Figure 1. Ptosis in complete third nerve palsy
Dr Brandon Powell OD
Nova Southeastern University, College of Optometry, Florida USA
Professor Joseph Sowka
OD FAAO DIPL
Director, The Glaucoma Service, Nova Southeastern University, College of Optometry, Florida USA
An 89-year-old man with poorly-controlled diabetes presented with complaints of constant diplopia for the past few days. The patient’s right lid had partial ptosis and his extra ocular motility in that eye was limited in adduction, supraduction and infraduction.
This was all consistent with incomplete third nerve palsy. Neuroimaging was obtained through the patient’s primary care physician but the study was inadequately directed. Nevertheless, no evidence of aneurysm or subarachnoid haemorrhage was seen. Two weeks later, the patient returned for follow-up with now complete ptosis and no movement in any of the previously mentioned gazes.
When a patient presents with a suspected palsy of cranial nerve three, it is imperative that the clinician knows all of the appropriate steps that need to be taken. There is almost no case where this condition does not suggest some underlying pathology that is either morbid or even mortal.
A recent study found causes of a third nerve palsy to be microvascular (42 per cent), trauma (12 per cent), neoplasm (11 per cent), post-surgery (10 per cent) and aneurysm (six per cent).1 Be aware that given an individual patient’s unique presentation, the risk of aneurysm may be much higher or lower in any given situation.
Microvascular diseases, such as diabetes and hypertension, should be of concern if they are causing neurological deficits but an aneurysm-causing compression on cranial nerve three is a cause of grave concern. The 30-day mortality for patients with subarachnoid haemorrhages caused by cerebral aneurysm rupture is as high as 45 per cent.2 Knowing the proper approach for this condition is paramount for any eye-care practitioner.
Step 1: Look at the PUPIL
The earlier mentioned patient had his pupils thoroughly examined for reaction to light directly, indirectly, and an afferent pupillary defect was searched for; the same testing was done when the patient returned two weeks later. On both visits, it was thoroughly confirmed that both pupils were briskly reactive to light directly and indirectly, and that there was no afferent pupillary defect in either eye.
Thus, he had ‘pupil sparing’. Pupil testing is an important way to determine the amount of suspicion there should be for a suspected aneurysm causing third nerve palsy. The ‘rule of the pupil’ is widely taught as the best way to determine if an aneurysm should be suspected.
Pupil fibres superficially travel with cranial nerve three and are vulnerable to compression from an aneurysm of the posterior communicating artery. These fibres are relatively immune to ischaemia from vascular infarct. However, this rule should apply only in cases of complete third nerve palsy.
Lee et al describe situations where the ‘rule of the pupil’ cannot be applied. If a patient has an incomplete third nerve palsy, which the authors describe as at least one extra ocular muscle having some function left or an incomplete ptosis, then the rule can no longer be applied and the patient should be worked up for a possible aneurysm. Additionally, third nerve palsies in conjunction with other non-ocular, neurological symptoms should no longer have the rule applied. In addition, evidence of aberrant regeneration means that the rule cannot be applied.3
If complete third nerve palsy is present, then the rule can be cautiously applied to determine if an aneurysm should be suspected. If the pupil reacts poorly to light, the patient should be immediately evaluated for an aneurysm. However, Kissel et al determined that it is not enough to look only for presence of pupillary light reaction.4 If there is partial internal dysfunction of the pupil with greater than 1 mm of anisocoria or diminished light reaction, then the suspicion of aneurysm should be high.
Figure 2. Pupil test determines a suspected aneurysm causing third nerve palsy
Step 2: Look at the PALSY
Patients with complete third nerve palsy without pupil involvement have a low risk of harbouring an intracranial aneurysm. If the palsy is incomplete or partial, then the patient should be suspected of having a developing aneurysm regardless of the pupillary state. Patients with partial third nerve palsy can have a pupil that is initially normal in function. Any partial third nerve palsy must be emergently evaluated for aneurysm regardless of pupillary state.
If a patient falls into any of the previously mentioned categories where an aneurysm is suspected, then neuroimaging needs to be done. To be on the safe side, even complete third nerve palsy with absolutely no pupil involvement may be best served by ruling out an intracranial aneurysm. Although extremely rare, it has been published that pupillary involvement may not appear in the case of an aneurysm until four months after initial paresis.4
The most common place for an aneurysm causing a third nerve palsy is on the posterior communicating artery, because the nerve runs parallel to this artery. The most sensitive and reliable non-invasive method of detecting an aneurysm is computerised tomography angiography and should be the first test that is requested. However, if the patient is pregnant or is a child, they should not be exposed to the radiation and magnetic resonance angiography is the next best option.5
Non-invasive scans may be performed or interpreted incorrectly. It is imperative to explain to a radiologist all thoughts on potential aetiologies so that the neuroimaging may be properly directed. Still, errors can be made. If the nerve and artery are anatomically far apart in a patient, then a very large aneurysm may be required to cause compression.
Conversely, if the artery and nerve are anatomically close together in a patient, then a very small aneurysm which may be missed on non-invasive imaging may result in palsy. In cases where an aneurysm is strongly suspected and non-invasive scans provide no evidence of such, digital subtraction angiography is required.6
Step 3: Look at the PATIENT
Age and related medical conditions are important when assessing patients with third nerve palsy. Microvascular palsies are uncommon in younger patients and alternative aetiologies should be considered in patients younger than 50 years. While older age and the presence of ischaemic vascular diseases such as diabetes, atherosclerosis, hypercholesterolaemia and hypertension, favour microvascular aetiology, they are not protective against an aneurysm. Microvascular aetiology should not be strongly suspected in patients not having ischaemic vascular diseases.
In a study conducted by Watanabe et al, on patients with cranial nerve three or four palsies caused by diabetes, about 70 per cent of these patients had other diabetic complications elsewhere in the body.7 A microvascular aetiology warrants referral to the patient’s primary care physician because hypertension, diabetes or high cholesterol that may be damaging a cranial nerve is probably affecting other organ systems elsewhere in the body. It may also be prudent to recommend erythrocyte sedimentation rate and C-Reactive Protein testing, since giant cell arteritis (GCA) can cause pupil sparing third nerve palsy that would mimic a microvascular aetiology.8
Improvement of microvascular palsy should be seen over time and the condition should resolve nearly completely. However, if there is no improvement over time, then a different aetiology should be considered. Presumed microvascular palsy may progress throughout one week and be unimproved at two weeks. However, microvascular palsy will not get progressively worse over the course of two weeks. Patients with presentation and risk factors characteristic of microvascular palsy can still have alternative causes, such as neoplasm, inflammation, GCA and brain stem infarction.9
An aetiology for the earlier mentioned patient was determined most likely to be microvascular due to his type 2 diabetes. The patient was taking insulin four times a day, was on maximum metformin therapy, and his medical records revealed blood sugar values that fluctuated from around 400 and dipped down to about 40. The patient was also being medically managed for hypertension and high cholesterol. The patient’s primary care physician was alerted and recommended to follow tighter diabetic control. The patient was informed that he should wear a patch over his affected eye to relieve the diplopia and that his condition should resolve within three months. Within several weeks, his palsy recovered.
If a patient presents with third nerve palsy, three steps should ensure that the patient receives the appropriate care needed to rule out any cases of aneurysm aetiology and that other aetiologies are properly managed. If an aneurysm is suspected, urgent hospital evaluation with appropriate neuroimaging is required. If aneurysmal cause is completely ruled out and there are microvascular risk factors, then patients should have these systemic diseases managed by the appropriate practitioners, while keeping other aetiologies in mind.
The authors thank Dr Sherrol Reynolds for her contribution to this article.
- Fang C, Leavitt JA, Hodge DO, et al. Incidence and etiologies of acquired third nerve palsy using a population-based method. JAMA Ophthalmol 2017; 135: 1: 23-28.
- Broderick JP, Brott TG, Duldner JE, et al. Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage. Stroke 1994; 25: 1: 1342-1347.
- Lee AG, Hayman LA, Brazis PW. The evaluation of isolated third nerve palsy revisited. Survey Ophthalmol 2002; 47: 2: 137-157.
- Kissel JT, Burde RM, Klingele TG, Zeig HE. Pupil-sparing oculomotor palsies with internal carotid: posterior communicating artery aneurysms. Ann Neurol 1983; 13: 1: 149-154.
- Chaudhary N, Davagnanam I, Ansari SA, et al. Imaging of intracranial aneurysms causing isolated third cranial nerve palsy. J Neuro-Ophthalmol 2009; 29: 3: 238-244.
- Elmalem VI, Hudgins PA, Bruce BB, et al. Underdiagnosis of posterior communicating artery aneurysm in non-invasive brain vascular studies. J Neuro-Ophthalmol 2011; 31: 2: 103-109.
- Watanabe K, Hagura R, Akanuma Y, et al. Characteristics of cranial nerve palsies in diabetic patients. Diabetes Research Clin Practice 1990; 10: 1: 19-27.
- Thurtell MJ, Longmuir RA. Third nerve palsy as the initial manifestation of giant cell arteritis. J Neuro-Ophthalmol 2014; 34: 3: 243-245.
- Tamhankar MA, Biousse V, Ying G-S, et al. Isolated third, fourth and sixth cranial nerve palsies from presumed microvascular versus other causes: a prospective study. Ophthalmology 2013; 120: 11: 2264-2269.