Ophthalmic Case Presentations:   Case #1

Two Cases of Unilateral Ptosis with Headache
 

Patient #1

Differential Diagnosis and Discussion:

Case 1: The findings in this patient are consistent with a partial peripheral 3rd cranial nerve palsy. Findings in a complete peripheral 3rd nerve palsy would include a fixed and dilated pupil, severe ptosis, and an eye turned outward and downward (due to the unopposed action of the lateral rectus and superior oblique muscles). In this case, there is residual pupillary and muscle function.


3rd Cranial Nerve Anatomy:  The 3rd cranial nerve originates from the rostral midbrain, coursing ventrally through the red nucleus and ipsilateral corticospinal tract. The nerve enters the subarachnoid space, passes between the posterior cerebral and superior cerebellar arteries, and lies medial to the posterior communicating artery. The nerve traverses the superolateral aspect of the cavernous sinus, and enters the orbit through the superior orbital fissure, branching into a superior and inferior branch. Pupillary fibers lie superficially in the nerve, and thus are subject to dysfunction from compression early.

In the evaluation of a 3rd cranial nerve palsy, it is important to determine:

• Involvement of the pupil.

• Involvement of other cranial nerves.

• Other neurological problems such as ataxia or hemiparesis.

Microvascular Infarct (Pupil sparing 3rd nerve palsy):

A pupil sparing 3rd nerve palsy in an older patient (over 55) with a history of diabetes or hypertension is commonly due to ischemic demyelination of the nerve. Headache or pain is common, and the palsy generally resolves over 3-4 months. MRI is indicated in atypical or non-resolving cases, or if the pupil becomes involved.


Compressive Lesions (Pupil involving 3rd nerve palsy, or partial 3rd nerve palsy with some pupil involvement):

The 3rd cranial nerve is subject to compressive injury at a variety of sites along its course:

• Subarachnoid Space Compression:

  • Supratentorial mass with herniation of the uncus - "Hutchinson's Sign" refers to a fixed, dilated pupil in this setting.

  • Aneurysm, most commonly of the posterior communication artery. Neurological consultation and urgent neuroimaging are required. MRI, MRA, and CT may miss aneurysms less than 5mm in diameter, thus arteriography may be appropriate.

  • Subarachnoid hemorrhage - often presenting with severe headache and photophobia.
     

• Meningeal Inflammation:

• Infectious meningitis

• Sarcoidosis

• Meningeal carcinomatosis

• Lymphoma

3rd Nerve Palsy with Neurological Findings:

As the third cranial nerve passes through the brainstem, vascular disease or compression from tumor may lead to involvement of brainstem structures as well as the 3rd cranial nerve. Specific named syndromes include:

• Weber's Syndrome - ipsilateral 3rd nerve paresis and contralateral hemiparesis due to involvement of the pyramidal tract

• Benedikt's Syndrome - ipsilateral 3rd nerve paresis and contralateral hemitremor, due to involvement of the red nucleus

• Nothnagel's Syndrome - ipsilateral 3rd nerve paresis and cerebellar ataxia, due to involvement of the superior cerebellar peduncle.

3rd Nerve Palsy with Other Cranial Nerve Involvement (Cavernous sinus or orbital causes):

The 3rd cranial nerve is accompanied by cranial nerves 4, 5, and 6 as they pass through the cavernous sinus. Also, the oculosympathetic fibers serving the pupil and eyelids pass through the cavernous sinus on the carotid artery. Cavernous sinus lesions include:

Vascular anomalies, such as carotid-cavernous fistulas or aneurysm

Neoplasms (pituitary, meningioma)

Inflammatory diseases (Tolosa-Hunt, sarcoidosis, sinus disease)

Trauma

 

The 4th cranial nerve function can be tested for in the presence of a 3rd cranial nerve palsy by looking for an in-torsional movement of the involved eye with attempted downgaze. If the involved eye in-torts, the 4th cranial nerve is functioning.

A 6th cranial nerve palsy leads to deficient abduction of the eye.

A 5th cranial nerve palsy leads to decreased periocular sensation, or decreased corneal sensation.


Other causes of 3rd nerve palsy (Note: Myasthenia Gravis can mimic a
palsy with ptosis and motility defects):

Localized orbital problems can lead to a 3rd nerve palsy, as well as other cranial nerve defects. Vision may be reduced due to optic nerve involvement, and there may be ocular pain, redness, proptosis, or ocular displacement.

Causes include tumor, hemorrhage, orbital cellulitis, and orbital inflammatory pseudotumor.

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Patient #2

Differential Diagnosis and Discussion:

Case 2: This patient's findings are most consistent with Horner's syndrome. Horner's syndrome represents a defect in the sympathetic pathway to the eyes, lids, and face. Manifestations usually include:

• Miosis of the involved pupil, more noticeable in the dark due to poor dilation of the pupil

• Mild ptosis of 2-3 mm, due to loss of function of "Mueller's muscle", a small lid muscle with sympathetic innervation that gives 2-3 mm of eyelid lift.

• Transient dilation of conjunctival and facial vessels

• Anhydrosis on the affected side of the face in some cases

Horner's Syndrome and Headache:

Causes of Horner's Syndrome associated with headache are usually "post-ganglionic" causes (see discussion below). These may include:
 

• Cluster Headache
  This typically involves males in their 3rd or 4th decades of life. The headache is severe, and usually unilateral in the frontal or fronto-parietal areas. An attack may last 30 minutes to 4 hours, several times a day over a 6-8 week period. There may a transient Horner's Syndrome, and this persists in 10% of cases. Cluster Headache may be precipitated by trauma.
  
  

• Raeder's Syndrome
  This syndrome usually involves middle aged or elderly males, and there is a severe unilateral headache in the distribution of the 5th cranial nerve. If other cranial nerves are involved, a mass or vascular lesion should be ruled out (pituitary, meningioma, ICA aneurysm, naso-pharyngeal cancer).
  If there is only the unilateral pain and a Horner's syndrome, this may represent a cluster headache. Symptoms resolve over weeks to months. Similar symptoms can arise from carotid artery dissection and fibromuscular dysplasia.
  

Consider imaging studies such as MRI, MRA, or even arteriography to rule-out structural lesions or vascular lesions in cases of Cluster Headache.

Anatomy of the Oculo-Sympathetic Pathways:

The sympathetic nerve fibers serving the face, eye, and eyelids originate in the hypothalamus and travel to the C8 - T2 level of the spinal cord. Second order neurons (Pre-ganglionic) leave the cord and travel over the lung apex to the subclavian and carotid arteries. These fibers terminate in the superior cervical ganglion. Third order neurons (Post-ganglionic) leave the ganglion and travel with the internal carotid artery to enter the skull, course through the cavernous sinus, and the enter the orbit with the ophthalmic artery and ciliary nerves. These sympathetic fibers allow pupil dilation and cause and eyelid opening of about 2-3 mm.

Sympathetic fibers to the face travel with the external carotid artery.
 
Causes of Horner's Syndrome:

These can be broken down in to Pre-ganglionic causes (prior to the synapse at the superior cervical ganglion), and Post-ganglionic causes.

Pre-ganglionic Causes:

• Lung apex tumor (Pancoast's tumor)

• Mediastinal mass

• Neck lesions such as thyroidectomy or thyroid neoplasm, trauma, lymphadenopathy

Post-ganglionic Causes:

• Migraine variants such as Cluster headache, Raeders syndrome

• Cavernous sinus or orbital lesion

• Internal artery dissection

• Carotid-cavernous fistula

• Nasopharyngeal carcinoma