aberrant regeneration of the oculomotor nerve: implications for … · oculomotor nerve injury (as...

RANIAL nerve palsies are a common neuroophthal-mic manifestation of disease involving the caver-nous sinus, brainstem, and skull base. Patients with

oculomotor nerve dysfunction usually present with a com-bination of ptosis, problems with adduction, elevation, de-pression, and variable mydriasis. Often CN III dysfunctionmay improve spontaneously, but occasionally the nervefails to recover completely. In a subset of these patientswith persistent partial CN III dysfunction, apparent cofiringof muscles innervated by the oculomotor nerve suggestssynkinetic miswiring. This process has been referred to asaberrant regeneration. Aberrant regeneration of the oculo-motor nerve has been a perplexing issue over the past cen-tury. As early as 1879, the phenomenon of lid retractionwith downward gaze or adduction, which would later betermed the “pseudo von-Graefe” sign, was reported in theliterature in association with recovery of the CN III.8 Therewas some confusion as to what was causing the lid retrac-tion. Theories ranged from proposed oculomotor nucleusinvolvement to suggestions that the frontalis muscle was

responsible. Parallels to regeneration of the facial nervewere also drawn when synkinesis of the seventh cranialnerve was studied in greater detail, probably because itmanifests with more obvious signs for both patients andtheir physicians.

Scientific evidence to support the idea of regeneratingfibers as a peripheral process came from Ramon y Cajal in1928 when he severed the sciatic nerve of a cat and foundthat the fibers originating from the proximal end of its 2trunks demonstrated haphazard regrowth without concernfor their original pathways.15 In 1935, Bielschowsky4 con-firmed the anatomy when he stated “in the course of heal-ing, some of the nerve fibers which proceed from the cen-tral part of the trunk of the third nerve do not find theiroriginal sheaths in the peripheral part of the nerve but goastray, so that they arrive at muscles to which they do notbelong. It seems that the nerve fibers in the course of heal-ing prefer certain ‘routes’ for growing in the wrong sheaths,so that in the majority of cases the impulse to look downand in produces the strongest contraction of the levator ofthe upper lid.” Alternatively, there may not be preferentialgrowth toward a given sheath, but rather the additionalinnervation to the levator is not appreciated in upward gazebecause the eyelids are already open.

Neurosurg. Focus / Volume 23 / November, 2007

Neurosurg Focus 23 (5):E14, 2007

Aberrant regeneration of the oculomotor nerve:implications for neurosurgeons

ERIC D. WEBER, M.D., AND STEVEN A. NEWMAN, M.D.

Department of Ophthalmology, University of Virginia Health System, Charlottesville, Virginia

PAberrant regeneration of cranial nerve III, otherwise known as oculomotor synkinesis, is an uncommon but well-described phenomenon most frequently resulting from trauma, tumors, and aneurysms. Its appearance usually followsan oculomotor palsy, but it can also occur primarily without any preceding nerve dysfunction. It is vital that neuro-surgeons recognize this disorder because it may be the only sign of an underlying cavernous tumor or PCoA aneurysm.The tumor most often implicated is a cavernous or parasellar meningioma, but any tumor that causes compression ordisruption along the course of the oculomotor nerve may cause primary or secondary misdirection. The most commonclinical signs of oculomotor synkinesis consist of elevation of the upper eyelid on attempted downward gaze or adduc-tion, adduction of the eye on attempted upward or downward gaze, and constriction of the pupil on attempted adduc-tion. The authors present the largest series of patients with oculomotor synkinesis, including those in whom it devel-oped after neurosurgical intervention, to illustrate various presentations. In addition, the various mechanisms thatcontribute to synkinesis are reviewed. Last, the treatment strategies for both oculomotor palsies and synkinesis are dis-cussed. (DOI: 10.3171/FOC-07/11/E14)

KEY WORDS • aberrant regeneration • Faden operation • oculomotor nerve •palsy • synkinesis

C

1

Abbreviations used in this paper: CN = cranial nerve; PCoA =posterior communicating artery.

Unauthenticated | Downloaded 10/06/20 07:35 PM UTC

Further groundbreaking work was published by Benderand Fulton2 in 1939 when they cut the CN III in experi-mental monkeys. First, they observed regeneration that wasnotable for vertical restriction and lid retraction on down-ward gaze that is now accepted as part of oculomotorsynkinesis. In addition, they also proved that some of thevertical limitation was due to relative restriction (cocon-traction of the superior and inferior rectus) by severingselectively the superior or inferior rectus muscles; this re-sulted in an increased vertical movement in a directionopposite the severed muscle, indicating that the verticallimitation was restrictive rather than residual paresis.2,3,21

Oculomotor nerve injury (as with other CN palsies) maybe categorized into 3 different degrees.16 First-degree in-juries, or conduction block, are those in which the continu-ity of the axon is maintained. In this setting, full functionreturns once the block is removed. Such endoneurial conti-nuity has been histopathologically confirmed in microvas-cular palsies,1 often occurring in patients with diabetes,hypertension, or other vascular disease. This anatomicalcontinuity offers a good explanation for why aberrancyrarely if ever occurs after an ischemic oculomotor nerveinsult. Sunderland22 further supported this idea with hiswork that suggested that an intact endoneurium preventedmisdirection. Second-degree injuries, or crush injuries, re-sult in disruption of the axon, while the endonurial tubesare preserved. Although there is wallerian degenerationdistal to the injury site, as the nerve regenerates it is con-fined to its original architecture, and aberrant regenerationgenerally does not occur. Third-degree injuries, however,are those in which the nerve and endoneurium are disrupt-ed. As the nerve regenerates, it may create an aberrant path-way as it attempts to bridge the severed endoneurium.

Synkinesis can manifest after a wide array of insults tothe oculomotor nerve. The classic presentation is after rup-ture of an intracranial aneurysm, commonly of the PCoA.Most of these develop acutely following aneurysmal rup-ture and therefore are often first seen by neurosurgeons. Inaddition, it can also be seen following trauma, developmentof mass lesions, and, rarely, ischemia. Surgery-inducedtrauma is also a reported cause, and aberrant regenerationfollowing neurosurgical manipulation in or around the cav-ernous sinus can be a major symptomatic complication ofthat surgery (SA Newman, unpublished data). Unfortu-nately, it can be missed under those circumstances becausesurgical success is based on patient survival and tumorresection, and minor morbidities such as synkinesis aregenerally overlooked or ignored, especially if the patient isnever seen by an ophthalmologist. While the lid retractionwith downward gaze and adduction is seldom more than aminor cosmetic disorder, the occurrence of cocontraction ofthe superior and inferior rectus muscles produces perma-nent limitation in vertical gaze and thus symptomaticdiplopia that may be very resistant to surgical correction.

Aberrant regeneration following an aneurysm- or sur-gery-induced CN III palsy is probably more common thanis currently recognized. Although lid retraction can be easyto recognize if a patient is asked to look in all nine positionsof cardinal gaze, it can also be missed easily if the clinicianis not looking for it and if the patient does not bring it totheir attention. Other forms of synkinesis are more difficultto appreciate, namely cocontraction of the vertical rectusmuscles. This can be mistaken for incomplete resolution of

CN III palsy unless there is significant globe retraction orthe intraocular pressure is checked in vertical gaze to con-firm a restrictive process.

Despite the classic teaching that aberrant regenerationwill not occur following diabetic ischemic oculomotor pa-resis, it has been reported. In 1957 Walsh reported 4cases,10,25 and it has even been reported on the contralateralside of a lesion9 or following an ischemic insult.13 These areboth highly unusual situations surrounding the appearanceof synkinesis. If it presents under these circumstances, evenin the setting of highly suspected ischemia, additional neu-roimaging is warranted. In the absence of a traumatic ori-gin, a parasellar lesion must be presumed and further studyis warranted.

There are some patients in whom CN III palsy never de-velops prior to synkinesis. In this situation, it is consideredprimary aberrant regeneration because there is no preced-ing palsy. This has rarely been reported with migrainousophthalmoplegia,5,11 but it is most commonly seen in pa-tients with parasellar/cavernous sinus meningiomas andcavernous sinus aneurysms.17,24 There have also been re-ported cases related to PCoA aneurysms.12 One such exam-ple of a PCoA aneurysm causing primary aberrancy wasdescribed by Cox and colleagues,7 who argued that an-eurysms at or near the cavernous sinus should be consid-ered in the differential diagnosis whenever an elderly pa-tient presents with ophthalmoplegia and signs of aberrancy,especially lid elevation on downward gaze. These casesbring into question the concept of misdirection down a pre-viously disrupted tract because the CN III in these patientswas never grossly disrupted. An alternative theory, ephap-tic neuronal transmission, has been suggested.

Ephaptic transmission differs from traditional neuronaltransmission in that it is the propagation of messages di-rectly between axons instead of at the synapse. This isthought to occur as a slow-growing lesion, such as a menin-gioma, allows subclinical destruction and concomitant re-generation of CN III fibers. This in turn may allow for elec-trical cross talk between individual fibers of the CN III,especially if their myelin sheaths have been damaged bythe slow compression. This has been a somewhat contro-versial mechanism, however, with the authors of numerousexperimental models arguing both sides of this debate.18,20–23

Furthermore, although this concept has been proven in ani-mal models, it has not been identified in the human oculo-motor nerve, and, as such, its role in synkinesis is uncertain.

Clinical Material and Methods

Following approval for a retrospective study by the insti-tutional review board at the University of Virginia HealthSystem, clinic charts of patients treated from January 1,1981, to July 31, 2007, were retrospectively reviewed forthe diagnosis code of aberrant regeneration involving theoculomotor nerve. There were a total of 56 patient recordsfound. Each patient had been fully evaluated by the sameneuroophthalmologist (S.A.N.). Additional data obtainedfrom outside institutions as part of the clinical care of thesepatients were included in the analysis. The variables stud-ied included patient age at initial presentation, initial diag-nosis or cause of CN III palsy, neurosurgical interventionsperformed before and after the onset of aberrant regenera-

E. D. Weber and S. A. Newman

2 Neurosurg. Focus / Volume 23 / November, 2007


tion, duration to discovery of oculomotor misdirection, ini-tial signs of the misdirection, any ocular interventions per-formed to improve binocularity or ptosis, and initial andfinal visual acuity.

Results

Of the 56 records reviewed, 2 were excluded because thedata were incomplete or the diagnosis of aberrant regener-ation was uncertain. Of the remaining 54 patients, 15 weremale and 39 were female. The leading primary diagnosiswas trauma. Twenty-five patients suffered a traumatic CNIII palsy, in 14 patients the cause was related to a tumor,and in 8 the cause was related to an aneurysm. The mostcommon tumor was a meningioma (8 patients); 3 patientsharbored a pituitary adenoma, the second most common tu-mor. There was 1 case of congenital oculomotor palsy, 1associated with zoster ophthalmicus and complete ophthal-moplegia, and 2 in which the origin was unclear despitemultiple workups.

The time to discovery of oculomotor misdirection varieddramatically, and ranged from 36 days to . 39 years. Thiswas due in part to the fact that not all patients were fol-lowed up by an ophthalmologist, and most patients whopresented with signs of aberrancy at their initial neurooph-thalmologic visit were more than 1 year from discovery oftheir initial lesion. Of the patients in whom evaluation wasperformed by an ophthalmologist within 6 months of theirinitial injury or surgery, the mean time to the first appear-ance of aberrant regeneration was 116 days (11 patients). Ifthe patients were seen between 6 months and 1 year aftertheir initial presentation (mean 247 days), they all had earlysigns of aberrant regeneration, even if the diagnosis was notmade at that time (19 patients). The mean age at the time ofinitial presentation of the cranial nerve palsy was 42 years(range 1 day–89 years). Eleven patients (20%) presentedinitially with additional CN deficits, the most commonbeing a CN VI palsy and the most dangerous being a CNV-1 palsy and with 2 of 4 patients developing vision-threat-ening neurotrophic corneal ulcers.

The most common presenting sign was vertical motilityrestriction. Forty-nine patients (91%) had significant verti-cal restriction at the onset of their misdirection syndrome.In 2 of these patients, intraocular pressure was measuredand documented in upward gaze; an increase in pressurewas noted in the affected eye as the patient attempted tolook up. Lid retraction was noted in 46 patients (85%),although this sign was often detected after the discovery ofvertical restriction. Thirty-five patients (65%) had persis-tent diplopia, and of these 15 (43%) opted to undergoextraocular muscle surgery, and 6 of these also requiringptosis correction. Three of those patients (20%) required asecond muscle procedure to further improve their extraoc-ular motility, and 2 (33%) required a second procedure tofurther improve their ptosis or upper-eyelid contour. Thishigh reoperative rate for ptosis surgery may reflect the factthat lid height is less predictable with the aberrant fibersinnervating the upper lid, and the surgery usually aims tounder correct the lid height in these cases to prevent exces-sive lagophthalmos. Table 1 provides a summary of ourresults.

Illustrative Case

This 21-year-old right-handed woman was referred forpersistent diplopia following a motor vehicle accident 2years earlier. She had been followed up by an ophthalmol-ogist since the accident and at her last examination wasnoted to have some return of CN III function without evi-dence of aberrant regeneration. On examination at our clin-ic, she exhibited limited elevation of the right eye andattempts at adduction caused a slight elevation of the righteyelid. Her intraocular pressure was recorded in straightgaze and found to be 13 mm Hg; when she attempted toelevate the right eye the pressure rose to 20 mm Hg, con-firming cocontraction and therefore aberrant regeneration.Once she was found to have stable misalignment of hereyes, she underwent a “recession” of her right lateral rectusmuscle and resection of her right medial rectus to correcther exodeviation. In addition, the tendons of the 2 muscleswere placed 1-tendon-width lower on the globe in an at-tempt to improve her right hypertropia. Postoperatively shehad an excellent cosmetic result with a normal appearancein straight-ahead gaze, but she had persistent diplopia sec-ondary to the extreme limitation of vertical movement ofthe right eye and her small area of binocularity.

Discussion

Unfortunately, it may not be possible to determine theexact percentage of patients with CN III palsy in whommisdirection subsequently develops. This is due in part tothe fact that patients in whom CN III function is recoveredwithout significant synkinesis may never present to an oph-


Aberrant regeneration of the oculomotor nerve

3

TABLE 1Summary of results obtained in 54

patients with oculomotor synkinesis*

Factor No. of Cases (%)

mean age at presentation 42 yrssexmale 15 (28)female 39 (72)

causetrauma 25 (46)tumor 14 (26)aneurysm 8 (15)hemorrhage 3 (6)congenital 1(2)unknown/other 3 (6)

neurosurgical intervention 25 (46)no. of days to presentation of AR if seen 116 days†

w/in 6 mos of primary diagnosisno. w/ additional CN deficits 11 (20)CN II (NLP vision) 2 (4)CN IV 4 (7)CN V 4 (7)CN VI 6 (11)CN VII 1 (2)

motility or ptosis op 15 (28)signs of misdirectionVR 49 (91)lid elevation or hang up w/ downglaze &/or adduction 46 (85)miosis w/ adduction, depression, or elevation 9 (17)

* AR = aberrant regeneration; NLP = no light perception; VR= verticalrestriction.

† For 11 patients.


thalmologist for further evaluation, and therefore a selec-tion bias would be created in any retrospective study. It isalso clear that without detailed quantitative motility analy-sis by a neuroophthalmologist, subtle cases of aberrant re-generation are commonly overlooked. What is clear fromthe cases presented in this series, however, is that there areseveral predominant factors that seem present in thepatients in whom misdirection develops: 1) a history oftrauma, 2) the presence of parasellar and cavernous tumorssuch as meningiomas, and 3) previous surgical manipula-tion.

Currently, there is not much that can be done to preventsynkinesis; the key is to recognize it so that patients can beappropriately referred for subspecialty management. Evenin the absence of misdirection, referral of patients with per-sistent motility deficits is warranted because of the poten-tial for intervention and subsequent improvement in theirquality of life. In addition, awareness of this phenomenonallows for more thorough preoperative counseling of neu-rosurgical patients.

Perhaps the most interesting findings of this review werethe frequency with which vertical restriction occurs withaberrant regeneration and that it is often the first sign. It isalso a very subtle finding in its early presentation, and with-out careful ophthalmological examination it can be easily

missed or confused with failure of CN III recovery. Theimages in Fig. 1 demonstrate that without careful examina-tion in all nine positions of cardinal gaze a patient canappear normal in primary gaze. Because cocontraction pro-ducing restriction is at fault here, checking intraocular pres-sure may be essential to establishing the diagnosis. In addi-tion, detection of other CN palsies with appropriate referralis essential to their proper management, especially in pa-tients with parasellar and cavernous sinus lesions in whoma trigeminal palsy can result in neurotrophic changes, aswas demonstrated in two of our patients in whom cornealulcers developed.

The treatment strategies are quite varied depending onthe unique clinical manifestations in each patient. In addi-tion, the goals and expectations of the patient must be con-sidered. There are two primary objectives for these pa-tients. First, ocular alignment with useful binocularity inprimary position and downward reading gaze allows pa-tients to perform most activities without being forced tohold their head in a strange position or use a patch. This ismost critical for children, who can develop torticollis,abnormal facial structures, and amblyopia if not correctedearly. The second objective is cosmesis, namely the correc-tion of ptosis and ocular misalignment, so that patients canregain a normal appearance.



FIG. 1. This patient presented with a headache and a CN III palsyand was found to have subarachnoid hemorrhage and a left PCoA an-eurysm. Two months after placement of an aneurysm clip, her ptosisimproved and she began to notice double vision. She was eventuallyreferred to a neuroophthalmologist for persistent issues with diplopiaand was found to have aberrant regeneration causing significant verti-cal restriction. Notice here that as she looks up or down, the left eyemoves far less than the right. Also notice how the left eyelid elevates indownward gaze. The binocular single-vision (BSV) field on the bottomleft demonstrates how the patient develops diplopia in up or downwardgaze.


With oculomotor synkinesis it can be difficult to achieveboth of the aforementioned goals, and sometimes one mustbe sacrificed for the other. Because of the severe limitationin vertical movement that patients can experience, therewill be a very limited area where fusion can occur anddiplopia avoided. Furthermore, the surgical correction canbe unpredictable, and therefore it may be difficult, if notimpossible, to get the eyes aligned in primary position.Under these circumstances, patients may prefer to havesome subtle ptosis to hide their diplopia. Alternatively,some patients would rather live with the double vision andhave a “normal” appearance with eyelids at equal heights.

Prior to surgical correction, an attempt to align the eyesusing botulinum toxin can be useful or at least informa-

tive.14 By injecting the nonparetic lateral rectus, you may beable to weaken the muscle enough to reduce the patient’shead turn. Unfortunately this effect will not last forever, butit may offer a preview of how a patient will respond to alateral rectus recession. The other advantage of using botu-linum toxin is that it reduces the potential contracture thatwill occur in the unopposed lateral rectus. Unfortunately,botulinum toxin is less likely to be useful in dealing withvertical diplopia and the limitation in upward and down-ward gaze.

There are a few surgical techniques that can be useful intreating oculomotor paresis and misdirection. The first isknown as the Faden operation or, more appropriately, aposterior fixation suture. This procedure aims to limit the



5

FIG. 2. A: Neuroimage obtained in a patient who underwent a pterional craniotomy for a cavernous sinus–clivusmeningioma and postoperatively developed a CN III palsy with subsequent oculomotor synkinesis. She underwent a left-sided inferior rectus recession with Faden suture. B: The patient looking in the nine cardinal gaze directions exhibitssevere limitation of vertical movements in the right eye and right upper lid elevation when she attempts to look down.C: Hess screen representing the patient prior to the Faden procedure, which demonstrates limitation of vertical gaze onthe right and secondary overaction on the unaffected side, so much so that the vertical movements were off the page.D: Postoperative Hess screen now demonstrating limitation of infraduction on the left eye. Note how the bottom lines oneach side are closer together. E: Preoperative binocular single-vision field, demonstrating the small island centrallywhere the patient can see without diplopia, but develops it as soon as she attempts to look down. F: Postoperative binoc-ular field has a larger central area of single vision, especially in downward gaze. Postoperatively, she was able to readwithout diplopia.


range of the nonparetic eye in a particular gaze of action bychanging the arc of contact of a given extraocular muscle.Although it may seem counterintuitive to operate on theuninvolved eye, and patients may have questions regardingits use, it is a very effective option in that it causes equalrestriction of both eyes. This is particularly useful whenthere is vertical restriction as a result of aberrancy; as apatient attempts to look down, to read for instance, the non-paretic eye will travel farther and cause diplopia. If youlimit that eye in downward gaze by placing a Faden sutureon that eye’s inferior rectus, then neither eye will be able todepress well, and the patient will have less diplopia whenlooking down.6 This can be best demonstrated by the use ofbinocular single-vision fields. The Faden operation is oneof the few methods of expanding the area of binocularity.Binocular single-vision fields also demonstrate that theFaden suture will not only shift the area of binocularity toprimary and the down-gazing reading position but willparadoxically enlarge the area of single vision, despite therestriction that it causes on the nonparalytic eye. Theimages in Fig. 2 demonstrate the results obtained in a pa-tient who underwent a Faden procedure.

There are other procedures available that attempt to putthe area of binocular single vision in a more useful locationfor the patient. Because of the significant vertical restric-tion, these patients will never be able to move their eyes intandem, especially vertically. If they can be aligned in pri-mary position and/or in a reading position, however, thenthe patient will generally be satisfied. One patient in ourstudy had to maintain an awkward chin-down head-tiltposition to see singly and ultimately developed arthritis inher neck.

Several of our patients underwent one or more of theaforementioned procedures for eye realignment. One typeof procedure is referred to as a recess–resect procedure, inwhich the medial rectus muscle is made shorter and tighter,while the lateral rectus is recessed further back on the globeto weaken it. This procedure allows the eye to adduct moreeffectively, because most patients with a persistent CN IIIpalsy are exotropic. Muscle surgery is often conducted withadjustable sutures, thus maximizing the chance of align-ment in desired positions. Unfortunately, due to the aber-rant signals reaching those muscles, no amount of strength-ening or weakening will stop their co-contraction; the bestthat we can hope for is an orthophoric appearance andbringing the affected eye’s small range of movement intothe patient’s area of central vision.

Conclusions

Aberrant regeneration of the CN III following surgicalintervention is likely more common than current literaturewould suggest. Although it is briefly mentioned in neuro-surgical texts in association with slowly progressive cav-ernous sinus masses, the persistent symptoms of misdi-rection are not discussed.26 Instead, the vertical motilitydisturbances that it causes are probably misinterpreted bymost surgeons as an incomplete recovery of the patient’sCN III palsy. It is one of the leading postoperative ophthal-mological morbidities following cavernous sinus surgery. Itis also a common complication of aneurysmal hemorrhageand subsequent surgery. Although surgical intervention for

life-threatening or disabling cranial tumors or aneurysmsshould not be avoided because of the potentially increasedrisk of postoperative oculomotor synkinesis, neurosur-geons should be aware of its existence and its clinical man-ifestations. Based on our findings, any patient with a newoculomotor nerve paralysis should undergo a full ophthal-mological examination to quantify ocular motility and todetermine the presence of other occult comorbidities,including trigeminal and other ocular motor dysfunction.With a better understanding of this entity, surgeons can bemore sensitive to the symptoms of diplopia and lid posi-tioning that may be apparent at presentation. Finally, sur-geons should realize that potential treatment strategies existfor some patients and therefore they need to recognize thiscondition early to refer their patients for evaluation andpossible treatment.

References

1. Asbury AK, Aldredge H, Hershberg R, Fisher CM: Oculomotorpalsy in diabetes mellitus: a clino-pathological study. Brain 93:555–566, 1970

2. Bender MB, Fulton JF: Factors in functional recovery followingsection of the oculomotor nerve in monkeys. J Neurol Neu-rosurg Psychiatry 4:285–292, 1939

3. Bender MB, Fulton JF: Functional recovery in ocular muscles of achimpanzee after section of oculomotor nerve. J Neurophysiol 1:144–151, 1938

4. Bielschowsky A: Lectures on motor anomalies of the eyes: II.Paralysis of individual eye muscles. Arch Ophthalmol 13:33–59, 1935

5. Boghen D, Chartrand JP, Laflamme P, Kirkham T, Hardy J, AubeM: Primary aberrant third nerve regeneration. Ann Neurol6:415–418, 1979

6. Buckley EG, Meekins BB: Fadenoperation for the management ofcomplicated incomitant vertical strabismus. Am J Ophthalmol105:304–312, 1988

7. Cox TA, Wurster JB, Godfrey WA: Primary aberrant oculomotorregeneration due to intracranial aneurysm. Arch Neurol 36:570–571, 1979

8. Gowers WR: The movements of the eyelids. Med Chir Trans62:429–440, 1879

9. Guy J, Engel HM, Lessner AM: Acquired contralateral oculomo-tor synkinesis. Arch Neurol 46:1021–1023, 1989

10. Hepler RS, Cantu RC: Aneurysms and third nerve palsies: ocularstatus of survivors. Arch Ophthalmol 77:604–608, 1967

11. Lepore FE, Glaser JS: Misdirection revisited. A critical appraisalof acquired oculomotor nerve synkinesis. Arch Ophthalmol 98:2206–2209, 1980

12. Levin PM: Intracanial aneurysms; clinicopathologic considera-tions of oculomotor-nerve regeneration and intracerebral hemor-rhage. AMA Arch Neurol Psychiatry 67:771–786, 1952

13. Messé SR, Shin RK, Liu GT, Galetta SL, Volpe NJ: Oculomotorsynkinesis following a midbrain stroke. Neurology 57:1106–1107, 2001

14. Metz HS, Mazow M: Botulinum toxin treatment of acute sixth andthird nerve palsy. Graefes Arch Clin Exp Ophthalmol 226:141–144, 1988

15. Ramon y Cajal S, DeFelipe J, Jones EG (eds): Cajal’s Degen-eration & Regeneration of the Nervous System. London:Oxford University Press, 1991

16. Sargent JC: Nuclear and infranuclear ocular motility disorders, inMiller NR, Newman NJ (eds): Walsh & Hoyt’s Clinical Neuro-Ophthalmology, ed 6. Philadelphia: Lippencott, Williams &Wilkins, 2004, pp 993–998

17. Schatz NJ, Savino PJ, Corbett JJ: Primary aberrant oculomotor




regeneration. A sign of intracavernous meningioma. Arch Neurol34:29–32, 1977

18. Sebag J, Sadun AA: Aberrant regeneration of the third nerve fol-lowing orbital trauma. Synkinesis of the iris sphincter. ArchNeurol 40:762–764, 1983

19. Sibony PA, Evinger C, Lessell S: Retrograde horseradish peroxi-dase transport after oculomotor nerve injury. Invest OphthalmolVis Sci 27:975–980, 1986

20. Sibony PA, Lessell S, Gittinger JW Jr: Acquired oculomotor syn-kinesis. Surv Ophthalmol 28:382–390, 1984

21. Slavin, ML, Einberg KR: Abduction defect associated with aber-rant regeneration of the oculomotor nerve after intracranialaneurysm. Am J Ophthal 121:580–582, 1996

22. Sunderland S: Nerve and Nerve Injuries. Edinburgh: ChurchillLivingstone, 1978

23. Tomasulo RA: Aberrant conduction in human peripheral nerve:ephaptic transmission? Neurology 32:712–719, 1982

24. Trobe JD, Glaser JS, Post JD: Meningiomas and aneurysms of thecavernous sinus: neuro-ophthalmological features. Arch Oph-thalmol 96:457–467, 1978

25. Walsh FB: Third nerve regeneration; a clinical evaluation. Br JOphthalmol 41:577–598, 1957

26. Winn HR (ed): Youmans Neurological Surgery. Philadelphia:Elsevier, 2004, p 321

Manuscript submitted August 20, 2007Accepted September 27, 2007Address correspondence to: Steven A. Newman, M.D., Depart-

ment of Ophthalmology, University of Virginia Health System,Charlottesville, Virginia 22908. email: [email protected].



7


aberrant regeneration of the oculomotor nerve: implications for … · oculomotor nerve injury (as...

Documents