Failure to Obtain Urgent Arterial Imaging in Acute Third Nerve Palsies

Isolated third nerve palsy may indicate an expanding posterior communicating artery aneurysm, thus necessitating urgent arterial imaging. This study aims to assess the rate and duration of delays in arterial imaging for new isolated third nerve palsies, identify potential causes of delay, and evaluate instances of delay-related patient harm.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Failure to Obtain Urgent Arterial Imaging in Acute Third Nerve Palsies Jennifer E. Chung, BA, Richard M. Schroeder, MD, Bradley Wilson, MA, Gregory P. Van Stavern, MD, Leanne Stunkel, MD Background: Isolated third nerve palsy may indicate an expanding posterior communicating artery aneurysm, thus necessitating urgent arterial imaging. This study aims to assess the rate and duration of delays in arterial imaging for new isolated third nerve palsies, identify potential causes of delay, and evaluate instances of delay-related patient harm. Methods: In this cross-sectional study, we retrospectively reviewed 110 patient charts (aged 18 years and older) seen between November 2012 and June 2020 at the neuroophthalmology clinic and by the inpatient ophthalmology consultation service at a tertiary institution. All patients were referred for suspicion of or had a final diagnosis of third nerve palsy. Demographics, referral encounter details, physical examination findings, final diagnoses, timing of arterial imaging, etiologies of third nerve palsy, and details of patient harm were collected. Results: Of the 110 included patients, 62 (56.4%) were women, 88 (80%) were white, and the mean age was 61.8 ± 14.6 years. Forty (36.4%) patients received arterial imaging urgently. Patients suspected of third nerve palsy were not more likely to be sent for urgent evaluation (P = 0.29) or arterial imaging (P = 0.082) than patients in whom the referring doctor did not suspect palsy. Seventy-eight of 95 (82%) patients with a final diagnosis of third nerve palsy were correctly identified by referring providers. Of the 20 patients without any arterial imaging before neuroophthalmology consultation, there was a median delay of 24 days from symptom onset to imaging, and a median delay of 12.5 days between first medical contact for their symptoms and imaging. One patient was harmed as a result of delayed imaging. Washington University in St. Louis School of Medicine (JEC), St. Louis, Missouri; Department of Ophthalmology (RMS), Indiana University School of Medicine, Indianapolis, Indiana; and Departments of Ophthalmology and Visual Sciences (BW, GPVS, LS) and Neurology (GPVS, LS), Washington University in St. Louis School of Medicine, St. Louis, Missouri. Supported in part by an unrestricted grant to the Washington University in St. Louis Department of Ophthalmology and Visual Sciences from Research to Prevent Blindness and by the WUSM Summer Research Program Dean’s Fellowship. The authors report no conflicts of interest. Address correspondence to Leanne Stunkel, MD, 660 S. Euclid, Box 8096, St. Louis, MO 63108; E-mail: [e-mail] Chung et al: J Neuro-Ophthalmol 2021; 41: 537-541 Conclusions: Third nerve palsies were typically identified correctly, but referring providers failed to recognize the urgency of arterial imaging to rule out an aneurysmal etiology. Raising awareness of the urgency of arterial imaging may improve patient safety. Journal of Neuro-Ophthalmology 2021;41:537–541 doi: 10.1097/WNO.0000000000001337 © 2021 by North American Neuro-Ophthalmology Society I solated third nerve palsies characteristically present with acute-onset diplopia and ptosis, with or without pupillary involvement. There are a variety of possible etiologies, ranging from benign etiologies such as microvascular ischemia to aneurysmal compression by the posterior communicating artery (PCommA), which may signal impending aneurysmal rupture. The first priority when assessing a case of new third nerve palsy is to immediately rule out aneurysm via appropriate arterial imaging (1–3), because delay could result in a preventable and potentially fatal event. Although there are very specific exceptions to this diagnostic workup (4–6), the general rule is to perform imaging for all suspected new third nerve palsies. Historically, specific criteria—a complete, pupilsparing third nerve palsy in a patient over the age of 50 with vascular risk factors—were assumed to indicate a microvascular etiology, and arterial imaging may have been deferred in favor of close observation. However, there have been reports of aneurysmal third nerve palsies presenting without pupillary involvement, and recent commentators advocate arterial imaging for all new-onset, isolated third nerve palsies (7–12). Concerningly, in some cases, third nerve palsies are correctly identified by a provider and referred to a neuroophthalmology clinic for further evaluation and treatment, but without prior arterial imaging performed and without urgency communicated to the consultant. While awaiting outpatient neuro-ophthalmology evaluation, patients may go weeks or months (13) without receiving this necessary imaging, exposing them to inappropriate risk should they indeed have a PCommA aneurysm. 537 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Prior studies on diagnostic error in neuro-ophthalmology have addressed diagnostic error of third nerve palsies through the lens of diagnostic label failures (12,14–17), which is a failure to correctly diagnose a condition. Specifically, prior studies assessing evaluation of third nerve palsy showed high rates of misdiagnosis (17) and misinterpretation of arterial imaging performed (15). However, prior studies have not evaluated the timeliness of appropriate arterial imaging in these patients. In this case, we instead investigate a “diagnostic process failure,” (14) in which the third nerve palsy may have been correctly identified by the referring provider, but the appropriate order of operations necessary to ensure patient safety is neglected. The objective of this study is to assess the rate and duration of delay in the arterial imaging required for evaluation of isolated third nerve palsies before neuroophthalmology consultation, to evaluate whether these delays are related to failure to recognize the diagnosis vs. failure to recognize the urgency of arterial imaging, and to evaluate patient harm resulting from these delays. METHODS Institutional review board approval was granted by the Human Research Protection Office at Washington University in St. Louis. This was a retrospective chart review of new patients either seen for suspicion of or found to have a final diagnosis of third nerve palsy between November 2012 and June 2020 by the neuro-ophthalmology clinic at Washington University in St. Louis and inpatient ophthalmology consultation service at Barnes-Jewish Hospital. Patients were identified from databases maintained by the neuroophthalmology service and inpatient ophthalmology consultation service by searching “third nerve palsy” and its various permutations, including “third nerve palsy,” “CN3 palsy,” “CNIII palsy,” “nerve 3 palsy,” and “oculomotor nerve palsy.” These patients’ referral records and neuroophthalmologic consultation documents were located in the electronic medical records system and reviewed. Patients for whom an isolated third nerve palsy was suspected by the referring provider or who were ultimately diagnosed with an isolated third nerve palsy at consultation were included in the study. Exclusion criteria included age ,18 years old, insufficient referral documentation to determine what referring doctors’ working diagnosis or plan had been, or nonisolated third nerve palsies. We defined an isolated third nerve palsy as examination findings that localize to a unilateral third nerve, without additional cranial neuropathies or focal neurologic examination findings. Nonisolated third nerve palsies were excluded because the localization would be different, with a much lower index of suspicion for PCommA aneurysm. In ambiguous cases, inclusion in the study was determined upon review by a fellowship-trained neuro-ophthalmologist. 538 All patients underwent a full examination as part of their clinical care. “Final” diagnosis was determined by the tertiary academic ophthalmology consultant or by a fellowship-trained neuro-ophthalmologist at the neuroophthalmology encounter. Data collected included demographic information (age, gender, and ethnicity), specialty of the referring provider, presenting complaints, physical examination findings documented by the referring provider, physical examination findings documented by the consultant, final diagnoses, arterial imaging performed both pre-neuro-ophthalmology and post-neuro-ophthalmology consultation, time between referral and neuro-ophthalmology consultation, timing of arterial imaging performed, etiologies of the third nerve palsy, and details of patient harm as a result of a delay in imaging. For continuous measures, the mean, SD, median, and interquartile range were calculated. For categorical measures, percentages were calculated. Statistical analyses were performed using SAS V9.4 (SAS Institutes, Cary, NC). Differences in proportions were tested using chi-square analysis. RESULTS One hundred thirty-six patients were initially identified by our search. Twenty-six were excluded for age ,18 years old or for presenting with additional focal symptoms (a nonisolated third nerve palsy). Of 110 total patients included in the study, 62 (56.4%) were women. The mean age was 61.8 years (±14.6 years). Eighty-eight (80%) were white, 20 (18.2%) were Black, one (0.9%) was Asian, and one (0.9%) was documented only as “Non-Hispanic.” Most patients were referred by ophthalmologists (48 patients, 43.6%) (Table 1). Optometry was the next most common referring specialty (17.3%), and 5 patients (4.6%) presented to the emergency department without referral. Of 110 patients, 97 (88.2%) had a presenting complaint of diplopia, 81 (73.6%) of ptosis, and 6 (5.5%) of anisocoria (Table 2). Twenty-seven of referring providers (25.7%) failed to document at least one cardinal physical examination component central to diagnosis of third nerve palsy—eye movements, ptosis, and/or anisocoria. Of all 110 patients, who were either suspected to have a third nerve palsy or who were found to have a final diagnosis of third nerve palsy, only 40 (36.4%) received urgent arterial imaging. Of the 70 patients who did not receive urgent arterial imaging, only 5 (7%) met the strict criteria that may be used to justify deferring imaging—only 5 were over the age of 50 and were documented to have a complete, pupil-sparing third nerve palsy (An additional 5 patients who did not receive urgent imaging were over the age of 50, and had insufficient documentation to determine Chung et al: J Neuro-Ophthalmol 2021; 41: 537-541 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. Specialty of provider referring to neuroophthalmology consultation Specialty #Of Patients Referred to Neuroophthalmology (n = 110) Ophthalmology Optometry Neurology Neurosurgery Primary care Medical oncology Emergency medicine Endocrinology Neuroradiology Radiation oncology Presented without referral 48 19 13 12 5 4 1 (43.6%) (17.3%) (11.8%) (10.9%) (4.6%) (3.6%) (0.9%) 1 1 1 5 (0.9%) (0.9%) (0.9%) (4.6%) whether they had a complete, pupil-sparing third nerve palsy). Of the 88 patients in whom the referring providers suspected third nerve palsy, only 38 (43%, 95% confidence interval [CI] = 33–54) were sent to the emergency department or for an urgent neuro-ophthalmology consult, and only 35 (40%, 95% CI = 30–50) received urgent arterial imaging (Table 3), with “urgent” defined as within 24 hours of the encounter. There was no significant association between suspicion for third nerve palsy and being sent for urgent evaluation (P = 0.29) or urgent arterial imaging (P = 0.082) (Table 3). One hundred included patients had a final diagnosis of third nerve palsy. Five patients who received a final diagnosis of third nerve palsy presented directly to the emergency room (there was no prior evaluation by a referring provider). Two of those 5 patients received urgent arterial imaging on presentation. The other 95 patients who received a final diagnosis of third nerve palsy had been evaluated by a referring provider. Of those 95, the referring provider had correctly suspected third nerve palsy in 78 patients (82%). However, only 37 (39%) received urgent arterial imaging. After excluding patients who did not receive any arterial imaging both pre-neuro-ophthalmology and post-neuroophthalmology consultation, wait times for imaging were assessed for 20 patients who did not have arterial imaging performed before their encounter with the neuroophthalmologist (Table 4). The median delay between symptom onset and arterial imaging was 24 days (interquartile range: 13.5–37.5), and the median delay between first medical contact and arterial imaging was 12.5 days (interquartile range: 9.5–27.3). As a result of a delay in imaging, one patient experienced harm, specifically delayed detection of a metastatic mass in the cavernous sinus. CONCLUSIONS In this study, rather than providers not appropriately identifying third nerve palsy, the delays in arterial imaging suggested a failure to recognize the urgency of arterial imaging to rule out PCommA aneurysm as an etiology. In more than 80% of patients with a final diagnosis of third nerve palsy, the diagnosis was correctly suspected by the referring provider. However, less than half of these patients were sent for urgent arterial imaging, and those suspected of third nerve palsy were no more likely to be sent for urgent arterial imaging or neuro-ophthalmology consultation than those in whom third nerve palsy was not suspected. TABLE 2. Clinical findings Presenting complaint (n = 110) Diplopia Ptosis Anisocoria Referral examination (n = 105)* Ptosis Mydriasis Elevation deficit Depression deficit Adduction deficit Neuroophthalmology examination (n = 110) Ptosis Mydriasis Elevation deficit Depression deficit Adduction deficit Present Absent No Documentation 97 (88.2%) 81 (73.6%) 6 (5.5%) 12 (10.9%) 28 (25.5%) 103 (93.6%) 1 (0.9%) 1 (0.9%) 1 (0.9%) 75 30 37 29 55 (71.4%) (28.6%) (35.2%) (27.6%) (52.4%) 20 61 42 49 31 (19%) (58.1%) (40%) (46.7%) (29.5%) 78 37 72 59 67 (70.9%) (33.6%) (65.5%) (53.6%) (60.9%) 32 71 38 51 43 (29.1%) (64.5%) (34.5%) (46.4%) (39.1%) 10 14 26 27 19 (9.5%) (13.3%) (24.8%) (25.7%) (18.1%) 0 (0%) 2 (1.8%) 0 (0%) 0 (0%) 0 (0%) *‟Referral Examination” findings exclude the 5 patients who presented without a referral. Chung et al: J Neuro-Ophthalmol 2021; 41: 537-541 539 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 3. Imaging after suspected of third nerve palsy Referred for Third Nerve Palsy Yes (n = 88) No (n = 17) No 38 (43%), 33–54 5 (29%), 8–51 50 (57%), 47-67 12 (71%), 49–92 TABLE 4. Delays for patients who did not receive arterial imaging before neuro-ophthalmology consultation 540 P Yes Although PCommA aneurysm is rare, delayed arterial imaging leaves patients vulnerable to a preventable aneurysmal rupture—a potentially lethal event. As prior studies on referral patterns have shown, non-urgent referrals to neuro-ophthalmology may result in delays of weeks to months (13). Patients whose arterial imaging was delayed until after neuro-ophthalmology consultation had a median delay of nearly 2 weeks between their first medical contact for these symptoms and arterial imaging. These results emphasize the important role referring providers play, not only in identifying third nerve palsies, but also in recognizing the urgency of arterial imaging and obtaining it quickly. This delay cannot be justified even by accounting for the historical practice of close observation in the setting of a complete, pupil-sparing third nerve palsy in patients over the age of 50, which could be presumed to have a microvascular etiology. Of those patients who did not receive urgent arterial imaging, less than 10% met the criteria to presume a microvascular origin. Most patients who did not receive immediate imaging were unequivocally inappropriately delayed. Of note, approximately one quarter of referring providers failed to document at least one cardinal physical examination component, suggesting an incomplete examination. An insufficient examination could contribute to providers being uncertain of a third nerve palsy diagnosis, thus referring to neuro-ophthalmology for confirmation. However, because of the potential lethality of a PCommA aneurysm rupture, any suspicion of a third nerve palsy requires immediate action—such as requesting urgent rather than routine neuro-ophthalmology referral. Mean (SD) Median 25th–75th percentile (IQR) Received Urgent Arterial Imaging No. (%), 95% CI Sent to ED or Urgent Neuroophthalmology Consult No. (%), 95% CI Days Between Symptom Onset and Arterial Imaging Days Between First Medical Contact and Arterial Imaging 32 (32.1) 24 13.5–37.5 (24) 23 (31.7) 12.5 9.5–27.3 (17.8) Yes No P 0.29 35 (40%), 30–50 53 (60%), 50–70 0.082 3 (18%), 0–36 14 (82%), 64–100 We also observed that only 2 of the 5 patients who presented directly to the emergency department without prior referral received urgent arterial imaging for their third nerve palsies. Although a small sample, this may merit further investigation, because it is imperative that emergency providers also recognize the diagnosis and the importance of urgently obtaining arterial imaging. This study has several limitations. First, all patients were gathered from a single tertiary neuro-ophthalmology clinic and the inpatient academic ophthalmology service at our institution, so the results may not be generalizable. Second, several patients presented to their neuro-ophthalmology encounter after their symptoms had partially or fully resolved over the time elapsed between their referring encounter and consultation. Because their symptoms had begun resolving, a microvascular etiology was confirmed at consultation, and further arterial imaging was no longer indicated. Thus, several patients who should likely have received arterial imaging at the time of their first medical contact did not ultimately receive it, and thus could not be included in the analysis of time delay to imaging. In addition, judgment of whether patient harm was because of delayed imaging is inherently subjective. Finally, in only including patients that were ultimately evaluated at our facility, we may have missed additional instances of third nerve palsies and delay-related patient harm that never presented for neuro-ophthalmology consultation. Although most providers accurately identified third nerve palsies, less than half appropriately obtained urgent arterial imaging to rule out an aneurysmal etiology. Raising awareness of the importance of urgent arterial imaging for isolated third nerve palsies may improve patient safety and aid subsequent providers during the diagnostic process, ultimately improving patient care. REFERENCES 1. Tamhankar MA, Volpe NJ. 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