Surgical management of third nerve palsy

Introduction

Clinical management of third nerve palsy is most challenging among all three ocular motor nerve palsies as four out of six extraocular muscles are involved and therefore must be approached in a different way. Other associated factors such as the presence of ptosis, pupillary involvement, amblyopia, aberrant regeneration, poor bell's phenomenon, superior oblique (SO) over action, and lateral rectus (LR) contracture may further complicate the matter.

Third nerve palsy can be isolated or can occur in association with other ocular nerve palsies. Isolated third nerve palsy may be unilateral or bilateral, complete or partial, pupil involving or pupil sparing, and congenital or acquired.

The common causes of isolated third nerve palsy in children are congenital (43%), trauma (20%), inflammation (13%), aneurysm (7%), and ophthalmoplegic migraine. Whereas, in the adult population, common etiologies are vasculopathic disorders (diabetes mellitus, hypertension), aneurysm, and trauma.

Treatment can be both nonsurgical and surgical. As nonsurgical modalities are not of much help, surgery remains the main-stay of treatment. Surgical strategies are different for complete and partial third nerve palsy.

Etiopathogenesis

Several studies have reviewed oculomotor, trochlear, and abducens cranial nerve palsies in the overall population. The largest of these was from the Mayo[1] clinic: 4000 cases of cranial nerve palsies were reviewed. According to this study, third nerve palsy contributed to 28% of the total cases of ocular nerve palsies. Sixth nerve palsy was the most common (43%), and fourth cranial nerve palsy (15%) was the least common.

Berlit[2] evaluated 412 patients with isolated and acquired ocular nerve palsies attending the acute centers of neurology Heidelberg and Mannheim between 1970 and 1984 in a retrospective study. Oculomotor nerve palsies were more frequent (41.7%) than the abducens (40%), the trochlear nerve (6.1%) or combined ocular motor nerve palsies (12.1%).

Paresis of oculomotor nerve showed no pupil involvement in 62.7% of patients; this applied in particular to III nerve palsies of vascular (69%), inflammatory (68%), and undetermined origin (71%). In 92% of patients with tumor and in 78.5% with aneurysm the pupil was fixed and dilated on examination. The result of this study was in contrast to other series which report sixth nerve palsy as the most common ocular motor nerve palsy followed by third and fourth nerve palsies.[345]

Rucker[6] in 1958 presented a comprehensive review of causes of paralysis of ocular motor nerve palsies. He included 1000 cases of cranial nerve palsies. Isolated third nerve palsy was present in 34% of the cases preceded by sixth nerve palsy in 41% of cases. In 28% of the cases of third nerve palsy, no cause could be determined. In rest of the cases, common causes were aneurysms (19%), vascular disease (18%), head trauma (15%), and neoplasm (10%). Rucker[7] again in 1966 undertook a study for another 1000 cases to determine the relative frequency of the various etiologies.

Richards et al.,[8] in 1992, reviewed 1278 cases of cranial nerve palsies. They included both congenital and acquired cases. The sixth nerve palsy was the most commonly affected nerve followed by the third and fourth cranial nerve palsies, respectively. For isolated third nerve palsy, vascular, and undetermined causes were the most common. Aneurysms were seen less commonly as the cause.

Green et al.,[1] in 1964, reviewed 130 patients of acquired third nerve palsy. Their study revealed that the incidence of isolated ocular nerve palsy is low in the first decade and increases each decade up to the seventh decade and then decreases precipitously. About 75% of the patients were over the age of 40 years. Vascular aneurysms were the most common cause in their series accounting for 29.2% of the total cases. Diabetes (19.2%), neuritis (15.4%), trauma (10.8%), tumors (3.8%), syphilis (9.2%), and miscellaneous (3.8%) were among other etiologies.

Harley,[9] in 1980, reviewed 121 pediatric patients with third, fourth, sixth, and multiple nerve palsies. Third nerve palsy accounted for 26% of all the cases. Among 42 cases of third nerve palsy, 15 were congenital, 4 were posttraumatic, 3 were postinflammatory, and 5 were with vascular etiology.

Thirty cases of isolated third nerve palsy under the age of 20 years were studied at John Hopkins Hospital over a period of 25 years by Miller.[10] Nearly 43% of the cases were of congenital etiology. Acquired were most commonly due to trauma and infection followed by neoplasms, aneurysms, and ophthalmoplegic migraine.

Tiffin et al.[11] performed a retrospective study of all patients with acquired III, IV or VI cranial nerve palsy who were seen in the orthoptic department at Ninewells Hospital, Dundee, over 9-year period from 1984 to 1992. A total of 165 cases were identified.

VI nerve palsies accounted for the majority of the patients (57%), with IV nerve palsies (21%) occurring more frequently than III nerve palsies (17%) and multiple palsies (5%). About 35% of cases were of unknown etiology and 32% of vascular etiology. About 57% of all patients made total recovery (in a median period of 3 months) and 80% made at least a partial recovery. The results are contrasted with those of previous studies.

Victor[12] studied 16 children with congenital unilateral oculomotor nerve palsy at John Hopkins Hospital. Ing et al.[13] reviewed 54 children with the third nerve palsy. In their series, 20% of the cases were congenital. Acquired cases were most commonly due to trauma (57%) followed by inflammation (13%). Ng and Lyons,[14] in 2005, studied 18 children under 14 years of age with oculomotor nerve palsy; of which, 10 were male and 8 were female. Thirteen of the 18 (72%) children were within an amblyogenic age group, defined as 8 years or less. The etiologic mechanisms were congenital in 6 patients (33%), traumatic in 5 (28%), neoplastic in 4 (22%), vascular in 2 (11%), and migrainous or parainfectious in 1 (6%).

The most common mechanism of isolated, congenital third nerve palsy is a perinatal injury to the peripheral nerve. Nuclear lesions are not presumed to be cause in these cases.[1215] Congenital cases show predominance for the right eye.[101213]

This is assumed to be related to birth trauma as left occipito-transverse position of the fetus is the most common position of occiput during labor.[13] Most of the congenital cases were thought to be isolated without any associated abnormalities; however, some reports have been made about the associations of congenital oculomotor nerve palsies. Balkan and Hoyt,[15] in 1984, have described few patients of congenital third nerve palsies with associated neurological deficits consisting of contralateral hemiplegia in 3 patients, monoplegia in 1 patient, generalized developmental delay in 2 patients. Keith,[16] in 1987, reported 1 patient with developmental delay and autism, 1 with spina bifia, 1 with Goldenhar's syndrome and 1 patient with enlarged ventricles and temporal lobe hypoplasia. Hamed,[17] in 1991, described 2 patients of congenital third nerve palsy with hemiparesis, 2 with hydrocephalus, 1 with spastic paraparesis, 1 with facial paresis, 1 with septo-optic dysplasia, 1 with optic tract syndrome, 1 with small R midbrain and paresis of cranial nerves VII-XII and 1 patient with Goldenhar's syndrome and hydrocephalus. After these case reports, Ing et al.,[13] in 1992, described 2 cases of congenital oculomotor nerve palsy with cerebral palsy and 1 with Mobius syndrome. In 1997, Tsaloumas and Willshaw[18] reported developmental delay, seizures, and behavioral problems in 3 patients of congenital third nerve palsy; cerebral palsy in 1 patient, brainstem infarct in 1 patient, cerebellar infarct in 1 patient, Chiari's malformation in 1 patient, midline midbrain lesion in 1 patient, and intraconal hemangioma in 1 patient. White et al.[19] have reported two cases of congenital third nerve palsy with facial hemangioma, cerebellar hemangioma, and apparent gaze palsy. Two cases of congenital oculomotor nerve palsy with neurological deficits and central nervous system (CNS) abnormalities were reported by Sun and Kao.[20] One of these patients had hypoplasia of midbrain and corpus collosum and another one had ventricular dilatation and absence of septum pellucidum (de Morsier's syndrome).

In 1999, Mudgil and Repka[21] reported cerebrovascular accident in 4 patients, arteriovenous malformation in 1 patient, posterior fossa arachnoid cyst in 1, Mobius in 1, craniocynostosis in 1, brainstem atrophy in 1, and ventriculomegaly in 1 patient. Recently, Ng and Lyons,[14] in 2005, described panhypopituitarism along with optic nerve hypoplasia, sensoryneural hearing loss, choroids plexus cyst in 1 patient of congenital oculomotor nerve palsy, and holoprosencephaly with CNS migration defect in 1 patient.

The incidence of amblyopia of affected eye is higher in congenital cases of third nerve palsy.[13] In Victor's study, 9 out of the 12 cases had amblyopia.[12] The best visual acuity in these amblyopic eye was 6/12. In a study by Ing et al., 5 of 11 cases of congenital palsy had vision of 6/12 or better.[13] Sometimes, nonpalsied eye may develop amblyopia instead of palsied eye. It could be possible either due to the fixation preference of the affected eye or coexisting nystagmus which gets dampened in more paretic eye.[22]

Pupil is in the majority of cases of third nerve palsy.[17] The involved pupil can be either fixed and dilated due to the loss of innervations to the papillary sphincter or miotic due to aberrant innervation.

Third nerve palsy is sometimes complicated due to aberrant innervation. This is seen in both acquired and congenital cases.[1013] Miller documented aberrant regeneration in 8 out of 13 congenital cases, whereas Victor[12] in 10 out of 16 cases. In case acquired third nerve palsy, etiology varies in different age groups. In children, trauma (20%), inflammation (13%), tumors (10%) are the most common causes, whereas in adults, vasculopathic etiologies, aneurysms, and trauma are the main etiologies.

Traumatic nerve palsies are more common in young adult males. In one study by Elston males accounted 16 out of 20 cases were males.[23] Third nerve is usually involved in severe, high-speed closed head injury by either avulsion from the mesencephalon, primary contusion necrosis or intra and perineural hemorrhage in the subarachnoid space.[24]

The third nerve can be involved at any level right from the level of its nucleus in the midbrain to its area of supply in the orbit.[25] Nuclear lesions are commonly due to vascular pathology, demyelination or neoplasms. These lesions have variable presentation depending on the involvement of various subnuclei. Nuclear lesions usually present as unilateral third nerve palsy with contralateral involvement of superior rectus (SR) and bilateral ptosis, or bilateral third nerve, with or without internal ophthalmoplegia.

Fascicular lesions like nuclear ones are also because of vascular pathology, demyelination or neoplasms.[25] These lesions may involve the surrounding brainstem structures and thus can present with signs of contralateral hemiplegia or contralateral intention tremor and ataxia.

Peripheral nerve involvement is relatively more common. The interpeduncular part can be involved by aneurysm, trauma, or meningitis. Isolated superior[26] or inferior division[27] palsy is relatively less common. Superior division involvement has been reported due to lesions in the anterior cavernous sinus.[28] Isolated inferior division palsy has been reported with local orbital disease or trauma, viral, ophthalmoplegic migraine, vasculitis, demyelinating disease, or unknown pathology.[29]

Third nerve involvement due to cavernous sinus pathology usually present with multiple nerve palsy. Orbital pathology may be in the form of pseudotumor, tolosa hunt syndrome, traumatic neuropathy, and tumor involvement. These patients usually have other localizing signs such as pain, paresthesias, proptosis, and compressive optic neuropathy.

Management

The management of patients with oculomotor nerve palsy is one of the most challenging issues for the strabismus surgeon. Each patient has different presentation depending on the extent of the paresis, recovery and presence of aberrant regeneration or other associated factors. Therefore, management of every patient varies accordingly.

In children, presence of amblyopia and loss of binocularity, due to the large angle of incomitant strabismus and associated ptosis further complicate the management of third nerve palsy.

Nonsurgical Management

The goal of management can be short- and long-term.

Nonsurgical options are usually indicated as short-term measures in the acute phase of acquired palsy, which may last as long as 6 months. It is also indicated as an alternative to surgery when it is contra-indicated.

Occlusion of one eye with a patch, opaque contact lens or blurred spectacle lens is helpful in case of distressing diplopia. In cases with levator palpebrae involvement, the ptosis itself acts as a natural patch for relieving diplopia.

Prisms can be of use in certain cases where surgery is contraindicated and in cases with partial paralysis of the third nerve with the residual function of medial rectus (MR). However, even in these cases, prism therapy has a limited role as aligning the visual axes with prisms can be difficult in view of multiplanar nature of diplopia.

Use of botulinum toxin is another nonsurgical option in the acute phase of partial third nerve paresis. This is, especially useful in cases of isolated involvement of MR muscle.

It paralyses the antagonist LR temporarily and thus neutralizes horizontal deviation in the primary position. It also prevents contracture of LR muscle. After recovery of the injected muscle, the remaining vertical deviation may need to be corrected by prisms or surgical therapy. Some patients may not need surgery later on. Use of botulinum toxin for vertical muscle imbalance is rarely indicated due to the high rate of complications associated with this. SR should not be injected as ptosis can occur if toxin is placed into the levator – SR complex. Injection of inferior rectus (IR) may be done in cases of isolated SR weakness.

For children who are susceptible to amblyopia, appropriate refractive error correction and occlusion therapy with a close follow-up is advised. This should be followed by early surgery after any progressive condition is ruled out.

Surgical Treatment

Surgical treatment depends on type (complete/incomplete) and severity of the paralysis and presence of other associated factors. Although various surgical options are there, success of these is hampered by the presence of associated factors such as pupillary involvement, ptosis, poor bell's phenomenon, and aberrant regeneration. Surgical treatment is advised after a period of 6 months in acquired palsies.

Complete Third Nerve Palsy

In complete palsy, goal of surgery is primary position alignment, compromising the ocular motility of the involved eye.

Surgery Only on the Affected Eye

Helveston[30] has described supra-maximal recessions of LR (14–16 mm) and large resection of MR (8–14 mm) for correcting the horizontal deviation in primary position.

Kattleman et al.[31] have also advised supramaximal medial and LR surgery for the correction of horizontal deviation in primary position. Large resection of a completely paretic muscle, however, accomplishes little. The eye may become exotropic again with time as the LR muscle undergoes chronic contracture and the resected muscle elongates.[3233]

Knapp[34] described a method of fixing the eye in the primary position with a Callahan suture after recessing all of the temporal tissue to the lateral rim of the orbital bone.

Köse et al.[33] advised achieving primary position alignment in patients of total third nerve palsy using surgery on the horizontal and IR muscles in one session.

According to them it is a safe, simple, and effective procedure and can be regarded as a first-choice operation in total oculomotor nerve palsy.

Villaseñor Solares et al.[35] advised ocular fixation to the nasal periosteum with SO tendon to achieve long-term primary position alignment in complete oculomotor paralysis. A maximal recession of LR muscle is done concurrently to weaken and correct contracture of the LR. This procedure is technically quite challenging.

Partial Third Nerve Palsy

In partial third nerve, the goals of surgery are, good primary position alignment, to create, center and enlarge the field of binocular single vision along with improving motility in certain cases, alleviation of abnormal head posture as well as the elimination of diplopia.

Surgical options vary depending on muscle involved, the amount of recovery and contracture of the direct antagonist of the paralyzed muscle.[2529]

MR resection along with antagonist LR recession can be done in cases of isolated MR involvement. Similarly, for isolated vertical muscle involvement, the paretic muscle with residual function is resected and the antagonist is recessed.

If the operated eye still remains hypertrophic, downward transposition of the horizontal muscles can be done. If the SO tendon has already been transposed to the SR muscle, the SO tendon can be re-mobilized and inserted on the superior aspect of MR muscle (Peter and Jackson transposition).[3637]

In cases of paresis of superior division of the third nerve where elevation is affected, transposition of medial and LR (Knapp's procedure) can be done near the insertion of SR if forced duction test (FDT) is negative for IR.

In case FDT is positive for IR, IR recession (5-6 mm) is recommended. All the lower lid retractors should be separated from the muscle properly to avoid postoperative lid changes.

In cases of palsy of inferior division of third nerve, Kushner[38] described horizontal muscle recession and resection combined with inferior transposition which was disappointing.

Knapp, in 1978,[39] suggested transposition of the LR muscle to the site of insertion of the IR and transposition of the SR to the MR area, combined with tenotomy of the SO muscle to align the eyes in primary position. Kushner also achieved satisfactory results with this procedure in five patients. Although transposition of a muscle does not actually create an effective duction in the direction in which the muscle is transposed, it does provide some active force in that direction. This is supposed to stabilize the eye and guard against a drift toward undercorrection. Weakening of SO corrects the abnormal intorsion due to unopposed action of SO muscle.

If there is no MR function but meaningful residual SR and IR function, both vertical rectus muscle may undergo a small resection (to enhance the transposition medially) and be transposed to the MR insertion.[26] In all situations, it is advised to measure torsion adequately and treat it appropriately.

In selective IR palsy, horizontal recti can be transposed inferiorly in relation to the IR.[40]

Surgery on Superior Oblique

Surgery on the Other Eye

Surgery is usually performed on the affected eye first. If the deviation is sufficiently large; however, horizontal muscle surgery may be necessary on the fellow eye.

Gottlob et al.[48] proposed that this is, especially beneficial in cases with signs of aberrant regeneration (e.g., lid opening in adducted position). The procedure of the horizontal recti in the unaffected eye is an effort to raise the affected blepharoptosis eyelid. In these cases, not only primary position alignment but also lid position was better after operating on horizontal recti of the fellow eye. The noninvolved eye of these patients was moved toward an adducted position and abducting impulses were, therefore, needed to gaze straight ahead. According to Hering's law, this stimulated nerve fibers to the medial recti muscles of the paralytic muscles that were subsequently innervating the levator palpebrae superioris muscle.

Main advantages proposed of this new approach were the need of a single surgery rather than multiple procedures, which reduces patient's discomfort, inconvenience and expense, and avoidance of complications of a conventional ptosis surgery (ectropion, entropion, and lid margin peaking). Noonan and O’Connor[52] later on utilized this concept of fixation duress in 1995 to correct vertical deviation and pseudoptosis in patients of third nerve palsy. They proposed that by decreasing the ability of the noninvolved eye to elevate, fixation duress was created which eliminated the secondary deviation that characteristically occurs in such patients when the involved eye fixates. As a result of this technique, both eyes in all patients on attempted fixation are under similar duress, therefore requiring equal amounts of stimulation to move into the primary position. When the fixation duress is sufficient, elimination of the hypotropia and pseudoptosis is achieved. The exotropia was corrected by a combination of the MR resection, LR recession of the paretic eye and an LR recession in the fellow eye. The amount of horizontal recti recession/resection was depending on the deviation measured with fixing eye. They also weakened the SR of the normal eye to limit the elevation of that eye. In certain cases where needed, IR of the non-involved eye was also resected. Only one patient had a residual exotropia of 20 PD. They achieved cosmetically satisfactory results in other two patients with this procedure.

Sato et al.[53] recommended myectomy of LR muscle to accomplish a super-maximal weakening effect of abduction in patients with complete third nerve palsy. Postoperatively, his patient still had an exotropia of 45 PD. Then, in the second sitting, he did resection of the MR and recession of LR of the nonaffected eye. Primary position alignment in his case was then achieved without any noticeable limitation of abduction in his cases.

Surgery Only on the Nonaffected Eye

Surgical techniques involving the normal eye were also recommended by Parulekar and Elston.[54] They described a surgical plan to simultaneously correct the ocular misalignment and the pseudoptosis resulting because of aberrant regeneration. They did large recession of the LR (7-8 mm) and a smaller MR resection on the nonparetic eye of four cases to correct the horizontal misalignment, the amount of surgery being based on the ocular deviation measured with the dominant eye fixing. To this, they combined downwards transposition of the insertions of the medial and lateral recti to correct the vertical deviation. No surgery was performed on the lids of the paretic eye. They used this technique successfully in four cases of third nerve palsy with aberrant regeneration (three traumatic and one congenital). This technique involved setting the nonparetic eye in a position of relative adduction. To maintain the eyes in the primary position, increased innervation of the LR of the nonparetic eye is needed and the paretic eye adducts. As a result of the misdirection-regeneration, the levator is stimulated and the ptotic lid is elevated in the primary position. Because near maximum innervation is flowing to the MR (so as a result to the levator) to maintain the eyes in the primary position, there is minimal further stimulation of the levator in attempted downgaze, and the pseudo-Von Grafe's sign is minimized.

Fellow eye muscle surgery is also described in certain cases of partially recovered third nerve having no diplopia/deviation in the primary position, but complaining of diplopia in the gaze of the affected muscle. In such cases, fade operation of the other eye synergist muscle is advised to provide comitance and to relieve diplopia in the affected gaze.

Conclusion

Although above-mentioned studies have reported satisfactory outcomes in a number of patients of the third nerve palsy with various surgical techniques, satisfactory ocular alignment still remains a challenge for an ophthalmologist in third nerve palsy.