Review Article Address correspondence to Dr Wayne T. Cornblath, University ofMichigan,W.K.KelloggEye Diplopia Due to Center, 1000 Wall St, Ann Arbor, MI 48105, [email protected]. Relationship Disclosure: Ocular Motor Cranial Dr Cornblath reports no disclosure. Unlabeled Use of Neuropathies Products/Investigational Use Disclosure: Dr Cornblath reports no Wayne T. Cornblath, MD, FAAN disclosure. * 2014, American Academy of Neurology. ABSTRACT Purpose of Review: Determining which cranial nerve(s) is (are) involved is a critical step in appropriately evaluating a patient with diplopia. Recent Findings: New studies have looked at the various etiologies of cranial nerve palsies in the modern imaging era. The importance of the C-reactive protein test in evaluating the possibility of giant cell arteritis has recently been emphasized. Summary: Dysfunction of the oculomotor (third), trochlear (fourth), or abducens (sixth) cranial nerve will produce ocular misalignment and resultant binocular diplopia or binocular blur. A misalignment in the vertical plane of as small as 200 2m is enough to produce diplopia. Diagnosing diplopia from a cranial nerve abnormality requires an understanding of structure (the anatomy of the cranial nerves from nucleus to muscle), function (the movements controlled by the cranial nerves), possible etiologies, and exceptions to the rules. Continuum (Minneap Minn) 2014;20(4):966–980. ANATOMY wall of the cavernous sinus. The third nerve The third cranial nerve (oculomotor) enters the superior portion of the cavernous starts in the midbrain as combined sinus; it then splits into a superior and midline nuclei divided into subnuclei inferior division as it enters the orbit through with a few anatomic quirks that are the superior orbital fissure. The superior helpful to know. The superior rectus division supplies the superior rectus and subnuclei innervate the contralateral levator palpebrae superioris muscles. The eye. The central caudal nucleus is a inferior division supplies the medial rectus, single nucleus that innervates both inferior rectus, and inferior oblique and, via levator palpebrae superioris muscles. the ciliary ganglion, innervates the pupillary These nuclei are located in a dorsal, sphincter and ciliary body. midline position. Thus, both eyes can The fourth cranial nerve (trochlear) be affected with a single nuclear lesion. nucleus is ventral to the cerebral aque- The fascicle of the third nerve projects duct at the pontomesencephalic junction. anteriorly, passing by the reticular forma- The axons for each nerve then exit the tion, red nucleus, substantia nigra, and brainstem dorsally (the only cranial nerve corticospinal tracts to enter the subarach- to do so) at the level of the inferior noid space via the interpeduncular fossa. colliculus, where they decussate. The In the subarachnoid space, the pupillary nerve then runs around the cerebral fibers are located in the superior and peduncle and enters the lateral wall of medial portion of the nerve. The third the cavernous sinus just below the third nerve passes by the posterior communi- nerve, entering the orbit through the cating artery, edge of the tentorium, and superior orbital fissure and innervating the uncus before entering the upper lateral superior oblique muscle. The fourth nerve 966 www.ContinuumJournal.com August 2014 Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINTS has the longest course and fewest axons FUNCTION h Diagnosing diplopia of the ocular motor nerves. With the The sixth cranial nerve (lateral rectus) from a cranial nerve decussation, the fourth nerve nucleus abducts the eye, and the medial rectus abnormality requires an innervates the contralateral superior (third nerve) adducts the eye. The understanding of oblique muscle. superior and inferior recti and oblique structure (the anatomy The sixth cranial nerve (abducens) muscles move the eye in more than of the cranial nerves nucleus is in the dorsal pons on the floor one direction, with primary, secondary, from nucleus to muscle), of the fourth ventricle adjacent to the and tertiary actions (Table 9-1). function (the movements facial nerve nucleus. The sixth nerve The superior rectus (third nerve) ele- controlled by the cranial nerves), the possible nucleus contains neurons that produce vates and intorts the eye with the internuclear neurons to innervate the etiologies, and exceptions inferior rectus (third nerve) depressing to the rules. contralateral medialrectusmusclevia and extorting the eye. The superior h the medial longitudinal fasciculus. The oblique (fourth nerve) depresses and Both the superior and inferior oblique muscles sixth nerve nucleus along with the fibers intorts the eye with the inferior from the facial nucleus form the facial abduct the eye. The oblique (third nerve) elevating and levator palpebrae colliculus. The axons from the sixth nerve extorting the eye. superioris (third nerve) nucleus run ventrally and caudally, lateral Both oblique muscles abduct the primarily elevates the to the corticospinal tract, and exit at the eye. The levator palpebrae super- eyelid, with the Mueller pontomedullary junction. The sixth nerve ioris (third nerve) primarily elevates muscle providing about then runs along the clivus until it pierces the eyelid, with the Mueller muscle 2 mm of eyelid elevation. the dura at the Dorello canal, goes over providing about 2 mm of eyelid the petrous ridge, and enters the cavern- elevation. ous sinus. In the cavernous sinus, the sixth nerve is in the middle, just lateral to DIAGNOSIS: LOCALIZATION the carotid artery and medial to the fourth In localizing cranial nerve palsies, cer- nerve. The sympathetic fibers to the pupil tain anatomic features can be helpful to and Mueller muscle are on the sixth nerve limit the possible locations. The first for a short distance in the cavernous consideration is whether a single cra- sinus. The sixth nerve enters the orbit nial nerve (isolated) is involved, and, in through the superior orbital fissure and the case of the third nerve, whether innervates the lateral rectus muscle. features that localize to the nucleus or TABLE 9-1 Extraocular Muscle Innervation and Action Muscle Innervation Actiona Superior rectus Oculomotor nerve Elevation, intorsionb, adduction (superior branch) Inferior rectus Oculomotor nerve Depression, extorsionc; adduction (inferior branch) Medial rectus Oculomotor nerve Abduction (inferior branch) Lateral rectus Abducens nerve Adduction Superior oblique Trochlear nerve Intorsionb, depression, abduction Inferior oblique Oculomotor nerve Extorsionc, elevation, abduction (inferior branch) a Primary action appears in bold. b Intorsion is the inward rotation of the upper pole of the vertical meridian of the eye. c Extorsion is the outward rotation of the upper pole of the vertical meridian of the eye. Continuum (Minneap Minn) 2014;20(4):966–980 www.ContinuumJournal.com 967 Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited. Ocular Motor Cranial Neuropathies superior and inferior divisions are Fourth Nerve Palsy present. The next consideration is Isolated nuclear lesions of the fourth whether multiple cranial nerves are nerve are rare and give rise to contra- involved, and, finally, whether other lateral palsies caused by the decussa- neurologic symptoms (eg, hemiparesis, tion. A nuclear fourth nerve palsy can ataxia) are present. also include ipsilateral internuclear ophthalmoplegia and Horner syn- Third Nerve Palsy drome or contralateral afferent pupil- Nuclear lesions in the third nerve will lary defect from involvement of the produce either bilateral ptosis or no medial longitudinal fasciculus, de- ptosis due to involvement or lack of scending oculosympathetic fibers, or involvement of the single subnucleus pupillary axons in the brachium of the controlling the levator. Similarly, one superior colliculus. Cavernous sinus or both pupils can be either involved lesions can produce fourth nerve or normal because of the rostral loca- palsies in combination with third, fifth tion of the paired Edinger-Westphal (V1, V2), and/or sixth nerve palsies. nuclei. Because of the crossed supe- rior rectus subnuclei, a nuclear lesion Sixth Nerve Palsy will have either bilateral dysfunction, In the brainstem, a nuclear lesion of the from involvement of the subnuclei sixth nerve produces a gaze palsy due to and crossing fibers, or contralateral the neurons innervating the contralateral superior rectus dysfunction, from medial rectus. A fascicular lesion pro- involvement of the crossing fibers duces an isolated abduction deficit. Sixth only. Fascicular lesions of the third nerve nuclear lesions can damage the nerve can be associated with hemi- adjacent medial longitudinal fasciculus paresis, ataxia, or tremor from involve- and produce a one-and-a-half syndrome. ment of adjacent corticospinal tracts, Fascicular lesions can be accompanied red nucleus, brachium conjunctivum, by hemiparesis, sensory change, or facial and cerebellar peduncles. Cavernous nerve palsy from involvement of the sinus lesions can produce third nerve coriticospinal tract, medial lemniscus, or palsies in combination with fourth, seventh nerve fascicle. A single clivus fifth (trigeminal) (V1, V2), and/or lesion, metastasis, or primary tumor can sixth nerve palsies. In the orbit, produce unilateral or bilateral sixth nerve either the superior or inferior division palsies, as illustrated in Case 9-1.Inthe of the third nerve