Real-world data analysis of cranial nerve III, IV, and VI palsies: demographics, association factors, and comparative all-cause mortality

Binocular diplopia is a distressing clinical condition that prompts clinicians to investigate underlying etiologies, particularly cranial nerve (CN) III, IV, or VI palsies. These may arise from microvascular ischemia, inflammation, trauma, compression, or neuromuscular junction disorders. This study aims to explore the association factors of these three ocular motor cranial nerve palsies and to compare their respective all-cause mortality rates using the real-world TriNetX Clinical Research Database (TriNetX CRD).

TriNetX is a global federated administrative database with real-time updates of electronic medical records (EMRs). We used the US Collaborative Network within the TriNetX platform to establish the patient cohorts. This network contains electronic health record data from more than 100 million patients across 68 US healthcare organizations (HCOs). This study utilized TriNetX platform to analyze the demographics and associated factors of ocular motor cranial nerve palsies, including diabetes, hypertension, acute myocardial infarction (AMI), overweight status, blood glucose and lipid profiles, body mass index (BMI), and history of brain aneurysm surgery, through intergroup comparisons using paired t-tests. All-cause mortality was assessed using Cox proportional hazards modeling and Kaplan–Meier survival analysis.

The average age at presentation was 63, 57, and 60 years for CN III, IV, and VI palsies, respectively, with a slight male predominance. CN VI palsy was the most common, followed by CN IV and CN III palsies. CN III and CN VI palsy cohorts were more commonly associated with diabetes, hypertension, AMI, overweight, and brain aneurysm surgery, suggesting a microvascular or compressive etiology. In contrast, the CN IV palsy cohort was younger and more similar to the general population in clinical and laboratory characteristics. Regarding all-cause mortality, the CN III palsy cohort had the poorest survival, followed closely by the CN VI group, while the CN IV group exhibited the most favorable survival outcome.

This study confirmed that CN VI palsy is the most frequent cause of ocular motor nerve palsy leading to binocular diplopia. Notably, CN III and VI palsies shared similar vascular and compressive association factors, while CN IV palsy appeared to be more frequently linked to congenital or traumatic origins. These differences were reflected in the mortality analysis, where CN III palsy showed the worst prognosis, CN VI a slightly better but comparable pattern, and CN IV the best survival outcome.

Using the TriNetX CRD, this study delineated the demographic profiles, associated clinical factors, and survival outcomes of patients with ocular motor cranial nerve palsies. The typical demographic was males in their late 50s to early 60s, with CN VI being the most frequently affected nerve. CN III and VI palsies were more often associated with microvascular and compressive conditions, which correlated with higher mortality. Conversely, CN IV palsy was associated with a younger population and more benign clinical profiles, reflected in better survival outcomes.