Bilateral INO in PSP

The diagnosis of internuclear ophthalmoplegia (INO) hinges on the disturbance of ocular motility which leads to adduction deficit on the affected side and abduction nystagmus on the contralateral side.[1] If the adduction deficit is seen bilaterally along with bilateral abduction nystagmus, then it is called a bilateral INO (BINO).[1] Frequently, BINO is associated with exotropia in the primary gaze which gives an appearance as if the eyes are looking sideways called as wall-eyed bilateral INO (WEBINO).[1]

A 79-year-old right-handed man presented with a 5-year history of symptoms suggestive of Parkinsonism. His initial symptoms included slowness in daily tasks, difficulty turning while walking, small handwriting, a decrease in the volume of voice, and dysphagia which required the placement of a PEG tube. His other symptoms included constipation, urinary urgency, and drooling. His wife mentioned short-term memory loss, and he would forget conversations. The dose of carbidopa/levodopa was increased gradually to 1000 mg a day which did not lead to any improvement. Recently, he complained of double vision especially when reading and was using prism glasses.

The patient's visual acuity with correction was 20/200 in the right eye (improving with a pinhole to 20/60-2) and 20/50 in the left eye (no improvement with pinhole). His color vision was normal. Pupils were equal and reactive to light with no relative afferent pupillary defect, and eyelid blinking rate was severely reduced. His eye movement testing showed slowed adduction saccades bilaterally with bilateral abducting nystagmus, but with no visible exotropia in primary position. There was slowing of vertical saccadic eye movements as well. Oculocephalic reflex (VOR) revealed a full range of eye movements. The conjugate up gaze was severely impaired, square-wave jerks were present, and convergence was intact [Video 1]. He had a mild cognitive impairment with a MoCA (Montreal Cognitive Assessment) score of 23/30 (losing 2 points for visuospatial, 1 point for naming, 1 point for attention, 1 point for language, and 2 points for delayed recall).

Brain MRI with contrast did not show any parenchymal lesion but showed reduced midbrain to pons ratio of 0.50 [Figure 1]. A midbrain to pons ratio of less than 0.52 is quite specific for progressive supranuclear palsy (PSP) based on a study of pathologically confirmed PSP cases.[2] Thus, this patient met the diagnostic criteria for probable PSP based on the signs seen on examination.[3]

Figure 1.

MRI brain shows reduced midbrain to pons ratio of 0.50 on the sagittal T1 image

A thorough eye movement exam is prudent in the clinical diagnosis of PSP. In the initial stages, there is impairment in the vertical eye movements, particularly downgaze and slowing of vertical saccades. However, in the later stages, complete ophthalmoplegia can be seen. In the initial description of PSP, degeneration in superior colliculi and pretectal regions were attributed as a cause of vertical gaze impairment.[4] Due to the involvement of supranuclear pathways, the term PSP was used.[4] Another reason proposed for a supranuclear etiology of impaired vertical eye movements was an intact VOR.[5] In the initial description of PSP, mild demyelination of medial longitudinal fasciculus (MLF) was also seen but attributed to the involvement of the oculomotor nucleus.[4] It is now widely believed that the defects in ocular motility seen with PSP can occur because of nuclear or supranuclear pathways.[6] The presence of bilateral INO in PSP (3 out of 4 cases) was first described in 1975.[5] There have been four other case reports of bilateral INO with PSP, out of which one was BINO[7] and three were WEBINO[8,9,10] [Table 1].

Table 1.

Clinical features of patients with bilateral INO in PSP

	Age	Sex	Convergence	Vertical eye movements	Horizontal eye movements	Oculo-cephalic reflex	Primary position
Mastaglia 1975[1]
Case 1	49	M	Impaired	Impaired	Impaired	Preserved	Orthotropic
Case 2	72	F	Impaired	Impaired	Impaired	Preserved	Orthotropic
Case 3	73	F	Impaired	Impaired	Impaired	Preserved	Orthotropic
Flint AC 2005[7]	71	M	Intact	Impaired	Impaired	Preserved	Exodeviation of the right eye
Ushio M 2008[8]	72	M	Absent	Impaired	Impaired	Preserved	Bilateral exotropia
Matsumoto H 2008[9]	72	M	Impaired	Impaired	Impaired	Preserved	Exotropia of one eye
De Souza LC 2017[10]	60	F	Impaired	Impaired	Impaired	Preserved	Bilateral exotropia

The possible explanation behind the development of exotropia seen in bilateral INO is not entirely known.[1] Some studies have suggested the involvement of medial rectus neurons in the MLF while others have suggested a lesion of the oculomotor nucleus in the midbrain.[1] Bilateral exotropia seen with BINO is usually related to the involvement of rostral midbrain.[9]

Convergence commands do not pass through the MLF and are sent from the midbrain directly to the medial rectus motor neurons.[11] Convergence is usually preserved in unilateral INO but may be affected in WEBINO or BINO.[11] In the presence of bilateral INO, convergence has limited localizing value because it is variable. Vertical nystagmus is common in WEBINO because of damage to the vestibulo-ocular motor pathways passing through the MLF.[1]

In our case, the likely localization of BINO is caudal midbrain or pons because exotropia was not seen in the primary position and convergence was intact. The involvement of bilateral MLF is the most likely explanation for BINO. MLF is considered as a common pathway for conjugate gaze. It is possible that there are separate pathways for VOR and saccadic or pursuit eye movements within the MLF. An ischemic stroke or a demyelinating plaque involves a larger area and involve all the pathways within the MLF leading to impaired VOR, saccadic, and pursuit eye movements. On the other hand, a degenerative condition such as PSP may involve selective pathways within the MLF responsible for saccadic or pursuit eye movements and spares the pathway responsible for VOR. Another possible reason could be a different pathway for VOR which is not properly understood and MLF may not be a part of it at all.

In summary, we are reporting a unique case of BINO with intact convergence and absence of exotropia in the primary position. This case expands the spectrum of oculomotor abnormalities seen with PSP.

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The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

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