Disease Duration Differentiates Freezing of Gait Response to Subthalamic and Nigral Stimulation for Parkinson's Disease in an Exploratory Multicenter Controlled Trial.
Freezing of gait (FoG) belongs to most pressing unmet symptoms in the treatment of Parkinson's disease.
To explore whether combined subthalamic and nigral (STN + SNr) deep brain stimulation improves FoG compared with optimized STN stimulation alone; to identify clinical variables associated with therapeutic response.
In this exploratory multicenter randomized controlled double-blind trial, we recruited patients from our existing cohorts and randomized them 1:1 to STN or STN + SNr. After baseline, patients were followed with close interim visits (visits 1-5) for 90 days (visit 6). The Freezing of Gait Assessment Course (FoG-AC) was the primary endpoint and was evaluated at P < 0.2 with exploratory intent. Secondary endpoints assessed responder rates, treatment dynamics, predictors of response, and patient preferences.
At V6, STN (n = 23) and STN + SNr (n = 22) FoG-AC outcomes did not differ significantly. We identified responders with clinically meaningful FoG improvement in both the STN (n = 7) and STN + SNr (n = 8) groups. In STN + SNr responders, mean disease duration was ~12 years, which was ~4.5 years shorter than in non-responders, but there were no differences in motor and cognitive functions. Treatment dynamics suggested that FoG responders improved slowly and gradually. The STN + SNr responder group showed numerically stronger FoG improvement compared with STN responders. Additionally, 15 STN compared to 10 STN + SNr patients wished to change treatment after the RCT phase and before unblinding. Both STN and STN + SNr treatment was safe.
Future trials evaluating adjunctive STN + SNr stimulation should stratify patients by disease duration to optimize outcomes.
To explore whether combined subthalamic and nigral (STN + SNr) deep brain stimulation improves FoG compared with optimized STN stimulation alone; to identify clinical variables associated with therapeutic response.
In this exploratory multicenter randomized controlled double-blind trial, we recruited patients from our existing cohorts and randomized them 1:1 to STN or STN + SNr. After baseline, patients were followed with close interim visits (visits 1-5) for 90 days (visit 6). The Freezing of Gait Assessment Course (FoG-AC) was the primary endpoint and was evaluated at P < 0.2 with exploratory intent. Secondary endpoints assessed responder rates, treatment dynamics, predictors of response, and patient preferences.
At V6, STN (n = 23) and STN + SNr (n = 22) FoG-AC outcomes did not differ significantly. We identified responders with clinically meaningful FoG improvement in both the STN (n = 7) and STN + SNr (n = 8) groups. In STN + SNr responders, mean disease duration was ~12 years, which was ~4.5 years shorter than in non-responders, but there were no differences in motor and cognitive functions. Treatment dynamics suggested that FoG responders improved slowly and gradually. The STN + SNr responder group showed numerically stronger FoG improvement compared with STN responders. Additionally, 15 STN compared to 10 STN + SNr patients wished to change treatment after the RCT phase and before unblinding. Both STN and STN + SNr treatment was safe.
Future trials evaluating adjunctive STN + SNr stimulation should stratify patients by disease duration to optimize outcomes.
Authors
Weiss Weiss, Cebi Cebi, Schütt Schütt, Fischer Fischer, Pavelka Pavelka, Kolber Kolber, Pötter-Nerger Pötter-Nerger, Hamel Hamel, Kühn Kühn, Hartmann Hartmann, Bötzel Bötzel, Köglsperger Köglsperger, Barbe Barbe, Kohl Kohl, Paschen Paschen, Hobert Hobert, Groppa Groppa, Warnecke Warnecke, Claus Claus, Krüger Krüger, Gharabaghi Gharabaghi,
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