Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome secondary to dorsal pontine infarction

A 71-year-old man with hypertension presented to the emergency department with sudden-onset diplopia. Neurological examination demonstrated exotropia of both eyes on primary, upgaze and downgaze position, as well as bilateral adduction deficits accompanied with nystagmus of the abducted eye on horizontal gaze. He also presented gaze-evoked vertical nystagmus and impaired convergence (figure 1A and online supplemental video 1). Direct and indirect pupil reflex to light were normal. MR scan of brain revealed bilateral symmetric diffusion restriction in the dorsal pons adjacent to the fourth ventricle, corresponding to bilateral medial longitudinal fasciculi (MLF) (figure 1B). Blood tests indicated impaired glucose tolerance. CSF testing showed normal open pressure, cell count, protein and glucose levels. Oligoclonal bands were negative and no malignant cells were found. Anti-central nervous system (anti-CNS) autoantibodies (antibodies against AQP4, MOG, NMDAR, AMPAR1, AMPAR2, LGI1, CASPR2, GABABR, IgLON5, and GQ1b) in both CSF and serum were negative. Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome secondary to pontine infarction was diagnosed. Clopidogrel 75 mg and atorvastatin 20 mg per day were prescribed. At 60-day follow-up, his eye movement abnormalities improved and MRI lesions disappeared (figure 1C).

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WEBINO is a rare ocular motor disorder which is characterised by binocular exotropia and bilateral internuclear ophthalmoplegia.1–3 Some cases are associated with other neuro-ophthalmic abnormalities including loss of convergence, vertical gaze paralysis, vertical nystagmus, ptosis, pupil abnormality and skew deviation. This patient showed exotropia in primary position, binocular adduction deficit, loss of convergence, which were the most common ocular motor abnormalities of WEBINO reported in the literature.

Inflammation has been suggested as the most common aetiology of WEBINO.4 However, we retrospectively summarised all 48 WEBINO cases published from 1985 to 2023 (online supplemental table 1), and found that infarction is the most frequent (21/48, 43.8%) followed by inflammation including demyelination, infection, non-infective inflammatory or immune-mediated conditions (11/48, 22.9%). Interestingly, the third most common cause is progressive supranuclear palsy (10/48, 20.8%), which is followed by brainstem compression (5/48, 10.4%) due to hydrocephalus, tumour or herniation. Other uncommon causes include microhaemorrhage, postoperative complication and toxic-metabolic injury. In summary, WEBINO can result from various underlying pathologies, with inflammation most common in the young, and stroke most common in the elderly. In rare situations, stroke-like onset WEBINO in elderly patients with a history of autoimmune diseases, CSF examination containing anti-CNS antibodies could provide additional information to help determine the aetiology,5 although we would accept that there will be a range of opinions as to whether the extensive antibody testing in this case was necessary.

Simultaneous lesions of bilateral MLF definitely contribute to the pathophysiology of WEBINO. However, damage in the medial rectus subnuclei of bilateral oculomotor nuclei6 or overexcitation of each median pontine reticular formation (PPRF)7 is still debated. Several patients, including this patient, do not show lesions of the medial rectus subnuclei or PPRF, suggesting that these two locations are not necessarily involved in WEBINO. Of 22 WEBINO caused by stroke in the literature (21 infarction and 1 microhaemorrhage), 10 (45.5%) involved midbrain, 6 (27.3%) involved pons and 6 affected both areas (27.3%). The patient presented here is one such case with an explicit ischaemic dorsal pontine lesion corresponding to bilateral MLF.

This case and literature review implicate stroke as the most common cause of WEBINO among elderly patients and emphasise the importance of its early recognition in the emergency department given the treatment is very time sensitive. As a general rule, sudden-onset WEBINO in the adult with cerebrovascular risk factors strongly suggests a dorsal brainstem infarction caused by small vessel disease or cardioembolism. A timely diagnosis of stroke-induced WEBINO is important so that acute treatment can be considered and for initiating secondary stroke preventive measures to potentially improve the prognosis.

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Footnotes

• L-YZ and MZ contributed equally.

• Contributors: L-YZ, MZ and X-YZ were responsible for caring of the patient, acquisition of data, analysis and interpretation of data, drafting and revising the manuscript. YuW, G-DW and YanW were responsible for the analysis and interpretation of data. X-YZ and Y-CW were responsible for supervising the study, coordinating the study and revising the manuscript. All authors approved the manuscript.

• Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

• Competing interests: No, there are no competing interests.

• Provenance and peer review: Not commissioned; externally peer reviewed.

• Supplemental material: This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. Data sharing not applicable as no datasets generated and/or analysed for this study.

Ethics statements

Patient consent for publication:

Consent obtained directly from patient(s)

Ethics approval:

This study involves human participants and was approved by the Institutional Review Board of Shanghai General Hospital (ethics approval number: 2024-312). Participants gave informed consent to participate in the study before taking part.

Acknowledgements

We thank the patient and his family for permission to publish this case report.

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