| Optic neuritis is an inflammatory optic neuropathy that affects many patients with multiple sclerosis (MS) at some point during their disease course. Differentiation of acute episodes of MS-associated optic neuritis from other autoimmune and inflammatory optic neuropathies is vital for treatment choice and further patient management, but is not always straightforward. Over the past decade, a number of new imaging, laboratory and electrophysiological techniques have entered the clinical arena. To date, however, no consensus guidelines have been devised to specify how and when these techniques can be most rationally applied for the diagnostic work-up of patients with acute optic neuritis. In this article, we review the literature and attempt to formulate a consensus for the investigation of patients with acute optic neuritis, both in standard care and in research with relevance to clinical treatment trials.

Manifestations of MOG-IgG-positive optic neuritis are diverse. Despite recurrent attacks with severe vision loss, the majority of patients have significant recovery and retain functional vision long-term.

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IMPORTANCE Among cranial nerve palsies, a third nerve palsy is important because a subset is caused by life-threatening aneurysms. However, there is significant disagreement regarding its incidence and the reported etiologies.OBJECTIVE To determine the incidence and etiologies of acquired third nerve palsy using a population-based method.DESIGN, SETTING, AND PARTICIPANTS All newly diagnosed cases of acquired third nerve palsy from January 1, 1978, through December 31, 2014, in Olmsted County, Minnesota, were identified using the Rochester Epidemiology Project, a record-linkage system of medical records for all patient-physician encounters among Olmsted County residents. All medical records were reviewed to confirm a diagnosis of acquired third nerve palsy and determine the etiologies, presenting signs, and symptoms. Incidence rates were adjusted to the age and sex distribution of the 2010 US white population. MAIN OUTCOMES AND MEASURESIncidence and etiologies of acquired third nerve palsies. The secondary outcome was incidence of pupil involvement in acquired third nerve palsies. RESULTSWe identified 145 newly diagnosed cases of acquired third nerve palsy in Olmsted County, Minnesota, over the 37-year period. The age-and sex-adjusted annual incidence of acquired third nerve palsy was 4.0 per 100 000 (95% CI, 3.3-4.7 per 100 000). The annual incidence in patients older than 60 was greater than patients younger than 60 (12.5 vs 1.7 per 100 000; difference, 10.8 per 100 000; 95% CI, 4.7-16.9; P < .001). The most common causes of acquired third nerve palsy were presumed microvascular (42%), trauma (12%), compression from neoplasm (11%), postneurosurgery (10%), and compression from aneurysm (6%). Ten patients (17%) with microvascular third nerve palsies had pupil involvement, while pupil involvement was seen in 16 patients (64%) with compressive third nerve palsies. CONCLUSIONS AND RELEVANCEThis population-based cohort demonstrates a higher incidence of presumed microvascular third nerve palsies and a lower incidence of aneurysmal compression than previously reported in non-population-based studies. While compressive lesions had a higher likelihood of pupil involvement, pupil involvement did not exclude microvascular third nerve palsy and lack of pupil involvement did not rule out compressive third nerve palsy.

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