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Focal Opercular Myoclonic - Anarthric Status Epilepticus (OMASE) is a rare form of focal motor status epilepticus caused by several etiologies. It is characterized by fluctuating dysarthria and epileptic myoclonus involving the bilateral glossopharyngeal musculature. We present the case of a 52-year-old woman who experienced gradual and progressive paralysis and myoclonus of facial and bulbar muscles; additional tests revealed the presence of right breast ductal adenocarcinoma and positive serum anti-Hu and anti-GAD65 antibodies. High doses of steroid pulses, anti-seizure therapy, and rituximab partially controlled myoclonus; the tumor resection improved dysphagia and dysarthria.
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OBJECTIVE: Timely treatment is one of the most relevant prognostic factors in patients with urgent epileptic seizures. Despite the available evidence, treatment times remain suboptimal. The aim of this study was to demonstrate the impact of the "seizure code" in an emergency department, focusing on both treatment times and hospital outcomes of patients with urgent epileptic seizures. METHODS: An ambispective cohort study was conducted in the emergency department of a public hospital in Bogotá, Colombia. Treatment times and hospital outcomes were evaluated both before and after the implementation of the seizure code. RESULTS: A total of 336 patients were included (94 in the pre-seizure code period and 242 in the post-seizure code period). Both cohorts were comparable in terms of clinical and demographic baseline characteristics. After the implementation of the seizure code, in-hospital treatment times improved among patients with status epilepticus and seizure cluster. For the group of patients with status epilepticus, the time from arrival to the first benzodiazepine decreased from a median of 100.5 min (IQR: 43-152.5) to a median of 20 min (IQR: 10-45) (p = .0063), and the time from arrival to the first non-benzodiazepine antiseizure medication decreased from a median of 155 min (IQR: 49-194) to a median of 39 min (IQR: 25-57) (p = .0071). For the group of patients with seizure cluster, the time from arrival to the first non-benzodiazepine antiseizure medication decreased from a median of 296 min (IQR: 112.5-409) to a median of 72 min (IQR: 46-111) (p < .001). The seizure code significantly decreased the risk of inappropriate benzodiazepine use (p = .0087), in-hospital seizure recurrence (p < .001), in-hospital mortality (p = .0074), and prolonged hospitalizations (more than 48 h) (p = .0475). SIGNIFICANCE: The seizure code shortens the time to treatment, reduces the length of hospital stay, decreases the risk of inappropriate benzodiazepine use, and lowers both the in-hospital seizure recurrence and in-hospital mortality among patients with urgent epileptic seizures.
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Resumen Introducción: El estado epiléptico refractario (EER) constituye una emergencia médica grave, donde la crisis no cede a pesar del tratamiento farmacológico convencional. Se describe como estado epiléptico superrefractario (EESR) la continua presencia de episodios con una duración de 24 horas o más. Este reporte de caso detalla la complejidad en el manejo y explora un enfoque multidisciplinario. Presentación del caso: Paciente masculino de 32 años con antecedente de epilepsia focal secundaria a traumatismo craneoencefálico en la niñez, quien ingresó en contexto de EESR, el cual recibió coma barbitúrico, plasmaféresis y dieta cetogénica. En los exámenes, la resonancia magnética reveló una lesión en la región frontotemporal insular derecha; en la tomografía por emisión de positrones se observaron zonas de hipermetabolismo y en el videoelectroencefalograma una continua actividad epileptiforme. Se optó por la cirugía paliativa, logrando la resolución exitosa del EESR y una clasificación Engels IA a los 14 meses. Discusión: El EESR es un evento neurológico crítico con pronóstico reservado y opciones terapéuticas desafiantes. Se describen opciones terapéuticas desde anticonvulsivantes, inmunoterapia y cirugía, donde el abordaje quirúrgico emerge como una opción eficaz, especialmente en casos con lesiones estructurales. La identificación temprana y la terapia adecuada son vitales para prevenir complicaciones. Conclusiones: El EESR representa un desafío crítico con alta carga de morbimortalidad, sin embargo, la cirugía de epilepsia muestra promisorios resultados en el contexto de causa cerebral estructural, responsable de la actividad epileptiforme. Se destaca la importancia de la identificación temprana y el manejo quirúrgico paliativo como opción viable, mejorando la calidad de vida de los pacientes.
Abstract Introduction: Refractory Status Epilepticus (RSE) is a serious medical emergency where the seizure does not subside despite conventional pharmacological treatment. The continuous presence of episodes lasting 24 hours or more is described as super-refractory status epilepticus (SRSE). This case report details the complex in teraphy management and explores a multidisciplinary approach. Case presentation: A 32-year-old male with a history of focal epilepsy secondary to head trauma in childhood. Enters emergency with a RSE episode. Barbiturate coma, plasmapheresis and ketogenic diet were administered. The Magnetic Resonance Imaging revealed a lesion in the right fronto-temporo-insular cortex, areas of hypermetabolism on Positron Emission Tomography and continuous epileptiform activity on video-electroencephalogram. Palliative surgery was chosen, achieving successful resolution of the SRSE and Engel Scale IA classification at 14 months of follow up. Discussion: The SRSE is a critical neurological event with a guarded prognosis and complex therapeutic options. Therapeutic options are described from anticonvulsants, immunotherapy and surgery. The surgical approach emerges as an effective option, especially in cases with structural injuries. Early identification and appropriate therapy are vital to prevent complications. Conclusions: SRSE represents a critical challenge with a high burden of morbidity and mortality. However, epilepsy surgery shows promising results in the context of the structural brain cause responsible for epileptiform activity. The importance of early identification and palliative surgical management as a viable option is highlighted, improving the quality of life of patients.
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Epilepsy is a condition marked by sudden, self-sustained, and recurring brain events, showcasing unique electro-clinical and neuropathological phenomena that can alter the structure and functioning of the brain, resulting in diverse manifestations. Antiepileptic drugs (AEDs) can be very effective in 30% of patients in controlling seizures. Several factors contribute to this: drug resistance, individual variability, side effects, complexity of epilepsy, incomplete understanding, comorbidities, drug interactions, and no adherence to treatment. Therefore, research into new AEDs is important for several reasons such as improved efficacy, reduced side effects, expanded treatment options, treatment for drug-resistant epilepsy, improved safety profiles, targeted therapies, and innovation and progress. Animal models serve as crucial biological tools for comprehending neuronal damage and aiding in the discovery of more effective new AEDs. The utilization of antioxidant agents that act on the central nervous system may serve as a supplementary approach in the secondary prevention of epilepsy, both in laboratory animals and potentially in humans. Chlorogenic acid (CGA) is a significant compound, widely prevalent in numerous medicinal and food plants, exhibiting an extensive spectrum of biological activities such as neuroprotection, antioxidant, anti-inflammatory, and analgesic effects, among others. In this research, we assessed the neuroprotective effects of commercially available CGA in Wistar rats submitted to lithium-pilocarpine-induced status epilepticus (SE) model. After 72-h induction of SE, rats received thiopental and were treated for three consecutive days (1st, 2nd, and 3rd doses). Next, brains were collected and studied histologically for viable cells in the hippocampus with staining for cresyl-violet (Nissl staining) and for degenerating cells with Fluoro-Jade C (FJC) staining. Moreover, to evaluate oxidative stress, the presence of malondialdehyde (MDA) and superoxide dismutase (SOD) was quantified. Rats administered with CGA (30 mg/kg) demonstrated a significant decrease of 59% in the number of hippocampal cell loss in the CA3, and of 48% in the hilus layers after SE. A significant reduction of 75% in the cell loss in the CA3, shown by FJC+ staining, was also observed with the administration of CGA (30 mg/kg). Furthermore, significant decreases of 49% in MDA production and 72% in the activity of SOD were seen, when compared to animals subjected to SE that received vehicle. This study introduces a novel finding: the administration of CGA at a dosage of 30 mg/kg effectively reduced oxidative stress induced by lithium-pilocarpine, with its effects lasting until the peak of neural damage 72 h following the onset of SE. Overall, the research and development of new AEDs are essential for advancing epilepsy treatment, improving patient outcomes, and ultimately enhancing the quality of life for individuals living with epilepsy.
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Ácido Clorogênico , Fármacos Neuroprotetores , Estresse Oxidativo , Pilocarpina , Ratos Wistar , Estado Epiléptico , Animais , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Pilocarpina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Ácido Clorogênico/farmacologia , Ácido Clorogênico/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Masculino , Ratos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Modelos Animais de Doenças , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Lítio/farmacologiaRESUMO
OBJECTIVE: The goal of this research was to evaluate the effect of DM type 2 (DM2) on SE severity, neurodegeneration, and brain oxidative stress (OS) secondary to seizures. METHODS: DM2 was induced in postnatal day (P) 3 male rat pups by injecting streptozocin (STZ) 100 mg/kg; control rats were injected with citrate buffer as vehicle. At P90, SE was induced by the lithium-pilocarpine administration and seizure latency, frequency, and severity were evaluated. Neurodegeneration was assessed 24 h after SE by Fluoro-Jade B (F-JB) staining, whereas OS was estimated by measuring lipid peroxidation and reactive oxygen species (ROS). RESULTS: DM2 rats showed an increase in latency to the first generalized seizure and SE onset, had a higher number and a longer duration of seizures, and displayed a larger neurodegeneration in the hippocampus (CA3, CA1, dentate gyrus, and hilus), the piriform cortex, the dorsomedial nucleus of the thalamus and the cortical amygdala. Our results also show that only SE, neither DM2 nor the combination of DM2 with SE, caused the increase in ROS and brain lipid peroxidation. SIGNIFICANCE: DM2 causes higher seizure severity and neurodegeneration but did not exacerbate SE-induced OS under these conditions. PLAIN LANGUAGE SUMMARY: Our research performed in animal models suggests that type 2 diabetes mellitus (DM2) may be a risk factor for causing higher seizure severity and seizure-induced neuron cell death. However, even when long-term seizures promote an imbalance between brain pro-oxidants and antioxidants, DM2 does not exacerbate that disproportion.
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Diabetes Mellitus Tipo 2 , Estado Epiléptico , Ratos , Animais , Masculino , Diabetes Mellitus Tipo 2/complicações , Espécies Reativas de Oxigênio/efeitos adversos , Pilocarpina/efeitos adversos , Convulsões , Estado Epiléptico/induzido quimicamente , Estresse OxidativoRESUMO
Clinical-electroencephalogram (EEG), as well as etiological and prognostic data on subtypes of nonconvulsive status epilepticus (NCSE) are yet to be established. Objective: Evaluate the clinical semiology and EEG findings and prognostic data of older adults with NCSE. Methodology: Characterize the clinical-EEG and prognostic data in the subtypes of NCSE in older adults consecutively admitted to the emergency room of the Pontifícia Universidade Católica de Campinas (PUC-Campinas) University Hospital. Results: When evaluating 105 older adults with altered consciousness, it was possible to diagnose NCSE in 50 (47.6%) older adults, with a mean age of 72.8 ± 8.8 years. NCSE-coma occurred in 6 cases, with NCSE-without coma in 44 cases. The etiology was structural in 41(82%) cases, metabolic in 5 cases, and unknown etiology in 4 cases. Twelve cases had a history of epileptic seizures. On the EEG, epileptiform discharges (EDs > 2.5â Hz) were present in 34(68%) cases and rhythmic delta activity /lateralized periodic patterns occurred in 35(70%) cases. There was clinical improvement after the initial pharmacological treatment in 36 cases and, within 30 days, 18 cases died. The better prognosis was associated with a good response to initial pharmacological treatment (n = 14) and with EDs > 2.5â Hz on EEG (Fisher's exact test; 26 vs 8; P = .012). Conclusion: Focal NCSE with impaired consciousness was the most frequent subtype. The most frequent finding on the EEG was the recording of focal/regional seizures. A high number of cases showed initial clinical improvement, but mortality was high. The favorable prognosis was associated with initial clinical improvement and the presence of EDs > 2.5â Hz. There was no relationship between EEG patterns and the etiology and subtypes of NCSE in older adults.
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Epilepsia , Estado Epiléptico , Humanos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Eletroencefalografia/efeitos adversos , Coma/diagnóstico , Estado Epiléptico/diagnóstico , Convulsões/complicações , Epilepsia/complicaçõesRESUMO
Dravet syndrome is currently considered as an developmental and epileptic encephalopathy and, recently, mandatory, alert, and exclusionary criteria have been proposed. Here, we describe three patients with Dravet syndrome with the typical early presentation including febrile and afebrile alternating hemiclonic seizures due to loss-of-function SCN1A variants. Subsequently, they developed episodes of febrile focal status epilepticus (SE) associated with hemiparesis and cerebral hemiatrophy with posterior focal seizures, as a consequence of Dravet syndrome. This sequence of events has been previously published in patients with Dravet syndrome and does not contradict the recent classification by the International League Against Epilepsy (ILAE). The ILAE guidance identifies "Focal neurological findings" as alert criteria and "MRI showing a causal focal lesion" as exclusionary criteria for making an initial diagnosis of Dravet syndrome at presentation. Our three patients would correspond to a severe phenotype, similar to the well-known presentation of generalized atrophy following prolonged status epilepticus. Common genetic findings in cases of diffuse and unilateral brain involvement may help explain these clinical presentations. Further genotype-phenotype studies may provide additional insights into this electroclinical behavior.
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Epilepsias Mioclônicas , Epilepsia , Convulsões Febris , Estado Epiléptico , Humanos , Mutação , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Epilepsia/diagnóstico , Estado Epiléptico/genética , Estado Epiléptico/complicações , Convulsões Febris/complicações , Atrofia , Paresia/complicaçõesRESUMO
INTRODUCTION: The growth hormone (GH) has been reported as a crucial neuronal survival factor in the hippocampus against insults of diverse nature. Status epilepticus (SE) is a prolonged seizure that produces extensive neuronal cell death. The goal of this study was to evaluate the effect of intracerebroventricular administration of GH on seizure severity and SE-induced hippocampal neurodegeneration. METHODOLOGY: Adult male rats were implanted with a guide cannula in the left ventricle and different amounts of GH (70, 120 or 220ng/3µl) were microinjected for 5 days; artificial cerebrospinal fluid was used as the vehicle. Seizures were induced by the lithium-pilocarpine model (3mEq/kg LiCl and 30mg/kg pilocarpine hydrochloride) one day after the last GH administration. Neuronal injury was assessed by Fluoro-Jade B (F-JB) staining. RESULTS: Rats injected with 120ng of GH did not had SE after 30mg/kg pilocarpine, they required a higher number of pilocarpine injections to develop SE than the rats pretreated with the vehicle, 70ng or 220ng GH. Prefrontal and parietal cortex EEG recordings confirmed that latency to generalized seizures and SE was also significantly higher in the 120ng group when compared with all the experimental groups. FJ-B positive cells were detected in the hippocampus after SE in all rats, and no significant differences in the number of F-JB cells in the CA1 area and the hilus was observed between experimental groups. CONCLUSION: Our results indicate that, although GH has an anticonvulsive effect in the lithium-pilocarpine model of SE, it does not exert hippocampal neuroprotection after SE.
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Anticonvulsivantes , Hormônio do Crescimento , Fármacos Neuroprotetores , Estado Epiléptico , Animais , Masculino , Ratos , Anticonvulsivantes/farmacologia , Hormônio do Crescimento/farmacologia , Lítio/efeitos adversos , Fármacos Neuroprotetores/farmacologia , Pilocarpina/efeitos adversos , Convulsões/tratamento farmacológico , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/induzido quimicamenteRESUMO
Seizure-mediated oxidative stress is a crucial mechanism in the pathophysiology of epilepsy. This study evaluated the antioxidant effects of daytime-restricted feeding (DRF) and the role of the Nrf2 signaling pathway in a lithium-pilocarpine model seizure model that induces status epilepticus (SE). We performed a lipoperoxidation assay and dihydroethidium fluorescence to measure oxidative stress markers in the hippocampus (malondialdehyde and reactive oxygen species). The protein content of Nrf2 and its downstream protein SOD2 was evaluated using Western blotting. The cellular distribution of the Nrf2 and SOD2 proteins in the pyramidal cell layer of both the CA1 and CA3 hippocampal subfields and astrocytes (GFAP marker) were quantified using immunofluorescence and immunohistochemistry, respectively. Our results indicate that DRF reduced the malondialdehyde levels and the production of reactive oxygen species. Furthermore, a significant increase in Nrf2 and SOD2 protein content was observed in animals subjected to restrictive diet. In addition, DRF increased the relative intensity of the Nrf2 fluorescence in the perinuclear and nuclear compartments of pyramidal neurons in the CA1 subfield. Nrf2 immunoreactivity and the astrocyte marker GFAP also increased their colocalization under DRF conditions. Additionally, SOD2 immunoreactivity was increased in CA1 pyramidal neurons but not in the CA3 region. Our findings suggest that DRF partially prevents oxidative stress by increasing the Nrf2 transcriptional factor and the SOD2 enzyme during the development of SE.
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Resumen El estado epiléptico (SE) es la emergencia neurológica más frecuente en neuropediatría. Es el resultado de la falla de los mecanismos responsables en terminar una crisis epiléptica o del inicio, que conduce a una crisis epiléptica prolongada. La incidencia estimada entre 3-42 casos por cada 100.000 personas por año. Tiene una distribución bimodal afectando a los extremos de la vida; niños y ancianos, las estimaciones de mortali dad son variables en función de la edad y la etiología, en los niños la mortalidad podría ser más baja que en adultos pero alcanza una alta morbilidad hasta un 66%. La definición ha cambiado en el transcurso de los años con el fin de especificar inicio de tratamiento y comple mentar con los datos científicos se ha establecido un tiempo t1 y un t2. El tiempo (t1) es el momento cuando el tratamiento debe comenzar, que varía dependiendo de la semiología, a los 5 minutos para una crisis con vulsiva tónico clónica generalizada y a los 10 minutos para una crisis focal. El segundo tiempo (t2) se refiere al daño neuronal. El tratamiento rápido y eficaz disminuye los riesgos de complicaciones cardíacas y respiratorias, ingreso a unidades de cuidados intensivos y muerte.
Abstract Status epilepticus (SE) is the most frequent neuro logical emergency in neuropediatrics. It is the result of the failure of the mechanisms responsible for terminat ing an epileptic seizure or its onset, which leads to a prolonged epileptic seizure. The estimated incidence between 3-42 cases per 100,000 people per year. It has a bimodal distribution, affecting children and the elderly at the extremes of life. Mortality estimates are variable depending on age and etiology. Mortality in children could be lower than in adults, but it reaches a high morbidity of up to 66%. The definition has changed over the years in order to specify the start of treatment and to complement it with the scientific data, a time t1 and a t2 have been established. The time (t1) is the moment when treatment should begin, which varies depending on the semiology, at 5 minutes for a generalized tonic-clonic seizure and at 10 minutes for a focal seizure. The second time (t2) refers to neuronal damage. Prompt and effective treatment decreases the risks of cardiac and respiratory complications, admission to intensive care units, and death.
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Status epilepticus (SE) is described as continuous and self-sustaining seizures, which triggers hippocampal neurodegeneration, inflammation, and gliosis. N-formyl peptide receptor (FPR) has been associated with inflammatory process. N-formyl-methionyl-leucyl-phenylalanine (fMLP) peptide plays an anti-inflammatory role, mediated by the activation of G-protein-coupled FPR. Here, we evaluated the influence of fMLP peptides on the behavior of limbic seizures, memory consolidation, and hippocampal neurodegeneration process. Male Wistar rats (Rattus norvegicus) received microinjections of pilocarpine in hippocampus (H-PILO, 1.2 mg/µL, 1 µL) followed by fMLP (1 mg/mL, 1 µL) or vehicle (VEH, saline 0.9%, 1 µL). During the 90 min of SE, epileptic seizures were analyzed according to the Racine's Scale. After 24 h of SE, memory impairment was assessed by the inhibitory avoidance test and the neurodegeneration process was evaluated in hippocampal areas. There was no change in latency and number of wet dog shake (WDS) after administration of fMLP. However, our results showed that the intrahippocampal infusion of fMLP reduced the severity of seizures, as well as the number of limbic seizures. In addition, fMLP infusion protected memory dysfunction followed by SE. Finally, the intrahippocampal administration of fMLP attenuated the process of neurodegeneration in both hippocampi. Taken together, our data suggest a new insight into the functional role of fMLP peptides, with important implications for their potential use as a therapeutic agent for the treatment of brain disorders, such as epilepsy. Schematic drawing on the neuroprotective and anticonvulsant role of fMLP during status epilepticus. Initially, a cannula was implanted in hippocampus and pilocarpine/saline was administered into the hippocampus followed by fMLP/saline (A-C). fMLP reduced seizure severity and neuronal death in the hippocampus, as well as protecting against memory deficit (D).
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Epilepsia , Estado Epiléptico , Ratos , Masculino , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , N-Formilmetionina Leucil-Fenilalanina/farmacologia , N-Formilmetionina Leucil-Fenilalanina/uso terapêutico , Pilocarpina/uso terapêutico , Ratos Wistar , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/complicações , Convulsões/tratamento farmacológico , Epilepsia/tratamento farmacológico , Peptídeos/uso terapêuticoRESUMO
Status epilepticus (SE) is the most frequent neurological emergency in neuropediatrics. It is the result of the failure of the mechanisms responsible for terminating an epileptic seizure or its onset, which leads to a prolonged epileptic seizure. The estimated incidence between 3-42 cases per 100,000 people per year. It has a bimodal distribution, affecting children and the elderly at the extremes of life. Mortality estimates are variable depending on age and etiology. Mortality in children could be lower than in adults, but it reaches a high morbidity of up to 66%. The definition has changed over the years in order to specify the start of treatment and to complement it with the scientific data, a time t1 and a t2 have been established. The time (t1) is the moment when treatment should begin, which varies depending on the semiology, at 5 minutes for a generalized tonicclonic seizure and at 10 minutes for a focal seizure. The second time (t2) refers to neuronal damage. Prompt and effective treatment decreases the risks of cardiac and respiratory complications, admission to intensive care units, and death.
El estado epiléptico (SE) es la emergencia neurológica más frecuente en neuropediatría. Es el resultado de la falla de los mecanismos responsables en terminar una crisis epiléptica o del inicio, que conduce a una crisis epiléptica prolongada. La incidencia estimada entre 3-42 casos por cada 100.000 personas por año. Tiene una distribución bimodal afectando a los extremos de la vida; niños y ancianos, las estimaciones de mortalidad son variables en función de la edad y la etiología, en los niños la mortalidad podría ser más baja que en adultos pero alcanza una alta morbilidad hasta un 66%. La definición ha cambiado en el transcurso de los años con el fin de especificar inicio de tratamiento y complementar con los datos científicos se ha establecido un tiempo t1 y un t2. El tiempo (t1) es el momento cuando el tratamiento debe comenzar, que varía dependiendo de la semiología, a los 5 minutos para una crisis convulsiva tónico clónica generalizada y a los 10 minutos para una crisis focal. El segundo tiempo (t2) se refiere al daño neuronal. El tratamiento rápido y eficaz disminuye los riesgos de complicaciones cardíacas y respiratorias, ingreso a unidades de cuidados intensivos y muerte.
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Estado Epiléptico , Adulto , Idoso , Criança , Humanos , Estado Epiléptico/diagnóstico , Estado Epiléptico/terapia , Convulsões , Coração , Hospitalização , Unidades de Terapia IntensivaRESUMO
Introducción: la necrosis laminar cortical es un término radiológico que describe la presencia de lesiones hiperdensas de localización cerebral, las cuales siguen una distribución giriforme y se observan con mayor sensibilidad en los estudios de resonancia magnética cerebral (RM). Esta condición patológica, que afecta a la corteza del cerebro, suele ser secundaria a una depleción de sus fuentes energéticas como consecuencia de hipoxia cerebral, alteraciones metabólicas, hipoglicemia, falla renal o hepática, intoxicaciones o infecciones. Presentación del caso: se reporta el caso de un hombre de 23 años, con antecedente de consumo crónico de alcohol, quien ingresó al servicio de urgencias de nuestra institución con un estado epiléptico. El estudio de resonancia magnética cerebral demostró la presencia de una necrosis laminar cortical con posterior déficit neurocognitivo y funcional. Conclusión: si se consideran las secuelas neurológicas potenciales asociadas a un estado epiléptico, relacionadas con necrosis laminar cortical cerebral, es necesario hacer un diagnóstico etiológico precoz, así como una atención terapéutica temprana a los pacientes.
Introduction: Cortical laminar necrosis (CLN) is radiologically defined as high-intensity cortical lesions on T1-weighted MRI images that follow a gyral distribution in the brain. Histopathologically, this pathological condition is characterized by necrosis of the cortex involving neurons, glial cells, and blood vessels. It is usually triggered by hypoxia, metabolic alterations, drugs, intoxications, or infections. Case description: We report the case of a 23-year-old man with a history of chronic alcohol abuse who was admitted to our institution with status epilepticus. The brain magnetic resonance imaging performed on this patient showed cortical laminar necrosis associated with subsequent neurocognitive deficits. Conclusion: Due to the potential neurological sequelae secondary to status epilepticus in relation to cortical laminar necrosis as permanent brain damage, it is necessary to provide early diagnosis and treatment for these patients.
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Estado Epiléptico , Hipóxia Encefálica , Córtex Cerebral , NeuroimagemRESUMO
Abstract Background: Status epilepticus (SE) is a neurological emergency. Non-convulsive status epilepticus (NCSE) can only be diagnosed by electroencephalogram (EEG) because the motor clinical symptoms are usually subtle or absent, with high mortality. The best treatment is still unknown. Objectives: Our aim was to assess anticonvulsive and anesthetic drugs in NCSE and their correlation with Epidemiology-based Mortality Score in Status Epilepticus (EMSE), Status Epilepticus Severity Score (STESS) and mortality. Methods: Retrospective, observational, descriptive, cross-sectional study. Ninety patients in intensive care unit over 18 years-old (57 females [63.3%] and 33 males [36.6%], mean age 63.5 years [SD ± 19]) with NCSE, at the Buenos Aires British Hospital. Data was collected between January 2018 and June 2021. An adjusted mul tivariate statistical analysis was performed. Ninety-five (95%) CI, p<0.05 as statistically significant. EMSE and STESS were used in this study. Results: Total mortality rate was 37.8% (34/90), and in patients ≥ 65 years-old (54/90) it was 40.7% (22/54). Patients with 0-2 STESS (11/90) were discharged, while those with STESS ≥ 3 (79/90) had a 43% death rate (34/79). Patients with EMSE < 34 (27/90) had 7.4% (2/27) death rate, while those with EMSE ≥ 34 (63/90) had 50.8% (32/63). No significant differences were found in survival with regard to the number of antiepileptic drugs administered. Pa tients treated with anesthetics presented a 2.6-fold death risk increase (95% CI 1.001-6.83). Discussion: It could be assumed that mortality rate increases 2.6-fold when patients are treated with anes thetic drugs, regardless of the number of antiepileptic drugs previously administered.
Resumen Introducción: El estado de mal epiléptico (SE) es una emergencia neurológica. El SE no convulsivo (SENC) se diagnostica únicamente por electroencefalograma de bido a la ausencia o sutileza de sintomatología clínica motora, con una mortalidad elevada. No se conoce aún el mejor tratamiento. Objetivos: Evaluar drogas anticonvulsivas y anestési cas en el SENC y su correlación con Epidemiology-based Mortality Score in Status Epilepticus (EMSE), Status Epilep ticus Severity Score (STESS) y el índice de mortalidad. Métodos: Estudio retrospectivo, observacional, de scriptivo, de corte transversal. Noventa pacientes ≥ 18 años (57 mujeres [63.3%] y 33 hombres [36.6%], media de edad 63.5 años [DS ± 19]) con diagnóstico de SENC, en el Hospital Británico. Estudio realizado entre enero 2018 y junio 2021. Análisis estadístico multivariado ajustado. IC 95% p< 0.05 como estadísticamente significativo. Se utilizaron escalas de EMSE y STESS. Resultados: La mortalidad total fue de 37.8% (34/90). Los pacientes ≥ 65 años (54/90) presentaron una mayor tasa de muerte 40.7% (22/54), todos aquellos con STESS de 0-2 (11/90) egresaron, mientras que entre los que presentaron ≥ 3 (79/90) el 43% (34/79) falleció. De los pacientes con EMSE < 34 (27/90) dos fallecieron (7.4%) y de aquellos con EMSE ≥ 34 (63/90) falleció el 50.8% (32/63). No hallamos diferencias significativas entre cantidad de drogas antiepilépticas utiliza das y supervivencia. Pacientes con anestésicos tuvieron un aumento del riesgo de muerte 2.6 veces (IC 95% 1.001-6.83). Discusión: De acuerdo a esto la mortalidad con drogas anestésicas aumenta, independientemente de la cantidad de drogas anticonvulsivas utilizadas previamente.
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Continuous ketamine infusions have been studied as an adjunctive agent for refractory status epilepticus (RSE) and super refractory status epilepticus (SRSE) in older children and adults. However, minimal information exists on the efficacy, safety, and dosing for continuous ketamine in young infants. We present the clinical course of 3 young infants with RSE and SRSE who received continuous ketamine in conjunction with other antiseizure medications. The condition of these patients was refractory to an average of 6 antiseizure medications before initiation of continuous ketamine infusion. For each patient, a continuous ketamine infusion was initiated at a rate of 1 mg/kg/hr with 1 patient requiring titration to a maximum of 6 mg/kg/hr. In 1 case, the concomitant use of continuous ketamine allowed for a reduction in the benzodiazepine continuous infusion rate. In all cases, ketamine was well tolerated especially in the setting of hemodynamic instability. Ketamine may provide a safe adjunct in the acute setting in severe RSE and SRSE. This is the first case series to document the use of continuous ketamine as a treatment modality in young infants with RSE or SRSE secondary to various underlying etiologies, without adverse events. Further studies are needed to evaluate the long-term safety and efficacy of continuous ketamine in this patient population.
RESUMO
BACKGROUND: Status epilepticus (SE) is a neurological emergency. Non-convulsive status epilepticus (NCSE) can only be diagnosed by electroencephalogram (EEG) because the motor clinical symptoms are usually subtle or absent, with high mortality. The best treatment is still unknown. OBJECTIVES: Our aim was to assess anticonvulsive and anesthetic drugs in NCSE and their correlation with Epidemiology-based Mortality Score in Status Epilepticus (EMSE), Status Epilepticus Severity Score (STESS) and mortality. METHODS: Retrospective, observational, descriptive, cross-sectional study. Ninety patients in intensive care unit over 18 years-old (57 females [63.3%] and 33 males [36.6%], mean age 63.5 years [SD ± 19]) with NCSE, at the Buenos Aires British Hospital. Data was collected between January 2018 and June 2021. An adjusted multivariate statistical analysis was performed. Ninety-five (95%) CI, p < 0.05 as statistically significant. EMSE and STESS were used in this study. RESULTS: Total mortality rate was 37.8% (34/90), and in patients = 65 years-old (54/90) it was 40.7% (22/54). Patients with 0-2 STESS (11/90) were discharged, while those with STESS = 3 (79/90) had a 43% death rate (34/79). Patients with EMSE < 34 (27/90) had 7.4% (2/27) death rate, while those with EMSE = 34 (63/90) had 50.8% (32/63). No significant differences were found in survival with regard to the number of antiepileptic drugs administered. Patients treated with anesthetics presented a 2.6-fold death risk increase (95% CI 1.001-6.83). DISCUSSION: It could be assumed that mortality rate increases 2.6-fold when patients are treated with anesthetic drugs, regardless of the number of antiepileptic drugs previously administered.
Introducción: El estado de mal epiléptico (SE) es una emergencia neurológica. El SE no convulsivo (SENC) se diagnostica únicamente por electroencefalograma debido a la ausencia o sutileza de sintomatología clínica motora, con una mortalidad elevada. No se conoce aún el mejor tratamiento. Objetivos: Evaluar drogas anticonvulsivas y anestésicas en el SENC y su correlación con Epidemiology-based Mortality Score in Status Epilepticus (EMSE), Status Epilepticus Severity Score (STESS) y el índice de mortalidad. Métodos: Estudio retrospectivo, observacional, descriptivo, de corte transversal. Noventa pacientes = 18 años (57 mujeres [63.3%] y 33 hombres [36.6%], media de edad 63.5 años [DS ± 19]) con diagnóstico de SENC, en el Hospital Británico. Estudio realizado entre enero 2018 y junio 2021. Análisis estadístico multivariado ajustado. IC 95% p < 0.05 como estadísticamente significativo. Se utilizaron escalas de EMSE y STESS. Resultados: La mortalidad total fue de 37.8% (34/90). Los pacientes = 65 años (54/90) presentaron una mayor tasa de muerte 40.7% (22/54), todos aquellos con STESS de 0-2 (11/90) egresaron, mientras que entre los que presentaron = 3 (79/90) el 43% (34/79) falleció. De los pacientes con EMSE < 34 (27/90) dos fallecieron (7.4%) y de aquellos con EMSE = 34 (63/90) falleció el 50.8% (32/63). No hallamos diferencias significativas entre cantidad de drogas antiepilépticas utilizadas y supervivencia. Pacientes con anestésicos tuvieron un aumento del riesgo de muerte 2.6 veces (IC 95% 1.001-6.83). Discusión: De acuerdo a esto la mortalidad con drogas anestésicas aumenta, independientemente de la cantidad de drogas anticonvulsivas utilizadas previamente.
Assuntos
Anestésicos , Estado Epiléptico , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Adolescente , Idoso , Anticonvulsivantes/uso terapêutico , Prognóstico , Estudos Retrospectivos , Estudos Transversais , Índice de Gravidade de Doença , Unidades de Terapia Intensiva , Anestésicos/uso terapêutico , Estado Epiléptico/tratamento farmacológico , EletroencefalografiaRESUMO
Introducción. El estado epiléptico constituye la emergencia neurológica más frecuente. Si bien la mortalidad en niños es baja, su morbilidad puede superar el 20 %. Objetivo. Conocer las pautas de manejo del estado epiléptico referidas por médicos pediatras que atienden esta patología en forma habitual. Población y métodos. Estudio descriptivo, transversal, basado en una encuesta a médicos de tres hospitales pediátricos monovalentes de gestión pública de la Ciudad Autónoma de Buenos Aires. Resultados. Se administraron 292 encuestas (la tasa de respuesta completa alcanzó el 86 %); el 77 % se administró a pediatras y el 16 %, a especialistas en cuidados intensivos. Un 47 % de los participantes refiere indicar la primera benzodiacepina en el tiempo correcto; el 56 % utilizar diazepam intrarrectal en ausencia de un acceso intravenoso; el 95 % elige lorazepam como benzodiacepina inicial en caso de contar con acceso intravenoso; el 58 % refiere iniciar la etapa de fármacos de segunda línea en tiempo adecuado; el 84 % opta por fenitoína como fármaco inicial de segunda línea, un 33 % no cronometra el tiempo durante el tratamiento. La adherencia global a las recomendaciones internacionales fue del 17 %. Conclusiones. Nuestro estudio advierte una baja adherencia referida de los pediatras a las guías internacionales, en particular en las decisiones tiempo-dependientes. También se observó mayor heterogeneidad en las conductas terapéuticas a medida que se avanza en el algoritmo de tratamiento.
Introduction. Status epilepticus is the most common neurological emergency. Although mortality in children is low, morbidity may exceed 20%. Objective. To evaluate the management of status epilepticus by pediatricians who usually treat this condition. Population and methods. Descriptive, cross-sectional study based on a survey administered to physicians from 3 pediatric hospitals in the City of Buenos Aires. Results. A total of 292 surveys were administered (complete response rate as high as 86%); 77% were administered to pediatricians and 16% to intensive care specialists. Forty-seven percent of the participants reported that they administer the first dose of a benzodiazepine within the correct timeframe; 56% use intrarectal diazepam when intravenous access is not available; 95% choose lorazepam as the initial benzodiazepine if an intravenous access is available; 58% initiate the administration of a second-line drug within the correct timeframe; 84% administer phenytoin as the first-choice, second-line drug; and 33% do not measure treatment time. Overall adherence to international recommendations was 17%. Conclusions. Our study highlights poor adherence of pediatricians to international guidelines, particularly in time-dependent decisions. Greater heterogeneity was observed in treatment approaches as the treatment algorithm progressed.
Assuntos
Humanos , Criança , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamento farmacológico , Argentina , Estudos Transversais , Diazepam/uso terapêutico , Hospitais Pediátricos , Anticonvulsivantes/uso terapêuticoRESUMO
AIMS: To compare the effect on mortality and length of hospital stay of propofol with that of sodium thiopentone for the management of dogs with status epilepticus (SE) and refractory status epilepticus (RSE). METHODS: In this cohort study, medical records of a veterinary referral clinic in Argentina were retrospectively searched for dogs that were hospitalised and required induction of therapeutic coma (TC) with either propofol or sodium thiopentone for the management of SE or RSE of any cause. A logistic regression model was performed to evaluate the association between the type of anaesthetic used and in-hospital mortality adjusting for the type of epilepsy (idiopathic, structural, or reactive). Kaplan-Meier estimated survival curves for the length of hospital stay by the type of anaesthetic drug were compared using the log-rank test (deaths were considered censored events). Cox proportional hazards regression was used to estimate hazard ratios for time to hospital discharge, unadjusted and adjusted for type of epilepsy. RESULTS: A total of 24 dogs with SE were included in the study: eight treated with propofol and 16 treated with sodium thiopentone. Four dogs treated with propofol (proportion = 0.50; 95% CI = 0.15-0.84), and eight treated with sodium thiopentone (proportion = 0.50; 95% CI = 0.50-0.74) died during hospitalisation. The median hospitalisation time was 43 (IQR 24-56) hours for dogs that were treated with propofol and 72 (IQR 64-96) hours for dogs that were treated with sodium thiopentone. There was no evidence of a difference in the median duration of TC in dogs treated with propofol (12 (IQR 8-24) hours) or with sodium thiopentone (12 (IQR 7.5-20) hours; p = 0.946). In the logistic regression model, no evidence of association between the anaesthetic protocol for the management of RSE and in-hospital mortality, adjusted for the type of epilepsy, was found (OR 1.09 (95% CI = 0.17-6.87); p = 0.925). Cox regression analysis revealed a difference in the time to hospital discharge, adjusted by the type of epilepsy, between treatment groups (HR = 0.05 (95% CI = 0.01-0.54); p = 0.013). CONCLUSIONS AND CLINICAL RELEVANCE: The time spent in hospital before discharge was longer in dogs with RSE treated with sodium thiopentone compared to those treated with propofol. However, as the sample size was very small, the results obtained in the present study should be analysed with caution. Further studies including a greater number of dogs are required.
Assuntos
Anestésicos , Doenças do Cão , Propofol , Estado Epiléptico , Cães , Animais , Tiopental/uso terapêutico , Tiopental/farmacologia , Propofol/uso terapêutico , Propofol/farmacologia , Estudos de Coortes , Estudos Retrospectivos , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/veterinária , Anestésicos/uso terapêutico , Sódio/uso terapêutico , Doenças do Cão/tratamento farmacológicoRESUMO
BACKGROUND: Development of effective drugs for epilepsy are needed, as nearly 30 % of epileptic patients, are resistant to current treatments. This study is aimed to characterize the anticonvulsant effect of dapsone (DDS), in the kainic acid (KA)-induced Status Epilepticus (SE) by recording the brain metabolic activity with an [18F]FDG-PET analysis. METHODS: Wistar rats received KA (10 mg/kg, i.p., single dose) to produce sustained seizures. [18F]FDG-PET and electroencephalographic (EEG) studies were then performed. DDS or vehicle were administered 30 min before KA. [18F]FDG uptake and EEG were evaluated at baseline, 2 and 25 h after KA injection. Likewise, caspase-8, 3 hippocampal activities and Fluoro-Jade B neuronal degeneration and Hematoxylin-eosin staining were measured 25 h after KA. RESULTS: PET data evaluated at 2 h showed hyper-uptake of [18F]FDG in the control group, which was decreased by DDS. At 25 h, hypo-uptake was observed in the control group and higher values due to DDS effect. EEG spectral power was increased 2 h after KA administration in the control group during the generalized tonic-clonic seizures, which was reversed by DDS, correlated with [18F]FDG-PET uptake changes. The values of caspases-8 activity decreased 48 and 43 % vs control group in the groups treated with DDS (12.5 y 25 mg/kg respectively), likewise; caspase-3 activity diminished by 57 and 53 %. Fewer degenerated neurons were observed due to DDS treatments. CONCLUSIONS: This study pinpoints the anticonvulsant therapeutic potential of DDS. Given its safety and effectiveness, DDS may be a viable alternative for patients with drug-resistant epilepsy.
Assuntos
Epilepsia , Estado Epiléptico , Ratos , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Ácido Caínico/farmacologia , Fluordesoxiglucose F18/metabolismo , Dapsona/farmacologia , Ratos Wistar , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/diagnóstico por imagem , Estado Epiléptico/tratamento farmacológico , Convulsões/metabolismo , Hipocampo/metabolismo , Epilepsia/metabolismoRESUMO
Introduction. Status epilepticus is the most common neurological emergency. Although mortality in children is low, morbidity may exceed 20%. Objective. To evaluate the management of status epilepticus by pediatricians who usually treat this condition. Population and methods. Descriptive, cross-sectional study based on a survey administered to physicians from 3 pediatric hospitals in the City of Buenos Aires. Results. A total of 292 surveys were administered (complete response rate as high as 86%); 77% were administered to pediatricians and 16% to intensive care specialists. Forty-seven percent of the participants reported that they administer the first dose of a benzodiazepine within the correct timeframe; 56% use intrarectal diazepam when intravenous access is not available; 95% choose lorazepam as the initial benzodiazepine if an intravenous line is available; 58% initiate the administration of a second-line drug within the correct timeframe; 84% administer phenytoin as the first-choice, second-line drug; and 33% do not measure treatment time. Overall adherence to international recommendations was 17%. Conclusions. Our study highlights poor adherence of pediatricians to international guidelines, particularly in time-dependent decisions. Greater heterogeneity was observed in treatment approaches as the treatment algorithm progressed.
Introducción. El estado epiléptico constituye la emergencia neurológica más frecuente. Si bien la mortalidad en niños es baja, su morbilidad puede superar el 20 %. Objetivo. Conocer las pautas de manejo del estado epiléptico referidas por médicos pediatras que atienden esta patología en forma habitual. Población y métodos. Estudio descriptivo, transversal, basado en una encuesta a médicos de tres hospitales pediátricos monovalentes de gestión pública de la Ciudad Autónoma de Buenos Aires. Resultados. Se administraron 292 encuestas (la tasa de respuesta completa alcanzó el 86 %); el 77 % se administró a pediatras y el 16 %, a especialistas en cuidados intensivos. Un 47 % de los participantes refiere indicar la primera benzodiacepina en el tiempo correcto; el 56 % utilizar diazepam intrarrectal en ausencia de un acceso intravenoso; el 95 % elige lorazepam como benzodiacepina inicial en caso de contar con acceso intravenoso; el 58 % refiere iniciar la etapa de fármacos de segunda línea en tiempo adecuado; el 84 % opta por fenitoína como fármaco inicial de segunda línea, un 33 % no cronometra el tiempo durante el tratamiento. La adherencia global a las recomendaciones internacionales fue del 17 %. Conclusiones. Nuestro estudio advierte una baja adherencia referida de los pediatras a las guías internacionales, en particular en las decisiones tiempo-dependientes. También se observó mayor heterogeneidad en las conductas terapéuticas a medida que se avanza en el algoritmo de tratamiento.