Helping craniopharyngioma survivors dream well and dream big

The brain governs the physical body and thinking — making its protection essential for everyone. But for children undergoing treatment for a brain tumor, the challenge becomes how to eliminate tumor cells in this difficult-to-reach location while minimizing damage.

As a result of treatment, patients can face long-term neurocognitive issues. For craniopharyngioma, a rare, non-cancerous brain tumor that occurs mostly in children, the stakes of treatment are high as children receiving care are still experiencing rapid brain development. To navigate these stakes and understand what interventions can best provide support for patients with craniopharyngioma, scientists are working to understand how children’s brains may be different after treatment and how those changes affect their daily lives.

One such researcher is Valerie Crabtree, PhD, Psychosocial Services vice-president and Department of Psychology & Biobehavioral Sciences member. As a clinical sleep psychologist, Crabtree provides interventions for children being treated for cancer who often experience disrupted sleep. Her work has identified that sleep in survivors of craniopharyngioma appears to be impacted even more than children facing other tumors.

“The tumor and treatment in craniopharyngioma can impact the hypothalamic pituitary axis, which is intimately involved in regulating our sleep-wake cycles,” Crabtree explained. “We knew that these patients experienced fatigue and sleep difficulties, but there had never been a large-scale study looking at their sleep.”

Published in Sleep Advances, corresponding author Crabtree, co-senior author Belinda Mandrell, PhD, RN, PNP, Division of Nursing Research director and Department of Pediatric Medicine associate member, and their colleagues observed sleep disruption in a large group of children treated for craniopharyngioma. The study was part of the RT2CR clinical trial led by Thomas Merchant, DO, PhD, Department of Radiation Oncology chair. St. Jude is one of the very few centers in the world that treats the rare disease, enabling the scientists to assemble a cohort of 94 patients enrolled in clinical trials using proton radiotherapy and limited surgery at the institution. Spearheaded by former St. Jude Pediatric Oncology Education (POE) Program student and first author Jordan Davidson, the researchers compared the cohort’s bodily functions during sleep to a group of healthy, similar-aged children from previous research at the start of therapy and then 36 months later.

“We saw that these children spent different amounts of time in each stage of sleep, compared to their peers,” Crabtree said. “We already knew that these children often experience issues with memory and excessive daytime sleepiness; this is a first step toward understanding why.”

Out-of-phase sleep

Children treated for craniopharyngioma were already known to have sleep issues, including some experiencing hypersomnia, or narcolepsy. These conditions cause extreme daytime sleepiness, including sudden, strong urges to sleep, despite getting the right amount of sleep each night. What remained unclear was what occurred during their sleep that fueled these conditions.

“We normally cycle through the four stages of sleep in order, from N1 to N2, followed by N3, then Rapid Eye Movement or REM sleep, several times a night,” Crabtree explained. “Our patients with craniopharyngioma had a little less N1 and a lot less N2 sleep, meaning they had less of the ‘entry’ into deeper sleep stages than their counterparts.”

Later in the cycle, the researchers found that N3 sleep was significantly increased, over 10% more than the comparison group, challenging their assumptions. “We were surprised, because we know these patients often have challenges with memory, and N3 sleep is when we consolidate memories,” Crabtree said. “We had anticipated they would have less N3 sleep, so we are now working to understand that more.”

In addition, the patients treated for craniopharyngioma spent about 2.63% less time in REM sleep, but only 36 months after starting treatment, not at baseline. That indicated that these patients are experiencing these sleep disruptions over the long term, not just during treatment. Together, the findings highlight the need for interventions and support to help children with craniopharyngioma long after therapy.

Supporting patients with sleep disruptions

Although the underlying biology causing sleep disruptions is still being studied, Crabtree and other sleep specialists already help survivors of craniopharyngioma cope. “I am a researcher on these studies, but I also clinically see most of these kids and teenagers,” she explained. “They have hopes and dreams, like any other kid or teenager, which hold special meaning for them, but narcolepsy or hypersomnia can make it challenging to manage their energy and alertness to meet those goals.”

Children experiencing sleep disorders can struggle to stay awake during even the most important events in their lives. They can also have other hormonal issues, such as diabetes insipidus that leads to frequently waking during the night and even more fatigue. Their time awake is a valuable and highly limited currency that they must decide how to spend.

“A lot of times in my role, I don’t just help them find ways to regulate their sleep, I help them define their values and strategize where to target their energy,” Crabtree said. “For many kids and teens that’s schoolwork, but kids also have other priorities, like wanting to hang out with their friends.”

As an example, a patient may want to have a sleepover with their friends on a Saturday. Crabtree helps counsel them to pre-load by sleeping extra on Thursday and Friday. This will let them stay up later on Saturday, before going to bed early on Sunday to post-load the sleep they lost. These sleep disorders regularly require patients to think about what they want out of life, and plan ahead in a way that their peers don’t have to, but Crabtree finds sharing these skills with them to be a cherished aspect of her career.

“I find a lot of meaning in helping our patients think about their values and goals and align their actions with them,” Crabtree said. “It’s a lot harder for them than a kid who doesn’t have to manage all of these health challenges and narcolepsy, but I help them realize it is possible to attain those dreams, it just requires much more work on the part of our kids, teens and families.”

Taking a long-term view for patients treated for craniopharyngioma

Understanding how treatment for craniopharyngioma impacts sleep, and how that disrupted sleep can affect the lives of survivors is critically important to ensure these children have a high quality of life. The study highlights how long-term support is crucial because these issues can manifest over time, not just during the acute phase of their tumor care.

“Treatment doesn’t mean the end of challenges for the children and adolescents we care for,” Crabtree said. “We need to recognize that there may be lifelong medical difficulties that they will face, but we can find ways to support them throughout the rest of their lives.”