RESUMEN
Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.
Asunto(s)
Enfermedad de Alzheimer/terapia , Núcleo Basal de Meynert/fisiología , Estimulación Encefálica Profunda/métodos , Resultado del Tratamiento , Anciano , Enfermedad de Alzheimer/diagnóstico , Electroencefalografía , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones , Escalas de Valoración Psiquiátrica , Calidad de VidaAsunto(s)
Estimulación Encefálica Profunda/métodos , Dependencia de Heroína/terapia , Núcleo Accumbens , Trastornos Relacionados con Alcohol/complicaciones , Trastornos Relacionados con Alcohol/terapia , Trastornos Relacionados con Anfetaminas/complicaciones , Trastornos Relacionados con Anfetaminas/terapia , Ansiedad/complicaciones , Ansiedad/terapia , Benzodiazepinas , Ensayos Clínicos como Asunto , Depresión/complicaciones , Depresión/terapia , Dependencia de Heroína/complicaciones , Dependencia de Heroína/diagnóstico , Humanos , Proyectos Piloto , Escalas de Valoración Psiquiátrica , Calidad de Vida , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/terapia , Resultado del TratamientoRESUMEN
Owing to a high response rate, deep brain stimulation (DBS) of the ventral striatal area has been approved for treatment-refractory obsessive-compulsive disorder (tr-OCD). Many basic issues regarding DBS for tr-OCD are still not understood, in particular, the mechanisms of action and the origin of side effects. We measured prepulse inhibition (PPI) in treatment-refractory OCD patients undergoing DBS of the nucleus accumbens (NAcc) and matched controls. As PPI has been used in animal DBS studies, it is highly suitable for translational research. Eight patients receiving DBS, eight patients with pharmacological treatment and eight age-matched healthy controls participated in our study. PPI was measured twice in the DBS group: one session with the stimulator switched on and one session with the stimulator switched off. OCD patients in the pharmacologic group took part in a single session. Controls were tested twice, to ensure stability of data. Statistical analysis revealed significant differences between controls and (1) patients with pharmacological treatment and (2) OCD DBS patients when the stimulation was switched off. Switching the stimulator on led to an increase in PPI at a stimulus-onset asynchrony of 200 ms. There was no significant difference in PPI between OCD patients being stimulated and the control group. This study shows that NAcc-DBS leads to an increase in PPI in tr-OCD patients towards a level seen in healthy controls. Assuming that PPI impairments partially reflect the neurobiological substrates of OCD, our results show that DBS of the NAcc may improve sensorimotor gating via correction of dysfunctional neural substrates. Bearing in mind that PPI is based on a complex and multilayered network, our data confirm that DBS most likely takes effect via network modulation.