Isolated Internal Ophthalmoplegia from Posterior Cerebral Artery Neurovascular Conflict

Abstract

We report a rare case of recurrent isolated internal ophthalmoplegia attributed to oculomotor nerve (CN III) compression by the posterior cerebral artery (PCA). A 30-year-old female patient presented with recurrent right-sided headaches, right periorbital pain, and slight anisocoria. Slit-lamp examination revealed normal anterior and posterior segments except for vermiform movements of the right pupil with a temporal hyporeactive flat area. Tonic pupils were ruled out with pilocarpine 0.1% testing. Suspecting an internal ophthalmoplegia, magnetic resonance imaging was ordered which demonstrated the right CN III indented by the PCA, fulfilling the criteria of a neurovascular conflict. The evaluation of unilateral mydriasis from internal ophthalmoplegia should prompt neuroimaging with exclusion of aneurysmal or compressive lesions. CN III palsy can rarely be caused by vascular anatomical variants because of the proximity of the posterior intracranial circulation and CN III. Newer, more precise imaging techniques will better help characterize neurovascular conflicts presenting as cranial nerve palsies.

Introduction

Oculomotor nerve (CN III) palsy, particularly with isolated internal ophthalmoplegia, is a medical emergency because compression from arterial aneurysm must be ruled out. CN III originates between the midbrain and pons at the level of the superior colliculus with its root exit zone at the medial aspect of the cerebral peduncle, inferior to the posterior cerebral artery (PCA) and superior to the superior cerebellar artery. The cisternal portion of CN III passes ventrally with a mediolateral and inferior direction to the posterior communicating artery (PCoA) until it reaches the roof of the cavernous sinus. The parasympathetic pupilloconstrictor fibers which run within the CN III from the Edinger-Westphal nucleus in the midbrain are particularly vulnerable to external compression causing pupillomotor abnormalities due to their superficial dorsomedial location; in contrast, ischemic/metabolic causes tend to affect the vasa nervosum in the center of CN III, leading to extraocular muscle palsy and diplopia [1]. Common causes of CN III palsy are vascular malformations, tumoral masses, or aneurysms from the basal artery or the PCoA [2]. Other anatomical variations such as developmental anomalies (persistent trigeminal artery, fetal origin of PCA), arterial loops, and dolichoectatic vessels can also lead to compressive palsy, a neurovascular conflict, and usually affect cranial nerves V, VII, VIII, IX, and X, rarely CN III [3]. Modern imaging techniques with high-resolution thin slices have demonstrated that non-aneurysmal vascular abnormalities are rare causes of compressive cranial nerve palsy in the cerebellopontine angle [4]. We report a rare, recurrent, isolated, non-aneurysmal internal ophthalmoplegia from neurovascular compression of CN III by the PCA.

Case Report

A 30-year-old, otherwise healthy, female patient presented to our emergency department complaining of recurrent right periorbital pain and right-sided intermittent headache over the past year at least twice per month, lasting a couple of hours, occasionally with nausea but without visual symptoms. She also reported a feeling of internal agitation and palpitations sometimes associated with the headaches which she attributed to work environment stress. Ophthalmologic examination revealed a visual acuity of 20/20 with normal accommodation from both eyes, normal anterior and posterior segments, and intraocular pressure; however, careful slit-lamp examination revealed segmental contraction similar to tonic pupil of the right pupillary margin with a hyporeactive flat area on the temporal side of the pupil. The left pupil was normal. Under photopic conditions, the right pupil was slightly larger than the left, with a slightly better miotic reaction on convergence than on illumination. Suspecting a tonic pupil, we conducted a pilocarpine 0.1% test which demonstrated increased relative pupil miosis on the right eye compared to the left (right pupil photopic/scotopic 6.46 mm/4.4 mm vs. left pupil photopic/scotopic 6.01 mm/3.41 mm before pilocarpine and right pupil photopic/scotopic 4.38 mm/3.77 mm vs. left pupil photopic/scotopic 6.01 mm/3.21 mm after pilocarpine eye drops) (Fig. 1a, b). Visual fields and fundus examination were normal. Orthoptic evaluation demonstrated a well-compensated exophoria at near. Her blood pressure was 145/95 mm Hg, and follow-up with her family physician was advised. Brain magnetic resonance imaging (MRI) with MR time-of-flight angiography is performed in addition to three-dimensional T2-weighted thin slice (0.6 mm), constructive interference steady state gradient echo sequences allowing reconstruction in any given plane, and fusion between the different sequences (Fig. 2). The time-of-flight and constructive interference steady state sequences were focused on the CN III which was further explored with coronal T2 sections. The MRI demonstrated the right CN III in full contact with the PCA but also indented and displaced by the artery; these findings fulfilled the criteria of a neurovascular conflict. No intracranial aneurysm or other anomaly was present (Fig. 3). Blood-pressure monitoring, ordered by her internist, confirmed mild arterial hypertension and mild heart rate elevation of 90 beats/min. Oral bisoprolol was prescribed, and on the last follow-up after 2 months, the patient reported normal blood pressure and significant improvement of her headaches, orbital pain, palpitations, and inner agitation. Pupillometry demonstrated almost symmetrical findings for both eyes (OD scotopic 4.38 mm, photopic 3.77 mm, OS scotopic 4.64 mm, photopic 3.21 mm).

Fig. 1.

Pupillometry test with pilocarpine 0.1%, (a) before and (b) 30 min after instillation. The right pupil miosis is more pronounced compared to the left (OD 0.67 mm, OS 0.2 mm in photopic conditions).

Fig. 2.

Image fusion of a high-resolution 3D T2-weighted MRI sequence and a time-of-flight angiography sequence, 0.6-mm-thin reformatted slices: axial (a); coronal (b); right sagittal (c). Arteries are displayed in color, cranial nerves and brain structures are displayed in black, and cerebrospinal fluid (CSF) is white. Axial, coronal, and sagittal images depicting the cisternal cranial nerves III (CN III) show close contact between the right posterior cerebral artery (PCA, black dashed arrow) and the right CN III (white arrow) which is indented and displaced infero-laterally. Note for comparison that the contralateral CN III (thin white arrow) is surrounded by CSF and there is no contact between the nerve and the left PCA (thin black arrow in b). MRI findings document neurovascular conflict involving the right PCA and CN III. The short arrow in a and b points at the basilar artery.

Fig. 3.

MRI angiography (lateral view) shows no intracranial aneurysm and normal vessels. The right and left PCAs are marked (white arrow).

Discussion

CN III disorders can be caused by a variety of anatomic or medical conditions including compression from aneurysms, trauma, neoplasms, post-neurosurgical conditions, diabetes mellitus, hypertension, post-viral infections, ophthalmoplegic migraine, and inflammations associated with ischemia [1]. Depending on the cause and site of CN III disturbance, external or internal CN III ophthalmoplegia can occur. External ophthalmoplegia describes extraocular muscle paresis and/or ptosis. Internal ophthalmoplegia affects the pupillary sphincter and ciliary muscle, causing pupillomotor abnormalities and/or decreased accommodation.

Anatomical variations of the intracranial circulation in the vicinity of CN III may cause a neurovascular conflict, producing isolated CN III paresis or palsy [5]. Such neurovascular compression tends to affect transitional zones between the central and peripheral myelin [6]. Jannetta [7] provided the first description of the most common neurovascular conflicts for cranial nerves V, VII, VIII, IX, and X including the following criteria: direct contact at a right angle between the cranial nerve and a vascular component, located in the root entry zone, the transition zone between central and peripheral myelin, and resulting in displacement of the cisternal segment of the respective cranial nerve. MRI with high-resolution T2-weighted imaging can identify the precise location of neurovascular compression while excluding other etiologies that may mimic neurovascular conflict [6].

Isolated internal ophthalmoplegia as presenting sign of neurovascular compression as described herein is exceedingly rare. Trechot et al. [8] described a neurovascular conflict between the PCoA with the same diameter as the PCA and the clinoid process pressing on CN III in 5 patients with pure internal ophthalmoplegia having unilateral unreactive mydriasis and ipsilateral headache. Albayram et al. [9] summarized the known cases of isolated internal ophthalmoplegia albeit without headache. The presence of headaches or periorbital discomfort is usually associated with aneurysmal compression, making our case possibly the first documented isolated internal ophthalmoplegia with headaches from PCA neurovascular conflict [3]. In the context of newly diagnosed hypertension, it is also possible that neurovascular conflict could have resulted from PCA pulsation, causing mechanical stress directly on the CN III [3, 10]. The significance of vasculopathic risk factors such as diabetes, hypertension, and hypercholesterolemia has already been demonstrated in patients with third nerve palsy as part of microvascular damage [11]. Besides, mild-to-moderate hypertension is not always asymptomatic, and the incidence of headache can be reduced with antihypertensive treatment, as in our case [12]. Furthermore, evolving vascular sclerotic changes may also contribute to mechanical compression of the CN III by the artery [10].

The pilocarpine 0.1% test led to a more pronounced miosis on the right eye compared to the left eye (mesopic and photopic in our case). However, as preganglionic injury can also produce end-organ supersensitivity, CN III palsy can also cause a positive pilocarpine test. Studies have shown that the degree of cholinergic supersensitivity is about the same in patients with CN III palsy and patients with tonic pupil [13]. This should not be surprising since parasympathetic fiber disturbance within CN III would cause some functional denervation. In contrast, a pathologic condition at the level of the ciliary ganglion would tend to lead to structural denervation with more profound shutdown of neurotransmitter release causing obvious hypersensitivity on pilocarpine 0.1% testing. We hypothesize that increased systemic hypertensive arterial changes and pulsations pressing on CN III triggered contributed to her symptomatic CN III neurovascular conflict.

Anisocoria is often viewed as an ominous sign requiring a systematic approach. The differential diagnostics of an isolated dilated, hyporeactive pupil in an awake, alert patient should include tonic pupil, pharmacological blockade, iris trauma, and iris synechia. Given the young age of our patient and the associated headache with nausea, benign episodic unilateral mydriasis should also be considered. Alternatively, this could also be a case of a tonic pupil in a patient who also happened to have a narrow space between the PCA and the CN III.

In conclusion, neurovascular conflict is a rare cause of episodic non-aneurysmal internal CN III palsy. Although the most usual cause of anisocoria is tonic pupil, coincidence with episodic segmental headache can justify a more thorough examination with neuroimaging. It is probable that with newer, more precise imaging techniques, the number of oculomotor palsies diagnosed as idiopathic will be reduced. The evaluation of unilateral mydriasis from internal ophthalmoplegia, depending on the severity and collateral clinical findings, should include neuroimaging with exclusion of aneurysmal or compressive lesions. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see www.karger.com/doi/10.1159/000529231).

Statement of Ethics

Ethical approval is not required for this study in accordance with local or national guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images in this manuscript.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

• No funding has been received for this study.

Author Contributions

Argyrios Chronopoulos, Andrea Consigli, James Scott Schutz, Minerva Becker, and Hermann Krastel have made substantial contributions to the conception, design, and drafting of the work and revising it critically for important intellectual content and in the final approval of the version to be published. Julia Heim and Lars-Olof Hattenbach have made substantial contributions to the management of resources, superivision, data curation, and its critical revision for important intellectual content. Lars-Olof Hattenbach gave the final approval of the version to be published.

Funding Statement

No funding has been received for this study.

Data Availability Statement

All data that support the findings of this study are included in this article. Further inquiries can be directed to the corresponding author.