Third Nerve Palsy (Oculomotor Nerve Palsy) Workup

Updated: Jan 06, 2022
  • Author: Fiona Costello, MD, FRCP; Chief Editor: Andrew G Lee, MD  more...
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Approach Considerations


Table 4:  Investigations to Consider in Evaluating Patients with Third Cranial Nerve Palsies (Open Table in a new window)



Serological Testing

Cell count with differential, hemoglobin AIC, serum sedimentation rate, c-reactive protein, free T3, free T4, TSH, prolactin, FSH, LH, free testosterone, lipid profile, IGF-1, morning cortisol, anti-acetylcholine receptor antibodies, anti-MuSK antibodies, serum lactate, connective tissue screen, genetic testing for mitochondrial disorders and oculopharyngeal muscular dystrophy.

Serological tests are indicated for suspected cases of diabetic microvascular ischemic cranial nerve palsy, pituitary macroadenomas, giant cell arteritis, myasthenia mimics, and thyroid related eye disease. Chronic progressive external ophthalmoplegia and oculopharyngeal muscular dystrophy can be evaluated with specific genetic testing.

Cerebrospinal Fluid Analysis

CSF cell count with differential, glucose, protein, cytopathology, gram stain, viral cultures, fungal cultures, and opening pressure as indicated

CSF analysis can help determine infectious (meningitis), inflammatory (cyto-albuminemic dissociation), malignant, and raised intracranial pressure mechanisms of third cranial nerve palsies.


CT head, cranial and orbital MRI with gadolinium and gadolinium enhanced views, cranial MRI or CT angiography/venography, catheter angiography, CT scan of the chest, whole body PET imaging, orbital ultrasound

CT imaging is needed acutely in the setting of ICH or hydrocephalus with raised intracranial pressure. CT or MRI with detailed vascular imaging can be used to localize lesions along the fascicle, in the cavernous sinus, in the region of the superior orbital fissure and orbital apices, and orbit. Orbital ultrasound can detect arterialized flow through the superior ophthalmic vein, and help localize cases of CCFs. CT imaging of the chest is needed to check for hilar lymphadenopathy in the case of sarcoid, and thymic hyperplasia/thymoma in suspected MG. Whole body PET CT is useful in detecting inflammatory conditions such as sarcoid and systemic diseases/neoplasms.


Nerve conduction studies (NCS), electromyography (EMG), repetitive nerve stimulation (RNS) studies and single fiber EMG.

EMG/NCS/SF-EMG and RNS studies can be used to identify cases of neuromuscular junction abnormalities (myasthenia gravis) versus mitochondrial disorders and OPMD.

Tissue Analysis

Temporal artery biopsy, muscle biopsy, lesion biopsy (pituitary tumors, lesions of the parasellar space and cavernous sinus)

TAB is needed to confirm a diagnosis of GCA, whereas characteristic findings on muscle biopsy will characterize underlying myopathies.

CSF: cerebrospinal fluid

TSH: thyroid stimulating hormoneFSH: follicule-stimuating hormoneLH: lutenizing hormone

CT: computer tomographyMRI: magnetic resonance imagingPET: positrion emission tomography

ICH: intracranial hypertension

MG: myasthenia gravis

EMG: electromyography

NCS: nerve conduction study

SF-EMG: single fibre electromyography

RNS : repetitive nerve stimulation

OPMD: oculopharyngeal muscular dystrophy

TAB: temporal artery biopsy

GCA: giant cell arteritis

The localization and management of acquired third cranial nerve palsies depend upon the patient’s clinical presentation (symptom onset, progression, age, pain, and associated findings) and related comorbidities (vascular risk factors, underlying cancers, etc).  For example, sudden onset headache, altered level of consciousness, and ophthalmoplegia should raise immediate concern for a vascular event such as pituitary apoplexy or subarachnoid hemorrhage. In this setting, patients need urgent cranial computed tomography (CT) imaging, which is the “go to” imaging modality in the setting of trauma, suspected intracranial hemorrhage, and quickly evolving hydrocephalus. [12]  For patients aged greater than 50 years, concern for giant cell arteritis should be paramount, prompting serological evaluation for acute phase reactants including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), with or without a temporal artery biopsy. Traditionally, older individuals (age>50 years) with vascular risk factors presenting with acute isolated ocular motor cranial mononeuropathy were sometimes  followed without neuro-imaging as spontaneous resolution of the palsy is expected in about 8–10 weeks. [34]  Yet, most physicians in the current era image patients with third cranial nerve palsies. Studies examining the role of MR imaging among patients with isolated ocular motor palsies have shown that this imaging modality detects neoplasms, infarcts, aneurysms, demyelination, and pituitary apoplexy in 43 cases (16.5%). [1, 35]