What type of concussion is it? The answer could affect treatment

Joe felt irritable and overwhelmed. Carla had blurry vision and didn’t feel safe to drive. Meg had a pounding headache. But all three of them received the same diagnosis: concussion.

Concussion symptoms vary for different people depending on their medical history, age, degree of injury and other factors. To develop the most effective, personalized treatments, concussion experts across the country are working to learn more about how these variables impact concussion symptoms and recovery.

The researchers — including pediatric emergency medicine physician Angela Lumba-Brown, MD, and neurosurgeon Jamshid Ghajar, MD, PhD, from Stanford’s Brain Performance Center — identified five categories of concussions, which have different symptoms and require different initial treatments:

  • Vestibular — Symptoms include dizziness, fogginess, lightheadedness, nausea, vertigo and disequilibrium. Initially treated with balance and vestibular-ocular training with a physical therapist.
  • Ocular-motor — Symptoms include difficulties with reading and driving, eye strain, problems changing focus between near and far, blurred or double vision, eye pain, vision-derived nausea and photophobia. Initially treated with dynamic vision training with an optometrist. 
  • Headache — Symptoms include different types of headaches, including migraines. Initially treated with headache management.
  • Cognitive — Symptoms include problems with attention, reaction time, working memory, new learning, memory retrieval, organization of thoughts and behavior. Initially treated with neuropsychological assessment and treatments.
  • Anxiety-Mood — Symptoms include nervousness, hypervigilance, ruminative thoughts, depressed mood, anger, irritability, loss of energy, fatigue and feeling more emotional, overwhelmed or hopeless. Initially treated with counseling, including cognitive-behavioral therapies.

The findings appear in Neurosurgery.

However, diagnosing concussions and selecting the correct treatments is a bit more complicated than this list may indicate, Ghajar and Lumba-Brown explained. “These subtypes are not mutually exclusive and they frequently cluster together,” Ghajar said.

This interdependence isn’t all bad news though, because the headache, cognitive and anxiety-mood concussion subtypes often resolve after treating for vestibular and ocular-motor concussion symptoms. Also, early cardiovascular exercise is recommended for all subtypes.

In addition, the experts determined the prevalence of these concussion subtypes in adults and children based on a meta-analysis of previous studies. The most common subtype depends on when a patient is seen, as well as their medical history and age.

“Early on, the headache subtype is the most prevalent for both adult and pediatric populations, and it usually co-exists with the vestibular and ocular-motor subtypes,” said Ghajar. “Weeks to months after injury, the mood subtype with symptoms of anxiety and depression predominates, usually because of inadequate interventions. The prevalence of the vestibular subtype was also very high for pediatric patients.”

The working group also found that sleep disturbance and cervical strain were commonly associated with all five concussion categories. Sleep disturbance symptoms include difficulty falling asleep, frequent awakenings and fatigue, whereas cervical strain symptoms include neck pain, neck stiffness and upper extremity weakness.

According to Lumba-Brown, this work is particularly important because it addresses subtypes in children, a vulnerable subset of patients with unique needs. “Children are expected to go to school daily. They often play sports or engage in risk-taking behaviors. And they often have difficulty expressing their symptoms,” said Lumba-Brown, who recently helped develop clinical guidelines for children with mild traumatic brain injury.

The experts said they hope that a better understanding of the different kinds of concussions and their prevalence will ultimately translate into improved treatment and faster recovery for patients of all ages. The team is now investigating the recovery trajectories for the different subtypes — from the acute period through three months following injury.

They offered clinicians guidance in light of the findings: “Clinicians should assess each subtype of impairment in the acute setting following injury, encourage early cardio exercise and provide prognostic counseling for mood and sleep disturbances.”

Photo by Staff Sgt. Jonathon Fowler/U.S. Air Force

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

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Creating a new primary care clinic for cancer survivors

As a cancer survivor, I know how finishing treatment can feel both happy and unsettling. I was ecstatic to be done with chemotherapy and radiation therapy, but I worried about recurrence and long-term treatment side effects. Whenever I went to a cancer checkup, I wore silly socks to remind myself to smile. And decades later, I still have to be vigilant with periodic screening tests like breast MRIs due to increased health risks from radiation.

Quality survivorship care requires a strong collaboration between oncology and primary care clinicians, particularly as patients complete their treatment. To help patients during this critical time, Stanford is piloting a cancer survivorship clinic embedded in the practice of primary care physician Jennifer Kim, MD. I recently corresponded with her to learn more.

What inspired you to focus on cancer survivorship care?

“When medical oncologist Lidia Schapira, MD, and I met about 2 years ago, we discussed her ideas of integrating primary care into survivorship at Stanford. All primary care practices, including my own, already care for survivors. As this is not a topic that I learned about in training, I wasn’t sure what would be different about calling it survivorship.

I learned more by attending national conferences and reviewing online curricula on survivorship. I also spent clinic days with oncologists as they saw patients. As I started to learn about survivorship, I realized that cancer and cancer treatment changes all aspects of patients’ health — medical, emotional and social — for the rest of their lives.”

How does your clinic work?

“Together with Lidia Schapira, I started Stanford’s Primary Care Cancer Survivorship clinic. I’m currently the only primary care physician doing this at Stanford and I see patients for two half days per week in the Hoover primary care clinic. My visits are consultative, meaning patients come to see me for one to several visits to discuss a complete survivorship plan, which they can bring back to their primary care physician for ongoing care.

The focus of my visits is to detail a full treatment history and make a personalized survivorship plan for issues such as cancer surveillance, potential long-term and late effects of treatment, psychosocial concerns, co-morbidities and preventative care. I create this history and plan together with the patient, so both the patient and their whole care team will understand the content.

Having the clinic embedded in my primary care clinic — a different building and environment than the oncology department — helps us physically and mentally shift gears and transition to a primary care-based survivorship plan.”

What have you learned?

“I’ve learned the most powerful survivorship lessons from my patients and their experiences. I’ve learned not to assume what my patients are struggling with. Instead, by asking about their experiences and listening to their concerns, I can better understand what is really important to each individual. I’ve also found that it is very important to be open about and sensitive to emotional and psychosocial issues, including fear of recurrence, anxiety, fertility and sexual health. These topics are rarely the focus of oncology visits and patients don’t know who to ask.

I now realize that survivors often struggle with the transition from oncology care back to primary care-based care. It’s a challenging, overwhelming and emotional time when many still have significant long-term effects of treatment and multiple specialist visits. Patients often voice a need for a ‘quarterback’ to help guide them through the next phase of recovery — finding health after cancer.”

Do you have any advice for other primary care physicians?

“Primary care physicians can and should be an essential part of survivorship and health after cancer. However, there are currently many barriers to survivorship being integrated into primary care — a knowledge gap, disparate electronic medical records, limited appointment time and patient concerns over whether primary care physicians are able to manage survivorship.

Many primary care physicians aren’t confident in their own survivorship knowledge, as there are so many cancers and so many treatments to keep track of, even in terms of surveillance recommendations and potential long-term effects. This is why shared care with specialists and continuing education can make a great impact in this area of increasing need.

With the help of a great team, Lidia and I are developing an online course with video, animation and text to help primary care physicians gain more knowledge, resources and confidence in their long-term care of survivors. We hope to distribute this widely when it is ready.

We’ve also started to create a patient-facing survivorship course that will focus on self-management, communication and resources. We hope this will help patients better navigate survivorship issues on their own and with their care team.”

Photo by Pamela Williams

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

How does radiation in space affect the brain?

Exposure to deep space poses many potential risks to the health of astronauts, but one of the biggest dangers is space radiation. Above Earth’s protective shielding, astronauts are exposed to radiation from energetic charged particles that increases their risk of cancer, damage to the central nervous system and a host of other health problems.

A new study has now investigated how chronic, space-like irradiation impacts the brain function of mice. To learn more, I spoke with Ivan Soltesz, PhD, a senior author on the study and a professor of neurosurgery and neurosciences at Stanford.

What was the goal of your study?

“Our basic question was ‘what happens to your brain during a mission to Mars?’ So far, only the Apollo astronauts have traveled far enough beyond the Earth’s protective magnetic field to be exposed to similar galactic cosmic radiation levels, albeit only for short durations.

In previous rodent studies, my lab observed that neuronal function is disrupted by low levels of radiation, a fraction of the dose used for cancer therapy. However, technical constraints required us to deliver the entire radiation dose within minutes, rather than across several months as during a mission to Mars. In the current study, we are the first to investigate the impact of prolonged radiation exposures, at Mars-relevant doses and dose rates, on the neurological function. We used a new neutron irradiation facility at Colorado State University.”

What part of the brain did you study?

“The hippocampus, which is critical for several important brain functions, including the formation of new memories and spatial navigation. And the medial prefrontal cortex, which is important for retrieving preexisting memories, making decisions and processing social information. Thus, deficits in either of these two brain regions could detrimentally impact the ability of astronauts to safely and successfully carry out a mission to Mars.”

What did you find?

“My lab at Stanford measured electrical properties of individual neurons from mice that were exposed to six months of chronic neutron radiation. We determined that after chronic radiation exposure, neurons in the hippocampus were less likely to respond to incoming stimuli and they received a reduced frequency of communication from neighboring neurons.

Our collaborators at UC, Irvine found that chronic neutron radiation also caused neuronal circuits in both the hippocampus and medial prefrontal cortex to no longer show long-lasting strengthening of their responses to electrical stimulation, normally referred to as long-term potentiation. Long-term potentiation is a cellular mechanism that allows memory formation.

Our collaborators also conducted behavioral tests. The mice displayed lasting deficits in learning, memory, anxiety and social behavior — even months after radiation exposure. Based on these results, our team predicts that nearly 1 in 5 astronauts would experience elevated anxiety behavior during a mission to Mars, while 1 in every 3 astronauts would struggle with memory recall.”

How can these findings facilitate safe space exploration?

“By understanding radiation risks, future missions can plan practical changes — such as locating astronaut sleeping spaces towards the center of the spacecraft where intervening material blocks more incoming radiation — that may help to mitigate the risks associated with interplanetary travel.

However, my lab believes the best way to protect astronauts from the harmful effects of space radiation is to understand at a basic science level how neuronal activity is disrupted by chronic radiation exposures.

One promising sign is that radiation exposures that occur in space rarely cause neurons in the brain to die, but rather cause smaller scale cellular changes. Thus, we should be able to develop strategies to modulate neuronal activity to compensate for radiation-induced changes. Our team is already starting a new set of chronic space-radiation experiments to test a candidate countermeasure drug.”

Would you ever go to space, given how harmful it is on the human body?

“The radiation risks we discovered are mostly a concern for travel beyond low earth orbit, such as months-long missions to Mars. Shorter trips to the moon — such as the Apollo missions — or months spent in Earth orbit aboard the International Space Station appear to pose a much lower risk of radiation-induced cognitive deficits. I would definitely like to go into space for at least a few quick orbits.

I’m also confident that my lab and others will expand our understanding of how chronic radiation impacts the nervous system and to develop the effective countermeasures needed to enable safe missions towards the moon or Mars within the next decade. However, I’m not sure I’m ready to leave my lab unattended for two years while I take a sabbatical to Mars.”

Photo by ColiN00B

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Stanford study shows the power of eco-friendly packaging for cigarettes

My eyes are drawn to eco-friendly packaging when I shop for groceries. It is how I pick my laundry detergent, dish soap and many other products from the litany of options. But I’ve learned to double-check whether these items are actually better for the environment, because there are a lot of misleading labels.

Companies know that pro-environmental marketing works. A new Stanford study shows it is even effective for cigarettes.

The researchers surveyed over 900 adults on their perception of two major cigarette brands: Pall Mall and Natural American Spirit. Pall Mall is marketed as a discount brand, while Natural American Spirit is marketed as environmentally friendly. For instance, the Natural American Spirit’s “Respect the Earth” campaign advertises a “zero-waste-to-landfill” facility and uses a logo with three tobacco leaves that mimics the recycling symbol.

The study participants were a mixture of current smokers, former smokers and people who have never smoked. All three groups consistently ranked Natural American Spirit cigarettes as being healthier and better for the environment than the Pall Mall cigarettes.

“Ecofriendly and natural food products are seen as safer for health,” said the study lead author Anna Epperson, PhD, a postdoctoral fellow with the Stanford Prevention Research Center, in a recent Stanford news release. “That couldn’t be farther from the truth when it comes to cigarettes.”

Both brands are actually manufactured by the same company, Reynolds American. And they have the same health impacts, including a significantly higher risk of heart disease, cancer and chronic obstructive pulmonary disease. They are also commonly discarded, resulting in toxic chemicals leaching into the soil and water supplies.

 “All commercially available cigarettes will kill more than half of long-term users if smoked as intended. Marketing language that obscures these health harms, even indirectly through questionable pro-environment claims, ought to be prohibited,” the study authors concluded.

This warning may be particularly important to the San Francisco Bay Area and other pro-environment and pro-health regions, where Natural American Spirit cigarettes are especially popular according to Epperson.

Photo by webyourlife

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Stanford researchers watch proteins assemble a protective shell around bacteria

Many bacteria and viruses are protected from the immune system by a thin, hard outer shell  — called an S-layer — composed of a single layer of identical protein building blocks.

Understanding how microbes form these crystalline S-layers and the role they play could be important to human health, including our ability to treat bacterial pathogens that cause serious salmonella, C. difficile and anthrax infections. For instance, researchers are working on ways to remove this shell to fight anthrax and other diseases.

Now, a Stanford study has observed for the first time proteins assembling themselves into an S-layer in a bacterium called Caulobacter crescentus, which is present in many fresh water lakes and streams.

Although this bacteria isn’t harmful to humans, it is a well-understood organism that is important to various cellular processes. Scientists know that the S-shell of Caulobacter crescentus is vital for the microbe’s survival and made up of protein building blocks called RsaA.  

A recent news release describes how the research team from Stanford and SLAC National Accelerator Laboratory were able to watch this assembly, even though it happens on such a tiny scale:

“To watch it happen, the researchers stripped microbes of their S-layers and supplied them with synthetic RsaA building blocks labeled with chemicals that fluoresce in bright colors when stimulated with a particular wavelength of light.

Then they tracked the glowing building blocks with single-molecule microscopy as they formed a shell that covered the microbe in a hexagonal, tile-like pattern (shown in image above) in less than two hours. A technique called stimulated emission depletion (STED) microscopy allowed them to see structural details of the layer as small as 60 to 70 nanometers, or billionths of a meter, across – about one-thousandth the width of a human hair.”

The scientists were surprised by what they saw: the protein molecules spontaneously assembled themselves without the help of enzymes.

“It’s like watching a pile of bricks self-assemble into a two-story house,” said Jonathan Herrmann, a graduate student in structural biology at Stanford involved in the study, in the news release.

The researchers believe the protein building blocks are guided to form in specific regions of the cell surface by small defects and gaps within the S-layer. These naturally-occurring defects are inevitable because the flat crystalline sheet is trying to cover the constantly changing, three-dimensional shape of the bacterium, they said.

Among other applications, they hope their findings will offer potential new targets for drug treatments.

“Now that we know how they assemble, we can modify their properties so they can do specific types of work, like forming new types of hybrid materials or attacking biomedical problems,” said Soichi Wakatsuki, PhD, a professor of structural biology and photon science at SLAC, in the release.

Illustration by Greg Stewart/SLAC National Accelerator Laboratory

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Predicting women at risk of preeclampsia before clinical symptoms

Many of my female friends became pregnant with their first child in their late 30s or early 40s, which increased their risk of common complications such as high blood pressure, gestational diabetes and preeclampsia.

Affecting over 8 million women worldwide, preeclampsia can lead to serious, even fatal, complications for both the mother and baby. The clinical symptoms of preeclampsia typically start at 20 weeks of pregnancy and include high blood pressure and signs of kidney or liver damage.

“Once these clinical symptoms appear, irreparable harm to the mother or the fetus may have already occurred,” said Stanford immunologist Brice Gaudilliere, MD, PhD.  “The only available diagnostic blood test for preeclampsia is a proteomic test that measures a ratio of two proteins. While this test is good at ruling out preeclampsia once clinical symptoms have occurred, it has a poor positive predictive value.”

Now, Stanford researchers are working to develop a diagnostic blood test that can accurately predict preeclampsia prior to the onset of clinical symptoms.

A new study conducted at Stanford was led by senior authors Gaudilliere, statistical innovator Nima Aghaeepour, PhD, and clinical trial specialist Martin Angst, MD, and co-first authors and postdoctoral fellows Xiaoyuan Han, PhD, and Sajjad Ghaemi, PhD. Their results were recently published in Frontiers in Immunology.

They analyzed blood samples from 11 women who developed preeclampsia and 12 women with normal blood pressure during pregnancy. These samples were obtained at two timepoints, allowing the scientists to measure how immune cells behaved over time during pregnancy.

“Unlike prior studies that typically assessed just a few select immune cell types in the blood at a single timepoint during pregnancy, our study focused on immune cell dynamics,” Gaudilliere explained. “We utilized a powerful method called mass cytometry, which measured the distribution and functional behavior of virtually all immune cell types present in the blood samples.”

The team identified a set of eight immune cell responses that accurately predicted which of the women would develop preeclampsia — typically 13 weeks before clinical diagnosis.

At the top of their list was a signaling protein called STAT5. They observed higher activity of STAT5 in CD4+ T-cells, which help regulate the immune system, at the beginning of pregnancy for all but one patient who developed preeclampsia.

“Pregnancy is an amazing immunological phenomenon where the mother’s immune system ‘tolerates’ the fetus, a foreign entity, for nine months,” said Angst. “Our findings are consistent with past studies that found preeclampsia to be associated with increased inflammation and decreased immune tolerance towards the fetus.”

Although their results are encouraging, more research is needed before translating them to the clinic.

The authors explained that mass cytometry is a great tool to find the “needle in the haystack.” It allowed them to survey the entire immune system and identify the key elements that could predict preeclampsia, but it is an exploratory platform not suitable for the clinic, they said.

“Now that we have identified the elements of a diagnostic immunoassay, we can use conventional instruments such as those used in the clinic to measure them in a patient’s blood sample.” Aghaeepour said.

First though, the team needs to validate their findings in a large, multi-center study. They are also using machine learning to develop a “multiomics” model that integrates these mass cytometry measurements with other biological analysis approaches. And they are investigating how to objectively define different subtypes of preeclampsia.

Their goal is to accurately diagnose preeclampsia before the onset of clinical symptoms.

 “Diagnosing preeclampsia early would help ensure that patients at highest risk have access to health care facilities, are evaluated more frequently by obstetricians specialized in high-risk pregnancies and receive treatment,” said Gaudilliere.

Women with preeclampsia can receive care through the obstetric clinic at Lucile Packard Children’s Hospital Stanford.

Photo by Pilirodriquez

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Explaining neuroscience in ongoing Instagram video series: A Q&A

At the beginning of the year, Stanford neuroscientist Andrew Huberman, PhD, pledged to post on Instagram one-minute educational videos about neuroscience for an entire year. Since a third of his regular followers come from Spanish-speaking countries, he posts them in both English and Spanish. We spoke soon after he launched the project. And now that half the year is over, I checked in with him about his New Year’s resolution.

How is your Instagram project going?

“It’s going great. I haven’t kept up with the frequency of posts that I initially set out to do, but it’s been relatively steady. The account has grown to about 13,500 followers and there is a lot of engagement. They ask great questions and the vast majority of comments indicate to me that people understand and appreciate the content. I’m really grateful for my followers. Everyone’s time is valuable and the fact that they comment and seem to enjoy the content is gratifying.”

What have you learned?

“The feedback informed me that 60 seconds of information is a lot for some people, especially if the topic requires new terms. That was surprising. So I have opted to do shorter 45-second videos and those get double or more views and reposts. I also have started posting images and videos of brains and such with ‘voice over’ content. It’s more work to produce, but people seem to like that more than the ‘professor talking’ videos.

I still get the ‘you need to blink more!’ comments, but fortunately that has tapered off. My Spanish is also getting better but I’m still not fluent. Neural plasticity takes time but I’ll get there.”

What is your favorite video so far?

“People naturally like the videos that provide something actionable for their health and well-being. The brief series on light and circadian rhythms was especially popular, as well as the one on how looking at the blue light from your cell phone in the middle of the night can potentially alter sleep and mood. I particularly enjoyed making that post since it combined vision science and mental health, which is one of my lab’s main focuses.”

What are you planning for the rest of the year?

“I’m kicking off some longer content through the Instagram TV format, which will allow people who want more in-depth information to get that. I’m also helping The Society for Neuroscience get their message out about their annual meeting. Other than that, I’m just going to keep grinding away at delivering what I think is interesting neuroscience to people that would otherwise not hear about it.”

Is it fun or an obligation at this point?

“There are days where other things take priority of course — research, teaching and caring for my bulldog Costello — but I have to do it anyway since I promised I’d post. However, it’s always fun once I get started. If only I could get Costello to fill in for me when I get busy…”

This is a reposting of my Scope story, courtesy of Stanford School of Medicine.