What's New in Orthopaedic Rehabilitation

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The PDF of the article you requested follows this cover page. This is an enhanced PDF from The Journal of Bone and Joint Surgery 2009;91:2296-2310. doi:10.2106/JBJS.I.00319 J Bone Joint Surg Am. Harish Hosalkar, Nirav K. Pandya, Jason Hsu and Mary Ann Keenan What's New in Orthopaedic Rehabilitation This information is current as of September 6, 2009 Reprints and Permissions Permissions] link. and click on the [Reprints and jbjs.org article, or locate the article citation on to use material from this order reprints or request permission Click here to Publisher Information www.jbjs.org 20 Pickering Street, Needham, MA 02492-3157 The Journal of Bone and Joint Surgery

Transcript of What's New in Orthopaedic Rehabilitation

The PDF of the article you requested follows this cover page.  

This is an enhanced PDF from The Journal of Bone and Joint Surgery

2009;91:2296-2310.  doi:10.2106/JBJS.I.00319 J Bone Joint Surg Am.Harish Hosalkar, Nirav K. Pandya, Jason Hsu and Mary Ann Keenan    

What's New in Orthopaedic Rehabilitation

This information is current as of September 6, 2009

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Permissions] link. and click on the [Reprints andjbjs.orgarticle, or locate the article citation on

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Publisher Information

www.jbjs.org20 Pickering Street, Needham, MA 02492-3157The Journal of Bone and Joint Surgery

Specialty Update

What’s New in OrthopaedicRehabilitation

By Harish Hosalkar, MD, MBMS(Orth), FCPS(Orth), DNB(Orth), Nirav K. Pandya, MD,Jason Hsu, MD, and Mary Ann Keenan, MD

Orthopaedic rehabilitation involves the care of patients whohave complex musculoskeletal problems that are global innature rather than being limited to one or two anatomic lo-cations. It is a specialty that combines biomechanics and bi-ology in a unique manner with an approach that focuses onimproving the functional outcome for individuals with mus-culoskeletal disability through surgical and nonsurgicalmanagement.

This specialty encompasses patients of all ages, a broadrange of anatomic locations, and a variety of musculoskeletaldysfunctions. Orthopaedic rehabilitation comprises all of thetraditional orthopaedic subspecialties, including amputationsurgery, prosthetic and orthotic management, neuromusculardiseases, and a variety of other neurologic disorders, with afocus on the musculoskeletal system as a whole as well as onthe linkages and couplings between bones, joints, muscles, andthe nervous system.

This specialty update highlights presentations and ad-vances in several areas of orthopaedic rehabilitation in recenttimes. Some abstracts of notable studies in this area of ex-pertise are also succinctly summarized.

Motion Analysis and Dynamic ElectromyographyGait analysis and dynamic electromyography are two essentialtools that are utilized by physicians who deal with both theoperative and nonoperative aspects of motion disorders. Thesemodalities allow not only for the diagnosis of pathologicconditions but also for a deeper understanding of normalmechanics and functional anatomy. Research that stems fromlaboratories utilizing these techniques has allowed for a better

understanding of both the need for and the outcomes of in-terventions (surgical and nonsurgical) that help to facilitatenormal gait and muscle function. There have been multipleexcellent studies in this area of investigation within the pastyear.

One of the dilemmas faced by physicians is the ability tostandardize the data that they receive from different motion-analysis laboratories. How uniform are the protocols andresults from different sites? Gorton et al.1 examined the kine-matic variability among twelve motion-analysis laboratories.They analyzed four sources of variability (examiners, trials,systems, and days), and they also recorded the change in var-iability following the implementation of a standardized gait-analysis protocol. At each of the twelve different sites after aninitial day of instrumentation/calibration, the same singlehealthy subject was evaluated for six consecutive days whileengaging in five kinematic trials examining pelvic tilt, pelvicobliquity, pelvic rotation, hip flexion, hip abduction, hip ro-tation, knee flexion, ankle dorsiflexion, and foot progressionangle. After all trials were completed at a particular site, aminimum standardized gait-analysis protocol was im-plemented, and the same subject returned to each laboratorywithin a three-month period (one year after the first set ofkinematic evaluations) for repeat testing. The authors foundthat without a standardized protocol, >75% of the overallvariance in measurements could not be attributed to the sys-tem (motion capture), between days, or within sessions. Themost likely etiology of the variance was the examiners, par-ticularly with regard to where the markers were being placedon the patients. After implementation of the minimum stan-dardized gait-analysis protocol, there was a 20% decrease inthe standard deviation of all of the kinematic measures exceptpelvic tilt and hip rotation (which had increases of 4% to 8%after implementation of the minimum standardized gait-

Specialty Update has been developed in collaboration with the Council ofMusculoskeletal Specialty Societies (COMSS) of the American Academy ofOrthopaedic Surgeons.

Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. One or more of theauthors, or a member of his or her immediate family, received, in any one year, payments or other benefits of less than $10,000 or a commitment oragreement to provide such benefits from a commercial entity ($1500 Honorarium from JBJS to Dr. Hosalkar for prior Orthopaedic Rehabilitation Update).

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analysis protocol). Furthermore, after implementation of theminimum standardized gait-analysis protocol, the range ofvalues between examiners decreased in all measures by anaverage of 29%, with only hip rotation showing an increase of19% in its range of values. The authors concluded that themost effective way to standardize kinematic measurementsbetween motion-analysis laboratories is to standardize themanner in which examiners place markers on their patients formotion analysis. The results of that study suggest that motion-analysis laboratories should implement a minimum standardgait-analysis protocol such as that utilized by Gorton et al. sothat patient data can be more reliably and accurately combinedfrom different sites. Training programs should be developed topromote uniform marker placement to reduce errors betweenexaminers and motion-analysis laboratories.

Stewart et al.2 examined the action of the hamstringmuscles during standing in crouch to better understand thecrouch gait pattern of patients with cerebral palsy. In an in-vestigation involving five healthy control subjects, the authorsutilized functional electrical stimulation to produce musclecontraction/stimulation while the subjects stood in the crouchposition with one foot on a force platform as well as with bothfeet flat on the ground. Subjects stood in a range of postureswith varying degrees (0�, 10�, 20�, 30�, 40�, 60�, and 80�) ofknee flexion. The hamstrings were stimulated for one secondwith the functional electrical stimulation system, and the re-sulting movements were recorded. The authors found that thehamstrings had a retroverting effect on the pelvis at all degreesof knee flexion while they served to extend the hip. Thisfinding suggests that in a patient with cerebral palsy with ex-cessive anterior pelvic tilt, the hamstring muscles can combatthis deformity. At the knee, the hamstring muscles were shownto act as knee flexors at low knee flexion, but as knee flexionincreased to a position of crouch, the hamstrings displayedactivity as knee extensors. This finding was due to the fact thatthe hamstring moment of the knee was shown to be the neteffect of two competing forces: the moment arm at the knee,promoting crouch, and the moment arm at the hip, promotingextension. This suggests that the hamstrings initiate kneeflexion from a neutral standing position. The hamstrings donot contribute to increased crouch at higher knee flexion an-gles. At high flexion angles, the hamstrings appear to combatknee flexion by promoting hip extension.

The clinical implications of that study suggest that ex-cessive hamstring force at the knee is unlikely to cause in-creased crouch. Rather, weakness of the hamstrings as hipextensors is more likely to be responsible for increased crouch.During neutral standing, the hamstring action leads to pelvicretroversion, hip extension, knee flexion, and ankle dorsi-flexion. As subjects are increasingly positioned in crouch (in-creased knee flexion), the hamstrings continue to retrovert thepelvis and extend the hip, yet they change from flexors toextenders of the knee joint. These findings are important forthe development of surgical interventions for patients with

cerebral palsy who have crouch gait. The authors recognizedthat additional study is necessary to specifically examine thegait of patients with cerebral palsy and to analyze their gait ina more dynamic fashion.

Reinbolt et al.3 further examined gait abnormalities thatare commonly seen in patients with cerebral palsy in a studyexamining the activity of the rectus femoris in stiff-knee gait.Stiff-knee gait is characterized by diminished knee motion anddelayed peak knee flexion during swing and is usually attrib-uted to abnormal prolongation of the rectus femoris into earlyswing. Rectus femoris transfer surgery is utilized to decreasethe muscle’s ability to extend the knee while maintaining itsability to generate a hip flexion moment. Because of varyingoutcomes in association with this procedure, the authorssought to determine the importance of pre-swing (prior totoe-off) rectus femoris activity (rather than early swing ac-tivity) as a contributor to decreased knee flexion in subjectswith a stiff-knee gait. They examined the results of gait analysisfor ten patients with cerebral palsy who had a stiff-knee gaitprior to the performance of a rectus femoris transfer. Noneof these patients used orthoses or assistive devices. They alsoevaluated fifteen healthy control subjects. The gait-analysisdata, including three-dimensional joint angles, ground-reaction forces and moments, and surface electromyographyrecordings, were then utilized to create a muscle-actuateddynamic simulation of each subject in which the rectus femorisactivity was eliminated during pre-swing, and separately dur-ing early swing, to determine resulting changes in knee flexionbased on muscle elimination.

The authors found that peak knee flexion increasedmore (7.5� ± 3.1� compared with 4.7� ± 3.6�; p = 0.035) whenthe rectus was eliminated during pre-swing rather than duringearly swing. Six subjects noted an increase in knee flexion thatwas 90% higher for the pre-swing elimination of rectus ac-tivity than for the early-swing elimination, three subjectsnoted an increase in knee flexion (within 10%) that wassimilar for both cases, and one subject noted a 37% decreasein knee flexion with pre-swing elimination. Given these re-sults, the authors concluded that pre-swing rectus femorisactivity is as important as early-swing activity. Furthermore,for some subjects, pre-swing rectus femoris activity may ac-tually limit knee flexion more than early-swing activity does.The authors suggested that pre-swing muscle forces generatethe initial conditions for swing phase (by increasing kneeflexion velocity at toe-off) and that excessive rectus forceduring double-limb stance may decrease knee velocity at toe-off and lead to a stiff-knee gait. That study is important for thesurgeon who is planning an intervention for the treatment of astiff-knee gait as both early-swing and pre-swing electromyo-graphy activity should be studied. In addition, the muscle-actuated dynamic simulation used in that study is a valuabletool for understanding the biomechanical forces underlyingpathologic gait by allowing the selective elimination of muscleactivity.

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Impaired walking is a major problem faced by patientswho have had a stroke, and inpatient and intensive outpatienttherapy has been successful for improving the gait of thesepatients. Dunsky et al.4 examined the problems with gait re-habilitation that patients face when they return home after astroke, specifically, the inability to integrate intensive gaitpractice in a home-based therapy program because of thespace, facilities, and personnel that are available. In particular,Dunsky et al. examined the use of home-based motor imagerytraining as a rehabilitation tool for gait rehabilitation in indi-viduals who have had a stroke. Motor imagery is a cognitiveoperation that allows for improved performance of certaintasks through the repetition of motor scenes and routines bymeans of imagery4,5. The purpose of the study was to confirm ifhome-based motor imagery training would improve walkingspeed and kinematic variables in individuals who were in thechronic phase of rehabilitation after a stroke. Seventeen pa-tients with hemiparesis stemming from a stroke participated inthe study, which involved six weeks of home-based motorimagery training provided by the same person in the patient’shome and five laboratory sessions (two before the start ofimagery training, one at intermediate term, one at the end ofimagery training, and one at three weeks after the end oftraining). Spatiotemporal and kinematic gait parameters, in-cluding stride length, step length, single and double-supporttimes, and ankle and knee ranges of motion, were measuredwith use of motion and gait-analysis systems. In addition,clinical and functional gait assessment was performed with useof the gait portion of the Tinetti Performance Oriented Mo-bility Assessment and the Modified Functional Walking Cat-egories Index. A full detailed description of the motor imagerytraining appears in the article4.

The authors found that after motor imagery training,mean gait speed increased and was maintained at the time ofthe latest follow-up, stride length increased by 18%, pareticstep length improved by 15%, nonparetic step length improvedby 16%, and average cadence increased by 8%. Furthermore,sagittal knee range of motion of the paretic joint improved by18%. There were no significant changes in range of motion ofthe ankle. There was also a 10% improvement in gait sym-metry, mainly because of a 13% increase in the paretic singlelimb-support period. There was no significant change in theparetic limb-support period, concomitant with a 10% decreasein the double limb-support period. In addition, there was a3-point improvement on the gait scale of the PerformanceOriented Mobility Assessment in fourteen of the seventeenparticipants and a one-category improvement in walking in-dependence as measured with the Modified FunctionalWalking Categories Index in eleven patients. The overall effectsize of the motor imagery was highest for stride length (0.759),followed by nonparetic step length, paretic step length, andwalking speed. Gait symmetry was the least-affected variable.

The authors concluded that although additional study isnecessary, home-based motor imagery exercises can improve

walking skills for patients with hemiparesis after a stroke. Afuture study comparing imagery training with no interventionas well as with non-imagery-based gait rehabilitation courses isnecessary. Yet, the study described above gives hope to thepatient who has had a stroke who can no longer participate inout-of-home, intensive gait rehabilitation, allowing for possi-ble improvement in gait while at home with use of motorimagery.

Amputation Surgery and ProstheticsTechnological advances have continued to lead to vastly im-proved prostheses for patients who have undergone amputa-tion. With the changing nature of military combat, there havebeen an increasing number of young men and women whohave sustained traumatic amputations. This has led to in-creased interest and research in the development of upper andlower extremity prostheses. Yet, even with this technologicaldrive, the key literature from the past year with regard toamputations and prosthetics has centered on traditional am-putation/prosthetic techniques, patient pain, and the psycho-logical effects of undergoing an amputation and/or wearing aprosthesis.

Distal tibiofibular bone bridging in patients with trans-tibial amputation has become a recent area of interest, al-though similar techniques were described as early as WorldWar I6. Strong proponents of the technique argue that thecreation of the bone bridge allows for direct end bearing.Those who are more moderate believe that although thetechnique increases the surface area for distributing mechan-ical load and prevents pain resulting from pathologic motionof the fibula, it should be reserved for young, active amputeeswho would benefit from a better terminal weight-bearingsurface (which would offset the morbidity from additionalsurgery)7. Pinzur et al.7 examined a series of twenty consecutivepatients who had a unilateral transtibial amputation as a resultof trauma who also underwent distal tibiofibular bone bridg-ing. These patients were compared with a historical controlgroup of fifteen highly functional, American control patientswith a transtibial amputation who had not undergone the bonebridging as well as a historical group of thirty-two Brazilianpatients who had undergone a transtibial amputation withdistal tibiofibular bone bridging in their home country. Thegroups were compared with regard to their scores on theProsthesis Evaluation Questionnaire, a validated outcomesmeasure that measures the effect of lower extremity amputa-tion on quality of life. The authors found that the ProsthesisEvaluation Questionnaire scores in the American bone-bridging group were similar to those in the American controlgroup. Both American groups scored lower than the Brazilianbone-bridging group in the social burden, ambulation, frus-tration, sounds, utility, and well-being domains of the Pros-thesis Evaluation Questionnaire.

The results of that study indicate that distal tibiofibularbone bridging may not lead to improved outcomes, particu-

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larly when it requires an additional operation. That study alsofurther highlights the need for prospective studies that notonly can examine the bone-bridging technique, but, moreimportantly, can facilitate further understanding of the resid-ual limb as an end-bearing surface in patients with transtibialamputation.

Following transtibial amputation, various types of rigid(i.e., plaster-of-Paris), semi-rigid, and soft dressings have beenused to facilitate rapid prosthetic fitting and rehabilitation.Rigid plaster-of-Paris dressings have been used for many yearsto control volume and to prevent edema, yet many surgeonscontinue to use soft dressings because they are easier to apply,allow access to wounds, and prevent pressure ulcers. Johannessonet al.8 examined a vacuum-formed removable rigid dressingthat potentially could provide the benefits of a rigid plaster-of-Paris dressing while at the same time allowing wound accessand ease of application. Twenty-seven patients undergoingtranstibial amputation because of peripheral vascular diseasewere randomized to receive either a conventional rigid dressingor the vacuum-formed rigid dressing for five to seven dayspostoperatively, followed by compression therapy with use of asilicone liner. Outcome measures included time to prostheticfitting and function with the prosthesis at three monthspostoperatively. Twenty-three patients (thirteen of fifteen inthe vacuum-formed group and ten of twelve in the traditionalplaster-of-Paris group) achieved prosthetic fitting at threemonths. Three patients were unable to achieve prosthetic fit-ting because of early death related to the medical conditions,and one patient in the plaster-of-Paris group had developmentof a 45� flexion contracture of the hip and knee and was unableto be fitted for a prosthesis. There was no difference betweenthe two dressings with regard to the rate of wound compli-cations or the time to prosthetic fitting (thirty-seven days inthe vacuum-formed group, compared with thirty-four days inthe plaster-of-Paris group). Furthermore, there were no sig-nificant differences between the two groups with regard tofunction with the prosthesis.

The results of that study suggest that the vacuum-formed rigid dressing can provide results similar to thoseprovided by a conventional rigid plaster-of-Paris dressing inthe immediate postoperative period for patients undergoingtranstibial amputation with regard to time to prosthetic fittingand function with the prosthesis, while still allowing access tothe wound and ease of application. Additional study is nec-essary to investigate the cost-effectiveness of this new tech-nology, its applications in other patient populations (patientswithout peripheral vascular disease), and how the outcomescompare with those associated with soft dressings.

Although the orthopaedic community has spent themajority of its time on the technical aspects of amputation, tworecent studies examined the development and treatment ofpain that the amputee experiences postoperatively, one of themajor clinical complaints that the orthopaedic surgeon has toaddress postoperatively. Schley et al.9 examined the potential

mechanisms for the development and origin of phantom-limbpain in a study of ninety-six upper limb amputees (all but oneof whom had undergone an amputation because of a traumaticinjury). Using a questionnaire, they assessed pre-amputationpain and the presence or absence of phantom pain, phantomsensation, stump pain, and stump sensation. The medianduration of follow-up in the study was 3.2 years. The authorsreported stump sensation to be the most prevalent finding intheir cohort (78.5%), followed by stump pain (61.5%),phantom sensation (53.8%), and phantom pain (44.6%).Phantom pain decreased in only 48.2% of the patients andeither remained stable or worsened in the remainder. A similarfinding was found for stump pain, with only 47.5% of thepatients noting reduction in the pain at the time of the ques-tionnaire. Interestingly, phantom pain occurred immediatelyafter amputation in only 28% of the amputees, within one yearin 10%, and after one year in 41%. The authors concluded thatstump pain/sensation is the initial predominating source ofpatient discomfort and that phantom pain/sensation is a long-term consequence (with some patients noting an onset almosta year after surgery).

That study indicates that clinicians must be fluid in theiruse of pain-relieving measures after amputation, dealing withstump pain/sensation initially and then focusing their effortson phantom pain/sensation at a later time with differentmodalities and pharmacologic measures. Furthermore, thatstudy demonstrates that a more nuanced approach to post-operative pain after amputation must be taken (by not simplygrouping all pain as ‘‘phantom’’ pain) and shows that phantompain may appear much later than originally thought and maybe a challenge to treat or alleviate.

In the same light, Wilson et al.10 examined modalitiesthat potentially could be used to deal with persistent pain afterlower extremity amputation; specifically, they performed adouble-blind, randomized trial evaluating the effect of keta-mine on pain and sensory processing after amputation. Fifty-three patients who were undergoing lower limb amputationparticipated in the study. After receiving a combined intrathecal-epidural anesthetic for surgery, patients either received anepidural infusion of racemic ketamine and bupivacaine (groupK) or saline solution and bupivacaine (group S). No otheranalgesics were allowed in the postoperative period (rangingfrom forty-eight to seventy-two hours) except the epiduralinfusions. Pain characteristics were assessed for twelve monthsafter surgery, with a specific focus on the prevalence and se-verity of postoperative pain. In the immediate postoperativeperiod while the epidural anesthetic was being infused, thepatients receiving ketamine and bupivacaine (group K) hadsignificantly lower pain scores than those receiving saline so-lution and bupivacaine (group S). After discontinuation of theepidural anesthetic until the time of the one-year follow-up,the rates of stump and phantom pain did not differ betweenthe two groups (21% and 50%, respectively, for group K,compared with 33% and 40%, respectively, for group S). In-

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terestingly, the levels of depression and anxiety were found todecrease significantly in group K during the course of thestudy, whereas a similar decrease was not seen in group S.

The results of that study suggest that epidural infusionsof ketamine combined with bupivacaine may be of value forthe control of post-amputation pain in the immediate post-operative period. Furthermore, ketamine may have a potentialeffect on decreasing postoperative levels of depression andanxiety; this observation requires additional study.

That study highlights another major battle that ampu-tees face in the postoperative period: depression and anxietyover the loss of the limb. Singh et al.11 examined the course ofsymptoms of depression and anxiety after amputation duringinpatient rehabilitation. One hundred and five patients whowere admitted to inpatient rehabilitation following a lowerlimb amputation were examined. The Hospital Anxiety andDepression Scale was utilized to assess symptoms of anxietyand depression at the times of admission and discharge, andthese symptoms were correlated with demographic and patientfeatures, including the level of amputation, the success of limb-fitting, age, and sex. At the time of admission, 26.7% of thepatients had symptoms of depression and 24.8% had anxiety;these values decreased significantly to 3.8% and 4.8%, re-spectively, at the time of discharge (at a mean of 54.3 dayslater). Patients who had higher levels of depression and anxietyrequired longer inpatient rehabilitation stays, and patients withdepression were more likely to have other medical comor-bidities or to live in isolation. The level of amputation, thesuccess of limb-fitting, age, and sex were not associated withthe failure of these symptoms to resolve.

The results of that study indicate that postoperativedepression and anxiety can resolve more rapidly (in a period ofnearly two months) than what was previously thought (in aperiod of several years). This finding indicates that, during theimmediate postoperative course, inpatient rehabilitationshould be focused on teaching the patient skills that can im-prove his or her function at the time of discharge as thesymptoms of depression and anxiety will rapidly resolve evenin patients who are in severe distress. Furthermore, patients atgreater risk for post-amputation depression (those who havemedical comorbidities or who are living alone) can be iden-tified, and additional support can be given to them both pre-operatively and postoperatively.

Pediatric NeurologyPediatric orthopaedic surgeons commonly deal with themusculoskeletal manifestations of cerebral palsy, workingclosely in a multidisciplinary fashion with pediatricians, neu-rologists, and therapists. Over the past year, several excellentstudies in this area have examined the use of botulinum toxinand baclofen, the outcomes of surgical interventions in thispatient population, and bracing as it affects gait.

Yang et al.12 examined the effects of botulinum toxin typeA on hip subluxation in patients with cerebral palsy. That study

retrospectively compared three different groups of patients: (1)a control group of patients who did not undergo any inter-vention, (2) a group of patients who underwent soft-tissuesurgery on the adductor muscles, and (3) a group of patientswho received botulinum toxin type A injection into the hipadductor muscles. One hundred and ninety-four patients withcerebral palsy were enrolled in the study. The Reimers hipmigration percentage was utilized to measure the degree of hipsubluxation on pelvic radiographs annually. The authorsfound that the overall annual change in the Reimers hip mi-gration percentage improved in both the soft-tissue surgerygroup (21.6% ± 4.4%) and the botulinum group (20.7% ±6.5%), whereas it worsened in the control group (4.4% ±11.3%). The differences between the intervention groups andthe control group were significant, although there was not asignificant difference between the botulinum and soft-tissue-surgery groups. Furthermore, the authors found that severalsubcohorts of patients were more likely to benefit from eitherof the interventions (botulinum toxin type A or soft-tissuesurgery), including patients younger than three years of age,higher-functioning patients, and patients with moderatelysubluxated hips. Future prospective studies examining botu-linum toxin type A as compared with soft-tissue surgery (aswell as combinations thereof) may lead to a viable nonsurgicaltreatment or improved surgical outcomes with combinedmeasures in these patients.

Continuing in the study of pharmacologic agents ef-fecting a change in patients with cerebral palsy, Shilt et al.13

examined the impact of intrathecal baclofen on the naturalhistory of scoliosis in cerebral palsy patients. Intrathecal bac-lofen has been shown to be an effective treatment for spasticityin patients with cerebral palsy; however, questions have beenraised as to whether progression of scoliosis occurs as a sideeffect of this treatment. The authors examined fifty patientswho received intrathecal baclofen as part of the treatment ofspasticity and compared them with fifty control patients whodid not receive the intervention. Annual progression of scoli-osis in these patients was compared with use of Cobb anglemeasurements. In addition, a multiple linear regression modelwas used to examine the differences between the two groupswhile controlling for age, sex, topographic involvement, andthe initial Cobb angle.

The results of that study showed that patients who re-ceived intrathecal baclofen as a treatment for spasticity hadprogression of neuromuscular scoliosis that was no differentfrom that in patients who did not undergo the treatment. Thatstudy should quell concerns that intrathecal baclofen can leadto progression of scoliosis that may not have otherwise oc-curred without intervention, allowing patients to continue toreceive the benefits from intrathecal baclofen treatment.

Turning from the pharmacologic interventions of bot-ulinum toxin and baclofen to surgical intervention, Goughet al.14 examined the outcome of surgical intervention for thetreatment of early deformity in young patients with bilateral

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spastic cerebral palsy who were able to walk. The initialmanagement of these young children generally has concen-trated on therapy, orthoses, and casting in the hopes of pre-venting deformity from occurring. Surgical interventions aredelayed to allow a more mature gait pattern and to prevent arecurrence of deformity as growth occurs. The authors soughtto determine if patients younger than eight years of age whohad bilateral spastic cerebral palsy and who underwent surgicalintervention could maintain an improvement in gait for atleast two years. This improvement would need to be greaterthan the deterioration that would be shown in children whodid not undergo surgical intervention. It was hoped that thiswould parallel the positive results associated with surgical in-tervention (and deterioration associated with conservativemeasures) seen in older patients with cerebral palsy.

The authors examined thirteen patients, seven years ofage and younger, with bilateral spastic cerebral palsy who hadundergone gait analysis and surgical intervention and com-pared them with eleven patients with bilateral spastic cerebralpalsy who also had undergone gait analysis and for whomsurgery was also recommended but was not performed. Thegross motor classification system was calculated, as was themean number of procedures in the surgical treatment group.In addition, the Gillette gait-analysis index, the mean mini-mum knee flexion in stance, the mean popliteal angle, and themean maximum passive dorsiflexion (knee extension) werecalculated. The authors found that the operative treatmentgroup had improvement in outcome measures, including theGillette gait index (p = 0.001), minimum knee flexion in stance(p < 0.001), and maximum degree of dorsiflexion (p <0.0001), through the time of the second postoperative gaitanalysis. The popliteal angle improved after surgery but re-turned to the preoperative baseline at the time of the secondpostoperative gait analysis. In the control group, four childrenhad improvement of >10% in the Gillette gait index, one re-mained stable, and six showed a deterioration of >10%. Thecontrol group also had an increase in minimum knee flexion instance.

The results of that study support the notion that surgicalintervention can be utilized to improve or maintain the mo-bility of the young patient with bilateral spastic cerebral palsywho is able to walk. It is important to note that the authors didnot advocate for routine operative management for this patientpopulation but proposed it is an effective option if traditionalnonoperative methods fail.

Whereas the previous study examined operative inter-ventions for pediatric patients with cerebral palsy, Smith et al.15

examined the use of two different types of braces for patientswith diplegic cerebral palsy and a jump gait pattern. Whereasankle-foot orthoses have been shown to help to facilitatenormal gait, we are not aware of any studies that have shownsuperiority of a hinged ankle-foot orthosis over a dynamicankle-foot orthosis in highly functional (Gross Motor Func-tion Classification System level-I) patients with cerebral palsy

who walk with a jump gait pattern. Fifteen children withspastic diplegic cerebral palsy and twenty children with normalgait were compared. Subjects were tested while barefoot, whilewearing the hinged orthosis, and while wearing the dynamicankle-foot orthosis. The authors found increases in stridelength and walking speed and decreases to normal cadence inassociation with both braces as compared with barefootwalking. Furthermore, when either of the two braces was worn,the cerebral palsy group did not differ from the control groupin terms of stride length, walking speed, or cadence. In addi-tion, the two braces equally improved ankle kinematic andkinetic parameters in the cerebral palsy group. Of note, al-though gait parameters did improve, the results on the Pedi-atric Outcomes Data Collection Instrument and the GrossMotor Function Measure were not different among the threegroups (indicating that there was no detectable change in thepatients’ perceived functional activities). The authors thoughtthat this finding may have been due to the already highfunctional level of the patients in the study.

The results of that study suggest that ankle-foot orthosesare indeed effective for the treatment of patients with diplegiccerebral palsy and a jump gait pattern. The specific brace that isutilized (hinged or dynamic) does not seem as important be-cause both were effective for normalizing gait. Additional studyis necessary to determine if there are other bracing factors(height of orthoses, cosmesis, cost, etc.) that may lead tovariable outcomes in terms of gait and the patient’s perceptionof functional improvement.

Heterotopic OssificationHeterotopic ossification is the abnormal development of bonein areas of the body other than skeletal tissue. It is commonlyknown to complicate total hip arthroplasty and has a strongassociation with traumatic brain injury as well as spinal cordinjury16. Heterotopic ossification also can cause complicationsin joints other than the hip in patients with or without neu-rologic injury. Although heterotopic ossification of theshoulder and elbow joints is usually described in patients withtraumatic brain injury, recent studies have shown significantrates of heterotopic ossification in patients without neurologicinsult who undergo common procedures such as hemiar-throplasty17 and reverse total shoulder arthroplasty18.

The role of bone morphogenetic protein (BMP) signal-ing as an important regulator of ectopic bone formationcontinues to be the focus of research attempting to elucidatethe pathophysiology behind heterotopic ossification. ExcessiveBMP signaling has been implicated as a major contributor toosteoblastic differentiation of mesenchymal stem cells. Patientswith the congenital disorder fibrodysplasia ossificans pro-gressiva have a mutation in the ACVR1 gene that is thought tolead to constitutive activation of BMP type-I receptor activity19.Activation of this group of receptors upregulates the tran-scription of genes important in growth and the differentiationof pluripotent mesenchymal stem cells that lead to the for-

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mation of ectopic bone. Yu et al.20 recently identified a smallmolecule that effectively inhibited transcriptional activity ofBMP type-I receptors and demonstrated disruption of theosteoblast differentiation signaling pathway. That group alsodescribed a transgenic mouse model of heterotopic ossificationthat mimics the intramuscular endochondral bone formationas well as the radiographic and functional outcomes of humanfibrodysplasia ossificans progressiva. Using this mouse model,they demonstrated how an inhibitor of BMP type-I receptorscan disrupt ectopic ossification. Kan et al.21 similarly describedan animal model of heterotopic ossification that implicateddysregulation of local progenitor cells as another cellularmechanism for ectopic bone formation.

Recombinant bone morphogenetic proteins such asrhBMP-2 and rhBMP-7 have a wide range of therapeuticapplications, including United States Food and DrugAdministration-approved use for the treatment of recalcitrantnonunions as well as for spine fusions. These two recombinantproteins have been shown to induce BMP-4 expression22,which is a crucial component of the heterotopic ossificationpathway. However, recent studies have suggested that diffusionof these materials into local soft tissue may lead to ectopic boneformation23-25. Axelrad et al.23 described four cases of hetero-topic ossification that occurred in patients with acute humeralfractures and humeral nonunions that were treated withrhBMP-2 or rhBMP-7. Symptomatic heterotopic ossificationoccurred in these patients between six and ten weeks after openreduction and internal fixation. Three of the four patientsunderwent excision of the ectopic ossification, with improve-ment in range of motion and pain relief. Wysocki and Cohen24

similarly described a case of ectopic ossification of the tricepsafter the use of BMP-7 to augment bone healing at the site of adistal humeral fracture. Lumbar fusion surgery utilizing BMP-2also has been shown to cause extensive bone formation in thepsoas and iliacus muscles25. Given the findings of those reports,rhBMP should be used with caution, especially in periarticularareas. We suggest maintaining meticulous hemostasis andavoiding wound irrigation after BMP placement to reduce theformation of ectopic bone in the surrounding area.

In a retrospective review of the medical complicationsand physical function of 121 patients with traumatic braininjury, Safaz et al.26 found a high rate of heterotopic ossifica-tion. The diagnosis was made on the basis of radiographicfindings and increased levels of serum alkaline phosphatase inpatients with clinical signs such as pain, decreased range ofmotion, swelling, and erythema. Twenty-one of the 121 pa-tients had development of heterotopic ossification in a total offorty-four joints, including twenty-three hips, nine elbows,seven knees, and five shoulders. With the exception of onepatient, all joints with heterotopic ossification were on theplegic side. Patients with heterotopic ossification had decreasedwalking ability as compared with patients without heterotopicossification. It is unclear whether heterotopic ossification re-sulted in physical limitations that restricted walking or whether

increased heterotopic ossification and decreased walkingability were each independently associated with injury severity.Mitsionis et al.27, in a recent study of fourteen patients in theintensive care unit who had substantial heterotopic ossifica-tion, reported that surgical excision of ectopic bone improvedrange of motion (in nineteen of twenty-three knees) and sit-ting ability (in thirteen of the fourteen patients). Improve-ments in walking ability were seen in eight of the fourteenpatients. The authors supported the role of surgical excisionfor the treatment of heterotopic ossification in the knee inorder to improve range of motion, sitting ability, and overallwalking ability.

Heterotopic ossification is a frequent complication aftertotal hip arthroplasty, with a reported prevalence of between15% and 90%. In a study of 103 surface replacement arthro-plasties and ninety-seven total hip arthroplasties, Rama et al.28

compared the prevalence and severity of heterotopic ossifica-tion associated with these two procedures. A significantlyhigher rate of severe heterotopic ossification was found in thesurface replacement group (12.6% [thirteen of 103] comparedwith 2.1% [two of ninety-seven]). This difference may be re-lated to the more extensive surgical approach to the femoralhead in surface replacement.

Other modalities for decreasing the rate of heterotopicossification in patients managed with hip replacement involvethe choice of pharmacologic thromboprophylaxis after totalhip arthroplasty. There is controversy over whether aspirindecreases the prevalence of heterotopic ossification. This the-ory was investigated by Bek et al.29, who retrospectively com-pared the prevalence and severity of heterotopic ossificationbetween sixty-seven patients using warfarin and sixty-six pa-tients using aspirin for postoperative thromboprophylaxis afterstaged bilateral total hip arthroplasty. At the time of follow-up,one year later, heterotopic ossification was seen in 124 hips(46.6%) in seventy-eight patients (59%) according to theBrooker classification system. A significantly lower rate ofheterotopic ossification was found for the patients using as-pirin for prophylaxis (forty-three hips; 34.7%) as comparedwith those using warfarin (eighty-one hips; 65.3%). In addi-tion, significantly more patients had Brooker class-III and IVheterotopic ossification in the warfarin group. Of note, in thewarfarin group, there was a significantly higher rate of treat-ment with use of fixation without cement, which previouslyhas been associated with an increased prevalence of hetero-topic ossification. However, the authors still concluded thataspirin may be more effective than warfarin for the preventionof heterotopic ossification after total hip arthroplasty.

Various studies comparing radiation therapy with in-domethacin for prophylaxis against heterotopic ossificationhave shown inconclusive results. Blokhuis and Frolke30 per-formed a systematic review of five studies involving 384 pa-tients that compared indomethacin (224 patients) withradiation therapy (160 patients) for prophylaxis against het-erotopic ossification after the fixation of acetabular fractures.

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As a result of the usual high-energy trauma associated withacetabular fractures, there is an increased frequency of con-comitant head injury that has been linked with an increasedrisk of ectopic ossification. Heterotopic ossification developedin five of 160 patients managed with radiation, compared withtwenty of 224 patients managed with indomethacin. The au-thors concluded that the current evidence supports the use ofradiation therapy after acetabular surgery when practical.When radiation is not feasible, indomethacin is considered tobe the gold standard for prophylaxis against heterotopic ossi-fication after acetabular surgery, as well as after total hiparthroplasty 31. For total hip arthroplasty, other nonsteroidalanti-inflammatory drugs such as naproxen and diclofenac havebeen shown to prevent clinically important heterotopic ossi-fication and can be considered as alternative first-line therapy.Although it should be used with caution because of a possiblyincreased risk of cardiovascular complications, celecoxib hasefficacy equal to indomethacin and is associated with signifi-cantly fewer gastrointestinal side effects.

Spinal Cord InjuryBasic science research investigating the role of the immunesystem after spinal cord injury has the potential to identifytherapeutic interventions aimed at improving functional re-covery after such an injury. However, reparative or protectiveimmune mediators must be distinguished from components ofthe inflammatory response that contribute to the substantialsecondary damage seen after injury. In addition, their temporalrelation to injury also must be clarified in order to allow for theoptimal targeting of specific aspects of the immune responsethat will limit secondary cell death, prevent axonal degenera-tion, and promote sensorimotor function recovery. Both im-munostimulatory and immunosuppressive therapeutics havehad promising results.

Infection is the leading cause of death in the post-acutephase of spinal cord injury. Although the high susceptibility toinfection following spinal cord injury was previously attributedto iatrogenic methylprednisolone therapy, recent literature hassupported the theory that spinal cord injury induces a sec-ondary immune depression syndrome, also termed spinal cordinjury-induced immune depression syndrome (SCI-IDS). Inboth an animal model32 and a human study 33, Riegger et al.monitored immune cell fluctuations after spinal cord injury. Inthe animal model, populations of innate and adaptive immunecells were monitored in rats undergoing experimentally in-duced spinal cord injury and were compared with those incontrol rats undergoing a sham operation. Decreased levels ofmonocytes, T-lymphocytes, B-lymphocytes, MHC II1 cells,and dendritic cells were seen as early as twenty-four hours afterthe injury, indicating suppression of the innate and adaptiveimmune system. Similar results were found in the humanstudy, with decreases in comparable cell lines evident attwenty-four hours after the injury. In another study, Campagnoloet al.34 showed a significant reduction in natural killer cells

when patients with a spinal cord injury were compared withnormal controls. The level of neurologic injury did not havean impact on the level of reduction in a decentralized ascompared with an intact sympathetic nervous system. Addi-tional investigation into the mechanism behind immune de-pression after spinal cord injury can provide the basis forfuture therapeutic interventions modulating these immuneresponses and decreasing the morbidity and mortality relatedto infection.

Other studies of spinal cord injury have investigated thetheory behind an intense inflammatory response causing sec-ondary damage at the site of injury. Leukocytosis is a well-known response to physical trauma, and animal studies haveshown that injury to the central nervous system causes a moreintense inflammatory response than general trauma does. In astudy of nine patients with a spinal cord injury, Bao et al.35

investigated the oxidative activity of human blood neutrophilsand monocytes and compared this profile with that for tenuninjured controls as well as six trauma controls who hadsustained severe osseous fractures but no central nervoussystem injury. Blood samples that were obtained six hours totwo weeks after the injury were analyzed for oxidative activitywith use of various methods. Neutrophil counts were higher inpatients with spinal cord injury and controls with a traumaticinjury as compared with normal controls. The oxidative burstactivity of neutrophils and monocytes was increased fourfoldto sixfold in comparison with that in uninjured subjectsstarting at twelve hours after the injury and continuing for aslong as one week, reaching a maximum increase at twenty-fourhours. This activity in the patients with spinal cord injury wasalso significantly greater in comparison with that in the con-trols with a traumatic injury. The authors suggested that thisinflammatory response could be a target for agents and in-terventions that limit the migration of neutrophils and mon-ocytes into the injured spinal cord and thereby decreasesecondary damage. Stammers et al.36 also recently described thetemporal expression of inflammatory cytokines in patientswith an acute spinal cord injury. Levels of IL-6, IL-10, IP-10,MCP-1, TNF-R1, and tau in cerebrospinal fluid were found tobe elevated within twenty-four hours after spinal cord injuryand tended to decrease over the next seventy-two hours. Asshown by Yaguchi et al.37 in a mouse model, immediate ad-ministration of IL-12 into a hemisectioned spinal cord in miceresulted in a significant increase in the number of activatedmicroglia and dendritic cells on immunohistochemical anal-ysis as well as a significant improvement in locomotor func-tion. This finding suggests that regulation of these cellularimmune responses may promote functional recovery.

Prediction of the outcome after spinal cord injury playsan important role in planning a rehabilitation program. It alsohelps in understanding the socioeconomic implications. TheNational Institute on Disability and Rehabilitation Research(NIDRR) Spinal Cord Injury Measures Meeting NeuroimagingCommittee advocated the need for future studies investigating

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the prognostic ability of magnetic resonance imaging. Furlanet al.38 conducted a multicenter prospective cohort study withuse of quantitative and qualitative magnetic resonance imagingparameters to predict long-term neurologic recovery in pa-tients with spinal cord injury. Sixty patients with a traumaticcervical spine injury were followed for an average of 6.7months. Clinical data, including the American Spinal InjuryAssociation Impairment Scale (AIS) grade, six qualitativemagnetic resonance imaging parameters (hemorrhage, edema,disc herniation, canal stenosis, swelling, and soft-tissue injury),and three quantitative magnetic resonance imaging parameters(maximum canal compromise, maximum spinal cord com-pression, and length of injury within the spinal cord), wererecorded. The study population was divided into two groups:one group with similar AIS scores at the times of admissionand follow-up and another group with conversion of at leastone AIS grade between the times of admission and follow-up.Analysis showed that neurologic improvement was associatedwith both the absence of hemorrhage and a smaller lesionlength, but neither parameter was significant. Additional in-vestigations are needed to define the role of magnetic reso-nance imaging in predicting clinical outcome.

Functional recovery following a spinal cord injury isthought to arise from multiple mechanisms. These includecompensation, whereby functional improvement occurs in-dependently from neurologic recovery, and neuroplasticity, inwhich reorganization of neuronal circuits leads to functionalimprovement. Repair mechanisms such as remyelination andregeneration of the damaged spinal tract are not thought tosignificantly contribute to functional recovery 39. Exercise maybe beneficial for enhancing neuroplasticity, as suggested by arecent study that showed elevated levels of neuroplasticity-related proteins in paraplegic elite athletes after exercise40. Amultitude of exercises can be employed for patients with aspinal cord injury, but it is difficult to assess which exercises arebest suited to increasing physical capacity and functional ac-tivity. Proponents of activity-dependent neuroplasticity sup-port the use of locomotor training such as functional electricalstimulation and weight-supported treadmill training for im-proving walking ability41. Many studies have supported upperbody and upper extremity training as an effective means ofimproving overall physical capacity42.

More specifically, hand cycling has recently been em-ployed as a mode of exercise in certain rehabilitation centersand even for tetraplegic patients with partially paralyzed armmuscles. This exercise modality is less strenuous than wheel-chair propulsion and is less likely to cause upper extremityoveruse injuries. Valent et al.43 investigated the effect of handcycling on physical capacity in 162 patients with a spinal cordinjury. The patients were separated into two groups; one groupperformed hand cycling at least once a week, and the othergroup did not perform hand cycling. Regression analysis re-vealed a significant relationship between hand cycling andincreases in peak power output, peak oxygen uptake, and el-

bow extension strength in paraplegic patients during clinicalrehabilitation. However, these results were no longer signifi-cant when analyzed one year after clinical rehabilitation. Theauthors suggested that patients in the hand-cycling groupreached a higher physical capacity on discharge, and, therefore,post-rehabilitation differences were not as apparent. As ex-pected, lower gains were found in tetraplegic patients, with nosignificant difference found at any time period, likely becauseof the heterogeneity of the group. Therefore, that study arguesfor regular hand-cycling training as an effective method forimproving aerobic physical capacity.

Upper extremity training is promising as an effectivemeans of rehabilitation for paraplegic patients42 but may not bethe optimal intervention for quadriplegic patients with limitedupper extremity function. Alternatively, surgical interventionsuch as upper extremity tendon transfers can play an impor-tant role in improving the ability of these patients to partici-pate in activities of daily living. Anderson et al.44 conducted asurvey of 137 patients with a cervical spinal cord injury todetermine how they viewed tendon transfer surgery. Fewerthan 50% of the patients had any knowledge of tendon transfersurgery, and tendon transfer surgery had been performed foronly 9% of the patients. Nearly 80% of the respondents re-ported that they would be willing to undergo tendon transfersurgery knowing that they would have decreased independencefor two to three months during recovery, with the ultimategoal of being more independent afterward. From the patient’sperspective, the optimal timing of surgery would be within fiveyears after the injury. The authors concluded that regainingarm and hand function is vitally important to this group ofpatients and that awareness of tendon transfer surgery needs tobe improved.

The diagnosis of traumatic brain injury in patients with atraumatic spinal cord injury presents a complex clinical chal-lenge. Conventional rehabilitation methods for patients with aspinal cord injury require the ability to acquire new knowledgeand skills to relearn and regain function; this ability is oftencompromised in patients with a traumatic brain injury. Asdocumented by Macciocchi et al.45, the diagnosis of concom-itant traumatic brain injury is often missed in the acute-caresetting, signifying the need to educate hospital staff on theimpact of having both diagnoses on the acute rehabilitationneeds. Patients who have a spinal cord injury with a con-comitant traumatic brain injury achieve smaller functionalgains than those without traumatic brain injury46, and a recentprospective case-matched control study by Bradbury et al.47

showed an association between prolonged loss of conscious-ness and significantly worse neuropsychological test perfor-mance. Furthermore, the authors found the FunctionalIndependence Measure cognitive subscale, a commonscreening test of cognitive status used for inpatient spinal cordrehabilitation programs, to be an inadequate measure of cog-nitive impairment. Not surprisingly, concomitant traumaticbrain injury was also associated with increased daily rehabili-

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tation costs and greater demands on clinician resources andspecialized services.

Life satisfaction after spinal cord injury was recentlyquantified in two studies. Van Koppenhagen et al.48 analyzeddeterminants of life satisfaction in adult patients with a spinalcord injury. At the commencement of active rehabilitation, 147patients were asked to retrospectively report life satisfactionbefore the injury. One year after discharge, participants wereasked to rate their current life satisfaction. The correlation ofthe results with demographic and lesion characteristics wasanalyzed, and moderate decreases in life satisfaction werefound between the two time points. Decreases in self-care,vocational situation, and sexual life were most significant.Partner relations, family life, and contacts with friends andacquaintances appeared to be least affected and were found tobe higher in some participants. High lesion level, pain, andsecondary impairments were also found to be significant de-terminants of life satisfaction. Chen et al.49 performed a similarbut longer-term prospective cohort study evaluating life sat-isfaction over a decade for adult patients with pediatric-onsetspinal cord injury. The authors examined life satisfaction for278 patients with an average age of 27.1 years; the average timesince the injury was 12.8 years. Satisfaction With Life Scalescores increased gradually over time. Injury severity did nothave an effect on satisfaction, but a lower level of injury (T7 toS5 as compared with C1 to T6) was associated with a signifi-cantly greater increase in life satisfaction over time. Patientswho were employed or who were students and those who weremarried or living with a partner had better life satisfaction,stressing the importance of spouse and peer support in reha-bilitation. Illicit drug use had a significantly negative associa-tion. The authors found several modifiable risk factors that, iftargeted for intervention, could minimize the risk of dimin-ishing life satisfaction.

Patients with a spinal cord injury often require longhospital stays in specialized spinal cord injury units, resultingin a high personal and economic burden of care. Becausepatients with spinal cord injury often live in areas wheremedical and nursing staff with spinal cord injury expertise isunavailable, telemedicine is emerging as an effective method ofimproving the quality of care after discharge.

Although telemedicine is conceptually effective, thenumber of valid studies quantifying improved functionaloutcomes and decreased clinical complications is scarce.Dallolio et al.50 conducted a multicenter randomized con-trolled trial of 127 patients with a spinal cord injury to eval-uate the six-month outcomes of telemedicine as comparedwith those of standard care. Telerehabilitation was performedat three different sites in Belgium and Italy with use of dedi-cated video-conferencing consisting of weekly sessions for thefirst two months, followed by biweekly sessions for fourmonths. Baseline functional measurements that were ob-tained ten days before hospital discharge were compared withfunctional outcomes at two and six months after discharge.

There were no significant differences between the two groupswith regard to the number or type of clinical complications orthe number of hospital readmissions. One of the three sitesshowed significantly higher gains in the telemedicine group,with improved grooming, dressing the upper and lower body,and bed/chair/wheelchair transfers contributing the most tothis difference. The telemedicine group reported significantlyhigher satisfaction with care. Along with telerehabilitation,Goodman et al.51 suggested that computer and Internet use bypatients with a spinal cord injury holds considerable potentialas a long-term treatment modality. Additional studies arerequired to quantify whether telemedicine can potentially becost saving.

Diabetes and Involvement of the Lower ExtremityDiabetes-related complications involving the lower extremityare associated with a high rate of morbidity and mortality andimpose a tremendous burden on the health-care system, andthe paucity of well-designed randomized clinical trials makes itdifficult for physicians to make sound evidence-based deci-sions. Hence, the outcomes of treatment are often poor. It iswell accepted that a multidisciplinary approach to the diabeticfoot is necessary for favorable results. In an effort to stan-dardize diagnosis and management, the International WorkingGroup on the Diabetic Foot has produced a series of systematicreviews and guidelines52-54.

Compared with healthy individuals, diabetic patientshave a tenfold increased risk for soft-tissue and bone infectionsof the lower extremity, with the health of as many as 20%of diabetic individuals being complicated by osteomyelitis.However, making the definitive diagnosis of osteomyelitis inthe diabetic foot is difficult because there is no highly sensitiveand specific diagnostic test available. This is further compli-cated by the late onset of radiographic features of osteomyelitison plain radiographs and the high rate of peripheral neurop-athy, which masks the usual symptoms of infection. Two sys-tematic reviews analyzed the accuracy of clinical examinationand imaging tests in the diagnosis of osteomyelitis in thispopulation. In the methodologically rigorous study by Dinhet al.55, a total of nine articles met the inclusion criteria for theanalysis. The ‘‘probe-to-bone’’ test (the ability to probe awound for bone without any intervening soft tissue) had asensitivity of 0.60 and a specificity of 0.91. Of the imagingmodalities, magnetic resonance imaging was more useful(sensitivity, 0.90; specificity, 0.79) than leukocyte scans andrelatively nonspecific bone scans. Butalia et al.56, in a review oftwenty-one studies, reported similar findings: the ‘‘probe-to-bone’’ test and an ulcer area of >2 cm2 were the most reliableclinical examination findings, and magnetic resonance imag-ing had the highest overall accuracy of the imaging modalities,with a weighted sensitivity and specificity of 89%. However,magnetic resonance imaging findings must be interpretedcautiously as previous studies attempting to correlate magneticresonance imaging findings with histologic findings have

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shown that marrow edema can be difficult to distinguish fromosteomyelitis. The detection of osteomyelitis in tarsal bones inparticular has a particularly low specificity57. The investigatorsconcluded that there is no examination or imaging feature thatreliably excludes osteomyelitis in the diabetic foot.

Diabetic patients with osteomyelitis of the foot have ahigh likelihood of requiring a lower extremity amputation.Therefore, prompt and effective treatment is necessary. Un-fortunately, there is currently no consensus for the standard fortreatment. Berendt et al.53 conducted a systematic review of1168 studies, but only nineteen met the inclusion criteria.There was little evidence to encourage surgical interventionover medical management. In addition, the results regardingthe choice and duration of antibiotics as well as those regardingthe effectiveness of other adjunctive therapies such as revas-cularization and hyperbaric oxygen therapy were inconclusive.The authors concluded that the quality of published work inthe area is poor, with few controlled randomized studies, andthat there are no data to support the superiority of one in-tervention over another at this time.

The treatment of infected wounds in the diabetic footusually consists of oral or parenteral antibiotics with poly-microbial coverage. Lipsky et al.58 conducted two consecutivedouble-blind, randomized, controlled, multicenter trials inwhich topical antimicrobial therapy was compared with oralantibiotic therapy for the treatment of mild diabetic foot in-fections. A total of 835 patients with infected full-thicknesswounds were randomized to either the local application of 2%pexiganan acetate cream twice daily or treatment with oralofloxacin twice daily for two to four weeks. Patients in thepexiganan treatment group received placebo tablets, whereasthose in the ofloxacin treatment group received placebo cream.There was a lower percentage of clinical improvement in thetopical treatment group at both four and six weeks, althoughthe difference was not significant. Bacterial resistance emergedin some patients taking ofloxacin but not those using thetopical cream. The authors concluded that topical pexiganan isa therapeutic alternative to broad-spectrum oral antibiotics forthe treatment of mildly infected diabetic foot ulcers, with thepossible benefit of reducing bacterial resistance seen in asso-ciation with oral antibiotic administration. In contrast,Hinchliffe et al.54, in a systematic review of interventions forenhancing the healing of chronic diabetic foot ulcers, did notfind any data to support the use of any topically applied pro-duct or dressing. Their study supported the use of systemichyperbaric oxygen therapy and topical negative-pressuretherapy.

Footwear and off-loading techniques are commonlyused for the prevention and treatment of diabetic plantar footulcers. These interventions include four main groups: castingtechniques such as total contact casts; footwear such as socks,insoles, and orthoses; surgical off-loading techniques such asAchilles tendon lengthening, arthroplasty, and osteotomy; andother off-loading techniques such as crutches, walkers, and

bracing. Bus et al.52 systematically reviewed twenty-one Level-Iand II studies as well as 108 Level-III studies to determinewhether the current literature supports the use of these ther-apeutic interventions for the prevention and treatment of di-abetic foot ulcers. Surgical off-loading techniques such asAchilles tendon lengthening, surgical excision of osseousprominences, joint arthroplasty, and metatarsal head resectionappear to provide a reduced risk of ulcer recurrence whencompared with nonsurgical measures. Studies with appropri-ate methodology evaluating footwear and off-loading devicesfor the prevention of ulcer recurrence were lacking. While totalcontact casting has been accepted as an effective treatment fordiabetic foot ulcers and evidence shows that it leads to healingof a higher proportion of plantar ulcers at a faster rate thanother off-loading modalities59, a recent study involving 901geographically diverse centers across the United States showedthat shoe modifications were used in favor of total contactcasting for the treatment of ulcers, with total contact castingbeing used at only 1.7% of the centers60.

The rate of complications for diabetic patients managedboth operatively and nonoperatively for ankle fractures ishigher than that for nondiabetic patients. Wukich and Kline61

reviewed the specific characteristics that must be consideredwhen treating ankle fractures in this patient population. Co-morbidities such as vasculopathy, neuropathy, and Charcotarthropathy must be taken into consideration as the risk ofcomplications is higher in diabetic patients with comorbiditiesthan in those without. Stable, nondisplaced fractures can besuccessfully treated with nonoperative measures, whereas un-stable fractures should be treated with surgical intervention.Although there is a trend toward the use of supplementalfixation for patients with neuropathy, there are insufficientdata to make this recommendation. Studies do support aprolonged period of non-weight-bearing for both nonopera-tive and operative interventions. Optimization of treatmentwill require additional studies in this area.

Chronic WoundsChronic wounds are defined as wounds that do not have an-atomic and functional integrity after three months62. TheWound Healing Society uses the TIME acronym to define theimportant elements of wound-healing. ‘‘T’’ refers to the re-moval of nonviable or unhealthy tissue, ‘‘I’’ refers to thepresence of inflammation and the control of infection, ‘‘M’’stresses the importance of moisture balance, and ‘‘E’’ refers tothe advancing wound edge and re-epithelialization. To addressthese four components, there are numerous treatment mo-dalities, including wound debridement, pressure off-loading,addressing vascular deficiency, and treatment of infection.Although these modalities are considered by many to be ac-cepted standards for wound care, the benefits and effectivenessof these therapies are based mainly on experience, withoutrandomized controlled trials to definitively support their use.In recent years, advanced therapies to augment these basic

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cornerstones of wound therapy have been investigated. Thesetherapies include, among others, specialized dressings, non-contact ultrasound, and negative-pressure wound therapy.Both the large number of treatment modalities available andthe various indications for each of these interventions makethe use of evidence supporting one treatment over anotherespecially challenging. In addition, many of the novel treat-ments are often expensive, adding to the already enormouscost of wound-care therapy.

The development of pressure wounds is a frequentcomplication in patients who have a spinal cord injury and isone of the most frequent causes of hospital readmission. Arecent study by Smith et al.63 highlighted the risk factorsfor the development of pressure ulcers in veterans with aspinal cord injury. A total of 2574 patients responded to theSpinal Cord Dysfunction Health Care Questionnaire that wasmailed to them. The primary outcome measure was thepresence or absence of one or more pressure ulcers duringthe past year. Thirty-six percent of respondents had one ormore pressure ulcers, with an average of 2.63 ulcers withinthat group. Analysis of demographic characteristics revealeda significantly lower prevalence of pressure ulcers in veteranswho were married or employed. Patient age was not a pre-dictor of ulcer formation, but patients who had sustainedthe injury more than twenty years ago were more likely tohave development of pressure wounds. Interestingly, only34.2% of veterans with service-connected injuries had de-velopment of pressure ulcers, compared with 44.9% of thosewith non-service-connected injuries. Also, veterans whoreported receiving all of their health care in the VeteransAdministration system were less likely to report any pressureulcers in comparison with veterans who received their carein a non-Veterans Administration setting. Medical comor-bidities that were associated with an increased prevalence ofpressure ulcers included diabetes, hypertension, and de-pression. Thus, the authors concluded that the use of moreaggressive prevention strategies should focus on individualswith a high burden of chronic illnesses such as diabetes ordepression. Furthermore, the prevalence of pressure ulcerswas also higher in current smokers, emphasizing the im-portance of smoking cessation as a crucial part of ulcerprevention.

The importance of patient education and a structuredfollow-up program for chronic ulcers in military veterans wasalso shown by Rintala et al.64. In a randomized controlled trialevaluating the effectiveness of a two-year structured follow-upprogram after surgical repair of stage-III or IV pressure ulcersin veterans with spinal cord injury, forty-one patients weredivided into three groups: Group 1 comprised twenty patientswho received enhanced education and monthly follow-upevaluations for as long as two years after discharge, Group 2included eleven patients who received monthly contacts for aslong as two years but no enhanced education during or afterhospitalization, and Group 3 included ten patients who re-

ceived minimal contact every three months for as long as twoyears. Enhanced education consisted of four one-hour one-on-one sessions with an occupational therapist with expertisein the prevention and treatment of pressure ulcers, and atleast one session was done with a family member or signifi-cant other. Patients in Group 1, who received enhanced ed-ucation, had a reduced rate of recurrence as compared withpatients in Groups 2 and 3 (33%, 60%, and 90%, respec-tively) and were ulcer-free for a significantly longer timeperiod as compared with patients in Groups 2 and 3 (19.6,10.1, and 10.3 months, respectively). Health status and thelevel of the spinal cord injury were not predictive of ulcerrecurrence or ulcer-free survival time. Although there wasinsufficient power to confirm the hypothesis, the study sug-gested that individualized one-on-one education and struc-tured follow-up effectively reduce ulcer recurrence in thispopulation.

Chronic wounds are prevalent in residents of long-term-care facilities, and the outcomes for these patients are poor.Takahashi et al. described the factors affecting chronic wound-healing65 as well as the long-term outcomes for these patients66.In a retrospective cohort study of 397 long-term-care residents,the investigators found that 66% of the ulcers did not heal.Residents with diabetes mellitus, peripheral vascular disease, agreater number of wounds, and a larger wound area had asignificantly greater odds ratio for wound nonhealing; aftermultivariate analysis, only the number of wounds and thehemoglobin level were significant predictors for nonhealing.In another study, involving 411 long-term-care residents,Takahashi et al. found that the number of chronic wounds hada significant association with six-month mortality afteradjustment for other comorbid health conditions, with anodds ratio of 1.32. The authors suggested that health-careproviders should set realistic expectations for patients withmultiple chronic nonhealing ulcers because their presenceindicates decreased overall patient health and portends ahigher mortality rate.

Recent evidence supporting the use of noncontact ul-trasound for the treatment of chronic wounds has been ac-cumulating. In a prospective randomized study of seventypatients with critical limb ischemia (defined as a transcuta-neous oximetry value of <40 mm Hg), Kavros et al.67 examinedthe impact of this therapy as an adjunct to conventionaltherapy. At twelve weeks, a significantly higher percentage ofpatients had >50% reduction in wound size when managedwith noncontact low-frequency ultrasound three times perweek as compared with those who received standard woundcare (63% compared with 29%). A similar retrospective reviewby Kavros et al.68 also showed a faster rate of healing in thegroup managed with ultrasound. Moreover, Bell and Cavorsi69

performed a retrospective review of seventy-six patients whoreceived conventional outpatient wound care with noncontactultrasound therapy for the treatment of nonhealing woundsand found a median wound area reduction of 79%. Serena

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et al.70 also showed that noncontact ultrasound reduced thebacterial quantity in chronic wounds. Those studies all con-tributed more data supporting the use of this relatively newform of wound therapy.

One of the more popular types of specialized dressingsfor the treatment of chronically infected wounds are silver-coated dressings, which are currently approved by the UnitedStates Food and Drug Administration for the treatment of fulland partial-thickness wounds, partial-thickness burns, skingrafts, donor sites, and dermal ulcers. Moore et al.71 reportedtheir experience with a silver-coated polymeric substrate-containing dressing in ninety-seven patients with diabetic, is-chemic, venous, or traumatic wounds. At a median of seventy-four days, thirty-five (36.1%) of the ninety-seven wounds hadcompletely healed. The median decrease in wound size was55.2% at 86.5 days. Of the multiple comorbidities that wereanalyzed in the study, only hypertension was associated with alower percentage of healing. Lo et al.72 also systematically re-viewed the use of silver-releasing dressings in the treatment ofinfected chronic wounds. Although there was a lack of well-designed studies with standardized outcomes measurements,all of the studies that were included showed positive effects ofsilver dressings.

Another approach to wound therapy that has gainedpopularity recently is topical negative-pressure therapy, alsoknown as vacuum-assisted closure. This therapy has receivedincreased attention for the treatment of traumatic wounds andwar wounds73. Webb and Pape74 discussed the two competingtheories behind the mechanism of action of this therapy. Thefirst mechanism involves tissue strain causing the release ofgrowth factors that stimulates tissue regeneration and angio-genesis. The second mechanism involves the removal of excessedematous fluid in the interstitium to allow for improvedmicrocirculation. A cycle in the typical wound involves therelease of inflammatory mediators from damaged tissue,capillary leakage, and increased pressure in the interstitial

space. This pressure leads to cell death resulting from dimin-ished metabolic exchange. The use of negative pressure todecrease the excess fluid and pressure in the interstitium al-leviates capillary afterload, decreases secondary necrosis, andthus decreases the risk of consequent infections. Dedmondet al.75 reported on the use of negative-pressure wound therapyfor the treatment of soft-tissue injuries in a study of fifty pa-tients with grade-III open tibial shaft fractures. The overallinfection rate with use of negative-pressure wound therapy was30%, with 22% of the patients requiring repeat surgery be-cause of infection. Higher rates were found in patients withgrade-IIIB and IIIC fractures. Five of the fifty patients requiredamputation, and 48% required surgery to facilitate fracture-healing. Free tissue transfer or rotational muscle flaps wererequired in seventeen patients. The authors compared theseresults with historical data and concluded that use of negative-pressure wound therapy does not increase the rate of infectionand may decrease the need for free tissue transfer or rotationalmuscle flaps.

Harish Hosalkar, MD, MBMS(Orth), FCPS(Orth), DNB(Orth)Rady Children’s Hospital,UCSD San Diego,3030 Children’s Way, Suite 410, San Diego, CA 92123.E-mail address: [email protected]

Nirav K. Pandya, MDJason Hsu, MDMary Ann Keenan, MDDepartment of Orthopaedic Surgery,Hospital of the University of Pennsylvania,3400 Spruce Street,Two Silverstein, Philadelphia, PA 19104.E-mail address for M.A. Keenan: [email protected]

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