An overview of the third, fourth and sixth cranial nerve palsies Palsies of the third, fourth and sixth cranial nerves have ophthalmological consequences.
W Marais, MB ChB, MMed (Ophth); S Barrett, MB ChB, MMed (Ophth) Consultants, Department of Ophthalmology, University of the Free State, Bloemfontein, South Africa
Correspondence to: W Marais ([email protected])
Third nerve (oculomotor • nuclear third nerve palsy will spare the Basilar part of CN III[2] nerve) ipsilateral, and a ect the contralateral, e basilar part of CN III Cranial nerve III (CN III) innervates the superior rectus. • starts as a series of ‘rootlets’ superior, inferior, medial recti and the • Medial rectus, inferior rectus and • leaves the midbrain on the medial aspect inferior oblique muscles. It also innervates inferior oblique subnuclei of the cerebral peduncle, before coalescing the levator palpebrae superioris and carries • paired to form the main trunk with it the parasympathetic innervations • innervate their corresponding ipsi- • then passes between the posterior to the pupil. Involvement of CN III will lateral muscles cerebral and superior cerebellar arteries produce a symptom complex that involves • lesions con ned to the nuclear com- • runs lateral to and parallel with the one or several of these muscles and usually plex are relatively uncommon posterior communicating artery results in double vision.[1] • most frequent cause of palsy are vascular • is unaccompanied by other cranial disease, primary tumours and metastases nerves, therefore isolated CN III is Components of CN III • involvement of the paired medial commonly basilar (Fig. 1). • nuclear complex rectus subnuclei causes a wall-eyed • fasciculus bilateral internuclear ophthalmoplegia Important causes of basilar CN III • basilar (WEBINO), characterised by exo- palsy • intracavernous tropia, and defective convergence Aneurysm • intraorbital and adduction. Lesions involving the Aneurysm of the posterior communicating • pupillomotor bres. entire nucleus are o en associated with artery at its junction with the internal involvement of the adjacent and caudal carotid artery typically presents as acute, Nuclear complex[2] fourth nerve nucleus. painful third nerve palsy with pupil • situated in the midbrain • Fasciculus[2] involvement. • at the level of the superior colliculus • consists of e erent bres which pass • ventral to the Sylvian aqueduct. from the third nerve nucleus through Head trauma the red nucleus and the medial aspect Head trauma resulting in extradural/ e nuclear complex is composed of the of the cerebral peduncle subdural haematoma (Fig. 2) causes a following paired and unpaired subnuclei:[2] • emerges from the midbrain and passes tentorial pressure cone with downward • Levator subnucleus into the interpeduncular space herniation of the temporal lobe and • unpaired caudal midline structure • causes of nuclear and fascicular lesions compresses the CN III as it passes over the • innervates both levator muscles are similar, except that demyelination tentorial edge, initially causing irritative • lesions con ned in this area will may a ect the fasciculus.[2] miosis followed by mydriasis and total CN therefore give rise to bilateral ptosis. III palsy. • Superior rectus subnuclei Midbrain fascicular third cranial • paired nerve palsies Intracavernous part of CN III[2] • innervates the respective contralateral Table 1 describes midbrain fascicular third e intracavernous part of CN III enters superior rectus cranial nerve palsies.[1,2] the cavernous sinus by piercing the dura
Table 1. Midbrain fascicular third cranial nerve palsies Syndrome Signs/characteristics Location of lesion Benedikt Ipsilateral CN III palsy Red nucleus Contralateral extrapyramidal signs Hemitremor/involuntary movements Nothnagel Ipsilateral CN III palsy Fasciculus Cerebellar ataxia Superior cerebellar peduncle Claude Combination of Benedikt and Nothnagel syndromes Weber Ipsilateral CN III palsy Cerebral peduncle Contralateral hemiparesis
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lateral to the posterior clinoid process Intracavernous CN III palsy is usually onset of diplopia as an aneurysm expands. (Fig. 3). Within the cavernous sinus the associated with Pupillary involvement may be the only sign CN III runs in the lateral wall above CN • CN IV of CN III palsy. IV. Anteriorly in the cavernous sinus it • CN VI divides into superior and inferior branches, • rst division of CN V. Signs of right CN III palsy[2] entering the orbit through the superior • weakness of the levator with ptosis orbital ssure within the annulus of Zinn. The intra-orbital part of CN III[2] • eye abducted in primary position due to e superior division innervates the unopposed action of the lateral rectus Important causes of intracavernous CN • levator muscle III palsy • superior rectus. • normal abduction • Diabetes – causes a vascular palsy usually • intorsion of the eye which increases sparing the pupil. e inferior division innervates the on down gaze due to intact function of • Pituitary apoplexy (haemorrhagic in- • medial rectus superior oblique muscle farction) may cause a CN III palsy if the • inferior rectus – the branch to the inferior • limited adduction due to weakness of gland swells laterally and impinges on oblique also contains parasympathetic medial rectus muscle the cavernous sinus. preganglionic bres from the Edinge- • limited supraduction due to weakness • Intracavernous pathology such as Westphal subnucleus of superior rectus and inferior oblique • aneurysm • sphincter pupillae. muscles • meningioma • limited infraduction due to weakness of • carotid-cavernous stula Lesions to the inferior division are inferior rectus muscle • granulomatous inammation (Tolosa- characterised by • dilated pupil with defective accom- Hunt syndrome). • limited abduction modation due to parasympathetic palsy. • limited infraduction • dilated pupil. Aberrant regeneration[1,2] • may follow acute traumatic and Superior and inferior palsies are commonly compressive (but not vascular) third traumatic or vascular. nerve palsies • the endoneural nerve sheaths remain Pupillomotor fibres[2] intact in vascular pathology, may be These fibres are located superficially in the breached in traumatic and compressive superomedial part of CN III. Their blood lesions supply comes from the pial blood vessels. • bizarre defects in ocular motility Fig. 1. Dorsal view of the course of the third The main trunk of CN III is supplied by • elevation of the upper eyelid on nerve. the vasa nervorum. Involvement of the attempted abduction or infraduction pupil is of great importance because it • caused by misdirection of regenerating differentiates a ‘surgical’ from a ‘medical’ axons which reinervate the wrong lesion. extraocular muscle • pupil may also be involved. Surgical CN III lesions[2] Causes include Causes of isolated CN III palsy[2,3] • trauma 1. Idiopathic – 25 % • aneurysms 2. Vascular disease • uncal herniation. • diabetes • hypertension ese lesions characteristically involve the • most common cause of pupil-sparing Fig. 2. Mechanism of third nerve palsy by pupil by compressing the pial blood vessels CN III extradural haematoma. and the super cially located pupillary • spontaneous recovery in 3 months bres. • diabetic CN III palsy may be associated with periorbital pain Medical CN III lesions[2] • occasionally the presenting feature of • causes include hypertension and diabetes diabetes • characteristically spare the pupil • pain is therefore not helpful in • the microangiopathy involves the vasa di erentiating aneurismal and diabetic nervorum, causing ischaemia of the main CN III nerve palsy trunk. 3. Aneurysm • the posterior communicating artery at its Fig. 3. Location of cranial nerves in the ese principles are not infallible. Pupillary junction with the internal carotid artery cavernous sinus viewed from behind. involvement may develop a few days a er • pupil involvement
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4. Trauma Fourth nerve (trochlear nerve) superior orbital ssure above and lateral • direct and secondary to subdural Anatomy of CN IV[2,3] to the annulus of Zinn. haematoma with uncal herniation Important features of CN IV • trivial head trauma not associated with • only cranial nerve to emerge from the Intraorbital part of CN IV loss of consciousness should alert one dorsal aspect of the brain (Fig. 4) • innervates the superior oblique. of a basal intracranial tumour causing • crossed cranial nerve – it means the nerve trunk to be stretched and that nerve nucleus innervates the Symptoms and signs of CN IV tethered contralateral superior oblique muscles palsy[5] 5. Miscellaneous (uncommon) • very long and slender nerve. A fourth nerve palsy typically causes • tumours diplopia that is worse in down gaze. Hence, • syphillis Components of CN IV patients almost always report diplopia (or • meningeal inammation • nucleus tendency to close one eye) while reading. • giant cell arteritis • fasciculus • vasculitis associated with collagen • trunk Signs of CN IV palsy[2] vascular disorders • intracavernous • acute onset of vertical diplopia in the • ophthalmoplegic migraine • intraorbital. absence of ptosis • internal carotid artery dissection • characterised by a head posture • myasthenia may also mimic intermittent Nucleus • features of nuclear, fascicular and pupil-sparing CN III palsy • located at level of the inferior colliculus peripheral CN IV are clinically identical • chemotherapeutic toxicity. ventral to the Sylvian aqueduct • all except the nuclear palsies produce a • caudal and continuous with CN III contralateral superior oblique weakness. Investigation of the third cranial nuclear complex. nerve palsies[1] Characteristics of a le CN IV palsy[2] Table 2 describes the investigation of third Fasciculus • le hypertropia (le over right) in cranial nerve palsies. • consists of axons which curve around primary position the aqueduct • increase in le hypertropia on right gaze Treatment of CN III lesions[2,4] • decussate completely in the anterior due to the le inferior oblique overaction Non-surgical medullary velum. • limitation of le infraduction on Non-surgical management is indicated adduction during the acute phase, which lasts as Trunk • normal le abduction long as 6 months, and also when de nitive • leaves the brainstem on the dorsal surface • normal le infraduction surgical management is contraindicated • caudal to the inferior colliculus and then • normal le elevation (e.g. by neurological disease or central curves laterally around the brainstem • abnormal head posture. fusion disruption). is includes: • runs forward beneath the free edge of the • Fresnel prisms if angle of deviation is tentorium small • like CN III, it passes between the • uniocular occlusion to avoid diplopia (if posterior cerebral artery and superior ptosis is partial) cerebellar artery • botulinum toxin injection of the • then pierces the dura and enters the uninvolved lateral rectus preventing cavernous sinus. contraction. Intracavernous part of CN IV Surgical • runs in the lateral wall of the sinus Surgical management is to be considered • inferior to CN III and above the rst only a er all spontaneous improvement has division of CN V ceased and not earlier than 6 months from • in the anterior part of the cavernous Fig. 4. Dorsal view of the course of the fourth the date of onset. sinus it rises and passes through the cranial nerve.
Table 2. Investigation of third cranial nerve palsies Under 10 years 11 - 50 years >50 years Anisocoria less than 2 mm MRI, MRA MRI, MRA. If negative, Observe without imaging* perform medical work-up Anisocoria greater than 2 mm MRI, MRA‡ MRI, MRA. If negative, MRI, MRA. If negative, catheter angiography catheter angiography *Determine the status of the blood pressure, glucose metabolism, and the presence of other medical risk factors. ‡ Catheter angiography may be justi ed if these tests are negative.
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Abnormal head posture[2] • Increase of the le hypertropia on le Surgical • the abnormal head posture avoids head tilt implicates the le superior is is o en the nal solution for these diplopia which is vertical, tortional and oblique. patients. worse on looking down • Increase of right hypertropia on le head • to intort the eye there is contralateral tilt implicates the right inferior rectus. Sixth nerve (abducent nerve) head tilt to the right • In the CN IV palsy a deviation is better e sixth cranial nerve • to alleviate the inability to depress the on opposite tilt (BOOT). • entirely motor in function eye in adduction, the face is turned • supplies the lateral rectus muscle to the right and the chin is slightly Double Maddox rod test[2,6] • abduction of the eye depressed • Red and green Maddox rods, with the • abducent nerve – abduction. • the le eye cannot look down and to the cylinders vertical, are placed in front of right or intort. either eye. Components of CN VI[2] • Each eye will therefore perceive a • nucleus Bilateral involvement[2] horizontal line. • fasciculus • always suspect bilateral involvement • In the presence of a cyclodeviation • basilar part until proven otherwise the line perceived will be tilted and • intracavernous and intraorbital. • right hypertropia in le gaze and le therefore distinct from that of the other hypertropia in right gaze eye. Nucleus • greater than 10 degrees of cyclodeviation • One Maddox rod is then rotated until • lies at the level of the pons on the double Maddox rod test fusion of the lines is achieved. • ventral to the oor of the fourth ventricle • V pattern esotropia • e amount of rotation can be measured • closely related to the horizontal gaze • bilaterally positive Bielschowsky test. in degrees, indication of the extent of the centre cyclodeviation. • an elevation in the oor of the fourth Special tests[2,3,5] • Unilateral CN IV palsy is characterised ventricle (facial colliculus) is produced Parks-Bielschowsky 3-step test is useful in by less than 10 degrees. by the fasciculus of the seventh nerve as it the diagnosis. • Bilateral cases may have greater than 20 curves around the sixth nucleus. degrees of cyclodeviation. Step 1 Lesions • Assess which eye is hypertropic in Causes of isolated CN IV palsy[2,3] • Lesions in and around the sixth nerve primary position when the patient is Congenital nucleus cause the following signs looking in the distance. • common • ipsilateral weakness of abduction as • Le hypertropia may be caused by • presents in adulthood when it de- a result of involvement of the sixth weakness of the following 4 muscles compensates nerve
• One of the depressors of the le eye: • unlike acquired lesions patients are not Flexocam CME islandad.pdf 1 2013/04/11 5:30 PM superior oblique and inferior rectus usually aware of the torsional aspect • One of the elevators of the right eye: • examination of old photos is helpful to superior rectus or inferior oblique. make the diagnosis. • In a CN IV palsy, the involved eye is higher. Trauma • Frequently causes bilateral CN IV palsy. Step 2 • Bilateral lesions are o en thought • Determine whether the le hypertropia to be unilateral until squint surgery C is greater in right gaze or le gaze. is performed, following which the • Increase on right gaze implicates either contralateral CN IV palsy is o en M the right superior rectus or left superior revealed. Y
oblique. CM • Increase on le gaze indicates either Vascular MY a right inferior oblique or le inferior • common, but aneurysms and tumours rectus. are extremely rare CY • In CN IV palsy the deviation is worse on • routine neuroimaging for isolated CN IV CMY
opposite gaze (WOOG). palsy is not required. K
Step 3 Treatment of CN IV palsy[1] • e Bielschowsky head tilt test is Non-surgical performed with a patient xating straight Prisms may be tried, but because of the ahead. incomitant and torsional nature of this • e head is tilted to the right and then ocular misalignment, they are o en not to the le . successful.
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• failure of horizontal gaze towards the side of the lesion due to involvement of the horizontal gaze centre in the PPRF (pontine paramedian reticular formation).
Fasciculus Passes ventrally to leave the brainstem at the pontomedullary junction, just lateral to the pyramidal prominence.
Syndromes related to fasciculus in- volvement:[2] 1. Foville syndrome Fig. 5. Lateral view of the course of the sixth cranial nerve. • involves the fasciculus as it passes through the PPRF • the other nerves are protected within • caused by vascular disease/tumours the wall of the sinus. CN VI is medially involving the dorsal pons situated and runs through the middle • characterised by ipsilateral involvement of the sinus in close relationship to the of CN V – CN VIII internal carotid artery and is therefore • central sympathetic bres more prone to damage • CN V – facial analgesia • intracavernous CN VI palsy is • CN VI palsy combined with gaze palsy accompanied by a post-ganglion Horner • CN VIII nuclear/fascicular damage – syndrome (Parkinson sign) facial weakness • CN VI palsy is joined by sympathetic • CN VIII – deafness branches from the paracarotid plexus. • central Horner syndrome. 2. Millard-Gubler syndrome Intraorbital part of CN VI It involves the fasciculus as it passes through Enters the orbit through the superior the pyramidal tract and is most frequently orbital ssure within the annulus of Zinn to caused by vascular diseases, tumours or innervate the lateral rectus muscles. Hope for Africa demyelination. Fig. 6. MR enhancement of acoustic neuroma. Hope for Africa Characterised by Diagnosis Ithemba le Afrika Congress 2013 • ipsilateral CN VI palsy Damages CN VI at the pontomedullary 1. Signs of le CN VI palsy Ithemba le Afrika Congress 2013 • contralateral hemiplegia (because the junction • left esotropia in the primary position AllergyAllergy / Immunodeficiency/ Immunodeficiency / Pulmonology/ Pulmonology & & Thoracic Thoracic Surgery Surgery pyramidal tracts decussate further • e rst symptom is hearing loss. due to unopposed action of the left Sun City, South Africa inferiorly) • e rst sign is diminished corneal medial rectus Sun City, South Africa • variable number of signs of a dorsal sensitivity. • esotropia worse for distance target and 5 5- -9 9June June 2013 2013 pontine lesion. • Always test for hearing and corneal less/absent for near xation sensation in all patients with CN VI • mark limitation of le abduction ALLSA I ASID I SATS www.ithembaleafrika.com Basilar part of CN VI palsy. • normal le adduction. ALLSA I ASID I SATS www.ithembaleafrika.com • leaves the brainstem at the ponto- 2. Nasopharyngeal tumours – invade the Congress Organisers medullary junction and enters the skull and its foramina and damage the nerve Patients also show compensatory face turn prepontine basilar cistern during its basal course. into the field of action of the paralysed Londocor Event Management • passes upwards close to the base of 3. Raised intracranial pressure – caused muscle to minimise diplopia, so that the Tel: +27 11 768 4355 the skull and is crossed by the anterior by posterior fossa tumours/idiopathic eye does not need to look towards the field E-mail: [email protected] inferior cerebellar artery intracranial hypertension causing a of action of the paralysed muscle. • pierces the dura below the posterior downward displacement of the brainstem clinoids and angles forward over the tip stretching CN VI over the petrous lip. Causes of the petrous bone, passing through 4. Basal skull fracture – causes both uni/ In contrast to CN III palsy, aneurysms or around the inferior petrosal sinus, bilateral palsies. rarely a ect CN VI, but vascular causes are through the Dorello canal (under the 5. Gradenigo syndrome – caused by acute common. petroclinoid ligament) to enter the petrositis. Petrositis is accompanied by facial cavernous sinus (Fig. 5). weakness, pain and hearing diculties. Management of CN VI palsy Non-surgical Important causes of damage to the basilar Intracavernous part of CN VI Children part of CN VI • runs forward below CN III, CN IV and • In children up to 4 years of age, 1. Acoustic neuroma (Fig. 6) rst division of CN V treatment of acute CN VI palsy is aimed
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at preventing amblyopia and preserving • with total paralysis, botulinum toxin is 2. Kanski JJ. Clinical Ophthalmology. 6th ed. binocular fusion. indicated 2 weeks a er onset. Edinburgh: Butterworth Heinemann Elsevier, • Parents should permit a head tilt. Surgical 2007:816-824. • If head posture disappears with • to be contemplated only a er all spon- 3. Fraser S, Wormald R. Epidemiology in persistence of the esodeviation – high taneous improvement has ceased glaucoma. In: Yano M, Duker JS, eds. suspicion of amblyopia. • not earlier than 6 months from date of Ophthalmology. 2nd ed. St Louis: Mosby • Alternate occlusion prevents secondary onset. Elsevier, 2009:1017-1019. contracture of muscles and also 4. Rosenbaum AL, Santiago AP. Clinical Strabismus amblyopia. Acknowledgement. We wish to thank Graham Management: Principles and Surgical Techniques. Carter for the illustrations. Philadelphia: WB Saunders, 1999:251-271. Adults 5. Von Noorden GK, Maumenee AE. Atlas of • Intervention is aimed at preventing References Strabismus 2nd ed. St Louis: CV Mosby, 1-191. secondary contracture of medial rectus. 1. Savino PJ, Danesh-Meyer H. Neuro- 6. Kline LB. Neuro-ophthalmology. Basic and • Botulinum toxin ophthalmology Colour Atlas and Synopsis of Clinical Science Course, section 5. American • Timing is variable: Clinical Ophthalmology. New York: McGraw- Academy of Ophthalmology 2009-2010;8:228- • depends on degree of incapacitation Hill Medical Publishing Division, 2003:152-160. 235.
In a nutshell • Cranial nerve III (CN III) innervates the superior, inferior, medial recti and the inferior oblique muscles. It also innervates the levator palpe- brae superioris and carries with it the parasympathetic innervations to the pupil. Involvement of CN III will produce a symptom complex that involves one or several of these muscles and usually results in double vision. • Cranial nerve IV is the only cranial nerve to emerge from the dorsal aspect of the brain. A fourth nerve palsy typically causes diplopia that is worse in down gaze. Hence, patients almost always report diplopia (or tendency to close one eye) while reading. • Cranial nerve VI is entirely motor in function. It supplies the lateral rectus muscle and is responsible for abduction of the eye.
Hope for Africa Ithemba le Afrika Congress 2013 Allergy / Immunodeficiency / Pulmonology & Thoracic Surgery Sun City, South Africa 5 - 9 June 2013
ALLSA I ASID I SATS www.ithembaleafrika.com Congress Organisers Londocor Event Management Tel: +27 11 768 4355 E-mail: [email protected]