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1.
Epilepsy Behav ; 153: 109687, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38368791

RESUMO

OBJECTIVE: We investigated neuropsychological outcome in patients with pharmacoresistant pediatric-onset epilepsy caused by focal cortical dysplasia (FCD), who underwent frontal lobe resection during adolescence and young adulthood. METHODS: Twenty-seven patients were studied, comprising 15 patients who underwent language-dominant side resection (LDR) and 12 patients who had languagenondominant side resection (n-LDR). We evaluated intelligence (language function, arithmetic ability, working memory, processing speed, visuo-spatial reasoning), executive function, and memory in these patients before and two years after resection surgery. We analyzed the relationship between neuropsychological outcome and resected regions (side of language dominance and location). RESULTS: Although 75% of the patients showed improvement or no change in individual neuropsychological tests after surgical intervention, 25% showed decline. The cognitive tests that showed improvement or decline varied between LDR and n-LDR. In patients who had LDR, decline was observed in Vocabulary and Phonemic Fluency (both 5/15 patients), especially after resection of ventrolateral frontal cortex, and improvement was observed in WCST-Category (7/14 patients), Block Design (6/15 patients), Digit Symbol (4/15 patients), and Delayed Recall (3/9 patients). In patients who underwent n-LDR, improvement was observed in Vocabulary (3/12 patients), but decline was observed in Block Design (2/9 patients), and WCST-Category (2/9 patients) after resection of dorsolateral frontal cortex; and Arithmetic (3/10 patients) declined after resection of dorsolateral frontal cortex or ventrolateral frontal cortex. General Memory (3/8 patients), Visual Memory (3/8 patients), Delayed Recall (3/8 patients), Verbal Memory (2/9 patients), and Digit Symbol (3/12 patients) also declined after n-LDR. CONCLUSION: Postoperative changes in cognitive function varied depending on the location and side of the resection. For precise presurgical prediction of neuropsychological outcome after surgery, further prospective studies are needed to accumulate data of cognitive changes in relation to the resection site.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Displasia Cortical Focal , Criança , Humanos , Adolescente , Adulto Jovem , Adulto , Resultado do Tratamento , Epilepsia/etiologia , Epilepsia/cirurgia , Epilepsia/psicologia , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/cirurgia , Memória de Curto Prazo , Testes Neuropsicológicos , Epilepsia do Lobo Temporal/cirurgia , Estudos Retrospectivos
2.
Biol Pharm Bull ; 47(1): 43-48, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37952977

RESUMO

The aim of this study was to evaluate the time-course changes in lamotrigine (LTG) concentration after addition of valproate (VPA) and the safety and tolerability of the combination therapy. We reviewed our therapeutic drug monitoring (TDM) database and found 345 patients on LTG who received add-on therapy with VPA. VPA had been added at least 12 weeks after patients finished stepwise LTG titration. Also, we retrospectively evaluated the LTG concentration after addition of VPA and the safety and long-term tolerability of LTG-VPA combination therapy. Plasma LTG concentration increased more than 1.5-fold within 15 d of addition of VPA and reached a peak at 30 d. The rate of increase in LTG concentration occurred in a VPA concentration-dependent manner. During the first 120 d after addition of VPA, adverse events were reported by 58 patients (16.8%), but no patient developed cutaneous reactions. Kaplan-Meier analysis showed estimated retention rates for LTG-VPA combination therapy of 74.5% at 5 years. At 5 years, the mean concentration of LTG was 11.1 µg/mL (43.3 µmol/L). Because addition of VPA leads to a marked increase in LTG concentration over a short period, TDM for LTG should be performed at the earliest from 14 d after starting VPA. At 120 d after starting VPA therapy, the higher LTG concentration due to addition of VPA is not associated with an increased risk of cutaneous reactions. Although LTG-VPA combination therapy increases LTG concentration, it is well tolerated and has a high long-term retention rate.


Assuntos
Triazinas , Ácido Valproico , Humanos , Lamotrigina/efeitos adversos , Ácido Valproico/efeitos adversos , Estudos Retrospectivos , Triazinas/efeitos adversos , Anticonvulsivantes , Quimioterapia Combinada
3.
Epilepsy Behav ; 143: 109213, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37126869

RESUMO

PURPOSE: To evaluate the effects of low-dose titration on the tolerability and safety of perampanel. METHODS: We retrospectively reviewed the records of 1065 patients who started perampanel therapy and compared the incidence of adverse events after standard titration (Group A: starting dose, 2 mg/day; titration speed, 2 mg/2 weeks or longer) and low-dose titration (Group B: starting dose, < 1 mg/day; titration speed, < 1 mg/2 weeks or longer). RESULTS: Adverse events were reported in 158 patients (14.8%) within the initial first 90 days of starting perampanel (mean concentration, 331 ng/mL). At 90 days, the cumulative incidence of adverse events was significantly higher in Group A than in Group B (24.5% vs. 16.3%, respectively; log-rank test p < 0.001). A Cox proportional hazards model also showed that low-dose titration decreased the incidence risk of adverse events (adjusted hazard ratio, 0.49; 95% confidence interval, 0.35-0.69). When the groups were stratified by use of enzyme-inducing antiseizure medications (inducers), Group A patients without inducers had a significantly higher cumulative incidence of adverse events than the other three subgroups (26.7%, p < 0.001). In patients taking 2 mg of perampanel, median concentrations in patients with or without inducers were 43 ng/mL and 204 ng/mL, respectively. CONCLUSION: Perampanel is generally initiated at 2 mg, but serum perampanel concentrations show substantial interindividual variation. Our study suggests that care must be taken when setting the starting dose of perampanel. In particular, low-dose titration is recommended in patients not taking inducers.


Assuntos
Anticonvulsivantes , Nitrilas , Humanos , Anticonvulsivantes/efeitos adversos , Estudos Retrospectivos , Piridonas/efeitos adversos , Resultado do Tratamento
4.
No Shinkei Geka ; 51(1): 33-42, 2023 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-36682747

RESUMO

Electroencephalogram(EEG)signals are mainly generated by postsynaptic potentials(EPSP)in the apical dendrites of pyramidal cells in the cortex. The mechanism of generation of interictal epileptiform discharges(IED)is paroxysmal depolarization shift(PDS). IEDs are negative towards the cortical surface and positive towards the white matter. To interpret EEG, readers should know normal EEG waveforms of wakefulness and sleep, normal variants such as wicket spikes or small sharp spikes, and artifacts such as eye movements or electromyography. Overinterpretation of EEG is a major cause of misdiagnosis; therefore, the accurate identification of IED is essential. The International Federation of Clinical Neurophysiology has proposed a criteria for the identification of IED. Long-term video-EEG is useful for correct diagnosis and localization of the epileptogenic zone in the setting of presurgical evaluation of intractable epilepsy and is also useful for the differential diagnosis of epileptic seizures and non-epileptic events. Clinical history and symptomatology are of utmost importance for correct diagnosis. Diagnosis should not be made using only EEG findings.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Humanos , Eletroencefalografia , Epilepsia/diagnóstico , Epilepsia/cirurgia , Convulsões , Vigília
5.
Ther Drug Monit ; 44(4): 585-591, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35213526

RESUMO

BACKGROUND: The purposes of this study were to assess drug interactions between rufinamide and concomitant antiepileptic drugs (AEDs) and to identify the therapeutic window for rufinamide. METHODS: Serum samples (n = 1531) were obtained from 178 patients (aged 2-57 years), and clinical records were retrospectively reviewed to evaluate the safety and efficacy of rufinamide (mean observation time, 1073 ± 846 days). RESULTS: Rufinamide exhibited linear pharmacokinetics at doses of up to 60 mg/kg (range, 50-3200 mg/d). Concomitant use of the enzyme-inducing AEDs such as phenytoin, carbamazepine, and phenobarbital reduced rufinamide concentrations by 43.4%, 13.2%, and 30.3%, respectively. By contrast, concomitant use of valproate significantly elevated rufinamide concentrations. Clinical response was seen in 41 patients (23.0%), with a median therapeutic concentration (interquartile range) of 20.6 mcg/mL (13.3-27.0). There was no difference in the therapeutic concentrations between seizure types, but patients with tonic/atonic seizures tended to have higher rufinamide concentrations. During the study period, adverse events were reported in 64 patients (35.8%), including somnolence, gastrointestinal disorders, dizziness, and irritability/behavior disorders. Conditional logistic regression analysis showed that patients administered a concentration greater than 20 mcg/mL had an 8.6-fold higher incidence of adverse events. CONCLUSIONS: Therapeutic drug monitoring for rufinamide is clinically useful for predicting drug interactions between rufinamide and concomitant AEDs. When a patient has tonic/atonic seizures, careful titration is required for concentrations greater than 20 mcg/mL.


Assuntos
Monitoramento de Medicamentos , Epilepsia , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacocinética , Interações Medicamentosas , Epilepsia/tratamento farmacológico , Humanos , Japão , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Resultado do Tratamento , Triazóis
6.
Epilepsy Behav ; 122: 108216, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34325156

RESUMO

OBJECTIVE: We performed a prospective, longitudinal, 2-year follow-up study to clarify psychiatric courses and outcomes after temporal lobe epilepsy surgery. METHODS: We assessed 141 patients (68 men, 73 women) aged 16 or older with structured interviews and psychiatric rating scales before surgery and 3 months, 1 year, and 2 years afterward. RESULTS: Fifty-two patients (36.9%) had a psychiatric condition before surgery or during the follow-up period or both. The number of patients with a psychiatric condition decreased from 31 (22.0%) before surgery to 14 (9.9%) at 2 years. On the basis of our results, we defined 5 courses of psychiatric conditions: course 0, no psychopathology (n = 89, 63.1%); course 1, remission or resolution of a presurgical psychiatric condition after surgery (n = 19, 13.5%); course 2, new onset, transient psychiatric condition after surgery (n = 19, 13.5%); course 3, new onset, persistent psychiatric condition after surgery (n = 2, 1.4%); and course 4, chronic psychiatric condition before and after surgery (n = 12, 8.5%). In 14/25 (56.0%) patients with a mood or anxiety disorder before surgery, the condition remitted or resolved after surgery (course 1). Eighteen of 110 patients (16.4%) without any psychopathology before surgery developed mood or anxiety disorders afterward, including major depressive disorder in 13 patients (courses 2 and 3); in more than half of these patients, the disorder manifested within 1 year. More patients with a past history of psychiatric conditions were found in course 2 than in course 0. The duration of epilepsy was longer in course 4 than in course 0, and age at epilepsy onset was lower in course 4 than in course 0. SIGNIFICANCE: Most patients with a psychiatric condition show a favorable outcome 2 years after surgery; however, some show a transient worsening or new onset of psychiatric conditions, in particular depression.


Assuntos
Transtorno Depressivo Maior , Epilepsia do Lobo Temporal , Epilepsia do Lobo Temporal/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento
7.
Epilepsy Behav ; 124: 108356, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34662853

RESUMO

PURPOSE: To identify the risk factors for psychiatric adverse effects associated with perampanel therapy. METHODS: We retrospectively evaluated the adverse effects of perampanel by reviewing clinical records from 895 Japanese patients with epilepsy (aged 1-86 years) who started perampanel therapy at National Epilepsy Center, Shizuoka, Japan, between June 2016 and December 2019. Patients were classified into 3 groups: those without adverse effects (Group I), those with psychiatric adverse effects (Group II), and those with common adverse effects (Group III). RESULTS: The number of patients assigned to each group was as follows: Group I, n = 641; Group II, n = 93; and Group III, n = 161. The mean follow-up period was 458 ±â€¯265 days (median, 511 days). Kaplan-Meier survival estimates showed that the median time to treatment failure was shorter in Group II than in Group III (294 vs. 392 days, respectively; log-rank test, p < 0.001). According to polytomous logistic regression, younger age (<16 years) was associated with a lower risk of common and psychiatric adverse effects. The risk factors for psychiatric adverse effects (Group II) were intellectual disability (adjusted odds ratio [AOR], 2.6; 95% confidence interval (CI), 1.5-4.5) and psychiatric comorbidity (AOR, 3.8; 95% CI, 2.3-6.3); in patients with intellectual disability, the occurrence of psychiatric adverse effects was concentration dependent. Patients with lamotrigine use had a 0.54-fold lower risk of psychiatric adverse effects. In Group III, concomitant use of inducers was associated with a decreased risk of common adverse effects (AOR, 0.68; 95% CI, 0.46-0.99). SIGNIFICANCE: We found clear differences in the risk factors for psychiatric adverse effects. In patients with intellectual disability, care must be taken when titrating perampanel, and therapeutic drug monitoring should be performed.

8.
Epilepsy Behav ; 123: 108240, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34375803

RESUMO

OBJECTIVE: Frontal lobectomy is often used as a surgical treatment for frontal lobe epilepsy, especially when a large epileptogenic zone in the frontal lobe is inferred from preoperative evaluation. The frontal lobe is important for cognitive functions such as executive functions and verbal fluency, but the neuropsychological outcome after a frontal or prefrontal lobectomy that includes both the dorsolateral prefrontal cortex and ventral prefrontal cortex has not been studied thoroughly. In the present study, we evaluated neuropsychological outcomes after patients with frontal lobe epilepsy received a frontal or prefrontal lobectomy. METHODS: We retrospectively reviewed the data of patients with frontal lobe epilepsy who underwent a frontal or prefrontal lobectomy that includes both the dorsolateral prefrontal cortex and ventral prefrontal cortex at 16 years or older from October 2004 to December 2014, with a minimum postoperative follow-up of 24 months. We analyzed and compared neuropsychological outcomes, including executive functions, verbal fluency, intelligence, and memory, before and after the operation. RESULTS: Eighteen patients were 16 years or older and underwent pre- and postoperative (2 years after the operation) neuropsychological evaluations. Patients showed significant deterioration only on the Benton Visual Retention Test. Performance on tests of frontal lobe functions, such as executive function and verbal fluency, showed no significant deterioration. CONCLUSIONS: Overall cognitive performance, including functions widely thought to depend on the frontal lobe, is stable after a frontal or prefrontal lobectomy to treat frontal lobe epilepsy.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Frontal , Epilepsia do Lobo Temporal , Epilepsia do Lobo Frontal/cirurgia , Função Executiva , Lobo Frontal/cirurgia , Humanos , Testes Neuropsicológicos , Estudos Retrospectivos
9.
Epilepsy Behav ; 92: 145-153, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30660057

RESUMO

PURPOSE: Cavernous malformation (CM) in the temporal neocortex causes intractable epilepsy. Whether to resect additional mesial temporal structures in addition to the lesionectomy is a still controversial issue. To clarify the need for the procedure, we retrospectively analyzed pre- and postoperative clinical data of patients with surgically removed CM. SUBJECTS AND METHODS: We included data from 18 patients with CM in the temporal neocortex who presented with intractable epilepsy. Eleven patients of our early series were treated with extended resection, i.e., lesionectomy and the resection of additional mesial temporal structures. Seven patients underwent lesionectomy, i.e., removal of the CM and of hemosiderin-stained surrounding brain tissue. Pathological assessments of the resected hippocampus were performed. Chronic intracranial electroencephalography (EEG) recordings were obtained in 6 patients. We performed perioperative neuropsychological assessments in all patients. RESULTS: The seizure outcome was recorded as Engel class I in 17 patients (94.4%); Ia = 12 (66.7%) Ib = 2 (11.1%), Ic = 1 (5.6%), Id = 2 (11.1%), and class IIb in one patient (5.6%). Adding resection of the mesial temporal structures to lesionectomy did not alter the seizure outcome. Pathology of hippocampus revealed limited neuronal loss in CA4. Ictal onsets in the ipsilateral lateral cortex were detected in all 6 patients who underwent intracranial EEG. In 4 patients each, we also detected ictal onsets from the ipsilateral mesial temporal structures and from the contralateral temporal lobe. Postoperatively, in the patients where their CM was located in the language-dominant hemisphere (n = 10), the full-scale intelligence quotient (IQ) and the performance IQ increased (p < 0.05), whereas the verbal memory (WMS-R) deteriorated in two of 5 patients. CONCLUSION: Excellent seizure outcomes were obtained even the lesionectomy alone. To confirm appropriate surgical strategy for lateral temporal CM with intractable epilepsy, further studies in large sample size are needed.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/cirurgia , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Neocórtex/cirurgia , Convulsões/cirurgia , Lobo Temporal/cirurgia , Adulto , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/patologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia/efeitos adversos , Epilepsia do Lobo Temporal/complicações , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hipocampo/patologia , Hipocampo/fisiopatologia , Hipocampo/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/complicações , Convulsões/patologia , Convulsões/fisiopatologia , Lobo Temporal/patologia , Lobo Temporal/fisiopatologia , Adulto Jovem
10.
Ther Drug Monit ; 40(6): 725-729, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30086086

RESUMO

BACKGROUND: It is well-known that the pharmacokinetics of various drugs are influenced by inflammation. This study evaluated the relationship between C-reactive protein (CRP; an inflammation marker) and the pharmacokinetics of perampanel. METHODS: Among 111 patients who underwent measurement of both CRP and perampanel, 23 patients had a serum CRP level exceeding 1.5 mg/dL (CRP-positive). We compared the concentration/dose ratio (CD ratio) of perampanel in these 23 patients between the times when they were CRP-positive and CRP-negative. To evaluate the effect of CRP on the CD ratio, multiple regression analysis was performed with the following covariates: CRP-positive status, body weight, and use of phenytoin, carbamazepine, or phenobarbital, and combinations of these drugs. RESULTS: In 10 patients using enzyme-inducing antiepileptic drugs (AEDs), the mean CD ratio increased by 53.5% [from 1389 to 2132 (ng/mL)/(mg/kg)] when they were CRP-positive. In 13 patients without enzyme-inducing AEDs, the mean CD ratio increased by 100.8% [from 3826 ng/mL to 7683 (ng/mL)/(mg/kg)] when they were CRP-positive. By multiple regression analysis, the CRP level was a significant independent determinant of the CD ratio of perampanel. Despite a marked increase of the CD ratio, no adverse events were reported. CONCLUSIONS: Irrespective of concomitant administration of enzyme-inducing AEDs, the serum perampanel concentration showed a marked increase in patients with inflammation. However, this increase was not associated with central nervous system toxicity. Although it is unknown whether the concentration of free and/or bound perampanel was increased, it seems likely that dose reduction is unnecessary for elevation of the serum perampanel level in patients with inflammation.


Assuntos
Inflamação/metabolismo , Piridonas/farmacocinética , Adolescente , Adulto , Anticonvulsivantes/farmacocinética , Proteína C-Reativa/metabolismo , Carbamazepina/farmacologia , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Método Duplo-Cego , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Nitrilas , Fenobarbital/farmacologia , Fenitoína/farmacologia , Piridonas/sangue , Fatores de Tempo , Adulto Jovem
11.
Ther Drug Monit ; 40(1): 144-147, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29095797

RESUMO

BACKGROUND: Several studies have demonstrated that renal impairment not only decreases renal clearance but also hepatic clearance of medications that are CYP3A4 substrates. We evaluated the influence of renal function on the pharmacokinetics of antiepileptic drugs metabolized by CYP3A4. METHODS: We retrospectively calculated the concentration/dose ratio (CD ratio) for topiramate and clobazam in an epilepsy patient with renal impairment. In addition, we determined the CD ratio of perampanel in 17 patients with normal renal function and compared it with that in the patient with renal impairment. RESULTS: A patient with frontal lobe epilepsy and mild renal impairment [creatinine clearance (CCr): 67.7 mL/min] was taking phenytoin and 3 CYP3A4 substrates (topiramate, clobazam, and perampanel). With progression of renal impairment (CCr: 28.1 mL/min), the CD ratios of topiramate and clobazam increased by about 2-fold. The mean CD ratio of perampanel was 1740 ± 966 ng·mL·mg·kg in the 17 patients with normal renal function using phenytoin. By contrast, the CD ratio of perampanel was markedly higher (range: 5327-9113 ng·mL·mg·kg) in the patient with renal impairment (CCr: <20 mL/min). CONCLUSIONS: These findings suggest that dose adjustment based on therapeutic drug monitoring is probably necessary when topiramate, clobazam, or perampanel is prescribed for patients with moderate-to-severe renal impairment.


Assuntos
Anticonvulsivantes/farmacocinética , Benzodiazepinas/farmacocinética , Citocromo P-450 CYP3A/metabolismo , Frutose/análogos & derivados , Piridonas/farmacocinética , Insuficiência Renal/sangue , Anticonvulsivantes/sangue , Benzodiazepinas/sangue , Clobazam , Frutose/sangue , Frutose/farmacocinética , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Nitrilas , Piridonas/sangue , Estudos Retrospectivos , Topiramato
12.
Hum Brain Mapp ; 38(9): 4511-4524, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28573679

RESUMO

Faces contain multifaceted information that is important for human communication. Neuroimaging studies have revealed face-specific activation in multiple brain regions, including the inferior occipital gyrus (IOG) and amygdala; it is often assumed that these regions constitute the neural network responsible for the processing of faces. However, it remains unknown whether and how these brain regions transmit information during face processing. This study investigated these questions by applying dynamic causal modeling of induced responses to human intracranial electroencephalography data recorded from the IOG and amygdala during the observation of faces, mosaics, and houses in upright and inverted orientations. Model comparisons assessing the experimental effects of upright faces versus upright houses and upright faces versus upright mosaics consistently indicated that the model having face-specific bidirectional modulatory effects between the IOG and amygdala was the most probable. The experimental effect between upright versus inverted faces also favored the model with bidirectional modulatory effects between the IOG and amygdala. The spectral profiles of modulatory effects revealed both same-frequency (e.g., gamma-gamma) and cross-frequency (e.g., theta-gamma) couplings. These results suggest that the IOG and amygdala communicate rapidly with each other using various types of oscillations for the efficient processing of faces. Hum Brain Mapp 38:4511-4524, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Tonsila do Cerebelo/fisiologia , Eletrocorticografia , Reconhecimento Facial/fisiologia , Lobo Occipital/fisiologia , Adulto , Tonsila do Cerebelo/fisiopatologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletrocorticografia/métodos , Epilepsias Parciais/fisiopatologia , Feminino , Humanos , Masculino , Modelos Neurológicos , Vias Neurais/fisiologia , Vias Neurais/fisiopatologia , Lobo Occipital/fisiopatologia , Estimulação Luminosa , Processamento de Sinais Assistido por Computador , Adulto Jovem
13.
Epilepsia ; 58(8): 1305-1315, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28622421

RESUMO

OBJECTIVE: Technology for localizing epileptogenic brain regions plays a central role in surgical planning. Recent improvements in acquisition and electrode technology have revealed that high-frequency oscillations (HFOs) within the 80-500 Hz frequency range provide the neurophysiologist with new information about the extent of the epileptogenic tissue in addition to ictal and interictal lower frequency events. Nevertheless, two decades after their discovery there remain questions about HFOs as biomarkers of epileptogenic brain and there use in clinical practice. METHODS: In this review, we provide practical, technical guidance for epileptologists and clinical researchers on recording, evaluation, and interpretation of ripples, fast ripples, and very high-frequency oscillations. RESULTS: We emphasize the importance of low noise recording to minimize artifacts. HFO analysis, either visual or with automatic detection methods, of high fidelity recordings can still be challenging because of various artifacts including muscle, movement, and filtering. Magnetoencephalography and intracranial electroencephalography (iEEG) recordings are subject to the same artifacts. SIGNIFICANCE: High-frequency oscillations are promising new biomarkers in epilepsy. This review provides interested researchers and clinicians with a review of current state of the art of recording and identification and potential challenges to clinical translation.


Assuntos
Ondas Encefálicas/fisiologia , Eletroencefalografia/métodos , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Guias como Assunto , Eletroencefalografia/normas , Humanos
14.
Ther Drug Monit ; 39(4): 446-449, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28703720

RESUMO

BACKGROUND: Perampanel is a new antiepileptic drug (AED) that acts as a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist and is mainly metabolized by cytochrome P450 (CYP) 3A4. This study evaluated the influence of concomitant AEDs on the serum concentration profile of perampanel. METHODS: A total of 215 serum samples obtained from 76 patients aged 12 years or older were analyzed for routine therapeutic drug monitoring, and the concentration-to-dose ratio (CD ratio) of perampanel was compared among patients on various AED regimens. RESULTS: In patients not taking concomitant enzyme-inducing AEDs, the mean CD ratio was 3963 ng·mL·mg·kg (range: 1793-13,299). By contrast, the mean CD ratio was lower in patients using enzyme-inducing AEDs [1760 (range: 892-3090), 2256 (range: 700-4703), and 1120 (range: 473-1853) ng·mL·mg·kg in patients taking phenytoin, phenobarbital, and carbamazepine, respectively], and carbamazepine had a significantly greater reduction in the CD ratio compared with phenytoin or phenobarbital (P < 0.001). Twenty-one patients responded with ≥50% reduction of seizure frequency from baseline, and their mean serum perampanel concentration was 450 ng/mL (range: 85-1500). CONCLUSIONS: There is a large interindividual variation in CD ratio of perampanel because its metabolism is highly susceptible to interactions with enzyme-inducing AEDs. Therapeutic drug monitoring could be clinically useful for determining the influence of AED CYP3A4 inducers on perampanel concentrations.


Assuntos
Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/sangue , Monitoramento de Medicamentos/métodos , Epilepsia/sangue , Piridonas/administração & dosagem , Piridonas/sangue , Adolescente , Adulto , Idoso , Criança , Quimioterapia Combinada , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Nitrilas , Estudos Retrospectivos , Adulto Jovem
15.
Ann Neurol ; 78(2): 295-302, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25974128

RESUMO

OBJECTIVE: We previously reported ictal very-high-frequency oscillations (VHFO) of 1,000 to 2,500Hz recorded by subdural macroelectrodes using a 10-kHz sampling rate. The purpose of this study was to clarify the clinical significance of ictal VHFO in neocortical epilepsy. METHODS: This study included 13 patients with neocortical epilepsy who underwent subdural electrode implantation and had at least 1 seizure recorded at a 10-kHz sampling rate and were followed for more than 2 years postoperatively. Extent of resection was determined considering the seizure onset zone (SOZ) and irritative zone, structural lesion, and functional areas. Areas showing VHFO and those with HFO were not taken into consideration. The presence or absence of VHFO (>1,000 Hz), HFO (200-1,000Hz) and SOZ, and completeness of resection of these areas were compared with postoperative seizure outcome. RESULTS: Seven patients had favorable (Engel class Ia) and 6 had unfavorable outcomes (other classes). VHFO was recorded in 6 of 7 patients with a favorable outcome. On the contrary, VHFO was recorded in only 1 of 6 patients with unfavorable outcome. The presence of VHFO was significantly associated with favorable outcome. VHFO was recorded on a limited number of electrodes, and VHFO-generating areas were resected completely, whereas HFO-generating areas and/or SOZ were not always resected completely in both favorable and unfavorable outcome groups. INTERPRETATION: The presence of ictal VHFO may be predictive of favorable outcome. Ictal VHFO may be a more specific marker than ictal HFO or SOZ for identifying the core of epileptogenic zone.


Assuntos
Ondas Encefálicas/fisiologia , Epilepsia do Lobo Frontal/fisiopatologia , Neocórtex/fisiopatologia , Adolescente , Adulto , Criança , Eletrodos Implantados , Eletroencefalografia , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/cirurgia , Epilepsia/fisiopatologia , Epilepsia/cirurgia , Epilepsia do Lobo Frontal/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neocórtex/cirurgia , Resultado do Tratamento , Adulto Jovem
16.
Epilepsia ; 57(2): e39-44, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26660199

RESUMO

In seizures with tonic posturing, differentiation of seizures originating in SSMA from seizures originating in cortices other than SSMA and spreading to SSMA has not been previously attempted. Twenty-two patients were studied with intractable focal epilepsy with tonic limb posturing as the most prominent semiology, who underwent resective surgery and obtained favorable postoperative seizure outcomes. These 22 patients were divided into an SSMA group (N = 12) and an extra-SSMA group (N = 10), according to the location of resection. Resection area in the extra-SSMA group was located in the dorsolateral frontal or prefrontal area in four patients, the frontal operculum (insula) in two, the parietal cortex in three, and the temporoparietal cortex in one patient. Video-recorded seizures were carefully reviewed. Tonic posturing characteristics and the presence or absence of accompanying symptoms were compared between groups. Incidence of preservation of consciousness was significantly higher in the SSMA group (p < 0.001). Patients in the SSMA group demonstrated a propensity for having unilateral or bilateral asymmetrical tonic limb posturing. In contrast, patients in the extra-SSMA group had a statistically significantly higher incidence of bilateral symmetrical tonic limb posturing (p < 0.05). These findings may be helpful in identifying seizure origin.


Assuntos
Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Motora Parcial/fisiopatologia , Lobo Parietal/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Córtex Sensório-Motor/fisiopatologia , Lobo Temporal/fisiopatologia , Adolescente , Adulto , Neoplasias Encefálicas/complicações , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/etiologia , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia , Epilepsias Parciais/etiologia , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/cirurgia , Epilepsia Motora Parcial/etiologia , Epilepsia Motora Parcial/cirurgia , Feminino , Lobo Frontal/fisiopatologia , Lobo Frontal/cirurgia , Gliose/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Humanos , Malformações Arteriovenosas Intracranianas/complicações , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical/complicações , Lobo Parietal/cirurgia , Córtex Pré-Frontal/cirurgia , Córtex Sensório-Motor/cirurgia , Lobo Temporal/cirurgia , Gravação em Vídeo , Adulto Jovem
17.
Epilepsy Behav ; 42: 14-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25499156

RESUMO

Absolute pitch (AP) ability is a rare musical phenomenon. In the literature, it has been suggested that the relative specialization for pitch processing is in the right temporal lobe in the non-AP population. Since the anatomic basis for absolute pitch is not fully understood and cases of temporal lobe epilepsy of AP possessors are extremely rare, applicability of resection as a treatment of epilepsy in this particular area should be evaluated with caution. In the present study, we examined an AP possessor who suffered from medically refractory temporal lobe epilepsy and underwent right selective amygdalohippocampectomy (SAH). The SAH procedure clearly avoided disturbing important structures for AP, inasmuch as postsurgically she preserved her AP ability and was seizure-free. She did well post-operatively in the test of pure sine wave tones with short reaction time, which could be identified as "true" absolute pitch.


Assuntos
Tonsila do Cerebelo/cirurgia , Epilepsia do Lobo Temporal/psicologia , Epilepsia do Lobo Temporal/cirurgia , Hipocampo/cirurgia , Música , Percepção da Altura Sonora , Cognição , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Procedimentos Neurocirúrgicos , Tempo de Reação , Resultado do Tratamento
19.
Epileptic Disord ; 26(3): 311-321, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38477907

RESUMO

OBJECTIVE: Enduring anterograde amnesia is caused by lesions in bilateral mesial temporal lobes. However, whether transient dysfunction of bilateral mesial temporal regions induces reversible amnesia has not been proven. We investigated this association in patients with epilepsy and analyzed the electroclinical correlation during pure amnestic seizures (PAS). PAS are defined as seizures with anterograde amnesia as the only ictal manifestation, accompanied by preserved responsiveness and other cognitive functions. METHODS: We retrospectively searched our intracranial EEG database to find PAS. Pure ictal amnesia was confirmed by immediate and comprehensive ictal examinations. RESULTS: Among 401 patients who underwent intracranial EEG recording, three patients with temporal lobe epilepsy (TLE) manifesting PAS were identified. The patients talked and behaved normally during seizure but did not remember the episodes afterwards. Ictal discharges were confined to bilateral mesial temporal regions, with no or mild involvement of surrounding structures. Spread of low-voltage fast activities to bilateral mesial temporal regions corresponded to onset of ictal anterograde amnesia. Two patients underwent unilateral mesial temporal resection and became seizure-free with improvement in cognitive functions. SIGNIFICANCE: PAS is a rare ictal semiology in TLE. Bilateral mesial temporal regions that play a critical role in memory encoding are presumably the symptomatogenic zones for PAS.


Assuntos
Epilepsia do Lobo Temporal , Convulsões , Humanos , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/cirurgia , Adulto , Masculino , Feminino , Estudos Retrospectivos , Convulsões/fisiopatologia , Amnésia Anterógrada/fisiopatologia , Amnésia Anterógrada/etiologia , Eletroencefalografia , Eletrocorticografia , Pessoa de Meia-Idade , Amnésia/fisiopatologia , Amnésia/etiologia , Lobo Temporal/fisiopatologia
20.
Sci Rep ; 14(1): 4269, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383855

RESUMO

The role of the amygdala in unconscious emotional processing remains a topic of debate. Past lesion studies have indicated that amygdala damage leads to impaired electrodermal activity in response to subliminally presented emotional stimuli. However, electrodermal activity can reflect both emotional and nonemotional processes. To provide behavioral evidence highlighting the critical role of the amygdala in unconscious emotional processing, we examined patients (n = 16) who had undergone unilateral resection of medial temporal lobe structures, including the amygdala. We utilized the subliminal affective priming paradigm in conjunction with unilateral visual presentation. Fearful or happy dynamic facial expressions were presented in unilateral visual fields for 30 ms, serving as negative or positive primes. Subsequently, neutral target faces were displayed, and participants were tasked with rating the valence of these targets. Positive primes, compared to negative ones, enhanced valence ratings of the target to a greater extent when they stimulated the intact hemisphere (i.e., were presented in the contralateral visual field of the intact hemisphere) than when they stimulated the resected hemisphere (i.e., were presented in the contralateral visual field of the resected hemisphere). These results suggest that the amygdala is causally involved in unconscious emotional processing.


Assuntos
Emoções , Medo , Humanos , Emoções/fisiologia , Medo/fisiologia , Lobo Temporal/cirurgia , Tonsila do Cerebelo/fisiologia , Campos Visuais , Inconsciência , Expressão Facial , Imageamento por Ressonância Magnética
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