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Let’s examine case-based examples to emphasize the top five neuro-ophthalmic disorders that should not be overlooked.
Let’s examine case-based examples to emphasize the top five neuro-ophthalmic disorders that should not be overlooked.
• Acute painful loss of vision in elderly due to giant cell arteritis
• Acute painful ophthalmoplegia due to orbital apex disease
• Acute painful bitemporal hemianopsia due to pituitary apoplexy
• Acute painful anisocoria with a small pupil due to a Horner syndrome
• Acute painful anisocoria with a large pupil due to a pupil involved third nerve palsy from aneurysm
Clinicians should be aware of the key and distinctive clinical and radiographic findings for each of these potentially vision- or life-threatening conditions.
A 75-year-old male presents with acute vision loss in the right eye to the 20/200 level associated with new headaches. This presentation is classic for giant cell arteritis (GCA). The diagnosis of GCA should be considered in any elderly patient with any acute neuro-ophthalmic complaint with or without pain.
The most common presenting symptoms of GCA, however, are intermittent or constant visual loss, new onset headaches, jaw claudication, and scalp tenderness.1-4
Hayreh et al reported 106 of 363 patients with biopsy-proven GCA. The odds of a positive biopsy were 9.0 times greater with jaw claudication (P < 0.0001), 3.4 times greater with neck pain (P=0.0085), 2.0 times greater with an erythrocyte sedimentation rate (ESR) of 47 to 107 mm/hour (P=0.0454), 3.2 times greater with C-reactive protein above 2.45 mg/dl (P=0.0208), and 2.0 times greater for age 75 years or more (P=0.0105).5
The treatment of choice for GCA is immediate high-dose systemic steroids; however the route is still controversial.3,6-8
Some authors have suggested high-dose IV steroids (e.g., methylprednisolone 1000 mg/day) for patients with visual loss or neurologic symptoms.3,6,9 In a retrospective study by Chan et al, the visual acuity of patients treated with high-dose IV steroids (1000 mg for three days) followed by oral steroids was significantly improved compared to those on oral steroids alone.6,9 No head-to-head IV vs. by mouth trial of steroids for GCA has performed, however.
A temporal artery biopsy (TAB) remains the gold standard for the diagnosis of GCA.3,6 Although a floridly positive or completely negative TAB can be relatively straightforward, it is important to always read the entire body of the ocular pathology report.
The finding of “no active lymphocytic infiltrate or no giant cells” can still be due to GCA because “healed or treated” GCA can produce findings. Focal disruption of the internal elastic lamina, areas of fibrosis, irregular intimal thickening, and lymphocytes in the adventitia may suggest healed arteritis.10 Immunohistochemistry stains for CD 68 positive macrophages might helpful in such cases to help establish the diagnosis of “healed or treated” GCA.
A 22-year-old female presents at 4:45 pm on a Friday with a severe headache, 20/20 visual acuity OU but blurred vision, and a normal fundus exam. Visual field shows a bitemporal hemianopia.
This is another uncommon but classic neuro-ophthalmic presentation of an emergent condition, pituitary apoplexy. Although typically the acute onset of severe headaches and painful vision loss (bitemporal hemianopsia) is common in apoplexy, some patients have less severe or absent headache, and the visual loss may be unilateral or bilateral and may or may not be the classic bitemporal hemianopic visual field loss.
The incidence of pituitary adenoma is approximately seven per 100,000 per year.11 Typically, the slow growth of benign pituitary adenomas produces painless and progressive neuro-ophthalmic symptoms.
In contrast, pituitary apoplexy often produces acute and painful visual loss.
Acute hemorrhage or infarct of the pre-existing pituitary adenoma leads to compression of the surrounding anatomical structures (e.g., cavernous sinus or optic chiasm) and thus can produce the clinical findings of acute, severe headache, vision loss, ophthalmoplegia, altered consciousness, and hypopituitarism.3
In one study of 62 patients with pituitary apoplexy by Semple et al, the average patient age was 51 years. The majority of patients (81 percent) had no previous history of pituitary tumor. The most common presenting symptom was headache (87 percent), followed by decreased vision (56 percent), visual field defects (34 percent), and cranial nerve palsies (45 percent).12
The compression or infarction of the normal pituitary gland may prevent the release of hormones leading to hypopituitarism. The majority of patients (73 percent) exhibit a deficiency of at least one hormone produced by the anterior.12 Panhypopituitarism, a deficiency of all anterior pituitary hormones, is a life-threatening endocrine emergency that may require urgent hormonal supplementation.
Emergent imaging with a non-contrast CT head and neurosurgical consultation is indicated in patients with acute compressive symptoms or diminished mental status in pituitary apoplexy.3 The hyperdense signal from hemorrhage in acute apoplexy may be difficult to differentiate from other hyperdense lesions in the pituitary region such as a meningioma, Rathke cleft cysts, craniopharyngioma, and aneurysms. Magnetic resonance (MR) scan with and without contrast is useful in differentiating these lesions.12
Neuro-surgical intervention may be necessary in patients with acute neurological symptoms, including neuro-ophthalmic symptoms. These patients require long-term follow-up for both visual and endocrinologic sequelae after pituitary apoplexy.3
A 45-year-old male with uncontrolled diabetes mellitus presents to the emergency room with acute painful ophthalmoplegia and diabetic ketoacidosis (DKA). Mucormycosis, most commonly cerebro-rhino-orbital mucormycosis, is a rare but aggressive fungal infection that can affect immunocompromised or metabolically compromised patients but especially patients in DKA.3
Diabetes mellitus is a common risk factor; however, 20 percent have no identifiable cause.13 Other common risk factors include immunosuppression, metabolic ketoacidosis, underlying neoplasm, acute renal failure, severe burns or trauma, and steroid therapy.14
Rapid recognition of disease and treatment initiation improves the survival rate.14 Early symptoms include sinus tenderness, headaches, and blood-tinged or purulent rhinorrhea.3 Rapid angioinvasion and tissue infarction may produce a black necrotic eschar over the infected area, but this is a late and negative prognostic finding. Painful ophthalmoplegia, chemosis, diminished acuity, and proptosis can be present with orbital invasion.3,15
Rhinocerebral mucormycosis has a high mortality rate, and thus it is imperative to rapidly recognize and treat the infection.
Initial imaging with CT may be preferred over MRI because it is faster and provides better sinus, orbit, and bone detail.3
Treatment involves correcting underlying systemic findings, such as DKA along with early aggressive surgical debridement and antifungal therapy with amphotericin B or posaconazole.3,16 In a study by Vehreschild et al, surgery and concomitant antifungal treatment with amphotericin B had the highest survival rate (70 percent) among 929 mucormycosis cases.16
A 65-year-old diabetic male presents with acute onset ophthalmoplegia and anisocoria. The pattern of ophthalmoplegia in a third nerve palsy involves the extraocular muscles mediating adduction, supraduction, and infraduction as well as the levator muscle, ciliary muscle, and iris sphincter.3,17
The third nerve palsy can be partial or complete based on the extent of the lesion and the pupil may or may not be involved.17 In a third nerve palsy, the anisocoria is greater in the light and is characterized by a dilated and poorly reactive or non-reactive pupil on the ipsilateral side.
This anisocoria is key in differentiating between ischemic and compressive causes of complete third nerve palsy. The parasympathetic fibers travel along the superficial surface of the oculomotor nerve to innervate the ciliary muscle, which makes them more susceptible to a compressive injury vs. the internally located motor fibers.17,18
The most worrisome compressive lesion causing a third nerve palsy is an aneurysm of the posterior communicating artery (PCOM).3,18 A neurologically isolated, painless, complete third nerve palsy without pupil involvement in a vasculopathic patient is generally at low risk for a compressive lesion and is more likely to be ischemic.3,18 However, a small percentage of PCOM aneurysms present with normal pupils initially, especially in partial third nerve palsies, and therefore neuroimaging and further work up may still be necessary.18
In an acute setting, a CT with CTA of the brain is the recommended first line imaging.3,18,19 A contrast CTA should be able to detect an aneurysm as small as 3 mm.20,21 If the CTA is negative, then the next line of testing is an MRI of brain and orbits with and without contrast and MRA.3,18
Despite the high combined sensitivities of CTA with MRI and MRA, standard catheter angiogram remains the gold standard depending on the index of suspicion for aneurysm.3
The prognosis of the third nerve palsy depends on the etiology. In cases of aneurysmal compression, improvement is generally seen following surgical or endovascular treatment. Third nerve palsies secondary to ischemia typically improve over four to 12 weeks.
A 35-year-old male presents with new onset headache and anisocoria after playing basketball. A right sided 2 mm ptosis, upside-down ptosis, and ipsilateral miosis was also present. The anisocoria was greater in the dark with a dilation lag of the pupil OD. The rest of the eye exam was normal.
Acute painful ptosis and miosis should be considered as an ipsilateral internal carotid dissection from damage to the oculosympathetic pathway producing a Horner syndrome (HS). Other causes for the HS include malignancy, stroke, and aneurysm.
Damage along any point of the oculosympathetic pathway can produce a HS. The first order neuron begins in the hypothalamus and descends posterolaterally in the brainstem to synapse in the ciliospinal center of budge at the level of C8-T2. This second order neuron then exits the spinal cord and travels over lung apex (Pancoast lung tumor) to synapse within the superior cervical ganglion at the bifurcation of the common carotid artery. The third order neuron ascends through the cavernous sinus via the adventitia of the internal carotid artery before traveling a short course on the abducens nerve and joining the first division of the trigeminal nerve where it travels through the superior orbital fissure to innervate the Mullers muscle and iris dilator.3
Pharmacologic testing is often helpful in confirming the diagnosis, but neuroimaging is recommended for all patients with a suspected HS clinically.
Pain (e.g., headache, eye pain, face pain, or neck pain) is the most common presenting symptom of a Horner syndrome from a carotid artery dissection but may be absent or variable in severity. The incidence is approximately 2.6 per 100,000 in the United States, and it can occur spontaneously or secondary to trauma.3,22 Most patients experience a positive clinical outcome with resolution or recanalization in 80 percent.23
Apraclonidine is a direct acting, non-selective alpha-agonist (predominantly alpha-2 activity) commonly used in diagnosing the HS. As a result of denervation hypersensitivity after a HS, a positive apraclonidine test will reverse the anisocoria due to dilation from up-regulation of the post-synaptic alpha-1 effect in the eye with the HS and the normal alpha-2 effect in the fellow eye (which produces slight pupillary constriction). This test has a high sensitivity and specificity.3,22,24
In the acute ER setting, a CT-CTA of the head and neck to thoracic level (T2) is the preferred initial study, and we do not generally recommend waiting for confirmation with topical apraclonidine.
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2. Smetana GW, Shmerling RH. Does this patient have temporal arteritis? JAMA. 2002 Jan 2;287(1):92-101.
3. Smith SV, Amram AL, Rodarte EM, Lee AG. Neuro-Ophthalmology Cases for the Neurologist. Neurol Clin. 2016 Aug;34(3):611-29.
4. Paraskevas KI, Boumpas DT, Vrentzos GE, Mikhailidis DP. Oral and ocular/orbital manifestations of temporal arteritis: a disease with deceptive clinical symptoms and devastating consequences. Clin Rheumatol. 2007 Jul;26(7):1044-1048.
5. Hayreh SS, Podhajsky PA, Raman R, Zimmerman B. Giant cell arteritis: validity and reliability of various diagnostic criteria. Am J Ophthalmol. 1997 Mar;123(3):285-296.
6. Fraser JA, Weyand CM, Newman NJ, Biousse V. The treatment of giant cell arteritis. Rev Neurol Dis. 2008 Summer;5(3):140-152.
7. Mazlumzadeh M, Hunder GG, Easley KA, Calamia KT, Matteson EL, Griffing WL, Younge BR, Weyand CM, Goronzy JJ. Treatment of giant cell arteritis using induction therapy with high-dose glucocorticoids: a double-blind, placebo-controlled, randomized prospective clinical trial. Arthritis Rheum. 2006 Oct;54(10):3310-3318.
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9. Chan CC, Paine M, O'Day J. Steroid management in giant cell arteritis. Br J Ophthalmol. 2001 Sep;85(9):1061-4.
10. Lee YC, Padera RF, Noss EH, Fossel AH, Bienfang D, Liang MH, Docken WP. Clinical course and management of a consecutive series of patients with “healed temporal arteritis.” J Rheumatol. 2012 Feb;39(2):295-302.
11. McDowell BD, Wallace RB, Carnahan RM, Chrischilles EA, Lynch CF, Schlechte JA. Demographic differences in incidence for pituitary adenoma. Pituitary. 2011 Mar;14(1):23-30.
12. Semple PL, Webb MK, de Villiers JC, Laws ER, Jr. Pituitary apoplexy. Neurosurgery. 2005;56(1):65-72; discussion 72-63.
13. Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, Sein M, Sein T, Chiou CC, Chu JH, Kontoyiannis DP, Walsh TJ. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005 Sep 1;41(5):634-53.
14. Jiang N, Zhao G, Yang S, Lin J, Hu L, Che C, Wang Q, Xu Q. A retrospective analysis of eleven cases of invasive rhino-orbito-cerebral mucormycosis presented with orbital apex syndrome initially. BMC Ophthalmol. 2016 Jan 12;16:10.
15. Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clinical microbiology reviews. 2000 Apr;13(2):236-301.
16. Vehreschild JJ, Birtel A, Vehreschild MJ, Liss B, Farowski F, Kochanek M, Sieniawski M, Steinbach A, Wahlers K, FÃ¤tkenheuer G, Cornely OA. Mucormycosis treated with posaconazole: review of 96 case reports. Crit Rev Microbiol. 2013 Aug;39(3):310-24.
17. Bruce BB, Biousse V, Newman NJ. Third nerve palsies. Semin Neurol. 2007 Jul;27(3):257-68.
18. Lee AG, Hayman LA, Brazis PW. The evaluation of isolated third nerve palsy revisited: an update on the evolving role of magnetic resonance, computed tomography, and catheter angiography. Surv Ophthalmol. 2002 Mar-Apr;47(2):137-57.
19. Jeong HW, Seo JH, Kim ST, Jung CK, Suh SI. Clinical practice guideline for the management of intracranial aneurysms. Neurointervention. 2014 Sep;9(2):63-71.
20. Vaphiades MS, Cure J, Kline L. Management of intracranial aneurysm causing a third cranial nerve palsy: MRA, CTA or DSA? Semin Ophthalmol. 2008 May-Jun;23(3):143-50.
21. Vaphiades MS, Roberson GH. Imaging of Oculomotor (Third) Cranial Nerve Palsy. Neurol Clin. 2017 Feb;35(1):101-113
22. Moodley AA, Spooner RB. Apraclonidine in the diagnosis of Horner's syndrome. S Afr Med J. 2007 Jul;97(7):506-7.
23. Pelkonen O, Tikkakoski T, Leinonen S, Pyhtinen J, Lepojarvi M, Sotaniemi K. Extracranial internal carotid and vertebral artery dissections: angiographic spectrum, course and prognosis. Neuroradiology. 2003 Feb;45(2):71-7.
24. Abrams DA, Robin AL, Pollack IP, deFaller JM, DeSantis L. The safety and efficacy of topical 1% ALO 2145 (p-aminoclonidine hydrochloride) in normal volunteers. Arch Ophthalmol. 1987 Sep;105(9):1205-7.