four primigravida patients (average age 21 .3 years) and seven multigravida patients (average age 30 .9 years) . In cases 2 and 9, the malformation was a venous angioma . Three patients presented in a comatose state with decerebrate posturing . Headache was a complaint for all noncomatose patients . Two patients had grand mal seizures at the time of hemorrhage . In 10 patients, the vascular malformation was excised . Six patients had good results, and one had a fair result. There were two maternal deaths (cases 6 and 7), and one case with a poor result secondary to severe arterial narrowing (case 1) . In case 8, the AVM was not operated on . There was one fetal death (case 3) . 0090-3019/901$3 .50 Age (yr) 26 19 38 25 39 27 37 Case no . 1 2 3 4 5 6 7 G3P2AO G3P2AO G2PIAO GIPOAO G4P3AO GIPOAO G3POA2 Parity Corpus callosum R basal ganglia Lhemiplegiathen decerebrate 34 weeks 36 weeks AVM AVM Headache, drowsiness Headache, I . hemiparesis 27 weeks AVM Corpus callosum Decerebrate AVM R lateral ventricle Headache, seizure Headache, lethargy, L hemiplegia, fetal distress 21 weeks 23 weeks Headache, dysphasia, R hemiparesis Presenting complaint l2 weeks Gestation at time of hemorrhage 23 weeks Venous angioma AVM AVM L parietotemporal R parietal L occipital Site Type of vascular malformation Table 1 . Patients with Ruptured Arteriovenous Malformation Rebled day 6 postpartum . Emergency craniotomy, evac of hematoma, and exc of AVM Craniotomy and exc of AVM 3 mo postdelivery Craniotomy with evac ICH . Aggressive mngt of ICP Exc of AVM 4 yrs after delivery Emergency CS followed by emergency evac of ICH. Exc AVM remnant 2 weeks later Emergency evac hematoma . Exc AVM 2 mo postdelivery Craniotomy and exc 9 days after hemorrhage Management Delivered stillborn by CS at 23 weeks Membrane ruptured at 34 weeks; CS done to avoid labor, infant well Infant well CS at 34 weeks immediately after cranioromy ; infant well CS at 36 weeks for fetal distress; infant well Good Good ; left with residual hemiparesis Progressive neurologic deterioration ; brain death Posrop gramnegative ventriculitis ; died I me later Good Spontaneous abortion just before hemorrhage CS at 36 weeks Outcome of infant Poor ; bilateral infarcts from arterial narrowing Good Outcome of mother Surg Neurol 1990 ;33:305-13 AVM and Pregnancy 307 Maternal Mortality Case 6 was a 27-year-old woman, gravida 3, para 2, who at 34 weeks of pregnancy had the sudden onset of left hemiplegia and progressed to decerebrate posturing . Computed tomography (CT) scan showed a right basal ganglia hemorrhage . An emergency craniotomy, evacuation of hematoma, and excision of AVM were performed. This was followed by a cesarean section in which a healthy baby was delivered . The patient remained comatose, and despite aggressive medical treatment with Mannitol (Astra Pharmaceutical Products, Inc ., Westboro, Mass-) and Lasix (Hoechst-Roussel Pharmaceuticals, Inc ., Sommerville, NJ), she progressed to brain death . Case 7 was a 37-year-old woman, gravida 3, para 2, who presented with headache and drowsiness at 36 weeks of pregnancy . Computed tomography scan showed intraventricular hemorrhage . Cerebral angiography revealed a corpus callosum AVM . A cesarean section was performed at 36 weeks for fetal distress. The infant was healthy . On the sixth postpartum day, she rebled and became comatose (Figure 1) . An emergency craniotomy, evacuation of hematoma, and excision of AVM were performed . The postoperative period was complicated by gram-negative ventriculitis . She remained in a vegetative state for a month and then died . Fetal Mortality Case 3 was a 38-year-old woman, gravida 4, para 3, who at 23 weeks gestation developed headache, lethargy, and hemiplegia . She also had evidence of fetal distress . An emergency cesarean section was performed and a stillborn fetus was delivered . This was followed by a craniotomy, evacuation of hematoma, and excision of right parietal AVM . Postoperative angiography showed residual AVM, which was excised 2 weeks later. The patient had a good outcome. Morbidity from "Vasospasm" Case 1 was a 26-year-old woman, gravida 3, para 0, who by history was 12 weeks pregnant when she was admitted with a left occipital hemorrhage . There was a history of vaginal bleeding the day before admission . Ultrasound of the pelvis could not detect a gestational sac . Serum human chorionic gonadotropin tested twice was 41 and 47 mIU/mL (normal nonpregnant, <10 mIU/mL ; 12 weeks pregnant, 500-200,000 mIU/mL) . We concluded that she had a spontaneous abortion before her admission . On the ninth day after admission, her condition worsened . The AVM was excised, and the hematoma 308 Surg Neurol 1990 ;33 :305-13 Sadasivan et al Figure 1 . rare 7 . (Lefty CT scan at time of admission (36 weeks gestation) shoes a little blood along the margin of the left lateral ventricle . (Right) CT Bran on sixth poitparttim day ehou~se rehemorrhage . evacuated . Angiograms the next day revealed severe narrowing of bilateral carotid, anterior cerebral, and middle cerebral arteries (Figure 2) . She sustained infarcts in both hemispheres and is in a vegetative state . was successfully managed and healthy infants delivered at term based on obstetric indications . The patients had elective craniotomy and excision of AVM between 2 to 16 years after their pregnancy, with four good results and one fair result . Unoperated Arteriovenous Malformation Case S was a 23-year-old woman, gravida 4, para 3, who at 32 weeks of pregnancy presented with headache . Magnetic resonance imaging (MRI) revealed a small left medial temporal lobe AVM and hematoma . At 34 weeks, a cesarean section was performed and a healthy infant delivered . Cerebral angiography showed no evidence of the AVM that was present on MRI . We believe the AVM was probably thrombosed . We intend to repeat angiography and MRI 1 year later . Unruptured Arteriovenous Malformations The clinical findings, management, and outcome of the patients with unruptured AVMs are summarized in Table 2. The four patients who presented with seizure during pregnancy were primigravid . Three had their first episode of grand mal seizure during the pregnancy . One patient (case 1) had the first episode ofgrand mal seizure at age 12 . She was seizure-free until her first pregnancy at age 21 . Case 16 was a 27-year-old woman, gravida 2, para 1, who complained of headache . A CT scan showed hydrocephalus and a third ventricular AVM . Cerebral angiography revealed the third ventricular AVM . She also had an AVM in the lung (Rendu-Osler-Weber syndrome) (Figure 3). She was treated with a ventriculoperitoneal shunt. The AVM was excised 3 years later . In all five cases of unruptured AVM, the pregnancy Discussion Robinson et al [22,23] have shown an association between pregnancy and hemorrhage from an AVM . They compared women younger than 45 years old who were diagnosed as having an AVM and were pregnant within 2 years of the diagnosis with similar women who were not pregnant within 2 years of the diagnosis . There was a 10% incidence of SAH in the nonpregnant group and an 85% incidence of SAH in the pregnant group . If a pregnant woman presents with a diagnosis of SAH, the chance of an AVM being the cause of the SAH is 50%, as compared with 10% in nonpregnant women . The risk of rebleed after a ruptured AVM is about 6% in the first year [29] . The risk of rebleed within the same pregnancy after a hemorrhage is 27% [22] . We have added our cases to others reported in the literature to create a composite graph showing the period in gestation when rupture occurred (Figure 4) [1,2,4,6,11,18,23,26] . This graph shows that AVMs tend to rupture between 20 weeks gestation and 6 weeks postpartum . The tendency to rupture may be related to hemodynamic, hormonal, and coagulation changes that occur during this period . Cardiac output rises during pregnancy by 30%-60% . The increase begins during the first trimester and reaches a maximum toward the end of the second trimester [13] . This high level is maintained AVM and Pregnancy until term . The levels return to the prepregnancy state several weeks after delivery . The period of increased risk of hemorrhage coincides with the period of raised cardiac output . The increase in cardiac output is greater than can be accounted for by the increase in uterine blood flow. This increase in cardiac output appears to be mediated by a decrease in systemic vascular resistance. The mechanism for this vasodilatation is not known, but it may be secondary to the rise in estrogens [27] . Fibrin formation may increase fivefold in pregnancy . This is accompanied by substantially increased fibrinolysis . Although fibrin formation should improve hemostasis, the increase in fibrinolysis makes the patient vulnerable to intravascular coagulation and its hemorrhagic complications [10] . The management of ruptured vascular malformations during pregnancy is difficult . When a pregnant patient is suspected of having SAH, a CT scan on the head with appropriate shielding of the abdomen should be done . Once the diagnosis is confirmed, the management is based on neurosurgical rather than obstetric criteria. Surg Neurol 1990 ;33 : 3 0 5 -13 309 Figure 2 . Case 1 . Angiogram shows severe arterial narrowing of right internal carotid artery, middle cerebral artery . and anterior cerebral artery 10 days after hemorrhage . If the patient has an intracranial hematoma and clinical evidence of herniation . emergency evacuation of the hematoma is necessary . There have been several reports of successful excision of AVMs in pregnant women using hypothermia [5 8 .9,18] . The risk of hypothermia to the fetus is unknown . During surgery of the pregnant patient, hypotension and osmotic diuretics should be avoided . Maternal hypotension causes fetal hypoxia . Osmotic diuretics such as Mannitol have been shown to cross the placenta and raise the osmolarity of fetal plasma [3,8] . This can result in fetal dehydration. Two of the vascular malformations in our patients were venous angiomas (Figure 5, The risk of hemorrhage from venous angioma is real though not well established statistically . Malik et al [17] reported nine patients with hemorrhage in their series of 21 cases of venous angioma. Two of the nine patients with 310 Surg Neurol 1990 ;33 :305-13 Sad asivan er al Table 2 . Patients with Unruptured Arteriovenoui Malformation During Pregnancy Case Age no . (yr) Parity Presentation 12 21 GIPOAO GMS at age 12 ; seizure- L,aationofAVM Management Outcome L frontoparietal AVM Continued to have seizures about 2 episodestyr for 6 yrs . Had 2nd child, craniommy . and cxc of First episode of GMS during pregnancy L parietotemporal AVM No deficits ; psychomotor Episode L body numbness at ages 7, 13, 17 ; headache at 3 me gestation ; 1st episode of GMS at 6 mn gestation Episode R body numbness at age 15 ; GMS during pregnancy R parietal AVM Psychomotor seizures fur I6 pr a . Craniotomy and cxc of AVM Craniotomy and exc of AVM 2 yrs later L frontoparietal AVM Progressive increased seizures and spastic R hemiparcsis 2 yrs . Craniotomy and exc of R hemiparcsis, dysphasia, impaired memory Corpus collosum AVM, 3rd ventricular AVNI Ventriculuperitiineal shunt, 3 yrs- post delivery craniotomy and exc of AVM free until first pregnancy Expressive dysphasia and dyscalculia; seizures AVM 16 14 30 GIPOAO GIPOAO 15 30 GIPOAO 16 27 G2P1AO seizures cinder control I, horn ouymous hemianopsia, seizures AVM L leg weakness and paresthesia; headache backache ; CT scan : hydrocephalus and 3rd ventricular AVM Transient diabetes illsipidus . Discovered to have pulmonary AVM (Rendu-Osler-W cher syndrome) Abbreviations : AVM, Arreriovenoos meltormation ; ex(, excision ; CMS . grind mal seio.iire L, Iet, R, rightr hemorrhage from venous angioma were pregnant at the time of hemorrhage . Pregnancy and/or the sex hormones may have a role in increasing the risk of hemorrhage from venous angioma . Angiographic arterial narrowing (vasospasm) after hemorrhage from an AVM is rare . There are few reports of radiologic evidence of arterial narrowing after hemorrhage from an AVM, bur the arterial narassociated with infarction rowing was not [20,24,25,28]. The occurrence of arterial narrowing and subsequent infarcts in case I is unusual . Again, the role of pregnancy in contributing to the arterial narrowing remains speculative . There are several considerations in the management of non-life-threatening, ruptured AVMs in pregnancy once the diagnosis is made : 1 . The pregnant patient is at increased risk of rebleed during the pregnancy and puerperium . This risk can be eliminated only by excision of the AVM . 2 . Surgery during pregnancy poses risks to the fetus and the mother . 3 . The technical difficulty and risks in excising the lesion need consideration . The size, location, arterial supply, and venous drainage, as well as the need for preoperative embolization in selected cases, should be considered . 4 . If the malformation is in an eloquent area, the patient may wish to postpone surgery to when it is easier for her and her family to deal with any disability, even a temporary one . In general, if we are dealing with an AVM that can be easily excised with low risk, we wait until the fetus is mature enough to he safely delivered (usually 34 to 38 weeks) . Cerebral angiography (if not performed previously) and excision of the AVM can then be performed . It is difficult to determine the best time to perform the elective surgery to excise the AVM . Puerperium is a period of increased risk of hemorrhage, and delaying surgery until after puerperium exposes the patient to this risk . We have generally performed the elective surgery about 2 months after the delivery when the hcmodynamic changes associated with pregnancy return to normal . We have presumed that this makes the surgery easier . Ilowever, a strong case can be made for surgery immediately after delivery . Case 7 in this report rebled on the sixth postdelivery day . Treatment in all cases should be individualized after discussion with the patient and her family . Surg Neurol 1990 ;33 :305-13 AVM and Pregnancy Figure 3 . Case 10 (Rendu-O.ler-Weber syndronme) . (Lefty CT scan with contrail enhancement shoos the third ventricular AVM . (Right) Right pulmonary angiogram shouu an AVM in the lung . It is unclear whether labor increases the risk of hemorrhage . Biller and Adams [4] reported a case of hemorrhage from an AVM during labor . One third of pregnant women have markedly elevated cerebrospinal fluid pressure during labor f 19} . The Valsalva effect during labor causes the venous pressure to rise and increases the stress on the abnormal veins in the AVM . We think it is probably safer to perform an elective cesarean section . The management of patients with unruptured AVM during pregnancy is based on obstetric criteria . The AVM is treated after delivery based on the same principles as in nonpregnant women . The unruptured AVM in most cases is diagnosed because of seizures . In 13% of all epileptic women, seizures first begin during a pregnancy [14,15} . Estrogens and chorionic gonadotropin appear to lower the seizure threshold . In the presence of an epileptogenic focus such as an AVM, the lowered threshold causes a seizure . No anticonvulsant is free of teratogenic risk . To minimize the teratogenic risk, it is probably safer to use monotherapy rather than multiple drug therapy . There are several good reviews in the management of 31 1 epilepsy in pregnancy [7,12,15,16,21]- Phenytoin or carbamazepine may be used . It is important to measure serum anticonvulsant levels throughout pregnancy . High or toxic levels should be avoided in the first trimester because this is the period of greatest teratogenic risk, and the risk may be dose dependent . 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