Summary: Scientists have developed a simple bedside “sniff test” that accurately identifies which patients in a vegetative state after traumatic brain injury are likely to regain consciousness.
Source: Weizmann Institute of Science
Key finding: A subtle change in nasal airflow in response to an odor — the sniff response — reliably predicted recovery of consciousness in patients who appeared unresponsive after traumatic brain injury. In a longitudinal study, every unresponsive patient who produced a sniff response later recovered consciousness during the follow-up period. Researchers say the inexpensive, noninvasive test could improve diagnosis and help guide treatment decisions.
Assessing consciousness after severe brain injury is often challenging. Standard bedside assessments and behavioral scales can misclassify patients as unresponsive in a significant number of cases, with some studies reporting error rates up to 40%. Misdiagnosis has serious consequences: it can affect choices about pain management, rehabilitation plans, and even decisions about life-sustaining treatment. To address this diagnostic gap, researchers from the Weizmann Institute of Science, in collaboration with specialists at Loewenstein Rehabilitation Hospital, investigated whether the olfactory system — one of the oldest and most primitive brain systems — could provide a sensitive marker of brain integrity and awareness.
The team focused on the sniff response, an automatic change in nasal breathing that occurs when humans encounter different odors. For example, an unpleasant smell typically triggers shorter, shallower sniffs, while pleasant odors may elicit larger inhalations. This reflexive response can occur without conscious effort in both wakefulness and sleep, making it a promising nonverbal, non-task-dependent measure for patients who cannot follow instructions.
In the study, 43 patients with severe brain injuries admitted to Loewenstein Rehabilitation Hospital were assessed repeatedly over time. The investigators presented odor-filled jars briefly beneath each patient’s nose — including pleasant scents (such as shampoo), unpleasant odors (such as rotten fish), and blank controls — and measured nasal airflow precisely to quantify inhalation volume for each presentation. Each odor was presented multiple times in random order across several sessions to ensure reliable measurement.
Results showed that patients diagnosed clinically as being in a vegetative state who nonetheless displayed an odor-dependent sniff response were highly likely to regain consciousness. Remarkably, all vegetative patients in the study who responded with a sniff pattern consistent with odor processing recovered consciousness at some point during the follow-up period. In several cases, the sniff response was the earliest detectable sign of recovery, appearing days, weeks, or even months before other clinical indicators. Beyond predicting recovery of awareness, the sniff response was also associated with longer-term outcomes: it predicted three-year survival with approximately 92% accuracy.
Because the sniff test is simple, inexpensive, and noninvasive, it offers practical advantages for clinical use. It can be performed at the bedside without moving critically ill patients or using complex equipment. The investigators suggest that adding this measure to standard assessments could reduce diagnostic errors and help clinicians tailor treatment plans more appropriately for patients with disorders of consciousness.
A clinical context
After a severe head injury, patients often pass through a coma, a state marked by closed eyes and absent sleep–wake cycles. Coma typically resolves within a couple of weeks, after which patients may improve rapidly, worsen, or enter a prolonged disorder of consciousness. When a patient opens their eyes but shows no clear signs of awareness, they are classified as being in a vegetative state. If sporadic, minimal signs of awareness are present, the diagnosis is a minimally conscious state. The Coma Recovery Scale—Revised is the current gold standard for behavioral assessment, but because of inherent variability and the possibility of misinterpretation, repeated testing is recommended. Neuroimaging and advanced electrophysiology have revealed cases in which patients diagnosed as vegetative nevertheless show covert awareness, such as when asked to imagine playing tennis; such findings underscore the need for additional objective, bedside-accessible tools.
Lead researcher Dr. Anat Arzi began this work during doctoral studies in Prof. Noam Sobel’s lab at the Weizmann Institute and continued it while a postdoctoral fellow at the University of Cambridge. The clinical collaboration included Dr. Yaron Sacher, head of Traumatic Brain Injury Rehabilitation at Loewenstein Rehabilitation Hospital. The study’s findings were published in the journal Nature under the title “Olfactory sniffing signals consciousness in unresponsive patients with brain injuries.”
Implications
This research highlights the prominent role of olfaction in human brain organization and shows that a straightforward physiological response can provide meaningful prognostic information. While further validation in larger, multicenter studies will strengthen the evidence base, the sniff test could become a valuable addition to assessments of patients with disorders of consciousness, helping clinicians make better-informed decisions about pain management, rehabilitation options, and long-term care planning.
About this research article
Source: Weizmann Institute of Science. Media contact: Gizel Maimon – Weizmann Institute of Science. Original research: “Olfactory sniffing signals consciousness in unresponsive patients with brain injuries,” Nature, doi: 10.1038/s41586-020-2245-5. Image: public domain.
Abstract (concise)
After severe brain injury it can be difficult to determine whether a patient is truly unresponsive or retains some awareness, and to predict recovery. The sniff response — an odor-dependent change in nasal airflow — taps brain systems involved in arousal and can serve as a nonverbal biomarker of consciousness. Repeated measurement of odor-evoked sniffs differentiated unresponsive from minimally conscious states at the group level, and at the single-patient level a sniff response in an unresponsive patient reliably signaled later recovery of consciousness and predicted longer-term survival. These results offer a low-cost, bedside tool for assessing consciousness and prognosis after brain injury.
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