Common Causes & Sites of Oculomotor Paralysis | Humans | Medical Science

Nuclear lesions occur in the brain stem and common causes include vascular’ infarctions, demyelination and brain stem tumours, like gliomas. Commonly neighbouring structures in the brain stem are also involved e.g. third nerve palsy with contralateral hemiplegia (Weber’s syndrome), third nerve palsy with contralateraltremordue to involvement of Red nucleus (Benedikt’s syndrome) and ipsilateral sixth and seventh nerve palsy with contralateral hemiplegia (Millard-Gubler syndrome). It is important to remember that owing to the multiplicity of the nuclei, nuclear third nerve palsies are often incomplete.

Infranuclear Lesions:

a. Unilateral or bilateral sixth nerve palsy results due to nerve stretching from raised intracranial pressure usually due to a posterior fossa space occupying lesion (false localising sign).

b. During cerebral herniation from a space occupying lesion in one hemisphere, the ipsilateral third nerve may be compressed between the herniated uncus and the free margin of the tentorium.

c. Any of the nerves may be involved by a process of basal meningitis (tubercular, syphilitic or carcinomatous) or by allergic process like in Guillain-Barre syndrome.

d. The third neire is commonly compressed by an aneurysm of the posterior communicating artery.

e. Localised meningitic process (secondary to mastoiditis) may involve the fifth, sixth and seventh cranial nerve (Gradinegos syndrome).

f. Any pathology in the region of the cavernous sinus or superior orbital fissure would involve all the oculomotor nerves along with the ophthalmic division of the fifth cranial nerve. Such lesions include cavernous sinus thrombosis, carotico-carvernous fistula, intracavernous aneurysm of internal carotid artery or a tumour (pituitary adenoma or a meningioma invading the cavernous sinus. Not an uncommon condition in our country is the syndrome of painful ophthalmoplegia (Tolosa-Hunt syndrome) which mimicks any cavernous sinus lesion.

The cause is perhaps an inflammatory process involving the periosteum of the superior orbital fissure or the sheath of the intracavernous carotid artery. There is intense pain in the distribution of the ophthalmic branch of Trigeminal along with rapid development of oculomotor palsies. The condition responds dramatically to corticosteroids.

Systemic medical disorders like diabetes and atherosclerosis at times causes isolated oculomotor lesion perhaps by causing small infarcts of the nerve trunks.

Diseases of the ocular muscles will closely mimick oculomotor nerve involvement. The common conditions are Thyrotoxicosis, Myesthenia Gravis and progressive ocular myopathy. In any case of isolated oculomotor palsy, it is important to think above and rule out Myesthenia by an Edrophonium Test.

The Pupils:

Anatomical Considerations:

Pupillary size is determined by the balance of action between a ring of constrictor fibres innervated by the parasympathetic and radially arranged dilator fibres innervated by the sympathetic. Parasympathetic overactivity thus causes pupillary constriction and paralyses pupillary dilatation. The reverse is the case with the sympathetic.

Parasympathetic Pathways and the Pupillary Reflexes:

When a beam of light is focussed on one eyeball, the pupil of the same side as well as of the opposite side constrict (light reflex). The light stimulus is carried from the ipsilateral retina by the optic nerve, the chiasma and the optic tract to the lateral geniculate body; wherefrom it is relayed to Edinger-Westphal nuclei of both sides lying in the midbrain.

This nucleus is in fact a part of the third nerve nucleus and gives rise to the pre-ganglionic parasympathetic fibres. These traverse with the third nerve and on entering the orbit terminate in the ciliary ganglion. The post­ganglionic fibres originate from this ganglion and pass as the short ciliary nerves which innervate sphincter pupillae muscle in the iris.

The parasympathetic fibres are also concerned with the accommodation reflex necessary for near vision where in addition to pupillary constriction, medial conjugate deviation of the eyes occurs to bring a near object to focus. The impluses originated from the visual cortex and then pass to the frontal lobe by way of occipito-frontal fibres. From here, descending fibres terminate in the midbrain around Edinger-Westphal nuclei as well as the third nerve nuclei which is necessary for causing pupillary constriction and medial convergence by contraction of both medial recti muscle. The final common pathway, is of course, the third cranial nerve itself.

Sympathetic Pathway:

The central sympathetic pathway, of course, starts in the hypothalamus and descends down in the cervical spinal cord to terminate around cells of the intermedio-lateral horn of the spinal grey column Preganglionic fibres start from here and pass out via the T₁ ventral nerve root and enter the cervical part of the sympathetic chain wherein they ascend up to the superior cervical ganglion.

Post-ganglionic fibres start from here and pass along the sheath of the internal carotid artery to enter the cranial cavity and orbit. In the eye they supply not only the dilator pupillae muscle but also the unstriped muscle of the eyelid (Mueller’s muscle) which elevates the eyelid passively.

Lesions of the Parasympathetic Pathway:

The end result is a dilated fixed pupil without any light reflex:

1. Optic atrophy always causes a fixed dilated pupil on the side of the lesion (amblyopic pupil).

2. Partial lesions of the optic nerve, (usually due to a demyelinating disease) cause afferent pathway lesion with a Muscus Gunri Pupil. The normal eye shows a brisk pupillary reaction to bright light. But in the abnormal eye, the reaction is slow and incomplete. It may be so brief that it may start to dilate immediately.

3. In a lesion of the optic tract with hemianopia, light focussed on the affected half field of vision will not elicit a light reflex (hemianopic Wernicke’s pupil). This test differentiates an, optic tract from a radiation lesion but in practice is usually very difficult to elicit due to dispersion of light in the eye.

4. Upper midbrain compressive or destructive lesions will also cause pupillary abnormalities e.g. in case of pinealoma. In this condition paralysis of upward gaze also occurs (Perinaud’s syndrome).

5. Lesions anywhere in the course of the third nerve may interrupt pupillary parasympathetic fibres. This, however, is not universally true as partial lesions are common where the pupil escapes. Compressive lesions are usually complete. Irregularity of pupillary size is the earliest sign of uncal herniation (causing ipsilateral third nerve compression) in a case of cerebral SOL.

6. Argyll-Robertson Pupil (ARP):

This is the hallmark of neurosyphilis but similar pupil may rarely be found in diabetes, peroneal muscular atrophy and facial hemiatrophy.

The characteristic features of ARP include:

(a) Small irregular pupils

(b) Loss of light reflex

(c) Preservation of accommodation reflex

(d) Absence of response to mydriatics

(e) Patchy depigmentation of the iris.

The site of the lesion responsible is debatable. Although originally thought to be in the periaqueductal grey matter in the midbrain, a more plausible site is perhaps in the region of the ciliary ganglion or in the substance of the iris itself:

7. Holmes-Adie (or Tonic) Pupil:

The tonic pupil is a widely dilated circular pupil which is usually unilateral and which reacts very slowly to light but smartly to accommodation. This is usually associated with the absence of knee and ankle jerks but the etiology is unknown. In most cases this is a chance finding but may be baffling to the clinician if this condition is not thought of.

8. Isolated loss of accommodation reflex only is a rarity. This classically occurs in diphtheria and is fully recoverable.

Lesions of the Sympathetic Pathway:

Lesions anywhere in the course of the sympathetic pathway to the eye causes a Horner’s syndrome.

The features of the fully developed syndrome include:

1. The affected pupil is smaller (miosis) due to reduced pupillo-dilator activity. This asymmetry is more obvious in darkness. The light and accomodation reflexes are present but reduced.

2. Mild to moderate ptosis of the eyelid — due to paralysis of the sympathetically innervated Mueller’s muscle.

3. Impairment of sweating (anhydrosis) of the affected half of the face. This results if the lesion is proximal to the superior cervical ganglion.

4. Exophthalmos (i.e. sunken eye due to dryness of the intraorbital structures) although described in literature, is rarely seen.

5. Loss of cilia-spinal reflex- this is a sympathetically mediated reflex wherein pinching the skin of the neck produces ipsilateral pupillary dilatation.

As Homer’s syndrome may result from either a pre-ganglionic (proximal to superior cervical ganglion) or a post-ganglionic lesion, it becomes at times important to differentiate between the two. This is usually done by using Adrenaline (1: 1000) eye drops. This produces no effect on a pre-ganglionic Horner pupil but causes marked dilatation in case of a post-ganglionic lesion due to phenomenon of denervation supersensitivity.

Common Causes of Horner’s Syndrome:

i. Central Lesions: (Pre-Ganglionic):

Brain Stem:

Vascular lesions (classically posterior inferior cerebeller artery occlusion causing Lateral Medullary Syndrome), demyelination and tumours.

Cervical Cord Lesions:

Syringomyelia and intramedullary tumours like gliomas and ependymomas.

ii. Peripheral Lesions:

D1 Root Lesions (Pre-Ganglionic):

The commonest cause is compression by an apical bronchogenic neoplasm (Pancoast Tumour). All cases of Horner’s syndrome must always have a chest X-ray for this reason.

Cervical Sympathetic Chain (Pre- And Post-Ganglionic):

Common causes of damage include neoplastic infiltration, surgical exploration, and trauma to the neck.

Intracranial Sympathetic Fibres: (Post-Ganglionic):

Theoretically, the internal carotid nerve plexus may be damaged by lesions in the cavernous sinus causing Horner’s syndrome. But this is rarely seen in clinical practice as parasympathetic damage due to involvement of the third nerve usually determines the pupillary response. A transient form of Horner’s syndrome due to involvement of ocular sympathetic fibres occurs during attacks of cluster headaches (a variant of migraine).

Pupillary Abnormalities in an Unconscious Subject:

Normally reacting equal pupils indicate a functioning brain stem and is a reassuring sign.

The earliest sign of progressive cerebral (uncal) herniation is an ipsilateral pupillary dilatation. Jonathan Hutchinson described sequential pupillary changes following rapidly rising intracranial pressure usually due to extradural haematoma following head injury. The pupil on the side of lesion is first constricted and then dilates; the same sequence of events then follows on the other side.

Bilateral fixed dilated pupils usually denote irreversible brain stem damage. The only toxic causes of such changes are glutethamide, atropine and amphetamine poisoning.

Bilateral pin-point pupil is also a ominous neurological sign usually occurring in pontine or intraventricular haemorrhage along with hyperpyrexia. Opiates, of course, produce similar pupillary abnormality.