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Horner Syndrome

Horner syndrome is a condition resulting from an interruption of the sympathetic innervation of the eyes. The syndrome is usually idiopathic Idiopathic Dermatomyositis but can be directly caused by head and neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess trauma, cerebrovascular disease, or a tumor Tumor Inflammation of the CNS. Horner syndrome is classified as 1st-order (central), 2nd-order (preganglionic), or 3rd-order (postganglionic) based on the location of the lesion along the sympathetic pathway. Partial ptosis Ptosis Cranial Nerve Palsies, miosis Miosis Pupil: Physiology and Abnormalities, and facial anhidrosis are the classical signs of Horner syndrome, making up a characteristic triad. Other associated neurologic signs may also be present depending on the location of the lesion and can aid in determining the cause. The syndrome is diagnosed by using cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics, apraclonidine Apraclonidine Glaucoma, or hydroxyamphetamine eye drops. Management of Horner syndrome requires treatment of the underlying condition.

Last updated: 22 Mar, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Horner syndrome, also known as oculosympathetic paresis Paresis A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. ‘general paresis’ and ‘general paralysis’ may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. Spinal Disk Herniation, is a condition resulting from the interruption of the sympathetic innervation to the eyes. The syndrome is characterized by the classic triad of: 

Epidemiology

  • Can affect Affect The feeling-tone accompaniment of an idea or mental representation. It is the most direct psychic derivative of instinct and the psychic representative of the various bodily changes by means of which instincts manifest themselves. Psychiatric Assessment any age, sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria, or ethnicity
  • Frequency: approximately 1 per 6000 individuals

Neuroanatomy

Horner syndrome can result from a lesion anywhere on the 3-neuron sympathetic pathway supplying the eye. The nerve supply starts from the posterolateral hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus and ends as the long ciliary nerves that supply the iris Iris The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers – the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. Eye: Anatomy dilator and Müller muscles (superior tarsal muscle).

  • 1st-order neuron: originates in the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus and descends to the first synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission in the cervical spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy, located at levels C8–T2 (also called the ciliospinal center of Budge).
  • 2nd-order neuron: Preganglionic pupillomotor fibers exit the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy at T1, travel through the brachial plexus Brachial Plexus The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (c5-c8 and T1), but variations are not uncommon. Peripheral Nerve Injuries in the Cervicothoracic Region, over the lung apex, ascending to the superior cervical ganglion located near the angle of the mandible Mandible The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. Jaw and Temporomandibular Joint: Anatomy and the bifurcation of the common carotid artery Common carotid artery The two principal arteries supplying the structures of the head and neck. They ascend in the neck, one on each side, and at the level of the upper border of the thyroid cartilage, each divides into two branches, the external and internal carotid arteries. Carotid Arterial System: Anatomy
  • 3rd-order neuron: Pupillomotor fibers ascend along the internal carotid artery Internal carotid artery Branch of the common carotid artery which supplies the anterior part of the brain, the eye and its appendages, the forehead and nose. Carotid Arterial System: Anatomy and enter the cavernous sinus where it is in close relation with the abducens nerve Abducens nerve The 6th cranial nerve which originates in the abducens nucleus of the pons and sends motor fibers to the lateral rectus muscles of the eye. Damage to the nerve or its nucleus disrupts horizontal eye movement control. The 12 Cranial Nerves: Overview and Functions (cranial nerve (CN) VI). These fibers enter the orbit Orbit The orbit is the cavity of the skull in which the eye and its appendages are situated. The orbit is composed of 7 bones and has a pyramidal shape, with its apex pointed posteromedially. The orbital contents comprise the eye, extraocular muscles, 5 cranial nerves, blood vessels, fat, the lacrimal apparatus, among others. Orbit and Extraocular Muscles: Anatomy with the ophthalmic branch (V1) of the trigeminal nerve Trigeminal nerve The 5th and largest cranial nerve. The trigeminal nerve is a mixed motor and sensory nerve. The larger sensory part forms the ophthalmic, mandibular, and maxillary nerves which carry afferents sensitive to external or internal stimuli from the skin, muscles, and joints of the face and mouth and from the teeth. Most of these fibers originate from cells of the trigeminal ganglion and project to the trigeminal nucleus of the brain stem. The smaller motor part arises from the brain stem trigeminal motor nucleus and innervates the muscles of mastication. The 12 Cranial Nerves: Overview and Functions (CN V) via the long ciliary nerves, which innervate the iris Iris The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers – the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. Eye: Anatomy dilator and Müller muscles.
Sympathetic pathway of eye

Sympathetic pathway of the eye

Image by Lecturio. License: CC BY-NC-SA 4.0

Classification

  • 1st-order, or central, Horner syndrome: caused by lesions of the sympathetic tracts in the brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem: Anatomy or cervicothoracic spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy
  • 2nd-order, or preganglionic, Horner syndrome: caused by lesions that involve the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy, thoracic outlet Thoracic Outlet Thoracic Outlet Syndrome, or lung apex. These lesions are usually acquired through trauma, surgery, or malignancy Malignancy Hemothorax (e.g., Pancoast tumor Pancoast Tumor Thoracic Outlet Syndrome).
  • 3rd-order, or postganglionic, Horner syndrome: caused by lesions of the internal carotid artery Internal carotid artery Branch of the common carotid artery which supplies the anterior part of the brain, the eye and its appendages, the forehead and nose. Carotid Arterial System: Anatomy, such as arterial dissection Arterial dissection Arterial dissection is a violation of the structural integrity of the arterial wall that results in blood accumulating between the layers. Dissection of the Carotid and Vertebral Arteries, thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus, cavernous sinus aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms, or injuries acquired during carotid artery stenting

Etiology

Most cases of Horner syndrome are idiopathic Idiopathic Dermatomyositis. Of the identified causes, the etiology depends on the location of the lesion. The causes vary between adult and pediatric populations. 

1st-order syndrome (central)

  • Hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus:
  • Brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem: Anatomy:
  • Spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy:
    • Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess trauma 
    • Pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types tumor Tumor Inflammation
    • Myelitis Myelitis Inflammation of the spinal cord. Relatively common etiologies include infections; autoimmune diseases; spinal cord; and ischemia. Clinical features generally include weakness, sensory loss, localized pain, incontinence, and other signs of autonomic dysfunction. Relapsing Fever
    • Syringomyelia Syringomyelia Longitudinal cavities in the spinal cord, most often in the cervical region, which may extend for multiple spinal levels. The cavities are lined by dense, gliogenous tissue and may be associated with spinal cord neoplasms; spinal cord traumatic injuries; and vascular malformations. Syringomyelia is marked clinically by pain and paresthesia, muscular atrophy of the hands, and analgesia with thermoanesthesia of the hands and arms, but with the tactile sense preserved (sensory dissociation). Lower extremity spasticity and incontinence may also develop. Central Cord Syndrome
    • Demyelination Demyelination Multiple Sclerosis (e.g., multiple sclerosis Multiple Sclerosis Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. Multiple Sclerosis)
    • Arteriovenous malformation Arteriovenous malformation Abnormal formation of blood vessels that shunt arterial blood directly into veins without passing through the capillaries. They usually are crooked, dilated, and with thick vessel walls. A common type is the congenital arteriovenous fistula. The lack of blood flow and oxygen in the capillaries can lead to tissue damage in the affected areas. Erysipelas (AVM)
    • Infarction
  • Arnold-Chiari malformation
  • Encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis

2nd-order syndrome (preganglionic)

  • Apical lung tumor Tumor Inflammation (e.g., Pancoast tumor Pancoast Tumor Thoracic Outlet Syndrome)
  • Subclavian artery lesions
  • Mediastinal tumors
  • Cervical rib
  • Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy malignancies
  • Birth trauma with injury to lower brachial plexus Brachial Plexus The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (c5-c8 and T1), but variations are not uncommon. Peripheral Nerve Injuries in the Cervicothoracic Region
  • Mandibular tooth abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
  • Lesions of the middle ear Middle ear The space and structures directly internal to the tympanic membrane and external to the inner ear (labyrinth). Its major components include the auditory ossicles and the eustachian tube that connects the cavity of middle ear (tympanic cavity) to the upper part of the throat. Acute Otitis Media (e.g., acute otitis media Acute Otitis Media Acute otitis media is an infection in the middle ear characterized by mucosal inflammation and retention of fluid. The most common pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The condition can present with fever, otalgia, and diminished hearing. Acute Otitis Media)
  • Iatrogenic Iatrogenic Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment. Anterior Cord Syndrome (e.g., central venous catheterization, chest tube placement Tube placement Surgical procedure involving the creation of an opening (stoma) into the chest cavity for drainage; used in the treatment of pleural effusion; pneumothorax; hemothorax; and empyema. Thoracic Surgery, thoracic surgery Thoracic Surgery Basic surgical intervention in the thoracic cavity has the primary goal of alleviating any malady that mechanically affects the function of the heart and lungs, which can be secondary to underlying pathologies or, most commonly, trauma. Interventions include tube thoracostomy, thoracentesis, and emergency thoracotomy. Thoracic Surgery)

3rd-order syndrome (postganglionic)

  • Internal carotid artery dissection Internal Carotid Artery Dissection The splitting of the vessel wall in one or both (left and right) internal carotid arteries. Interstitial hemorrhage into the media of the vessel wall can lead to occlusion of the internal carotid artery and aneurysm formation. Cranial Nerve Palsies
  • Carotid cavernous fistula Fistula Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. Anal Fistula
  • Trauma
  • Herpes zoster Herpes Zoster Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Shingles (also known as herpes zoster) is more common in adults and occurs due to the reactivation of VZV. Varicella-Zoster Virus/Chickenpox
  • Nasopharyngeal carcinoma Nasopharyngeal carcinoma A carcinoma that originates in the epithelium of the nasopharynx and includes four subtypes: keratinizing squamous cell, non-keratinizing, basaloid squamous cell, and papillary adenocarcinoma. It is most prevalent in southeast Asian populations and is associated with Epstein-Barr virus infections. Somatic mutations associated with this cancer have been identified in npcr, bap1, ubap1, ErbB2, ErbB3, mll2, pik3ca, kras, nras, and arid1a genes. Epstein-Barr Virus, lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum
  • Cluster or migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess

Etiology of Horner syndrome in children

  • Congenital Congenital Chorioretinitis (diagnosed 4 weeks after birth):
    • Trauma to the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess and brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem: Anatomy during birth
    • Congenital Congenital Chorioretinitis infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • Neuroblastoma Neuroblastoma Neuroblastoma is a malignancy that arises from the neural crest cell derivatives along the sympathetic chain (neuroblasts) and is most commonly located in the adrenal medulla. The tumor often presents in childhood with a flank mass that crosses the midline. Neuroblastoma
    • Idiopathic Idiopathic Dermatomyositis
  • Acquired:
    • Neuroblastoma Neuroblastoma Neuroblastoma is a malignancy that arises from the neural crest cell derivatives along the sympathetic chain (neuroblasts) and is most commonly located in the adrenal medulla. The tumor often presents in childhood with a flank mass that crosses the midline. Neuroblastoma
    • Rhabdomyosarcoma
    • Brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem: Anatomy AVMs
    • Brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem: Anatomy tumors (glioma)
    • Demyelination Demyelination Multiple Sclerosis ( brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem: Anatomy)
    • Carotid artery thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus
    • Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess trauma
    • Postsurgical (e.g., after jugular cannulation, thoracic surgery Thoracic Surgery Basic surgical intervention in the thoracic cavity has the primary goal of alleviating any malady that mechanically affects the function of the heart and lungs, which can be secondary to underlying pathologies or, most commonly, trauma. Interventions include tube thoracostomy, thoracentesis, and emergency thoracotomy. Thoracic Surgery, or neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess surgery)

Pathophysiology

Horner syndrome is the result of the disruption of the sympathetic supply to the eye. The symptoms depend on the location of the lesion, and the severity depends on the severity of denervation. 

  • Denervation of the nerves that supply the Müller muscle (superior tarsal muscle) causes ptosis Ptosis Cranial Nerve Palsies. Partial ptosis Ptosis Cranial Nerve Palsies can occur because the levator palpebrae superioris Levator palpebrae superioris Orbit and Extraocular Muscles: Anatomy muscle is unaffected.
  • Denervation of the nerves that supply the iris Iris The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers – the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. Eye: Anatomy dilator muscle causes miosis Miosis Pupil: Physiology and Abnormalities of the affected side: 
    • Upon exam, anisocoria Anisocoria Unequal pupil size, which may represent a benign physiologic variant or a manifestation of disease. Pathologic anisocoria reflects an abnormality in the musculature of the iris (iris diseases) or in the parasympathetic or sympathetic pathways that innervate the pupil. Physiologic anisocoria refers to an asymmetry of pupil diameter, usually less than 2mm, that is not associated with disease. Pupil: Physiology and Abnormalities and a lag of pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities dilation can be seen. 
    • The light and accommodation Accommodation Refractive Errors pupillary reflexes remain normal. 
  • Denervation of the nerves that supply the facial sweat glands Sweat glands Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. Soft Tissue Abscess causes anhidrosis:
    • Depends on the degree of disruption of the sympathetic supply
    • Seen in 1st- or 2nd-order lesions, but not a prominent feature of 3rd-order lesions

Clinical Presentation

  • Classic triad of Horner syndrome: 
  • Ocular signs:
    • Pupils: 
      • Miosis Miosis Pupil: Physiology and Abnormalities on the affected side
      • Anisocoria Anisocoria Unequal pupil size, which may represent a benign physiologic variant or a manifestation of disease. Pathologic anisocoria reflects an abnormality in the musculature of the iris (iris diseases) or in the parasympathetic or sympathetic pathways that innervate the pupil. Physiologic anisocoria refers to an asymmetry of pupil diameter, usually less than 2mm, that is not associated with disease. Pupil: Physiology and Abnormalities (difference in the pupillary size) that is more prominent in the dark.
      • Dilation lag (the constricted pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities takes 15–20 seconds longer to dilate when a light source is moved away from the eye.)
    • Eyelids Eyelids Each of the upper and lower folds of skin which cover the eye when closed. Blepharitis:
      • Mild (< 2 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma) ptosis Ptosis Cranial Nerve Palsies of the upper eyelid
      • Inverse ptosis Ptosis Cranial Nerve Palsies of the lower eyelid (lower lid rests at a higher level than normal) 
      • Combined: decreased palpebral aperture compared to the other eye
    • Extraocular movements may be affected in lesions of the brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem: Anatomy or the cavernous sinus.
  • Associated neurologic signs:
    • Signs of brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem: Anatomy lesions:
      • Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia
      • Diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis
      • Lateralized weakness
      • Vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo
    • Signs of spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy (myelopathic) lesions:
    • Brachial plexopathy Plexopathy Neuropathy is a nerve pathology presenting with sensory, motor, or autonomic impairment secondary to dysfunction of the affected nerve. The peripheral nerves are derived from several plexuses, with the brachial and lumbosacral plexuses supplying the major innervation to the extremities. Mononeuropathy (affecting a single nerve) and plexopathy (affecting the plexus) can occur from trauma, compression, and systemic diseases. Mononeuropathy and Plexopathy: pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and weakness in the arm Arm The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm: Anatomy or hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy
    • Cranial neuropathy Neuropathy Leprosy 
  • In infants and children, the Harlequin sign (facial flushing) is more apparent than anhidrosis. 
  • Iris Iris The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers – the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. Eye: Anatomy heterochromia (different-colored irides) may be seen in children with congenital Congenital Chorioretinitis Horner syndrome. In these cases, the affected eye has a lighter color. 
Horner syndrome

Right-sided miosis Miosis Pupil: Physiology and Abnormalities and ptosis Ptosis Cranial Nerve Palsies suggestive of Horner syndrome

Image: “Myosis and eyelid ptosis Ptosis Cranial Nerve Palsies were noted on the right side” by Case Reports in Endocrinology. License: CC BY 4.0

Diagnosis and Management

Clinical diagnosis

  • Horner syndrome is clinically diagnosed by the presence of ptosis Ptosis Cranial Nerve Palsies and dilation lag in the affected eye. 
  • Anhidrosis is also usually observed on the same side as the affected eye but is not necessary for diagnosis. 
  • Painful acute anisocoria Anisocoria Unequal pupil size, which may represent a benign physiologic variant or a manifestation of disease. Pathologic anisocoria reflects an abnormality in the musculature of the iris (iris diseases) or in the parasympathetic or sympathetic pathways that innervate the pupil. Physiologic anisocoria refers to an asymmetry of pupil diameter, usually less than 2mm, that is not associated with disease. Pupil: Physiology and Abnormalities is highly suggestive of Horner syndrome. 

Pharmacologic tests

  • Topical cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics can be used to confirm the diagnosis of Horner syndrome:
    • Cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics blocks reuptake of norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS from the synaptic cleft Synaptic cleft Synapses and Neurotransmission and will cause dilation of the pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities in case of an intact sympathetic pathway. Cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics has no effect on eyes with impaired sympathetic innervation.
    • 1 hour after the application of 2 drops of 10% cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics, a normal pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities dilates more than the Horner pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities, increasing the degree of anisocoria Anisocoria Unequal pupil size, which may represent a benign physiologic variant or a manifestation of disease. Pathologic anisocoria reflects an abnormality in the musculature of the iris (iris diseases) or in the parasympathetic or sympathetic pathways that innervate the pupil. Physiologic anisocoria refers to an asymmetry of pupil diameter, usually less than 2mm, that is not associated with disease. Pupil: Physiology and Abnormalities.
    • Anisocoria Anisocoria Unequal pupil size, which may represent a benign physiologic variant or a manifestation of disease. Pathologic anisocoria reflects an abnormality in the musculature of the iris (iris diseases) or in the parasympathetic or sympathetic pathways that innervate the pupil. Physiologic anisocoria refers to an asymmetry of pupil diameter, usually less than 2mm, that is not associated with disease. Pupil: Physiology and Abnormalities ≥ 1 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma after cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics administration is considered a positive result.
  • Topical apraclonidine Apraclonidine Glaucoma is used as an alternative agent to confirm Horner syndrome: 
    • An α-adrenergic agonist that causes pupillary dilation in the Horner pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities and mild pupillary constriction in the normal eye by down-regulating norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS
    • A reversal of anisocoria Anisocoria Unequal pupil size, which may represent a benign physiologic variant or a manifestation of disease. Pathologic anisocoria reflects an abnormality in the musculature of the iris (iris diseases) or in the parasympathetic or sympathetic pathways that innervate the pupil. Physiologic anisocoria refers to an asymmetry of pupil diameter, usually less than 2mm, that is not associated with disease. Pupil: Physiology and Abnormalities after the application of 2 drops of 0.5% apraclonidine Apraclonidine Glaucoma is suggestive of Horner syndrome.
    • Apraclonidine Apraclonidine Glaucoma should not be used in infants.
  • Topical hydroxyamphetamine is used to differentiate 1st-order and 2nd-order Horner syndrome: 
    • Hydroxyamphetamine causes a release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS from intact adrenergic nerve endings, causing pupillary dilation.
    • 1 hour after the application of 1% hydroxyamphetamine eye drops, dilation of both pupils indicates a lesion of the 1st- or 2nd-order neuron. 
    • If the miotic pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities fails to dilate, it indicates a 3rd-order Horner syndrome.
    • Pholedrine can be used as an alternative to hydroxyamphetamine. The test is performed using 1% pholedrine.

Imaging

  • Imaging is used in conjunction with medical tests to confirm the etiology and locate the site of the lesion.
  • MRI of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy is indicated in cases with signs indicative of spinal lesions. 
  • Head CT is also advised in cases of Horner syndrome with a history of or clinical signs suggesting stroke. 
  • Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests followed by a CT scan must be performed in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship when pulmonary malignancy Malignancy Hemothorax is suspected. 

Management

  • Depends on the underlying cause
  • Prompt recognition of the condition and diagnosis of the underlying etiology is necessary to reduce worsening of the condition. 
  • The acute painful onset of Horner syndrome should be considered a medical emergency, as it might indicate a carotid artery dissection Carotid artery dissection The splitting of the vessel wall in one or both (left and right) internal carotid arteries. Interstitial hemorrhage into the media of the vessel wall can lead to occlusion of the internal carotid artery and aneurysm formation. Dissection of the Carotid and Vertebral Arteries.
  • Vascular surgical care is necessary in cases of carotid artery dissection Carotid artery dissection The splitting of the vessel wall in one or both (left and right) internal carotid arteries. Interstitial hemorrhage into the media of the vessel wall can lead to occlusion of the internal carotid artery and aneurysm formation. Dissection of the Carotid and Vertebral Arteries
  • Neurosurgical care should be provided in cases of Horner syndrome related to aneurysms. 

Differential Diagnosis

  • Adie pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities: disorder of parasympathetic denervation of the pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities that results in poor light constriction but better accommodation Accommodation Refractive Errors. Adie pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities is mostly idiopathic Idiopathic Dermatomyositis. The affected pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities initially appears abnormally dilated at rest and has a poor pupillary constriction in bright light. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship complain of difficulty adapting to dark conditions and photophobia Photophobia Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. Migraine Headache. No treatment is required, but topical physostigmine Physostigmine A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. Cholinomimetic Drugs may provide relief. 
  • Argyll-Robertson pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities: characterized by small and irregular pupils that constrict briskly to near targets but react with little to no constriction to light. Argyll-Robertson pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil’s size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Pupil: Physiology and Abnormalities is frequently associated with iris Iris The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers – the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. Eye: Anatomy atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation and is a highly specific sign of neurosyphilis Neurosyphilis Infections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils. Syphilis and is treated by managing the underlying cause. 
  • Chronic anterior uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea: condition that affects the anterior uvea Uvea The pigmented vascular coat of the eyeball, consisting of the choroid; ciliary body; and iris, which are continuous with each other. Eye: Anatomy, iris Iris The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers – the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. Eye: Anatomy, and ciliary body Ciliary body A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. Eye: Anatomy. The symptoms of uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea are pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, redness Redness Inflammation, and photophobia Photophobia Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. Migraine Headache. The symptoms respond well to antiinflammatory drugs. Chronic anterior uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea occurs in association with other chronic inflammatory conditions. 
  • Pupillary sphincter tear: occurs because of trauma and can cause unilateral or bilateral mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship report glare, haloes in brightly lit conditions, and trouble reading. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with atonic, mydriatic pupils report worse glare at night and inability to focus Focus Area of enhancement measuring < 5 mm in diameter Imaging of the Breast on near objects. The tear requires surgical repair. 
  • Aponeurotic ptosis Ptosis Cranial Nerve Palsies: most common type of acquired ptosis Ptosis Cranial Nerve Palsies. Aponeurotic ptosis Ptosis Cranial Nerve Palsies occurs because of outstretching of the levator muscle and is usually seen in elderly patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship usually present with asymmetrical ptosis Ptosis Cranial Nerve Palsies or partial vision Vision Ophthalmic Exam loss. Surgical treatment is required. 
  • Ocular myasthenia: ocular representation of myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis. Ocular myasthenia results in ocular muscle fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia and weakness. In myasthenia, antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions that block the acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors are produced, resulting in muscle fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia and paralysis in some cases. Diagnosis relies on an edrophonium Edrophonium A rapid-onset, short-acting cholinesterase inhibitor used in cardiac arrhythmias and in the diagnosis of myasthenia gravis. It has also been used as an antidote to curare principles. Myasthenia Gravis sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia test. Treatment involves anticholinesterase agents. 

References

  1. Kedar, S., Biousse, V., Newman, N.J. (2018). Horner syndrome. UpToDate. Retrieved June 24, 2021, from https://www.uptodate.com/contents/horner-syndrome
  2. Khan, Z., Bollu, P.C. (2021). Horner syndrome. StatPearls. Retrieved June 24, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK500000/
  3. Bardorf, C.M. (2019). Horner syndrome. Emedicine. Retrieved June 24, 2021, from https://emedicine.medscape.com/article/1220091
  4. Kanagalingam, S., Miller, N.R. (2015). Horner syndrome: clinical perspectives. Eye and Brain 2015:35–46. https://doi.org/10.2147/EB.S63633 

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