Acquired Oculomotor Nerve Palsy
Acquired oculomotor nerve palsy (OMP) is an ocular pathology resulting from damage to third cranial nerve. It can presents in different ways causing somatic extraocular muscle dysfunction (superior, inferior, and medial recti; inferior oblique; and levator palpebrae superioris) and autonomic (pupillary sphincter and ciliary) muscles. 
- 1 Disease Entity
- 1.1 Disease
- 1.2 Etiology
- 1.3 Risk Factors
- 1.4 General Pathology
- 1.5 Pathophysiology
- 1.6 Lesions of Oculomotor Nucleus (Midbrain)
- 1.7 Lesions of Oculomotor Nerve Fascicles (Leaving the 3rd nerve nucleus)
- 1.8 Lesions in the Subarachnoid space
- 1.9 Lesions within the Cavernous Sinus and Superior Orbital Fissure
- 1.10 Lesions within the Orbit
- 1.11 Primary prevention
- 2 Diagnosis
- 3 Management
- 4 References
Partial and complete 3rd nerve palsy
Clinical findings of acquired third nerve palsy may depend on the affected area of the oculomotor nerve track. It can be divided into partial or complete palsy. Complete 3rd nerve palsy presents with complete ptosis, with the eye positioned downward and outward with the inability to adduct, infraduct, or supraduct, as well as dilated pupil with sluggish reaction. Partial 3rd nerve palsy may be more common, and can present with variable duction limitation of the affected extraocular muscles and with variable degree of ptosis and/or pupillary dysfunction. 
There are many etiologies for oculomotor palsy including vasculopathic process, trauma, compression (e.g. aneurysm), infiltrative (e.g. leukemia), toxic (e.g. chemotherapy) etc.
Risk factors may coincide with underlying etiology listed above and can include Diabetes mellitus, Hypertension, Vasculitis, Trauma, Infections, Tumor, Aneurysm etc.
The manifestations may depending on the location of the lesion. In some cases, the precise site of the lesion is clear, whereas in others, the location of the lesion is speculative.
To understand the pathophysiology of the oculomotor nerve palsy it is essential to know its pathway. The following flowchart represents the anatomic course of cranial nerve III with designated description of clinical manifestations
Lesions of Oculomotor Nucleus (Midbrain)
Usually produce bilateral defects. This is explained by the anatomy of the nucleus. It is divided in subnuclei according to the innervated area. Each superior recti (SR) are innervated by the contralateral CN III subnucleus; thereby a nuclear CN III palsy would produce paralysis of the contralateral SR. Both levator palpebrae superioris are innervated by one subnuclei (central caudal nucleaus); therefore a nuclear lesion would produce bilateral ptosis. Patients with damage to the oculomotor nuclear complex need not have ipsilateral pupillary dilation, but when involved, it may indicate dorsal rostral damage. often caused by ischemia, usually from embolic or thrombotic occlusion of small, dorsal perforating branches of the mesencephalic portion of the basilar artery.
Lesions of Oculomotor Nerve Fascicles (Leaving the 3rd nerve nucleus)
Lesions at this level can produce complete or incomplete palsies. The majority of the time it cannot be differentiated from lesion outside of the midbrain. When the lesion is adjacent to CN III nucleus (midbrain) it can produce several manifestations that have been described according to other neurological manifestations. Lesion at the superior cerebellar peduncle (Nothnagel’s Syndrome) presents with ipsilateral 3rd nerve palsy and cerebellar ataxia.Lesions at the Red Nucleus (Benedikt's Syndrome) are characterized by ipsilateral 3rd nerve palsy and contralateral involuntary movement. Lesions at the Red Nucleus and superior cerebellar peduncle (Claude Syndrome) presents with ipsilateral 3rd nerve palsy, contralateral ataxia, asynergy and tremor. Lesions at the cerebral peduncle (Weber’s Syndrome) produces ipsilateral 3rd nerve palsy and contralateral hemiplegia. It is important to remember that lesions can present combination of these findings depending on the degree of the insult. In addition, although it is classic that CN III separates in superior and inferior ramii at the superior orbital fissure, sometimes lesions at the fascicles can produce isolated dysfunction of either the superior and inferior division. The most common causes include ischemic, hemorrhagic, compressive, infiltrative, traumatic, and rarely, infiltrative and demyelinating process.
Lesions in the Subarachnoid space
This space is defined as the area traveled by the oculomotor nerve between the ventral surfaces of the midbrain to the entrance of the cavernous sinus, also known as the interpeduncular fossa. Oculomotor nerve damage in this area can produce varied presentations. CN III palsy with fixed dilated pupil, it is important to recall that pupillary fibers occupy a peripheral location and receive more collateral blood supply that the main trunk of the nerve. This is why they are susceptible to compression (e.g. aneurysm). The most common known etiology is a posterior communicating artery aneurysm. This is a medical emergency. CN III palsy without pupil involvement, as mentioned above pupillary fibers occupy a peripheral location and receive more collateral blood supply that the main trunk of the nerve. For this reason are less susceptible to ischemia.. This is why in most of the cases patients have diabetes mellitus, systemic hypertension, atherosclerosis and in some cases migraine. Nevertheless, compressive masses or aneurysm can also cause it. On the course to the cavernous sinus the CN III rest on the edge of the tentorium cerebelli. The edge of the uncal portion overlies the tentorium for this reason in the setting of increased intracranial pressure this brain section can herniate producing displacement of the midbrain compressing the ipsilateral oculomotor nerve. This causes ipsilateral ophthalmoplegia and mydriasis. The most common cause of uncal herniation is intracranial hemorrhages.
Lesions within the Cavernous Sinus and Superior Orbital Fissure
Lesion at these zones can produce isolated CN III palsy, but it is most commonly associated with other cranial nerves dysfunctions. Differentiating between lesions at the cavernous sinus versus the superior orbital fissure can be challenging and sometimes the literatures describe it as sphenocavernous syndrome. It presents as paresis of oculomotor, trochlear and abducens nerves with associated maxillary division of trigeminal nerve, producing pain. This can be caused by primary (direct invasion) or secondary (intracranial/intraorbital lesion compressing these areas) lesions. Most common causes are tumor (e.g. meningiomas) There is another described pathology within the cavernous sinus and superior orbital fissure that presents with painful ophthalmoplegia known as Tolosa Hunt Syndrome. It is described as an idiopathic granulomatous inflammation. This is a diagnosis of exclusion, therefore tumors, metastasis or aneurysm must be ruled out with neuroimaging. Although tumor are the most common causes of lesions at this zone, vascular processes can also produce damages to the structures present in it. Cavernous sinus thrombosis, carotid cavernous fistulas, syphilis, vasculitis, and/or autoimmune connective tissue diseases (e.g. systemic lupus erythematosus) can produce painful ophthalmolegias typical of cavernous sinus syndrome.
Lesions within the Orbit
Lesions within the orbit are associated with visual loss, ophthalmopleagia and proptosis. Third nerve ophthalmoplegia can be associated with trochlear and abducens nerve palsies. It is important to remember that at the orbit the oculomotor nerve divides into superior and inferior division. This can cause partial oculomotor nerve palsies. Most common etiologies: trauma, masses, inflammation, and/or infiltrative processes.
Although there are many risk factors, some of them can be controlled to minimize the risk of acquiring oculomotor nerve palsy. It is encouraged to maintain blood pressure and glycemic control which are the most common causes of vasculopathic third nerve palsy.
Acquired oculomotor nerve palsy is a clinical diagnosis.
The most common ocular manifestations are diplopia and ptosis. In addition, depending on affected section of the third craneal nerve track it can also produce other neurologic manifestations as involuntary movements, hemiplegia, and altered mental status.
Consist on complete ophthalmic exam including visual acuity, ductions and versions, levator function, pupils reaction to light and to accommodation. In addition, general physical and/or neurological evaluation should be consider.
The presenting signs depend on the affected area of 3rd nerve track. In some cases, the precise site of the lesion is clear, whereas in others, the location of the lesion is speculative. It can present in different ways causing somatic extraocular muscle dysfunction (superior, inferior, and medial recti; inferior oblique; and levator palpebrae superioris) and autonomic (pupillary sphincter and ciliary) muscles.
Symptoms depend on the location of the lesion. The most common ocular complaint is diplopia secondary to somatic extraocular muscle dysfunction, but pain and ptosis can also me present.
Diagnosis is made by physical examination.
Acquired oculomotor nerve palsy can be secondary to many etiologies. Nevertheless, neuroimaging is usually done specifically if intracranial pathology is suspected. In a conscious patient presenting with ophthalmoplegia, ptosis and mydriasis a compressive etiology, as an intracranial aneurysm, must be ruled out. If an intracranial aneurysm is suspected, a computed tomography angiography (CTA) and/or magnetic resonance imaging (MRI and MRA) should be performed, with a 90% sensitivity in aneurysms of 3mm or greater in diameter, although the gold standard is the digital substraction angiography (DSA).
If a patient presents with complete oculomotor nerve palsy without pupil involvement it is most likely to be related to ischemic process, but compression and inflammation should also be considered. Evaluation and management will vary according to patient’s systemic illnesses, age, and associated symptoms. Nevertheless, basic workup is recommended. This may include the following: vital signs (e.g. blood pressure), complete blood count (CBC), sedimentation rate (ESR), C-reactive protein (CRP) comprehensive metabolic panel (CMP), central nervous system imaging (MRI or CT), angiographic study (MRA, CTA or catheter angiogram) can also be used to ruled out acute intracranial pathology, especially if ophthalmoplegia is associated with pain. 
- Myasthenia Gravis
- Thyroid associated orbitopathy
- Internuclear ophthalmoplegia
- Chronic progressive external ophthalmoplegia
- Orbital pseudotumor
- Giant cell arteritis
Acquired oculomotor nerve palsy evaluation depends on signs and symptoms, patient’s age and systemic diseases. Management depends on the presented scenarios. In a conscious patient presenting with ophthalmoplegia, ptosis and mydriasis a compressive etiology, as an intracranial aneurysm, must be ruled out. In the other hand if a patient presents with complete oculomotor nerve palsy without pupil involvement it is most likely to be related to ischemic process, but compression and inflammation should also be considered. The majority of complete or incomplete CN III palsy without pupil involvement are secondary ischemic process. These patients observe an improvement after the first 4 weeks with full resolution in 12 weeks of the insult. Those patients presenting with that are left with a residual deficit can consider prisms or strabismus surgery after 6 months of stability to maximize the possibility of spontaneous resolution and surgical outcome. In these cases the main goal of strabismus surgery is to provide alignment in primary and reading position.
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