Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Más filtros











Base de datos
Intervalo de año de publicación
1.
Epilepsia ; 65(8): e148-e155, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38837761

RESUMEN

In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1-1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3-2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3-8.9)-particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3-21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5-20.1)-than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ = .519, p = .005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.


Asunto(s)
Dieta Cetogénica , Inmunoterapia , Estado Epiléptico , Humanos , Estado Epiléptico/terapia , Estado Epiléptico/tratamiento farmacológico , Masculino , Femenino , Dieta Cetogénica/métodos , Inmunoterapia/métodos , Inmunoterapia/tendencias , Adolescente , Adulto , Epilepsia Refractaria/terapia , Epilepsia Refractaria/dietoterapia , Niño , Anticuerpos Monoclonales Humanizados/uso terapéutico , Persona de Mediana Edad , Preescolar , Anticonvulsivantes/uso terapéutico , Adulto Joven , Rituximab/uso terapéutico , Manejo de la Enfermedad
2.
Epilepsia ; 65(6): e87-e96, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38625055

RESUMEN

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions.


Asunto(s)
Fiebre , Estado Epiléptico , Humanos , Estado Epiléptico/etiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Fiebre/etiología , Fiebre/complicaciones , Adulto Joven , Adolescente , Epilepsia Refractaria/etiología , Niño , Convulsiones Febriles/etiología , Electroencefalografía , Anciano , Imagen por Resonancia Magnética , Síndromes Epilépticos , Preescolar
3.
BMJ Case Rep ; 12(5)2019 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-31118171

RESUMEN

Anticollapsin-responsive mediator protein 5 (CRMP-5) IgG is an antibody generally associated with small-cell lung cancer, which is known to cause paraneoplastic neurological syndromes, including encephalitis, myelitis and neuropathy. HIV escape is a phenomenon in which a patient with low or undetectable levels of HIV RNA in plasma is found to have elevated levels in cerebrospinal fluid (CSF). We present a case of a 58-year-old HIV-positive woman with undetectable plasma viral load who developed a subacute flaccid paraparesis. Over the course of 4 months, she had a broad inflammatory and infectious workup that was unrevealing until repeat imaging showed an inflammatory myelitis. Workup was notable for elevated HIV RNA copies in CSF, as well as anti-CRMP-5 autoantibodies in serum. Despite changing her antiretroviral therapy and multiple modalities of immunomodulation, the patient failed to respond adequately to treatment. This case illustrates a complex clinical picture with a unique presentation of anti-CRMP-5 myelitis.


Asunto(s)
Sistema Nervioso Central/virología , Infecciones por VIH/líquido cefalorraquídeo , Hidrolasas/inmunología , Proteínas Asociadas a Microtúbulos/inmunología , Mielitis/inmunología , Antirretrovirales/uso terapéutico , Autoanticuerpos/sangre , Femenino , VIH/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , Inmunoglobulina G/sangre , Persona de Mediana Edad , Mielitis/tratamiento farmacológico , Mielitis/virología , ARN Viral/líquido cefalorraquídeo , Resultado del Tratamiento
4.
Neurology ; 92(18): e2118-e2126, 2019 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-30413631

RESUMEN

OBJECTIVE: To determine the safety, tolerability, and efficacy of fluoxetine for proven or presumptive enterovirus (EV) D68-associated acute flaccid myelitis (AFM). METHODS: A multicenter cohort study of US patients with AFM in 2015-2016 compared serious adverse events (SAEs), adverse effects, and outcomes between fluoxetine-treated patients and untreated controls. Fluoxetine was administered at the discretion of treating providers with data gathered retrospectively. The primary outcome was change in summative limb strength score (SLSS; sum of Medical Research Council strength in all 4 limbs, ranging from 20 [normal strength] to 0 [complete quadriparesis]) between initial examination and latest follow-up, with increased SLSS reflecting improvement and decreased SLSS reflecting worsened strength. RESULTS: Fifty-six patients with AFM from 12 centers met study criteria. Among 30 patients exposed to fluoxetine, no SAEs were reported and adverse effect rates were similar to unexposed patients (47% vs 65%, p = 0.16). The 28 patients treated with >1 dose of fluoxetine were more likely to have EV-D68 identified (57.1% vs 14.3%, p < 0.001). Their SLSS was similar at initial examination (mean SLSS 12.9 vs 14.3, p = 0.31) but lower at nadir (mean SLSS 9.25 vs 12.82, p = 0.02) and latest follow-up (mean SLSS 12.5 vs 16.4, p = 0.005) compared with the 28 patients receiving 1 (n = 2) or no (n = 26) doses. In propensity-adjusted analysis, SLSS from initial examination to latest follow-up decreased by 0.2 (95% confidence interval [CI] -1.8 to +1.4) in fluoxetine-treated patients and increased by 2.5 (95% CI +0.7 to +4.4) in untreated patients (p = 0.015). CONCLUSION: Fluoxetine was well-tolerated. Fluoxetine was preferentially given to patients with AFM with EV-D68 identified and more severe paralysis at nadir, who ultimately had poorer long-term outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with EV-D68-associated AFM, fluoxetine is well-tolerated and not associated with improved neurologic outcomes.


Asunto(s)
Antivirales/uso terapéutico , Enfermedades Virales del Sistema Nervioso Central/tratamiento farmacológico , Fluoxetina/uso terapéutico , Mielitis/tratamiento farmacológico , Enfermedades Neuromusculares/tratamiento farmacológico , Niño , Preescolar , Femenino , Fluoxetina/administración & dosificación , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
5.
PM R ; 9(1): 63-75, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27317916

RESUMEN

Pain after stroke is commonly reported but often incompletely managed, which prevents optimal recovery. This situation occurs in part because of the esoteric nature of poststroke pain and its limited presence in current discussions of stroke management. The major specific afflictions that affect patients with stroke who experience pain include central poststroke pain, complex regional pain syndrome, and pain associated with spasticity and shoulder subluxation. Each disorder carries its own intricacies that require specific approaches to treatment and understanding. This review aims to present and clarify the major pain syndromes that affect patients who have experienced a stroke in order to aid in their diagnosis and treatment.


Asunto(s)
Dolor Crónico/etiología , Síndromes de Dolor Regional Complejo/etiología , Dolor de Hombro/etiología , Accidente Cerebrovascular/complicaciones , Dolor Crónico/fisiopatología , Síndromes de Dolor Regional Complejo/fisiopatología , Humanos , Espasticidad Muscular/etiología , Espasticidad Muscular/fisiopatología , Dimensión del Dolor , Dolor de Hombro/fisiopatología , Accidente Cerebrovascular/fisiopatología
6.
J Vis ; 14(9)2014 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-25104829

RESUMEN

Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the brain, influencing neural development, plasticity, and repair (Chen et al., 2004; Thoenen, 1995). The BDNF gene contains a single-nucleotide polymorphism (SNP) called Val(66)Met. The Met allele interferes with intracellular BDNF-trafficking, decreases activity-dependent BDNF secretion, and consequently is often associated with a shift from plasticity to stability in neural circuits (Egan et al., 2003). We investigated the behavioral consequences of the presence of the Met allele by comparing how 40 heterozygous subjects with the Val/Met genotype and 35 homozygous subjects with the Val/Val genotype performed on visuomotor tasks (reaching and navigation) under two conditions: normal vision and completely left-right reversed vision. As expected, subjects did not differ in their short-term ability to learn the tasks with normal vision (p = 0.58). Intuitively, it would be expected that homozygous Val/Val subjects with a propensity for greater BDNF-induced activity-dependent plasticity would learn new tasks more quickly than heterozygous Val/Met subjects with decreased BDNF secretion (Gilbert, Li, & Piech, 2009). However, we found the opposite here. When short-term mechanisms of visuomotor adaptation were engaged to compensate for the misalignment of visual and somatomotor information created by the left-right reversal of vision, heterozygous Val/Met subjects learned significantly more quickly than their homozygous Val/Val counterparts (p = 0.027). Our results demonstrate the paradoxical finding that the presence of the Met allele, which is thought to promote cortical stability, here improves immediate visuomotor adaptation to left-right-reversed visual input.


Asunto(s)
Adaptación Ocular/genética , Factor Neurotrófico Derivado del Encéfalo/genética , Anteojos , Reconocimiento Visual de Modelos/fisiología , Polimorfismo de Nucleótido Simple , Desempeño Psicomotor/fisiología , Adolescente , Adulto , Alelos , Cromatografía Líquida de Alta Presión , Femenino , Lateralidad Funcional/fisiología , Genotipo , Humanos , Aprendizaje/fisiología , Masculino , Plasticidad Neuronal/fisiología , Reacción en Cadena de la Polimerasa , Visión Binocular/genética , Vías Visuales/fisiología , Adulto Joven
7.
J Neurosci ; 31(17): 6392-7, 2011 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-21525279

RESUMEN

Aquaporin-4 (AQP4) is the major water channel in the CNS and is primarily expressed in astrocytes. Little is known about the potential for AQP4 to influence synaptic plasticity, although many studies have shown that it regulates the response of the CNS to injury. Therefore, we evaluated long-term potentiation (LTP) and long-term depression (LTD) in AQP4 knock-out (KO) and wild-type mice. KO mice exhibited a selective defect in LTP and LTD without a change in basal transmission or short-term plasticity. Interestingly, the impairment in LTP in KO mice was specific for the type of LTP that depends on the neurotrophin BDNF, which is induced by stimulation at theta rhythm [theta-burst stimulation (TBS)-LTP], but there was no impairment in a form of LTP that is BDNF independent, induced by high-frequency stimulation. LTD was also impaired in KO mice, which was rescued by a scavenger of BDNF or blockade of Trk receptors. TrkB receptors, which mediate effects of BDNF on TBS-LTP, were not altered in KO mice, but p75NTR, the receptor that binds all neurotrophins and has been implicated in some types of LTD, was decreased. The KO mice also exhibited a cognitive defect, which suggests a new role for AQP4 and astrocytes in normal cognitive function. This defect was evident using a test for location-specific object memory but not Morris water maze or contextual fear conditioning. The results suggest that AQP4 channels in astrocytes play an unanticipated role in neurotrophin-dependent plasticity and influence behavior.


Asunto(s)
Acuaporina 4/deficiencia , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Trastornos de la Memoria , Neuroglía/metabolismo , Plasticidad Neuronal/fisiología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/genética , Potenciales de Acción/fisiología , Animales , Biofisica/métodos , Carbazoles/farmacología , Distribución de Chi-Cuadrado , Modelos Animales de Enfermedad , Estimulación Eléctrica/métodos , Inhibidores Enzimáticos/farmacología , Inmunoprecipitación , Técnicas In Vitro , Alcaloides Indólicos/farmacología , Depresión Sináptica a Largo Plazo/genética , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Trastornos de la Memoria/genética , Trastornos de la Memoria/patología , Trastornos de la Memoria/fisiopatología , Ratones , Ratones Noqueados , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/genética , Técnicas de Placa-Clamp , Receptor trkB/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA