Unequal pupils and ptosis
BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j643 (Published 23 February 2017) Cite this as: BMJ 2017;356:j643
- Andrew Malem, ST3 ophthalmology
- Correspondence to A Malem andrew.malem{at}cantab.net
A 69 year old woman was referred by her primary care doctor to the eye emergency department with a dilated left pupil and ptosis of her right upper lid. She had visited her primary care doctor because of an upper respiratory tract infection and was unconcerned about her unequal pupil size (anisocoria), stating that she “has had odd pupils and a droopy right lid since being a teenager.” She had no ocular or medical history and was not taking any oral or topical medication. She denied any history of trauma, neck pain, weight loss, diplopia, or anhydrosis. On examination she had a partial right upper lid ptosis (fig 1) and her right pupil, which was the abnormal one, was constricted and showed a dilatation lag. Both pupils constricted to light and accommodation and there was no relative afferent pupillary defect. Iris colour was equal on both sides. Visual acuity was 6/9 in both eyes and intraocular pressures were 12 mm Hg and 14 mm Hg in the right and left, respectively. Ocular motility was full and funduscopy showed healthy optic discs. She had no other neurological signs. One drop of apraclonidine 1% was applied to both eyes. After one hour there was dilation of the constricted pupil and improvement in the ptosis.
Photograph of patient in room light and distance fixation showing right upper lid ptosis (A) and right miosis (B)
1. What is the diagnosis and what are the differential diagnoses?
Short answer
Right Horner’s syndrome. The differential diagnoses for a unilateral constricted pupil include pharmacological anisocoria, local iris pathology, and physiological anisocoria. Ptosis, which must be differentiated from pseudoptosis, can be classified as involutional, neurogenic, myogenic, or mechanical (Table 1, Table 2).
Differential diagnoses for a unilaterally constricted pupil
Differential diagnoses for ptosis
Discussion
Horner’s syndrome occurs when the oculosympathetic innervation is interrupted. It can represent an underlying medical or surgical emergency, therefore timely and appropriate management can be lifesaving. A triad of miosis, partial ptosis, and anhydrosis is often described, but such a classic presentation is unusual, and loss of sudomotor control to the face, resulting in anhydrosis, might or might not be present.1 The anisocoria is best visualised in dim light because of impaired pupil dilatation. In Horner’s syndrome the eye can appear sunken. This is caused by narrowing of the palpebral aperture, and not by true eyeball retraction (pseudoenophthalmos). Iris heterochromia can be present when the Horner’s is congenital or chronic.
The diagnosis of Horner’s syndrome is clinical, but can also be confirmed with the administration of topical drops containing cocaine 4% or 10%, or more recently apraclonidine 0.5% or 1%. On administration of cocaine to both eyes, the affected pupil does not dilate but the normal pupil does.2 With apraclonidine there is an improvement of the ptosis and dilation of the constricted pupil (fig 2).345
Before administration of apraclonidine 1%, showing right sided ptosis and miosis (A), and one hour post application showing resolution of right upper lid ptosis and right pupil dilation (B)
2. What is the aetiology of this condition?
Short answer
Pathology along the oculosympathetic pathway, which could be central (in the brainstem/spinal cord), preganglionic (in the lung apex/brachial plexus/neck), or postganglionic (in the upper neck/middle ear/cavernous sinus/orbit). The most important, life threatening cause is a carotid artery dissection.
Discussion
Horner’s syndrome can be caused by central, preganglionic, or postganglionic lesions occurring anywhere along the oculosympathetic pathway.
The common signs of a lesion along this pathway are ipsilateral miosis and partial ptosis. If the central or preganglionic fibres are affected, facial anhydrosis will also be present. If the lesion affects postganglionic fibres, anhydrosis can be limited or absent.6
Central causes result from brainstem and spinal cord pathology, and include tumours, trauma, ischaemia, malformations, meningitis, and demyelination.
Preganglionic lesions can occur anywhere from the sympathetic chain to the superior cervical ganglion and include apical lung tumours (Pancoast syndrome) and brachial plexus injuries, acquired during birth or later. Neck pathology, including dissection or aneurysms of the common carotid artery, neck tumours, neck trauma, and goitre can also cause a preganglionic Horner’s syndrome. Uncommonly, epidural anaesthesia or iatrogenic injury can result in preganglionic lesions.
Postganglionic lesions can arise anywhere from the superior cervical ganglion to the iris. Possible causes include upper neck pathology (dissection of the internal carotid artery and trauma), middle ear infections (otitis media, varicella zoster virus), cavernous sinus disease (thrombosis, fistula, infection, tumours), and orbital pathology (tumours, Tolosa Hunt). Uncommonly, cluster headaches and migraines may be associated with the features of Horner’s syndrome.
A sudden onset painful Horner’s syndrome should be assumed to be a carotid dissection until proved otherwise and requires emergency investigation and management.
3. What further investigations are necessary?
Short answer
Computed tomography angiography or magnetic resonance angiography of the brain/cervical and upper thoracic spine—same day for acute painful cases; within six weeks for subacute cases.
Discussion
There is a wide variety of possible aetiologies that can cause Horner’s syndrome, therefore a detailed history, the presence of other clinical and neurological signs, and the results of pharmacological testing collectively help guide which investigations are required.
Congenital Horner’s syndrome occurs most commonly secondary to birth trauma with injury to the carotid artery sympathetic plexus.7 If there is no clear traumatic history, or a child develops a Horner’s syndrome with no known underlying cause, urinary testing for vanillylmadelic acid and neuroimaging in the form of magnetic resonance imaging of the brain, neck, or chest is indicated to assess for a neuroblastoma mass lesion.8
Acquired Horner’s syndrome can be further investigated by additional testing with hydroxyamphetamine 36 hours after apraclonidine/cocaine drops. This testing can provide further information on the location of the oculosympathetic lesion.9 There are, however, problems with false negatives when using hydroxyamphetamine, especially in the first week after developing a Horner’s syndrome. Neuroimaging, if required, should not be delayed so that hydroxyamphetamine testing can be performed.710 The use of 1:1000 adrenaline can also help in differentiating preganglionic from postganglionic lesions caused by denervation hypersensitivity.
Central causes of Horner’s often present with significant accompanying neurological signs and initial magnetic resonance imaging of the brain and cervical or upper thoracic spine is indicated.11
Preganglionic lesions and postganglionic lesions should have either computed tomography angiography or magnetic resonance angiography imaging spanning from the aortic arch to the circle of Willis.
For patients with an acute onset Horner’s syndrome associated with pain, trauma, or malignancy, same day computed tomography angiography spanning from the circle of Willis or orbits to T4/T5 should be performed.11 In subacute cases with no localising signs, pain, trauma, or history of malignancy, the same computed tomography angiography protocol should be performed within six weeks.11 If iodine contrast is contraindicated, magnetic resonance angiography should be performed.
Patient outcome
A review of old photographs confirmed a longstanding Horner’s syndrome present since the age of 19. The patient underwent a routine magnetic resonance angiography of the brain and cervical and upper thoracic spine and no lesion was found. In light of the longstanding, non-progressive nature and lack of identifiable lesion, the patient was given a diagnosis of right idiopathic Horner’s syndrome.
Footnotes
I have read and understood the BMJ policy on declaration of interests and declare the following interests: none