New ‘sniff test’ predicts recovery of consciousness in brain

Summary: Researchers have developed a sniff test that can detect which patients in a vegetative state following a TBI will regain consciousness.

Source: Weizmann Institute of Science

If an unconscious person responds to smell through a slight change in their nasal airflow pattern – they are likely to regain consciousness. This is the conclusion from a new study conducted by Weizmann Institute scientists and colleagues at the Loewenstein Rehabilitation Hospital, Israel. According to the findings, published in the journal Nature, 100% of the unconscious brain-injured patients who responded to a “sniff test” developed by the researchers regained consciousness during the four-year study period. The scientists think that this simple, inexpensive test can aid doctors in accurately diagnosing and determining treatment plans according to the patients’ degree of brain injury. The scientists conclude that this finding once again highlights the primal role of the sense of smell in human brain organization. The olfactory system is the most ancient part of the brain, and its integrity provides an accurate measure of overall brain integrity.

Following severe brain injury, it is often difficult to determine whether the person is conscious or unconscious, and current diagnostic tests can lead to an incorrect diagnosis in up to 40% of cases. “Misdiagnosis can be critical as it can influence the decision of whether to disconnect patients from life support machines,” says Dr. Anat Arzi, who led the research. “In regard to treatment, if it is judged that a patient is unconscious and doesn’t feel anything, physicians may not prescribe them painkillers that they might need.” Arzi commenced this research during her doctoral studies in the group of Prof. Noam Sobel of the Weizmann Institute of Science’s Neurobiology Department and continued it as part of her postdoctoral research at the University of Cambridge’s Department of Psychology.

The “consciousness test” developed by the researchers – in collaboration with Dr. Yaron Sacher, Head of the Department of Traumatic Brain Injury Rehabilitation at Loewenstein Rehabilitation Hospital – is based on the principle that our nasal airflow changes in response to odor; for example, an unpleasant odor will lead to shorter and shallower sniffs. In healthy humans, the sniff-response can occur unconsciously in both wakefulness and sleep.

The study included 43 brain-injured patients in the Loewenstein Rehabilitation Hospital. The researchers briefly placed jars containing various odors under the patients’ noses, including a pleasant scent of shampoo, an unpleasant smell of rotten fish, or no odor at all. At the same time, the scientists precisely measured the volume of air inhaled through the nose in response to the odors. Each jar was presented to the patient ten times in random order during the testing session, and each patient participated in several such sessions. “Astonishingly, all patients who were classified as being in a ‘vegetative state’ yet responded to the sniff test, later regained consciousness, even if only minimal. In some cases, the result of the sniff test was the first sign that these patients were about to recover consciousness – and this reaction was observed days, weeks and even months prior to any other signs,” says Arzi. Moreover, the sniff response not only predicted who would regain consciousness, it also predicted with about 92% accuracy who would survive for at least three years.

“The fact that the sniff test is simple and potentially inexpensive makes it advantageous,” explains Arzi. “It can be performed at the patients’ bedside without the need to move them – and without complicated machinery.”

A mindful tennis game

After a severe head injury, patients may fall into a comatose state – their eyes are closed and they do not have sleep-wake cycles. A coma usually lasts for about two weeks, after which there may either be a rapid improvement and return to consciousness, deterioration leading to death, or it could lead to a condition defined as “disorder of consciousness.” When spontaneous eye opening occurs but there is no evidence that the patients are aware of themselves or their surroundings, they are then diagnosed as being in a “vegetative state.” Alternatively, if a patient displays consistent signs of awareness, even if they are minimal and unstable, the patient will be classified as being in a “minimally conscious state.” The gold standard diagnostic tool for assessing the level of consciousness is the Coma Recovery Scale (Revised), which examines responses to various stimuli: eye movements while tracking an object; turning the head toward a sound; response to pain, among others. Since the rate of diagnosis errors may reach up to 40%, it is recommended to repeat the test at least five times.

This shows a nose
The olfactory system is the most ancient part of the brain, and its integrity provides an accurate measure of overall brain integrity. Image is in the public domain.

However, misdiagnosis may also occur when the test is conducted repeatedly. “In a well-known study, a patient diagnosed as being in a ‘vegetative state’ following a car accident was scanned in an MRI machine. While in the scanner, the researchers asked the patient to imagine that she was playing tennis and observed that her brain activity was similar to the brain activity of healthy people when they also imaged playing a tennis game. Suddenly, they realized: ‘hold on a minute, she’s there. She hears us and is responding to our requests. She simply has no way of communicating’,” says Arzi. “There are also known cases of people who were diagnosed in a ‘vegetative state,’ but when they regained consciousness, they were able to recount in detail what was occurring while supposedly vegetative. Diagnosing the level of consciousness of a patient who has suffered a severe head injury is a major clinical challenge. The sniff test we have developed may provide a simple tool to tackle this challenge.”

Prof. Noam Sobel is head of the Azrieli National Institute for Human Brain Imaging and Research; his research is supported by the Norman and Helen Asher Center for Human Brain Imaging; the Nadia Jaglom Laboratory for the Research in the Neurobiology of Olfaction; the Adelis Foundation; and the Rob and Cheryl McEwen Fund for Brain Research. Prof. Sobel is the incumbent of the Sara and Michael Sela Professorial Chair of Neurobiology.

About this neuroscience research article

Weizmann Institute of Science
Media Contacts:
Gizel Maimon – Weizmann Institute of Science
Image Source:
The image is in the public domain.

Original Research: Closed access
“Olfactory sniffing signals consciousness in unresponsive patients with brain injuries”. by Anat Arzi, Liron Rozenkrantz, Lior Gorodisky, Danit Rozenkrantz, Yael Holtzman, Aharon Ravia, Tristan A. Bekinschtein, Tatyana Galperin, Ben-Zion Krimchansky, Gal Cohen, Anna Oksamitni, Elena Aidinoff, Yaron Sacher & Noam Sobel.
Nature doi:10.1038/s41586-020-2245-5


Olfactory sniffing signals consciousness in unresponsive patients with brain injuries

After severe brain injury, it can be difficult to determine the state of consciousness of a patient, to determine whether the patient is unresponsive or perhaps minimally conscious, and to predict whether they will recover. These diagnoses and prognoses are crucial, as they determine therapeutic strategies such as pain management, and can underlie end-of-life decisions. Nevertheless, there is an error rate of up to 40% in determining the state of consciousness in patients with brain injuries. Olfaction relies on brain structures that are involved in the basic mechanisms of arousal, and we therefore hypothesized that it may serve as a biomarker for consciousness. Here we use a non-verbal non-task-dependent measure known as the sniff response to determine consciousness in patients with brain injuries. By measuring odorant-dependent sniffing, we gain a sensitive measure of olfactory function. We measured the sniff response repeatedly over time in patients with severe brain injuries and found that sniff responses significantly discriminated between unresponsive and minimally conscious states at the group level. Notably, at the single-patient level, if an unresponsive patient had a sniff response, this assured future regaining of consciousness. In addition, olfactory sniff responses were associated with long-term survival rates. These results highlight the importance of olfaction in human brain function, and provide an accessible tool that signals consciousness and recovery in patients with brain injuries.

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