PROGNOSTIC VALUE OF MOTOR EVOKED POTENTIALS IN MOTOR FUNCTION RECOVERY OF UPPER LIMB AFTER STROKE

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1 J Rehabil Med 2009; 41: ORIGINAL REPORT PROGNOSTIC VALUE OF MOTOR EVOKED POTENTIALS IN MOTOR FUNCTION RECOVERY OF UPPER LIMB AFTER STROKE Assuta Pizzi, MD 1, Riccardo Carrai, MD 1, Catuscia Falsii, MD 1, Moica Martii, MD 1, Soia Verdesca, MD 1 ad Atoello Grippo, MD 2 From the 1 Fodazioe Do Carlo Gocchi Olus IRCCS Cetro S. Maria agli Ulivi, Pozzolatico ad 2 Departmet of Neurophysiopathology, Azieda Ospedaliera Careggi, Florece, Italy Objective: To determie the progostic value of cliical assessmet ad motor evoked potetials for upper limb stregth ad fuctioal recovery after acute stroke, ad to establish the possible use of motor evoked potetials i rehabilitatio. Desig: A prospective study. Subjects: Fifty-two patiets with hemiparesis were erolled oe moth post-stroke; 38 patiets cocluded the study at 12 moths. Methods: Motor evoked potetials were recorded at baselie ad after oe moth. Upper limb muscular stregth (Medical Research Coucil Scale, ) ad fuctioal tests (Frechay Arm Test, Barthel Idex) were used as depedet outcome variables 12 moths later. Motor evoked potetials were classified as preset or abset. Predictive values of motor evoked potetials ad were evaluated. Results: At 12 moths, patiets with baselie recordable motor evoked potetials showed a good fuctioal recovery (positive predictive value 94%). The absece of motor evoked potetials did ot exclude muscular stregth recovery (egative predictive value 95%). Motor evoked potetials had a higher positive predictive value tha oly i patiets with < 2. Coclusio: Motor evoked potetials could be a supportive tool to icrease the progostic accuracy of upper limb motor ad fuctioal outcome i hemiparetic patiets, especially those with severe iitial paresis ( < 2) ad/or with motor evoked potetials abset i the post-stroke acute phase. Key words: motor evoked potetials, rehabilitatio, stroke, upper limb, outcome. J Rehabil Med 2009; 41: Correspodece address: Assuta Pizzi, Director of the Departmet of Neurorehabilitatio, Fodazioe Do C. Gocchi ONLUS, Cetro S. Maria agli Ulivi, Via Impruetaa 124, Pozzolatico, Florece, Italy. apizzi@ dogocchi.it Submitted November 20, 2007; accepted April 17, 2009 INTRODUCTION The ability to evaluate the expected level of motor ad fuctioal recovery after stroke may help i early decisio-makig o medical ad rehabilitatio treatmets as well as i research trials for assessmet of itervetio effects. To estimate the risk/beefit ratio of some treatmet strategies, a accurate progosis for fuctioal recovery is required (1, 2). The iitial grade of paresis is geerally the most importat predictor for motor recovery (3 5). toe chages, disturbaces of deep sesatio ad cosciousess i the acute phase are also cosidered as importat predictors of the degree of further fuctioal recovery (6). However, o sigle factor ca be related strogly eough to allow a accurate predictio (3) ad combied stroke scales have limitatios, oly partially predictig fuctioal outcome (7, 8). Cliical evaluatio may ofte be questioable ad icoclusive, especially i o-cooperative or severely cogitively impaired patiets. The isufficiet predictive stregth of cliical parameters has geerated research usig euroimagig (ifarctio size, localizatio of the lesio) ad europhysiological parameters (2, 7). Motor evoked potetials (MEP) have bee studied to determie the extet of brai damage ad to predict motor recovery i patiets with stroke (9 13). Evaluatio of MEP i the acute phase of stroke (10, 12 17) showed a relatioship betwee motor recovery ad the degree of motor system impairmet, as attested by cetral motor coductio time (CMCT) (18), MEP threshold ad MEP amplitude (9, 10, 14). However, some authors have expressed doubts that MEP have a progostic value (18, 19). This discrepacy may be attributed to heterogeeous methodologies. Studies differed regardig the time of MEP recordig (12, 20), type ad degree of vascular damage, severity of patiets cliical impairmets, europhysiological parameters measured (10, 12, 13) ad outcome measures used (Barthel Idex (BI), Frechay Arm Test (), Medical Research Coucil scale ()). I a rehabilitative cotext, fuctioal as well as motor recovery should be cosidered as outcome measures. Oly oe previous study has ivestigated both europhysiological ad cliical parameters for the predictio of stroke outcome (21). The authors foud that i the acute phase (2 5 weeks after stroke) europhysiological measures aloe were of limited value i predictig motor outcome of the arm. MEP predictive value was still limited eve at 2 moths after stroke. The log-term outcome was best predicted through the combied use of cliical variables ad MEP. After stroke, patiets are usually admitted to a rehabilitatio cetre from a stroke uit or itesive care uit followig 2009 The Authors. doi: / Joural Compilatio 2009 Foudatio of Rehabilitatio Iformatio. ISSN

2 Motor evoked potetials i stroke 655 a period of hospitalizatio of approximately 15 days. It may the be useful to assess MEP predictive values. The aims of this study were: (i) to estimate progostic value of MEP recorded from differet muscles i terms of upper limb stregth ad fuctioal recovery i patiets with stroke; (ii) to assess MEP predictive values at differet times after stroke oset durig post-acute rehabilitatio; ad (iii) to study the relatioship of europhysiological ad cliical predictors. METHODS Subjects Ipatiets with hemiparesis followig first stroke i life, admitted to the euro-rehabilitatio departmet of S. Maria agli Ulivi Cetre, Florece, over a period of 12 moths, from September 2004 to September 2005, were cosecutively erolled. Stroke diagosis was based o the World Health Orgaizatio (WHO) defiitios (22). Sydrome diagosis was categorized accordig to Oxfordshire Commuity Stroke Project classificatios (23). The study-populatio was selected cosiderig as iclusio criteria: (i) the presece of hemiparesis secodary to a first stroke i life, cofirmed by computed tomography sca or magetic resoace imagig; (ii) Mii-Metal State Examiatio (MMSE) (24) score 21; (iii) ability to participate i the rehabilitatio programme ad to stad daily treatmet; (iv) absece of previous fractures i the affected upper limb; (v) absece of ay other eurological disorder. Subjects with a MMSE score < 21, that precluded active cooperatio i the study, ad subjects with severe aphasia were excluded. All subjects agreed to participate i the study by sigig a coset form approved by the iteral ethics board. Cliical assessmet Cliical assessmet was performed by 2 of the authors (CF, SV) blided to the europhysiological results ad icluded upper limb muscular stregth evaluatio ad fuctioal tests. stregth was assessed at deltoid, biceps, extesor digitorum commuis (EDC) ad abductor digiti miimi (ADM) usig scale as follows: 0 o movemet; 1 a flicker or trace of movemet; 2 movemet whe gravity is elimiated; 3 movemet agaist gravity; 4 movemet agaist gravity ad resistace; ad 5 ormal stregth (25). Upper limb fuctioal abilities were tested usig the. This scale cosists of 5 pass/fail tasks; the patiet scores 1 for each task that is completed successfully. Oly the affected upper limb is evaluated. Patiets scorig 5 out of 5 are likely to use their affected upper limb, eve if they feel it as abormal (26). Fuctioal capacity i activities of daily life (ADL) was moitored usig the BI (rage 0 100; the higher the score, the greater the idepedece i ADL) (27, 28). Trascraial magetic stimulatio Trascraial magetic stimulatio (TMS) studies were coducted accordig to the stadard criteria published by the Iteratioal Federatio of Cliical Neurophysiology (29). We used moophasic electromagetic stimulators (Magstim 200; Magstim Co., Whitlad, Dyfed, UK) with a roud flat coil cetred horizotally at the vertex. Stimulatio itesity was set at 100% of the maximum stimulator output. The subjects were sittig i a armchair i a quiet room. TMS was performed while subjects were cotractig the target cotralateral muscle or the ipsilateral homologous muscle, if o volutary movemet could be produced i the cotralateral muscle. MEP were recorded with surface electrodes (BIONEN, Florece, Italy) from the followig muscles: ADM, EDC, Biceps ad Deltoid. A Medelec Syergy (versio 8.2) machie (Oxford Istrumets Medical Systems, Old Wokig, UK) amplified (0.1 5 mv) ad filtered (10 Hz 3 khz) the sigal, the stored it o hard disk. We used a sigle pulse TMS techique. Five cosecutive resposes i a 100-ms post-stimulus period were aalysed. We measured size of MEP iduced by TMS expressed as amplitude ratio, where MEP was the average of 5 cosecutive peak-to-peak (most egative to the most positive peak) resposes amplitude ad CMAP was the Compoud Actio Potetial of target muscle, evoked by supramaximal electrical peripheral erve stimulatio (ular erve at the wrist for ADM, radial erve for EDC, brachial plexus at ERB poit for biceps ad deltoid). The procedure was performed for both upper limbs i all subjects. MEP were cosidered abset if o respose higher tha 50 µv could be obtaied after 5 stimuli at 100% itesity. Study desig Patiets were evaluated at baselie (T0), after oe moth (T1) ad after 12 moths (T2). MEP recordig was made at baselie ad at T1. From baselie to T1 all patiets participated i a rehabilitatio programme therapy: they received 1 h of daily idividual physical therapy, based o the Bobath techique (30), for 5 days a week; if eeded, patiets uderwet 1 h of occupatioal therapy ad 1 h of speech therapy. Data aalysis Statistical aalysis was performed usig the StatView Software Package (SAS Istitute, Ic., Cary, NC, USA). Descriptive statistics for cliical ad istrumetal parameters were calculated at each recordig time. The baselie differeces of epidemiological, cliical (, ad BI) ad europhysiological (MEP) parameters betwee patiets who completed the study ad patiets lost to follow-up were statistically tested with a χ 2 test. To determie whether the presece/absece of MEP was predictive of a differet fuctioal recovery assessed with BI, we calculated ANOVA for repeated measures cosiderig MEP presece/absece as betwee-factor ad time of assessmet as withi-factor (T0, T1, T2). p was derived from paired t-test. Statistical sigificace was set at p equal to 0.05 or less. Data aalysis cosisted of determiatio of the relatioship betwee MEP ad as progostic determiats ad outcome data, usig stadard 2 2 cotigecy tables. MEP were dichotomized ito preset (ormal respose or reduced amplitude ratio) ad abset. stregth assessed at T0 was dichotomized ito 2 ad < 2. Outcome parameters were also dichotomized. Stregth recovery was classified as preset ( ) or abset ( < 4). Fuctioal recovery was classified as preset ( 2; BI 60) or abset ( < 2; BI < 60). The progostic test properties were expressed as sesitivity ad specificity, positive predictive value (PPV) ad egative predictive value (NPV). Sesitivity refers to the proportio of patiets who experieced motor or fuctioal recovery, with MEP preset ad 2 at T0. Specificity refers to the proportio of patiets who did ot experiece motor or fuctioal recovery, with MEP abset ad < 2 at T0. A sesitive progostic test will rarely miss patiets who will achieve Table I. Demographic ad cliical data of the study populatio ( = 52) Cliical data Geder, me/wome 27/25 Mea age, years (rage) 62 (21 86) Mea time from stroke, days (rage) 33 (10 60) Affected upper limb, right/left 21/31 Haemorrhagic lesios 20 Cortical/subcortical 5/15 Ischaemic lesios 32 Partial aterior circulatio ifarct 30 Total aterior circulatio ifarct 0 Lacuar ifarct 2 Posterior circulatio ifarct 0 Had domiace, right/left 52/0 Iitial Barthel idex, mea (SD) 38 (30.1) SD: stadard deviatio.

3 656 A. Pizzi et al. Table II. Ratio motor evoked potetials/compoud muscle actio potetial () amplitude ratio at basal evaluatio (T0) ad at evaluatio after oe moth from baselie (T1) Deltoid Biceps EDC ADM Mea (SD) Mea (SD) Mea (SD) Mea (SD) No-affected arm 65.3 (38.7) (31.5) (28.4) (16.7) 52 Affected arm T (23.0)*** (29.6)** (23.7)** (22.7)*** 27 Affected arm T (33.8) (29.3) (27.8)* (20.8)* 29 Affected vs healthy arm: **p < 0.01; ***p < 0.001; affected arm T0 vs affected arm T1: *p < ADM: abductor digiti miimi; EDC: extesor digitorum commuis; SD: stadard deviatio. motor or fuctioal recovery. A specific test will rarely misclassify patiets who will ot achieve motor or fuctioal recovery. PPV refers to the probability that patiet with MEP preset, or with 2, at T0 will have a favourable outcome, ad it assesses the reliability of a positive test. NPV refers to the probability that a patiet has a ufavourable outcome whe MEP are abset, or with < 2, at T0 ad it assesses the reliability of a egative test. Furthermore, we calculated the likelihood ratio for a positive result (LR+) (95% cofidece iterval, CI), takig ito accout both specificity ad sesitivity. LR+ expresses the odds that a give fidig would occur i a patiet with, as opposed to without, the target coditio. With the LR+ above 1, the probability of the coditio beig preset icreases. Multiple logistic regressio was performed to establish whether the combiatio of MEP resposes recorded from the 4 differet muscles improved outcome predictio. RESULTS From a populatio of 130 post-stroke patiets admitted to the euro-rehabilitatio departmet, we erolled 52 cosecutive patiets. Epidemiological features are reported i Table I. Six patiets (11.5%) died prior to the fial assessmet, 4 (7.7%) withdrew, ad 4 (7.7%) were lost to the oe-year follow-up, as a result of recurret stroke, ocological comorbidity or peumological complicatios. This subgroup was ot sigificatly differet for epidemiological (age, sex), cliical (baselie, ad BI) ad europhysiological (baselie MEP) parameters, with respect to the group of patiets eligible for the complete follow-up period ( = 38, 73.1%). Motor evoked potetial data The umber of patiets with MEP preset ad amplitude ratio values at T0 ad T1 are reported i Table II. MEP were preset from at least oe muscle i 28 (73.6%) at T0 ad i 36 patiets (94.7%) at T1. I patiets with MEP preset i the affected side, MEP/ CMAP amplitude ratio was sigificatly reduced i all muscles with respect to the uaffected side. At T1, amplitude ratio icreased i all muscles, but chages were statistically sigificat oly for EDC ad ADM. Medical Research Coucil Scale, Frechay Arm Test ad Barthel Idex, accordig to Motor evoked potetials presece/ absece Table III shows chage over time (at T0, T1, T2) of the umber of patiets i relatio to stregth ad fuctioal outcomes assessed with, ad BI, accordig to presece/ absece of baselie MEP. At T2, 22 patiets (58.1%) showed a good recovery of muscular stregth proximally (deltoid), whereas oly 13 patiets (34.2%) showed stregth recovery distally (EDC). Fuctioal recovery of upper limb ( 2) was preset i 17 patiets (44.7%), whereas global fuctioal recovery (BI 60) was preset i 29 patiets (76.3%). From T0 to T2, BI score icreased sigificatly [F (1,35) = 58.7, p < ] i all patiets ad the icrease was ot sigificatly differet betwee patiets with or without MEP at T0. At T0, BI score was 32 i patiets without MEP, ad 52 i patiets with MEP; at T2, BI score icreased to 70 i patiets without baselie MEP, ad to 84 i patiets with baselie MEP. ANOVA showed that the BI score was sigificatly higher i patiets with MEP preset tha i those with MEP abset. Post hoc aalysis showed a sigificat BI score differece betwee patiets with MEP preset ad MEP abset oly at T0 (72 vs 48, respectively; p < 0.05). Table III. Number of patiets variatio evaluated at T0, T1 ad T2 for stregth ad fuctioal recovery by meas of Medical Research Coucil Scale (), Frechay Arm Test score () ad Barthel Idex score (BI), accordig to presece/absece of motor evoked potetials (MEP) at T0 MEP < 4 2 < 2 BI 60 BI < 60 T0 T1 T2 T0 T1 T2 T0 T1 T2 T0 T1 T2 T0 T1 T2 T0 T1 T2 Deltoid Biceps EDC ADM T0: at baselie; T1: after oe moth; T2: after 12 moths; EDC: extesor digitorum commuis; ADM: abductor digiti miimi.

4 Motor evoked potetials i stroke 657 Table IV. Progostic values of motor evoked potetials (MEP) presece/absece at T0 ad at T1 for stregth recovery ( ) after 12 moths ( = 38) MEP T0 T1 Sesitivity % Specificity % PPV % NPV % LR+ (CI) < 4 < 4 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 Deltoid ( ) 3.0 ( ) Biceps ( ) 3.2 ( ) EDC ( ) 3.1( ) ADM ( ) 2.7( ) T0: at baselie; T1: after 1 moth; EDC: extesor digitorum commuis; ADM: abductor digiti miimi; : Medical Research Coucil Scale; PPV: positive predictive value; NPV: egative predictive value; LR+: likelihood ratio; CI: 95% cofidece iterval. Progostic values of Motor evoked potetials MEP sesitivity, specificity, PPV, NPV ad LR+ i predictig muscular stregth ad fuctioal outcomes at 12 moths are reported i Tables IV ad V. MEP absece at T0 ad at T1 had a egative progostic sigificace for both muscular stregth ad fuctioal recovery, although their absece did ot exclude stregth recovery, mostly at proximal muscles. However, stregth recovery did ot always lead to fuctioal recovery. I fact, the NPVs for deltoid ad biceps were lower for stregth recovery tha for fuctioal recovery. MEP predictive value for fuctioal recovery was higher tha that for muscular stregth (LR+ values betwee 6.1 ad 19.7; Table V). For both ad, LR+ values were lower at T1 tha at T0. Reductio of predictive power at T1 was due to a icrease i sesitivity prior to a reductio i specificity. Progostic values of Medical Research Coucil Scale Predictive values of ( < 2 vs 2) evaluated at differet times (T0 vs T2, ad T1 vs T2) for stregth ad fuctioal recovery are reported i Tables VI ad VII. had a high predictive value for both muscular stregth ad fuctioal recovery, with a high specificity (patiets with 2 had a good probability of recovery at T2), yet with a low sesitivity (patiets with < 2 could have stregth ad fuctioal recovery at T2). predictive values did ot chage from T0 to T1. Progostic values of Motor evoked potetials accordig to recorded muscle At T0 ad at T1, LR+ of was higher tha LR+ of MEP for both muscular stregth ad fuctioal recovery, except for stregth recovery at deltoid ad for fuctioal recovery at ADM at T0, ad for stregth recovery at biceps at T1 (Tables IV ad V). MEP had a higher LR+ for fuctioal recovery respect to oly at ADM. A multivariate aalysis, icludig all the muscles from which we recorded MEP, showed a percetage of correctly predicted cases similar to that obtaied from uivariate aalysis o the ADM oly (95% vs 94.5%, respectively). Takig ito accout ADM (Fig. 1), 10 out of 11 patiets with baselie 2 had fuctioal recovery: PPV (95%) ad specificity (95%) showed a good predictive accuracy. Despite a baselie < 2, 7 out of 27 patiets had fuctioal recovery, as expressed by a sesitivity value of 58% ad NPV value of 74% (Table VII). Aalysig oly the subgroup of 27 patiets with baselie < 2, MEP were preset i 8 patiets. MEP progostic values for fuctioal recovery were higher tha those calculated for the whole sample: sesitivity 87%, NPV 94%, specificity 94%, PPV 87%, ad LR Table V. Progostic values of motor evoked potetials (MEP) presece/absece at T0 ad at T1 for upper limb fuctioal recovery ( 2) after 12 moths ( = 38) MEP T0 T1 Sesitivity % Specificity % PPV % NPV % LR+ (CI) 2 < 2 2 < 2 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 Deltoid ( ) 2.4 ( ) Biceps ( ) 1.2 ( ) EDC ( ) 3.3 ( ) ADM ( ) 3.8 ( ) T0: at baselie; T1: after oe moth; EDC: extesor digitorum commuis; ADM: abductor digiti miimi; : Frechay Arm Test; PPV: positive predictive value; NPV: egative predictive value; LR+: likelihood ratio; CI: 95% cofidece iterval.

5 658 A. Pizzi et al. Table VI. Progostic values of Medical Research Coucil Scale () at T0 ad at T1 for stregth recovery ( ) after 12 moths ( = 38) T0 T1 Sesitivity % Specificity % PPV % NPV % LR+ (CI) < 4 < 4 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 Deltoid ( ) 12.0 ( ) < Biceps ( ) 1.9 ( ) < EDC ( ) 13.5 ( ) < ADM ( ) 18.8 ( ) < T0: at baselie; T1: after oe moth; EDC: extesor digitorum commuis; ADM: abductor digiti miimi; PPV: positive predictive value; NPV: egative predictive value; LR+: likelihood ratio; CI: 95% cofidece iterval. DISCUSSION We related the presece/absece of MEP with both muscular stregth ad fuctioal recovery, usig, BI ad the (a specific scale for upper limb fuctioal assessmet), respectively. Our data cofirm that the presece/absece of MEP may predict upper limb recovery, ot oly with regard to muscular stregth, but maily with regard to specific fuctioal abilities. Patiets were followed up for 12 moths. We chose this period because, although physiological recovery of ijured tissue is geerally completed withi 3 moths (21), cliical improvemet cotiues, eve if it is less impressive, as a result of reorgaizatio (31) ad other positive o-biological factors (3). Progostic value of Motor evoked potetials At 12 moths, may patiets with baselie recordable (eve if pathological) MEP showed a good fuctioal recovery. MEP absece, however, did ot exclude muscular stregth recovery, maily i proximal muscles. Yet, i the majority of cases, the segmetal stregth icrease did ot correspod to a satisfactory fuctioal recovery (NPV of MEP for fuctioal recovery betwee 86% ad 95%). Our predictive values of MEP for fuctioal recovery recorded from 4 muscles (specificity 85 95%; sesitivity 88 94%) were higher tha those reported by Escudero et al. (14) (from abductor pollicis brevis: specificity 80%; sesitivity 77%) ad Heald et al. (32) (from pectoralis major, biceps ad triceps brachii ad thear muscles: specificity 58%; sesitivity 79%). This could be due to differet fuctioal tests used, the beig a more specific upper limb fuctioal test tha the BI used i other studies. I our sample, patiets without MEP had a BI score slightly iferior to that of patiets with MEP, but differeces were ot statistically sigificat. A higher BI score was ot associated with a superior predictivity of upper limb fuctioal recovery. This may be explaied by compesatory strategies o fuctioal improvemet ivolvig the o-paretic limb (33). We foud that BI was ot able to show upper limb fuctioal chages of segmetal activities, probably because it is a scale that evaluates ADL globally. Aalysig the differet muscles to record MEP from, our data suggest that presece/absece of MEP at ADM appears to be the most sigificat predictor for fuctioal recovery (LR+ 19.7). This is probably due to a cetral role of distal muscles i maual tasks. Fig. 1. Cliical ad europhysiological evaluatio of abductor digiti miimi (ADM) for progosis of upper limb fuctioal recovery. : Medical Research Coucil scale; MEP: motor evoked potetials; : Frechay Arm Test; NPV: egative predictive value; PPV: positive predictive value.

6 Motor evoked potetials i stroke 659 Table VII. Progostic values of Medical Research Coucil Scale () at T0 ad T1 for upper limb fuctioal recovery ( 2) after 12 moths ( = 38) T0 T1 Sesitivity % Specificity % PPV % NPV % LR+ (CI) 2 < 2 2 < 2 T0 T1 T0 T1 T0 T1 T0 T1 T0 T1 Deltoid ( ) 16.1 ( ) < Biceps ( ) 1.4 ( ) < EDC ( ) 13.5 ( ) < ADM ( ) 13.5 ( ) < T0: at baselie; T1: after oe moth; EDC: extesor digitorum commuis; ADM: abductor digiti miimi; : Frechay Arm Test; PPV: positive predictive value; NPV: egative predictive value; LR+: likelihood ratio; CI: 95% cofidece iterval. Progostic value of Motor evoked potetials vs progostic value of cliical assessmet For muscular stregth recovery, baselie MEP presece had a higher predictive value tha cliical examiatio at proximal muscles, as show by LR+ of 12.9 at deltoid (Table IV). Hedricks et al. (34) reported that MEP seemed to be more predictive tha cliical evaluatio to assess fuctioal recovery. I our study MEP presece was superior to cliical assessmet i predictig fuctioal recovery oly if recorded from ADM. Recordig MEP from more tha oe muscle did ot icrease predictive value. The presece of 2 at baselie is highly predictive of recovery. The reasoable questio that follows is whether it is useful to apply to europhysiological studies requirig special equipmet, traied persoel ad time. To optimize the idicatio of MEP, we suggest a algorithm (Fig. 1) to recogize i which patiets MEP may provide additioal iformatio to cliical assessmet for fuctioal outcome. I patiets with baselie 2 cliical evaluatio aloe has a highly predictive value for fuctioal recovery. I patiets with baselie < 2, MEP recordig would be helpful to icrease progostic accuracy of fuctioal recovery. The combied applicatio of muscle stregth assessmet ad MEP parameters had stroger predictive value tha muscle power evaluatio aloe i patiets with < 2 (Fig. 1), i agreemet with Feys et al. (21). Methodological cosideratios I the literature there is o cosesus o timig of MEP recordig. Timmerhuis & Oosterloo (11) reported that early determiatio of MEP had predictive value; Catao et al. (9) foud that oly at oe moth after stroke MEP correlated sigificatly with outcome. This discrepacy may be explaied by various pathophysiological processes aside from direct tissue damage, such as perilesioal oedema, spreadig depressio, diaschisis ad/or mass effect. These factors may iterfere with MEP parameters i the acute phase of stroke, leadig to a overestimatio of the damage (35). Accordig to Catao et al. (9), i our study absece of MEP recorded i acute post-stroke phase had a high rate of false egatives (patiets with MEP abset who showed fuctioal recovery). To improve progosis we suggest that MEP recordig is repeated at admissio i the rehabilitatio cetre, i patiets who were show to have MEP abset i a previous examiatio. Feys et al. (21) foud that, i the acute phase, europhysiological measures aloe were of limited value i predictig motor recovery; at 2 moths after stroke oset, MEP could provide additioal valuable iformatio to cliical assessmet i patiets with moderate hemiparesis. These authors used regressio aalysis ad multivariate aalysis for statistical aalysis ad they did ot estimate predictive values i terms of sesibility ad specificity. I our populatio, however, predictive value of MEP recorded betwee 45 ad 90 days after stroke (T1) decreased for muscular stregth ad for fuctioal recovery i all muscles. MEP appearace at T1 did ot ecessarily lead to a improved outcome, as show by a reductio i MEP PPV. Escudero et al. (14) reported that patiets with MEP appearace over time had cliical improvemet, assessed with BI, whereas we used specific upper limb fuctioal scales. A limitatio of our study is the large rage of time of baselie MEP recordig (15 60 days). However, i a post-acute rehabilitatio cetre, patiets are admitted with differet cliical severity, sometimes after log periods of hospitalizatio i itesive care uits due to post-stroke iter-curret medical complicatios. Aother limitatio is that the size of sample, with mixed ischaemic ad haemorrhagic stroke at differet locatios, did ot allow cases stratificatio for statistical aalysis. I coclusio, our study cofirms that MEP have a sigificat predictive value regardig fuctioal recovery at 12 moths. I a cliical rehabilitative cotext, use of europhysiological studies i combiatio with cliical evaluatio is reasoable. Our data suggest that MEP may be helpful i predictig fuctioal recovery if recorded at ADM from 2 weeks to 2 moths after stroke oset. Subsequetly, MEP predictive values decreased, as show by a reductio i MEP PPV. Cosiderig the cliical applicability of MEP, the proposed algorithm may assist i decisio-makig about medical ad rehabilitatio treatmets.

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