Risk for Brain Arteriovenous Malformation Rupture During Pregnancy and Puerperium

Neurosurgery 93:918–923, 2023

The hemorrhage risk of unruptured and untreated cerebral arteriovenous malformations (AVMs) has been shown to be higher for female patients than male patients in their child bearing ages. Although it has been neurosurgical practice to advise female patients in their childbearing ages to postpone pregnancy until proven AVM obliteration, there is no literature consensus regarding this potential hemorrhage risk increase.

OBJECTIVE: To accurately quantify the risk increase for AVM hemorrhage during pregnancy.

METHODS: This study is based on data from previous publications, consisting of known age at the first AVM hemorrhage in 3425 patients. The risk increase during pregnancy could be calculated from the difference in age distribution for the first AVM hemorrhage between male patients and female patients, taking the average pregnancy time per female into account. A comparison was also made with data for all hospital discharges (13751) in Germany 2008 to 2018 with the diagnosis brain AVM.

RESULTS: The average pregnancy and puerperium time was 1.54 years per female in the patient population, which was used to determine the annual AVM hemorrhage risk during pregnancy to be around 9%. The increased risk during pregnancy was further evidenced by analysis of a subgroup of 105 female patients, for which pregnancy status at the time of hemorrhage was known.

CONCLUSION: The quantified annual risk for AVM hemorrhage during pregnancy is about 3 times higher than that of male patients at corresponding age. This provides an important basis for advising female patients with patent AVMs about the increased risk for hemorrhage that a pregnancy would entail.

Risk of First Hemorrhage of Brain Arteriovenous Malformations During Pregnancy

Neurosurgery 85:E806–E814, 2019

Recommendations on the management of brain arteriovenous malformations (bAVM) with respect to pregnancy are based upon conflicting literature.

OBJECTIVE: To systematically review the reported risk and annualized rate of first intracranial hemorrhage (ICH) from bAVM during pregnancy and puerperium.

METHODS: MEDLINE, EMBASE, and Scopus databases were searched for relevant articles in English published before April 2018. Studies providing a quantitative risk of ICH in bAVM during pregnancy were eligible.

RESULTS: From 7 initially eligible studies, 3 studies met the criteria for providing quanti- tative risk of first ICH bAVM during pregnancy. Data from 47 bAVM ICH during pregnancy across 4 cohorts were extracted for analysis. Due to differences in methodology and defini- tions of exposure period, it was not appropriate to combine the cases. The annualized risk of first ICH during pregnancy for these 4 cohorts was 3.0% (95% confidence interval [CI]: 1.7- 5.2%); 3.5% (95% CI: 2.4-4.5%); 8.6% (95% CI: 1.8-25%); and 30% (95% CI: 18-49%). Only the last result from the last cohort could be considered significantly increased in comparison with the nonpregnant period (relative rate 6.8, 95% CI: 3.6-13). The limited number of eligible studies and variability in results highlighted the need for enhanced rigor of future research.

CONCLUSION: There is no conclusive evidence of an increased risk of first hemorrhage during pregnancy from bAVM. Because advice to women with bAVM may influence the management of pregnancy or bAVM with significant consequences, we believe that a retrospective multicenter, case crossover study is urgently required.

Meningiomas in pregnancy: timing of surgery and clinical outcomes as observed in 104 cases and establishment of a best management strategy

Acta Neurochir (2018) 160:1521–1529

There is a strong correlation between the level of circulating female sex hormones and the parturient growth of meningiomas. As a result, rapid changes in meningioma size occur during pregnancy, putting both the mother and fetus at risk. Large, symptomatic meningiomas require surgical resection, regardless of the status of pregnancy. However, the preferred timing of such complex intervention is a matter of debate. The rarity of this clinical scenario and the absence of prospective trials make it difficult to reach evidence-based conclusions. The aim of this study was to create evidencebased management guidelines for timing of surgery for pregnancy-related intracranial meningiomas.

Method The English literature from 1990 to 2016 was systematically reviewed according to PRISMA guidelines for all surgical cases of pregnancy–related intracranial meningiomas. Cases were divided into two groups: patients who have had surgery during pregnancy and delivered thereafter (group A) and patients who delivered first (group B). Groups were compared for demographic, clinical and radiological features, as well as for neurosurgical, obstetrical and neonatological outcomes. Statistical analysis was performed to assess differences.

Results A total of 104 surgical cases were identified and reviewed, of which 86 were suitable for comparison and statistical analysis. Thirty-five patients (40%) underwent craniotomy for resection during pregnancy or at delivery (group A) and 51 patients (60%) underwent surgery after delivery (group B). Groups showed no significant differences in characteristics such as age at diagnosis, number of gestations, presenting symptoms, tumor site and tumor size. Despite a comparable distribution over the gestational trimesters, group A had significantly more patients diagnosed prior to the 27th gestational week (46 vs 17.5%, p = 0.0075). Group Awas also associated with a significantly higher rate of both emergent craniotomies (40 vs 19.6%, p = 0.0048) and emergent Caesarian deliveries (47 vs 17.8%, p = 0.00481). The time from diagnosis to surgery was significantly longer in group B (11 weeks vs 1 week in group A, p = 0.0013). The rate of premature delivery was high but similar in both groups (∼70%). Risks of maternal mortality or fetal mortality were associated with group A (odds ratio = 14.7), but did not reach statistical significance.

Conclusions While surgical resection of meningioma during pregnancy may be associated with increased maternal and fetal mortalities, the overall neurosurgical, obstetrical and neonatological outcomes, as well as many clinical characteristics, are similar to patients undergoing resection postpartum. We believe that fetal survival chances have a significant impact on decision-making, as patients diagnosed at a later stage in pregnancy (≥27th week of gestation) were more likely to undergo delivery first. This complicated clinical scenario requires the close cooperation of multiple disciplines. While the mother’s health and well-being should always be paramount in guiding management, we hope that the overall good outcomes observed by this systematic review will encourage colleagues to aim for term pregnancies whenever possible in order to reduce prematurity-related problems.

Lumbar disk herniation during pregnancy: a review on general management and timing of surgery

Acta Neurochir (2018) 160:1361–1370

Objective Provide an overview of existing management strategies to suggest a guideline for surgical management of lumbar disk herniation in pregnant women based on time of presentation.

Methods We performed a narrative review on the topic using the PubMed database. A total of 63 relevant articles published after 1992 were identified, of which 17 fulfilled selection criteria.

Results A total of 22 published cases of spine surgery for disk herniation during pregnancy were found in 17 studies on the topic. Prone positioning was reported in the majority of cases during the first and early second trimester. C-sections were performed prior to spine surgery in the prone position for the majority of patients operated during the third trimester. The left lateral position with continued pregnancy was preferred during the latter half of the second trimester when delivery of the fetus cannot yet be performed but surgery is indicated.

Conclusion Spine surgery during pregnancy is a rare scenario but can be performed safely when needed if providers adhere to general guidelines. Surgical approaches and overall management are influenced by the stage of pregnancy.

Spinal epidural hematomas: personal experience and literature review of more than 1000 cases

J Neurosurg Spine 27:198–208, 2017

The goal of this study was to identify factors that contribute to the formation of acute spinal epidural hematoma (SEH) by correlating etiology, age, site, clinical status, and treatment with immediate results and long-term outcomes.

METHODS The authors reviewed their series of 15 patients who had been treated for SEH between 1996 and 2012. In addition, the authors reviewed the relevant international literature from 1869 (when SEH was first described) to 2012, collecting a total of 1010 cases. Statistical analysis was performed in 959 (95%) cases that were considered valid for assessing the incidence of age, sex, site, and clinical status at admission, correlating each of these parameters with the treatment results. Statistical analysis was also performed in 720 (71.3%) cases to study the incidence of etiological factors that favor SEH formation: coagulopathy, trauma, spinal puncture, pregnancy, and multifactorial disorders. The clinical status at admission and long-term outcome were studied for each group. Clinical status was assessed using the Neuro-Grade (NG) scale.

RESULTS The mean patient age was 47.97 years (range 0–91 years), and a significant proportion of patients were male (60%, p < 0.001). A bimodal distribution has been reported for age at onset with peaks in the 2nd and 6th decades of life. The cause of the SEH was not reported in 42% of cases. The etiology concerned mainly iatrogenic factors (18%), such as coagulopathy or spinal puncture, rather than noniatrogenic factors (29%), such as genetic or metabolic coagulopathy, trauma, and pregnancy. The etiology was multifactorial in 11.1% of cases. The most common sites for SEH were C-6 (n = 293, 31%) and T-12 (n = 208, 22%), with maximum extension of 6 vertebral bodies in 720 cases (75%). At admission, 806 (84%) cases had moderate neurological impairment (NG 2 or 3), and only lumbar hematoma was associated with a good initial clinical neurological status (NG 0 or 1). Surgery was performed in 767 (80%) cases. Mortality was greater in patients older than 40 years of age (9%; p < 0.01). Sex did not influence any of these data (p > 0.05).

CONCLUSIONS Factors that contribute to the formation of acute SEH are iatrogenic, not iatrogenic, or multifactorial. The treatment of choice is surgery, and the results of treatment are influenced by the patient’s clinical and neurological status at admission, age, and the craniocaudal site.

Birth desires and intentions of women diagnosed with a meningioma

Petroclival meningioma outcomes

J Neurosurg 122:1151–1156, 2015

To the authors’ knowledge, no previous study has examined the impact of meningioma diagnosis on women’s birth desires and intentions. In an exploratory study, the authors surveyed women affected by meningioma to determine their attitudes toward childbearing and the influences, including physician recommendations, on this major life decision and compared their responses to those of women in the general population.

Methods Meningioma survivors from the Meningioma Mommas online support group participated in an online survey that included questions on their birth desires and intentions, whether the risk of disease recurrence influenced their reproductive decisions, and risks communicated to them by their physicians. Using chi-square and rank-sum tests, the authors compared the survey participants’ responses with those of the general population as assessed by the 2006– 2010 National Survey of Family Growth. Logistic regression was used to adjust for differences in age, race, ethnicity, education, parity, pregnancy status, and infertility status in these populations.

Results Respondents with meningioma were more likely than those in the general population to report wanting a baby (70% vs 54%, respectively), intending to have a baby (27% vs 12%, respectively), and being very sure about this intention (10% vs 2%, respectively). More than half (32 of 61) of the women of childbearing age reported being advised by a physician about potential risk factors for recurrence of the meningioma, and pregnancy was the most commonly cited risk factor (26 of 61). The most common factor influencing birth desires and intentions was risk of the meningioma returning and requiring more treatment, which was reported by nearly two-thirds of the women in their childbearing years.

Conclusions A majority of the meningioma survivors of childbearing age who completed the survey reported a desire for children, although concern about the risk of meningioma recurrence was an important factor for these women when making reproductive decisions. Physicians are in a position to educate their patients on potential risk factors for recurrence and to provide contact information for services such as counseling and family planning.

Cerebral Aneurysms in Pregnancy and Delivery: Pregnancy and Delivery Do Not Increase the Risk of Aneurysm Rupture

Microsurgical clipping of true posterior communicating

Neurosurgery 72:143–150, 2013

It is not known what effect pregnancy or delivery has on the risk of rupture of an intracranial aneurysm, and, consequently, the optimal management of unruptured aneurysms in pregnancy is unclear.

OBJECTIVE: To study the effect of pregnancy and delivery on the risk of rupture of intracranial aneurysms and to delineate trends in neurosurgical and obstetric management of pregnant women with intracranial aneurysms.

METHODS: The Nationwide Inpatient Sample data were analyzed for years 1988 to 2009 to estimate the risk of aneurysm rupture during pregnancies and deliveries. We calculated the risk by dividing the observed number of patients with ruptured aneurysm during pregnancy and delivery by the expected number based on the incidence among women of pregnancy age.

RESULTS: There were 714 and 172 hospitalizations involving ruptured aneurysms with pregnancy and delivery, respectively. Assuming 1.8% prevalence of unruptured aneurysms among all women of pregnancy age, we estimated that 48 873 women hospitalized for pregnancy and 312 128 women hospitalized for delivery had unruptured aneurysms. The risks of rupture during pregnancy and deliveries were 1.4% (95% confidence interval [CI] = [1.35, 1.57]) and 0.05% (95% CI = [0.0468, 0.0634]), respectively. Of 218 deliveries performed with unruptured aneurysm, 153 were cesarean deliveries (70.18%, 95% CI = [64.06, 76.30%]), suggesting that the rate of cesarean deliveries in patients with unruptured aneurysms is significantly higher than in the general population (P < .001).

CONCLUSION: We were not able to find an increased association between pregnancy or delivery and the risk of rupture of cerebral aneurysms. The significantly higher rate of cesarean deliveries performed in patients with unruptured aneurysms may not be necessary.

Meningiomas in Pregnancy

Neurosurgery 71:951–961, 2012

Dramatic growth of meningiomas is occasionally encountered during pregnancy. While cell proliferation is often assumed, hemodynamic changes have also been touted as a cause.

OBJECTIVE: We identified 17 meningiomas resected during pregnancy or within 3 weeks post-partum and characterized them to determine the cause of occasional rapid growth in pregnancy.

METHODS: Seventeen tumors were identified from searches at 4 university centers. All available clinical records, radiology images, and tissue specimens were reviewed, with immunohistochemical studies performed as needed.

RESULTS: Sixteen patients underwent tumor resection and 1 died of complications prior to surgery. Average patient age was 32 years. Nine experienced onset of symptoms in the third trimester or within 8 days post-partum. Principle physical findings included visual complaints (59%) and cranial nerve palsies (29%). Ten tumors (59%) were located in the skull base region. The Ki-67 labeling index was low (0.5-3.6%) in 11 of 13 benign (grade I) tumors and elevated (11-23.2%) in 3 of 4 atypical (grade II) meningiomas. Eight (50%) tumors featured hypervascularity with at least focal CD34- positive hemangioma-like microvasculature. Fourteen (82%) showed evidence of intraand/ or extracellular edema, 1 so extensive that its meningothelial nature was not apparent. Five tumors (29%) exhibited intratumoral hemorrhage and/or necrosis.

CONCLUSION: Our series suggests that pregnancy-associated meningiomas located in the skull base are likely to require surgical intervention for visual complaints and cranial nerve palsies. The rapid tumor growth is more often due to potentially reversible hemodynamic changes rather than hormone-induced cellular proliferation.

Hemorrhage From Arteriovenous Malformations During Pregnancy

Neurosurgery 71:349–356, 2012 DOI: 10.1227/NEU.0b013e318256c34b

Previous hemorrhage, deep venous drainage, and deep location are established risk factors for arteriovenous malformation (AVM) hemorrhage. Although pregnancy is an assumed risk factor, there is a relative paucity of data to support this neurosurgical tenet.

OBJECTIVE: To elucidate the hemorrhage rate of AVMs during pregnancy.

METHODS: We reviewed the records of 54 women with an angiographic diagnosis of an AVM at our institution. Annual hemorrhage rates were calculated as the ratio of the number of bleeds to total number of patient-years of follow-up. Patient-years of followup were tallied assuming lesion presence from birth until AVM obliteration. The Cox proportional hazards model for hemorrhage with pregnancy as the time-dependent variable was used to calculate the hazard ratio.

RESULTS: Five hemorrhages in 4 patients occurred over 62 pregnancies, yielding a hemorrhage rate of 8.1% per pregnancy or 10.8% per year. Over the remaining 2461.3 patient-years of follow-up, only 28 hemorrhages occurred, yielding an annual hemorrhage rate of 1.1%. The hazard ratio for hemorrhage during pregnancy was 7.91 (P = 2.23 x 10-4), increasing to 18.12 (P = 7.31 x 10-5) when limiting the analysis to patient follow-up up to age 40.

CONCLUSION: Because of the increased risk of hemorrhage from AVMs during pregnancy, we recommend intervention in women who desire to bear children, particularly if the AVM has bled. If the AVM is discovered during pregnancy, we recommend early intervention if it has ruptured; if it is unruptured, we recommend comprehensive counseling, weighing risks of intervention against continuation of pregnancy without intervention.