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1.
Zhonghua Er Ke Za Zhi ; 59(9): 767-771, 2021 Sep 02.
Artigo em Chinês | MEDLINE | ID: mdl-34645217

RESUMO

Objective: To summarize the genotypes and clinical features of neonatal-onset genetic epilepsy. Methods: Patients (114 cases) with identified gene variants were collected from May 2013 to May 2019 in Peking University First Hospital, retrospectively. The genotype, clinical, electroencephalographic and neuroimaging characteristics were analyzed. Results: A total of 141 neonatal-onset epilepsy patients with identified gene variants were enrolled, including 76 males and 65 females and involving 33 epilepsy genes. Top five genes were KCNQ2 (56 cases), SCN2A (25 cases), STXBP1 (9 cases), CDKL5 (8 cases) and KCNT1 (6 cases), accounting for 73.8% (104/141). The age of seizure onset was 3(1-28) days of age, 71.6% (101/141) were within 1 week of age. The age of genetic diagnosis was 4 months (1 month to 13 years) of age. A total of 130 patients presented focal seizures; 47 patients presented epileptic spasms. Other seizure types included generalized tonic-clonic seizures, clonic seizures, myoclonic seizures, tonic seizures and absence seizures. Fifty-eight patients experienced multiple seizure types. The results of video-electroencephlogram (VEEG) were abnormal in 127 patients and in 62 patients clinical seizures were captured. Global developmental delay was presented in 122 patients. Epilepsy syndromes were diagnosed in 59 patients. Thirteen patients were diagnosed as Ohtahara syndrome (OS), 9 as epilepsy of infancy with migrating focal seizures (EIMFS), 17 as West syndrome (WS), 4 as OS developed to WS, 9 as benign neonatal epilepsy (BNE), 2 as benign familiar neonatal-infantile epilepsy (BFNIE), 2 as benign infantile epilepsy (BIE) and 3 as benign familial infantile epilepsy (BFIE). Sixty-seven patients were diagnosed as unclassified early infantile epileptic encephalopathy (EIEE), 13 patients could not be diagnosed as any epilepsy syndrome, and 2 patients were diagnosed as pyridoxine-dependent epilepsy. Forty-six patients had abnormal neuroimaging including cortical atrophy, corpus callosum dysplasia and cerebellar atrophy, involving 19 genes. Conclusions: Neonatal-onset epilepsy is related to many different genes. Seizure onset age of most patients is within one week after birth. Focal seizures and epileptic spasms are more common. Some patients show abnormal neuroimaging.


Assuntos
Epilepsia , Espasmos Infantis , Idoso , Eletroencefalografia , Epilepsia/genética , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas do Tecido Nervoso , Canais de Potássio Ativados por Sódio , Estudos Retrospectivos , Convulsões , Espasmos Infantis/genética
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(10): 981-984, 2021 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-34625937

RESUMO

OBJECTIVE: To explore the genetic basis for a girl with febrile convulsion as the main manifestation. METHODS: The child was subjected to whole exome sequencing (WES) and copy number variation sequencing(CNV-seq). Fluorescence quantitative PCR was carried out to validate the microdeletion in her family. RESULTS: The 7-year-old girl was diagnosed with febrile convulsion (complex type) for having fever for 3 days, mild cough and low thermal convulsion once. Her father, mother and aunt also had a history of febrile convulsion. A heterozygous deletion with a size of approximately 1.5 Mb was detected in the 16p13.11 region by WES and CNV-seq. The deletion has derived from her father and was confirmed by fluorescence quantitative PCR. CONCLUSION: 16p13.11 microdeletion syndrome has significant clinical heterogeneity. Different from those with epilepsy, mental retardation, autism, multiple malformations, carriers of 16p13.11 deletion may only manifest with febrile convulsion. Deletion of certain gene(s) from the region may be related to febrile convulsion and underlay the symptom of this child.


Assuntos
Epilepsia , Convulsões Febris , Criança , Variações do Número de Cópias de DNA , Feminino , Humanos , Convulsões/genética , Convulsões Febris/genética , Sequenciamento Completo do Exoma
3.
Georgian Med News ; (318): 67-71, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628381

RESUMO

To monitor the functional state of the brain of children with epilepsy, we developed an original modification of the method of study ingserialmotorreactions (tapping) using touch screen devices, which all owsdistant multiple examination and to obtain aninformativeset of performance indicators and their dynamics. Clinical and anamnestic; clinical and neurological research methods were also used. Examination materials of 21 children with epilepsy (13 boys, 8 girls), aged from 6 to 18 years were analyzed. The presence of significant differences in serial motor responses between patients with recurrent seizures and children with no seizures in all age groups allows us to consider the proposed option of tapping as a reliable source of additional information about the functional state of the brain of children with epilepsy, for data processing of which can be used «Big Data¼ methods.


Assuntos
Epilepsia , Encéfalo , Criança , Epilepsia/diagnóstico , Feminino , Humanos , Masculino , Convulsões
4.
Transl Psychiatry ; 11(1): 537, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663783

RESUMO

The neuropilin receptors and their secreted semaphorin ligands play key roles in brain circuit development by regulating numerous crucial neuronal processes, including the maturation of synapses and migration of GABAergic interneurons. Consistent with its developmental roles, the neuropilin 2 (Nrp2) locus contains polymorphisms in patients with autism spectrum disorder (ASD). Nrp2-deficient mice show autism-like behavioral deficits and propensity to develop seizures. In order to determine the pathophysiology in Nrp2 deficiency, we examined the hippocampal numbers of interneuron subtypes and inhibitory regulation of hippocampal CA1 pyramidal neurons in mice lacking one or both copies of Nrp2. Immunostaining for interneuron subtypes revealed that Nrp2-/- mice have a reduced number of parvalbumin, somatostatin, and neuropeptide Y cells, mainly in CA1. Whole-cell recordings identified reduced firing and hyperpolarized shift in resting membrane potential in CA1 pyramidal neurons from Nrp2+/- and Nrp2-/- mice compared to age-matched wild-type controls indicating decrease in intrinsic excitability. Simultaneously, the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) are reduced in Nrp2-deficient mice. A convulsive dose of kainic acid evoked electrographic and behavioral seizures with significantly shorter latency, longer duration, and higher severity in Nrp2-/- compared to Nrp2+/+ animals. Finally, Nrp2+/- and Nrp2-/- but not Nrp2+/+, mice have impaired cognitive flexibility demonstrated by reward-based reversal learning, a task associated with hippocampal circuit function. Together these data demonstrate a broad reduction in interneuron subtypes and compromised inhibition in CA1 of Nrp2-/- mice, which could contribute to the heightened seizure susceptibility and behavioral deficits consistent with an ASD/epilepsy phenotype.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Epilepsia , Animais , Transtorno do Espectro Autista/genética , Comorbidade , Hipocampo , Humanos , Interneurônios , Camundongos , Neuropilina-2/genética
5.
No Shinkei Geka ; 49(5): 986-993, 2021 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-34615758

RESUMO

Post-traumatic seizures and epilepsy are major complication of traumatic brain injury. Early and late and seizures have different implications for prognosis and management. Early seizures, which occur within one week of the trauma, are acute symptomatic events. On the other hand, presence of late seizures indicate epilepsy. Patients with early seizures are treated with anti-epileptic drugs(AEDs)within weeks to avoid status epilepticus, which may increase cerebral blood flow and increase intracranial pressure. Because prophylactic administration of AEDs reduces the incidence of early seizures but not late seizures, it is recommended to limit it to one week. A long-term AED administration is recommended for patients with late seizures, because late seizures represent epilepsy. AED should be selected according to the considerations of age and comorbidity that apply to other individuals with new-onset epilepsy. Since epileptic seizures often cause serious accidents, such as traffic accidents, drowning, burns, falls and others, lifestyle guidance for patients and their families is important.


Assuntos
Epilepsia , Convulsões , Humanos , Convulsões/tratamento farmacológico , Convulsões/etiologia
7.
Zhonghua Er Ke Za Zhi ; 59(10): 859-864, 2021 Oct 02.
Artigo em Chinês | MEDLINE | ID: mdl-34587683

RESUMO

Objective: To summarize the clinical characteristics and the features of electroencephalograph (EEG) of children with DEPDC5 gene variants related epilepsy. Methods: The clinical data, gene variation, EEG and head magnetic resonance image (MRI) of 20 epileptic children with DEPDC5 gene variants admitted to Department of Pediatrics, Peking University First Hospital from May 2017 to November 2020 were retrospectively analyzed. Results: Twenty patients with heterozygous DEPDC5 gene variants were enrolled, 8 of 20 patients were nonsense variants, 6 were missense variants, 3 were frame-shift variants, 2 were splicing variants, and 1 was large fragment deletion. Sixteen cases had hereditary variation and 4 had de novo variation. Fifteen of variations were novel. Nine were male, while 11 were female. Their latest follow-up age ranged from 10 months to 13 years and one month.The epilepsy onset age ranged from 3 hours to 11 years and 3 months, the median age was 10.5 months. Twelve (60%) patients had developmental delay. Nineteen patients had focal seizures, 7 had epileptic spasms, 1 had multiple seizure types including tonic, atypical absence, dystonic and myoclonic seizures. Epileptic form discharges were observed in 18 patients during the interictal phase, and 11 were focal discharges, 7 were multifocal discharges. Ten (50%) patients had abnormal brain MRI, including focal cortical dysplasia in 5 patients, undefined malformation of cortical development in 4 patients, hemimegalencephaly in 1 patient. Four patients were diagnosed as West syndrome and one patient was diagnosed as Lennox-Gastaut syndrome. Fourteen (70%) patients were diagnosed as drug-resistant epilepsy. Four patients became seizure-free by treatment with anti-epileptic drugs. Three children were treated with surgery, and 2 of them became seizure-free, 1 had more than 75% reduction in seizures. Conclusions: DEPDC5 gene variant epilepsy is inherited with incomplete penetrance and focal seizure is the major seizure type. However, epileptic spasms, generalized seizures can also be observed. Half of the patients brain malformations. Most of the patients are drug-resistant epilepsy. Patients with clear epileptogenic zones can be treated with surgery. Treatment-resistant patients are more likely to be complicated with developmental delay.


Assuntos
Epilepsia , Espasmos Infantis , Criança , Eletroencefalografia , Epilepsia/genética , Feminino , Proteínas Ativadoras de GTPase , Genótipo , Humanos , Lactente , Masculino , Fenótipo , Estudos Retrospectivos
9.
J Vet Intern Med ; 35(5): 2350-2358, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34472639

RESUMO

BACKGROUND: Implantable vagus nerve stimulation (VNS) devices can be used to treat epilepsy in dogs. Adverse effects and short-term complications associated with delivering suggested therapeutic electrical stimulation (>1.5 mA) are not well-described. OBJECTIVES: To compare complications and adverse effects observed with standard and rapid protocols of current increase. ANIMALS: Sixteen client-owned dogs with idiopathic epilepsy. METHODS: Nonrandomized, nonblinded prospective cohort study. Surgical complications, stimulation-related adverse effects, modifications to stimulator settings, number of hospital visits, and time to reach 1.5 mA stimulation current without intolerable adverse effects were described in dogs receiving current increases every 1 to 3 weeks (slow ramping) and dogs receiving current increases every 8 to 12 hours (fast ramping). RESULTS: Self-resolving surgery site seromas formed in 6 dogs. No other surgical complications were observed. Fourteen dogs reached 1.5 mA. Coughing (11/14 dogs; 5 slow, 6 fast ramping) was the most common adverse effect. Intolerable coughing that limited current increases despite changing other stimulus parameters occurred in 6/7 of the fast-ramping group and in none of the slow-ramping group. Median time to 1.5 mA was 72 days (range, 28-98) in the slow-ramping group and 77 days (range, 3-152) in the fast-ramping group. Median number of clinic visits was 6 for the slow-ramping group (range, 5-6) and 3 for the fast-ramping group (range, 1-7). CONCLUSIONS AND CLINICAL IMPORTANCE: Coughing is a common adverse effect of VNS in dogs and generally is well tolerated, particularly if current is increased slowly and other stimulation parameters are adapted for effect.


Assuntos
Doenças do Cão , Epilepsia , Estimulação do Nervo Vago , Animais , Doenças do Cão/terapia , Cães , Epilepsia/terapia , Epilepsia/veterinária , Estudos Prospectivos , Próteses e Implantes , Nervo Vago , Estimulação do Nervo Vago/efeitos adversos , Estimulação do Nervo Vago/veterinária
11.
Neurol India ; 69(4): 1014-1017, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34507432

RESUMO

Phenytoin is a commonly used antiepileptic drug for various types of seizure disorders except for absent seizures. Long-term dose-dependent neurological side effects of phenytoin therapy include cerebellar atrophy, cerebral atrophy, and brain stem atrophy. Skull hyperostosis, gum hypertrophy, and megaloblastic anemia are other known effects of long-term therapy. We present four cases depicting clinical and neuroimaging findings of phenytoin-induced toxicity.


Assuntos
Epilepsia , Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Humanos , Fenitoína/efeitos adversos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 786-790, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511166

RESUMO

OBJECTIVES: To study the clinical effect of mouse nerve growth factor (mNGF) in the treatment of children with global developmental delay (GDD). METHODS: A prospective clinical trial was conducted in 60 children with GDD who were treated in the First Affiliated Hospital of Anhui Medical University between July 2016 and July 2017. These children were randomly divided into two groups: conventional rehabilitation treatment and mNGF treatment group (n=30 each). The children in the conventional rehabilitation treatment group were given neurodevelopmental therapy, and those in the mNGF treatment group were given mNGF treatment in addition to the treatment in the control group. The evaluation results of the Gesell Developmental Scale were compared between the two groups before and after treatment. RESULTS: Before treatment and after 1.5 months of treatment, there was no significant difference in the developmental quotient (DQ) of each functional area of the Gesell Developmental Scale between the mNGF treatment and conventional rehabilitation treatment groups (P>0.05). After 3 months of treatment, the mNGF treatment group had significantly higher DQs of gross motor, fine motor, and personal-social interaction than the conventional rehabilitation treatment group (P˂0.05). The incidence rate of transient injection site pain after injection of mNGF was 7% (2/30), and there was no epilepsy or other serious adverse reactions. CONCLUSIONS: In children with GDD, routine rehabilitation training combined with mNGF therapy can significantly improve their cognitive, motor, and social abilities.


Assuntos
Epilepsia , Animais , Camundongos , Estudos Prospectivos , Habilidades Sociais
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 791-796, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511167

RESUMO

OBJECTIVES: To study the difference in cognitive impairment between the children with benign childhood epilepsy with centrotemporal spikes (BECT) and attention deficit hyperactivity disorder (ADHD) and those with BECT or ADHD alone. METHODS: A prospective study was performed on 80 children with BECT and ADHD, 91 children with BECT, and 70 children with ADHD , who were diagnosed with the diseases for the first time. Seventy children of the same age who underwent physical examination were enrolled as the healthy control group. Event-related potential P300, Wechsler Intelligence Scale for Children, and integrated visual and auditory continuous performance test were used to measure and compare each index between groups. RESULTS: Compared with the healthy control group, the BECT+ADHD group, the BECT group, and the ADHD group had a significantly prolonged P300 latency, a significant reduction in the amplitude of P300, and significant reductions in the scores of verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ), auditory response control quotient (ARCQ), visual response control quotient, full response control quotient (FRCQ), auditory attention quotient (AAQ), visual attention quotient, and full attention quotient (P<0.05). Compared with the BECT group, the BECT+ADHD group had a significantly prolonged P300 latency, a significant reduction in the amplitude of P300, and significant reductions in the scores of VCI, PRI, WMI, PSI, FSIQ, and FRCQ (P<0.05). Compared with the ADHD group, the BECT+ADHD group had a significantly prolonged P300 latency, a significant reduction in the amplitude of P300, and significant reductions in the scores of VCI, PRI, FSIQ, ARCQ, FRCQ, and AAQ (P<0.05). CONCLUSIONS: Compared with the children with BECT or ADHD alone, the children with both BECT and ADHD have basically the same fields of cognitive impairment but a higher degree of cognitive impairment in some fields.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Disfunção Cognitiva , Epilepsia , Criança , Disfunção Cognitiva/etiologia , Humanos , Estudos Prospectivos , Escalas de Wechsler
14.
Zh Nevrol Psikhiatr Im S S Korsakova ; 121(8. Vyp. 2): 35-40, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34553579

RESUMO

Stroke is the leading cause of death and disability in the world. The prevalence of post-stroke epilepsy increases with the increase in the number of stroke cases. Epilepsy may develop in 10% of post-stroke cases and first-diagnosed seizures may develop in 55%. Most often they occur in people who have had intracerebral or subarachnoid haemorrhage. A huge number of factors influence the development of post-stroke seizures and epilepsy. The role of some of them is not in doubt. However, in most cases, the influence of a factor remains controversial and participation in the development of post-stroke epilepsy is not fully proven. The management of post-stroke epilepsy is of great clinical importance, since patients with seizures after a stroke have a higher mortality and disability than those without seizures. Attacks worsen the quality of life of patients, can slow the recovery of functions damaged as a result of a stroke, and aggravate cognitive impairment. Social consequences of post-stroke epilepsy play an important role as well.


Assuntos
Epilepsia , Acidente Vascular Cerebral , Epilepsia/epidemiologia , Epilepsia/etiologia , Humanos , Qualidade de Vida , Fatores de Risco , Convulsões/epidemiologia , Convulsões/etiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia
15.
Int J Mol Sci ; 22(17)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34502487

RESUMO

Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019). Cannabidiol (CBD) is increasingly used to treat epilepsy. The outbreak of the SARS-CoV-2 pandemic in 2019 created new challenges in the effective treatment of epilepsy in COVID-19 patients. The purpose of this review is to present data from the last few years on drug-drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food. Literature data was collected mainly in PubMed, as well as google base. The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented. We pay a special attention to the new potential interactions of the applied first-generation AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital and primidone), on decreased concentration of some medications (atazanavir and remdesivir), or their compositions (darunavir/cobicistat and lopinavir/ritonavir) used in the treatment of COVID-19 patients. CBD interactions with AEDs are clearly defined. In addition, nutrients, as well as diet, cause changes in pharmacokinetics of some AEDs. The understanding of the pharmacokinetic interactions of the AEDs seems to be important in effective management of epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , COVID-19/tratamento farmacológico , Canabidiol/uso terapêutico , Interações Medicamentosas , Nutrientes/metabolismo , Anticonvulsivantes/química , Anticonvulsivantes/farmacocinética , COVID-19/virologia , Canabidiol/química , Canabidiol/farmacocinética , Carbamazepina/química , Carbamazepina/farmacocinética , Carbamazepina/uso terapêutico , Clobazam/química , Clobazam/farmacocinética , Clobazam/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/patologia , Humanos , SARS-CoV-2/isolamento & purificação
16.
Fortschr Neurol Psychiatr ; 89(9): 445-458, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34525483

RESUMO

Automatic computer-based algorithms for the detection of epileptiform potentials and seizure patterns on EEG facilitate a time-saving, objective method of quantitative EEG interpretation which is available 7/24. For the automatic detection of interictal epileptiform potentials sensitivities range from 65 to 99% with false positive detections of 0,09 to 13,4 per minute. Recent studies documented equal or even better performance of automatic spike detection programs compared with experienced human EEG readers. The seizure detection problem-one of the major problems in clinical epileptology-consists of the fact that the majority of focal onset seizures with impaired awareness and of seizures arising out of sleep occur unnoticed by patients and their caregivers. Automatic seizure detection systems could facilitate objective seizure documentation and thus help to solve the seizure detection problem. Furthermore, seizure detection systems may help to prevent seizure-related injuries and sudden unexpected death in epilepsy (SUDEP), and could be an integral part of novel, seizure-triggered on-demand therapies in epilepsy. During long-term video-EEG monitoring seizure detection systems could improve patient safety, provide a time-saving objective and reproducible analysis of seizure patterns and facilitate automatic computer-based patient testing during seizures. Sensitivities of seizure detection systems range from 75 to 90% with extratemporal seizures being more difficult to detect than temporal seizures. The false positive alarm rate ranges from 0,1 to 5 per 24 hours. Finally, machine learning algorithms, especially deep learning approaches, open a new highly promising era in automatic spike and seizure detection.


Assuntos
Epilepsia , Convulsões , Algoritmos , Eletroencefalografia , Epilepsia/diagnóstico , Humanos , Convulsões/diagnóstico
17.
BMC Neurol ; 21(1): 367, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556045

RESUMO

BACKGROUND: Many antiseizure medications (ASMs) control seizures by blocking voltage-dependent sodium channels. Polymorphisms of sodium channel genes may affect the response to ASMs due to altering the effect of ASMs on blocking sodium channels. METHODS: We conducted a retrospective study of epilepsy patients followed up at the Neurological Department of Kaohsiung Chang Gung Memorial Hospital, Taiwan between January 2010 and December 2018. We categorized the patients into response, partial response, and failure to sodium channel blocking ASM groups. Sodium channel blocking ASMs included phenytoin, carbamazepine, lamotrigine, oxcarbazepine, lacosamide, zonisamide, topiramate, and valproic acid. A subgroup of predominant sodium channel blocking ASMs included phenytoin, carbamazepine, lamotrigine, oxcarbazepine, and lacosamide. Associations between the response of ASMs and single-nucleotide polymorphisms of SCN1A, SCN1B, SCN2A, and SCN9A were analyzed. RESULTS: Two hundred Taiwanese patients and 21 single-nucleotide polymorphisms among SCN1A, SCN1B, SCN2A, and SCN9A were evaluated. We found allele C of rs55742440 in SCN1B was statistically significantly associated with not achieving seizure-free with sodium channel blocking ASMs. For the predominant sodium channel blocking ASMs group, no SNPs were associated with the response of ASMs. CONCLUSION: Single-nucleotide polymorphism in SCN1B was associated with the response to sodium channel blocking ASMs. This highlights the possibility that beta subunits may affect the function of sodium channels and resulted in different responsiveness to ASMs.


Assuntos
Epilepsia , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/genética , Humanos , Lamotrigina/uso terapêutico , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Estudos Retrospectivos , Canais de Sódio/genética , Canais de Sódio/uso terapêutico
18.
Int J Mol Sci ; 22(18)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34576077

RESUMO

Kv1.2 channels, encoded by the KCNA2 gene, are localized in the central and peripheral nervous system, where they regulate neuronal excitability. Recently, heterozygous mutations in KCNA2 have been associated with a spectrum of symptoms extending from epileptic encephalopathy, intellectual disability, and cerebellar ataxia. Patients are treated with a combination of antiepileptic drugs and 4-aminopyridine (4-AP) has been recently trialed in specific cases. We identified a novel variant in KCNA2, E236K, in a Serbian proband with non-progressive congenital ataxia and early onset epilepsy, treated with sodium valproate. To ascertain the pathogenicity of E236K mutation and to verify its sensitivity to 4-AP, we transfected HEK 293 cells with Kv1.2 WT or E236K cDNAs and recorded potassium currents through the whole-cell patch-clamp. In silico analysis supported the electrophysiological data. E236K channels showed voltage-dependent activation shifted towards negative potentials and slower kinetics of deactivation and activation compared with Kv1.2 WT. Heteromeric Kv1.2 WT+E236K channels, resembling the condition of the heterozygous patient, confirmed a mixed gain- and loss-of-function (GoF/LoF) biophysical phenotype. 4-AP inhibited both Kv1.2 and E236K channels with similar potency. Homology modeling studies of mutant channels suggested a reduced interaction between the residue K236 in the S2 segment and the gating charges at S4. Overall, the biophysical phenotype of E236K channels correlates with the mild end of the clinical spectrum reported in patients with GoF/LoF defects. The response to 4-AP corroborates existing evidence that KCNA2-disorders could benefit from variant-tailored therapeutic approaches, based on functional studies.


Assuntos
4-Aminopiridina/uso terapêutico , Ataxia Cerebelar/congênito , Ataxia Cerebelar/genética , Epilepsia/tratamento farmacológico , Epilepsia/genética , Canal de Potássio Kv1.2/genética , Sequência de Aminoácidos , Encéfalo/diagnóstico por imagem , Ataxia Cerebelar/diagnóstico por imagem , Ataxia Cerebelar/tratamento farmacológico , Criança , Pré-Escolar , Epilepsia/diagnóstico por imagem , Humanos , Lactente , Canal de Potássio Kv1.2/química , Imageamento por Ressonância Magnética , Masculino , Simulação de Dinâmica Molecular , Adulto Jovem
19.
Int J Mol Sci ; 22(17)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34502246

RESUMO

Close to one-third of patients with epilepsies are refractory to current anti-seizure medications; however, trials with cenobamate suggest effectiveness in such patients with focal onset seizures. We searched for data published or otherwise reported on cenobamate and outlined these here. Despite being marketed in the USA, few studies are yet published in full, and trials are ongoing. Nevertheless, cenobamate showed potential for a high degree of efficacy in reducing seizures with an unprecedented seizure-free rate of up to 28%. Rare cases of hypersensitivity reactions seen in early trials seem to be avoided by the current recommended titration schedule. Other adverse events were rated mild-to-moderate and most commonly included dizziness, drowsiness, and headache. If data are confirmed in further published trials, cenobamate will be a welcome new treatment and further analyses may identify those that will benefit the most.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamatos/uso terapêutico , Clorofenóis/uso terapêutico , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Tetrazóis/uso terapêutico , Epilepsia/patologia , Humanos , Convulsões/patologia
20.
BMC Neurol ; 21(1): 363, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34537017

RESUMO

BACKGROUND: When MRI fails to detect a potentially epileptogenic lesion, the chance of a favorable outcome after epilepsy surgery becomes significantly lower (from 60 to 90% to 20-65%). Hybrid FDG-PET/MRI may provide additional information for identifying the epileptogenic zone. We aimed to investigate the possible effect of the introduction of hybrid FDG-PET/MRI into the algorithm of the decision-making in both lesional and non-lesional drug-resistant epileptic patients. METHODS: In a prospective study of patients suffering from drug-resistant focal epilepsy, 30 nonlesional and 30 lesional cases with discordant presurgical results were evaluated using hybrid FDG-PET/MRI. RESULTS: The hybrid imaging revealed morphological lesion in 18 patients and glucose hypometabolism in 29 patients within the nonlesional group. In the MRI positive group, 4 patients were found to be nonlesional, and in 9 patients at least one more epileptogenic lesion was discovered, while in another 17 cases the original lesion was confirmed by means of hybrid FDG-PET/MRI. As to the therapeutic decision-making, these results helped to indicate resective surgery instead of intracranial EEG (iEEG) monitoring in 2 cases, to avoid any further invasive diagnostic procedures in 7 patients, and to refer 21 patients for iEEG in the nonlesional group. Hybrid FDG-PET/MRI has also significantly changed the original therapeutic plans in the lesional group. Prior to the hybrid imaging, a resective surgery was considered in 3 patients, and iEEG was planned in 27 patients. However, 3 patients became eligible for resective surgery, 6 patients proved to be inoperable instead of iEEG, and 18 cases remained candidates for iEEG due to the hybrid FDG-PET/MRI. Two patients remained candidates for resective surgery and one patient became not eligible for any further invasive intervention. CONCLUSIONS: The results of hybrid FDG-PET/MRI significantly altered the original plans in 19 of 60 cases. The introduction of hybrid FDG-PET/MRI into the presurgical evaluation process had a potential modifying effect on clinical decision-making. TRIAL REGISTRATION: Trial registry: Scientific Research Ethics Committee of the Medical Research Council of Hungary. TRIAL REGISTRATION NUMBER: 008899/2016/OTIG . Date of registration: 08 February 2016.


Assuntos
Epilepsia , Preparações Farmacêuticas , Eletroencefalografia , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Estudos Prospectivos
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