A controversial question: Can morphometry and clinical history be enough to diagnose hippocampal dysplasia?

The presence of dysmorphic neurons with strong cytoplasmatic accumulation of heavy non-phosphorylated neurofilament is crucial for the diagnostics of focal cortical dysplasia type II (FCDII). While ILAE's classification describes neocortical dysplasias, some groups have reported patients with mesial t abnormal neurons in the hippocampus of mesial temporal lobe epilepsy. Here we report a patient with such abnormal neurons in the hippocampus and compared it with previous reports of hippocampal dysplasia. Finally, we discuss the need for diagnostic criteria of hippocampal dysplasia.

Ketogenic therapy in childhood and adolescence: recommendations of the Brazilian experts group.

Ketogenic dietary therapies (KDTs) are a safe and effective treatment for pharmacoresistant epilepsy in children. There are four principal types of KDTs: the classic KD, the modified Atkins diet (MAD), the medium-chain triglyceride (MCT) diet, and the low glycemic index diet (LGID). The International Ketogenic Diet Study Group recommends managing KDTs in children with epilepsy. However, there are no guidelines that address the specific needs of the Brazilian population. Thus, the Brazilian Child Neurology Association elaborated on these recommendations with the goal of stimulating and expanding the use of the KD in Brazil.

As terapias dietéticas cetogênicas (TDC) são um tratamento seguro e eficaz para epilepsia farmacorresistente em crianças. Existem quatro tipos principais de TDCs: a dieta cetogênica (DC) clássica, a dieta de Atkins modificada (DAM), a dieta de triglicerídeos de cadeia média (DTCM) e a dieta de baixo índice glicêmico (DBIG). O Grupo Internacional de Estudos de Dietas Cetogênicas (International Ketogenic Diet Study Group) propõe recomendações para o manejo da DC em crianças com epilepsia. No entanto, faltam diretrizes que contemplem as necessidades específicas da população brasileira. Assim, a Associação Brasileira de Neurologia Infantil elaborou essas recomendações com o objetivo de estimular e expandir o uso da DC no Brasil.

Ketogenic therapy in childhood and adolescence: recommendations of the Brazilian experts group / Terapia cetogênica na infância e adolescência: recomendações do grupo de especialistas brasileiros

Abstract Ketogenic dietary therapies (KDTs) are a safe and effective treatment for pharmacoresistant epilepsy in children. There are four principal types of KDTs: the classic KD, the modified Atkins diet (MAD), the medium-chain triglyceride (MCT) diet, and the low glycemic index diet (LGID). The International Ketogenic Diet Study Group recommends managing KDTs in children with epilepsy. However, there are no guidelines that address the specific needs of the Brazilian population. Thus, the Brazilian Child Neurology Association elaborated on these recommendations with the goal of stimulating and expanding the use of the KD in Brazil.

Resumo As terapias dietéticas cetogênicas (TDC) são um tratamento seguro e eficaz para epilepsia farmacorresistente em crianças. Existem quatro tipos principais de TDCs: a dieta cetogênica (DC) clássica, a dieta de Atkins modificada (DAM), a dieta de triglicerídeos de cadeia média (DTCM) e a dieta de baixo índice glicêmico (DBIG). O Grupo Internacional de Estudos de Dietas Cetogênicas (International Ketogenic Diet Study Group) propõe recomendações para o manejo da DC em crianças com epilepsia. No entanto, faltam diretrizes que contemplem as necessidades específicas da população brasileira. Assim, a Associação Brasileira de Neurologia Infantil elaborou essas recomendações com o objetivo de estimular e expandir o uso da DC no Brasil.

Minimum effective sodium valproate dose in genetic generalized epilepsies.

INTRODUCTION: Sodium valproate (VPA) is the most effective antiseizure medication (ASM) in genetic generalized epilepsies (GGEs). However, the frequent adverse effects and the high risk inflicted on the exposed offspring make it imperative to search for the lowest daily VPA dose able to control seizures for most patients. In the current published series, the VPA value of <1000 mg was the most adopted. OBJECTIVE: This study aims to provide a cutoff VPA value below which a given daily dose can be considered a low dose in patients with GGEs. METHODS: This retrospective, observational cohort study included patients with clinical and electroencephalographic diagnoses of GGEs based on the ILAE criteria. Patients were followed up for at least two years using VPA in mono- or polytherapy. Clinical data, VPA dose, and associated ASMs were analyzed. Adverse effects were also evaluated. We related seizure control to VPA doses through uni- and multivariate statistical analyses. RESULTS: From 225 patients, 169 (75%) had good seizure control, with most (60%) receiving monotherapy. The cutoff daily VPA dose capable of distinguishing these patients from those without seizure control was up to 1000 mg (p = 0.006) in univariate analyses and up to 700 mg in multivariate analyses. For patients in polytherapy, the cutoff was up to 1750 mg and 1800 mg in uni- and multivariate analyses, respectively. CONCLUSIONS: The lowest daily VPA dose in monotherapy able to control seizures for most GGE patients was up to 700 mg, a value that can be used as a low dose criterion in studies assessing the therapeutic VPA ranges. Patients using higher VPA doses or in polytherapy present a lower probability of seizure control.

COVID-19 and epilepsy: How are people with epilepsy in Brazil?

PURPOSE: During COVID-19 pandemic the global population is facing an important psychosocial distress. The aim of this study was to evaluate how people with epilepsy (PWE) in Brazil is dealing with the pandemic, in relation to seizure frequency, access to antiseizure medicines (ASM), medical follow-up, and well-being. METHODS: An online questionnaire survey among PWE (group 1) and caregivers (group 2) was applied in the social networks of the Brazilian Association of Epilepsy, the official Brazilian chapter of the International Bureau for Epilepsy. The questionnaire was composed of 46 generic questions in four areas, namely, demographics and baseline clinical data as well as epilepsy and quality-of-life impact by COVID-19 pandemic based on the domains of the abbreviated World Health Organization Quality of Life (WHOQOL-BREF) instrument. RESULTS: The questionnaire was answered by 464 participants including 380 (81.9%) PWE (78.7% female; age 34.3 yrs.; ±9.76) and 84 (18.1%) caregivers (patients' age 14.1 yrs.; ±10.30). During the COVID-19 pandemic, 36.8% of PWE and 36.4% of caregivers reported difficulties in accessing the epilepsy healthcare provider, and visits occurred normally only in 29.7% of PWE and in 34.5% of the caregivers group. Telehealth was not provided for 66.6% of group 1 and for 58.5% of group 2. Lack of availability of ASM was reported by 21.9% of PWE and 28.0% of caregivers in public dispensing units and by 19.2% and 17.8%, respectively, in private pharmacies. Increase in seizures during pandemic was mentioned by 26.3% and 27.9% of groups 1 and 2, respectively. Patients who had increase in seizure frequency had more frequently reported problems with treatment and in quality-of-life concepts. Fear of having a more severe COVID-19 presentation because of epilepsy was reported by 74.5% of PWE and by 89.8% of caregivers. Dissatisfaction with current health status was reported by 36.7% and 38.1% in groups 1 and 2, respectively, and that the support from others has decreased (56.1% and 66.1%, in groups 1 and 2) during the pandemic. The factors with higher Odds Ratio of increase in seizure frequency during pandemic were age >41 yrs., treatment in public healthcare system, drug-resistant epilepsy, adversities in getting ASM in public dispensing units, difficulties with prescription renewals, current financial problems and belief that epilepsy or ASM are risk factors for contracting COVID-19. CONCLUSION: During COVID-19 pandemic in Brazil, PWE and caregivers reported increase in seizures in one-fourth of the patients and several difficulties, namely problems in accessing the healthcare system including ASM dispensation, telehealth, and fear of having a more severe COVID-19 because of epilepsy. There were also physical, psychological, and social concerns which affected quality-of-life-related aspects in this population. These facts may increase treatment gap in epilepsy in Brazil as well in other developing countries.

Validation of the Health-Related Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) for Brazilian Portuguese.

OBJECTIVE: The present study aimed to validate the 55-item Health-Related Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) in Brazilian Portuguese and evaluate the relation of its results with clinical data and caregiver burden. METHODS: The QOLCE-55 was submitted to translation, back-translation, and cultural adaptation in a pilot sample with 20 subjects. To ensure the psychometric properties of validation, the validation of the QOLCE-55 was carried out in a sample of 45 patients with epilepsy aged between 4 and 18 years and their parents or caregivers and compared with the results of other quality-of-life instruments, namely, the QVCE-50 and QOLIE-AD-48, as well as with the SDQ, abrief behavioral screeningquestionnaire. The WASI and SON-R 2½-7 [a] were used for evaluation of intelligence quotient (IQ) and the Burden Interview for the caregiver burden. RESULTS: Internal consistency measured by Cronbach's alpha coefficient was moderate (0.692; p = 0.264), and the test-retest reliability analyzed by the intraclass correlation coefficient was satisfactory when compared with the results by different examiners on the same day (0.951; p = 0.001) and at different times (0.778; p = 0.001). This version of the QOLCE-55 presented a strong correlation with the QVCE-50 (0.904; p < 0.001) and SDQ (-0.428; p = 0.004) but a low correlation with the QOLIE-AD-48 (0.094; p = 0.729). This version also presented a correlation with IQ (R = 0.456, p = 0.003) and an inverse correlation with the Burden Interview (-0.390; p = 0.012). Low quality of life was associated with the presence of tonic-clonic seizures (p = 0.005), polytherapy (p = 0.003), and low socioeconomic conditions (p = 0.005). CONCLUSIONS: The Brazilian Portuguese version of the QOLCE-55 was confirmed as a reliable and valid scale to assess quality of life in children and adolescents with epilepsy. Behavioral problems, caregiver burden, tonic-clonic seizures, polytherapy, and socioeconomic precariousness were associated with low quality-of-life values, while IQ was positively correlated with the quality of life in this population.

Neuropsychiatric Symptoms of Alzheimer's Disease in Down Syndrome and Its Impact on Caregiver Distress.

BACKGROUND: Neuropsychiatric symptoms (NPS) are non-cognitive manifestations common to dementia and other medical conditions, with important consequences for the patient, caregivers, and society. Studies investigating NPS in individuals with Down syndrome (DS) and dementia are scarce. OBJECTIVE: Characterize NPS and caregiver distress among adults with DS using the Neuropsychiatric Inventory (NPI). METHODS: We evaluated 92 individuals with DS (≥30 years of age), divided by clinical diagnosis: stable cognition, prodromal dementia, and AD. Diagnosis was determined by a psychiatrist using the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). NPS and caregiver distress were evaluated by an independent psychiatrist using the NPI, and participants underwent a neuropsychological assessment with Cambridge Cognitive Examination (CAMCOG-DS). RESULTS: Symptom severity differed between-groups for delusion, agitation, apathy, aberrant motor behavior, nighttime behavior disturbance, and total NPI scores, with NPS total score being found to be a predictor of AD in comparison to stable cognition (OR for one-point increase in the NPI = 1.342, p = 0.012). Agitation, apathy, nighttime behavior disturbances, and total NPI were associated with CAMCOG-DS, and 62% of caregivers of individuals with AD reported severe distress related to NPS. Caregiver distress was most impacted by symptoms of apathy followed by nighttime behavior, appetite/eating abnormalities, anxiety, irritability, disinhibition, and depression (R2 = 0.627, F(15,76) = 8.510, p < 0.001). CONCLUSION: NPS are frequent and severe in individuals with DS and AD, contributing to caregiver distress. NPS in DS must be considered of critical relevance demanding management and treatment. Further studies are warranted to understand the biological underpinnings of such symptoms.

Impulsiveness, personality traits and executive functioning in patients with juvenile myoclonic epilepsy.

PURPOSE: To evaluate impulsiveness in adult patients with JME and its relationship with personality traits and executive functioning. METHODS: Patients completed psychiatric evaluation (DSM IV), Barratt Impulsiveness Scale (BIS-11), Neo Revised Personality Inventory (NEO PI-R) and executive functioning evaluation comprising Controlled Oral Word Association (COWA), Digit Span, Trail Making Tests (TMT), Stroop Test (ST) and Wisconsin Card Sorting Test (WSCT). Healthy controls (63 % female, mean age 35.7 yrs. (±8.37)) were examined to allow calculation of z-scores. RESULTS: 50 patients (70 % female; mean age 32.5 yrs. (±9.2)) presented higher scores of Total (z=-0.37; p = 0.005) and Motor Impulsiveness (z=-0.79; p < 0.001) on BIS-11. Motor Impulsiveness was associated with higher rates of mild psychiatric disorders (depression and anxiety) (p = 0.035) and worse myoclonic seizure control (p = 0.007). NEO PI-R showed differences on Neuroticism (z=-0.60; p < 0.001), Openness (z = 0.38; p = 0.043), Agreeableness (z=-0.38; p = 0.033) and Conscientiousness (z=-0.53; p = 0.003). There were positive correlations between BIS-11 and Neuroticism with Total, Motor and Non-Planning Impulsiveness, on the other hand, Conscientiousness was negatively correlated with these as well as with Attentive Impulsiveness. Patients performance was worse than that of controls on COWA (z=-0.43; p = 0.009) and WCST's Total Number of Completed Categories (z=-2.08; p = 0.005), Trials Taken to Complete First Category (z=-1.56; p = 0.013), Percentage of Total Errors (z=-1.56; p < 0.001), Perseverative Errors (z=-0.73; p = 0.002), Non-Perseverative Errors (z=-1.05; p = 0.003) and Conceptual Level Responses (z=-1.52; p < 0.001). Non-Planning Impulsiveness correlated with Performance (ST and TMT). CONCLUSION: Patients with JME present with impulsive behavior, personality features and executive dysfunction which are linked and may lead to lack of commitment in treatment and affect other aspects of life.

Neuropsychological findings related to the presence of pre-surgical comorbid depression in Latin-American patients with mesial temporal lobe epilepsy and hippocampal sclerosis.

PURPOSE: To evaluate the neuropsychological findings related to the presence of pre-surgical comorbid depression in Latin-American patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS). METHOD: Patients with drug-resistant MTLE and unilateral, left (L-) or right (R-) HS were studied. To diagnose depression, psychiatrists with expertise in epilepsy applied a semi-structured interview based on DSM. The depression group (DG) included patients with a psychiatric diagnosis in addition to a Beck Depression Inventory (BDI) score >16 points, and the non-depression group (NDG) included those without this diagnosis and with a BDI score ≤16. We analysed two clusters of neuropsychological tests, which evaluated memory (Complex Rey Figure III, Logical Memory II and RAVLT VII) and attention plus executive functions (Stroop I/II/III and Trail Making A/B). Moreover, we calculated the z-scores (Zs) using a local control group. The DG was compared to the NDG, independently and according to the HS side, using non-parametrical analyses. Due to the multivariate analysis, the p-value was corrected by applyingpost hoc Bonferroni adjustment. RESULTS: We analysed 65 patients. The NDG included 51 (78.4 %) patients, and the DG included 14 (21.5 %) patients. Pre-surgical comorbid depression occurred in eight patients with L- (n = 29) and in six patients with R-MTLE-HS (n = 36). All of these groups had similar gender, age, IQs, and years of schooling. Compared to the healthy subjects, the L-MTLE-HS patients had lower Zs in verbal episodic memory tests [Logical Memory II (p < 0.001), and RAVLT VII (p < 0.001)], and the R-MTLE-HS patients had lower scores in visual episodic memory [Complex Rey Figure III (p < 0.001)]. In the analysis of the DGvs. NDG, there were no differences in the clusters of tests of memory or in those of attention and executive functions. Moreover, when we analysed the patients according to HS side, no neuropsychological difference was observed in the DG and NDG in terms of L- and R-MTLE-HS. CONCLUSIONS: The patients with MTLE and unilateral HS in this study showed no differences in memory, attention and executive functions in relation to the presence of pre-surgical comorbid depression and independently of HS side. In this series from Latin-America, this psychiatric comorbidity did not affect cognition more than epilepsy alone.

Dysfunctional personality beliefs and executive performance in patients with juvenile myoclonic epilepsy.

BACKGROUND: This article intends to verify the association of dysfunctional beliefs of personality disorders with the executive performance in people with juvenile myoclonic epilepsy (JME). METHODS: Fifty-two patients (35 women, 67.3%) with JME aged 18-50 yrs. (32.3 ±â€¯9.7) were evaluated between May 2017 and April 2018 and compared with controls. All subjects were submitted to the Personality Beliefs Questionnaire (PBQ) (Beck & Beck, 1991; Savoia et al., 2006), Dysexecutive Questionnaire (DQ; Wilson et al., 1996; Macuglia et al., 2016), estimated intelligence quotient (IQ) using Vocabulary and Block Design tests, attention and executive functions evaluation (Controlled Oral Word Association (COWA), Digit Span, Trail Making Tests (TMT) A and B, Stroop and Wisconsin Card Sorting Test (WCST)). The inclusion criteria were as follows: diagnosis of JME (ILAE, 1989); age ≥18 yrs., schooling ≥ 11 yrs. and IQ ≥70. The inclusion criteria for the control group were the same except diagnosis of epilepsy. RESULTS: Compared with controls, patients presented higher scores in PBQ for personality disorders, namely Narcissistic (z = -0.79; p < 0.001), Borderline (z = -0.58; p = 0.002), Paranoid (z = -0.43; p = 0.017), and Histrionic (z = -0.39; p = 0.041). Executive functions were impaired when compared with controls in TMT A (z = -0.97; p = 0.038), TMT B (z = -0.65; p = 0.023), and COWA (z = -0.51; p = 0.001). Patients showed higher WCST scores for Errors (z = -1.62; p ≤ 0.001), Perseverative Errors (z = -0.77; p = 0.001), Non-Perseverative Errors (z = -1.01; p = 0.001), Conceptual Level Response (z = -1.56; p ≤ 0.001), Completed Categories (z = -2.12; p = 0.002), and Failure to Maintain Context (z = -0.49; p = 0.015). Personality Beliefs Questionnaire results showed correlation with lower values in TMT A, Antisocial (r = -0.298; p = 0.032), Narcissistic (r = -0.303; p = 0.029), Schizoid (r = - 0.410; p = 0.003), Histrionic (r = -0.341; p = 0.013), Passive-aggressive (r = -0.341; p = 0.015), and Obsessive-compulsive (r = -0.319; p = 0.021); TMT B results showed a trend for Obsessive-compulsive traits (r = -0.261; p = 0.052); COWA was correlated to Dependent (r = 0.319; p = 0.021); and Digit Span to Passive-aggressive (r = 0.287; p = 0.039). On WCST, Failure to Maintain Context was correlated to Avoidant (r = 0.335; p = 0.017). The DQ was not correlated with PBQ. CONCLUSION: People with JME presented dysfunctional beliefs of personality disorder that were correlated with executive dysfunction. These findings reinforce the need for psychological rehabilitation in these patients.

Revisiting personality in epilepsy: Differentiation of personality in two epilepsies starting in adolescence.

PURPOSE: The purpose of this study was to investigate personality characteristics and clinical parameters in two well-defined epilepsies: mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE/HS) and juvenile myoclonic epilepsy (JME) through NEO Revised Personality Inventory (NEO-PI-R) and Neurobehavior Inventory (NBI) standardized instruments. METHODS: One hundred patients undergoing corticoamygdalohippocampectomy (CAH), 100 patients with JME, and 100 control subjects answered the personality measures. Clinical parameters such as psychiatric symptoms, seizure frequency, duration of epilepsy, and side of the lesion in MTLE/HS group were investigated. Statistical analysis consisted of the mean and standard deviation (SD) of each variable. Student's t-test or Fisher exact test were used according to the variable studied. RESULTS: The three groups were within the average range of NEO-PI-R and NBI, although 'tendencies' and differences were demonstrated. The MTLE/HS and control subjects had a similar profile: low scores in Neuroticism and high in Conscientiousness (r = -0.330; p < 0.001/r = -0.567; p < 0.001, respectively) in opposition to what occurred in JME, low in Conscientiousness and high in Neuroticism (r = -0.509; p = 0.005). The NBI 'sense of personal destiny' trait was higher (3.15; p = 0.003) in MTLE/HS than in JME and controls. The JME 'law and order' scores were lower than in other groups (p = 0.024). A tendency towards specific NBI traits differentiates MTLE/HS (Factor 3) from JME (Factor 1) groups. Psychiatric symptoms and seizure frequency were correlated with worse scores in NBI and, especially, in Neuroticism domain of NEO-PI-R. CONCLUSION: Specific personality features were linked to each epileptic disease. These findings highlight the importance of considering unique features linked to epilepsy conditions in daily clinical observation to develop support programmes.

The validity and reliability of the CAMDEX-DS for assessing dementia in adults with Down syndrome in Brazil

Objective: Alzheimer's disease occurs at a higher prevalence and an earlier age in individuals with Down syndrome (DS) than typically developing individuals. However, diagnosing dementia in individuals with intellectual disability remains a challenge due to pre-existing cognitive deficits. The aim of this study was to investigate the validity and reliability of the Brazilian version of the Cambridge Examination for Mental Disorders of Older People with Down's syndrome and Others with Intellectual Disabilities (CAMDEX-DS) for individuals with DS. Methods: Two psychiatrists, working independently, evaluated 92 adults with DS ≥ 30 years of age. The concurrent validity of the CAMDEX-DS was analyzed in relation to the gold standard of established international criteria. In a subgroup of 20 subjects, the concurrent validity of the CAMDEX-DS was analyzed in relation to an independent objective assessment of cognitive decline over three years. We analyzed the inter-rater reliability of cognitive assessment. Results: The diagnostic accuracy of the CAMDEX-DS compared to the gold standard was 96.7%. CAMDEX-DS-based diagnosis was considered consistent with cognitive decline. The probability of a participant with dementia having cognitive decline was 83%. Inter-rater reliability for the participant assessment was good, with a kappa of > 0.8 for 93% of the CAMDEX-DS items. Conclusion: The CAMDEX-DS can be considered the first valid and reliable instrument for evaluating dementia in adults with DS in Brazil. Its use in such individuals could improve clinical practice and research.

Frontal-subcortical behaviors during Alzheimer's disease in individuals with Down syndrome.

There is evidence that frontal-subcortical circuits play an important role in the initial presentation of dementia in Down syndrome (DS), including changes in behavior, a decline in working memory and executive dysfunction. We evaluated 92 individuals with DS (≥30 years of age), divided into 3 groups by diagnosis-stable cognition, prodromal dementia, and Alzheimer's disease. Each individual was evaluated with an executive protocol developed for people with intellectual disabilities and was rated for behaviors related to frontal lobe dysfunction (disinhibition, executive dysfunction, and apathy) by an informant using the Frontal Systems Behavior Scale. Informant-reported behaviors related to frontal lobe dysfunction were found to correlate negatively with executive function performance. Disinhibition and executive dysfunction were associated with the clinical stage of dementia. The odds of having Alzheimer's disease increased in parallel with increases in the domain and total Frontal Systems Behavior Scale scores (p ≤ 0.5). Disinhibition, executive dysfunction and apathy should be taken into consideration during the clinical evaluation of adults with DS, and future studies should consider the intersection of neuropathology, brain connectivity, and behavior.

The validity and reliability of the CAMDEX-DS for assessing dementia in adults with Down syndrome in Brazil.

OBJECTIVE: Alzheimer's disease occurs at a higher prevalence and an earlier age in individuals with Down syndrome (DS) than typically developing individuals. However, diagnosing dementia in individuals with intellectual disability remains a challenge due to pre-existing cognitive deficits. The aim of this study was to investigate the validity and reliability of the Brazilian version of the Cambridge Examination for Mental Disorders of Older People with Down's syndrome and Others with Intellectual Disabilities (CAMDEX-DS) for individuals with DS. METHODS: Two psychiatrists, working independently, evaluated 92 adults with DS ≥ 30 years of age. The concurrent validity of the CAMDEX-DS was analyzed in relation to the gold standard of established international criteria. In a subgroup of 20 subjects, the concurrent validity of the CAMDEX-DS was analyzed in relation to an independent objective assessment of cognitive decline over three years. We analyzed the inter-rater reliability of cognitive assessment. RESULTS: The diagnostic accuracy of the CAMDEX-DS compared to the gold standard was 96.7%. CAMDEX-DS-based diagnosis was considered consistent with cognitive decline. The probability of a participant with dementia having cognitive decline was 83%. Inter-rater reliability for the participant assessment was good, with a kappa of > 0.8 for 93% of the CAMDEX-DS items. CONCLUSION: The CAMDEX-DS can be considered the first valid and reliable instrument for evaluating dementia in adults with DS in Brazil. Its use in such individuals could improve clinical practice and research.

Epilepsy for primary health care: a cost-effective Latin American E-learning initiative.

A lack of neurologists in Latin America forces primary health care providers to manage epilepsy. With the main goal of improving diagnostic and therapeutic management of patients with epilepsy through training of physicians in the primary health care level, the International League Against Epilepsy Education Commission (2013-2017) created a low-cost, regional, virtual course. The course, set-up in Moodle platform, was structured in eight modules, each lasting for a week. Teaching was based on written didactic material, videos, and interactive discussions, both in Spanish and Portuguese. Topics included epidemiology, diagnosis, classification, treatment, prognosis, social issues, and epilepsy policies. Each course was limited to 50 participants and priority was given to general practitioners. Certification was given to those approving the final examination. Since 2015, five courses have been developed, involving 143 participants from 17 countries and 21 tutors. Of the participants, 61% worked in primary health care services. A total of 129 participants (90%) completed the course, and 110 submitted the final examination with an approval rate of 95%. From 85 participants completing the course evaluation, 98% would recommend the course to other colleagues, and 99% showed interest in taking other similar courses. High self-confidence for the management of patients with epilepsy increased from 21% at baseline to 73% after the course. The online course on epilepsy for primary care physicians in Latin America was shown to be a cost-effective course, with good retention and excellent approval rates. Our current challenges include periodic updating, complete self-sustainability, and exploring different strategies to reach our target audience more effectively.

Prognosis of Juvenile myoclonic epilepsy with eye-closure sensitivity.

PURPOSE: Eye closure sensitivity (ECS) has been described as a reflex trait in juvenile myoclonic epilepsy (JME). However, there is no consensus regarding its significance on prognosis. The aim of this study is to clarify the long-term impact of ECS documented by a clinical interview and a video-EEG neuropsychological protocol (VNPP) in a series of 133 JME patients. METHODS: Data from 22 JME patients with ECS confirmed by a VNPP (Group 1) were compared with those of 20 JME patients without any reflex traits (Group 2). They were followed for a mean of 8.21 years (SD=±5.044). The frequency of seizures was assessed using a diary. Except for photosensitivity (PS), any other reflex traits occurrence, drugs/alcohol abuse intake, noncompliance, and Jeavons syndrome, were considered exclusion criteria. RESULTS: Group 1 had a lower age at epilepsy onset (p = 0.028), higher incidence of febrile seizures (13.6%), and familial history of epilepsy (p = 0.023). Only 18.2% had self-perception of eyelid myoclonia (EM) (kappa coefficient = 0.193), which persisted in 77.3% of patients. Limb myoclonia, tonic-clonic seizures (TCS) and/or myoclonic-tonic-clonic seizures (MTCS), as well as absences were more frequent (p = 0.015; p = 0.013; p = 0.011, respectively) in Group 1. PS did not influenced frequency of EM (p = 1.0), absences (p = 0.648), or TCS/MTCS (p = 0.934). Psychiatric comorbidities were not different between groups. CONCLUSIONS: ECS is related to a worse outcome regarding control of all seizure types, persistence of EM, and higher frequency of limb myoclonia, as well as the total number of TCS and/or MTCS.

Variant Intestinal-Cell Kinase in Juvenile Myoclonic Epilepsy.

BACKGROUND: In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis. METHODS: Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase ( ICK). We calculated Bayesian logarithm of the odds (LOD) scores for cosegregating variants, odds ratios in case-control associations, and allele frequencies in the Genome Aggregation Database. We performed functional tests of the effects of variants on mitosis, apoptosis, and radial neuroblast migration in vitro and conducted video-EEG studies in mice lacking a copy of Ick. RESULTS: A variant, K305T (c.914A→C), cosegregated with epilepsy or polyspikes on EEG in 12 members of the family affected with juvenile myoclonic epilepsy. We identified 21 pathogenic ICK variants in 22 of 310 additional patients (7%). Four strongly linked variants (K220E, K305T, A615T, and R632X) impaired mitosis, cell-cycle exit, and radial neuroblast migration while promoting apoptosis. Tonic-clonic convulsions and polyspikes on EEG resembling seizures in human juvenile myoclonic epilepsy occurred more often in knockout heterozygous mice than in wild-type mice (P=0.02) during light sleep with isoflurane anesthesia. CONCLUSIONS: Our data provide evidence that heterozygous variants in ICK caused juvenile myoclonic epilepsy in 7% of the patients included in our analysis. Variant ICK affects cell processes that help explain microdysgenesis and polyspike networks observed on EEG in juvenile myoclonic epilepsy. (Funded by the National Institutes of Health and others.).

ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology.

The International League Against Epilepsy (ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century.

Absence epilepsy: Continuum of clinical presentation and epigenetics?

PURPOSE: Although absence seizures do predominate in childhood they may occur at all ages and clinical presentation varies widely. Albeit considered a benign seizure type, chronic evolution with therapeutic refractoriness is possible in some patients with absences. The aim of this paper is to summarize the main syndromic presentation of absence seizures and its outcome regarding treatment and prognosis. METHOD: We performed a review of literature with emphasis in historic and classical manuscripts about absence epilepsy. RESULTS: Absence was described in the beginning of last century as a seizure type with good evolution, but it is still difficult to preview a strict prognosis for an individual patient. Some positive early predictors were reported such as response to initial treatment and seizure onset in childhood. Genetic aspects are not yet well understood although some families have been reported with rare mutations in ion channel coding genes. CONCLUSION: Absence seizures are present in different epilepsy syndromes and nosological classification is not always possible. Outcome depends on clinical variables such as age of onset, presence of other seizure types and initial response to treatment.