Uncovering the Complex Relationship Between ADHD and Epilepsy Surgery Outcomes

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurobehavioral comorbidities in people with epilepsy, particularly in children, and is associated with greater functional impairment, academic challenges, and reduced quality of life. While ADHD does not inherently preclude epilepsy surgery, it may influence the decision-making process for families and clinicians, sometimes leading to hesitancy or delay.

Recently, at the 2025 American Epilepsy Society (AES) Annual Meeting, held December 5-9 in Atlanta, Georgia, investigators presented findings from a Pediatric Epilepsy Research Consortium (PERC) surgery database to test whether youths with epilepsy who have elevated ADHD symptoms are less likely to achieve seizure freedom post epilepsy surgery. The trial, led by Janelle Wagner, PhD, and others, included over 3000 youths, aged 5-18 with refractory epilepsy, who are undergoing any phase of epilepsy surgery evaluation.

Among the 44% of patients who had elevated ADHD symptoms, a univariate analysis showed that this group was 1.15 times less likely to achieve seizure freedom (B = -0.412; P = .04) after surgery compared with those who did not have comorbid ADHD symptoms. Despite these results, the addition of demographic and epilepsy covariates in the regression model ultimately made the relationship between ADHD and post-surgery seizure freedom non-significant (P = .61).

Following the meeting, NeurologyLive^® caught up with Wagner to discuss the findings in greater detail, and how ADHD symptoms may relate to postoperative outcomes. Wagner, a clinical psychologist and research professor at the Medical University of South Carolina, reviewed prior studies that came before this investigation, as well as the need for research to better understand ADHD subtype differences, definitions of “elevated” symptoms, and the importance of long-term follow-up. Lastly, Wagner also touched on future priorities, including examining ADHD trajectories after surgery and exploring the influence of social determinants of health on surgery outcomes.

NeurologyLive: Can you provide background on what the existing literature has shown about ADHD and its impact on epilepsy surgery outcomes?

Janelle Wagner, MD: ADHD is a commonly co-occurring concern in pediatric epilepsy, with 30-40% of clinical samples of youth with epilepsy demonstrating clinical levels of ADHD symptoms. Different from the general youth population, in pediatric epilepsy populations, there is no increased risk for boys compared to girls, and the inattentive subtype is more common than the combined type (inattention and hyperactivity/impulsivity) (Auvin et al 2018). There is limited data on the impact of epilepsy surgery on ADHD symptoms in youth with epilepsy, particularly in the United States. In a Canadian study of 71 youth who underwent resective surgery, Puka & Smith 2016 showed that 1) ADHD symptoms improved from baseline to post surgery, and 2) ADHD symptoms were significantly lower post-surgery in youth who experienced seizure freedom compared to those who continued to have seizures. Notably, post-surgery follow-up ranged from 4 – 11.7 years (M=6.96, SD=2.25). In a study with 107 Swedish youth, Reilly et al 2019 reported on ADHD symptoms two years post any type of epilepsy surgery (e.g., resection, hemispherectomy, corpus callosotomy, etc). For youth ages 6 and older and with IQ>50, ADHD symptoms were significantly lower following surgery. Youth who experienced seizure freedom and those with right hemisphere surgery showed significant improvement in ADHD symptoms two years after surgery.

Describe your results in detail - what stands out from a clinical perspective? What are the main takeaways from the research?

Our study builds on the extant literature by examining ADHD symptoms in a large, multi-site US sample of over 400 youth.We found a similar rate of elevated ADHD symptoms, with 44% of our sample demonstrating elevated (at-risk, clinical) ADHD symptoms. Confirming previous studies, age at epilepsy onset and age of surgery were related to ADHD symptoms at baseline; however, these relationships became non-significant in multi-variate analyses. Similarly, in univariate analyses, youth with elevated ADHD symptoms pre-surgery were 1.15 times less likely than CYE without elevated ADHD symptoms to achieve seizure freedom following surgery. In the multivariate analysis, this relationship was no longer significant, but none of the epilepsy characteristics (e.g., ASMs, IQ, type of surgery, seizure focus, etc) predicted seizure freedom either. Further research is necessary to explore these complex relationships between baseline ADHD, seizure freedom, and post-surgery ADHD symptoms.

What other future types of research will better help unravel the complex relationship between ADHD and post-surgery seizure freedom?

Our next step is to examine post-surgery ADHD symptoms in this large multi-site sample. Our poster presented at the American Epilepsy Society, like the Reilly study, included all types of epilepsy surgery, and it will be important to consider whether surgery is considered palliative or a possible cure in future research that examines seizure freedom and ADHD symptoms. Given the higher rate of inattentive ADHD in youth with epilepsy, it will also be important to look at the different ADHD subtypes. Notably, depending on the assessment measure used, this may be difficult as some frequently used measures do not include separate measurement of inattention and hyperactive/impulsive behaviors. Other considerations are what constitutes “elevated” ADHD symptoms (at risk vs clinical vs at risk + clinical). Finally, the length of time following surgery is important to consider. The Reilly study was limited to 2-year follow up; whereas, our poster and the Puka paper allowed for a range of follow-up time.

Do we think sociodemographic factors play a role in the relationship between epilepsy surgery, ADHD, and seizure freedom?

This is a very important question as we consider the role that social determinants of health (SDH) may play in epilepsy surgery. A recent paper by the PERC Surgery Group (Berl, Wagner et al 2025) reported that there were no significant differences based on race/ethnicity or sex in over 1100 youth who were offered epilepsy surgery; however, White patients were 1.88 times more likely than Black patients to actually complete surgery. It will be necessary for future research to flesh out the relationship of SDH to seizure freedom and ADHD symptoms post-epilepsy surgery.

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REFERENCES
1. Auvin S, Wirrell E, Donald KA, Berl M, Hartmann H, Valente KD, Van Bogaert P, Cross JH, Osawa M, Kanemura H, Aihara M, Guerreiro MM, Samia P, Vinayan KP, Smith ML, Carmant L, Kerr M, Hermann B, Dunn D, Wilmshurst JM. Systematic review of the screening, diagnosis, and management of ADHD in children with epilepsy. Consensus paper of the Task Force on Comorbidities of the ILAE Pediatric Commission. Epilepsia. 2018 Oct;59(10):1867-1880. doi: 10.1111/epi.14549. Epub 2018 Sep 3. PMID: 30178479.
2. Berl M, Wagner JL, Caraway A, Loblein H, Novotny EJ, et al & the PERC Surgery Workgroup. (in press). Disparities across the pediatric epilepsy surgery journey: Referral, recommendation, and completion from a national consortium. Epilepsia.
3. Puka, K., Smith, M.L. Long-term outcomes of behavior problems after epilepsy surgery in childhood. J Neurol 263, 991–1000 (2016). https://doi.org/10.1007/s00415-016-8089-0.
4. Reilly C, Hallböök T, Viggedal G, Rydenhag B, Uvebrant P, Olsson I. Parent-reported symptoms of ADHD in young people with epilepsy before and two years after epilepsy surgery. Epilepsy Behav. 2019 May;94:29-34. doi: 10.1016/j.yebeh.2019.02.003. Epub 2019 Mar 16. PMID: 30884404.