Published online Mar 20, 2026. doi: 10.5662/wjm.v16.i1.108291
Revised: May 21, 2025
Accepted: August 8, 2025
Published online: March 20, 2026
Processing time: 306 Days and 8.1 Hours
Isolated third, fourth, and sixth cranial nerve palsies (CNP) in elderly people occur commonly due to microvascular ischemia. Ischemic isolated CNP share several atherosclerotic risk factors that are responsible for stroke which include hypertension, diabetes mellitus and dyslipidemia. Hyperhomocysteinemia is atherogenic and hence is also considered as an independent risk factor for stroke. So indirectly, elevated homocysteine in CNP may act as a risk factor for stroke.
To determine the incidence of isolated ischemic CNP secondary to elevated serum homocysteine (predisposing them to a greater risk of stroke), and if serum homocysteine levels need to be checked routinely in all isolated CNP by neuro-ophthalmologists.
This is a retrospective case study, in which 66 patients diagnosed with ischemic isolated CNP were enrolled. Informed written consent was obtained from all who participated in this study. Data of these patients were collected from the electronic medical records and were analyzed. Complete anterior, posterior segment and neuro-ophthalmic examinations were done, in addition to routine blood investigations and serum homocysteine.
The mean age was 55 years old. Gender wise, 74.24% affected were males and 25.76% were females. The sixth nerve was affected in 68.18% cases. Of 66 patients, 37 cases (56.06%) had elevated serum homocysteine. In patients > 40 years and without any systemic risk factors, 63.2% had elevated serum homocysteine. In patients < 40 years and without systemic risk, 66.7% had high serum homocy
In cases without systemic risk factors, serum homocysteine may indirectly act as a risk factor for developing stroke in patients having isolated ischemic CNP. According to our study, patients with or without risk factors and those above 40 years, 56.06% patients with isolated ocular motor palsy had elevated serum homocysteine. This implies that the level of elevated serum homocysteine was statistically significant (P < 0.05) in these patients; thus, indirectly showing a greater predilection towards developing a stroke. In this small pilot study, we show that even in neuro-ophthalmology serum homocysteine should be routinely checked for all patients with isolated ischemic CNP. This might reduce the incidence of patients developing a stroke.
Core Tip: This retrospective study of 66 patients with isolated ischemic cranial nerve palsies found elevated serum homocysteine in over half the cases, including those without traditional vascular risk factors. The findings suggest homocysteine may be an independent risk factor for stroke, supporting routine testing in such patients which may help identify stroke risk early and guide preventive care.