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Nervous system

Horner’s syndrome

Clinical signs, classically of ipsilateral ptosis, pupillary miosis, and facial anhidrosis secondary to the interruption of the oculosympathetic pathway.

Clinical signs, classically of ipsilateral ptosis, pupillary miosis, and facial anhidrosis secondary to the interruption of the oculosympathetic pathway.

History:

The Swiss doctor Johan Friedrich Horner (1831 – 86) described in 1869 a 40-year-old woman who had a headache and who was red, dry and hot in the right half of the face. It seemed as if her right eye was a little sunken and in addition she had slightly drooping eyelids and anisokoria with the least pupil on this side. Horner concluded that the symptom complex must be due to a paralysis of the sympathetic fibres on the neck. This immortalized his name, but it should be mentioned that the French physiologist Claude Bernard (1813 – 1878) had already in 1852 described a similar syndrome in guinea pigs that were cut over sympathetic fibers on the neck, and that Silas Weir Mitchell (1829 – 1914) in 1864 described an isolated Horner triad in a 24-year-old soldier with a gunshot wound to the neck.

Johann Friedrich Horner
Johann Friedrich Horner (27 March 1831 – 20 December 1886) was an ophthalmologist based at the University of Zurich, Switzerland. Horner’s syndrome, a disorder of the sympathetic nervous system, was named after him following his description of the condition in 1869. His name is also associated with “Horner’s muscle”, the lacrimal portion of the orbicularis oculi muscle that is sometimes referred to as the “tensor tarsi muscle”. With Alexios Trantas (1867–1960), the “Horner-Trantas spots” are named, being defined as small whitish-yellow chalky concretions of the conjunctiva around the corneal limbus.

Anatomy

Oculosympathetic pathway:

Anatomy of the oculosympathetic pathway
Anatomy of the oculosympathetic pathway: Sympathetic fibers in the posterolateral hypothalamus pass through the lateral brain stem and to the ciliospinal center of Budge and Waller in the intermediolateral gray column of the spinal cord at C8–T1. Preganglionic sympathetic neurons exit from the ciliospinal center of Budge and Waller and pass across the pulmonary apex and ascend up the carotid sheath to the superior cervical ganglion. The postganglionic sympathetic neurons originate in the superior cervical ganglion and travel up the wall of the internal carotid artery. Once the fibers reach the cavernous sinus, they travel with the abducens nerve before joining the ophthalmic division of the trigeminal nerve and entering the orbit with its nasociliary branch. From here, they divide into two long ciliary nerves to reach the iris dilator muscle. | Glaser JS, editor. Neuro-ophthalmology. 1st ed. Hagerstown MD, USA: Harper & Row; 1978.

Etiopathogenesis

Horner syndrome
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Central (1st-order neuron) Horner syndrome:

1st-order neurons are located in the posterolateral hypothalamus, and from there, sympathetic fibers pass through the lateral brain stem and extend to the ciliospinal center of Budge & Waller in the intermediolateral gray column of the spinal cord at C8–T1
  • Central Horner syndrome caused by damage to any of these structures is ipsilateral to the lesion:
    • Pontine haemorrhage
    • Lateral medullary syndrome
    • Spinal cord lesion above T1 (eg, Brown-Séquard syndrome, late-stage syringomyelia)
  • C/F: Anhidrosis of face, arm and trunk
First-order neuron lesions on MRI
Examples of first-order neuron lesions on magnetic resonance imaging (MRI). (a) Axial T2-weighted image of a hypothalamic inflammatory lesion (white arrow), (b) axial T2-weighted image of a right pontine cavernoma (white arrow), (c) diffusion-weighted imaging demonstrating restriction in a lateral medullary infarct (white arrow), and (d) corresponding subtracted 3D maximum-intensity projection time-of-flight (TOF) magnetic resonance angiogram (MRA) showing absence of signal in the V3 and V4 segments of the left vertebral artery (white arrow) from arterial dissection resulting in the left posterior inferior cerebellar artery (PICA) infarct seen in (c). Sagittal cervical spine T2-weighted acquisitions demonstrating (e) multiple intramedullary demyelinating lesions (white arrowheads) in a patient with multiple sclerosis and (f) a Chiari I malformation causing crowding at the craniocervical junction (white arrow) and an extensive syringomyelia. | Davagnanam, I., Fraser, C. L., Miszkiel, K., Daniel, C. S., & Plant, G. T. (2013). Adult Horner’s syndrome: a combined clinical, pharmacological, and imaging algorithm. Eye (London, England), 27(3), 291–298. https://doi.org/10.1038/eye.2012.281

Preganglionic (2nd-order neuron) Horner syndrome:

Preganglionic (2nd-order) sympathetic neurons exit from the ciliospinal center of Budge and Waller and pass across the pulmonary apex. They then ascend through the stellate ganglion and up the carotid sheath to synapse at the superior cervical ganglion, located at the level of the bifurcation of the common carotid artery and the angle of the jaw.
  • eg. Pancoast tumour (Bronchogenic carcinoma of the superior fissure on apex of lung)
  • C/F: Anhidrosis of face
Second-order neuron lesions on CT angiography (CTA)
Examples of second-order neuron lesions on computed tomographic angiography (CTA): (a) Axial image of multiple enhancing nodules within the thyroid gland (white arrows), (b) coronal reformatted image of multiple enlarged enhancing jugular chain lymph nodes in a patient with known disseminated carcinoma (white arrows), (c) axial image on lung windows showing a left apical bronchogenic carcinoma/Pancoast tumour (black arrow), and (d) coronal reformatted image on bone windows demonstrating bilateral cervical ribs (white arrows).Davagnanam, I., Fraser, C. L., Miszkiel, K., Daniel, C. S., & Plant, G. T. (2013). Adult Horner’s syndrome: a combined clinical, pharmacological, and imaging algorithm. Eye (London, England), 27(3), 291–298. https://doi.org/10.1038/eye.2012.281

Postganglionic (3rd-order neuron) Horner syndrome:

Postganglionic (3rd-order) sympathetic neurons originate in the superior cervical ganglion, travel in the wall of the internal carotid artery, and continue on to the cavernous sinus. Within the cavernous sinus, the fibers briefly travel with the abducens nerve before joining the ophthalmic division of the trigeminal nerve and entering the orbit with its nasociliary branch (Figure 3A and B). The sympathetic fibers in the nasociliary nerve divide into the two long ciliary nerves that travel with the lateral and medial suprachoroidal vascular bundles to reach the anterior segment of the eye and innervate the iris dilator muscle.
  • eg. Carotid dissection (painful)
  • C/F: No anhidrosis
Oculosympathetic fibers
(A) Cadaver dissection showing oculosympathetic fibers (S) attaching (lower arrow) to the abducens nerve (VI) within the cavernous sinus. After running with the nerve for a short distance, they separate from the nerve (upper arrow) and join with the first division of the trigeminal nerve (V1) to enter the orbit. | Notes: II, optic nerve; III, oculomotor nerve; V, trigeminal ganglion. | Copyright © 1978 Wiley-Liss, Inc. Parkinson D, Johnston J, Chaudhuri A. Sympathetic connections to the fifth and sixth cranial nerves. Anat Rec. Wiley Publishers. 1978;191:221–226.49 || (B) Artist’s drawing showing that the post-ganglionic oculosympathetic fibers briefly travel with the abducens nerve (VI) before joining the ophthalmic division (V1) of the trigeminal nerve. Thereafter, the sympathetic fibers enter the orbit with its nasociliary branch. | Copyright © 2005, Lippincott Williams. Adapted with permission from Kardon R. Anatomy and physiology of the autonomic nervous system. In: Miller NR, Biousse V, Kerrison JB, editors. Walsh and Hoyt’s Clinical Neuro-Ophthalmology. 6th ed. Baltimore, MD, USA: Lippincott-Williams & Wilkins; 2005.134

Bilateral Horner syndrome:

Associated systemic disorders:
  • Diabetic autonomic neuropathy
  • Amyloidosis
  • Pure autonomic failure
  • Anderson-Fabry disease
  • Familial dysautonomia
  • Paraneoplastic syndrome

Presentation

Classic Horner’s syndrome triad:

  1. Ptosis (slight drooping of eyelid: muller muscle palsy)
  2. Anhidrosis (absence of sweating) and flushing of affected side of face
  3. Miosis (pupil constriction)
A 74-year-old buffoon presenting with Horner's syndrome
Right Horner syndrome in a 74-year-old buffoon. Note right-sided upper lid ptosis, right miosis, and “upside-down” ptosis (ie, elevation) of the right lower lid. | Image courtesy: S Bhimji MD

Other features:

  • Upside down ptosis
  • Ocular hypotony
  • Conjunctival hyperemia
  • Enophthalmos (sunken eyeball)
  • Hypochromic heterochromia iridis (lighter colored iris in abnormal eye; seen only in congenital Horner’s syndrome)
  • Inferior eyelid elevation (inferior tarsal muscle palsy)

Diagnosis

Topical cocaine test: Diagnosis

Cocaine acts an indirect sympathomimetic inhibiting the reuptake of norepinephrine from the synaptic cleft. Cocaine solution (ranging from 2% to 10%) is instilled into both eyes. Both eyes are evaluated after at least 30 or more minutes for an optimal response. Denervation in the affected eye causes it to dilate poorly compared to the normal one. Anisocoria of 0.8 mm or more is considered diagnostic.
  • Detect presence of HS
  • The test does not help in identifying the level of lesion.
Cocaine Testing for Horner Syndrome
Cocaine Testing for Horner Syndrome: (A) Right Horner syndrome in a 72-year-old man. Note right ptosis and anisocoria with the smaller pupil on the right side. Both pupils reacted briskly to light stimulation. (B) After topical administration of 10% cocaine drops in both eyes, there is marked dilation of the left pupil but the right pupil dilates only very slightly. This response indicates that the patient has a right Horner syndrome. | Kanagalingam, S., & Miller, N. R. (2015). Horner syndrome: clinical perspectives. Eye and Brain, 7, 35–46. https://doi.org/10.2147/EB.S63633

Topical hydroxy-amphetamine/adrenaline test: Localization

Two drops of 1% hydroxyamphetamine solution are instilled into both eyes. The affected eye (third-order lesion) will not dilate as well as the normal eye. While in the case of intact postganglionic fibers (first and second-order lesions), the affected pupil dilates to an equal or greater extent.
  • Localization of the lesion (hydroxyamphetamine stimulates the release of stored norepinephrine from the postganglionic terminals into the synapse. Postganglionic third-order lesions can be differentiated from presynaptic second-order or first-order ones.)

Topical apraclonidine test:

TEST OF CHOICE due to good sensitivity and overall practicality. Apraclonidine acts as a weak α1-agonist and strong α2-agonist. It is categorized as an ocular hypotensive agent. The upregulation of α1-receptors in Horner syndrome translates into an exaggerated response of the iris dilators (denervation supersensitivity) to an agonist agent like apraclonidine. A 0.5-1% solution is instilled in both eyes. The affected eye will show mydriasis, while the normal eye is predominantly insensitive. Consequent instillation of the solution results in evident reversal of anisocoria (the affected pupil dilates and the normal pupil constricts). This is because of the stronger α2-agonist activity of compared to the weaker α1-agonist activity of apraclonidine.
Apraclonidine Testing for Horner Syndrome
Apraclonidine Testing for Horner Syndrome: (A) Left Horner syndrome in a 25-year-old man. Note left ptosis and anisocoria with the smaller pupil on the left. Both pupils reacted briskly to light stimulation. (B) Forty-five minutes after topical instillation of 1% apraclonidine in both eyes, there is reversal of anisocoria, with the right pupil now smaller than the left. Note also improvement in the left-sided ptosis. | Kanagalingam, S., & Miller, N. R. (2015). Horner syndrome: clinical perspectives. Eye and Brain, 7, 35–46. https://doi.org/10.2147/EB.S63633

Differential diagnosis:

  • Physiological anisocoria (in 20% of the normal population)
  • Pathological anisocoria: Tonic pupil, Argyll Robertson pupils, pharmacologic pupillary blockade, oculomotor nerve palsy, ocular surgery, and iris atrophy (following inflammation/trauma)

Management

Treatment options are based on the diagnosis and management of the underlying cause.

Fasanella-Servat operation:

Tarso-conjunctivo-mullerectomy: Retraction of muller’s muscle
Fasanella–Servat operation
The Fasanella–Servat operation is one of the simplest operations for ptosis and is used mainly in mild to moderate blepharoptosis with good levator function. It can correct up to 2 mm of congenital ptosis and 2.5–4 mm of acquired ptosis. Since its creation in 1961, the operation has become more refined. Many of its modifications have been oriented at increasing the amount of correction of ptosis, secure a proper contour, and preventing ocular surface abrasions. Proper patient selection is fundamental for its effectiveness. | Servat J. (2018) Tarsal–Conjunctival–Müller’s Muscle Resection (Fasanella–Servat Operation). In: Levine M., Allen R. (eds) Manual of Oculoplastic Surgery. Springer, Cham. https://doi.org/10.1007/978-3-319-74512-1_21

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