The Genetics of Tuberous Sclerosis Complex and Related mTORopathies: Current Understanding and Future Directions.

The mechanistic target of rapamycin (mTOR) pathway serves as a master regulator of cell growth, proliferation, and survival. Upregulation of the mTOR pathway has been shown to cause malformations of cortical development, medically refractory epilepsies, and neurodevelopmental disorders, collectively described as mTORopathies. Tuberous sclerosis complex (TSC) serves as the prototypical mTORopathy. Characterized by the development of benign tumors in multiple organs, pathogenic variants in TSC1 or TSC2 disrupt the TSC protein complex, a negative regulator of the mTOR pathway. Variants in critical domains of the TSC complex, especially in the catalytic TSC2 subunit, correlate with increased disease severity. Variants in less crucial exons and non-coding regions, as well as those undetectable with conventional testing, may lead to milder phenotypes. Despite the assumption of complete penetrance, expressivity varies within families, and certain variants delay disease onset with milder neurological effects. Understanding these genotype-phenotype correlations is crucial for effective clinical management. Notably, 15% of patients have no mutation identified by conventional genetic testing, with the majority of cases postulated to be caused by somatic TSC1/TSC2 variants which present complex diagnostic challenges. Advancements in genetic testing, prenatal screening, and precision medicine hold promise for changing the diagnostic and treatment paradigm for TSC and related mTORopathies. Herein, we explore the genetic and molecular mechanisms of TSC and other mTORopathies, emphasizing contemporary genetic methods in understanding and diagnosing the condition.

Measurable transitions during seizures in intracranial EEG: A stereoelectroencephalography and SPECT study.

OBJECTIVE: Ictal Single Photon Emission Computed Tomography (SPECT) and stereo-electroencephalography (SEEG) are diagnostic techniques used for the management of patients with drug-resistant focal epilepsies. While hyperperfusion patterns in ictal SPECT studies reveal seizure onset and propagation pathways, the role of ictal hypoperfusion remains poorly understood. The goal of this study was to systematically characterize the spatio-temporal information flow dynamics between differently perfused brain regions using stereo-EEG recordings. METHODS: We identified seizure-free patients after resective epilepsy surgery who had prior ictal SPECT and SEEG investigations. We estimated directional connectivity between the epileptogenic-zone (EZ), non-resected areas of hyperperfusion, hypoperfusion, and baseline perfusion during the interictal, preictal, ictal, and postictal periods. RESULTS: Compared to the background, we noted significant information flow (1) during the preictal period from the EZ to the baseline and hyperperfused regions, (2) during the ictal onset from the EZ to all three regions, and (3) during the period of seizure evolution from the area of hypoperfusion to all three regions. CONCLUSIONS: Hypoperfused brain regions were found to indirectly interact with the EZ during the ictal period. SIGNIFICANCE: Our unique study, combining intracranial electrophysiology and perfusion imaging, presents compelling evidence of dynamic changes in directional connectivity between brain regions during the transition from interictal to ictal states.

The landscape of drug resistant absence seizures in adolescents and adults: Pathophysiology, electroclinical spectrum and treatment options.

The persistence of typical absence seizures (AS) in adolescence and adulthood may reduce the quality of life of patients with genetic generalized epilepsies (GGEs). The prevalence of drug resistant AS is probably underestimated in this patient population, and treatment options are relatively scarce. Similarly, atypical absence seizures in developmental and epileptic encephalopathies (DEEs) may be unrecognized, and often persist into adulthood despite improvement of more severe seizures. These two seemingly distant conditions, represented by typical AS in GGE and atypical AS in DEE, share at least partially overlapping pathophysiological and genetic mechanisms, which may be the target of drug and neurostimulation therapies. In addition, some patients with drug-resistant typical AS may present electroclinical features that lie in between the two extremes represented by these generalized forms of epilepsy.

Whole exome sequencing identifies variable expressivity of CLN6 variants in Progressive myoclonic epilepsy affected families.

Progressive myoclonic epilepsies (PMEs) are a group of neurodegenerative disorders, predominantly affecting adolescents and, characterized by generalized worsening myoclonus epilepsies, ataxia, cognitive deficits, and dementia. To date, several genes, having implications in diverse phenotypic expressions associated with PMEs, have been identified. Genetic diagnosis is available for most of the adolescence-onset myoclonic epilepsies. This study aimed to elucidate the genetic basis of PMEs in three multiplex Pakistani families exhibiting clinically variable phenotypes. Causative variant(s) in the studied families, and mode of segregation were identified by Whole Exome Sequencing (WES) of the probands, followed by bi-directional Sanger sequencing for final validation. We identified homozygous recessive CLN6 missense variant c.768 C>G (p.Asp256Glu) in Family 1, and c.889 C>A (p.Pro297Thr) variant in Family 2. While in Family 3, we found a homozygous variant (c.316dup) that caused a frameshift mutation, leading to a premature stop codon in the CLN6 protein, resulting in a truncated protein (p.Arg106ProfsTer26). Though CLN6 is previously identified to underlie late infantile and adolescent onset neuronal ceroid lipofuscinosis, this study supports and expands the phenotypic spectrum of CLN6 mutations and signifies diagnositc potential CLN6 variants for PMEs. Diverse pathological effects of variant c .768 C>G were observed in Family 1, with same genotypes, suggesting clinical heterogeneity and/or variable expressivity that might be the implication of pleiotropic effects of the gene in these cases.

The burden of epilepsy on long-term outcome of genetic developmental and epileptic encephalopathies: A single tertiary center longitudinal retrospective cohort study.

BACKGROUND: This retrospective cohort analysis highlighted neurodevelopmental outcome predictors of genetic developmental and epileptic encephalopathies (DEE). PATIENTS AND METHODS: Patients' demographic, clinical and molecular genetics data were collected. All patients underwent clinical, developmental, and neuropsychological assessments. RESULTS: We recruited 100 participants (53 males, 47 females) with a mean follow-up lasting 10.46 ± 8.37 years. Age at epilepsy-onset was predictive of poor adaptive and cognitive functions (VABS-II score, r = 0.350, p = 0.001; BRIEF control subscale, r = -0.253; p = 0.031). Duration of epilepsy correlated negatively with IQ (r = -0.234, p = 0.019) and VABS-II score (r = -0.367, p = 0.001). Correlations were found between delayed/lacking EEG maturation/organization and IQ (r = 0.587, p = 0.001), VABS-II score (r = 0.658, p = 0.001), BRIEF-MI and BRIEF-GEC scores (r = -0.375, p = 0.001; r = -0.236, p = 0.033), ASEBA anxiety (r = -0.220, p = 0.047) and ADHD (r = -0.233, p = 0.035) scores. The number of antiseizure medications (ASMs) correlated with IQ (r = -0.414, p = 0.001), VABS-II (r = -0.496, p = 0.001), and BRIEF-MI (r = 0.294, p = 0.012) scores; while age at the beginning of therapy with ASEBA anxiety score (r = 0.272, p = 0.013). The occurrence of status epilepticus was associated with worse adaptive performances. The linear regression analysis model showed that delayed/lacking EEG maturation/organization had a significant influence on the IQ (R2 = 0.252, p < 0.001) and the BRIEF-GEC variability (R2 = 0.042, p = 0.036). The delayed/lacking EEG maturation/organization and the duration of epilepsy also had a significant influence on the VABS-II score (R2 = 0.455, p = 0.005). CONCLUSIONS: Age at seizure-onset, EEG maturation/organization, duration of epilepsy, occurrence of status epilepticus, age at the introduction and number of ASMs used are reliable predictors of long-term outcomes in patients with genetic DEE.

Drug resistant epilepsies: A multicentre case series of steroid therapy.

PURPOSE: Our study aimed to evaluate the effectiveness of corticosteroids on seizure control in drug-resistant epilepsies (DREs). Our primary goal was to assess the response to steroids for various underlying etiologies, interictal electroencephalographic (EEG) patterns and electroclinical seizure descriptions. Our second goal was to compare steroid responsiveness to different treatment protocols. METHODS: This is a retrospective multicentre cohort study conducted according to the STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology). The following data were collected for each patient: epilepsy etiology, interictal EEG pattern, seizure types and type of steroid treatment protocol administered. RESULTS: Thirty patients with DRE were included in the study. After 6 months of therapy, 62.7 % of patients experienced reduced seizure frequency by 50 %, and 6.6 % of patients experienced complete seizure cessation. Findings associated with favourable response to steroids included structural/lesional etiology of epilepsy, immune/infectious etiology and focal interictal abnormalities on EEG. Comparing four different steroid treatment protocols, the most effective for seizure control was treatment with methylprednisolone at the dose of 30 mg/kg/day administered for 3 days, leading to greater than 50 % seizure reduction at 6 months in 85.7 % of patients. Treatment with dexamethasone 6 mg/day for 5 days decreased seizure frequency in 71.4 % of patients. Hydrocortisone 10 mg/kg administered for 3 months showed a good response to treatment in 71 %. CONCLUSIONS: In our study, two-thirds of patients with DRE experienced a significant seizure reduction following treatment with steroids. We suggest considering steroids as a potential therapeutic option in children with epilepsy not responding to conventional antiseizure medicines (ASM).

Role of Perampanel in the Management of Pediatric Epilepsies in Asia: Expert Opinion.

Management of pediatric epilepsies poses unique challenges around diagnosis, treatment options, comorbidities, and the potential for these factors to interact with processes in the developing brain. In pediatric patients, broad-spectrum antiseizure medications (ASMs) with minimal potential for adverse events (AEs) and limited impact on cognition and behavior are preferred. Perampanel is a first-in-class ASM with broad-spectrum efficacy, a tolerable safety profile, minimal negative impact on cognitive function, and other features that make it a viable treatment option in this patient population. However, evidence and experience of its use in pediatric patients are less extensive than in adult patients. Experts in pediatric epilepsy across the region convened at a series of meetings to discuss the use of perampanel in pediatric patients, including dose optimization, AE prevention and management, and considerations in particular groups. This article summarizes key evidence for perampanel in the pediatric population and consolidates the experts' recommendations for using the ASM in managing pediatric epilepsies.

Distinct manifestations and potential mechanisms of seizures due to cortical versus white matter injury in children.

PURPOSE: To study seizure manifestations and outcomes in children with cortical versus white matter injury, differences potentially explaining variability of epilepsy in children with cerebral palsy. METHODS: In this population-based retrospective cohort study, MRIs of children with cerebral palsy due to ischemia or haemorrhage were classified according to presence or absence of cortical injury. MRI findings were then correlated with history of neonatal seizures, seizures during childhood, epilepsy syndromes, and seizure outcomes. RESULTS: Of 256 children studied, neonatal seizures occurred in 57 and seizures during childhood occurred in 93. Children with neonatal seizures were more likely to develop seizures during childhood, mostly those with cortical injury. Cortical injury was more strongly associated with (1) developing seizures during childhood, (2) more severe epilepsy syndromes (infantile spasms syndrome, focal epilepsy, Lennox-Gastaut syndrome), and (3) less likelihood of reaching > 2 years without seizures at last follow-up, compared to children without cortical injury. Children without cortical injury, mainly those with white matter injury, were less likely to develop neonatal seizures and seizures during childhood, and when they did, epilepsy syndromes were more commonly febrile seizures and self-limited focal epilepsies of childhood, with most achieving > 2 years without seizures at last follow-up. The presence of cortical injury also influenced seizure occurrence, severity, and outcome within the different predominant injury patterns of the MRI Classification System in cerebral palsy, most notably white matter injury. CONCLUSIONS: Epileptogenesis is understood with cortical injury but not well with white matter injury, the latter potentially related to altered postnatal white matter development or myelination leading to apoptosis, abnormal synaptogenesis or altered thalamic connectivity of cortical neurons. These findings, and the potential mechanisms discussed, likely explain the variability of epilepsy in children with cerebral palsy and epilepsy following early-life brain injury in general.

Epilepsy surgery as a treatment option for select patients with PCDH19-related epilepsy.

PCDH19 is a common epilepsy gene causing medication resistant epilepsy with fever-related seizures. Traditionally, patients with PCDH19-related epilepsy have not been considered surgical candidates. This retrospective review evaluated three patients with pathogenic variants in PCDH19 who presented with seizures in childhood, had one seizure semiology, became medication resistant, and had concordant imaging, seizure semiology and electrographic findings. All three patients ultimately underwent temporal lobectomy, resulting in seizure freedom. These findings suggest epilepsy surgery can be an effective treatment option for select patients with PCDH19-related epilepsy and a single seizure semiology.

Genetic Background of Epilepsy and Antiepileptic Treatments.

Advanced identification of the gene mutations causing epilepsy syndromes is expected to translate into faster diagnosis and more effective treatment of these conditions. Over the last 5 years, approximately 40 clinical trials on the treatment of genetic epilepsies have been conducted. As a result, some medications that are not regular antiseizure drugs (e.g., soticlestat, fenfluramine, or ganaxolone) have been introduced to the treatment of drug-resistant seizures in Dravet, Lennox-Gastaut, maternally inherited chromosome 15q11.2-q13.1 duplication (Dup 15q) syndromes, and protocadherin 19 (PCDH 19)-clusterig epilepsy. And although the effects of soticlestat, fenfluramine, and ganaxolone are described as promising, they do not significantly affect the course of the mentioned epilepsy syndromes. Importantly, each of these syndromes is related to mutations in several genes. On the other hand, several mutations can occur within one gene, and different gene variants may be manifested in different disease phenotypes. This complex pattern of inheritance contributes to rather poor genotype-phenotype correlations. Hence, the detection of a specific mutation is not synonymous with a precise diagnosis of a specific syndrome. Bearing in mind that seizures develop as a consequence of the predominance of excitatory over inhibitory processes, it seems reasonable that mutations in genes encoding sodium and potassium channels, as well as glutamatergic and gamma-aminobutyric (GABA) receptors, play a role in the pathogenesis of epilepsy. In some cases, different pathogenic variants of the same gene can result in opposite functional effects, determining the effectiveness of therapy with certain medications. For instance, seizures related to gain-of-function (GoF) mutations in genes encoding sodium channels can be successfully treated with sodium channel blockers. On the contrary, the same drugs may aggravate seizures related to loss-of-function (LoF) variants of the same genes. Hence, knowledge of gene mutation-treatment response relationships facilitates more favorable selection of drugs for anticonvulsant therapy.

Genome-Based Therapeutics: Era of Precision Medicine in Genetic Epilepsies and Epileptic Encephalopathies.

Introduction: The recent evolution of genomics has led to the development of targeted therapeutics, revolutionizing medical approaches. This study aimed to assess the impact of genetic testing on the current epilepsy management paradigm with a specific focus on the variability of outcomes subsequent to genetic diagnoses. Methodology: Data were collected retrospectively from a cohort of children aged 1-18 years, diagnosed with refractory epilepsy of confirmed genetic origin. The participants received care at a quaternary care center's pediatric neurology clinic from August 2019 to June 2021. The collected information included demographic characteristics, seizure types, EEG findings, imaging abnormalities, genetic diagnoses, attempted treatments, and seizure outcomes. Results: Among the 210 children with confirmed genetic diagnoses, 74 were included in the study. The gender distribution comprised 45 males and 29 females. Within the cohort, 68/74 exhibited single gene variations, with 23 cases associated with sodium/potassium/calcium channelopathies. Precision medicine could be applied to 25/74 cases. 17/74 children (22.97%) experienced a reduction of up to 50% in seizure frequency due to precision medicine implementation. Conclusion: While our study indicates the significance of genetic insights in adapting treatment approaches for pediatric epilepsy, it is important to temper our conclusions. The retrospective nature of our study confines our ability to definitively gauge the extent of precision medicine's utility. Our findings suggest the potential of genetic information to enhance epilepsy management, but the true impact of precision medicine can only be established through prospective investigations.

Epilepsias generalizadas idiopáticas / Idiopathic generalized epilepsies

Resumen Las epilepsias generalizadas idiopáticas (EGI) son un grupo de epilepsias generalizadas edad de pendientes, subgrupo de las Epilepsias genéticas generalizadas(EGG), con hallazgos electro-clínicos característicos y herencia poligénica. Las EGI inclu yen 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 com binación de crisis de ausencias, mioclonías, tónica-clónicas omioclónica-tónica-clónicas con patrón elec troencefalográfico de punta onda lenta de 2.5 a 6cps y activación con la hiperventilación y fotoestimula ción, Sobresalen de las EGG por compartir atributos particulares como el buen pronóstico con control frecuente de las crisis, la no evolución a encefalopa tías 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 importan te para el uso adecuado del recurso, evitando estudios innecesarios, adecuada orientación del pronóstico y un tratamiento óptimo.

Abstract 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 myoclonic-tonic-clonic with common electroencephalographic pat terns 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, attention-deficit/hyperactivity disorder (ADHD), and learning dis abilities, 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.

[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.

Are Genetic Therapies for Epilepsy Ready for the Clinic?

In recent years, there has been a significant increase in preclinical studies to test genetic therapies for epilepsy. Some of these therapies have advanced to clinical trials and are being tested in patients with monogenetic or focal refractory epilepsy. This article provides an overview of the current state of preclinical studies that show potential for clinical translation. Specifically, we focus on genetic therapies that have demonstrated a clear effect on seizures in animal models and have the potential to be translated to clinical settings. Both therapies targeting the cause of the disease and those that treat symptoms are discussed. We believe that the next few years will be crucial in determining the potential of genetic therapies for treating patients with epilepsy.

Atypical Presentations of Childhood Simple Partial Seizures: a Case Series.

Childhood epilepsy can masquerade as a variety of psychiatric disorders or behavioural abnormalities. Differentiating between simple partial seizure and psychiatric disorders remains a challenge. We report on three children with simple partial seizure, each presented atypically with migraine, tingling sensations, and/or crying spells. When dealing with atypical symptomatology, clinicians should utilise a multidirectional, rather than unidirectional, diagnostic approach when making their diagnosis.

ILAE Genetics Literacy series: Progressive myoclonus epilepsies.

Progressive Myoclonus Epilepsy (PME) is a rare epilepsy syndrome characterized by the development of progressively worsening myoclonus, ataxia, and seizures. A molecular diagnosis can now be established in approximately 80% of individuals with PME. Almost fifty genetic causes of PME have now been established, although some remain extremely rare. Herein, we provide a review of clinical phenotypes and genotypes of the more commonly encountered PMEs. Using an illustrative case example, we describe appropriate clinical investigation and therapeutic strategies to guide the management of this often relentlessly progressive and devastating epilepsy syndrome. This manuscript in the Genetic Literacy series maps to Learning Objective 1.2 of the ILAE Curriculum for Epileptology (Epileptic Disord. 2019;21:129).

Caring for Children with Dravet Syndrome: Exploring the Daily Challenges of Family Caregivers.

While Polish studies focus on the symptoms, causes and treatment of people suffering from Dravet syndrome (DS), much less is known about the situation of the family caregivers of DS children. This study was designed to explore the experiences, daily challenges and needs related to caring for DS children. An anonymous self-administered online questionnaire was developed. The survey was completed by 75 family caregivers affiliated with the Association for People with Severe Refractory Epilepsy DRAVET.PL on Facebook. Most caregivers felt burdened by their children's reduced mobility (57.3%), mood swings (57.3%), lack of access to rehabilitation and medicine (56%) and healthcare expenses (50.7%). Caregivers also complained of a lack of time to themselves (76%) and work restrictions resulting from caregiving (72%). They consequently reported experiencing fatigue (84%), a deterioration of mental health (60%) and intimacy problems with their spouse/partner (53.4%). An important source of strain was a prolonged diagnostic odyssey and the constant struggle over the healthcare services for DS children. Since DS caregivers' problems and needs are often overlooked, they may be described as the forgotten people in DS. Healthcare professionals should be educated about the challenges related to caring for DS child, psycho-social status and coping resources of DS caregivers, and should focus on identification, monitoring and supporting caregivers' physical and mental well-being and needs.

The test-retest reliability and minimal detectable change of the six-minute walk test, timed up and go test, and 30-second chair stand test in people with epilepsy.

BACKGROUND: The available evidence suggests that people with epilepsy have reduced cardio-respiratory fitness and muscle strength endurance, and impaired balance and mobility. The 6-minute walk test (6MWT), Timed Up and Go (TUG), and 30-second chair stand test (30CST) are physical performance tests frequently used in clinical practice. OBJECTIVE: To establish the test-retest reliability and minimal detectable change of the 6MWT, TUG, and 30CST in people with epilepsy. METHODS: The study was designed as an observational study. Forty-one people with epilepsy (23 females, 18 males; mean age 34.7 ± 10.4 years) participated. The 6MWT, TUG, and 30CST were tested by a trained physiotherapist during two sessions, which were conducted 7-14 days apart. The test-retest reliability of measures was assessed using the intra-class correlation coefficients (ICC) using two-way random effects and absolute agreement methods. The 95% limits of agreement, standard error of measurement (SEM), and minimal detectable change (MDC95) were calculated. RESULTS: The 6MWT (ICC = 0.92, SEM = 15.8, MDC95 = 43.8), TUG (ICC = 0.95, SEM = 3.2, MDC95 = 0.5) and 30CST (ICC = 0.92, SEM = 1.0, MDC95 = 2.8) performance measurements demonstrated excellent test-retest reliability. The 95% limits of agreement was calculated, as illustrated in a Bland-Altman plot. CONCLUSION: The 6MWT, TUG, and 30CST are reliable for measuring physical performance. The findings of this study can support researchers and clinicians to decide if a change score of a person with epilepsy is likely to be measurement error or true change.