Glioblastoma Multiforme in Pregnancy

Abstract

Brain tumors in pregnancy are uncommon occurrences. A 48-year- old female at 36 2/7 weeks of gestation presented with right-sided weakness and parasthesias, a facial droop, and an unsteady gait. Brain imaging studies revealed a left-sided parietal lesion impinging upon the lateral ventricle. She underwent a cesarean delivery and then a craniotomy with resection of a glioblastoma multiforme two days later. Despite treatment with radiation and chemotherapy, she died nine months later. Glioblastoma multiforme is a rare diagnosis during pregnancy which may present as a neurologic emergency.

Keywords: Glioblastoma multiforme, brain tumors, pregnancy

Introduction

Brain tumors are relatively rare occurrences during pregnancy [I]. Depending on the size, location, and etiology of the lesion, these neoplasms may manifest themselves with subtle signs of intracranial involvement or as advanced neurologic emergencies. The physician is then faced with multiple dilemmas with respect to treatment of the disease, antepartum management, and the optimal setting for delivery of the infant.

Case

A 48-year-old nulliparous woman at 36 2/7 weeks of gestation presented with a four-day history of worsening right-sided weakness, right upper extremity numbness, right-sided facial droop, and an unsteady gait. Her pregnancy had been uncomplicated following assisted reproduction via in vitro fertilization with a donor oocyte. She denied having headaches, visual disturbances, nausea, vomiting or seizures.

Initial physical examination revealed a hemodynamically stable woman (blood pressure 130/80, pulse 84/min) who was alert and oriented with slight slurring of speech and a mild right-sided facial droop. Her motor examination revealed 3/5 strength of the right upper extremity (deltoid, biceps, triceps, grasp) and 4/5 strength of the right lower extremity (hamstrings, quadriceps, plantar, and dorsiflexion). The strength of the left extremities was within normal limits. Sensation was diminished on the right upper extremity, and an unsteady gait was noted upon ambulation. The remainder of her physical exam was within normal limits.

The patient was admitted for further evaluation with the underlying suspicion of either a cerebrovascular accident or an intracranial lesion. Her hemoglobin, hematocrit, platelet count, coagulation profile, liver and renal function tests were normal. Other laboratory tests such as rheumatoid factor, antinuclear antibodies, anticardiolipin antibodies, Lyme tilers, and HIV were negative. Her urine was negative for protein. An echocardiogram and carotid Doppler studies were normal. Magnetic resonance imaging (MRI) of the head and neck revealed a left parietal lesion measuring 2.5 cm x 3.0 cm x 3.0 cm impinging upon the left lateral ventricle with noted vasogenic edema (Figure 1). The suspicion was of a neoplasm most likely of glial origin.

The patient’s clinical course was complicated by moderate progression of the neurologic symptoms on the first hospitalization day. Dexamethasone intravenous therapy was started to reduce intracranial inflammation. Obstetrically, there was reassuring fetal testing; however, the mother’s condition deteriorated and the decision was made to deliver the fetus. After extensive discussion with the patient and her family a two-staged operative approach was agreed upon. A cesarean delivery followed by craniotomy at a later date was chosen to allow for maternal-neonatal bonding following the delivery.

Figure 1. (a) Magnetic resonance imaging of the head and neck revealing a left parietal lesion measuring 2.5 3.0 3.0 cm impinging upon the left lateral ventricle with noted vasogenic edema, (b) Transverse image.

On the second hospitalization day, the patient underwent an uncomplicated cesarean delivery under general anesthesia. Due to the increased intracranial pressure, general anesthesia was felt to be safer than regional anesthesia. A live-born male infant was delivered weighing 2807 grams with an Apgar score of 9 at 1 and 5 mins. The neonate was discharged home on the second day of life in the care of the patient’s family.

The patient was transferred to the neurosurgery step-down unit for close surveillance. Her post-cesarean course was uncomplicated until the second postoperative day when she developed immobility of the right upper extremity and 1/5 motor strength of the right lower extremity. The patient was transferred to another institution for immediate treatment of the intracranial lesion. At the receiving institution, a stereotactic biopsy was performed revealing a preliminary diagnosis of glioblastoma. Later that same day, the patient underwent a craniotomy with resection of the intracranial lesion confirming the diagnosis of glioblastoma multiforme. Shortly after recuperating from surgery, the patient began both radiation therapy and adjuvant chemotherapy due to the aggressive nature of the tumor. The patient eventually succumbed to her illness nine months after the initial diagnosis.

Discussion

Brain tumors in pregnancy are relatively rare occurrences with an incidence of 15 per 100,000. Relative to a non-pregnant population, malignant tumors have been described to be less common in pregnant women [I]. Nevertheless, despite the apparent paucity of lesions, each sub-type of intracranial neoplasm still appears to be represented in similar frequency as compared to the non-pregnant population [2].

During pregnancy, brain tumors may increase in size leading to the manifestation of clinical symptoms. To explain this phenomenon, early authors focused on theories such as accelerated growth rates, vascular engorgement, and increased fluid content of the tumor [3]. These intracranial neoplasms have at times demonstrated hormone- related growth, with progression of neurologic symptoms during pregnancy and remission postpartum [4]. Steroid receptors have been identified primarily in meningiomas, with progesterone receptors notably more prominent than estrogen receptors [5]. Ultimately, multiple factors probably play a role in this process.

Clinical presentation during pregnancy may be mild in onset or may emerge rapidly as in our case. Typical presenting symptoms include headache, nausea and vomiting, motor dysfunction, visual disturbances, seizures, loss of consciousness and incontinence. In the acute presentation, prompt care is imperative to stabilize the mother and ensure fetal well-being before the onset of any further complications such as intracranial hemorrhage or cerebral herniation. Unfortunately, the diagnosis of a brain tumor may be delayed due to the similarity of symptoms with pregnancy related conditions such as preeclampsia [6]. In making the diagnosis, both MRI and computed tomography have been utilized as imaging modalities. Once the diagnosis is confirmed, the physician faces a multitude of concerns with respect to treatment of the disease, antepartum management, and the optimal setting for delivery of the infant. With such a dynamic situation, it is prudent to manage each case on a patient-to-patient basis.

Factors to consider in the initial treatment include the severity of the maternal symptoms, the extent and location of the tumor, the gestational age of the fetus and ultimately the wishes of the patient. Corticosteroids are usually administered in an attempt to reduce intracranial inflammation, while also protecting against complications associated with fetal prematurity. The benefit of anticonvulsants outweighs the risks of teratogenicity especially when the patient is beyond the first trimester. More definitive treatment such as craniotomy, radiation, and/or chemotherapy must be chosen on an individual basis. The benefits and risks to the mother and fetus should be assessed before decisions regarding treatment can be made.

In 2000, Tewari et al. [7] suggested a management algorithm for symptomatic brain tumors in pregnancy. The algorithm was based on the published information on this topic during the previous 50 years. A woman presenting during the first or early second trimesters of pregnancy whose condition is stable should be allowed to continue with the pregnancy if she so wishes. Neurosurgery or radiotherapy may be considered in the early second trimester. Similarly, a woman who presents in the late second or early third trimesters and is stable should be able to continue with the pregnancy. Antepartum fetal surveillance must be initiated; once fetal maturity is documented the woman should be delivered and appropriate treatment given (tumor resection, radiation). A woman who has worsening of the symptoms, manifests new deficits, or has evidence of increased tumor growth or metastases, may be offered radiotherapy [7]. Delivery should occur once fetal maturity is established, followed by tumor resection. For the woman with acute deterioration or mental status changes, an urgent cesarean delivery under general anesthesia should be accomplished, followed by cerebral decompression and tumor resection [7].

When the diagnosis is made at term, women should be delivered expeditiously and, in the presence of a mass effect, preferably by cesarean under general anesthesia. This would theoretically decrease the risk of cerebral herniation [7]. Vaginal delivery should be reserved for the clinically stable women. The avoidance of regional anesthesia is prudent due to the risk\s of cerebral herniation with placement of an epidural catheter [8].

Tumor resection may be performed at the time of delivery or in the postpartum period.

In our case, the tumor was a glioblastoma multiforme, a high grade malignant glioma. This type of neoplasm derived from astrocytes is well known for its rapid clinical progression and does not metastasize outside the central nervous system as was demonstrated in this patient. Seizures and hemiparesis are two of the signs and symptoms typically seen with high-grade gliomas. In some severe cases, glioblastoma multiforme has presented in pregnancy with the acute onset of intracranial hemorrhage [4].

The initial treatment plan for glioblastoma multiforme involves maximal surgical resection of the mass, with the hope of maintaining function in the surrounding intracranial structures [9]. Unfortunately, it is rare for these tumors to be cured by surgical resection alone [9]. Postoperatively, radiation therapy and adjuvant chemotherapy are given [9]. Unfortunately, despite all interventions, prognosis is poor. With all of this in mind, it is evident that the patient and the obstetrician face many difficult decisions when the diagnosis of glioblastoma multiforme is encountered.

References

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6. 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.

7. Tewari KS, Cappuccini F, Asrat T, et al. Obstetric emergencies precipitated by malignant brain tumors. Am J Obstet Gynecol 2000;182:1215-1221.

8. Su TM, Lan CM, Yang LC, et al. Brain tumor presenting with fatal herniation following delivery under epidural anesthesia. Anesthesiology 2002;96:508-509.

9. Batchelor T. Management of high grade malignant astrocytorna. In: Rose BD, editor. Up To Date: Clinical reference library, Wellesley, MA; 2003.

ANDREW P. MACKENZIE, GARY LEVINE, DAVID CARRY, & REINALDO FIGUEROA

Department of Obstetrics and Gynecology, Winthrop University Hospital, Mineola, New York, USA

(Received 17 June 2004; revised 25 August 2004; accepted 7 September 2004)

Correspondence: Reinaldo Figueroa, MD, Department of Obstetrics and Gynecology, Winthrop-Universiry Hospital, 259 First Street, Mineola, New York 11501, USA. Tel: (516) 6632264. Fax: (516) 7427821. E-mail:rfigueroa@winthrop.org

Copyright CRC Press Jan 2005