ABSTRACT
Non-paralytic pontine exotropia (NPPE) is a rare condition characterized by internuclear ophthalmoplegia associated with exotropia in the contralateral eye. We report a case of an 82-year-old woman with acute onset of right eye exotropia and adduction deficit of the left eye. Magnetic resonance imaging showed areas of restricted diffusion in the left paramedian midbrain, left precentral gyri, and right superior parietal gyri. She recovered after 3 days. On the seventh day after onset, the left eye appears with an esotropia, a finding never described before in NPPE. For a better understanding of the pathophysiology and recognition of NPPE, more reports like this are essential to encourage more publications on the topic and the creation of guidelines for this type of ophthalmoplegia.
KEYWORDS: Stroke, exotropia, vertebrobasilar, pons, internuclear ophthalmoplegia
Introduction
Non-paralytic pontine exotropia (NPPE) is a rare condition characterized by the association of internuclear ophthalmoplegia (INO) and exotropia in the contralateral eye, first reported by Bogousslavsky and Regli in 1983.1 Since then, few reports have described the occurrence of NPPE as a manifestation of vertebrobasilar stroke, and its pathophysiology is still under investigation. Our goal is to expand medical knowledge about NPPE and its variants.
Case report
An 82-year-old woman presented to an emergency department with acute onset of perioral paresthesia and binocular diplopia upon awakening. She had a past medical history of cervical spondylosis, hypothyroidism, and cataracts. On neurological examination, the patient showed bilateral dehiscence of the levator palpebrae, mild dysarthria, right ataxic-hemiparesis syndrome, central facial palsy on the right, and peripheral facial palsy on the left. In the primary gaze position, the patient preferred fixation with her left eye, in which she has better vision, accompanied by right eye exotropia; in contrast, during right eye fixation, the exotropia vanished. Motor ocular examination revealed a left INO characterized by an adduction deficit of the left eye and abduction nystagmus of the right eye during gaze to the right (Figure 1). There was no restriction in the left, up, or down gaze, and no skew deviation, characterizing a nonparalytic exotropia. Additional findings were slow saccades to the left, due to paramedian pontine reticular formation (PPRF) compromise, with normal smooth eye pursuit, and downbeat nystagmus on downgaze. The vestibulo-ocular reflex was normal, suggesting that the nucleus of the sixth nerve was intact. Convergence of the right eye was normal; however, convergence of the left eye appeared with some exotropia, without light-near dissociation. Isochoric and photoreactive pupils were observed in both eyes, with a dark iris surrounded by an arcus senilis (which gives the impression of a dilated pupil, which was not the case). Fundoscopic exam showed moderate cataract (right eye > left eye), regular optic disc with physiological contour and excavation, and free macula. Best-corrected visual acuity was 20/100 in the right eye and 20/80 in the left eye.
Figure 1.
Ocular motility on admission: primary gaze with left eye fixation (a), eye disposition on left gaze (b), right gaze (c), down gaze (d), up gaze (e), and near vergency test (f).
On magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI) evidenced acute infarcts in the left paramedian midbrain, left precentral gyri, and right superior parietal gyri (Figure 2). T2-weighted FLAIR demonstrated areas of hyper signal in the left paramedian midbrain, left pons, and cortical areas (Figure 3). Dual antiplatelet therapy with aspirin and clopidogrel was started, and 3 days later, the ocular motor abnormalities disappeared. One week later, the left eye became esotropic with the Hirschberg test, now suggesting a fascicular left abducens paresis (Figure 4), with normal ocular motility, which took 2 weeks for complete resolution.
Figure 2.
DWI with restricted diffusion, shown by the red arrows, in the left paramedian midbrain (a and b), left precentral gyri (c), and right superior parietal gyri (d). No restriction on lower (e) or upper (f) pons.
Figure 3.
T2 FLAIR with hypersignal, shown by the red arrows, in left pons (a), left paramedian midbrain (b), and cortical areas (c and d).
Figure 4.
Ocular motility on the seventh day: primary gaze (a), eye disposition on right gaze (b), left gaze (c), up gaze (d), and down gaze (e).
Discussion
The control of voluntary horizontal eye movements originates in the frontal eye field (FEF) to the contralateral PPRF, which contains excitatory burst neurons that project to the ipsilateral abducens nucleus, composed of motoneurons that send axons to the ipsilateral lateral rectus muscle and internuclear neurons that project, via the contralateral medial longitudinal fasciculus (MLF), to the oculomotor nucleus on medial rectus motoneurons. When stationary, maintaining gaze in the central position depends on symmetric inputs from the bilateral FEF, superior colliculus, and vestibular nucleus, and unilateral lesions that lead to loss of function of these can lead to tonic conjugate deviations of gaze toward the unaffected side (lesion on PPRF) or toward the side of the lesion (lesion on FEF). MLF involvement can cause INO, manifested by an adduction deficit of the eye ipsilateral to the lesion during horizontal gaze to the opposite direction, generally accompanied by abduction nystagmus of the contralateral eye.2
Combined lesions of the PPRF and MLF can cause the paralytic pontine exotropia (PPE), first reported by Sharpe J, et al. in 1974, consisting of paralysis of ipsilateral horizontal gaze (due to the PPRF lesion), INO (due to the MLF lesion), and a tendency of both eyes to deviate ipsilaterally during primary gaze (due to unopposed and overactive impulse from the contralateral PPRF). However, due to the MLF lesion, only the contralesional eye deviates as a contralesional exotropia in the primary gaze (as the MLF lesion prevents the ipsilesional eye from receiving the asymmetrical impulse), usually described during attempts at forward gaze with the ipsilesional eye fixing (fixation with the eye on the side of the lesion possibly stimulates the superior colliculus on the same side, mainly activating the contralateral PPRF).3,4
In contrast, the NPPE, first reported by Bogousslavsky and Regli in 1983, consists of INO and exotropia of the eye on the unaffected side during primary gaze (possibly by the same mechanism), without paralysis of ipsilateral horizontal gaze, but with slowing of ipsilateral saccades (showing a relatively preserved capacity of PPRF function), with faster recovery of exotropia in NPPE patients compared with PPE patients, suggesting that NPPE may be a partial or less severe form of PPE.1,5
In the 1990s, Komiyama et al. presented the first methodical evaluation of NPPE after reviewing seven clinical cases of patients with INO and contralateral non-paralytic exotropia.5 Three of his subjects had slowing of ipsilateral saccades, and all presented enhancement of the exotropia with near convergence or fixation. Some of his patients also presented ocular findings associated with brainstem lesions, such as skew deviation and central vestibular nystagmus, in addition to the NPPE. More recently, Lopes et al. reported a case of NPPE with the additional finding of slowing of ipsilateral saccades and downbeat nystagmus on downgaze, with normal convergence.6 The localization of the lesions that may cause NPPE is still to be cleared. Usually, these patients have MRI lesions in variable brainstem locations, such as the lower, mid, or upper pons and lower midbrain, but not a paramedian midbrain lesion.5,6 Analyzing the recovery pattern of cases of Komiyama et al., there were six patients with complete recovery (with an exotropia recovery rate of 1 to 15 days and an INO recovery rate of 1 day to 2 months) and one patient with partial recovery.5
Our case of NPPE evolved to transient esotropia, which suggests that both the PPRF and the abducens fascicle were ischemic; the former improved faster than the latter. The sixth nerve nucleus was always intact. In addition, our case suggests an unusual correlation between paramedian midbrain infarct and NPPE. The downbeat nystagmus on downgaze, only described before in NPPE in another case report,6 perhaps is explained by injury to the fibers of the interstitial nucleus of Cajal related to downward gaze fixation; in other words, a vertical neural integrator nystagmus.
There are four pontine structures that control horizontal gaze and can be differentially affected by ischemia/infarction: 1. PPRF, 2. sixth nerve nucleus, 3. MLF, and 4. abducens fascicle (surrounding the facial colliculus). Variations in the degree of ischemic insult on dorsal lateral pontine ocular motor neurons will have an impact on the ipsilesional horizontal eye position.
Regarding other alterations present in the neurological examination, the patient presents central facial palsy on the right due to an infarct in the left precentral gyri and peripheral facial palsy on the left due to possible previous infarct in the facial nucleus on the left pons (T2 hyper signal without restriction on diffusion).
Conclusion
Case reports like this are essential for demonstrating the importance of rapid recognition of abnormal findings during ocular motor examination and differentiation of a central lesion from a peripheral one. For this proposal, it is generally assumed that conjugate gaze deficits represent a central lesion, and unconjugated deficits represent a peripheral lesion, but in many cases, this simple distinction is not enough. The PPE and NPPE are examples of central lesions that present with a combination of tonic gaze deviation in the primary gaze with INO, or, in other words, a central unconjugated deficit. That said, recognizing and interpreting rare central presentations is crucial in the emergency department, and quick decisions based on this change the patient’s prognosis. Finally, it is essential to highlight that more studies are needed to characterize the pathophysiology and presentation of the NPPE.
Funding Statement
The author(s) reported there is no funding associated with the work featured in this article.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Ethics declaration
The patient filled an informed consent. The Local Ethics Committee and the Brazilian National Ethics Committee (CAAE: 78807923.3.0000.0273) approved the study.
References
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