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1.
Seizure ; 69: 258-264, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129365

RESUMO

PURPOSE: SUDEP is the first cause of mortality related to epilepsy. However, in Spain there are no published cases or series from Epilepsy Monitoring Units that could expose the characteristics of SUDEP in our population. METHOD: We reviewed all patients treated at our Spanish Epilepsy Reference Centre who died between 2010-2018. SUDEP cases were classified as definite, probable, possible or near-SUDEP. Epilepsy type, demographics and case detection issues were described. RESULTS: From 1250 evaluated patients, 102 died during the study period. Seven patients were diagnosed with SUDEP or near-SUDEP: two definite SUDEP, one definite SUDEP plus, two probable SUDEP and two near-SUDEP. Specific problems for detection and registration of SUDEP inherent to the Spanish healthcare system and the legal framework were defined. Only 43% of cases were known by the referral neurologist. SUDEP incidence was 1.3 per 1000 patient/year, comprising 0.56% of all deaths in our cohort. Two cases were female, the average age was 36 years (18-61). All patients had focal epilepsy and suffered from generalized tonic-clonic seizures. All witnessed cases occurred after a focal to bilateral tonic-clonic seizure. Four cases occurred during sleep and all non-witnessed cases were found in prone position. One case occurred during video-EEG monitoring. CONCLUSIONS: Our casuistic represents the first Epilepsy Monitoring Unit based case series of SUDEP conducted in Spain. The incidence in our population agrees with the reported in other countries. However, in our population, SUDEP is probably underdiagnosed due to administrative and legal issues.


Assuntos
/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Epilepsias Parciais/mortalidade , Epilepsias Parciais/fisiopatologia , Epilepsia Tônico-Clônica/mortalidade , Epilepsia Tônico-Clônica/fisiopatologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Espanha/epidemiologia , Adulto Jovem
3.
Epilepsy Res ; 146: 1-8, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30053674

RESUMO

A promising alternative for the treatment of refractory epilepsy is electrical stimulation (ES) of the central nervous system. Based on the premise that epilepsy is a result of neural hypersynchronization, we have previously demonstrated that a novel non-standard form of electrical stimulation with randomized inter-pulse intervals, termed non-periodic stimulation (NPS), applied to the amygdala is robustly anticonvulsant. This investigation also suggested that NPS attains its therapeutic effect by desynchronization of epileptiform activity. Here, we further explored the desynchronization hypothesis by testing how the efficacy of NPS in the suppression of convulsive behaviors depends on morphological, spatial, and temporal parameters of stimulus. For this purpose, we varied the number of pulse phases (monopolar versus bipolar square pulses), side of stimulation (right versus left), number of application hemispheres (unilateral versus bilateral), and interhemispheric temporal synchronicity (synchronous versus asynchronous), while measuring the impact on the anticonvulsant action of NPS. Wistar rats received a controlled infusion of the convulsant agent pentylenetetrazole (PTZ, 10 mg/min), together with one of six variations of NPS applied to the amygdala. A stimulated PTZ-free group of animals was also performed as a positive control. Latency to convulsive behavior was used to measure seizure threshold. Animals receiving NPS displayed significant higher threshold for forelimb clonus and generalized tonic-clonic seizures for all patterns. Thresholds seemed to increase gradually from mono to biphasic, unilateral to bilateral, and synchronous to asynchronous stimuli. Thus, combined biphasic, bilateral, and asynchronous stimulation resulted in the greatest seizure threshold. PTZ free animals did not develop any observable convulsive behavior or other uncommon motor activity. These results confirm that NPS has anticonvulsant properties and that biphasic, bilateral, and asynchronous stimulation enhances its efficacy. The fact that lack of synchronism between stimuli of each hemisphere maximizes NPS anticonvulsant power is evidence to desynchronization as tool for suppression of seizures.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Estimulação Encefálica Profunda/métodos , Convulsões/fisiopatologia , Convulsões/terapia , Animais , Sincronização Cortical , Modelos Animais de Doenças , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/terapia , Estimulação Elétrica/métodos , Epilepsia Tônico-Clônica/fisiopatologia , Epilepsia Tônico-Clônica/terapia , Membro Anterior/fisiopatologia , Masculino , Pentilenotetrazol , Distribuição Aleatória , Ratos Wistar , Fatores de Tempo
4.
Epilepsia ; 58(11): 1861-1869, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28980702

RESUMO

OBJECTIVE: A prospective multicenter phase III trial was undertaken to evaluate the performance and tolerability in the epilepsy monitoring unit (EMU) of an investigational wearable surface electromyographic (sEMG) monitoring system for the detection of generalized tonic-clonic seizures (GTCSs). METHODS: One hundred ninety-nine patients with a history of GTCSs who were admitted to the EMU in 11 level IV epilepsy centers for clinically indicated video-electroencephalographic monitoring also received sEMG monitoring with a wearable device that was worn on the arm over the biceps muscle. All recorded sEMG data were processed at a central site using a previously developed detection algorithm. Detected GTCSs were compared to events verified by a majority of three expert reviewers. RESULTS: For all subjects, the detection algorithm detected 35 of 46 (76%, 95% confidence interval [CI] = 0.61-0.87) of the GTCSs, with a positive predictive value (PPV) of 0.03 and a mean false alarm rate (FAR) of 2.52 per 24 h. For data recorded while the device was placed over the midline of the biceps muscle, the system detected 29 of 29 GTCSs (100%, 95% CI = 0.88-1.00), with a detection delay averaging 7.70 s, a PPV of 6.2%, and a mean FAR of 1.44 per 24 h. Mild to moderate adverse events were reported in 28% (55 of 199) of subjects and led to study withdrawal in 9% (17 of 199). These adverse events consisted mostly of skin irritation caused by the electrode patch that resolved without treatment. No serious adverse events were reported. SIGNIFICANCE: Detection of GTCSs using an sEMG monitoring device on the biceps is feasible. Proper positioning of this device is important for accuracy, and for some patients, minimizing the number of false positives may be challenging.


Assuntos
Eletromiografia/métodos , Epilepsia Tônico-Clônica/diagnóstico , Epilepsia Tônico-Clônica/fisiopatologia , Monitorização Ambulatorial/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
5.
J Integr Neurosci ; 16(4): 429-439, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28891522

RESUMO

Previous studies suggested that the patients with generalized tonic-clonic seizure had structural abnormalities in the thalamus, cingulated cortex and some other specific brain regions. Concurrently, the abnormality in thalamocortical network and basal ganglia network has been found in idiopathic generalized epilepsy. The cingulated cortex, a nexus of information processing and regulation in human brain, is implicated in the propagation of generalized spike in IGE and the previous studies have suggested that the structural features and functional connectivity of the cingulated cortex have been changed. The aim of this study was to demonstrate the alterations in the cingulated cortex in generalized tonic-clonic seizure by combining morphological and functional connectivity magnetic resonance imaging. 19 patients with generalized tonic-clonic seizure and 19 age-and gender-matched healthy controls were involved in the study. The three-dimensional high-resolution T1-weighted magnetic resonance imaging data were acquired for voxel-based morphometry analysis, two-sample t-test run on the T1-weighted structural images revealed clusters exhibiting significant decreases in grey-matter volume in the generalized tonic-clonic seizure group, located within the cingulated cortex, thalamus, frontal lobe, temporal lobe, and cerebellum. The decreased gray matter volume in the cingulated cortex indicating that the cingulated cortex has structural impairments in generalized tonic-clonic seizure patients. The bilateral cingulated cortex, as detected with decreased gray matter volume in patients with generalized tonic-clonic seizure through voxel-based morphometry analysis, was selected as seed regions for functional connectivity analysis. Compared with controls, we found decreased functional connectivity to left anterior cingulated cortex (ROI1) in the cuneus, frontal lobe and precentral gyrus. There was no significant result when seeding at the right anterior cingulum gyrus (ROI2). The results of the ROI3 (left middle cingulum) revealed the significantly decreased functional connectivity in the parietal lobe and frontal lobe. Seeding at the ROI4 (right middle cingulum), decreased functional connectivity showed in the occipital lobe, temporal lobe, frontal lobe. Seeding at the ROI5 (left posterior cingulum), decreased functional connectivity showed in the temporal lobe and frontal lobe. Seeding at the ROI6 (right posterior cingulum), decreased functional connectivity showed in the cuneus and frontal lobe. We did not find any increased functional connectivity of the posterior cingulated cortex (ROI3-ROI6) for the generalized tonic-clonic seizure patients in comparison to the controls (p<0.001). Our findings demonstrated that the abnormalities of the functional connectivity were likely to be related to the decreased gray matter volume in the cingulated cortex.


Assuntos
Epilepsia Generalizada/diagnóstico por imagem , Epilepsia Generalizada/fisiopatologia , Epilepsia Tônico-Clônica/diagnóstico por imagem , Epilepsia Tônico-Clônica/fisiopatologia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Adolescente , Adulto , Mapeamento Encefálico , Epilepsia Generalizada/patologia , Epilepsia Tônico-Clônica/patologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Giro do Cíngulo/patologia , Humanos , Imagem Tridimensional , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Tamanho do Órgão , Descanso , Adulto Jovem
6.
Epilepsia ; 58(6): 1005-1014, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28387951

RESUMO

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.


Assuntos
Córtex Cerebral/fisiopatologia , Estimulação Encefálica Profunda/métodos , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/terapia , Terapia por Estimulação Elétrica/métodos , Eletroencefalografia , Neocórtex/fisiopatologia , Adolescente , Adulto , Mapeamento Encefálico , Estimulação Encefálica Profunda/instrumentação , Terapia por Estimulação Elétrica/instrumentação , Eletrodos Implantados , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/terapia , Epilepsia Parcial Complexa/fisiopatologia , Epilepsia Parcial Complexa/terapia , Epilepsia Motora Parcial/fisiopatologia , Epilepsia Motora Parcial/terapia , Epilepsia Tônico-Clônica/fisiopatologia , Epilepsia Tônico-Clônica/terapia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Zh Nevrol Psikhiatr Im S S Korsakova ; 117(11. Vyp. 2): 23-32, 2017.
Artigo em Russo | MEDLINE | ID: mdl-29359716

RESUMO

AIM: To study a group of patients with secondary generalized tonic-clonic seizures (SGTCS) in view of nosology, medical history, clinical, electroencephalographic and neuroimaging features. MATERIAL AND METHODS: The study included 471 patients, 244 (51.8%) men and 227 (48.2%) women. RESULTS: SGTCS were observed in many epileptic syndromes. The most frequent were symptomatic focal epilepsy (33.8%), cryptogenic focal epilepsy (23.8%), rolandic epilepsy (12.6%), FEBL-BEDC syndrome (12.3%). Other forms of epilepsy were less frequent. The onset of epilepsy ranged over a wide age range from the first month of life to 18 years. The average age of onset was 5.7±4.96 years. SGTCS as the only type of paroxysms were observed in 28.3% of cases. Two or more types of seizures were observed in 71.7% of patients, three or more types in 39.3%. Epileptiform activity on EEG during long VEM was detected in 91.3% of patients with SGTCS. In 37.2% of patients, benign epileptiform discharges of childhood were recorded. Treatment with antiepileptic drugs (AEP) led to complete remission in 57.1% of cases of epilepsy associated with SGTCS. A reduction of the frequency of seizures by 50% or more was found in 33.6% of patients treated with AEP. No effect was observed in 9.3% of patients. CONCLUSION: Significant differences in the prognosis and therapeutic approaches to specific epileptic syndromes associated with SGTCS necessitate the use of the entire spectrum of diagnostic measures, which should include careful history taking, clinical examination, video-EEG monitoring with the inclusion of sleep dynamics, MRI / CT brain, genetic testing.


Assuntos
Epilepsias Parciais , Epilepsia Tônico-Clônica , Síndromes Epilépticas , Convulsões , Anticonvulsivantes , Criança , Pré-Escolar , Eletroencefalografia , Epilepsias Parciais/complicações , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/fisiopatologia , Epilepsia Tônico-Clônica/complicações , Epilepsia Tônico-Clônica/diagnóstico por imagem , Epilepsia Tônico-Clônica/fisiopatologia , Síndromes Epilépticas/complicações , Síndromes Epilépticas/diagnóstico por imagem , Síndromes Epilépticas/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Convulsões/etiologia
8.
Neurology ; 87(17): 1802-1805, 2016 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-27664987

RESUMO

OBJECTIVE: To evaluate and identify the frequency of hand postures during generalized convulsions in patients with genetic generalized epilepsy (GGE), localization-related epilepsy (LRE), and nonepileptic attacks (NEA). METHODS: We retrospectively analyzed 98 consecutive videos of generalized convulsions in 62 patients who were admitted for diagnostic video-EEG monitoring. Demographics were recorded, and hand postures were subdivided into fanning, fisting, index-finger pointing (IFP), clawing, and flaccid posturing. Hand postures were then compared between patients with GGE, LRE, and NEA for each stage of the convulsion and for the whole event. RESULTS: In patients with LRE, 96% had IFP, where fanning occurred in 91.3% of GGE (and only at onset), and the flaccid hand posture occurred in 56.0% of NEA. Fisting, fanning, and IFP postures all occurred significantly more frequently during epileptic seizures than during NEA (74.0% vs 32.0%, p = 0.0003; 60.3% vs 20.0%, p = 0.0005; 83.6% vs 12.0%, p < 0.0001). The claw hand posture was present only during NEA, and the flaccid posture occurred significantly more frequently during NEA than during epileptic seizures (56.0% vs 15.1%, p = 0.0001). CONCLUSIONS: Distinct ictal hand or finger posturing is present in patients with GGE, LRE, and NEA. The presence of any fisting, fanning, clawing, IFP, or flaccid hand posturing can help distinguish epileptic seizures from NEA. IFP suggests LRE while fanning with evolution suggests GGE. Overall, hand posturing during seizures provides unique information and aids in the differential diagnosis and classification of epilepsy.


Assuntos
Epilepsia Generalizada/patologia , Epilepsia Generalizada/fisiopatologia , Epilepsia Tônico-Clônica/patologia , Epilepsia Tônico-Clônica/fisiopatologia , Mãos/fisiopatologia , Postura/fisiologia , Adolescente , Adulto , Estudos de Coortes , Eletroencefalografia , Epilepsia Generalizada/diagnóstico por imagem , Epilepsia Tônico-Clônica/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Gravação de Videoteipe , Adulto Jovem
9.
Epilepsy Res ; 126: 147-56, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27500381

RESUMO

OBJECT: The intention of our study was to identify predictive characteristics for long-term seizure control and running down phenomenon after surgical treatment of pharmacoresistant mesiotemporal lobe epilepsy (mTLE) with and without associated cortical dysplasia. MATERIALS AND METHODS: Our study comprises a consecutive series of 458 patients who underwent surgical treatment for intractable mTLE at the Epilepsy Center Freiburg. Data evaluated included semiology, duration and frequency of seizures, results of presurgical diagnostics including video-EEG monitoring, MRI, PET and SPECT as well as postoperative seizure outcome. Results were evaluated forming two groups: Group A consisted of isolated mesiotemporal lesions. Group B comprised patients with mTLE and additional focal cortical dysplasia (FCD). Statistical evaluation was based on the Kaplan Meier survival analysis, using log-rank-tests and a multivariate regression model. Postoperative running down phenomenon was defined as seizure freedom after a period of gradual reduction of postoperative seizure frequency. This was compared to patients with ongoing epilepsy. RESULTS: Complete seizure freedom was achieved in 65.0% of investigated patients at 1year and in 56.5% at long-term follow-up of ≥5 years after surgery. Corresponding results were 64.2% and 56.8% at 1 and ≥5 years, respectively in group A and 66.4% and 56.0%, respectively in group B. Predictive for favorable postoperative outcome in the total group were younger age at surgery, shorter duration of epilepsy, absence of secondarily generalized tonic-clonic seizures (SGTCS), presence of strictly ipsilateral temporal interictal epileptiform discharges (IEDs), complete resection of the lesion as well as absence of postoperative epileptiform activity and of early postoperative seizures. In subgroup analyses, patients of group A demonstrated longer postoperative seizure-free intervals with adolescent age at surgery, short duration of epilepsy before surgery and absence of SGTCS, whereas in patients of group B ipsilateral temporal seizure onset and strictly unilateral IEDs in EEG as well as complete resection were predictors for favorable seizure outcome. Furthermore, absence of early postoperative seizures and of spikes in EEG were predictive factors for long-term seizure-freedom in both subgroups. The running down phenomenon was found in 33 (7.2%) patients. None of the parameters evaluated demonstrated significant predictive power. Only late seizure onset and neoplastic lesions showed a trend for postoperative gradual seizure reduction in multivariate analyses. CONCLUSION: Depending on the presence or absence of focal cortical dysplasia in addition to mesiotemporal structural alterations, predictors of long-term seizure control differed regarding the relevant clinical and electrophysiological features. This is important for specific patient counseling in respective groups.


Assuntos
Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/cirurgia , Malformações do Desenvolvimento Cortical/complicações , Malformações do Desenvolvimento Cortical/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia Tônico-Clônica/complicações , Epilepsia Tônico-Clônica/fisiopatologia , Epilepsia Tônico-Clônica/cirurgia , Feminino , Seguimentos , Lateralidade Funcional , Humanos , Estimativa de Kaplan-Meier , Masculino , Malformações do Desenvolvimento Cortical/fisiopatologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/complicações , Convulsões/fisiopatologia , Convulsões/cirurgia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
10.
Neurotherapeutics ; 13(3): 603-13, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27137202

RESUMO

Previously, we developed electroresponsive hydrogel nanoparticles (ERHNPs) modified with angiopep-2 (ANG) to facilitate the delivery of the antiseizure drug phenytoin sodium (PHT). However, the electroresponsive characteristics were not verified directly in epileptic mice and the optimal preparation formula for electroresponsive ability is still unclear. Here, we further synthesized PHT-loaded ANG-ERHNPs (ANG-PHT-HNPs) and PHT-loaded nonelectroresponsive hydrogel nanoparticles (ANG-PHT-HNPs) by changing the content of sodium 4-vinylbenzene sulfonate in the preparation formulae. In vivo microdialysis analysis showed that ANG-PHT-ERHNPs not only have the characteristics of a higher distribution in the central nervous system, but also have electroresponsive ability, which resulted in a strong release of nonprotein-bound PHT during seizures. In both electrical- (maximal electrical shock) and chemical-induced (pentylenetetrazole and pilocarpine) seizure models, ANG-PHT-ERHNPs lowered the effective therapeutic doses of PHT and demonstrated the improved antiseizure effects compared with ANG-PHT-HNPs or PHT solution. These results demonstrate that ANG-ERHNPs are able to transport PHT into the brain efficiently and release them when epileptiform activity occurred, which is due to the content of sodium 4-vinylbenzene sulfonate in formula. This may change the therapeutic paradigm of existing drug treatment for epilepsy into a type of on-demand control for epilepsy in the future.


Assuntos
Anticonvulsivantes/administração & dosagem , Sistemas de Liberação de Medicamentos , Epilepsia Tônico-Clônica/tratamento farmacológico , Nanopartículas/uso terapêutico , Fenitoína/administração & dosagem , Animais , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Epilepsia Tônico-Clônica/fisiopatologia , Hidrogel de Polietilenoglicol-Dimetacrilato , Masculino , Nanopartículas/química , Fenitoína/farmacocinética , Fenitoína/uso terapêutico , Ratos , Ratos Sprague-Dawley
11.
Epilepsia ; 57 Suppl 1: 4-16, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26749012

RESUMO

The risk of dying suddenly and unexpectedly is increased 24- to 28-fold among young people with epilepsy compared to the general population, but the incidence of sudden unexpected death in epilepsy (SUDEP) varies markedly depending on the epilepsy population. This article first reviews risk factors and biomarkers for SUDEP with the overall aim of enabling identification of epilepsy populations with different risk levels as a background for a discussion of possible intervention strategies. The by far most important clinical risk factor is frequency of generalized tonic-clonic seizures (GTCS), but nocturnal seizures, early age at onset, and long duration of epilepsy have been identified as additional risk factors. Lack of antiepileptic drug (AED) treatment or, in the context of clinical trials, adjunctive placebo versus active treatment is associated with increased risks. Despite considerable research, reliable electrophysiologic (electrocardiography [ECG] or electroencephalography [EEG]) biomarkers of SUDEP risk remain to be established. This is an important limitation for prevention strategies and intervention studies. There is a lack of biomarkers for SUDEP, and until validated biomarkers are found, the endpoint of interventions to prevent SUDEP must be SUDEP itself. These interventions, be they pharmacologic, seizure-detection devices, or nocturnal supervision, require large numbers. Possible methods for assessing prevention measures include public health community interventions, self-management, and more traditional (and much more expensive) randomized clinical trials.


Assuntos
Morte Súbita/epidemiologia , Epilepsia Tônico-Clônica/epidemiologia , Idade de Início , Anticonvulsivantes/uso terapêutico , Biomarcadores , Morte Súbita/prevenção & controle , Eletrocardiografia , Eletroencefalografia , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Epilepsia/fisiopatologia , Epilepsia Tônico-Clônica/tratamento farmacológico , Epilepsia Tônico-Clônica/fisiopatologia , Humanos , Medição de Risco , Fatores de Risco , Autocuidado , Fatores de Tempo
12.
Epilepsia ; 57(3): 412-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26763069

RESUMO

OBJECTIVE: The pathophysiology of sudden unexpected death in epilepsy (SUDEP) remains undetermined. Seizures are accompanied by respiratory dysfunction (RD). Postictal generalized electroencephalography (EEG) suppression (PGES) may follow generalized tonic-clonic seizures (GTCS). Following GTCS patients have impaired arousal and may be motionless. Patients with SUDEP are usually prone. Postictal immobility (PI) may contribute to SUDEP by not permitting repositioning of the head to allow unimpeded ventilation. To determine whether RD and/or ictal characteristics are associated with PI, we analyzed patients with GTCS in the epilepsy monitoring unit. METHOD: We investigated for associations between PI duration and PGES, ictal/postictal oxygen saturation (SpO2 ), end-tidal CO2 (ETCO2 ), seizure localization, duration, and tonic and total convulsive phase duration. We investigated for linkage between PGES and these measures. RESULTS: Seventy patients with 181 GTCS and available SpO2 and/or ETCO2 data were studied. Simple linear regression analysis by seizures showed that PI duration was associated with peak periictal ETCO2 (p = 0.03), duration of oxygen desaturation (p = 0.005) and with SpO2 nadir (p = 0.02). PI duration was not associated with tonic, convulsive phase or total seizure duration. Analysis by patients also showed significant association of PI with RD. Duration of PI was longer following seizures with PGES (p < 0.001). PGES was not associated with the tonic, convulsive phase or total seizure duration. SpO2 nadir was lower in seizures with PGES (p = 0.046), ETCO2 peak change (p = 0.003) was higher, and duration of ETCO2 elevation (p = 0.03) was longer. Multivariable regression analysis showed that PGES and severe RD were associated with PI duration. SIGNIFICANCE: The duration of PI and presence of PGES are associated with periictal RD. The duration of PI is also associated with the presence of PGES. Seizure duration or duration of the convulsive phase is not associated with PI or PGES. Interventions aimed at reversing impaired arousal and PI may reduce SUDEP risk.


Assuntos
Eletroencefalografia/métodos , Epilepsia Tônico-Clônica/epidemiologia , Epilepsia Tônico-Clônica/fisiopatologia , Transtornos Respiratórios/epidemiologia , Transtornos Respiratórios/fisiopatologia , Índice de Gravidade de Doença , Adulto , Morte Súbita/epidemiologia , Epilepsia Tônico-Clônica/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Respiratórios/diagnóstico , Adulto Jovem
13.
Clin EEG Neurosci ; 47(2): 162-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25420625

RESUMO

Rufinamide (RFD) is a novel drug that was recently approved as an adjunctive treatment for Lennox-Gastaut syndrome. Despite its reported effectiveness in generalized seizures (tonic, atonic, or tonic-clonic) in this syndrome, few data on its use in idiopathic generalized epilepsy are available. Indeed, the scientific evidence to date is limited to anecdotal cases or isolated clinical experiences. We report an uncommon, though paradigmatic, case of a woman affected by juvenile absence epilepsy (JAE) who, following a prolonged seizure-freedom period and the consequent withdrawal of valproate, presented a seizure relapse accompanied by a worsening in her electroclinical pattern. In view of this atypical evolution of JAE, characterized by drug-resistant seizures (absence and generalized tonic-clonic) and the progressive increase in electroencephalographic (EEG) abnormalities, several antiepileptic drugs were used, though to no benefit. The use of RFD instead led to a gradual control of the seizures and normalization of the EEG findings. In addition to this clinical experience, we briefly review the literature on the use of RFD in refractory generalized epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Epilepsia Tônico-Clônica/tratamento farmacológico , Triazóis/uso terapêutico , Adulto , Progressão da Doença , Eletroencefalografia , Epilepsia Tipo Ausência/complicações , Epilepsia Tipo Ausência/fisiopatologia , Epilepsia Generalizada/fisiopatologia , Epilepsia Tônico-Clônica/complicações , Epilepsia Tônico-Clônica/fisiopatologia , Feminino , Humanos , Resultado do Tratamento
14.
Brain Res ; 1631: 80-91, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26620541

RESUMO

The dorsal raphe nucleus (DRN) is a key structure of the endogenous pain inhibitory system. Although the DRN is rich in serotoninergic neurons, cholinergic neurons are also found in that nucleus. Both ictal and inter-ictal states are followed by post-ictal analgesia. The present study investigated the role of cholinergic mechanisms in postictal antinociceptive processes using microinjections of atropine and mecamylamine, muscarinic and nicotinic cholinergic receptor antagonists, respectively, in the DRN of rats. Intraperitoneal injection of pentylenetetrazole (PTZ) (at 64mg/kg) caused tonic and tonic-clonic seizures. The convulsive motor reactions were followed by an increase in pain thresholds, a phenomenon known as post-ictal analgesia. Pre-treatment of the DRN with atropine or mecamylamine at 1µg, 3µg and 5µg/0.2µL decreased the post-ictal antinociceptive phenomenon. The present results showed that the post-ictal analgesia was mediated by muscarinic and nicotinic cholinergic receptors in the DRN, a structure crucially involved in the neural network that organises post-ictal hypoalgesia.


Assuntos
Núcleo Dorsal da Rafe/fisiopatologia , Limiar da Dor/efeitos dos fármacos , Receptores Muscarínicos/fisiologia , Receptores Nicotínicos/fisiologia , Transmissão Sináptica/fisiologia , Acetilcolina/farmacologia , Analgésicos/farmacologia , Animais , Atropina/farmacologia , Núcleo Dorsal da Rafe/efeitos dos fármacos , Epilepsia Tônico-Clônica/metabolismo , Epilepsia Tônico-Clônica/fisiopatologia , Neurônios GABAérgicos/metabolismo , Masculino , Mecamilamina/farmacologia , Antagonistas Muscarínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Medição da Dor/métodos , Limiar da Dor/fisiologia , Ratos , Ratos Wistar , Neurônios Serotoninérgicos/fisiologia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/fisiopatologia , Transmissão Sináptica/efeitos dos fármacos
15.
Eur Rev Med Pharmacol Sci ; 19(22): 4249-53, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26636510

RESUMO

OBJECTIVE: The study reported here discusses the duration of the generalized tonic-clonic seizures (GTCS) among frontal lobe epilepsy (FLE), medial temporal lobe epilepsy (MTLE) and idiopathic generalized epilepsy (IGE). PATIENTS AND METHODS: The study was done by analyzing the data from patients who had undergone video-EEG in 2009 and had GTCS during the monitoring. The patients were selected for the frontal lobe epilepsy (FLE), medial temporal lobe epilepsy (MTLE), and idiopathic generalized epilepsy (IGE). Once they met the criteria, the durations of all the phases were measured, then discussed if there were any difference in duration for different epilepsies. RESULTS: On comparison of the total duration of various types of seizures it was found that the duration of FLE (177 ± 212.6 sec.) was significantly different from the duration of MTLE (104.6 ± 51.8 sec.) and IGE (63.9 ± 28.2 sec.). It can be found in the comparison of GTCS that the duration of phase 6,7 of FLE (63.5 ± 30.9 sec.) was statistically significant compared with MTLE (37.3 ± 13.8 sec.) and IGE (46.4 ± 30.1 sec.). The duration of various types of epilepsy in the generalized tonic-clonic period was not statistically significant. CONCLUSIONS: Through this study, we found the differences of the duration of different types of epilepsies that provide the clinical basis for further studies of seizure mechanism and neural network conduction.


Assuntos
Eletroencefalografia/métodos , Epilepsia Tônico-Clônica/diagnóstico , Epilepsia Tônico-Clônica/fisiopatologia , Convulsões/diagnóstico , Convulsões/fisiopatologia , Adolescente , Adulto , Epilepsia do Lobo Frontal/diagnóstico , Epilepsia do Lobo Frontal/fisiopatologia , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/fisiopatologia , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Gravação em Vídeo/métodos , Adulto Jovem
16.
PLoS One ; 10(11): e0141221, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26555229

RESUMO

Exposure to repetitive seizures is known to promote convulsions which depend on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by a modified 6-Hz corneal stimulation model of psychomotor seizures. Mice received up to 4 sessions of 6-Hz corneal stimulation with fixed current amplitude of 32 mA and inter-stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures always appeared in frontal cortex, but only at the fourth stimulation they involved the hippocampus, suggesting the establishment of an epileptogenic process. Duration of seizure non-motor component progressively decreased after the second session, whereas convulsive seizures remained unchanged. In addition, a more severe seizure phenotype, consisting of tonic-clonic generalized convulsions, was predominant after the second session. Immunohistochemistry and double immunofluorescence experiments revealed a significant increase in neuronal activity occurring in the lateral amygdala after the fourth session, most likely due to activity of principal cells. These findings indicate a predominant role of amygdala in promoting progressively more severe convulsions as well as the late recruitment of the hippocampus in the seizure spread. We propose that the repeated 6-Hz corneal stimulation model may be used to investigate some mechanisms of epileptogenesis and to test putative antiepileptogenic drugs.


Assuntos
Complexo Nuclear Basolateral da Amígdala/metabolismo , Córnea/fisiopatologia , Estimulação Elétrica/efeitos adversos , Epilepsia Parcial Complexa/etiologia , Epilepsia Generalizada/etiologia , Hipocampo/fisiopatologia , Proteínas do Tecido Nervoso/biossíntese , Proteínas Proto-Oncogênicas c-fos/biossíntese , Animais , Complexo Nuclear Basolateral da Amígdala/fisiopatologia , Modelos Animais de Doenças , Eletrodos Implantados , Eletroencefalografia , Epilepsia Parcial Complexa/genética , Epilepsia Parcial Complexa/fisiopatologia , Epilepsia Generalizada/genética , Epilepsia Generalizada/fisiopatologia , Epilepsia Tônico-Clônica/etiologia , Epilepsia Tônico-Clônica/genética , Epilepsia Tônico-Clônica/fisiopatologia , Regulação da Expressão Gênica , Masculino , Camundongos , Microglia/patologia , Rede Nervosa/fisiopatologia , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , Neurônios/patologia , Fenótipo , Proteínas Proto-Oncogênicas c-fos/genética , Índice de Gravidade de Doença , Método Simples-Cego , Gravação em Vídeo
18.
Bull Exp Biol Med ; 159(1): 1-3, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26033576

RESUMO

Pretreatment with mGluR1 antagonist AIDA (1 mg/kg) nearly completely prevented the onset of tonic-clonic seizures and increased generation of NO in the cerebral cortex of rats with genetically determined audiogenic reaction to acoustic stimulation. Administration of mGluR5 antagonist MPEP (10 mg/kg) before audiogenic exposure was followed by a significant decrease in the degree of seizure and partially prevented increased generation of NO due to acoustic stimulation. These data indicate that mGlu receptors and NO play an important role in the pathogenetic mechanisms of audiogenic seizures.


Assuntos
Estimulação Acústica/efeitos adversos , Epilepsia Reflexa/prevenção & controle , Epilepsia Tônico-Clônica/prevenção & controle , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Indanos/uso terapêutico , Proteínas do Tecido Nervoso/antagonistas & inibidores , Óxido Nítrico/fisiologia , Piridinas/uso terapêutico , Receptor de Glutamato Metabotrópico 5/antagonistas & inibidores , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Epilepsia Reflexa/etiologia , Epilepsia Reflexa/fisiopatologia , Epilepsia Tônico-Clônica/etiologia , Epilepsia Tônico-Clônica/fisiopatologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Indanos/farmacologia , Masculino , Proteínas do Tecido Nervoso/fisiologia , Óxido Nítrico/biossíntese , Piridinas/farmacologia , Ratos , Ratos Mutantes , Receptor de Glutamato Metabotrópico 5/fisiologia , Receptores de Glutamato Metabotrópico/fisiologia
19.
Epilepsy Behav ; 49: 111-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25935513

RESUMO

INTRODUCTION: Identifying seizures with prolonged duration during video-electroencephalographic (EEG) monitoring is of importance to inform clinicians when to start emergency treatment of seizures to prevent status epilepticus. The aims of this study were to assess the clinical and EEG seizure duration (SD) in consecutive patients with epilepsy who underwent prolonged video-EEG monitoring and to identify a seizure type-dependent time point to start emergency treatment based on the likelihood that seizures will not stop spontaneously. Furthermore, we sought to determine predictors of SD and explored the relationship between antiepileptic drug (AED) serum levels and SD. MATERIAL AND METHODS: We retrospectively analyzed 1796 seizures in 200 patients undergoing video-EEG monitoring between January 2006 and March 2008. RESULTS: Focal simple seizures lasted significantly shorter (clinical SD: 28s, EEG SD: 42 s) compared with focal complex seizures (clinical SD: 64 s, EEG SD: 62 s), and both seizure types lasted significantly shorter compared with secondarily generalized tonic-clonic seizures (GTCSs; clinical SD: 90 s, EEG SD: 96 s). There was no difference between the duration of the convulsive phase of primary GTCSs (defined as nonfocal) and that of secondarily GTCSs (each 65 s). Cumulative clinical SD (99%) was 7 min in focal complex seizures and 11 min in focal simple seizures. Mixed linear regression model demonstrated that history of status epilepticus (P = 0.034), temporal lobe seizure onset (P = 0.040), and MRI lesions (P = 0.013) were significantly associated with logarithmic EEG SD in focal epilepsies recorded with scalp electrodes. We found significant negative correlations between the AED serum level and the EEG SD in patients treated with monotherapy: carbamazepine (P < 0.001), levetiracetam (P = 0.001), oxcarbazepine (P = 0.001), and valproic acid (P = 0.038) but not with lamotrigine monotherapy and EEG SD. DISCUSSION: Based on the results of this study, we propose 2 min of convulsive seizure activity (irrespective of focal or generalized onset) as a prolonged seizure, which could serve as a time point to consider treatment to prevent status epilepticus. In focal complex seizures, we suggest an upper limit of 7 min, and in focal simple seizures 11 min, as definition of prolonged seizures. History of status epilepticus, temporal seizure onset, and lesional MRI findings are factors associated with significantly longer SD. Negative correlations of carbamazepine, levetiracetam, oxcarbazepine, and valproic acid serum levels and SD suggest a prolonging effect on seizures during withdrawal of these AEDs during video-EEG monitoring sessions. This article is part of a Special Issue entitled "Status Epilepticus".


Assuntos
Eletroencefalografia/tendências , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/fisiopatologia , Epilepsia Tônico-Clônica/diagnóstico , Epilepsia Tônico-Clônica/fisiopatologia , Gravação em Vídeo/tendências , Adolescente , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Eletroencefalografia/métodos , Epilepsias Parciais/tratamento farmacológico , Epilepsia Tônico-Clônica/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Fatores de Tempo , Gravação em Vídeo/métodos , Adulto Jovem
20.
Neurotoxicology ; 48: 100-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25783504

RESUMO

The synthetic rodenticide, tetramethylenedisulfotetramine (TMDT), is a persistent and highly lethal GABA-gated Cl(-) channel blocker. TMDT is clandestinely produced, remains popular in mainland China, and causes numerous unintentional and deliberate poisonings worldwide. TMDT is odorless, tasteless, and easy to manufacture, features that make it a potential weapon of terrorism. There is no effective treatment. We previously characterized the effects of TMDT in C57BL/6 mice and surveyed efficacies of GABAergic and glutamatergic anticonvulsant treatments. At 0.4 mg/kg i.p., TMDT produced neurotoxic symptomatology consisting of twitches, clonic and tonic-clonic seizures, often progressing to status epilepticus and death. If administered immediately after the occurrence of the first clonic seizure, the benzodiazepine diazepam (DZP) effectively prevented all subsequent seizure symptoms, whereas the NMDA receptor antagonist dizocilpine (MK-801) primarily prevented tonic-clonic seizures. The latter agent, however, appeared to be more effective at preventing delayed death. The present study further explored these phenomena, and characterized the therapeutic actions of DZP and MK-801 as combinations. Joint treatment with both DZP and MK-801 displayed synergistic protection against tonic-clonic seizures and 24 h lethality as determined by isobolographic analysis. Clonic seizures, however, remained poorly controlled. A modification of the treatment regimen, where DZP was followed 10 min later by MK-801, yielded a reduction in both types of seizures and improved overall outcome. Simultaneous monitoring of subjects via EEG and videography confirmed effectiveness of this sequential regimen. We conclude that TMDT blockage at GABAA receptors involves early activation of NMDA receptors, which contribute to persistent ictogenic activity. Our data predict that a sequential combination treatment with DZP followed by MK-801 will be superior to either individual therapy with, or simultaneous administration of, these two agents in treating TMDT poisoning.


Assuntos
Anticonvulsivantes/farmacologia , Hidrocarbonetos Aromáticos com Pontes/toxicidade , Sistema Nervoso Central/efeitos dos fármacos , Diazepam/farmacologia , Maleato de Dizocilpina/farmacologia , Epilepsia Tônico-Clônica/prevenção & controle , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas GABAérgicos/toxicidade , Animais , Ondas Encefálicas/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiopatologia , Progressão da Doença , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Eletroencefalografia , Epilepsia Tônico-Clônica/induzido quimicamente , Epilepsia Tônico-Clônica/metabolismo , Epilepsia Tônico-Clônica/fisiopatologia , Ácido Glutâmico/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/metabolismo , Estado Epiléptico/fisiopatologia , Estado Epiléptico/prevenção & controle , Fatores de Tempo , Gravação em Vídeo , Ácido gama-Aminobutírico/metabolismo
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