In a groundbreaking large-scale study utilizing electronic health records, investigators at Vanderbilt University Medical Center (VUMC) have meticulously determined the prevalence of functional seizures and comprehensively characterized the associated comorbidities, shedding critical light on a condition that has historically been underdiagnosed and misunderstood. This extensive research, spearheaded by Dr. Lea Davis, an associate professor of Medicine and a distinguished investigator at the Vanderbilt Genetics Institute, has confirmed long-suspected links between functional seizures and a range of psychiatric disorders, including post-traumatic stress disorder (PTSD), anxiety, and depression, alongside a significant association with sexual assault trauma. Perhaps most notably, the study has identified a novel and significant association between functional seizures and cerebrovascular disease, a finding that could reshape diagnostic pathways and treatment strategies.
Functional seizures, also known as psychogenic nonepileptic seizures (PNES), are characterized by sudden attacks or spasms that closely mimic epileptic seizures but are not accompanied by the aberrant brain electrical patterns that define epilepsy. This distinction is crucial, as it necessitates a fundamentally different approach to diagnosis and management. Historically, individuals experiencing functional seizures have faced a protracted diagnostic odyssey, often enduring an average of seven years before receiving an accurate diagnosis. This delay can lead to significant emotional distress, inappropriate and ineffective treatments, and a profound sense of invalidation for patients.
The research team’s findings, meticulously detailed in the esteemed journal JAMA Network Open, underscore the magnitude of this diagnostic challenge. According to Slavina Goleva, a graduate student in Molecular Physiology and Biophysics and the first author of the study, approximately 80% of patients who experience functional seizures are initially misdiagnosed with epilepsy and subsequently treated with anti-epileptic drugs. This widespread misdiagnosis highlights the limitations of relying solely on conventional diagnostic tools and emphasizes the critical role of specialized assessments like video electroencephalogram (video-EEG) monitoring for accurate identification.
Dr. Davis’s personal journey into the realm of functional seizures was ignited by a compelling NPR story several years prior. The narrative offered a deeply personal account of the patient experience, revealing the pervasive stigma and systemic difficulties individuals faced within the healthcare system. "The story gave the patient perspective on these seizures — the stigma that patients felt and the difficulties they experienced in the medical system," Dr. Davis recalled. "I felt like studies within electronic health records could potentially be really impactful for this community." This empathetic motivation fueled the VUMC team’s determination to leverage the vast repository of electronic health record data to illuminate this often-overlooked condition.
Developing a Novel Diagnostic Algorithm
The path to identifying patients with functional seizures within the VUMC electronic health record (EHR) system was not without its complexities. Working collaboratively with Dr. Kevin Haas, an associate professor of Neurology, the researchers developed a sophisticated algorithm designed to pinpoint individuals with functional seizures. "We initially recognized that finding these patients within the EHR would be a challenge because the ICD (International Classification of Diseases) codes are not as specific as they are for a lot of diseases," Goleva explained. To overcome this inherent limitation, the team expanded their search parameters beyond standard ICD codes to include Current Procedural Terminology (CPT) codes. Furthermore, they employed advanced natural language processing (NLP) techniques to meticulously scan the medical records for a comprehensive list of keywords associated with the condition.
The accuracy of this algorithm was rigorously validated through manual chart reviews conducted by Goleva and Dr. Haas. This dual approach, combining algorithmic identification with human expertise, ensured a high degree of confidence in the study’s cohort selection.
Unprecedented Prevalence Data
The study encompassed an immense dataset, drawing from the VUMC-EHR system and including over 2.3 million patients aged 18 and older who received care between 1989 and 2018. Within this vast population, the researchers successfully identified 3,341 patients diagnosed with functional seizures. A striking demographic observation was that 74% of these individuals were women, a finding that aligns with existing literature but is now quantified with unprecedented precision.
Crucially, the study provided the first direct calculation of the prevalence of functional seizures. The VUMC team calculated a prevalence rate of 0.14%, translating to 140 cases per 100,000 people. This figure significantly surpasses previous estimates, which had ranged widely from 2 to 33 cases per 100,000 people. "Our report is the first direct calculation of the prevalence of functional seizures," Goleva stated. She also prudently noted that the specialized nature of the epilepsy monitoring unit at VUMC, which likely attracts patients with complex seizure disorders, might contribute to a higher observed prevalence within the VUMC-EHR compared to the general population. Nevertheless, this substantial increase in the estimated prevalence suggests that functional seizures are considerably more common than previously appreciated, implying a greater public health burden.
Unraveling Complex Comorbidities
Beyond establishing prevalence, the VUMC study delved deeply into the constellation of comorbidities associated with functional seizures. The research team validated established links between functional seizures and psychiatric disorders, including PTSD, anxiety, and depression. They also reaffirmed the strong association with a history of sexual assault trauma. This validation lends significant weight to the understanding that functional seizures often co-occur with significant psychological distress and trauma.
However, the study’s most groundbreaking revelation was the identification of a novel association between functional seizures and cerebrovascular disease, encompassing conditions such as stroke. This discovery opens up an entirely new avenue of inquiry into the potential underlying mechanisms of functional seizures and suggests that neurological events impacting brain vasculature might play a role in their development or manifestation. "The findings were reported in the journal JAMA Network Open," the article stated.
The researchers also quantified the impact of sexual assault trauma, finding that it explained approximately a quarter of the increased rate of functional seizures observed among women. This finding underscores the profound and lasting effects of trauma on physical health and highlights the critical need for trauma-informed care in the management of functional seizures.
"Functional seizures are not occurring in isolation; patients who are experiencing these seizures are also experiencing a higher burden of additional health care issues," Dr. Davis emphasized. This statement encapsulates the complex, multifaceted nature of functional seizures and underscores the importance of a holistic approach to patient care.
Implications for Diagnosis and Treatment
The implications of these findings for clinical practice are profound. The VUMC team strongly advocates for a re-evaluation of diagnostic pathways, particularly for individuals presenting with seizure-like activity. Dr. Haas emphasized the critical need for timely and accurate diagnosis: "If there is a suspicion that someone presenting with seizures could have functional seizures rather than epileptic seizures, it’s critical to refer those patients to an epilepsy monitoring unit for accurate diagnosis and appropriate treatment."
Historically, the care of patients with functional seizures has been fragmented, often falling into a gap between neurological and psychiatric specialties. However, the VUMC researchers are actively working to bridge this divide. "Historically, even once diagnosed, care of these patients has often fallen through the cracks between neurology and psychiatry, but we are now actively developing a more integrated approach to care for this patient population," Dr. Haas stated. This development signals a promising shift towards more collaborative and comprehensive care models.
The researchers’ recommendations for clinical practice are clear and actionable: patients experiencing seizures, particularly those with pre-existing psychiatric comorbidities or a history of sexual assault trauma, should be promptly referred for video-EEG assessment. Furthermore, individuals who develop seizures following a stroke and do not exhibit a positive response to conventional anti-epileptic medications should also be considered for early video-EEG evaluation. This proactive approach aims to reduce diagnostic delays and ensure that patients receive the most appropriate and effective treatment.
The study also highlighted that a significant proportion of patients referred for video-EEG monitoring are ultimately diagnosed with functional seizures, with figures indicating that up to 30% fall into this category. This statistic further reinforces the need for increased awareness and utilization of video-EEG in the diagnostic workup of seizure disorders.
Addressing Diagnostic Gaps and Future Research
The absence of a specific ICD code for functional seizures remains a significant point of contention for the researchers, particularly given the condition’s prevalence. Dr. Davis expressed her frustration: "It’s frustrating that there is no ICD code for functional seizures, given how common the diagnosis is and the fact that codes exist for strange things like alligator bite, second occurrence. It really emphasizes how little attention this population of patients has gotten." This lack of specific coding hinders data collection, research funding, and ultimately, the prioritization of care for this patient group.
Looking ahead, the VUMC investigators are actively pursuing further research to unravel the underlying mechanisms of functional seizures. They are currently exploring the genetic underpinnings of the condition through genome-wide association studies utilizing biobanks, including Vanderbilt’s own BioVU. This genetic research holds the potential to identify susceptibility factors and contribute to a more nuanced understanding of the disease.
The study’s significant findings were made possible through the collaborative efforts of numerous individuals and was supported by substantial grants from the National Institutes of Health (NIH) and the National Science Foundation. The NIH grants provided funding for various aspects of the research, including grants MD015722, NS102371, MH113362, HG009086, HD098859, DC016977, NS105746, MH120736, HG010652, HG009034, and TR000445. Slavina Goleva was also supported by a Graduate Research Fellowship from the National Science Foundation, underscoring the commitment to fostering the next generation of researchers in this critical field. The contributions of other authors, including Allison Lake and Eric Torstenson, were also integral to the success of this impactful study.
The comprehensive findings from Vanderbilt University Medical Center represent a pivotal advancement in the understanding of functional seizures. By providing robust data on prevalence and a deeper insight into associated comorbidities, this research is poised to transform diagnostic practices, improve patient outcomes, and bring much-needed attention and resources to a condition that has long been underserved by the medical community. The newly identified association with cerebrovascular disease, in particular, opens exciting avenues for future investigation and offers hope for more targeted and effective interventions.