Neuro-Ophthalmic Emergencies: Three Diagnoses Not to Be Missed in Primary Care
Neuro-ophthalmic symptoms and signs are the key to diagnosing certain systemic conditions that are considered true emergencies, such as giant cell arteritis, increased intracranial pressure with papilledema, and acute third cranial nerve palsy secondary to intracranial aneurysm. These symptoms and signs may be first encountered by the primary care or emergency department physician; it is critical that they be recognized immediately upon presentation to facilitate expeditious management, which in some cases will save patients' lives and vision.
- Suspect giant cell arteritis in patients older than 50 years with amaurosis fugax or ischemic visual loss, and elevated ESR and CRP levels.
- Papilledema may present with chronic headache and blurred vision.
- In patients with papilledema and suspected increased intracranial pressure, immediate brain neuroimaging is mandatory.
- In complete third cranial nerve palsy, the affected eye is usually deviated downward and outward.
- When encountering a patient with acute third nerve palsy, evaluate for a serious neurologic or medical condition, such as intracranial aneurysm or giant cell arteritis.
Neuro-ophthalmology is a subspecialty that focuses on the eye and its relationship to the central nervous system. Although the eye is often regarded as an independently functioning organ that is separate from the rest of the body, on occasion, ocular-related signs and symptoms may be the harbinger of serious systemic or neurologic disease. Because some neuro-ophthalmic findings are considered true medical emergencies, it is critical that primary care and emergency department physicians recognize them immediately to prevent blindness and, in some cases, to save the patient's life. The following clinical vignettes demonstrate the typical presentation of 3 systemic disorders that may present with classic neuro-ophthalmic symptoms and signs and require immediate attention.
Case 1: Giant Cell Arteritis
An 82-year-old woman with well-controlled hypertension complains of malaise for 2 months, decreased appetite, and a 10-lb weight loss. She also reports a headache for the past 3 weeks, with the pain localized to the right temple (Figure 1) and tenderness when palpated. In addition, she describes a "veil"that intermittently obstructs the top half of her vision in the right eye. These episodes of transient visual loss are recurrent, lasting 15 to 20 minutes, and then resolve spontaneously.
Suspecting giant cell arteritis (GCA), the physician orders laboratory studies, which show: erythrocyte sedimentation rate (ESR), 90 mm/hour; C-reactive protein (CRP) level, 12.3 mg/L; anemia (hemoglobin, 9.2 g/dL; hematocrit, 29.6); platelet count, 485 X 109/L; white blood cell count, normal. Two days later, while awaiting temporal artery biopsy, the patient complains of acute, painless visual loss in the right eye.
The consulting ophthalmologist notes severely reduced visual acuity at the level of hand motion in that eye and a large relative afferent pupillary defect (Marcus-Gunn pupil). The dilated funduscopic examination of the optic nerve and retina is shown in Figure 2. The patient is diagnosed with a central retinal artery occlusion associated with presumed GCA. She is hospitalized and treated with intravenous (IV) corticosteroids. Aright temporal artery biopsy reveals active vasculitis, with the presence of giant cells, thickening of the media wall, and narrowing of the vessel lumen. Although her headaches resolve, and her appetite and energy return to normal with the corticosteroid therapy, the diminished vision in her right eye does not improve. Vision in her left eye remains stable. She is discharged with a prescribed regimen of oral corticosteroids, which are tapered over the next 12 months, as her ESR and CRP levels normalize.
GCA, also known as temporal arteritis, is a vasculitis that mainly affects medium-sized vessels and occasionally also involves larger-caliber vessels. The condition is seen in patients older than 50 years. Incidence increases with advancing age, with a rate of 2.1 per 100,000 person-years in those 50 to 59 years old and 46.0 in those aged 70 to 79 years.1 Although symptoms may be nonspecific and onset may be insidious, GCAcan cause tremendous ocular and systemic morbidity and even mortality.2 Once vision loss develops from ischemic vasculitis, if the first eye is left untreated, the other eye usually becomes involved within 1 to 2 weeks2 (Table 1).
The diagnosis of GCA can be tentatively made based on elevated ESR and CRP levels. The normal value for ESR can be approximated in men by dividing the age by 2, and in women by adding 10 to the age then dividing by 2.3 Another valuable test is the complete blood cell count; patients with temporal arteritis usually have anemia of chronic disease (normocytic, normochromic) as well as thrombocytosis. The gold standard for diagnosis is temporal artery biopsy.2
Once GCA is suspected, treatment with either oral or IV corticosteroids should be instituted immediately, even before biopsy.4 Timely systemic intervention is crucial to prevent ophthalmic complications, such as permanent visual loss from ischemic optic neuropathy or retinal arterial occlusion, as well as systemic complications that can result in cerebral, cardiac, or renal vasculitis.5-7
In addition to the systemic symptoms of GCA, this patient had episodes of transient visual loss, or "amaurosis fugax." This occurs secondary to the intermittent ischemia of the retinal circulation caused by the vasculitis. Although initially transient, the ischemia can progress to cause permanent, severe visual loss from central retinal artery occlusion.2 Any patient older than 50 years with amaurosis fugax or ischemic visual loss should be evaluated for GCA and also undergo cardiovascular studies (ie, carotid ultrasound, echocardiography) to rule out a source of thromboemboli.2
Case 2: Increased Intracranial Pressure
A 26-year-old woman comes to the emergency department complaining of daily headaches for the past 5 months. She has a history of migraines, although her last episode was 5 years ago. Over the past month, she has noted blurry vision in both eyes, which did not improve with new glasses. She has no other systemic or neurologic symptoms. General examination and blood pressure findings are unremarkable. Neurologic examination is nonfocal. Distance visual acuity is 20/30 in each eye. Aconscientious medical student uses a direct ophthalmoscope to view her optic nerves, and finds optic-disc swelling, blurring of the disc margins, and hemorrhages (Figure 3). The patient is sent for an immediate magnetic resonance imaging (MRI) scan, which reveals a large frontal mass consistent with meningioma (Figure 4). The mass had caused increased intracranial pressure (ICP) and papilledema from obstructive hydrocephalus.
Headache and blurry vision are 2 nonspecific symptoms that often go hand in hand. The symptoms improve in the majority of patients with headache medications and/or use of glasses for blurry vision. However, the examining physician should be concerned when the headache is acute, severe, or refractory to therapy and is accompanied by blurred vision. Blood pressure should first be measured to rule out malignant hypertension, which can cause severe headaches and optic-disc swelling. The next issue to address is possible increased ICP from an intracranial mass lesion, subarachnoid hemorrhage, hydrocephalus, chronic meningitis, or pseudotumor cerebri8 (Table 2).
The term "papilledema" is reserved for optic-disc swelling secondary to increased ICP. Papilledema may be bilateral, unilateral, or asymmetric. In the early stages, central visual acuity is preserved, while peripheral visual field defects, such as an increased blind spot, may occur. When papilledema becomes chronic, the risk increases for permanent optic nerve damage and significant visual loss.9
If optic-nerve head swelling is noted, and increased ICP is suspected, immediate brain neuroimaging is mandatory. Computed tomography (CT) may be performed if MRI is not readily available. If no mass lesion is visible on neuroimaging, a lumbar puncture should be performed to measure cerebrospinal fluid (CSF) opening pressure (normal, <200 mm H2O) and to examine CSF composition for signs of meningitis and subarachnoid hemorrhage.10 Although the management of increased ICP should be directed at the underlying etiology, acetazolamide may be given as a temporizing measure to lower CSF production, thereby reducing ICP and papilledema.
Case 3: Brain Aneurysm
A70-year-old man whose medical history is significant only for arthritis awakens one morning with a severe headache and difficulty opening his left eyelid. He looks in the mirror, lifts the eyelid with his finger, and notes the eye has drifted outward (Figure 5). He also has double vision. He immediately presents to the emergency department, and the resident physician observes a dilated pupil (Figure 6). The patient is diagnosed with complete left third nerve palsy with pupillary involvement. He immediately undergoes a brain CT scan, which shows subarachnoid hemorrhage. Subsequent imaging of the brain with magnetic resonance angiography (MRA) reveals an aneurysm of the left posterior communicating artery. The patient is successfully treated with endovascular coiling of the aneurysm. His headache remits, and the ptosis and motility deficit resolve within several months.
The third cranial nerve, also known as the oculomotor nerve, innervates 5 extraocular muscles: the superior rectus, medial rectus, inferior rectus, inferior oblique, and levator palpebrae. The nerve's parasympathetic fibers are responsible for pupillary miosis and accommodation. The nucleus of the nerve is located within the midbrain; its nerve fascicle courses ventrally in the brainstem and exits into the subarachnoid space between the posterior cerebral and superior cerebellar arteries in the vicinity of the posterior communicating artery. The nerve then travels through the cavernous sinus and superior orbital fissure on its way toward the orbit to innervate individual extraocular muscles.11,12
In complete third cranial nerve palsy, the primary symptoms are ptosis and diplopia from ocular misalignment. The affected eye is commonly deviated downward and outward. The patient may not complain of diplopia if the ptosis is severe enough to cover the eye. If parasympathetic fibers are involved, pupil dilatation may cause symptomatic glare in bright light, and paralysis of accommodation may cause blurred vision for near objects.
The status of the pupil is essential in determining appropriate management for an acute third nerve palsy (Figure 7). Because the pupillary fibers travel in the periphery of the nerve, they are most likely to be involved when the cause is a compressive lesion, such as an intracranial aneurysm or mass. Pupil involvement in the context of third nerve palsy therefore necessitates immediate neuroimaging, with MRI/MRA and possible cerebral angiography, to rule out a posterior communicating artery aneurysm.12 This condition is a neurologic and medical emergency, because sudden rupture of the aneurysm with massive subarachnoid hemorrhage may lead to devastating neurologic deficits and even death.
Pupillary involvement in third nerve palsy may also be caused by impending cerebral herniation from an intracranial mass or hydrocephalus that compresses the nerve in the subarachnoid space. When the pupil is fixed and dilated before ophthalmoplegia or ptosis develops in this context, it is referred to as a "Hutchinson's pupil."13
When the pupil is spared in an otherwise complete third nerve palsy, the problem is likely ischemia in the central core of the nerve, which in turn results from insufficiency of the small vessels that supply the nerve trunk.11 Such ischemia tends to be associated with preexisting microvascular disease, such as diabetes, hypertension, or dyslipidemia, and/or advanced age.14 GCAas an etiologic factor in ischemic palsy should also be considered in the elderly.15
The key finding in patients with microvascular palsy is relative sparing of the pupillary sphincter, with complete or near complete palsy of all the extraocular muscles innervated by the third cranial nerve, including the levator palpebrae.16 Patients may also have severe pain in the eye or orbit. Although the pathogenesis is not well understood, eye pain in itself does not suggest aneurysm as the cause, but it should prompt laboratory studies for GCA. Fortunately, nearly all patients with an ischemic microvascular third nerve palsy usually experience spontaneous remission of the palsy within 6 to 12 weeks. No direct medical treatment can alter the course of the condition, thus management is close observation to ensure that the pupil remains spared. Should the pupil become dilated at any time during follow-up or the palsy be incomplete at onset, immediate neuroimaging is warranted.17
When encountering a patient with acute third nerve palsy, physicians must be alert to elements in the history and physical examination that point to a serious neurologic or medical condition, such as intracranial aneurysm or GCA, respectively.14 Failure to undertake an adequate workup for aneurysm in a patient with third cranial nerve palsy can have devastating consequences. However, performing cerebral angiography to definitively rule out aneurysm in patients with ischemic third cranial nerve palsy carries risks that include stroke.18,19
The neuro-ophthalmic manifestations of potentially serious systemic or neurologic disease may present either insidiously or acutely. GCA typically affects older patients who report headache, scalp tenderness, weight loss, malaise, and intermittent visual disturbances. Papilledema may present with chronic headache and blurred vision. Oculomotor nerve palsy is indicated by complete ptosis and an eye that is deviated down and out. Understanding the presenting symptoms and signs of these disorders should help primary care physicians appropriately diagnose and manage patients in a timely fashion and prevent adverse outcomes.
1. All the following are signs and symptoms of GCA, except:
- Reduced ESR
- Increased CRP
2. Which of these statements about papilledema is NOT true?
- It can be asymmetric
- Central visual acuity is usually affected in the early stages
- Patients may report tinnitus
- It may be a sign of meningitis
3. All the following conditions are associated with complete oculomotor nerve palsy, except:
- Eye deviation inward
- Eye deviation outward
4. Which of the following diagnostic techniques is NOT generally recommended?
- Carotid ultrasound and cardiac echography for amaurosis fugax
- Temporal artery biopsy for GCA
- Blood pressure measurement for headache and blurry vision
- Brain neuroimaging for pupil-sparing oculomotor nerve palsy
5. Which of these treatments is NOT appropriate?
- IV corticosteroids for GCA
- Neuroimaging within 3-5 days for papilledema
- Acetazolamide for papilledema
- Observation for ischemic microvascular third nerve palsy
(Answers at end of reference list)
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Answers: 1. A; 2. B; 3. C; 4. D; 5. B