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1.
Nat Commun ; 10(1): 3572, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395890

RESUMO

How are memories transferred from short-term to long-term storage? Systems-level memory consolidation is thought to be dependent on the coordinated interplay of cortical slow waves, thalamo-cortical sleep spindles and hippocampal ripple oscillations. However, it is currently unclear how the selective interaction of these cardinal sleep oscillations is organized to support information reactivation and transfer. Here, using human intracranial recordings, we demonstrate that the prefrontal cortex plays a key role in organizing the ripple-mediated information transfer during non-rapid eye movement (NREM) sleep. We reveal a temporally precise form of coupling between prefrontal slow-wave and spindle oscillations, which actively dictates the hippocampal-neocortical dialogue and information transfer. Our results suggest a model of the human sleeping brain in which rapid bidirectional interactions, triggered by the prefrontal cortex, mediate hippocampal activation to optimally time subsequent information transfer to the neocortex during NREM sleep.


Assuntos
Hipocampo/fisiologia , Consolidação da Memória/fisiologia , Modelos Psicológicos , Córtex Pré-Frontal/fisiologia , Sono de Ondas Lentas/fisiologia , Adulto , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/terapia , Eletrodos Implantados , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Adulto Jovem
2.
Nutrients ; 11(8)2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31349661

RESUMO

The classical ketogenic diet (cKD) is an isocaloric, high fat, very low-carbohydrate diet that induces ketosis, strongly influencing leptin and ghrelin regulation. However, not enough is known about the impact of a long-term cKD. This study evaluated the effects of a 12-month cKD on ghrelin and leptin concentrations in children, adolescents and adults affected by the GLUT1-Deficiency Syndrome or drug resistant epilepsy (DRE). We also investigated the relationship between the nutritional status, body composition and ghrelin and leptin variations. We carried out a longitudinal study on 30 patients: Twenty-five children and adolescents (15 females, 8 ± 4 years), and five adults (two females, 34 ± 16 years). After 12-monoths cKD, there were no significant changes in ghrelin and leptin, or in the nutritional status, body fat, glucose and lipid profiles. However, a slight height z-score reduction (from -0.603 ± 1.178 to -0.953 ± 1.354, p ≤ 0.001) and a drop in fasting insulin occurred. We found no correlations between ghrelin changes and nutritional status and body composition, whereas leptin changes correlated positively with variations in the weight z-score and body fat (ρ = 0.4534, p = 0.0341; ρ = 0.5901, p = 0.0135; respectively). These results suggest that a long-term cKD does not change ghrelin and leptin concentrations independently of age and neurological condition.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/dietoterapia , Dieta Cetogênica , Epilepsia Resistente a Medicamentos/dietoterapia , Grelina/sangue , Leptina/sangue , Proteínas de Transporte de Monossacarídeos/deficiência , Adolescente , Adulto , Biomarcadores/sangue , Erros Inatos do Metabolismo dos Carboidratos/sangue , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/fisiopatologia , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/sangue , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/fisiopatologia , Feminino , Humanos , Itália , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Proteínas de Transporte de Monossacarídeos/sangue , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
3.
J Clin Neurophysiol ; 36(5): 365-370, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31166226

RESUMO

PURPOSE: We aimed to determine whether clinical EEG reports obtained from children in the intensive care unit with refractory status epilepticus could provide data for comparative effectiveness research studies. METHODS: We conducted a retrospective descriptive study to assess the documentation of key variables within clinical continuous EEG monitoring reports based on the American Clinical Neurophysiology Society's standardized EEG terminology for children with refractory status epilepticus from 10 academic centers. Two pediatric electroencephalographers reviewed the EEG reports. We compared reports generated using free text or templates. RESULTS: We reviewed 191 EEG reports. Agreement between the electroencephalographers regarding whether a variable was described in the report ranged from fair to very good. The presence of electrographic seizures (ES) was documented in 46% (87/191) of reports, and these reports documented the time of first ES in 64% (56/87), ES duration in 72% (63/85), and ES frequency in 68% (59/87). Reactivity was documented in 16% (31/191) of reports, and it was more often documented in template than in free-text reports (40% vs. 14%, P = 0.006). Other variables were not differentially reported in template versus free-text reports. CONCLUSIONS: Many key EEG features are not documented consistently in clinical continuous EEG monitoring reports, including ES characteristics and reactivity assessment. Standardization may be needed for clinical EEG reports to provide informative data for large multicenter observational studies.


Assuntos
Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia/métodos , Hospitais Pediátricos , Estado Epiléptico/diagnóstico , Estado Epiléptico/fisiopatologia , Adolescente , Criança , Pré-Escolar , Eletroencefalografia/tendências , Feminino , Hospitais Pediátricos/tendências , Humanos , Lactente , Unidades de Terapia Intensiva/tendências , Masculino , Monitorização Fisiológica/métodos , Monitorização Fisiológica/tendências , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/fisiopatologia , Adulto Jovem
4.
Seizure ; 70: 12-19, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31234050

RESUMO

PURPOSE: Resective epilepsy surgery based on an invasive EEG-monitors performed with subdural grids (SDG) or depth electrodes (stereo-electroencephalography, SEEG) is considered to be the best option towards achieving seizure-free state in drug-resistant epilepsy. The authors present a meta-analysis, due to the lack of such a study focusing on surgical outcomes originating from SDG- or SEEG-monitors. METHOD: English-language studies published until May 2018, highlighting surgical outcomes were reviewed. Outcome measures including total number of SDG- or SEEG-monitors and resective surgeries; consecutively followed surgical cases; surgical outcomes classified by Engel in overall, temporal/extratemporal and lesional/nonlesional subgroups were analyzed. RESULTS: 19 articles containing 1025 SDG-interventions and 16 publications comprising 974 SEEG-monitors were researched. The rate of resective surgery deriving from SDG-monitoring hovered at 88.8% (95%CI:83.3-92.6%) (I2 = 77.0%;p < 0.001); in SEEG-group, 79.0% (95%CI:70.4-85.7%) (I2 = 72.5%;p < 0.001) was measured. After SDG-interventions, percentage of post-resective follow-up escalated to 96.0% (95%CI:92.0-98.1%) (I2 = 49.1%;p = 0.010), and in SEEG-group, it reached 94.9% (95%CI:89.3-97.6%) (I2 = 80.2%;p < 0.001). In SDG-group, ratio of seizure-free outcomes reached 55.9% (95%CI:50.9-60.8%) (I2 = 54.47%;p = 0.002). Using SEEG-monitor, seizure-freedom occurred in 64.7% (95%CI:59.2-69.8%) (I2 = 11.9%;p = 0.32). Assessing lesional cases, likelihood of Engel I outcome was found in 57.3% (95%CI:48.7%-65.6%) (I2 = 69.9%;p < 0.001), using SDG; while in SEEG-group, it was 71.6% (95%CI:61.6%-79.9%) (I2 = 24.5%;p = 0.225). In temporal subgroup, ratio of seizure-freedom was found to be 56.7% (95%CI:51.5%-61.9%) (I2 = 3.2%;p = 0.412) in SDG-group; whereas, SEEG-group reached 73.9% (95%CI:64.4%-81.6%); (I2 = 0.00%;p = 0.45). Significant differences between seizure-free outcomes were found in overall (p = 0.02), lesional (p = 0.031), and also, temporal (p = 0.002) comparisons. CONCLUSIONS: SEEG-interventions were associated, at least, non-inferiorly, with seizure-freedom compared with SDG-monitors in temporal, lesional and overall subgroups.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Eletrocorticografia , Eletrodos Implantados , Monitorização Neurofisiológica , Procedimentos Neurocirúrgicos , Epilepsia Resistente a Medicamentos/diagnóstico , Eletrocorticografia/instrumentação , Humanos , Monitorização Neurofisiológica/instrumentação , Convulsões/diagnóstico , Convulsões/cirurgia , Resultado do Tratamento
5.
J Clin Neurophysiol ; 36(5): 371-374, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31107715

RESUMO

PURPOSE: Magnetoencephalography (MEG) is a noninvasive tool used clinically for presurgical evaluation of patients with medically intractable epilepsy. These recordings require patients to lie still for prolonged periods of time in a magnetically shielded room. Children or uncooperative adults with epilepsy may require sedation to reduce movement artefact and obtain high-quality recordings. Potential challenges related to the use of total intravenous anesthesia in the MEG environment include limited access to the patient's airway, remote location, suppression of cortical activity, and increased patient care expenses. We report our experience with intranasal dexmedetomidine as sedation for intractable epilepsy patients undergoing MEG. METHODS: Sleep deprivation occurred the night before MEG testing. Intranasal dexmedetomidine (2 µg/kg) was administered and oxygen saturation, blood pressure, and pulse rate were recorded continuously on a monitor outside the magnetically shielded room. A recording of spontaneous neuromagnetic activity was immediately followed by median nerve electrical stimulation. RESULTS: Twenty-six patients (mean age 12.2 ± 4.2 years) with medically intractable epilepsy were recorded using this protocol. There were no failures of sedation, and although patients experienced transient bradycardia, none required intervention and the recording did not need to be stopped. In all cases, artefact-free MEG recordings were obtained with sufficient interictal discharges available for source analysis. CONCLUSIONS: Our experience suggests that intranasal dexmedetomidine is an advantageous sedation option for children and adults with intractable epilepsy who are undergoing MEG. Further research is needed to determine the best ways to apply these methods to younger children and those with developmental disabilities.


Assuntos
Dexmedetomidina/administração & dosagem , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Hipnóticos e Sedativos/administração & dosagem , Magnetoencefalografia/métodos , Administração Intranasal , Adolescente , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Criança , Epilepsia Resistente a Medicamentos/fisiopatologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Masculino , Estudos Retrospectivos
6.
Brain Stimul ; 12(5): 1101-1110, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31126871

RESUMO

RATIONALE: Refractory status epilepticus (RSE) is the persistence of status epilepticus despite second-line treatment. Super-refractory SE (SRSE) is characterized by ongoing status despite 48 h of anaesthetic treatment. Due to the high case fatality in RSE of 16-39%, off label treatments without strong evidence of efficacy in RSE are often administered. In single case-reports and small case series totalling 28 patients, acute implantation of VNS in RSE was associated with 76% and 26% success rate in generalized and focal RSE respectively. We performed an updated systematic review of the literature on efficacy of VNS in RSE/SRSE by including all reported patients. METHODS: We systematically searched EMBASE, CENTRAL, Opengre.eu, and ClinicalTrials.gov, and PubMed databases to identify studies reporting the use of VNS for RSE and/or SRSE. We also searched conference abstracts from AES and ILAE meetings. RESULTS: 45 patients were identified in total of which 38 were acute implantations of VNS in RSE/SRSE. Five cases had VNS implantation for epilepsia partialis continua, one for refractory electrical status epilepticus in sleep and one for acute encephalitis with refractory repetitive focal seizures. Acute VNS implantation was associated with cessation of RSE/SRSE in 74% (28/38) of acute cases. Cessation did not occur in 18% (7/38) of cases and four deaths were reported (11%); all of them due to the underlying disease and unlikely related to VNS implantation. Median duration of the RSE/SRSE episode pre and post VNS implantation was 18 days (range: 3-1680 days) and 8 days (range: 3-84 days) respectively. Positive outcomes occurred in 82% (31/38) of cases. CONCLUSION: VNS can interrupt RSE and SRSE in 74% of patients; data originate from reported studies classified as level IV and the risk for reporting bias is high. Further prospective studies are warranted to investigate acute VNS in RSE and SRSE.


Assuntos
Ensaios Clínicos como Assunto/métodos , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/terapia , Estado Epiléptico/diagnóstico , Estado Epiléptico/terapia , Estimulação do Nervo Vago/métodos , Adulto , Anticonvulsivantes/uso terapêutico , Bases de Dados Factuais , Epilepsia Resistente a Medicamentos/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sono/fisiologia , Estado Epiléptico/fisiopatologia
7.
World Neurosurg ; 127: 370-374, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30995553

RESUMO

The carotid sinus nerve branches off the glossopharyngeal nerve just after its appearance from the jugular foramen, descends along the internal carotid artery, and enters the carotid sinus. There have been many studies of the pathway and the course of the carotid sinus nerve and its communications with surrounding nerves. The intercommunication is exceedingly complicated. Acknowledgment of its anatomic diversity can be important in specific operations dealing with this area. Herein we review the anatomy, variations, pathology, and clinical applications of the carotid sinus nerve.


Assuntos
Seio Carotídeo/anatomia & histologia , Seio Carotídeo/inervação , Nervo Glossofaríngeo/anatomia & histologia , Seio Carotídeo/patologia , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/cirurgia , Nervo Glossofaríngeo/patologia , Nervo Glossofaríngeo/cirurgia , Humanos
8.
Continuum (Minneap Minn) ; 25(2): 362-380, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30921014

RESUMO

PURPOSE OF REVIEW: Drug-resistant epilepsy is a potentially life-threatening condition affecting one-third of people living with epilepsy. Despite existing evidence of improved outcomes in patients who received surgical treatment compared to continued medical treatment, epilepsy surgery remains underused in patients with drug-resistant epilepsy. This article discusses the gap between evidence and practice and common misconceptions about epilepsy surgery and reviews the current diagnostic and therapeutic surgical options. RECENT FINDINGS: Three randomized controlled trials comparing the medical versus surgical treatment for patients with drug-resistant epilepsy have shown the superiority of surgery in controlling seizures and improving patients' quality of life. In addition to resective surgery, neuromodulation through devices such as responsive neurostimulation and vagal nerve stimulation have also shown efficacy in seizure control that increases over time. Diagnostic and therapeutic surgical tools are tailored to the needs of each patient. SUMMARY: Appropriate patients with drug-resistant epilepsy benefit more from epilepsy surgery than from continuing medical treatment. These patients should be referred to comprehensive epilepsy centers where a thorough presurgical workup and surgical options can be provided. The gap between evidence and practice can be bridged by education, community outreach, and providers' earnest efforts to improve the quality of life of patients with epilepsy.


Assuntos
Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/terapia , Epilepsia Resistente a Medicamentos/cirurgia , Humanos
9.
Medicine (Baltimore) ; 98(8): e14698, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813219

RESUMO

RATIONALE: The phenotypic spectrum caused by SCN2A mutations includes benign neonatal/infantile seizures, Ohtahara syndrome, infantile spasms, West syndrome, and other unclassified epileptic phenotypes. Mutations in SCN2A have been implicated in neonatal seizure cases. Here, we described a Chinese family with 2 members having juvenile-onset myoclonus and identified a novel SCN2A point mutation within this family. PATIENT CONCERNS: The 21-year-old male proband suffered from frequent myoclonus at 11 years old with subsequent progressive ataxia. His elder maternal half-sister also experienced myoclonus. Genomic DNA of the patients was extracted from the peripheral blood cells of the proband, elder maternal half-sister, parents, and uncle of the proband. Targeted next-generation sequencing was used to screen gene mutations in the proband. The potential functional effects of mutations within SCN2A were predicted In silico analyses. DIAGNOSES: Genetic testing revealed a novel SCN2A variant, c.T4820C, which contains a highly conserved amino acid substitution within segment S5 (p.V1607A). This mutation was predicted to produce a dysfunctional Nav1.2 protein by Mutation Taster and Protein Variation Effect Analyzer (PROVEAN). Genotype-phenotype correlation showed an incomplete penetrance of p.V1607A. INTERVENTIONS: The proband was treated by multiple antiepileptic drugs. These included carbamazepine, oxcarbazepine, valproate, and topiramate. OUTCOMES: The duration of follow up was 2 years, and the proband developed drug-resistant epilepsy. LESSONS: The case gives us the lesson that SCN2A mutation can contribute to juvenile-onset myoclonus. Our findings extend the spectrums of SCN2A mutations and the clinical features of patients with SCN2A mutations.


Assuntos
Carbamazepina , Epilepsia Mioclônica Juvenil , Canal de Sódio Disparado por Voltagem NAV1.2/genética , Adulto , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Ataxia/diagnóstico , Ataxia/etiologia , Carbamazepina/administração & dosagem , Carbamazepina/efeitos adversos , Progressão da Doença , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/genética , Eletroencefalografia/métodos , Feminino , Testes Genéticos/métodos , Humanos , Masculino , Anamnese , Mutação , Epilepsia Mioclônica Juvenil/diagnóstico , Epilepsia Mioclônica Juvenil/tratamento farmacológico , Epilepsia Mioclônica Juvenil/genética , Exame Neurológico/métodos , Oxcarbazepina/administração & dosagem , Oxcarbazepina/efeitos adversos , Linhagem , Ácido Valproico/administração & dosagem , Ácido Valproico/efeitos adversos
10.
Neurology ; 92(17): 802-810, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30894443

RESUMO

New-onset refractory status epilepticus (NORSE) is a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurologic disorder, with new onset of refractory status epilepticus (RSE) that does not resolve after 2 or more rescue medications, without a clear acute or active structural, toxic, or metabolic cause. Febrile infection-related epilepsy syndrome is a subset of NORSE in which fever began at least 24 hours prior to the RSE. Both terms apply to all age groups. Until recently, NORSE was a poorly recognized entity without a consistent definition or approach to care. We review the current state of knowledge in NORSE and propose a roadmap for future collaborative research. Research investigating NORSE should prioritize the following 4 domains: (1) clinical features, etiology, and pathophysiology; (2) treatment; (3) adult and pediatric evaluation and management approaches; and (4) public advocacy, professional education, and family support. We consider international collaboration and multicenter research crucial in achieving these goals.


Assuntos
Epilepsia Resistente a Medicamentos/terapia , Estado Epiléptico/terapia , Epilepsia Resistente a Medicamentos/diagnóstico , Humanos , Pesquisa , Estado Epiléptico/diagnóstico
11.
Seizure ; 67: 65-70, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30909164

RESUMO

PURPOSE: Suicidality including suicidal ideation and attempt has been a critical issue in people with epilepsy, especially in people with drug-resistant epilepsy (PWDRE). Clinicians commonly ask about adverse effects of antiepileptic drugs (AEDs) using something like the Liverpool Adverse Events Profile (LAEP) at epilepsy clinics, but suicide is usually not of interest. A high risk of suicidality can increase mortality by committing suicide in PWDRE. This study aimed to investigate whether clinicians can discern a high risk of suicidality in PWDRE by referring to the LAEP. METHODS: We recruited PWDRE, aged from 19 to 68. They completed the 21-item LAEP, the suicidality module of the Mini International Neuropsychiatric Interview, and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). Through receiver operating characteristic curve analysis, we tested the usefulness of LAEP to detect a high risk of suicide. By this, we determined each cutoff point of the total LAEP score and the number of severe LAEP items, for detecting the risk. RESULTS: A hundred forty-four PWDRE participated in this study. Among them, 36 PWDRE (25.0%) had a high risk of suicidality. Either >45 of the total LAEP score or >8 of the number of severe LAEP items was a suggested optimal cutoff point for discerning the high risk of suicidality. LAEP had a correlation with the suicidality item of the NDDI-E. CONCLUSION: The LAEP may inform a high risk of suicidality in PWDRE. Referring to this, clinicians can discern suicidal problems in their epilepsy clinics.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia Resistente a Medicamentos/diagnóstico , Suicídio , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Escalas de Graduação Psiquiátrica , Curva ROC , Medição de Risco , Adulto Jovem
12.
J Clin Neurophysiol ; 36(3): 195-203, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30925509

RESUMO

PURPOSE: Patients undergoing epilepsy surgery often require invasive EEG, but few studies have examined the signal characteristics of contacts on the surface of the brain (electrocorticography, ECOG) versus depth contacts, used in stereoelectroencephalography (SEEG). As SEEG and ECOG have significant differences in complication rates, it is important to determine whether both modalities produce similar signals for analysis, to ultimately guide management of medically intractable epilepsy. METHODS: Twenty-seven patients who underwent SEEG (19), ECOG (6), or both (2) were analyzed for quantitative measures of activity including spectral power and phase-amplitude coupling during approximately 1 hour of wakefulness. The position of the contacts was calculated by coregistering the postoperative computed tomography with a reconstructed preoperative MRI. Using two types of referencing schemes-local versus common average reference-the brain regions where any quantitative measure differed systematically with contact depth were established. RESULTS: Using even the most permissive statistical criterion, few quantitative measures were significantly correlated with contact depth in either ECOG or SEEG contacts. The factors that predicted changes in spectral power and phase-amplitude coupling with contact depth were failing to baseline correct spectral power measures, use of a local rather than common average reference, using baseline correction for phase-amplitude coupling measures, and proximity of other grey matter structures near the region where the contact was located. CONCLUSIONS: The signals recorded by ECOG and SEEG have very similar spectral power and phase-amplitude coupling, suggesting that both modalities are comparable from an electrodiagnostic standpoint in delineation of the epileptogenic network.


Assuntos
Mapeamento Encefálico/métodos , Eletrocorticografia/métodos , Eletroencefalografia/métodos , Adulto , Encéfalo/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/cirurgia , Feminino , Humanos , Masculino , Adulto Jovem
13.
Epileptic Disord ; 21(1): 112-116, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30767894

RESUMO

Dynamin-1-like protein (DNM1L) gene variants have been linked to childhood refractory epilepsy, developmental delay, encephalopathy, microcephaly, and progressive diffuse cerebral atrophy. However, only a few cases have been reported in the literature and there is still a limited amount of information about the symptomatology and pathophysiology associated with pathogenic variants of DNM1L. We report a 10-year-old girl with a one-year history of mild learning disorder and absence seizures who presented with new-onset focal status epilepticus which progressed to severe encephalopathy and asymmetric hemispheric cerebral atrophy. Differential diagnosis included mitochondrial disease, Rasmussen's encephalitis, and autoimmune encephalitis. Disease progressed from one hemisphere to the other despite anti-seizure medications, hemispherectomy, vagus nerve stimulator, ketogenic diet, and immunomodulators. Continued cerebral atrophy and refractory seizures evolved until death four years after initial presentation. Post-mortem whole-exome sequencing revealed a pathogenic DNM1L variant. This paper presents a novel case of adolescent-onset DNM1L-related intractable epilepsy and encephalopathy.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Epilepsia Resistente a Medicamentos , Encefalite , GTP Fosfo-Hidrolases/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas Mitocondriais/genética , Adolescente , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/genética , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/fisiopatologia , Progressão da Doença , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/genética , Epilepsia Resistente a Medicamentos/imunologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Encefalite/diagnóstico , Encefalite/genética , Encefalite/imunologia , Encefalite/fisiopatologia , Evolução Fatal , Feminino , Humanos
14.
J Neurol ; 266(4): 910-920, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30701313

RESUMO

BACKGROUND: Refined localization of the epileptogenic zone (EZ) in patients with pharmacoresistant focal epilepsy proceeding to resective surgery might improve postoperative outcome. We here report seizure outcome after stereo EEG (sEEG) evaluation with individually planned stereotactically implanted depth electrodes and subsequent tailored resection. METHODS: A cohort of consecutive patients with pharmacoresistant focal epilepsy, evaluated with a non-invasive evaluation protocol and invasive monitoring with personalized, stereotactically implanted depth electrodes for sEEG was analyzed. Co-registration of post-implantation CT scan to presurgical MRI data was used for 3D reconstructions of the patients' brain surface and mapping of neurophysiology data. Individual multimodal 3D maps of the EZ were used to guide subsequent tailored resections. The outcome was rated according to the Engel classification. RESULTS: Out of 914 patients who underwent non-invasive presurgical evaluation, 85 underwent sEEG, and 70 were included in the outcome analysis. Median follow-up was 31.5 months. Seizure-free outcome (Engel class I A-C, ILAE class 1-2) was achieved in 83% of the study cohort. Patients exhibiting lesional and non-lesional (n = 42, 86% vs. n = 28, 79%), temporal and extratemporal (n = 45, 80% vs. n = 25, 84%), and right- and left-hemispheric epilepsy (n = 44, 82% vs. n = 26, 85%) did similarly well. This remains also true for those with an EZ adjacent to or distant from eloquent cortex (n = 21, 86% vs. n = 49, 82%). Surgical outcome was independent of resected tissue volume. CONCLUSION: Favourable post-surgical outcome can be achieved in patients with resistant focal epilepsy, using individualized sEEG evaluation and tailored navigated resection, even in patients with non-lesional or extratemporal focal epilepsy.


Assuntos
Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/cirurgia , Eletrocorticografia , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/cirurgia , Neuronavegação , Adolescente , Adulto , Encéfalo/fisiopatologia , Encéfalo/cirurgia , Mapeamento Encefálico , Criança , Pré-Escolar , Estudos de Coortes , Epilepsia Resistente a Medicamentos/diagnóstico , Eletrocorticografia/métodos , Eletrodos Implantados , Epilepsias Parciais/diagnóstico , Feminino , Humanos , Imagem Tridimensional , Masculino , Pessoa de Meia-Idade , Neuronavegação/métodos , Medicina de Precisão/métodos , Cuidados Pré-Operatórios/métodos , Convulsões/diagnóstico , Convulsões/fisiopatologia , Convulsões/cirurgia , Adulto Jovem
15.
Epileptic Disord ; 21(1): 122-127, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30782583

RESUMO

Focal cortical dysplasia is a common cause of medically refractory epilepsy in infancy and childhood. We report a neonate with seizures occurring within the first day of life. Continuous video-EEG monitoring led to detection of left motor seizures and a right frontal EEG seizure pattern. Brain MRI revealed a lesion within the right frontal lobe without contrast enhancement. The patient was referred for epilepsy surgery due to drug resistance to vitamin B6 and four antiepileptic drugs. Lesionectomy was performed at the age of two and a half months, and histopathological evaluation confirmed the diagnosis of focal cortical dysplasia type IIb (FCD IIb). The patient is free of unprovoked seizures without medication (Engel Class I) and is normally developed at 36 months after surgery. The case study demonstrates that FCD IIb may cause seizures within the first day of life and that epilepsy surgery can be successfully performed in medically intractable patients with a clearly identifiable seizure onset zone within the first three months of life. Although radical surgery such as hemispherectomy and multi-lobar resections are over-represented in early infancy, this case also illustrates a favourable outcome with a more limited resection in this age group.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Malformações do Desenvolvimento Cortical do Grupo II/cirurgia , Pré-Escolar , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/etiologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia , Feminino , Humanos , Imagem por Ressonância Magnética , Malformações do Desenvolvimento Cortical do Grupo II/complicações , Malformações do Desenvolvimento Cortical do Grupo II/diagnóstico
16.
Curr Opin Neurol ; 32(2): 213-219, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30694920

RESUMO

PURPOSE OF REVIEW: Precise localization of the epileptogenic zone is imperative for the success of resective surgery of drug-resistant epileptic patients. To decrease the number of surgical failures, clinical research has been focusing on finding new biomarkers. For the past decades, high-frequency oscillations (HFOs, 80-500 Hz) have ousted interictal spikes - the classical interictal marker - from the research spotlight. Many studies have claimed that HFOs were more linked to epileptogenicity than spikes. This present review aims at refining this statement in light of recent studies. RECENT FINDINGS: Analysis based on single-patient characteristics has not been able to determine which of HFOs or spikes were better marker of epileptogenic tissues. Physiological HFOs are one of the main obstacles to translate HFOs to clinical practice as separating them from pathological HFOs remains a challenge. Fast ripples (a subgroup of HFOs, 250-500 Hz) which are mostly pathological are not found in all epileptogenic tissues. SUMMARY: Quantified measures of HFOs and spikes give complementary results, but many barriers still persist in applying them in clinical routine. The current way of testing HFO and spike detectors and their performance in delineating the epileptogenic zone is debatable and still lacks practicality. Solutions to handle physiological HFOs have been proposed but are still at a preliminary stage.


Assuntos
Biomarcadores , Encéfalo/fisiopatologia , Epilepsia Resistente a Medicamentos/diagnóstico , Eletroencefalografia/métodos , Mapeamento Encefálico , Epilepsia Resistente a Medicamentos/classificação , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia/classificação , Humanos
17.
J Neurol ; 266(4): 844-859, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30684208

RESUMO

OBJECTIVE: Abnormal and dynamic epileptogenic networks cause difficulties for clinical epileptologists in the localization of the seizure onset zone (SOZ) and the epileptogenic zone (EZ) in preoperative assessments of patients with refractory epilepsy. The aim of this study is to investigate the characteristics of time-varying effective connectivity networks in various non-seizure and seizure periods, and to propose a quantitative approach for accurate localization of SOZ and EZ. METHODS: We used electrocorticogram recordings in the temporal lobe and hippocampus from seven patients with temporal lobe epilepsy to characterize the effective connectivity dynamics at a high temporal resolution using the full-frequency adaptive directed transfer function (ffADTF) measure and five graph metrics, i.e., the out-degree (OD), closeness centrality (CC), betweenness centrality (BC), clustering coefficient (C), and local efficiency (LE). The ffADTF effective connectivity network was calculated and described in five frequency bands (δ, θ, α, ß, and γ) and five seizure periods (pre-seizure, early seizure, mid-seizure, late seizure, and post-seizure). The cortical areas with high values of graph metrics in the transient seizure onset network were compared with the SOZ and EZ identified by clinical epileptologists and the results of epilepsy resection surgeries. RESULTS: Origination and propagation of epileptic activity were observed in the high time resolution ffADTF effective connectivity network throughout the entire seizure period. The seizure-specific transient seizure onset ffADTF network that emerged at seizure onset time remained for approximately 20-50 ms with strong connections generated from both SOZ and EZ. The values of graph metrics in the SOZ and EZ were significantly larger than that in the other cortical areas. More cortical areas with the highest mean of graph metrics were the same as the clinically determined SOZ in the low-frequency δ and θ bands and in Engel Class I patients than in higher frequency α, ß, and γ bands and in Engel Class II and III patients. The OD and C were more likely to localize the SOZ and EZ than CC, BC, and LE in the transient seizure onset network. CONCLUSION: The high temporal resolution ffADTF effective connectivity analysis combined with the graph theoretical analysis helps us to understand how epileptic activity is generated and propagated during the seizure period. The newly discovered seizure-specific transient seizure onset network could be an important biomarker and a promising tool for more precise localization of the SOZ and EZ in preoperative evaluations.


Assuntos
Epilepsia Resistente a Medicamentos/fisiopatologia , Eletrocorticografia/métodos , Epilepsia do Lobo Temporal/fisiopatologia , Hipocampo/fisiopatologia , Convulsões/fisiopatologia , Lobo Temporal/fisiopatologia , Adulto , Mapeamento Encefálico/métodos , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/terapia , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Cuidados Pré-Operatórios , Processamento de Sinais Assistido por Computador , Adulto Jovem
18.
Nat Commun ; 10(1): 203, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30643130

RESUMO

Memories of experiences that occur around the same time are linked together by a shared temporal context, represented by shared patterns of neural activity. However, shared temporal context may be problematic for selective retrieval of specific memories. Here, we examine intracranial EEG (iEEG) in the human temporal lobe as participants perform a verbal paired associates memory task that requires the encoding of distinct word pairs in memory. We find that the rate of change in patterns of low frequency (3-12 Hz) power distributed across the temporal lobe is significantly related to memory performance. We also find that exogenous electrical stimulation affects how quickly these neural representations of temporal context change with time, which directly affects the ability to successfully form memories for distinct items. Our results indicate that the ability to retrieve distinct episodic memories is related to how quickly neural representations of temporal context change over time during encoding.


Assuntos
Epilepsia Resistente a Medicamentos/fisiopatologia , Memória Episódica , Rememoração Mental/fisiologia , Lobo Temporal/fisiologia , Adulto , Mapeamento Encefálico/instrumentação , Mapeamento Encefálico/métodos , Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/métodos , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/terapia , Eletrodos Implantados , Eletroencefalografia , Feminino , Humanos , Masculino , Comportamento Verbal/fisiologia
19.
Trials ; 20(1): 44, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30642370

RESUMO

BACKGROUND: Recent clinical observations have reported the potential benefit of vagus nerve stimulation (VNS) as an adjunctive therapy for pediatric epilepsy. Preliminary evidence suggests that VNS treatment is effective for seizure reduction and mental development in young participants between 3 and 6 years of age who suffer from intractable epilepsy. However, robust clinical evidence for quantifying the difference of the efficacy and safety of VNS treatment in this specific patient population has yet to be reported. METHODS/DESIGN: A two-armed, multicenter, randomized, double-blind, prospective trial will be carried out to evaluate whether VNS is beneficial and safe for pediatric epilepsy. Pediatric participants aged between 3 to 6 years old with intractable epilepsy will be recruited and randomly assigned to experimental and control groups with a 1:1 allocation using a computer-generating randomization schedule. Before enrollment, informed consent will be signed by the parents of the participants and the study researchers. Participants in the experimental group will receive electrical stimulation over 24 weeks under standard stimulation parameters. Participants in the control group will not receive any stimulation during the 12 weeks of the double-blind period. The guardians of the participants are required to keep a detailed diary to record seizure activity. Outcome assessments including seizure frequency, Gesell Mental Developmental Scale scores, use of antiepileptic drugs and dosages, and adverse events will be collected at baseline, 6, 12, 18 and/or 24 weeks after electrical stimulation is initiated. The effects of treatment will be analyzed with time and treatment group comparisons. DISCUSSION: This trial will evaluate quantitative differences in efficacy and safety with/without VNS treatment for pediatric participants aged between 3 to 6 years with intractable epilepsy and will explore whether the current age range of VNS therapy can be expanded. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03062514 , Registered on 23 February 2017.


Assuntos
Ondas Encefálicas , Encéfalo/fisiopatologia , Epilepsia Resistente a Medicamentos/terapia , Estimulação do Nervo Vago , Fatores Etários , Criança , Comportamento Infantil , Desenvolvimento Infantil , Pré-Escolar , Método Duplo-Cego , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/fisiopatologia , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Estimulação do Nervo Vago/efeitos adversos
20.
J Neurosurg Sci ; 63(1): 50-60, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29671293

RESUMO

The goal of any epilepsy surgery is to improve patient's quality of life by achieving seizure freedom or by reducing the frequency of severely debilitating seizures. To achieve this goal, non-invasive and invasive diagnostic methods must precisely delineate the epileptogenic zone (EZ), which is defined as the area that needs to be resected to obtain seizure freedom. At the same time, the correct identification of eloquent brain areas is inevitable to avoid new neurological deficits from surgery. In recent years, the technical advances in diagnostics have enabled us to achieve these goals in an increasing number of cases. As a consequence, and with new surgical treatment options available, the number of patients who might benefit from epilepsy surgery is constantly increasing. Especially in pediatric epilepsy, early surgical intervention is becoming frequently advocated as it has been shown to improve cognitive and behavioral outcome. Specialized epilepsy centers and multidisciplinary teams are required to provide adequate care and treatment. The goal of this review is to describe important diseases that are accessible to epilepsy surgery and to give an overview of current diagnostic methods. The focus lies on established as well as novel techniques in epilepsy surgery. The presurgical work-up and patient selection is outlined.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Procedimentos Neurocirúrgicos/métodos , Radiocirurgia/métodos , Estimulação do Nervo Vago/métodos , Epilepsia Resistente a Medicamentos/diagnóstico , Humanos
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