Bilateral Pedunculopontine Nucleus Stimulation for Progressive Supranuclear Palsy

Abstract

The pedunculopontine nucleus (PPN) is a potential target for gait disorders. We report 4 cases of bilateral PPN stimulation in progressive supranuclear palsy (PSP) patients with short-term (6 months) and long-term (18 months) follow-ups. Patients with PSP who had gait disturbances, but were able to walk with or without assistance, were selected. The patients' median age was 64 years and the disease duration 3 years. Bilateral PPN deep brain stimulation (DBS) was performed. The pacemaker was programmed using a bipolar mode and lower frequencies (20-45 Hz). The PSP rating scores (PSPRS) and their gait subscores (No. 25, 26, 27 and 28) along with PSP staging scores were used as primary end points. The total Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS III and the 39-item Parkinson's Disease Questionnaire were considered as secondary end points. Video recordings of the gaits were performed before surgery and at the 6- and 18-month follow-ups. These were retrospectively reviewed by a blinded neurologist for the primary end points. At the 6- and 18-month follow-ups, the median change in PSPRS was from 33 (baseline) to 37.5 and 47, respectively. Similarly, the PSP staging changed from 3 to 2.5 and 3.5, item 25 from 1.5 to 2 and 3.5, item 26 from 2.5 to 2 and 3.5, item 27 from 3.5 to 3 and 3.5 and item 28 from 1.5 to 1.5 and 3. Two patients in the study with the PSP-parkinsonism phenotype experienced improvement in their gait until the last follow-up. Bilateral PPN DBS can be safely performed in PSP patients despite mid-brain atrophy.

Peduncolopontine nucleus stimulation in progressive supranuclear palsy: a randomised trial

“…To date, PPN DBS effects on PSP have been described in a few open studies with smaller samples of patients 3–6. One study with two patients with RS-PSP did not find clinical benefit in the UPDRS and PSPRS scores, although a minimal and transient gait improvement was observed 6. The other available studies involved different PSP phenotypes 3 4 6.…”

Deep brain stimulation for movement disorders

“…Progressive supranuclear palsy might improve after PPN DBS [106], also combined with GPi [107]. Finally, ballism may respond to GPi DBS or Vop DBS [108].…”

Normal and pathological neuronal distribution of the human mesencephalic locomotor region

“…Much of the data concerning PPN DBS proposed for PD and a few PSP patients to alleviate FOG and falls has been extrapolated from experimental data . Although proof‐of‐concept clinical trials were promising, subsequent double‐blind trials reported heterogeneous and disappointing results . The difficulty of interpreting these results may be the result of factors, including clinical heterogeneity of patients and complexity of gait evaluation, with FOG being an intermittent symptom and difficult to pin point.…”

“…24,25 Although proof-of-concept clinical trials were promising, subsequent double-blind trials reported heterogeneous and disappointing results. [26][27][28][29][30][31][32][33][34][35][36][37][38] The difficulty of interpreting these results may be the result of factors, including clinical heterogeneity of patients and complexity of gait evaluation, with FOG being an intermittent symptom and difficult to pin point. The major source of discrepancy remains the heterogeneity of the neurosurgical target between patients 37 and teams 36 because of the difficulty of delineating the PPN and CuN, which have indistinct boundaries.…”