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1.
Cereb Cortex ; 34(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38342686

RESUMO

Communication, especially conversation, is essential for human social life. Many previous studies have examined the neuroscientific underpinnings of conversation, i.e. language comprehension and speech production. However, conversation inherently involves two or more people, and unless two people actually interact with one another, the nature of the conversation cannot be truly revealed. Therefore, in this study, we used two magnetoencephalographs that were connected together, and simultaneously recorded brain activity while two people took turns speaking in a word association/alphabet completion task. We compared the amplitude modulation of the alpha- and beta-band rhythms within each of the 62 brain regions under semantic (word association; less predictable) and non-semantic (alphabet completion; more predictable) conditions. We found that the amplitudes of the rhythms were significantly different between conditions in a wide range of brain regions. Additionally, significant differences were observed in nearly the same group of brain regions after versus before each utterance, indicating that a wide range of brain areas is involved in predicting a conversation partner's next utterance. This result supports the idea that mentalizing, e.g. predicting another person's speech, plays an important role in conversation, and suggests that the neural network implicated in mentalizing extends over a wide range of brain regions.


Assuntos
Percepção da Fala , Fala , Humanos , Semântica , Comunicação , Encéfalo , Magnetoencefalografia
2.
Brain Dev ; 46(2): 114-117, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37914622

RESUMO

BACKGROUND: Lacosamide (LCM) has become commonly used for focal onset seizures due to its high tolerability and low drug interactions. Unlike patients on hemodialysis (HD), pharmacokinetic data and dosing recommendations for patients undergoing peritoneal dialysis (PD) are scant. CASE REPORT: A 2-year-old girl with end-stage kidney disease undergoing PD suffered prolonged focal onset seizures. The patient had congenital anomalies of the kidney and urinary tract associated with branchio-oto-renal syndrome due to an EYA1 gene mutation. She also had neurological sequelae from post-resuscitation encephalopathy at the age of one month. Antiseizure medication with few drug interactions, less impact on the neurodevelopmental state and possibility of intravenous administration was preferred. LCM met those criteria and was carefully administered. Although the patient had recurrent prolonged seizures during the titration periods, LCM could be continued without any apparent side effects. The blood levels of LCM increased linearly to the optimal level. We confirmed excretion of LCM in the PD fluid. Kidney transplantation was done three months after and her seizures were well controlled. CONCLUSIONS: LCM might be a promising option for patients undergoing PD. Due to the lower removal efficacy in PD compared with in HD, close attention should be paid to possible drug excess.


Assuntos
Epilepsias Parciais , Epilepsia Generalizada , Diálise Peritoneal , Insuficiência Renal , Humanos , Criança , Feminino , Pré-Escolar , Lacosamida/uso terapêutico , Anticonvulsivantes , Acetamidas/efeitos adversos , Resultado do Tratamento , Epilepsias Parciais/tratamento farmacológico , Convulsões/tratamento farmacológico , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/tratamento farmacológico
3.
Brain Dev ; 46(1): 49-56, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37657962

RESUMO

OBJECTIVE: Transcutaneous auricular vagus nerve stimulation (taVNS) was performed in two patients suffering structural focal epilepsy with preserved intellectual ability to show the feasibility of taVNS for specific patient groups. CASE PRESENTATIONS: Patient 1 was a 24-year-old woman with frontal lobe epilepsy who had weekly hyperkinetic seizures despite multiple anti-seizure medications. Patient 2 was a 27-year-old woman with parietal lobe epilepsy and focal cortical dysplasia in the vicinity of the lipoma in the corpus callosum. She experienced weekly focal-impaired awareness seizures even with anti-seizure medication. taVNS was applied to the left earlobe of both patients at 1.5 mA, 25 Hz, 250 µs pulse width, and 30 s stimulation with 30 s rest for 4 h per day. Over an 8-week baseline and 20 weeks of stimulation, the rate of reduction in seizure frequency was evaluated, along with quality-of-life using the Short-Form 36-Item Health survey. RESULTS: At baseline, we measured up to 11 and 12 focal seizures per week in Patient 1 and 2, respectively, with both patients achieving seizure freedom after 4 and 20 weeks taVNS, respectively. Patient 1 and 2 were observed for 18 and 14 months, respectively, including the clinical trial and follow-up observation period. Quality-of-life ratings increased in both patients, and no significant adverse events occurred during the study period. During the maintenance period after 20 weeks, seizures remained absent in Patient 1, and seizures remained reduced in Patient 2. CONCLUSION: Our results demonstrate that taVNS may be a promising tool for structural focal epilepsy with preserved cognitive function. A multicenter double-blind clinical trial is needed to confirm the role of taVNS as an anti-seizure tool.


Assuntos
Epilepsia do Lobo Frontal , Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Adulto , Feminino , Humanos , Adulto Jovem , Convulsões/terapia , Convulsões/etiologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Nervo Vago/fisiologia , Estimulação do Nervo Vago/métodos
4.
Brain Dev ; 46(3): 149-153, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38103972

RESUMO

BACKGROUND: Most long-term affected spinal muscular atrophy (SMA) type 1 patients have severe impairment of motor function and are dependent on mechanical ventilation with tracheostomy. The efficacy and safety of nusinersen in these patients have not been established. METHODS: We retrospectively evaluated the efficacy of intrathecal nusinersen treatment in patients with SMA type 1 who continued treatment for at least 12 months. There were three patients enrolled in our study (3, 4 and 16 years of age) who had severe impairment of gross motor function without head control or the ability to roll over. All three needed mechanical ventilation with tracheostomy and tube feeding. Motor function was assessed using the Children s Hospital of Philadelphia infant test of neuromuscular disorders (CHOP-INTEND) and the caregivers' evaluations. Concurrently, we examined nerve conduction longitudinally and compared compound motor action potential (CMAP) amplitudes. RESULTS: All patients continued nusinersen administration without significant adverse events for more than three years. While CHOP-INTEND scores did not remarkably increase, according to the caregivers, all three patients had improved finger or facial muscle movements that enabled them to make their intentions understood. Some CMAPs before treatment were not identified but became traces after nusinersen administration. CONCLUSIONS: The improvement in motor function that leads to smoother communication could be a basis for continuing nusinersen treatment. Currently available motor function scorings are not efficient for assessing therapeutic interventions in SMA patients with medical care complexity. Longitudinal nerve conduction studies could be an objective indicator.


Assuntos
Atrofia Muscular Espinal , Atrofias Musculares Espinais da Infância , Criança , Lactente , Humanos , Estudos Retrospectivos , Potenciais de Ação , Atrofias Musculares Espinais da Infância/tratamento farmacológico , Oligonucleotídeos/uso terapêutico , Atrofia Muscular Espinal/tratamento farmacológico
5.
Sci Rep ; 13(1): 19729, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957228

RESUMO

Small amounts of epidermal growth factor receptor (EGFR) T790M mutation (micro-T790M), which is detected using droplet digital PCR (ddPCR) but not conventional PCR, in formalin-fixed and paraffin-embedded (FFPE) samples have been investigated as a predictive factor for the efficacy of EGFR-tyrosine kinase inhibitors (TKIs). However, the predictive value of micro-T790M remains controversial, possibly owing to the failure to examine artificial T790M in FFPE specimens. Therefore, we examined the predictive value of micro-T790M in first-generation (1G), second-generation (2G), and third-generation (3G) EGFR-TKI efficacy using a new method to exclude FFPE-derived artificial mutations in our retrospective cohort. The primary objective was time to treatment failure (TTF) of 1G, 2G, and 3G EGFR-TKIs according to micro-T790M status. In total, 315 patients with EGFR-positive non-small cell lung cancer treated with 1G, 2G, and 3G EGFR-TKIs were included in this study. The proportion of patients positive for micro-T790M in the 1G, 2G, and 3G EGFR-TKI groups was 48.2%, 47.1%, and 47.6%, respectively. In the micro-T790M-positive group, the TTF was significantly longer in the 2G and 3G EGFR-TKI groups than in the 1G TKI group. No differences in the micro-T790M-negative group were observed. Micro-T790M status detected using ddPCR, eliminating false positives, may be a valuable predictor of EGFR-TKI efficacy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Estudos Retrospectivos , /uso terapêutico
6.
Front Pharmacol ; 14: 1273633, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849734

RESUMO

Introduction: Dravet syndrome (DS) is an intractable epilepsy syndrome concomitant with neurodevelopmental disorder that begins in infancy. DS is dominantly caused by mutations in the SCN1A gene, which encodes the α subunit of a voltage-gated Na channel. Pre-synaptic inhibitory dysfunction is regarded as the pathophysiological mechanism, but an effective strategy for ameliorating seizures and behavioral problems is still under development. Here, we evaluated the effects of KRM-II-81, a newly developed positive allosteric modulator for α 2/3 subunit containing GABAA receptors (α2/3-GABAAR) in a mice model of DS both in vivo and at the neuronal level. Methods: We used knock-in mice carrying a heterozygous, clinically relevant SCN1A mutation (background strain: C57BL/6 J) as a model of the DS (Scn1a WT/A1783V mice), knock-in mouse strain carrying a heterozygous, clinically relevant SCN1A mutation (A1783V). Seizure threshold and locomotor activity was evaluated by using the hyperthermia-induced seizure paradigm and open filed test, respectively. Anxiety-like behavior was assessed by avoidance of the center region in locomotor activity. We estimated a sedative effect by the total distance traveled in locomotor activity and grip strength. Inhibitory post synaptic currents (IPSCs) were recorded from a hippocampal CA1 pyramidal neuron in an acutely prepared brain slice. Results: KRM-II-81 significantly increased the seizure threshold of Scn1a WT/A1783V mice in a dose-dependent manner. A low dose of KRM-II-81 specifically improved anxiety-like behavior of Scn1a WT/A1783V mice. A sedative effect was induced by relatively high dose of KRM-II-81 in Scn1a WT/A1783V mice, the dose of which was not sedative for WT mice. KRM-II-81 potentiated IPSCs by increasing its decay time kinetics. This effect was more prominent in Scn1a WT/A1783V mice. Discussion: Higher activation of α2/3-GABAAR by KRM-II-81 suggests a compensatory modification of post synaptic inhibitory function against presynaptic inhibitory dysfunction in Scn1a WT/A1783V. The increased sensitivity for KRM-II-81 may be relevant to the distinct dose-dependent effect in each paradigm of Scn1a WT/A1783V mice. Conclusion: Selective activation for α2/3-GABAAR by KRM-II-81 could be potential therapeutic strategy for treating seizures and behavioral problems in DS.

7.
J Cancer Res Clin Oncol ; 149(13): 12435-12442, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37439826

RESUMO

PURPOSE: Vascular endothelial growth factor (VEGF) inhibitors are widely used in chemotherapy for non-small lung cancer (NSCLC). The purpose of the current study was to examine the impact of background cardiovascular risk factors on VEGF inhibitor-related adverse vascular events (VEGF-related AVEs) in patients with NSCLC who also had comorbidities. METHODS: We conducted a retrospective study of 118 NSCLC patients treated with bevacizumab or ramucirumab from April 2010 to December 2022. We compared baseline cardiovascular risk factors with VEGF-related AVEs. RESULTS: VEGF-related AVEs and discontinuation due to VEGF-related AVEs were reported in 54 patients and 21 patients, respectively. VEGF-related AVEs were significantly more common with male sex, smoking history, history of hypertension, dyslipidemia, diabetes mellitus, or cardiovascular disease. Discontinuation due to VEGF-related AVEs was significantly more common in patients with history of hypertension or chronic kidney disease. VEGF-related AVEs were significantly more common in patients with ≥ 3 cardiovascular risk factors than patients with < 3. Discontinuation due to VEGF-related AVEs was significantly more common in patients with ≥ 4 cardiovascular risk factors than patients with < 4. Multivariate analysis demonstrated that male sex, hypertension, and ≥ 6 cycles of VEGF inhibitors were each associated with VEGF-related AVEs and hypertension was associated with discontinuation due to VEGF-related AVEs. CONCLUSION: Our study demonstrated that history of hypertension was independently associated with increased risk of both VEGF-related AVEs and discontinuation due to VEGF-related AVEs. In conclusion, we need to be aware of VEGF-related AVEs when using VEGF inhibitors for patients with ≥ 3 cardiovascular risk factors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Doenças Cardiovasculares , Hipertensão , Neoplasias Pulmonares , Humanos , Masculino , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/induzido quimicamente , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/efeitos adversos , Fatores de Risco de Doenças Cardíacas , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Hipertensão/tratamento farmacológico
9.
Sci Rep ; 13(1): 5685, 2023 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-37069177

RESUMO

Angelman syndrome is a neurodevelopmental disorder caused by loss of function of the maternally expressed UBE3A gene. Treatments for the main manifestations, including cognitive dysfunction or epilepsy, are still under development. Recently, the Cl- importer Na+-K+-Cl- cotransporter 1 (NKCC1) and the Cl- exporter K+-Cl- cotransporter 2 (KCC2) have garnered attention as therapeutic targets for many neurological disorders. Dysregulation of neuronal intracellular Cl- concentration ([Cl-]i) is generally regarded as one of the mechanisms underlying neuronal dysfunction caused by imbalanced expression of these cation-chloride cotransporters (CCCs). Here, we analyzed the regulation of [Cl-]i and the effects of bumetanide, an NKCC1 inhibitor, in Angelman syndrome models (Ube3am-/p+ mice). We observed increased NKCC1 expression and decreased KCC2 expression in the hippocampi of Ube3am-/p+ mice. The average [Cl-]i of CA1 pyramidal neurons was not significantly different but demonstrated greater variance in Ube3am-/p+ mice. Tonic GABAA receptor-mediated Cl- conductance was reduced, which may have contributed to maintaining the normal average [Cl-]i. Bumetanide administration restores cognitive dysfunction in Ube3am-/p+ mice. Seizure susceptibility was also reduced regardless of the genotype. These results suggest that an imbalanced expression of CCCs is involved in the pathophysiological mechanism of Ube3am-/p+ mice, although the average [Cl-]i is not altered. The blockage of NKCC1 may be a potential therapeutic strategy for patients with Angelman syndrome.


Assuntos
Síndrome de Angelman , Epilepsia , Simportadores , Camundongos , Animais , Simportadores de Cloreto de Sódio-Potássio/genética , Simportadores de Cloreto de Sódio-Potássio/metabolismo , Bumetanida/farmacologia , Síndrome de Angelman/tratamento farmacológico , Síndrome de Angelman/genética , Cloretos/metabolismo , Simportadores/genética , Simportadores/metabolismo , Epilepsia/tratamento farmacológico , Epilepsia/genética , Receptores de GABA-A
10.
Acta Neuropathol Commun ; 11(1): 33, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36864519

RESUMO

Focal cortical dysplasia is the most common malformation during cortical development, sometimes excised by epilepsy surgery and often caused by somatic variants of the mTOR pathway genes. In this study, we performed a genetic analysis of epileptogenic brain malformed lesions from 64 patients with focal cortical dysplasia, hemimegalencephy, brain tumors, or hippocampal sclerosis. Targeted sequencing, whole-exome sequencing, and single nucleotide polymorphism microarray detected four germline and 35 somatic variants, comprising three copy number variants and 36 single nucleotide variants and indels in 37 patients. One of the somatic variants in focal cortical dysplasia type IIB was an in-frame deletion in MTOR, in which only gain-of-function missense variants have been reported. In focal cortical dysplasia type I, somatic variants of MAP2K1 and PTPN11 involved in the RAS/MAPK pathway were detected. The in-frame deletions of MTOR and MAP2K1 in this study resulted in the activation of the mTOR pathway in transiently transfected cells. In addition, the PTPN11 missense variant tended to elongate activation of the mTOR or RAS/MAPK pathway, depending on culture conditions. We demonstrate that epileptogenic brain malformed lesions except for focal cortical dysplasia type II arose from somatic variants of diverse genes but were eventually linked to the mTOR pathway.


Assuntos
Neoplasias Encefálicas , Displasia Cortical Focal , Malformações do Desenvolvimento Cortical do Grupo I , Malformações do Sistema Nervoso , Humanos , Malformações do Desenvolvimento Cortical do Grupo I/genética , Encéfalo
11.
Brain Dev ; 45(6): 343-347, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36870920

RESUMO

OBJECTIVE: The efficacy of the mechanistic target of rapamycin inhibitor, sirolimus, was recently reported for patients more than 6 years of age by Kato et al. We evaluated the efficacy and safety of sirolimus in a 2-year-old patient with recurrent focal seizures with impaired consciousness after focal cortical dysplasia (FCD) type IIa resection. METHODS: The patient was a 2-year-old girl who had recurrent seizures after undergoing FCD resection at 4 months of age. The initial dose of sirolimus was 0.5 mg/day and was gradually increased using the trough blood concentration before oral administration as an index, and evaluation was performed at 92 weeks. RESULTS: The trough blood level of sirolimus was increased to 6.1 ng/mL and maintenance therapy was started at 40 weeks. Focal seizures with impairment of consciousness with tonic extension of the limbs decreased. No critically serious adverse events occurred. CONCLUSION: Sirolimus was effective against epileptic seizures from FCD type II even for a child under 5 years of age. There were no critically serious adverse events and administration could be continued.


Assuntos
Epilepsia Generalizada , Epilepsia , Displasia Cortical Focal , Malformações do Desenvolvimento Cortical , Criança , Feminino , Humanos , Pré-Escolar , Sirolimo/uso terapêutico , Sirolimo/farmacologia , Convulsões/tratamento farmacológico , Convulsões/etiologia , Convulsões/cirurgia , Epilepsia/tratamento farmacológico , Epilepsia/etiologia , Epilepsia/cirurgia , Malformações do Desenvolvimento Cortical/complicações , Malformações do Desenvolvimento Cortical/tratamento farmacológico , Imageamento por Ressonância Magnética
12.
Asia Ocean J Nucl Med Biol ; 11(1): 93-96, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36619191

RESUMO

A 2-year-old girl started to wobble without any specific triggers, so the patient was admitted to our hospital's pediatric department. The entire cerebellum showed severe atrophy on MRI and much lower uptake than that in the cerebral cortex on perfusion SPECT. The diagnosis of opsoclonus-myoclonus syndrome (OMS) was suspected. MRI visualized a small mass behind the inferior vena cava. Although its uptake on I-123 MIBG scintigraphy was inconclusive, the mass was surgically removed, and the diagnosis of neuroblastoma was pathologically confirmed. OMS is one of the paraneoplastic neurological syndromes with cerebellar ataxia, myoclonus of the trunk and extremities, and opsoclonus as its main symptoms. Approximately 50% of children cases with OMS are associated with neuroblastoma. The prognosis for neuroblastoma itself with OMS is relatively good, but the neurological prognosis is very poor. If there is decreased blood flow in the cerebellum of an infant, it may be necessary to search for neuroblastoma.

13.
Microbiol Resour Announc ; 12(1): e0113922, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36537808

RESUMO

Arthrospira platensis is a filamentous cyanobacterium that is cultivated and used worldwide as a source of food and food additives. Here, we report the complete genome sequence (6,818,916 bp) of A. platensis NIES-39, one of the model strains of A. platensis, providing an improved reference genome sequence for this strain.

14.
Front Psychol ; 13: 904995, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059767

RESUMO

Background: Difficulty in distinguishing between self-generated actions and those generated by others is a core feature of schizophrenia. This is thought to be underpinned by the failure of corollary discharge. However, few studies have investigated these events using somatosensory evoked potentials (SEPs) and somatosensory evoked magnetic fields (SEFs). Methods: The study included 15 right-handed patients with schizophrenia and 16 healthy controls. SEP and SEF were elicited by electrical stimuli to the left median nerve at intervals of 1-3 s. In the external condition, stimuli were externally induced by a machine. In the self-condition, stimuli were induced by tapping the participants' own right index finger. Peak amplitude at C4' in SEP and root mean square in 10 channels on the right primary somatosensory area in SEF were analyzed. Results: Although there was a significant main effect of condition at N20m, and a significant main effect of condition and group at P30m, no significant interactions of condition and group were found in either N20m or P30m. The post-hoc Wilcoxon signed-rank test revealed that the peak value of P30m in the external condition was significantly higher than that in the self-condition in the healthy control group only. In addition, there was a significant positive correlation between the peak value of P30m in the self-condition and a positive symptom score. Conclusion: In the current study, we did not find abnormalities of corollary discharge in primary sensory areas in patients with schizophrenia. Further investigations with more cases may reveal the possibility of corollary discharge disturbance in the primary sensory cortex.

15.
Front Neurosci ; 16: 790057, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35983225

RESUMO

Auditory communication is an essential form of human social interaction. However, the intra-brain cortical-oscillatory drivers of auditory communication exchange remain relatively unexplored. We used improvisational music performance to simulate and capture the creativity and turn-taking dynamics of natural auditory communication. Using magnetoencephalography (MEG) hyperscanning in musicians, we targeted brain activity during periods of music communication imagery, and separately analyzed theta (5-7 Hz), alpha (8-13 Hz), and beta (15-29 Hz) source-level activity using a within-subjects, two-factor approach which considered the assigned social role of the subject (leader or follower) and whether communication responses were improvisational (yes or no). Theta activity related to improvisational communication and social role significantly interacted in the left isthmus cingulate cortex. Social role was furthermore differentiated by pronounced occipital alpha and beta amplitude increases suggestive of working memory retention engagement in Followers but not Leaders. The results offer compelling evidence for both musical and social neuroscience that the cognitive strategies, and correspondingly the memory and attention-associated oscillatory brain activities of interlocutors during communication differs according to their social role/hierarchy, thereby indicating that social role/hierarchy needs to be controlled for in social neuroscience research.

16.
PLoS One ; 17(6): e0270090, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35737703

RESUMO

Communication is one of the most important abilities in human society, which makes clarification of brain functions that underlie communication of great importance to cognitive neuroscience. To investigate the rapidly changing cortical-level brain activity underlying communication, a hyperscanning system with both high temporal and spatial resolution is extremely desirable. The modality of magnetoencephalography (MEG) would be ideal, but MEG hyperscanning systems suitable for communication studies remain rare. Here, we report the establishment of an MEG hyperscanning system that is optimized for natural, real-time, face-to-face communication between two adults in sitting positions. Two MEG systems, which are installed 500m away from each other, were directly connected with fiber optic cables. The number of intermediate devices was minimized, enabling transmission of trigger and auditory signals with almost no delay (1.95-3.90 µs and 3 ms, respectively). Additionally, video signals were transmitted at the lowest latency ever reported (60-100 ms). We furthermore verified the function of an auditory delay line to synchronize the audio with the video signals. This system is thus optimized for natural face-to-face communication, and additionally, music-based communication which requires higher temporal accuracy is also possible via audio-only transmission. Owing to the high temporal and spatial resolution of MEG, our system offers a unique advantage over existing hyperscanning modalities of EEG, fNIRS, or fMRI. It provides novel neuroscientific methodology to investigate communication and other forms of social interaction, and could potentially aid in the development of novel medications or interventions for communication disorders.


Assuntos
Encéfalo , Comunicação , Magnetoencefalografia , Adulto , Encéfalo/fisiologia , Humanos , Magnetoencefalografia/métodos
17.
Epilepsia Open ; 2022 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-35633311

RESUMO

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study. METHODS: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes. RESULTS: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10-3 % per case, p<0.001) and EEG monitoring (-3.81*10-3 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001). SIGNIFICANCE: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care.

18.
Brain Dev ; 44(6): 380-385, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35241306

RESUMO

OBJECTIVE: Childhood epilepsy with centrotemporal spikes (CECTS) is known as age-limited focal epilepsy syndrome in childhood. Lacosamide is a third-generation antiepileptic drug. This study aimed to evaluate the efficacy of lacosamide monotherapy for the treatment of CECTS. METHODS: We enrolled 18 patients (6 girls and 12 boys) who met the following criteria: 1) the age of onset of the seizures was between 3 and 13 years of age; 2) showing at least hemifacial and/or oropharyngeal seizures; 3) interictal discharges in central and/or middle temporal electrodes; 4) no intellectual disability; 5) treatment duration of lacosamide monotherapy over 6 months. We retrospectively collected and analyzed clinical data and treatment information. We evaluated the seizure occurrences during 0-3, 4-6, and 7-12 months from the treatment initiation and the last 6 months of the follow-up. We also evaluated the outcomes as seizure-free if the patients developed no seizures both over 6 months and 3 times of pretreatment mean seizure interval at the last follow-up. RESULTS: Of the patients, 39%, 67% and 72% were seizure-free during 0-3, 4-6, and 7-12 months from treatment initiation, respectively. Finally, 83% of the patients achieved seizure freedom. Seizure freedom was achieved in 72% during the first 4 months of treatment. All patients continued lacosamide monotherapy during the study, although four patients showed transient fatigue or somnolence. CONCLUSIONS: Lacosamide showed good efficacy for controlling seizures with fewer adverse effects, and therefore may be a good candidate as a first-line medication for the treatment of new-onset CECTS.


Assuntos
Anticonvulsivantes , Epilepsias Parciais , Epilepsias Parciais/tratamento farmacológico , Feminino , Humanos , Lactente , Lacosamida/uso terapêutico , Masculino , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Resultado do Tratamento
19.
Epileptic Disord ; 24(1): 82-94, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35118943

RESUMO

OBJECTIVE: To examine the current medical and psychosocial status of patients with epilepsy, aiming to facilitate appropriate application of the Intractable/Rare Diseases Act of Japan. METHODS: By analysing the cross-sectional data of patients registered in the tertiary hospital-based Epilepsy Syndrome Registry of Japan, we investigated the proportion of patients who met the severity criteria as defined by the Act (seizure frequency of at least once a month, or presence of intellectual/neurological/psychiatric symptoms, or both) and whether there are candidate syndrome/diseases to be added to the existing list in the Act. RESULTS: In total, 2,209 patients were registered. After excluding self-limited/idiopathic epilepsies, 1,851 of 2,110 patients (87.7%) met the severity criteria. The patients were classified into eight main epilepsy syndromes (594 patients), 20 groups based on aetiology (1,078 patients), and three groups without known aetiology (427 patients). Most of the groups classified by syndrome or aetiology had high proportions of patients satisfying the severity criteria (>90%), but some groups had relatively low proportions (<80%) resulting from favourable outcome of surgical therapy. Several small groups with known syndrome/aetiology await detailed analysis based on a sufficiently large enough number of patients registered, some of whom may potentially be added to the list of the Act. SIGNIFICANCE: The registry provides data to examine the usefulness of the severity criteria and list of diseases that are operationally defined by the Act. Most epilepsy patients with various syndromes/diseases and aetiology groups are covered by the Act but some are not, and the list of designated syndromes/diseases should be complemented by further amendments, as suggested by future research.


Assuntos
Epilepsia , Convulsões , Comorbidade , Estudos Transversais , Epilepsia/epidemiologia , Síndromes Epilépticas , Inquéritos Epidemiológicos , Humanos , Japão/epidemiologia , Sistema de Registros , Convulsões/epidemiologia , Centros de Atenção Terciária
20.
Ann Clin Transl Neurol ; 9(2): 181-192, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35040598

RESUMO

OBJECTIVE: To determine whether sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, reduces epileptic seizures associated with focal cortical dysplasia (FCD) type II. METHODS: Sixteen patients (aged 6-57 years) with FCD type II received sirolimus at an initial dose of 1 or 2 mg/day based on body weight (FCDS-01). In 15 patients, the dose was adjusted to achieve target trough ranges of 5-15 ng/mL, followed by a 12-week maintenance therapy period. The primary endpoint was a lower focal seizure frequency during the maintenance therapy period. Further, we also conducted a prospective cohort study (RES-FCD) in which 60 patients with FCD type II were included as an external control group. RESULTS: The focal seizure frequency reduced by 25% in all patients during the maintenance therapy period and by a median value of 17%, 28%, and 23% during the 1-4-, 5-8-, and 9-12-week periods. The response rate was 33%. The focal seizure frequency in the external control group reduced by 0.5%. However, the background characteristics of external and sirolimus-treated groups differed. Adverse events were consistent with those of mTOR inhibitors reported previously. The blood KL-6 level was elevated over time. INTERPRETATION: The reduction of focal seizures did not meet the predetermined level of statistical significance. The safety profile of the drug was tolerable. The potential for a reduction of focal seizures over time merit further investigations.


Assuntos
Epilepsia/complicações , Malformações do Desenvolvimento Cortical do Grupo I/complicações , Inibidores de Proteínas Quinases/farmacologia , Convulsões/tratamento farmacológico , Convulsões/etiologia , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adolescente , Adulto , Criança , Humanos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Adulto Jovem
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