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d memory : StrategiesW. Poon, J ., J . L .

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fry of cognitive aging .

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'on of adult age differ-pons in working mem-1~. Psychological Sci-

nd knowledge as de-ences in verbal tasks .ychological Sciences,

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ocessing-speed theoryognition . Psychologi-

~ ;1) . A compendium oflministration, norms,

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Journal of Clinical and Experimental Neuropsychology

1380-3395/97/1903-421$12.001997, Vol . 19, No. 3, pp . 421-431

© Swets & Zeitlinger

A Review of Mild Head Trauma . q 17

Part I : Meta-analytic Review of Neuropsychological Studies*

Laurence M. Binder', Martin L . Rohling2 , and Glenn J. Larrabee 3'Oregon Health Sciences University, 2University of Nebraska-Lincoln, and 3 lndependent Practice, Sarasota,

Florida, USA

Current debates about mild head trauma (MHT)outcome and the etiology of postconcussive syn-drome (PCS) echo those of the 19th century(Benton, 1989 ; Trimble, 1981) . Erichsen (1882)proposed that patients with posttraumatic physi-cal symptoms who had no observable findingsmight have microscopic alterations in nervoussystem structure . In response, Page (1885) ar-gued that these patients were suffering frompurely psychic disorders .

The topic has received renewed clinical andresearch attention in recent years . The issue ofcausation, either psychogenic or organic,remains contentious . In an earlier review thefirst author (Binder, 1986) concluded that MHTcould sometimes cause persisting brain damagebut did not specify how frequent or severe thepersisting impairment might be . In the decadesince that review the literature has proliferated,

# We thank Robert Rosenthal, Stephanie Griffin, and Alan Feingold for their comments .Address correspondence to : L. M . Binder, 4900 S .W. Griffith Drive, Suite 244, Beaverton, OR 97005-2913,USA .Accepted for publication : January 8, 1997

ABSTRACT

We conducted a meta-analytic review of neuropsychological studies of mild head trauma (MHT) . Studieswere included if they met these criteria : patients studied at least 3 months after MHT ; patients selectedbecause of a history of MHT rather than because they were symptomatic ; and attrition rate of less than 50%for longitudinal studies . Studies of children were not considered . We found a total of 8 published paperswith 11 samples that met these criteria . Using the g statistic, the overall effect size of 0.07 was nonsignifi-cant, but the d statistic yielded an effect size of 0 .12, p < . 03 . Measures of attention had the largest effect,g = 0.17 . p < .02 and d = 0.20, p < .006 . Severity of injury accounted for far more variance than did specificneuropsychological domain, however . The small effect size suggests that the maximum prevalence ofpersistent neuropsychological deficit is likely to be small and neuropsychological assessment is likely tohave positive predictive value of less than 50% . Consequently, clinicians will more likely be correct whennot diagnosing brain injury than when diagnosing a brain injury in cases with chronic disability after MHT .

and patients with MHT are increasingly seen forneuropsychological evaluations .

We have reviewed countless neuropsycholog-ical and medical opinions relating cognitive def-icits of individual patients to MHT and braininjury, and we discovered _a few who cited theprevious review (Binder, 1986) in support oftheir positions. In many cases, diagnoses ofbrain damage were poorly supported by the data,and the clinicians' understanding of the injury,psychosocial and medical background of thepatient, and psychometric data was inadequate .The apparent widespread misunderstanding ofthe sequelae of MHT and the quantity of litera-ture published in the past decade makes anotherreview timely.

We have chosen to separate the review intotwo parts . This, the first part, includes a meta-analytic review of studies of neuropsychological

outcome after MHT. We hypothesized that MHTwould have an effect significantly greater thanzero. In addition, we examined the effect sizesfor different neuropsychological domains, againhypothesizing a significant difference from zero .The results of the meta-analytic review wereused to produce estimates of the prevalence ofchronic neuropsychological morbidity . The sec-ond part of the review (Binder, 1997) discussesthe clinical implications of these findings in re-lation to studies of the prevalence of symptoms,neurodiagnostic findings, and psychiatric issues .

The distinction between prospective and clin-ical studies is critical when reviewing this litera-ture (Dikmen, Reitan, Temkin, & Machamer,1992) . Clinical studies (e.g ., Leininger, Gram-ling, Farrell, Kreutzer, & Peck, 1990) enroll pa-tients who are available for study because theyare symptomatic . Symptomatic patients maydiffer in many ways from asymptomatic pa-tients . While clinical studies often are of interest(e.g ., Uomoto & Esselman, 1993), their method-ology cannot be employed to determine the ex-tent and frequency of neuropsychological defi-cits after MHT. Consequently, the present re-view only considers prospective and quasi-pro-spective studies . We use the term "quasi-pro-spective" to refer to investigations that focusedon another variable of interest such as alcohol-ism while also analyzing data on the basis of ahistory of MHT. Both prospective and quasi-prospective studies are distinguishable fromclinical studies because participants are selectedon the basis of a history of head injury ratherthan on the basis of complaints associated withhead injury. Chronically symptomatic patientsare atypical (see Binder, 1997) . Clinical studiesthat demonstrate neuropsychological abnormali-ties associated with MHT do not provide infor-mation about causality (Dikmen et al ., 1992) .

METHOD

The previous review (Binder, 1986) included allneuropsychological studies known to the author atthat time . For this review, a number of proceduresinsured that the literature review was complete .Numerous reviews published by other authors

were consulted . The first author has received semi-monthly MEDLINE searches on the topic since1986 . Finally, every issue of PsycScan: Neuropsy-chology through 1994 was reviewed .

We used specific criteria for selecting neuro-psychological studies for inclusion in the meta-analytic review. These included screening out allstudies of children as well as studies that includedmoderate and severely brain-injured persons unlesswe could compute effect sizes for a homogeneousgroup of MHT patients . As discussed above, weexcluded clinical studies . Also excluded were stud-ies of patients with Glasgow Coma Scale scoresknown to be less than 13 . We excluded studies ofwhiplash and acute cervical strain without evi-dence of head trauma . Patients were not excludedin one study, despite the presence of neuroimagingabnormalities (Dikmen, Machamer, Winn, &Temkin, 1995), because the MHT patients in thisstudy were carefully defined as those who mostquickly recovered their ability to follow com-mands, that is, in less than 1 hr .

Not all studies which we included employedneuroimaging . One study defined MHT as occur-ring when the posttraumatic amnesia (PTA) lengthwas less than 24 hr after admission to a hospital forclosed-head injury (Montgomery, Fenton,McClelland, MacFlynn, & Rutherford, 1991) . Twoother studies also used depth and length of uncon-sciousness to determine head-injury severity(Hugenholtz, Stuss, Stethem, & Richard, 1988 ;Ruff et al., 1989) .

Quasi-prospective studies often dealt with MHTas an issue of secondary interest as opposed to cap-turing patients in the hospital immediately afterclosed-head injury . One investigation examinedthe effect of a history of MHT in asymptomaticHIV-1. infection (Bornstein et al ., 1993) and de-fined MHT as a loss of consciousness greater than1 min but less than or equal to 24 hr . Anotherstudy examined a group of alcoholics who hadhead injuries with a loss of consciousness of lessthan 60 min (Alterman, Goldstein, Shelly, &Bober, 1985) . We included a study of asympo-matic college students who had PTA less than 2days and who were exposed to a challenge of simu-lated high altitude oxygen deprivation (Ewing,McCarthy, Gronwall, & Wrightson, 1980). Finally,we included a study of Australian Rules footballplayers, who compete without protective headgear,at least 1 year after concussion (Cremona-Mete-yard & Geffen, 1994) . In this sports injury study,MHT criteria included 2 to 20 min of change ofconsciousness, no hospitalizations, and less than24 hr of posttraumatic amnesia (PTA) .

i

MHT wasauthors, but `cluded in ourmild head injicriteria and fcothers studiedand used a specommands fopatients categinvestigatorsMHT used bythe studies hgeneous with itinguished thewere more sev

Attrition h,follow-up stu(with attrition iliterature provtimes is selectilow-up study isymptomatic(Alves, Macci(psychologicalthe effect size clini, Nichelli,tion that also sWe also elimirdata that couldcause they lacktion of an effectstudies by the s ;reported on the1988 ; Stuss, S1989) . Essenti,were reported b,MacFlynn, Moi(1984). We anal

Meta-analyti ,tion of individiwhich, after weisingle case to b ,this meta-analy,,pared to the nultest . In order tois necessary to ible. Multiple saitreated separate]The Three Centeal., 1989) inclucjects from threeAustralian Rulesindependent San(Cremona-Meteyspective studies,cluded .

ting neuro-t the meta-Zing out all~atincludedsons unlessmogeneousabove, we

I were stud-cale scoresI studies ofithout evi-)t excludediroimagingWinn, &

ants in thiswho mostflow com-

employedf as occur-TA) lengthiospital forFenton,

1991). Twoi of uncon-y severityard, 1988 ;

with MHTsed to cap-ately afterexaminedrnptomatic3) and de-'eater thanAnotherwho had

ass of lessShelly, &F asympo-ass than 2;e of simu-i (Ewing,)) . Finally,s footballheadgear,)na-Mete-ury study,change ofless than

MHT was not defined uniformly by previousauthors, but we are confident that the studies in-cluded in our meta-analysis belong in a review ofmild head injury. Some investigators used severalcriteria and focused exclusively on MHT, whereasothers studied the spectrum of closed-head injuryand used a specific criterion such as time to followcommands for categorizing severity level . Somepatients categorized as mild (or minor) by someinvestigators would not meet the definition ofMHT used by other investigators. However, all ofthe studies had populations that were homo-geneous with respect to severity because they dis-tinguished their MHT subjects from those whowere more severely injured.

Attrition has been a serious problem in somefollow-up studies. We chose to exclude studieswith attrition rates of 50% or greater because theliterature provided evidence that attrition some-times is selective . Patients who continued in a fol-low-up study were three times more likely to besymptomatic than subjects who dropped out(Alves, Macciocchi, & Barth, 1993) . In a neuro-psychological study with attrition greater than 50%the effect size of MHT increased with time (Genti-lini, Nichelli, & Schoenhuber, 1989), an observa-tion that also suggests selective loss of subjects .We also eliminated studies that did not providedata that could be entered into a meta-analysis be-cause they lacked sufficient detail for the calcula-tion of an effect size . We aggregated data from twostudies by the same group of authors, because theyreported on the same sample (Hugenholtz et al .,1988; Stuss, Stethem, Hugenholtz, & Richard,1989). Essentially the same reaction time datawere reported by Montgomery et al . (1991) and byMacFlynn, Montgomery, Fenton, and Rutherford(1984). We analyzed data from Montgomery et al .

Meta-analytic methodology involves computa-tion of individual effect sizes for each samplewhich, after weighting for sample size, becomes asingle case to be used in subsequent analyses . Inthis meta-analysis, aggregated results were com-pared to the null hypothesis with a one-sample ttest. In order to increase the power of the t test, itis necessary to include as many samples as possi-ble. Multiple samples from the same studies weretreated separately in order to increase sample size .The Three Center study (Levin et al ., 1987; Ruff etal., 1989) included MHT cases and control sub-jects from three sites in the United States . TheAustralian Rules football study also included twoindependent samples that we treated separately(Cremona-Meteyard & Geffen, 1994) . Quasi-pro-spective studies, described above, also were in-cluded .

Some data suggest sub-acute neuropsychologi-cal deficits within the first few weeks after MHT(see Binder, 1986 and Levin, 1989 for reviews)although evidence of full recovery within 1 monthalso exists (McLean, Temkin, Dikmen, & Wyler,1983; Newcombe, Rabbitt, & Briggs, 1994) . Webelieve that the critical issue is the chronicity ofthese deficits . Thus, our review focused on resid-ual deficits after MHT. In order to address thisquestion of chronicity, we chose to include onlythose studies that examined patients at least 3months post injury to determine if they were sig-nificantly different from control subjects .

In summary, each study we included met thefollowing criteria : (1) collection of subjects basedon history of MHT rather than symptomatology,whether prospectively or late after injury (quasi-prospectively) ; (2) inclusion of descriptive statis-tics from which effect sizes (Cohen, 1988 ; Rosen-thal, 1991) could be computed ; (3) subject attritionrate under 50%; (4) exclusion of moderate and se-vere closed-head-injured patients ; and (5) inclu-sion of only adult patients . The studies that we an-alyzed are summarized in Table 1 .

Two methods were used to calculate effectsizes . The first method involved use of the stan-dard deviation of the control group (d statistic ; Co-hen, 1988), because neuropsychologists typicallyestimate deviation from normal based upon controlgroup data in their clinical work. However, somemeta-analytic experts (e .g ., Rosenthal, 1991) advo-cate pooling standard deviations in order to avoidskewing results when samples have disparate vari-ances . Therefore, we also computed the g statisticbased upon pooled SDs .

The SD of a control group is typically smallerthan the SD of a patient group . Larger effect sizesresult from smaller SDs . Therefore, d was expectedto be larger than g . In order to calculate an overalleffect size, one effect size was computed for eachstudy for the d and g statistics separately after av-eraging the results from all dependent variables .Effect sizes were weighted by the MHT samplesize for each study .

After calculating the overall effect size, we cal-culated effect sizes for various neuropsychologicaldomains and compared the effect sizes across do-mains to effect sizes across levels of head-injuryseverity . Then, using the MHT effect sizes, weestimated with different methods the prevalence ofabnormality. Finally, based on our estimates ofprevalence of neuropsychological impairment, wecalculated the positive predictive value of abnor-mal neuropsychological test results .

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Ewing et al . (1980) 0.737 0.737 10 to 2.2 yearsAlterman et al ., (1985) -0.181 -0.208 25 25 remoteHugenholtz et al ., (1988)a 0.466 0.371 22 22 3 monthsRuff et al. (1989), Bronxb 0.260 0.187 16 26 3 monthsRuff et al. (1989), Galveston -0.411 -0.461 6 12 3 monthsRuff et al. (1989), San Diego 0.317 0.112 10 18Montgomery et al . (1991) -0.154 -0.228 26 26 6 monthsBornstein et al . (1993) 0.278 0.223 24 24 14.8 yearsDikmen et al. (1995) 0.019 0.023 161 121 1 yearCremona-Meteyard & Geffen (1994 ; Expt 1)` 0.821 0.523 6 9 1 yearCremona-Meteyard & Geffen (1994; Expt 2)Y 0.444 0.245 8 9 I year or more s

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RESULTS

Overall Effect of MHTResults based upon the more liberal d statisticare reported first . The 11 studies included 314MHT patients and 308 control subjects . Samplesizes, as shown in Table 1, ranged from 18 to282. After weighting for sample size, the meaneffect size of the 11 samples was 0 .12 (SD =0.18). This figure indicates that the weightedmean effect size was equivalent to about oneeighth of a standard deviation . A one-sample,one-tailed t test indicated that the effect size wassignificantly different from zero, t(10) = 2 .16, p< .03 .

Comparable computations were performedwith the more conservative g statistic . Afterweighting for sample size, the mean effect sizewas 0.07, (SD = 0.17), t(10) = 1 .30, p < .12 .

Effect Sizes of Specific NeuropsychologicalDomainsFollowing Dikmen et al . (1995), we assignedneuropsychological measures to one of sevendomains (Table 2) . Our assignments of test mea-sures to domain was guided by factor analyticresearch (Larrabee & Curtis, 1992 ; 1995 ;Larrabee, Kane, Schuck, & Francis, 1985 ;Leonberger, Nicks, Larrabee, & Goldfader,1992). Some of these domains are self-explana-tory, for example, memory acquisition and de-layed memory . Mental flexibility measures in-cluded the Category Test and the WisconsinCard Sorting Test . Performance measures in-cluded WAIS-R Performance IQ, PorteusMazes, and Wechsler Memory Scale Visual Re-productions . Examples of attention measuresincluded simple and complex reaction time tests,digit span, Trail Making Test, Parts A and B,Stroop Color Word Test, and the Paced AuditorySerial Addition Test (although Trail MakingTest, Part B is more closely associated with gen-eral intellectual factors than with attentionalmeasures in some factor analytic work [Larrabee& Curtis, 1992, 1995]) . We did not include theHalstead Impairment Index as a domain becausenone of the other measures in the meta-analyticreview fell into that category .

MILD HEAD TRAUMA : PART I

425

Only three of the seven domains were exam-ined in six or more of the independent samples .These domains were attention, memory acquisi-tion, and performance skills . After weighting forsample size, one sample t tests were performedon the d and g statistics from those domains, asshown in Table 2 . Of these three neuropsycho-logical domains, only attention had an effectsignificantly greater than zero of 0 .17 for g and0.20 for d . These effect sizes are small .

Next, we contrasted the neuropsychologicaldomain-related findings with findings related tohead injury severity of the Seattle group (Dik-men et al ., 1995), whose research contributed51 % of the MHT subjects in our meta-analysis .Dikmen et al . quantified head-injury severity bythe variable of time to follow commands . Theirsix groups ranged from patients who followedcommands in less than 1 hr (the only group in-cluded in our MHT meta-analysis) to patientswith comas of more than 28 days. Dikmen et al .found a curvilinear relationship between dura-tion of coma and neuropsychological effects thatwe have summarized as effect sizes using g . Theeffect sizes were as follows : less than 1 hr 0.02 ;1-24 hr 0 .23; 2-5 days 0 .45; 6-13 days 0 .69 ;14-28 days 1 .33; 29 days or more. 2 .30 .

Prevalence of NeuropsychologicalImpairmentIn order to estimate the prevalence of neuropsy-chological impairment, we analyzed the degreeof shift of the MHT performance distribution inour 11 samples relative to the control perfor-mance distribution . The average effect size, d =0.12, describes an average shift downward of0.12 SD for MHT patients as compared with thedistribution of neuropsychological scores ofcontrol subjects . Two different cut-offs for im-pairment have been recommended. Heaton,Grant, and Matthews_ (1991) define abnormalityas falling 1 .1 SD or more below the demographi-cally corrected mean (T score of 39 or below, z< -1 .10) . Abnormality is defined as the bottom5% of control group performance by Benton,Hamsher, Varney, and Spreen (1983), a perfor-mance equivalent to -1 .65 SD below the mean .The former approach yielded a specificity of88% and a false positive rate of 12% in a sample

Table 2. Effect Sizes for Specific Cognitive Processes .

Memory

279AcquisitionDelayed

185RecallManual

185DexterityPerf.

242SkillsCogn. Flex .

210AbstractionVerbal

210SkillsTotals

314M&SD

Note. MHT = Mild head trauma; ES = Effect size ; AttlConc = Attention and concentration ; Perf. = Performance; Cogn. Flex . = Cognitive flexibility . Values forg and d are weighted for sample size . Totals are for all 11 samples .

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226 468 6 .02( .04)

170 380 3 -.09( .19)

170 380 3 -.09( .04)

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.20 3.24( .21) p < .006.19 1.84

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with structural brain damage identified byneuroimaging . The fifth percentile cutoffmethod yields a false positive rate of 5% for in-dividual measures, and we are unaware of anystudies of its sensitivity.

We applied negative z score cut-offs to theabove effect sizes . Negative z scores define thecut-off score for abnormality in a normativesample. Effect sizes were added to the negativez scores to determine the prevalence of impair-ment associated with a history of MHT in excessof the false positive rate in control subjects . Us-ing the z = -1 .65 figure corresponding to thefifth centile cut-off, the increase in prevalenceof abnormality is 1 .4% in a normal distributionfor the overall effect size, d = 0 .12. If z = -1 .1corresponding to Tscores below 40, the increasein abnormality is 2 .8%. For the domain of atten-tion, d = 0.20, the respective figures are 2 .4%and 4.8% .

Available data suggest that the assumption ofa normal distribution for MHT patients is notmet, however. In the Seattle study (Dikmen etal ., 1995) the median scores for the MHT groupexceeded the mean scores for most variables,indicating that the distribution was skewed tothe left . Consequently, our prevalence figuresare slightly underestimated . In order to calculateprecise estimates of prevalence, we require dataon right- and left-tailed effect sizes (Feingold,1995) which were not reported in any of thestudies in the present meta-analytic sample .

As a second method of estimating the preva-lence of MHT-associated neuropsychologicalimpairment, we applied the U1 statistic. Basedon the d statistic, U1 describes the amount of thetwo population distributions combined that arenot overlapping (Cohen, 1988, p. 21-22) . U1/2describes the amount of the two population dis-tributions that are not overlapping at the left tailof the sample distributions (i .e ., the prevalenceof impairment). An effect size of d = 0 . 12 isequivalent to U112 = 4.6% . An effect size of d =0.20 is equivalent to U1/2 = 7 .4% .

To provide a third method of estimating prev-alence of neuropsychological impairment asso-ciated with MHT, the weighted effect size of0.12 was converted to a correlation coefficientof r = .06 (Rosenthal, 1991) . Approximately 6%

of the participants had cognitive deficits in asso-ciation with a history of MHT, based upon themore liberal d statistic . Alternatively, there wasa reduction in level of performance of 6% inassociation with a history of MHT . The g statis-tic value of 0 .07 was equivalent to r = .04(Rosenthal, 1991) . Based upon the g statistic,the weighted mean effect size suggested thatabout 4% of the participants had cognitive defi-cits in association with a history of MHT. Alter-natively, there was a reduction in level of per-formance of 4% in association with a history ofMHT.

Positive Predictive Value of Neuropsychologi-cal TestingThe positive predictive value (PPV ; Baldes-sarini, Finklestein, & Arana, 1983) of a test orset of tests is defined as the likelihood that apathological condition is present when a testresult is abnormal (i .e., the likelihood of accu-racy of an abnormal test result) . Precise calcula-tions of diagnostic accuracy (Baldessarini et al .,1983) require knowledge of prevalence, sensi-tivity, and specificity . In order to provide rea-sonable estimates of sensitivity and specificity,we assume that detection of a relatively subtleproblem is more difficult than is the detection ofan obvious neurological problem . Therefore, wealso assume that sensitivity and specificity ofneuropsychological diagnosis of persisting braindysfunction after MHT cannot exceed the sensi-tivity and specificity of neuropsychologicalmeasures in a comparison of normative subjectswith a mixed neurological group with structuralbrain damage identified either by CT or MRscanning (Heaton et al ., 1991) . In the Heaton etal. study, the sensitivity of the Average Impair-ment Rating from-the Halstead Reitan Batterywas 80% and the specificity was 88% when Tscores above 39 were classified as normal .

In order to obtain a series of estimates of thePPV of neuropsychological assessment measu-res in patients with a history of MHT, we as-sumed a range of values for sensitivity and spec-ificity. We initially assumed sensitivity to be80% and specificity to be 88% (Heaton et al .,1991). The prevalence of persisting brain dys-function is estimated based upon the estimate

428

LAURENCE M. BINDER ET AL .

based on z scores of 4 .8% for the prevalence ofthe largest effect size, that of attention . This fig-ure suggests that about 5% of the population ofMHT patients is affected . Alternatively, scoreswere reduced by 5% for all MHT patients .

As shown in Table 3, when the prevalence ofbrain injury was 5%, the PPV was only 32%when both sensitivity and specificity were set at.90. It is improbable that neuropsychologicalprocedures have sensitivity and specificity val-ues as high as .90 when assessing subtle braindysfunction, because these values were smallerin a study of well-documented structural braindamage (Heaton et al ., 1991) . Reductions in sen-sitivity or specificity result in further reductionsof PPV and increases in the negative predictivevalue (NPV), the accuracy of normal or negativetest results . NPV was 98-99% in every calcula-tion included in Table 3 . The figures summa-rized in Table 3 suggest that the clinician assess-ing a case of MHT is more likely to be correctwhen diagnosing no brain injury and less likelyto be correct when diagnosing brain injury .

DISCUSSION

This review examined 11 independent samplesfrom eight publications which met our inclusioncriteria for neuropsychological investigations ofthe persisting effects of MHT suffered in adult-hood. Where - appropriate, we aggregated datafrom different publications (Hugenholtz et al .,1988 ; Stuss et al., 1989) . We used two differentcomputational methods and obtained slightlydifferent results with each method . With themore liberal d statistic, the overall effect of

MHT was significant. With the g statistic, theoverall effect was nonsignificant . Using eitherstatistic, the size of the overall effect was unim-pressive and suggestive of clinical nonsigni-ficance . The effect size of 0 .12 is equivalent to 2points for WAIS-R IQ or for Wechsler MemoryScale-Revised (WMS-R) General Memory(Wechsler, 1981, 1987) . The attention effect of0.20 is equivalent to 3 points on the Atten-tion/Concentration Index of the WMS-R . Thesevalues are smaller than the measurement errors(Wechsler, 1981, 1987) . Hence, it can be arguedthat the average effect of MHT on neuropsycho-logical performance is undetectable .

By comparison, the effect size of financialincentives on symptoms and impairment afterclosed-head injury is 0.47 (Binder & Rohling,1996). Our effect sizes also can be comparedwith the neuropsychological effects of hyperten-sion. Although the neuropsychological effects ofhypertension are not widely recognized, 13 sam-ples summarized in a review (Waldstein,Manuck, Ryan, & Muldoon, 1991) yielded amean d of 0 .67 . Waldstein et al . chose not tocompute overall effect sizes . The unweightedmean effect size of 0.67 for hypertension wasobtained after omitting an outlier sample . Priorto removal of this outlier, 14 samples yielded anunweighted mean d = 0.94. The value of d =0.67 which we computed from their review isnot directly comparable to our effect sizes forMHT because it is not weighted for sample size .The unweighted effect sizes in this MHT sampleford and g were 0.23 and 0.14, respectively.

Neuropsychological domain accounted forless variability than head-injury severity . Theeffect size for attention was nearly identical to

Table 3 . Possible Positive and Negative Predictive Values of Neuropsychological Diagnosis with TraumaticBrain Injury Prevalence of .05 .

Note. PPV = Positive predictive value. NPV = Negative predictive value .

the overall effect size iverely injured group inmen et al., 1995) . The o,four most severely injwere two to ten times grsize of attention in our 1jects . We conclude that cical reports of head injitempt to estimate the sfactor that may be m(choice of measures in a itery .

We estimated PPV tcwhen estimates of senwere artificially high .subject to criticism, heargue that far more thaseen in clinical settingsare impaired or brain-irwho fully recover usualpsychological evaluaticwith our estimate was resection : MHT data areprevalence figures geneslight underestimates . Cstatistic to the r statisticsulted in slightly larger e

Some readers also mzresults of this review wetof the neuropsychologicWe found some evidencebetween neuropsycholo€When we adapted a preNet al., 1995) of categoriability areas, we foundsize of .20 (based on d)tention . None of the otherthat were studied in 6 orwas significantly greatcingly, the studies showinMHT used experimentaland had the smallest sar.yard & Geffen, 1994 ; ENcannot determine if theseobtained reliably from l,collecting more data .

Although one study laccounted for 51% of th'meta-analysis, it is unl1

Sensitivity Specificity PPV NPV

.80 .88 .26 .99

.90 .70 .14 .99

.90 .90 .32 .99

.70 .90 .27 .98

.70 .80 .16 .98

.70 .70 .11 .98

statistic, theUsing either

,ffect was unim-ziical nonsigni-,equivalent to 2

echsler Memoryneral Memorytention effect ofon the Atten-WMS-R. These

asurement errorsit can be arguedn neuropsycho-able.

size of financialnnpairment afternder & Rohling,an be comparedects of hyperten-

ological effects ofognized, 13 sam-

,iew (Waldstein,1991) yielded aal . chose not toThe unweighted

hypertension wastlier sample . Priorsamples yielded anThe value of d =om their review isour effect sizes forted for sample size .n this MHT sample

'0 .14, respectively .lnain accounted for

'.-injury severity. The'as nearly identical to

agnosis with Traumatic

NPV

.99

.99.99.98.98.98

the overall effect size for the second least se-verely injured group in the Seattle study (Dik-men et al., 1995) . The overall effect sizes for thefour most severely injured groups in Seattlewere two to ten times greater than was the effectsize of attention in our 11 samples of MHT sub-jects . We conclude that clinical neuropsycholog-ical reports of head injured patients should at-tempttempt to estimate the severity of the injury, afactor that may be more important than the

Ichoice of measures in a neuropsychological bat-tery .

We estimated PPV to be far under 50% evenwhen estimates of sensitivity and specificitywere artificially high . Our estimate of PPV issubject to criticism, however. Clinicians mayargue that far more than 5% of MHT patientsseen in clinical settings with chronic symptomsare impaired or brain-injured, because personswho fully recover usually will not seek neuro-psychological evaluation. The other problemwith our estimate was referred to in the Resultssection : MHT data are skewed left and so theprevalence figures generated by our data areslight underestimates. Conversion of the d or gstatistic to the r statistic (Rosenthal, 1991) re-sulted in slightly larger estimates of prevalence .

Some readers also may question whether theresults of this review were affected by the natureof the neuropsychological measures employed .We found some evidence of an interactive effectbetween neuropsychological domain and MHT .When we adapted a previous method (Dikmen,et al ., 1995) of categorizing tests into specificability areas, we found that the largest effectsize of .20 (based on d) was for measures of at-tention . None of the other two discrete processesthat were studied in 6 or more of the I 1 sampleswas significantly greater than zero . Interest-ingly, the studies showing the largest effects ofMHT used experimental measures of attentionand had the smallest samples (Cremona-Mete-yard & Geffen, 1994 ; Ewing et al ., 1980) . Onecannot determine if these larger effects could beobtained reliably from larger samples withoutcollecting more data .

Although one study (Dikmen et al ., 1995)accounted for 51% of the MHT subjects in themeta-analysis, it is unlikely that this sample

skewed our results . A large sample is morelikely than is a small sample to yield a result thatis closer to the population mean. Further evi-dence that this sample did not skew our results isobtained from the methodology employed by theresearchers. Confidence in the Dikmen study isstrengthened by the use of control subjects in-volved in orthopedic traumas, a group morecomparable on premorbid features to head-in-jured subjects than noninjured control subjects .The Dikmen group also was successful in virtu-ally eliminating attrition from their sample . Dik-men et al . (1995) used a variety of measures andtheir results were similar to the overall effect ofthe 11 samples . The effect size of the Dikmenstudy was not the smallest ; 2 samples yieldednegative effect sizes .

Subject attrition may have slightly enhancedthe effect size in the meta-analysis . Attritionwas a serious problem in four samples includedin the analysis (Hugenholtz et al ., 1988 ; Ruff etal ., 1989) with losses of about 40% of the MHTpatients . Although subjects who withdrew didnot differ at the outset from subjects who contin-ued in the research in these studies, other inves-tigators showed that dropouts were more likelyto be asymptomatic than subjects who returnedfor followup (Alves et al ., 1993) . Furthermore,in a study not included here because of the ex-treme attrition rate (Gentilini et al ., 1989), theeffect size of MHT increased with time, an ob-servation strongly suggesting the presence ofselective attrition . In the largest study includedin the meta-analysis (Dikmen et al ., 1995), attri-tion was minimal .

Research has furthered our understanding ofthe neuropsychological effects of MHT sincepublication of the the first author's earlier re-view (Binder, 1986) . Further work is stillneeded, however. Our data suggest that mea-sures of attention may be the most sensitive in-dicators of dysfunction associated with MHT.Future investigations of the long-term neuropsy-chological effect of MHT might use clinical rat-ings of the extent of abnormality on comprehen-sive test batteries in patients and controls in ad-dition to statistical comparisons . Neuropsycho-logical studies with other clinical populationshave shown that clinical ratings sometimes are

more sensitive than are parametric statisticalcomparisons and also provide supplemental in-

formation (Filley, Heaton, Thompson, Nelson,& Franklin, 1990) . Conceivably, the neuropsy-chological effect of MHT varies from patient topatient in such a way that parametric measuresmask an effect which could be detected by clini-cal ratings .

Although the practice effect for MHT sub-jects and control subjects is thought to be similar(Dikmen et al ., 1995), we also recommend thatfuture investigations reduce the confound ofpractice effects by not testing subjects after asubacute interval such as 1 month . Instead, in-vestigators should wait until an interval such asa year has passed to allow possible deficits toreach a plateau. Orthopedic trauma patients of-fer the best chance of controlling for nonspecificinjury and premorbid factors (Asarnow et al .,1995 ; Dikmen, et al., 1995) .

Meta-analysis is the best method of aggregat-ing disparate results of this literature on thelongterm neuropsychological effect of MHT(Rosenthal, 1991) . The meta-analysis providessome support for the hypothesis that there is anassociation between MHT and cognitive deficitsin a small percentage of MHT patients, or thatthere is a small reduction in cognitive function-ing in a larger percentage of patients . However,we suggest that the small effect sizes shouldforce a clinician to exercise considerable cautionbefore diagnosing brain injury after MHT. Anassociation does not prove causality; the occur-rence of closed-head injury is not random . Theclinical interpretation of these results and otherrelevant literature is discussed in Binder (1997) .

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