Focal electroclinical features in generalized tonic-clonic seizures: Decision flowchart for a diagnostic challenge.

OBJECTIVE: Bilateral tonic-clonic seizures with focal semiology or focal interictal electroencephalography (EEG) can occur in both focal and generalized epilepsy types, leading to diagnostic errors and inappropriate therapy. We investigated the prevalence and prognostic values of focal features in patients with idiopathic generalized epilepsy (IGE), and we propose a decision flowchart to distinguish between focal and generalized epilepsy in patients with bilateral tonic-clonic seizures and focal EEG or semiology. METHODS: We retrospectively analyzed video-EEG recordings of 101 bilateral tonic-clonic seizures from 60 patients (18 with IGE, 42 with focal epilepsy). Diagnosis and therapeutic response were extracted after ≥1-year follow-up. The decision flowchart was based on previous observations and assessed concordance between interictal and ictal EEG. RESULTS: Focal semiology in IGE was observed in 75% of seizures and 77.8% of patients, most often corresponding to forced head version (66.7%). In patients with multiple seizures, direction of head version was consistent across seizures. Focal interictal epileptiform discharges (IEDs) were observed in 61.1% of patients with IGE, whereas focal ictal EEG onset only occurred in 13% of seizures and 16.7% of patients. However, later during the seizures, a reproducible pattern of 7-Hz lateralized ictal rhythm was observed in 56% of seizures, associated with contralateral head version. We did not find correlation between presence of focal features and therapeutic response in IGE patients. Our decision flowchart distinguished between focal and generalized epilepsy in patients with bilateral tonic-clonic seizures and focal features with an accuracy of 96.6%. SIGNIFICANCE: Focal semiology associated with bilateral tonic-clonic seizures and focal IEDs are common features in patients with IGE, but focal ictal EEG onset is rare. None of these focal findings appears to influence therapeutic response. By assessing the concordance between interictal and ictal EEG findings, one can accurately distinguish between focal and generalized epilepsies.

Resting-state brain activity distinguishes patients with generalised epilepsy from others.

PURPOSE: Epilepsy is a prevalent neurological disorder characterised by repetitive seizures. It is categorised into three types: generalised epilepsy (GE), focal epilepsy (FE), and combined generalised and focal epilepsy. Correctly subtyping the epilepsy is important to select appropriate treatments. The types are mainly determined (i.e., diagnosed) by their semiologies supported by clinical examinations, such as electroencephalography and magnetoencephalography (MEG). Although these examinations are traditionally based on visual inspections of interictal epileptic discharges (IEDs), which are not always visible, alternative analyses have been anticipated. We examined if resting-state brain activities can distinguish patients with GE, which would help us to diagnose the type of epilepsy. METHODS: The 5 min resting-state brain activities acquired using MEG were obtained retrospectively from 15 patients with GE. The cortical source of the activities was estimated at each frequency band from delta to high-frequency oscillation (HFO). These estimated activities were compared with reference datasets from 133 healthy individuals and control data from 29 patients with FE. RESULTS: Patients with GE showed larger theta in the occipital, alpha in the left temporal, HFO in the rostral deep regions, and smaller HFO in the caudal ventral regions. Their area under the curves of the receiver operating characteristic curves was around 0.8-0.9. The distinctive pattern was not found for data from FE. CONCLUSION: Patients with GE show distinctive resting-state brain activity, which could be a potential biomarker and used complementarily to classical analysis based on the visual inspection of IEDs.

Idiopathic Generalized Epilepsy: Misunderstandings, Challenges, and Opportunities

The idiopathic generalized epilepsies (IGE) make up a fifth of all epilepsies, but <1% of epilepsy research. This skew reflects misperceptions: diagnosis is straightforward, pathophysiology is understood, seizures are easily controlled, epilepsy is outgrown, morbidity and mortality are low, and surgical interventions are impossible. Emerging evidence reveals that patients with IGE may go undiagnosed or misdiagnosed with focal epilepsy if EEG or semiology have asymmetric or focal features. Genetic, electrophysiologic, and neuroimaging studies provide insights into pathophysiology, including overlaps and differences from focal epilepsies. IGE can begin in adulthood and patients have chronic and drug-resistant seizures. Neuromodulatory interventions for drug-resistant IGE are emerging. Rates of psychiatric and other comorbidities, including sudden unexpected death in epilepsy, parallel those in focal epilepsy. IGE is an understudied spectrum for which our diagnostic sensitivity and specificity, scientific understanding, and therapies remain inadequate.

Juvenile idiopathic epilepsy in Egyptian Arabian foals, a potential animal model of self-limited epilepsy in children.

BACKGROUND: Juvenile idiopathic epilepsy (JIE) is categorized as a generalized epilepsy. Epilepsy classification entails electrocortical characterization and localization of epileptic discharges (ED) using electroencephalography (EEG). HYPOTHESIS/OBJECTIVES: Characterize epilepsy in Egyptian Arabian foals with JIE using EEG. ANIMALS: Sixty-nine foals (JIE, 48; controls, 21). METHODS: Retrospective study. Inclusion criteria consisted of Egyptian Arabian foals: (1) JIE group diagnosed based on witnessed or recorded seizures, and neurological and EEG findings, and (2) control group of healthy nonepileptic age-matched foals. Clinical data were obtained in 48 foals. Electroencephalography with photic stimulation was performed under standing sedation in 37 JIE foals and 21 controls. RESULTS: Abnormalities on EEG were found in 95% of epileptic foals (35 of 37) and in 3 of 21 control asymptomatic foals with affected siblings. Focal ED were detected predominantly in the central vertex with diffusion into the centroparietal or frontocentral regions (n = 35). Generalization of ED occurred in 14 JIE foals. Epileptic discharges commonly were seen during wakefulness (n = 27/37 JIE foals) and sedated sleep (n = 35/37 JIE foals; 3/21 controls). Photic stimulation triggered focal central ED in 15 of 21 JIE foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Juvenile idiopathic epilepsy has a focal onset of ED at the central vertex with spread resulting in clinical generalized tonic-clonic seizures with facial motor activity and loss of consciousness. Electroencephalography with photic stimulation contributes to accurate phenotyping of epilepsy. Foals with this benign self-limiting disorder might serve as a naturally occurring animal model for self-limited epilepsy in children.

Epilepsy with generalized tonic-clonic seizures alone: Electroclinical features and prognostic patterns.

OBJECTIVE: Epilepsy with generalized tonic-clonic seizures alone (GTCA) is a common but poorly characterized idiopathic generalized epilepsy (IGE) syndrome. Hence, we investigated electroclinical features, seizure outcome, and antiseizure medication (ASM) withdrawal in a large cohort of GTCA patients. METHODS: In this multicenter retrospective study, GTCA patients defined according to the diagnostic criteria of the International League Against Epilepsy (2022) were included. We investigated prognostic patterns, drug resistance at the last visit, and ASM withdrawal, along with their prognostic factors. RESULTS: We included 247 patients with a median (interquartile range [IQR]) age at onset of 17 years (13-22) and a median follow-up duration of 10 years (IQR = 5-20). Drug resistance at the last visit was observed in 40 (16.3%) patients, whereas the median latency to achieve 2-year remission was 24 months (IQR = 24-46.5) with a median number of 1 (IQR = 1-2) ASM. During the long-term follow-up (i.e., 202 patients followed ≥5-years after the first ASM trial), 69 (34.3%) patients displayed an early remission pattern and 36 (17.9%) patients displayed a late remission pattern, whereas 16 (8%) and 73 (36.3%) individuals had no-remission and relapsing-remitting patterns, respectively. Catamenial seizures and morning predominance of generalized tonic-clonic seizures (GTCS) independently predicted drug resistance at the last visit according to multivariable logistic regression. Treatment withdrawal was attempted in 63 (25.5%) patients, with 59 (93.7%) of them having at least a 12-month follow-up after ASM discontinuation. At the last visit, 49 (83%) of those patients had experienced GTCS recurrence. A longer duration of seizure freedom was the only factor predicting a higher chance of successful ASM withdrawal according to multivariable Cox regression. SIGNIFICANCE: GTCA could be considered a relatively easily manageable IGE syndrome, with a low rate of drug resistance and a high prevalence of early response to treatment. Nevertheless, a considerable proportion of patients experience relapsing patterns of seizure control, highlighting the need for appropriate counseling and lifestyle recommendations.

Prenatal diagnosis of developmental and epileptic encephalopathy 9 with a 10.05-Mb microdeletion at Xq21.31q22.1 inherited from mother: A case report and literature review.

BACKGROUND: Developmental and epileptic encephalopathy 9 (DEE9) is characterized by early infantile seizures and mild-to-severe neuropsychiatric symptoms. Despite being an X-linked dominant disorder, DEE9 mainly affects heterozygous females or mosaic males, while hemizygous males are less affected. PCDH19 gene has been documented as the causative gene. METHODS: Karyotyping analysis and copy number variation sequencing (CNV-seq) were performed on a pregnant woman with epilepsy, together with her husband, son, and fetus. RESULTS: A disease-causing microdeletion, seq[GRCh37] del(X)(q21.31q22.1) (90310001-100360000), was identified in the pregnant woman and her female fetus. The microdeletion includes the entire PCDH19 gene and is classified as "pathogenic" according to the American College of Medical Genetics and Genomics guidelines. CONCLUSION: In this case study, we have not only identified the epilepsy type of the woman as DEE9 but have also made an unfavorable prognosis for her fetus. Our findings from this prenatal case provide valuable clinical resources for prenatal diagnosis and genetic counseling, while also implying the potential of CNV-seq as a viable method for uncovering PCDH19-related epilepsy.

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.

Idiopathic generalized epilepsy with phantom absences, absence status, and generalized tonic-clonic seizures: A case report.

RATIONALE: Phantom absences refer to mild and short-lasting absence seizures, which are usually accompanied by infrequent generalized tonic-clonic seizures and absence status. Generally, phantom absences do not impair the individual neurological functions. Herein, we report the case of a young woman with idiopathic generalized epilepsy, phantom absences, absence status, and generalized tonic-clonic seizures. PATIENT CONCERNS: A 31-year-old woman presented with a 16-year history of paroxysmal convulsions. DIAGNOSES: Electroencephalogram (EEG) showed recurrent universal and synchronized 3~4 Hz spike waves and spike-slow waves in the interictal phase with normal background activity. During the ictal phases, EEG revealed bursts of 3~4 Hz spike waves and spike-slow waves that were universal, synchronized, and symmetrical. Additionally, there was 1 seizure episode induced by a 3-Hz flash in the current case. Based on these findings, a diagnosis of idiopathic generalized epilepsy was made. INTERVENTIONS: The patient was treated with oral sodium valproate, and the epileptic seizures were controlled. OUTCOMES: The frequency of absence seizures was significantly reduced and there were no generalized tonic-clonic seizures. LESSONS: Idiopathic generalized epilepsy with phantom absences, absence status, and generalized tonic-clonic seizures is an extremely rare condition. EEG is the exclusive method for diagnosis. Antiepileptic drugs are effective for controlling epileptic seizures in this disease.

[Idiopathic generalized epilepsies]. / Epilepsias generalizadas idiopáticas.

Idiopathic generalized epilepsies (IGE) is a group of epilepsies age-dependent, a subgroup of EGG genetic generalized epilepsies, with electro-clinical features and polygenic inheritance. Four syndromes comprising the IGEs: childhood absence epilepsy (CAD), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and generalized tonic-clonic seizures epilepsy. Clinically characterized by the presence of one or a combination of absence seizures, myoclonus, tonic-clonic, or myoclonictonic- clonic with common electroencephalographic patterns of 2.5-5.5 Hz generalized spike-wave and activated by hyperventilation or photic stimulation. They generally have a good prognosis for seizure control, not evolve to an epileptic encephalopathy. Frequent clinical overlap between the first three, being able to evolve between them; the probability and age of remission varies in each one. About 80% responding to broad-spectrum anti-seizure drugs such as valproic acid, may worsen with sodium or GABAergic blockers. Development is typically normal; however, they are frequently associated with mood disorders, attentiondeficit/ hyperactivity disorder (ADHD), and learning disabilities, but do not have cognitive deficits. The recognition of this group of EGI is important for the adequate use of the resources, avoiding unnecessary studies, adequate orientation of the prognosis and an optimal treatment.

Las epilepsias generalizadas idiopáticas (EGI) son un grupo de epilepsias generalizadas edad dependientes, subgrupo de las Epilepsias genéticas generalizadas(EGG), con hallazgos electro-clínicos característicos y herencia poligénica. Las EGI incluyen las cuatro epilepsias generalizadas clásicas más comunes de las EGG: la epilepsia de ausencias de la infancia (EAI), epilepsia de ausencias juveniles (EAJ), epilepsia mioclónica juvenil (EMJ) y la epilepsia con crisis tónico clónicas generalizadas. Clínicamente caracterizadas por la presencia de una o una combinación de crisis de ausencias, mioclonías, tónicaclónicas omioclónica-tónica-clónicas con patrón electroencefalográfico de punta onda lenta de 2.5 a 6cps y activación con la hiperventilación y fotoestimulación, Sobresalen de las EGG por compartir atributos particulares como el buen pronóstico con control frecuente de las crisis, la no evolución a encefalopatías epilépticas, frecuente superposición clínica entre las tres primeras, pudiendo evolucionar entre ellas; la probabilidad y edad de remisión varía en cada una. Más del 80% se controlan adecuadamente con medicamentos anticrisis de amplio espectro como el ácido valproico y pueden empeorar con bloqueadores de sodio o gabaérgicos. Si bien los pacientes son previamente sanos con neurodesarrollo normal, frecuentemente se asocian con trastornos del ánimo, déficit de atención e hiperactividad (TDAH) y problemas del aprendizaje pero no presentan déficit cognitivo. El reconocimiento de este grupo de EGI es importante para el uso adecuado del recurso, evitando estudios innecesarios, adecuada orientación del pronóstico y un tratamiento óptimo.

Precision medicine: Vinpocetine as a potential treatment for GABRG2-related epilepsy.

INTRODUCTION: Pathogenic variants of the GABRG2 gene, encoding a GABAA receptor subunit, have been associated with various epileptic syndromes and drug-resistant epilepsy. Vinpocetine has been previously reported efficacious in a patient harboring a GABRB3 pathogenic variant, encoding another GABAA receptor subunit. CASE PRESENTATION: We describe a patient with GABRG2-related drug-resistant epilepsy who improved after vinpocetine treatment. An 8-year-old boy with a family history of epilepsy was diagnosed with early onset absence epilepsy at 6 months of age and was treated unsuccessfully with sodium valproate and ethosuximide. At 6 years of age, he developed generalized tonic-clonic seizures and increasing absences despite lamotrigine add-on as well as learning difficulties. Brain MRI was normal and video-EEG telemetry showed multiple myoclonic absences. An epilepsy gene panel analysis showed a GABRG2 pathogenic variant, c.254 T > A p.(Ile85Lys) (NM_198903.2), inherited from the proband's father. Seizures were resistant to several medications. After treatment with vinpocetine add-on, the patient showed a dramatic initial response, further reduction of seizures, and improvement of his cognitive functions. CONCLUSION: This case illustrates that vinpocetine could be considered in drug-resistant epilepsies related to GABRG2 in accordance with the principles of precision medicine.

Calgary score and modified calgary score in the differential diagnosis between syncope and genetic generalized epilepsy in children.

The purpose of the study is to explore the use of Calgary scoring (CS) and Modified Calgary scoring (MCS) in the differentiation of genetic generalized epilepsy and syncope in children. The study involved 117 patients aged < 18 years who presented to our hospital's pediatric neurology outpatient clinic with TLOC between June 2020 and June 2022. In addition to CS and MCS scoring, all patients were subjected to statistical analysis based on their age, sex, number of episodes and distribution during the day, duration of syncope, and family history. Seventy-one patients with syncope and 46 with epilepsy were included in the study. At a CS value > - 1, sensitivity was 86.9% and specificity 63.4%, while at an MCS value > - 1, sensitivity was 76.1% and specificity 71.8%. CS had less specificity and sensitivity in predicting epilepsy when focal epilepsies were excluded. Abnormal behavior noted by bystanders, including witnessed unresponsive, unusual posturing, or limb jerking? (Q5) emerged as the most important question for the detection of epilepsy. Compared with other syncope findings, loss of consciousness during prolonged sitting or standing (Q9) emerged as the most important for the detection of syncope.

Reading epilepsy today: A scoping review and meta-analysis of reports of the last three decades.

BACKGROUND AND AIM: Reading-induced seizures are presumed to be rare phenomena attributed to an epilepsy syndrome not clearly belonging to either focal or generalized epilepsies. The aim of the article was to summarize knowledge and recent developments in the field of reading-induced seizures by reviewing all cases for which data were reported within the last three decades. METHODS: A scoping systematic review of demographic, clinical, electroencephalography (EEG) and imaging data of cases with reading-induced seizures reported in PubMed and Web of Science between 1991-01-01 and 2022-08-21 and a meta-analysis of the findings. RESULTS: The review included 101 case reports of epilepsy with reading-induced seizures (EwRIS) from 42 articles. The phenomenon was more prevalent among males (67, 66.3% vs. 34, 33.7%) with an average age of onset of 18.3 ± 7.9 years. When reported, 30.8% of patients had a family history of epilepsy. Orofacial reflex myocloni (ORM) were the most frequent manifestation (68, 67.3% cases), other presentations, mostly in addition to ORM, included visual, sensory or cognitive symptoms, non-orofacial myoclonic seizures, and absence seizures. Within the sample, 75 (74.3%) patients were identified as having primary reading epilepsy (PRE), 13 (12.9%) idiopathic generalised epilepsy (IGE) and 13 (12.9%) focal epilepsies. Advanced EEG and functional imaging data suggest that the basic mechanism of reading-induced seizures is probably similar despite different symptoms and consists of upregulation of the complex cerebral subsystem involved in reading. Ictogenesis and resulting symptomatology may then depend on predominant sensory or proprioceptive stimuli during reading. CONCLUSION: In most cases, reading-induced seizures were confirmed to belong to a particular epilepsy syndrome of PRE. However, there were substantial subgroups with IGE and focal epilepsies. Most likely, reading-induced seizures occur as an abnormal response to extero- or proprioceptive input into an upregulated cortical network subserving reading. Most recent researchers consider EwRIS a system epilepsy.

Diagnosis and treatment of late-onset myoclonic epilepsy in Down syndrome (LOMEDS): A systematic review with individual patients' data analysis.

INTRODUCTION: The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS), in people suffering from cognitive decline in Down syndrome (DS). In this review, we analyzed available data on the diagnostic and therapeutic management of individuals with LOMEDS. METHODS: We performed a systematic search of the literature to identify the diagnostic and therapeutic management of patients with LOMEDS. The following databases were used: PubMed, Google Scholar, EMBASE, CrossRef. The protocol was registered on PROSPERO (registration code: CRD42023390748). RESULTS: Data from 46 patients were included. DS was diagnosed according to the patient's clinical and genetic characteristics. Diagnosis of Alzheimer's dementia (AD) preceded the onset of epilepsy in all cases. Both myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were reported, the latter preceding the onset of MS in 28 cases. EEG was performed in 45 patients, showing diffuse theta/delta slowing with superimposed generalized spike-and-wave or polyspike-and-wave. A diffuse cortical atrophy was detected in 34 patients on neuroimaging. Twenty-seven patients were treated with antiseizure medication (ASM) monotherapy, with reduced seizure frequency in 17 patients. Levetiracetam and valproic acid were the most used ASMs. Up to 41% of patients were unresponsive to first-line treatment and needed adjunctive therapy for seizure control. CONCLUSIONS: AD-related pathological changes in the brain may play a role in LOMEDS onset, although the mechanism underlying this phenomenon is still unknown. EEG remains the most relevant investigation to be performed. A significant percentage of patients developed a first-line ASM refractory epilepsy. ASMs which modulate the glutamatergic system may represent a good therapeutic option.

Clinical presentation and evaluation of epilepsy with eyelid myoclonia: Results of an international expert consensus panel.

OBJECTIVE: The objective of this study was to determine areas of consensus among an international panel of experts for the clinical presentation and diagnosis of epilepsy with eyelid myoclonia (EEM; formerly known as Jeavons syndrome) to improve a timely diagnosis. METHODS: An international steering committee was convened of physicians and patients/caregivers with expertise in EEM. This committee summarized the current literature and identified an international panel of experts (comprising 25 physicians and five patients/caregivers). This international expert panel participated in a modified Delphi process, including three rounds of surveys to determine areas of consensus for the diagnosis of EEM. RESULTS: There was a strong consensus that EEM is a female predominant generalized epilepsy syndrome with onset between 3 and 12 years of age and that eyelid myoclonia must be present to make the diagnosis. There was a strong consensus that eyelid myoclonia may go unrecognized for years prior to an epilepsy diagnosis. There was consensus that generalized tonic-clonic and absence seizures are typically or occasionally seen in patients. There was a consensus that atonic or focal seizures should lead to the consideration of reclassification or alternate diagnoses. There was a strong consensus that electroencephalography is required, whereas magnetic resonance imaging is not required for diagnosis. There was a strong consensus to perform genetic testing (either epilepsy gene panel or whole exome sequencing) when one or a combination of factors was present: family history of epilepsy, intellectual disability, or drug-resistant epilepsy. SIGNIFICANCE: This international expert panel identified multiple areas of consensus regarding the presentation and evaluation of EEM. These areas of consensus may be used to inform clinical practice to shorten the time to the appropriate diagnosis.

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.

Spike and wave discharges detection in genetic absence epilepsy rat from Strasbourg and patients with genetic generalized epilepsy.

OBJECTIVE: Generalised spike and wave discharges (SWDs) are pathognomonic EEG signatures for diagnosing absence seizures in patients with Genetic Generalized Epilepsy (GGE). The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is one of the best-validated animal models of GGE with absence seizures. METHODS: We developed an SWDs detector for both GAERS rodents and GGE patients with absence seizures using a neural network method. We included 192 24-hour EEG sessions recorded from 18 GAERS rats, and 24-hour scalp-EEG data collected from 11 GGE patients. RESULTS: The SWDs detection performance on GAERS showed a sensitivity of 98.01% and a false positive (FP) rate of 0.96/hour. The performance on GGE patients showed 100% sensitivity in five patients, while the remaining patients obtained over 98.9% sensitivity. Moderate FP rates were seen in our patients with 2.21/hour average FP. The detector trained within our patient cohort was validated in an independent dataset, TUH EEG Seizure Corpus (TUSZ), that showed 100% sensitivity in 11 of 12 patients and 0.56/hour averaged FP. CONCLUSIONS: We developed a robust SWDs detector that showed high sensitivity and specificity for both GAERS rats and GGE patients. SIGNIFICANCE: This detector can assist researchers and neurologists with the time-efficient and accurate quantification of SWDs.

Photosensitive occipital lobe epilepsy: Delineation of an under-recognized reflex epilepsy syndrome according to the new ILAE criteria and long-term follow-up.

OBJECTIVE: Photosensitive occipital lobe epilepsy (POLE) should be suspected in patients with occipital lobe seizures triggered by photic stimuli, who have normal motor-mental development and brain imaging. We aimed to examine the clinical, electrophysiological, and prognostic features of POLE, which is a rare and under-investigated syndrome. METHODS: Archives from two tertiary epilepsy centers were retrospectively scanned and patients with normal neurological examination and cranial imaging were identified with POLE if they had: (1) seizures consistently triggered by photic stimuli; (2) non-motor seizures with visual symptoms; and (3) photosensitivity documented on EEG. The clinical and electrophysiological features and prognostic factors were evaluated for patients who had follow-up ≥5 years. RESULTS: We identified 29 patients diagnosed with POLE with a mean age of 20.1 ± 7.6 years. In one-third of the patients, POLE syndrome overlapped with genetic generalized epilepsy (GGE). The overlap group had higher rates of febrile seizure history and self-induction; when compared to pure POLE patients, their EEGs showed more frequent interictal generalized epileptic discharges and posterior multiple spikes during intermittent photic stimulation. During long-term follow-up, the remission rate for POLE was 80%, but EEG photosensitivity persisted in three quarters of patients despite clinical remission, and more than half had relapsed after clinical remission. SIGNIFICANCE: This first long-term follow-up study, utilizing newly suggested criteria of the International League Against Epilepsy, showed that POLE syndrome shows a notable overlap with GGE but also has distinctive features. POLE has a good prognosis; however, relapses are common, and photosensitivity persists as an EEG finding in the majority of patients.

Differential diagnosis of familial adult myoclonic epilepsy.

OBJECTIVE: Familial adult myoclonic epilepsy (FAME) is an under-recognized disorder characterized by cortical myoclonus, generalized tonic-clonic seizures, and additional clinical symptoms, which vary depending on the FAME subtype. FAME is caused by pentanucleotide repeat expansions of intronic TTTCA/TTTTA in different genes. FAME should be distinguished from a range of differential diagnoses. METHODS: The differential diagnoses and frequent presentations leading to misdiagnosis of FAME were investigated from the available literature and reported based on an expert opinion survey. RESULTS: The phenotypic features of FAME, including generalized tonic-clonic and myoclonic seizures, are also seen in other epilepsy syndromes, such as juvenile myoclonic epilepsy, with a resultant risk of misdiagnosis and lack of identification of the underlying cause. Cortical myoclonus may mimic essential tremor or drug-induced tremor. In younger individuals, the differential diagnosis includes progressive myoclonus epilepsies (PMEs), such as Unverricht-Lundborg disease, whereas, in adulthood, late-onset variants of PMEs, such as sialidoses, myoclonus epilepsy, and ataxia due to potassium channel pathogenic variants should be considered. PMEs may also be suggested by cognitive impairment, cerebellar signs, or psychiatric disorders. Electroencephalography (EEG) may show similarities to other idiopathic generalized epilepsies or PMEs, with generalized spike-wave activity. Signs of cortical hyperexcitability may be seen, such as an increased amplitude of somatosensory evoked potentials or enhanced cortical reflex to sensory stimuli, together with the neurophysiological pattern of the movement disorder. SIGNIFICANCE: Recognition of FAME will inform prognostic and genetic counseling and diagnosis of the insidious progression, which may occur in older individuals who show mild cognitive deterioration. Distinguishing FAME from other disorders in individuals or families with this constellation of symptoms is essential to allow the identification of underlying etiology.

Deep phenotyping of frontal lobe epilepsy compared to other epilepsy syndromes.

AIMS: Frontal lobe epilepsy (FLE) is understudied and often misdiagnosed. We sought to comprehensively phenotype FLE and to differentiate FLE from other focal and generalised epilepsy syndromes. METHODS: This was a retrospective, observational cohort study of 1078 cases of confirmed epilepsy in a tertiary neurology centre in London. Data sources were electronic health records, investigation reports and clinical letters. RESULTS: 166 patients had FLE based on clinical findings and investigations-97 with identifiable electroencephalography (EEG) foci in frontal areas (definite FLE), while 69 had no frontal EEG foci (probable FLE). Apart from EEG findings, probable and definite FLE did not differ in other features. FLE was distinct from generalized epilepsy, which tended to present with tonic-clonic seizures and be due to genetic causes. FLE and temporal lobe epilepsy (TLE) both featured focal unaware seizures and underlying structural or metabolic aetiology. FLE, TLE and generalized epilepsy differed in their EEG (P = 0.0003) and MRI (P = 0.002) findings, where FLE had a higher rate of normal EEG and abnormal MRI findings compared to TLE. CONCLUSIONS: EEG is often normal for FLE, and abnormalities are commonly identified with MRI. There was no difference in the clinical features of definite and probable FLE, suggesting they represent the same clinical entity. The diagnosis of FLE can be made even when scalp EEG is normal. This large medical cohort provides hallmark features of FLE that differentiate it from TLE and other epilepsy syndromes.

A Single-center Analysis of Three Japanese Patients with Mahjong-related Seizures.

Mahjong is one of the most popular Chinese tile games played in Japan. Mahjong-related seizures (MRS) are rare praxis-induced seizures. We identified three patients with MRS from February 2000 to February 2021. All cases were men, with a middle-age onset, generalized convulsive seizures, and lack of non-provoked, myoclonic, and absence seizures. All patients had no or non-specific neuroimaging or electroencephalogram abnormalities. They did not have features linked to idiopathic generalized epilepsy. All patients were seizure-free after behavioral adjustments, although one patient required anti-seizure medication and avoided long duration games. These changes may help other patients with MRS continue playing Mahjong.