Differential effects of levodopa and subthalamic nucleus deep brain stimulation on bradykinesia in Parkinson's disease.

Cardinal symptoms of Parkinson's disease (PD) respond well to treatment with levodopa and deep brain stimulation (DBS) of the subthalamic nucleus (STN). However, it has remained unclear whether levodopa and STN-DBS have differential effects on bradykinesia. We investigated 8 PD-patients with STN-electrodes in four conditions: STN-DBS and levodopa (ON(MED)/ON(STIM)), STN-DBS only (OFF(MED)/ON(STIM)), levodopa only (ON(MED)/OFF(STIM)), without STN-DBS/levodopa (OFF(MED)/OFF(STIM)). Fourteen volunteers served as controls. Subjects performed fastest possible (1) pronation/supination of the forearm (diadochokinesia) and (2) flexion and extension of the index finger (finger movements). Movements were recorded using a 3D-ultrasound-system. Maximum frequency, amplitude, and smoothness of movements were determined. During OFF(MED)/OFF(STIM), all parameters were worser than in all other conditions. In proximal diadochokinesia, OFF(MED)/ON(STIM) significantly improved the amplitude and frequency, whereas ON(MED)/OFF(STIM) had no significant effect. In contrast, we found a stronger effect of levodopa (ON(MED)/OFF(STIM)) on amplitudes of distal finger movement than on amplitudes of diadochokinesia. Combination of treatments during ON(MED)/ON(STIM) further improved both movements. However, maximum frequency remained lower in PD-patients during ON(MED)/ON(STIM) compared with controls. This study demonstrates a better effect of levodopa on distal finger movements and STN-DBS on proximal diadochokinesia. Furthermore, a complementary effect of both therapies on brain areas involved in bradykinesia can be assumed.

Timmermann L ，Braun M ，Groiss S ，Wojtecki L ，Ostrowski S ，Krause H ，Pollok B ，Südmeyer M ，Ploner M ，Gross J ，Maarouf M ，Voges J ，Sturm V ，Schnitzler A ... -  《-》

Field H1 of Forel vs Subthalamic Nucleus Electrical Stimulation in Parkinson's Disease: Long-term Effects on Motor Symptoms and Quality of Life.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) relieves motor symptoms, including levodopa-responsive gait disorders in Parkinson's disease (PD). Traditionally, STN-DBS is not indicated to treat severe, clinically resistant axial symptoms. In this scenario, field H1 of Forel (FF) stimulation (FF-DBS) is likely a feasible option, given it improves motor symptoms, including freezing of gait (FOG), as shown by a short-term study. However, no data are available about the long-term effects of this therapy. Finally, no study has compared the long-term effects of FF and STN-DBS. We report the long-term outcome (>five years) of bilateral FF-DBS in patients with PD. We also compare the effects of FF-DBS and STN-DBS on motor symptoms, cognition, and quality of life. We studied 22 patients (ten with FF-DBS and 12 with STN-DBS). Motor symptoms, cognition, quality of life, and gait symptoms were assessed using the motor part of the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS III), the Mattis Dementia Rating Scale, the 39-item PD quality of life (PDQ-39), and the FOG questionnaire (FOG score) respectively. The levodopa equivalent daily dose was recorded. Comparisons of the FF and STN-DBS results were conducted. The mean follow-up was 6.18 years (95% CI: 5.57-6.78). Compared with the preoperative period, patients with FF had an average reduction of 32.2% in the MDS-UPDRS III scores (p < 0.01), a decrease of 35.3% in the FOG scores (p < 0.01), and an improvement of 25.9% in the PDQ-39 (p < 0.01). There was a 7.5% decrease in cognition (p < 0.01). Levodopa equivalent dose (LED) was reduced by 26.3% (p < 0.01). The STN group had an average reduction of 39.4% in the MDS-UPDRS III scores (p < 0.01), a decrease of 23.7% in the FOG scores (p < 0.01), and an improvement of 33.2% in the PDQ-39 scores (p < 0.01). Cognition decreased by 1.6% (p < 0.01) and LED by 15.06% (p = 0.02). Patients with FF-DBS were older than those with STN-DBS at the time of surgery: 61.2 years and 55.7 years, respectively (p = 0.02), and had longer duration of disease (p = 0.02). Patients with FF-DBS had a greater reduction in FOG (p = 0.02) than did the STN group and presented with a greater decrease in cognition (p < 0.01) after five years. STN-DBS had a greater effect on quality of life. Both FF-DBS and STN-DBS relieved motor symptoms and improved quality of life over a long-term period. Patients with FF-DBS had a higher reduction in both FOG and in LED than did those with STN-DBS. These data support our hypothesis that FF-DBS is a safe and efficient option for treating motor symptoms in PD, including FOG in advanced stages.

Rodrigues JPA ，Rocha MSG ，Laube KAC ，Iglesio R ，Filho PRT ，Freitas JL ，Figueiredo EG ，Carlotti CG Jr ，Soriano DC ，Godinho F ... -  《-》

Effects of the combined treatment of bilateral subthalamic nucleus stimulation and levodopa on balance and mobility in Parkinson's disease.

Nazan ŞE ，Gökçe GGY ，Tanju U ，Sehur ÖS ... -  《-》

Clinical and Brain Morphometry Predictors of Deep Brain Stimulation Outcome in Parkinson's Disease.

Subthalamic deep brain stimulation (STN-DBS) is known to improve motor function in advanced Parkinson's disease (PD) and to enable a reduction of anti-parkinsonian medication. While the levodopa challenge test and disease duration are considered good predictors of STN-DBS outcome, other clinical and neuroanatomical predictors are less established. This study aimed to evaluate, in addition to clinical predictors, the effect of patients' individual brain topography on DBS outcome. The medical records of 35 PD patients were used to analyze DBS outcomes measured with the following scales: Part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III) off medication at baseline, and at 6-months during medication off and stimulation on, use of anti-parkinsonian medication (LED), Abnormal Involuntary Movement Scale (AIMS) and Non-Motor Symptoms Questionnaire (NMS-Quest). Furthermore, preoperative brain MRI images were utilized to analyze the brain morphology in relation to STN-DBS outcome. With STN-DBS, a 44% reduction in the UPDRS-III score and a 43% decrease in the LED were observed (p<0.001). Dyskinesia and non-motor symptoms decreased significantly [median reductions of 78,6% (IQR 45,5%) and 18,4% (IQR 32,2%) respectively, p=0.001 - 0.047]. Along with the levodopa challenge test, patients' age correlated with the observed DBS outcome measured as UPDRS-III improvement (ρ= -0.466 - -0.521, p<0.005). Patients with greater LED decline had lower grey matter volumes in left superior medial frontal gyrus, in supplementary motor area and cingulum bilaterally. Additionally, patients with greater UPDRS-III score improvement had lower grey matter volume in similar grey matter areas. These findings remained significant when adjusted for sex, age, baseline LED and UPDRS scores respectively and for total intracranial volume (p=0.0041- 0.001). However, only the LED decrease finding remained significant when the analyses were further controlled for stimulation amplitude. It appears that along with the clinical predictors of STN-DBS outcome, individual patient topographic differences may influence DBS outcome. Clinical Trial Registration Number: NCT06095245, registration date October 23, 2023, retrospectively registered.

Koivu M ，Sihvonen AJ ，Eerola-Rautio J ，Pauls KAM ，Resendiz-Nieves J ，Vartiainen N ，Kivisaari R ，Scheperjans F ，Pekkonen E ... -  《-》

Detailed investigation of the levodopa response rates in distinct motor subscores in Parkinson's disease patients with and without STN-DBS.

Onder H ，Oksuz M ，Comoglu S 《-》