Reply to “Assessment of the diagnostic utility of the electroencephalogram in pediatric emergencies”: the importance of not overlooking psychogenic nonepileptic seizures in the pediatric population

Dear Editor:

We read with great interest the article published by Abenza Abildúa et al.¹ in Neurología, presenting a retrospective, descriptive, observational study of the diagnostic utility of urgent electroencephalography (EEG) in children and adolescents (ages 0-16 years) between January and December 2022. In their sample of 70 patients, 47 (67.14%) presented normal EEG findings. Of these, 10 were ultimately diagnosed with epilepsy. None of the patients who visited the emergency department due to suspected syncope or paroxysmal episodes (n = 6 [8.6%] and n = 11 [15.7%], respectively; n = 17 [24.3%] in total) presented EEG abnormalities, in line with findings from previous series.^1,2

We would like to underscore the importance of considering psychogenic nonepileptic seizures (PNES) in the pediatric emergency setting, and the major role played by EEG in their accurate diagnosis and subsequent management, an aspect not addressed in the study by Abenza Abildúa et al.¹

In a previous study, multivariate analysis revealed that age between 5 and 10 years (OR = 5.68 [95% CI, [1.64-19.75]; P < 0.006) and seizure duration > 5 minutes (OR = 13.54 [95% CI, 2.08-88.14]; P< .006) were significantly associated with a higher likelihood of abnormal EEG findings.²

EEG plays an essential role in preventing misdiagnosis of epilepsy in patients with paroxysmal events, and particularly in cases of prolonged PNES, which may occur in pediatric patients (8-14 years) misdiagnosed with status epilepticus (up to 3% of boys and 7% of girls).³

PNES have mainly been described in adults, with fewer reports in the pediatric population.^4,5 Despite the potential negative consequences of misdiagnosis (eg, unnecessary complementary tests and administration of antiseizure drugs [ASDs]), little information is available on the real prevalence, clinical features, diagnosis, treatment, and prognosis of PNES in pediatric patients.⁵

PNES are defined as paroxysmal episodes characterised by motor and/or behavioural disorders, which mimic epileptic seizures but are not caused by cerebral neuronal dysfunction, nor are they associated with epileptiform EEG activity.^5,6

Several terms have been used in the literature to refer to PNES, including pseudoseizures, psychogenic seizures, hysterical epilepsy, pseudoepileptic seizures, and nonphysiologic or functional seizures.^4,5 In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), PNES are classified under “somatic symptom and related disorders” as “functional neurological symptom disorder (conversion disorder).”⁷ The International Classification of Diseases, 11th Revision (ICD-11) uses the term “dissociative neurological symptom disorder, with nonepileptic seizures.”⁸ The term “psychogenic nonepileptic seizures” is preferred, as it underscores their nonepileptic nature and the suspected psychogenic origin.⁵

In adults, the prevalence of PNES ranges from 2 to 33 cases per 100 000 population, with an incidence rate of 1.4 cases per 100 000 person-years; in contrast, epilepsy has a prevalence rate of 47 cases per 100 000 population. The prevalence rate of PNES in adolescents aged 15-19 years has recently been estimated at 60 cases per 100 000 population. However, up to 5%-20% of patients with an initial diagnosis of epilepsy actually present PNES, and 20% of patients with PNES have a diagnosis of epilepsy. PNES are more likely to affect women (70%-80% of patients diagnosed with PNES).^9,10

Although the underlying pathophysiological mechanisms of PNES remain unclear, functional neuroimaging studies have detected changes in brain networks that may constitute the basis of the disorder, as well as increased resting-state functional connectivity between motor regions and regions involved in emotional processing.⁹ Great emphasis has historically been placed on the psychogenic mechanisms of PNES, which was considered to be a “conversion disorder” secondary to deep-rooted trauma. However, this explanation is incomplete. More comprehensive psychosocial models propose that a combination of cognitive and personality traits, such as alexithymia and dissociation, may increase the risk of developing functional symptoms and PNES.⁹

Subtle motor activity (resembling hypokinetic or dialeptic seizures, associated with altered level of consciousness), normally prolonged non-responsive fixed gaze, is more frequently observed in patients younger than 13 years of age. Marked motor activity, such as generalised nonrhythmic jerks or jerks in the limbs (similar to those observed in hyperkinetic seizures), is more frequently observed in adolescents, and resembles the activity observed in adults. The subtle motor activity seen in younger children is more likely to be mistaken for epileptic seizures, contributing to delayed diagnosis.⁷ Furthermore, boys are more frequently reported to present tonic-clonic–like movements, whereas girls more commonly present atonic falls.¹¹

In a study of 80 pediatric patients with PNES (mean age: 10.5 [1.6] years), the median time to diagnosis was 5 months (quartiles 1 and 3: 0.5-48), and 36 patients (45%) were already taking ASDs. The most frequent semiology was dialeptic (42.5%; n = 34), followed by mixed (28.8%; n = 23), motor (15%; n = 12), and nonepileptic aura (13.8%; n = 11). Family problems were the most frequent stressors, followed by school-related issues. The most prevalent psychiatric comorbidity was adjustment disorder, and 50% of patients reported somatic complaints.⁶

In another study, based on clinical and video-EEG data from 88 hospitalised pediatric patients with PNES, a total of 143 typical PNES events were recorded; these were classified as motor symptoms (38%; n = 55), sensory symptoms (27%; n = 39), unresponsiveness (18%; n = 25), abnormal behaviours (10%; n = 15), and visceral symptoms (6%; n = 9). Sixty-nine patients (78.4%) presented symptoms from a single semiology category, whereas the remaining 19 (21.6%) presented symptoms from at least 2 categories.¹²

Rapid and accurate diagnosis of PNES can be challenging. A detailed medical history obtained from eyewitnesses is essential, and should include data on potential trigger factors and psychiatric, neurological, and medical comorbidities. The “rule of 2s,” which yields a positive predictive value of 85%, consists of the following 3 criteria: 1) at least 2 PNES per week; 2) refractory to at least 2 ASDs; and 3) at least 2 EEGs without epileptiform abnormalities.⁵

Prolonged video-EEG study (≥ 24 hours) with recording of a seizure¹³ is the gold standard for diagnosing PNES.¹⁴ The detection of an event not associated with epileptiform EEG abnormalities, together with a consistent medical history, suggests a diagnosis of PNES.⁷ Hyperventilation, intermittent photic stimulation, and/or verbal suggestion are considered appropriate techniques.⁵

Short-term (nap) video-EEG combined with induction techniques may be a reasonable approach in areas with limited resources. However, interictal epileptiform abnormalities could be missed.⁵

Treatment should be interdisciplinary, involving neurology, psychiatry, psychology, pediatric nursing, and social work, and the patient’s parents.⁵ In a study following up 63 pediatric patients with PNES for 12 months, complete remission was achieved in 32% (n = 20), with improvements being observed in 89% of the sample (n = 56). Patients and families receiving counselling at one month after the event were more likely to achieve remission (P = 0.005). Seizures were documented on video-EEG in less than half of the sample (44%; n = 28).¹⁰ However, video-EEG evidence of PNES was not associated with increased likelihood of diagnosis acceptance (P = 1.0), seeking counselling (P = 0.59), or seizure freedom at 12 months (P = 0.79). Therefore, although video-EEG evidence of PNES events may be useful for diagnosis, it should not be considered sufficient to ensure patient acceptance of the diagnosis and an increase in remission rates; rather, PNES requires holistic, interdisciplinary management.¹⁰

In fact, an association has been shown between interdisciplinary management of PNES and a reduction in healthcare resource utilisation in the 12 months following referral, including a significant decrease in emergency department visits (up to a 75% decrease) and unnecessary diagnostic procedures.¹⁵

In conclusion, though PNES are frequent, they are underdiagnosed in the pediatric population; a considerable proportion of cases are misdiagnosed as epilepsy and treated with ASDs. Diagnosis is challenging, especially in children with both epileptic and nonepileptic seizures. The availability of video-EEG has improved the diagnosis of PNES, allowing better differentiation between these events and epileptic seizures. Prolonged video-EEG monitoring (≥ 24 hours) is the gold standard for diagnosis, although it should be complemented with an assessment of underlying psychological stressors and associated comorbidities.

Further real-world studies are warranted to better classify PNES in the pediatric population, facilitating early, appropriate diagnosis and treatment. A structured on-call neurology and pediatric clinical neurophysiology team is essential for this purpose.

Funding

This study received no public or private funding.