Localization and Suggested Imaging and Workup

Findings that suggest a cortical or brain stem lesion include altered mental status, weakness or numbness in the extremities, ataxia, vertigo, and/or bilateral cranial nerve deficits. MRI of the brain with and without gadolinium should be obtained.

Bilateral cranial nerve deficits can also occur due to pathology in the subarachnoid space such as infectious or carcinomatous meningitis. In addition to neuroimaging, select patients may require lumbar puncture.

In contrast, multiple unilateral cranial nerve deficits suggest a brain stem, cavernous sinus (CNs III, IV, V₁, V₂, VI), or orbit (CNs III, IV, V₁, VI) lesion. Cavernous sinus and orbit lesions may also cause proptosis. MRI with and without gadolinium of the orbit is the preferred imaging modality for orbital lesions. CT or magnetic resonance (MR) venography is helpful for diagnosing cavernous sinus thrombosis, whereas CT or MR angiography is helpful for diagnosing a carotid-cavernous fistula.

All patients with isolated CN III palsy should undergo urgent MR or CT angiography of the brain to assess for intracranial aneurysm. Several studies have demonstrated that the presence of vascular risk factors and/or physical exam findings such as pupil involvement do not reliably distinguish between subacute causes such as microvascular ischemia and serious acute neurological disease.^3,4,6

Most, if not all, patients with isolated CN IV or VI palsy should also undergo an urgent MRI of the brain with and without gadolinium. Historically, urgent neuroimaging was deferred in selected patients with isolated CN IV or VI palsy lacking high-risk features. However, this practice has been called into question by recent studies that have shown a significant proportion of patients have structural lesions evident on MRI that dictate changes in early management.⁴

Conclusion

Knowing the differential diagnosis and how to distinguish among the diverse causes of diplopia should enhance your confidence in your ability to assess important emergency neurological conditions. A thorough history and exam as well as appropriate neuroimaging and diagnostic testing can clinch the diagnosis, thereby saving a patient’s sight and maybe even their life.

Dr. Strong is a clinical instructor in the department of emergency medicine at Brigham and Women’s Hospital in Boston.

References

1. Nazerian P, Vanni S, Tarocchi C, et al. Causes of diplopia in the emergency department: diagnostic accuracy of clinical assessment and of head computed tomography. Eur J Emerg Med. 2014;21(2):118-124.
2. Tan A, Faridah H. The two-minute approach to monocular diplopia. Malays Fam Physician. 2010;5(3):115-118.
3. 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.
4. Tamhankar MA, Biousse V, Ying GS, 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.
5. Ross AG, Jivraj I, Rodriguez G, et al. Retrospective, multicenter comparison of the clinical presentation of patients presenting with diplopia from giant cell arteritis vs other causes. J Neuroophthalmol. 2019;39(1):8-13.
6. Chou KL, Galetta SL, Liu GT, et al. Acute ocular motor mononeuropathies: prospective study of the roles of neuroimaging and clinical assessment. J Neurol Sci. 2004;219(1-2):35-39.