Aron George and Gary Oh

A 45-year-old male was referred to outpatient ophthalmology for assessment of right iris having intermittent episodes of asymmetric dilation of the right pupil.

Recurrent episodes of pupil dilation were reported lasting approximately 10 minutes once a day for 2–3 months and then decreased to once a month for the last year. These episodes of pupil dilation were accompanied with tingling in the right cheek. In addition, the patient experienced intermittent blurring of the vision in the right eye with aching around her eyes, especially on the right.

??What are the signs and symptoms???

A 45-year-old male was referred to outpatient ophthalmology for assessment of right iris having intermittent episodes of asymmetric dilation of the right pupil.

Recurrent episodes of pupil dilation were reported lasting approximately 10 minutes once a day for 2–3 months and then decreased to once a month for the last year. These episodes of pupil dilation were accompanied with tingling in the right cheek. In addition, the patient experienced intermittent blurring of the vision in the right eye with aching around her eyes, especially on the right.

??What is the dDx???

DIFFERENTIAL DIAGNOSIS

Cavernous sinus aneurysm Lateral medullary infarction ICA dissection Thrombosis/Stroke Tumor Demyelinating lesion

??What further testing do you need???

Uncorrected visual acuity of 20/20 bilateral eyes Slight (1–2 mm) right-sided ptosis. Right pupil smaller than left. Right iris asymmetrically hypoplastic, inferior sphincter

cuff hypoplastic, however upper portion normal. Right pupil fails to dilate after 4% cocaine eye drops

supports Dx of unilateral right Horner’s syndrome. The rest of the ocular and visual examination was

normal. Emergent MRI and magnetic resonance angiography

(MRA) revealed a severe left ICAD (Internal Carotid Artery Dissection).

Oral anticoagulants and steroids started. Spontaneous resolution occurred three months later

upon confirmation with repeat MRI/MRA.

??What is the diagnosis???

Horner’s SyndromeDue to ICAD

History Horner’s syndrome (oculosympathetic paresis)

first described by three American army physicians in 1864 in a soldier shot through the throat.

In 1869, Johann Friedrich Horner, a Swiss ophthalmologist, described the classic triad.

Incidence

Dependent upon diagnosis

Signs/Symptoms/Pathophysiology Triad: Ipsilateral Ptosis, Miosis, and Anhidrosis PTOSIS

Minor (less than 2 mm) Müller's muscle paralysis (not LPS), sympathetic pathway. LPS NOT affected (CNIII palsies cause more profound upper lid

ptosis). MIOSIS

Iris constrictor muscle unopposed (iris dilator muscle broken) Anisocoria (1-2mm) more prominent in dim light, delayed

ipsilateral pupil dilatation.   ANHYDROSIS

Anhidrosis is not a feature of postganglionic or third-order lesions. Sympathetic fibers (Superior Cervical Ganglion) cause ipsilateral

facial sweating and vasodilation (oculosympathetic pathway) This sign is frequently not apparent to patients or clinicians.

OTHER POSSIBLE SIGNS Other SNS includes ipsilateral conjunctival injection, nasal

stuffiness, and increased near point of accommodation ICAD - Neck or facial pain should be presumed to be

caused by carotid dissection until proven otherwise. Emergent diagnostic tests .

Cavernous Sinus - Ipsilateral extraocular pareses (CN VI Palsy), in the absence of other brainstem signs

Brainstem - Brainstem signs (diplopia, vertigo, ataxia, lateralized weakness)

Cervico-Thoracic Cord - Myelopathic features (bilateral or ipsilateral weakness, long tract signs, sensory level, bowel and bladder impairment)

Lung Apex - Arm pain and/or hand weakness (brachial plexus lesions).

First-order syndrome Brainstem or cervicothoracic spinal cord sympathetic tract lesion Most common: lateral medullary infarction (Wallenberg

syndrome) Sx/Sx: vertigo and ataxia (which overshadow the Horner's

syndrome), abnormal eye movements, ipsilateral limb ataxia, and a dissociated sensory loss (loss of ipsilateral facial pain/temperature sensation and contralateral trunk). Hoarseness and dysphagia are also often present

Strokes, tumors, and demyelinating lesions affecting the sympathetic tracts in the hypothalamus, midbrain, pons, medulla, or cervicothoracic spinal cord.

Syringomyelia and cervical cord trauma when the intermediolateral columns are affected.

Sx/Sx: weakness, sensory deficit, homonymous hemianopia, diplopia, or ataxia.

Myelopathic features (unilateral or bilateral long tract signs, sensory level) indicate a lesion in the cervical or thoracic spine 

Anhidrosis is present in central or preganglionic (first or second-order) lesions .

Second-order syndrome Trauma or surgery involving the spinal cord,

thoracic outlet, or lung apex (malignancy). Sx/Sx: Ipsilateral axillary or arm pain Lumbar epidural anesthesia due to

pharmacologic disruption of the preganglionic neuron as it exits the spinal cord (obstetrical procedures) 

Anhidrosis is present in central or preganglionic (first or second-order) lesions .

Third-order syndrome Neck or facial pain presume carotid dissection until proven otherwise.

Emergent diagnostic tests should be obtained Antecedent history of neck trauma. Acute carotid dissection are at

high risk for cerebral infarction, (within the first few weeks or within days), after onset of Horner's syndrome

Causes: Internal carotid artery (dissection, thrombosis), cavernous sinus aneurysm, carotid endarterectomy and carotid artery stenting.

Other lesser causes: neck masses, otitis media, and pathology involving the cavernous sinus. Abnormalities of eye movements (CN VI palsy), commonly occur when the cavernous sinus is involved

Cluster headache - unilateral eye or temple pain and lacrimation (1-2h)

Anhidrosis is NOT a feature of postganglionic/third-order lesions.- SNS responsible for facial sweating and vasodilation branch off at the superior cervical ganglion from the remainder of the oculosympathetic pathway

???What is the recommended testing??

Confirming Horner‘s syndrome before obtaining costly and unnecessary tests is helpful.

Confirmatory topical 10 % cocaine or 0.5 % apraclonidine eyedrops. Cocaine

NE reuptake blocker at the sympathetic nerve synapse. Pupillary dilation in eyes with intact sympathetic innervation.

Cocaine has no effect in eyes with impaired sympathetic innervation, regardless of the lesion location.

Normal pupil dilates more than Horner's pupil, increasing anisocoria (>1 mm or more positive)

Apraclonidine Weak alpha-1 and strong alpha-2 activity; the former mediates pupillary dilation,

while the latter downregulates NE release at the neuromuscular junction In a Horner's pupil, denervation supersensitivity to the alpha-1 receptor will cause

that pupil to dilate (usually by about 2 mm), while alpha-2 stimulation in the normal eye will cause that pupil to constrict slightly (usually by <1 mm).

Thus, apraclonidine instilled in both eyes causes anisocoria reversal. If Horner's syndrome is clear clinically, then avoid cocaine or apraclonidine

drops as their administration will interfere with the hydroxyamphetamine test for localization

Hydroxyamphetamine eye drops Because cocaine may interfere with the uptake and efficacy of

hydroxyamphetamine drops, require 24 to 72 hours between the two tests.

Differentiate between pre- and post- ganglionic Horner's. Pre - first or second order (brainstem /cervical cord and chest /neck) Post - third order (above the superior cervical ganglion at the carotid

bifurcation). Causes NE release from intact adrenergic nerve endings. Pupillary

dilation. After administration, dilation of both pupils indicate a lesion of the 1st or 2nd order neuron (preganglionic). If the smaller pupil fails to dilate it indicates a lesion of the 3rd order (postganglionic).

No pharmacologic test to distinguish between first and second order lesions.

Positive for postganglionic Horner's lesions when the anisocoria increases by at least 1 mm

Neuroimaging Most cases require imaging (MRI), unless obvious trauma or after a surgical

procedure. Neuro findings + positive hydroxyamphetamine test identify high-yield sites of

investigation: Brainstem symptoms

(eg, lateralized weakness or sensory deficit, homonymous hemianopia, diplopia, ataxia) indicate a brain MRI searching for demyelination or tumor

Myelopathic features (ipsilateral or bilateral long tract signs) and/or a sensory level will typically accompany

cervicothoracic lesions. When present, an MRI of the cervical spinal cord is indicated. Pain of the neck or face

Emergent evaluation for carotid artery dissection. An MRI of the neck and magnetic resonance angiography (MRA) will detect most internal carotid artery dissections. Gold standard: conventional angiography

Ophthalmoparesis (CN VI palsy) with no other brainstem signs MRI cavernous sinus.

Preganglionic Horner's syndrome (second-order syndrome) without neurologic symptoms Chest MRI or CT scan to evaluate the lung apex and paravertebral area

???What is the recommended treatment??

Treatment

Dependent on diagnosis When a patient is seen in an emergency department

with acute painful anisocoria highly suggestive of Horner syndrome, it is essential to immediately obtain appropriate investigations to look for a cervical artery dissection, or a cavernous sinus lesion. In this setting, pharmacologic testing would only delay appropriate testing and management.

In our case the patient was started on oral anticoagulants and oral steroids. Spontaneous resolution occurred three months later uponconfirmation with repeat MRI/MRA

??What is the prognosis??

Prognosis Dependent on diagnosis In our case the prognosis of cerebral and cervical artery

dissection is related primarily to the severity of possible associated ischemic stroke or subarachnoid hemorrhage

Morbidity and mortality of acute cervicocephalic arterial dissection varies according to the specific arteries involved and location of the lesion.

Complete or excellent recovery occurs in 70 to 85 percent of patients with extracranial dissection, with major disabling deficits in 10 to 25 percent, and death in 5 to 10 percent of cases

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