Stimulation of the pedunculopontine and cuneiform nuclei for freezing of gait and falls in Parkinson disease: Cross-over single-blinded study and long-term follow-up.

INTRODUCTION: Deep brain stimulation (DBS) of the mesencephalic locomotor region, composed of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, has been proposed to treat dopa-resistant gait and balance disorders in Parkinson's disease (PD). Here, we report the long-term effects of PPN- or CuN-DBS on these axial disorders. METHODS: In 6 PD patients operated for mesencephalic locomotor region DBS and prospectively followed for more than 2 years, we assessed the effects of both PPN- and CuN-DBS (On-dopa) in a cross-over single-blind study by using clinical scales and recording gait parameters. Patients were also examined Off-DBS. RESULTS: More than 2 years after surgery, axial and Tinetti scores were significantly aggravated with both PPN- or CuN-DBS relative to before and one year after surgery. Gait recordings revealed an increased double-stance duration with both PPN- or CuN-DBS, higher swing phase duration with CuN-DBS and step width with PPN-DBS. With PPN- versus CuN-DBS, the step length, velocity and cadence were significantly higher; and the double-stance and turn durations significantly lower. Irrespective the target, we found no significant change in clinical scores Off-DBS compared to On-DBS. The duration of anticipatory postural adjustments as well as step length were lower with versus without PPN-DBS. We found no other significant changes in motor, cognitive or psychiatric scores, except an increased anxiety severity. CONCLUSION: In this long-term follow-up study with controlled assessments, PPN- or CuN-DBS did not improve dopa-resistant gait and balance disorders with a worsening of these axial motor signs with time, thus indicating no significant clinical effect.

Pedunculopontine and Cuneiform Nuclei Deep Brain Stimulation for Severe Gait and Balance Disorders in Parkinson's Disease: Interim Results from a Randomized Double-Blind Clinical Trial.

BACKGROUND: Dopa-resistant freezing of gait (FOG) and falls represent the dominant motor disabilities in advanced Parkinson's disease (PD). OBJECTIVE: We investigate the effects of deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), comprised of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, for treating gait and balance disorders, in a randomized double-blind cross-over trial. METHODS: Six PD patients with dopa-resistant FOG and/or falls were operated for MLR-DBS. Patients received three DBS conditions, PPN, CuN, or Sham, in a randomized order for 2-months each, followed by an open-label phase. The primary outcome was the change in anteroposterior anticipatory-postural-adjustments (APAs) during gait initiation on a force platformResults:The anteroposterior APAs were not significantly different between the DBS conditions (median displacement [1st-3rd quartile] of 3.07 [3.12-4.62] cm with sham-DBS, 1.95 [2.29-3.85] cm with PPN-DBS and 2.78 [1.66-4.04] cm with CuN-DBS; p = 0.25). Step length and velocity were significantly higher with CuN-DBS vs. both sham-DBS and PPN-DBS. Conversely, step length and velocity were lower with PPN-DBS vs. sham-DBS, with greater double stance and gait initiation durations. One year after surgery, step length was significantly lower with PPN-DBS vs. inclusion. We did not find any significant change in clinical scales between DBS conditions or one year after surgery. CONCLUSION: Two months of PPN-DBS or CuN-DBS does not effectively improve clinically dopa-resistant gait and balance disorders in PD patients.