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Pediatric Neurology 48 (2013) 424e431

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Pediatric Neurology

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Review Article

Rehabilitation of Children With Traumatic Brain Injury: A Critical Review

Galit Tal MD, Emanuel Tirosh MD *

The Hannah Khoushy Child Development Center, Bnai Zion Medical Center, Haifa, Israel

article information

Article history:Received 27 February 2012Accepted 26 November 2012

a

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* Communications should be addressed to: DKhoushy Child Development Center; Bnai Zi4940; Haifa, Israel.

E-mail address: tirosh-e@b-zion.org.il

0887-8994/$ - see front matter � 2013 Elsevier Inc. Ahttp://dx.doi.org/10.1016/j.pediatrneurol.2012.11.008

bstract

he purpose of this critical review of the English literature published between 1975 and009 was to assess the quality of the evidence for the efficacy of rehabilitation intervention

after traumatic brain injury in children. “Evidence for intervention studies” was used toclassify the research strength of design and report. Only a minority (16/439) of the publishedstudies has been related to traumatic brain injury in children and has used a scientific orquasiscientific design. Only one study met the criteria of class I “evidence for intervention”studies. However, this study included adults, as well as children. The other 15 studies,although reporting positive results, had many methodologic deficiencies, and consequentlytheir validity is questionable. Although the methodologic and ethical difficulties involved areacknowleged, a multicenter approach is required to achieve valid conclusions. Use of designssuch as comparative effectiveness research might prove to be a practical solution. High-quality intervention research would facilitate stronger evidence-based counseling for chil-dren and families requiring posttraumatic brain injury intervention and to policy makers.

� 2013 Elsevier Inc. All rights reserved.

Introduction

Acquired brain injury (ABI) is a general term referring toevents such as traumatic brain injury (TBI), central nervoussystem infection, stroke, hypoxia, tumor, and radiationtreatments, with marked variability in outcome. Of thecauses of ABI, traumatic brain injury (TBI) has been reportedas the major cause of morbidity and death [1,2]. In theUnited States, the Centers for Disease Control and Preven-tion has estimated that 250 of every 100,000 people willsustain a brain injury every year [3]. Severe TBI has beenstrongly associated with persistent moderate or severedisability [4,5]. Approximately 25% of the children andyouth with acquired brain injury will require rehabilitationservices [3]. It is assumed that brain plasticity provides thefoundation for recovery that can be enhanced by rehabili-tative intervention. The less optimal recovery after severeearly brain injury as compared with later sustained injuryhas been recently acknowledged [5,6]. Despite the large

r. E. Tirosh; The Hannahon Medical Center; POB

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number of patients and massive resources invested inrehabilitation programs after TBI, very little is known aboutthe efficacy (and more so effectiveness) of such interven-tions [7-11]. In view of the natural course after TBI there areethical and methodologic difficulties in the evaluation ofthe treatment impact [11]. The randomized controlled trialdesign is widely accepted as providing the best evidence inscientific terms. In rehabilitation research, however, it iscontroversial because of ethical and practical problems,such as deprivation of possible valuable intervention, thesmall number of cases in any one center at a certain point oftime, the diversity of patient disease, the diversity of reha-bilitation goals and the difficulty in applying a uniformtherapeutic approach [12]. Three review articles on cogni-tive rehabilitation after ABI in children found a critical lackof randomized controlled studies addressing treatmentefficacy [8-10]. The purpose of this article is to review theliterature for evidence-based studies related to the effec-tiveness of rehabilitation in children who have sustainedTBI between 1975 and 2009. Studies pertaining to func-tional physical and cognitive outcomes were the focus ofthe review. Unlike previous reviews focusing specifically oncognitive outcomes [8-10] or ABI [6], we have addressed allpossible functional outcomes.

Table 1. Definition of classification of evidence for intervention studies

Definition for Classification

Class I Prospective, randomized controlled clinical trials withblind assessment of outcome in a representativepopulation. The primary outcome, inclusion and exclusioncriteria clearly defined. Drop outs and crossover to theother group are minimal. Baseline characteristics shouldbe similar between groups.

Class II Prospective matched group cohort study ina representative population with blind assessment ofoutcome or a randomized controlled trial with onesignificant flow (e.g., primary outcome not clearlydefined).

Class III All other controlled trials (including well defined naturalhistory controls or patients serving as own controls) ina representative population where outcome is blindlyassessed or independently derived by objective outcomemeasurement.

Class IV Evidence from uncontrolled studies, case series, casereports, or expert opinion.

G. Tal, E. Tirosh / Pediatric Neurology 48 (2013) 424e431 425

Materials and Methods

A computerized search of the literature published in English, duringthe years 1975 to 2009, by use of the Pubmed, Cochrane, and MD Consultdatabases, was performed. We used the following entries in differentcombinations: rehabilitation, traumatic brain injury, children or pedi-atrics, intervention, outcome, effectiveness or efficacy, and review. Theinclusion criteria were as follow: (1) Children under the age of 18 yearswere included in the report; (2) the study pertained to children whosustained TBI; (3) the intervention took place in either an inpatient orcommunity framework; (4) the follow-up period was at least 3 months;and (5) a defined outcome of interest was assessed.

Two pediatricians in the field of child development and neurologydid the preliminary search independently. The literature search yielded460 articles, of which 456 had abstracts. All abstracts were studiedindependently by a pediatrician involved with child development andrehabilitation and a certified neurodevelopmental pediatrician. Of the456 abstracts read, 439 were found to be irrelevant as agreed to by thetwo reviewers (adult studies, neonatal studies, and technique descrip-tions with no outcome assessment, studies addressing emotional/behavioral aspects or family function only and case reports). Single-subject research design suggested for the assessment of rehabilitationoutcome [13] has not been included in our review, because only a largenumber of replicated studies and properly calculated effect size allowtheir results to be generalized. Only 16 studies were found to be relevantto this review, and their full text was critically reviewed. After a discus-sion between the reviewers, a consensus was reached with regard toclass assignment. The studies were defined and classified as “evidencefor intervention” studies on the basis of the system by Edlund et al. [14]as class I (strongest) -IV (weakest) (Table 1). This classification systemhas previously been used in other reviews pertaining to rehabilitation[9,10]. Thus a comprehensive conclusion stemming from these reviewscan be generated.

Results

Description and classification of the 16 research articles[15-30] are summarized in Table 2.The reviews are listedfrom the weakest (IV) to the strongest (I) evidence and inchronological order. The following are the included researchreports in order from class IV to I evidence-class and theirmain methodologic problems.

The reports assigned class IV evidence for intervention:the seemingly retrospective descriptive research by Bergeret al. [15] included 38 children, with 44.7% resulting from

TBI, with no differential analysis of this subgroup. Theintervention was used during the inpatient period only butincluded a follow-up period of 6 months, while being backin the community. The intervention is reported in generalterms and therefore cannot be replicated from the basis ofthe report, and the outcome measures other than the levelof vigilance were descriptive. No control or contrast groupwas included, and the results were not statisticallyanalyzed.

One research report [16] pertained specifically to prag-matic skills in six adolescents, of whom five sustaineda closed head injury. Although the procedure and instru-ment, as well as the intervention, are well described, anda wash-out period of few months has been included, nocontrol or contrast group was used. Therefore the resultscannot be attributed specifically to the intervention per se.

The retrospective, descriptive, uncontrolled study byPace et al. [17] included 77 participants with ABI, who wereenrolled in a home-based rehabilitation program. Sixty-eight percent of the participants were younger than age20 years, of whom 73% sustained TBI. Both predeterminedindividualized clinical goals and family satisfaction(assessed in 45 of the families) were used as outcomes ofinterest. The intervention is described in general terms only.However, the follow-up period lasted 12 months.

Another uncontrolled, retrospective descriptive study byDumas et al. [18] also included 79 children undergoinginpatient intervention only and included children in theiracute state after TBI. This study defined the outcome ofinterest and used a valid measure of assessment pertainingto different functional skills.

The report of Chen et al. [19] pertained to a retrospectiveanalysis of an acute rehabilitation service, using a psycho-metrically valid and reliable instrument. The data werefrom 910 children, of whom 336 suffered TBI. Twelve of 32institutes agreed to participate. The interval between thetime of diagnosis and rehabilitation onset was significantlyshorter in children with TBI. These two factors were animportant source of bias. A differential analysis of outcomein patients with TBI as compared with other causes wasperformed. The analysis of the outcomes of interest was ofcorrelative nature but related to the total amount of reha-bilitation time rather than to the specific methods ordisciplines involved.

Conversely the second study by Dumas et al. [20] with anextended cohort of inpatients, some of whom were alsoincluded in the first study, focused on the contribution ofphysical therapy (PT) to the recovery of children older than2 years of age who sustained TBI. The study was uncon-trolled, and retrospective data extractionwas obtained froma daily-standardized recording system. The valid measure-ment used was the same as in the first study. Because theexact nature of PT administered to each patient could not bespecified, the authors resorted to an analysis of the effect ofPT intensity only.

In 2005, Abdullah et al. [21] reported a descriptive studyof 36 children who suffered mild to severe head injury.Children with prolonged hypoxia, dilated pupils, or surgicalinterventionwere not included in the cohort. The follow-uplasted 12 months. All patients received “traditional” treat-ment with no designated rehabilitation program because ofa lack of facilities. The outcome of interest was cognitive

Table 2. Description and classification of the reviewed articles

Author Year[No]

ClassificationEvidence

Sample Characteristics Study Design Evaluated Outcomes

Berger et al.1997 [15]

IV 31 patients (average 7.8 years),during inpatient rehabilitationfollowing ABI (44.7% TBI) TFI:3.90 days

Retrospective uncontrolled study.Evaluates the course of rehabilitationand the outcome 6 months after theend of inpatient rehabilitation (GOSand goals achievements),

21% were defined as achieving goodrehabilitation, although nearly 45% ofpatients displayed severe impairment.After6months further improvementwasfound in 40% of patients, however onlyslightly changing the overall GOS values

Wiseman-Hakeset al. 1998[16]

IV 6 adolescents with pragmaticcommunication deficitssecondary to ABI (83% TBI) TFI:4 months-9 years.

Prospective uncontrolled study.Evaluates a method of group trainingfor adolescents with pragmatic deficitssecondary to ABI, using standard scoresbefore treatment, immediately aftertreatment and6months post treatment.

Significant differences in thepretreatment-to-posttreatment periodand were maintained at follow-up.

Pace et al. 1999[17]

IV 77 patients with ABI (73% TBI)TFI: not reported

Prospective uncontrolled study.Individual goals achievement followinghome-base rehabilitation program.Assessment at discharge from theprogram, and at 6 and 12 monthsfollow up.

77% of individualized outcome goalswere achieved at discharge, 80% at 6months and 78% at 12 months

Dumas et al.2002 [18]

IV 79 children and adolescentswith TBI, mean age 9.9 years.TFI: 34-53 days.

Retrospective descriptive study. Thepatients were assessed using PEDIfunctional skills and care givenassistance domains of self-care,mobility and social function, onadmission and discharge

At discharge significant improvementwas noted within all three domains(the greatest) change was in mobility.

Chen et al. 2004[19]

IV 814 pediatric patients whoreceived inpatientrehabilitation (41% after TBI)TFI: 1-1525

Retrospective cohort design. Collectingrecords of pediatric patients whoreceived inpatient rehabilitation andtheir functional assessment. Data wereextracted from patient billing ortreatment records or both and theWeeFIM data base.

Most children improved after receivingrehabilitation. Children > 7 years andthosewith traumatic injurymade largergains. The amount of total treatment,combined or discipline-specific,significantly contribute to gains in self-care, mobility, and cognition

Dumas et al.2004 [20]

IV 80 children and adolescentswith TBI, admitted to inpatientrehabilitation. TFI: 6-78 days

Retrospective cohort study. Describethe types and intensity of PTintervention used during inpatientrehabilitation. To examine therelationship between the intensity ofPT procedurals intervention andmobility changes throughout theintervention using standardized scales(data were collected from the hospitalmedical records).

The intensity of PT intervention in aninpatient rehabilitation hospital isrelated to positive changes infunctional mobility scores and theachievement of a minimal clinicalimportant difference.

Abdullah et al.2005 [21]

IV 36 patients with mild to severehead trauma (92% with severeTBI) TFI: not applicable.

Prospective uncontrolled study.Assessment of patients at 3, 6, and 12months after the occurring event forneuropsychological functions.

No general improvement whencompared to the western literature

Dumas et al.2008 [22]

IV 452 pediatric patients whoreceived inpatientrehabilitation (65% followingABI) TFI: not reported

Prospective uncontrolled study.Evaluating the proportion of childrenwho achieved minimal importantdifference during inpatientrehabilitation, using change scores(Average length of stay: 46.3 days).

More than 55% of the children achievedMID. Highest proportion in mobility.Greater chance of achieving MID: olderage >10 years, longer length of stay,lower admission PEDI score anda diagnosis of ABI.

Tepas et al.2009 [23]

IV 60 children, mean age11.2 years, with TBI and initialGCS score of 8 or lower. TFI:0-24 days

Retrospective, uncontrolled study.Correlation between the delay (daysbetween release from ICU) andinitiation of inpatient rehabilitation),the outcome and the rehabilitationefficiency (assessed at the end of theinpatient rehabilitation).

Delay was significantly correlated withboth outcomes and rehabilitationefficiency.

Melchers 1999[24]

III 45 children and adolescentswith severe TBI. TFI: 48 hours.

Controlled, prospective randomizedstudy. Assessing the effectiveness ofearly stimulation in coma (while thepatient is on ICU) andneuropsychological therapy afterregaining consciousness, comparedwith routine treatment. Follow-up: 6,12, and 24 months after trauma.

Higher score of intelligence in theexperimental group. Over the time ofone year the development of nonverballearning potential is better in theexperimental group. Lesspsychopathological alternations in theexperimental group and better qualityof life.

(continued on next page)

G. Tal, E. Tirosh / Pediatric Neurology 48 (2013) 424e431426

Table 2 (continued )

Author Year[No]

ClassificationEvidence

Sample Characteristics Study Design Evaluated Outcomes

Swaine et al.2000[25]

III 64 children with head injury(mild moderate and severe)TFI: 4 weeks

Retrospective controlled trial.Assessing the rehabilitation outcome atleast 2 years after the TBI usinga telephone interview with the parentsafter a new, more coordinated,comprehensive rehabilitation programvs the old rehabilitation program in thesame institute.

No statistical significant differenceswere found between the two groups inrespect to mean WeeFIM/FIM scoresand mean PARSIII scores (a scale toassess psychosocial adjustment ofchildren with chronic physicalillness).The historic group (1993) hadpoorer scores on the withdrawalsubscale (in the PARSIII.

Braga et al.2005 [26]

II 87 children with moderate orsevere TBI during the chronicpost injury stages TFI: 6-30months

Randomized controlled trial. Theoutcome after 12 months of family-supported intervention for childrenwith chronic impairment after TBI wascompared with the outcome aftermonths of clinician-deliveredintervention. Outcomes were assessedwith formal scales.

Both groups benefited from theirintervention, but only the family-supported group results achievedstatistical significance.

van’t Hooft et al.2005 [27]*

II 38 children with ABI, 9-16years of age (55% followingTBI). TFI: 1-5 years

Randomized control study. Testing theeffectiveness of a cognitive trainingprogram, 6 months after the end of theprogram.

Significant improvements in memoryand attention performance were shownin the treatment group as comparedwith control subjects.

van’t Hoof et al.2007 [28]

II 38 children with ABI (55% TBI)TFI: 1-5 years

Randomized control study. Thetreatment group was trained witha broad-based cognitive trainingprogram. The control group had a dailyactivity freely chosen by the parent,child or teacher. The two groups havebeen assessed prior to the interventionand 6 months after the training wascompleted.

The treatment group exhibited morepersistent improvement with respectto complex tasks of attention andmemory. No difference on simplereaction time test.

Katz-Leureret al. 2009[29]

II 20 children aged 7-13 years:10 after TBI and10 with CPTFI: �12 months

Randomized controlled study. Toevaluate the feasibility and efficacy ofa home-based exercise program(experimental group). The controlgroup had regular daily activities.Measurement tools-valid functionaltests and assessing isometric strengthat the end of the intervention (6 weeks)and at 6 months follow-up.

There was a positive significant changein the balance performance in theexperimental group. In all otheroutcomes, no significant differenceswere found.

Zhu et al.2001 [30]

I 36 children and adults aftermoderate and severe TBI Meanage 33 (12-56/57) years.TFI: 4-99 days

A randomized controlled assessor-blind study Assessing the outcome inthe early posttraumatic stage (6 mspost injury) following intensiverehabilitation (4 hr/day, physiotherapy,occupational therapy and speechtherapy) vs 2 hr/day (conventionalgroup) assessments after 2, 3 and6 months.

At 2 and 3 months there was a trend ofmore patients in the study groupachieving full FIM scores, but thecontrol group appeared to be catchingup toward 6 months.

Abbreviations:ABI ¼ Acquired brain injuryCP ¼ Cerebral palsyFIM ¼ Functional independence measureGCS ¼ Glasgow Coma ScaleGOS ¼ Glasgow Outcome ScaleICU ¼ Intensive care unitMID ¼ Minimal important differencePEDI ¼ Pediatric Evaluation of Disability InventoryPARS ¼ Personal Adjustment and Role Skills ScalePT ¼ Physical therapyTBI ¼ Traumatic brain injuryTFI ¼ Time following injuryWeeFIM ¼ Functional Independence Measure For Children

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G. Tal, E. Tirosh / Pediatric Neurology 48 (2013) 424e431428

functions, and the measurements were commonly usedintelligence scales. In the discussion, the authors comparetheir results, indicating no improvement of cognitivefunctions over time, to other studies with interventions andpoint to the probable value of rehabilitation to the cognitiveoutcome after TBI.

The third study by Dumas et al. [22] pertained to childrenwith ABI, including TBI, and examined the proportion ofchildren who achieved “minimally important difference”derived from the same measure used in their other twostudies. The analyzed data were retrieved retrospectivelyfrom standardized records. The details of the inpatientintervention were not reported, and diagnostic groups, aswell as severity of the injury, were not accounted for in theanalysis.

The retrospective chart review reported by Tepas et al.[23] addressed the possible importance of “time sinceinjury” for the start of rehabilitation on outcome. Thismethod might be regarded as a proxy to the directmeasurement of the effectiveness of intervention. Sixtychildren with TBI were assessed with a valid instrument incorrelating the functional outcome of interest with the timedelay before entry to the program. However, the analysisdid not account for the initial functional level of theparticipants, but their level of severity of injury at the veryacute stage. Furthermore the bias introduced by the eventspossibly contributing to the delay in enrollment to theprogram as well as that related to other interventionspossibly occurring prior to the start of the intervention,were not controlled for.

All of these studies lacked in reporting level of intraraterand interrater reliabilities and attributed positive effects torehabilitation intervention.

Two studies were assigned class III evidence [24,25].One study [24], however, used a randomized controlledtrial design and reported a 12-month follow-up in lessthan 50% of the participants. The neuropsychologicalintervention has been described in detail but reported anunequal distribution of severity of TBI between groups andno blind assessment of the outcome. Although noted bythe authors, the final analysis after full recruitment of thepatients and completion of the study has not been re-ported in the literature sources searched for the purpose ofthis review.

The other study by Swaine et al. [25] included 26 chil-dren, constituting 30% of the eligible sample who sustainedTBI. A historical contrast group of 38 nonmatched childrenexposed to a less-comprehensive service 2 years earlier wasused. The intervention is described in general terms only.An acceptable valid instrument, administered by telephoneto the parents by blind interviewers, with no evidence forinterrater reliability, was used. A recall bias and no controlfor events since the end of the rehabilitation program up tothe time of the interview at 2 and 4 years after the injurywere not accounted for.

Four reports were assigned as class II evidence. Thestudy by Braga et al. [26] investigated the effectiveness oftrained parents (study group) as compared with profes-sionals - delivered rehabilitation program on motor andcognitive outcome in 72 of 87 children after TBI. Partici-pants were randomly assigned to study and comparisongroups; however, the same therapists administered both

types of interventions with a predetermined hypothesisthat the study group would derive more benefit. Assess-ments were performed with blind researchers, usinginstruments, one of which had no established psycho-metric properties at the time of the study. This study usedboth clinical and statistical analysis. Although referring thereader to data pertaining to the distribution of timeelapsed from the injury until the time of the intervention(ranging 6-30 months), no such information was reported.This potential bias is highly important because the analysisdemonstrated the significant effect of this interval on theoutcome.

The first of two reports by van’t Hooft et al. [27] included18 (12 with TBI) and 20 (9 with TBI) children randomlyassigned to the study and comparison groups, respectively,with the rest of the children sustaining ABI of differentcauses, including brain tumors. The studied cognitivetraining was administered by a coach who was trainedweekly by a psychologist, whereas the parents of thecomparison group were instructed to play interactivelywith their children with no exposure to computers ortelevision games. They reported on their activities usingweeklymailed diaries and telephone contacts. Standardizedcognitivemeasures were used to assess outcome before andat the end of the 17-week program. There is no indicationwith regard to the assessors and their reliability, as well astheir blindness to group assignment.

The second report by van’t Hooft et al. [28] pertained tothe same study. However, results were evaluated 6 monthsafter completion of the training. Two drawbacks to thisstudy are the lack of control over the possible continuedexposure of the children in the study group or controlsubjects during the time from intervention (contamination)and again the lack of information related to the assessorsand their independence.

The report by Katz-Leurer et al. [29] included childrenwith cerebral palsy (n ¼ 10) and children after TBI(n ¼ 10) who were randomly assigned to the study andcontrast groups. The intervention consisting of homebased exercises, as well as the outcome measures, havebeen reported in detail. A differential analysis of theoutcomes related to TBI has not been reported, andneither the assessors nor participants were blind to theirgroup assignment.

Class I evidence was only assigned to the study by Zhuet al. [30]. This study evaluated the effectiveness of a 2-(n ¼ 21) versus 4- (n ¼ 15) hour multidisciplinary inpatientrehabilitation program. Assessments were carried outindependently by therapists not involved in the programwith standardized measures up to 6 months after theinjury. However, it should be noted that, although agedistribution (12-56 years) was equally distributed in thetwo groups, no differential analysis related to age wasreported.

Discussion

It is generally accepted that rehabilitation is effective forpatients with TBI [31], although there have been a limitednumber of research reports evaluating the effectiveness ofrehabilitation interventions, especially for children andadolescents. Unfortunately, ethical and methodologic

G. Tal, E. Tirosh / Pediatric Neurology 48 (2013) 424e431 429

problems consistently confound rehabilitation research,therefore rendering the RCT often impractical [10].

Some of the major points of concern are as follow: theoutcomes measured, preferably including measures ofquality of life, have often been unrelated to daily functionsand of limited clinical relevance. The use of control subjects(i.e., no treatment) on the basis of the existing practices isunacceptable whereas a comparison group (an alternativemode of treatment) is highly difficult to design and requiresa large, well-matched sample size. Yet a few of the studiesovercame this problem and included a comparison group intheir design. Although some of the studies included in thisreview pertained to a well-defined but not necessarilyrepresentative group of patients, although being a morepractical and potentially valid approach, the inclusion ofparticipants with different underlying mechanisms andtherefore an expected different natural courses and prog-nosis renders their results less valid. The reliability andvalidity of the measurements used were not consistentlyascertained, and the assessments were carried out by anindependent examiner. Finally the statistical analysis, whenperformed, was not always related to the initial clinicalseverity, and proper analysis accounting for repeatedmeasures, not found in this review, may in future studiescontrol for possible type I or II errors.

The integrative critical summary of the literatureaddressing the efficacy of rehabilitation in childrenwith TBIraises concerns related to this list of weaknesses.

With regard to general design, only one of 16 researchreports included in this review used sufficient methodicrigor required by class I [30], suggesting a significant rela-tionship between treatment intensity and outcome (doseresponse).

However, after 6 months, this difference was not evident.The cohort in this study, however, included children andadults aged 12 to 56 years, with a mean age of 33 years.Although four studies were assigned as evidence class II, themajor flaws such as heterogenic groups and lack of inde-pendent assessment of outcome renders their results lessvalid [26-29].

There were two reports with a large sample size of814 and 452 patients, respectively [19,22]. Both studiesshowed a significant improvement after hospital reha-bilitation, with larger gains for older children aged 7years after TBI and 10 years of age after acquired braininjury, respectively. Both articles suffer from a long list ofmethodologic flaws (well acknowledged by the authors),including a variety of underlying causes for their braininjuries. The separate analysis of outcome as related tointervention in children who sustained TBI within thegroup of children with ABI is not feasible; this lastlimitation is true for most other studies that pertained toABI included in this review.

Ten of the articles described the severity of the traumaticbrain injury, mostly on the basis of the Glasgow coma scale.Only four of them referred to the correlation between theseverity and outcome after the intervention. Only sixstudies described the intervention characteristics insufficient detail to enable replication of the study. Four ofthe studies did not accurately describe the time elapsedbetween the end of the acute phase (discharge from

the intensive care unit) and the commencement ofrehabilitation.

Except for one article [25], all of the results supporteda clinically and some statistically significant improvementafter a rehabilitation program and emphasized the impor-tance of a variety of factors such as a short delay betweenrelease from the intensive care unit and initiation of reha-bilitation [15] and the importance of a coordinatedcomprehensive rehabilitation program [17,25].

Three articles [16,27,28] pertained specifically to cogni-tive rehabilitation after acquired brain injury. All of themaddressed specific cognitive rehabilitation programs ortechniques. All of them evaluated the cognitive improve-ment with standardized scales, and all showed significantimprovement after cognitive rehabilitation. In these threestudies, as found in most of the reviewed articles, there aresignificant methodologic problems, such as absence ofdetails on the injury severity or a heterogeneous cause (e.g.,brain tumor and TBI) or lack of independent assessment ofoutcome [27,28].

Three articles [17,26,29] examined home rehabilitationprograms, carried out by family members and multidisci-plinary professional teams. All three articles support theidea of home-based rehabilitation and the involvement ofthe family. However, different flaws in design, for example,a heterogeneous diagnostic group such as cerebral palsyand TBI, as well as a lack of independent assessment ofoutcome, weakens the validity of their results. Of thesestudies the study reported by Braga et al. [26], althoughusing a randomized design and therefore of a relativelyrobust method, included children up to 12 years only andused two primary outcome measures, of which one(SARAH scale of motor development) had no establishedpsychometric properties. Observer reliability and whetherpreintervention or postintervention measurements wereperformed by independent researchers, detailed informa-tion related to the interventions’ characteristics anddistribution of time interval between groups were not re-ported. Therefore this study, assigned as class I evidence ina previous report [10], is qualified as class II in this review.Interestingly one report [21] due to the lack of modernrehabilitation resources in a community in Malaysia couldassess the spontaneous psychomotor improvement duringthe first year after TBI in children. The results of this reportshowed the poor recovery when children and their fami-lies are deprived of rehabilitative services as comparedwith results obtained after rehabilitation programs re-ported from other countries.

A review of the literature seeking evidence-based studieson rehabilitation after TBI in children revealed three relevantreview articles [8-10]. All reviews referred to rehabilitationafter acquired brain injury and did not focus on TBI. Theconclusion in all of the reviews was that there was a criticallack of evidence-based studies in the field of children’srehabilitation. In a recent Cochrane review of treatment fordysarthria after acquired brain injury in children andadolescents, a critical lack of studies addressing treatmentefficacywas found [7]. Because the inclusion criteria in thesereview articles were not necessarily identical to ours, theirreference list might include articles not reviewed by us andvice versa. However, because both the classification used in

G. Tal, E. Tirosh / Pediatric Neurology 48 (2013) 424e431430

three of these reviews and their final conclusions are thesame, a general critical view can be concluded.

Although the number of studies related to the acutephase treatment in TBI in children is rather extensive,evidence-based studies concerning the rehabilitation phaseare lacking. This scarcity of research in the face of consid-erable invested effort and resources by the child himself,the family and the service providers are surprising. To makeinformed decisions that will lead to the best outcomes forthe children and their families, more knowledge about theefficacy of rehabilitation is needed [2].

Although evidence from randomized clinical trialsremains central to the assessment of efficacy of interven-tions and for creating clinical guidelines, it appears that thelisted methodologic difficulties often renders properlydesigned randomized controlled trials impractical. There-fore model-based evaluations are a valuable resource forhealth care decision makers [32], and possibly theseprocedures would lead to objective exploratory studies ofthe disease-modifying effects of rehabilitation. A feasibleapproach in studying the effects of different interventions isthe method of “comparative effectiveness research” [33].This approach uses analysis of groups of patients for anassociation between specific medical interventions andpatient outcomes without randomization and usuallyentails a collaborative multicenter study. A collaborativemulticenter approach with such a design would preferablytarget a variety of outcomes of interest, measured routinelybefore and after the intervention, including a period ofpostintervention follow-up to assess the degree of sustain-able long-term effects. Because it appears that the mainresources for such studies would be national agencies witha health and economic interests, daily functional outcomesand quality of life of both the child and parents seemreasonable main outcomes of interest. Recently an attemptto delineate an accepted list of functions for research andclinical purposes has been reported [34]. The use of a single-subject research design, if repeatedly implemented could bevaluable. However, it should be reserved for the unusualcase of a unique patient and or an innovative intervention.

Such a design, if properly used, including measurementsof effect size, could be a preliminary step before a morerigorous design necessary for an acceptable evidence-basedintervention. The heterogeneity in patients’ characteristics,intervention methods, and intensity of rehabilitationshould be accounted for in these methodologic approaches.

We are indebted to Prof. Michael Jaffe for reviewing the manuscript and to RivkaAbiry for her assistance in the preparation of the manuscript.

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