A new screening tool may provide an early warning signal of neurologic deterioration in patients in critical care units, according to findings from a retrospective study presented at the Neuroscience Advanced Practice Provider Educational Conference (Neuro-APP) Conference held virtually and in San Diego, CA, January 5 to 8, 2022.

Greater difference in left and right eye Neurological Pupil index scores (NPi-Diff) may be an effective early quantitative measure to indicate neurologic decline even in patients in neurocritical care units with normal pupillary light reflex (PLR), reported the researchers.

“This is a potential game changer because we do not have to wait until the patient is abnormal before we know that they are heading in the wrong direction,” senior author DaiWai M. Olson, PhD, RN, FNCS, professor of neurology and neurosurgery and director of the Neuroscience Nursing Research Center at the University of Texas Southwestern Medical Center in Dallas.

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“Most neuroprognostic tools use parts of the clinical examination including pupils but, until now, pupil examinations were subjective,” Dr Olson said. “Automated pupillometry provides objective trendable data that did not exist 10 years ago, so it’s time to start updating the science.”

Study Design

The NPi is a summary score of the pupillary light reflex (PLR) as measured via automated infrared pupillometry. The NPi-Diff is the absolute difference between left and right eye NPi readings.

The researchers analyzed registry data from 2752 subjects who underwent 3519 pupillometry assessments. All of the patients were admitted to neurocritical care; diagnoses included brain tumors, stroke, and subarachnoid hemorrhage, according to lead author Sanjay Neerukonda, BS, also of UT Southwestern Medical Center.

All patients had normal PLR (NPi ≥3.0) and NPi values measured within 72 hours of hospital admission. Scores on the NPi-Diff were categorized as less than 0.7 (small difference) and 0.7 or greater (large difference and potentially clinical relevant).


The mean Glasgow Coma Scale (GCS) score in this cohort was 12.06 (SD, 3.41) and the mean NPi-Diff was 0.36 (SD, 0.33). A total of 571 assessments (16%) had an NPi-Diff 0.7 or greater, indicating potentially clinical relevant findings.

The mean GCS score for patients with NPi-Diff 0.7 or greater was significantly lower (indicating poorer outcomes) than that for patients with NPi-Diff less than 0.7 (10.76 vs 13.15; P <.0001; Figure). After controlling for age, sex, race, and diagnosis, lower GCS remained significantly correlated with greater NPi-Diff (R= -0.26877; P <.0001).

Figure. Glasgow Coma Scale score by category of Neurological Pupil index (NPi) Difference. Reprinted with permission of Neerukonda et al.

The study findings suggest a negative correlation between NPi-Diff and GCS, the study authors noted. “Monitoring for NPi-Diff values ≥0.7 should be considered even when both NPi values reflect a normal PLR [≥3.0],” they concluded.

The study authors also noted that these findings need to be replicated in future research and emphasized that NPi-Diff may serve primarily as an early warning. “If the left and right pupils start to function differently even when they are both still normal, it could signal impending failure and allow for earlier intervention by the health care team,” Dr Olson concluded.


Neerukonda SV, Schneider NJ, Aiyagari V, Olson DM. Differences in left and right pupillary function is a prognostic of neurological deterioration. Neuroscience Advanced Practice Provider Educational Conference (Neuro-APP) Conference. San Diego, CA, January 5-8, 2022.