Same injury, different brain

Five years ago, Odette Harris, MD, professor of neurosurgery and a brain trauma expert, began to weave an age-old question into her research: What are the differences between men and women?

Harris had not intended to bring sex differences into her work, but while analyzing brain trauma data from the Department of Veterans Affairs, she realized there’s a big gender difference in the aftermath of traumatic brain injuries, and no one was talking about it.

In fact, in her analysis, Harris, director of the Traumatic Brain Injury Center of Excellence at the VA Palo Alto Health Care System, found several unexpected trends: Women with brain injury trauma and other severe injuries typically saw higher rates of depression, substance abuse, memory problems and homelessness, among other troubles, than men with brain trauma.

Initially, Harris was wary of widely sharing her findings. “I was concerned that this information could be weaponized or misconstrued. We’re not saying women don’t do as well as men, or women aren’t as strong as men. That’s not it at all,” she said.

“We’re saying that women and men experience brain injuries differently, and we need to treat them as such. This is a challenge in our field that deserves attention.”

To better understand the nature of brain trauma in women — physiologically, psychologically and socially — Harris teamed up with colleagues, including Maheen Adamson, PhD, a clinical scientific research director for Rehabilitation Services at the VA Palo Alto and a clinical associate professor of neurosurgery at Stanford School of Medicine.

Using data from surveys, neuropsychological testing and brain imaging, they have conducted matched analyses comparing male and female patients, meaning that, sex aside, the comparison groups’ specifics — age, severity of injury and time since the injury — were equal.

Their work has so far revealed some big differences in the brains and behavior of men and women with post-trauma injuries — insights that could guide treatment for women who have suffered debilitating injuries to the head.

Lisette Meylan is grateful for the new direction. In 2004, her daughter, Mariela, who was on duty in Kuwait, suffered severe head and other injuries when a car hit her and four other soldiers as they changed a flat on their truck.

She survived the accident but ended up in a coma, receiving care in a nursing home for veterans in Washington, D.C. “Her doctors told me I needed to be prepared for my daughter to never wake up,” Meylan said.

But Meylan could not give up on her daughter, so she moved her closer to home, in Livermore, California, to the VA’s Livermore division. There, Meylan and her daughter’s care team tried different therapies to wake her from a vegetative state.

It seemed all but hopeless. Two years passed. Then, one day, Meylan saw a light blinking on her phone’s message machine, indicating a new voicemail.

She played the recording: “This is Mariela, I’m your daughter, and I love you.”

“Those were the first words she’d spoken in two years,” said Meylan. Since then, her daughter’s recovery has been challenged by physical and mental hurdles, such as learning to walk again, but she has progressed immensely.

“My biggest challenge is my memory,” said Mariela Meylan. That’s more common for women who have experienced multiple traumatic injuries, compared with men, according to Adamson.

“My short-term memory has been affected the most. But through the support of my family and my team of practitioners, I’m able to continue to heal and show up for my life.”

In 2014, she participated in a storytelling workshop run by Harris for women who’ve experienced traumatic brain injury to share their stories with other women who have the diagnosis and health care professionals.

“Patients like Mariela are the reason we do this. The stories of their strength, perseverance and motivation give my research a purpose and motivate me to never stop discovering.”

Maheen Adamson, PhD, a clinical associate professor of neurosurgery

Through intensive physical therapy at the Livermore VA, she now regularly practices yoga, rides horses and swims. She lives with her mother, who helps her navigate other day-to-day activities, like making meals.

“Patients like Mariela are the reason we do this,” said Adamson. “The stories of their strength, perseverance and motivation give my research a purpose and motivate me to never stop discovering.”

Surveys and analysis of health record data by the Stanford researchers and others continue to find stark differences in how men and women experience severe brain injury.

But there’s also a physical clue: The imaging research suggests a link between a physical trait of women’s brains — a thinning of part of the cortex — and the tendency to experience a different array of post-brain injury symptoms than men do.

Their analysis will help fill in research gaps. “Females account for 15% of the traumatic brain cases we see, yet the studies investigating TBI comprise data almost exclusively from men,” said Adamson.

Setting women up to succeed

In her deep dive into the Armed Forces Health Surveillance Center data from 2000 to 2010, Harris found several key differences in the aftermath of severe head trauma for men and women, including that women are four times more likely to abuse drugs, seven times more likely to be homeless and about three times more likely to be unemployed.

Women with traumatic brain injury are also 30% more likely than males to suffer from post-traumatic stress disorder. And they experience higher rates of vertigo — the feeling that the environment is moving (often spinning) around you.

Part of the research goal is to figure out how best to set women up for success after brain trauma. It’s not always the same as what’s best for men. “For instance, when we see unemployment in males with traumatic brain injury, our approach is to assist in education and skills training,” said Harris.

“So the knee-jerk reaction is to find ways to increase education and training when we see unemployment in women with traumatic brain injury. But we found that female veterans were better educated and more likely to have a college degree than their male counterparts.”

So education and skills training might not be as helpful for women as it is for men.

Bringing it back to the brain

What’s causing the differences in the impact of brain injury trauma on women and men?

In 2016, Adamson began investigating, using neuropsychological testing and brain imaging. The tests gauged general brain function and memory, among other abilities. The imaging portion of the study, which comprised 70 veterans (28 women and 42 men) used MRI to measure the thickness of the cortex, the thin outer layer of the brain’s cerebrum.

“Scientists have looked at how cortical thickness changes in a variety of neurological diseases, such as schizophrenia, and we thought it made sense to start there for this research, too,” said Adamson.

Under healthy conditions, women’s cortex is about 6% thicker than men’s. In the MRI study, injured brains of all veterans exhibited signs of cortical thinning, only for women it was significantly worse.

“We’re seeing a shift toward looking at differences between male and female traumatic brain injury more deeply, and my hope is that that trend will extend to other groups within the traumatic brain injury patient population.”

Odette Harris, MD, professor of neurosurgery

The brains of the women she studied had more patches of cortical thinning, especially in regions that regulate emotion and decision-making. Scientists know cortical thinning is not good, but it’s too early to say how the condition impacts behavior or overall health of the brain.

Researchers are recruiting more participants to further explore how cortical thinning impacts symptoms and post-brain injury outcomes for women, said Adamson. “We’re just hitting the tip of the iceberg here.”

She and Harris are also considering other populations of brain trauma survivors and how their experiences differ.

“I see our research as aligning well with a shift we’re seeing at the national level — incorporating gender, race, ability and other differences into science and patient health,” said Harris.

“We’re seeing a shift toward looking at differences between male and female traumatic brain injury more deeply, and my hope is that that trend will extend to other groups within the traumatic brain injury patient population. That’s what will enable us to improve outcomes and ensure equitable care for all people, not just women.”

— Contact Hanae Armitage at harmitag@stanford.edu