Case report: A variant of wall-eyed bilateral internuclear ophthalmoplegia from unilateral pons infarction

Case presentation

A 55-year-old man experienced diplopia and ophthalmoplegia and was admitted to our hospital 3 days after the onset of the double vision. He had a history of hypertension for more than 20 years. His highest blood pressure was 180/104 mmHg. Neurologic examination and cover test showed exotropia of the left eye, alternating exotropia, and bilateral internuclear ophthalmoplegia with impaired convergence. Vertical saccades and smooth pursuit of the left eye were also limited (see Supplementary Video). Pupillary, levator function, and bilateral abducent nucleus were normal. No other positive signs of the nervous system were found in physical examination. Besides, no abnormalities were found after liver and kidney function checks, blood tests, and the coagulation markers detection. Moreover, no abnormality was found in the levels of hepatitis B surface antigen (HbsAg), hepatitis B core antibody (HbcAb), hepatitis Be antigen (HBeAg), anti-hepatitis B e antibody (anti-HBe), anti-hepatitis B core antibody (anti-HBc), anti-hepatitis C virus (anti-HCV), anti-human immunodeficiency virus (anti-HIV), anti-treponema pallidum (anti-TP) antibody, anti-streptolysin O (ASO), rheumatoid factor (RF), C-reactive protein (CRP), and the autoantibodies. The lumbar puncture showed that the pressure was about 120 mmH2O, and the cerebrospinal fluid (CSF) analysis was normal. Consequently, the patient underwent an MRI scan, which suggests an acute infarction in the left of the pontine tegmentum involving the left medial longitudinal fasciculus (MLF) (Figure 1). The patient was finally diagnosed with pons infarction.

FIGURE 1

Figure 1. Brain MRI: Diffusion-weighted images reveal a focal ischemic stroke in the dorsal pons (arrows).

The patient received anticoagulation and anti-platelet aggregation therapy. There was no stroke recurrence, and diplopia returned to a healthy level after the patient's discharge from the hospital 6 months.

Discussion

Wall-eyed bilateral internuclear ophthalmoplegia is a syndrome that involves bilateral adduction deficits, bilateral abducting nystagmus, and a large angle exotropia in primary gaze (Sharpe et al., 1974). WEBINO is mainly caused by cerebrovascular disorders (CVD), multiple sclerosis, neurodegenerative disorders, and infections (Sakamoto et al., 2012). WEBINO syndrome caused by CVD has been reported by several studies (Chen and Lin, 2007). Studies have shown that the disease is often associated with brainstem ischemia and hydrocephalus, immunotherapy of tumors, and diseases such as multiple sclerosis. This study summarized 39 case reports, including 42 WEBINO patients (Inocencio and Ballecer, 1985; Lana et al., 1990; Fay and Strominger, 1999; Korkmaz et al., 2002; Ozer et al., 2005; Chen and Lin, 2007; Kim et al., 2008; Matsumoto et al., 2008, 2019; Ushio et al., 2008; Jacob et al., 2010; Sierra-Hidalgo et al., 2010; Shinoda et al., 2011; Beh and Frohman, 2012; Jadhav and Prasad, 2012; Sakamoto et al., 2012; Bar et al., 2014; Chakravarthi et al., 2014; de Mora et al., 2014; Mathis et al., 2014; Muralidhar et al., 2014; Nakajima et al., 2014; Toufeeq and Dave, 2014; Agarwal et al., 2015; Ljevak et al., 2015; Man et al., 2015; de Souza et al., 2017; Sajjadi et al., 2017; Zou and Chen, 2017; Keereman et al., 2018; Papageorgiou et al., 2018; Im et al., 2020; Vázquez-Justes et al., 2020; Yazdi et al., 2020; Ansari et al., 2021; Jo et al., 2021; Petrik et al., 2021; Sinha et al., 2021; Wako et al., 2022). The age range of the patients was 12–85 years; 26 were male (61.9%), 15 were female (35.7%), and the gender of one was unknown. In the analysis of the clinical data of neuro-ophthalmological signs in WEBINO patients, 37 (88.1%) cases of exotropia in the first eye-position, 38 (90.5%) cases of bilateral intraocular disorders, 22 (52.4%) cases of convergence barrier, six (14.3%) cases of blepharoptosis, 18 (42.9%) cases of vertical gaze disorder, six (14.3%) cases of vertical nystagmus, eight (19.0%) cases of pupillary anomalies, and two (4.8%) cases of reversed dip. Among the studies, the lesion site summary showed that 28 (66.7%) cases occurred in the midbrain, 14 (33.3%) in the pons, nine (21.4%) in both the midbrain and the pons, and one (2.4%) in the brainstem. Among the causes of morbidity in WEBINO patients, 26 (61.9%) had cardiovascular and cerebrovascular diseases, ten (23.8%) neurological diseases, three (7.1%) infectious diseases, two (4.8%) tumor-related diseases, one (2.4%) alcohol overdose, and one (2.4%) drug-immune reaction. More details are shown in Table 1.

TABLE 1

Table 1. Analysis of clinical data of WEBINO patients.

Here we reported a single case of a patient with atypical WEBINO with unilateral exotropia (Supplementary Video) as the main clinical manifestation. The dissociated abducting nystagmus, impaired convergence, and supranuclear vertical gaze palsy implied a lesion of bilateral MLF. Yet, most of the infarcts in the left median dorsal pons cause unilateral, not bilateral, lesion of MLF (Gossman, 2006). The mechanism for the atypical clinical presentation in this patient may be due to the proximity of the unilateral lesion to the midline resulting in bilateral MLF lesions combined with converging fiber involvement resulting in WEBINO. Still, the causal pathophysiology remains unclear and disputed.

Data availability statement

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author/s.

Ethics statement

The studies involving human participants were reviewed and approved by the Ethics Committee of Harrison International Peace Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Author contributions

JH and TW organized and proofread the writing of the manuscript. DC and TW wrote the manuscript draft. All authors contributed to the article and approved the submitted version.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's note

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Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnins.2022.974645/full#supplementary-material

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