Life-threatening diplopia with pupil involvement

Life-threatening diplopia with pupil involvement

Andrew G. Lee

Department of Ophthalmology, Neurology, and Neurosurgery, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA

Introduction

The comprehensive ophthalmologist may have to emergently evaluate the patient with diplopia and an abnormal pupil. Three potentially life threatening etiologies will be discussed in this manuscript: 1. Pituitary apoplexy; 2. Mucormycosis; and 3. Aneurysm. Earlier diagnosis and earlier treatment for these conditions makes a difference and prompt neuroimaging is required. A case-based format will be used to illustrate key points in the discussion.

Case 1: Pituitary apoplexy

A 25-year-old female presents with severe (10/10) headache, a right RAPD, a bitemporal hemianopsia, and a third nerve palsy on the right. The patient is the last patient of the day, 4:45 PM, on Friday. What should be done?

An emergent CT-scan, followed by an MRI that night confirmed pituitary apoplexy. The patient underwent successful neurosurgical decompression of a necrotic pituitary adenoma. Pituitary apoplexy may present to the ophthalmologist. Acute and severe headache is often the first symptom but visual loss and diplopia may be the presenting or only features. Hemorrhage or necrosis may occur within a preexisting pituitary macroadenoma and mass effect from expansion into the adjacent cavernous sinus may produce ophthalmoplegia with or without pupil involvement. Medical management of pan-hypopituitarism and prompt surgical decompression may be life or vision-saving.1-5

Address for correspondence: A.G. Lee, MD, Department of Ophthalmology, 200 Hawkins Drive, PFP, Univerisity of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. E-mail: andrewlee@uiowa.edu

Eye on the Bayou, New Concepts in Glaucoma, Cataract and Neuro-Ophthalmology, pp. 11–17 Transactions of the 54th Annual Symposium of the New Orleans Academy of Ophthalmology, New Orleans, LA, USA, February 18-20, 2005

edited by Jonathan D. Nussdorf

© 2006 Kugler Publications, The Hague, The Netherlands

Case 2: Mucormycosis

A 35-year-old female with a history of recent diabetic ketoacidosis presented with a complete ophthalmoloplegia, a dilated pupil, and an optic neuropathy in the left eye. A CT-scan showed ‘orbital cellulitis and pansinusitis’ and she was treated with antibiotics at an outside hospital but continued to worsen.

The patient underwent otolaryngologic evaluation and sinus surgery showed fungal elements consistent with Mucor. Rhino-orbital-cerebral mucormycosis is associated with a poor prognosis. The diagnosis should be considered in patients with an acute orbital presentation (e.g., proptosis, inflammatory signs) associated with multiple cranial nerve palsies or complete ophthalmoplegia. Concomitant ipsilateral optic neuropathy, or retinal or orbital infarction should increase the suspicion for Mucor. The classic ‘black eschar’ may not be seen. Early local and systemic antifungal treatment and surgical debridement might be life-saving.6-7

Posterior communicating artery aneurysm

The patient with the pupil-involved third nerve palsy is one of highest stakes encounters for the ophthalmologist in clinical practice. Patients with severe headache (i.e., “the worst headache of my life”) or meningeal signs should undergo a non-contrast CT-scan of the head to rule out subarachnoid hemorrhage. Appropriate referral to a neurologist or neurosurgeon for further urgent evaluation and management is critical. Patients with non-isolated third nerve palsies should undergo evaluation and appropriate neuroimaging (i.e., orbital and cranial MRI with contrast along the course of the third cranial nerve and MRA) directed at the topographical localization of the clinical findings (e.g., orbit, superior orbital fissure, cavernous sinus, subarachnoid space, or brainstem).

Although most isolated third nerve palsies in adults are due to ischemia, some of these patients are harboring a life-threatening intracranial aneurysm.8-33 Detection of the aneurysm prior to rupture might lead to rapid endovascular coiling or surgical clipping (Fig. 1). Delay in diagnosis and treatment after rupture and subarachnoid hemorrhage is associated with a much worse prognosis.8

Classification of isolated third nerve palsy

The isolated third nerve palsy can be classified based upon the degree of involvement of the external muscles (i.e., lid and extraocular muscles of the third nerve) and the internal muscles (i.e., the pupil). A complete external dysfunction third nerve palsy is defined as one that significantly involves all of the external branches of the third nerve (e.g., all of the extraocular muscles innervated by the third nerve and the lid). A third nerve palsy that either does not involve all of the branches of the third nerve (e.g., superior divisional palsy) or does not involve all of the external muscles to a significant degree is considered an incomplete external dysfunction third nerve palsy for the purposes of this discussion. Third nerve palsies with complete external dysfunction may be further subdivided by degree of internal dysfunction (i.e., no internal dysfunction, partial internal dysfunction, or complete internal dysfunction).9,11

Fig. 1. Magnetic resonance angiography (MRA) shows posterior communicating artery aneurysm.

Isolated complete external dysfunction third nerve palsy with normal internal function (i.e., ‘pupil sparing’)

A neurologically-isolated third nerve palsy with a completely normal pupil and completely palsied extraocular muscles with complete ptosis is almost never caused by an aneurysm. A single case has been reported due to a basilar artery aneurysm but this is the exception and not the rule.10 The isolated, complete external dysfunction, ‘pupil-spared’ (i.e., normal internal function) third nerve palsy is most commonly caused by ischemia (e.g., diabetes). Neuroimaging may be deferred in adults with known vasculopathic risk factors (e.g. diabetes, hypertension) and a neurologically-isolated, complete (external dysfunction) but ‘pupil-sparing’ third cranial nerve palsy. Other authors have reported finding alternative etiologies for a presumed vasculopathic ocular motor cranial neuropathy on initial neuroimaging however and initial neuroimaging might still be considered.

Isolated incomplete external dysfunction third nerve palsy with no internal dysfunction (i.e., no pupil involvement)

Patients with an isolated incomplete external dysfunction and no internal dysfunction (e.g., divisional palsy) probably should undergo neuroimaging (e.g., MR-scan to rule out a mass lesion and an MRA or CTA). If the MRI and MRA (or CTA) are normal, cerebral angiography should still be considered to investigate the presence of an aneurysm or less likely a carotid cavernous sinus fistula. Although the MRI and MRA (or CTA) combination will usually show an aneurysm large enough to cause a third nerve palsy, cerebral angiography remains the ‘gold standard’ for the diagnosis of cerebral aneurysms. The combination of an adequately performed and interpreted MRI and MRA (or CTA) may be up to 98% sensitive in the detection of an aneurysm that will bleed.19-23 Wong et al. reviewed using CTA as the first line imaging for isolated third nerve palsy presenting without subarachnoid hemorrhage. Nine of 34 (26%) patients had structural lesions as the etiology for the third nerve palsy and five had posterior communicating artery aneurysms. All the aneurysms were detected by CTA. The presence or absence of pain was not of diagnostic value for intracranial aneurysm in this study. They concluded that a ‘good quality’ CTA was sufficient to detect a compressive aneurysm but that if the CTA results were ‘inconclusive’ that the patient should undergo catheter angiography.23

Table 1. Risk of aneurysm based upon the degree of internal and external dysfunction of the third nerve

* Catheter angiography should be considered if the risk of aneurysm is higher than the risk of angiography. Angiography may be deferred if the risk of angiography is higher (e.g., elderly or frail individual with renal failure) than the risk of aneurysm (e.g., child younger than ten years of age). Post-test likelihood of aneurysm can be modified by performing an MRI with MRA or CTA combination.

The clinician must determine in consultation with their local neuroradiologist the sensitivity and specificity of the MRA or CTA technique at their individual institutions. The risk of the angiography must be weighed against the risk of aneurysm in the individual patient.19-23

Isolated incomplete or complete external dysfunction third nerve palsy with partial internal dysfunction (i.e., ‘relative pupil-sparing’ or ‘partial pupil-involvement’)

Isolated partial or relative internal dysfunction or ‘relative pupil-sparing’ third nerve palsy patients should probably undergo MRI and MRA (or CTA). Although

this presentation is often due to ischemia, a compressive lesion including aneurysm remains in the differential diagnosis.24-27 Cullom et al. reviewed ten ‘relative pupil-sparing’ third nerve palsies and none had an aneurysm.24 On the other hand, in another study of 24 isolated ‘relative pupil-sparing’ third nerve palsies, ten had a tumor or aneurysm.26 As above, cerebral angiography may still be needed if the MRI and MRA (or CTA) are negative because of the small but real possibility of a cerebral aneurysm. There is insufficient evidence in the literature to recommend reliance on the MRI with MRA (or CTA) alone in this setting. Chou et al. reported that among 25 patients with presumed microvascular third nerve palsy, seven (28%) had some degree of pupil involvement and three of these seven (43%) had greater than 2 mm of anisocoria.17

Isolated complete or incomplete external dysfunction, but complete internal dysfunction (‘the pupil-involved third nerve palsy’)

Complete internal dysfunction (i.e., ‘pupil involvement’) is a sign of a compressive lesion such as aneurysm. An initial MRI and MRA (or CTA) combination should be performed to rule out non-aneurysmsal etiologies for third nerve palsy but even if the study is negative, a cerebral angiogram should still be strongly considered for the ‘pupil involved’ third nerve palsy.28-32 The decision to proceed or not to proceed with catheter angiography in this setting should be determined on an individual basis. The clinician needs to weigh the risk of aneurysm and the risk of angiography in the decision making process.

Summary

In summary, diplopia with pupil involvement can be a sign of life-threatening disease of the cavernous sinus or orbital apex (e.g., pituitary apoplexy or Mucormycosis). The clinician should be aware that the patient with an isolated third nerve palsy may be harboring an intracranial aneurysm. The degree of completeness of external dysfunction and internal dysfunction (pupil involvement) should drive the decision making. If the risk of aneurysm is low (e.g., isolated presumed vasculopathic ‘pupil-spared’ complete third nerve palsy) or the risk of angiography is high (e.g., elderly patient with high risk of renal failure or risk of stroke), then an MRI and MRA (or CTA) combination is a reasonable screening study. In patients with a moderate or uncertain risk of aneurysm (e.g., partial external dysfunction or partial internal dysfunction third nerve palsy), MRI and MRA (or CTA) combination may not be sufficient to exclude aneurysm. The clinician should consult with their neuroradiologist regarding their respective institution’s MRA or CTA and which might be better screening study locally (i.e., institutional experience with one technique or another, quality of the technology, and availability of the study). Although cranial contrast MRI is superior to CT for the evaluation of the third nerve (e.g., enhancement of the third nerve, cavernous sinus) one individual institution’s CTA may be better than their MRA or vice versa. In some cases therefore a MRI with MRA followed by CTA might be necessary. In high-risk cases for aneurysm (i.e., ‘pupil involved third nerve palsy’), catheter angiography may still be required despite a negative MRI and MRI (or CTA) combination.

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