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1.
Drugs Today (Barc) ; 57(7): 449-454, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34268532

RESUMO

Fenfluramine hydrochloride, initially utilized as a weight loss drug in the 1970s and later removed from the market for adverse cardiopulmonary side effects, has since been repurposed as an antiseizure medicine (ASM). The potential antiseizure effects of fenfluramine were first identified in patients with photosensitive epilepsy in the 1980s but it was not rigorously explored as a treatment option until 30 years later. Compared with other ASMs, fenfluramine offers a novel mechanism by acting on serotonin and σ1 receptors, demonstrated in vitro and in vivo in animal models of Dravet syndrome. Results from a large double-blind, placebo-controlled trial demonstrated robust efficacy for seizure reduction in patients with Dravet syndrome, and met its primary endpoint with the 0.7 mg/kg/day fenfluramine treatment group experiencing a 62.3% or greater reduction in mean monthly convulsive seizure frequency (MCSF) compared with placebo. Here we provide a comprehensive review of the preclinical and clinical activity of fenfluramine, a recently approved drug for treatment of epilepsy in patients with Dravet syndrome.


Assuntos
Epilepsias Mioclônicas , Espasmos Infantis , Animais , Anticonvulsivantes/uso terapêutico , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/genética , Fenfluramina/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Convulsões/tratamento farmacológico , Espasmos Infantis/tratamento farmacológico
2.
Medicina (Kaunas) ; 57(6)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201098

RESUMO

Data regarding older age bipolar disorder (OABD) are sparse. Two major groups are classified as patients with first occurrence of mania in old age, the so called "late onset" patients (LOBD), and the elder patients with a long-standing clinical history, the so called "early onset" patients (EOBD). The aim of the present literature review is to provide more information on specific issues concerning OABD, such as epidemiology, aetiology and treatments outcomes. We conducted a Medline literature search from 1970-2021 using the MeSH terms "bipolar disorder" and "aged" or "geriatric" or "elderly". The additional literature was retrieved by examining cross references and by a hand search in textbooks. With sparse data on the treatment of OABD, current guidelines concluded that first-line treatment of OABD should be similar to that for working-age bipolar disorder, with specific attention to side effects, somatic comorbidities and specific risks of OABD. With constant monitoring and awareness of the possible toxic drug interactions, lithium is a safe drug for OABD patients, both in mania and maintenance. Lamotrigine and lurasidone could be considered in bipolar depression. Mood stabilizers, rather than second generation antipsychotics, are the treatment of choice for maintenance. If medication fails, electroconvulsive therapy is recommended for mania, mixed states and depression, and can also be offered for continuation and maintenance treatment. Preliminary results also support a role of psychotherapy and psychosocial interventions in old age BD. The recommended treatments for OABD include lithium and antiepileptics such as valproic acid and lamotrigine, and lurasidone for bipolar depression, although the evidence is still weak. Combined psychosocial and pharmacological treatments also appear to be a treatment of choice for OABD. More research is needed on the optimal pharmacological and psychosocial approaches to OABD, as well as their combination and ranking in an evidence-based therapy algorithm.


Assuntos
Antipsicóticos , Transtorno Bipolar , Idoso , Anticonvulsivantes/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/etiologia , Humanos , Lítio/uso terapêutico , Ácido Valproico/uso terapêutico
3.
Molecules ; 26(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34074008

RESUMO

C-11 is a hybrid compound derived from 2-(2,5-dioxopyrrolidin-1-yl) propanamide, with a wide spectrum of anticonvulsant activity and low neurotoxicity. The aim of this study was to determine the effects of C-11 on the protective action of various antiepileptic drugs (i.e., carbamazepine CBZ, lacosamide LCM, lamotrigine LTG, and valproate VPA) against maximal electroshock-induced seizures (MES) in mice, as well as its neuroprotective and physicochemical/pharmacokinetic properties. Results indicate that C-11 (30 mg/kg, i.p.) significantly enhanced the anticonvulsant action of LCM (p < 0.001) and VPA (p < 0.05) but not that of CBZ and LTG in the MES test. Neither C-11 (30 mg/kg) alone nor its combination with other anticonvulsant drugs (at their ED50 values from the MES test) affected motor coordination; skeletal muscular strength and long-term memory, as determined in the chimney; grip strength and passive avoidance tests, respectively. Pharmacokinetic characterization revealed that C-11 had no impact on total brain concentrations of LCM or VPA in mice. Qualitative analysis of neuroprotective properties of C-11, after a single administration of pilocarpine, revealed no protective effect of this substance in the tested animals. Determination of physicochemical descriptors showed that C-11 meets the drug-likeness requirements resulting from Lipinski and Veber's rules and prediction of gastrointestinal absorption and brain penetration, which is extremely important for the CNS-active compounds.


Assuntos
Anticonvulsivantes/farmacologia , Eletrochoque , Animais , Anticonvulsivantes/uso terapêutico , Modelos Animais de Doenças , Camundongos , Força Muscular/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Pilocarpina/toxicidade , Desempenho Psicomotor/efeitos dos fármacos
4.
J Clin Neurosci ; 89: 279-282, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34119281

RESUMO

Awake craniotomy is an established procedure for resecting brain tumors in eloquent lesions, and intraoperative seizure is one of the most important complications. Phenytoin is normally used to control intraoperative seizures. Recently, phenytoin was replaced with levetiracetam at our institution because the latter has fewer side effects. While the phenytoin dose is calibrated in accordance with the serum concentration, there is currently no consensus on a method of monitoring the serum concentration of levetiracetam or the effective concentration range needed to control intraoperative seizures during awake craniotomy. The present study therefore aimed to determine whether monitoring the serum levetiracetam concentration is useful for controlling intraoperative seizures during awake craniotomy. The intraoperative serum concentration of levetiracetam during awake craniotomy was measured in 34 patients and compared with that of phenytoin in 33 patients undergoing the same procedure. The levetiracetam concentration inversely correlated with body surface area (BSA) and estimated glomerular filtration rate (eGFR). Levetiracetam was superior to phenytoin in terms of the correlation between the serum concentration and the dose adjusted for BSA and eGFR (correlation coefficient, 0.49 vs 0.21). Furthermore, the serum levetiracetam concentration in patients with intraoperative seizures was below the 95% confidence interval (CI) of the regression line whereas the serum phenytoin concentration of two patients with seizures was within the 95% CI, indicating that evaluating the serum levetiracetam concentration against the BSA and eGFR-adjusted dosage may be useful in preventing intraoperative seizures during awake craniotomy by allowing prediction of the seizure risk and enabling more accurate dosage calibration.


Assuntos
Anticonvulsivantes/sangue , Craniotomia/métodos , Levetiracetam/sangue , Convulsões/tratamento farmacológico , Vigília , Adulto , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Neoplasias Encefálicas/cirurgia , Humanos , Levetiracetam/efeitos adversos , Levetiracetam/uso terapêutico , Pessoa de Meia-Idade , Fenitoína/efeitos adversos , Fenitoína/sangue , Fenitoína/uso terapêutico , Convulsões/prevenção & controle
5.
Epilepsy Behav ; 121(Pt A): 108080, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34062447

RESUMO

PURPOSE: Following reports that an index of visual surround suppression (SI) may serve as a biomarker for an imbalance of cortical excitation and inhibition in different psychiatric and neurological disorders including epilepsy, we evaluated whether SI is associated with seizure susceptibility, seizure spread, and inhibitory effects of antiseizure medication (ASM). METHODS: In this prospective controlled study, we examined SI with a motion discrimination task in people with genetic generalized epilepsy (GGE) and focal epilepsy with and without focal to bilateral tonic-clonic seizures. Cofactors such as GABAergic ASM, attentional-executive functioning, and depression were taken into account. RESULTS: Data of 45 patients were included in the final analysis. Suppression index was not related to epilepsy or seizure type, GABAergic ASM treatment or mood. However, SI correlated with attentional-executive functioning (r = 0.32), which in turn was associated with ASM load (r = -0.38). Repeated task administration (N = 7) proved a high stability over a one-week interval (rtt = 0.89). CONCLUSIONS: Our results do not support the hypothesis that SI is a reliable biomarker for mechanisms related to inhibition of seizure spread or seizure frequency, i.e., it does not seem to reflect inhibitory capacities in epilepsy. Likewise, SI did not differentiate GGE from focal epilepsy, nor was it influenced by ASM load or mode of action. Thus, in epilepsy, no added value of including SI to routine diagnostics can be concluded.


Assuntos
Epilepsias Parciais , Epilepsia , Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Epilepsia/tratamento farmacológico , Humanos , Estudos Prospectivos , Convulsões/tratamento farmacológico
6.
Epilepsy Behav ; 121(Pt A): 108069, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34077902

RESUMO

INTRODUCTION: The main of the present study was to assess the effectiveness and tolerability of perampanel (PER) in association with 1 or 2 concomitant antiseizure medications (ASMs) in patients with epilepsy throughout a follow-up period of 24 months or longer in a real-world setting. METHODS: This retrospective, observational, multi-center study collected data from both underage (<18 years old) and adult patients who had started PER in association with 1 or 2 ASMs. Only patients who had started PER and were followed up for at least 24 months were included. Response to treatment was analyzed at the 24-, 36-, and 48-month visits by considering the last visit undergone by patients. Subgroup analyses were performed according to age, gender, and epilepsy type and patients were categorized following PER treatment in concomitance with 1 or 2 ASMs to evaluate the factors affecting the achievement of seizure freedom (SF) at the 24-month FU. RESULTS: Ninety-four patients were included (mean age 36.89 years; 51.1% female). At the 24-month follow-up visit, 90 (95.74%) patients were still receiving PER concomitantly with 1 or 2 ASMs. The mean PER dose was 6.02 mg/day and SF was achieved by 33 (35.1%) patients. A significantly higher SF rate was found in patients who had started PER with only 1 ASM when compared to those who had started PER with 2 concomitant ASMs. Effectiveness was maintained also in the subgroups of patients with a 36- or 48-month follow-up visit. Adult patients had a higher final daily dosage of PER than underage patients. Logistic regression found that the lowest number of previously failed ASMs was associated with a higher SF rate (p = 0.036). CONCLUSION: Perampanel demonstrated a good effectiveness in association with 1 or 2 ASMs in both pediatric and adult patients, without having to use a high dose of the drug. The possibility to present SF was higher when PER was added early. Finally, the maintenance of effectiveness was observed also in the subgroups of patients with a follow-up of 36 and 48 months.


Assuntos
Anticonvulsivantes , Epilepsia , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Criança , Epilepsia/tratamento farmacológico , Feminino , Seguimentos , Humanos , Masculino , Piridonas/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
7.
Medicine (Baltimore) ; 100(22): e25468, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087819

RESUMO

RATIONALE: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a condition characterized by biphasic convulsions and disturbance of consciousness. In Japan, the most common pediatric cases of acute encephalopathy are associated with infection. AESD usually occurs in early childhood, with the characteristic magnetic resonance imaging (MRI) appearance called "bright tree appearance." The disease often has neurological sequelae and interferes with the schooling of children and their activities of daily living; however, there are few clinical case reports of hemiplegia caused by AESD. PATIENT CONCERNS: A case with right-sided hemiplegia due to AESD in an 11-month-old girl who was followed up to 30 mo of age. DIAGNOSES: The patient was diagnosed with overlap AESD and hemiconvulsion-hemiplegia-epilepsy syndrome (HHE syndrome), based on the clinical course and imaging findings. DNA tests of her blood and cerebrospinal fluid revealed the presence of human herpesvirus 6. INTERVENTIONS: Pharmacotherapy and rehabilitation therapy. OUTCOME: Gross motor function has recovered considerably, but she had a mild developmental delay at 30 mo old. LESSONS: Hemiplegia due to AESD was extremely rare, and appropriate rehabilitation treatment resulted in recovery of physical function. However, as mild developmental delay was observed, the patient was referred to a specialized facility before entering school.


Assuntos
Encefalopatia Aguda Febril/complicações , Hemiplegia/etiologia , Anticonvulsivantes/uso terapêutico , Feminino , Hemiplegia/tratamento farmacológico , Hemiplegia/reabilitação , Humanos , Lactente , Imageamento por Ressonância Magnética
8.
Medicine (Baltimore) ; 100(22): e26136, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087865

RESUMO

RATIONALE: Periventricular nodular heterotopia-7 (PVNH7) is a neurodevelopmental disorder associated with improper neuronal migration during neurogenesis in cortex development caused by pathogenic variants in the NEDD4L gene. PATIENT CONCERNS: We report the case of a polystigmatized 2-year-old boy having significant symptomatologic overlap with PVNH7, such as delayed psychomotor and mental development, seizures and infantile spasms, periventricular nodular heterotopia, polymicrogyria, cleft palate, 2 to 3 toe syndactyly, hypotonia, microretrognathia, strabismus, and absent speech and walking. The patient showed also distinct symptoms falling outside PVNH7 symptomatology, also present in the proband's older brother, such as blue sclerae, hydronephrosis, transversal palmar crease (found also in their father), and bilateral talipes equinovarus. In addition, the patient suffered from many other symptoms. DIAGNOSES: The boy, his brother and their parents were subjected to whole-exome sequencing. Because of uncertainties in symptomatology and inheritance pattern, the top-down approach was hard to apply. Using the bottom-up approach, we identified a known pathogenic variant, NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys, in the proband's genome that absented in any other analyzed family member, suggesting its de novo origin. INTERVENTIONS AND OUTCOMES: The patient was treated with Convulex 300 mg/mL for the successful seizure control and Euthyrox 25mg for the treatment of thyroid malfunction. He also took various supplements for the metabolism support and digestion regulation. Moreover, the patient underwent the corrective surgeries of cleft palate and talipes equinovarus. LESSONS: We successfully identified the causative mutation NM_001144967.2(NEDD4L):c.2677G>A:p.Glu893Lys explaining symptoms overlapping those reported for PVNH7. Symptoms shared with the brother were not explained by this variant, since he was not a carrier of the pathogenic NEDD4L variant. These are most likely not extended phenotypes of PVNH7, rather an independent clinical entity caused by a yet unidentified genetic factor in the family, highlighting thus the importance of thorough evaluation of symptomatology and genomic findings in affected and unaffected family members, when such data are available.


Assuntos
Ubiquitina-Proteína Ligases Nedd4/genética , Heterotopia Nodular Periventricular/genética , Heterotopia Nodular Periventricular/fisiopatologia , Anticonvulsivantes/uso terapêutico , Pré-Escolar , Suplementos Nutricionais , Humanos , Masculino , Heterotopia Nodular Periventricular/terapia , Tiroxina/uso terapêutico
9.
J Enzyme Inhib Med Chem ; 36(1): 1230-1235, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: covidwho-1254219

RESUMO

The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid-base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.


Assuntos
Acetazolamida/uso terapêutico , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Inibidores da Anidrase Carbônica/uso terapêutico , Anidrases Carbônicas/sangue , Equilíbrio Ácido-Base/efeitos dos fármacos , Doença da Altitude/sangue , Doença da Altitude/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Bicarbonatos/sangue , COVID-19/sangue , COVID-19/diagnóstico por imagem , COVID-19/virologia , Dióxido de Carbono/sangue , Tosse/sangue , Tosse/tratamento farmacológico , Tosse/patologia , Tosse/virologia , Reposicionamento de Medicamentos , Dispneia/sangue , Dispneia/tratamento farmacológico , Dispneia/patologia , Dispneia/virologia , Febre/sangue , Febre/tratamento farmacológico , Febre/patologia , Febre/virologia , Humanos , Concentração de Íons de Hidrogênio , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/sangue , Hipóxia/tratamento farmacológico , Hipóxia/patologia , Hipóxia/virologia , Oximetria , Projetos de Pesquisa , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
10.
BMC Neurol ; 21(1): 251, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187396

RESUMO

BACKGROUND: Epilepsy is a severe chronic neurologic disease with a prevalence of 0.7% worldwide; anti-seizure medications (ASMs) are the mainstay of epilepsy treatment. The effects of sociodemographic factors on the characteristics of initial treatment in patients with newly diagnosed focal epilepsy in Western China are unknown. This study was conducted to explore sociodemographic factors associated with initial treatment characteristics. METHODS: Patients with focal epilepsy on continuous ASM treatment who visited to our epilepsy center at Sichuan Provincial People's Hospital between January 2018 and December 2019 were recruited. Data on initial treatment status and sociodemographic variables were obtained from the patients with a questionnaire designed by our researchers. We examined whether sociodemographic factors were associated with epileptic patients' access to neurologists and prescriptions of individual ASMs. RESULTS: A total of 569 patients completed this study. We found that patients with a higher education level, aged < 16 years, and with a higher household disposable income were more likely to receive treatment from a neurologist than their counterparts. Patients with a lower personal income level and who were treated at a junior hospital were more likely to receive prescriptions for carbamazepine, and those who were younger than 16 years were less likely to receive prescriptions for carbamazepine and oxcarbazepine. Patients with a higher education level, with a higher household disposable income level, who were younger than 16 years, and who were treated at a senior hospital were more likely to receive prescriptions for levetiracetam than their counterparts. Adult, female patients with focal epilepsy treated at a senior hospital were more likely to receive prescriptions for lamotrigine. CONCLUSIONS: This observation suggests that sociodemographic characteristics are associated with access to neurologists and prescriptions of individual antiepileptic drugs. These data may help public health officials establish guidelines for doctors and distribute resources according to the needs of different patient groups.


Assuntos
Anticonvulsivantes , Epilepsias Parciais , Adolescente , Adulto , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , China , Epilepsias Parciais/tratamento farmacológico , Epilepsias Parciais/epidemiologia , Feminino , Humanos , Masculino , Fatores Socioeconômicos , Adulto Jovem
11.
BMC Neurol ; 21(1): 226, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34154568

RESUMO

OBJECTIVE: We aim to compare the effect of long-term anti-seizure medication (ASM) monotherapy on the risk of death and new ischemic stroke in patients with post-stroke epilepsy (PSE). PATIENTS AND METHODS: We identified all hospitalized patients (≥ 20 years) with a primary diagnosis of ischemic or hemorrhagic stroke from 2001 to 2012 using the National Health Insurance Research Database in Taiwan. The PSE cohort were defined as the stroke patients (1) who had no epilepsy and no ASMs use before the index stroke, and (2) who had epilepsy and ASMs use after 14 days from the stroke onset. The patients with PSE receiving ASM monotherapy were enrolled and were categorized into phenytoin, valproic acid, carbamazepine, and new ASM groups. We employed the Cox regression model to estimate the unadjusted and adjusted hazard ratios (HRs) with 95 % confidence intervals (CIs) of death and new ischemic stroke within 5 years across all groups, using the new ASM group as the reference. RESULTS: Of 6962 patients with PSE using ASM monotherapy, 3917 (56 %) were on phenytoin, 1623 (23 %) on valproic acid, 457 (7 %) on carbamazepine, and 965 (14 %) on new ASMs. After adjusting for confounders, compared with new ASM users, phenytoin users had a higher risk of death in 5 years (HR: 1.64; 95 % CI: 1.06-2.55). On the other hand, all ASM groups showed a similar risk of new ischemic stroke in 5 years. CONCLUSIONS: Among patients with PSE on first-line monotherapy, compared to new ASMs, use of phenytoin was associated with a higher risk of death in 5 years.


Assuntos
Anticonvulsivantes , Epilepsia , Acidente Vascular Cerebral , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/etiologia , Epilepsia/mortalidade , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade , Taiwan
12.
J Enzyme Inhib Med Chem ; 36(1): 1230-1235, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34074197

RESUMO

The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid-base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.


Assuntos
Acetazolamida/uso terapêutico , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Inibidores da Anidrase Carbônica/uso terapêutico , Anidrases Carbônicas/sangue , Equilíbrio Ácido-Base/efeitos dos fármacos , Doença da Altitude/sangue , Doença da Altitude/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Bicarbonatos/sangue , COVID-19/sangue , COVID-19/diagnóstico por imagem , COVID-19/virologia , Dióxido de Carbono/sangue , Tosse/sangue , Tosse/tratamento farmacológico , Tosse/patologia , Tosse/virologia , Reposicionamento de Medicamentos , Dispneia/sangue , Dispneia/tratamento farmacológico , Dispneia/patologia , Dispneia/virologia , Febre/sangue , Febre/tratamento farmacológico , Febre/patologia , Febre/virologia , Humanos , Concentração de Íons de Hidrogênio , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/sangue , Hipóxia/tratamento farmacológico , Hipóxia/patologia , Hipóxia/virologia , Oximetria , Projetos de Pesquisa , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
13.
BMC Neurol ; 21(1): 217, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34102997

RESUMO

BACKGROUND: Lacosamide (LCM) is the antiepileptic drug approved by the U.S. Food and Drug Administration in 2008 that facilitates slow activation of the voltage-gated sodium channels. Neutropenia and cardiac events including sinus node dysfunction (SND) and atrioventricular block have been previously reported as adverse effects of LCM. To date, there have been no reports of severe agranulocytosis resulting in death associated with LCM. Additionally, there have been no reports of concomitant SND and agranulocytosis after LCM administration. Herein we report the first case of LCM-induced severe SND followed by agranulocytosis. CASE PRESENTATION: The patient with focal epilepsy was initiated on LCM 100 mg/day and the dose was increased to 200 mg/day on the 9th hospital day. Severe SND developed on the 10th hospital day and LCM was discontinued. Thereafter agranulocytosis appeared on the 11th hospital day, and the patient died from septic shock on the 15th hospital day. CONCLUSIONS: This case illustrates the need for careful follow-up of the electrocardiogram and the complete blood cell counts when initiating LCM. Moreover, it should be noticed that various side effects may occur simultaneously in the early period of LCM use, even for a short time and at low dosages.


Assuntos
Agranulocitose/induzido quimicamente , Anticonvulsivantes/efeitos adversos , Lacosamida/efeitos adversos , Síndrome do Nó Sinusal/induzido quimicamente , Idoso , Anticonvulsivantes/uso terapêutico , Eletrocardiografia , Epilepsias Parciais/tratamento farmacológico , Feminino , Humanos , Lacosamida/uso terapêutico
14.
J Trop Pediatr ; 67(2)2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34089322

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of levetiracetam (LEV) in comparison to phenytoin (PHT) as second line antiseizure medication (ASM) for Pediatric convulsive status epilepticus (SE). DATA SOURCE: PubMed, Embase, Google scholar/Google, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials. STUDY SELECTION: Randomized controlled trials (RCTs) assessing LEV and PHT as second line agent for convulsive SE in children <18 years published between 1 January 2000 and 30 November 2020. DATA EXTRACTION: The data were pooled regarding the proportion of children achieving seizure cessation within 5-60 min of completion of study drug infusion (primary outcome); and seizure cessation within 5 min, time to achieve seizure cessation, seizure recurrence between 1 to 24 h, intubation and cardiovascular instability (secondary outcomes). Data were analyzed using RevMan version 5.4 and quality analysis was done using Cochrane risk-of-bias tool. The study protocol was registered with PROSPERO. DATA SYNTHESIS: Twelve RCTs with 2293 children were included. Seizure cessation within 5-60 min was similar with both the drugs [82% in LEV vs. 77.5% in PHT, risk ratio (RR) = 1.04, 95% confidence interval (95% CI) 0.97-1.11, p = 0.30]. Seizure recurrences within 1-24 h was higher with PHT in comparison to LEV (16.6% vs. 9.7%, RR = 0.63, 95% CI 0.44-0.90, p = 0.01). Higher proportion of children in PHT group required intubation and mechanical ventilation (21.4% vs. 14.2%, RR = 0.54, 95% CI 0.30-0.98, p = 0.04). Seizure cessation within 5 min, time to achieve seizure cessation, and cardiovascular instability were similar with both the drugs. Three RCTs were at low risk of bias and nine were at high risk of bias. CONCLUSION: The efficacy of LEV is similar to PHT as second line ASM for Pediatric convulsive SE. Seizure recurrences between 1 to24 h and requirement of intubation and mechanical ventilation were significantly higher with PHT in comparison to LEV.


Assuntos
Fenitoína , Estado Epiléptico , Anticonvulsivantes/uso terapêutico , Criança , Humanos , Levetiracetam/uso terapêutico , Fenitoína/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estado Epiléptico/tratamento farmacológico
15.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073930

RESUMO

Combination therapy with two or three antiseizure medications (ASMs) is sometimes a preferred method of treatment in epilepsy patients. (1) Background: To detect the most beneficial combination among three ASMs, a screen test evaluating in vivo interactions with respect to their anticonvulsant properties, was conducted on albino Swiss mice; (2) Methods: Classification of interactions among lacosamide (LCM) and selected second-generation ASMs (lamotrigine (LTG), pregabalin (PGB), oxcarbazepine (OXC), and topiramate (TPM)) was based on the isobolographic analysis in the mouse maximal electroshock-induced seizure (MES) model. Interactions among LCM and second-generation ASMs were visualized using a polygonogram; (3) Results: In the mouse MES model, synergy was observed for the combinations of LCM + TPM + PGB and LCM + OXC + PGB. Additivity was reported for the other combinations tested i.e., LCM + LTG + TPM, LCM + LTG + PGB, LCM + LTG + OXC, and LCM + OXC + TPM in this seizure model. No adverse effects associated with triple ASM combinations, containing LCM and second-generation ASMs were observed in mice; (4) Conclusions: The combination of LCM + TPM + PGB was the most beneficial combination among the tested in this study, offering synergistic suppression of tonic-clonic seizures in mice subjected to the MES model. Both the isobolographic analysis and polygonogram method can be recommended for experimental epileptology when classifying interactions among the ASMs.


Assuntos
Anticonvulsivantes/uso terapêutico , Quimioterapia Combinada/métodos , Epilepsia/tratamento farmacológico , Lacosamida/uso terapêutico , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/efeitos adversos , Modelos Animais de Doenças , Interações Medicamentosas , Sinergismo Farmacológico , Eletrochoque , Lacosamida/efeitos adversos , Lamotrigina/efeitos adversos , Lamotrigina/uso terapêutico , Masculino , Camundongos , Oxcarbazepina/efeitos adversos , Oxcarbazepina/uso terapêutico , Pregabalina/efeitos adversos , Pregabalina/uso terapêutico , Topiramato/efeitos adversos , Topiramato/uso terapêutico
16.
Braz J Med Biol Res ; 54(9): e11097, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34133540

RESUMO

Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5'-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication.


Assuntos
Epilepsia , Ácido Valproico , Anticonvulsivantes/uso terapêutico , Criança , Epilepsia/tratamento farmacológico , Epilepsia/genética , Humanos , Polimorfismo de Nucleotídeo Único , Convulsões/tratamento farmacológico , Convulsões/genética , Ácido Valproico/uso terapêutico
17.
Arq Neuropsiquiatr ; 79(4): 290-298, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34133509

RESUMO

BACKGROUND: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. OBJECTIVE: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. METHODS: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. RESULTS: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. CONCLUSION: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Adulto , Anticonvulsivantes/uso terapêutico , Criança , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Levetiracetam/uso terapêutico , Qualidade de Vida , Resultado do Tratamento
18.
Neurol India ; 69(3): 692-697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34169870

RESUMO

Background and Purpose: Epilepsy during pregnancy is a therapeutic challenge. Since the 1990s, the number of licensed antiepileptic drugs has substantially increased, but safety data on managing epilepsy during conception, pregnancy, and postpartum period use of newer generation antiepileptic drugs and birth defects are limited. We analyzed efficacy and safety of levetiracetam during pregnancy in northeast Indian women with active epilepsy (WWAE) which is being presented here. Design: Hospital based retrospective study. Patients and Methods: A retrospective analysis was conducted based on clinical records at a tertiary care teaching hospital and referral center in Northeast India between June 2008 through June 2018 without any personal identifying information. The Obstetric data from pregnancy register was supplemented with detailed neurologic data retrieved from medical records. Results: Of 103 women with active epilepsy, 47 (45.6%) received levetiracetam as monotherapy and 56 (54.4%) as polytherapy. During pregnancy, the seizure frequency was unchanged, or the change was better in the majority (61.1%) of the patients. With one twin pregnancy, there were 96 live births, 5 spontaneous abortions, 2 induced abortions, 1 stillbirth. However, the rate of small for gestational age was higher in WWAE, Apgar score at 5 min was lower in infants of WWAE, and the need for care in the neonatal ward and neonatal intensive care was higher. Seven of 103 exposed pregnancies had a major congenital malformation (6.79%), all 7 were exposed to other antiepileptic drugs. Generalized epilepsy accounted for 57.2%. Conclusion: Pregnancy course is uncomplicated and neonatal outcome is good in the majority of women with active epilepsy with proper antenatal and neurologic care. Levetiracetam taken in monotherapy can be considered as safer alternative for women with epilepsy of childbearing age. Long-term follow-up of neuropsychological and cognitive development of the children of WWAE is still needed.


Assuntos
Anormalidades Induzidas por Medicamentos , Epilepsia , Complicações na Gravidez , Anormalidades Induzidas por Medicamentos/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Criança , Epilepsia/tratamento farmacológico , Feminino , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Levetiracetam/uso terapêutico , Gravidez , Complicações na Gravidez/tratamento farmacológico , Estudos Retrospectivos , Centros de Atenção Terciária
19.
Cochrane Database Syst Rev ; 5: CD011922, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33973646

RESUMO

BACKGROUND: Any type of seizure can be observed in Alzheimer's disease. Antiepileptic drugs seem to prevent the recurrence of epileptic seizures in most people with Alzheimer's disease. There are pharmacological and non-pharmacological treatments for epilepsy in people with Alzheimer's disease, however there are no current systematic reviews to evaluate the efficacy and tolerability of these treatments. This review aims to investigate these different modalities. This is an updated version of the Cochrane Review previously published in 2018. OBJECTIVES: To assess the efficacy and tolerability of pharmacological or non-pharmacological interventions for the treatment of epilepsy in people with Alzheimer's disease (including sporadic Alzheimer's disease and dominantly inherited Alzheimer's disease). SEARCH METHODS: For the latest update, on 3 August 2020 we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 31 July 2020). CRS Web includes randomized or quasi-randomized controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups, including Cochrane Epilepsy. In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings; we also contacted trial authors and pharmaceutical companies. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials investigating treatment for epilepsy in people with Alzheimer's disease, with the primary outcomes of proportion of participants with seizure freedom and proportion of participants experiencing adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to there being limited available data. MAIN RESULTS: We included one randomized controlled trial (RCT) on pharmacological interventions; the trial included 95 participants. No studies were found for non-pharmacological interventions. Concerning the proportion of participants with seizure freedom, no significant differences were found for the comparisons of levetiracetam versus lamotrigine (RR) 1.20, 95% CI 0.53 to 2.71; 67 participants; very low-certainty evidence), levetiracetam versus phenobarbital (RR 1.01, 95% CI 0.47 to 2.19; 66 participants; very low-certainty evidence), or lamotrigine versus phenobarbital (RR 0.84, 95% CI 0.35 to 2.02; 57 participants; very low-certainty evidence). It seemed that levetiracetam could improve cognition and lamotrigine could relieve depression, while phenobarbital and lamotrigine could worsen cognition, and levetiracetam and phenobarbital could worsen mood. The risk of bias relating to allocation, blinding and selective reporting was unclear. We judged the certainty of the evidence for all outcomes to be very low. AUTHORS' CONCLUSIONS: This review does not provide sufficient evidence to support levetiracetam, phenobarbital or lamotrigine for the treatment of epilepsy in people with Alzheimer's disease. Regarding efficacy and tolerability, no significant differences were found between levetiracetam, phenobarbital and lamotrigine. Large RCTs with a double-blind, parallel-group design are required to determine the efficacy and tolerability of treatment for epilepsy in people with Alzheimer's disease.


Assuntos
Doença de Alzheimer/complicações , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Fenobarbital/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/administração & dosagem , Cognição/efeitos dos fármacos , Depressão/complicações , Depressão/tratamento farmacológico , Feminino , Humanos , Lamotrigina/administração & dosagem , Levetiracetam/administração & dosagem , Masculino , Fenobarbital/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Prevenção Secundária
20.
Epilepsy Behav ; 121(Pt A): 108031, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33992932

RESUMO

There is no definite proven or accepted strategy in the management of patients with focal epilepsy uncontrolled by the first anti-seizure medication (ASM). Clinical studies failed to find a significant difference in efficacy or tolerability between alternative monotherapy and/or adjunctive therapy in these patients. A second ASM is often added, the efficacy of the combination is assessed, and the dose of the first drug can be gradually reduced and withdrawn. If seizures recur, the effective combination therapy can be reinstated. In this review, we discussed experimental and clinical data about the efficacy and tolerability of the most frequently used combinations of ASMs. Animal studies suggested that the most favorable combinations are those between ASMs with different or multiple mechanisms of action, whereas combining drugs with similar pharmacodynamic properties is often associated with additive or infra-additive efficacy and additive or synergistic toxicity. Clinical studies have shown that levetiracetam (LEV) can be favorably combined with the sodium channel blockers (SCBs) lacosamide (LCM) and lamotrigine (LTG). Lamotrigine is particularly effective when associated with valproate (VPA) and possibly with LEV and topiramate (TPM). Carbamazepine (CBZ) has negative pharmacokinetic interactions with several ASMs and should not be combined with other SCBs; it could be effectively and safely combined with gabapentin (GBP) and LEV. Valproic acid has enzyme inhibiting properties and can be cautiously used with SCBs; its combination with TPM or zonisamide (ZNS) may be associated with higher toxicity.


Assuntos
Epilepsia , Animais , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Humanos , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Convulsões/tratamento farmacológico
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