Key steps and barriers in the journey of patients with epilepsy through the National Healthcare System in Spain: The EPIPASS qualitative study.

OBJECTIVE: Epilepsy requires continuous medical attention from multiple healthcare specialists, specialized facilities, and community-based care. In Spain, there is no standardized approach to epilepsy care. The aim of this study was to identify the factors impacting on the delivery of high-quality care by exploring key steps and barriers along the patient journey through the Spanish National Healthcare System (NHS). METHODS: A qualitative study was conducted using opinions and experiences of neurologists, nurses, patients, and caregivers shared in discussion meetings. Using thematic content analyses, relevant aim-focused statements were coded according to prespecified issues in a discussion map (i.e., key steps and barriers), and sub-coded according to emerging issues. Thematic saturation and co-occurrence of key steps/barriers were evaluated to identify the most relevant factors impacting on the delivery of high-quality care. RESULTS: Sixty-five stakeholders took part in discussion meetings (36 neurologists, 10 nurses, 10 patients, and nine caregivers). Six key steps on the patient journey were identified: emergency care, diagnosis, drug therapy, follow-up, referral, and interventional treatment. Of these, follow-up was the most relevant step impacting on the delivery of high-quality patient care, followed by drug therapy and diagnosis. Emergency care was considered a hot-spot step with impact throughout the patient journey. Communication (among HCPs and between HCPs and patients) was a barrier to the delivery of high-quality care at several stages of the patient journey, including drug therapy, follow-up, referral, and interventional treatment. Resource availability was a barrier for diagnosis (especially for confirmation), drug therapy (drug availability), and referral (lack of professionals and specialized centers, and long waiting lists). SIGNIFICANCE: This is the first study capturing perspectives of four key stakeholders involved in epilepsy care in Spain. We provide an overview of the patient journey through the Spanish NHS and highlight opportunities to improve the delivery of patient-centered care with a chronicity perspective. PLAIN LANGUAGE SUMMARY: Patients with epilepsy may require prolonged medical care. In Spain, care is provided by a range of specialist and non-specialist centers. In this study, a team of Spanish neurologists, nurses, patients and caregivers identified barriers that affect the delivery of high-quality care for patients with epilepsy at each stage of their journey through the Spanish NHS. Specific epilepsy training for healthcare providers, appropriate resources for diagnosing and treating patients, and good communication between healthcare workers and patients were identified as important factors in providing high-quality care for patients with epilepsy.

The impact of developmental and epileptic encephalopathies on families: a qualitative study.

Developmental and epileptic encephalopathies (DEEs) cause disability and dependence affecting both children and the family. The aim of the study was to describe the perspective of parents of children with DEEs regarding the impact of the disease on the family. We carried out a qualitative study based on the interpretivist paradigm. Twenty-one participants were selected using purposive sampling. Parents of children with DEEs of SCN1A, KCNQ2, CDKL5, PCDH19, and GNAO1 variants were included. In-depth interviews and researcher notes were used for data collection. A thematic analysis was performed on the data. Three themes were identified in the results: (a) Assuming conflicts and changes within the couple, causing them to distance themselves, reducing their time and intimacy and leading them to reconsider having more children; (b) impact of the disorder on siblings and grandparents, where siblings perceived DEE as a burden in their lives, felt neglected, and needed to grow and mature alone; conversely, the grandparents suffered for their grandchildren and the parents, in addition to perceiving that their health worsened, and (c) reconciling the care of the child with family life and work; this led the parents to share tasks, abandon or reduce working hours and ask for help.Conclusions: Caring for a child with DEE can result in neglect of social, psychological, emotional, recreational, educational, or occupational needs and obligations that ultimately impact all family members. What is Known: • Children with DEE may develop seizures and experience developmental and cognitive problems. • Caring for a child with DEE has a social and psychological impact on the entire family.

Incidence and predictors of posttraumatic epilepsy and cognitive impairment in patients with traumatic brain injury: A retrospective cohort study in Malaysia.

OBJECTIVE: Posttraumatic epilepsy (PTE) significantly impacts morbidity and mortality, yet local PTE data remain scarce. In addition, there is a lack of evidence on cognitive comorbidity in individuals with PTE in the literature. We sought to identify potential PTE predictors and evaluate cognitive comorbidity in patients with PTE. METHODS: A 2-year retrospective cohort study was employed, in which adults with a history of admission for traumatic brain injury (TBI) in 2019 and 2020 were contacted. Three hundred one individuals agreed to participate, with a median follow-up time of 30.75 months. The development of epilepsy was ascertained using a validated tool and confirmed by our neurologists during visits. Clinical psychologists assessed the patients' cognitive performance. RESULTS: The 2-year cumulative incidence of PTE was 9.3% (95% confidence interval [CI] 5.9-12.7). The significant predictors of PTE were identified as a previous history of brain injury [hazard ratio [HR] 4.025, p = .021], and intraparenchymal hemorrhage (HR: 2.291, p = .036), after adjusting for other confounders. TBI patients with PTE performed significantly worse on the total ACE-III cognitive test (73.5 vs 87.0, p = .018), CTMT (27.5 vs 33.0, p = .044), and PSI (74.0 vs 86.0, p = .006) than TBI patients without PTE. A significantly higher percentage of individuals in the PTE group had cognitive impairment, compared to the non-PTE group based on ACE-III (53.6% vs 46.4%, p = .001) and PSI (70% vs 31.7%, p = .005) scores at 2 years post-TBI follow-up. SIGNIFICANCE: This study emphasizes the link between TBI and PTE and the chance of developing cognitive impairment in the future. Clinicians can target interventions to prevent PTE by identifying specific predictors, which helps them make care decisions and develop therapies to improve patients' quality of life.

Providing quality care for people with CDKL5 deficiency disorder: A European expert panel opinion on the patient journey.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a developmental and epileptic encephalopathy caused by variants in the CDKL5 gene. The disorder is characterized by intractable early-onset seizures, severe neurodevelopmental delay, hypotonia, motor disabilities, cerebral (cortical) visual impairment and microcephaly. With no disease-modifying therapies available for CDD, treatment is symptomatic with an initial focus on seizure control. Another unmet need in the management of people with CDD is the lack of evidence to aid standardized care and guideline development. To address this gap, experts in CDD and representatives from patient advocacy groups from Denmark, Finland, France, Germany, Italy, Poland, Spain, and the United Kingdom convened to form an Expert Working Group. The aim was to provide an expert opinion consensus on how to ensure quality care in routine clinical practice within the European setting, including in settings with limited experience or resources for multidisciplinary care of CDD and other developmental and epileptic encephalopathies. By means of one-to-one interviews around the current treatment landscape in CDD, insights from the Expert Working Group were collated and developed into a Europe-specific patient journey for individuals with CDD, which was later validated by the group. Further discussions followed to gain consensus of opinions on challenges and potential solutions for achieving quality care in this setting. The panel recognized the benefit of early genetic testing, a holistic personalized approach to seizure control (taking into consideration various factors such as concomitant medications and comorbidities), and age- and comorbidity-dependent multidisciplinary care for optimizing patient outcomes and quality of life. However, their insights and experiences also highlighted much disparity in management approaches and resources across different European countries. Development of standardized European recommendations is required to align realistic diagnostic criteria, treatment goals, and management approaches that can be adapted for different settings. PLAIN LANGUAGE SUMMARY: Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare condition caused by a genetic mutation with a broad range of symptoms apparent from early childhood, including epileptic seizures that do not respond to medication and severe delays in development. Due to the lack of guidance on managing CDD, international experts and patient advocates discussed best practices in the care of people with CDD in Europe. The panel agreed that early testing, a personalized approach to managing seizures, and access to care from different disciplines are beneficial. Development of guidelines to ensure that care is standardized would also be valuable.

What have we learned from the real-world efficacy of FFA in DS and LGS? A post-marketing study in clinical practice.

OBJECTIVE: To evaluate the effectiveness and tolerability of fenfluramine (FFA) in routine clinical practice treating real-world populations with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). METHODS: This was a retrospective analysis of patients with DS or LGS who initiated FFA treatment from 2018 to 2022 at a single center. Patient demographics, medical history, seizure characteristics, and treatment outcomes were collected from electronic medical records. Duration of FFA treatment, dosage regimens, seizure frequency, seizure severity, improvements in cognitive, social, and motor outcomes, and adverse events were extracted and analyzed. Effectiveness was assessed using ≥50 % sustained reduction in monthly seizure frequency vs baseline for ≥2 consecutive months at 12 months; seizure freedom was a secondary measure. RESULTS: Seizure frequency data was available for 56 of 68 patients included in the study. At 12 months, 50 patients (89.3 %) remained on FFA treatment; 58 % of these patients achieved a ≥50 % sustained response and 10 % experienced seizure freedom. Cognitive, motor, and social improvement were noted in 70.7 %, 36.2 %, and 27.6 % of patients, respectively. The total number of concomitant antiseizure medications was reduced by ≥1 in 29.4 % of patients. No differences were found between DS and LGS patients in these outcomes; age at start of FFA and age at the 12-month timepoint did not have an effect. At least one AE was experienced by 59.7% of patients; in 86.5% of the cases, AEs were plausibly related to treatment. While 70.3% of AEs were self-resolving and 81.8% of the remaining patients experienced mild AEs, 1 patient experienced a serious AE unrelated to FFA which resulted in the patient's death. There were no cases of pulmonary arterial hypertension or ventricular heart disease. SIGNIFICANCE: The effectiveness and tolerability of FFA treatment in patients with DS or LGS in this retrospective analysis of real-world data were consistent with those seen in randomized clinical trials.

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.

Intervención grupal con adolescentes con epilepsia refractaria: programa terapéutico educativo / Intervenció grupal amb adolescents amb epilèpsia refractària: programa terapèutic educatiu / Group intervention with adolescents with refractory epilepsy: a therapeutic educational programme

Se presentauna intervención grupal terapéutico-educativa con adolescentes con diagnóstico de epilepsia refractaria en elque se trabajaron diferentes áreas psicológicas: personal, cognitiva, social y tiempo libre. La valoración se realizóa partir de la descripción clínica, el cuestionario SENA y la plataforma NEURONUP, valorando que una interven-ción específica ayuda a los pacientes a crear una mayor conciencia y capacidad de implicarse en los objetivos,permitiendo mejoras en su autoconcepto y autocuidado.(AU)

We presenta therapeutic-educational group intervention with adolescents diagnosed with refractory epilepsy in which diffe-rent psychological areas were worked on: personal, cognitive, social, and free time. The assessment was basedon the clinical description, the SENA questionnaire, and the NEURONUP platform, evaluating that a specific inter-vention helps patients to create greater awareness and capacity to become involved in the objectives, allowingimprovements in their self-concept and self-care.(AU)

Es presenta unaintervenció grupal terapèutica i educativa amb adolescents amb diagnòstic d'epilèpsia refractària en què es vantreballar diferents àrees psicològiques: personal, cognitiva, social i temps lliure. La valoració es va realitzar a partirde la descripció clínica, el qüestionari SENA i la plataforma NEURONUP i es va veure que una intervenció espe-cífica ajuda els pacients a crear una major consciència i capacitat d'implicar-se en els objectius, cosa que permetmillores en el seu autoconcepte i en la pròpia cura.(AU)

Análisis del impacto familiar y necesidades del síndrome de Dravet en España / Analysis of the family impact and needs of Dravet's syndrome in Spain

Introducción: El síndrome de Dravet (SD) es una encefalopatía epiléptica, iniciada en la infancia, con un gran impacto en la vida de los pacientes y los familiares. Actualmente se necesitan mejoras en su diagnóstico y tratamiento: existen dos fármacos aprobados para el tratamiento del SD en Europa, aunque hay nuevos tratamientos en desarrollo o en vías de comercialización próximamente. Objetivos: Comprender la situación del SD en España e identificar las oportunidades de mejora. Sujetos y métodos: Análisis de los datos de una macroencuesta europea en la que los cuidadores de pacientes con SD manifestaron su experiencia con la enfermedad. Resultados: Datos de 57 familias con hijos con SD (edad media: 9 años). El tiempo hasta el diagnóstico, generalmente tras otro erróneo (80%), se incrementa en los pacientes de mayor edad (el 80% de los adultos: retraso diagnóstico > 4 años). La demora induce un mayor uso de fármacos antiepilépticos contraindicados. Las crisis (87% de los casos; las más frecuentes, tonicoclónicas: 90%) y las hospitalizaciones (60% de los casos) continúan hasta la edad adulta. La gravedad de la enfermedad y el número de hospitalizaciones se correlacionan con el impacto en los cuidadores y la familia. La eficacia de los tratamientos y el futuro de los pacientes son las mayores preocupaciones. Conclusiones: Para mejorar el manejo y la calidad de vida de los pacientes con SD y los familiares, es necesario un diagnóstico temprano y la incorporación de nuevos tratamientos que ayuden al control de las crisis epilépticas y de las comorbilidades de la enfermedad

Introduction: Dravet's syndrome (DS) is an epileptic encephalopathy that starts in infancy and has an important impact on the lives of patients and their relatives. There is currently a need for improvement in diagnosis and treatment: two drugs have been approved for the treatment of DS in Europe, although new treatments are under development or are scheduled for commercialisation soon. AIMS. To understand the situation of DS in Spain and to identify opportunities for improvement. Subjects and methods: The study will involve an analysis of data from a European macro-survey in which carers of patients with DS expressed their experience with the disease. Results: Data from 57 families with children with DS (mean age: 9 years). The time to diagnosis, usually after another misdiagnosis (80%), increases in older patients (80% of adults: diagnostic delay > 4 years). The delay induces an increased use of contraindicated antiepileptic drugs. Seizures (87% of cases; the most frequent, tonic-clonic: 90%) and hospitalisations (60% of cases) continue into adulthood. The severity of the illness and the number of hospitalisations correlate with impact on caregivers and family. The effectiveness of treatments and the future of patients are the greatest concerns. Conclusions: In order to improve the management and quality of life of patients with DS and their families, it is necessary to have an early diagnosis and to incorporate new treatments that help to control the epileptic seizures and the comorbidities of the disease

Migraña con edema palpebral prolongado: serie de 10 casos / Migraine with prolonged eyelid edema: a series of 10 cases

Introducción. La migraña puede cursar con síntomas autonómicos craneales propios de las cefaleas trigeminoautonómicas, lo que plantea dificultades en el diagnóstico. Objetivo. Describir una serie de diez pacientes con edema palpebral asociado a la migraña. Pacientes y métodos. Diez pacientes atendidos en la consulta de cefaleas de tres hospitales (nueve mujeres, un varón; edad: 26-53 años), con edema palpebral recurrente asociado a la migraña. Resultados. Según los criterios diagnósticos de la Clasificación Internacional de las Cefaleas (ICHD-III, versión beta), ocho pacientes presentaban migraña sin aura, una tenía migraña con aura y otra, migraña crónica. El edema palpebral aparecía durante las crisis de migraña más intensas, y tenía mayor duración que la cefalea. Se descartaron causas farmacológicas o sistémicas del edema en todos los casos. Otros síntomas autonómicos asociados fueron la inyección conjuntival (n = 3), el lagrimeo (n = 2) y la rinorrea (n = 1). Tanto el dolor como el edema asociado respondieron a los tratamientos sintomáticos y preventivos de la migraña. Conclusiones. El edema palpebral es un posible acompañante de la migraña. Aparece en algunos pacientes con los episodios de mayor intensidad, y responde al tratamiento sintomático y preventivo de la migraña (AU)

Introduction. Migraine may present with cranial autonomic symptoms typical of trigeminal-autonomic cephalalgias, thus posing diagnostic difficulties. Aim. To report a series of patients with prominent eyelid oedema associated with migraine. Patients and methods. Ten patients attending the headache offices in three hospitals (nine women, one man; age: 26-53 years-old) with recurrent eyelid oedema as a migraine accompaniment. Results. According to the diagnostic criteria of the International Classification of Headache Disorders (ICHD-III, beta version), eight patients had migraine without aura, one had migraine with aura, and one had chronic migraine. Eyelid oedema appeared during the most severe headache attacks, and had longer duration than the pain. Pharmacological or systemic causes of the oedema were ruled out in all cases. Other associated autonomic symptoms were conjunctival injection (n = 3), lacrimation (n = 2) and rhinorrhoea (n = 1). Both the pain and the oedema improved with symptomatic and preventive therapies for migraine. Conclusions. Eyelid oedema may occasionally be a migraine accompaniment. It appears in some patients during their most severe migraine attacks, and may improve with the acute and preventive treatment for migraine (AU)