ABSTRACT
Como parte de las terapias alternativas para el control de síntomas refractarios en enfermedades avanzadas destaca el uso de cannabidiol. Este se ha estudiado en patologías como enfermedad de Alzheimer, Parkinson y trastornos convulsivos. Los síndromes convulsivos están presentes en todos los grupos etarios. Dentro de este, la epilepsia es refractaria hasta en un 40 % de los pacientes, quienes han demostrado disminución en la frecuencia de convulsiones con el uso concomitante de cannabidiol y antiepilépticos convencionales, con efectos secundarios leves, como diarrea y somnolencia. Con el objetivo de determinar el uso del cannabidiol para el control de síntomas neurológicos refractarios en pacientes con síndromes convulsivos y enfermedades neurodegenerativas, se realizó una búsqueda bibliográfica en Pubmed, Scopus y Embase. Se incluyeron metaanálisis, artículos originales, revisiones sistemáticas y bibliográficas, y documentos de la Organización Panamericana de la Salud, publicados entre 2017 y 2022. Los efectos del cannabidiol lo convierten en una alternativa, adicional a la terapéutica convencional, para el control de síntomas en trastornos neurológicos, disminuyendo de forma sostenida el número total de episodios con un perfil de seguridad aceptable. Existe limitada información respecto al uso de cannabidiol en enfermedades neurodegenerativas, por lo que no se ha evidenciado su efectividad
As part of the alternative therapies for the control of refractory symptoms in advanced diseases, the use of cannabidiol stands out. It has been studied in pathologies such as Alzheimer's disease, Parkinson's disease, and convulsive disorders. Convulsive syndromes are present in all age groups. Within this group, epilepsy is refractory in up to 40 % of patients, who have shown a decrease in the frequency of seizures with the concomitant use of cannabidiol and conventional antiepileptics, with mild side effects such as diarrhea and drowsiness. To determine the use of cannabidiol for the control of refractory neurological symptoms in patients with seizure syndromes and neurodegenerative diseases, a literature search was performed in PubMed, Scopus, and Embase. Meta-analyses, original articles, systematic and literature reviews, and documents from the Pan American Health Organization, published between 2017 and 2022, were included. The effects of cannabidiol make it an alternative, in addition to conventional therapeutics, for symptom control in neurological disorders, sustainably decreasing the total number of episodes with an acceptable safety profile. There is limited information regarding the use of cannabidiol in neurodegenerative diseases, the reason its effectiveness has not been demonstrated.
Subject(s)
Seizures , Syndrome , Cannabidiol , Neurodegenerative Diseases , Anticonvulsants , Nervous System DiseasesABSTRACT
Objetivo: Reportamos resultados sobre la efectividad, seguridad y tolerancia del cannabidiol como adyuvante terapéutico en pacientes pediátricos con encefalopatías epilépticas del desarrollo (EED) resistentes al tratamiento farmacológico y no farmacológico tras un seguimiento promedio de 20 meses. Métodos: Se realizó un estudio de cohorte prospectivo para evaluar la eficacia, la seguridad y la tolerancia del aceite de cannabis medicinal enriquecido con CBD añadido a los medicamentos anticonvulsivos estándar en niños con EED resistentes a los medicamentos atendidos en un único centro. Resultados: Entre octubre de 2018 y marzo de 2020, se incluyeron 59 pacientes. La edad media en el momento del inicio del protocolo fue de 10,5 años (rango, 2-17 años). La mediana de la duración del tratamiento fue de 20 meses (rango, 12-32). La mediana de edad en el momento de la primera convulsión fue de 8 meses (rango, 1 día - 10 años). Al final del seguimiento, el 78% de los niños tenía una disminución ≥ 50% en frecuencia de las crisis y el 47,5% tenía una disminución > 75%. Siete pacientes (11,9%) estaban libres de convulsiones. El número de crisis se redujo de una mediana de 305/mes a 90/mes, que supone una reducción media del 57% y una mediana del 71% (p < 0,0001). Los efectos adversos fueron en su mayoría leves o moderados. El CBD se interrumpió en 17 pacientes (28,8%) por falta de respuesta al tratamiento, aumento de la frecuencia de las convulsiones, intolerancia al fármaco o cumplimiento terapéutico insuficiente. Conclusión: En los niños con EED resistentes a los fármacos, el tratamiento a largo plazo del cannabis medicinal enriquecido con CBD como terapia adyuvante resultó ser seguro, bien tolerado y eficaz. Las reducciones sostenidas en la frecuencia de las convulsiones y la mejora de los aspectos de la vida diaria se observaron en comparación con nuestros preliminares (AU)
Objective: We report results on the effectiveness, safety, and tolerance of cannabidiol (CBD) as add-on therapy in children with developmental and epileptic encephalopathies (DEE) resistant to pharmacological and non-pharmacological treatment after a mean follow-up of 20 months. Methods: A prospective cohort study was conducted to evaluate the efficacy, safety, and tolerability of CBD-enriched medical cannabis oil added to standard antiseizure medications in children with drug-resistant DEEs seen at a single center. Results: Between October 2018 and March 2020, 59 patients were included. The median age at protocol initiation was 10.5 years (range, 2-17 years). Median treatment duration was 20 months (range, 12-32). The median age at the time of the first seizure was 8 months (range, 1 day - 10 years). At the end of follow-up, 78% of the children had a decrease ≥ 50% in seizure frequency and 47.5% had a decrease of > 75%. Seven patients (11.9%) were seizure free. The number of seizures was reduced from a median of 305/month to 90/month, accounting for a mean reduction of 57% and a median of 71% (p < 0.0001). Adverse effects were mostly mild or moderate. CBD was discontinued in 17 patients (28.8%) due to lack of response to treatment, increased seizure frequency, drug intolerance, or poor compliance. Conclusion: In children with drug-resistant DEE, long-term treatment with CBD-enriched medicinal cannabis as add-on therapy proved to be safe, well tolerated, and effective. Sustained reductions in seizure frequency and improvement in aspects of daily living were observed compared to our preliminary results (AU)
Subject(s)
Humans , Child, Preschool , Child , Adolescent , Cannabidiol/therapeutic use , Treatment Outcome , Epilepsy/drug therapy , Medical Marijuana/therapeutic use , Lennox Gastaut Syndrome/drug therapy , Drug Resistant Epilepsy/drug therapy , Hospitals, Pediatric , Anticonvulsants/therapeutic use , Prospective Studies , Cohort StudiesABSTRACT
OBJETIVO: Determinar los riesgos y beneficios del uso de vigabatrina comparada con hormona adrenocorticotrópica (ACTH) para el tratamiento de espasmos infantiles. MÉTODO: Se realizó una búsqueda en Epistemonikos. Se extrajeron datos desde las revisiones identificadas. Se realizó un metaanálisis a partir de estudios primarios y se utilizó el método GRADE para la presentación de resultados. RESULTADOS: Se identificaron nueve revisiones sistemáticas. Se observó que el uso de vigabatrina en comparación con ACTH disminuye la resolución de espasmos (RR 0,8, IC 95% 0,65 - 0,98) y podría disminuir la resolución de hipsarritmia (RR 0,71, IC 95% 0,48 - 1,05). No fue posible determinar si el uso de vigabatrina disminuye el riesgo de desarrollar efectos adversos (RR 0,75, IC 95% 0,23 - 2,45) por certeza de evidencia muy baja. CONCLUSIONES: La evidencia parece inclinarse a favor del uso de ACTH. Sin embargo debe considerarse la necesidad de nuevas investigaciones para esclarecer su seguridad.
OBJECTIVE: To determine the risks and benefits of the use of vigabatrin compared to ACTH for the treatment of infantile spasms. METHOD: A search in Epistemonikos was performed. Data were extracted from the identified reviews. A meta-analysis was performed from primary studies and the GRADE method was used to present the results. RESULTS: Nine systematic reviews were identified. Vigabatrin use compared to ACTH was found to decrease resolution of spasms (RR 0.8, 95% CI 0.65 - 0.98) and might decrease resolution of hypsarrhythmia (RR 0.71, 95% CI 0 .48 - 1.05). It was not possible to determine whether the use of vigabatrin reduces the risk of developing adverse effects (RR 0.75, 95% CI 0.23 - 2.45) due to very low certainty of evidence. CONCLUSIONS: The evidence seems to lean in favor of the use of ACTH. However, the need for new research should be considered to clarify its safety.
Subject(s)
Humans , Spasms, Infantile/drug therapy , Adrenocorticotropic Hormone/therapeutic use , Vigabatrin/therapeutic use , Anticonvulsants/therapeutic use , GRADE ApproachABSTRACT
ABSTRACT Background: Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. Objective: To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Methods: Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Results: Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.
RESUMO Antecedentes: A epilepsia apresenta comorbidades neuropsiquiátricas como depressão, transtorno bipolar e ansiedade. Os medicamentos que visam o tratamento da epilepsia podem ser úteis para a epilepsia e suas comorbidades neuropsiquiátricas. Objetivo: Investigar os efeitos da modulação serotonérgica em citocinas pró-inflamatórias e as convulsões no modelo de convulsão induzida por pentilenotetrazol (PTZ) em ratos. Métodos: Ratos Wistar machos foram injetados intraperitonealmente com serotonina, inibidor seletivo da recaptação da serotonina fluoxetina, sumatriptano agonista do receptor 5-HT1B / D ou solução salina 30 min antes do tratamento com PTZ. As crises comportamentais foram avaliadas pela escala de Racine. As concentrações de IL-1β, IL-6 e TNF-α no soro e tecido cerebral foram determinadas por ELISA. Resultados: A serotonina e a fluoxetina, mas não o sumatriptano, aliviaram as convulsões induzidas por PTZ ao prolongar os tempos de início das convulsões mioclônicas e tônico-clônicas generalizadas. O efeito anticonvulsivo da fluoxetina foi maior do que o da serotonina. Da mesma forma, a serotonina e a fluoxetina, mas não o sumatriptano, reduziram os aumentos induzidos por PTZ nos níveis de IL-1β e IL-6 no soro e no tecido cerebral. Nenhum dos medicamentos administrados, incluindo PTZ, alterou as concentrações de TNF-α. Conclusões: Nossos achados sugerem que a serotonina endógena e exógena exibe efeitos anticonvulsivantes por suprimir a neuroinflamação. Aparentemente, os receptores 5-HT1B / D não medeiam os efeitos anticonvulsivantes e anti-neuroinflamatórios da serotonina.
Subject(s)
Humans , Animals , Male , Rats , Pentylenetetrazole/adverse effects , Epilepsy/drug therapy , Seizures/chemically induced , Seizures/drug therapy , Serotonin/adverse effects , Fluoxetine/adverse effects , Interleukin-6 , Tumor Necrosis Factor-alpha , Rats, Wistar , Sumatriptan/adverse effects , Anticonvulsants/adverse effectsABSTRACT
Abstract Metabolic syndrome (MetS), an epidemic defined as a group of interconnected physiological, biochemistry, clinical, and metabolic factors, directly increases the risk of cardiovascular disease, atherosclerosis, type 2 diabetes, and death. MetS therapy includes diet, physical exercise, and a poly-pharmacological intervention. Cannabis is mainly recognized for its recreational uses and has several medical applications for neurological diseases, due to its hypnotic, anxiolytic, antinociceptive, anti-inflammatory, and anticonvulsant activities. Although several clinical observations in Cannabis smokers suggest metabolic effects, its utility in metabolic disorders is unclear. This review aims to determine under what conditions Cannabis might be useful in the treatment of MetS. Cannabis contains 120 phytocannabinoids, of which Δ9-THC mediates its psychoactive effects. Cannabinoids exert biological effects through interactions with the endocannabinoid system, which modulates several physiologic and metabolic pathways through cannabinoid receptors (CB1/CB2). Signaling through both receptors inhibits neurotransmitter release. In general, endocannabinoid system stimulation in Cannabis smokers and Δ9-THC signaling through CB1 have been implicated in MetS development, obesity, and type 2 diabetes. In contrast, CB1 antagonists and non-psychotropic phytocannabinoids like cannabidiol reduce these effects through interactions with both cannabinoid and non-cannabinoid receptors. These pharmacological approaches represent a source of new therapeutic agents for MetS. However, more studies are necessary to support the therapeutic potential of Cannabis and cannabinoids in metabolic abnormalities
Subject(s)
Cannabis/adverse effects , Metabolic Syndrome/drug therapy , Biochemistry/classification , Cannabinoids/adverse effects , Cardiovascular Diseases , Receptors, Cannabinoid/analysis , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Diabetes Mellitus/pathology , Atherosclerosis/pathology , Anticonvulsants/classificationABSTRACT
Abstract The treatment of epilepsy is complex and a matter of concern is the interchangeability among different formulations available for antiepileptic drugs. To evaluate the effects of interchangeability among carbamazepine formulations on patients with epilepsy. This is a prospective cohort study that included adult outpatients diagnosed with epilepsy and under pharmacological treatment with carbamazepine. Before switching the brand/manufacturer, the "Interchangeable Pharmaceutical Product in the Treatment of Epilepsies" questionnaire was applied. The questionnaires "Adverse Events Profile" and Quality of Life in Epilepsy-31, so as the plasma carbamazepine concentrations, were evaluated before and after the brand/ manufacturer switch. Physical-chemical tests aiming to assess tablets quality were performed in accordance with the Brazilian Pharmacopoeia 5th edition. The study population was composed by 14 patients (mean age: 44.6 years), with 10 of females. From those interviewed, 10 had no knowledge about the three antiepileptic drugs formulations available. The frequency of adverse event "problems with skin" incresead (p=0.023) and "upset stomach" decreased (p=0.041) after the changeover. The adverse events profile was associated with only two quality of life domains: "energy/fatigue" (p=0.048) and "total score" (p=0.018). Divergent results between generic and reference formulations were observed in purity-water test (reference: 1.96%, generic: 4.84%) and dissolution test, in which the generic formulation presented 66.27 to 85.77% of carbamazepine dissolved after the third level. Conclusions: Objective differences before and after the brand/manufacturer switch were not observed, in spite of patients' perceptions. Despite that, more studies in the field are necessary, especially on the interchangeability among generic antiepileptics, in order to better elucidate switching consequences on patients' life.
Subject(s)
Humans , Male , Female , Adult , Patients/classification , Carbamazepine/adverse effects , Drugs, Generic/analysis , Epilepsy/pathology , Interchange of Drugs , Anticonvulsants/analysisABSTRACT
Objective: The aim of this study was to assess the bone density of the mandible in adolescents with cerebral palsy (CP) treated with antiepileptic drugs using one beam computed tomography (CBCT). Methods: The study was carried out with 18 adolescents aged 1218 years, undergoing routine dental treatment at the dental clinic of APCD-São Caetano do Sul. CBCT scans were of divided into two groups: G1 adolescents with CP using antiepileptic drugs and G2 normoactive adolescents. A single dentomaxillofacial radiologist assessed and evaluated the images using Dental Slice software and Image J. Fisher's exact tests as well as paired and unpaired Student's t-tests were performed. Results: Groups differed significantly with regard in the values of density (p < 0.001), with G1 presenting lower values compare to G2. G1 showed significantly lower density means on the right side, left side, and right/left sides of the mandible edge than G2 (p < 0.001). Conclusion: CP patients using antiepileptic drugs show evidence of bone mineral density loss of the mandible.(AU)
Objetivo: O objetivo deste estudo foi avaliar a densidade ótica óssea da mandíbula em adolescentes com paralisia cerebral (PC) tratados com drogas antiepilépticas por meio de tomográfica computadorizada de feixe cônico (TCFC). Métodos: O estudo foi realizado com 18 adolescentes de 12 a 18 anos, em tratamento odontológico de rotina na clínica odontológica da APCD-São Caetano do Sul. As TCFC foram divididas em dois grupos: G1 adolescentes com PC em uso de antiepilépticos e G2 adolescentes normoativos. Um único radiologista dentomaxilofacial assessou e avaliou as imagens usando usando os softwares Dental Slice e Image J. Os testes exatos de Fisher, bem como os testes t de Student pareados e não pareados foram realizados. Resultados: Os grupos diferiram significativamente quanto aos valores de densidade óptica (p <0,001), com o grupo G1 apresentando valores menores em relação ao G2. O grupo G1 apresentou médias de densidade óptica significativamente menores nos lados direito, esquerdo e direito / esquerdo da borda da mandíbula do que o G2 (p <0,001). Conclusão: Pacientes com PC em uso de drogas antiepilépticas apresentam evidências de perda de densidade óssea da mandíbula (AU)
Subject(s)
Humans , Male , Female , Adolescent , Osteoporosis , Bone Density , Cone-Beam Computed Tomography , AnticonvulsantsABSTRACT
Epilepsy is a chronic neurologic disease that comes third after cerebrovascular and Alzheimer's disease. Anti-epileptic drugs may affect certain hematological parameters of epileptic patients. Few researches investigated hematological adverse effects of antiepileptic drugs in Libya. Thus, the aim was to evaluate hematological parameters in epileptic children who are on antiepileptic drugs. This retrospective study included 83 pediatric patients with epilepsy recruited from Benghazi Children Hospital, Department of Neurology, from December 2017 to April 2018. Data collected included demographic characteristics, types of epilepsy, anti-epileptic drugs and serum hematological parameters. Hematological parameters recorded included: hemoglobin, hematocrit, platelet, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration and white blood cell count. In all treated patients, regardless of the number of antiepileptic drugs therapy used, the average levels of hematological parameters were significantly lower in treated group compared to control group (11.64 gm per dl, 34.53%, 27.74 pg and 33.13 gm per dl, respectively). A significant increase (12.12109 per l) in white blood cell counts in treated group was found. Average hemoglobin, hematocrit and mean cell hemoglobin concentration levels were significantly lower in patients on poly-therapy compared to mono-therapy and control groups. Average white blood cell counts were significantly increased in patients on anti-epileptic drugs. In sodium valproate users, levels of hematological parameters were significantly decreased but significantly increased in white blood cell counts. In diazepam users, significant increases in white blood cells and platelet but no difference in other parameters observed. There were no differences in all hematological parameters among patients using carbamazepine except for platelet counts (significantly decreased). In conclusion, there is substantial effect of the anti-epileptic drugs, especially sodium valproate, on hematological parameters of children despite the effects were not critical as the changes were still in the normal range.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Drug Therapy , Drug-Related Side Effects and Adverse Reactions , Epilepsy , Anticonvulsants , Hematologic AgentsABSTRACT
Medication adherence is a fundamental determinant of effective treatment. However, people with epilepsy have poor compliance with their treatment because of the chronic nature of the disease. Limited studies have been conducted to address antiepileptic medication adherence in Africa, including Ethiopia. Thus, the aim of this study was to assess antiepileptic drug adherence and its asociated factors among patients with epilepsy attending outpatient department of Amanuel Mental Specialized Hospital. METHODS: A cross-sectional study design was conducted on 439 patients with epilepsy in Amanuel Mental Specialized Hospital. Medication adherence reporting scale-5 (MARS-5) was used to assess adherence to antiepileptic drugs. The Oslo social support, Jacob perceived stigma scale, and hospital anxiety and depression scale (HADS) were the instruments used to assess associated factors. Simple and multiple linear regression analysis models were fitted. Then, the adjusted unstandardized beta (ß) coefficient at a 95% confidence level was used. RESULTS: The mean (SD) score of antiepileptic medication adherence was 16.38(±3.76) with 95%CI:(16.03, 16.72). Depressive symptoms (ß= -1.35, 95% CI: (-2.04, -0.65)), anxiety symptoms (ß=-1.12,95%CI:(-1,79, -0.44), perceived stigma (ß= -1.64, 95% CI: -2.16, -1.12), being single (ß=-0.67, 95%CI: -1.20, -0.14), presence of seizure per month (ß=-2.11,95% CI: (-2.81, -1.41) and antiepileptic drug adverse effect (ß=-0.07,95%CI: -0.11, -0.03) were factors associated with anti-epileptic medication adherence. CONCLUSION: The results suggest that the mean score of adherences to antiepileptic drugs was poor as compared to other settings. Antiepileptic medication adherence screening tool should be included in the patient's treatment protocol
Subject(s)
Epilepsy , Medication Adherence , Health Services Accessibility , AnticonvulsantsABSTRACT
El estado epiléptico refractario de inicio reciente (NORSE) es una emergencia neurológica que conlleva una elevada morbimortalidad, y como tal, genera altos costos debido a su complejo plan terapéutico y al requerimiento de una evaluación rápida y secuencial. Es una entidad clínica de mal pronóstico y su principal etiología es la encefalitis autoinmune, sin embargo, es de difícil diagnóstico y en ocasiones no se logra establecer una causa clara. Se describe el caso de una paciente joven sin antecedentes clínicos de importancia, quien presentó múltiples episodios convulsivos refractarios a anticonvulsivantes y sedación profunda, sin tolerar retiro de la sedoanalgesia por reaparición de crisis en el electroencefalograma. Presentó estudios de líquido cefalorraquídeo, infecciosos, neuroimágenes y de autoinmunidad sin alteraciones. Cursó con neumonía asociada al cuidado de la salud, que evolucionó a disfunción orgánica múltiple y fallecimiento. No se encontraron alteraciones anatomopatológicas post mortem que explicaran la causa del estado epiléptico. El estado epiléptico refractario de inicio reciente es una condición que representa un reto tanto diagnóstico como terapéutico. Se describe su abordaje diagnóstico y las opciones de tratamiento, además, se realiza una revisión corta de la literatura disponible hasta el momento
New-onset refractory status epilepticus (NORSE) is a neurological emergency with high morbidity and mortality, that results in elevated costs due to its complex therapeutic management and the requirement for a rapid and sequential evaluation. It is a condition with a poor prognosis and its main etiology is autoimmune encephalitis. However, it is difficult to diagnose and sometimes a clear cause cannot be established. The case of a young female with no relevant medical history is described. She presented multiple seizure episodes refractory to anticonvulsants and deep sedation, without tolerating withdrawal of sedoanalgesia due to reappearance of seizures in the electroencephalogram. She presented studies of cerebrospinal fluid, infections, neuroimaging and autoimmunity without alterations. She had healthcare-associated pneumonia, which progressed to multiple organ dysfunction and death. No post-mortem anatomopathological alterations were found to explain the cause of the status epilepticus. New-onset refractory status epilepticus is a condition that represents both a diagnostic and therapeutic challenge. Its diagnostic approach and treatment options are described, as well as a brief review of the available literature
Subject(s)
Humans , Status Epilepticus , Autoimmune Diseases , Epilepsy , AnticonvulsantsABSTRACT
Abstract Recent studies suggested that safranal exerts anticonvulsant properties. The present study aimed to investigate the effect of safranal on epileptic activities in the amygdala electrical kindling model in male rats. Animals were implanted with a recording electrode on the skull and a tripolar in the amygdala. After 10 days of recovery, the afterdischarge (AD) threshold of each animal was determined and stimulated once daily the AD threshold for full kindling development. Then, parameters including afterdischarge duration (ADD), stage 4 latency (S4L), stage 5 duration (S5D), and stimulation threshold were determined before and after injection of safranal (0.05, 0.1, 0.2 ml/ kg; i.p). While the dose of 0.05 ml/kg had no significant effect, the dose of 0.1 ml/kg increased the AD threshold as well as S4L and decreased the S5D (P<0.05). Injection of 0.2 ml/kg of the safranal significantly decreased the ADD and S5D (P<0.05) and 83.3% of animals had no stage 4 and stage 5 of kindling (P<0.001). Based on the obtained data safranal has anticonvulsant effects dosedependently. It seems that a dose of 0.2 ml/kg is the minimum effective dose. Further investigation is warranted to conduct the clinical implications for the treatment of epileptic disorders
Subject(s)
Animals , Male , Rats , Seizures/prevention & control , Epilepsy/pathology , Anticonvulsants/administration & dosage , Amygdala/physiopathologyABSTRACT
Introducción. La epilepsia del lóbulo temporal suele producir déficits mnésicos, atencionales y del lenguaje. En la mayoría de los casos, se trata con fármacos an-tiepilépticos, pero falla en un tercio de ellos. Por tal razón, una opción terapéutica es la lobectomía temporal, que contribuye a menguar las crisis. Sin embargo, los procedimientos quirúrgicos pueden conllevar secuelas, entre ellas consecuencias a nivel cognitivo. Para contrarrestar dichos efectos, se acostumbra llevar a cabo una rehabilitación neuropsicológica que va en pro de recuperar, fortalecer y sostener en el tiempo habilidades que ya venían afectándose desde antes de la cirugía. Objetivo. Brindar una reflexión en torno a la intervención neuropsicológica de la epilepsia en el lóbulo temporal. Método. La reflexión sobre el tema parte de un interés clínico y posteriormente se fue ampliando a partir de la revisión de la literatura en diferentes bases de datos como PubMed, Medline y Scopus entre los años 2000 y 2021. Reflexión. Son amplias las opciones terapéuticas a nivel neuropsicológico y pueden contribuir de manera positiva en la recuperación del paciente, por lo cual los profe-sionales requieren conocer las posibilidades de ello para poder utilizar las estrategias más adecuadas según cada caso y brindar opciones que beneficien la calidad de vida, teniendo en cuenta que ninguna es más efectiva que otra. Conclusión. Como resultado, se presenta un panorama general de la rehabilitación neuropsicológica en pacientes pre y posquirúrgicos con lobectomía, haciendo énfasis en la rehabilitación neuropsicológica tradicional y la rehabilitación basada en inteli-gencia artificial, realidad virtual y computación
Introduction. Temporal lobe epilepsy usually produces mnestic, attentional, and language deficits. In most cases, it is treated with antiepileptic drugs, but one third of them fail, so one therapeutic option is temporal lobectomy, which helps to reduce seizures. However, surgical procedures can have sequelae, including cognitive con-sequences. To counteract these effects, neuropsychological rehabilitation is usually carried out in order to recover, strengthen, and sustain in time skills that were already affected before the surgery. Objective. To provide a reflection on the neuropsychological intervention of tem-poral lobe epilepsy. Method. The reflection on the subject starts from a clinical interest and was sub-sequently expanded from the review of the literature in different databases such as PubMed, Medline, and Scopus between 2000 and 2021. Reflection. There are many therapeutic options at the neuropsychological level and they can contribute positively to the patient's recovery, so professionals need to know the possibilities in order to use the most appropriate strategies according to each case and provide options that benefit the quality of life, taking into account that none is more effective than the other one.Conclusion. As a result, an overview of neuropsychological rehabilitation in pre- and post-surgical patients with lobectomy is presented, with emphasis on traditional neuropsychological rehabilitation and rehabilitation based on artificial intelligence, virtual reality, and computation
Subject(s)
Rehabilitation/psychology , Epilepsy , Epilepsy, Temporal Lobe , Neurological Rehabilitation/psychology , Temporal Lobe , Anterior Temporal Lobectomy , Drug Resistant Epilepsy , Neurological Rehabilitation , Anticonvulsants , NeuropsychologyABSTRACT
OBJECTIVES@#To study the clinical phenotype and genetic features of 16p11.2 microdeletion-related epilepsy in children.@*METHODS@#The medical data of 200 children with epilepsy who underwent a genetic analysis of epilepsy by the whole exon sequencing technology were collected retrospectively, of whom 9 children with epilepsy had 16p11.2 microdeletion. The clinical phenotype and genetic features of the 9 children with 16p11.2 microdeletion were analyzed.@*RESULTS@#The detection rate of 16p11.2 microdeletion was 4.5% (9/200). The 9 children with 16p11.2 microdeletion were 3-10 months old. They experienced focal motor seizures with consciousness disturbance, and some of the seizures developed into generalized tonic-clonic seizures. The interictal electroencephalogram showed focal or multifocal epileptiform discharge, and all 9 children responded well to antiepileptic drugs. The 9 children had a 16p11.2 deletion fragment size of 398-906 kb, and the number of deleted genes was 23-33 which were all pathogenic mutations. The mutation was of maternal origin in 2 children, of paternal origin in 1 child, and de novo in the other children.@*CONCLUSIONS@#16p11.2 microdeletion can be detected in some children with epilepsy. Most of the 16p11.2 microdeletion is de novo mutation and large gene fragment deletion. The onset of 16p11.2 microdeletion-related epilepsy in children is mostly within 1 year of life, and the epilepsy is drug-responsive.
Subject(s)
Anticonvulsants , Epilepsy/genetics , Humans , Phenotype , Retrospective Studies , Seizures/geneticsABSTRACT
Abstract Regarding the proven anticonvulsant effect of Zhumeria majdae essential oil (ZMEO) in previous studies we were prompted to investigate the ZMEO effects on the tolerance to the anticonvulsant effects of morphine and the morphine withdrawal syndrome. Tolerance to the morphine anticonvulsant effect was induced in mice by subcutaneous injection of 2.5 mg/kg of morphine for 4 days. Subsequent doses of ZMEO (20 mg/kg) were used to study the expression and development of morphine tolerance. Clonidine was used as the standard drug to inhibit the morphine withdrawal syndrome symptoms. To study the ZMEO effect on withdrawal syndrome, mice received appropriate morphine values for 4 days and on the fifth day, 60 min before administration of naloxone. The effective dose of ZMEO was determined and the number of jumps, stands and changes in the dry stool weight, as symptoms of withdrawal syndrome were evaluated. The dose of 20 mg/kg of ZMEO decreased the tolerance in development and expression groups significantly. Counting the number of jumping, standing and defecation were assessed 30 min after morphine and 1 h after the vehicle and clonidine. The dose of 40 mg/kg ZMEO decreased all the signs of withdrawal syndrome significantly. ZMEO was analyzed by GC/MS and linalool (53.1%) and camphor (23.8%) were characterized as the main components. The results suggest that ZMEO possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms.
Resumo Em relação ao efeito anticonvulsivante comprovado do óleo essencial de Zhumeria majdae (ZMEO) em estudos anteriores, fomos instigados a investigar os efeitos do ZMEO em relação à tolerância aos efeitos anticonvulsivantes da morfina e da síndrome de abstinência de morfina. A tolerância ao efeito anticonvulsivante da morfina foi induzida em camundongos por injeção subcutânea de 2,5 mg/kg de morfina por 4 dias. Doses subsequentes de ZMEO (20 mg/kg) foram utilizadas para estudar a expressão e o desenvolvimento da tolerância à morfina. A clonidina foi usada como droga padrão para inibir os sintomas da síndrome de abstinência da morfina. Para estudar o efeito do ZMEO na síndrome de abstinência, os camundongos receberam valores apropriados de morfina por 4 dias e, no 5º dia, 60 minutos antes da administração de naloxona. A dose efetiva de ZMEO foi determinada, e o número de saltos e de permanência e as alterações no peso das fezes secas, conforme os sintomas da síndrome de abstinência, foram avaliados. A dose de 20 mg/kg de ZMEO diminuiu significativamente a tolerância nos grupos de desenvolvimento e expressão. A contagem do número de saltos, permanência e defecação foi avaliada 30 minutos após a morfina e 60 minutos após o veículo e a clonidina. A dose de 40 mg/kg de ZMEO diminuiu significativamente todos os sinais da síndrome de abstinência. O ZMEO foi analisado por GC/MS, e linalol (53,1%) e cânfora (23,8%) foram caracterizados como os principais componentes. Os resultados sugerem que o ZMEO apresenta constituintes que possuem atividade contra a tolerância aos efeitos anticonvulsivantes da morfina e aos sintomas de abstinência da morfina.
Subject(s)
Animals , Rabbits , Substance Withdrawal Syndrome/drug therapy , Oils, Volatile , Pentylenetetrazole/toxicity , Pentylenetetrazole/therapeutic use , Seizures/chemically induced , Seizures/drug therapy , Morphine/therapeutic use , Anticonvulsants/therapeutic useABSTRACT
OBJETIVO: Reportar el caso de una gestante con miastenia grave (MG) más preeclampsia-eclampsia y crisis miasténica en el puerperio mediato, y realizar una revisión de la literatura sobre el manejo farmacológico. MÉTODO: Se presenta el caso de una mujer de 26 años con MG, primigesta de 36 semanas de gestación, quien cursó con eclampsia y recibió fenitoína por 24 horas. Tuvo parto espontáneo sin complicaciones y crisis miasténica al día 11 del puerperio asociada a infección de vías urinarias y sepsis. Se realiza revisión de la literatura en PubMed, Cochrane, Embase, LILACS y Scopus, empleando los términos "Hypertension, Pregnancy-Induced", "Preeclampsia" y "Eclampsia", combinados con "Myasthenia Gravis", durante el periodo de publicación de 1960 a junio 2020, en inglés y español. RESULTADOS: Se encontraron 12 reportes de caso, dos con eclampsia y MG; el caso aquí reportado es el número 13. Ocho pacientes no recibieron medicamentos profilácticos de eclampsia y tres de ellas convulsionaron. En las que se usó sulfato de magnesio, todas cursaron con crisis miasténica. CONCLUSIONES: La evidencia actual en cuanto a la profilaxis y el tratamiento de la eclampsia y la MG corresponde a reportes de casos. El uso de sulfato de magnesio está contraindicado en pacientes con MG, por lo que se han utilizado fenitoína y levetiracetam.
OBJECTIVE: To report a case of pregnant women with myasthenia gravis (MG), plus preeclampsia-eclampsia and myasthenic crisis in the mediate puerperium; to conduct a literature review regarding its pharmacological management. METHOD: 26-year-old primigravida with 36 weeks of gestation and previous history of MG, who developed eclampsia and was treated with phenytoin for 24 hours, with later spontaneous delivery without any complications nor new seizures; and myasthenic crisis on day 11 of the puerperium associated with urinary tract infection and sepsis. A literature review was conducted in PubMed, Cochrane, Embase, LILACS and Scopus, using the controlled vocabulary "Hypertension, Pregnancy-Induced", "Preeclampsia" and "Eclampsia", combined with "Myasthenia Gravis", between 1960 and June 2020, in English and Spanish. RESULTS: 12 case reports were found, two of these with eclampsia and MG, the case reported here was number 13. In eight cases patients did not receive any prophylactic drugs for eclampsia and three of them had convulsions. In the cases where magnesium sulfate was used, all developed myasthenic crisis. CONCLUSIONS: The current evidence regarding prophylactic management and treatment corresponds to case reports. The use of magnesium sulfate is contraindicated in patients with MG, therefore phenytoin and levetiracetam have been used.
Subject(s)
Humans , Female , Pregnancy , Adult , Pre-Eclampsia/drug therapy , Eclampsia/drug therapy , Myasthenia Gravis/complications , Pre-Eclampsia/prevention & control , Hypertension, Pregnancy-Induced , Eclampsia/prevention & control , Magnesium Sulfate/therapeutic use , Anticonvulsants/therapeutic useABSTRACT
ABSTRACT: Drug reactions with eosinophilia and systemic symptoms (DRESS) are rare and potentially fatal adverse hypersen-sitivity reaction to some drugs, especially anticonvulsants.The syndrome affects not only the skin but also other organs, especially the liver. The incidence can vary from 1 to 5 cases per 10.000 patients exposed to anticonvul-sants. The recognition of the syndrome is of fundamental importance since the mortality rate is between 10 and 40%. Once the diagnosis is established, the triggering drug must be identified and discontinued. Corticosteroids are usually associated with therapy. Autoimmune sequelae have been reported, including vitiligo and rarely alopecia. Alopecia universalis is a variant of alopecia areata, characterized by hair loss throughout the body. We report a case of DRESS, associated with two autoimmune dermatological diseases: alopecia universalis and vitiligo. (AU)
RESUMO: A reação a drogas com eosinofilia e sintomas sistêmicos (DRESS) é uma rara e potencialmente fatal reação adversa de hipersensibilidade, decorrente de alguns medicamentos, principalmente os anticonvulsivantes. A síndrome não afeta apenas a pele, mas também outros órgãos, principalmente o fígado. A incidência pode variar de 1 a 5 casos por 10.000 pacientes expostos aos anticonvulsivantes. O reconhecimento da síndrome é de fundamental importân-cia devido a taxa de mortalidade entre 10-40%. Uma vez estabelecido o diagnóstico, deve-se identificar o medica-mento desencadeante e suspendê-lo. O corticosteróide geralmente é associado na terapia. Sequelas autoimunes foram relatadas, incluindo vitiligo e raramente alopecia. A alopecia universal é uma variante da alopecia areata, caracterizada pela perda de pelos em todo o corpo. Relatamos um caso de DRESS, associado a duas doenças au-toimunes dermatológicas: alopecia universal e vitiligo. (AU)
Subject(s)
Humans , Male , Adult , Vitiligo , Drug Eruptions , Drug Hypersensitivity , Eosinophilia , Drug Hypersensitivity Syndrome , AnticonvulsantsABSTRACT
RESUMO Objetivo: Identificar evidências atuais sobre topiramato para o estado de mal epiléptico refratário. Métodos: Foi revisada a literatura para investigar a eficácia do topiramato no tratamento de estado de mal epiléptico refratário. Os termos de busca utilizados foram: "status epilepticus", "refractory", "treatment" e "topiramate". Não se empregaram restrições. Resultados: A busca identificou 487 artigos que descreviam o uso de topiramato para tratamento de estado de mal epiléptico refratário e seus resultados. Relatos de caso, revisões e experimentos em animais foram excluídos. Após exclusão de duplicatas e aplicação dos critérios de inclusão e exclusão, restaram nove estudos. Realizaram-se análises descritivas e qualitativas, com os seguintes resultados: as taxas de resposta, definidas como término de crises até 72 horas após administração de topiramato, variaram entre 27% e 100%. A mortalidade variou de 5,9% a 68%. Desfechos funcionais positivos, definidos como alta hospitalar, volta à funcionalidade basal ou reabilitação, foram documentados por sete estudos, e as taxas variaram entre 4% e 55%. A maioria dos estudos reportou apenas efeitos colaterais leves ou ausentes. Conclusão: Topiramato foi efetivo em abortar estado de mal epiléptico refratário, apresentando baixa mortalidade e boa tolerabilidade. Portanto, topiramato poderia ser uma boa opção como terceira linha para estado de mal epiléptico refratário, porém mais estudos são necessários.
ABSTRACT Objective: To identify current evidence on the use of topiramate for refractory status epilepticus. Methods: We reviewed the literature to investigate the efficacy of topiramate in the treatment of refractory status epilepticus. The search terms used were "status epilepticus", "refractory", "treatment" and "topiramate". No restrictions were used. Results: The search yielded 487 articles that reported using topiramate as a treatment for refractory status epilepticus and its outcomes. Case reports, review articles, and animal experiments were excluded. After excluding duplicates and applying inclusion and exclusion criteria, nine studies were included for analyses. Descriptive and qualitative analyses were performed, and the results were as follows: response rates (defined as termination in-hospital until 72 hours after the administration of topiramate) varied from 27% to 100%. The mortality rate varied from 5.9% to 68%. Positive functional long-term outcomes, defined as discharge, back to baseline or rehabilitation, were documented by seven studies, and the rates ranged between 4% and 55%. Most studies reported no or mild adverse effects. Conclusion: Topiramate was effective in terminating refractory status epilepticus, presented relatively low mortality and was well tolerated. Therefore, topiramate could be a good option as a third-line therapy for refractory status epilepticus, but further studies are necessary.
Subject(s)
Humans , Animals , Status Epilepticus/drug therapy , Anticonvulsants/adverse effects , Topiramate/adverse effectsABSTRACT
Introdução: As reações cutâneas graves a medicamentos (RCGM) compreendem um grupo de doenças caracterizadas por hipersensibilidade tardia a um ou vários tipos de fármacos. Por ser uma doença potencialmente fatal, o diagnóstico precoce, bem como o início do tratamento, são de suma importância. Objetivo: Analisar a evolução das RCGM em pacientes pediátricos acompanhados em dois hospitais da cidade de São Paulo, SP. Método: Trata-se de um estudo retrospectivo baseado na análise de prontuários de pacientes atendidos no período de 2002 a 2018 em dois hospitais da capital paulista. Resultados: Não houve diferença entre os sexos, prevaleceu a faixa etária dos adolescentes, e os medicamentos mais implicados com o desenvolvimento das lesões cutâneas foram os anticonvulsivantes, sendo os principais a carbamazepina e fenitoína, sem diferença entre eles, seguidos dos antibióticos betalactâmicos. No tratamento, todos os pacientes fizeram uso de corticoides sistêmicos e anti-histamínicos, sendo que oito pacientes também receberam imunoglobulina intravenosa e um recebeu ciclosporina. A taxa de mortalidade foi baixa e, em relação às complicações e sequelas, a autoimunidade foi a mais encontrada. Conclusão: Os casos de RCGM são eventos raros na faixa etária pediátrica, todavia de alta morbimortalidade e risco de sequelas. O diagnóstico e tratamento precoces contribuem para um melhor prognóstico, sendo de suma importância a identificação da medicação associada, bem como a retirada da mesma.
Background: Severe cutaneous adverse reactions (SCARs) comprise a group of diseases characterized by late hypersensitivity to one or more types of drugs. Because they are potentially fatal, early diagnosis and initiation of treatment are of paramount importance. Objective: To analyze the evolution of SCARs in pediatric patients followed up in two hospitals in São Paulo, SP, Brazil. Methods: This is a retrospective study based on the analysis of medical records of patients treated between 2002 and 2018 in two hospitals in the state capital. Results: There was no difference between sexes, and the age group of adolescents prevailed. Anticonvulsants were the drugs most implicated in the development of skin lesions, especially carbamazepine and phenytoin, with no difference between them, followed by betalactam antibiotics. During treatment, all patients used systemic corticosteroids and antihistamines; eight patients also received intravenous immunoglobulin and one received cyclosporine. The mortality rate was low, and regarding complications and sequelae, autoimmunity was the most commonly found. Conclusion: Cases of SCAR are rare events in the pediatric age group, but morbidity, mortality, and risk of sequelae are high. Early diagnosis and treatment contribute to a better prognosis, and identification of the associated medication as well as its withdrawal are extremely important.
Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Carbamazepine , Autoimmunity , Drug Hypersensitivity , Drug-Related Side Effects and Adverse Reactions , Anti-Bacterial Agents , Therapeutics , Pharmaceutical Preparations , Medical Records , Risk , Retrospective Studies , Immunoglobulins, Intravenous , Early Diagnosis , Histamine Antagonists , AnticonvulsantsABSTRACT
Analisar o nível de conhecimento dos usuários de anticonvulsivantes e dos cirurgiões-dentistas a res peito das manifestações orais ocasionadas pela medicação. Trata-se de um estudo transversal realizado no munícipio de Vitória de Santo Antão, em Pernambuco, no qual participaram 30 Odontólogos e 16 usuários de anticonvulsivantes das unidades de saúde da família do município. Foram aplicados questionários sobre o conhecimento dos profissionais e percepção dos usuários sobre as manifestações orais ocasionadas pela medicação. Para avaliar associação entre duas variáveis categóricas foi utilizado teste Exato de Fisher, quando a condição para utilização do teste Qui-quadrado não foi verificada. A análise dos dados demonstrou que 86,7% dos cirurgiões-dentistas conhecem os anticonvulsivantes e 50,0% dos usuários não receberam orientação do dentista sobre a medicação e os seus efeitos adversos. Há escassez de conhecimentos específicos sobre os efeitos adversos do uso de anticonvulsivantes na cavidade bucal por parte dos usuários e cirurgiões-dentistas... (AU)
To analyze the knowledge level of anticonvulsants users and the dental surgeons concerning the oral manifestations caused by the medication. A cross-sectional study conducted in Vitória de Santo Antão, Pernambuco, Brazil, with participation of 30 dentists and 16 anticonvulsants users from the city's family health units. Questionnaires about the knowledge of professionals and users' perception of manifestations in the oral cavity caused by the medication. Fisher's Exact test was used to assess the association between two categorical variables when the condition for using the chi-square test was not verified. The data analysis showed that 86,7% of dental surgeons know the anticonvulsants and 50,0% of users do not receive orientation from the dentist about the medication and its adverse effects. There is a shortage of specific knowledge about the adverse effects of the use of anticonvulsants in the oral cavity, by users and dental surgeons... (AU)