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Amputation With Osseointegration for Patients With Intractable Complex Regional Pain Syndrome

A Report of 3 Cases

Hoellwarth, Jason Shih MD1,2,a; Al-Jawazneh, Shakib Sameeh MD2,3; Tetsworth, Kevin MD, FRACS4; Lu, William PhD2; Roberts, Claudia B.Physio(Hons)2; Al Muderis, Munjed MB ChB, FRACS, FAOrthA2

Author Information
doi: 10.2106/JBJS.CC.20.00267
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  • Associated Video
  • Disclosures

Abstract

Complex regional pain syndrome type 1 (CRPS1) is diagnosed using the Budapest criteria (Table I)1. Although treatment algorithms exist2,3, many patients experience insufficient improvement4,5. Appropriate-level amputation reliably relieves recalcitrant pain, but fewer than 100 patients have been reported6, so very little outcomes data exist. Wearing traditional socket prostheses (TSPs) can present challenges impairing rehabilitation.

TABLE I - Budapest Research Diagnostic Criteria for Complex Regional Pain Syndrome Type 1
Fulfillment of Diagnostic Requirement
Diagnostic Categories and Criteria Patient 1 Patient 2 Patient 3
A Continuing pain, which is disproportionate to any inciting event Persistent disabling pain despite healed tissues, therapy, and multiple medications Persistent disabling pain despite healed tissues, therapy, and multiple medications Persistent disabling pain despite healed tissues, therapy, and multiple medications
B Must report at least one symptom in each of the 4 following categories
Category Description
Sensory Reports of hyperalgesia and/or allodynia Pain to light touch Pain to clothing movement Pain to clothing movement
Vasomotor Reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry Skin color change Heat changes and skin flushing Photographs of violet skin flushing
Sudomotor/Edema Reports of edema and/or sweating changes and/or sweating asymmetry Swelling and edema Unilateral swelling Unilateral sweating
Motor/Trophic Reports of decreased range of motion and/or motor dysfunction (weakness, tremor, and dystonia) and/or trophic changes (hair, nail, and skin) Hair growth difference Muscle atrophy, hair density reduction Muscle atrophy, hair density reduction
C Must display at least one sign at time of evaluation in 2 or more of the following categories
Category Description
Sensory Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or deep somatic pressure and/or joint movement) Pain to light palpation Pain to clothing movement Pain to clothing and light palpation
Vasomotor Evidence of temperature asymmetry and/or skin color changes and/or asymmetry Skin redness Palpable temperature difference, color change
Sudomotor/Edema Evidence of edema and/or sweating changes and/or sweating asymmetry Unilateral sweating
Motor/Trophic Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, and dystonia) and/or trophic changes (hair, nail, and skin) Knee motion only a few degrees Hair density reduction 20° knee motion, hair difference
D There is no other diagnosis that better explains the signs and symptoms True True True

Osseointegration (OI), schematically portrayed in Fig. 1, surgically implants a bone-anchored prosthesis that attaches to an external limb via a transcutaneous adapter. Amputees generally report better rehabilitation, mobility, and quality of life (QOL)8 with OI than TSPs.

Fig. 1
Fig. 1:
Osseointegration is a surgical technique that permanently anchors a metal implant directly to the skeleton. The Osseointegrated Prosthetic Limb (OPL) type A (Permedica Medical Manufacturing, Lecco, Italy) is shown here. This exploded schematic positions the components arranged at approximately the proximal-distal levels at which they would be once assembled and implanted transfemoral amputee. 1, proximal cap screw; 2, OPL body; 3, safety screw; 4, dual cone abutment adapter; 5, permanent locking propeller screw; 6, proximal connector; and 7, prosthetic connector.

This report describes 3 consecutive patients with severe, unremitting CRPS1, recalcitrant to conservative interventions, managed with amputation and osseointegration.

All patients consented to publication of deidentified images and clinical descriptions.

Cases

Patient 1 presented as a 24-year-old woman. Between 11 and 21 years old, multiple right patella dislocations were treated with arthroscopic lateral release, medializing tibial tubercle osteotomy, and trochleoplasty (summarized in Table I and Table II). She subsequently developed pain to light touch, dramatic temperature differences, swelling, color changes, and hair growth asymmetry. In the preceding 2 years, physical modalities (physiotherapy and hydrotherapy), pain-focused procedures (ketamine infusion, lumbar sympathectomy, and nerve stimulator), and oral medications (pregabalin, amitriptyline, duloxetine, valproate, opiates, and tramadol) were attempted, without relief. Physical examination identified that she walked using 2 crutches, excluding the right leg. Gentle skin brushing or palpation of her leg elicited pain. The right knee displayed redness and multiple areas of skin breakdown. Active and passive knee motions were only a few degrees before becoming painful. Her initial 36-Item Short Form Survey Instrument (SF-36) bodily pain score was very severe (0/100), and her pain interference score was extreme (0/100). She requested amputation for pain relief, specifically seeking osseointegration for improved rehabilitation.

TABLE II - Patient Summaries*
Patient 1 Patient 2 Patient 3
Age At CRPS, sex 24 yo Woman 35 yo Man 24 yo Woman
Clinical summary CRPS1 for 3.5 years after 10 years of surgeries for recurrent right patella dislocations. CRPS1 for 17 months after 3 years of surgeries attempting to manage tibia infected nonunion. CRPS1 for 4 years after patella dislocation and several surgeries.
Months since OI 76 24 12
Pre-OI SF-36 (higher better)
 Bodily pain 0/100 0/100 0/100
 Pain interference 0/100 0/100 0/100
Post-OI SF-36 (higher better)
 Bodily pain 60/100 40/100 60/100
 Pain interference 80/100 60/100 80/100
Pre-OI mobility One leg weight-bearing using 2 crutches. One leg weight-bearing using 2 crutches. Wheelchair and one leg crutch in home.
Current mobility Independent, unaided. Two crutches, both legs. Independent, unaided.
Pre-OI carry items in hands walking? No, needed 2 crutches. No, needed 2 crutches. No, needed 2 crutches.
Post-OI carry items in both hands walking Easily. No, using 2 crutches. Easily.
Pre-osseointegration pain management Physiotherapy, spinal stimulator, mood stabilizers, antidepressants, and opiates. Ketamine infusions, extremity blocks. Oral tapentadol, long acting morphine, pregabalin, and amitriptyline. Physiotherapy. Dorsal root ganglion and spinal cord stimulators, intrathecal clonidine and hydromorphone. Oral baclofen, amitriptyline, and tapentadol.
Current pain management No pain, no medications. Long acting oral morphine, amitriptyline. No pain, no oral medications, intrathecal pump being tapered for planned removal.
Pre-OI employment or hobby Unable to work, quit school because of pain. Project manager desk job with travel Unable to participate in work or hobbies.
Current employment or hobby Occupational Therapist Same job but increased performance with better pain control Has not sought employment. Hikes on beaches and dunes.
Pre-OI car driving No. Yes. No.
Current Car Driving Yes. Yes. Yes.
Daily prosthesis wear hours 16+ 8 16+
*OI= osseointegration, Pre-OI = patient performance reflects situation immediately before surgery, and SF-36 = 36-Item Short Form Survey Instrument.

We counseled that amputation might alleviate her symptoms but recommended seeking additional surgical consultations. Returning 2 years later, she reported worsening pain and functional performance. Pharmacotherapy and physiotherapy were unbeneficial. Other surgeons also recommended amputation. In November 2013, right transfemoral amputation with implant insertion was done; 3 months later, the transcutaneous adapter was placed. Within 3 months, she walked without assistive devices. Currently, 76 months postosseointegration, she experiences mild phantom pain, walks on both legs without assistive devices, and works as an occupational therapist. She walks 5 km several days weekly, navigates hills and stairs, and carries items in both hands while walking. She takes no medication for pain. Her SF-36 bodily pain score is moderate (60/100), and her pain interference score is slight (80/100).

Patient 2 presented as a 35-year-old medically discharged soldier. At age 30, he sustained an open left tibia fracture. Persistent infection after surgical reconstruction resulted in transfemoral amputation. He subsequently reported severe pain over most of his residual left limb, pain when clothing brushed his leg, palpable temperature asymmetry with intermittent blushing, profuse leg sweating without his prosthesis, and reduced hair density with quadriceps and gluteal atrophy. Unsuccessful therapeutic efforts included physiotherapy, pain-focused procedures (ketamine infusions and extremity blocks), and oral medications (morphine, pregabalin, tapentadol, and amitriptyline). Despite multiple prosthetic fittings, he could not walk because of frequent severe limb pain. Physical examination identified he mobilized using 2 crutches, without a prosthesis, excluding his amputated leg. Pain to light touch was elicited globally about the left residual limb without a dermatomal or nerve distribution pattern. During the encounter, his left leg began sweating, whereas the right remained dry. There was obvious decreased hair density and reduced thigh circumference. Previous magnetic resonance imaging identified no neuroma. His initial SF-36 bodily pain score was very severe (0/100), and his pain interference score was extreme (0/100). Evaluation by a psychiatrist identified no psychiatric origins of pain. He initially declined surgery but returned one year later requesting revision amputation and osseointegration.

In March 2018, revision amputation and osseointegration with a transcutaneous adapter insertion was done. By 6 months, he walked with one cane and wore clothing without pain but had focal posterior leg pain. In November 2018, he had sciatic nerve targeted muscle reinnervation (TMR). In January 2019, without consulting us, he had lipocontouring done that disrupted the TMR (confirmed by the nerve conduction test). Revision TMR in December 2019 significantly reduced this pain. Currently, 24 months after osseointegration, he takes oral amitriptyline and is weaning oral morphine. His best mobility was single cane ambulation, although currently he walks with both legs using 2 crutches. Six months after osseointegration, his SF-36 bodily pain score was moderate (40/100) with a pain interference score of slight (80/100). Currently, his bodily pain score is moderate (40/100) with a pain interference score of moderate (60/100).

tPatient 3 presented as a 24-year-old woman. Fig. 2 shows representative photographs. At age 20, heavy boxes fell on her left leg, causing lateral patella dislocation and meniscal tears. Despite 2 knee arthroscopies with meniscal debridement and lateral release, her pain and intermittent instability persisted, leaving her unable to bear weight on the leg. She developed pain to light touch such as clothing contact, intermittent violaceous skin flushing, unilateral sweating, marked atrophy, leg hair asymmetry, and progressive knee motion reduction. Unsuccessful previous interventions included physiotherapy (graded sensory desensitization and mirror box therapy), ketamine infusions, dorsal root ganglion stimulator (removed due to spasms), spinal cord stimulator (removed due to no benefit), intrathecal pump (delivering clonidine and hydromorphone; this she retained, despite minimal benefit), and oral medications (baclofen, amitriptyline, and tapentadol). A medializing tibial tubercle osteotomy resolved her dislocations but did not improve pain. Her mobility was limited to room-to-room distances using crutches, and she was dependent on a wheelchair for all situations outside her home. Physical examination (highlights shown in Video 1) identified that she mobilized using a wheelchair with the left leg inside a “tented blanket” that allowed the leg to remain untouched while relatively controlling temperature. Light touch elicited severe pain distal to the midthigh with hyperesthesia over most of the distal leg. There was palpable temperature asymmetry, especially distal to the knee. Passive knee motion was restricted to 10° to 20°; further motion elicited pain. Her leg muscles were atrophied, and hair density and thickness were less than the right. Although the muscle atrophy could be explained by prolonged leg disuse, in context, CRPS1 was the most likely diagnosis. Her initial SF-36 bodily pain score was very severe (0/100), and her pain interference score was extreme (0/100).

Photographic progression of patient 3. Frames A and B were taken before surgery and demonstrate

Fig. 2-A
Fig. 2-A:
(Fig. 2-A) the patient protecting her leg from exposure, and
Fig. 2-B
Fig. 2-B:
(Fig. 2-B) experiencing dramatic color difference.
Fig. 2-c
Fig. 2-c:
(Fig. 2-C) One week after surgery, she was painless to skin touch and implant impaction.
Fig. 2-d
Fig. 2-d:
(Fig. 2-D) 3 months after surgery, the incision and stoma are stable and dry. Frames E-G show the patient at 6 months after surgery able to navigate without an assistive device
Fig. 2-e
Fig. 2-e:
(Fig. 2-E) stairs,
Fig. 2-f
Fig. 2-f:
(Fig. 2-F) shallow beach water,
Fig. 2-g
Fig. 2-g:
(Fig. 2-G) walking her dog on a leash.

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In March 2019, she underwent single stage transfemoral amputation with osseointegration, transcutaneous adapter placement, and sciatic nerve TMR. One week later, she had no pain with skin palpation (Video 2). At 2 weeks, she walked with one crutch (Video 3). Currently, 12 months after osseointegration, she walks without assistive devices on surfaces including sand, shallow water, and stairs (Video 4). She takes no oral medications, and her intrathecal pump is being tapered for removal. Her SF-36 response to bodily pain is moderate (60/100), and her pain interference response is slight (80/100).

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Discussion

The etiology of CRPS1 remains incompletely understood. Contemporary literature suggests the inflammatory, autoimmune, vasomotor, central nervous, and peripheral nervous systems may be involved, perhaps with additional overlying psychosomatization3,9-11. Despite investigations identifying structural changes including inordinate bone density loss12 and demyelinated peripheral nerves13, consistently effective therapies remain elusive.

Therefore, some CRPS1 patients request amputation for pain relief. Amputating a limb without identified malignancy or untreatable infection, albeit debilitating, can be controversial7,14-18. Because of CRPS1's rarity and the reluctance of pain specialists to refer patients for amputation despite ineffective conservative management7, organizing comparative trials remains difficult19. A 2019 review of amputation for CRPS1 identified only 96 reported adults (107 amputations)6. Two-thirds had QOL improvement. One-third used a prosthesis. The most common reasons for disuse were residual limb pain (37%) or symptom recurrence (46%). The best comparison reported 19 patients who had amputation and 19 who only considered amputation. The amputee cohort had better pain and disability scores despite only 10/19 (53%) using a prosthesis20. A better postoperative rehabilitation solution could improve QOL and mobility after amputation.

We believe that osseointegration, which eliminates the skin-compressing socket, provides that solution. The outcomes and considerations of routine adult osseointegration are well described (implant options8,21, enhanced mobility22-24, improved QOL25,26, a periprosthetic fracture rate of 6% that is fully recoverable with device retention27, a 6% rate of infection requiring debridement28, finite element analysis29-31, and bone remodeling32-35). We have done over 500 transfemoral osseointegration procedures. No patients have died, required a more proximal amputation, or had systemic complications from OI. We therefore consider OI safe and beneficial for appropriately selected patients (Table III). With further experience, OI indications have expanded to include arthroplasty patients36,37 and diabetic38 and vascular39 amputees with controlled disease states. We are cautiously optimistic that OI can optimize rehabilitation for CRPS1 patients considering amputation, provided other criteria are met. As always, optimizing social and psychiatric factors remains critical14,17.

TABLE III - Typical Osseointegration Inclusion and Exclusion Criteria
Criteria Reason
Inclusion Age at least 18 years. Legal self-consent.
Current amputees with significant dissatisfaction regarding prosthesis fit or pain, mobility, or skin breakdown. Objective, identifiable deficit in the current patient lifestyle.
Patients with a full lower limb but with musculoskeletal pain, deformity, or weakness distal to the amputation level who desire amputation for pain management or improved mobility after removal of the deformed or weak joint and muscles. Objective, identifiable quality of life impairment that can be objectively improved by amputation, and patients likely would experience better rehabilitation with osseointegration than standard socket prosthesis.
Patients with recent amputations who wished to try osseointegration instead of a traditional socket prosthesis. Honoring patient choice.
Patient with sufficient resources and willingness to pursue surgery, postoperative rehabilitation, and prosthesis procurement. Rehabilitation and prosthesis fitting are all required for appropriate, safe improvement after osseointegration surgery.
Exclusion Females currently or intending to become pregnant within the year after surgery. Unnecessary risk to fetus due to potential for falls or other unforeseen adverse events.
Active infection at any location. Unacceptably high and modifiable infection risk.
Active malignancy or ongoing/planned treatment for malignancy at any location. High risk for infection, impaired biology for osseointegration, impaired patient stamina for rehabilitation.
Skeletal immaturity. Unknown risk, given the current knowledge of osseointegration outcomes and biological impact.
Amputee with no mobility, socket, or skin problems. No expected immediate, and uncertain eventual, benefit from additional surgical intervention.
Patients with psychiatric concern identified during pre-operative consultation with a psychiatrist. Minimize risk of performing surgery for a patient whose expressed deficits are psychiatric-based instead of musculoskeletal-based, and thus unlikely to improve with surgery.
Patients considered too medically ill, too muscularly weak, or insufficiently dedicated to improve after osseointegration. Avoid harming patients with surgery that may be either unlikely to benefit them or possibly pose a health risk.
Uncontrolled modifiable chronic diseases that are likely to increase infection risk (e.g., diabetes mellitus, and peripheral vascular disease). Avoid unnecessary, modifiable risk for infection

In summary, we emphasize that amputation for CRPS1 should be considered only when conservative therapies inadequately alleviate debilitating pain. Amputation, not OI, addresses the pain. OI seems not to reprovoke symptoms while conferring the mobility and prosthesis satisfaction advantages versus TSP consistently reported in the amputee rehabilitation literature.

References

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