Incidence and Types of Cardiac Arrhythmias in the Peri-Ictal Period in Patients Having a Generalized Convulsive Seizure.

BACKGROUND AND OBJECTIVES: Generalized convulsive seizures (GCSs) are the main risk factor of sudden unexpected death in epilepsy (SUDEP), which is likely due to peri-ictal cardiorespiratory dysfunction. The incidence of GCS-induced cardiac arrhythmias, their relationship to seizure severity markers, and their role in SUDEP physiopathology are unknown. The aim of this study was to analyze the incidence of seizure-induced cardiac arrhythmias, their association with electroclinical features and seizure severity biomarkers, as well as their specific occurrences in SUDEP cases. METHODS: This is an observational, prospective, multicenter study of patients with epilepsy aged 18 years and older with recorded GCS during inpatient video-EEG monitoring for epilepsy evaluation. Exclusion criteria were status epilepticus and an obscured video recording. We analyzed semiologic and cardiorespiratory features through video-EEG (VEEG), electrocardiogram, thoracoabdominal bands, and pulse oximetry. We investigated the presence of bradycardia, asystole, supraventricular tachyarrhythmias (SVTs), premature atrial beats, premature ventricular beats, nonsustained ventricular tachycardia (NSVT), atrial fibrillation (Afib), ventricular fibrillation (VF), atrioventricular block (AVB), exaggerated sinus arrhythmia (ESA), and exaggerated sinus arrhythmia with bradycardia (ESAWB). A board-certified cardiac electrophysiologist diagnosed and classified the arrhythmia types. Bradycardia, asystole, SVT, NSVT, Afib, VF, AVB, and ESAWB were classified as arrhythmias of interest because these were of SUDEP pathophysiology value. The main outcome was the occurrence of seizure-induced arrhythmias of interest during inpatient VEEG monitoring. Moreover, yearly follow-up was conducted to identify SUDEP cases. Binary logistic generalized estimating equations were used to determine clinical-demographic and peri-ictal variables that were predictive of the presence of seizure-induced arrhythmias of interest. The z-score test for 2 population proportions was used to test whether the proportion of seizures and patients with postconvulsive ESAWB or bradycardia differed between SUDEP cases and survivors. RESULTS: This study includes data from 249 patients (mean age 37.2 ± 23.5 years, 55% female) who had 455 seizures. The most common arrhythmia was ESA, with an incidence of 137 of 382 seizures (35.9%) (106/224 patients [47.3%]). There were 50 of 352 seizure-induced arrhythmias of interest (14.2%) in 41 of 204 patients (20.1%). ESAWB was the commonest in 22 of 394 seizures (5.6%) (18/225 patients [8%]), followed by SVT in 18 of 397 seizures (4.5%) (17/228 patients [7.5%]). During follow-up (48.36 ± 31.34 months), 8 SUDEPs occurred. Seizure-induced bradycardia (3.8% vs 12.5%, z = -16.66, p < 0.01) and ESAWB (6.6% vs 25%; z = -3.03, p < 0.01) were over-represented in patients who later died of SUDEP. There was no association between arrhythmias of interest and seizure severity biomarkers (p > 0.05). DISCUSSION: Markers of seizure severity are not related to seizure-induced arrhythmias of interest, suggesting that other factors such as occult cardiac abnormalities may be relevant for their occurrence. Seizure-induced ESAWB and bradycardia were more frequent in SUDEP cases, although this observation was based on a very limited number of SUDEP patients. Further case-control studies are needed to evaluate the yield of arrhythmias of interest along with respiratory changes as potential SUDEP biomarkers.

Drug-resistant idiopathic generalized epilepsy: A meta-analysis of prevalence and risk factors.

BACKGROUND: Idiopathic generalized epilepsy (IGE) is a common epilepsy syndrome with early age onset and generally good seizure outcomes. This study aims to determine the incidence and predictive risk factors for drug-resistant IGE. METHODS: We systematically searched three databases (PubMed, Embase, and Cochrane Library) in November 2022 and included 12 eligible studies which reported long-term outcomes (mean = 14.05) after antiseizure medications (ASMs) from 2001 to 2020. We defined drug resistance as the persistence of any seizure despite ASMs treatment (whether as monotherapies or in combination) given the criteria of drug resistance varied in original studies. A random-effects model was used to evaluate the prevalence of refractory IGE. Studies reporting potential poor prognostic factors were included for subsequent subgroup meta-analysis. RESULTS: The pooled prevalence of drug resistance in IGE cohorts was 27% (95% CI: 0.19-0.36). Subgroup analysis of the risk factors revealed that the psychiatric comorbidities (odds ratio (OR): 4.87, 95% confidence interval (CI): 2.97-7.98), combined three seizure types (absences, myoclonic jerks, and generalized tonic-clonic seizures) (OR: 5.37, 95% CI: 3.16-9.13), the presence of absence seizure (OR: 4.38, 95% CI: 2.64-7.28), generalized polyspike trains (GPT) (OR: 4.83, 95% CI: 2.42-9.64), sex/catamenial epilepsy (OR: 3.25, 95% CI: 1.97-5.37), and status epilepticus (OR: 5.94, 95% CI: 2.23-15.85) increased the risk of poor prognosis. Other factors, including age onset, family history, and side effects of ASMs, were insignificantly associated with a higher incidence of refractory IGE. CONCLUSION: Drug resistance is a severe complication of IGE. Further standardized research about clinical and electroencephalography factors is warranted.

Psychiatric comorbidity in relation to clinical characteristics of epilepsy: A retrospective observational study.

PURPOSE: Prevalence of psychiatric disorders in people with epilepsy is high. However, diagnostic validity and information about the nature of the seizure disorders are often poor in population-based studies. In a well validated and classified patient sample, we investigated psychiatric comorbidity according to clinical characteristics. METHOD: Participants in The Trøndelag Health Study (HUNT) with ≥ 2 diagnostic epilepsy codes during 1987-2019 were identified. Medical records were reviewed, and epilepsy was validated and classified according to ILAE. Psychiatric comorbidity was defined by ICD-codes. RESULTS: In 448 individuals with epilepsy, 35% had at least one psychiatric disorder (anxiety and related disorders 23%, mood disorders 15%, substance abuse and personality disorders 7%, and psychosis 3%). Comorbidity was significantly higher in women than in men (p = 0.007). The prevalence of psychiatric disorders was 37% in both focal and generalized epilepsy. In focal epilepsy, it was significantly lower when etiology was structural (p = 0.011), whereas it was higher when the cause was unknown (p = 0.024). Comorbidity prevalence was 35% both in patients achieving seizure freedom and in those with active epilepsy but 38% among 73 patients with epilepsy resolved. CONCLUSION: Just over one third of people with epilepsy had psychiatric comorbidities. The prevalence was equal in focal and generalized epilepsy but was significantly higher in focal epilepsy of unknown cause compared to lesional epilepsy. Comorbidity was independent of seizure control at last follow-up but was slightly more common in those with resolved epilepsy, often having non-acquired genetic etiologies possibly linked to neuropsychiatric susceptibility.

[Idiopathic generalized epilepsies: Analysis of 101 patients]. / Epilepsias generalizadas idiopáticas: análisis de 101 pacientes.

INTRODUCTION: Idiopathic generalized epilepsies (IGI) are an electroclinical syndrome that includes four subsyndromes according to the ILAE 2017 classification. The long-term prognosis of these syndromes is uncertain due to the scarcity and heterogeneity of the studies. The objective of this study is to analyze the long-term prognosis of these syndromes, pharmacological treatment and the seizure recurrence. METHOD: Observational and retrospective study of a serie of patients diagnosed with EGI. Epidemiological variables, pharmacological treatment, freedom of seizures and recurrence after withdrawal of treatment were collected. RESULTS: We included 101 patients, the majority women (56.4%), with a median evolution of epilepsy of 17 years (interquartile range: 7-31). The most frequent syndrome was juvenile myoclonic epilepsy (46.5%), followed by epilepsy with generalized tonic-clonic seizures alone (25.7%), juvenile absence epilepsy (13.9%) and childhood absence epilepsy (13.9%). The 71.29% were on monotherapy and 20.79% on polytherapy, with significant differences between the different syndromes (P=.001). The most widely used drug was valproic acid. 39.6% presented seizure remission at 5 years, but we did not observe significant differences between the different syndromes (P=.982). The recurrence rate was 71.4% after withdrawal of treatment. CONCLUSION: Juvenile myoclonic epilepsy was the most frequent subtype of IGE. We observed significant differences in terms of polytherapy in the different syndromes, although not in the rates of remission of seizures at one year and at five years. The majority of patients with treatment withdrawal relapsed.

Seizure Analysis Presented to Emergency Department in Saudi Arabia: New VS Chronic Cases.

Background: Epilepsy, characterized by recurrent unprovoked seizures, poses a significant global burden on individuals and healthcare systems. Accurate identification of underlying causes is vital for optimal intervention. However, studies reveal a lack of standardized approaches, potentially resulting in unnecessary investigations. Objective: We aimed to highlight the importance of avoiding unnecessary testing to minimize healthcare costs and resource waste. Methods: In the Emergency Department of King Fahd Hospital of the University (KFUH) in Alkhobar, a retrospective cross-sectional study encompassed 190 patients presenting with seizures from January 1, 2020, to December 31, 2022. The study aimed to elucidate the epidemiological profile and distinguish clinical and demographic factors between new onset seizures and known cases. Results: The study included 190 epilepsy cases, with 51.1% known and 48.9% new onset. Generalized tonic-clonic seizures were prominent (43.2%), and non-compliance (24.2%) was a leading cause. New onset seizures were associated with abnormal CT findings (p=0.025), drug use (74.2%), and intoxication (6.5%). Demographically, Saudis showed higher new onset prevalence (82.8%, p=0.001). Conclusion: The average length of stay was 5.93 hours, and the distribution of new vs. known cases was nearly equal among the 190 patients. Laboratory findings showed no significant associations with either group, mostly falling within the normal range. To optimize care further, we recommend continued refinement of protocols, emphasis on medication compliance.

Genetic generalized epilepsies in adults - challenging assumptions and dogmas.

Genetic generalized epilepsy (GGE) syndromes start during childhood or adolescence, and four commonly persist into adulthood, making up 15-20% of all cases of epilepsy in adults. These four GGE syndromes are childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy and epilepsy with generalized tonic-clonic seizures alone. However, in ~20% of patients with GGE, characteristics of more than one syndrome are present. Novel insights into the genetic aetiology, comorbidities and prognosis of the GGE syndromes have emerged and challenge traditional concepts about these conditions. Evidence has shown that the mode of inheritance in GGE is mostly polygenic. Neuropsychological and imaging studies indicate similar abnormalities in unaffected relatives of patients with GGE, supporting the concept that underlying alterations in bilateral frontothalamocortical networks are genetically determined. Contrary to popular belief, first-line anti-seizure medication often fails to provide seizure freedom in combination with good tolerability. Nevertheless, long-term follow-up studies have shown that with advancing age, many patients can discontinue their anti-seizure medication without seizure relapses. Several outcome predictors have been identified, but prognosis across the syndromes is more homogeneous than previously assumed. Overall, overlap in pathophysiology, seizure types, treatment responses and outcomes support the idea that GGEs are not separate nosological entities but represent a neurobiological continuum.

The burden of disease of idiopathic/genetic generalized epilepsy - A nationwide online survey.

The aim of the study was to assess the self-reported burden of disease in people with idiopathic/genetic generalized epilepsy and risk factors associated with high disease burden. We performed a nationwide online survey on epilepsy characteristics/treatment, quality of life/daily living followed by Standardized Assessment of Personality-Abbreviated Scale, Major Depression Inventory, Barratt Impulsiveness Scale (brief) and the brief Epilepsy Anxiety Survey Instrument. The survey was sent to 275 representative patients with IGE ('Funen cohort') and later publicly distributed via the Danish Epilepsy Association. The characteristics of the responders of the 'Funen cohort' (n = 119) did not differ from non-responders and previously assessed data. Out of 753 persons accessing the public survey, 167 had probable IGE. As compared to the 'Funen cohort', patients from the public survey reported similar age, time since last seizure, years with disease, seizure types, and IGE syndromes but more current and previously tried anti-seizure medications (ASMs). In both cohorts, patients had higher scores for depression, impulsivity, and personality disorders as compared to Danish normal values irrespective of seizure control or medication. Higher depression and anxiety scores but neither impulsivity nor personality disorders were associated with ongoing seizures. Overall health condition was estimated as bad by 28%. In the last four weeks, 20.4% reported limitations of activities of daily living due to epilepsy; 27.8% felt fed up because of their epilepsy. Patients with high subjective disease burden had more current ASMs, shorter time since last seizure and increased scores for depression, anxiety, impulsivity, and personality disorders. In conclusion, having IGE was associated with higher scores for impulsivity, depression, and personality disorders irrespective of seizure control and current treatment. High subjective disease burden was common and associated with ongoing seizures, absence/myoclonic seizures and high scores for impulsivity, depression, anxiety, and personality disorders.

Female preponderance in genetic generalized epilepsies.

INTRODUCTION: Epilepsy is more prevalent in men but Genetic Generalized Epilepsies (GGE) seem to be more common in women. A predominant maternal inheritance has been previously described in GGE. Our objective was to determine sex and inheritance patterns in a GGE population compared to mesial temporal lobe epilepsy with hippocampal sclerosis (MTLEHS). METHODS: We performed a prospective observational study including adult GGE and MTLEHS patients followed up at a tertiary epilepsy center from January 2016 to December 2019. Patients' familial history was obtained by a detailed questionnaire. Clinical and demographic data was retrieved from clinical notes. RESULTS: A cohort of 641 patients, 403 with GGE and 238 with MTLEHS, was analyzed. GGE was more common in women than MTLEHS (58.8% vs 44.5%, OR=1.63, p = 0.004). Compared to MTLEHS patients, more GGE patients had familial history of epilepsy (45.4% vs 25.2%; p<0.001). The GGE group had a higher percentage of female relatives with epilepsy (55% vs 37%; p = 0.006). The prevalence of maternal inheritance was not different between GGE and MTLEHS groups (62.9% vs 57.7%; p = 0.596). Photosensitivity was more common in females than in males (44.7% vs 34.3%, p = 0.036). CONCLUSION: There is a female preponderance in GGE when compared to MTLEHS, as both GGE patients and their affected relatives are more frequently women. The prevalence of maternal inheritance was not higher in GGE than in MTLEHS.

Social outcome and psychiatric comorbidity of generalized epilepsies - A case-control study.

OBJECTIVE: To investigate social outcome and psychiatric comorbidity of patients with idiopathic/genetic generalized epilepsies (IGEs) and its subtypes (epilepsy with generalized tonic-clonic seizures alone [EGTCS], juvenile absence epilepsy [JAE], and juvenile myoclonic epilepsy [JME]). METHODS: A cohort of 402 adult patients with IGE from the Danish island Funen was matched with 4020 randomly selected geography-, age-, and sex-matched controls via the Danish Civil Registration System. Based on register data, we compared social status measured by cohabitant status, educational attainment, income, affiliation to labor market, and psychiatric comorbidity. RESULTS: As compared to controls, patients with IGE had similar cohabitant status but fewer children (no children: 59.0% vs 50.9%), and lower educational level (primary school only: 46.0% vs 37.3%), employment rate (outside of workforce: 56.7% vs 46.5%), and income (low income: 32.6% vs 24.9%) (P < 0.001 for all comparisons). Having IGE was associated with higher a proportion of psychiatric comorbidity (IGE, 22.6%; controls, 13.0%) (P < 0.001). Seizure-free patients did not differ from controls; patients with persistent seizures had lower incomes and employment rates. In the IGE subgroup analyses, JME was associated with worse social status in all parameters studied (eg, 65.9% of JME patients were outside the workforce vs 44.5% of matched controls; P < 0.001), whereas no adverse social status was identified in patients with EGTCS and JAE. SIGNIFICANCE: Patients with IGE in general and JME in particular have poorer social status and more psychiatric comorbidity than matched population controls without epilepsy. Poor seizure control was associated with social status and may contribute to negative socioeconomic consequences associated with IGE.

Sex differences in characteristics of idiopathic generalized epilepsies.

PURPOSE: We compared the demographic, clinical, and electroencephalographic (EEG) characteristics between females and males with idiopathic generalized epilepsy (IGE). METHODS: In this retrospective study, all patients with a clinical diagnosis of IGE were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, from 2008 through 2019. Age, gender, age at seizure onset, seizure type(s), epilepsy risk factors, and EEG findings of all patients were registered routinely. RESULTS: Six hundred one patients with IGE were studied: 361 patients (60%) were females, and 240 people (40%) were males. The mean age at onset of seizures was 1.3 years earlier in males compared with that in females. Myoclonic seizures were more frequently reported by females than that by males. Photoparoxysmal response during intermittent photic stimulation in the EEG laboratory was more often observed in females than that in males. The difference in the syndromic diagnosis between the sexes was significant (p = 0.02). Among male patients, 88% were on valproate, and among female patients, 49% were on valproate (p = 0.0001). At the last follow-up visit, 83 males (61%) and 108 females (49%) were seizure-free (p = 0.02). CONCLUSION: There are significant demographic, clinical, and electrographic differences between females and males with IGEs. The reasons behind these sex differences among patients with IGE are not clear. However, it is likely that sex hormones and sex chromosome genes-related brain differences play a role in the development of these differences. These interesting findings and the proposed hypothesis should be explored in future studies.

Case Report: Nakalanga Syndrome Revisited: Long-Term Follow-Up of a Patient Living in Western Uganda, 1994-2018.

Nakalanga syndrome is a childhood developmental disorder that has been reported from various parts of sub-Saharan Africa with the major sign of retarded growth, regularly combined with physical deformities, impaired mental and pubertal development, and epilepsy. We present a follow-up over a 24-year period of a patient living in the Itwara onchocerciasis focus of western Uganda. We demonstrate the strong similarity of Nakalanga syndrome to the more recently described Nodding syndrome, and we discuss the possible causation of both disorders by onchocerciasis. We suggest that the growing knowledge about the tight interconnections between Nakalanga and nodding syndrome, other forms of epilepsy, and onchocerciasis should be taken into consideration in a revised classification system.

Are Sub-Saharan epileptic people less photosensitive? A Senegalese study of photoparoxysmal response in a reference epilepsy centre.

The photoparoxysmal response (PPR) is defined as the occurrence of generalized spike, spike-wave or polyspike-wave discharges consistently elicited by intermittent photic stimulation (IPS). PPR is not well studied in Sub-Saharan African people. We prospectively studied the epidemiological, clinical, and EEG characteristics of PPR among consecutive patients recorded at the clinical neurophysiology unit of Fann University Hospital (Dakar, Senegal). Among 6,808 EEG recordings including 3,065 pathological EEGs, we collected 56 EEGs with PPR (0.8% of all recorded EEGs and 1.8% of anormal EEGs), from 31 women and 25 men (sex ratio: 0.8). The mean age was 13.3 years (range: 8 months to 59 years). The peak of photosensitivity was found in the range of 6 to 10 years. Of the PPR cases, 12 had clinical manifestations during IPS. Generalized epilepsy was diagnosed in 23 (41%) patients and 18 (32%) had focal epilepsies. The most epileptogenic stimulation frequencies were between 12 and 24 Hz (range: 1-28 Hz). PPR were mainly triggered during eye closure (64%), and 41 patients (73% of PPR cases) were classified as Type 4 (Waltz classification). Our results confirm lower rates of photosensitivity in African Sub-Saharan people compared with others. Although the current data do not support a role of short-term ambient light levels, subject to consistent data from larger cohorts, it may be interesting to study the probable epigenetic-mediated protective role of sunshine against photosensitivity.

Vagus nerve stimulation in patients with therapy-resistant generalized epilepsy.

BACKGROUND: For patients with generalized epilepsy who do not respond to antiseizure medications, the therapeutic options are limited. Vagus nerve stimulation (VNS) is a treatment mainly approved for therapy-resistant focal epilepsy. There is limited information on the use of VNS on generalized epilepsies, including Lennox-Gastaut Syndrome (LGS) and genetic generalized epilepsy (GGE). METHODS: We identified patients with a diagnosis of generalized epilepsy (including LGS and GGE), who underwent VNS implantation at the London Health Sciences Centre and Western University, London, Ontario, since this treatment became available in Canada in 1997 until July 2018. We assessed response to the treatment, including admissions to hospital and complications. RESULTS: A total of 46 patients were included in this study with a history of therapy-resistant generalized epilepsy. The mean age at implantation was 24 years (interquartile range [IQR] = 17.8-31 years), significantly younger in the LGS group (p = 0.02) and 50% (n = 23) were female. The most common etiologies were GGE in 37% (n = 17) and LGS in 63% (n = 29). Median follow-up since VNS implantation was 63 months (IQR: 31-112.8 months). Of the LGS group 41.7% (n = 12) of patients had an overall seizure reduction of 50% or more, and 64.7% (n = 11) in the GGE group without statistical significance between the groups. The best response in seizure reduction was seen in generalized tonic-clonic seizures, with a significant reduction in the GGE group (p = 0.043). There was a reduction of seizure-related hospital admissions from 91.3% (N = 42) preimplantation, to 43.5% (N = 20) postimplantation (p < 0.05). The frequency of side effects due to the stimulation was almost equal in both groups (62.1% in LGS and 64.7% in GGE). CONCLUSIONS: Vagus nerve stimulation should be considered as a treatment in patients with therapy-resistant generalized epilepsy, especially in cases with GGE.

Clinico-electrographic characteristics and classification of genetic generalized epilepsy in Oman.

PURPOSE: There is a lack of information on the annual incidence of genetic generalized epilepsy (GGE) in the Arab countries, especially Oman. Ascertaining the true burden of illness has crucial implications for health policies and priorities. We aim to study the clinico-electrographic characteristics, classification, and annual incidence of GGE in Oman. METHOD: Using the cross-sectional data of EEGs obtained from all patients with GGE who presented to Sultan Qaboos University hospital (major referral center for epilepsy in Oman) from January 2007 to June 2014. Analyses were performed using univariate statistics. RESULTS: Approximately 10,423 patients had EEG studies during the study period of which 376 patients (3.6 %) had EEG abnormalities suggestive of GGE. Forty two percent of the 376 GGE patients were male with ages ranging from 3 to 58 years. We were able to classify 273 patients to one of the GGE syndromes. Forty-three percent of 130 patients had a positive family history of epilepsy in their first or second-degree relatives. The generalized tonic-clonic seizure was the most common seizure type observed in 242 patients (64 %; 95 %CI: 59.2 %-68.9 %). Juvenile myoclonic epilepsy was the most common epilepsy syndrome (41 % of the total GGE patients) encountered in our region. A significant female predominance (9.7 % vs 2.5 %; p = 0.016) was observed in juvenile absence epilepsy. Certain interictal focal EEG abnormalities did not exclude a diagnosis of GGE. An average annual GGE incidence of 2.9 % (95 % CI: 2.6 %-3.2 %) was observed during the study period. CONCLUSION: This hospital-based study is the first of its kind in the Arabian Gulf region, classifying the different subcategories of GGE. Our results indicate that GGE is a common epilepsy subtype in Oman. A prospective population-based epidemiological study is required to estimate the precise frequency of GGE in Oman.

Idiopathic (genetic) generalized epilepsies with absences: clinical and electrographic characteristics and seizure outcome.

PURPOSE: We compared various syndromes of idiopathic (genetic) generalized epilepsy (IGE) with absences based on their demographic, clinical, and electroencephalographic (EEG) findings, and their seizure outcome. METHODS: In this retrospective study, all patients with a clinical diagnosis of childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), idiopathic epilepsy with phantom absences (PAs), and Jeavons syndrome (JS) were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, from 2008 until 2019. Age, gender, age at seizure onset, seizure type(s), epilepsy risk factors, history of seizure-related injuries, EEG findings, and seizure outcome of all patients were registered routinely. RESULTS: Six hundred one patients with IGE were registered at our epilepsy clinic. Two hundred thirteen patients (35.4%) were diagnosed as having IGE with absences [111 patients (52.1%) had JAE, 82 patients (38.5%) had CAE, 12 people (5.6%) had JS, and eight patients (3.8%) had PA]. A history of experiencing generalized tonic-clonic seizures and a history of seizure-related injury were significantly different between the syndromes. There were no significant differences between the syndromes with regard to their EEG findings. Seizure outcome showed a trend to be different between the syndromes of IGE (p = 0.06). CONCLUSION: Syndromes of IGE with absences are common occurrences at epilepsy clinics. Making a syndromic diagnosis could have significant clinical implications. In doing so, interictal EEG cannot differentiate between different syndromes of IGE and the key element in making a correct syndromic diagnosis is a detailed clinical history.

Immunogenetic protective factors in Genetic Generalized Epilepsy.

BACKGROUND: Genetic Generalized Epilepsies (GGEs) are a heterogeneous group of syndromes characterized by generalized seizure activity that affects both hemispheres, with mainly genetic causes. Neuroinflammation has been established as an important mechanism in epileptogenesis. The ability to develop an appropriated immune response is strongly determined by immunogenetic factors. In this setting, our aim was to evaluate potential associations between GGEs and immunogenetic factors. METHODS: The rs16944 (IL-1ß -511 T > C) polymorphism and the HLA-DRB1 locus were genotyped in a Portuguese GGE population. Association with two clinicopathological features, photosensitivity and refractoriness, was investigated. This case-control study included 323 GGE patients (187 F, 136 M, 34.0 ± 13.9 years of age), 145 of which with JME diagnosis (88 F, 57 M, 34.1 ± 14.0 years), and 282 healthy controls (174 F, 108 M, 37.7 ± 11.6 years). RESULTS: Decreased frequencies of the HLA-DRB1*09 and DRB1*13 alleles were observed in the GGE population. HLA-DRB1*07 frequency was increased in JME. Rs16944 allelic frequencies were similar between patients and controls. CONCLUSIONS: These results, not entirely consistent with previous reports, suggest that HLA molecules may have a complex role in epileptogenesis.

Obstructive sleep apnea risk in patients with focal versus generalized epilepsy.

OBJECTIVE: Obstructive sleep apnea (OSA) is common in patients with epilepsy (PWE), and treatment may improve seizure control. However, OSA is often undiagnosed in PWE, and understanding of the risk profile for OSA is important. In this study, we sought to determine if OSA risk is similar in patients with generalized versus focal epilepsy. METHODS: We recruited 115 patients presenting to the Rutgers-Robert Wood Johnson Epilepsy Clinic with focal or generalized epilepsy. Obstructive sleep apnea risk was assessed using the Sleep Apnea Scale of the Sleep Disorders Questionnaire (SA-SDQ). Sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Demographic and clinical information was gathered from the electronic medical record. Unadjusted and adjusted analyses were carried out to assess differences in the SA-SDQ between patients with generalized versus focal epilepsy. Further analyses were done to assess the relationship between seizure frequency, epilepsy type, and the SA-SDQ. RESULTS: Unadjusted mean SA-SDQ scores, as well as scores high enough to represent likely OSA, were similar in patients with generalized versus focal epilepsy. However, in adjusted analyses, patients with generalized epilepsy had a significantly higher mean SA-SDQ score. Older age, higher body mass index (BMI), and a history of hypertension (HTN) were also associated with higher SA-SDQ scores. Sleep Apnea Scale of the Sleep Disorders Questionnaire scores were not significantly affected by the presence of a seizure within the prior one month or six months. Average ESS scores and the percentage of scores consistent with an abnormal degree of sleepiness were statistically similar in patients with generalized versus focal epilepsy. SIGNIFICANCE: Our study suggests that patients with generalized epilepsy have a higher risk of OSA. Further studies measuring OSA directly as well as assessing potential benefits of treatment are needed.

Genetic/idiopathic generalized epilepsies: Not so good as that!

Genetic or idiopathic generalized epilepsies (IGEs) account for 15-20% of all epilepsies. These syndromes have always been considered as good prognosis forms of epilepsy over time; however, for some patients, there is a need to maintain antiseizure drugs (ASD) for a long-time. Drug resistance is not uncommon (7-15%). Lifestyle remains essential and is an integral part of the treatment. Comorbidities such as obstructive sleep apnea syndrome must be considered and treated. A highly underestimated condition is the risk of sudden unexpected death in epilepsy (SUDEP). Very few data are available about the prevalence of SUDEP in IGE, but patients with generalized tonic-clonic seizures (GTCS) are exposed to this risk. IGEs are also characterized by a specific pharmalogical sensisitivity but may be aggravated by ASDs. Historically, the treatment of IGEs has relied mostly on valproate but this drug should be avoided in women of childbearing potential. Women with IGE not treated with valproate are more likely to have unsatisfactory seizure control. Female gender appears now as a new risk factor for drug-resistance. Finally, aside from the typical forms, there are epilepsies that fulfill most of the criteria of IGE, but that have an unusual history with GTCS, absences, falls, and drug resistance. Patients do not have psychomotor regression, brain magnetic resonance imaging is normal. EEG shows generalized fast rhythms during NREM sleep. These patients with refractory generalized epilepsy with sleep-related fast activities do not belong to a well-established syndromic category. These cases are considered "intermediary" between IGE and epileptic encephalopathies.

Clinical characterization of status epilepticus in childhood: a retrospective study in 124 patients.

PURPOSE: The aim of this study is to describe demographic data, semiology and etiology in a pediatric population with status epilepticus (SE) and refractory SE (RSE). METHOD: We retrospectively reviewed patients with the following inclusion criteria: i) age between two months and eighteen years; ii) SE diagnosis; iii) admission from January 2001 to December 2016; iv) available clinical data. RESULTS: We enrolled 124 patients. Mean and median age was 4.6 ± 4.2 years and 3.3 [1.2-7.5] years respectively. SE had a "de novo" onset in 66.9%. Focal convulsive-SE was the most common semiology (50.8%) whilst generalised (32.3%) and nonconvulsive-SE (NCSE) (16.9%) were less represented. Some etiologies showed a different age distribution: febrile in youngest age (p = 0.002, phi 0.3) and idiopathic-cryptogenic in older children (p = 0.016, phi 0.2). A statistical significance correlation was detected between semiology and etiology (p < 0.001, Cramer's V 0.4), chemotherapy and NCSE (n = 6/21 vs 3/103, p < 0.001) as well as PRES and NCSE (n = 7/21 vs 5/103, p < 0.001). Only 17.7% had a RSE. No correlation was found in demographic and clinical data, but NCSE, acute and idiopathic-cryptogenic etiologies were more frequently associated to RSE. Encephalitis was the most common diagnosis in acute etiologies whereas unknown epilepsy in idiopathic-cryptogenic group. CONCLUSION: Most of our findings were previously described however we found a significant role of non-antiepileptic treatments (chemotherapy-dialysis) and comorbidity (PRES) determining acute etiology and NCSE. Acute (mostly encephalitis), idiopathic-cryptogenic (mainly unknown-epilepsy) and NCSE were frequently detected in RSE. In the above mentioned conditions a high level of suspicion was recommended.

Rapid eye movement (REM) sleep and seizure control in idiopathic generalized epilepsy.

BACKGROUND: Sleep and epilepsy are bedfellows, and they affect each other reciprocally. Despite the well-known relationship between sleep and epilepsy, data about the impact of sleep on seizure control and responsiveness to therapy are scarce. OBJECTIVE: The aim of this work was to study the impact of sleep architecture in drug-naïve patients with idiopathic generalized epilepsy (IGE) on seizure control and responsiveness to treatment. METHODS: This is a prospective cohort study conducted on thirty newly diagnosed patients with IGE attending the epilepsy clinic in Alexandria University Hospital in Egypt and thirty healthy controls. All recruited subjects had a baseline overnight polysomnographic study, then patients were given sodium valproate in therapeutic doses and followed up for six months for assessment of seizure control. After follow-up, they were classified into fully controlled and inadequately controlled patients, and a comparison between them was made. RESULTS: Of the recruited patients, 13 were fully controlled. Rapid eye movement (REM) sleep % was significantly lower among inadequately controlled patients (9.01 ±â€¯6.23) than fully controlled group (19.6 ±â€¯9.01) and controls (18.17 ±â€¯4.85) (p = 0.002), and the REM sleep latency was significantly longer among the inadequately controlled patients (115.7 ±â€¯72.8 min) than fully controlled patients (54.6 ±â€¯77.3 min) and controls (68.75 ±â€¯37.95 min) (p = 011). On univariate regression analysis, the Odd's ratio (OR) for REM sleep percentage was 3.04 (p = 0.001). CONCLUSION: Rapid eye movement sleep percentage and latency can contribute to seizure control in IGE.