various regions of the cerebral hemispheres such as the temporal lobe, temporo-occipital regions, the angular gyrus, or frontal lobes. The precise anatomic pathways responsible for “cerebral” or cortical ptosis have not been defined, but the blepharoptosis in these cases may be related to a disruption of the cortico-bulbar fibers that connect to the third nerve nucleus in the midbrain. Cortical blepharoptosis is most commonly unilateral and contralateral to the lesion in the brain, although bilateral cortical ptosis has also been reported with extensive nondominant hemispheric lesions [1]. There may be other signs of cortical dysfunction such as gaze deviation, ocular motor apraxia, and facial nerve weakness, with the latter masking the blepharoptosis due to the presence of concomitant eyelid retraction. Given its rarity, cortical or cerebral blepharoptosis is a diagnosis of exclusion; an abnormality should be present in neuroimaging studies, and clinical signs of other conditions, such as myasthenia gravis, oculomotor palsy, or external ophthalmoplegia, should be absent. Treatment is mainly supportive since cortical ptosis is usually transient, lasting weeks to months before resolving [1, 2].

The extrapyramidal system may affect the eyelid position by modifying the normal supranuclear control of the blink reflex or contributing to apraxia of eyelid opening (AEO). Patients with AEO demonstrate an inability to initiate eyelid opening, despite the presence of normal levator excursion. AEO is thought to be related to an interruption of the supranuclear signal which initiates levator action, or due to a lack of coordinated inhibition of the antagonistic orbicularis contraction during eyelid opening [4]. Patients display symmetric, bilateral ptosis, and marked frontalis contraction during voluntary attempts to open the eyelids [5]. AEO may be seen in otherwise healthy patients or in association with CVA, progressive supranuclear palsy (PSP), Wilson’s disease, Parkinson’s disease, and benign essential blepharospasm [4–6]. Treatment of AEO is initially aimed at the underlying etiology, but if that strategy fails the blepharospasm component can be treated with low dose botulinum toxin injections (into the pretarsal orbicularis). Recalcitrant cases of AEO may respond to bilateral frontalis sling ptosis repair.

Third Nerve (Oculomotor) Palsy

Diagnosis

Third nerve palsy is a common cause of neurogenic ptosis. The diagnosis of a third nerve palsy as the cause of an acquired blepharoptosis should not be missed since the ptosis is always accompanied by other ophthalmic findings, such as extraocular muscle paresis and pupillary mydriasis. The blepharoptosis is usually profound with markedly diminished levator excursion (<10 mm) (Fig. 12.1a). There is typically a large-angle exotropia and hypotropia; the eye on the involved side is deviated “down and out” from residual tone in the fourth cranial nerve (superior oblique muscle) and sixth cranial nerve (lateral rectus muscle). Clinically, patients with even a subtle third nerve palsy demonstrate an incomitant, vertical strabismus, which may not be noted by the patient due to the presence of the ptosis. Therefore, clinicians should have a low suspicion for evaluating ptosis patients for subclinical strabismus with alternate cover testing or the single Maddox rod in all cardinal positions of gaze. Rarely, a patient with an orbital process demonstrates a superior division third nerve palsy, involving the superior rectus and levator muscles and sparing the pupil (Fig. 12.2a, b). These patients typically present with a progressive blepharoptosis and a hypotropia on the involved side which increases in upgaze. A useful method for assessing ptosis patients for subtle superior rectus weakness is the single Maddox rod. If there is no vertical separation of the two images in a binocular patient in upgaze, oculomotor nerve palsy is not the cause of the blepharoptosis or there is concurrent pathology on the contralateral side.

The pupil in a third nerve palsy patient is ­typically mid-dilated (Fig. 12.1b) (never >7–8 mm) causing an anisocoria more noticeable in a brightly-lit room (Fig. 12.1c). The pupillary dilation results from dysfunction of the parasympathetic fibers which originate in the Edinger–Westphal subnucleus of the oculomotor nuclear complex. These preganglionic fibers

Fig. 12.1  Fifty-four-year-old woman with an acute right third nerve palsy causing profound blepharoptosis (a), strabismus (b), and mid-dilated pupil (c). Three-

dimensional reformation of computed tomography angiogram showing a right posterior communicating artery aneurysm (d, arrow)

Fig. 12.2  Seventy-two-year-old woman who presented with a superior division third nerve palsy causing right upper lid ptosis and superior rectus weakness without anisocoria (a). Coronal magnetic resonance imaging study

demonstrating a mass lesion in the superior orbit (b). Orbital biopsy demonstrated an undifferentiated adenocarcinoma, and the patient was found to have widespread metastatic disease from an unidentified primary malignancy

travel with the third nerve fascicle and peripheral nerve before joining the branch to the inferior oblique muscle in the orbit and synapsing at the ciliary ganglion. As a rule, pupillary dilation is always present in a third nerve palsy except in the following scenarios: discrete nuclear lesions (sparing the Edinger–Westphal subnucleus), ischemic third nerve palsies involving the subarachnoid segment, superior division third nerve palsies in the orbit, and cavernous sinus lesions which produce a concurrent Horner syndrome. One of the more difficult settings to diagnose a third nerve palsy is following severe orbital trauma. The presentation of traumatic third nerve palsy may be identical to a patient with a traumatic mydriasis, traumatic ptosis, and extraocular motility limitation due to an orbital fracture. Pharmacologic testing is not effective in reducing the etiology of the mydriasis in this setting since both conditions respond to 1% pilocarpine. A careful clinical examination may reveal the diffuse, saccadic slowing of a third nerve palsy and the relative preservation of abduction. Blunt trauma to the levator muscle should resolve spontaneously by 3 months (rarely by 6 months), whereas traumatic third nerve palsy typically demonstrates incomplete recovery and evidence of aberrant regeneration (Fig. 12.3). Adie’s tonic pupil should not be confused with a pupilinvolving third nerve palsy given the absence of ptosis and strabismus with the former condition.

In difficult cases, pharmacologic testing with dilute pilocarpine (0.1%) can be used to demonstrate the denervation supersensitivity of Adie’s tonic pupil.

Localization of a Third Nerve Palsy

The third nerve may be affected anywhere along its pathway from the oculomotor nucleus within the midbrain to its distal branches innervating the levator superioris muscle within the orbit (Fig. 12.4). Localization of the lesion responsible for a third nerve palsy is based on both the neuroimaging findings and the clinical symptoms and signs. Blepharoptosis arising from a nuclear midbrain lesion is typically bilateral, symmetric, and associated with other signs of dorsal mesencephalic dysfunction. Both levator muscles are controlled by a single midline subnucleus located at the caudal end of the oculomotor nerve complex; therefore, a nuclear lesion almost always produce bilateral ptosis. Rarely, a discrete nuclear lesion involving the caudal region of the oculomotor complex may produce an isolated midbrain ptosis without other third nerve signs. More commonly, a nuclear lesion is present with bilateral oculomotor abnormalities since the superior rectus muscle has contralateral nuclear innervation. Fascicular lesions of the

Fig. 12.3  Twenty-one-year-old patient diagnosed with a traumatic right third nerve palsy following a motor vehicle accident. Note the severe ptosis and the “down and

out” position of the right eye (a). In downgaze, the patient demonstrates aberrant regeneration causing upper lid retraction (b)

oculomotor nerve within the brainstem are present with partial or complete signs of unilateral oculomotor nerve dysfunction, often in association with a contralateral hemiplegia, rubral tremor, or cerebellar ataxia. Benedikt syndrome of the upper midbrain causes ipsilateral third cranial nerve palsy, contralateral flapping hand tremor (rubral tremor from red nucleus involvement), and ataxia. Weber syndrome results from a slightly more ventral lesion with the involvement of the cerebral peduncle giving rise to contralateral hemiplegia or hemiparesis along with ipsilateral third cranial nerve palsy.

Blepharoptosis that accompanies a lesion of the subarachnoid segment is typically profound and invariably accompanied by ophthalmoplegia. In this location, the fibers to the levator muscle

travel in proximity with the neurons innervating the extraocular muscles. However, pupillary involvement with lesions involving the subarachnoid portion of the third nerve can vary depending on the etiology. The pupillary fibers from the Edinger–Westphal nucleus are located superficially in the superomedial aspect of the nerve and an intrinsic ischemic insult (e.g., diabetic third nerve palsy) commonly spares the pupil. Conversely, an extrinsic, compressive third nerve injury from a posterior communicating artery aneurysm almost always causes pupillary dilation. Involvement of the third nerve within the cavernous sinus should not occur in isolation since the sixth, fourth, and fifth cranial nerves travel together before entering the superior orbital fissure. The sixth nerve is particularly