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# Targeted Muscle Reinnervation (TMR) — Comprehensive Outline
## 1. What is targeted muscle reinnervation (TMR) and what are its underlying principles, history, and relevant anatomy/levels?
### a) When and by whom was TMR developed and first reported clinically?
- Originators: Todd A. Kuiken and Gregory A. Dumanian (Center for Bionic Medicine, Rehabilitation Institute of Chicago/Northwestern).
- First clinical case: ~2002; published 2004 (bilateral shoulder disarticulation).
- Foundational work: Kuiken hyper-reinnervation rat model (1995); finite element/signal modeling (2001).
- Timeline:
- 1995: animal model.
- ~2002: procedural development.
- 2004: first published human case.
- 2008+: expanded series and refinements.
- Evidence: Multiple series, systematic reviews, and an RCT (Dumanian et al. 2019) support benefit for prosthetic control and neuroma/phantom limb pain (PLP) reduction.
- Pearl: Early animal studies showed transferred nerves histologically resembled normal nerve, supporting clinical translation.
### b) What principle explains how TMR prevents neuroma formation and restores function?
- Central principle: **“Somewhere to go and something to do.”** Redirect regenerating axons into denervated muscle to avoid chaotic neuroma formation.
- Mechanism: End-to-end (or end-to-side) coaptation at the motor point → axons grow into muscle fibers, forming functional units.
- Supporting data:
- Rabbit model: transferred nerves resembled uninjured nerves.
- Clinical: near elimination of symptomatic neuromas when performed at index amputation; delayed TMR also effective.
- Surgical pearls: coapt near motor point; fully denervate target; stabilize neurorrhaphy; avoid tension.
- Pitfalls: poor candidates include brachial plexus avulsion, inadequate motor targets, poor soft tissue vascularity.
### c) How does TMR “bioamplify” signals for myoelectric prosthesis control?
- Concept: Reinnervated muscles amplify tiny motor axon signals into recordable EMG signals.
- Practical effect: each transferred nerve → discrete muscle segment → independent EMG channel.
- Clinical outcomes:
- Myers et al.: 80% doubled usable EMG signals; dexterity improved up to 271% in tasks.
- More channels enable proportional, simultaneous multi-DOF prosthetic control.
- Timeline: robust EMG at ~3–6 months (longer for distant targets).
- Pearls: thin subcutaneous tissue improves EMG detection; ≥4–5 cm muscle segments recommended.
### d) Which upper-extremity nerves and levels are commonly involved?
- Common levels: shoulder disarticulation, transhumeral, transradial.
- Donor nerves: median, ulnar, radial, musculocutaneous; sensory nerves (medial/lateral antebrachial cutaneous).
- Example mappings:
- **Shoulder**: Median → sternal pectoralis; Musculocutaneous → clavicular pectoralis; Ulnar → pectoralis minor; Radial → thoracodorsal/long thoracic.
- **Transhumeral**: Median → short head biceps; Ulnar → brachialis; Radial → lateral triceps branch.
- **Transradial**: Median → FDS; Ulnar → FCU; Radial → FDP/AIN branches.
- Note: size mismatch common (large donor vs small motor branch); standard epineurial sutures suffice.
### e) Which lower-extremity nerves and levels are commonly involved?
- Levels: above-knee (AKA), below-knee (BKA).
- **AKA**: Tibial division → biceps femoris/semimembranosus; Common peroneal → semitendinosus; Saphenous → gracilis.
- **BKA**: Posterior tibial → gastrocnemius/soleus/tibialis posterior; Deep peroneal → tibialis anterior/peroneals; Superficial peroneal → peroneus longus/brevis.
### f) What is targeted sensory reinnervation (TSR) and how does it relate to TMR?
- TSR: reroutes transected sensory nerves to cutaneous targets, enabling referred sensation and prosthetic feedback. Often performed alongside TMR.
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## 2. For which patients is TMR indicated, what are contraindications, and what preoperative assessments are required?
### a) Primary vs secondary indications
- **Primary (preemptive)**: At index amputation (or ≤14 days) to prevent neuroma/PLP and optimize future prosthetic control.
- **Secondary (delayed)**: For symptomatic neuroma, refractory pain, or poor EMG/prosthetic signals. Effective even decades later.
- Evidence: Primary reduces neuroma/PLP rates; delayed reliably reduces pain and restores prosthesis tolerance.
### b) Principal goals
1. Prevent/treat neuroma & reduce PLP/RLP.
2. Bioamplify signals for prosthetic control.
3. Preserve options for reconstruction/sensory feedback.
- Timelines: wound healing ~6 weeks; usable EMG signals ~3–6 months (longer for distant targets).
- Outcomes: improved pain, prosthesis wear, signal quality, and patient satisfaction.
### c) Contraindications
- **Absolute**: preganglionic brachial plexus avulsion, active infection, critical limb ischemia.
- **Relative**: uncontrolled systemic disease (diabetes, malnutrition, cardiopulmonary instability), demyelinating neuropathies, centralized pain syndromes.
- **Practical**: lack of suitable motor targets or inadequate distal nerve length.
### d) Preoperative assessment
- History/exam: pain mapping, prosthesis tolerance, Tinel sign.
- Imaging/adjuncts:
- High-resolution ultrasound (visualize neuroma).
- Ultrasound-guided diagnostic block (predicts response).
- MRI selectively (deep/multiple lesions).
- Prosthetics: baseline surface EMG, prosthetist input.
### e) Verifying motor targets
- Clinical: confirm voluntary contraction; mark motor points and Tinels.
- Intraop: nerve stimulator to identify true motor branches.
- Optimization: ≥4–5 cm muscle segments; adipofascial separation; soft-tissue thinning for EMG pickup.
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## 3. How is TMR performed—technique, level-specific strategies, and perioperative care?
### a) Core technique
1. Mobilize amputated nerves proximally to healthy fascicles.
2. Identify motor points with stimulator; denervate selected segment.
3. End-to-end epineurial coaptation with fine monofilament; stabilize with epimysial tacking.
4. Thin/shape soft tissue to optimize EMG signals.
### b) Secondary TMR for neuroma
- Indication: refractory neuroma pain.
- Approach: excise to healthy fascicles (often 4–6 cm), mobilize, transfer to motor point.
- Outcome: reduces pain and enables prosthetic use.
### c) Managing size mismatch
- Large donor → small motor recipient.
- Strategy: interrupted epineurial sutures; cinch donor epineurium to recipient; offload with epimysial tacking.
- Avoid fascicular matching attempts.
### d) Shoulder/forequarter mappings
- Median → sternal pectoralis
- Musculocutaneous → clavicular pectoralis
- Ulnar → pectoralis minor/lateral pectoral branch
- Radial → thoracodorsal or long thoracic
### e) Transhumeral mappings
- Median → medial biceps motor point
- Ulnar → brachialis
- Radial (distal) → lateral triceps branch
- Preserve native innervation to one biceps/triceps head for elbow control.
### f) Distal UE and LE options
- **Transradial**: Median → FDS; Ulnar → FCU; Radial → AIN/FDP branches.
- **AKA**: tibial → hamstrings; peroneal → hamstrings; saphenous → gracilis.
- **BKA**: posterior tibial → gastrocnemius/soleus/tibialis posterior; deep peroneal → tibialis anterior/peroneals; superficial peroneal → peroneus longus/brevis.
### g) Optimizing EMG intraoperatively
- Thin subcutaneous tissue over electrode fields.
- Use adipofascial flaps between segments.
- Fully denervate target segment.
- Coapt directly at motor entry point.
### h) Postoperative care
- Standard wound care; drains/quilting for seroma prevention.
- Resume prosthesis at ~6 weeks.
- New EMG sites become usable ~3–6 months.
- Close collaboration with prosthetist/rehab team essential.
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## 4. Outcomes, evidence, and limitations
### a) Pain outcomes
- **Immediate TMR**: significantly lower pain scores and near-zero neuroma rates.
- **Delayed TMR**: consistently reduces chronic pain; restores prosthesis tolerance.
- **RCT**: small trial shows benefit in pain scores at 1 year.
### b) Prosthetic outcomes
- More usable EMG signals, greater DOF, improved dexterity and ADL scores.
- High prosthesis wear and tolerance rates.
### c) Systematic review summary
- 338 patients / 341 limbs.
- Mean age ~47.
- Indications: trauma, infection, tumor most common.
- Mean 2.2 nerve transfers/limb.
- Average follow-up ~22 months.
### d) Immediate vs delayed comparison
- Immediate: best for **prevention** (neuroma, PLP/RLP).
- Delayed: effective **therapy** for chronic pain and poor prosthesis tolerance.
### e) Complications
- Seroma, rare infection, transient PLP flares.
- Symptomatic neuroma at coaptation site: not reported in large series.
### f) Evidence limitations
- Mostly retrospective/prospective cohorts; one small RCT.
- Heterogeneous populations, variable techniques and outcomes.
- Need for multicenter, standardized trials.
### g) Outcome measurement gaps
- PROMIS/NRS inadequate for amputee-specific domains (prosthesis wear, usable EMG channels, DOF, sensory outcomes).
- Need validated amputee-specific instruments.
### h) Adoption recommendations
- Strong preference for TMR **at amputation** when feasible — many authors argue this should be standard of care.
- Delayed TMR remains effective for salvage.
- Multidisciplinary planning and standardized outcome collection essential for best practice.