Gestational Parasellar Mass as a Cause of Painful Third Nerve Palsy Followed by Spontaneous Improvement During the Puerperium

Clinical Correspondence Gestational Parasellar Mass as a Cause of Painful Third Nerve Palsy Followed by Spontaneous Improvement During the Puerperium Editha D. Johnson, DO, Jeffrey R. DeSanto, MD, Michael R. Leonardi, MD, Jorge C. Kattah, MD T he diagnosis of painful ophthalmoplegia during pregnancy is challenging because of the limitations of available testing during this time. An interdisciplinary approach to management is essential because the safety of both the mother and fetus is paramount. In this report, we describe a patient in her third trimester of pregnancy with unilateral, painful third nerve palsy from a presumed hormone-responsive petroclival meningioma. The tumor was effectively managed with close observation. After delivery of the infant, there was near complete resolution of pain and diplopia, despite radiographic stability of the mass. We highlight the differential diagnosis and review the literature on hormone-responsive meningiomas. CASE REPORT A 39-year-old multiparous woman, in the late third trimester of an otherwise normal pregnancy (30th week), was admitted to the obstetrics inpatient unit for evaluation of left facial pain and diplopia. She reported a 1-month history of left burning periorbital pain and intermittent blurred vision with photophobia and tearing. Recently, she had noticed binocular diplopia. On examination, the patient had a 4-mm ptosis of the left upper eyelid and a partial left third cranial nerve palsy. This primarily affected left eye adduction and supraduction; there was a 30-prism diopter exotropia and a 5-prism diopter hypotropia in primary gaze. The exotropia increased to greater than 45-prism diopters in right gaze, and the hypotropia increased to 10-prism diopters in upgaze (Fig. 1). The pupils were spared, measuring 3 mm in diameter, and were reactive to light stimulus. There was hypoesthesia to pin-prick involving the left V1 and V2 branches of the trigeminal nerve. The left corneal reflex, elicited with a cotton swab, was present, although decreased; there was hyperesthesia to touch along the left V3 region. The left motor V3 function was normal. By contrast, right ocular ductions and right trigeminal nerve examination Departments of Neurology (EDJ, JCK), Radiology (JRD), and Maternal and Fetal Medicine (MRL), University of Illinois College of Medicine at Peoria, Peoria, Illinois. The authors report no conflicts of interest. Address correspondence to Editha D. Johnson, DO, Department of Neurology, University of Illinois College of Medicine at Peoria, 530 NE Glen Oak Avenue, Peoria, IL 61637; E-mail: [e-mail] 502 were normal. Ocular bruit was absent. The visual fields to confrontation were normal. Formal right visual field examination, plotted with a Humphrey automated perimeter, was normal. However, the patient could not complete the left visual field because of pain. Direct and indirect ophthalmoscopy were both normal, and slit-lamp biomicroscopy was unremarkable. Noncontrast T2 and FLAIR MRI of the brain revealed a left petroclival mass. This extended to the cavernous sinus, was isointense to brain parenchyma, and displayed radiographic characteristics strongly suggestive of meningioma (Fig. 2A, B). Narrowing of the lumen of the left cavernous carotid artery, which was surrounded by the intracavernous mass, was also identified. The pituitary gland was mildly enlarged. We proposed initial neurosurgical intervention with open biopsy and possible partial tumor resection, followed by additional postpartum surgery, if needed. However, a final consensus was reached favoring close clinical monitoring and reassessment after delivery. At the follow-up visit 4 weeks prepartum, the pain was well controlled with opiates, and the afferent and efferent visual examinations were unchanged. Formal visual fields were normal. Owing to narcotic use for pain control, both pupils were 2 mm; the pupillary reaction to light was difficult to visualize but symmetric. Labor was induced at 39 week gestation, and a healthy newborn was delivered. One month into the puerperium, she had an unexpected and complete resolution of ocular pain and ptosis. Three months later, the patient had only occasional transient diplopia. She had a residual left exotropia in right gaze that measured 16-prism diopters; this decreased over time to 4-prism diopters in 2 serial follow-up monthly visits. The hypotropia resolved. Follow-up brain MRI with contrast, at 3 months postpartum, revealed a radiographically unchanged left petroclival/ cavernous sinus mass with a normal pituitary gland (Fig. 2C–E). Our patient remained in good health. She was without recurrence of her neurological symptoms as of the last visit 6 months later. The patient did not present at further appointments, and attempts to contact her have been unsuccessful. DISCUSSION The differential diagnosis of a central nervous system lesion with painful ophthalmoplegia during pregnancy includes Johnson et al: J Neuro-Ophthalmol 2019; 39: 502-505 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. A. Partial left third nerve palsy with ptosis of left upper eyelid and exotropia that is, increased in right gaze with mild hypotropia. The right eye is normal. B. Complete resolution of the partial left third nerve palsy 3 months postpartum. a variety of presentations, as summarized in Table 1. In our patient, neuroimaging revealed a petroclival and cavernous sinus mass with characteristic features of a meningioma. There is ample evidence supporting surgical intervention at different stages of pregnancy with excellent outcomes (1–5); however, there is always the possibility for serious complications with preterm delivery. For our patient, subsequent to case review by an interdisciplinary team, a decision for close neurological and obstetrical surveillance was rendered. In the event of rapid progression of symptoms or suspected chiasmal compression, emergent surgical intervention would be provided. Although pathologic diagnosis is not available in our case, a discussion of meningioma during pregnancy is relevant due to radiographic characteristics of the lesion and its symptomatic debut during the third trimester of pregnancy. In 1929, Cushing described the case of a 32-year-old woman with a tuberculum sella meningioma during pregnancy; this caused progressive decline in visual acuity that spontaneously improved after delivery but recurred and FIG. 2. A and B. Axial T2 and FLAIR MRI sequences highlighting the hypointense left petroclival and cavernous sinus mass with characteristic features of a meningioma. C–E. T2 and contrast-enhanced T1 axial and coronal images, 3 months postpartum. Note also diminutive appearance of the left cavernous carotid artery lumen. Johnson et al: J Neuro-Ophthalmol 2019; 39: 502-505 503 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence TABLE 1. Cavernous sinus pathologies Emergent/urgent Vascular Aneurysm Cavernous sinus thrombosis Cavernous carotid fistula Dural ateriovenous fistula Pituitary apoplexy Nonemergent/urgent Noninfectious—inflammatory Granulomatosis with polyangitis Lymphocytic hypophysitis Inflammatory psuedotumor Tolosa–Hunt Sarcoidosis Infectious Actinomycosis Aspergillosis Cavernous sinus thrombophlebitis Mucormycosis Herpes zoster Neoplasm Primary Chondroma Hemangioma Lymphoma Meningioma Neurogenic tumor: schwannoma neurofibroma Local spread Pituitary adenoma Nasopharyngeal carcinoma Base of skull tumor: chondrosarcoma, osteosarcoma Secondary Metastases Breast, gastrointestinal, lung, and skin Others Traumatic progressed to vision loss in a subsequent pregnancy (6). This marked one of the first published reports of symptomatic gestational meningioma linked to vision changes, followed by postpartum regression. Growing literature in the form of meta-analyses, retrospective reports, and case–control studies suggests that hormonal modulation is associated with a risk of meningioma (7–10). This may explain the 2-fold higher incidence of benign meningioma in women. Specifically, the use of hormone replacement therapy, oral contraceptives in premenopausal women, and multiparty are considered possible risk factors for meningioma development (6,8). Furthermore, hormonal influence on meningioma growth has been identified during pregnancy. Although the incidence of meningioma in pregnant and nonpregnant women is similar, the biological and clinical manifestations during pregnancy differ dramatically (10). Recurrent symptomatic meningioma also is well documented among multiparous women, further supporting hormonal influence (6). 504 The typical slow growth rate of meningioma in the pregravid woman may undergo a sudden, accelerated course during gestation (10). Progesterone levels surge exponentially in the early and midpregnancy, followed by a plateau in the late pregnancy. This physiological change during pregnancy, along with histological evidence of upregulated progesterone receptors (PR) in meningioma (11), supports a theoretical hormonal-mediated mechanism for accelerated meningioma growth during the late second trimester. Undoubtedly, additional factors must be considered, given remaining unanswered questions, such as the higher incidence of PR-positive meningioma in women of advanced age, despite declining serum progesterone levels. Furthermore, the hormone-induced cell proliferation hypothesis assumes a reversal of cell proliferation in the postpartum phase—possibly, through an apoptosis mechanism— although this has yet to be established. Instead, it is believed that increased tumor size may be due exclusively to vascular changes causing peritumoral edema or engorgement of tumor-associated blood vessels, during pregnancy (12). In 1951, Weyand et al (13) showed the presence of “foamy and swollen” cytoplasm in resected meningiomas from 2 pregnant women, and reported this as intracellular edema. Later in 2012, a retrospective study that reviewed the clinical and histopathological features of 17 pregnant patients identified intracellular or extracellular edema in 14 (82%) of resected samples (14). In normal pregnancy, serum vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) levels are elevated; these factors are essential for uterine and vascular remodeling to meet the demands of the growing fetus (15). Although their roles in meningioma have yet to be elucidated, both VEGF and MMP-9 expression are also elevated in benign and malignant meningiomas and may play a key role in tumor angiogenesis, peritumoral brain edema, and tumor recurrence (16,17). Theoretically, these factors may contribute to the accelerated meningioma growth seen in pregnancy with spontaneous reduction postpartum. In our patient, image analysis revealed the diminished lumen of the left cavernous carotid and the encircling mass (Fig. 2A–E). Thus, we hypothesize that the mass also surrounded, compressed, or stretched the oculomotor and the first and second divisions of the left trigeminal nerves. To explain the observed spontaneous improvement, we draw an analogy to extensive experimental compressive peripheral nerve injury research (18). Neurapraxia (Grade-1 compressive peripheral nerve injury) is characterized primarily by focal demyelination, ischemia, and venous congestion, generally without axonal injury (axonotmesis). This is found in Type 2 compression injury (18). In our case, we suspect that a Grade-1 compressive neuropathy causing a partial oculomotor and trigeminal nerve dysfunction, with spontaneous improvement postpartum, may also have contributed to her prepartum presentation. Retrospectively, stability of the ophthalmoparesis in the last 8 weeks of pregnancy predicted a favorable outcome. Johnson et al: J Neuro-Ophthalmol 2019; 39: 502-505 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence CONCLUSION In summary, the differential diagnosis of cavernous sinus lesions during pregnancy is broad, and medical management may be challenging. Our patient illustrates the development, in late pregnancy, of neurological manifestations of a presumed petroclival meningioma. An interdisciplinary approach to management should be implemented because a hasty decision may negatively affect the outcome of an otherwise normal pregnancy. In select cases, patients with neuro-ophthalmologic manifestations of a presumed meningioma during pregnancy may be best served by careful monitoring. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: E. D. Johnson, J. C. Kattah, J. R. DeSanto, and M. R. Leonardi; b. Acquisition of data: E. D. Johnson and J. C. Kattah; c. Analysis and interpretation of data: E. D. Johnson and J. C. Kattah. Category 2: a. Drafting the manuscript: E. D. Johnson and J. C. Kattah; b. Revising it for intellectual content: E. D. Johnson and J. C. Kattah. Category 3: a. Final approval of the completed manuscript: E. D. Johnson, J. C. Kattah, J. R. DeSanto, and M. R. Leonardi. 6. 7. 8. 9. 10. 11. 12. 13. REFERENCES 1. Galal A, Faisal A, Al-Werdany M, El Shehaby A, Lotfy T, Moharram H. Determinants of postoperative visual recovery in suprasellar meningiomas. Acta Neurochir (Wien). 2010;152:69–77. 2. Moscovici S, Fraifeld S, Cohen JE, Dotan S, Elchalal U, Shoshan Y, Spektor S. 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