Clinical Reasoning: Young woman with orbital pain and diplopia

Section 1

A 27-year-old woman presented with acute onset of double vision, right-sided orbital pain exacerbated by ocular movements, and ipsilateral conjunctival hyperemia. Her personal medical history was negative and she denied any recent illness, journey, or sick contact. Family history was positive for Hashimoto thyroiditis in her mother. Neurologic evaluation revealed complete lateral and partial upward gaze palsy in her right eye, with binocular horizontal diplopia. The remaining clinical examination was unremarkable; in particular, pupillary reflex was preserved and there was no evidence of ptosis, conjunctival chemosis, proptosis, eye discharge, or visual defects.

Before being referred to our center, the patient had undergone an ophthalmologic evaluation, comprehensive of fundoscopic analysis, which turned out normal: the visual acuity was 20/20 bilaterally and no red desaturation was found.

Section 2

Ophthalmoplegia represents a diagnostic challenge, with a considerable number of causative conditions, involving the brainstem, orbits, nerves, muscles, or neuromuscular junction.¹ Indeed, the wide spectrum of differential diagnosis promptly requires the correct localization of the underlying lesion. Our patient presented with gaze palsy in right eye abduction (lateral rectus muscle, right cranial nerve VI) and elevation (superior rectus muscle, right cranial nerve III), without pupillary defects, neither sign suggestive of central/peripheral nervous system involvement on neurologic examination. A cranial multiple neuropathy involving cranial nerve IV and partially III should be considered. Of note, after entering the orbit, the oculomotor nerve divides into a superior branch, supplying the superior rectus and the levator palpebrae superioris, and an inferior branch, reaching the medial and inferior rectus, the inferior oblique, and the ciliary ganglion, whose postganglionic axons innervate the sphincter pupillae and the ciliaris. The right eye upward gaze palsy in our patient could then indicate an involvement of the superior branch of cranial nerve III, though sparing the levator palpebrae superioris.

Two other possible causes are a muscle disease and a neuromuscular junction defect. Regarding the last possibility, the patient denied any fluctuation of symptoms, nor was fatigability unveiled through clinical evaluation.

Notably, diplopia was associated, since the beginning, with orbital pain, which narrows down the possible causes to those conditions determining painful ophthalmoplegia.² Accordingly, we should take the following into account:

• Vascular diseases (such as carotid cavernous fistula, cavernous sinus thrombosis, intracavernous carotid artery, or posterior cerebral artery aneurysm)

• Infectious processes involving the orbit (i.e., herpes zoster virus) or basilar meningitis (i.e., tuberculosis, fungi, Listeria)

• Inflammatory diseases (such as Tolosa-Hunt syndrome, orbital pseudotumor, optic neuritis, vasculitis, neurosarcoidosis)

• Neoplastic processes, locally infiltrative, either metastatic (i.e., lymphoproliferative diseases, orbital bone tumor) or meningeal carcinomatosis

• Other conditions: Wernicke syndrome, ophthalmoplegic migraine, traumatic lesions

The acute onset of symptoms suggested a vascular, infectious, or inflammatory disease, more likely than a neoplastic condition. Another remarkable element was the presence of autoimmune disorders in the patient's family history.

Section 3

Blood examinations, comprehensive of blood cell count, inflammation markers, glucose profile, thyroid function, angiotensin-converting enzyme, and a complete autoimmune screening (including anti–acetylcholine receptor antibodies), were normal, except for borderline levels of anticardiolipin immunoglobulin G antibodies (36 GPL U/mL) and low immunoglobulin A levels (4 mg/dL).

CT angiography of the head was then performed rapidly, in order to exclude any possible vascular diseases involving the cavernous sinus. In particular, we considered carotid cavernous fistula, an abnormal communication between arteries and veins, usually presenting with unilateral orbital pain, ocular inflammation, and cranial nerve palsy, although other frequent features, like reduced vision and pulsating exophthalmos, were not present in our patient. CT scan excluded vascular abnormalities, unveiling, indeed, a thickening involving the right medial rectus muscle (figure, A and B). Given this evidence, we focused on the differential diagnosis for orbital masses:

• Tolosa-Hunt syndrome, due to an orbital granulomatous inflammation causing episodic unilateral periorbital pain and ophthalmoplegia, with possible involvement of other cranial nerves

• Malignant orbital disease, usually presenting with an insidious onset of orbital signs, whereas an abrupt onset is not uncommon³

• Orbital infections, in the form of orbital cellulitis or pyomyositis, determining ocular and systemic signs of inflammation³

• Orbital pseudotumor, an inflammatory process of the orbit's structures that can cause periorbital edema, erythema, proptosis, ptosis, diplopia, and pain exacerbated by ocular movements; in particular, this category includes orbital myositis, in which the focal involvement of extraocular muscles manifests with painful ophthalmoplegia and ocular inflammation, typically unilateral³

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Figure Neuroradiologic study

(A) CT reveals enlargement of the right medial rectus muscle and, less prominently, the inferior rectus muscle, as indicated by the arrows. (B) CT angiography excludes vascular abnormality of the right intracranial carotid artery and adjacent cavernous sinus. On brain MRI, (C) coronal T2-weighted image and (D) axial fluid-attenuated inversion recovery T2-weighted sequence with fat saturation confirm thickening involving the right medial and inferior rectus muscle with hyperintense signal (arrows).

MRI scan of the brain, including sequences dedicated to the orbits, confirmed the enlargement of the medial rectus muscle and, less prominently, inferior rectus muscle, with T2 hyperintensity and not significant contrast enhancement after gadolinium chelates administration (figure, C and D). The optic nerve showed regular signal intensity and displayed no contrast enhancement.

The neuroradiologic (in particular brain MRI) findings clarified the anatomic site of the lesion and the clinical signs observed at neurologic examination, which were due to a hyperactivity of the medial and inferior rectus muscle, with a limitation of the ocular movements controlled by the antagonist extraocular muscles, mimicking a deficit of cranial nerves VI and III.

Section 4

Clinical, laboratory, and neuroradiologic findings led to the diagnosis of idiopathic orbital myositis.

Of note, a mass within the extraocular muscles may also represent an orbital lymphoma, mimicking orbital myositis. However, lymphomas generally involve the superolateral quadrant of the orbit, infiltrating adjacent structures, with well-defined margins, less hyperintense signal in T2 because of high cellularity, and lower apparent diffusion coefficient values on diffusion-weighted imaging.⁴

In order to exclude any neoplastic or infectious processes, the patient underwent lumbar puncture, with CSF being normal.

Treatment with prednisone (1 mg/kg/day) was started with an immediate and dramatic response, followed by complete resolution of the symptoms in a few days. Corticosteroids were gradually tapered after 2 weeks. One-year follow-up showed no relapses.

Section 5

Although a definitive diagnosis of idiopathic orbital myositis requires an orbital biopsy, usually an extensive diagnostic workup, corroborated by a notable clinical response to medication and appropriate follow-up, allows excluding with reasonable certainty other underlying conditions. Specific guidelines are not yet available, but biopsy is generally performed in steroid-resistant cases or when the presence of a neoplastic process is suspected based on MRI.⁴

Moreover, increasing evidence suggests an association between idiopathic orbital myositis and giant cell myocarditis, a rare life-threatening condition presenting with heart failure, ventricular arrhythmias, and heart block. Seven cases have been described in the literature, with patients generally developing cardiac involvement a few months after the orbital symptoms onset, in most cases leading to death. When recognized timely, giant cell myocarditis represents a potentially treatable condition with steroids, calcineurin inhibitors, antimetabolites, and cytolytic therapies, although sometimes requiring immunosuppression and heart transplant.⁵ Accordingly, our patient underwent an extensive cardiologic evaluation, comprehensive of ECG/echocardiogram, which turned out normal.