- Email: [email protected]
But it's not all there
s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 4 9 2 e4 9 9
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/survophthal
Clinical challenges
But it’s not all there Jared D. Peterson, MDa, Jurij R. Bilyk, MDb,*, Robert C. Sergott, MDc a
Wills Eye Institute, Philadelphia, Pennsylvania, USA Skull Base Division, Neuro-Ophthalmology Service, Wills Eye Institute, Philadelphia, Pennsylvania, USA c Director, Neuro-Ophthalmology Service, Wills Eye Institute, Philadelphia, Pennsylvania, USA b
article info
(In keeping with the format of a clinical pathologic conference, the abstract and key words appear at the end of the article.)
Article history: Received 2 January 2012 Received in revised form 3 February 2012 Accepted 7 February 2012 Available online 10 July 2012 Peter Savino and Helen DaneshMeyer, Editors
1.
Case report
A 44-year-old white man presented to the Wills Eye Emergency Room with headache. The patient, who had no significant past medical history and no chronic history of headaches, first noticed the pain 5 days earlier while doing his normal exercise routine at the gym. While performing leg lifts, he had the onset of transient lightheadedness in addition to a headache that localized behind both eyes. The headache resolved by the following morning, only to return the next day, with the pain worse on the left side. Later that day he looked in a mirror and saw that his pupils were of different size. The patient was sure that this was a new finding and that the right side was abnormal. What are your thoughts and concerns in a patient who presents with an acute onset headache? Does the presence of anisocoria narrow the diagnosis?
2.
Comments
2.1.
Comments by Robert C. Sergott, MD
Depending on the setting, headaches can either be a very helpful piece of the clinical picture or add very little. In a patient with a history of headaches, it is easy to give very little credence to this complaint or to ignore it completely, justifying it to be their “baseline”. For this reason, in patients with a history of headache, it is very important to ask specific questions regarding the nature of the headache to determine whether it is similar to their typical pain. Headaches that are markedly different from a patient’s typical pattern or that are new in onset, such as in this case, should be considered as significant. The presence of anisocoria in this case also helps to validate that something is most likely awry. Although the anisocoria could represent the sudden discovery of a longstanding condition, this is a potentially dangerous assumption, especially when paired with a headache of new onset. Conditions
* Corresponding author: Jurij R. Bilyk, MD, Wills Eye Institute, 840 Walnut Street, Suite 930, Philadelphia, PA 19107. E-mail address: [email protected] (J.R. Bilyk). 0039-6257/$ e see front matter ª 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.survophthal.2012.02.009
s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 4 9 2 e4 9 9
Fig. 1 e Clinical photograph showing 2 mm of anisocoria with the right pupil larger than the left.
that can account for both should top the differential diagnosis. In particular, the most dangerous causes of anisocoria with headache should be considered first, namely, oculomotor nerve palsy and Horner syndrome (HS). The initial exam should focus on trying to identify the abnormal pupil, which will help differentiate these two conditions.
3.
Case report (continued)
Visual acuity was 20/30 bilaterally. Two millimeters of anisocoria were present, with the right pupil larger than the left
Fig. 2 e Pupillary sizes in ambient and dim lighting. Note that the difference in anisocoria remains the same, consistent with physiologic anisocoria. In a patient with a sympathetic defect (Horner syndrome), the anisocoria should increase in the dark. The opposite would occur in a parasymapthetic defect (pupil-involving oculomotor nerve palsy, Adie pupil).
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(Fig. 1). The degree of anisocoria was evaluated in well-lit and dim conditions (Fig. 2). There was no ptosis, and upper eyelid excursions were normal. The lower eyelid positions were symmetric. Extraocular motility (EOM) was full, and the patient was orthophoric. Confrontation visual fields were full bilaterally. Anterior segment examination and direct ophthalmoscopic examination of the optic nerve heads were unremarkable. With the anisocoria as noted in light and dark conditions, full EOM, and the absence of ptosis, what other nonpharmacologic examination techniques can help identify which is the abnormal pupil? What is your differential diagnosis? Because the anisocoria appears physiologic, and no abnormality is noted in eyelid or EOM examination, is it reasonable to assume that the patient simply discovered his physiologic anisocoria and should we reassure him?
4.
Comments (Continued)
4.1.
Comments by Dr. Sergott
A normal efferent pupillary response is the result of a balance between sympathetic and parasympathetic innervation to the iris. When a patient presents with anisocoria, the first step is to determine which arm of the autonomic nervous system is affected. The most straightforward method of differentiation is to measure pupillary diameter in ambient and dim light. If the sympathetic pathway is abnormal, then dilation of the affected pupil in dark conditions will be impaired, and the anisocoria will be greater in the dark. The opposite is true if the parasympathetics are the culprit; parasympathetic innervation causes pupillary constriction, and deficiencies are most notable in ambient lighting. If the amount of anisocoria remains unchanged in normal and dim lighting, physiologic anisocoria is likely. The clinician, however, must also remember that pupillary testing in light and dark conditions may lead to ambiguous results for a variety of reasons. First, as a general rule, patients with darker irides are more difficult to assess. Second, the autonomic system injury may not be complete and cause a slow, but intact, pupillary response. In other words, an abnormal pupil may be sluggish, but eventually reactive. If the clinician allows enough time to elapse between changing the lighting conditions and checking the pupils, autonomic dysfunction may be misdiagnosed as physiologic anisocoria. When examining pupils, it is as important to document briskness of response for both constriction and dilation as size. There are several nonpharmacologic findings that help identify the abnormal pupil in this situation. To identify deficiencies in the parasympathetic response, poor pupillary reactivity is often seen in cases of acute oculomotor nerve palsy or tonic (Adie) pupils. Vermiform movements or sectoral reactivity suggest a subacute or chronic tonic pupil. Interruption of sympathetic innervation leads to mild upper eyelid ptosis secondary to paresis of Mu¨ller muscle. So-called “reverse ptosis” may occur because the sympathetics innervate not only the superior tarsal (Mu¨ller) muscle in the upper lid, but also the analogous inferior tarsal muscle in the lower
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lid. The inferior tarsal muscle retracts the lower lid, and its paresis in HS results in an elevation of the lower lid. Transient conjunctival hyperemia may occur as a result of the loss of sympathetic vasoconstriction. Finally, because sympathetic fibers are responsible for pupillary dilation, loss of sympathetic innervation leads to a lag in dilation compared to the unaffected side. Most neuro-ophthalmology texts include absence of sweating over the forehead of the affected side, but the majority of patients will not notice this, even when it is present.
5.
Case report (Continued)
The pupils reacted briskly to light, with no evidence of sectoral dilation or vermiform movements on the right; on the left, a subtle dilation lag was noted at the slit-lamp. How does this help with the diagnosis? Can Horner syndrome occur without ptosis? What is your next step?
6.
Comments (Continued)
6.1.
Comments by Dr. Sergott
Normal reactivity of the larger right pupil, in addition to a lack of ptosis and external ophthalmoplegia, effectively rules out a right third nerve dysfunction. Dilation lag of the smaller left pupil implicates this side as the abnormal one, making HS more likely. Even with this finding of subtle dilation lag, however, the clinical diagnosis is by no means definitive because of the absence of ptosis and other associated findings. Clinically, the ptosis in HS is not severe, with a disparity in the margin to reflex distance of only 1e3 mm, consistent with the function of Mu¨ller muscle. It is possible to have HS without ptosis; one population-based study of pediatric HS found that roughly 20% of patients did not present with ptosis.19 In many cases, clinical examination alone is sufficient to raise or rule out the possibility of HS, especially if reverse ptosis and nonphysiologic anisocoria are present. To help confirm the diagnosis in this case with equivocal findings, pharmacologic testing is the next step. What pharmacologic test do you use? The availability of cocaine in a comprehensive ophthalmologist’s office is limited at best. What are your thoughts on the use of apraclonidine in the diagnosis of HS in general and in this case in particular? Do you still use hydroxyamphetamine?
7.
Comments (Continued)
7.1.
Comments by Dr. Sergott
A variety of pharmacologic tests are available to confirm the diagnosis of HS and offer clues as to the etiology and duration, but many of these agents are difficult to obtain and maintain in a standard office setting.15 Four topical pharmacologic agents have been used for the diagnosis of HS: cocaine
(4e10%), hydroxyamphetamine, dilute phenylephrine (1%), and apraclonidine (0.5%). Of these, two are impractical: hydroxyamphetamine is very difficult to obtain and cannot be used on the same day as cocaine, prompting Trobe to comment that hydroxyamphetamine testing is “a waste of time”22,23; diluted phenylephrine must be mixed properly to give reasonably reliable results and requires an unspecified lag for the development of denervation supersensitivity before it works.22 The remaining two agents, cocaine and apraclonidine, still have a place in the diagnosis of HS.22 Under normal conditions, there is a continuous release of norepinephrine (NE) from presynaptic sympathetic nerve terminals. Cocaine works by blocking the reuptake of NE, leading to accumulation and pupillary dilation. In cases of HS, the oculosympathetic pathway is interrupted and less NE is released from the presynaptic terminals. When cocaine blocks the reuptake of NE, the affected side, with its decrease level of norepinephrine, fails to dilate (Fig. 3).17 Two drops of cocaine solution are placed in each eye, and the patient is reassessed 20 minutes to 1 hour later.23 The major advantage of cocaine testing is that it does not require denervation supersensitivity to work; a positive cocaine test should be seen even in acute cases of HS. Disadvantages of topical cocaine include difficulty in obtaining and maintaining the medication (Schedule II drug and short shelf life), corneal toxicity, and the possibility of positive urine drug screening for up to 48 hours following the test.10,15,22 In contrast to topical cocaine, apraclonidine (AC) 0.5% is easily obtained. AC is an alpha-2 agonist that also has a weak alpha-1 agonist effect. The drug is used mainly for its alpha-2 effect on the ciliary body to reduce aqueous production in the treatment of glaucoma or to prevent intraocular pressure spikes following anterior segment laser procedures. Under physiologic conditions, AC leads to a slight miosis of the pupil as well as a mild upper lid retraction. In cases of HS where denervation hypersensitivity has developed, the weak alpha-1 agonist effect will serve to dilate the affected pupil. Thus, in a case of subacute
Fig. 3 e External appearance after instillation of 10% cocaine drops OU. Note the marked dilation of the right pupil compared to the left, proving the presence of a left Horner syndrome. Bilateral instillation of cocaine is important: The uninvolved pupil acts as a control and cocaine drops have a short shelf life. Lack of dilation in the control eye suggests either bilateral Horner syndrome or, more likely, cocaine drops past their expiration date. The great advantage of cocaine over phenylephrine and apraclonidine testing is that cocaine testing does not require the development of denervation hypersensitivity.
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Fig. 4 e Apraclonidine testing in a different patient, 3 months after resection of a left cervical schwannoma. Left: baseline clinical appearance. Right: after instillation of AC drops OU. Note the reversal of anisocoria and bilateral upper eyelid retraction after AC testing.
or chronic HS, the unaffected pupil will become miotic and the affected pupil will dilate, causing a reversal of the anisocoria (Fig. 4).15,22 Another advantage of AC testing is that it provides a positive finding (pupillary dilation) on the affected side. The main disadvantage is that it requires denervation hypersensitivity to work5 and it is not known how long this takes to develop, making a negative AC test unreliable in acute, or possibly even subacute, cases of HS.15 In the present case, because the onset of symptoms occurred within a matter of days, cocaine is the preferred pharmacologic test. If cocaine is not available, AC can be used, but, as just mentioned, would be helpful only if the test is positive. If the AC test is negative, it provides no reassurance that an acute HS is not present, and neuroimaging would still be warranted. In a case of acute HS where no pharmacologic testing is available, urgent neuroimaging should be performed to rule out carotid dissection.
8.
Case report (Continued)
Cocaine drops were available from the pharmacy. Two drops of 10% cocaine were instilled into both eyes, leading to marked dilation in the right eye and minimal to no dilation in the left eye (Fig. 3). Now that a left sympathetic lesion has been confirmed, what is your next step? If imaging is needed, what modality would you use and what anatomy would you image? What is the timing of the imaging (the patient presented on a Saturday morning)? When can imaging for HS be done on a non-urgent basis?
9.
Comments (Continued)
9.1.
Comments by Dr. Sergott
Our patient presented to an emergency room, where imaging was both readily available and convenient; a new-onset HS
may present to an outpatient office, however. In these situations, the timing for referral and imaging is critical. Where internal carotid artery (ICA) dissection is suspected (history of head/neck trauma, head or neck pain, periorbital tingling or other dysesthesia, etc.), urgent imaging is warranted if the symptoms have occurred within 4 weeks.22 This recommendation is based on the time range of development of the most feared complication of ICA dissection, hemispheric stroke. One study of 146 consecutive patients with extracranial carotid dissection showed that, of the 27 patients who developed either ocular or hemispheric stroke, 67% occurred within the first week, with 89% within the first two weeks. The mean interval from onset to development of stroke was 6.2 days, but the range was anywhere from 1 hour to 31 days.3,4 Therefore, in HS that is of 1 month or longer duration, imaging can be done on a less urgent basis, but as Trobe points out, should not be “unnecessarily delayed.”22 The patient in this case has an acute onset, painful HS that requires urgent imaging. If he had been seen in an office setting, the appropriate action would be to refer him urgently to an emergency room for this. Imaging is required in almost all patients with HS, with only a few exceptions. A congential HS in an adult need not be worked up further, and the etiology of HS following neck or lung surgery is obvious. Once the urgency of imaging is determined, the next issue is what to image. A common clinical reflex with HS is to order imaging of the brain, which in fact is one area of the head and neck anatomy that does not require radiologic examination.22 The oculosympathetic pathway is best conceptualized as a three-neuron system with two relay centers that begins in the posterior lateral aspect of the hypothalamus. From here, the first order neuron travels down the brainstem and into the spinal cord, where it synapses in the first relay center, the ciliospinal center of Budge-Waller, located at the C8eT2 levels of the spinal cord.17 From there the second order neuron reverses course and travels cephalad, passing over the apex of the lung to synapse in the second relay center, the superior cervical ganglion, located at C2eC3, which lies roughly at the level of the angle of the mandible. The main cluster of postganglionic fibers leaving the superior cervical ganglion course up the neck as
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a neural net wrapped around the common and internal carotid arteries to reenter the skull base and the orbit via the cavernous sinus.15,17,22,23 Thus, the anatomic routing of the oculosympathetic pathway spans the skull base to the lung apex and does not include the majority of the central nervous system; the anatomy to image is the skull base, neck, and lung apex. Similarly, an orbital or cavernous sinus process rarely, if ever, causes an isolated HS. Within the compact and richly innervated cavernous sinus, HS without other cranial neuropathy in the setting of a mass is highly unlikely. In the orbit, sympathetic fibers travel with arterial and sensory nerve branches, arborizing into a diffuse and complex system immediately in the orbital apex.20 Isolated HS from an orbital process is anatomically untenable. Thus, dedicated orbital and cavernous sinus imaging are also not necessary. Often, clinical clues lead the clinician to the specific anatomy involved.1 As an example, in patients who have HS secondary to a Pancoast tumor, a history of smoking, and complain of scapular pain, imaging of the thorax is likely to provide the answer. When the clinical history is vague, and especially in an acute HS, imaging of the arteries of head and neck to rule out carotid artery dissection is of paramount importance. To this end, both soft tissue and vascular imaging must be performed. The next question is what imaging to order. Whether the sensitivity and specificity for diagnosis of carotid dissection is better with magnetic resonance image (MRI)/magnetic resonance angiogram (MRA) or computed tomography (CT)/CT angiography (CTA) is debatable,15,22 and studies comparing the two have shown no significant difference.16 In short, both modalities are adequate to make the diagnosis, and often the final decision of what to order depends on the availability of each and the preference of the neuroradiologist. Discuss with the radiologists their preferences at the time the study is
ordered. Conventional arteriography should be avoided, because it may propagate an ICA dissection intracranially.
10.
Case report (Continued)
After discussion with the radiology team, MRI/MRA of the head and neck was obtained and showed an extracranial dissection of the left ICA just inferior to the petrous bone (Fig. 5). This was confirmed by CT/CTA (Fig. 6). What treatment, if any, is proven to be beneficial for ICA dissection? How should these patients be managed? What do you tell the patient regarding his risk of stroke? If the patient has been symptomatic for more than 4 weeks, do you ever manage the subacute carotid dissection with observation alone?
11.
Comments (Continued)
11.1.
Comments by Dr. Sergott
The treatment of carotid dissection is unproven, although most experts offer either antiplatelet or anticoagulation therapy in an attempt to decrease the risk of subsequent stroke. Unfortunately, no randomized, controlled trial exists comparing the efficacy of antiplatelet versus anticoagulation therapy in carotid dissection. Two meta-analyses13,14 and a sizable prospective, nonrandomized trial8 all concluded that there is insufficient evidence to demonstrate therapeutic superiority of either antiplatelet therapy or anticoagulation. A randomized controlled trial comparing the two treatments is unlikely to be forthcoming, given the logistical challenges.
Fig. 5 e Magnetic resonance angiogram images demonstrating an internal carotid artery dissection (arrows) just below the petrous segment. Note the narrowing and irregularity of the vessel wall.
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Fig. 6 e Confirmatory computed tomography angiography. Three-dimensional image on the right. The extent of the internal carotid artery dissection is bracketed.
Because of the low annual incidence of spontaneous ICA dissection (ranging from 1.7 to 2.9 per 100,000 population9,12,18) a sufficiently large enrollment to power such a study would be challenging. In addition, if stroke is considered the main outcome of interest, the low incidence of stroke among dissection patients (estimated at 0.3% in a study by Georgiadis et al8) would necessitate even larger numbers. One estimate is that approximately 3,000 ICA dissections would need to adequately power a conclusive study.11
Thrombolysis and carotid stenting are other treatments that have been employed for ICA dissection,2,6,7,24 but again, sufficient evidence is lacking regarding efficacy or distinct advantage over systemic anticoagulation. A systematic review found insufficient data in the literature to perform a metaanalysis for thrombolysis or stenting. That said, in the limited extant literature, the complication rates for thrombolysis in ICA dissection were no greater than those seen for other ischemic stroke. Likewise, complication rates for
Fig. 7 e Axial computed tomography angiography images. A: The petrous segment of the internal carotid artery (arrow) on presentation, demonstrating a normal lumen. B: On follow-up imaging 13 days later, note that the lumen is narrower (arrow), consistent with propagation of the dissection.
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Fig. 8 e Axial magnetic resonance angiogram images. A: On presentation, the prepetrous internal carotid artery is shown with an intimal flap (arrow). B: Six weeks later, the dissection has resolved and the lumen shows no irregularity.
stenting appeared similar for carotid dissection compared to atherosclerotic carotid disease.14
12.
Case report (Continued)
The patient was admitted to the Neurosurgery Service and started on intravenous heparin. The heparin was stopped on the next hospital day, and he was discharged home on aspirin two days after admission. His symptoms had improved slightly; on two consecutive days after discharge, however, he described “explosive arguments” at work. Following the second, his previously intermittent headache became constant and of a much greater intensity. He called the office for advice. What should the patient be advised to do at this point? What are the concerns at this point?
13.
Comments (Continued)
13.1.
Comments by Dr. Sergott
He is only about one week out from onset of symptoms, which still places him in the highest risk group for ischemic stroke. For this reason, he should be instructed to go immediately to the emergency room for urgent evaluation and repeat imaging.
14.
cerebral ischemia. He was re-admitted, and his medication regimen was changed from aspirin to clopidogrel (Plavix). He was also advised to take some time off from work. The patient avoided the workplace and other stressors for a period of 3e4 weeks, over which time his symptoms improved markedly. Repeat imaging approximately 6 weeks later showed complete resolution of the dissection (Fig. 8). Three months after onset of symptoms he had minimal, if any, anisocoria and a negative apraclonidine test. He did have a slight return of the retroorbital pain when he was fatigued. Once an ICA dissection is resolved, what is the risk of recurrence? What long-term follow-up is recommended for these patients? For what length of time should antiplatelet or anticoagulation therapy be continued?
15.
Comments (Concluded)
15.1.
Comments by Dr. Sergott
Recurrence of ICA dissections is rare, with a risk ranging from 1% per year at a tertiary referral center to 0.3% per year in a multicenter study that more closely approximates a community setting.12,18,21 Length of treatment with antiplatelet therapy or anticoagulation for cervical artery dissections is not well established, but is typically either 3 or 6 months.12 Recommended follow-up is variable and largely based on the treating physician’s preference.
Case report (Continued) 16.
The patient returned to the emergency room and repeat images showed extension of the ICA dissection into the carotid canal (Fig. 7). There was no evidence of stroke or
Disclosure
The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.
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references
1. Almog Y, Gepstein R, Kesler A. Diagnostic value of imaging in Horner syndrome in adults. J Neuroophthalmol. 2010;30:7e11 2. Assadian A, Senekowitsch C, Rotter R, et al. Long-term results of covered stent repair of internal carotid artery dissections. J Vasc Surg. 2004;40:484e7 3. Biousse V, D’Anglejan-Chatillon J, Touboul PJ, et al. Time course of symptoms in extracranial carotid artery dissections. A series of 80 patients. Stroke. 1995;26:235e9 4. Biousse V, Touboul PJ, D’Anglejan-Chatillon J, et al. Ophthalmologic manifestations of internal carotid artery dissection. Am J Ophthalmol. 1998;126:565e77 5. Dewan MA, Harrison AR, Lee MS. False-negative apraclonidine testing in acute Horner syndrome. Can J Ophthalmol. 2009;44:109e10 6. DuBose J, Recinos G, Teixeira PG, et al. Endovascular stenting for the treatment of traumatic internal carotid injuries: expanding experience. J Trauma. 2008;65:1561e6 7. Fuentes B, Masjuan J, de Lecinana MA, et al. Benefits of intravenous thrombolysis in acute ischemic stroke related to extra cranial internal carotid dissection. Dream or reality? Int J Stroke. 2012;7:7e13 8. Georgiadis D, Arnold M, von Buedingen HC, et al. Aspirin vs anticoagulation in carotid artery dissection: a study of 298 patients. Neurology. 2009;72:1810e5 9. Giroud M, Fayolle H, Andre N, et al. Incidence of internal carotid artery dissection in the community of Dijon. J Neurol Neurosurg Psychiatry. 1994;57:1443 10. Jacobson DM, Berg R, Grinstead GF, et al. Duration of positive urine for cocaine metabolite after ophthalmic administration: implications for testing patients with suspected Horner syndrome using ophthalmic cocaine. Am J Ophthalmol. 2001;131:742e7 11. Kasner SE, Dreier JP. A fresh twist on carotid artery dissections. Neurology. 2009;72:1800e1
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12. Lee VH, Brown RD Jr,, Mandrekar JN, et al. Incidence and outcome of cervical artery dissection: a population-based study. Neurology. 2006;67:1809e12 13. Lyrer P, Engelter S. Antithrombotic drugs for carotid artery dissection. Cochrane Database Syst Rev;CD000255 14. Menon R, Kerry S, Norris JW, et al. Treatment of cervical artery dissection: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2008;79:1122e7 15. Mughal M, Longmuir R. Current pharmacologic testing for Horner syndrome. Curr Neurol Neurosci Rep. 2009;9:384e9 16. Provenzale JM, Sarikaya B. Comparison of test performance characteristics of MRI, MR angiography, and CT angiography in the diagnosis of carotid and vertebral artery dissection: a review of the medical literature. AJR Am J Roentgenol. 2009;193:1167e74 17. Reede DL, Garcon E, Smoker WR, et al. Horner’s syndrome: clinical and radiographic evaluation. Neuroimaging Clin N Am. 2008;18:369e85, xi. 18. Schievink WI, Mokri B, Whisnant JP. Internal carotid artery dissection in a community. Rochester, Minnesota, 1987e1992. Stroke. 1993;24:1678e80 19. Smith SJ, Diehl N, Leavitt JA, et al. Incidence of pediatric Horner syndrome and the risk of neuroblastoma: a population-based study. Arch Ophthalmol. 2010;128:324e9 20. Thakker MM, Huang J, Possin DE, et al. Human orbital sympathetic nerve pathways. Ophthal Plast Reconstr Surg. 2008;24:360e6 21. Touze E, Gauvrit JY, Moulin T, et al. Risk of stroke and recurrent dissection after a cervical artery dissection: a multicenter study. Neurology. 2003;61:1347e51 22. Trobe JD. The evaluation of Horner syndrome. J Neuroophthalmol. 2010;30:1e2 23. Walton KA, Buono LM. Horner syndrome. Curr Opin Ophthalmol. 2003;14:357e63 24. Zinkstok SM, Vergouwen MD, Engelter ST, et al. Safety and functional outcome of thrombolysis in dissection-related ischemic stroke: a meta-analysis of individual patient data. Stroke. 2011;42:2515e20
abstract Key words:
A 44-year-old man presented with acute onset headache and isolated anisocoria. Dilation
anisocoria
lag was noted in the smaller pupil and Horner syndrome was suspected despite the lack of
Horner syndrome
eyelid ptosis. Cocaine testing confirmed the clinical diagnosis, and urgent neuroimaging
carotid dissection
found an internal carotid artery dissection. The patient was managed with systemic
pharmacologic testing
anticoagulation with a good final outcome. Horner syndrome should be suspected in any
apraclonidine
patient with aniscoria and dilation lag, despite the absence of eyelid ptosis or other associated findings.
ª 2013 Elsevier Inc. All rights reserved.
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/survophthal
Clinical challenges
But it’s not all there Jared D. Peterson, MDa, Jurij R. Bilyk, MDb,*, Robert C. Sergott, MDc a
Wills Eye Institute, Philadelphia, Pennsylvania, USA Skull Base Division, Neuro-Ophthalmology Service, Wills Eye Institute, Philadelphia, Pennsylvania, USA c Director, Neuro-Ophthalmology Service, Wills Eye Institute, Philadelphia, Pennsylvania, USA b
article info
(In keeping with the format of a clinical pathologic conference, the abstract and key words appear at the end of the article.)
Article history: Received 2 January 2012 Received in revised form 3 February 2012 Accepted 7 February 2012 Available online 10 July 2012 Peter Savino and Helen DaneshMeyer, Editors
1.
Case report
A 44-year-old white man presented to the Wills Eye Emergency Room with headache. The patient, who had no significant past medical history and no chronic history of headaches, first noticed the pain 5 days earlier while doing his normal exercise routine at the gym. While performing leg lifts, he had the onset of transient lightheadedness in addition to a headache that localized behind both eyes. The headache resolved by the following morning, only to return the next day, with the pain worse on the left side. Later that day he looked in a mirror and saw that his pupils were of different size. The patient was sure that this was a new finding and that the right side was abnormal. What are your thoughts and concerns in a patient who presents with an acute onset headache? Does the presence of anisocoria narrow the diagnosis?
2.
Comments
2.1.
Comments by Robert C. Sergott, MD
Depending on the setting, headaches can either be a very helpful piece of the clinical picture or add very little. In a patient with a history of headaches, it is easy to give very little credence to this complaint or to ignore it completely, justifying it to be their “baseline”. For this reason, in patients with a history of headache, it is very important to ask specific questions regarding the nature of the headache to determine whether it is similar to their typical pain. Headaches that are markedly different from a patient’s typical pattern or that are new in onset, such as in this case, should be considered as significant. The presence of anisocoria in this case also helps to validate that something is most likely awry. Although the anisocoria could represent the sudden discovery of a longstanding condition, this is a potentially dangerous assumption, especially when paired with a headache of new onset. Conditions
* Corresponding author: Jurij R. Bilyk, MD, Wills Eye Institute, 840 Walnut Street, Suite 930, Philadelphia, PA 19107. E-mail address: [email protected] (J.R. Bilyk). 0039-6257/$ e see front matter ª 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.survophthal.2012.02.009
s u r v e y o f o p h t h a l m o l o g y 5 8 ( 2 0 1 3 ) 4 9 2 e4 9 9
Fig. 1 e Clinical photograph showing 2 mm of anisocoria with the right pupil larger than the left.
that can account for both should top the differential diagnosis. In particular, the most dangerous causes of anisocoria with headache should be considered first, namely, oculomotor nerve palsy and Horner syndrome (HS). The initial exam should focus on trying to identify the abnormal pupil, which will help differentiate these two conditions.
3.
Case report (continued)
Visual acuity was 20/30 bilaterally. Two millimeters of anisocoria were present, with the right pupil larger than the left
Fig. 2 e Pupillary sizes in ambient and dim lighting. Note that the difference in anisocoria remains the same, consistent with physiologic anisocoria. In a patient with a sympathetic defect (Horner syndrome), the anisocoria should increase in the dark. The opposite would occur in a parasymapthetic defect (pupil-involving oculomotor nerve palsy, Adie pupil).
493
(Fig. 1). The degree of anisocoria was evaluated in well-lit and dim conditions (Fig. 2). There was no ptosis, and upper eyelid excursions were normal. The lower eyelid positions were symmetric. Extraocular motility (EOM) was full, and the patient was orthophoric. Confrontation visual fields were full bilaterally. Anterior segment examination and direct ophthalmoscopic examination of the optic nerve heads were unremarkable. With the anisocoria as noted in light and dark conditions, full EOM, and the absence of ptosis, what other nonpharmacologic examination techniques can help identify which is the abnormal pupil? What is your differential diagnosis? Because the anisocoria appears physiologic, and no abnormality is noted in eyelid or EOM examination, is it reasonable to assume that the patient simply discovered his physiologic anisocoria and should we reassure him?
4.
Comments (Continued)
4.1.
Comments by Dr. Sergott
A normal efferent pupillary response is the result of a balance between sympathetic and parasympathetic innervation to the iris. When a patient presents with anisocoria, the first step is to determine which arm of the autonomic nervous system is affected. The most straightforward method of differentiation is to measure pupillary diameter in ambient and dim light. If the sympathetic pathway is abnormal, then dilation of the affected pupil in dark conditions will be impaired, and the anisocoria will be greater in the dark. The opposite is true if the parasympathetics are the culprit; parasympathetic innervation causes pupillary constriction, and deficiencies are most notable in ambient lighting. If the amount of anisocoria remains unchanged in normal and dim lighting, physiologic anisocoria is likely. The clinician, however, must also remember that pupillary testing in light and dark conditions may lead to ambiguous results for a variety of reasons. First, as a general rule, patients with darker irides are more difficult to assess. Second, the autonomic system injury may not be complete and cause a slow, but intact, pupillary response. In other words, an abnormal pupil may be sluggish, but eventually reactive. If the clinician allows enough time to elapse between changing the lighting conditions and checking the pupils, autonomic dysfunction may be misdiagnosed as physiologic anisocoria. When examining pupils, it is as important to document briskness of response for both constriction and dilation as size. There are several nonpharmacologic findings that help identify the abnormal pupil in this situation. To identify deficiencies in the parasympathetic response, poor pupillary reactivity is often seen in cases of acute oculomotor nerve palsy or tonic (Adie) pupils. Vermiform movements or sectoral reactivity suggest a subacute or chronic tonic pupil. Interruption of sympathetic innervation leads to mild upper eyelid ptosis secondary to paresis of Mu¨ller muscle. So-called “reverse ptosis” may occur because the sympathetics innervate not only the superior tarsal (Mu¨ller) muscle in the upper lid, but also the analogous inferior tarsal muscle in the lower
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lid. The inferior tarsal muscle retracts the lower lid, and its paresis in HS results in an elevation of the lower lid. Transient conjunctival hyperemia may occur as a result of the loss of sympathetic vasoconstriction. Finally, because sympathetic fibers are responsible for pupillary dilation, loss of sympathetic innervation leads to a lag in dilation compared to the unaffected side. Most neuro-ophthalmology texts include absence of sweating over the forehead of the affected side, but the majority of patients will not notice this, even when it is present.
5.
Case report (Continued)
The pupils reacted briskly to light, with no evidence of sectoral dilation or vermiform movements on the right; on the left, a subtle dilation lag was noted at the slit-lamp. How does this help with the diagnosis? Can Horner syndrome occur without ptosis? What is your next step?
6.
Comments (Continued)
6.1.
Comments by Dr. Sergott
Normal reactivity of the larger right pupil, in addition to a lack of ptosis and external ophthalmoplegia, effectively rules out a right third nerve dysfunction. Dilation lag of the smaller left pupil implicates this side as the abnormal one, making HS more likely. Even with this finding of subtle dilation lag, however, the clinical diagnosis is by no means definitive because of the absence of ptosis and other associated findings. Clinically, the ptosis in HS is not severe, with a disparity in the margin to reflex distance of only 1e3 mm, consistent with the function of Mu¨ller muscle. It is possible to have HS without ptosis; one population-based study of pediatric HS found that roughly 20% of patients did not present with ptosis.19 In many cases, clinical examination alone is sufficient to raise or rule out the possibility of HS, especially if reverse ptosis and nonphysiologic anisocoria are present. To help confirm the diagnosis in this case with equivocal findings, pharmacologic testing is the next step. What pharmacologic test do you use? The availability of cocaine in a comprehensive ophthalmologist’s office is limited at best. What are your thoughts on the use of apraclonidine in the diagnosis of HS in general and in this case in particular? Do you still use hydroxyamphetamine?
7.
Comments (Continued)
7.1.
Comments by Dr. Sergott
A variety of pharmacologic tests are available to confirm the diagnosis of HS and offer clues as to the etiology and duration, but many of these agents are difficult to obtain and maintain in a standard office setting.15 Four topical pharmacologic agents have been used for the diagnosis of HS: cocaine
(4e10%), hydroxyamphetamine, dilute phenylephrine (1%), and apraclonidine (0.5%). Of these, two are impractical: hydroxyamphetamine is very difficult to obtain and cannot be used on the same day as cocaine, prompting Trobe to comment that hydroxyamphetamine testing is “a waste of time”22,23; diluted phenylephrine must be mixed properly to give reasonably reliable results and requires an unspecified lag for the development of denervation supersensitivity before it works.22 The remaining two agents, cocaine and apraclonidine, still have a place in the diagnosis of HS.22 Under normal conditions, there is a continuous release of norepinephrine (NE) from presynaptic sympathetic nerve terminals. Cocaine works by blocking the reuptake of NE, leading to accumulation and pupillary dilation. In cases of HS, the oculosympathetic pathway is interrupted and less NE is released from the presynaptic terminals. When cocaine blocks the reuptake of NE, the affected side, with its decrease level of norepinephrine, fails to dilate (Fig. 3).17 Two drops of cocaine solution are placed in each eye, and the patient is reassessed 20 minutes to 1 hour later.23 The major advantage of cocaine testing is that it does not require denervation supersensitivity to work; a positive cocaine test should be seen even in acute cases of HS. Disadvantages of topical cocaine include difficulty in obtaining and maintaining the medication (Schedule II drug and short shelf life), corneal toxicity, and the possibility of positive urine drug screening for up to 48 hours following the test.10,15,22 In contrast to topical cocaine, apraclonidine (AC) 0.5% is easily obtained. AC is an alpha-2 agonist that also has a weak alpha-1 agonist effect. The drug is used mainly for its alpha-2 effect on the ciliary body to reduce aqueous production in the treatment of glaucoma or to prevent intraocular pressure spikes following anterior segment laser procedures. Under physiologic conditions, AC leads to a slight miosis of the pupil as well as a mild upper lid retraction. In cases of HS where denervation hypersensitivity has developed, the weak alpha-1 agonist effect will serve to dilate the affected pupil. Thus, in a case of subacute
Fig. 3 e External appearance after instillation of 10% cocaine drops OU. Note the marked dilation of the right pupil compared to the left, proving the presence of a left Horner syndrome. Bilateral instillation of cocaine is important: The uninvolved pupil acts as a control and cocaine drops have a short shelf life. Lack of dilation in the control eye suggests either bilateral Horner syndrome or, more likely, cocaine drops past their expiration date. The great advantage of cocaine over phenylephrine and apraclonidine testing is that cocaine testing does not require the development of denervation hypersensitivity.
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Fig. 4 e Apraclonidine testing in a different patient, 3 months after resection of a left cervical schwannoma. Left: baseline clinical appearance. Right: after instillation of AC drops OU. Note the reversal of anisocoria and bilateral upper eyelid retraction after AC testing.
or chronic HS, the unaffected pupil will become miotic and the affected pupil will dilate, causing a reversal of the anisocoria (Fig. 4).15,22 Another advantage of AC testing is that it provides a positive finding (pupillary dilation) on the affected side. The main disadvantage is that it requires denervation hypersensitivity to work5 and it is not known how long this takes to develop, making a negative AC test unreliable in acute, or possibly even subacute, cases of HS.15 In the present case, because the onset of symptoms occurred within a matter of days, cocaine is the preferred pharmacologic test. If cocaine is not available, AC can be used, but, as just mentioned, would be helpful only if the test is positive. If the AC test is negative, it provides no reassurance that an acute HS is not present, and neuroimaging would still be warranted. In a case of acute HS where no pharmacologic testing is available, urgent neuroimaging should be performed to rule out carotid dissection.
8.
Case report (Continued)
Cocaine drops were available from the pharmacy. Two drops of 10% cocaine were instilled into both eyes, leading to marked dilation in the right eye and minimal to no dilation in the left eye (Fig. 3). Now that a left sympathetic lesion has been confirmed, what is your next step? If imaging is needed, what modality would you use and what anatomy would you image? What is the timing of the imaging (the patient presented on a Saturday morning)? When can imaging for HS be done on a non-urgent basis?
9.
Comments (Continued)
9.1.
Comments by Dr. Sergott
Our patient presented to an emergency room, where imaging was both readily available and convenient; a new-onset HS
may present to an outpatient office, however. In these situations, the timing for referral and imaging is critical. Where internal carotid artery (ICA) dissection is suspected (history of head/neck trauma, head or neck pain, periorbital tingling or other dysesthesia, etc.), urgent imaging is warranted if the symptoms have occurred within 4 weeks.22 This recommendation is based on the time range of development of the most feared complication of ICA dissection, hemispheric stroke. One study of 146 consecutive patients with extracranial carotid dissection showed that, of the 27 patients who developed either ocular or hemispheric stroke, 67% occurred within the first week, with 89% within the first two weeks. The mean interval from onset to development of stroke was 6.2 days, but the range was anywhere from 1 hour to 31 days.3,4 Therefore, in HS that is of 1 month or longer duration, imaging can be done on a less urgent basis, but as Trobe points out, should not be “unnecessarily delayed.”22 The patient in this case has an acute onset, painful HS that requires urgent imaging. If he had been seen in an office setting, the appropriate action would be to refer him urgently to an emergency room for this. Imaging is required in almost all patients with HS, with only a few exceptions. A congential HS in an adult need not be worked up further, and the etiology of HS following neck or lung surgery is obvious. Once the urgency of imaging is determined, the next issue is what to image. A common clinical reflex with HS is to order imaging of the brain, which in fact is one area of the head and neck anatomy that does not require radiologic examination.22 The oculosympathetic pathway is best conceptualized as a three-neuron system with two relay centers that begins in the posterior lateral aspect of the hypothalamus. From here, the first order neuron travels down the brainstem and into the spinal cord, where it synapses in the first relay center, the ciliospinal center of Budge-Waller, located at the C8eT2 levels of the spinal cord.17 From there the second order neuron reverses course and travels cephalad, passing over the apex of the lung to synapse in the second relay center, the superior cervical ganglion, located at C2eC3, which lies roughly at the level of the angle of the mandible. The main cluster of postganglionic fibers leaving the superior cervical ganglion course up the neck as
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a neural net wrapped around the common and internal carotid arteries to reenter the skull base and the orbit via the cavernous sinus.15,17,22,23 Thus, the anatomic routing of the oculosympathetic pathway spans the skull base to the lung apex and does not include the majority of the central nervous system; the anatomy to image is the skull base, neck, and lung apex. Similarly, an orbital or cavernous sinus process rarely, if ever, causes an isolated HS. Within the compact and richly innervated cavernous sinus, HS without other cranial neuropathy in the setting of a mass is highly unlikely. In the orbit, sympathetic fibers travel with arterial and sensory nerve branches, arborizing into a diffuse and complex system immediately in the orbital apex.20 Isolated HS from an orbital process is anatomically untenable. Thus, dedicated orbital and cavernous sinus imaging are also not necessary. Often, clinical clues lead the clinician to the specific anatomy involved.1 As an example, in patients who have HS secondary to a Pancoast tumor, a history of smoking, and complain of scapular pain, imaging of the thorax is likely to provide the answer. When the clinical history is vague, and especially in an acute HS, imaging of the arteries of head and neck to rule out carotid artery dissection is of paramount importance. To this end, both soft tissue and vascular imaging must be performed. The next question is what imaging to order. Whether the sensitivity and specificity for diagnosis of carotid dissection is better with magnetic resonance image (MRI)/magnetic resonance angiogram (MRA) or computed tomography (CT)/CT angiography (CTA) is debatable,15,22 and studies comparing the two have shown no significant difference.16 In short, both modalities are adequate to make the diagnosis, and often the final decision of what to order depends on the availability of each and the preference of the neuroradiologist. Discuss with the radiologists their preferences at the time the study is
ordered. Conventional arteriography should be avoided, because it may propagate an ICA dissection intracranially.
10.
Case report (Continued)
After discussion with the radiology team, MRI/MRA of the head and neck was obtained and showed an extracranial dissection of the left ICA just inferior to the petrous bone (Fig. 5). This was confirmed by CT/CTA (Fig. 6). What treatment, if any, is proven to be beneficial for ICA dissection? How should these patients be managed? What do you tell the patient regarding his risk of stroke? If the patient has been symptomatic for more than 4 weeks, do you ever manage the subacute carotid dissection with observation alone?
11.
Comments (Continued)
11.1.
Comments by Dr. Sergott
The treatment of carotid dissection is unproven, although most experts offer either antiplatelet or anticoagulation therapy in an attempt to decrease the risk of subsequent stroke. Unfortunately, no randomized, controlled trial exists comparing the efficacy of antiplatelet versus anticoagulation therapy in carotid dissection. Two meta-analyses13,14 and a sizable prospective, nonrandomized trial8 all concluded that there is insufficient evidence to demonstrate therapeutic superiority of either antiplatelet therapy or anticoagulation. A randomized controlled trial comparing the two treatments is unlikely to be forthcoming, given the logistical challenges.
Fig. 5 e Magnetic resonance angiogram images demonstrating an internal carotid artery dissection (arrows) just below the petrous segment. Note the narrowing and irregularity of the vessel wall.
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Fig. 6 e Confirmatory computed tomography angiography. Three-dimensional image on the right. The extent of the internal carotid artery dissection is bracketed.
Because of the low annual incidence of spontaneous ICA dissection (ranging from 1.7 to 2.9 per 100,000 population9,12,18) a sufficiently large enrollment to power such a study would be challenging. In addition, if stroke is considered the main outcome of interest, the low incidence of stroke among dissection patients (estimated at 0.3% in a study by Georgiadis et al8) would necessitate even larger numbers. One estimate is that approximately 3,000 ICA dissections would need to adequately power a conclusive study.11
Thrombolysis and carotid stenting are other treatments that have been employed for ICA dissection,2,6,7,24 but again, sufficient evidence is lacking regarding efficacy or distinct advantage over systemic anticoagulation. A systematic review found insufficient data in the literature to perform a metaanalysis for thrombolysis or stenting. That said, in the limited extant literature, the complication rates for thrombolysis in ICA dissection were no greater than those seen for other ischemic stroke. Likewise, complication rates for
Fig. 7 e Axial computed tomography angiography images. A: The petrous segment of the internal carotid artery (arrow) on presentation, demonstrating a normal lumen. B: On follow-up imaging 13 days later, note that the lumen is narrower (arrow), consistent with propagation of the dissection.
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Fig. 8 e Axial magnetic resonance angiogram images. A: On presentation, the prepetrous internal carotid artery is shown with an intimal flap (arrow). B: Six weeks later, the dissection has resolved and the lumen shows no irregularity.
stenting appeared similar for carotid dissection compared to atherosclerotic carotid disease.14
12.
Case report (Continued)
The patient was admitted to the Neurosurgery Service and started on intravenous heparin. The heparin was stopped on the next hospital day, and he was discharged home on aspirin two days after admission. His symptoms had improved slightly; on two consecutive days after discharge, however, he described “explosive arguments” at work. Following the second, his previously intermittent headache became constant and of a much greater intensity. He called the office for advice. What should the patient be advised to do at this point? What are the concerns at this point?
13.
Comments (Continued)
13.1.
Comments by Dr. Sergott
He is only about one week out from onset of symptoms, which still places him in the highest risk group for ischemic stroke. For this reason, he should be instructed to go immediately to the emergency room for urgent evaluation and repeat imaging.
14.
cerebral ischemia. He was re-admitted, and his medication regimen was changed from aspirin to clopidogrel (Plavix). He was also advised to take some time off from work. The patient avoided the workplace and other stressors for a period of 3e4 weeks, over which time his symptoms improved markedly. Repeat imaging approximately 6 weeks later showed complete resolution of the dissection (Fig. 8). Three months after onset of symptoms he had minimal, if any, anisocoria and a negative apraclonidine test. He did have a slight return of the retroorbital pain when he was fatigued. Once an ICA dissection is resolved, what is the risk of recurrence? What long-term follow-up is recommended for these patients? For what length of time should antiplatelet or anticoagulation therapy be continued?
15.
Comments (Concluded)
15.1.
Comments by Dr. Sergott
Recurrence of ICA dissections is rare, with a risk ranging from 1% per year at a tertiary referral center to 0.3% per year in a multicenter study that more closely approximates a community setting.12,18,21 Length of treatment with antiplatelet therapy or anticoagulation for cervical artery dissections is not well established, but is typically either 3 or 6 months.12 Recommended follow-up is variable and largely based on the treating physician’s preference.
Case report (Continued) 16.
The patient returned to the emergency room and repeat images showed extension of the ICA dissection into the carotid canal (Fig. 7). There was no evidence of stroke or
Disclosure
The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.
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references
1. Almog Y, Gepstein R, Kesler A. Diagnostic value of imaging in Horner syndrome in adults. J Neuroophthalmol. 2010;30:7e11 2. Assadian A, Senekowitsch C, Rotter R, et al. Long-term results of covered stent repair of internal carotid artery dissections. J Vasc Surg. 2004;40:484e7 3. Biousse V, D’Anglejan-Chatillon J, Touboul PJ, et al. Time course of symptoms in extracranial carotid artery dissections. A series of 80 patients. Stroke. 1995;26:235e9 4. Biousse V, Touboul PJ, D’Anglejan-Chatillon J, et al. Ophthalmologic manifestations of internal carotid artery dissection. Am J Ophthalmol. 1998;126:565e77 5. Dewan MA, Harrison AR, Lee MS. False-negative apraclonidine testing in acute Horner syndrome. Can J Ophthalmol. 2009;44:109e10 6. DuBose J, Recinos G, Teixeira PG, et al. Endovascular stenting for the treatment of traumatic internal carotid injuries: expanding experience. J Trauma. 2008;65:1561e6 7. Fuentes B, Masjuan J, de Lecinana MA, et al. Benefits of intravenous thrombolysis in acute ischemic stroke related to extra cranial internal carotid dissection. Dream or reality? Int J Stroke. 2012;7:7e13 8. Georgiadis D, Arnold M, von Buedingen HC, et al. Aspirin vs anticoagulation in carotid artery dissection: a study of 298 patients. Neurology. 2009;72:1810e5 9. Giroud M, Fayolle H, Andre N, et al. Incidence of internal carotid artery dissection in the community of Dijon. J Neurol Neurosurg Psychiatry. 1994;57:1443 10. Jacobson DM, Berg R, Grinstead GF, et al. Duration of positive urine for cocaine metabolite after ophthalmic administration: implications for testing patients with suspected Horner syndrome using ophthalmic cocaine. Am J Ophthalmol. 2001;131:742e7 11. Kasner SE, Dreier JP. A fresh twist on carotid artery dissections. Neurology. 2009;72:1800e1
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12. Lee VH, Brown RD Jr,, Mandrekar JN, et al. Incidence and outcome of cervical artery dissection: a population-based study. Neurology. 2006;67:1809e12 13. Lyrer P, Engelter S. Antithrombotic drugs for carotid artery dissection. Cochrane Database Syst Rev;CD000255 14. Menon R, Kerry S, Norris JW, et al. Treatment of cervical artery dissection: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2008;79:1122e7 15. Mughal M, Longmuir R. Current pharmacologic testing for Horner syndrome. Curr Neurol Neurosci Rep. 2009;9:384e9 16. Provenzale JM, Sarikaya B. Comparison of test performance characteristics of MRI, MR angiography, and CT angiography in the diagnosis of carotid and vertebral artery dissection: a review of the medical literature. AJR Am J Roentgenol. 2009;193:1167e74 17. Reede DL, Garcon E, Smoker WR, et al. Horner’s syndrome: clinical and radiographic evaluation. Neuroimaging Clin N Am. 2008;18:369e85, xi. 18. Schievink WI, Mokri B, Whisnant JP. Internal carotid artery dissection in a community. Rochester, Minnesota, 1987e1992. Stroke. 1993;24:1678e80 19. Smith SJ, Diehl N, Leavitt JA, et al. Incidence of pediatric Horner syndrome and the risk of neuroblastoma: a population-based study. Arch Ophthalmol. 2010;128:324e9 20. Thakker MM, Huang J, Possin DE, et al. Human orbital sympathetic nerve pathways. Ophthal Plast Reconstr Surg. 2008;24:360e6 21. Touze E, Gauvrit JY, Moulin T, et al. Risk of stroke and recurrent dissection after a cervical artery dissection: a multicenter study. Neurology. 2003;61:1347e51 22. Trobe JD. The evaluation of Horner syndrome. J Neuroophthalmol. 2010;30:1e2 23. Walton KA, Buono LM. Horner syndrome. Curr Opin Ophthalmol. 2003;14:357e63 24. Zinkstok SM, Vergouwen MD, Engelter ST, et al. Safety and functional outcome of thrombolysis in dissection-related ischemic stroke: a meta-analysis of individual patient data. Stroke. 2011;42:2515e20
abstract Key words:
A 44-year-old man presented with acute onset headache and isolated anisocoria. Dilation
anisocoria
lag was noted in the smaller pupil and Horner syndrome was suspected despite the lack of
Horner syndrome
eyelid ptosis. Cocaine testing confirmed the clinical diagnosis, and urgent neuroimaging
carotid dissection
found an internal carotid artery dissection. The patient was managed with systemic
pharmacologic testing
anticoagulation with a good final outcome. Horner syndrome should be suspected in any
apraclonidine
patient with aniscoria and dilation lag, despite the absence of eyelid ptosis or other associated findings.
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