Is Anisocoria a Red Flag or a False Alarm? When Unequal Pupils Shouldn't Trigger Stroke Panic

Avery Sinclair in Health & Wellness December 2025 • 4 min read.

"Understanding when anisocoria—unequal pupil sizes—should prompt immediate action and when it's likely a benign finding can optimize stroke response protocols and resource allocation."

In the high-stakes environment of emergency medicine, stroke codes represent some of the most time-sensitive and resource-intensive protocols. When a patient presents with symptoms suggestive of a stroke, a rapid and coordinated response is essential to minimize potential brain damage. One such symptom that often triggers a stroke code is anisocoria, a condition characterized by unequal pupil sizes.

Anisocoria can indeed be a sign of serious neurological issues, including stroke. However, it can also arise from more benign causes, creating a diagnostic dilemma for clinicians. The decision to activate a full stroke code—mobilizing specialized teams, advanced imaging, and potentially administering thrombolytic medications like alteplase—must be made swiftly. Yet, unnecessary activations can strain resources, delay care for other patients, and expose individuals to the risks associated with treatments they may not need.

New research is shedding light on the complexities of anisocoria in the context of stroke assessment. A recent study published in the Journal of Stroke and Cerebrovascular Diseases investigates how often anisocoria leads to the administration of alteplase, a critical drug used to treat ischemic stroke. By understanding the likelihood of stroke in patients presenting with anisocoria, medical professionals can refine their approach to stroke code activations and ensure that resources are used effectively.

Decoding Anisocoria: What the Research Reveals About Stroke Likelihood

Unequal pupil sizes in a medical context.

The study, conducted by Victoria A. Chang, Dawn M. Meyer, and Brett C. Meyer, retrospectively analyzed data from patients treated with alteplase at a comprehensive stroke center. The goal was to determine how frequently anisocoria, either in isolation or accompanied by other neurological deficits, prompted alteplase administration. The researchers categorized patients into three groups: those with isolated anisocoria [A+(only)], those with anisocoria and other findings [A+(other)], and those without anisocoria [A-].

The findings revealed a crucial insight: no patients with isolated anisocoria received alteplase. This suggests that unequal pupil size alone, in the absence of other neurological symptoms, is unlikely to be indicative of a stroke requiring immediate thrombolytic intervention. However, anisocoria was present in nearly 10% of patients who did receive alteplase, but these individuals also exhibited other neurological deficits.

Isolated Anisocoria: Zero cases of alteplase administration.
Anisocoria with Other Findings [A+(other)]: Approximately 10% of alteplase recipients.
Higher NIHSS Scores: The A+(other) group had significantly higher baseline National Institutes of Health Stroke Scale (NIHSS) scores, indicating more severe neurological deficits.
Posterior Circulation Events: A significant majority (83%) of A+(other) patients without pre-existing anisocoria experienced posterior circulation events or diffuse subarachnoid hemorrhage.

These results highlight the importance of considering the broader clinical picture when assessing patients with anisocoria. While unequal pupil sizes should not be dismissed, they should be evaluated in the context of other neurological signs and symptoms. The presence of additional deficits, such as weakness, speech difficulties, or visual disturbances, significantly increases the likelihood of a stroke and the potential need for alteplase.

The Bigger Picture: Refining Stroke Response for Better Patient Outcomes

This study offers valuable insights for optimizing stroke response protocols. By recognizing that isolated anisocoria is unlikely to warrant alteplase administration, hospitals and emergency medical services can refine their assessment algorithms and resource allocation. This may involve enhanced training for first responders and emergency room staff to differentiate between benign anisocoria and the more concerning presentations associated with stroke. Ultimately, the goal is to ensure that patients receive the right care, at the right time, without unnecessary delays or interventions.

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This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.jstrokecerebrovasdis.2018.09.029, Alternate LINK

Title: Isolated Anisocoria As A Presenting Stroke Code Symptom Is Unlikely To Result In Alteplase Administration

Subject: Cardiology and Cardiovascular Medicine

Journal: Journal of Stroke and Cerebrovascular Diseases

Publisher: Elsevier BV

Authors: Victoria A. Chang, Dawn M. Meyer, Brett C. Meyer

Published: 2019-01-01

Everything You Need To Know

What is anisocoria, and why does it often trigger stroke alerts?

Anisocoria is a condition characterized by unequal pupil sizes. It often triggers stroke alerts because it can be a sign of serious neurological issues, including stroke. However, anisocoria can also result from benign causes, making it crucial to differentiate between stroke-related and harmless instances to avoid unnecessary stroke code activations, which can strain resources and delay care for other patients.

When should anisocoria not be considered a sign warranting immediate stroke intervention, such as the administration of alteplase?

Anisocoria should not be considered a sign warranting immediate stroke intervention, like administering alteplase, when it presents in isolation, meaning without any other neurological deficits. Research indicates that patients with isolated anisocoria are unlikely to require thrombolytic intervention. The absence of additional symptoms, such as weakness, speech difficulties, or visual disturbances, suggests a lower likelihood of stroke.

How did the study by Chang, Meyer, and Meyer categorize patients presenting with anisocoria, and what were the key findings regarding alteplase administration in each group?

The study categorized patients into three groups: those with isolated anisocoria [A+(only)], those with anisocoria and other neurological findings [A+(other)], and those without anisocoria [A-]. The key finding was that no patients with isolated anisocoria received alteplase. Approximately 10% of patients who received alteplase had anisocoria along with other neurological deficits. This highlights that anisocoria, when accompanied by other neurological signs, is more indicative of a condition requiring alteplase.

What is the significance of higher NIHSS scores in patients presenting with anisocoria, and how does this relate to posterior circulation events?

Higher National Institutes of Health Stroke Scale (NIHSS) scores in patients with anisocoria and other findings [A+(other)] indicate more severe neurological deficits, suggesting a greater likelihood of stroke. A significant majority (83%) of A+(other) patients without pre-existing anisocoria experienced posterior circulation events or diffuse subarachnoid hemorrhage. This suggests that anisocoria, when coupled with a high NIHSS score, may point towards specific types of stroke or hemorrhage affecting the posterior circulation of the brain. These are important factors when assessing the need for immediate interventions like alteplase.

How can hospitals and emergency medical services optimize their stroke response protocols based on the research findings regarding anisocoria?

Hospitals and emergency medical services can optimize their stroke response protocols by refining assessment algorithms and resource allocation, especially when evaluating patients with anisocoria. Enhanced training for first responders and emergency room staff can improve the differentiation between benign anisocoria and presentations associated with stroke. By recognizing that isolated anisocoria is unlikely to warrant alteplase administration, resources can be directed more efficiently towards patients who exhibit anisocoria along with other neurological deficits, improving the overall quality and timeliness of stroke care.