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Within the midbrain, the third nerve nucleus is composed of a complex of subnuclei. The fascicular portion of the nerve courses through the red nucleus and exists in the midbrain just medial to the cerebral peduncle. The cisternal portion of the nerve is a single structure that divides into a superior branch and an inferior branch in the region of the cavernous sinus and superior orbital fissure.
To describe 2 patients with superior divisional third cranial nerve paresis resulting from a lesion involving the cisternal portion of the nerve prior to its anatomical bifurcation.
Case 1 was a 77-year-old man with a superior divisional third nerve palsy as the presenting manifestation of a posterior communicating artery aneurysm. Case 2 was a 41-year-old woman who developed a superior divisional third nerve palsy following anterior temporal lobectomy for epilepsy.
In both cases, the presumed location of the lesion was the cisternal portion of the third cranial nerve.
Although the anatomical division of the third cranial nerve occurs in the region of the anterior cavernous sinus or superior orbital fissure, there is a topographical arrangement of the motor fibers within the cisternal portion of the nerve. The clinical evaluation of a patient with a third cranial nerve paresis requires an understanding of the regional neuroanatomy and topographical organization of the nerve.
The levator palpebrae superioris, pupillary sphincter muscle, and 4 of the 6 extraocular muscles (superior rectus, inferior rectus, medial rectus, and inferior oblique muscles) are innervated by the third cranial nerve (CN). Depending on the cause and anatomical location of the lesion, a variety of abnormal ocular motility patterns and neurological manifestations can be associated with CN III dysfunction (Table). Ptosis may or may not be present; the pupil may be involved (dilated), spared, or relatively spared; and 1, 2, 3, or all 4 of the extraocular muscles may be affected to various degrees. Anatomically, CN III exits the midbrain as 1 nerve dividing into a superior and inferior division within the region of the anterior cavernous sinus and superior orbital fissure. Clinically, a superior divisional CN III paresis is characterized by upper eyelid ptosis and limitation of supraduction, particularly with the eye in an abducted position. Lesions involving the fascicular, cisternal, cavernous sinus, or orbital portions of the nerve can result in a divisional CN III paresis.2-4 Specifically, superior divisional CN III palsy has been described in association with craniotomy, basilar apex, superior cerebellar, and posterior cerebral artery aneurysms, meningitis, diabetes mellitus, sphenoid sinusitis, ophthalmoplegic migraine, and a postviral illness.4-9 We report 2 unique cases of superior divisional CN III paresis: the first case occurring from an internal carotid and posterior communicating artery (PComA) aneurysm, and the second case following anterior temporal lobectomy for medically resistant epilepsy. These 2 cases highlight the topographical organization of the fibers within the cisternal portion of CN III.
A 77-year-old man was referred to the Neuro-Ophthalmology Service at the University of Florida, Gainesville, with a 6-month history of diplopia on upgaze and right retrobulbar pain. Prior to referral, a cranial magnetic resonance image and an intracranial magnetic resonance angiograph were interpreted as normal. In addition, a 4-week trial with pyridostigmine bromide for presumed ocular myasthenia gravis did not improve the double vision.
The ocular and neurological examination results were normal aside from mild limitation of supraduction of the right eye with a 2–prism diopter (PD) right hypotropia on upgaze only and 1 mm of right upper eyelid ptosis. The pupil sizes were equal and symmetrically reactive to light. A review of the magnetic resonance angiograph revealed a PComA aneurysm. Four-vessel catheter angiography confirmed a 7-mm posterior and slightly inferior projecting PComA aneurysm (Figure 1A and B). A craniotomy was performed, and 4 aneurysm clips were placed sequentially across the base of the aneurysm. Intraoperatively, the aneurysm was found to be thin-walled and adherent to the dorsal portion of the third nerve and posterior clinoid process. Postoperatively, there was significant limitation of supraduction of the right eye with right upper eyelid ptosis (Figure 2). Over the next 3 months, the double vision improved and single binocular vision was achieved with prism glasses in primary gaze.
Case 1. A, Cerebral angiogram, right internal carotid artery injection, anteroposterior projection, demonstrates right posterior communicating artery aneurysm. B, Artist's drawing of the surgical view of the posterior communicating artery aneurysm compressing the superior aspect of the third cranial nerve (CN).
Nine positions of gaze. Note the right upper eyelid ptosis (center panel of center row). There is limitation of elevation of the right eye (center panel of the upper row) that is most pronounced on abduction (left panel of the upper row).
A 41-year-old woman underwent a right anterior temporal lobectomy for intractable and medically resistant seizures. The posterior resection margin was 4 cm from the tip of the temporal lobe. The anterior portions of the superior temporal gyrus, hippocampal and parahippocampal gyrus, lateral amygdala, and uncus were removed. The resection of the medial temporal structures extended back to the level of the collicular plate. A retractor system was used to expose the medial temporal structures. No intraoperative complications were noted. Immediately following surgery, the patient noted binocular vertical double vision.
The neuro-ophthalmic examination results were pertinent for equal pupil sizes and briskly reactive pupillary light reflexes. There was 1 mm of right upper eyelid ptosis and mild limitation of elevation of the right eye (Figure 3). In primary position, there was an 8–PD right hypotropia that increased to 16 PD in upgaze. The patient was straight in downgaze. A magnetic resonance image revealed absence of the anterior temporal lobe with no abnormality of CN III (Figure 4). Three months later, the double vision resolved in primary gaze, but there was persistent mild right upper eyelid ptosis and mild limitation of supraduction of the right eye.
Nine positions of gaze. There is slight right upper eyelid ptosis (center panel of center row) and limitation of elevation of the right eye (center panel of the upper row) (the left panel of the center row is missing, but eye movements in that gaze were normal).
A T2-weighted, coronal view of cranial magnetic resonance imaging demonstrates postoperative changes consistent with right anterior temporal lobectomy. There was no abnormality of the third cranial nerve noted on any of the other sequences or images (not shown).
The CN III nucleus comprises a complex of subnuclei located within the midbrain, ventral to the periaqueductal gray matter. The motor neurons of each subnuclei innervate their corresponding ipsilateral extraocular muscles except for the superior rectus subnuclei, which innervate the contralateral superior rectus muscle, and the midline levator palpebrae subnuclei, which innervate the ipsilateral and contralateral levator palpebrae muscles.10 The fascicular fibers of CN III pass through the red nucleus and spread out laterally within the midbrain, maintaining an anatomical arrangement of the fibers.11,12 The nerve exits the midbrain just medial to the cerebral peduncle as 10 to 15 rootlets merging to form a single nerve, and then it passes between the posterior cerebral and superior cerebellar arteries, traveling adjacent to as well as inferior and lateral to the PComA to arrive at the superolateral aspect of the cavernous sinus (Figure 5).14 During its course through the subarachnoid space, CN III is in close proximity to the mesial temporal lobe (Figure 6). Within the cavernous sinus, CN III is located in the dural fold of its lateral wall. In most cases, the anatomical bifurcation of CN III into a superior and inferior division occurs in the region of the anterior cavernous sinus or superior orbital fissure. In the orbit, the 2 divisions branch out to innervate the various extraocular muscles and pupillary sphincter muscle, the latter through the ciliary ganglion.
Axial and lateral view of the course of the third cranial nerve (CN). EW indicates Edinger-Westphal; V1, first division of the trigeminal nerve; V2, second division of the trigeminal nerve; V3, third division of the trigeminal nerve. Reprinted from Foroozan et al,13 copyright 2004, with permission from Elsevier.
Basal view of the brain at the level of the midbrain, showing the relationship of the mesial temporal lobe to the third cranial nerve (CN).
Although the subarachnoid or cisternal portion of CN III is a single structure, based on previous clinical observations, there is a topographic arrangement of the fibers within the nerve but the precise anatomical arrangement in humans has not been specified. The few localization studies performed in animals have demonstrated some anatomical variation in the location of the superior branch fibers. In the rat, Atasever et al15 demonstrated that as CN III emerges from the midbrain, the superior rectus fibers are localized dorsally with dorsolateral extension; within the cisternal portion of the nerve, the fibers spread dorsomedially with dorsolateral extension. In the cat, Miyazaki16 showed that the superior branch fibers of CN III are located in a dorsolateral position in the cisternal portion of the nerve. In contrast to the limited knowledge of the anatomical arrangement of the motor fibers of the cisternal portion of CN III, it is well established that the parasympathetic fibers serving pupillary miosis are located in a superficial and dorsomedial position along the nerve.17,18
Classically, a PComA aneurysm results in CN III dysfunction with pupil involvement. However, there has been considerable discussion in the literature19 regarding the degree of external and internal ophthalmoplegia that may help clinically differentiate an ischemic CN III paresis from a compressive (aneurysmal) CN III paresis. In regard to the description of aneurysmal CN III paresis, the literature is vague because many of the published case series and retrospective studies categorize the CN III dysfunction as incomplete, complete, partial, or total and fail to provide enough detailed information to determine whether a divisional CN III paresis was present. Guy and Day20 described 5 patients with intracranial aneurysms resulting in superior divisional CN III palsy. The location of the lesion was at the expected site of the anatomical bifurcation of CN III in only 1 patient with an intracavernous carotid artery aneurysm. In the remaining 4 patients, the aneurysm location was at the superior cerebellar–posterior cerebral artery junction and the basilar artery apex. Although we were able to find only 2 detailed cases identifying a superior divisional CN III paresis in the setting of a PComA aneurysm, it may be that this type of presentation is not as uncommon as described in the literature owing to the nomenclature used in describing CN III deficits.21,22
Ocular motility dysfunction following anterior temporal lobectomy has been reported to occur in as many as 15% of patients and is most commonly attributed to CN IV paresis.23,24 Although CN III dysfunction can infrequently occur after surgery, we were unable to find a previously reported case of a superior divisional CN III paresis following anterior temporal lobectomy. Since 1992 at the University of Florida, only 1 case of CN III dysfunction (case 2 in this article) and 1 case of CN IV paresis have been noted in 313 consecutive cases of anterior temporal lobectomy (S.N.R., unpublished data, 2005). In a recent prospective study24 of 47 patients who underwent anterior temporal lobectomy and amygdalohippocampectomy, 9 (19%) of patients had postoperative diplopia. In all of the patients, the diplopia was due to a transient CN IV paresis. The mechanisms attributed to injury to CN IV include decompensation of a congenital CN IV palsy, ischemic injury, direct surgical trauma, and inadvertent surgical traction or compression.23,24 The cisternal portion of CN III runs in close proximity to the mesial temporal lobe, thereby making it susceptible to injury from pathological processes within this area (Figure 6).25
The 2 cases reported in this article add further evidence of a topographical organization of the cisternal CN III and also emphasize the need for more clinical and anatomical studies to better define the precise arrangement of the neural fibers within the cisternal portion of CN III. Clinicians should be aware that a superior divisional CN III paresis may be indicative of an intracranial lesion, and appropriate diagnostic radiologic studies should be performed.
Correspondence: M. Tariq Bhatti, MD, Department of Ophthalmology, University of Florida College of Medicine, Box 100284 JHMHSC, Gainesville, FL 32610-0284 (email@example.com).
Accepted for Publication: December 28, 2005.
Author Contributions:Study concept and design: Bhatti. Acquisition of data: Bhatti, Eisenschenk, Roper, and Guy. Analysis and interpretation of data: Bhatti and Roper. Drafting of the manuscript: Bhatti. Critical revision of the manuscript for important intellectual content: Bhatti, Eisenschenk, Roper, and Guy. Administrative, technical, and material support: Bhatti, Eisenschenk, Roper, and Guy. Study supervision: Eisenschenk, Roper, and Guy.
Bhatti MT, Eisenschenk S, Roper SN, Guy JR. Superior Divisional Third Cranial Nerve Paresis: Clinical and Anatomical Observations of 2 Unique Cases. Arch Neurol. 2006;63(5):771–776. doi:10.1001/archneur.63.5.771
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