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Patient presents with long-term droopy eyelid
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Images: Borgman CJ
A 69-year-old African-American female presented for a regularly scheduled annual eye exam with the chief complaint of a droopy left upper eyelid of 8 years duration. She also reported diplopia upon manually lifting her left eyelid.
Her medical history was positive for type 2 diabetes mellitus, hypertension and hypercholesterolemia of 15 years duration and a history of cerebrovascular accident 8 years prior to this visit. The cerebrovascular accident left the patient as a right-sided hemiplegic. Medications included: 25 units of insulin, simvastatin 80 mg, clopidogrel 75 mg, metoprolol 50 mg, valsartan 160 mg and diphenhydramine 25 mg as needed. She denied any allergies to medications.
Humphrey Visual Field Analyzer (Carl Zeiss Meditec), 30-2 protocol, of the patient’s right eye showing a left inferior quadrantanopsia associated with her right occipital lobe infarct. Repeat visual field testing 3 years later showed stable defects in both eyes.
Blood pressure was measured manually in-office as 140/70 mm Hg. She reported being followed by her primary care physician and her neurologist consistently every 6 months since her stroke 8 years earlier.
Best-corrected visual acuities measured 20/25 OD and 20/70 OS with a mild compound hyperopic astigmatic correction in both eyes. Confrontation visual fields showed bilateral left inferior quadrantanopic field defects. Pupils in the right eye measured 2 mm and 3 mm in photopic and scotopic conditions, respectively, and measured 4 mm and 4 mm in the left eye in photopic and scotopic conditions, respectively. Extraocular motilities showed severe ptosis of the left upper eyelid and a complete cranial nerve III/oculomotor nerve palsy in the left eye with “down and out” posture in primary gaze. Slit lamp exam revealed bilateral moderately severe nuclear cataracts greater in the left eye than the right, to account for the difference in visual acuities.
Intraocular pressure was measured at 14 mm Hg OD and 15 mm Hg OS with Goldmann tonometry. Dilated fundus exam was within normal limits in both eyes with no evidence of diabetic nor significant hypertensive retinopathy in either eye. Resultant baseline threshold visual field testing confirmed the presence of left inferior quadrantanopic defects in both eyes.
What’s your diagnosis?
See answer on the next page.
Humphrey Visual Field Analyzer, 30-2 protocol, of the patient’s left eye showing a clear left inferior quadrantanopsia associated with her right occipital lobe infarct. Repeat visual field testing 3 years later showed stable defects in both eyes.
Differential diagnoses we considered in this case based on the patient’s clinical findings were: Horner’s syndrome, Adie’s tonic pupil, pharmacologic dilation, myasthenia gravis, thyroid orbitopathy and third nerve palsy secondary to aneurysmal compression.
Ruling out differential diagnoses
Horner’s syndrome results in subtle lid ptosis (1 mm to 2 mm) and anisocoria in which the constricted pupil is the abnormal pupil due to sympathetic innervation insult. Some of the more common etiologies of Horner’s syndrome include: carotid artery dissections, strokes, tumors of the brainstem or lungs, and iatrogenic surgical causes. The abnormal pupil in this case was dilated, not constricted, so this was ruled out quickly with standard pupil testing.
Adie’s tonic pupil could cause an anisocoria similar to this case, but the oculomotor dysfunction would be absent, so that was ruled out rather quickly as well.
Pharmacologic dilation is always possible but would not have resulted in the oculomotor dysfunction seen in this case. In addition, the pupil dilation was clinically measured as stable over an 8-year period, which would also argue against a pharmacologically dilated pupil, as it would have certainly worn off over an 8-year time frame without repeated exposure, and the patient denied any use of eye drops.
Myasthenia gravis should also always be considered in oculomotor problems or lid ptosis but will typically worsen when a patient is fatigued or at end of the day and is classically reported as a fluctuating diplopic state. This patient also had pupillary involvement, which never occurs with myasthenia, and her oculomotor dysfunction did not fluctuate, therefore making myasthenia gravis unlikely.
Thyroid orbitopathy should also be considered in cases like this and certainly can occur even without a history of thyroid dysfunction (euthyroid), as in this case. However, known clinical findings would have appeared on the neuroimaging as enlarged extraocular muscles with tendon-sparing properties, and this was noticeably absent, making thyroid orbitopathy also unlikely in this case.
Lastly, aneurysmal compression of the third nerve, usually by the posterior communicating artery of the circle of Willis, should always be considered in pupil-involved oculomotor nerve palsies, as these are absolutely life-threatening and should be treated as emergencies. However, this was ruled out acutely with emergent neuroimaging 8 years earlier in which no aneurysm was found on MRA, in addition to 8 years of close follow-up by her neurologist. Expectedly, if the patient did have an aneurysm large enough to cause her oculomotor palsy, it could be said that it likely (although certainly not a guarantee) would have worsened or potentially ruptured over that 8-year period, making aneurysmal compression unlikely 8 years later when we finally took over care of this patient. Therefore, a different cause of her pupil-involved third nerve palsy seemed most likely, and the patient’s medical records were requested.
Medical record review
Upon receiving and reviewing the patient’s previous neuroimaging records, it was found that a hemorrhagic stroke of the left thalamus extending into the left midbrain as well as a second ischemic event involving the right superior occipital lobe (cuneus) from a posterior cerebral artery occlusion had occurred. This was confirmed via acute MRI and MRA neuroimaging 8 years earlier, thus establishing two separate insults/lesions to explain this patient’s unfortunate ocular findings.
Her stroke coincided with all the findings in this case: the onset of diplopia, left complete oculomotor nerve palsy, visual field defects and contralateral hemiplegia. Therefore, the clinical findings outlined in this particular case is a great example of what has been termed “Weber’s syndrome,” named after Sir Herman David Weber, who described the first case of this in the early 19th century. Weber’s syndrome is a fascicular syndrome of the oculomotor nerve that results in ipsilateral third nerve palsy/paresis and contralateral hemiplegia/paresis due to dual involvement of the crus cerebri and the ipsilateral oculomotor nerve fascicle.
The oculomotor nucleus is located in the midbrain of the brainstem, and its fascicles travel ventrally through the midbrain and through the superior orbital fissure of the orbit to innervate specific ocular structures. The midbrain is supplied via small branches of the posterior cerebral arteries and basilar artery branches on each respective side. The oculomotor nerve innervates all extraocular muscles of the eye except the lateral rectus and superior oblique muscle. Additionally, it also innervates the levator palpebrae muscle, allows convergence of the eyes due to its relationship with the Edinger-Westphal nucleus and also carries the parasympathetic fibers destined for the iris sphincter resulting in pupillary miosis when functioning properly.
Oculomotor nerve paresis/palsy can include the following findings: lid ptosis secondary to weakening of the levator muscle, restriction of all eye movements except abduction and incyclotorsion when looking inferior nasal in the affected eye, pupillary mydriasis/anisocoria and lack of convergence. Oculomotor nerve dysfunction is typically related to fascicular involvement caused by hypertension, diabetes, arteriovenous malformations, aneurysms and demyelination, although other rarer causes, such as leukemia, do exist.
Oculomotor nerve dysfunction due to midbrain stroke is considered rare, especially hemorrhagic strokes of the midbrain. Most cases of hemorrhagic midbrain stroke involving the third cranial nerve present acutely in 70%, subacute in 20% and chronic in 10%, as in this case (Mizushima et al.). Neuro-ophthalmologic findings are found in approximately 81% of hemorrhagic midbrain stroke cases. About two-thirds of patients recover with no neurologic defects or minor permanent deficits, and only about 4% of cases actually end in mortality. Approximately 37% of midbrain hemorrhages have an idiopathic origin.
Pure midbrain strokes have been reported in approximately 0.6% to 2.3% of all admitted ischemic strokes (Kim et al. and Bogousslavsky et al). The average age of onset is 49 years to 65 years with a slight male predominance (Kim et al. and Mizushima et al.). Vascular risk factors reported are: hypertension (78%), diabetes mellitus (48%), tobacco use (23%), hypercholesterolemia (17%), coronary heart disease (10%), atrial fibrillation (5%) and patent foramen ovale (2.5%) (Kim et al. and Chen et al.). Gait ataxia and limb ataxia are found in approximately 68% and 50% of patients, respectively, while limb weakness is seen in 55% of patients, although of that 55%, only 23% had definitive hemiparesis, as in our patient’s case, indicating heavy involvement of the crus cerebri and ultimately the corticospinal tracts (Kim et al.). General oculomotor dysfunction was found in 53% of patients, with third nerve palsy and internuclear ophthalmoplegia being the most common at 35% and 13%, respectively.
Upper, middle, lower infarcts
It has been reported that there are three types of midbrain infarcts: upper, middle and lower. Upper midbrain infarcts result in vertical gaze disturbances, as in Parinaud’s or dorsal midbrain syndromes. Middle infarcts result in Weber’s syndrome-like findings showing third nerve palsy and contralateral hemiplegia. Lower infarcts can be associated with trochlear and trigeminal nerve palsies. Lesions of the lower midbrain tend to affect the extraocular muscles and spare the pupil fibers, whereas lesions spanning both the upper and lower midbrain tend to affect both the pupil as well as extraocular muscles, because of the presence of the Edinger-Westphal nucleus, which sits superior to the oculomotor nuclei. This would explain the anisocoria nicely in this case, as the superior midbrain was most affected from the hemorrhagic stroke that originated in the thalamus superior to the midbrain.
Thalamic infarcts can occur simultaneously with midbrain infarcts. This is best explained via blood supply to both of these areas; the basilar artery has a small branch that supplies the paramedian parts of the thalamus and midbrain. When this branch is implicated via embolus or hemorrhage, combined infarcts of the thalamus and midbrain can occur. This would explain the hemorrhagic stroke in our case perfectly.
This patient’s management
Schematic cross-section of the patient’s midbrain demonstrating location of the lesion (red shaded area) and the structures implicated leading to the patient’s left oculomotor nerve palsy with pupil involvement.
In this patient’s case, the hemorrhagic lesion in the left midbrain stemming from thalamic infarction was responsible for her clinical findings of oculomotor nerve palsy with pupillary involvement. It was also responsible for the contralateral hemiplegia secondary to involvement of the ipsilateral corticospinal tract fibers in the left crus cerebri as the corticospinal tract fibers cross over to the contralateral side of the body in the upper medulla, which is inferior to the lesion in this case.
The patient’s quadrantanopic visual field defects were stable with repeat visual field testing 3 years after the initial onset and consistent with a superior occipital lobe infarct secondary to occlusion of her right distal posterior cerebral artery found on MRA, as the occipital lobe is primarily nourished via the posterior cerebral artery (PCA).
The PCA is a major branch off of the basilar artery, which wraps posterior-laterally around the midbrain, ultimately ending in the ipsilateral occipital lobes. Small branches of the PCA feed the midbrain area where the oculomotor nerve is housed so interruptions of blood flow in those branches can lead to oculomotor nerve dysfunction, as seen in this case. If the distal part of the PCA becomes compromised, infarction of the occipital lobe can occur, leading to potential visual acuity loss and/or visual field defects, depending on which part of the occipital lobe is implicated. Simultaneous involvement of surrounding structures such as the pons, thalamus and cerebellum are not uncommon with midbrain strokes.
Unique case
The unique aspect of this case is not necessarily the presence of the Weber’s syndrome (which, admittedly, is rare enough), but both the presence of Weber’s syndrome and the presence of a left inferior quadrantanopic visual field defect in both eyes. It is rare for two lesions to simultaneously cause separate issues as in this particular case, but it has been reported in the literature previously.
“Ockham’s razor” is a philosophical approach named after William Ockham that grossly suggests that the simplest explanation is more likely to be accurate than more complicated explanations. This means that it would be more likely that one lesion from one single ischemic event caused all of this patient’s unfortunate issues rather than multiple lesions. In this case, however, neuroimaging confirmed two separate lesions, making this a rare case of two lesion locations with simultaneous onset ultimately leading to this overall clinical picture. Undoubtedly, the patient’s vasculopathic risk factors are the likely culprit for her unfortunate ocular findings.
Unfortunately, after 8 years since the onset, it is unlikely that the patient will improve any further. Given her stability, she is being monitored by her internist, neurologist and us every 6 months. In the case of acute onset and clinical findings found in this case, MRI (with and without contrast) with emphasis on the midbrain should be ordered urgently.
This case highlights nicely the importance of having a good understanding of neuroanatomy in order to work through the odd clinical cases we may run across, as well as underlying the importance of continuous study/review even after our academic days are technically completed.
- References:
- Adamec I, et al. Neuro-Ophthalmology. 2011;doi:10.3109/01658107.2011.580892.
- Bogousslavsky J, et al. Neurology. 1994;doi:10.1212/WNL.44.11.2032.
- Chen L, et al. J Neurol. 2009;doi:10.1007/s00415-009-5054-1.
- Ilsen PF, et al. J Am Optom Assoc. 1998;69(12):766-74.
- Khalil M, et al. J Coll Physicians Surg Pak. 2009;doi:10.2009/JCPSP.668669.
- Kim JS, et al. Neurology. 2005;doi:10.1212/01.WNL.0000156520.46056.6B.
- Mizushima H, et al. Surg Neurol. 2002;doi:10.1016/S0090-3019(02)00902-3.
- Murakami M, et al. Clin Neurol Neurosurg. 1994;doi:10.1016/0303-8467(94)90061-2.
- Muthu V, et al. Perm J. 2015;doi:10.7812/TPP/14-126.
- Savino PJ, Danesh-Meyer H. Neuro-ophthalmology. Color Atlas of Synopsis of Clinical Ophthalmology: Wills Eye Hospital. Singapore: McGraw-Hill; 2003:152-160.
- Silverman IE, et al. Arch Neurol. 1995;doi:10.1001/archneur.1995.00540300117021.
- Umasankar U, et al. Neurol India. 2003;51(3):388-389.
- For more information:
- Christopher J. Borgman, OD, FAAO, is a clinical instructor at the Southern College of Optometry. He can be reached at cborgman@sco.edu.
- Rachel Kenney, OD, recently graduated from Southern College of Optometry and now works and resides in the central Kentucky area. She can be reached at rkenney@sco.edu.
- Edited by Leo P. Semes, OD, FAAO, a professor of optometry, University of Alabama at Birmingham and a member of the Primary Care Optometry News Editorial Board. He may be reached at lsemes@uab.edu.
Disclosures: Borgman and Kenney reported no relevant financial disclosures.