The term 'Diplopia' is derived from the Greek; diplous meaning double and ops meaning eye. Diplopia causes significant difficulty with depth perception and orientation of objects. Adults are capable of expressing this symptom unlike children; in addition, in children the image from the defective eye is suppressed due to the immature visual system.

There is no information available regarding its epidemiology.

A number of pathological processes can cause ocular nerve (3rd, 4th, & 6th cranial nerves) palsies produce binocular diplopia, encountered in neurological practice.

THIRD [OCULOMOTOR] NERVE:

Neuro-Anatomy: This nerve innervates by the Superior division - the Levator palpebrae superioris and  the Superior rectus muscle and

by the Inferior division - the Inferior rectus, the Medial rectus, the Inferior oblique, the Sphincter pupillae, and the Ciliary muscle.

The nuclear complex of the third (oculomotor) nerve is situated in the mid-brain at the level of the superior colliculus, inferior to the sylvian aqueduct. It is composed of the following paired and unpaired subnuclei:

·        The levator subnucleus is an unpaired caudal midline structure which innervate both levator muscles. Lesions confined to this area will therefore give rise to bilateral ptosis.

·        The superior rectus subnuclei are paired and innervate their respective contralateral superior rectus muscles.

·        The medial rectus, the inferior rectus and the inferior oblique subnuclei are paired and innervate their corresponding ipsilateral muscles.

Lesions involving purely the third nerve nuclear complex are relatively uncommon.

 The most frequent causes are vascular disease, demyelination, primary tumors, and metastases.

Lesions involving the entire nucleus cause an  ipsilateral third nerve palsy with  ipsilateral sparing and contralateral weakness of elevation.

Lesions involving the paired medial rectus subnuclei cause a wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) characterized by defective convergence and adduction.

The fasciculus consists of efferent fibers which pass from the third nerve nucleus through the red nucleus and the medial aspect of the cerebral peduncle. They then emerge from the mid-brain and pass into the interpeduncular space. Benedikt's syndrome involves the fasciculus as it passes through the red nucleus. It is characterized by an ipsilateral third nerve palsy and a contralateral hemitremor.

Weber's syndrome involves the fasciculus as it passes through the cerebral peduncle. It is characterized by an ipsilateral third nerve palsy and a contralateral hemiparesis.

The basilar part starts as a series of 'rootlets' which leave the mid-brain before coalescing to form the main trunk. The nerve then passes between the posterior cerebral artery and the superior cerebellar artery, running lateral to and parallel with the posterior communicating artery because the nerve traverses the base of the skull unaccompanied by any other cranial nerves, isolated third nerve palsies are frequently basilar.

The following two are important causes:       1. Aneurysms at the junction of the posterior communicating artery and the internal carotid artery. 2.    Extradural hematomas, which may cause a tentorial pressure cone with downward herniation of the temporal lobe. This compresses the third nerve as it passes over the tentorial edge initially causing a fixed dilated pupil followed by a total third nerve palsy.

The intracavernous part enters the cavernous sinus by piercing the dura just lateral to the posterior clinoid process. Within the cavernous sinus, the third nerve runs in the lateral wall and occupies a superior position above the fourth nerve. In the anterior part of the cavernous sinus, the nerve divides into superior and inferior branches which enter the orbit through the superior orbital fissure within the annulus of Zinn. The following are important causes of intracavernous third nerve palsies: Diabetes which may cause a vascular palsy.

Pituitary apoplexy which may cause a third nerve palsy as a result of hemorrhagic infarction of a pituitary adenoma (e.g after childbirth), with lateral extension into the cavernous sinus.

Intercavernous lesions such as aneurysms, meningiomas, carotid-cavernous fistulae and Granulomatous inflammation (Tolosa-Hunt syndrome) may all cause third nerve palsies.

Because of its close proximity to other cranial nerves, intracavernous third nerve palsies are usually associated with involvement of the fourth and sixth nerves and the first division of the trigeminal nerve; the pupil is frequently spared.

The intraorbital part divides into the following:

The superior division which innervates the levator and superior rectus muscles.

The inferior division which innervates the medial rectus, the inferior rectus and the inferior oblique muscles. The inferior branch of the third nerve within the orbit also contains the parasympathetic fibers from the Edinger-Westphal subnucleus, which innervate the sphincter pupillae and the ciliary muscle. Lesions of the inferior division are characterized by limited adduction and depression, and a dilated pupil.

The main causes of both superior and inferior division palsies are trauma and vascular disease.

Pupillomotor fibers: The location of these parasympathetic fibers in the trunk of the third nerve is clinically very important. Between the brain stem and the cavernous sinus, the pupillary fibers are located superficially in the superior median part of the nerve. They derive their blood supply from the pial blood vessels, whereas the main trunk of the third nerve is supplied by the vasa nervosum. The presence or absence of pupillary involvement is of great importance because it frequently differentiates a so-called 'surgical' from a 'medical' lesion.

Surgical lesions such as aneurysms, trauma and uncal herniation characteristically involve the pupil by compressing the pial blood vessels and the superficially located pupillary fibers.

Medical lesions such as hypertension and diabetes usually spare the pupil. This is because the microangipathy associated with medical lesions involves the vasa nervosum, causing neural infarction of the main trunk of the nerve, but sparing the superficial pupillary fibers.

Clinical features of third (Oculomotor) nerve palsy:

•         Ptosis due to weakness of levator

•         Eyeball is divergent and slightly downwards due to unopposed action of the lateral rectus (N VI) and     superior oblique (N IV) muscles.

•         Intorsion of the eyeball on attempted down gaze, due to action of superior oblique muscle.

•         Ocular movements are restricted in all directions [elevation, depression & adduction] except outwards (due to lateral rectus)

•         Pupil is dilated, and does not constrict to light or convergence. Difficulty for small print  is  present

POST TRAUMATIC LEFT OCULOMOTOR NERVE PALSY

Complete ptosis with ecchymoses	Left exotropia
Adduction Restricted	Abduction Normal
Elevation restricted	Depression restricted

Aberrant regeneration may occasionally follow acute traumatic and aneurysmal, but not vascular, third nerve palsies. The bizarre defects in ocular motility, such as elevation of the upper eyelid on attempted adduction or depression, are caused by misdirection of sprouting axons reinnervating the wrong extraocular muscle. The pupil may also be involved in some cases.

Causes of isolated third nerve palsy:

In order of frequency the following are causes of an isolated third nerve palsy:

Idiopathic : about 25% have no known cause.

Vascular disease such as hypertension and diabetes are the most common causes of a pupil-sparing third nerve palsy. All patients should therefore have blood pressure measurement and urine analysis. In most cases recovery occurs within 3 months. Diabetic third nerve palsies are often associated with periobital pain and are occasionally the presenting feature of diabetes. The presence of pain is not helpful in differentiating between an aneurysmal and a diabetic third nerve palsy because both are frequently accompanied by pain.

Trauma is also a common cause. However, the development of a third nerve palsy following relatively trivial head trauma, not associated with loss of consciousness, should alert the clinician to the possibility of an associated basal intracranial tumour which has caused the nerve trunk to be stretched and tethered.

An aneurysm at the junction of the posterior communicating artery with the internal carotid is a very important cause of an isolated painful third nerve palsy with involvement of the pupil.

Miscellaneous uncommon causes include tumors, vasculitis associated with collagen vascular disorder and syphilis. 

As with all ocular motor nerve palsies, surgical treatment should be contemplated only after all spontaneous improvement has ceased. This is usually not earlier than 6 months from the date of onset.  

FOURTH [TROCHLEAR] NERVE:

Neuro-anatomy:The fourth nerve differs from other cranial nerves as follows:

It is the only cranial nerve to emerge from the dorsal aspect of the brain.

It is the only crossed cranial nerve; this means that the fourth nerve nucleus innervates the contralateral superior oblique muscle.

It is the longest and most slender of all cranial nerves.

The nucleus of the fourth nerve is located at the level of the inferior colliculus beneath the sylvian aqueduct. It is caudal to, and continuous with, the third nerve nuclear complex.

The fasciculus consists of axons which curve around the aqueduct and decussate completely in the anterior medullary velum.

The trunk leaves the brain stem on the dorsal surface, just caudal to the inferior colliculus. It then curves forward around the brain stem, runs beneath the free edge of the tentorium, and (like the third nerve) passes between the posterior cerebral artery and the superior cerebellar artery. It then pierces the dura and enters the cavernous sinus.

The intracavernous part runs laterally and inferiorly to the third nerve and above the first division of the fifth. In the anterior part of the cavernous sinus it rises and passes through the superior orbital fissure above the annulus of Zinn.

The intraorbit part innervates the superior oblique muscle.

Clinical features of fourth nerve palsy:

The clinical features of a nuclear, fascicular and a peripheral fourth nerve palsy are clinically indistinguishable.

·        Hyper deviation (involved  eye is higher) as a result of  weakness of the superior oblique muscle. This is more obvious when the head is titled to the ipsilateral shoulder (Bielschowsky’s head tilt  test).

·        Excyclotorsion which is compensated for by a head tilt to the opposite shoulder.

·        Limited depression in adduction.

·       Diplopia which is vertical and worse on looking down. In order to avoid diplopia the patient may adopt an abnormal head posture with a downward head tilt and a face turn to the opposite side.·      

Post Traumatic Right Trochlear Nerve Palsy

Right hyper tropia in primary gaze with head straight.	Eyes aligned with head tilt to the left side.	Post operative-Eyes aligned with head straight. (Surgery done after four to six  months to the right inferior oblique and left inferior rectus in two stages.)

Causes of isolated fourth nerve palsy:

1.Congenital lesions are frequent, though symptoms may not develop until adult life. Abnormal head posture [ocular torticollis]in old photographs when available can be of help.

2.Trauma often causes bilateral palsies as the slender nerves are vulnerable as they decussate in the anterior medullary velum through impact with the tentorial edge.

3.Vascular lesions are common but aneurysms and tumors are rare.

Medical investigations are the same as for a pupil sparing third nerve palsy. 

SIXTH [ABDUCENS] NERVE

Neuro-anatomy: The nucleus of the sixth (abducens) nerve lies in the midpoint of the pons, inferior to the floor of the fourth ventricle, where it is closely related to the fasciculus of the seventh nerve. An isolated sixth nerve palsy is therefore never nuclear in origin.

A lesion in and around the sixth nerve nucleus causes the following signs:

·        Failure of horizontal gaze towards the side of the lesion resulting from involvement of the horizontal gaze centre in the pontine paramedian reticular formation (PPRF).

·        Ipsilateral weakness in abduction as a result involvement of the nucleus.

·        Ipsilateral facial nerve palsy caused by concomitant involvement of the facial fasciculus which is also common.

The fasciculus consists of emerging fibres which pass ventrally to leave the brain stem at the pontomedullary junction, just lateral to the pyramidal prominence.

Foville’s syndrome involves the fasciculus as it passes through the PPRF and is characterized by the following ipsilateral signs: sixth nerve palsy combined with a gaze palsy, facial weakness caused by damage to the facial nucleus or fasciculus, facial analgesia from involvement of the sensory portion of the fifth nerve, Horner’s syndrome and deafness. Millard-Gubler syndrome involves the fasciculus as it passes through the pyramidal tract and is characterized by ipsilateral sixth nerve palsy, contralateral hemiplegia and variable number of signs of a dorsal pontine lesion.

The basilar part leaves the mid-brain  at the pontomedullary function and enters the prepontine basilar cistern. It then passes upwards close to the base of the pons and is crossed by the anterior inferior cerebellar artery. It pierces the dura below the posterior clinoids and angels forwards over the tip of the petrous bone, passing through or around the inferior petrosal sinus, through Dorello’s canal (under the petroclinoid ligament) to enter the cavernous sinus.

The following are important causes which may damage the basilar portion of the nerve.

1.                 An acoustic neuroma may damage the sixth nerve as it leaves the mid-brain at the pontomedullary junction. It should be emphasized that the first symptom of an acoustic neuroma is hearing loss and the first  sign is a diminished corneal sensitivity. It is therefore very important to test hearing and corneal sensation in all patients with sixth nerve palsy.

2.                 A nasopharyngeal tumor may invade the skull and its foramina and damage the nerve during its basilar course.

3.              Raised intracranial pressure associated with posterior fossa tumors or benign intracranial hypertension (pseudotumor cerebri) may cause a downward displacement of the brain stem: This may stretch the sixth nerve over the petrous tip between its point of emergence from the brain stem and its dural attachment on the clivus. In this situation, the sixth nerve palsy, which may be bilateral, is a false localizing sign.

4.                 A basal skull fractures may cause both unilateral and bilateral palsies.

The intracavernous part runs forwards below the third and fourth nerves, as well as the first division of the fifth. Although the other nerves are protected within the wall of the sinus, the sixth is most medially situated and runs through the middle of the sinus in close relation to the internal carotid artery. It is therefore more prone to damage than the other nerves. Occasionally, an intracavernous sixth nerve palsy is accompanied by a postganglionic Horner’s syndrome because in it’s intracavernous course the sixth nerve is joined by the sympathetic branches from the paracarotid  plexus. The causes of intracavernous sixth nerve and third nerve lesions are similar.

The intraorbital part enters the orbit through the superior orbital fissure within the annulus of Zinn to innervate the lateral rectus muscle.

Clinical features of sixth nerve palsy:

Left esotrpoia	Normal adduction of left eye	Abduction restricted in the left eye

      Defective abduction is caused by weakness of the lateral rectus with normal adduction.

      In the primary position, there is a convergent strabismus as a result of the unopposed action of the medial rectus. 

      The face is turned into the field of action of the paralyzed muscle to minimize diplopia, so that the eyes are turned away from the field of action of the paralyzed muscle. For example, a patient with a left sixth nerve palsy will turn the face to the left.

      Horizontal diplopia is worse in the field of action of the paralyzed muscle and least away from its field of action.

      Most of the causes of an isolated sixth nerve palsy have already been mentioned, but, in contrast to third nerve palsy, aneurysms rarely cause a sixth nerve palsy. Vascular causes (especially diabetes and hypertension) are, however, common.

PARALYTIC SQUINT

It is the mis-alignment of the visual axes as a result of paresis, or paralysis of one or more extra-ocular muscles. It is characterized by impaired movement in the field of action of the muscle or muscles,  and thus the angle of deviation varies in different directions of gaze.

CLINICAL FEATURES:

Binocular diplopia

An object appears double with both eyes remain open. This occurs when the image of an object does not fall on the corresponding points of the retina of the both eyes. Image of an object falls on the fovea of one eye, and on the extra foveal area of the opposite eye.

Causes

1.     Paralysis or paresis of the extra-ocular muscles (commonest)

2.     Displacement of the eyeball, by a space occupying lesion in the orbit, by fracture of orbital wall or by pressure of fingers.

3.     Mechanical restriction of the movements of the globe e.g. pterygium, symblepharon, thyroid ophthalmopathy etc.

4.     Deviation of rays of light in one eye, as in decentered spectacles.

5.     Disparity of image size between two eyes, as in acquired high aniso-metropia.

In diplopia one image is distinct (true image), and the other is indistinct (false image). Binocular diplopia disappears when one eye is closed. Depending on the position of the false image in relation to midline, binocular diplopia may be uncrossed or crossed.

·        False orientation of the object: object is projected too far in the direction of paralyzed muscle, due to increase in secondary deviation.

·        Vertigo and nausea: They are partly due to diplopia, and partly due to false orientation.

·        Secondary angle of deviation is more than the primary deviation.

·        Restriction of ocular movements in the direction of action of paralyzed muscle.

·        Compensatory head posture:

In paralytic squint to neutralize diplopia, the chin may be elevated or depressed.

The face turned to right or left side.

The head tilted to the right or left shoulder (ocular torticollis).

This head posture, is to neutralize the angle of deviation, or to separate    the images maximally, so as to avoid diplopia.

In paralysis of horizontal rectus muscle, the face is turned to field of action of the paralyzed muscle, but the head is not tilted. As, in right lateral rectus palsy, the patient keeps his face turned to the right.

In case of cyclo-vertical muscle palsy, it is more complicated, and less valuable diagnostically. As in superior oblique palsy, the head is tilted on the side of the normal eye, the face is turned opposite to normal side, and the chin is depressed.

·        Visual acuity is normal in both eyes, and there is no amblyopia. 

Different types of ocular paralysis:

Total ophthalmoplegia: It means involvement of both extrinsic and intrinsic muscles of the eyeball. In unilateral cases, the lesion is in the cavernous sinus, or in the superior orbital fissure, and in bilateral cases, the lesion is widespread in the brain-stem (due to inflammatory cause).

Clinical signs:

Ptosis.

·        The eyeball is slightly proptosed and divergent (due to anantomical positon of rest).

·        No movement of the eyeball in any direction

·        Fixed dilated pupil (no reaction to light, accommodation and convergence).

·        Total loss of accommodation.

External ophthalmoplegia: It is due to paralysis of extrinsic muscles which includes six extra-ocular muscles and the levator. It is due to nuclear lesion without affecting the Edinger-Westphal nucleus, which supplies the intrinsic muscles.

Signs are same as total ophthalmoplegia except, that the pupillary reaction and accommodation are normal.

Investigations of paralytic squint:

History, careful complete clinical examination and appropriate investigations including radio imaging to identify the causative factor

Diplopia Charting/Hess Lee’s Screening initially to identify the eye muscle affected and later at four to six weeks to know about the progress.

Measurement of angle of deviation by synoptophore or prism bar.

Forced duction test (FDT): This test is used to differentiate defective ocular movements due to physical restriction, from a muscle paralysis.

After topical anesthesia, the insertion of the affected muscle is grasped with fixation forceps, and gently attempted to rotate the eyeball in the field of action of weak muscle. FDT-‘Positve’ means, it is difficult to move the globe with the forceps (e.g., contracture of muscle as in thyroid myopathy, trapped muscle in orbital floor fracture etc.)

FDT is ‘negative’ in case of muscle   paralysis.

Treatment of paralytic squint:

Treatment must be directed to the cause of paralysis.

    Ischemic lesion can resolve spontaneously

    For the relief of diplopia: [if present only in the practical field of fixation i.e in the straight and down gazes]

    Occlusion of affected eye temporarily.

    Suitable prism correction for minor diplopia.

    Observation for at least 6 months, so that maximum amount of spontaneous recovery could take place.

     Recession of contra-lateral synergist may be done for the nerve palsy. Alternately, various type of muscle transposition operations may be undertaken.

     Botulinum toxin injection – to treat the antagonist muscle to prevent its contracture.

CRANIAL NERVE SYNDROMES:

These syndromes were of help for topo graphical localization prior to radio imaging techniques.

WEBER                                  Ipsilateral third nerve palsy

                                             Contralaterl hemiparesis

BENEDICT                              Ipsilateral third nerve palsy

                                             Contralateral hemi tremor

MILLARD- GUBLAR                Ipsilateralsixth nerve palsy

                                             Ipsilateral seventh nerve

                                             Contra lateral hemiplegia

FOVILLE                                Ipsilateral sixth nerve palsy

                                                            Gaze palsy

                                                            Facial weakness

                                                            Facial analgesia

                                                            Horner’s syndrome

                                                            Deafness

GRADENIGO                           Petrositis

TOLOSA HUNT                        Painful ophthalmoplegia due to granulomatous lesion in

                                             cavernous sinus