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(2023)Objective
To evaluate the safety and feasibility of deep brain stimulation (DBS) of the cerebellar dentate nucleus paired with rehabilitation for chronic (1-3 years) post-stroke upper limb impairment.
Study Summary
• Patients showed a median 7-point improvement on the FM-UE scale and 15 points in those with some preserved motor function at baseline.
• These functional gains were associated with evidence of cortical reorganization on PET scans.
Intervention
Unilateral deep brain stimulation (DBS) of the cerebellar dentate nucleus, delivered continuously for 4-8 months, combined with intensive physical rehabilitation in patients 1 to 3 years after their ischemic stroke.
Study Design
Arms: Array
Outcome
• For the secondary efficacy outcome, patients achieved a median improvement of 7 points on the Fugl-Meyer Assessment (FM-UE) score during the DBS + rehabilitation phase.
• The subgroup of patients (n=7) with preserved distal motor function at baseline achieved a median improvement of 15 points on the FM-UE, exceeding the minimal clinically important difference.
Bottom Line
Deep brain stimulation of the cerebellar dentate nucleus is safe and feasible in patients with chronic post-stroke upper-extremity impairment. The intervention was associated with significant and clinically meaningful improvements in motor function, especially in patients with some preserved distal function at baseline, and these gains were correlated with cortical reorganization.
Major Points
- This was a phase I, open-label, non-randomized, single-arm trial involving 12 individuals with chronic (1-3 years post-stroke) moderate-to-severe upper-extremity impairment.
- All participants were implanted with a DBS device targeting the cerebellar dentate nucleus contralateral to the stroke lesion and underwent a multi-phase rehabilitation protocol.
- The primary outcome was safety and feasibility. No serious perioperative or stimulation-related adverse events were reported.
- For secondary outcomes, participants showed a median improvement of 7 points on the Upper-Extremity Fugl-Meyer Assessment (FM-UE) during the 4-8 month DBS + rehabilitation phase (P=0.0005).
- A post-hoc analysis revealed that the 7 participants with partial preservation of distal motor function at baseline had a much larger median improvement of 15 FM-UE points during the DBS + rehab phase.
- Functional gains were directly correlated with increased metabolism in the ipsilesional cortex on PET imaging, suggesting treatment-induced neuroplasticity.
Study Design
- Study Type
- Open-label, non-randomized, single-arm, phase I trial
- Randomization
- No
- Blinding
- Open-label
- Sample Size
- 12
- Follow-up
- Long-term follow-up was 10 months after the end of the DBS + rehab phase, with total individual participation spanning 20-24 months.
- Centers
- 1
- Countries
- United States
Primary Outcome
Definition: Safety as measured by the incidence of serious adverse events during study participation.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 0 study-related serious adverse events were encountered in 12 participants. | - |
Limitations & Criticisms
- The study has limitations inherent to a phase I investigation, including an open-label, non-randomized, single-arm design.
- The small sample size of 12 participants limits statistical power and the ability to generalize findings.
- It is not possible to distinguish with certainty the effects of rehabilitation alone from the effects of DBS combined with rehabilitation without a randomized control group.
- The heterogeneity in baseline impairment level across the sample may have influenced results.
Citation
Nature Medicine. 2023;29:2366-2374.