The diagnostic dilemma of a pregnant woman presenting with an isolated sixth nerve palsy: A case report

Introduction

Acute neurological conditions requiring hospitalization in pregnancy are rare, the most common reason being seizures. ¹ Isolated cranial nerve palsies are uncommon in pregnant women. The literature is limited to case reports/series regarding isolated sixth nerve palsy in pregnancy. ^2–9 We report a case of a woman with preeclampsia in her third pregnancy, who developed an isolated sixth nerve palsy and was found to have aseptic cavernous sinus thrombosis.

Case report

A 25-year-old woman presented to her local hospital at 37 weeks of gestation with sudden-onset diplopia and a week long history of a left-sided unilateral headache. She was referred to the emergency department of a tertiary centre as Magnetic Resonance (MR) Imaging was inconclusive, which showed only altered signals in the left cavernous sinus on T2-weighted images. There was no history of head injury, syncope, seizures, ear discharge or toothache. There was no history suggestive of systemic vasculitis. After the diagnosis of gestational hypertension at 32 weeks, blood pressure remained under control on labetalol (100 mg three times a day). There was no family history of thrombosis. At admission, her blood pressure was 140/92 mm Hg and urine dipstick showed 2+ protein, suggesting the diagnosis of preeclampsia. Neurological examination revealed normal higher mental functions, sensory and motor function. Ocular examination showed a left-sided isolated lateral rectus palsy. Pupils were equal and reactive to light. Dental, ear, nose and throat examination were also normal. On obstetric examination, uterine fundal height was noted to be 32cm with a normal fetal heart rate on auscultation. Fundus examination showed grade II hypertensive retinopathy, but no papilledema. Ultrasound examination revealed stage 1 fetal growth restriction (FGR) with reduced diastolic flow in the umbilical arteries (umbilical pulsatility index of 1.1). Haemoglobin, platelet count, renal and liver function tests were normal. In view of preeclampsia with FGR, labour was induced with oxytocin as her pre-induction Bishop score was 7. She delivered a male infant weighing 2040 grams with Apgar scores of 8,9 and 9 at 1,5 and 10 minutes respectively. Postnatally a MR venogram of her brain was performed in view of persistent diplopia. This showed dilatation of the left cavernous sinus compared to the right, and a signal abnormality in the left cavernous sinus appearing hyperintense on T1-weighted image, hypointense on T2-weighted image and showing “blooming” on gradient echo (GRE) images suggestive of thrombosis. There was also a filling defect in the left cavernous sinus on post-contrast T1-weighted images consistent with cavernous sinus thrombosis (Figures 1 and 2). Her computed tomographic (CT) angiography revealed normal intracranial arterial appearances. There was no clinical evidence for infection. She was started on enoxaparin 60mg per day (weight adjusted dose) for thrombo-prophylaxis in view of pre-eclampsia and immobilization in the postpartum period. It was continued until 6 weeks post-partum. She was advised to do ophthalmic exercises and was provided with a spectacle occluder. At her six week follow-up appointment she reported improvement of diplopia with partial recovery of ocular movements. The patient had made a complete recovery by three months postpartum.

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Figure 1.

(a) T1-weighted coronal magnetic resonance image showing hyperintense signal (white arrow) in the left cavernous sinus. (b) T2-weighted coronal magnetic resonance image showing hypointense signal (white arrow) in the left cavernous sinus.

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Figure 2.

(a) T2* GRE axial coronal magnetic resonance image showing hypointense signal with “blooming” (black arrow) in the left cavernous sinus. (b) Contrast-enhanced T1-weighted axial magnetic resonance image showing non-enhancing filling defect (white arrow) in the left cavernous sinus.

Discussion

Pregnant women presenting with visual symptoms suggestive of isolated cranial nerve palsies are uncommon and the exact incidence is unknown. The sixth nerve is a purely somatic nerve and runs the longest intracranial course of all the cranial nerves. After arising from the abducens nucleus located in the caudal pons at the level of the facial colliculus, it exits the brainstem ventrally at the border of the pons and medulla. It then climbs superiorly along the ventral surface of the pons. On reaching the apex of the petrous portion of the temporal bone, it makes a sharp turn anteriorly to enter the cavernous sinus. The sixth nerve then travels through the cavernous sinus close to internal carotid artery, to enter the orbit through the superior orbital fissure. The third, fourth and fifth cranial nerves lie on the lateral wall of the cavernous sinus.

Possible causes of sixth nerve pathology in pregnancy include inflammation of the nerve, downward displacement of the nerve secondary to oedema/increased intracranial pressure and vasospasm of the vessels to the nerve. ² In pregnant women with an isolated sixth nerve palsy, reported causes include head trauma, preeclampsia, thrombosis of cerebral sinuses including the cavernous sinus. Neuroimaging with plain MR or MR venogram remains the most important investigation. MR angiography or Digital Subtraction venography may be needed in some cases to rule out the possibility of carotid-cavernous fistula. ²

Cavernous sinus thrombosis (CST) may occur secondary to thrombophlebitis from infections (typically from the middle third of the face, sinuses, ears, teeth, or mouth) or following trauma, iatrogenic injuries, or pro-thrombotic conditions. A case of septic cavernous sinus thrombosis was reported in a 24-year-old woman during pregnancy, following development of an intra-orbital abscess related to a dental infection. She underwent abscess drainage and dental extraction and was managed with antibiotics, heparin and methylprednisolone. ³

Although blindness and blurring of vision are reported as common ophthalmic symptoms with preeclampsia, isolated sixth nerve palsy is an unusual ophthalmic presentation. Most of the women described in the literature presented with headache or diplopia, and on evaluation had normal neuroimaging. A sudden rise in blood pressure causing vasoconstriction in the posterior and basilar circulation close to the nerve might explain the isolated sixth nerve palsy. It is considered to be a benign condition. Spontaneous recovery within six weeks to three months has been reported. ^4–7

Tolosa–Hunt syndrome presents with painful ophthalmoplegia and involvement of multiple cranial nerves and is caused by granulomatous deposition in the cavernous sinus for which no other cause is found. Most of these patients show a tremendous response to corticosteroid therapy. Litwin and Leung reported a case of Tolosa–Hunt syndrome in a woman who presented at 37 weeks into her second pregnancy with a unilateral headache and isolated sixth nerve palsy. Her MR imaging showed enhancement of the superior cavernous sinus and she had progressive recovery after treatment with prednisolone. ⁸

The sixth nerve with its long subarachnoid course reflects changes due to the rise in intracranial pressure. It can be the result of stretching of the nerve in its long course, or compression against the petrous ligament or the ridge of the petrous temporal bone. Unilateral or bilateral sixth nerve palsy is regarded as the most common “false localizing sign” of raised intracranial pressure. Isolated sixth nerve palsy can occur in space-occupying neoplasms such as meningioma or chordoma with nerve involvement in the skull base, petrous apex or clivus. ⁹

Isolated single or multiple cranial nerve involvement is rare in cerebral venous sinus thrombosis during pregnancy and postpartum. Involvement of the transverse sinus or sigmoid sinus can result in cranial nerve involvement. ² Thrombosis of the anterolateral pontine vein and the lateral medullary vein together with the draining petrous veins and the veins of the lateral recess can result in isolated cranial nerve syndromes. Munira et al. reported a woman who presented at eight weeks into her third pregnancy with diplopia and bilateral sixth nerve palsy. She was diagnosed with a right transverse and superior sagittal sinus thrombosis after MR imaging. She received anticoagulation for one year and was reported to make a complete recovery. ¹⁰

To alleviate diplopia, occlusion of the one eye (spectacle occluder) is recommended. Management of isolated sixth nerve palsy is directed towards the underlying aetiology. It varies from anticoagulation in thrombotic causes or steroids for non-thrombotic inflammation to antibiotics in septic cases, and surgery in case of an intracranial lesion. In the case described here, there was no infective pathology involving the area draining to the cavernous sinus and a dilatation noted in the left sinus was thought to be the reason for the development of ipsilateral lateral rectus palsy. There was therefore no indication for antibiotics or surgical intervention.

In women presenting with an isolated sixth nerve palsy, a thorough history and examination are mandatory. The majority of women with preeclampsia and an isolated sixth nerve palsy have no additional pathology on imaging, but we would still advocate imaging in these women as a lack of underlying pathology cannot be assumed.