Brain volumes and white matter diffusion across the adult lifespan in temporal lobe epilepsy.

OBJECTIVE: Typical aging is associated with gradual cognitive decline and changes in brain structure. The observation that cognitive performance in mesial temporal lobe epilepsy (TLE) patients diverges from controls early in life with subsequent decline running in parallel would suggest an initial insult but does not support accelerated decline secondary to seizures. Whether TLE patients demonstrate similar trajectories of age-related gray (GM) and white matter (WM) changes as compared to healthy controls remains uncertain. METHODS: 3D T1-weighted and diffusion tensor images were acquired at a single site in 170 TLE patients (aged 23-74 years) with MRI signs of unilateral hippocampal sclerosis (HS, 77 right) and 111 healthy controls (aged 26-80 years). Global brain (GM, WM, total brain, and cerebrospinal fluid) and regional volumes (ipsi- and contralateral hippocampi), and fractional anisotropy (FA) of 10 tracts (three portions of corpus callosum, inferior longitudinal, inferior fronto-occipital and uncinate fasciculi, body of fornix, dorsal and parahippocampal-cingulum, and corticospinal tract) were compared between groups as a function of age. RESULTS: There were significant reductions of global brain and hippocampi volumes (greatest ipsilateral to HS), and FA of all 10 tracts in TLE versus controls. For TLE patients, regression lines run in parallel to those from controls for brain volumes and FA (for all tracts except the parahippocampal-cingulum and corticospinal tract) versus age across the adult lifespan. INTERPRETATION: These results imply a developmental hindrance occurring earlier in life (likely in childhood/neurodevelopmental stages) rather than accelerated atrophy/degeneration of most brain structures herein analyzed in patients with TLE.

Clinical management and diagnosis of CLN2 disease: consensus of the Brazilian experts group.

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative genetic disease that affects children in early life. Its classic form is rapidly progressive, leading to death within the first 10 years. The urge for earlier diagnosis increases with the availability of enzyme replacement therapy. A panel of nine Brazilian child neurologists combined their expertise in CLN2 with evidence from the medical literature to establish a consensus to manage this disease in Brazil. They voted 92 questions including diagnosis, clinical manifestations, and treatment of the disease, considering the access to healthcare in this country. Clinicians should suspect CLN2 disease in any child, from 2 to 4 years old, with language delay and epilepsy. Even though the classic form is the most prevalent, atypical cases with different phenotypes can be found. Electroencephalogram, magnetic resonance imaging, molecular and biochemical testing are the main tools to investigate and confirm the diagnosis. However, we have limited access to molecular testing in Brazil, and rely on the support from the pharmaceutical industry. The management of CLN2 should involve a multidisciplinary team and focus on the quality of life of patients and on family support. Enzyme replacement therapy with Cerliponase α is an innovative treatment approved in Brazil since 2018; it delays functional decline and provides quality of life. Given the difficulties for the diagnosis and treatment of rare diseases in our public health system, the early diagnosis of CLN2 needs improvement as enzyme replacement therapy is available and modifies the prognosis of patients.

Lipofuscinose ceróide neuronal (CLN2) é uma doença genética neurodegenerativa rara que afeta crianças nos primeiros anos de vida. A sua forma clássica é rapidamente progressiva, levando à morte nos primeiros 10 anos. A necessidade de um diagnóstico precoce aumenta com a disponibilidade do tratamento de terapia enzimática. Um painel de nove neurologistas infantis brasileiros combinou sua experiência em CLN2 com evidências da literatura médica para estabelecer um consenso no manejo desta doença no Brasil. Eles votaram 92 questões abordando diagnóstico, manifestações clínicas e tratamento, considerando o acesso à saúde no Brasil. Deve-se suspeitar de CLN2 em qualquer criança de 2 a 4 anos de idade que apresente atraso de linguagem e epilepsia. Apesar da forma clássica ser a mais prevalente, podem ser encontrados casos atípicos com diferentes fenótipos. Eletroencefalograma, ressonância magnética, testes moleculares e bioquímicos são as principais ferramentas para investigar e confirmar o diagnóstico. No entanto, o acesso aos testes moleculares é limitado no Brasil, necessitando contar com o apoio da indústria farmacêutica. O manejo da CLN2 deve envolver uma equipe multidisciplinar e focar na qualidade de vida dos pacientes e no apoio familiar. A terapia de reposição enzimática com Cerliponase alfa é um tratamento inovador aprovado no Brasil desde 2018; ele retarda o declínio funcional e proporciona qualidade de vida. Diante das dificuldades para o diagnóstico e tratamento de doenças raras em nosso sistema público de saúde, o diagnóstico precoce de CLN2 precisa de melhorias pois a terapia de reposição enzimática está disponível e modifica o prognóstico dos pacientes.

Clinical management and diagnosis of CLN2 disease: consensus of the Brazilian experts group / Manejo clínico e diagnóstico da doença CLN2: consenso do grupo de especialistas brasileiros

Abstract Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare neurodegenerative genetic disease that affects children in early life. Its classic form is rapidly progressive, leading to death within the first 10 years. The urge for earlier diagnosis increases with the availability of enzyme replacement therapy. A panel of nine Brazilian child neurologists combined their expertise in CLN2 with evidence from the medical literature to establish a consensus to manage this disease in Brazil. They voted 92 questions including diagnosis, clinical manifestations, and treatment of the disease, considering the access to healthcare in this country. Clinicians should suspect CLN2 disease in any child, from 2 to 4 years old, with language delay and epilepsy. Even though the classic form is the most prevalent, atypical cases with different phenotypes can be found. Electroencephalogram, magnetic resonance imaging, molecular and biochemical testing are the main tools to investigateand confirm the diagnosis. However, we have limited access to molecular testing in Brazil, and rely on the support from the pharmaceutical industry. The management of CLN2 should involve a multidisciplinary team and focus on the quality of life of patients and on family support. Enzyme replacement therapy with Cerliponase α is an innovative treatment approved in Brazil since 2018; it delays functional decline and provides quality of life. Given the difficulties for the diagnosis and treatment of rare diseases in our public health system, the early diagnosis of CLN2 needs improvement as enzyme replacement therapy is available and modifies the prognosis of patients.

Resumo Lipofuscinose ceróide neuronal (CLN2) é uma doença genética neurodegenerativa rara que afeta crianças nos primeiros anos de vida. A sua forma clássica é rapidamente progressiva, levando à morte nos primeiros 10 anos. A necessidade de um diagnóstico precoce aumenta com a disponibilidade do tratamento de terapia enzimática. Um painel de nove neurologistas infantis brasileiros combinou sua experiência em CLN2 com evidências da literatura médica para estabelecer um consenso no manejo desta doença no Brasil. Eles votaram 92 questões abordando diagnóstico, manifestações clínicas e tratamento, considerando o acesso à saúde no Brasil. Deve-se suspeitar de CLN2 em qualquer criança de 2 a 4 anos de idade que apresente atraso de linguagem e epilepsia. Apesar da forma clássica ser a mais prevalente, podem ser encontrados casos atípicos com diferentes fenótipos. Eletroencefalograma, ressonância magnética, testes moleculares e bioquímicos são as principais ferramentas para investigar e confirmar o diagnóstico. No entanto, o acesso aos testes moleculares é limitado no Brasil, necessitando contar com o apoio da indústria farmacêutica. O manejo da CLN2 deve envolver uma equipe multidisciplinar e focar na qualidade de vida dos pacientes e no apoio familiar. A terapia de reposição enzimática com Cerliponase alfa é um tratamento inovador aprovado no Brasil desde 2018; ele retarda o declínio funcional e proporciona qualidade de vida. Diante das dificuldades para o diagnóstico e tratamento de doenças raras em nosso sistema público de saúde, o diagnóstico precoce de CLN2 precisa de melhorias pois a terapia de reposição enzimática está disponível e modifica o prognóstico dos pacientes.

Telemedicine for Individuals with epilepsy: Recommendations from the International League Against Epilepsy Telemedicine Task Force.

Worldwide, People with Epilepsy (PWE) are confronted with several barriers to face-to-face consultations. These obstacles hamper appropriate clinical follow-up and also increase the treatment gap for Epilepsy. Telemedicine holds the potential to enhance management as follow-up visits for PWE are focused on more on clinical history and counselling rather than physical examination. Besides consultation, telemedicine can also be used for remote EEG diagnostics and tele-neuropsychology assessments. In this article, the Telemedicine Task Force of the International League Against Epilepsy (ILAE) outlines recommendations regarding optimal practice in utilizing in the management of individuals with epilepsy. We formulated recommendations for minimum technical requirements, preparing for the first tele-consultation and the specificities for follow-up consultations. Special considerations are necessary for specific populations, including paediatric patients, patients who are not conversant with tele-medicine and those with intellectual disability. Telemedicine for individuals with epilepsy should be vigorously promoted with the aim of improving the quality of care and ultimately reduce the wide clinician access related treatment gap across several regions of the globe.

Gut microbiome in neuropsychiatric disorders.

BACKGROUND: Neuropsychiatric disorders are a significant cause of death and disability worldwide. The mechanisms underlying these disorders include a constellation of structural, infectious, immunological, metabolic, and genetic etiologies. Advances in next-generation sequencing techniques have demonstrated that the composition of the enteric microbiome is dynamic and plays a pivotal role in host homeostasis and several diseases. The enteric microbiome acts as a key mediator in neuronal signaling via metabolic, neuroimmune, and neuroendocrine pathways. OBJECTIVE: In this review, we aim to present and discuss the most current knowledge regarding the putative influence of the gut microbiome in neuropsychiatric disorders. METHODS: We examined some of the preclinical and clinical evidence and therapeutic strategies associated with the manipulation of the gut microbiome. RESULTS: targeted taxa were described and grouped from major studies to each disease. CONCLUSIONS: Understanding the complexity of these ecological interactions and their association with susceptibility and progression of acute and chronic disorders could lead to novel diagnostic biomarkers based on molecular targets. Moreover, research on the microbiome can also improve some emerging treatment choices, such as fecal transplantation, personalized probiotics, and dietary interventions, which could be used to reduce the impact of specific neuropsychiatric disorders. We expect that this knowledge will help physicians caring for patients with neuropsychiatric disorders.

Utility of Functional MRI and Magnetoencephalography in the Diagnosis of Infantile Spasms and Hypsarrhythmia.

SUMMARY: Neuroimaging and neurophysiology techniques can add a significant contribution to the comprehension of infantile spasms (IS) and hypsarrhythmia. Functional MRI and magnetoencephalography (MEG) are two noninvasive tools that can be used in young children with IS. In the past two decades, interesting data about IS have emerged from functional MRI and MEG studies. Regarding their clinical utility, MEG has supported the concept that epileptic spasms can have a focal origin. Moreover, MEG might contribute to the localization of the epileptogenic zone in children with IS under investigation for epilepsy surgery. Functional MRI data have contributed to improve the knowledge about the physiopathology of IS and hypsarrhythmia. It has demonstrated abnormal brainstem involvement during the high-amplitude slow waves of hypsarrhythmia and cortical involvement during the epileptiform discharges. Since the feasibility of these techniques has been demonstrated in infants, it is possible that, in the future, larger functional MRI and MEG studies might contribute to the treatment and the definition of the long-term prognosis of children with IS.

Gut microbiome in neuropsychiatric disorders / O microbioma intestinal nas doenças neuropsiquiátricas

ABSTRACT Background: Neuropsychiatric disorders are a significant cause of death and disability worldwide. The mechanisms underlying these disorders include a constellation of structural, infectious, immunological, metabolic, and genetic etiologies. Advances in next-generation sequencing techniques have demonstrated that the composition of the enteric microbiome is dynamic and plays a pivotal role in host homeostasis and several diseases. The enteric microbiome acts as a key mediator in neuronal signaling via metabolic, neuroimmune, and neuroendocrine pathways. Objective: In this review, we aim to present and discuss the most current knowledge regarding the putative influence of the gut microbiome in neuropsychiatric disorders. Methods: We examined some of the preclinical and clinical evidence and therapeutic strategies associated with the manipulation of the gut microbiome. Results: targeted taxa were described and grouped from major studies to each disease. Conclusions: Understanding the complexity of these ecological interactions and their association with susceptibility and progression of acute and chronic disorders could lead to novel diagnostic biomarkers based on molecular targets. Moreover, research on the microbiome can also improve some emerging treatment choices, such as fecal transplantation, personalized probiotics, and dietary interventions, which could be used to reduce the impact of specific neuropsychiatric disorders. We expect that this knowledge will help physicians caring for patients with neuropsychiatric disorders.

RESUMO Antecedentes: Os transtornos neuropsiquiátricos são uma importante causa de morte e invalidez no mundo. Os mecanismos subjacentes a esses transtornos incluem uma constelação de etiologias estruturais, infecciosas, imunológicas, metabólicas e genéticas. Avanços nas técnicas de sequenciamento do DNA têm demonstrado que a composição do microbioma entérico é dinâmica e desempenha um papel fundamental não apenas na homeostase do hospedeiro, mas também em várias doenças. O microbioma entérico atua como mediador na sinalização das vias metabólica, neuroimune e neuroendócrina. Objetivo: Apresentar os estudos mais recentes sobre a possível influência do microbioma intestinal nas diversas doenças neuropsiquiátricas e discutir tanto os resultados quanto a eficácia dos tratamentos que envolvem a manipulação do microbioma intestinal. Métodos: foram examinadas algumas das evidências pré-clínicas e clínicas e estratégias terapêuticas associadas à manipulação do microbioma intestinal. Resultados: os táxons-alvo foram descritos e agrupados a partir dos principais estudos para cada doença. Conclusões: Entender a fundo a complexidade das interações ecológicas no intestino e sua associação com a suscetibilidade a certas doenças agudas e crônicas pode levar ao desenvolvimento de novos biomarcadores diagnósticos com base em alvos moleculares. Além disso, o estudo do microbioma intestinal pode auxiliar na otimização de tratamentos não farmacológicos emergentes, tais como o transplante de microbiota fecal, o uso de probióticos e intervenções nutricionais personalizadas. Dessa forma, terapias alternativas poderiam ser usadas para reduzir o impacto dos transtornos neuropsiquiátricos na saúde pública. Esperamos que esse conhecimento seja útil para médicos que cuidam de pacientes com diversos transtornos neuropsiquiátricos.

Inflammatory and neurotrophic factor plasma levels are related to epilepsy independently of etiology.

OBJECTIVE: Inflammation plays an essential role in epilepsy. Studies indicate that cytokines and neurotrophic factors can act in neuroexcitability and epileptogenesis. We aimed to investigate the association between plasma inflammatory and neurotrophic markers, seizure frequency, and chronic epilepsy subtypes. METHODS: We studied 446 patients with epilepsy and 166 healthy controls. We classified patients according to etiology and seizure frequency. We measured plasma levels of interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-γ (IFNγ), tumor necrosis factor α (TNFα), soluble TNF receptor 1 (sTNFr1), sTNFr2, brain-derived neurotrophic factor (BDNF), neurotrophic factor 3 (NT3), NT4/5, ciliary neurotrophic factor (CNTF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) by enzyme-linked immunosorbent assay or cytometric bead array. RESULTS: The plasma levels of BDNF, NT3, NGF, and sTNFr2 were higher, whereas IL-2, IL-4, IL-6, IL-10, IL-17, IFNγ, TNFα, CNTF, and sTNFr1 were lower in patients than controls. IL1, GDNF, and NT4/5 were similar between groups. These markers did not correlate with age, sex, and epilepsy duration. The molecule sTNFr2 was the best marker to discriminate patients from controls (area under the curve = .857), also differing between patients with frequent and infrequent seizures. SIGNIFICANCE: This large cohort confirmed that patients with epilepsy have abnormal levels of plasma inflammatory and neurotrophic markers independent of the underlying etiology. Plasma level of sTNFr2 was related to seizure frequency and discriminated people with or without epilepsy with good accuracy, making it a potential biomarker for epilepsy and seizure burden.

Cerebral Structure and Function in Stroke-free Patients with Atrial Fibrillation.

OBJECTIVES: Atrial fibrillation (AF) is associated with high risk of dementia and brain atrophy in stroke-free patients, but the mechanisms underlying this association remain unclear. We aimed to examine the brain volume and connectivity of paramount cognitive brain networks in stroke-free patients with AF without dementia. MATERIALS AND METHODS: Twenty-six stroke-free patients with AF and 26 age and sex-matched subjects without AF were submitted to a 3-tesla brain structural and functional MRI. An extensive clinical evaluation excluded stroke, dementia, low cardiac output, carotid stenosis and metabolic diseases without optimal therapy. We used CHA2DS2-VASc score to classify the cardiovascular risk factor burden and a broad neuropsychological battery to assess the cognitive performance. Voxel based morphometry analysis of. structural MRI defined whole-brain gray and white matter volumes. Finally, we used eco-plannar MRI images to compare the differences of functional connectivity of 7 large-scale resting-state networks between AF patients and controls. RESULTS: Taking into account the history of hypertension and heart failure, AF was associated to volume decrease of the right basal frontal lobe and right inferior cerebellum. Decreased connectivity of the ventral Default Mode Network (vDMN) was observed in the AF group. No disruption of connectivity was observed in the executive, visuospatial and salience networks. CONCLUSION: Individuals with AF without stroke or dementia have subtle reduction of gray and white matter, restricted to frontal areas and cerebellum. These patients show decreased vDMN connectivity, without other large-scale brain network disruption.

Multimodal Analysis of SCN1A Missense Variants Improves Interpretation of Clinically Relevant Variants in Dravet Syndrome.

Objective: We aimed to improve the classification of SCN1A missense variants in patients with Dravet syndrome (DS) by combining and modifying the current variants classification criteria to minimize inconclusive test results. Methods: We established a score classification workflow based on evidence of pathogenicity to adapt the classification of DS-related SCN1A missense variants. In addition, we compiled the variants reported in the literature and our cohort and assessed the proposed pathogenic classification criteria. We combined information regarding previously established pathogenic amino acid changes, mode of inheritance, population-specific allele frequencies, localization within protein domains, and deleterious effect prediction analysis. Results: Our meta-analysis showed that 46% (506/1,101) of DS-associated SCN1A variants are missense. We applied the score classification workflow and 56.5% (286/506) of the variants had their classification changed from VUS: 17.8% (90/506) into "pathogenic" and 38.7% (196/506) as "likely pathogenic." Conclusion: Our results indicate that using multimodal analysis seems to be the best approach to interpret the pathogenic impact of SCN1A missense changes for the molecular diagnosis of patients with DS. By applying the proposed workflow, most DS related SCN1A variants had their classification improved.

Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis.

This meta-analysis paper describes the analysis of observational clinical studies on the treatment of refractory epilepsy with cannabidiol (CBD)-based products. Beyond attempting to establish the safety and efficacy of such products, we also investigated if there is enough evidence to assume any difference in efficacy between CBD-rich extracts compared to purified CBD products. The systematic search took place in February/2017 and updated in December/2017 using the keywords "epilepsy" or "Dravet" or "Lennox-Gastaut" or "CDKL5" combined with "Cannabis," "cannabinoid," "cannabidiol," or "CBD" resulting in 199 papers. The qualitative assessment resulted in 11 valid references, with an average impact factor of 8.1 (ranging from 1.4 to 47.8). The categorical data of a total of 670 patients were analyzed by Fischer test. The average daily dose ranged between 1 and 50 mg/kg, with treatment length from 3 to 12 months (mean 6.2 months). Two thirds of patients reported improvement in the frequency of seizures (399/622, 64%). There were more reports of improvement from patients treated with CBD-rich extracts (318/447, 71%) than patients treated with purified CBD (81/175, 46%), [corrected] with statistical significance (p < 0.0001). Nevertheless, when the standard clinical threshold of a "50% reduction or more in the frequency of seizures" was applied, only 39% of the individuals were considered "responders," and there was no difference (p = 0.52) [corrected] between treatments with CBD-rich extracts (122/330, 37%) [corrected] and purified CBD (94/223, 42%). Patients treated with CBD-rich extracts reported lower average dose (6.0 mg/kg/day) [DOSAGE ERROR CORRECTED] than those using purified CBD (25.3 mg/kg/day). [DOSAGE ERROR CORRECTED] The reports of mild (158/216 76% vs. 148/447, 33% p < 0.001) and severe (41/155, 26% vs. 23/328, 7% p < 0.0001) [corrected] adverse effects were more frequent in products containing purified CBD than in CBD-rich extracts. CBD-rich extracts seem to present a better therapeutic profile than purified CBD, at least in this population of patients with refractory epilepsy. The roots of this difference is likely due to synergistic effects of CBD with other phytocompounds (aka Entourage effect), but this remains to be confirmed in controlled clinical studies.

Higher IQ in juvenile myoclonic epilepsy: Dodging cognitive obstacles and "masking" impairments.

Executive deficits and impulsiveness are extensively reported in juvenile myoclonic epilepsy (JME). Previous literature suggests that intelligence may mediate these deficits. In this study, we evaluated and compared the performance of adults with JME with high and low intelligence quotient (IQ) and controls on tasks for executive function (EF) and impulsive traits. We investigated the neuropsychological performance of 53 adults with JME and below average IQ (57% women; 26.9 [±7.88] years; mean IQ: 89.8 [±5.1]), 26 adults with JME and average or above average IQ (53.8% women; 28.2 [±9.33] years; mean IQ: 110.7 [±8.3]), 38 controls with below average IQ (55% women; 28.4 [±8.4] years; mean IQ: 90.1 [±5.8]), and 31 controls with average or above average IQ (61.3% women; 32.20 [±11.3] years; mean IQ: 111.6 [±10.5]) with a comprehensive battery of neuropsychological tests that measure executive/attentional function. Impulsive traits were assessed using the Cloninger et al.'s Temperament and Character Inventory (novelty seeking (NS) domain). The group with JME with higher IQ presented worse performance compared with controls with higher IQ on Controlled Oral Word Association (COWA) and Wisconsin Card Sorting Test (WCST) (errors). This group showed worse performance than controls with lower IQ on Stroop Color-Word Test (SCT) 1, Trail Making (TM) A, COWA, and WCST (errors). Patients with lower IQ showed worse performance than controls with higher IQ on Digit Span Forward (DSF), Digit Span Backward (DSB), SCT1, SCT2, SCT3, TM A, COWA, and WCST (errors and failure to maintain set). Patients with lower IQ showed worse performance than controls with lower IQ on DSF, DSB, SCT1, SCT2, SCT3, TM A, TM B, COWA, and WCST (errors and failure to maintain set). Patients from groups with low and high IQ showed higher scores than controls with higher and lower IQ on impulsivity for NS1 and NS2 (except for patients with higher IQ versus controls with lower IQ). Adults with JME and higher IQ show less evidence of EF deficits compared with those with JME and below average IQ, suggesting that a higher degree of intellectual efficiency may act as a compensatory mechanism. However, it does not minimize some aspects of impulsive traits. Patients with JME and higher cognitive reserve may create strategies to dodge their cognitive obstacles. In this context, intelligence may protect and, at the same time, "mask" impairments that could be detected earlier.

Default Mode Network Disruption in Stroke-Free Patients with Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a widely accepted risk for causing stroke. However, recent studies show AF as a risk factor for dementia, even without causing stroke. The mechanisms by which dementia develops in stroke-free patients with AF are still poorly understood and the association of AF with abnormal function of brain networks activities, such as the default mode network (DMN), has not been previously studied. We aimed to determine whether, in the absence of stroke and dementia, patients with AF have abnormal resting-state brain networks compared to controls without AF. METHODS: Twenty-one stroke-free patients with AF and 21 age- and sex-matched controls without AF underwent brain functional magnetic resonance imaging acquired at a 3.0 Tesla scanner. During the exam, the subjects were instructed to lie still with eyes closed. At first-level analysis, connectivity of the DMN was obtained for all subjects. Second-level analysis compared the DMN connectivity between AF patients and controls with a general linear model (two-sample t test, p < 0.05, False Discovery Rate corrected, minimum of 50 contiguous voxels). RESULTS: Patients with AF compared with controls showed decreased connectivity in regions of the DMN including the frontal lobe (left medial frontal gyrus, left superior frontal gyrus and anterior cingulate), left angular gyrus, and bilateral precuneus. CONCLUSIONS: Stroke-free patients with AF have evidence of abnormal DMN connectivity. This study adds evidence to the occurrence of cerebral dysfunction in patients with AF.

Is inpatient ictal video-electroencephalographic monitoring mandatory in mesial temporal lobe epilepsy with unilateral hippocampal sclerosis? A prospective study.

OBJECTIVE: To compare surgical outcome in mesial temporal lobe epilepsy (MTLE) patients with unilateral hippocampal sclerosis (MTLE-HS) who had or did not have preoperative video-electroencephalographic monitoring (VEEG). METHODS: A prospective study was undertaken with 166 consecutive pharmacoresistant unilateral MTLE-HS patients. All patients were investigated with detailed seizure semiology, serial routine outpatient EEG, magnetic resonance imaging, neuropsychological evaluation, and if necessary, other examinations. Postoperative follow-up ranged between 2 and 16 years. Patients were divided into: (1) patients operated on based on routine outpatient EEG information, with >80% of EEGs with unilateral interictal epileptiform discharges (IEDs) ipsilateral to HS or ictal events (n = 71); and (2) patients submitted to preoperative VEEG (n = 95). To avoid the bias generated by ictal recordings, we performed a subanalysis of: (1) patients without preoperatively ictal recordings (n = 80) and (2) patients with ictal recordings in VEEG or routine outpatient EEG (n = 86). RESULTS: Groups were similar regarding gender, age at surgery, seizure onset, preoperative seizure frequency, and duration of follow-up. Overall, 136/166 (81.92%) were classified as Engel I seizure outcome, with no difference between groups; 76.84% and 88.73% of patients with and without VEEG, respectively, had Engel I postoperative seizure outcome (P = .77). The time lag until surgery was shorter in the group without VEEG (80 vs 38 months; P = .01). Considering ictal recordings, 76.74% of patients with seizures recorded and 87.50% without ictal recordings had Engel I outcome (P = .11). SIGNIFICANCE: We performed the first prospective study in a tertiary epilepsy center comparing surgical outcomes in unilateral MTLE-HS patients investigated preoperatively with and without VEEG. Based on the surgical outcome, VEEG is not imperative in patients with unilateral MTLE-HS who have compatible semiology and clearly ipsilateralized IEDs evaluated by a multidisciplinary and experienced epilepsy group.

Corrigendum: Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis.

[This corrects the article DOI: 10.3389/fneur.2018.00759.].

Sleep onset uncovers thalamic abnormalities in patients with idiopathic generalised epilepsy.

The thalamus is crucial for sleep regulation and the pathophysiology of idiopathic generalised epilepsy (IGE), and may serve as the underlying basis for the links between the two. We investigated this using EEG-fMRI and a specific emphasis on the role and functional connectivity (FC) of the thalamus. We defined three types of thalamic FC: thalamocortical, inter-hemispheric thalamic, and intra-hemispheric thalamic. Patients and controls differed in all three measures, and during wakefulness and sleep, indicating disorder-dependent and state-dependent modification of thalamic FC. Inter-hemispheric thalamic FC differed between patients and controls in somatosensory regions during wakefulness, and occipital regions during sleep. Intra-hemispheric thalamic FC was significantly higher in patients than controls following sleep onset, and disorder-dependent alterations to FC were seen in several thalamic regions always involving somatomotor and occipital regions. As interactions between thalamic sub-regions are indirect and mediated by the inhibitory thalamic reticular nucleus (TRN), the results suggest abnormal TRN function in patients with IGE, with a regional distribution which could suggest a link with the thalamocortical networks involved in the generation of alpha rhythms. Intra-thalamic FC could be a more widely applicable marker beyond patients with IGE.