Viswas Dayal1, Ali Rajabian2, Marjan Jahanshahi2, Iciar Aviles-Olmos2, Dorothy Cowie2, Amy Peters2, Brian Day2, Jonathan Hyam2, Harith Akram2, Patricia Limousin2, Marwan Hariz2,3, Ludvic Zrinzo2, Thomas Foltynie2. 1. Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom, v.dayal@ucl.ac.uk. 2. Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom. 3. Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
Abstract
BACKGROUND: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has been investigated for the treatment of levodopa-refractory gait dysfunction in parkinsonian disorders, with equivocal results so far. OBJECTIVES: To summarize the clinical outcomes of PPN-DBS-treated patients at our centre and elicit any patterns that may guide future research. MATERIALS AND METHODS: Pre- and post-operative objective overall motor and gait subsection scores as well as patient-reported outcomes were recorded for 6 PPN-DBS-treated patients, 3 with Parkinson's disease (PD), and 3 with progressive supranuclear palsy (PSP). Electrodes were implanted unilaterally in the first 3 patients and bilaterally in the latter 3, using an MRI-guided MRI-verified technique. Stimulation was initiated at 20-30 Hz and optimized in an iterative manner. RESULTS: Unilaterally treated patients did not demonstrate significant improvements in gait questionnaires, UPDRS-III or PSPRS scores or their respective gait subsections. This contrasted with at least an initial response in bilaterally treated patients. Diurnal cycling of stimulation in a PD patient with habituation to the initial benefit reproduced substantial improvements in freezing of gait (FOG) 3 years post-operatively. Among the PSP patients, 1 with a parkinsonian subtype had a sustained improvement in FOG while another with Richardson syndrome (PSP-RS) did not benefit. CONCLUSIONS: PPN-DBS remains an investigational treatment for levodopa-refractory FOG. This series corroborates some previously reported findings: bilateral stimulation may be more effective than unilateral stimulation; the response in PSP patients may depend on the disease subtype; and diurnal cycling of stimulation to overcome habituation merits further investigation.
BACKGROUND: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has been investigated for the treatment of levodopa-refractory gait dysfunction in parkinsonian disorders, with equivocal results so far. OBJECTIVES: To summarize the clinical outcomes of PPN-DBS-treated patients at our centre and elicit any patterns that may guide future research. MATERIALS AND METHODS: Pre- and post-operative objective overall motor and gait subsection scores as well as patient-reported outcomes were recorded for 6 PPN-DBS-treated patients, 3 with Parkinson's disease (PD), and 3 with progressive supranuclear palsy (PSP). Electrodes were implanted unilaterally in the first 3 patients and bilaterally in the latter 3, using an MRI-guided MRI-verified technique. Stimulation was initiated at 20-30 Hz and optimized in an iterative manner. RESULTS: Unilaterally treated patients did not demonstrate significant improvements in gait questionnaires, UPDRS-III or PSPRS scores or their respective gait subsections. This contrasted with at least an initial response in bilaterally treated patients. Diurnal cycling of stimulation in a PDpatient with habituation to the initial benefit reproduced substantial improvements in freezing of gait (FOG) 3 years post-operatively. Among the PSPpatients, 1 with a parkinsonian subtype had a sustained improvement in FOG while another with Richardson syndrome (PSP-RS) did not benefit. CONCLUSIONS: PPN-DBS remains an investigational treatment for levodopa-refractory FOG. This series corroborates some previously reported findings: bilateral stimulation may be more effective than unilateral stimulation; the response in PSPpatients may depend on the disease subtype; and diurnal cycling of stimulation to overcome habituation merits further investigation.
Authors: Maria Stamelou; Gesine Respondek; Nikolaos Giagkou; Jennifer L Whitwell; Gabor G Kovacs; Günter U Höglinger Journal: Nat Rev Neurol Date: 2021-08-23 Impact factor: 42.937