By aya abbas

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Article topic: Horner’s Syndrome
Authors: Aya Abbas, Aya Merheb.
Editors: Odette El Ghawi, Joseph Akiki
Reviewer: Ethar Hazaimeh

Keywords: Horner’s syndrome, sympathetic, ptosis, miosis, anhidrosis.

Abstract

Horner’s syndrome is a rare neurological disorder characterized by a disruption in the sympathetic nerve pathway, leading to a distinct cluster of clinical signs. These include ptosis (drooping of the upper eyelid), miosis (constricted pupil), and anhidrosis (decreased sweating) on the affected side of the face. The syndrome can arise from lesions along the sympathetic chain, from the hypothalamus to the cervical spinal cord and into the sympathetic fibers running to the eye. Common etiologies include trauma, tumors, carotid artery dissection, or iatrogenic causes following surgical procedures. Diagnosis is typically clinical, supported by pharmacologic testing with agents like apraclonidine or cocaine drops. Treatment focuses on addressing the underlying cause, as the symptoms are generally not life-threatening but may indicate serious pathology. Early detection and management of the primary condition are essential to improving patient outcomes.

Introduction

Horner’s syndrome refers to a rare neurological condition characterized by a triad of ipsilateral miosis (constricted pupil), ptosis (drooping of the upper eyelid), and anhidrosis (absence of sweating), resulting from an oculosympathetic nerve disruption or injury [1]. It is infrequently encountered in clinical practice, with an incidence of approximately 1 in 6,000, and can occur at any age or ethnic group [2].

Damage to the sympathetic nerve fibers, which extend from the hypothalamus to the eye, can occur at three distinct sites and is classified into central, preganglionic, and postganglionic types.

Neuroanatomy

Understanding the oculosympathetic pathway is important to fully understanding the etiology, clinical presentation, and management of Horner’s syndrome.

In this pathway, the first-order (central) neuron originates from the posterolateral hypothalamus and descends through the brainstem to the intermediolateral column of the spinal cord at the level of C8 to T2, which is known as the ciliospinal center of Budge. From the ciliospinal center of Budge in the spinal cord, the second-order sympathetic neurons exit the spinal cord and ascend through the thoracic cavity. These fibers run alongside the apex of the lung and subclavian artery, then synapse at the superior cervical ganglion located at the level of the carotid artery bifurcation. After synapsing at the superior cervical ganglion, the third-order neurons follow the internal carotid artery into the skull, passing through the cavernous sinus. From here, they travel with the ophthalmic division of the trigeminal nerve (cranial nerve V1) to innervate the pupil and eyelid muscles, including the dilator pupillae and Müller’s muscle.s [3].

Figure 1 shows the neuroanatomy of the oculosympathetic pathway [3].

Figure 1: Neuroanatomy of the oculosympathetic pathway [3].

Etiology and pathogenesis

The etiology of Horner’s syndrome is highly dependent on the site of the lesion. The first-order neuron is typically affected by intracranial causes, as reported in the literature [4-6]. These causes include cerebral vascular accidents (CVA), multiple sclerosis, Arnold-Chiari malformation, encephalitis, meningitis, lateral medullary syndrome, syringomyelia, intracranial tumors (such as pituitary or basal skull tumors), spinal trauma above the T2-T3 level, and spinal cord tumors.

Meanwhile, second-order neuron lesions arise from different causes. Trauma or tumors are the most common causes of preganglionic Horner’s syndrome [7,8]. These can result from direct spinal cord damage or tension on the brachial plexus. Surgical trauma and epidural spinal anesthesia are examples of iatrogenic injuries frequently causing damage. Lung and mediastinal malignancies can also affect this neuron, such as in Pancoast syndrome, where a tumor at the apex of the lung causes pain in the arms and shoulders. Therefore, in any patient presenting with new-onset Horner’s syndrome and shoulder or arm discomfort without a history of trauma, the possibility of undetected cancer should be considered.

Lastly, the third-order neuron may be affected by pathologies involving the cavernous sinus, skull base, or internal carotid artery [9]. Lesions can result from carotid artery dissection, cavernous sinus pathology, or cluster headaches.

Clinical presentation and complications

The symptomology of Horner’s syndrome is highly dependent on the location of the lesion in the sympathetic pathway, and the severity depends on the degree of denervation [10].

Ptosis

The sympathetic nerve innervates the superior tarsal muscle, which assists in elevating the upper eyelid. When this muscle is denervated, it leads to ptosis, although it is less pronounced than the ptosis seen in oculomotor nerve (CN III) palsy, which affects the levator palpebrae superioris. The levator palpebrae superioris is primarily responsible for lifting the upper eyelid, while the superior tarsal muscle helps maintain this elevated position. This explains the partial ptosis seen in Horner’s syndrome. Additionally, denervation of the lower eyelid muscle, which functions similarly to the superior tarsal muscle, can cause the lower eyelid to appear slightly elevated [11].

Miosis

The sympathetic autonomic nervous system innervates the pupillary dilator, which consists of radial muscle fibers that dilate the pupil when activated. This results in pupil enlargement during the sympathetic “fight or flight” response. In Horner’s syndrome, the pupillary dilator in one eye loses its sympathetic tone. As a result, the parasympathetic tone to the pupillary sphincter becomes relatively unopposed, causing the pupil in the affected eye to be smaller than that of the opposite eye [12].

Anhidrosis

Anhidrosis refers to the absence of sweating, and its extent depends on the location of the lesion in the sympathetic pathway. When anhidrosis is caused by a first-order neuron lesion, it affects the ipsilateral side of the body, as this corresponds to the area supplied by the sympathetic system from its central origin. In contrast, anhidrosis caused by a second-order neuron lesion primarily affects the ipsilateral face. In cases of third-order neuron (postganglionic) injuries, only a small region of the face is involved, typically near the ipsilateral brow, as this occurs after the vasomotor and sudomotor fibers have branched off [2].

Enophthalmos

Enophthalmos, a posterior displacement of the eyeball within the orbit, is one of the characteristic features of Horner’s syndrome. It is believed to be a result of the paralysis of the smooth muscle within the orbit, particularly the Müller’s muscle, which helps maintain the eyeball’s position. The injury responsible for enophthalmos typically involves the oculosympathetic pathway, where disruption occurs at any point from the hypothalamus down to the sympathetic chain. Although the enophthalmos is usually mild and may not always be easily visible, it contributes to the constellation of signs that help in the clinical diagnosis of Horner’s syndrome.

Workup and Diagnosis

Horner’s syndrome should be suspected in patients exhibiting anisocoria, where both pupils show normal constriction to light but differ in size [13].

Pharmacological tests

Pharmacologic tests are often helpful in confirming Horner’s syndrome, as there are many potential causes of anisocoria and ptosis.

Apraclonidine serves as a diagnostic tool for Horner’s syndrome by leveraging its mechanism of action as a strong α-2 adrenergic agonist and a weak α-1 adrenergic agonist. In Horner’s syndrome, the affected pupil becomes hypersensitive to adrenergic stimulation due to denervation, which leads to an exaggerated dilation of the pupil when exposed to apraclonidine. This reversal of anisocoria is a key indicator of a positive diagnosis [14].

 Cocaine works by blocking the reuptake of noradrenaline at the iris, causing the pupil in a normal eye to dilate. In Horner’s syndrome, due to sympathetic denervation, there is a reduced release of noradrenaline, leading to diminished pupil dilation and thus an increase in anisocoria between the affected and unaffected eyes [15]. Cocaine is often preferred for use in children because apraclonidine can cause central nervous system depression. Additionally, most cases of isolated anisocoria in children are likely physiological and do not necessitate neuroimaging [16].

 The hydroxyamphetamine test induces pupil dilation by releasing norepinephrine from postganglionic nerve endings. In postganglionic Horner’s syndrome, reduced norepinephrine stores result in poor pupil dilation, aiding in the identification of the lesion. However, the test can produce false negatives, particularly in cases such as internal carotid artery (ICA) dissection, which may mislead clinicians [17].

Digital Pupillometry

A study demonstrated that digital pupillometry is an objective and effective tool for diagnosing Horner’s syndrome. It showed high diagnostic accuracy by measuring inter-eye differences in pupil size and dilation lag (T75), which were comparable to the traditional apraclonidine test. This suggests that digital pupillometry can be reliably used to diagnose Horner’s syndrome, potentially offering an alternative to apraclonidine testing [18].

Neuroimaging

After diagnosis, imaging studies such as magnetic resonance imaging (MRI), computed tomography (CT), or ultrasound are performed to identify potential tumors causing the damage [19]. An MRI of the brain or cervicothoracic medulla is effective in identifying the cause of central injuries. If a lesion is suspected in the lung, mediastinum, or ventral neck, a CT scan with contrast is typically sufficient, though an MRI may be necessary if the cervical spine or brachial plexus is involved. MRI angiography is preferred for detecting carotid dissection, particularly near the skull base, as it is more sensitive than CT or ultrasound. Additionally, when Horner’s syndrome is accompanied by weakness in the 3rd, 4th, 5th, or 6th cranial nerves, focused MRI examinations of the cavernous sinus, paratrigeminal area, or orbital apex are recommended [20].

Treatment and Management

Horner’s syndrome does not have a direct treatment. Management is centered on addressing the underlying cause responsible for the syndrome’s symptoms. For instance, if the syndrome is due to an underlying cancer, treatment will focus on diagnosing and managing that specific cancer to alleviate the associated symptoms of Horner’s syndrome [19].

The prognosis

The prognosis of Horner syndrome varies depending on the underlying cause. Early and accurate diagnosis, followed by appropriate evaluation using imaging techniques like MRI or CT scans, is critical for identifying the cause. While some causes are benign, others may be life-threatening. Proper identification of the underlying etiology and timely intervention are essential for improving outcomes. Regular follow-ups are also important to monitor any potential changes in the condition [13].

Recent updates

A recent study suggests that younger patients may have a higher likelihood of developing Horner’s syndrome following an interscalene brachial plexus block, particularly when the procedure is guided by both ultrasound and nerve stimulation. This finding underscores the importance of employing precise techniques to minimize the risk of this complication [21].

Post-thyroidectomy Horner’s syndrome (Tx-HS) is a rare complication associated with thyroid surgery, with a reported prevalence ranging from 0.03% to 5%. Symptoms can appear within hours after surgery, although most cases improve within 2 to 6 months. Management is generally conservative, focusing on monitoring for post-operative complications such as collections. Early diagnosis and the use of precise surgical techniques are essential for achieving better patient outcomes [22].