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doi:10.1111/jog.12546
J. Obstet. Gynaecol. Res. Vol. 41, No. 3: 464–467, March 2015
Recurrent brain tumor with hydrocephalus in pregnancy Enes Taylan, Ali Akdemir, Burak Zeybek, Ahmet Mete Ergenoglu and Ahmet Ozgur Yeniel Department of Obstetrics and Gynecology, Ege University School of Medicine, Izmir, Turkey
Abstract Brain tumors during pregnancy are very rare. Diagnosis of this condition is difficult because the symptoms imitate pregnancy-related ailments. The management of this condition also presents challenges. This case report aims to present a successful treatment and delivery of a patient with recurrent brain tumor during pregnancy with hydrocephalus. Key words: brain tumor, cesarean section, convulsion, hydrocephalus, pregnancy.
Introduction Primary malignant brain tumors during pregnancy are very rare with an incidence of 2.6–15 per 100 000.1–3 The management of this condition still presents many challenges. Initial diagnosis is difficult because symptoms imitate pregnancy-related conditions and treatment options are limited because of the risks of teratogenicity associated with chemotherapy. This case report presents the successful management and delivery of a pregnant woman with recurrent brain tumor, which most likely caused severe epileptic seizures and hydrocephalus.
Case Three years before admission to our clinic, a 21-yearold patient presented to our hospital’s emergency department with complaints of severe headache, projectile vomiting and syncope. An emergency magnetic resonance imaging (MRI) revealed a large mixed hemorrhagic and necrotic mass with surrounding edema in the right hemisphere likely to be high-grade thalamocallosal glial tumor with a dimension of 5 × 4 × 4 cm (Fig. 1). The patient underwent successful debulking neurosurgery that confirmed her diagnosis
of glioblastoma (World Health Organization [WHO] grade IV). Subsequently, she underwent 60 Gy in 30 fractions of computed tomography planned conformal external beam radiotherapy for 6 weeks with concomitant oral temozolomide at 75 mg/m2 daily. After serial MRI imaging every 6 months for 18 months, there was no evidence of recurrence. The patient then resigned from serial monitoring. Three years after initial diagnosis, the patient was admitted to our emergency department for a second time with complaints of headache, convulsion, bilateral weakness and balance difficulties. A new cranial diffusion MRI showed a severe communicating hydrocephalus and recurrent tumor in the previous operation locus (Fig. 2). Although glioblastoma (WHO grade IV) is a high-grade tumor, it rarely metastasizes outside the central nervous system and abdominal ultrasound showed a normal looking 24-week fetus and placenta. A multidisciplinary team provided information for the patient and her family about the following options: (i) termination of pregnancy; and (ii) palliative neurosurgery followed by delivery by elective cesarean section at 34 weeks’ gestation and postnatal temozolomide chemotherapy. The patient and her family declined the option of termination and she
Received: March 8 2014. Accepted: July 28 2014. Reprint request to: Dr Enes Taylan, Department of Obstetrics and Gynecology, Ege University School of Medicine, Bornova, Izmir 35100, Turkey. Email: [email protected]
464
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Recurrent brain tumor in pregnancy
Figure 1 Thalamocallosal glial tumor in the right hemisphere.
Figure 3 Cranial magnetic resonance imaging at 32 weeks of gestation shows stable, non-expanding brain tumor.
underwent ventriculoperitoneal-shunting operation. After the operation, the patient was transferred to our obstetrics service and followed up until 34 weeks’ gestation. During this course the patient was given levetiracetam and sodium valproate by a neurologist to reduce the frequency of epileptic seizures. Furthermore, two doses of betamethasone (12 mg) were given for both promoting fetal lung maturity and reducing maternal peritumoral edema at 24 weeks’ of gestation. After a successful 10 weeks of monitoring by ultrasound, non-stress test of the fetus and effective anticonvulsant therapy with cranial MRI imaging showing a non-expanding tumor (Fig. 3), a cesarean section was performed at 34 weeks’ gestation under general anesthesia. A live-born female infant was delivered weighing 1750 g in good condition. Later that day the patient was transferred to the neurosurgery service with a hemodynamically stable condition for planned temozolomide chemotherapy.
Discussion Figure 2 Recurrent brain tumor during pregnancy.
Primary malignant brain tumors during pregnancy are very rare with an incidence of 2.6–15/100.000.1–3
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
465
E. Taylan et al.
However, its impact on the course of pregnancy is critical and management of these patients has unique challenges with ethical and religious factors influencing the decision-making process. Despite many advances in treatment, the prognosis is still poor. Brain tumors during pregnancy can present with numerous symptoms depending on the size, location and the origin of the lesions. Typical common symptoms include headache, vomiting, seizures, syncope, balance disorders and cognitive dysfunction, which may mimic pregnancy-related conditions, such as preeclampsia and eclampsia, and unfortunately cause delay in diagnosis.4,5 Moreover, pregnancy may lead to an increase in the size of brain tumors due to fluid accumulation and vascular engorgement related to hormonal changes, which induce progression of neurologic symptoms.6,7 Management of these patients depends on acuity of presentation, location, size of the tumor, severity and progression of symptoms and gestational age. Once the diagnosis is confirmed, a multidisciplinary approach must be carried out in order to discuss treatment options and risks comprehensively with patients and their families. Pharmacological treatment options include corticosteroids and anticonvulsant agents. Steroids, particularly betamethasone, may help to reduce the peritumoral edema and promote fetal lung maturity.7 Dexamethasone is commonly used for neurosurgical patients, however repeated doses of dexamethasone during the antenatal period may cause decreased birthweight and decreased neurological development of the fetus.8,9 Thus, in our case we used two doses of betamethasone 12 mg intramuscularly at 24 weeks’ gestation primarily for fetal lung maturation in case of preterm delivery. This corticosteroid treatment may have also helped to reduce brain edema. Also, lamotrigine, levetiracetam and carbamazepine are the safest anticonvulsants in which benefits outweigh the risks of teratogenicity.10–12 Other treatment options include tumor resection, chemotherapy and radiotherapy. Despite the known teratogenicity of chemotherapeutic agents and radiation, McGrane et al.11 reported a successful pregnancy and delivery in a patient with glioblastoma treated with external beam radiotherapy over 6 weeks with concomitant oral 75 mg/m2 temozolomide daily. Tewari et al.12 developed an algorithm for the management of brain tumors in pregnancy. Within this algorithm, during the first or early second trimester and late second or third trimesters of pregnancy a stable patient should be allowed to continue with preg-
466
nancy, and surgery should be delayed. Second trimester is the ideal time for surgery during pregnancy. Once fetal lung maturity is established, the patient should be delivered. For patients clinically unstable with neurological deterioration and mental status changes, an immediate cesarean section under general anesthesia, followed by tumor resection was recommended to minimize the risk of cerebral herniation. Vaginal delivery is another option for clinically stable patients. In our case, the patient was in the late second trimester and clinically stable. She wanted to continue her pregnancy and declined the options of chemotherapy and radiotherapy as she had already received the maximum radiation exposure during the initial treatment 3 years before. Ventriculoperitoneal shunting operation was considered and performed in order to treat the hydrocephalus and decrease intracranial pressure. In some cases, brain tumor growth may accelerate during pregnancy depending on multiple factors, such as increased systemic and cerebral blood volume, growth factors and progesterone, which enhances tumor cell growth via progesterone receptor (PR) – B.12–14 Fortunately, in our case, during the 10 weeks of follow-up, recurrent tumor size and related edema were steady, the patient was clinically stable and ventriculoperitoneal shunt functioned without failure. In conclusion, management of brain tumors during pregnancy alters with a myriad of factors that must be assessed in a multidisciplinary approach involving tumor resection, chemotherapy and radiotherapy. The aim of treatment is to achieve well-being for both fetus and mother. Despite many advances in treatment, prognosis is still very poor.
Acknowledgments The authors wish to thank to Maciej Rojna from Nicolaus Copernicus University, Collegium Medicum at Bydgoszcz.
Disclosure The authors state that there is no conflict of interest.
References 1. Haas JF, Jänisch W, Staneczek W. Newly diagnosed primary intracranial neoplasms in pregnant women: A populationbased assessment. J Neurol Neurosurg Psychiatry 1986; 49: 874– 880.
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Recurrent brain tumor in pregnancy
2. Bondy ML, Scheurer ME, Malmer B et al. Brain tumor epidemiology: Consensus from the Brain Tumor Epidemiology Consortium. Cancer 2008; 113: 1953–1968. 3. Roelvink NC, Kamphorst W, van Alphen HA, Rao BR. Pregnancy-related primary brain and spinal tumors. Arch Neurol 1987; 44: 209–215. 4. Chaudhuri P, Wallenburg HC. Brain tumors and pregnancy. Presentation of a case and a review of the literature. Eur J Obstet Gynecol Reprod Biol 1980; 11: 109–114. 5. Mackenzie AP, Levine G, Garry D, Figueroa R. Glioblastoma multiforme in pregnancy. J Matern Fetal Neonatal Med 2005; 17: 81–83. 6. Michelsen JJ, New PF. Brain tumour and pregnancy. J Neurol Neurosurg Psychiatry 1969; 32: 305–307. 7. Isla A, Alvarez F, Gonzalez A, García-Grande A, Perez-Alvarez M, García-Blazquez M. Brain tumor and pregnancy. Obstet Gynecol 1997; 89: 19–23. 8. Lee BH, Stoll BJ, McDonald SA, Higgins RD, National Institute of Child Health and Human Development Neonatal Research Network. Adverse neonatal outcomes associated
9.
10.
11.
12.
13. 14.
with antenatal dexamethasone versus antenatal betamethasone. Pediatrics 2006; 117: 1503–1510. Newnham JP, Jobe AH. Should we be prescribing repeated courses of antenatal corticosteroids? Semin Fetal Neonatal Med 2009; 14: 157–163. Jayasekera BA, Bacon AD, Whitfield PC. Management of glioblastoma multiforme in pregnancy. J Neurosurg 2012; 116: 1187–1194. McGrane J, Bedford T, Kelly S. Successful pregnancy and delivery after concomitant temozolomide and radiotherapy treatment of glioblastoma multiforme. Clin Oncol (R Coll Radiol) 2012; 24: 311. Tewari KS, Cappuccini F, Asrat T et al. Obstetric emergencies precipitated by malignant brain tumors. Am J Obstet Gynecol 2000; 182: 1215–1221. Fuglsang J, Ovesen P. Aspects of placental growth hormone physiology. Growth Horm IGF Res 2006; 16: 67–85. González-Agüero G, Gutiérrez AA, González-Espinosa D et al. Progesterone effects on cell growth of U373 and D54 human astrocytoma cell lines. Endocrine 2007; 32: 129–135.
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
467
doi:10.1111/jog.12546
J. Obstet. Gynaecol. Res. Vol. 41, No. 3: 464–467, March 2015
Recurrent brain tumor with hydrocephalus in pregnancy Enes Taylan, Ali Akdemir, Burak Zeybek, Ahmet Mete Ergenoglu and Ahmet Ozgur Yeniel Department of Obstetrics and Gynecology, Ege University School of Medicine, Izmir, Turkey
Abstract Brain tumors during pregnancy are very rare. Diagnosis of this condition is difficult because the symptoms imitate pregnancy-related ailments. The management of this condition also presents challenges. This case report aims to present a successful treatment and delivery of a patient with recurrent brain tumor during pregnancy with hydrocephalus. Key words: brain tumor, cesarean section, convulsion, hydrocephalus, pregnancy.
Introduction Primary malignant brain tumors during pregnancy are very rare with an incidence of 2.6–15 per 100 000.1–3 The management of this condition still presents many challenges. Initial diagnosis is difficult because symptoms imitate pregnancy-related conditions and treatment options are limited because of the risks of teratogenicity associated with chemotherapy. This case report presents the successful management and delivery of a pregnant woman with recurrent brain tumor, which most likely caused severe epileptic seizures and hydrocephalus.
Case Three years before admission to our clinic, a 21-yearold patient presented to our hospital’s emergency department with complaints of severe headache, projectile vomiting and syncope. An emergency magnetic resonance imaging (MRI) revealed a large mixed hemorrhagic and necrotic mass with surrounding edema in the right hemisphere likely to be high-grade thalamocallosal glial tumor with a dimension of 5 × 4 × 4 cm (Fig. 1). The patient underwent successful debulking neurosurgery that confirmed her diagnosis
of glioblastoma (World Health Organization [WHO] grade IV). Subsequently, she underwent 60 Gy in 30 fractions of computed tomography planned conformal external beam radiotherapy for 6 weeks with concomitant oral temozolomide at 75 mg/m2 daily. After serial MRI imaging every 6 months for 18 months, there was no evidence of recurrence. The patient then resigned from serial monitoring. Three years after initial diagnosis, the patient was admitted to our emergency department for a second time with complaints of headache, convulsion, bilateral weakness and balance difficulties. A new cranial diffusion MRI showed a severe communicating hydrocephalus and recurrent tumor in the previous operation locus (Fig. 2). Although glioblastoma (WHO grade IV) is a high-grade tumor, it rarely metastasizes outside the central nervous system and abdominal ultrasound showed a normal looking 24-week fetus and placenta. A multidisciplinary team provided information for the patient and her family about the following options: (i) termination of pregnancy; and (ii) palliative neurosurgery followed by delivery by elective cesarean section at 34 weeks’ gestation and postnatal temozolomide chemotherapy. The patient and her family declined the option of termination and she
Received: March 8 2014. Accepted: July 28 2014. Reprint request to: Dr Enes Taylan, Department of Obstetrics and Gynecology, Ege University School of Medicine, Bornova, Izmir 35100, Turkey. Email: [email protected]
464
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Recurrent brain tumor in pregnancy
Figure 1 Thalamocallosal glial tumor in the right hemisphere.
Figure 3 Cranial magnetic resonance imaging at 32 weeks of gestation shows stable, non-expanding brain tumor.
underwent ventriculoperitoneal-shunting operation. After the operation, the patient was transferred to our obstetrics service and followed up until 34 weeks’ gestation. During this course the patient was given levetiracetam and sodium valproate by a neurologist to reduce the frequency of epileptic seizures. Furthermore, two doses of betamethasone (12 mg) were given for both promoting fetal lung maturity and reducing maternal peritumoral edema at 24 weeks’ of gestation. After a successful 10 weeks of monitoring by ultrasound, non-stress test of the fetus and effective anticonvulsant therapy with cranial MRI imaging showing a non-expanding tumor (Fig. 3), a cesarean section was performed at 34 weeks’ gestation under general anesthesia. A live-born female infant was delivered weighing 1750 g in good condition. Later that day the patient was transferred to the neurosurgery service with a hemodynamically stable condition for planned temozolomide chemotherapy.
Discussion Figure 2 Recurrent brain tumor during pregnancy.
Primary malignant brain tumors during pregnancy are very rare with an incidence of 2.6–15/100.000.1–3
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
465
E. Taylan et al.
However, its impact on the course of pregnancy is critical and management of these patients has unique challenges with ethical and religious factors influencing the decision-making process. Despite many advances in treatment, the prognosis is still poor. Brain tumors during pregnancy can present with numerous symptoms depending on the size, location and the origin of the lesions. Typical common symptoms include headache, vomiting, seizures, syncope, balance disorders and cognitive dysfunction, which may mimic pregnancy-related conditions, such as preeclampsia and eclampsia, and unfortunately cause delay in diagnosis.4,5 Moreover, pregnancy may lead to an increase in the size of brain tumors due to fluid accumulation and vascular engorgement related to hormonal changes, which induce progression of neurologic symptoms.6,7 Management of these patients depends on acuity of presentation, location, size of the tumor, severity and progression of symptoms and gestational age. Once the diagnosis is confirmed, a multidisciplinary approach must be carried out in order to discuss treatment options and risks comprehensively with patients and their families. Pharmacological treatment options include corticosteroids and anticonvulsant agents. Steroids, particularly betamethasone, may help to reduce the peritumoral edema and promote fetal lung maturity.7 Dexamethasone is commonly used for neurosurgical patients, however repeated doses of dexamethasone during the antenatal period may cause decreased birthweight and decreased neurological development of the fetus.8,9 Thus, in our case we used two doses of betamethasone 12 mg intramuscularly at 24 weeks’ gestation primarily for fetal lung maturation in case of preterm delivery. This corticosteroid treatment may have also helped to reduce brain edema. Also, lamotrigine, levetiracetam and carbamazepine are the safest anticonvulsants in which benefits outweigh the risks of teratogenicity.10–12 Other treatment options include tumor resection, chemotherapy and radiotherapy. Despite the known teratogenicity of chemotherapeutic agents and radiation, McGrane et al.11 reported a successful pregnancy and delivery in a patient with glioblastoma treated with external beam radiotherapy over 6 weeks with concomitant oral 75 mg/m2 temozolomide daily. Tewari et al.12 developed an algorithm for the management of brain tumors in pregnancy. Within this algorithm, during the first or early second trimester and late second or third trimesters of pregnancy a stable patient should be allowed to continue with preg-
466
nancy, and surgery should be delayed. Second trimester is the ideal time for surgery during pregnancy. Once fetal lung maturity is established, the patient should be delivered. For patients clinically unstable with neurological deterioration and mental status changes, an immediate cesarean section under general anesthesia, followed by tumor resection was recommended to minimize the risk of cerebral herniation. Vaginal delivery is another option for clinically stable patients. In our case, the patient was in the late second trimester and clinically stable. She wanted to continue her pregnancy and declined the options of chemotherapy and radiotherapy as she had already received the maximum radiation exposure during the initial treatment 3 years before. Ventriculoperitoneal shunting operation was considered and performed in order to treat the hydrocephalus and decrease intracranial pressure. In some cases, brain tumor growth may accelerate during pregnancy depending on multiple factors, such as increased systemic and cerebral blood volume, growth factors and progesterone, which enhances tumor cell growth via progesterone receptor (PR) – B.12–14 Fortunately, in our case, during the 10 weeks of follow-up, recurrent tumor size and related edema were steady, the patient was clinically stable and ventriculoperitoneal shunt functioned without failure. In conclusion, management of brain tumors during pregnancy alters with a myriad of factors that must be assessed in a multidisciplinary approach involving tumor resection, chemotherapy and radiotherapy. The aim of treatment is to achieve well-being for both fetus and mother. Despite many advances in treatment, prognosis is still very poor.
Acknowledgments The authors wish to thank to Maciej Rojna from Nicolaus Copernicus University, Collegium Medicum at Bydgoszcz.
Disclosure The authors state that there is no conflict of interest.
References 1. Haas JF, Jänisch W, Staneczek W. Newly diagnosed primary intracranial neoplasms in pregnant women: A populationbased assessment. J Neurol Neurosurg Psychiatry 1986; 49: 874– 880.
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Recurrent brain tumor in pregnancy
2. Bondy ML, Scheurer ME, Malmer B et al. Brain tumor epidemiology: Consensus from the Brain Tumor Epidemiology Consortium. Cancer 2008; 113: 1953–1968. 3. Roelvink NC, Kamphorst W, van Alphen HA, Rao BR. Pregnancy-related primary brain and spinal tumors. Arch Neurol 1987; 44: 209–215. 4. Chaudhuri P, Wallenburg HC. Brain tumors and pregnancy. Presentation of a case and a review of the literature. Eur J Obstet Gynecol Reprod Biol 1980; 11: 109–114. 5. Mackenzie AP, Levine G, Garry D, Figueroa R. Glioblastoma multiforme in pregnancy. J Matern Fetal Neonatal Med 2005; 17: 81–83. 6. Michelsen JJ, New PF. Brain tumour and pregnancy. J Neurol Neurosurg Psychiatry 1969; 32: 305–307. 7. Isla A, Alvarez F, Gonzalez A, García-Grande A, Perez-Alvarez M, García-Blazquez M. Brain tumor and pregnancy. Obstet Gynecol 1997; 89: 19–23. 8. Lee BH, Stoll BJ, McDonald SA, Higgins RD, National Institute of Child Health and Human Development Neonatal Research Network. Adverse neonatal outcomes associated
9.
10.
11.
12.
13. 14.
with antenatal dexamethasone versus antenatal betamethasone. Pediatrics 2006; 117: 1503–1510. Newnham JP, Jobe AH. Should we be prescribing repeated courses of antenatal corticosteroids? Semin Fetal Neonatal Med 2009; 14: 157–163. Jayasekera BA, Bacon AD, Whitfield PC. Management of glioblastoma multiforme in pregnancy. J Neurosurg 2012; 116: 1187–1194. McGrane J, Bedford T, Kelly S. Successful pregnancy and delivery after concomitant temozolomide and radiotherapy treatment of glioblastoma multiforme. Clin Oncol (R Coll Radiol) 2012; 24: 311. Tewari KS, Cappuccini F, Asrat T et al. Obstetric emergencies precipitated by malignant brain tumors. Am J Obstet Gynecol 2000; 182: 1215–1221. Fuglsang J, Ovesen P. Aspects of placental growth hormone physiology. Growth Horm IGF Res 2006; 16: 67–85. González-Agüero G, Gutiérrez AA, González-Espinosa D et al. Progesterone effects on cell growth of U373 and D54 human astrocytoma cell lines. Endocrine 2007; 32: 129–135.
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
467
