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OBJECTIVE: This study was undertaken to identify preoperative predictive factors of long-term motor outcome in a large cohort of consecutive Parkinson disease (PD) patients with bilateral subthalamic nucleus deep brain stimulation (STN-DBS). METHODS: All consecutive PD patients who underwent bilateral STN-DBS at the Grenoble University Hospital (France) from 1993 to 2015 were evaluated before surgery, at 1 year (short-term), and in the long term after surgery. All available demographic variables, neuroimaging data, and clinical characteristics were collected. Preoperative predictors of long-term motor outcome were investigated by performing survival and univariate/multivariate Cox regression analyses. Loss of motor benefit from stimulation in the long term was defined as a reduction of less than 25% in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III scores compared to the baseline off-medication scores. As a secondary objective, potential predictors of short-term motor outcome after STN-DBS were assessed by performing univariate and multivariate linear regression analyses. RESULTS: In the long-term analyses (mean follow-up = 8.4 ± 6.26 years, median = 10 years, range = 1-17 years), 138 patients were included. Preoperative higher frontal score and off-medication MDS-UPDRS part III scores predicted a better long-term motor response to stimulation, whereas the presence of vascular changes on neuroimaging predicted a worse motor outcome. In 357 patients with available 1-year follow-up, preoperative levodopa response, tremor dominant phenotype, baseline frontal score, and off-medication MDS-UPDRS part III scores predicted the short-term motor outcome. INTERPRETATION: Frontal lobe dysfunction, disease severity in the off-medication condition, and the presence of vascular changes on neuroimaging represent the main preoperative clinical predictors of long-term motor STN-DBS effects. ANN NEUROL 2021;89:587-597.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson/terapia , Núcleo Subtalámico , Adulto , Anciano , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/epidemiología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/psicología , Función Ejecutiva , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pruebas Neuropsicológicas , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Pronóstico , Modelos de Riesgos Proporcionales , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: In most centers, the surgery of deep brain stimulation (DBS) is performed using a stereotactic frame. Compared with frame-based technique, frameless stereotaxy reduces the duration of surgical procedure and patient's discomfort, with lead placing accuracy equivalent after the learning curve. Although several studies have investigated the targeting accuracy of this technique, only a few studies reported clinical outcomes, with data of short-term follow-up. OBJECTIVE: To assess clinical efficacy and safety of frameless bilateral subthalamic nucleus (STN) DBS in Parkinson's disease (PD) patients at 1- and 3-year follow-up. METHODS: Consecutive PD patients who underwent bilateral STN-DBS with a manual adjustable frameless system were included in the study. The data were collected retrospectively. RESULTS: Eighteen PD patients underwent bilateral STN-DBS implant and were included in the study. All patients completed 1-year observation and ten of them completed 3-year observation. At 1-year follow-up, motor efficacy of STN stimulation in off-med condition was of 30.1% (P = 0.003) and at 3-year follow-up was of 36.3%, compared with off-stim condition at 3-year follow-up (P = 0.005). Dopaminergic drugs were significantly reduced by 31.2% 1 year after the intervention (P = 0.003) and 31.7% 3 years after the intervention (P = 0.04). No serious adverse events occurred during surgery. CONCLUSIONS: Frameless stereotaxy is an effective and safe technique for DBS surgery at 1- and 3-year follow-up, with great advantages for patients' discomfort during surgery.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Humanos , Neuronavegación , Enfermedad de Parkinson/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Previous investigations have reported on the motor benefits and safety of chronic extradural motor cortex stimulation (EMCS) for patients with Parkinson's disease (PD), but studies addressing the long-term clinical outcome are still lacking. In this study, nine consecutive PD patients who underwent EMCS were prospectively recruited, with a mean follow-up time of 5.1 ± 2.5 years. As compared to the preoperatory baseline, the Unified Parkinson's Disease Rating Scale (UPDRS)-III in the off-medication condition significantly decreased by 13.8% at 12 months, 16.1% at 18 months, 18.4% at 24 months, 21% at 36 months, 15.6% at 60 months, and 8.6% at 72 months. The UPDRS-IV decreased by 30.8% at 12 months, 22.1% at 24 months, 25% at 60 months, and 36.5% at 72 months. Dopaminergic therapy showed a progressive reduction, significant at 60 months (11.8%). Quality of life improved by 18.0% at 12 months, and 22.4% at 60 months. No surgical complication, cognitive or behavioral change occurred. The only adverse event reported was an infection of the implantable pulse generator pocket. Even in the long-term follow-up, EMCS was shown to be a safe and effective treatment option in PD patients, resulting in improvements in motor symptoms and quality of life, and reductions in motor complications and dopaminergic therapy.
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OBJECTIVE: To evaluate the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson disease (PD) patients on motor complications beyond 15 years after surgery. METHODS: Data about motor complications, quality of life (QoL), activities of daily living, the UPDRS motor scores, dopaminergic treatment, stimulation parameters, and side effects of STN-DBS were retrospectively retrieved and compared between before surgery, at 1 year and beyond 15 years after bilateral STN-DBS. RESULTS: Fifty-one patients with 17.06 ± 2.18 years STN-DBS follow-up were recruited. Compared to baseline, the time spent with dyskinesia and the time spent in the off state were reduced by 75% (p<0.001) and by 58.7% (p<0.001), respectively. Moreover, dopaminergic drugs were reduced by 50.6% (p<0.001). The PDQL total score, and the emotional function and social function domains improved of 13.8% (p=0.005), 13.6% (p=0.01) and 29.9% (p<0.001), respectively. Few and mostly manageable device-related adverse events were observed during the follow-up. CONCLUSIONS: STN-DBS is still effective beyond 15 years from the intervention, notably with significant improvement in motor complications and stable reduction of dopaminergic drugs. Furthermore, despite the natural continuous progression of PD with worsening of levodopa-resistant motor and non-motor symptoms over the years, STN-DBS patients could maintain an improvement in QoL. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, for patients with PD, STN-DBS remains effective at treating motor complications 15 years after surgery.
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INTRODUCTION AND OBJECTIVES: In recent years, Botulinum Toxin has been shown to be efficacious and safe in the treatment of sialorrhea, but scanty data are available on its long term use. The aim of this study was to investigate adverse events, discriminate differences in safety, and evaluate the efficacy of long-term use of both abobotulinumtoxinA and rimabotulinumtoxinB ultrasound-guided injections for sialorrhea in a retrospective trial. Moreover we review the literature on this topic. PATIENTS AND METHODS: Consecutive patients with severe sialorrhea and receiving at least two ultrasound-guided intrasalivary glands abobotulinumtoxinA 250 U or rimabotulinumtoxinB 2500 U injections were included. Clinical and demographic data were collected. Safety and tolerability were assessed on the basis of patients' self-reports. Efficacy was assessed by recording the duration of benefit and by the Drooling Severity Scale and Drooling Frequency Scale 4 weeks after intervention. A review of literature was performed using 'Botulinum Toxin' and/or 'drooling' and/or 'sialorrhea' and/or 'hypersalivation' as keywords. RESULTS: Sixty-five patients (32 Amyotrophic Lateral Sclerosis and 33 Parkinson's Disease) were treated in a total of 317 sessions (181 rimabotulinumtoxinB and 136 abobotulinumtoxinA). Both serotypes induced a clear-cut benefit in 89% of injections. Mean benefit duration was 87 days (range 30-240), similar for abobotulinumtoxinA and rimabotulinumtoxinB but significantly shorter in Amyotrophic Lateral Sclerosis group compared to Parkinson's Disease (p < 0.001). Older age was positively correlated to benefit duration (p = 0.003). Botulinum Toxin-related and injection-related side effects complicated respectively 8,2% and 1,5% of treatments. The only Botulinum Toxin-related adverse event was a change of saliva thickness, mostly rated mild to moderate and more frequent in Amyotrophic Lateral Sclerosis patients (p = NS). CONCLUSIONS: Both 250 U abobotulinumtoxinA and 2500 U rimabotulinumtoxinB administered by ultrasound-guided intrasalivary gland injection are safe and effective in treating sialorrhea, even in long-term follow-up. Older age is significantly associated with longer benefit duration. Parkinson's Disease patients showed a more favorable safety-efficacy ratio than did Amyotrophic Lateral Sclerosis patients, due to lower adverse events (p = NS) and longer benefit duration (p < 0.001).