Injecting Ice Cold Saline Can Protect the Brains of Cardiac Arrest Patients

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 For Dr. Sarah Perman, it is not enough for a cardiac arrest patient’s heart to work properly again. “What we care about is not just survival to when they’re discharged from the hospital,” she said, “but neurologic recovery at discharge.”
 

 While a medical resident, Perman once cared for an elderly cardiac arrest patient. The attending team felt that the patient would have a grave prognosis. Their quick conclusion surprised Perman, who “started to learn that there was some generalized hesitancy” in treating cardiac arrest patients who have chronic heart conditions or do not initially respond to a defibrillator. The patient’s relatives still wanted the doctors to try everything they could, so they started therapeutic hypothermia, which was a success. After cooling the patient’s body temperature and a period of rewarming, the patient was revived and could go home.
 
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<figcaption>A nurse attends to a patient during a simulated emergency.
 
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 Dr. Perman, now an assistant professor of emergency medicine at the University of Colorado, and her colleagues
 <a href="http://circ.ahajournals.org/content/early/2015/11/10/CIRCULATIONAHA.115.016317.abstract">
 found
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 that lowering the body’s internal temperature can help preserve neurological function for cardiac arrest patients with heart rhythms that do not respond to defibrillators. This controlled cooling is called therapeutic hypothermia, or TH, which is versatile enough to be carried out within ambulances and emergency rooms. Medical responders can cool the chest and limbs with ice packs or thread a catheter carrying cold saline through their patient.
 

 Coauthor Dr. Benjamin Abella said most research and treatment effort has been placed on patients with shockable rhythms. With so little data on patients with nonshockable rhythms, hospitals are hesitant to use this therapy.
 

 The American Heart Association estimates 530,000 individuals suffer cardiac arrest per year in the United States. For every minute a patient does not receive treatment, survival decreases by 7%.
 

 “The human body has no real good mechanism to come back from a cardiac arrest,” said EMT Elizabeth Watkins. During cardiac arrest, the heart stops pumping blood and oxygen throughout the body. This is especially bad news for the brain, as cerebral fluid can also build up and put pressure on the brain. Death can result in minutes.
 

 Defibrillators can restore shockable rhythms, while other rhythms are nonshockable and do not respond to electrical activity. Without treatment, survival chances for nonshockable patients are slim—as low as 10%.
 
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<figcaption>Dr. Benjamin Abella explains how therapeutic hypothermia can aid recovery in patients with nonshockable heart rhythms.
 
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 TH can help preserve the neurobiology of comatose patients that have a pulse. This sort of corporeal refrigeration slows down the rate of cell death and acid build-up in the brain. Two landmark trials in 2002 endorsed TH for patients with shockable rhythms. This treatment, as Dr. Perman and her team found, could also benefit people who may not initially benefit from a defibrillator.
 

 Drs. Perman and Abella’s team gathered data from 262 adult patients with non-shockable rhythms and paired them on characteristics such as age. “You have to make sure you’re comparing apples to apples,” Dr. Abella explained. Half of the patients had received TH, the other half did not.
 

 The researchers were especially interested in how well neurologic function was preserved after TH, and so they then compared each patient’s recovery through a Cerebral Performance Category (CPC) test. This widely used clinical measurement describes level of consciousness on a scale of 1—someone who is stable and alert enough to go home—to 5—death. The researchers found that patients who received TH had 3.5 times better neurologic recovery (a CPC of “1” or “2”) compared to those who did not.
 

 Drs. Perman and Abella’s study was published in
 
 Circulation
 
 . For Watkins, the EMT, a future study in TH effectiveness should examine patients who receive TH while they are in cardiac arrest. Starting TH sooner, rather than when patients regain a pulse, “decreases metabolic demand and causes less stress on the heart overall.” A drawback is that drugs typically given with cardiac arrest, like amiodarone, may not be as effective while going through a chilled body.
 

 In order to understand how to better apply TH, Dr. Perman is looking to a bigger sample size. Thankfully, “there’s been a push for a national cardiac arrest database.” A September 2015 Institute of Medicine report outlined this is a major strategy to improve cardiac arrest survival.
 

 “Cardiac arrest is a fairly grave occurrence and outcomes are not great, but we are doing everything we can to improve outcomes,” Dr. Perman said.
 
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 Photo credit:
 <a href="https://www.flickr.com/photos/codnewsroom/8637906595">
 COD Newsroom/Flickr (CC BY), Benjamin Abella/University of Pennsylvania
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Newly Discovered ‘Stop Neurons’ Could Save Your Life

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 Neuroscientists have known since the 1960s what nerves tell a person’s legs to step off the curb to cross the street. But until now, they had no idea which hold the person back to avoid getting hit by a car.
 

 By stimulating nerve cells with light, a group of neuroscientists at the Karolinska Institut in Stockholm both defined the aptly named “stop neurons” and saw how they work in walking mice. The team used a “bottom-up approach” to explore how the spinal cord, lower in the chain of neural command, communicates with the brain stem, which is higher in the chain.
 
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<figcaption>"Stop neurons" tell our bodies to stop moving.
 
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 Nerve cells that give rise to other functions we do not consciously think about, like breathing and keeping balance, are located in same area—effectively, as coauthor Ole Kiehn puts it, “one big mess of integrated networks.”
 

 To find the stop neurons, Kiehn and Julien Bouvier first modified a mouse’s brain stem to be sensitive to light stimulation, then sliced it into smaller and smaller segments. They removed parts until light no longer stimulated the segment. From this, the researchers pinpointed a cluster of “stop neurons” that extend down part of the spinal cord that, when stimulated tell the spinal cord to halt locomotion.
 

 What particularly surprised Bouvier was that “those stop cells are excitatory.” In order to stop motion, the cells need to be stimulated. It’s not enough to simply interrupt the locomotion signal.
 

 Bouvier compares it to driving a car. As long as you press the gas pedal, your car will move forward. Going into the study, scientists thought that releasing the pedal would eventually stop the car, or gradually mute the instructions to keep walking. ”But what we found was a brake pedal used only to stop,” Bouvier said.
 

 Watching the pathway unfold in mice supported their earlier findings. When the researchers pulsed light on stop neurons, the mice came to a stop. Light did not have an effect on mice that had blocked stop neurons—instead of stopping, they kept walking.
 
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<figcaption>A mouse rigged for an optogenetics experiment is given a blue activation signal.
 
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 Interestingly, the mice that could stop did so smoothly. They finished the step they were about to do. This behavior is very different from freezing, an all-over muscle contraction in response to fear. Bouvier said the smooth stopping allows animals to “keep posture,” making them less likely to fall or lose balance.
 

 The study,
 <a href="http://www.cell.com/cell/pdfExtended/S0092-8674(15)01477-4" target="_blank">
 published
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 in the November issue of Cell, is a step toward understanding how the body controls marching orders at the neural level and beyond the muscular level. Thomas Knopfel, a professor of neuroscience at Imperial College London, thinks Bouvier’s study “might be a step forward with medical problems associated with the brain and spinal cord.”
 

 Leg paralysis from a damaged nerve can disrupt communication between the brain and spinal cord. Knopfel speculated that an implantable device could be connected to this injured nerve, which could help patch this faulty circuit and help a patient learn to move his or her leg again. The same technology the researchers at Karolinska used—called optogenetics—could be used to make this device.
 

 Kiehn speculated that stop neuron activity might contribute to motor symptoms of Parkinson’s disease. One common symptom of late stage Parkinson’s is an involuntary “freezing gait.” Kiehn thinks this could be a sign that the locomotion “start signal” does not work properly, or that stop neurons may be less active than normal. Future tests will involve trying to identify these neurons in diseased mice.
 

 Bouvier has further questions in further exploring stop neurons and understanding how the spinal cord is controlled by brain stem. Among them: Are these neurons a “general brake for all behaviors?”
 

 We may not consciously think about every time we start and stop to walk, but locomotion is the output of many brain activities. Stop neurons are a critical link in this chain of command; they are the neural brake pedal that saves us from cars having to slam theirs’ in the crosswalk. “Even though movement may sound like a boring, noncognitive behavior, it is really one of the most important behaviors,” Kiehn said.
 
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 Photo credits:
 <a href="https://www.flickr.com/photos/41994141@N08/5982297252/">
 O. Bendorf/Flickr (CC BY-NC-ND), Julien Bouvier
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Flashlight-Sized Probe Can Spot Cancer Cells in Real Time

Malignant tumor strongholds and their microscopic spies can’t hide in the thicket of flesh much longer, for surgeons have a new weapon: a device that sheds light on their location. Literally.


 “Any state of disease will alter the cells and molecules in our body,” said Dr. Stephen Boppart, a professor of bioengineering at the University of Illinois who invented the device. Every molecule scatters light different ways, he said, “leaving a distinct optical scattering signature.” The new device senses cancer cells’ unique signatures, letting surgeons know which areas around the tumor are cancerous and which are safe to leave alone.

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 The tissues surrounding a tumor, known as the margin, are a hot spot for cancerous cells. Since the malignant parts of the margin are invisible to the naked eye, surgeons have to use their judgment to determine how much of it to remove. If they abscind too much, the patient loses healthy tissue, too little and the cancer cells that remain could quietly form a new tumor.


 Today, surgeons send samples from the margin to the lab, and unfortunately results often come back positive for cancer cells. Breast cancer patients run a 30-50% chance of getting called back to the hospital for repeat surgeries.


 Boppart’s team built upon existing imaging techniques, which often require large equipment, and repackaged them into a microscope the size of a flashlight, allowing the device to be used during procedures to guide a surgeon’s hand.


 The device works because tumors are much more densely packed than healthy tissue and cancerous cells are organized differently than healthy ones. When certain wavelengths of light are shone on them, cancerous areas light up like cellular cities at night. The technology Boppart used, known as optical coherence tomography (OCT), has successfully identified malignant and healthy tissue in breast tissue samples outside of the body. However, Boppart points out, “it’s more important to look at what’s inside and not removed.”

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 Surgeons can glide the probe in the tumor cavity and see a cross-sectional map of tissue on a nearby monitor, similar to an ultrasound. OCT, though, offers surgeons a ten- to 100-times greater resolution than ultrasound technology.


 The probe has important advantages over other imaging techniques that have been used in cancer surgery patients. One involves labeling the margin with a fluorescent dye that can highlight patches of malignant tissue. But even then there is a chance that the dye won’t label everything. Further, Conor Evans, who researches OCT at Harvard Medical School, emphasized the difficulty in researching contrast dyes and getting them approved by the FDA. OCT doesn’t require a dye to be injected into the patient, which makes it easier to get approved.


 Another existing technique—using radio frequency waves—is label-free, but it is slow compared with OCT. With a radio frequency device, the surgeon must point the probe, wait a few minutes to get results, and then repeat the process.


 OCT’s instant feedback means surgeons will not have to wait hours or days for results from the histology lab, where tissue samples are typically sent to determine whether they are malignant.


 So far, Boppart’s probe can successfully distinguish apart healthy and cancerous tissue with 92% sensitivity and detection. Though it has only been tested on breast tumors, he claims the device will be useful with any sort of solid tumor removal. Boppart now hopes to develop algorithms that will automatically flag for surgeons suspicious areas in the margin.


 The new OCT probe is FDA approved and will likely available in 2016. Soon, it may help catch cancer’s rogue microscopic spies in their tracks, helping patients avoid further operations.

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 Photo credit: Alex Jerez and Stephen Boppart/Beckman Institute for Advanced Science and Technology

Margaux Phares

Articles

Injecting Ice Cold Saline Can Protect the Brains of Cardiac Arrest Patients

Newly Discovered ‘Stop Neurons’ Could Save Your Life

Flashlight-Sized Probe Can Spot Cancer Cells in Real Time

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