Aneurysmal Third Cranial Nerve Palsy
Patients with third nerve palsy present with binocular oblique diplopia and unilateral eyelid ptosis. The ocular motility examination shows limitation of adduction, supraduction, and infraduction of varying degrees. The ptosis is sometimes complete. The state of the pupil bears particular importance owing to the possibility of an intracranial aneurysm compressing the third cranial nerve. Since a ruptured aneurysm has a high rate of mortality, differentiating aneurysmal from ischemic third nerve palsies is critical.
The pupil can be described as spared or involved. If the pupil is “spared,” it is equal in size and reactivity to the other pupil—indicating no efferent or parasympathetic defect. The pupils should be examined in bright light conditions to maximally stimulate parasympathetic effect. Pupil involvement in third nerve palsy occurs when the ipsilateral pupil is dilated and poorly responsive to light and accommodation.
The most common cause of third nerve palsy is microvascular ischemia, often secondary to diabetes mellitus, hypertension, and atherosclerosis (among the more common risk factors). If there is total ophthalmoplegia and pupil sparing in an individual with vasculopathic risk factors, it is reasonable to conservatively follow these patients closely for the first week, watching for pupil changes. These ischemic third nerve palsies usually resolve spontaneously within several weeks; thus, further investigation is typically not necessary.
A pupil-involved third nerve palsy requires urgent neuroimaging (MRI and MRA or CTA) regardless of the degree of ophthalmoplegia (partial or complete). CT angiogram (CTA) and MR angiogram (MRA) are noninvasive tests that can detect cerebral aneurysms as small as 3 to 5 mm in diameter. If noninvasive testing is negative and suspicion for an aneurysm remains, then conventional 4-vessel cerebral catheter angiography is recommended.
A third nerve palsy due to aneurysmal compression is a medical emergency. If the aneurysm has bled, patients may have a sudden severe headache, meningismus, photophobia, or be obtunded. The presence of pain does not reliably differentiate aneurysmal third nerve palsy from ischemic third nerve palsy, as both can cause discomfort. The most common site of an aneurysm causing a third nerve palsy is at the junction of the posterior communicating artery and internal carotid artery (Figure 4a and 4b). Other aneurysms that can potentially cause third nerve palsy are intracavernous carotid artery aneurysms, basilar artery aneurysms, and superior cerebellar artery aneurysms.
Sixth Cranial Nerve Palsy
Sixth nerve palsy constitutes a neuro-ophthalmic emergency in the setting of increased intracranial pressure. The increased intracranial pressure causes downward displacement of the brainstem that results in stretching of one or both abducens nerves, causing binocular horizontal diplopia. The esotropia is incomitant, even in cases of bilateral sixth nerve palsy. Sixth nerve palsy associated with papilledema is highly suggestive of increased intracranial pressure due to an intracranial mass lesion or idiopathic intracranial hypertension/pseudotumor cerebri. In this setting, urgent neuroimaging is recommended, preferably an MRI and magnetic resonance venogram (MRV). A neurosurgical consultation is required if a mass lesion is found. However, if the imaging studies are negative, a lumbar puncture with specific attention to cerebrospinal fluid (CSF) opening pressure is warranted.
Wernicke encephalopathy is due to a nutritional deficiency of thiamine (vitamin B1) and usually occurs in alcoholics or malnourished individuals. The condition was initially described as a triad of acute mental confusion, ataxia, and ophthalmoplegia. The ocular motor findings in Wernicke encephalopathy are protean, including bilateral but asymmetric abducens palsy, internuclear ophthalmoplegia, gaze-evoked nystagmus, vertical nystagmus (upbeat or downbeat), one-and-a-half syndrome, vertical or horizontal gaze palsy, and impaired vestibulo-ocular responses. In some cases, it may even progress to total ophthalmoplegia, coma, and death. MRI may demonstrate brainstem and/or cerebellar lesions to account for the ophthalmoplegia.
It is paramount to note that the clinical condition will worsen if intravenous glucose is administered without parenteral thiamine supplementation. Thiamine can be administered at initial doses of 100 to 200 mg intravenously, but some alcoholics can require more. After thiamine is given, there will be a rapid improvement of the ocular motor signs but complete recovery may take days to weeks. Some patients can also have a concomitant magnesium deficiency that needs to be addressed.