RESUMO
With the advent of high-throughput sequencing and computational methods, genetic testing has become an integral part of contemporary clinical practice, particularly in epilepsy. The toolbox for genetic testing has evolved from conventional chromosomal microarray and epilepsy gene panels to state-of-the-art sequencing techniques in the modern genomic era. Beyond its potential for therapeutic benefits through precision medicine, optimizing the choice of antiseizure medications, or exploring nonpharmacological therapeutic modalities, genetic testing carries substantial diagnostic, prognostic, and personal implications. Developmental and epileptic encephalopathies, the coexistence of neurodevelopmental comorbidities, early age of epilepsy onset, unexplained drug-refractory epilepsy, and positive family history have demonstrated the highest likelihood of yielding positive genetic test results. Given the diagnostic efficacy across different testing modalities, reducing costs of next-generation sequencing tests, and genetic diversity of epilepsies, exome sequencing or genome sequencing, where feasible and available, have been recommended as the first-tier test. Comprehensive clinical phenotyping at the outset, corroborative evidence from radiology and electrophysiology-based investigations, reverse phenotyping, and periodic reanalysis are some of the valuable strategies when faced with inconclusive test results. In this narrative review, the authors aim to simplify the approach to genetic testing in epilepsy by guiding on the selection of appropriate testing tools in the indicated clinical scenarios, addressing crucial aspects during pre- and post-test counseling sessions, adeptly navigating the traps posed by uncertain or negative genetic variants, and paving the way forward to the emerging testing modalities beyond DNA sequencing.
Assuntos
Epilepsia , Testes Genéticos , Humanos , Epilepsia/genética , Epilepsia/diagnóstico , CriançaRESUMO
Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) consisting of epileptic spasms, as well as one or both of developmental regression or stagnation and hypsarrhythmia on EEG. A myriad of aetiologies are associated with the development of IESS; broadly, 60% of cases are thought to be structural, metabolic or infectious in nature, with the remainder genetic or of unknown cause. Epilepsy genetics is a growing field, and over 28 copy number variants and 70 single gene pathogenic variants related to IESS have been discovered to date. While not exhaustive, some of the most commonly reported genetic aetiologies include trisomy 21 and pathogenic variants in genes such as TSC1, TSC2, CDKL5, ARX, KCNQ2, STXBP1 and SCN2A. Understanding the genetic mechanisms of IESS may provide the opportunity to better discern IESS pathophysiology and improve treatments for this condition. This narrative review presents an overview of our current understanding of IESS genetics, with an emphasis on animal models of IESS pathogenesis, the spectrum of genetic aetiologies of IESS (i.e., chromosomal disorders, single-gene disorders, trinucleotide repeat disorders and mitochondrial disorders), as well as available genetic testing methods and their respective diagnostic yields. Future opportunities as they relate to precision medicine and epilepsy genetics in the treatment of IESS are also explored.
Assuntos
Epilepsia , Síndromes Epilépticas , Espasmos Infantis , Animais , Medicina de Precisão , Espasmos Infantis/genética , Epilepsia/genética , Síndromes Epilépticas/genética , Espasmo/complicaçõesRESUMO
There are numerous challenges pertaining to epilepsy care across Ontario, including Epilepsy Monitoring Unit (EMU) bed pressures, surgical access and community supports. We sampled the current clinical, community and operational state of Ontario epilepsy centres and community epilepsy agencies post COVID-19 pandemic. A 44-item survey was distributed to all 11 district and regional adult and paediatric Ontario epilepsy centres. Qualitative responses were collected from community epilepsy agencies. Results revealed ongoing gaps in epilepsy care across Ontario, with EMU bed pressures and labour shortages being limiting factors. A clinical network advising the Ontario Ministry of Health will improve access to epilepsy care.
RESUMO
BACKGROUND: The ketogenic diet may be difficult for some patients and their families to implement and can impact physical, emotional, and social well-being. METHODS: Through principles of fundamental qualitative description, we completed an exploratory study on parents' experiences and expectations on the use and efficacy of the ketogenic diet for children with medically refractory epilepsy. RESULTS: Seventeen parents (10 mothers and 7 fathers) of 12 children with epilepsy participated. At the time of the interview, parents had experienced an average of 25 months of ketogenic diet treatment for their child (range 2 months to 98 months). Half of the caregivers learned about the ketogenic diet from their neurologist, whereas the remainder had heard about it from another source (ie, the internet). Most caregivers' (n = 13) diet expectations were related to seizure control. However, child development (n = 5) and quality of life (n = 5) were also crucial to some. Physical impacts of the diet were most commonly gastrointestinal for children (n = 9). Social and emotional effects were noted in some older children with typical development. Most caregivers described negative impacts on finances (n = 15), relationships (n = 14), and emotional well-being (ie, stress) (n = 12). Caregivers benefited from the ketogenic diet team's regular communication, close follow-up, and family-centered care. CONCLUSIONS: Despite the impacts that the ketogenic diet may have on caregivers' emotional and social well-being, the positive impacts of the diet were felt to outweigh any perceived risks. Effects (both positive and negative) on quality of life and child development (eg, social, emotional, cognitive) are essential for caregivers and require additional investigation.
Assuntos
Dieta Cetogênica , Epilepsia Resistente a Medicamentos , Pais , Pesquisa Qualitativa , Convulsões , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Pessoa de Meia-Idade , Cuidadores/psicologia , Desenvolvimento Infantil , Recursos Comunitários , Tomada de Decisões , Dieta Cetogênica/efeitos adversos , Dieta Cetogênica/economia , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/dietoterapia , Emoções , Saúde da Família/economia , Objetivos , Educação em Saúde , Pais/psicologia , Equipe de Assistência ao Paciente , Qualidade de Vida , Medição de Risco , Convulsões/complicações , Convulsões/dietoterapia , Convulsões/prevenção & controle , Resultado do TratamentoRESUMO
OBJECTIVE: Electroencephalography (EEG) is an essential tool for the diagnosis and management of epilepsy. There is a gap in EEG education for residents in Canadian neurology programs as EEG is only listed in the training requirements as a procedural skill. There is currently no standardized EEG curriculum among Canadian epilepsy fellowship programs. METHODS: We conducted two iterations of a structured virtual EEG course from June to October 2021, and from March to June 2022. Trainees were recruited via Canadian neurology residency and epilepsy fellowship programs and were required to join the Canadian League Against Epilepsy (CLAE) as junior members. We obtained trainee demographic information before and after each course as well as analytical data on the video recordings posted on the CLAE website. RESULTS: A total of 77 trainees registered for the two courses; majority of trainees were adult neurology residents (34%) and adult epilepsy fellows (32%). Prior theoretical EEG teaching was reported as limited by more than half (53%) of participants. The average number of unique viewers per recorded video in 2021 was 29.7 interquartile range (16-35.5), while in 2022, the average was 22.5, interquartile range (16-28). Post-course questionnaire data revealed that 82% of participants strongly agreed that the course enhanced their knowledge. All participants were either likely (27%) or very likely (73%) to recommend the course to their peers. SIGNIFICANCE: National virtual EEG education is both feasible and accessible; therefore, this is a promising modality of teaching to meet the significant demand for high-quality EEG education among neurology trainees.
Assuntos
Currículo , Eletroencefalografia , Estudos de Viabilidade , Bolsas de Estudo , Internato e Residência , Humanos , Canadá , Neurologia/educação , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Adulto , Competência Clínica/normas , Competência Clínica/estatística & dados numéricos , Educação de Pós-Graduação em Medicina , MasculinoRESUMO
The 2017 classification of the epilepsies of International League Against Epilepsy (ILAE) defined three diagnostic levels, including seizure type, epilepsy type and epilepsy syndrome. Epilepsy syndromes have been recognized as distinct electroclinical entities well before the first ILAE classification of Epilepsies and Epilepsy Syndromes in 1985. A formally accepted classification of epilepsy syndromes was not available, and hence, the 2017-2021 Nosology and Definitions Task Force of ILAE was formulated. The ILAE position papers were published in 2022, which classified epilepsy syndromes into (1) syndromes with onset in neonates and infants (up to 2 years of age), (2) syndromes with onset in childhood, (3) syndromes that may begin at a variable age and (4) idiopathic generalized epilepsies. This classification recognized the concept of etiology-specific syndrome. These papers have addressed the specific clinical and laboratory features of epilepsy syndromes and specify the rationale for any significant changes in terminology or definition. This paper will review some pertinent changes and essential points relevant to pediatricians.
Assuntos
Epilepsia Generalizada , Epilepsia , Síndromes Epilépticas , Recém-Nascido , Humanos , Epilepsia/diagnóstico , Convulsões/diagnóstico , PediatrasRESUMO
BACKGROUND: This study aimed to determine the parent-child agreement of the Hague Restrictions in Childhood Epilepsy Scale (HARCES) and identify the clinical factors associated with parent-child disagreement and the restrictions. METHODS: Data come from a clinical sample of 90 children ages 9-17 (mean age = 12.9, SD = 6.9, 54% male) attending a pediatric neurology clinic. Parents completed the HARCES, and children completed a modified child-friendly scale (HARCES-M). The parent-child agreement was assessed using intraclass correlation coefficients (ICC) and paired t-tests to compare parent and child responses. Logistic regression examined clinical factors associated with disagreement > 0.5 standard deviation. Associations between clinical factors and restriction scores were examined using linear regression. RESULTS: Parent-child agreement on the HARCES was poor (ICC = 0.36, 95% CI: 0.03, 0.58), and parents reported fewer restrictions in daily activities (t(89) = 2.45, p = .016) and to attend parties (t(89) = 2.12, p = .038); however, the overall restrictions scores were not different (t(89) = 1.55, p = .125). The presence of convulsive seizures (OR = 0.20, 95% CI: 0.05, 0.75) and longer duration of epilepsy (OR = 1.19, 95% CI: 1.01, 1.41) were associated with parent-child disagreement. No clinical factors were significantly related to either the HARCES or HARCES-M scores. CONCLUSIONS: The disagreement in perceptions of restrictions highlights the need to use child-reported measures along with parental reports to comprehensively understand restrictions on children with epilepsy fully. More research is needed to understand what factors explain parent- and child-rated restrictions due to epilepsy.
Assuntos
Epilepsia , Qualidade de Vida , Humanos , Masculino , Criança , Feminino , Convulsões , Pais , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: This longitudinal cohort study aimed to identify trajectories of parent well-being over the first 2 years after their child's evaluation for candidacy for epilepsy surgery, and to identify the baseline clinical and demographic characteristics associated with these trajectories. Parent well-being was based on parent depressive and anxiety symptoms and family resources (i.e., family mastery and social support). METHODS: Parents of 259 children with drug-resistant epilepsy (105 of whom eventually had surgery) were recruited from eight epilepsy centers across Canada at the time of their evaluation for epilepsy surgery candidacy. Participants were assessed at baseline and 6-month, 1-year, and 2-year follow-up. The trajectories of parents' depressive symptoms, anxiety symptoms, and family resources were jointly estimated using multigroup latent class growth models. RESULTS: The analyses identified three trajectories: an optimal-stable group with no/minimal depressive or anxiety symptoms, and high family resources that remained stable over time; a mild-decreasing-plateau group with mild depressive and anxiety symptoms that decreased over time then plateaued, and intermediate family resources that remained stable; and a moderate-decreasing group with moderate depressive and anxiety symptoms that decreased slightly, and low family resources that remained stable over time. Parents of children with higher health-related quality of life, fathers, and parents who had higher household income were more likely to have better trajectories of well-being. Treatment type was not associated with the trajectory groups, but parents whose children were seizure-free at the time of the last follow-up were more likely to have better trajectories (optimal-stable or mild-decreasing-plateau trajectories). SIGNIFICANCE: This study documented distinct trajectories of parent well-being, from the time of the child's evaluation for epilepsy surgery. Parents who present with anxiety and depressive symptoms and low family resources do not do well over time. They should be identified and offered supportive services early in their child's epilepsy treatment history.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Criança , Humanos , Estudos Longitudinais , Qualidade de Vida , Pais , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia/diagnóstico , DepressãoRESUMO
PURPOSE: Seizure freedom is an important predictor of health-related quality of life (HRQOL) after pediatric epilepsy surgery. This study aimed to identify the pre-operative predictors of HRQOL 2 years after epilepsy surgery in children with drug-resistant epilepsy. METHODS: This multicenter prospective cohort study assessed pre-operative predictors including child (demographics and clinical variables), caregiver (including caregiver depressive and anxiety symptoms) and family characteristics. HRQOL was assessed using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE)-55 pre-operatively and 2-years after surgery. Univariable linear regression analyses were done to identify significant preoperative predictors of HRQOL 2-years after surgery, followed by multivariable regression. RESULTS: Ninety-five children underwent surgery, mean age was 11.4 (SD=4.2) years, and 59 (62%) were male. Mean QOLCE scores were 57.4 (95%CI: 53.8, 61.0) pre-operatively and 65.6 (95%CI: 62.0, 69.1) after surgery. Univariable regression showed fewer anti-seizure medications (ß=-6.1 [95%CI: -11.2, -1.0], p = 0.019), older age at seizure onset (ß=1.6 [95%CI: 0.8, 2.4], p<0.001), higher pre-operative HRQOL (ß=0.7 [95%CI: 0.5, 0.8], p<0.001), higher family resources (ß=0.6 [95%CI: 0.3, 0.9], p<0.001), better family relationships (ß=1.7 [95%CI: 0.3, 3.1], p = 0.017) and lower family demands (ß=-0.9 [95%CI: -1.5, -0.4], p<0.001) were associated with higher HRQOL after surgery. Caregiver characteristics did not predict HRQOL after surgery (p>0.05). Multivariable regression showed older age at seizure onset (ß=4.6 [95%CI: 1.6, 7.6], p = 0.003) and higher pre-operative HRQOL (ß=10.2 [95%CI: 6.8, 13.6], p<0.001) were associated with higher HRQOL after surgery. CONCLUSION: This study underscores the importance of optimizing pre-operative HRQOL to maximize HRQOL outcome after pediatric epilepsy surgery.
RESUMO
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related deaths in children and adults with epilepsy. The incidence of SUDEP in children and adults is equal, approximately 1.2 per 1000-person years. Although inroads have been made in our understanding of SUDEP, its pathophysiology remains unknown. The most important risk factor for SUDEP is the presence of tonic-clonic seizures. Recently there has been growing interest in the contribution of genetic risk factors to SUDEP deaths. Pathogenic variants in epilepsy-related and cardiac genes have been found in some cases of SUDEP post-mortem. Pleiotropy may occur in which a single gene when altered may cause multiple phenotypes (i.e., epilepsy and cardiac arrhythmia). Recently it has been shown that some developmental and epileptic encephalopathies (DEEs) may also be at heightened risk of SUDEP. In addition, polygenic risk has been postulated to effect SUDEP risk with current models evaluating the additive effect of variants in multiple genes. However, the mechanisms underpinning polygenic risk in SUDEP are likely more complex than this. Some preliminary studies also highlight the feasibility of detecting genetic variants in brain tissue post-mortem. Despite the advances in the field of SUDEP genetics, the use of molecular autopsy remains underutilized in SUDEP cases. Several challenges exist concerning genetic testing post-mortem in SUDEP cases, such as interpretation, cost of testing, and availability. In this focused review, we highlight the current landscape of genetic testing in SUDEP cases, its challenges, and future directions.
Assuntos
Epilepsia , Morte Súbita Inesperada na Epilepsia , Humanos , Epilepsia/complicações , Morte Súbita/epidemiologia , Morte Súbita/etiologia , Encéfalo/patologia , Arritmias Cardíacas/genética , Fatores de RiscoRESUMO
OBJECTIVE: To understand how knowledge of sudden unexpected death in epilepsy (SUDEP) impacted the lives of adult persons with epilepsy (PWE) and primary caregivers of both adults and children with epilepsy. METHODS: The principles of fundamental qualitative description guided this descriptive and exploratory qualitative study to document patients' and caregivers' perceptions and experiences. A purposeful sample of individuals (18 years or older) diagnosed with epilepsy or primary caregivers of PWE completed a single in-depth, semi-structured, one-to-one telephone interview. Categories of findings were developed using directed content analysis. RESULTS: A total of twenty-seven participants completed the study. This consisted of eight adult females and six adult males with epilepsy, ten female caregivers, and three male caregivers of PWE. All participants had become aware of SUDEP at least 12 months before their interview. Most were not informed about SUDEP by their treating neurologist and instead learned about SUDEP via alternative sources (e.g., the internet). All participants believed that knowledge of SUDEP outweighed the risks of being informed about it. Anxiety/fear related to SUDEP disclosure was generally not long-lasting. Caregivers of PWE were more directly impacted by SUDEP disclosure than adult PWE. Caregivers were more likely to make lifestyle/management changes due to learning about SUDEP (e.g., increased supervision and co-sleeping). Participants agreed that follow-up clinical support should be provided after SUDEP disclosure. CONCLUSIONS: Disclosure of SUDEP risk may have more significant impacts on caregivers of PWE than adult PWE in the form of lifestyle changes and epilepsy management. After SUDEP disclosure, follow-up support should be offered to PWE and their caregivers, which should be incorporated into future guidelines.
Assuntos
Epilepsia , Morte Súbita Inesperada na Epilepsia , Adulto , Criança , Humanos , Masculino , Feminino , Morte Súbita , Cuidadores , Pesquisa Qualitativa , Fatores de RiscoRESUMO
OBJECTIVE: Epileptic Encephalopathy / Developmental Epileptic Encephalopathy with spike-and-wave activation in sleep (EE/DEE-SWAS) is defined as an epilepsy syndrome characterized by neurodevelopmental regression temporally related to the emergence of significant activation of spike-wave discharges in EEG during sleep. The availability of genetic testing has made it evident that monogenic and chromosomal abnormalities play an aetiological role in the development of EE/DEE-SWAS. We sought to review the literature to better understand the genetic landscape of EE/DEE-SWAS. METHODS: In this systematic review, we reviewed cases of EE/DEE-SWAS associated with a genetic aetiology, collecting information related to the underlying aetiology, onset, management, and EEG patterns. RESULTS: One hundred and seventy-two cases of EE/DEE-SWAS were identified. Genetic causes of note included pathogenic variants in GRIN2A, ZEB2, CNKSR2 and chromosome 17q21.31 deletions, each of which demonstrated unique clinical characteristics, EEG patterns, and age of onset. Factors identified to raise suspicion of a potential genetic aetiology included the presentation of DEE-SWAS and onset of SWAS under the age of five years. Treatment of EE/DEE-SWAS due to genetic causes was diverse, including a combination of anti-seizure medications, steroids, and other clinical strategies, with no clear consensus on a preferred or superior treatment. Data collected was significantly heterogeneous, with a lack of consistent use of neuropsychology testing, EEG patterns, or use of established clinical definitions. CONCLUSIONS: Uniformity concerning the new definition of EE/DEE-SWAS, guidelines for management and more frequent genetic screening will be needed to guide best practices for the treatment of patients with EE/DEE-SWAS.
Assuntos
Epilepsia Generalizada , Síndromes Epilépticas , Humanos , Pré-Escolar , Sono/genética , Testes Genéticos , Eletroencefalografia , Proteínas Adaptadoras de Transdução de SinalRESUMO
OBJECTIVES: The purpose of this longitudinal cohort study was to examine the variables that influence health-related quality of life (HRQOL) after epilepsy surgery in children. We examined whether treatment type (surgical vs medical therapy) and seizure control are related to other variables that have been shown to influence HRQOL, namely depressive symptoms in children with epilepsy or their parents, and the availability of family resources. METHODS: In total, 265 children with drug-resistant epilepsy were recruited from eight epilepsy centers across Canada at the time of their evaluation for candidacy for epilepsy surgery and were assessed at baseline, 6-month, 1-year, and 2-year follow-up. Parents completed the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) and measures of family resources and depression; children completed depression inventories. Causal mediation analyses using natural effect models were used to evaluate the extent to which the relationship between treatment and HRQOL was explained by seizure control, child and parent depressive symptoms, and family resources. RESULTS: Overall, 111 children underwent surgery and 154 were treated with medical therapy only. The HRQOL scores of surgical patients were 3.4 points higher (95% confidence interval [CI]: -0.2, 7.0) relative to medical patients at the 2-year follow-up after adjusting for baseline covariates, with 66% of the effect of surgery attributed to seizure control. Child or parent depressive symptoms and family resources had negligible mediation effects between treatment and HRQOL. The effect of seizure control on HRQOL was not mediated by child or parent depressive symptoms, or by family resources. SIGNIFICANCE: The findings demonstrate that seizure control is on the causal pathway between epilepsy surgery and improved HRQOL in children with drug-resistant epilepsy. However, child and parent depressive symptoms and family resources were not significant mediators. The results highlight the importance of achieving seizure control to improve HRQOL.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Criança , Humanos , Qualidade de Vida , Estudos Longitudinais , Epilepsia/tratamento farmacológico , Epilepsia/cirurgia , Epilepsia/diagnóstico , Estudos de Coortes , Epilepsia Resistente a Medicamentos/cirurgia , Inquéritos e Questionários , ConvulsõesRESUMO
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death in children and adults living with epilepsy. Several recent clinical practice guidelines have recommended that all individuals living with epilepsy and their caregivers be informed about SUDEP as a part of routine epilepsy counseling. Furthermore, several studies over the last two decades have explored the state of SUDEP counseling. Patients with epilepsy and their families want to be informed about the risk of SUDEP at or near the time of diagnosis, and preferably in person. Despite guideline recommendations, many pediatric and adult neurologists do not routinely inform individuals with epilepsy and their families about SUDEP. Some neurologists discuss SUDEP with only a subset of patients with epilepsy, such as those with risk factors like frequent generalized or focal to bilateral tonic-clonic seizures, nocturnal seizures, noncompliance, or medically refractory epilepsy. Proponents of routine SUDEP counseling argue that patients with epilepsy and their families have a "right to know" and that counseling may positively impact epilepsy self-management (i.e., behavioral modification and risk reduction). Some neurologists still believe that SUDEP counseling may cause unnecessary stress and anxiety for patients and their families (although this is erroneous) and that they also have a "right not to know." This narrative review explores the current gaps in SUDEP counseling, patients' and caregivers' perspectives of SUDEP counseling, and SUDEP prevention.
Assuntos
Epilepsia Reflexa , Morte Súbita Inesperada na Epilepsia , Adulto , Humanos , Criança , Morte Súbita Inesperada na Epilepsia/etiologia , Convulsões , Fatores de Risco , AconselhamentoRESUMO
OBJECTIVE: ST3GAL3-related developmental and epileptic encephalopathy (DEE-15) is an autosomal recessive condition characterized by intellectual disability, language and motor impairments, behavioral difficulties, stereotypies, and epilepsy. Only a few cases have been reported, and the epilepsy phenotype is not fully elucidated. METHODS: A retrospective chart review of two siblings with ST3GAL3-related DEE was completed. In addition, we reviewed all published cases of ST3GAL3-related congenital disorder of glycosylation. RESULTS: Two brothers presented with global developmental delay, motor and language impairment, hypotonia, and childhood-onset seizures. Seizures started between 2.5 and 5 years and had tonic components. Both siblings had prolonged periods of seizure freedom on carbamazepine. Tremor was present in the younger sibling. Whole exome sequencing revealed two novel pathogenic variants in ST3GAL3, (a) c.302del, p.Phe102Serfs*34 and (b) c.781C>T, p.Arg261*, which were inherited in trans. Magnetic resonance imaging showed T2 hyperintensities and restricted diffusion in the brainstem and middle cerebellar peduncle in the older sibling, also described in two reported cases. A review of the literature revealed 24 cases of ST3GAL3-related CDG. Twelve cases had information about seizures, and epilepsy was diagnosed in 8 (67%). The median age of seizure onset was 5.5 months. Epileptic spasms were most common (67%). Four children were diagnosed with Infantile Epileptic Spasms syndrome and Lennox Gastaut syndrome (57%). Most children (n = 6, 75%) had seizures despite anti-seizure medication treatment. SIGNIFICANCE: Seizures related to ST3GAL3-related DEE often occur in infancy and may present as epileptic spasms. However, seizure onset may also occur outside of infancy with mixed seizure types and show good response to treatment with prolonged seizure freedom. Tremor may also be uniquely observed in this condition.
Assuntos
Epilepsia , Espasmos Infantis , Humanos , Masculino , Epilepsia/genética , Epilepsia/diagnóstico , Fenótipo , Estudos Retrospectivos , Espasmo , Espasmos Infantis/genética , TremorRESUMO
PURPOSE: To understand the experiences of bereaved relatives of individuals who passed due to sudden unexpected death in epilepsy (SUDEP) and to explore the impacts of death in their lives. METHODS: The principles of fundamental qualitative description informed all design decisions. Stratified purposeful sampling included 21 bereaved relatives (parent, sibling, or spouse/partner), aged at least 18 years, of persons who passed away because of SUDEP. In-depth one-to-one interviews were conducted. Directed content analysis was used to code, categorize, and synthesize the interview data. RESULTS: There was some criticism of emergency response and medical professionals involved in providing insensitive or poor care immediately after SUDEP occurred. Personal hardships described by participants following SUDEP included loss of personal identity, feeling depressed, experiencing guilt, having panic attacks, requiring therapy, as well as having difficulty with anniversaries, dates, and cleaning up a child's room. Bereaved spouses and parents in particular spoke of experiencing challenges in maintaining other relationships following the death. Some participants spoke of experiencing increased financial hardships. Ways of coping included keeping oneself busy, honoring the memory of the loved one, relying on friends and families, and engaging in advocacy/community work, including raising awareness on epilepsy and SUDEP. CONCLUSIONS: Sudden unexpected death in epilepsy affected several aspects of the day-to-day lives of bereaved relatives. Though methods of coping were similar to the usual strategies adopted by all bereaved relatives, advocacy work related to raising awareness about epilepsy and SUDEP was unique to this group. Guidelines on SUDEP should ideally include recommendations for trauma-informed support and assessment for depression and anxiety to the bereaved relatives as well.
Assuntos
Epilepsia , Morte Súbita Inesperada na Epilepsia , Adolescente , Adulto , Humanos , Morte Súbita/etiologia , Emoções , Epilepsia/terapia , Pais , Fatores de RiscoRESUMO
Importance: Health-related quality of life (HRQOL) is regarded as a key outcome for evaluating treatment efficacy. However, it is uncertain how HRQOL evolves after epilepsy surgery compared with medical therapy, such as whether it continues to improve over time, improves and then remains stable, or deteriorates after a period of time. Objective: To assess trajectory of HRQOL over 2 years in children with drug-resistant epilepsy (DRE) treated with surgery compared with medical therapy. Design, Setting, and Participants: Prospective cohort study assessing HRQOL longitudinally over 2 years. Participants were children recruited from 8 epilepsy centers in Canada from 2014 to 2019 with suspected DRE aged 4 to 18 years who were evaluated for surgery. Data were analyzed from May 2014 to December 2021. Exposures: Epilepsy surgery or medical therapy. Main Outcomes and Measures: HRQOL was measured using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE)-55. HRQOL and seizure frequency were assessed at baseline, 6-month, 1-year, and 2-year follow-ups. Clinical, parent, and family characteristics were assessed at baseline. A linear mixed model was used to evaluate HRQOL over time, adjusting for baseline clinical, parent, and family characteristics. Results: There were 111 surgical and 154 medical patients (mean [SD] age at baseline was 11.0 [4.1] years; 118 [45%] were female). At baseline, HRQOL was similar among surgical and medical patients. HRQOL of surgical patients was 3.0 (95% CI, -0.7 to 6.8) points higher at 6-month, 4.9 (95% CI, 0.7 to 9.1) points higher at 1-year, and 5.1 (95% CI, 0.7 to 9.5) points higher at 2-year follow-ups compared with medical patients. Surgical patients experienced greater improvements in social functioning relative to medical patients, but not for cognitive, emotional, and physical functioning. At 2-year follow-up, 72% of surgical patients were seizure-free, compared with 33% of medical patients. Seizure-free patients reported higher HRQOL than those who were not. Conclusions and Relevance: This study provided evidence on the association between epilepsy surgery and children's HRQOL, with improvement in HRQOL occurring within the first year and remaining stable 2 years after surgery. By demonstrating that surgery improved seizure freedom and HRQOL, which has downstream effects such as better educational attainment, reduced health care resource utilization, and health care cost, these findings suggest that the high costs of surgery are justified, and that improved access to epilepsy surgery is necessary.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Criança , Humanos , Feminino , Masculino , Qualidade de Vida/psicologia , Estudos Prospectivos , Epilepsia/cirurgia , Resultado do Tratamento , Epilepsia Resistente a Medicamentos/cirurgiaRESUMO
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality in children and adults living with epilepsy. The incidence of SUDEP is comparable in both children and adults; it is approximately 1.2 per 1000 person years. The pathophysiology of SUDEP is not well understood but may involve mechanisms such as cerebral shutdown, autonomic dysfunction, altered brainstem function, and cardiorespiratory demise. Risk factors for SUDEP include the presence of generalized tonic-clonic seizures, nocturnal seizures, possible genetic predisposition, and non-adherence to antiseizure medications. Pediatric-specific risk factors are not fully elucidated. Despite recommendations from consensus guidelines, many clinicians still do not follow the practice of counseling their patients about SUDEP. SUDEP prevention has been an area of important research focus and includes several strategies, such as obtaining seizure control, optimizing treatment regimens, nocturnal supervision, and seizure detection devices. This review discusses what is currently known about SUDEP risk factors and reviews current and future preventive strategies for SUDEP.
Assuntos
Epilepsia Reflexa , Morte Súbita Inesperada na Epilepsia , Adulto , Humanos , Criança , Morte Súbita Inesperada na Epilepsia/epidemiologia , Morte Súbita Inesperada na Epilepsia/etiologia , Morte Súbita/epidemiologia , Morte Súbita/etiologia , Morte Súbita/prevenção & controle , Convulsões/complicações , Fatores de RiscoRESUMO
The ketogenic diet (KD) is a widely used therapeutic option for individuals with medically refractory epilepsy. As the diet's name implies, ketosis is a historically important component of the diet, but it is not well understood how important ketosis is for seizure control. The ketogenic ratio is defined as the ratio of fat to carbohydrate plus protein by weight in the diet (grams). Traditionally, the classic KD contains a 4:1 ratio, and a very high proportion of fat in the diet. The classic KD, with its high proportion of fat and limited carbohydrate intake can be restrictive for patients with epilepsy. Recently, there is experience with use of lower ketogenic ratios and less-restrictive diets such as the modified Atkins diet and the low glycemic index treatment. In this narrative review, we examine the role of ketosis and ketogenic ratios in determining the efficacy of the KD in children with epilepsy.
Assuntos
Dieta Cetogênica , Epilepsia Resistente a Medicamentos , Epilepsia , Cetose , Criança , Humanos , Epilepsia/tratamento farmacológico , Corpos Cetônicos/uso terapêutico , Carboidratos/uso terapêutico , Resultado do Tratamento , Dieta com Restrição de CarboidratosRESUMO
PURPOSE: This study evaluated the sensitivity of nonconvulsive seizure detection by non-neurophysiologist physicians and nurses using a panel of quantitative EEG (QEEG) trends in the setting of a pediatric intensive care unit. METHODS: Forty-five 1-hour QEEG epochs were obtained retrospectively from 10 patients admitted to the McMaster Children's Hospital pediatric intensive care unit, which included 184 electrographic seizures. Each epoch constituted 4 QEEG trends, a seizure probability marker, automated seizure detector, rhythmicity spectrograms, and amplitude-integrated EEG. Six pediatric residents and 5 pediatric intensive care unit nurses analyzed the epochs for possible seizures after a 15-minute power point presentation. This was compared with the gold standard of a board-certified epileptologist interpreting the conventional EEG data for seizures. RESULTS: Sensitivity of seizure detection for pediatric residents and intensive care unit nurses were 0.90. The specificity was 0.87 and 0.89, respectively. The interrater agreement among the pediatric residents was moderate with a kappa (κ) value of 0.45 (confidence interval: 0.41-0.49), and among the nurses were moderate with a κ value of 0.59 (confidence interval: 0.54-0.63). A post hoc analysis involving 2 neurophysiologists demonstrated a sensitivity of 0.90 and a specificity of 0.93 (confidence interval: 0.90-0.96) for seizure detection and a substantial interrater agreement of κ = 0.76 (confidence interval: 0.61-0.91). CONCLUSIONS: A panel of QEEG trends can be used by non-neurophysiologists in a pediatric critical care setting to detect nonconvulsive seizures with a reasonable accuracy, which may expedite subclinical seizure identification and timely intervention.