Third Nerve Palsies

What Are the Clinical Features of a Third Cranial Nerve Palsy?

The oculomotor nerve (third cranial nerve) supplies four extraocular muscles (medial, superior and inferior recti, and inferior oblique) as well as the levator of the lid, and contains parasympathetic fibers that supply the sphincter of the pupil and the ciliary body A complete peripheral third nerve palsy (TNP) thus causes ptosis, a fixed and dilated pupil, and a down (hypotropic) and out (exotropic) resting eye position. Partial TNPs may cause (in combination or isolation) variable ptosis; variable paresis of eye adduction, elevation, and depression; and variable pupillary involvement. In this section, we discuss the localization of TNPs associated with other neurologic signs (nonisolated TNPs) and TNPs without other associated neurologic or neuro-ophthalmologic deficits (isolated TNPs) (Lee, 1999).

Is the TNP Isolated or Nonisolated? Can the TNP Be Localized?

Is the TNP Due to a Nuclear Lesion?

Is the TNP Due to a Fascicular Lesion?

Lesions of the third nerve fascicle often accompany nuclear lesions because infarction is a common cause of a nuclear TNP, and the paramedian branches near the top of the basilar artery often feed both structures. For example, infarction of the dorsal paramedian midbrain may cause bilateral ptosis associated with unilateral paresis of all other muscles innervated by the oculomotor nerve (pupil spared) with sparing of the contralateral superior rectus muscle (Liu, 1991). These unique findings suggest a lesion of the proximal third nerve fascicles and the central caudal subnucleus. Third nerve fascicular lesions are often caused by infarction, hemorrhage, or demyelination. Pure fascicular lesions cause a unilateral peripheral type of oculomotor palsy. Involvement of brainstem structures other than the fascicle of the third nerve identifies the mesencephalic location of the lesion (Liu, 1992). Concomitant damage of the red nucleus and superior cerebellar peduncle causes contralateral ataxia and outflow tract cerebellar tremor (Claude’s syndrome), whereas a more anterior lesion, affecting the peduncle, gives rise to oculomotor palsy with contralateral hemiparesis (Weber’s syndrome). The TNP with Weber’s syndrome may affect or spare the pupillary fibers (Saeki, 1996). Larger lesions that affect the oculomotor fascicle and the red nucleus/substantia nigra region may produce TNP with contralateral choreiform movements or tremor (Benedikt’s syndrome) (Borras, 1997), sometimes associated with contralateral hemiparesis if the cerebral peduncle is also involved. A pupil-sparing TNP associated with binocular ocular torsion to the contralateral side—thereby indicating a left-sided midbrain lesion that included the fascicle of the third nerve and the supranuclear integration centers for torsional eye movements, the interstitial nucleus of Cajal, and the rostral interstitial nucleus of the MLF—has been described with a paramedian rostral midbrain infarction in a diabetic with giant cell arteritis (Dichgans, 1995). Ipsilateral TNP and contralateral downbeat nystagmus may be caused by unilateral paramedian thalamopeduncular infarction (Oishi, 1997).

Rarely, a unilateral or bilateral fascicular third nerve lesion may occur in isolation without other ocular motor or neurologic signs or symptoms (see below) (Andreo, 1994; Barbas, 1995; Getenet, 1994; Kim, 1993; Newman, 1990; Thömke, 1995). Fascicular lesions, even when bilateral, may occasionally spare the pupil(s). Bilateral preganglionic internal ophthalmoplegia has been described with bilateral partial oculomotor fascicular lesions (Hashimoto, 1998a). Because of the intraaxial topographic arrangement of fibers, fascicular lesions may cause TNP limited to specific oculomotor-innervated muscles (Ksiazek, 1994). Fascicular lesions have resulted in the following:

Based on these clinical studies, it has been proposed that individual third nerve fascicles in the ventral mesencephalon are arranged topographically from lateral to medial as follows: inferior oblique, superior rectus, medial rectus and levator palpebrae, inferior rectus, and pupillary fibers (Castro, 1990). A rostral-caudal topographic arrangement has also been suggested with pupillary fibers most superior, followed by fibers to the inferior rectus, inferior oblique, medial rectus, superior rectus, and levator, in that order (Saeki, 2000a; Schwartz, 1995). This model also accounts for the description of superior and inferior division oculomotor palsies. The superior division paresis involves the superior rectus and levator muscles without involvement of other groups (Guy, 1989a; Hriso, 1990; Ksiazek, 1989). The inferior division oculomotor palsies cause paresis of inferior rectus, inferior oblique, medial rectus, and pupillary fibers with sparing of the superior rectus and levator (Abdollah, 1990; Eggenberger, 1993; Ksiazek, 1989). Both divisional palsies may be associated with intraaxial midbrain lesions. Thus, although superior and inferior divisional TNP have classically been localized to anterior cavernous sinus or posterior orbital lesions, a divisional TNP may occur from damage at any location along the course of the oculomotor nerve, from the fascicle to the orbit (Ksiazek, 1989).

Fascicular TNP may occasionally be associated with ipsilateral ptosis and contralateral eyelid retraction (plus-minus lid syndrome) (Gaymard, 1992; Vetrugno, 1997). This syndrome occurs with a small lesion located in the paramedian mesencephalon. There is involvement of the ipsilateral levator palpebrae fascicles as they emerge from the central caudal nucleus (the central caudal nucleus is spared), and the inhibitory pathways projecting on the levator palpebrae motor neurons immediately before their entrance in the central caudal nucleus. The plus-minus syndrome has been described with bilateral glioma extending to the paramedian midbrain and thalamic-mesencephalic infarction; it also may occur with peripheral processes such as peripheral TNP, myasthenia gravis, orbital myositis, congenital ptosis, or orbital trauma.

Is the TNP Due to a Subarachnoid Lesion?

Compression of the third nerve by an aneurysm characteristically causes dilatation and unresponsiveness of the pupil. Compressive subarachnoid lesions may occasionally spare the pupil, however. Two explanations have been proposed: (1) compression may be evenly distributed and the relatively pressure-resistant, smaller-caliber pupillomotor fibers escape injury; or (2) the lesion compresses only the inferior portion of the nerve and spares the dorsally situated pupillomotor fibers. The TNP due to an aneurysm may be incomplete with at least one element of nerve dysfunction (i.e., ptosis, mydriasis, or extraocular muscle weakness) being absent. Ptosis has been described in isolation as the sole manifestation of third nerve compression by a posterior communicating artery aneurysm (Good, 1990). Rarely, aneurysmal TNP may even be transient and clear spontaneously (Greenspan, 1990).

A normal pupil in the setting of a complete somatic oculomotor paresis, however, essentially excludes a diagnosis of aneurysm (see below). A single patient has been described in whom a painless, pupil-sparing but otherwise complete oculomotor paresis was the only sign of an aneurysm arising from the basilar artery (Lustbader, 1988). Conversely, an isolated pupillary paralysis without ptosis or ophthalmoparesis is rarely caused by an aneurysm or other subarachnoid lesion (Kaye-Wilson, 1994; Wilhelm, 1995). Koennecke and Seyfert reported a patient with a common carotid artery dissection from intraoperative trauma whose mydriasis preceded a complete TNP by 12 hours (Koennecke, 1998).

Is the TNP Due to a Cavernous Sinus Lesion?

Is the TNP Due to an Orbital Lesion?

Lesions within the orbit that produce third nerve dysfunction usually produce other ocular motor dysfunction as well as optic neuropathy and proptosis (Goldberg, 1990a,b). Lesions may extend from the cavernous sinus to the orbital apex and vice versa so that a clear distinction between the two syndromes may be impossible. Isolated involvement of the muscles innervated by either the superior or the inferior oculomotor branch has classically been localized to an orbital process: often trauma, tumor, or infection, or a sphenocavernous lesion (Stefanis, 1993). However, as we noted, the functional division of the third nerve is present probably even at the fascicular level, and a divisional pattern may occur from damage anywhere along the course of the nerve. Superior division or inferior division third nerve paresis may occur with subarachnoid lesions (Guy, 1985), and isolated superior division paresis has been described with a superior cerebellar-posterior cerebral artery junction aneurysm that compressed and flattened the interpeduncular third nerve from below (Guy, 1989b). Superior branch palsy has also been described with basilar artery aneurysm, intracavernous carotid aneurysm, migraine, diabetes, lymphoma, sphenoidal abscess, sphenoid sinusitis, frontal sinus mucocele, viral illness, meningitis, and after craniotomy (Chotmongkol, 1992, 1999; Ehrenpries, 1995; Guy, 1989b; Manabe, 2000; O’Halloran, 1999; Saeki, 2000c; Silva, 1999; Stefanis, 1993). Even ophthalmoplegic migraine may cause recurrent paroxysmal superior division oculomotor palsy. Isolated superior division-like paresis may be mimicked by myasthenia gravis (Dehaene, 1995). Isolated inferior division involvement has occurred with trauma, mesencephalic infarction and tumor (Abdollah, 1990; Eggenberger, 1993; Ksiazek, 1989), basilar artery aneurysm (Kardon, 1991), parasellar tumors (e.g., meningioma, schwannoma) (Carlow, 1990), viral illness, orbital dural arteriovenous malformation (Gray, 1999), as part of a more generalized vasculitic or demyelinating neuropathy (Cunningham, 1994), and in association with elevated antigalactocerebroside and anti-GM1 antibodies (Go, 2000). Inferior division involvement with tumors may be pupil-sparing, perhaps because of insidious tumor growth sparing pressure-resistant pupillomotor fibers.

Partial or complete TNP may rarely follow dental anesthesia, presumably due to inadvertent injection of an anesthetic agent into the inferior dental artery or superior alveolar artery with subsequent retrograde flow into the maxillary, middle meningeal, and finally the lacrimal branch of the ophthalmic artery.

What Is the Evaluation of Nonisolated TNP?

Does the Patient Have an Acquired Isolated TNP with a Normal Pupillary Sphincter with Completely Palsied Extraocular Muscles (Type 4A TNP)?

TNP with a normal pupillary sphincter and completely palsied extraocular muscles is almost never due to an intracranial aneurysm. However, a single patient has been described in whom a painless, pupil-sparing, but otherwise complete TNP was the only sign of an aneurysm arising from the basilar artery (Lustbader 1988). A similar painful TNP palsy has been described with an aneurysm in the cavernous sinus (Ikeda, 2001), and pupillary sparing may rarely occur with pituitary adenoma. This type of TNP is most commonly caused by ischemia, especially associated with diabetes mellitus. In a retrospective review of 34 consecutive cases of isolated atraumatic TNP, diabetes mellitus was the most common etiology accounting for 46% of the cases (Renowden 1993). Ischemic TNP may also occur with giant cell arteritis (Berlit, 1991; Bondenson, 1997; Da vies, 1994; Renowden, 1993; Richards, 1992) and systemic lupus erythematosus. Pupil-sparing TNP has also been reported with sildenafil citrate (Viagra) (Donahue, 1998) and cocaine use (Migita, 1998). Significant risk factors for ischemic oculomotor nerve palsies include diabetes, left ventricular hypertrophy, and elevated hematocrit (Jacobson, 1994). Obesity, hypertension, and smoking are also probable risk factors. Ischemic damage to the trigeminal fibers in the oculomotor nerve may be the source of pain in ischemic-diabetic TNPs (Bortolami, 1993).