Third-nerve palsy can result from a lesion anywhere along its anatomic path, which begins in the brainstem nucleus, continues within the subarachnoid space, traverses the cavernous sinus, and terminates within the orbit. Contralateral hemiplegia suggests brainstem involvement. Impoant: Contralateral hemiplegia suggests brainstem involvement. In cases of isolated oculomotor palsy, the subarachnoid space is the most likely site of pathology. The differential includes a posterior communicating aery aneurysm, uncal herniation, compressive neoplasms, inflammatory lesions, or trauma. Causes for third-nerve palsy within the cavernous sinus include neoplasms, carotid aery aneurysm, cavernous sinus thrombosis, and carotid-cavernous fistula. Orbital lesions causing third-nerve palsies may be due to inflammation, trauma, neoplasms, and mucoceles. Isolated third-nerve palsy is common with diabetic or hypeensive disease, likely due to microvascular ischemia. In this situation, the palsy rarely affects the pupil, and may be extremely painful. Ref: Levsky M.E., DeFlorio P. (2010). Chapter 2. Ophthalmologic Conditions. In K.J. Knoop, L.B. Stack, A.B. Storrow, R.J. Thurman (Eds), The Atlas of Emergency Medicine, 3e.