Depression may negatively affect the change in freezing of gait following subthalamic nucleus stimulation in Parkinson's disease.

To assess the influence of preoperative depression on the change in freezing of gait (FOG) following subthalamic nucleus stimulation (STN-DBS) in patients with Parkinson's disease (PD). One hundred and twelve PD patients were included who received bilateral STN-DBS. Of these, 33 had no preoperative depression (PD-ND) and the other 79 had preoperative depression (PD-D). Each PD-ND patient was matched with one PD-D patient by the propensity score for which sex, age at PD onset, disease duration, UPDRS-III score during off-medication state, levodopa-equivalent daily dose, and mini mental state examination were the independent variables. We compared both a FOG-questionnaire (FOG-Q) and the axial score from UPDRS-III between the two groups over 12-month follow-up. During the off-medication state, FOG-Q at 12-month was decreased with STN-DBS in both PD-ND (-52.9%, p < 0.001) and PD-D (-24.2%, p < 0.001) with a significant difference in the change of FOG in favor of PD-ND (p = 0.001). Similarly, there was an improvement in the axial score for both PD-ND (-66.1%, p < 0.001) and PD-D (-45.3%, p < 0.001) at 12-month with a significant difference between the groups. (p = 0.005). During the on-medication state, both the FOG-Q and axial score at 12-month were not improved with STN-DBS in the PD-ND and PD-D with no difference between the groups. Our findings suggest that preoperative depression negatively affects the outcome of FOG following STN-DBS in the off-medication state but not in the on-medication state.

Kim R ，Kim HJ ，Kim A ，Kim Y ，Kim AR ，Shin CW ，Paek SH ，Jeon B ... -  《-》

Long-term effect of subthalamic nucleus deep brain stimulation on freezing of gait in Parkinson's disease.

Kim R ，Kim HJ ，Shin C ，Park H ，Kim A ，Paek SH ，Jeon B ... -  《-》

Effects of deep brain stimulation of the subthalamic nucleus on freezing of gait in Parkinson's disease: a prospective controlled study.

Freezing of gait (FOG) is a debilitating gait disorder in Parkinson's disease (PD) with partial responsiveness to dopaminergic medication. To date, notions about the effects of subthalamic deep brain stimulation (STN-DBS) on FOG remain controversial. To compare the effects of bilateral STN-DBS and continued best medical treatment (BMT) on FOG occurrence, FOG severity and clinical outcomes in PD patients at 6 and 12 months follow-up. In this prospective, controlled study, 41 PD patients with at least 5 years disease duration participated. Twenty-four subjects (20 with FOG) were treated with STN-DBS and seventeen (15 with FOG) continued BMT. The primary outcome was the New Freezing of Gait Questionnaire (NFOGQ) at 6 months postsurgery. Other outcomes were the NFOGQ at 12 months and clinical outcomes (Unified Parkinson's Disease Rating Scale III (UPDRS III), timed gait, falls and quality of life) at both time points. STN-DBS increased the likelihood to convert from being a freezer to a non-freezer at 6 and 12 months follow-up (relative risk reduction=0.4). However, 45% of baseline freezers still experienced FOG 6 and 12 months postsurgery although with reduced severity. Three baseline non-freezers (1/2 BMT-treated, 2/4 STN-DBS-treated) developed FOG during follow-up. STN-DBS-induced benefits on FOG were mostly mediated by baseline levodopa equivalent dose, altered medication-intake and reduced motor fluctuations. In contrast to continued BMT, STN-DBS reduced FOG occurrence and severity at 6 months postsurgery with largely sustained effects at 12 months follow-up. Longer follow-up periods are needed to test whether FOG improvements after STN-DBS persist with disease progression.

Vercruysse S ，Vandenberghe W ，Münks L ，Nuttin B ，Devos H ，Nieuwboer A ... -  《-》

Effect of high-frequency subthalamic neurostimulation on gait and freezing of gait in Parkinson's disease: a systematic review and meta-analysis.

The aim of this meta-analysis was to summarize the short- and long-term effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on gait and freezing of gait (FOG) in Parkinson's disease and to detect predictors of post-stimulation outcome. A comprehensive review of the literature was conducted up to October 2015 using Medline Ovid databases for studies analyzing the effect of bilateral STN-DBS on FOG and/or gait. Sixteen studies with available data for the gait item (no. 29) of the Unified Parkinson's Disease Rating Scale (UPDRS) and six studies with the FOG item (no. 14) were included. Data were summarized for the following follow-up periods: 6-15, 24-48 and >48 months. For the medication (Med)-Off/stimulation(Stim)-On condition compared with baseline Med-Off, STN-DBS significantly improved gait on average from 2.43 to 0.96, 2.53 to 1.31 and 2.56 to 1.40 points at 6-15, 24-48 and >48 months, respectively (P < 0.05). Pre-operative levodopa responsiveness of UPDRS-III and Med-Off severity of gait were the predictors of this beneficial effect. STN-DBS significantly improved FOG for the Med-Off/Stim-On condition compared with baseline on average from 2.26 to 0.82, 2.43 to 1.13 and 2.48 to 1.38 points at 6-15, 24-48 and >48 months, respectively (P < 0.05). There was no significant effect in the Med-On/Stim-On condition. This meta-analysis showed a robust improvement of gait and FOG by STN-DBS for more than 4 years in the Med-Off/Stim-On condition. No beneficial effect was found for the On state of medication. Pre-operative levodopa responsiveness of global motor performance (UPDRS-III) is the strongest predictor of the effect of deep brain stimulation on gait.

Schlenstedt C ，Shalash A ，Muthuraman M ，Falk D ，Witt K ，Deuschl G ... -  《-》

Asymmetric STN DBS for FOG in Parkinson's disease: A pilot trial.

In Parkinson's disease (PD), freezing of gait (FOG) is a highly disabling gait disorder. Though deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficient treatment for advanced PD, the management of STN DBS refractory FOG remains challenging. To evaluate the long-term impact on FOG of unilateral stimulation reduction in PD treated with bilateral STN DBS. Patients with bilateral STN DBS for at least one year and refractory FOG were included in a randomized, double blind, cross-over clinical trial. They were randomized to chronic (CHR) vs. experimental (EXP) stimulation (30% amplitude reduction contralateral to the least affected body side), each condition for 4 weeks. Gait and FOG were assessed both in the OFF and ON medication conditions. Primary outcome was the difference in the FOG percentage during gait assessment and in a composite gait score in CHR vs. EXP stimulation. The study was stopped early for futility. Of the 12 patients included, eight dropped out because of re-emerging of PD symptoms. In the four patients who sustained the experimental condition, the FOG percentage did not improve, whether in the OFF (CHR: 13.4% vs. EXP: 16.8%) or in the ON (CHR: 19.5% vs. EXP: 19.8%) medication condition. There was no change in the composite gait score (CHR: 5.5 ± 1.3 vs. EXP: 6.3 ± 3.3). Most patients did not tolerate the unilateral amplitude reduction of STN DBS in the long-term. Moreover, this strategy failed to improve FOG in patients who could sustain the procedure. CLINICALTRIAL. NCT02704195.

Meoni S ，Debȗ B ，Pelissier P ，Scelzo E ，Castrioto A ，Seigneuret E ，Chabardes S ，Fraix V ，Moro E ... -  《-》