Millard-Gubler Syndrome in a Patient with Preeclampsia. Case Report and Review of Combined Intra- and Extra-Axial Facial and Abducens Nerve Injuries

ABSTRACT

Millard-Gubler syndrome is a pontine syndrome caused by a lesion in the lower pons region. It is characterised by ipsilateral facial paralysis and VI paresis and contralateral brachiocrural palsy. We present the case of a female patient, G4P2A1, at 21 weeks of gestation, with preeclampsia, complaints of blurred vision, diplopia, and right hemiparesis, in whom a clinical diagnosis of Millard-Gubler syndrome was made. Neuroimaging showed an intraparenchymal haemorrhage towards the central portion of the bulbopontine junction. An extensive aetiological study was carried out to determine the cause of the hypertensive disorder syndrome during pregnancy. The patient improved satisfactorily from the neurological deficit after delivery of an early stillbirth.

Introduction

Cerebrovascular complications associated with pregnancy present a multifaceted spectrum, manifesting during pregnancy, childbirth, and the postpartum period. This spectrum encompasses conditions such as cerebrovascular disease (CVD), preeclampsia/eclampsia, cerebral venous thrombosis, posterior reversible encephalopathy syndrome (PRES), and reversible cerebral vasoconstriction syndrome (RCVS). Although the overall incidence of pregnancy-related stroke is 34 per 100,000 deliveries, noteworthy variations exist among different ethnic groups, and these events are relatively uncommon in young women. The critical period of heightened risk extends from the third trimester through the initial 6 weeks postpartum, with a discernible but slightly elevated risk persisting up to 12 weeks postpartum.¹

The aetiology of preeclampsia is unknown. This condition is delineated by the onset of hypertension after the 20th week of gestation in individuals previously normotensive, sometimes accompanied by proteinuria, thrombocytopenia, renal failure, impaired liver function, pulmonary oedema, or neurological symptoms.² It can also manifest in patients with pre-existing chronic arterial hypertension, introducing a heightened risk of up to 40 times for ischaemic CVD.³

Millard-Gubler syndrome (MGS) is caused by a lesion in the ventral pons that involves fibres of cranial nerves VI and VII and the corticospinal tract.⁴ The medial lemniscus and the spinothalamic tract are usually spared in this syndrome, which explains the absence of sensory symptoms. Some factors, such as age and the mechanism of injury, must be considered as the nontraumatic vascular causes occur mainly in adults (pontine infarction, silent cavernous angiomas), whereas the traumatic and neoplastic causes occur more frequently in young people (cavernoma and astrocytomas).

In this report, we detail the case of a pregnant woman at 21 weeks of gestation, where the initial neurological manifestation of preeclampsia was a left sixth cranial nerve neuropathy, ipsilateral facial palsy, and right hemiplegia. This constellation of neurological signs is consistent with Millard-Gubler Syndrome, which in this case was caused by an intraparenchymal haemorrhage related to severe preeclampsia.

Case report

A 33-year-old chronically hypertensive woman, G4P2A1, at 21 weeks of gestation, was referred to our centre from a primary care clinic due to challenging blood pressure control, unresponsive to three doses of 40 mg of labetalol, and concurrent tension-type headache. Upon evaluation in the emergency room, her blood pressure registered at 184/102 mmHg, the rest of the vital signs were normal, and no foetal heart sounds were found on ultrasound; accompanied by complaints of blurred vision and diplopia.

Ophthalmological examination revealed uncorrected visual acuity of 20/30 in both eyes, normal pupils with no relative afferent pupillary defect, esotropia, left eye abduction limitation, (Figure 1), visual field full at confrontation, asteroid hyalosis in both eyes, well-defined optic disc margins, spontaneous venous pulsations and grade III hypertensive retinopathy. Neurological assessment revealed right hemiparesis, dysarthria, left infranuclear facial paralysis, right Babinsky reflex and normal muscle tone consistent with a pontine lesion.

Figure 1.

(a) Primary gaze position, mild supranuclear left facial palsy. (b) Dextroversion. (c) Levoversion.

Following admission to the intensive care unit (ICU), thrombocytopenia, elevated lactic dehydrogenase, and proteinuria were noted, and an obstetric curettage was performed. A non-contrast computed tomographic (CT) scan revealed a 20-mm hyperdense lesion in the left parasagittal basis pontis, consistent with an intraparenchymal haemorrhage. Subsequent investigations, including cardiac imaging and biochemical analyses, excluded cardiac amyloidosis and endocrinological causes of resistant arterial hypertension. Brain magnetic resonance angiogram (MRA) was normal in both arterial and venous phases; brain magnetic resonance imaging (MRI) showed a 15 × 13 mm infratentorial intraparenchymal haemorrhage in the brainstem towards the central portion of the bulbopontine junction (Figure 2). Despite a reduction in haemorrhage observed on a follow-up CT, the patient opted for discharge against medical advice, precluding further complementary studies for thrombophilia.

Figure 2.

Non-contrast and contrasted brain MRI T1-weight images in sagittal, coronal and axial sections.

Discussion

We reviewed the PubMed, LILACS, and Embase databases and were unable to identify any case reports of MGS occurring in the setting of preeclampsia. This rare ventral pontine syndrome is diagnosed clinically and requires confirmation by neuroimaging and a study of its aetiology according to the findings. In understanding the intricate brainstem associations between the abducens and facial nerves, it is crucial to delineate their topographical and clinical distinctions. Four notable scenarios highlight the diverse presentations:

1. Lesions within the pons may affect either the nucleus of the facial nerve or its intrapontine axons (fascicles).

   These lesions usually affect neighbouring structures, such as the abducens fascicle (lateral rectus paralysis), abducens nucleus (horizontal gaze palsy that cannot be overcome by Doll’s head manoeuvre), the paramedian pontine reticular formation (horizontal gaze palsy that can be overcome by Doll’s head manoeuvre), the corticospinal tract (contralateral hemiplegia), and occasionally the spinal tract and nucleus of the trigeminal nerve and the spinothalamic tract (ipsilateral facial and contralateral body sensory disturbances). Nuclear and fascicular lesions of the facial nerve result in a peripheral type of facial nerve palsy. With complete lesions, there is unilateral paralysis of all mimetic facial muscles, with loss of frontal wrinkling and facial asymmetry at rest and with motion.⁵

2. A nuclear sixth and facial colliculus lesion can lead to a Genu seventh and ipsilesional horizontal gaze palsy.

3. Isolated peripheral facial and abducens nerve palsy is a syndrome caused by a discrete lesion in the caudal tegmental pons involving the facial nerve fascicle (or nucleus) and the abducens nerve fascicle. It is characterised by the following signs: Peripheral-type facial palsy, ipsilateral abduction weakness and no other neurologic abnormalities

4. Peripheral skull base lesions may simultaneously affect these two nerves. Differentiating between infranuclear fascicular seventh nerve palsy and an extraaxial facial and abducens palsy within the petrous bone poses a diagnostic challenge. A key discriminative factor lies in fascicular lesions, where taste preservation in the anterior two-thirds of the tongue is observed, providing a valuable clinical marker in the assessment of these complex neurological presentations. Another differential diagnosis is Eight-and-a-half syndrome is caused by a lesion in the dorsal tegmentum of the caudal pons involving the PPRF or abducens nucleus and the medial longitudinal fasciculus (MLF), as well as the nucleus and fasciculus of the facial nerve. It is characterised by Internuclear ophthalmoplegia (INO) in addition to horizontal gaze palsy (one-and-a-half syndrome) and ipsilateral lower motor neuron-type facial palsy.⁵

Although haemorrhagic CVD is relatively rare during pregnancy and the postpartum period, with an incidence of up to 6 per 100,000 in published series, pregnancy increases the risk of bleeding more than ischaemic stroke (relative risk of 2.5 and 28.5 during pregnancy and the puerperium, respectively) and usually occurs in the third trimester.^6,7

The leading causes of pregnancy-related bleeding are preeclampsia-eclampsia, followed by intracerebral aneurysms and arteriovenous malformations. The characteristics of our patient are not typical of patients with CVD related to pregnancy, as they occurred in the second trimester, with severe preeclampsia at a very early stage and with an initial neurological manifestation that constituted the Millard-Gubler syndrome. Furthermore, according to the literature, the main causes for MGS in young patients are tumours, infectious diseases (neurocysticercosis and tuberculosis), demyelinating diseases (multiple sclerosis), and viral infections (rhomboid encephalitis).⁴

Intracerebral aneurysms and arteriovenous malformation were ruled out by means of MRA. However, considering the history of abortion, additional studies were planned to rule out associated thrombophilic conditions that could have caused ischaemic CVD with haemorrhagic transformation, which could not be performed because the patient was discharged against medical advice from the hospital for personal reasons. However, severe preeclampsia alone is sufficient to explain the patient’s clinical condition, and exams for thrombophilia should be performed 2 or 3 months after the event.

Conclusions

This case underscores the propensity of patients with pre-eclampsia to manifest diverse neurological complications, notably brainstem syndromes, arising from intra-axial haemorrhages associated with severe hypertension. Additionally, it emphasises the critical need for meticulous investigations aimed at unravelling the underlying aetiology and formulating precise treatment strategies. This emphasises the indispensable role of a multidisciplinary approach in navigating the intricate complexities inherent in such cases.

Funding Statement

The author(s) reported there is no funding associated with the work featured in this article.

Authors’ contributions

All authors participated in the construction of this case report. The article was researched and written by Dr Sanchez and Dr Bautista, with the supervision of Dr Bonilla and Dr Salamanca who assisted with edits and guidance.

Consent for publication

The patient authorised the publication of the report and signed an informed consent form.

Ethics approval and consent to participate

This research was considered to have minimum risk. It adhered to the ethical principles of the Declaration of Helsinki.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Case report based on clinical chart data, patient observation, and analysis of diagnostic tests.