Wall-Eyed Bilateral Internuclear Ophthalmoplegia Syndrome in a Patient With Progressive Supranuclear Palsy: A Case Report and Literature Review

Article information

J Mov Disord. 2023;16(2):227-230

Publication date (electronic) : 2023 May 24

doi : https://doi.org/10.14802/jmd.22056

Aryun Kim¹, Yu Jin Jung², Dallah Yoo³, Chaewon Shin^4,5,, Seong-Hae Jeong^5,6

¹Department of Neurology, Chungbuk National University Hospital, Cheongju, Korea

²Department of Neurology, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

³Department of Neurology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea

⁴Department of Neurology, Chungnam National University Sejong Hospital, Sejong, Korea

⁵Department of Neurology, Chungnam National University College of Medicine, Daejeon, Korea

⁶Department of Neurology, Chungnam National University Hospital, Daejeon, Korea

Corresponding author: Chaewon Shin, MD, PhD Department of Neurology, Chungnam National University Sejong Hospital, 20 Bodeum 7-ro, Sejong 30099, Korea / Tel: +82-44-995-4751 / Fax: +82-44-995-5597 / E-mail: chroma0202@gmail.com

Received 2022 April 10; Revised 2023 January 30; Accepted 2023 April 3.

Dear Editor,

Patients with progressive supranuclear palsy (PSP) present features including vertical gaze palsy, pseudobulbar palsy, dysarthria, axial rigidity, and dementia. In the revised clinical diagnostic criteria of PSP of the Movement Disorders Society, ocular motor dysfunction was proposed as one of the four core functional domains [1]. Ocular motor dysfunction includes three main features: O1) vertical supranuclear gaze palsy, O2) slow velocity of vertical saccades, and O3) frequent macro square wave jerks or “eyelid opening apraxia”. There have been several case reports of wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) in patients with PSP (Supplementary Table 1 in the online-only Data Supplement). However, WEBINO has not yet been established as a clinical feature in patients with PSP. Herein, we report a case of PSP with WEBINO and review previous case reports.

A 63-year-old man came to the clinic with dysphonia and bradykinesia. He had developed a husky voice and slow gait 4 months prior. He reported getting slower when taking a shower and occasionally experienced drooling. He denied having rapid eye movement sleep behavior disorder, constipation, or voiding difficulties. He had experienced a small left cerebellar infarction, which occurred 1 year prior, and reported hypertension, gout, and asthma. On neurological examination, he showed a masked face and mild bradykinesia in the left hand. 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT) positron emission tomography (PET) showed decreased uptake in the bilateral basal ganglia (Figure 1), which was worse on the right side. There was no evidence of Parkinson-plus syndrome on the initial brain magnetic resonance imaging (MRI) scan. We started levodopa to control his parkinsonism, which worked for several months. However, the response became poor despite a dose increase of up to 450 mg per day. He complained of postural instability with a relatively rapid progression in the last 3 years.

Figure 1.

Neuroimaging findings of the patient. A: Marked midbrain atrophy and medial and anterior temporal lobe atrophy are seen in the axial view of the brain MRI scan, which was taken 6 years after onset. B: There are no abnormal findings in the basal ganglia and high frontal and parietal cortices. C: The “humming bird sign” is seen on the sagittal view. D: 18F-FP-CIT PET shows severely decreased dopamine transporter uptake in the bilateral basal ganglia. E: Photographs of oculomotor abnormalities in the index case. Gaze positions: primary position, lateral (left and right arrow), upward (upper arrow), and downward (lower arrow). 18F-FP-CIT, 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane; PET, positron emission tomography; MRI, magnetic resonance imaging.

On a subsequent visit, 4 years after the initial presentation, the patient developed horizontal diplopia, especially while looking at the close objects. His eyes showed bilateral exotropia in the primary eye position and vertical gaze limitations (Figure 1). Spontaneous saccadic intrusions were present, which increased without fixation (Supplementary Figure 1 in the online-only Data Supplement). In his horizontal gaze, an adduction deficit with abducting nystagmus was shown, which was compatible with WEBINO syndrome (Supplementary Video 1 in the online-only Data Supplement). Convergence was impaired, while the oculocephalic response was preserved, which was confirmed by a video-assisted head impulse test.

He also had frequent blepharospasm. We reconsidered his clinical manifestations and tried to find another cause of WEBINO. He did not have autonomic dysfunction, such as urinary retention, severe orthostatic hypotension or cerebellar ataxia. Follow-up brain MRI revealed severe atrophy of the midbrain (Figure 1) and no other new intra-axial brain lesions contributing to WEBINO. We increased the levodopa dose to 600 mg per day for 6 months, but it was not effective. The patient was barely able to walk with a cane and experienced frequent falls more than once a day, which was compatible with a Hoehn and Yahr stage 4 rating.

Until the development of WEBINO and vertical gaze limitations, the patient could have been diagnosed with suggestive PSP with predominant parkinsonism (A2 + CC1). However, he ultimately satisfied the clinical criteria for probable Richardson’s syndrome (PSP-RS) [1]. His core clinical features, including O1 (vertical supranuclear gaze palsy) and A2 (parkinsonism, akinetic-rigid, predominantly axial, and levodopa-resistant), confirmed the final diagnosis [2].

WEBINO in the clinical course of PSP can make diagnosis challenging. This patient was diagnosed with PSP-RS based on his asymmetric parkinsonism with poor response to levodopa, early postural instability, and neuro-ophthalmologic findings [1].

WEBINO consists of primary gaze exotropia, bilateral adduction impairment, and abducting nystagmus in both eyes. WEBINO syndrome has been reported in patients with brainstem infarction, tumor, multiple sclerosis, infection, head trauma, inflammation, poor nutrition (Wernicke’s encephalopathy or pernicious anemia), toxic/metabolic conditions, and congenital malformation (Arnold-Chiari malformation). These conditions result in disturbance of the bilateral medial longitudinal fasciculus (MLF) [3]. The MLF carries signals for horizontal conjugation from the abducens nucleus to the contralateral medial rectus subnucleus of the oculomotor nerve. Weakening of the medial rectus muscle due to MLF lesions prompts the higher oculomotor centers to increase innervation to the medial rectus to compensate for the paresis. The contralateral lateral rectus also receives additional innervation as the corresponding synergist muscle, resulting in abducting nystagmus. However, the cause of primary gaze exotropia in WEBINO is still controversial. On neuroimaging studies, WEBINO is not necessarily pontine in origin, and the responsible lesion can extend into the midbrain as well [4]. Other studies have claimed that small subgroups of medial rectus neurons embedded within the MLF are responsible for exotropia, leaving the oculomotor nerve nucleus intact [5]. Some studies have reported that the paramedian pontine reticular formation is also functionally involved in exotropia in patients with WEBINO syndrome.

There have been eight case reports of WEBINO in patients with PSP (Supplementary Table 1 in the online-only Data Supplement). Disease duration at the onset of WEBINO varies by case. Two cases showed WEBINO in the progressive course of PSP, as in our case, but not on initial examination. This difference might be attributed to tau burdens and cell-type-specific distribution patterns in the different clinical subtypes of PSP. In a recent study of distribution patterns of tau pathology in patients with PSP, significant differences in the tau burden as well as tau cytopathology distinguished the clinical subtypes [6]. Patients with PSP-P usually showed less total tau accumulation in the neocortical regions, selected subcortical regions, and brainstem nuclei than those with PSP with corticobasal syndrome (PSP-CBS) and PSP with predominant speech and language disorder (PSP-SL) [6]. According to the staging scheme in that study, common early vulnerability patterns mainly affecting the pallido-nigro-luysian axis characterize all PSP clinical subtypes. Subsequently, tau pathology propagates rostrally to neocortical regions and caudally to the cerebellum, including the dentate nucleus. The development of WEBINO in this patient after initial parkinsonism without significant cortical symptoms implies that tau pathology progressed caudally and impaired conjugated eye movements of the MLF bilaterally.

In summary, WEBINO should be considered as an oculomotor dysfunction in patients with PSP that can develop in the progressive course of the disease. WEBINO is not present in patients with other Parkinson syndromes, which suggests that it is a clinical indication of PSP in the differential diagnosis of parkinsonism.