Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-35896379

RESUMO

BACKGROUND: Valosin-containing protein (VCP) disease, caused by mutations in the VCP gene, results in myopathy, Paget's disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype-phenotype correlation data are limited. This study characterises patients with mutations in VCP gene and investigates genotype-phenotype correlations. METHODS: Descriptive retrospective international study collecting clinical and genetic data of patients with mutations in the VCP gene. RESULTS: Two hundred and fifty-five patients (70.0% males) were included in the study. Mean age was 56.8±9.6 years and mean age of onset 45.6±9.3 years. Mean diagnostic delay was 7.7±6 years. Symmetric lower limb weakness was reported in 50% at onset progressing to generalised muscle weakness. Other common symptoms were ventilatory insufficiency 40.3%, PDB 28.2%, dysautonomia 21.4% and FTD 14.3%. Fifty-seven genetic variants were identified, 18 of these no previously reported. c.464G>A (p.Arg155His) was the most frequent variant, identified in the 28%. Full time wheelchair users accounted for 19.1% with a median time from disease onset to been wheelchair user of 8.5 years. Variant c.463C>T (p.Arg155Cys) showed an earlier onset (37.8±7.6 year) and a higher frequency of axial and upper limb weakness, scapular winging and cognitive impairment. Forced vital capacity (FVC) below 50% was as risk factor for being full-time wheelchair user, while FVC <70% and being a full-time wheelchair user were associated with death. CONCLUSION: This study expands the knowledge on the phenotypic presentation, natural history, genotype-phenotype correlations and risk factors for disease progression of VCP disease and is useful to improve the care provided to patient with this complex disease.

2.
Muscle Nerve ; 63(4): 572-576, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33428242

RESUMO

INTRODUCTION: We utilized the Pooled Resource Open-Access Clinical Trials (PRO-ACT) database to investigate whether melatonin use among patients with amyotrophic lateral sclerosis (ALS) was associated with slower disease progression and prolonged survival. METHODS: This retrospective analysis of the PRO-ACT database addresses the impact of melatonin on progression and overall survival of ALS. A Cox proportional hazards ratio model was performed to investigate the effect that melatonin had on time to death. For secondary outcome measures, linear mixed effects regression models were used to ascertain the effect of melatonin on change in standardized ALS Functional Rating Scale (sALSFRS) and percentage predicted forced vital capacity (FVC) scores. RESULTS: Melatonin users had a significantly decreased annualized hazard death rate compared with the non-melatonin users (hazard ratio, 0.241; 95% confidence interval, 0.088-0.659; P = .0056). The melatonin users also had a slower rate of decline in sALSFRS score (t = 2.71; P = .0069) and change in percent predicted FVC score (t = 2.94; P = .0035) compared with the non-melatonin users. DISCUSSION: Our findings suggest that melatonin may be beneficial for patients with ALS. Due to the nature of this database, our results are solely intended to be hypothesis-generating and no strong associations can be made. Given the low cost and favorable safety profile of melatonin, the hypotheses generated warrant further investigation.


Assuntos
Esclerose Lateral Amiotrófica/tratamento farmacológico , Progressão da Doença , Melatonina/farmacologia , Insuficiência Respiratória/tratamento farmacológico , Adulto , Esclerose Lateral Amiotrófica/fisiopatologia , Bases de Dados Factuais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/complicações , Estudos Retrospectivos , Fatores de Tempo
3.
medRxiv ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38826433

RESUMO

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder where progressive neuron loss is driven by impaired brain bioenergetics, particularly mitochondrial dysfunction and disrupted cellular respiration. Terazosin (TZ), an α-1 adrenergic receptor antagonist with a known efficacy in treating benign prostatic hypertrophy and hypertension, has shown potential in addressing energy metabolism deficits associated with PD due to its action on phosphoglycerate kinase 1 (PGK1). This study aimed to investigate the safety, tolerability, bioenergetic target engagement, and optimal dose of TZ in neurologically healthy subjects. Methods: Eighteen healthy men and women (60 - 85 years old) were stratified into two cohorts based on maximum TZ dosages (5 mg and 10 mg daily). Methods included plasma and cerebrospinal fluid TZ concentration measurements, whole blood ATP levels, 31 Phosphorous magnetic resonance spectroscopy for brain ATP levels, 18 F-FDG PET imaging for cerebral metabolic activity, and plasma metabolomics. Results: Our results indicated that a 5 mg/day dose of TZ significantly increased whole blood ATP levels and reduced global cerebral 18 F-FDG PET uptake without significant side effects or orthostatic hypotension. These effects were consistent across sexes. Higher doses did not result in additional benefits and showed a potential biphasic dose-response. Conclusions: TZ at a dosage of 5 mg/day engages its metabolic targets effectively in both sexes without inducing significant adverse effects and provides a promising therapeutic avenue for mitigating energetic deficiencies. Further investigation via clinical trials to validate TZ's efficacy and safety in neurodegenerative (i.e., PD) contexts is warranted.

4.
W V Med J ; 109(1): 16-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23413542

RESUMO

Laparoscopic adjustable gastric banding is being increasingly utilized for therapy of obesity in the United States. It is a relatively newer technique and little is known about neurologic complications resulting from this procedure. We present a case of disabling peripheral neuropathy occurring after gastric banding. While this type of complication has seen following older weight loss techniques, it has only rarely been documented following adjustable gastric banding. The patient was treated with adjustment of the lap band in combination with plasmapheresis. Plasmapheresis is a novel therapy for treatment of this type of neuropathy and resulted in significant improvement in the patients' strength and functioning.


Assuntos
Gastroplastia/efeitos adversos , Obesidade/cirurgia , Doenças do Sistema Nervoso Periférico/terapia , Plasmaferese , Adulto , Anti-Inflamatórios/uso terapêutico , Feminino , Humanos , Laparoscopia , Limitação da Mobilidade , Debilidade Muscular/etiologia , Doenças do Sistema Nervoso Periférico/etiologia , Prednisona/uso terapêutico
6.
Curr Cardiol Rev ; 18(2): e040821195265, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34348632

RESUMO

Implantable Cardioverter-Defibrillator (ICD) therapy is indicated for patients at risk for sudden cardiac death due to ventricular tachyarrhythmia. The most commonly used risk stratification algorithms use Left Ventricular Ejection Fraction (LVEF) to determine which patients qualify for ICD therapy, even though LVEF is a better marker of total mortality than ventricular tachyarrhythmias mortality. This review evaluates imaging tools and novel biomarkers proposed for better risk stratifying arrhythmic substrate, thereby identifying optimal ICD therapy candidates.


Assuntos
Cardiomiopatia Dilatada , Desfibriladores Implantáveis , Taquicardia Ventricular , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/terapia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Humanos , Medição de Risco/métodos , Fatores de Risco , Volume Sistólico , Taquicardia Ventricular/complicações , Taquicardia Ventricular/terapia , Função Ventricular Esquerda
7.
Muscle Nerve ; 41(2): 260-1, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19918777

RESUMO

Thenar atrophy occurs in patients with severe carpal tunnel syndrome (CTS) of long-standing duration. In this report we present a young woman with mild bilateral CTS, based on electrophysiological studies, in whom marked thenar atrophy was on a congenital basis related to the VATER association (vertebral anomalies, anal atresia, tracheoesophageal fistula, and radial or renal abnormalities).


Assuntos
Síndrome do Túnel Carpal/diagnóstico , Mãos , Atrofia Muscular/diagnóstico , Índice de Gravidade de Doença , Adulto , Síndrome do Túnel Carpal/complicações , Anormalidades Congênitas/genética , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Atrofia Muscular/genética
8.
J Peripher Nerv Syst ; 15(3): 216-26, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21040144

RESUMO

We sought to determine the clinical, electrophysiological, neuroimaging, and pathological features of inflammatory pseudotumor of nerve. Five patients were identified. All cases presented with a gradually progressive mononeuropathy with symptoms of weakness, sensory loss, and prominent neuropathic pain. The median duration of symptoms was 7 months (range 3-36 months). Electrophysiological results were in keeping with chronic axonal mononeuropathies with variable findings of active denervation and reinnervation. MRI demonstrated irregular, large masses involving and surrounding nerve with heterogenous signal characteristics on T1- and T2-weighted and post-contrast sequences. Histopathological features of the nerve slightly varied but shared commonalities including chronic inflammatory infiltrates, increased collagen, and increased numbers of microvessels. Axonal degeneration and decreased density of myelinated fibers were also noted. Three patients were treated with weekly courses of intravenous steroids for 3 months. All reported improvement in pain and weakness. Inflammatory pseudotumor of nerve is not a neoplasm and has reactive features of inflammation, increased vascularity, and marked fibrosis. It presents as a progressive axonal mononeuropathy with weakness, sensory loss, and pain that may be episodic. The primary pathophysiology is unknown but the inflammation and response to treatment suggests that there may be an immune component.


Assuntos
Granuloma de Células Plasmáticas/patologia , Granuloma de Células Plasmáticas/terapia , Doenças do Sistema Nervoso Periférico/patologia , Adulto , Antígenos CD/metabolismo , Biópsia/métodos , Progressão da Doença , Eletromiografia/métodos , Feminino , Granuloma de Células Plasmáticas/complicações , Granuloma de Células Plasmáticas/tratamento farmacológico , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/etiologia , Esteroides/uso terapêutico
9.
Arch Neurol ; 63(3): 453-7, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16533976

RESUMO

BACKGROUND: Classic Fabry disease, an X-linked recessive lysosomal storage disease due to the deficient activity of alpha-galactosidase A, typically presents in early childhood with acroparesthesias, angiokeratomas, hypohidrosis, and corneal dystrophy. The neuropathic pain presumably results from glycosphingolipid accumulation in the vascular endothelium and in small-caliber nerve fibers, and is treatable by enzyme replacement therapy. Later-onset variants with residual alpha-galactosidase A activity lack vascular endothelial involvement and classic symptoms, which lead to the development of cardiac and/or renal disease after the fourth decade of life. OBJECTIVE: To expand the later-onset Fabry phenotype to include cramp-fasciculation syndrome without small-fiber neuropathy. METHODS: A 34-year-old man who presented with chronic exercise-induced pain, fasciculations, and cramps of the feet and legs, and his similarly affected mother, were evaluated. Clinical, biochemical, and molecular studies were performed. RESULTS: Clinical evaluation suggested the diagnosis of Fabry disease, which was confirmed by reduced plasma and leukocyte alpha-galactosidase A activities (8.8% and 13.4% of normal, respectively) due to a missense A143T mutation. His mother was heterozygous for the A143T mutation. CONCLUSION: The presentation of cramps and fasciculations without apparent small-fiber neuropathy expands the phenotype of later-onset Fabry disease.


Assuntos
Doença de Fabry/complicações , Doenças Neuromusculares/etiologia , Adulto , Idade de Início , Doença de Fabry/genética , Doença de Fabry/metabolismo , Humanos , Leucócitos/metabolismo , Masculino , Microscopia Eletrônica de Transmissão/métodos , Mutação de Sentido Incorreto , Doenças Neuromusculares/genética , Doenças Neuromusculares/metabolismo , Pele/metabolismo , Pele/patologia , Pele/ultraestrutura , alfa-Galactosidase/genética , alfa-Galactosidase/metabolismo
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa