Epilepsia Open最新文献

Neuroimaging investigations are fundamental in the diagnosis of patients with epilepsy. The International League Against Epilepsy (ILAE) harmonized neuroimaging of epilepsy structural sequences (HARNESS-MRI) protocol was intended as a generalizable structural MRI protocol. The European Reference Network for Rare and Complex Epilepsies, EpiCARE, includes 50 centers, across 26 countries, with expertise in epilepsy. We investigated adherence to the HARNESS-MRI protocol across EpiCARE. A survey on the clinical use of imaging and postprocessing methods in epilepsy patients was distributed among the centers. A descriptive analysis was performed, and results were compared to existing guidelines, as well as a previous survey in 2016. 79% of centers were adhering to the HARNESS-MRI protocol in all epilepsy patients. All centers were acquiring 3D T1-weighted sequences, 90% were acquiring 3D FLAIR and 87% were acquiring high in-plane 2D coronal T2 MRI sequences in all epilepsy patients. In comparison, in 2016, only 50% of centers were following MRI recommendations at the time. Across European expert epilepsy centers, there has been increased harmonization of MRI sequences since the introduction of the HARNESS-MRI protocol. This standardization supports optimal radiological review at individual centers as well as enabling harmonization of multicenter datasets for research. PLAIN LANGUAGE SUMMARY: Neuroimaging investigations are a fundamental component of epilepsy diagnosis. The International League Against Epilepsy (ILAE) has created guidelines about what MRI images to obtain in all epilepsy patients. In this study, we assessed the adherence of expert European epilepsy centers to these guidelines and found that 79% are acquiring the minimum set of MRI scans in all epilepsy patients. Standardization of MRI imaging serves to improve epilepsy diagnosis across Europe.

Ketogenic diets (KDs) are recommended as precision therapy for glucose transporter 1 deficiency syndrome (GLUT-1 DS) but there are no recommendations for optimal implementation in this population. We administered an online survey targeting clinicians with experience implementing KDs in GLUT-1 DS, focusing on diet selection, initiation, and management. Respondents were primarily experienced registered dietitian nutritionists (RDNs) from 34 centers in 10 countries. Most reported a preference for carbohydrate counting or ratios under 3:1. KD-related laboratory monitoring (including blood ketones) and vitamin/mineral supplementation did not differ for GLUT-1 DS patients compared to the epilepsy population. Routine use of exogenous ketones was not endorsed for improved ketosis, whereas MCT oil is a commonly used supplement. Respondents overwhelmingly endorsed discussing and implementing gastrostomy feedings to support continued dietary therapy when medically indicated. Most but not all providers (80%) were familiar with the 2020 consensus guidelines. Our survey demonstrates practice variability among experienced dietitians, particularly in diet type and ratio. Identified challenges carry clinical significance, as the diet is a precision therapy in GLUT1-DS. Further research is needed to examine the outcomes of different approaches to KDs in GLUT-1 DS before consensus about the most effective interventions can be reached. PLAIN LANGUAGE SUMMARY: Glucose transporter deficiency syndrome is a genetic condition caused by an inability to move sugar (glucose) into the brain, which is needed for proper brain function. Ketogenic diets (low in carbohydrate and high in fat) are the established treatment to help control symptoms. Although the diet is effective, it can be challenging. To understand these challenges, we surveyed experts in ketogenic diet management and found significant variability regarding specifics of how the diet is managed. More research is needed before one approach can be endorsed as most effective.

Objective: To investigate how etiology and seizure localization influence ictal scalp electroencephalographic (EEG) patterns in temporal lobe epilepsy (TLE).

Methods: We retrospectively analyzed ictal EEG features from 504 focal seizures recorded in 189 TLE patients with various etiologies who underwent resective surgery.

Results: For seizure onset patterns (SOPs), α/β onset was more common in the low-grade tumor group (38.4%) than in the hippocampal sclerosis (HS) group (14.1%, p < 0.001). The ictal EEG duration was shorter in the tumor group compared to the focal cortical dysplasia (FCD), HS, and non-specific groups (p < 0.05). Among mesial TLE patients, SOPs varied depending on the etiology. Within both the tumor and non-specific groups, SOPs and the spreading time to the contralateral hemisphere differed between mesial and neocortical origins. Ictal pattern (87.7%) and ictal theta activity (83.9%) correctly lateralized the seizure in most cases.

Significance: The ictal scalp pattern in TLE is influenced by both etiology and seizure localization. TLE associated with low-grade tumors exhibits distinct ictal EEG characteristics. Furthermore, ictal pattern and ictal theta activity are equally effective in lateralizing seizures, regardless of etiology.

Plain language summary: This research examined how brain activity during seizures in people with temporal lobe epilepsy can be different based on what caused the epilepsy and where in the brain the seizure starts. We found that seizures caused by brain tumors have unique patterns in the brain's electrical activity. Additionally, we discovered that specific patterns and types of brain waves can help determine which side of the brain the seizure is occurring on, regardless of its cause.

Objective: Dravet syndrome is a developmental and epileptic encephalopathy characterized by drug-resistance, lifelong seizures, and significant comorbidities including intellectual and motor impairment. Receiving a diagnosis of Dravet syndrome is challenging for parents/caregivers, and little research has focused on how the diagnosis should be given. A Delphi consensus process was undertaken to determine key aspects for healthcare professionals (HCPs) to consider when communicating a Dravet syndrome diagnosis to parents/caregivers.

Methods: Following a literature search and steering committee review, 34 statements relating to the first diagnosis consultation were independent- and anonymously voted on (from 1, totally inappropriate, to 9, totally appropriate) by an international group of expert child neurologists, neuropsychiatrists, nurses, and patient advisory group (PAG) representatives. The statements were divided into five chapters: (i) communication during the first diagnosis consultation, (ii) information to be delivered during the first diagnosis consultation, (iii) points to be reiterated at the end of the first diagnosis consultation, (iv) information to be delivered at subsequent consultations, and (v) communication around genetic testing. Statements receiving ≥ 75% of the votes with a score of ≥7 and/or with a median score of ≥8 were considered consensual.

Results: The statements were evaluated by 44 HCPs and PAG representatives in the first round of voting; 29 statements obtained strong consensus, 3 received good consensus, and 2 did not reach consensus. The committee reformulated and resubmitted 4 statements for evaluation (42/44 voters): 3 obtained strong consensus and 1 remained not consensual. The final consensual recommendations include guidance on consultation setting, key disease aspects to convey, how to discuss genetic testing results, disease evolution, and the risk of SUDEP, among other topics.

Significance: It is hoped that this international Delphi consensus will facilitate a better-structured initial diagnosis consultation and offer further support for parents/caregivers at this challenging time of learning about Dravet syndrome.

Plain language summary: Diagnosis of Dravet syndrome, a rare and severe form of childhood-onset epilepsy, is often challenging to give to parents. This international study developed guidance and recommendations to help healthcare professionals better structure and personalize this disclosure. By following this advice, doctors can provide more tailored support to families, improving their understanding and management of the condition.

The potential of dietary interventions, particularly the use of the ketogenic diet in patients with Psychogenic Non-Epileptic Seizures (PNES), remains underexplored. This study aimed to assess the feasibility of a 6-week ketogenic diet (Modified Atkins Diet, MAD) intervention in adult patients with PNES and to compare its effects on PNES frequency and other variables against a control healthy diet (CD). A feasibility pilot randomized controlled trial was conducted at a tertiary neurology hospital, enrolling outpatients diagnosed with PNES and assigning them to either MAD or CD. Baseline and follow-up assessments (at 2, 4, and 6 weeks) included evaluation of mental health, PNES frequency, and metabolic measures. Descriptive and inferential methods, including repeated measures ANOVA, were used for statistical analysis. Seventeen patients (mean age 28.23 ± 7.1) were randomly allocated to receive either MAD (n = 12) or CD (n = 5). The entire sample exhibited a significant decrease in monthly PNES frequency (p = 0.01, Hedges ES = 0.618) without differences between groups. The MAD group showed significant improvement in PNES frequency, depression, and anxiety at week six. Results demonstrate that the implementation of MAD is feasible in patients with PNES and suggest that it may reduce seizure frequency and symptoms of depression and anxiety. These findings warrant further investigation in larger, powered studies to demonstrate efficacy. PLAIN LANGUAGE SUMMARY: This study explored the potential benefits of the Modified Atkins Diet (MAD) in reducing the frequency of psychogenic non-epileptic seizures (PNES). The results showed that the diet is safe, well-tolerated, and may decrease the occurrence of PNES, as well as symptoms of depression and anxiety. These findings suggest that dietary modifications could be a helpful complement to PNES treatment, though larger studies are necessary to confirm these outcomes.

Musicogenic epilepsy (ME) is characterized by seizures triggered by music. The epileptogenic focus in this rare reflex epilepsy is often in the temporal lobe, although the precise localization is still unclear. A correlation between ME and the presence of GAD65 antibodies indicates a potential immunological pathogenic mechanism. We evaluated a 32-year-old woman with drug-resistant temporal lobe epilepsy as a candidate for epilepsy surgery. In the absence of clear clinical lateralizing signs, video-EEG monitoring with intracranial electrodes inserted through the foramen ovale was performed to record from the amygdalo-hippocampal regions. The foramen ovale electrodes revealed bilateral, asynchronous, and independent seizure onsets in the mesial temporal regions triggered by music. Testing for GAD65 antibodies confirmed high-titer positivity. The efficacy of epilepsy surgery in antiGAD65-positive ME patients remains limited. We highlight the use of semi-invasive recording with foramen ovale electrodes in ME, as it can reveal bilateral seizures of mesial origin that contraindicate surgery and support the consideration of immunotherapy options. PLAIN LANGUAGE SUMMARY: Musicogenic epilepsy is a type of epilepsy in which music triggers seizures. Our understanding of its origin and cause is still limited. We assessed a patient with music-induced seizures to see if surgery was an option. Since noninvasive tests before surgery were not clear, we used a minimally invasive method with electrodes inserted through a small opening in the skull called the foramen ovale to record the seizures. Thus, we found that the seizures started independently from both temporal lobes, contraindicating epilepsy surgery. We also found high levels of GAD65 antibodies indicating an immunological pathogenic mechanism.

New Onset Refractory Status Epilepticus (NORSE) is a rare and severe condition characterized by refractory seizures in individuals without a prior history of epilepsy. This case report describes a 37-year-old woman diagnosed with anti-glutamic acid decarboxylase 65 (anti-GAD65) antibody-positive encephalitis-related NORSE. Her seizures were refractory to multiple interventions, including anti-seizure medications, anesthetics, immunotherapies, a ketogenic diet, and electroconvulsive therapy. Seizures recurred twice during the tapering of anesthetic medications. However, after 32 days of treatment, the seizures were successfully controlled. To maintain seizure control and facilitate the weaning of anesthetics, a Vagus Nerve Stimulator (VNS) was implanted using a novel rapid titration protocol. This allowed for the successful tapering of anesthetics by day 50, with no recurrence of seizures. At her 9-month follow-up, the patient remained seizure-free and had an improved quality of life. This case highlights that early initiation of immunosuppressive treatment may lead to a favorable prognosis. The novel application of VNS therapy assisted seizure control in NORSE, thus encouraging further research investigating the potential role of VNS in this condition. PLAIN LANGUAGE SUMMARY: New Onset Refractory Status Epilepticus (NORSE) is a rare and severe condition characterized by relentless seizures in individuals without a prior epilepsy history. This report shares the case of a 37-year-old woman with NORSE, associated with a high anti-glutamic acid decarboxylase 65 antibody titer. Her seizures were super-refractory, requiring multiple anti-seizure medications, anesthetics, immunotherapies, a ketogenic diet, and electroconvulsive therapy. Seizures recurred twice during the tapering of anesthetic medications. However, by hospital day 32, the seizures were successfully controlled with these interventions. To further stabilize seizure control and enable the successful discontinuation of anesthetics, a Vagus Nerve Stimulator (VNS) was implanted. The patient had no further seizures and gradually recovered back to her pre-disease baseline. This case suggests that a novel rapid VNS titration protocol could be a promising treatment option for NORSE, warranting further investigation.

Protein-activated kinases mediate spine morphogenesis and synaptic plasticity. PAK3 is part of the p21-activated kinases (PAKs) family of Ras-signaling serine/threonine kinases. Pathogenic variants in the X-linked gene PAK3 have been described in patients with neurodevelopmental syndromes. We analyzed an Italian family with sleep-related hypermotor epilepsy, intellectual disability, psychiatric and behavioral problems, and dysmorphic facial features. A novel PAK3 c.342_344del (p.Lys114del) inframe deletion was detected in the family. Protein structure analysis supported deleterious impact of p.Lys114 deletion through loss or partial loss of autoinhibition of PAK3 protein kinase activity. The male proband had drug-resistant hypermotor seizures and moderate intellectual disability. His brother had drug-responsive hypermotor seizures and mild intellectual disability. Both brothers were hemizygous and had psychiatric and behavioral problems as well as dysmorphic facial features. Their mother had never had seizures but was shown to be mosaic for the PAK3 pathogenic variant. She had normal intellect but did have short stature and dysmorphic facial features similar to her sons. This is the first reported association of a PAK3 pathogenic variant with sleep-related hypermotor epilepsy. PAK3 testing should be considered in families with suspected X-linked sleep-related hypermotor epilepsy and intellectual disability, including for mosaicism in mildly affected females. PLAIN LANGUAGE SUMMARY: We studied an Italian family with sleep-related hypermotor epilepsy, intellectual disability, psychiatric and behavioral problems, and dysmorphic facial features. A novel PAK3 c.342_344del (p.Lys114del) inframe deletion was detected in the family. Protein structure analysis supported deleterious impact of p.Lys114 deletion through loss or partial loss of autoinhibition of PAK3 protein kinase activity. This is the first reported association of a PAK3 pathogenic variant with sleep-related hypermotor epilepsy. PAK3 testing should be considered in families with suspected X-linked sleep-related hypermotor epilepsy and intellectual disability, including for mosaicism in mildly affected females.