What are the etiologies and pathophysiology of Horner syndrome?

Pathophysiology and Etiologies of Horner Syndrome

Anatomical Pathway and Mechanism of Injury

Horner syndrome results from disruption of the three-neuron oculosympathetic pathway extending from the hypothalamus to the eye, with the specific location of damage determining both the etiology and clinical presentation. 1

The sympathetic pathway consists of:

• First-order (central) neurons: Originate in the hypothalamus and descend through the brainstem to synapse in the intermediolateral gray matter of the spinal cord at C8-T2 levels 1, 2

• Second-order (preganglionic) neurons: Exit the spinal cord at T1-T2, ascend through the thorax alongside the lung apex, travel up the cervical sympathetic chain, and synapse at the superior cervical ganglion in the neck 1

• Third-order (postganglionic) neurons: Ascend from the superior cervical ganglion along the internal carotid artery through the cavernous sinus, where they run in close proximity to cranial nerves III, IV, and V1, making them vulnerable to carotid artery pathology and inflammatory processes 1

Major Etiologies by Anatomical Location

First-Order (Central) Lesions

Central lesions cause Horner syndrome accompanied by other neurological deficits:

• Brainstem pathology: Stroke, demyelination, or tumors affecting the hypothalamic-spinal pathway, typically presenting with motor or sensory changes, ataxia, vertigo, dizziness, or nausea 1, 3

• Spinal cord lesions: High cervical or upper thoracic cord pathology at C8-T2 levels 2

Second-Order (Preganglionic) Lesions

Preganglionic lesions are most commonly caused by:

• Thoracic pathology: Pancoast tumors (apical lung tumors), mediastinal masses, or thoracic trauma affecting the sympathetic chain as it exits T1-T2 and ascends through the chest 4, 1

• Cervical trauma or surgery: Disruption of the cervical sympathetic chain 5

• Thoracic disk herniation: T1-T2 intervertebral disk herniation can compress the sympathetic fibers at their origin, though this is rare 2

Third-Order (Postganglionic) Lesions

Postganglionic lesions are the most common type and frequently present with pain or headache:

• Carotid artery dissection: The most critical postganglionic cause, accounting for approximately 2% of all ischemic strokes and up to 15% in younger patients 4, 6. Dissection results from an intimal tear initiating an intramural hematoma that disrupts sympathetic fibers traveling along the carotid artery 6. The classic presentation includes sudden onset of ipsilateral head or neck pain with Horner syndrome, followed by cerebral or retinal ischemia in 50-95% of cases 4, 3, 6

• Cavernous sinus pathology: Aneurysms, thrombosis, or inflammatory processes affecting the internal carotid artery and adjacent sympathetic fibers, often presenting with concurrent cranial nerve palsies (III, IV, VI) 1, 3

• Skull base tumors: Nasopharyngeal carcinoma or other malignancies infiltrating the skull base at the foramen lacerum, encasing the internal carotid artery and potentially invading Meckel's cave, presenting with trigeminal pain and hypoesthesia that can mimic carotid dissection 7

• Cluster headache: Transient postganglionic Horner syndrome during acute cluster headache episodes 5

Associated Conditions and Risk Factors

• Fibromuscular dysplasia (FMD): A nonatherosclerotic, noninflammatory vascular disease causing arterial wall thickening, most common in middle-aged women, with approximately 15% association with carotid dissection 4

• Connective tissue disorders: Various pathological associations increase dissection risk, including bicuspid aortic valve (observed in 1-5% of carotid dissections) 4

• Trauma: Penetrating neck trauma, excessive or sudden neck movement (particularly for vertebral artery dissection), or high-speed motor vehicle accidents 4, 6

Critical Pathophysiological Distinctions

The level of sympathetic pathway disruption determines the pattern of anhidrosis:

• Central and preganglionic lesions cause hemifacial anhidrosis (entire half of face) 8
• Postganglionic lesions cause minimal or absent anhidrosis, as sudomotor fibers branch off earlier in the pathway 8, 5

Carotid dissection pathophysiology creates the characteristic clinical triad: The intimal tear disrupts sympathetic fibers causing ipsilateral Horner syndrome, while luminal narrowing or thromboembolism causes hemispheric ischemia manifesting as contralateral hemiparesis, localizing the lesion to the carotid artery on the side of the Horner syndrome 6

Common Pitfalls

Idiopathic Horner syndrome is a diagnosis of exclusion only after comprehensive workup, as life-threatening causes like carotid dissection must be ruled out urgently, particularly in younger patients presenting with the classic triad of traumatic mechanism, ipsilateral Horner syndrome, and contralateral hemiparesis 3, 6

Postganglionic lesions from skull base tumors can mimic carotid dissection on CT angiography, requiring detailed MRI with careful attention to the skull base to differentiate infiltrative lesions from vascular pathology 7