Do Not Forget Epilepsy in Celiac Disease Patients!

Dear Editor, A 10-year-old girl was brought in by her family because of episodes characterized by sudden awakening from sleep, purposeless hand and arm movements, occasional blank staring, unresponsiveness to her surroundings, and short periods of failure to recognize familiar people. These attacks generally lasted from 20 s to 2 min, after which she regained awareness and returned to sleep. She had never experienced such episodes during the day. Her complaints had persisted for more than a year, initially occurring once or twice a month and increasing to two or three times a week in recent months. At other healthcare centers, routine daytime wake and sleep electroencephalographies (EEGs) were reported as normal, and the events were interpreted as sleep-related movements. Accordingly, melatonin therapy was initiated; however, no clinical improvement was observed. Her medical history revealed that she had been diagnosed with celiac disease (CD) at approximately 2 years of age because of growth retardation; however, she had not been adhering to a gluten-free diet. Physical examination was unremarkable, and her growth and developmental parameters were appropriate for her age. Routine laboratory tests were within normal limits except for mild iron deficiency, and tissue transglutaminase immunoglobulin A levels were positive, consistent with dietary noncompliance. Brain magnetic resonance imaging showed no abnormalities. Despite repeatedly normal routine wake and sleep EEGs, the persistence of unexplained nocturnal paroxysmal events raised concern for an underlying epileptic etiology. Given that the episodes occurred exclusively during sleep, overnight video-EEG monitoring was performed, during which typical electroclinical seizures were recorded [Video 1]. {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video 1","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_7snnb54u"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} Based on these findings, the patient was diagnosed with focal epilepsy with impaired awareness, and antiepileptic treatment with levetiracetam (20 mg/kg/day) was initiated. During follow-up, seizure frequency gradually decreased, resulting in complete seizure remission. In parallel, a gluten-free diet was reestablished, and adherence was ensured. After 2 years of antiepileptic therapy, the medication was discontinued. No seizure recurrence was observed during the subsequent 2-year follow-up period, and the patient remains under ongoing observation. Discussion This case emphasizes that paroxysmal events occurring in children with CD—initially interpreted as non-epileptic—should be carefully evaluated for possible epilepsy. Although the increased prevalence of epilepsy among individuals with CD compared with the general population is well established, diagnostic delay may occur, particularly when attacks arise exclusively during sleep, leading to epilepsy being frequently overlooked. In the present case, seizure-like symptoms that had persisted for more than 1 year and gradually increased in frequency were initially considered non-epileptic because routine wake and sleep EEGs were normal, resulting in a delay in diagnosis. This case demonstrates that normal routine EEG findings do not exclude epilepsy and that the diagnostic approach should be broadened in patients with sleep-related, unexplained paroxysmal events. Indeed, epileptic activity in this patient was identified only through long-term overnight video-EEG monitoring. This finding clearly highlights the high diagnostic value of video-EEG in children with CD who present with suspicious clinical features despite normal routine EEGs. CD is an autoimmune enteropathy that develops in genetically predisposed individuals following gluten ingestion and may be accompanied by various neurological complications in addition to gastrointestinal manifestations. Epilepsy is among the most frequently associated neurological conditions in CD and shows a particularly strong association with occipital lobe epilepsy.[1-3] Işıkay and Kocamaz[3] reported biopsy-proven CD in 15.7% of children with childhood partial epilepsy of the occipital type. In the present case, the detection of occipital-origin epileptiform discharges on video-EEG is consistent with the existing literature. The pathophysiology of neurological involvement in CD has not yet been fully elucidated. However, gluten-related autoimmune mechanisms—including antibody cross-reactivity, immune complex deposition, and possible direct neurotoxic effects—are thought to play a role.[4] In addition, prolonged exposure to gluten and poor dietary adherence may contribute to both the emergence and persistence of neurological manifestations. In the present case, the reintroduction and effective maintenance of a strict gluten-free diet in combination with antiepileptic therapy resulted in complete seizure resolution, indicating that the epileptic process may be reversible with early diagnosis and appropriate intervention. In children with persistent paroxysmal events, long-term video-EEG recordings are crucial when routine EEGs are normal. Because routine EEG examinations are typically limited to 30–60 min, their diagnostic yield for capturing paroxysmal events is relatively low. While interictal discharges can be detected by routine EEG in approximately one out of five patients, extending the recording duration may increase the detection rate to nearly one out of three patients. Therefore, video-EEG monitoring is considered the gold standard for the diagnostic evaluation of paroxysmal events.[5] The likelihood of capturing epileptic seizures or paroxysmal attacks during video-EEG monitoring has been reported to be up to ten times higher than that of routine EEG.[5-7] Whereas routine EEG provides information primarily on interictal abnormalities, video-EEG enables direct recording of the event itself, allowing accurate differentiation between epileptic and non-epileptic attacks, assessment of actual event frequency, identification of potential triggers, localization of the epileptogenic focus, and determination of individualized treatment strategies.[6-8] Despite its high diagnostic value, video-EEG monitoring is limited by its cost and the need for appropriate facilities, equipment, and trained personnel, including physicians, technicians, and nursing staff. A recent study reported that 24-h video-EEG monitoring captured 90% of events, whereas 48-h monitoring detected all events.[8] Long-term video-EEG monitoring allows for prompt initiation of appropriate treatment in patients with epileptic seizures, facilitating early seizure control and exerting a positive impact on quality of life and cognitive function. Moreover, in patients with non-epileptic attacks such as cardiac or psychogenic events, video-EEG is essential to prevent misdiagnosis, avoid unnecessary antiepileptic drug use, and ensure timely referral to condition-specific treatments. In conclusion, epilepsy should always be considered in children with CD, particularly in the presence of unexplained paroxysmal events occurring exclusively during sleep. Normal routine EEG findings should not exclude the diagnosis; in such cases, long-term overnight video-EEG monitoring should be considered a critical diagnostic tool for early diagnosis, appropriate treatment, and the prevention of potential neurological sequelae. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Ethical policy and institutional review board statement As it is a letter to the editor, ethics approval was not deemed necessary. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Author contributions Methodology: SI; software: SI; validation: SI; formal analysis: SI; investigation: SI; resources: SI; data curation: SI; writing—original draft: SI and AKB; writing—review and editing: SI and AKB; visualization: SI; supervision: SI; project administration: SI. All authors reviewed and approved the final version of the manuscript.