Ahmad Beydoun

Objective: Paroxysmal events resembling epileptic seizures frequently lead to diagnostic error and unnecessary treatment exposure. While non-epileptic paroxysmal events (NEPE) are recognized as common seizure mimics, the age-dependent structure of the differential diagnosis and patterns of antiseizure medication (ASM) exposure remain incompletely characterized. Methods: We conducted a prospective national referral cohort study of consecutive patients referred for evaluation of suspected new-onset seizures. All patients underwent standardized clinical assessment, video-electroencephalography, and longitudinal follow-up. NEPE were classified into five predefined diagnostic subgroups, and multinomial logistic regression was used to model age-related diagnostic probabilities. Results: Of 1,877 patients referred over 4 years, 428 (22.8%) were diagnosed with NEPE, including 305 pediatric and 123 adult cases. Syncope was the most frequent diagnosis (30.8%), followed by functional seizures (21.7%). Distinct age-dependent distributions of non-epileptic diagnoses emerged: infantile mimics (including breath-holding spells and Sandifer syndrome) predominated in early childhood, behavioral-movement phenomena peaked in childhood, functional seizures increased during adolescence and young adulthood, and syncope became progressively more prevalent with advancing age. Developmental delay was strongly associated with behavioral-movement diagnoses (OR 10.60, 95% CI 3.45–32.61). Pre-referral ASM exposure occurred in 102 patients (23.8%), with patients with functional seizures three times more likely to be treated before diagnostic clarification than those with syncope (adjusted OR 3.08, 95% CI 1.47–6.46). Significance: NEPE follow predictable age-related distributions that may guide early clinical assessment. The high rate of ASM exposure prior to diagnostic clarification, particularly in functional seizures, highlights the clinical consequences of early misdiagnosis. Incorporation of age-based clinical reasoning may improve diagnostic accuracy and reduce unnecessary treatment exposure in patients with paroxysmal events.

Objective: To determine the extent to which electroclinical information available at initial evaluation allows classification of idiopathic generalized epilepsy (IGE) syndromes, and to assess the contributions of seizure semiology and age at seizure onset to early syndromic diagnosis. Methods: We prospectively analyzed a cohort of patients with new‐onset seizures who underwent a structured clinical evaluation, including detailed history‐taking, 3‐h video‐EEG, and epilepsy‐protocol MRI. Seizure semiology was assessed at three levels: index seizure, initial seizure type, and seizure types identified at initial evaluation. Syndromic classification followed International League Against Epilepsy criteria. Final electroclinical diagnosis, established after longitudinal follow‐up, served as reference. Within patients ultimately diagnosed with one of the four IGE syndromes, baseline data were used to determine whether the final syndrome could be assigned at initial evaluation. Results: Of 2699 patients evaluated, 498 (18.4%) met criteria for genetic generalized epilepsy, of whom 401 (80.5%) were classified as having one of the IGE syndromes. Based on initial evaluation, the correct syndrome could be assigned in 366 patients (91.3%), whereas 7 (1.7%) would have been misclassified and 28 (7.0%) were not assignable. Non‐assignability was confined to absence epilepsies, reflecting overlap between childhood (CAE) and juvenile absence epilepsy (JAE), whereas misclassification occurred only in juvenile myoclonic epilepsy (JME) presenting with isolated generalized tonic–clonic (GTC) seizures. Classification based on the index seizure alone showed limited accuracy (63.6%), whereas incorporation of seizure types identified through structured history improved classification to 95.0%. Myoclonic seizures were highly specific for JME, whereas absence and GTC seizures required integration with additional features. Age at seizure onset strongly differentiated CAE from JAE (AUC 0.935). Significance: Electroclinical classification of IGE syndromes is frequently achievable at initial evaluation when based on seizure semiology and age at onset. When classification is not possible, limitations follow predictable electroclinical patterns, supporting a structured, history‐driven diagnostic approach. Plain Language Summary: This study examined how accurately doctors can identify specific types of generalized epilepsy when patients are first evaluated. Among 401 patients with generalized epilepsy, the correct epilepsy syndrome could be identified in more than 90% at the first visit. Looking beyond the first seizure and asking about all seizure types together with age at seizure onset greatly improved diagnosis. While some overlap exists between specific types (like childhood versus juvenile absence epilepsy), a thorough clinical evaluation from the start provides reliable diagnostic direction for patients and supports early and accurate diagnosis.

Background: Health-related quality-of-life (HRQOL) is a central outcome in pediatric epilepsy, yet the relative influence of disease severity versus treatment-related burden remains unclear. This study aimed to evaluate HRQOL and assess the respective contributions of clinical characteristics and treatment adverse events in children with epilepsy. Methods: A cross-sectional analysis of 101 children enrolled in a prospective cohort in Lebanon was conducted. HRQOL was assessed using the Arabic QOLCE-55, and treatment-related adverse effects were measured using the Liverpool Adverse Events Profile (LAEP). Multivariable linear regression models, including hierarchical domain-specific analyses, were used to identify factors independently associated with HRQOL. Results: HRQOL was moderately reduced, with a median QOLCE-55 score of 66 (IQR 55.68–79.41). The physical domain was the most affected (44.44; IQR 30.55–59.72), while the social domain was the least impaired (82.14; IQR 67.85–96.42). In multivariable analysis, higher adverse-effect burden was the strongest factor associated with poorer overall HRQOL (B = −0.97, 95% CI –1.28 to −0.67; p < 0.001), whereas most seizure-related variables were not significant after adjustment. Inclusion of LAEP substantially improved model performance (Δ R ² up to 0.310) and was associated with poorer HRQOL across all domains. Longer epilepsy duration remained associated with poorer physical HRQOL, and focal epilepsy with lower social and emotional scores. Conclusion: In this cohort, HRQOL was more strongly associated with treatment-related adverse effects than with most seizure-related variables. Treatment tolerability appears to represent an important and modifiable correlate of well-being. Routine assessment of adverse effects may enhance patient-centered care.

Objective: To assess the diagnostic contributions of semiology, Electroencephalography (EEG), brain magnetic resonance imaging (MRI), and longitudinal follow‐up both, individually and in combination in classifying seizure type (focal‐to‐bilateral tonic–clonic (FBTC) vs. generalized‐onset bilateral tonic–clonic (GBTC)) in children with new‐onset bilateral tonic–clonic (BTC) seizures. Methods: We prospectively evaluated 249 consecutive children who presented with new‐onset BTC seizures. All patients underwent detailed clinical assessment, a 3‐h sleep‐deprived EEG, an epilepsy protocol brain MRI, and standardized follow‐up. Seizures were classified as FBTC or GBTC using predefined criteria. We assessed the diagnostic yield of each modality and their incremental value in improving classification. Results: Seizure semiology alone allowed classification in 22% of children. EEG findings enabled classification in 53%, with the highest yield (72%) among children aged 5–10 years. MRI revealed epileptogenic lesions in 14%, with structural abnormalities identified in 50% of children with developmental delay. Combining semiology, EEG, and MRI increased the classification yield to 73%, and follow‐up further improved this to 81%. Notably, 30.8% of children ultimately diagnosed with GBTC seizures exhibited focal features such as head version or tonic posturing, underscoring the limited specificity of these signs in pediatric BTC seizures. Significance: Accurate classification of new‐onset BTC seizures in children cannot rely on semiology alone. A multimodal approach—integrating EEG, MRI, and clinical follow‐up—is essential to improve diagnostic accuracy. Our findings emphasize the nonspecific nature of certain focal features in GBTC seizures and advocate for a cautious, evidence‐based approach when interpreting semiological signs. These results have direct implications for ASM selection and early management decisions in pediatric epilepsy. Plain Language Summary: Children who experience a first‐time convulsive seizure need an accurate diagnosis to guide appropriate treatment. In our study of 249 children with new onset bilateral tonic–clonic seizures, we found that no single diagnostic tool, whether seizure description, EEG, or MRI, was sufficient on its own. However, when these tools were combined, clinicians were able to correctly determine the seizure type in more than 80% of cases. We also found that some signs typically considered focal, such as head turning, may still appear in generalized seizures. These findings underscore the importance of a multimodal approach to ensure optimal diagnosis and treatment planning for children with new onset seizures.

Objective: This prospective study aims to characterize the spectrum of epilepsy syndromes among adult patients newly diagnosed with genetic generalized epilepsy (GGE). Additionally, it aims to examine their clinical characteristics, evaluate their response to treatment, and assess the feasibility of treatment discontinuation across each syndrome. Methods: Patients identified for this study were recruited from a prospective multicenter study evaluating patients with new‐onset unprovoked seizures enrolled between March 2010 and March 2020. Participants underwent a comprehensive evaluation including a 3‐h sleep‐deprived video‐EEG recording and an epilepsy protocol brain MRI with repeat EEG at each follow‐up. Included were patients 18 years and older and meeting criteria for GGE. Treatment responses, antiseizure medication (ASM) withdrawal success rates, and achievement of a two‐year terminal seizure remission were assessed. Results: A total of 67 patients with a mean age at seizure onset of 21.9 years were included, constituting 16% of the entire GGE cohort. The most frequently diagnosed electroclinical syndrome was GTCA in 34 patients (50.7%), followed by JME in 21 patients (31.3%) and GGE not otherwise specified (GGE‐NOS) in 12 patients (17.9%). Most patients responded well to monotherapy with valproate and levetiracetam as the most frequently prescribed ASMs. ASM tapering was attempted in 28 patients and was more frequently successful in patients with GTCA and GGE‐NOS (60%) compared with JME (12.5%). A two‐year terminal seizure freedom for all seizure types was achieved in 85.3% of patients with GTCA, 83.3% of those with GGE‐NOS, and 23.8% of those with JME. Significance: This study provides comprehensive insights into the epidemiology, clinical features, and treatment outcomes of adult‐onset GGE. It emphasizes the necessity of considering GGE in adults with new‐onset seizures, highlighting the efficacy of ASM therapies and suggesting that certain electroclinical syndromes may not mandate lifelong treatment, underscoring the pivotal role of accurate diagnosis. Plain Language Summary: This study evaluated adults experiencing their first seizures who were diagnosed with a type of epilepsy called genetic generalized epilepsy (GGE). We found that this condition can begin in adulthood, and many patients have a family history of seizures. Most responded well to treatment, frequently with just one medication, and only a few continued to have seizures. In some, particularly those with generalized tonic–clonic seizures (whole‐body convulsions), treatment could be safely stopped after several seizure‐free years. These findings highlight the importance of accurate diagnosis and provide reassurance that good seizure control is achievable for most adults with GGE.

Background: Cerebral arteriovenous malformations (AVMs) are rare congenital vascular anomalies, often presenting with intracranial hemorrhage or seizures. Posterior reversible encephalopathy syndrome (PRES) is a distinct neurological condition characterized by vasogenic edema, primarily affecting posterior brain regions and typically associated with hypertensive crises, eclampsia, or immunosuppressive therapies. However, its occurrence following neurosurgical interventions is exceptionally rare. This case report documents the first instance of PRES following the resection of a Spetzler-Martin grade I frontal AVM, emphasizing the importance of early recognition and management of this rare complication. Case Description: A 27-year-old woman underwent navigation-assisted resection of a right frontal AVM. The procedure was uneventful; however, in the immediate postoperative period, she experienced a generalized tonic-clonic seizure, agitation, dysconjugate gaze, and altered consciousness. Brain magnetic resonance imaging revealed diffuse high fluid-attenuated inversion recovery signal abnormalities in the brainstem, cerebellum, thalami, basal ganglia, and cerebral hemispheres, consistent with central PRES. The patient was managed with supportive care, resulting in a full clinical and radiographic recovery within 3 weeks. Follow-up imaging confirmed the resolution of PRES-related changes, and she remained seizure-free after antiseizure medication tapering. Conclusion: This case underscores the critical importance of early neuroimaging in evaluating unexpected postoperative neurological symptoms. Recognizing central PRES and its atypical radiographic patterns enables timely diagnosis and appropriate management, avoiding unnecessary interventions. The pathophysiology likely involves postoperative endothelial dysfunction and disrupted autoregulation. This report underscores the importance of considering PRES in postoperative neurological complications and calls for further research into its mechanisms and optimal management.

Objective: The WADA test is used to determine cerebral language dominance and assess the risk of postoperative amnesia following mesial temporal lobe resection. This study aims to explore the correlation between automated measures of hippocampal volume and WADA memory scores and to evaluate whether these volumetric measurements can reliably predict WADA memory scores.Methods: This study included patients who underwent a comprehensive presurgical assessment along with bilateral WADA testing. Hippocampal volumes were measured from high-resolution brain MRIs using automated software (volBrain), which were harmonized and normalized to whole brain volume. These harmonized and normalized volumes were then correlated with ipsilateral WADA memory scores and stratified according to brain MRI findings. A similar analysis was conducted between hippocampal volume asymmetry and WADA memory score asymmetry (WMA). A Receiver Operating Characteristic (ROC) curve was generated to compare the sensitivity and specificity in predicting successful WADA outcomes based on ipsilateral harmonized normalized hippocampal volumes.Results: In patients with mesial temporal sclerosis (MTS), significant positive correlations were found between harmonized normalized hippocampal volumes and ipsilateral WADA memory scores, as well as between harmonized hippocampal volume asymmetries and WMA. However, no significant correlations were found in patients with epileptogenic lesions other than MTS or those with normal brain MRIs. A harmonized normalized hippocampal volume threshold of ≥ 28.94 units was identified as a predictor of a WADA memory score exceeding 50% following contralateral carotid artery injection, with a sensitivity of 62.1% and a specificity of 100%.Significance: This study indicates that hippocampal volumetry could potentially serve as an alternative to the WADA test in patients with MTS. Conversely, in individuals with normal MRI results or other types of epileptogenic lesions, hippocampal volumetry does not reliably predict memory deficits, necessitating the use of the WADA test or functional MRI for planning resections of mesial temporal structures in the dominant hemisphere.

Background: Antiseizure medications (ASM) exhibit considerable interindividual variability in terms of efficacy and adverse events. Genetic variation is thought to contribute to these differences in clinical outcomes. Specifically, the response to valproic acid (VPA), a widely used ASM, is influenced by multiple pharmacogenetic factors. However, and in contrast to other ASMs such as phenytoin and carbamazepine, there is a paucity of data on the association between VPA and various gene variants. The aim of this study was hence to evaluate the influence of candidate pharmacogenetic variants on VPA efficacy, toxicity and serum concentrations in a homogeneous cohort of patients newly diagnosed with genetic generalized epilepsies (GGE).Methods: In this prospective cohort study, demographic, clinical and treatment outcomes of GGE patients were retrieved from their medical records. Whole exome sequencing was performed in collaboration with Epi25. Gene variants associated with VPA efficacy, metabolism and toxicities were retrieved from PharmGKB. An analysis was then conducted to explore potential associations between these gene variants and VPA clinical outcomes.Results: Of the 166 patients included, 60 (36.1%) experienced treatment failure while 106 (63.9%) achieved treatment success. After adjusting for VPA maintenance dose, carriers of the rs3892097 (CYP2D6) variant were 2.5 times more likely to experience treatment failure compared to wildtype (p = 0.026). The rs1057910 variant (CYP2C9*3) was associated with increased serum VPA concentrations (p = 0.034). Moreover, the rs1137101 variant (LEPR gene, a metabolism regulator) was significantly associated with a higher risk of weight gain (regression coefficient of 3.430 [0.674; 6.186], p = 0.015) and a higher frequency of hair loss (OR = 3.394 [1.157; 9.956], p = 0.026), while the rs4480 variant (SOD2 gene, encoding for a mitochondrial scavenging enzyme) was correlated with a lower frequency of hair loss (OR = 0.276 [0.089; 0.858], p = 0.026).Conclusion: These findings highlight the role of genetic factors in VPA treatment and underscore the potential for developing therapeutic strategies to enhance patient outcomes and minimize adverse effects.