Ophthalmologist presents guidelines for third-nerve palsies

Columbus, OH-When a patient presents with an acute third-nerve palsy, what is the best course of action, and what is the most cost-effective way to reach a diagnosis? Susan Benes, MD, described various case scenarios to guide ophthalmologists with what often can be difficult cases.

“We judge third-nerve palsies by the company they keep,” said Dr. Benes, a neuro-ophthalmologist at The Eye Center of Columbus and The Ohio State University Havener Eye Institute. “Pain is a symptom, and pain does not differentiate between good and bad third-nerve palsies. Pain is common with microvascular third-nerve palsies and acutely expanding aneurysms, but it is not always present with tumors and slowly expanding aneurysms.”

She explained that a third-nerve palsy with any second neurologic or orbital sign is not truly isolated and requires imaging. For example, a third-nerve palsy and proptosis, enophthalmos, any cranial neuropathy, or orbital or cavernous sinus findings require that the brain and orbits be checked, she emphasized, adding that the same is true for third-nerve palsies with new vision loss or other neurologic abnormalities.

An isolated third-nerve palsy can have a few variations that include: (a) a divisional third-nerve palsy, (b) a third-nerve palsy with aberrant regeneration, (c) a pupil-involved, third-nerve palsy, and (d) a pupil-sparing, third-nerve palsy. For example, superior division palsies with weakness of only the levator muscle and superior rectus can occur anywhere from the orbit through the cavernous sinus to the midbrain and require imaging to localize the lesion. Inferior division palsies include dysfunction of any of these branches: medial rectus muscle, inferior rectus, inferior oblique, or the pupil. They occur in orbital, sinus, and cavernous sinus lesions and require imaging.

There is a caveat to this, however.

“Rarely, if ever, is an ischemic ‘innocent’ third-nerve palsy divisional; it almost always involves both divisions, sparing only the pupil,” Dr. Benes pointed out.

Third-nerve palsies with aberrant regeneration (superior division lid elevation cross-talking with either inferior division adduction or depression) are usually chronic and due to compression, but they also may follow months after a clear history of serious head injury. This cavernous sinus nerve injury requires imaging.

Imaging is required in isolated third-nerve palsies with an enlarged slowly reacting pupil or any third-nerve palsy and confusing pupil size or reactivity, as with an ipsilateral Horner’s syndrome, a diabetic patient with damaged ciliary nerves from panretinal laser photocoagulation, a sluggish pupil, or a sphincter pathology from trauma to the eye or zoster infection.

In the absence of any pupillary abnormality, equal in size and equally briskly reactive, a patient with a third-nerve palsy that is stable may be observed most of the time. These patients are largely vasculopathic, and the vasonervorum to the third nerve is the pathophysiology to the sectoral or peripheral third-nerve injury that allows pupil sparing. This last group of pupil-sparing, third-nerve palsies accounts for about 70% of cases of isolated third-nerve palsies.

“Traditional wisdom states that [patients with diabetes, hypertension, or hyperlipidemia and] pupil-sparing, third-nerve palsies can be observed,” Dr. Benes commented. “This is especially true in older adults over the age of 50. Observing has been defined as repeated check-ups at 1 day, 1 week, 4 weeks, and 6 weeks. [Imaging] is considered if the third-nerve palsy is no longer isolated or if there has been no improvement after 4 to 6 weeks.

“Observation, however, is controversial, because from 2% (my experience) to 11% (University of Pennsylvania experience) of important findings in people with isolated pupil-sparing, third-nerve dysfunction [imaged] later may have underlying multiple sclerosis, lacunar stroke, or rarely masses not discovered on day 1,” she said. “This is probably more likely in the younger adults under 45.”

Isolated third-nerve palsies with pupil involvement (larger and/or poorer reaction) require imaging, but what imaging should be ordered?

Dr. Benes conducted a poll of neuro-radiologists in Ohio and found that magnetic resonance imaging (MRI) with contrast was their first choice as the first imaging test in adults because most third-nerve palsies referred to them were neither isolated nor due to aneurysms. Emergency room physicians who were polled had a different opinion based on stroke protocol; they chose computed tomography (CT) of the brain without contrast to rule out acute hemorrhagic stroke to define whether the option of using thrombolytic drugs in progressive neurologic decline was reasonable and to prove there was no subdural blood suggesting a ruptured aneurysm. However, they were more likely to see unstable patients with altered mental status. The surveyed pediatricians also favored CT because it is usually available in the emergency room and can be performed quickly and without sedation.

The costs of the various imaging technologies differ considerably. CT performed in a hospital is expensive, ranging from $1,000 to $2,500. In contrast, outpatient facilities, with lower overhead, may charge only a third of the hospital fees, Dr. Benes explained.

MRI studies are also cheaper in outpatient facilities and can be scheduled more easily and quickly than in hospitals with competing inpatient demand.

For unstable (comatose, altered mentation, hypotensive, hypertensive, febrile, etc.) patients brought to the hospital emergency department, CT was the doctors’ first choice. For stable walk-in adult patients, MRI with contrast was recommended first by neuroradiologists.

Third-nerve palsies due to aneurysms are the greatest fear of physicians, according to Dr. Benes. A full 98% of these cases involve the pupil. Imaging choices to demonstrate an aneurysm are magnetic resonance angiography (MRA), CT angiography (CTA), and catheter angiography. However, the study that is ordered depends on the proximity of the patient to different facilities and facility preferences for finding aneurysms.

“CTAs are very expensive, have a high dose of radiation, and interpretation can be difficult because many aneurysms develop at the skull base where there may be bony artifacts that confuse radiologists,” Dr. Benes explained. “However, in ideal circumstances, the images are exquisite. CTAs are far less frequently used in pediatric patients both because of the radiation dose and the need for a large fast bolus of contrast [material] through tiny veins that are too slow for optimal image acquisition and quality.

“MRA is the most common choice in stable adults because the [images] are easy to read for most radiologists and the test does not require contrast,” she explained. “However, MRA shows only flow within vessels, and, if it were the only [imaging performed] in a patient, lesions not affecting flow would be missed, including tumors, infiltrating processes, and parenchymal signal changes from multiple sclerosis or stroke.”

Cerebral catheterization procedures are the most expensive as well as the riskiest of the three imaging options, but they provide exquisite detail. These are almost invariably performed in a hospital setting and have the advantage of providing intravascular access to definitive lesions and also simultaneous intervention in many cases.

Ophthalmologists ordering imaging on stable outpatients with third-nerve palsies often use outpatient MRI facilities, costing the medical system about $2,200, whereas patients referred to an emergency room and then admitted to a hospital, undergoing first a CT study, then either an MRA or CTA, then consultations, cost the system more than $16,000. Both screening methods require referral for definitive catheter angiography should an aneurysm be discovered, according to Dr. Benes.

When examining patients with third-nerve palsies, she provided the following guidelines.

“[Perform imaging in] all children with third-nerve palsies, all divisional third-nerve palsies, all third-nerve palsies with aberrant regeneration, and all pupil-involved, third-nerve palsies,” she said. “You can observe an adult whose third-nerve palsy is accompanied by ipsilateral numbness, pain, burning, or itching, in first or second division of the fifth nerve, suggesting a zoster etiology; and treat with antivirals, steroids, and antineuralgia therapy; and watch closely for secondary neurologic deficits that require imaging. Textbooks say we can observe pupil-sparing, third-nerve palsies, but some claim that as many as 11% of these patients have a serious pathology that would be missed with simple observation. We must inform the patient and the family that there is a risk for conservative follow-up, and they must agree to repeat examinations over the first 6 weeks or until improvement is noted. They must understand they need to report to the emergency room if there would be any worsening for assessment and [imaging].”

She continued, “So, can we continue to observe and accept a 2% (or more) risk rate of delayed discovery of another pathology if [imaging is not performed] on day 1? Will the patients be reliable and return for repeated assessments? This subject is very thought provoking,” she concluded.

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