RESUMEN
OBJECTIVE: Trials for additional or alternative treatments for cervical dystonia (CD) are scarce since the introduction of botulinum neurotoxin (BoNT). We performed the first trial to investigate whether dystonic jerks/tremor in patients with CD respond to the selective serotonin reuptake inhibitor (SSRI) escitalopram. METHODS: In a randomised, double-blind, crossover trial, patients with CD received escitalopram and placebo for 6 weeks. Treatment with BoNT was continued, and scores on rating scales regarding dystonia, psychiatric symptoms and quality of life (QoL) were compared. Primary endpoint was the proportion of patients that improved at least one point on the Clinical Global Impression Scale for jerks/tremor scored by independent physicians with experience in movement disorders. RESULTS: Fifty-threepatients were included. In the escitalopram period, 14/49 patients (29%) improved on severity of jerks/tremor versus 11/48 patients (23%) in the placebo period (P=0.77). There were no significant differences between baseline and after treatment with escitalopram or placebo on severity of dystonia or jerks/tremor. Psychiatric symptoms and QoL improved significantly in both periods compared with baseline. There were no significant differences between treatment with escitalopram and placebo for dystonia, psychiatric or QoL rating scales. During treatment with escitalopram, patients experienced slightly more adverse events, but no serious adverse events occurred. CONCLUSION: In this innovative trial, no add-on effect of escitalopram for treatment of CD with jerks was found on motor or psychiatric symptoms. However, we also did not find a reason to withhold patients treatment with SSRIs for depression and anxiety, which are common in dystonia. TRIAL REGISTRATION NUMBER: NTR2178.
Asunto(s)
Citalopram/uso terapéutico , Trastornos Distónicos/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Tortícolis/tratamiento farmacológico , Temblor/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Estudios Cruzados , Método Doble Ciego , Trastornos Distónicos/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Tortícolis/complicaciones , Resultado del Tratamiento , Temblor/complicacionesRESUMEN
Early-onset Parkinson's disease (EOPD) has been associated with recessive mutations in parkin (PARK2). About half of the mutations found in parkin are genomic rearrangements, i.e., large deletions or duplications. Although many different rearrangements have been found in parkin before, the exact breakpoints involving these rearrangements are rarely mapped. In the present study, the exact breakpoints of 13 different parkin deletions/duplications, detected in 13 patients out of a total screened sample of 116 EOPD patients using Multiple Ligation Probe Amplification (MLPA) analysis, were mapped using real time quantitative polymerase chain reaction (PCR), long-range PCR and sequence analysis. Deletion/duplication-specific PCR tests were developed as a rapid and low cost tool to confirm MLPA results and to test family members or patients with similar parkin deletions/duplications. Besides several different deletions, an exon 3 deletion, an exon 4 deletion and an exon 7 duplication were found in multiple families. Haplotype analysis in four families showed that a common haplotype of 1.2 Mb could be distinguished for the exon 7 duplication and a common haplotype of 6.3 Mb for the deletion of exon 4. These findings suggest common founder effects for distinct large rearrangements in parkin.
Asunto(s)
Exones , Eliminación de Gen , Duplicación de Gen , Mutación , Enfermedad de Parkinson/genética , Ubiquitina-Proteína Ligasas/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Puntos de Rotura del Cromosoma , Mapeo Cromosómico , Análisis Mutacional de ADN , Femenino , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Linaje , Reacción en Cadena de la Polimerasa/métodos , Adulto JovenRESUMEN
Many clinicians regard levodopa as a last resort in the symptomatic treatment of Parkinson's disease. Here we critically review the arguments that are typically used to postpone the start of levodopa for as long as possible. We will point out that most concerns are invalid. Levodopa remains the most effective and best tolerated Parkinson's drug to date, and should have an important role in all therapeutic strategies, both as monotherapy in early Parkinson's disease and as part of combination therapy in advanced disease. Regardless of disease stage, the choice of a particular drug should not be driven by fear of long term complications but by the clinical condition of the patient at the time, with an emphasis on functioning in everyday life and any comorbidity. A 'phobia' for levodopaor, indeed, for any other antiparkinsonian medicationis unacceptable according to current evidence.
Asunto(s)
Dopaminérgicos/administración & dosificación , Dopaminérgicos/efectos adversos , Levodopa/administración & dosificación , Levodopa/efectos adversos , Enfermedad de Parkinson/tratamiento farmacológico , Dopaminérgicos/metabolismo , Resistencia a Medicamentos/fisiología , Discinesia Inducida por Medicamentos/epidemiología , Discinesia Inducida por Medicamentos/prevención & control , Humanos , Levodopa/metabolismoAsunto(s)
Agonistas de Dopamina/efectos adversos , Fibrosis/inducido químicamente , Enfermedades de las Válvulas Cardíacas/inducido químicamente , Pergolida/efectos adversos , Agonistas de Dopamina/uso terapéutico , Ecocardiografía , Fibrosis/epidemiología , Enfermedades de las Válvulas Cardíacas/epidemiología , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Pergolida/uso terapéutico , Factores de RiesgoRESUMEN
The pathophysiology of Parkinson's disease is marked by the loss of dopaminergic neurons, which leads to striatal dopaminergic deficiency. This causes resting tremor, hypokinesia, rigidity, bradykinesia, and loss of postural reflexes. Most current treatments for Parkinson's disease aim to restore striatal dopamine signaling by increasing the supply of dopamine with oral levodopa (L-dopa), stimulating dopamine receptors directly using dopamine agonists, or inhibiting the reuptake of endogenous dopamine. L-dopa is standard therapy for patients with Parkinson's disease. However, with continued treatment and disease progression, the response to oral dopaminergic drugs becomes unstable and motor fluctuations emerge, including off periods and dyskinesia. Direct duodenal-administered infusible L-dopa/carbidopa is effective for the management of refractory motor fluctuations in some patient populations. However, enteral infusions cannot mimic the function of the normal dopaminergic brain, and around-the-clock constant-rate administration carries the risk of causing refractory off periods associated with severe immobility and hyperpyrexia. Subthalamic nucleus (STN) deep brain stimulation (DBS) is also a promising treatment. DBS passes a high-frequency electrical current into the target area, mimicking the effect of lesioning the stimulated area. However, this treatment requires invasive surgery and is appropriate for a limited segment of the patient population. This supplement provides a rationale for the use of continuous dopaminergic receptor stimulation and offers guidelines on the individualization of treatment decisions, with special focus on continuous L-dopa infusion and STN DBS. Erik Wolters, MD, PhD, offers an introduction to the impact of continuous L-dopa infusion. Andrew J. Lees, MD, FRCP, provides an overview of the physiologic response to L-dopa and reviews clinical pharmacologic studies of intravenous and intraduodenal L-dopa. Jens Volkmann, MD, discusses selection criteria for STN DBS and duodenal L-dopa/carbidopa infusion. Teus van Laar, MD, PhD, and Ad Hovestadt, MD, discuss the first data from a Dutch cohort study of duodenal L-dopa/carbidopa.
Asunto(s)
Agonistas de Dopamina/uso terapéutico , Levodopa/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Agonistas de Dopamina/sangre , Vías de Administración de Medicamentos , Humanos , Inyecciones Intravenosas , Levodopa/sangre , Trastornos del Movimiento/epidemiología , Trastornos del Movimiento/prevención & controlRESUMEN
Two older female patients with a history of psychotic depression were treated with a combination of an antipsychotic and an antidepressant. Both developed persistent tardive dyskinesia with severe tongue protrusion. Botulinum toxin was injected into the genioglossal area and the embarrassing tongue protrusion practically disappeared. Both patients chose to continue taking botulinum toxin.