Epilepsy is a devastating neurological disease that affects one in 200 children and adolescents in Canada, causing seizures that can occur sporadically or daily. Thirty to 40 per cent of patients do not respond to drug treatments or stop responding after initial success.

A University of Alberta researcher is hoping to shed light on treatment-resistant or refractory epilepsy. If the team in Qiumin Tan’s lab is successful in learning more about the etiology — or cause — of this sub-set of the disease, it might someday lead to new management strategies. Children and adolescents whose epilepsy is not well-controlled are at a higher risk of death from the disorder and are more likely to have learning disabilities, depression, anxiety and other problems.

“Refractory epilepsy really affects every single aspect of their lives,” says Tan, an assistant professor in the Department of Cell Biology and Canada Research Chair in Molecular Genetics of Human Disease. Funding for her lab includes a WCHRI innovation grant and a partnership grant that enabled her Canadian Institutes of Health Research Early Career Investigator Award.

Epilepsy presents a complex challenge to researchers because it is caused by many different mechanisms that disturb brain circuitry. “The etiology is not simple,” explains Tan. “We cannot attribute it to one single cause.”

Her research is focused on Cajal-Retzius cells, nerve cells that are normally found in the brain only during embryonic development, dying off once they’ve completed their work. However, these Cajal-Retzius cells have been found in the brain tissues of patients undergoing epilepsy surgery, leading Tan’s research team to question why they lingered and if that could contribute to seizures in refractory epilepsy.

While Tan’s research is at the most fundamental stage at this point, it could contribute to future epilepsy management. If researchers can understand why these cells are not dying and if their persistence contributes to seizures, future technologies could be developed to either silence or activate the cells, which might help with seizures, she explains.

To study these Cajal-Retzius cells, Tan and her research team are using a lab model they developed for another major research project in which they are investigating a rare neurodevelopmental disorder caused by a mutation in the capicua (CIC) gene. Thirty to 40 per cent of people with the CIC mutation also have epilepsy.

There are very few patients in the world with the CIC disorder. One of them is Seta Atamian’s 26-year-old daughter Natalie, who lives in Boston with her family and needs a 24-hour team of caregivers. Atamian says Natalie is significantly delayed developmentally and has about three to 10 major seizures a month. “We are constantly afraid of her not breathing or dying during a seizure.”

Atamian met Tan in 2015 when Tan was a postdoctoral fellow at Baylor College of Medicine in Houston, conducting research on the CIC gene mutation. While she knows that Tan’s research may not lead to treatment anytime soon, she is grateful for her work.

“To know that there’s a researcher out there who’s completely willing to dedicate her career to events that arise out of this mutation and in a broader sense, to helping children with epilepsy, it’s really a gift.”

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Qiumin Tan is supported by the Stollery Children’s Hospital Foundation through the Women and Children’s Health Research Institute.

School-based immunizations for children and adolescents in Alberta dropped dramatically in the first two years of the COVID-19 pandemic, according to newly-published research.

And while a significant amount of catch-up has occurred since then, it’s likely that some Alberta students still haven’t been immunized with vaccines they should have received in Grade 6 or Grade 9, says Hannah Sell, whose study was published in the journal Vaccine.

Sell was a master’s student in the School of Public Health when she carried out her research in 2021. Her graduate studentship study was part of a larger project called Vaccination in a Pandemic, overseen by Shannon MacDonald, an associate professor in the Faculty of Nursing and adjunct professor in the School of Public Health.

“It’s an important issue because school-based immunization programs historically have been a way to present an equal opportunity for children to be up-to-date on their immunizations,” says Sell. Many parents who work multiple jobs or have transportation and language issues have challenges getting their kids vaccinated elsewhere.

Sell examined the pandemic’s impact on two immunizations: HPV vaccines, normally given in Grade 6 to prevent cervical and some other cancers later in life; and meningococcal vaccine, given in Grade 9 to protect adolescents from meningitis and other potentially fatal illnesses. The shots are given by public health nurses who come to the schools.

Sell analysed data from several Alberta Ministry of Health databases, including the provincial immunization repository, to look at the number of children vaccinated in school programs in 2019-20 and 2020-21, compared to 2017-18.

The rates for HPV coverage in Alberta were already lower pre-pandemic than public health officials would like, but they fell even further once the pandemic hit. In 2017-18, 66.4 per cent of eligible students received their HPV shots, but that fell to 5.6 per cent in 2019-20, followed by 6.6 per cent in 2020-21. For the meningococcal vaccine, there was no dramatic drop in 2019-20 because most students received their shots before the pandemic hit, but in 2020-21, only 54.6 per cent received their shots, compared to 86.8 per cent pre-pandemic. Rates were even lower in private schools.

Public health officials developed catch-up strategies but priority was given to infant immunizations because those children were at higher risk. Catch-up programs for school-aged vaccinations began later in 2020 and in 2021 but varied by zone, sometimes taking place in schools — when they were open — and sometimes in community clinics. Sell followed the 2019-20 cohort for a year and found that coverage rates did recover but were still lagging behind pre-pandemic numbers.

“We need additional strategies to get these kids caught up,” says MacDonald, who was Sell’s research supervisor. “We do not want to have our cervical cancer rates spiking 20 years from now because these kids didn’t get their HPV vaccinations.”

Findings from Sell’s study and MacDonald’s larger project have been shared with policy-makers and other public health officials, in hopes of influencing program and resource planning in the event of another pandemic.

Sell, who now works as an epidemiologist at the BC Centre for Disease Control, says she’s grateful to WCHRI for the studentship that supported her project. “This study was a perfect opportunity to build my analysis skills and also make connections and get practice communicating with different stakeholders. It was a kicking-off point for my current career.”

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Hannah Sell was supervised by Shannon MacDonald. Her graduate studentship was funded by the Stollery Children’s Hospital Foundation through the Women and Children’s Health Research Institute.

When the February forecast called for a sudden temperature swing, Thilinie Rajapakse revised her outlook to expect a busy week at the hospital.

Weather changes can trigger migraine, and the pediatric neurologist at the Stollery Children’s Hospital headache clinic is mindful of conditions that could make her young patients miserable.

She’s also on top of opportunities to make their lives better.

In the coming months, Rajapakse will recruit patients to participate in international clinical trials testing two ground-breaking new migraine drugs on youngsters aged six to 17. The medications — eptinezumab and atogepant, both recently approved in North America for adults — are what she calls a “revolution” in migraine treatment.

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“As researchers and clinicians, we felt like there was an onus to try this in children,” says Rajapakse, an assistant professor in the Department of Pediatrics. “We’re treating pediatric migraine pretty well — but not nearly as well as it could be treated, and not as well as it is already treated for adults.”

Migraine is a neurological disorder of sensory processing involving nerves and vessels of the head that has been around for thousands of years. The throbbing headaches, often accompanied by nausea, vomiting and sensitivity to light, can occur upwards of 15 days per month for chronic migraineurs. The condition affects close to seven per cent of children — that translates to about two or three kids in every child’s classroom — and is considered one of the world’s most disabling maladies.

But for a long time, treatment was haphazard, with doctors throwing everything from anti-seizure meds to anti-depressants at it, Rajapakse says.

That was Taylor Ness’s experience after she began getting daily migraines in junior high. Her family doctor prescribed physiotherapy, acupuncture and different medications but nothing worked.

“Then she told me, ‘Oh, you might just have to live with it,’” recalls Ness, now in her first year of engineering at the University of Alberta. “As a 15-year-old girl, that’s really not what you want to hear.”

Eptinezumab and atogepant are different in that they’re designed specifically to prevent migraines by inhibiting the actions of a specific molecule — the calcitonin gene-related peptide. Eptinezumab is given intravenously every three months; atogepant is a daily pill.

Being part of a clinical trial is a big commitment for researchers and support from WCHRI is critical to making it happen, Rajapakse says.

It’s also a big commitment for families and patients. During the trial, youngsters must stop using other preventative treatments and for the 12-week double-blind phase may only get a placebo. After that, all participants get the medication, Rajapakse says. “Which is why I’m OK with this. It’s also a way for me to get the new drug for my patients.”

The Stollery’s headache clinic is a frontrunner in exploring new ways to manage migraine; Rajapakse says clinic founder and fellow WCHRI member Lawrence Richer, a “forward-thinking” pediatric neurologist who is now a vice-dean of research at the University of Alberta, blazed the trail.

In 2018, Rajapakse started the clinic’s interventional headache program offering injection therapies like Botox or nerve blocks to patients like Ness. The teen says the nerve block was a life-changer, decreasing the frequency of her migraines from several times a week to once or twice a month.

When Ness aged out of the pediatric clinic in the summer of 2022, she went from being Rajapakse’s patient to becoming the clinic’s first patient research partner and advocate. Ness helps provide the medical team with perspective on how patients might feel about different treatment options — like whether it’s scary, cumbersome or cool.

Ness sees her role as a chance to help young migraineurs know there is “a light at the end of the tunnel.”

For Rajapakse, the new patient research and advocate role is another way to understand and solve the problem.

“No one dies from migraine … so it’s not the top thing that the medical community gets really worried about,” she says. “However, it causes a lot of pain and disability and reduces quality of life significantly for millions of people.”

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Thilinie Rajapakse is supported by the Stollery Children’s Hospital Foundation through the Women and Children’s Health Research Institute.

Robbie Seale’s youngest son — a teen with fetal alcohol spectrum disorder (FASD) — had been waiting years to see a psychiatrist when a dangerous episode forced an emergency trip to the hospital. They waited for hours in a padded room where he couldn’t hurt himself, then were sent home with a doctor’s appointment set for a few days later.

The doctor, recalls the mother of five, “took the inventory of what was happening with our son and what our education and skill levels are around FASD.”

“Then he said, ‘You are doing everything you can. Goodbye.’” Seale’s long wait to see a doctor was over but all she’d received was yet another reminder that the health care profession was woefully unprepared to help children like hers.

Seale adopted four children who’d been exposed to alcohol before birth; three have FASD, a brain-based condition that packs a host of troubles including depression, anxiety, attention difficulties and an inability to handle stress.

And although about 90 per cent of people with FASD have at least one mental health issue, Seale’s struggle to get help is the unfortunate norm, says Jacqueline Pei. Pei is a psychologist, professor in the Faculty of Education and WCHRI researcher.

There are training gaps among health professionals and a prevailing stigma around the condition, she says. “We end up with a group of folks who almost become ineligible for service because they’re too complex.”

Changing that situation is the goal of a research project being co-led by Pei in Edmonton and her counterpart Carly McMorris in Calgary.

The mission includes identifying the barriers that prevent FASD kids from accessing mental health services. Then they’ll be working with front-line health professionals from all over Alberta to brainstorm strategies to mitigate these barriers.

“Kids with FASD are all very different,” says McMorris, a psychologist and member of the Alberta Children’s Hospital Research Institute (ACHRI). Her research focuses on improving the mental health of people with neurodevelopmental conditions, such as autism and FASD.

“Having one perspective is not always helpful when working with kiddos who have complex needs,” she says. “Multiple people with multiple perspectives tackling the same issue is what is needed.”

Pei, a neuropsychology expert who started her career working with young offenders, says the problem has long been a topic of conversation for her and McMorris.

Thanks to a team grant from WCHRI and ACHRI, they’ve got the momentum to do something about it, Pei says.

The grant allowed them to hire two research assistants to do a literature review. Pei says the document will be the conversational starting point for “a meeting of the minds” — a brainstorming session with a cross-section of Alberta psychologists, clinical social workers, caregivers and people with FASD.

The multi-day, in-person sessions will produce a draft of some practical treatment ideas that health-care providers can start using immediately.

“Getting everyone in one room is, I think, something that should be the standard,” McMorris says. “Jacquie and I can highlight what we know from the research; but we’re not feet on the ground, working with these individuals every day.”

The meeting’s other goal is to draft an application for a large federal grant — hopefully one large enough to kickstart the significant, cross-Canada work needed to change the mental health system for FASD adolescents, says Pei.

Supporting the mental health of youth with FASD has the power to improve how they experience all of life’s ages and stages, from school and employment to social situations and relationships, Pei says.

“It’s time we get some evidence … and a concerted plan that reaches health-care providers right across the country.”

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Jacqueline Pei is supported by the Stollery Children’s Hospital Foundation through the Women and Children’s Health Research Institute. Carly McMorris is supported by the Alberta Children’s Hospital Foundation through the Alberta Children’s Hospital Research Institute.

Colleen Norris has dedicated her academic career to working in women’s health research and now, after her appointment in August 2022 as Cavarzan Chair in Mature Women’s Health Research, she has the opportunity to expand beyond her area of expertise — from women’s heart health to a broader spectrum of mature women’s health.

That’s a natural transition for Norris. She believes women’s heart health is the “canary in the coal mine” of women’s health research. “Research into women’s cardiovascular health is telling us a lot about women’s health in general and we need to pay attention to it,” she says.

Norris focuses on sex and gender factors that impact women’s heart disease, including under-diagnosis, treatment outcomes and health-related quality of life afterward. Her studies have found that even when women with heart disease are properly diagnosed, treated with the same medications as men and put through the same rehab programs, they tend to report a worse quality of life afterward, experiencing more physical limitations, chest pain and other health-related issues.

Women and men are different right down to the cellular level, so it’s no wonder diseases progress differently, says Norris, professor and clinician scientist in the Faculties of Nursing, Medicine & Dentistry and the School of Public Health at the University of Alberta.

But she also points out that there’s more than biology going on when it comes to women’s health outcomes. Gender disparities and gender roles — such as how much time you spend doing housework, whether you are a child’s primary caregiver and whether you have emotional support at home — add up to extra stress that affects women disproportionately, contributing not just to mental health issues but also to cancer, heart disease and other illnesses.

In her Cavarzan Chair in Mature Women’s Health Research role, Norris is particularly interested in mature women’s health research that includes the context of their stage in life. “Let’s start blending the life cycle of a mature woman — whether that is perimenopause, menopause or postmenopause — with all her other health concerns,” she says. “For too long, researchers and clinicians have ignored that connection.”

One of Norris’s goals is to push scientists to make it easier for women to participate in clinical trials, which still typically include far more men than women. Researchers often complain that it’s difficult to get women involved in clinical trials, says Norris. But they need to do more to make that happen, especially for older women who may not have support at home to allow them to participate.

Another project, well underway, is a sex and gender questionnaire that will be given to women coming to the Lois Hole Hospital for Women for any health concerns. The questionnaire, being developed with the help of a cohort of women in one of Norris’s research projects, asks about a range of sex and gender factors that could affect women’s health — everything from menstruation to pregnancy experiences, babies’ birthweight, child-rearing responsibilities, and stress levels at work and home.

Along with specific initiatives such as these, Norris is using her term as Cavarzan Chair in Mature Women’s Health Resarch to promote interdisciplinary and collaborative women’s health research and be a mentor for junior researchers to develop their talent. She takes her role as ambassador and champion seriously, to link research with practice for the benefit of women.

“Let’s work together to move this whole science forward, to move women’s health into the spotlight it deserves.”

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Colleen Norris’s research and the Cavarzan Chair in Mature Women’s Health Research are supported by the Alberta Women’s Health Foundation through the Women and Children’s Health Research Institute.

More than 5,000 Afghan refugees have arrived in Alberta since the Taliban took power in their country in 2021. Adjusting to their new lives in Canada — new language and culture, new education and health-care systems — is a daily challenge for virtually all of these newcomers.

University of Alberta researcher Cristian Neves is completing a project he hopes will help one part of that group — Afghan women — obtain the kind of health-care services they need. His study is being done at the New Canadians Health Centre (NCHC) in Edmonton. More than 1,100 refugees, about half of them women, from all parts of the world have used the centre’s services since it opened in August 2021.

 

“I always wanted to make a contribution to the Afghan community, especially Afghan women, because they have been really neglected, and they lost all their rights due to the regime in their country,” says Neves, a second-year graduate student studying community engagement in the School of Public Health. Although his research focuses on services offered at NCHC, he says the results could be helpful for other refugee organizations.

Neves is a newcomer himself, having arrived in 2021 from Chile, where he trained as a clinical psychologist and family therapist.

Health care plays a critical role in the well-being of refugees. For Afghan women who have come from a country where they were not allowed to visit a doctor without a male chaperone, navigating the Canadian system will take time, says Neves. Many arrive with unresolved mental and physical health problems.

Neves’s project involves one-on-one interviews with Afghan women who use NCHC’s services, followed by focus groups with the centre’s clinical staff. The aim is to talk to the women about their health-care needs, expectations, recommendations and any feedback they have about their experiences at NCHC.

“It’s not that I’m giving them a voice — they already have a voice,” Neves stresses. “I’m helping channel those voices to create change.”

Astrid Velasquez, NCHC’s executive director, welcomes the study. “The more we know about our clients, the more we know about their expectations and the way they take on these new experiences in Edmonton or in Canada, the better we can serve them,” says Velasquez.

She was particularly grateful that Neves chose to work with the newly-arrived Afghan women, who she says are already creating a tight-knit community. “I was very excited that Cristian wanted to concentrate on this because, as you know, women are often forgotten, especially when they come from a very strong male society.”

Neves’s research project is supported by the Evaluation Capacity Network and the U of A’s Community-University Partnership, a collaboration between researchers, community organizations and practitioners aimed at improving the well-being of children and families in Edmonton. He is also enrolled in Patient and Community Engagement Training (PaCET), a WCHRI-funded program that teaches graduate students how to conduct engaged research in women and children’s health.

For Neves, the opportunity to do this focused community research has been rewarding. “Back in Chile, I didn’t have many opportunities to conduct research that could create some change. To be able to do it here is amazing.”

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Cristian Neves is supervised by Rebecca Gokiert in the School of Public Health and his PaCET supervisor is Tehseen Ladha in the Faculty of Medicine & Dentistry. Gokiert and Ladha are co-directors of research and evaluation at the New Canadians Health Centre. Neves’ research is supported by the Alberta Women’s Health Foundation through the Women and Children’s Health Research Institute.

Almost one in every three babies in Canada is delivered by cesarian section (c-section) rather than vaginal delivery. The rate has been growing steadily since the early 1980s when just one in 20 babies were delivered surgically.

C-sections have small but significant risks for mothers, such as infections, blood loss, blood clots, bladder injury and other complications. Women may also suffer mental health difficulties if a cesarean delivery is performed on an emergency basis, as the experience can be distressing or even traumatic.

Department of Pediatrics professor Piush Mandhane is leading a project to measure the effectiveness of an assessment tool, a short questionnaire that allows physicians and pregnant women to assess their emergency c-section risk ahead of labour. “Existing tools are meant for women already known to be at high risk of c-sections — like those with prior c-sections — or women already in active labour,” he says. “We could not identify anything available to help women and their doctors manage the risk of a potential emergency c-section.”

The new emergency cesarean delivery risk prediction model is designed for women in low-risk pregnancies and can predict their likelihood of {{c-section}} at any stage of pregnancy. The information gives doctors time to refer patients for psychological counseling to prepare for a potential emergency c-section, as well as health interventions like weight management programs that may help prevent the procedure.

The development of the prediction model was led by Mandhane’s former PhD student and trainee Tun Mon, and a team of researchers including Mandhane and fellow WCHRI member Padma Kaul. The questionnaire was developed using data from the CHILD birth cohort study. CHILD, a large longitudinal project that Mandhane helps lead, has been gathering data on the health of more than 3,400 Canadian children, as well as their mothers, for over 12 years. The final version of the emergency c-section questionnaire is based on six variables, including hypertension, antenatal depression, previous vaginal delivery, age, height and BMI.

After completing the model, the team published a research paper in October 2022, but Mandhane notes that a single paper cannot change the practice of medicine. Now, he and a team of researchers are testing the model — a three-minute questionnaire — in Brazil (work being led by graduate student Fabiana Mamede, a nurse-midwife), rural Alberta (Grande Prairie and Red Deer) and Edmonton. Once the tool is validated in these settings, Mandhane and his team hope to take it to specific populations of people, including Indigenous communities in Alberta.

Validating a model like this is good science, says Mandhane, but it can be difficult to gather funding for validation work. “Without WCHRI support, this work would be just another research paper sitting on a pile of a billion other papers.”

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Piush Mandhane is supported by the Stollery Children’s Hospital Foundation and the Alberta Women’s Health Foundation through the Women and Children’s Health Research Institute.

Neonatal sepsis is a blood infection that affects a high number of premature babies. Researchers already know that having sepsis at birth can result in developmental delays for children, while having low iron at birth predisposes them to chronic conditions such as cognitive deficits, cardiovascular disease, hypertension or diabetes later in life. Still unknown is how infection and low iron may be connected as part of a bigger puzzle.

“We wanted to know the effect of iron deficiency in combination with neonatal sepsis on the short-term and long-term health of the offspring,” says researcher and WCHRI postdoctoral fellowship awardee Forough Jahandideh. She is digging deeper into the issue in an effort to give babies the best chance for healthy futures.

The goal of her lab work is to eventually apply early treatments while the baby is still in the critical time period of development after birth and, ultimately, prevent chronic diseases from happening in adulthood.

Jahandideh was the primary driver behind this new stream of studies on the relationship between neonatal iron deficiency and sepsis, alongside supervisor Stephane Bourque in the Department of Anesthesiology & Pain Medicine. In Bourque’s lab, students were already examining various pieces of the iron deficiency puzzle, including diagnosis, treatment and its developmental effects.

After starting work on the sepsis-iron deficiency project, they found that the existing animal lab model for neonatal sepsis wasn’t useful when it came to reproducibility, which is needed for quality research.

They subsequently put a lot of emphasis on getting the lab model right, not only for their own studies, but potentially for use by many others who are doing research into the impact of other early life stressors.

“Even with all the efforts and all the good work that each individual lab has done, not all studies are reproducible or can eventually benefit patients,” says Jahandideh. “We were trying to see how we could help solve that, so that any data that is generated in a lab setting is useful and can hopefully be translated later for patients.”

Over the course of her postdoctoral work, Jahandideh succeeded in developing both a new animal lab model of sepsis and a scoring system to monitor neonatal animal health over time, laying the groundwork for other students in Bourque’s lab who are continuing with studies into neonatal sepsis and iron deficiency.

Jahandideh herself has gone on to start a position as a clinical research associate at the Ottawa Hospital Research Institute, where she continues to study sepsis and hone in on the quality of research as part of the National Preclinical Sepsis Platform — a network dedicated to improving preclinical models of sepsis.

She says that support from WCHRI has been fundamental to her success, mentioning professional development opportunities, meeting new people, and support with grant applications as some of the ways the Institute helped her career flourish.

“Without this fellowship, I didn’t have a chance to step into this field,” she says.

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Forough Jahandideh was supervised by Stephane Bourque. Her research was supported by the Stollery Children’s Hospital Foundation and the Alberta Women’s Health Foundation through the Women and Children’s Health Research Institute.