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SCS for Post-Stroke Hemiparesis

Spinal Cord Stimulation Improves Motor Function and Spasticity in Chronic Post-Stroke Upper Limb Hemiparesis

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Year of Publication: 2025

Authors: Roberto M. de Freitas, Shovan Bhatia, Erynn Sorensen, ..., Marco Capogrosso

Journal: medRxiv

Citation: medRxiv preprint doi: https://doi.org/10.1101/2025.08.01.25332445

Link: https://doi.org/10.1101/2025.08.01.25332445

PDF: https://pmc.ncbi.nlm.nih.gov/articles/PM....25332445v1.pdf

Clinical Question

Can cervical epidural spinal cord stimulation safely and effectively improve motor function and reduce spasticity in individuals with chronic post-stroke upper-limb hemiparesis?

Bottom Line

Cervical SCS is safe and provides immediate assistive improvements in strength, dexterity, and spasticity, with therapeutic effects emerging over 4 weeks, regardless of impairment severity. Spared sensory function may predict responsiveness.

Major Points

  • First-in-human pilot trial (NCT04512690) testing cervical epidural SCS in 7 participants with chronic hemiparesis (FMA 15-35)
  • Two percutaneous 8-contact leads implanted unilaterally in cervical epidural space (C3-T1) for 4 weeks
  • Immediate assistive effects: average +32% strength increase and +5.6 FMA points with SCS ON
  • 3/7 participants with residual corticospinal connectivity (MEP+) regained hand/finger function
  • Therapeutic effects emerged despite only 8.6 hours of motor activity (5.5 hours with SCS ON)
  • Participants improved by average +6.6 FMA points at study end compared to baseline
  • Spasticity decreased in all participants (MAS scores)
  • No serious adverse events occurred; 14 mild AEs documented
  • Spared sensory function may be a determinant of SCS responsiveness
  • 85% of maximum FMA improvement achieved by week 2

Design

Study Type: Non-randomized, open-label, prospective pilot study

Randomization:

Blinding: Evaluator blinded for FMA assessments; participants served as their own controls (SCS ON vs OFF)

Enrollment Period: Not specified

Follow-up Duration: 4 weeks (with implant) + 1 month follow-up post-explant

Centers: 1

Countries: USA

Sample Size: 7

Analysis: Bootstrap analysis with 10,000 samples for paired comparisons; 95% confidence intervals; Pearson correlations for EMG-kinematic relationships

Inclusion Criteria

  • Ages 21-70 years
  • Ischemic or hemorrhagic stroke >6 months prior
  • Upper limb hemiparesis with baseline FMA scores 7-40
  • Passed rigorous medical evaluation
  • No severe comorbidities
  • No previously implanted medical devices
  • Not claustrophobic
  • Not pregnant or breastfeeding
  • Not receiving anticoagulant, anti-spasticity, or anti-epileptic medications during study

Exclusion Criteria

  • Severe comorbidities
  • Previously implanted medical devices
  • Claustrophobia
  • Pregnancy or breastfeeding
  • Receiving anticoagulant medications
  • Receiving anti-spasticity medications
  • Receiving anti-epileptic medications

Baseline Characteristics

CharacteristicControlActive
NoteWithin-subject design - all participants served as their own controls
N7
Age range30-70 years
Sex4 female, 3 male
Years post-stroke2-10 years (range)
Stroke type3 hemorrhagic, 4 ischemic
Baseline FMA motor15-35 (range), mean ~26.3
Baseline FMA sensory2-12 (range)
MEP status3 MEP+, 3 MEP-, 1 likely MEP+
SSEP status5 SSEP+, 2 SSEP-
Hand opening ability3 yes, 4 no
Same participants - within-subject crossover designSCS ON condition

Arms

FieldControlSCS ON
InterventionNo spinal cord stimulation - baseline motor function assessmentCervical epidural spinal cord stimulation via two 8-contact percutaneous leads (C3-T1 levels) positioned lateral to spinal midline, targeting ipsilateral dorsal roots. Parameters: 40-100Hz frequency, 0.2-8mA amplitude, 200-400μs pulse width, monopolar or bipolar configurations
DurationAssessed throughout 4-week period4 weeks (leads implanted), used during ~5.5 hours of motor activities

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Safety - assessed by systematically documenting all adverse eventsPrimaryN/A14 mild adverse events, 0 moderate or severe adverse events, 0 serious adverse events. All AEs resolved without sequelae
Assistive effects on strength (MVC across joints)SecondaryBaseline MVC valuesMean +32% increase across joints (shoulder flexion +28%, elbow extension +35%, elbow flexion +34%, grip +55%)Significant for multiple joints (bootstrap 95% CI)
Assistive effects on FMA motor score (week 2)SecondarySCS OFF: mean change from baseline +1.00SCS ON: mean +5.57 points from baselineSignificant (bootstrap analysis)
Effective improvement on FMA motor score (week 4)SecondaryBaseline FMASCS ON at week 4: mean +6.57 points from baselineSignificant
Therapeutic effects on FMA motor score (week 4 OFF)SecondaryBaseline FMA OFFWeek 4 SCS OFF: mean +5.14 points from baselineSignificant
Assistive effects on arm kinematics (reach phase)SecondarySCS OFF conditionSignificant improvements in path efficiency (+14.6%), log dimensionless jerk (+9.6%), velocity peaks (n.s.)p<0.05 for most metrics
Therapeutic effects on spasticity (MAS total score)SecondaryBaseline MASWeek 4 OFF: mean reduction of 5.57 points across participantsClinically significant (MCID >0.76)
Hand/finger function restorationSecondaryBaseline hand function3/7 participants with MEP+ or residual hand opening regained hand/finger movements with SCS ONIndividual participant analysis
Mild AE - Pain at lead exit siteAdverseN/A1 event (SCS01) - resolved with suture replacement
Mild AE - Shortness of breathAdverseN/A1 event (SCS04) - related to stimulation at C3/C4 levels at high amplitude (5mA), resolved immediately by discontinuing stimulation. Protocol modified
Mild AE - Lead migrationAdverseN/A1 event (SCS05) - mediolateral migration, no negative effects on motor function
Other mild AEsAdverseN/A11 additional mild AEs across participants (phlebitis, bruising, headache, vomiting, pain, etc.) - all resolved spontaneously or with minimal intervention

Subgroup Analysis

Exploratory analysis suggested spared sensory function (FMA sensory scores) may be a stronger determinant of responsiveness than baseline motor impairment or CST integrity. MEP+ status associated with hand/finger function restoration but not overall FMA improvement. Hemorrhagic stroke patients also benefited.

Criticisms

  • Small sample size (n=7) limits generalizability and statistical power
  • No control group performing only motor assessments - limits interpretation of therapeutic effects
  • Open-label design - participants and some assessors aware of stimulation status
  • Short intervention duration (4 weeks) - long-term effects unknown
  • Heterogeneous cohort with variable stroke types, locations, and severities
  • Protocol modification after adverse event (avoiding C3/C4 stimulation) may have limited proximal muscle recruitment
  • Minimal motor activity performed (8.6 hours total) - combination with formal rehabilitation not tested
  • Temporary implant only - long-term implantation feasibility not assessed
  • Single-center study
  • Lack of sham stimulation control
  • Evaluator blinding only for FMA assessments, not other outcomes

Funding

National Institutes of Health Brain Initiative grant no. UG3NS123135-01A1 and internal funding from University of Pittsburgh Department of Neurological Surgery, Carnegie Mellon University Department of Mechanical Engineering and Neuroscience Institute, and University of Pittsburgh Department of Physical Medicine and Rehabilitation

Based on: SCS for Post-Stroke Hemiparesis (medRxiv, 2025)

Authors: Roberto M. de Freitas, Shovan Bhatia, Erynn Sorensen, ..., Marco Capogrosso

Citation: medRxiv preprint doi: https://doi.org/10.1101/2025.08.01.25332445

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