RESUMO
ALSUntangled reviews alternative and off label treatments with a goal of helping patients make more informed decisions about them. Here we review ketogenic diets. We shows that these have plausible mechanisms, including augmenting cellular energy balance and reducing excitotoxicity, neuroinflammation and oxidative stress. We review a mouse model study, anecdotal reports and trials in ALS and other diseases. We conclude that there is yet not enough data to recommend ketogenic diets for patients with ALS, especially in light of the many side effects these can have.
Assuntos
Esclerose Lateral Amiotrófica , Dieta Cetogênica , Animais , Humanos , Camundongos , Esclerose Lateral Amiotrófica/dietoterapia , Modelos Animais de DoençasRESUMO
Over the past two decades complementary and alternative medicine treatments relying on dubious science have been embraced by medical academia. Despite low to nonexistent prior probability that testing these treatments in randomized clinical trials (RCTs) will be successful, RCTs of these modalities have proliferated, consistent with the principles of evidence-based medicine, which underemphasize prior plausibility rooted in science. We examine this phenomenon and argue that what is needed is science-based medicine rather than evidence-based medicine.
Assuntos
Ensaios Clínicos como Assunto , Medicina Integrativa/métodos , Terapia por Quelação/métodos , Terapias Complementares , Medicina Baseada em Evidências , Homeopatia/métodos , Humanos , Medicina Integrativa/tendências , Ensaios Clínicos Controlados Aleatórios como Assunto , Ciência/tendências , Toque Terapêutico/métodos , Estados UnidosRESUMO
Myasthenia gravis (MG) is an immune-mediated disorder with a variable response to treatment. In this study, patients with refractory MG who were treated with rituximab were identified. A review of patients referred to the Yale Neuromuscular Clinic was performed. Patients with refractory MG who were treated with rituximab were reviewed for response to treatment. Patients who had muscle-specific kinase (MuSK(+)) or acetylcholine receptor (AChR(+)) antibodies were included. Six patients were identified who met the criteria described. All patients tolerated rituximab without side effects and had a reduced need for immunosuppressants and/or improvement in clinical function. Patients with refractory MG appeared to respond to rituximab in this small, retrospective study. This result suggests that a larger, prospective trial is indicated.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Murinos , Inibidores da Colinesterase/uso terapêutico , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Pessoa de Meia-Idade , Miastenia Gravis/imunologia , Prednisona/uso terapêutico , Brometo de Piridostigmina/uso terapêutico , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Estudos Retrospectivos , Rituximab , Resultado do TratamentoRESUMO
We performed a retrospective chart review on 53 muscle-specific kinase antibody (MuSK-Ab)-positive myasthenia gravis (MG) patients at nine university-based centers in the U.S. Of these, 66% were Caucasian, 85% were women, and age of onset was 9-79 years. Twenty-seven patients were nonresponsive to anticholinesterase therapy. Myasthenia Gravis Foundation of America improvement status was achieved in 53% patients on corticosteroids, 51% with plasma exchange, and in 20% on intravenous immunoglobulin (IVIG). Thymectomy was beneficial in 7/18 patients at 3 years. Long-term (> or =3 years) outcome was very favorable in 58% of patients who achieved remission and/or minimal manifestation status. Overall, 73% improved. There was one MG-related death. This survey reinforces several cardinal features of MuSK-Ab-positive MG, including prominent bulbar involvement and anticholinesterase nonresponsiveness. Facial or tongue atrophy was rare. Most patients respond favorably to immunotherapy. The best clinical response was to corticosteroids and plasma exchange, and the poorest response was to IVIG. Long-term outcome is favorable in about 60% of cases.
Assuntos
Miastenia Gravis/imunologia , Miastenia Gravis/terapia , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Adolescente , Adulto , Idade de Início , Idoso , Criança , Intervalo Livre de Doença , Eletromiografia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunoterapia , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Troca Plasmática , Prednisona/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Índice de Gravidade de Doença , Timectomia , Resultado do Tratamento , Estados UnidosRESUMO
OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a devastating, and currently incurable, neuromuscular disease in which oxidative stress and mitochondrial impairment are contributing to neuronal loss. Coenzyme Q10 (CoQ10), an antioxidant and mitochondrial cofactor, has shown promise in ALS transgenic mice, and in clinical trials for neurodegenerative diseases other than ALS. Our aims were to choose between two high doses of CoQ10 for ALS, and to determine if it merits testing in a Phase III clinical trial. METHODS: We designed and implemented a multicenter trial with an adaptive, two-stage, bias-adjusted, randomized, placebo-controlled, double-blind, Phase II design (n = 185). The primary outcome in both stages was a decline in the ALS Functional Rating Scale-revised (ALSFRSr) score over 9 months. Stage 1 (dose selection, 35 participants per group) compared CoQ10 doses of 1,800 and 2,700 mg/day. Stage 2 (futility test, 75 patients per group) compared the dose selected in Stage 1 against placebo. RESULTS: Stage 1 selected the 2,700 mg dose. In Stage 2, the pre-specified primary null hypothesis that this dose is superior to placebo was not rejected. It was rejected, however, in an accompanying prespecified sensitivity test, and further supplementary analyses. Prespecified secondary analyses showed no significant differences between CoQ10 at 2,700 mg/day and placebo. There were no safety concerns. INTERPRETATION: CoQ10 at 2,700 mg daily for 9 months shows insufficient promise to warrant Phase III testing. Given this outcome, the adaptive Phase II design incorporating a dose selection and a futility test avoided the need for a much larger conventional Phase III trial.
Assuntos
Esclerose Lateral Amiotrófica/tratamento farmacológico , Antioxidantes/uso terapêutico , Ubiquinona/análogos & derivados , Esclerose Lateral Amiotrófica/mortalidade , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Ubiquinona/administração & dosagem , Ubiquinona/efeitos adversos , Ubiquinona/uso terapêuticoAssuntos
Síndrome da Imunodeficiência Adquirida/psicologia , Negação em Psicologia , Infecções por HIV/psicologia , Internet , Síndrome da Imunodeficiência Adquirida/etiologia , Atitude Frente a Saúde , Causalidade , Cultura , Infecções por HIV/complicações , Humanos , Disseminação de Informação , Opinião PúblicaRESUMO
BACKGROUND: A 15-year-old boy presented with recurrent episodes of erythema and burning pain in the distal extremities, which he had experienced since early childhood. The episodes were triggered by heat or exertion. His medical history revealed an extensive six-generation family history of similar symptoms. INVESTIGATIONS: Neurological examination, MRI brain scan, electromyography, skin biopsy, laboratory blood testing, and DNA analysis. DIAGNOSIS: Juvenile onset primary erythromelalgia. MANAGEMENT: Genetic counseling, and symptomatic management of neuropathic pain.
Assuntos
Eritromelalgia/genética , Saúde da Família , Neuralgia/genética , Canais de Sódio/genética , Potenciais de Ação/genética , Adolescente , Eletromiografia/métodos , Eritromelalgia/complicações , Eritromelalgia/patologia , Gânglios Espinais/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Mutação , Canal de Sódio Disparado por Voltagem NAV1.7 , Neuralgia/etiologia , Neurônios/fisiologia , Fenilalanina/genética , Valina/genéticaRESUMO
This study investigated the use of fiberoptic endoscopic evaluation of swallowing (FEES) to both diagnose pharyngeal dysphagia and make treatment recommendations in 17 consecutive patients with a new diagnosis of amyotrophic lateral sclerosis (ALS) and complaints of dysphagia. Ten of 17 (59%) patients exhibited pharyngeal dysphagia with aspiration or aspiration risk with clear liquids, i.e., 5 of 8 (63%) limb and 5 of 9 (56%) bulbar. If depth of bolus flow was a problem, thickened liquids and single, small bolus sizes were recommended. If bolus retention was a problem, a small clear liquid bolus after each puree or solid bolus was recommended to aid pharyngeal clearing. Five of 17 (30%) patients required multiple FEES evaluations because of disease progression. For the first time in patients with ALS, FEES was shown to be successful in assessing preswallow anatomy and physiology, diagnosing pharyngeal dysphagia, and providing objective data for appropriate therapeutic interventions to promote safer oral intake. Visual biofeedback provided by FEES was successful for both patient and family education and to investigate individualized therapeutic strategies that, if successful, can be implemented immediately. Serial FEES allows for objective monitoring of dysphagia symptoms and timely implementation of diet changes and/or therapeutic strategies to continue safer oral intake and maintain optimum quality of life.