Magnetic resonance imaging findings in Kenyans and South Africans with active convulsive epilepsy: An observational study.

OBJECTIVE: Focal epilepsy is common in low- and middle-income countries. The frequency and nature of possible underlying structural brain abnormalities have, however, not been fully assessed. METHODS: We evaluated the possible structural causes of epilepsy in 331 people with epilepsy (240 from Kenya and 91 from South Africa) identified from community surveys of active convulsive epilepsy. Magnetic resonance imaging (MRI) scans were acquired on 1.5-Tesla scanners to determine the frequency and nature of any underlying lesions. We estimated the prevalence of these abnormalities using Bayesian priors (from an earlier pilot study) and observed data (from this study). We used a mixed-effect modified Poisson regression approach with the site as a random effect to determine the clinical features associated with neuropathology. RESULTS: MRI abnormalities were found in 140 of 240 (modeled prevalence = 59%, 95% confidence interval [CI]: 53%-64%) of people with epilepsy in Kenya, and in 62 of 91 (modeled prevalence = 65%, 95% CI: 57%-73%) in South Africa, with a pooled modeled prevalence of 61% (95% CI: 56%-66%). Abnormalities were common in those with a history of adverse perinatal events (15/23 [65%, 95% CI: 43%-84%]), exposure to parasitic infections (83/120 [69%, 95% CI: 60%-77%]) and focal electroencephalographic features (97/142 [68%, 95% CI: 60%-76%]), but less frequent in individuals with generalized electroencephalographic features (44/99 [44%, 95% CI: 34%-55%]). Most abnormalities were potentially epileptogenic (167/202, 82%), of which mesial temporal sclerosis (43%) and gliosis (34%) were the most frequent. Abnormalities were associated with co-occurrence of generalized non-convulsive seizures (relative risk [RR] = 1.12, 95% CI: 1.04-1.25), lack of family history of seizures (RR = 0.91, 0.86-0.96), convulsive status epilepticus (RR = 1.14, 1.08-1.21), frequent seizures (RR = 1.12, 1.04-1.20), and reported use of anti-seizure medication (RR = 1.22, 1.18-1.26). SIGNIFICANCE: MRI identified pathologies are common in people with epilepsy in Kenya and South Africa. Mesial temporal sclerosis, the most common abnormality, may be amenable to surgical correction. MRI may have a diagnostic value in rural Africa, but future longitudinal studies should examine the prognostic role.

Developmental epileptic encephalopathy in DLG4-related synaptopathy.

OBJECTIVE: The postsynaptic density protein of excitatory neurons PSD-95 is encoded by discs large MAGUK scaffold protein 4 (DLG4), de novo pathogenic variants of which lead to DLG4-related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy is present in 50% of the individuals, it has not been investigated in detail. We describe here the phenotypic spectrum of epilepsy and associated comorbidities in patients with DLG4-related synaptopathy. METHODS: We included 35 individuals with a DLG4 variant and epilepsy as part of a multicenter study. The DLG4 variants were detected by the referring laboratories. The degree of ID, hypotonia, developmental delay, and motor disturbances were evaluated by the referring clinician. Data on awake and sleep electroencephalography (EEG) and/or video-polygraphy and brain magnetic resonance imaging were collected. Antiseizure medication response was retrospectively assessed by the referring clinician. RESULTS: A large variety of seizure types was reported, although focal seizures were the most common. Encephalopathy related to status epilepticus during slow-wave sleep (ESES)/developmental epileptic encephalopathy with spike-wave activation during sleep (DEE-SWAS) was diagnosed in >25% of the individuals. All but one individual presented with neurodevelopmental delay. Regression in verbal and/or motor domains was observed in all individuals who suffered from ESES/DEE-SWAS, as well as some who did not. We could not identify a clear genotype-phenotype relationship even between individuals with the same DLG4 variants. SIGNIFICANCE: Our study shows that a subgroup of individuals with DLG4-related synaptopathy have DEE, and approximately one fourth of them have ESES/DEE-SWAS. Our study confirms DEE as part of the DLG4-related phenotypic spectrum. Occurrence of ESES/DEE-SWAS in DLG4-related synaptopathy requires proper investigation with sleep EEG.

Coexistence of temporal lobe epilepsy and idiopathic generalized epilepsy.

OBJECTIVE: We investigated the frequency of coexistence of temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE) in a retrospective database study. We also explored the underlying pathomechanisms of the coexistence of TLE and IGE based on the available information, using bioinformatics tools. METHODS: The first phase of the investigation was a retrospective study. All patients with an electro-clinical diagnosis of epilepsy were studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2023. In the second phase, we searched the following databases for genetic variations (epilepsy-associated genetic polymorphisms) that are associated with TLE or syndromes of IGE: DisGeNET, genome-wide association study (GWAS) Catalog, epilepsy genetic association database (epiGAD), and UniProt. We also did a separate literature search using PubMed. RESULTS: In total, 3760 patients with epilepsy were registered at our clinic; four patients with definitely mixed TLE and IGE were identified; 0.1% of all epilepsies. We could identify that rs1883415 of ALDH5A1, rs137852779 of EFHC1, rs211037 of GABRG2, rs1130183 of KCNJ10, and rs1045642 of ABCB1 genes are shared between TLE and syndromes of IGE. CONCLUSION: While coexistence of TLE and IGE is a rare phenomenon, this could be explained by shared genetic variations.

Ezogabine impacts seizures and development in patients with KCNQ2 developmental and epileptic encephalopathy.

Genetic variants in KCNQ2 are associated with a range of epilepsies, from self- limited (familial) neonatal-infantile epilepsy to developmental and epileptic encephalopathy (DEE). We retrospectively reviewed clinical data from eight patients with KCNQ2-related DEE who were treated with ezogabine. Treatment was initiated at a median age of 8 months (range, 7 weeks to 2.5 years) and continued for a median of 2.6 years (range, 7 months to 4.5 years). Five individuals had daily seizures at baseline and experienced at least 50% seizure reduction with treatment, sustained in four. One individual with two to four yearly seizures improved to rare events. Two individuals were seizure-free; treatment targeted cognition and development. Developmental improvements were reported in all eight patients. Weaning of ezogabine was associated with increased seizure frequency (N = 4), agitation and irritability (N = 2), poor sleep (N = 1), and developmental regression (N = 2). These data suggest that treatment with ezogabine is effective at reducing seizure burden and is associated with improved development. Minimal side effects were observed. Weaning was associated with increased seizures and behavioral disturbances in a subset. An approach targeting potassium channel dysfunction with ezogabine is warranted in patients with KCNQ2-related DEE.

Impact of timing of antiseizure medication withdrawal on seizure recurrence in glioma patients: a retrospective observational study.

BACKGROUND: Withdrawal of antiseizure medication treatment (ASM) can be considered after completion of antitumour treatment in glioma patients who no longer suffer from seizures. We compared the risk for recurrent seizures after ASM withdrawal between patients with short-term, medium-term versus long-term seizure freedom after antitumour treatment. METHODS: In this retrospective observational study, the primary outcome was time to recurrent seizure, from the starting date of no ASM treatment up to 36 months follow-up. Cox proportional hazards models were used to study the effect of risk factors on time to recurrent seizure. Stratification was done with information known at baseline. Short-term seizure freedom was defined as ≥ 3 months, but < 12 months; medium-term as 12-24 months; and long-term as ≥ 24 months seizure freedom from the date of last antitumour treatment. RESULTS: This study comprised of 109 patients; 31% (34/109) were in the short-term, 29% (32/109) in the medium-term, and 39% (43/109) in the long-term group. A recurrent seizure was experienced by 47% (16/34) of the patients in the short-term, 31% (10/32) in the medium-term, and 44% (19/43) in the long-term group. Seizure recurrence risk was similar between patients in the short-term group as compared to the medium-term (cause-specific adjusted hazard ratio [aHR] = 0.65 [95%CI = 0.29-1.46]) and long-term group (cause-specific aHR = 1.04 [95%CI = 0.52-2.09]). CONCLUSIONS: Seizure recurrence risk is relatively similar between patients with short-term, medium-term, and long-term seizure freedom after completion of antitumour treatment.

Association of symptoms of psychiatric disease and electroencephalographic patterns in idiopathic generalized epilepsy.

OBJECTIVE: Idiopathic generalized epilepsies (IGE) are genetic epilepsies with alterations of thalamo-frontocortical circuits that play a major role in seizure generation and propagation. Psychiatric diseases and drug resistance are strongly associated, but it remains unknown if they are symptoms of the same pathophysiological process. Hypothesizing that the same network alterations are associated with the frequency of epileptic discharges (ED) and psychiatric symptoms, we here tested the association of self-reported psychiatric symptoms and IGE severity estimated by electroencephalographic (EEG) biomarkers. METHODS: Idiopathic generalized epilepsies patients were asked to fill out four validated psychiatric screening tools assessing symptoms of personality disorders (Standard Assessment of Personality- Abbreviated Scale), depression (Major Depression Inventory), impulsiveness (Barratt Impulsiveness Scale), and anxiety (brief Epilepsy Anxiety Survey Instrument). Blinded to results and clinical data on the patients, we analyzed the patients' EEGs, assessed, and quantified ED. The number and duration of ED divided by the duration of the EEG served as a proxy for the severity of IGE that was correlated with the results of the psychiatric screening. RESULTS: Paired data from 64 patients were available for analysis. The duration of EDs per minute EEG was inversely associated with the time since the last seizure. The number of patients with generalized polyspike trains (n = 2), generalized paroxysmal fast activity (n = 3), and prolonged epileptiform discharges (n = 10) were too low for statistically meaningful analyses. Self-reported symptoms of depression, personality disorder, and impulsivity were not associated with EDs. In contrast, the duration of EDs per minute EEG was associated with self-reported symptoms of anxiety in univariate analyses, not significant, however, following adjustment for time since the last seizure in regression models. SIGNIFICANCE: Self-reported symptoms of psychiatric diseases were not strongly associated with EDs as the best available quantifiable biomarker of IGE severity. As expected, the duration of EDs per minute and anxiety was inversely associated with time since the last seizure. Our data argue against a direct link between the frequency of EDs - as an objective proxy of IGE severity - and psychiatric symptoms.

Shorter duration of slow wave sleep is related to symptoms of depression in patients with epilepsy.

Slow wave sleep duration and spectral abnormalities are related to both epilepsy and depression, but it is unclear how depressive symptoms in patients with epilepsy are affected by slow wave sleep duration and clinical factors, and how the spectral characteristics of slow wave sleep reflect a potential interaction of epilepsy and depression. Long-term video-EEG monitoring was conducted in 51 patients with focal epilepsy, 13 patients with generalized epilepsy, and 9 patients without epilepsy. Slow wave sleep segments were manually marked in the EEG and duration as well as EEG power spectra were extracted. Depressive symptoms were documented with the Beck Depression Inventory (BDI). At least mild depressive symptoms (BDI > 9) were found among 23 patients with focal epilepsy, 5 patients with generalised epilepsy, and 6 patients who had no epilepsy diagnosis. Slow wave sleep duration was shorter for patients with at least mild depressive symptoms (p =.004), independently from epilepsy diagnosis, antiseizure medication, age, and sex. Psychoactive medication was associated with longer slow wave sleep duration (p =.008). Frontal sigma band power (13-15 Hz) during slow wave sleep was higher for patients without epilepsy and without depressive symptoms as compared to patients without depressive symptoms but with focal epilepsy (p =.005). Depressive symptoms affect slow wave sleep duration of patients with epilepsy similarly as in patients without epilepsy. Since reduced slow wave sleep can increase the likelihood of seizure occurrence, these results stress the importance of adequate treatment for patients with epilepsy who experience depressive symptoms.

Methodology for classification and definition of epilepsy syndromes with list of syndromes: Report of the ILAE Task Force on Nosology and Definitions.

Epilepsy syndromes have been recognized for >50 years, as distinct electroclinical phenotypes with therapeutic and prognostic implications. Nonetheless, no formally accepted International League Against Epilepsy (ILAE) classification of epilepsy syndromes has existed. The ILAE Task Force on Nosology and Definitions was established to reach consensus regarding which entities fulfilled criteria for an epilepsy syndrome and to provide definitions for each syndrome. We defined an epilepsy syndrome as "a characteristic cluster of clinical and electroencephalographic features, often supported by specific etiological findings (structural, genetic, metabolic, immune, and infectious)." The diagnosis of a syndrome in an individual with epilepsy frequently carries prognostic and treatment implications. Syndromes often have age-dependent presentations and a range of specific comorbidities. This paper describes the guiding principles and process for syndrome identification in both children and adults, and the template of clinical data included for each syndrome. We divided syndromes into typical age at onset, and further characterized them based on seizure and epilepsy types and association with developmental and/or epileptic encephalopathy or progressive neurological deterioration. Definitions for each specific syndrome are contained within the corresponding position papers.

Accelerated long-term forgetting in adult patients with genetic generalized epilepsy.

OBJECTIVE: Accelerated long-term forgetting (ALF) has been demonstrated among children but not adults with genetic generalized epilepsy (GGE). We investigated (1) how forgetting patterns of verbal and visuospatial material differ between patients with GGE and healthy controls (HCs) and (2) whether ALF is associated with ictal or interictal epileptic activity. METHODS: Forty-two patients with GGE (39, 92.9% experiencing seizures) were compared to 57 HCs in word, logical story, and Rey-Osterrieth complex figure recall tasks by testing after intervals of 30 min and 4 weeks. Ambulatory electroencephalography (EEG) was performed before testing to detect generalized epileptic activity, and patients were asked to document the number of seizures during the 4-week interval. RESULTS: A two-way repeated measures ANOVA indicated that individuals with GGE have different forgetting patterns in comparison to HCs in tasks of word (delay by group interaction F1.5, 142.5  = 4.5, p = .02, ηp2  = .04) and figure (F2, 194  = 15.9, p < .001, ηp2  = .14) but not story (F1.6 151.1  = .5, p = .58, ηp2  = .005) recall. Last learning trial-adjusted scores of word recall were comparable between HCs and patients with epilepsy (PWEs) at 30 min (p = .21) but not at 4 weeks (p = .006). Individuals with GGE performed worse than HCs in figure recall at 30 min and 4 weeks (p < .001), with lower performance after the 4-week interval present only among seizure-positive and EEG-positive individuals (p < .001) during subgroup analysis. Performance on memory tests was unrelated to overall seizure frequency, the number of antiseizure drugs used, and epilepsy duration. SIGNIFICANCE: Our study supports the presence of ALF in a task of word recall among adult patients with GGE. The pattern of forgetting visuospatial information suggests greater forgetting of material before the first delay and ongoing deficits among PWEs with epileptic activity. Future studies should confirm our findings and investigate the functional or pathological mechanisms of memory dysfunction in GGE.

Ictal apnea: A prospective monocentric study in patients with epilepsy.

BACKGROUND AND PURPOSE: Ictal respiratory disturbances have increasingly been reported, in both generalized and focal seizures, especially involving the temporal lobe. Recognition of ictal breathing impairment has gained importance for the risk of sudden unexpected death in epilepsy (SUDEP). The aim of this study was to evaluate the incidence of ictal apnea (IA) and related hypoxemia during seizures. METHODS: We collected and analyzed electroclinical data from consecutive patients undergoing long-term video-electroencephalographic (video-EEG) monitoring with cardiorespiratory polygraphy. Patients were recruited at the epilepsy monitoring unit of the Civil Hospital of Baggiovara, Modena Academic Hospital, from April 2020 to February 2022. RESULTS: A total of 552 seizures were recorded in 63 patients. IA was observed in 57 of 552 (10.3%) seizures in 16 of 63 (25.4%) patients. Thirteen (81.2%) patients had focal seizures, and 11 of 16 patients showing IA had a diagnosis of temporal lobe epilepsy; two had a diagnosis of frontal lobe epilepsy and three of epileptic encephalopathy. Apnea agnosia was reported in all seizure types. Hypoxemia was observed in 25 of 57 (43.9%) seizures with IA, and the severity of hypoxemia was related to apnea duration. Apnea duration was significantly associated with epilepsy of unknown etiology (magnetic resonance imaging negative) and with older age at epilepsy onset (p < 0.001). CONCLUSIONS: Ictal respiratory changes are a frequent clinical phenomenon, more likely to occur in focal epilepsies, although detected even in patients with epileptic encephalopathy. Our findings emphasize the need for respiratory polygraphy during long-term video-EEG monitoring for diagnostic and prognostic purposes, as well as in relation to the potential link of ictal apnea with the SUDEP risk.

SYNGAP1-related developmental and epileptic encephalopathy: The impact on daily life.

SYNGAP1-developmental and epileptic encephalopathy (SYNGAP1-DEE) has been recently featured as a distinct genetic disease characterized by global psychomotor delay mainly involving language, moderate-to-severe cognitive impairment, autism spectrum disorder, and a generalized epilepsy with spontaneous and reflex seizures. The severity and variability of function impairment and the impact on patients' and caregivers' daily life are still poorly acknowledged. The SYNGAP1 Italian Family Association developed a survey, shared online with caregivers, exploring several issues, including: epilepsy outcome, comorbidities, daily-living skills, hospitalizations, rehabilitation treatments, economic burden, and COVID-19 pandemic impact. Caregivers of 13 children and adolescents participated in the survey. They most often show a fine and gross-motor impairment and a drug-resistant epilepsy with possibility to experience pluridaily absence seizures that may lead to periods of psychomotor regressions. Eating and sleep problems are reported in the majority. Most parents are concerned about language impairment, behavioral issues and lack of autonomy in daily-living activities. Specific neuropsychological evaluations for autism should be early considered in order to identify intervention strategies involving alternative communication strategies, which can positively affect behavior and quality of life. Rehabilitation treatment should aim to the acquisition and consolidation of personal autonomy.

Generalized, focal, and combined epilepsies in families: New evidence for distinct genetic factors.

OBJECTIVE: To determine the roles of shared and distinct genetic influences on generalized and focal epilepsy operating in individuals who manifest features of both types (combined epilepsies), and in families manifesting both generalized and focal epilepsies in separate individuals (mixed families). METHODS: We analyzed the deeply phenotyped Epi4K cohort of multiplex families (≥3 affected individuals per family) using methods that quantify the aggregation of phenotypes within families and the relatedness of individuals with different phenotypes within family pedigrees. RESULTS: The cohort included 281 families containing 1021 individuals with generalized (n = 484), focal (304), combined (51), or unclassified (182) epilepsies. The odds of combined epilepsy was higher in relatives of participants with combined epilepsy than in relatives of those with other epilepsy types (odds ratio [OR] 5.2, 95% confidence interval [CI] 1.7-16.1, P = .004). Individuals with combined epilepsy co-occurred in families more often than expected by chance (P = .03). Within mixed families, individuals with each type of epilepsy were more closely related to relatives with the same type than to relatives with other types (P < .001). SIGNIFICANCE: These findings suggest that distinct genetic influences underlie the recently recognized entity of combined epilepsies, just as generalized epilepsies and focal epilepsies each have distinct genetic influences. Mixed families may in part reflect chance co-occurrence of these distinct genetic influences. These conclusions have important implications for molecular genetic studies aimed at identifying genetic determinants of the epilepsies.

Doing without valproate in women of childbearing potential with idiopathic generalized epilepsy: Implications on seizure outcome.

OBJECTIVE: Valproate (VPA) use in women with idiopathic generalized epilepsy (IGE) who are of reproductive age has been a matter of concern and debate, which eventually led to the recent restrictions by regulatory agencies. The aim of our study was to investigate the relationship between VPA avoidance/switch and seizure outcome in women of childbearing potential. METHODS: We retrospectively reviewed data from female patients with IGE, 13-50 years of age, followed since 1980. We evaluated the prescription habits, and the rate of VPA switch for other antiepileptic drugs (AEDs) and its prognostic implications. Seizure remission (SR) was defined as the absence of any seizure type more than 18 months before the last medical observation. The main aim of the study was to assess (a) possible changes in seizure outcome related to VPA switch for other AEDs, especially in patients planning a pregnancy; and (b) possible differences in SR based on the presence/absence of VPA at last observation. RESULTS: One hundred ninety-eight patients were included in the study. Overall SR at last medical observation was 62.7%. SR significantly differed between subjects taking and those not taking VPA (P < .001) at last visit. Multiple regression models showed that taking VPA at last medical observation was strongly associated with SR in both the general population (P < .001) and the juvenile myoclonic epilepsy (JME) group (P < .001). Thirty-six (70.6%) of 51 patients who switched from VPA during follow-up experienced a clinical worsening. Switching back to VPA was more frequently associated with SR at last observation (P < .001). In those patients who substituted VPA in view of a pregnancy, SR and drug burden (monotherapy vs polytherapy) differed significantly before and after the switch. SIGNIFICANCE: Our study suggests that VPA avoidance/switch might be associated with unsatisfactory seizure control in women with IGE who are of childbearing potential. Our findings further highlight the complexity of the therapeutic management of female patients of reproductive age.

Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures.

OBJECTIVE: We aimed to describe the extent of neurodevelopmental impairments and identify the genetic etiologies in a large cohort of patients with epilepsy with myoclonic atonic seizures (MAE). METHODS: We deeply phenotyped MAE patients for epilepsy features, intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder using standardized neuropsychological instruments. We performed exome analysis (whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets to identify genetic etiologies. RESULTS: We analyzed 101 patients with MAE (70% male). The median age of seizure onset was 34 months (range = 6-72 months). The main seizure types were myoclonic atonic or atonic in 100%, generalized tonic-clonic in 72%, myoclonic in 69%, absence in 60%, and tonic seizures in 19% of patients. We observed intellectual disability in 62% of patients, with extremely low adaptive behavioral scores in 69%. In addition, 24% exhibited symptoms of autism and 37% exhibited attention-deficit/hyperactivity symptoms. We discovered pathogenic variants in 12 (14%) of 85 patients, including five previously published patients. These were pathogenic genetic variants in SYNGAP1 (n = 3), KIAA2022 (n = 2), and SLC6A1 (n = 2), as well as KCNA2, SCN2A, STX1B, KCNB1, and MECP2 (n = 1 each). We also identified three new candidate genes, ASH1L, CHD4, and SMARCA2 in one patient each. SIGNIFICANCE: MAE is associated with significant neurodevelopmental impairment. MAE is genetically heterogeneous, and we identified a pathogenic genetic etiology in 14% of this cohort by exome analysis. These findings suggest that MAE is a manifestation of several etiologies rather than a discrete syndromic entity.

Trait impulsivity correlates with active myoclonic seizures in genetic generalized epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is a common subtype of genetic generalized epilepsy (GGE) arising in adolescence and is often associated with executive function (EF) deficits. Some EF components like response inhibition have been extensively evaluated in JME, but few studies have focused upon trait impulsivity or compared between GGE subtypes. The aim of the present study was to compare the association of trait impulsivity in JME with other GGE subtypes. METHODS: Patients with GGE aged between 14 and 40 years (n = 137) were divided into those with JME (n = 92) and those with other GGEs (n = 45: 8 childhood absence epilepsy (CAE), 22 juvenile absence epilepsy (JAE), and 15 epilepsy with generalized tonic-clonic seizures only (EGTCS)). The study participants were recruited through medical records of the general population of Buskerud County and the neighboring municipalities, covering 477,000 people or 9.1% of Norway's total population. All participants underwent a clinical interview including the Barratt Impulsiveness Scale (BIS), an established measure of trait impulsivity. We controlled for other potential predictors of BIS score using analysis of covariance (ANCOVA). RESULTS: There were no differences between JME and other types of GGE for BIS scores, but the presence of myoclonic seizures within the last year, irrespective of GGE subtype, was independently associated with significantly increased behavioral impulsivity. CONCLUSIONS: This study demonstrates that trait impulsivity in GGE is most strongly related to the recent occurrence of myoclonic seizures rather than GGE subtype.

Accelerated long-term forgetting is not evident in adults with genetic generalized epilepsy irrespective of the paradigm used.

Accelerated long-term forgetting (ALF) is a recently discovered memory disorder characterized by intact acquisition and retention over short delays, followed by abnormally fast rates of forgetting. Accelerated long-term forgetting has been repeatedly found in children, but not in adults, with genetic generalized epilepsy (GGE). It is possible that this discrepancy is due to a difference in paradigms used in these studies. The current study aimed to determine whether adults with GGE displayed ALF using two paradigms, one that required complete learning and another one that did not. In addition, we explored the relationships with everyday memory difficulties, working memory, mood, and epilepsy variables. Fourteen adults with GGE were compared with 16 healthy controls on two verbal memory tests: a modified version of the California Verbal Learning Test learned to a criterion of 100% (complete learning) and Logical Memory from the Wechsler Memory Scale (Fourth Edition) presented only once (incomplete learning). Recall was tested at 2 min, 30 min, and 1 week, and recognition at 1 week only. Working memory, everyday memory, and mood were also assessed. We found no evidence of ALF on either of the two verbal memory paradigms on recall or recognition tests although patients displayed significantly poorer working memory. Moreover, patients with GGE reported significantly more memory difficulties in everyday life, and these were associated with greater mood disturbances but not with memory tests scores. Greater number of antiepileptic drugs and epilepsy severity also related to memory scores on some tests. Our study suggests that a difference in paradigms used to investigate ALF in children and adults with GGE is unlikely to explain the differences in findings. The study tentatively raises a hypothesis that developmental factors may play a role in ALF in patients with GGE; children with GGE may grow out of ALF. Nevertheless, this hypothesis would need to be tested in a longitudinal study that would follow patients from childhood to early adulthood.

Novel mutation of SCN9A gene causing generalized epilepsy with febrile seizures plus in a Chinese family.

Generalized epilepsy with febrile seizures plus (GEFS+) is a complex familial epilepsy syndrome. It is mainly caused by mutations in SCN1A gene, encoding type 1 voltage-gated sodium channel α-subunit (NaV1.1), and GABRA1 gene, encoding the α1 subunit of the γ-aminobutyric acid type A (GABAA) receptor, while seldom related with SCN9A gene, encoding the voltage-gated sodium channel NaV1.7. In this study, we investigated a Chinese family with an autosomal dominant form of GEFS+. DNA sequencing of the whole coding region revealed a novel heterozygous nucleotide substitution (c.5873A>G) causing a missense mutation (p.Y1958C). This mutation was predicted to be deleterious by three different bioinformatics programs (The polyphen2, SIFT, and MutationTaster). Our finding reports a novel likely pathogenic SCN9A Y1958C heterozygous mutation in a Chinese family with GEFS+ and provides additional supports that SCN9A variants may be associated with human epilepsies.

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.

A new approach for assessing executive functions in everyday life, among adolescents with Genetic Generalised Epilepsies.

Studies have characterised relationships between cognitive status and a variety of clinical epilepsy factors. The aim of this study was to describe a new approach for assessing executive functions in everyday life and its unique expression in adolescents with Genetic Generalised Epilepsies (GGEs) compared with typical peers. Twenty adolescents with a diagnosis of GGEs and 20 typical healthy peers, matched by age and gender, were studied. Assessment of everyday executive function was carried out using: (1) the Weekly Calendar Planning Activity (WCPA), a direct performance based and outcome measure of strategy use and cognitive performance; and (2) Behavior Rating Inventory of Executive Function (BRIEF) parental report. Adolescents with GGEs demonstrated significantly less accuracy, less efficiency and fewer strategies used, as measured by the WCPA. Parents of adolescents with GGEs rated their child's daily performance as less efficient compared with typical peers. Better ratings of executive function (low BRIEF score) were associated with greater WCPA accuracy in the entered appointments. The WCPA provides a useful evaluation of cognitive performance for adolescents with GGEs and a functionally relevant information on task efficiency, self-monitoring and effective strategy use. Direct observation of performance supplements parental ratings and has strong potential to guide intervention and measure outcomes.

Two Different Manifestations of Neonatal Vascular Injury: Dyke-Davidoff-Masson Syndrome and Crossed Cerebellar Atrophy.

Dyke-Davidoff-Masson syndrome (DDMS) was first described in 1933 as a clinical condition characterized by hemiatrophy, hyperpneumatization of paranasal sinuses, contralateral hemiparesis, facial asymmetry, seizures, and mental retardation.1 DDMS can be of 2 types: congenital and acquired. The congenital type can be caused by various conditions experienced during fetal or early childhood development, including ischemia, infarction, trauma, infections, and hemorrhage. The acquired type is mostly associated with hemorrhage, trauma, and infections experienced after 1 month of age. DDMS can manifest alone or can be accompanied by crossed cerebellar atrophy (CCA) which is a newly discovered radiological marker characterized by prominent cortical sulci and loss of cerebellar parenchyma. The congenital type of DDMS is known to be accompanied by ipsilateral cerebellar atrophy and the acquired type is known to be accompanied by contralateral cerebellar atrophy.2,3 Supratentorial events may lead to destruction in the cortico-ponto-cerebellar pathways, mostly in the contralateral side of the body (80%) due to decussation.4 In this report, we present 2 cases of DDMS accompanied by CCA to emphasize the possibility that the DDMS cases with severe intrauterine hemorrhage can be accompanied by contralateral CCA and migratory abnormalities rather than ipsilateral CCA and clinical survey.