Motor recovery after stroke Morphological and functional brain alterations

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1 Moto ecovey afte stoke Mophological and functional bain alteations atizia antano, 1 ita Fomisano, Monica icci, 1 Vittoio Di ieo, 1 Umbeto Sabatini, Buno Di ofi, 1 obeto ossi, uigi Bozzao 1 and Gian uigi enzi 1 Bain (1996), 119, depatment of Neuological Sciences, Univesity of ome 'a Sapienza'; ICCS.Santa ucia, ome and ^Istituto Mediteaneo di Neuoscienze Sanatix, ozzilli (IS), Italy Coespondence to: atizia antano, MD, Depatment of Neuological Sciences, Univesity of ome 'a Sapienza', Viale dell'univesita ome, Italy Summay The aim of this study was to evaluate the elationships of mophological and CBF pattens with both the seveity and the evolution of the moto deficit in the late phase of stoke and, in paticula, to identify mophological and/o functional bain alteations associated with a pesistent sevee moto deficit o a poo, delayed moto ecovey. We analysed CT/ MI and single photon emission tomogaphy (SET) findings fom 7 patients studied in the chonic phase of stoke (mean duation±sd=.6±1.6 months), whom we wee able to follow clinically fo a peiod of months. The eventual degee of moto ecovey coelated significantly (negatively) with the time since stoke at enty, but not with the seveity of neuological impaiment at enty. The volume, side and location (cotical o subcotical) of the infact did not coelate with eithe the seveity o the evolution of the moto deficit. atients with a CT/MI lesion of the paietal lobe (n = 8) showed a moe sevee moto deficit than those with othe cotical locations. The seveity of the moto deficit coelated significantly (negatively) with CBF values in the supplementay moto aea (SMA) and paietal aeas of the damaged hemisphee, and in the contalateal undamaged pimay moto cotex. The degee of moto impovement coelated significantly (positively) with CBF values in the contalateal undamaged thalamus, lentifom and caudate nuclei, and pemoto cotex. In the late phase of stoke, the seveity of the moto deficit may be positively associated with the functional impaiment of associative paietal and fontal aeas of the damaged hemisphee. The functional impaiment of the basal ganglia-fontal netwok in the undamaged hemisphee seems to be elated to a poo, delayed moto ecovey. Keywods: moto deficit; moto ecovey; stoke; single photon emission tomogaphy; ceebal blood flow Abbeviations: CBF = ceebal blood flow; SET = single photon emission tomogaphy; SMA = supplementay moto aea Intoduction ecovey fom a moto deficit caused by stoke is a complex, multifactoial pocess. Following the acute phase of stoke, in which egession of oedema and epefusion of aeas of ischaemic penumba ae pobably the decisive factos, othe mechanisms such as neuonal eaangements and adaptive esponses have been hypothesized to explain the slow but steady impovement in moto function, which may go on fo many months (Goldstein and Davis, 199). ecent studies, using activation ET methodology, suggest that moto ecovey is in pat due to the extension of moto aeas in the affected hemisphee, and in pat to the ecuitment of ipsilateal moto pathways (Chollet et al., 1991; Weille et al., 199). It should be bone in mind, howeve, that these studies wee conducted on selected goups of patients who, a few months afte stoke, had made an almost complete ecovey. Only a small pecentage of patients ae left with no, o minimal, disability afte a stoke (Stallones et al., 197; Gesham et al., 1975; Gesham et al., 1979). Most patients show a moe sevee and pesistent moto deficit which affects thei daily activities in vaying degees (Duncan et al., 199). Classical studies epot that the estitution of moto function occus spontaneously within the fist months afte injuy (Twitchell, 1951; Van Buskik, 195). The moto impovement may go on fo up to one yea, albeit to a lesse degee (Ahlsio et al., 198; Kotila et al., 198). If we assume that spontaneous moto ecovey is geneally completed within the fist months, we need to addess the question of Oxfod Univesity ess 1996 on 5 July 18

2 185. antano et al. which pocesses subsequently lead to the futhe impovement obseved in some patients. In a pevious wok, we obseved a significant coelation between moto deficit seveity at -6 months afte stoke and the hypopefusion of the stuctually intact contalateal SMA (antano et al., 1995). Similaly, moto ecovey was found to be associated with the metabolic impovement in associative moto aeas of the damaged hemisphee in patients studied by ET in both the acute and chonic phases of stoke (Di ieo et al., 199). These findings could be meaningful fo the pognostic evaluation of hemiplegic stoke patients. If egession of the hypometabolism obseved in the acute phase of stoke is due to the esolution of ischaemic penumba, be it spontaneous o theapy-induced, the hypopefusion in undamaged ceebal aeas in the chonic phase may be due to diaschisis, which is potentially evesible as well. Fo these easons, we analysed CT/MI and SET findings fom 7 patients studied in the chonic phase of stoke (-7 months), whom we wee able to follow clinically fo a peiod of months. The aim of this study was to evaluate the elationships of mophological and CBF pattens with both the seveity and the evolution of the moto deficit in the late phase of stoke, and, in paticula, to identify mophological and/o functional bain alteations associated with a pesistent sevee moto deficit o a poo, delayed moto ecovey. atients and methods Thity-seven stoke patients (18 male and 19 female, mean age±sd = 6.7±11.7) who wee hospitalized fo moto deficit ehabilitation, wee included in the study. Inclusion citeia wee: (i) age anging between and 85 yeas; (ii) fist-eve stoke causing a modeate to sevee faciobachio-cual hemipaesis/hemiplegia; (iii) pesistence of the moto deficit which equied hospitajization in a ehabilitation cente; (iv) inteval since stoke > months; (v) single ischaemic lesion in the intenal caotid atey teitoy at CT7 M scan; (vi) absence of othe neuological o psychiatic diseases. At enty, the time elapsed since stoke was.6±1.6 months (ange -7). All patients wee submitted to a neuological evaluation, including the assessment of moto deficit seveity by means of the Adams' scale (scoe fom = nomal to 8 = hemiplegia; Adams et al, 1987), CT and/o MI and SET- CBF study. The Adams' scale was again used to assess the patients' moto deficit afte months (Adams ( )); an index (%) of moto ecovey was then calculated fom this and the scoe (AdamS(i)) obtained at enty as: [1 X (AdamS(i)-Adams ( ))/Adams ( i ) ]. All the patients wee teated with physical theapy and, when necessay, with specific teatment fo neglect o aphasia. Clinical data ae shown in Table 1. A Siemens-Somatom C high-esolution scanne was used fo CT scans in 7 patients, while M images wee ecoded with a T ESA-TOM Ansaldo M 5 in the emaining 1 patients. The extent of the ischaemic lesion was quantified by using a dedicated softwae that allows the measuement of the lesioned aea fom CT o M (T ) images using a video-display and cuso system, accoding to a method peviously descibed (antano et al., 199). atients wee divided into two goups depending on whethe the infact was cicumscibed to subcotical stuctues o also affected the ceebal cotex. A Tomomatic 56 (Medimatic, Denmak) equipped with a high esolution collimato was used fo bain activity ecoding afte i.v. injection of mci of Tc 99 " 1 hexa methyl-popylene amine oxime. The patient's head was positioned with the obitomeatal line pependicula to the floo by using a lase efeence system and ink dots on the skin. The head was then fixed to the head holde by tape. The SET studies wee pefomed at est (eyes closed, eas unplugged) in a dimly lit oom, with extenal stimuli educed to a minimum. The scan stated 5 min afte tace administation and lasted 5 min. Six to nine tansvese slices wee obtained fom each patient, fom the ceebellum to the cotical mantle (slice thickness = 1 mm; inteslice cente to cente distance = mm; spatial esolution in the tansvese plane = 9 mm). Data analysis was esticted to 1 ceebal aeas involved in moto contol (pimay moto cotex, pemoto cotex, SMA, pefontal cotex, supeio and infeio paietal cotices, caudate nucleus, lentifom nucleus, thalamus and ceebellum), identified on SET slices on the basis of a efeence atlas (Damasio and Damasio, 1989), accoding to a method peviously descibed (antano et al., 1995). In these ceebal aeas, an asymmety index was calculated fom the atio between counts' in homologous egions in the damaged (d) and undamaged (u) hemisphee as (1 - dju). Fo the ceebellum, the side which was contalateal to the supatentoial lesion was consideed the damaged one. Howeve, since this method assumes that the aeas of the undamaged hemisphee ae nomally pefused, wheeas evidence exists both of emote effects of the infact on the contalateal hemisphee (enzi et al., 198; Seitz et al., 199) and of a possible involvement of the undamaged hemisphee in moto ecovey pocesses (Chollet et al., 1991; Weille et al., 199), we completed ou analysis by nomalizing counts in the 'moto' aeas (in both the damaged and undamaged hemisphee) to the visual cotex of the undamaged hemisphee. Ten age-matched patients with no histoy of ceebovascula disease and nomal CT scans wee used as contols. Statistical analysis was pefomed using analysis of vaiance (ANOVA), simple and stepwise egessions, and non-paametic tests. Owing to the exploatoy natue of this study, we decided not to apply any coection fo multiple compaisons. on 5 July 18

3 Moto ecovey afte stoke 1851 Table 1 Clinical and neuoadiological data of 7 patients with hemiplegic stoke No. Sex/ age (yeas) Months since stoke Adams scoe Moto ecovey Sensoy loss (D/S) Aphasia/ neglect esion volume (cm ) Side ocation M/59 F/7 M/77 F/61 F/67 M/6 M/7 M/6 M/65 M/6 M/71 M/ M/1 M/ M/6 M/5 F/65 F/9 F/7 M/56 F/65 F/8 F/7 M/ F/5 F/6 M/8 F/6 M/5 F/7 F/55 F/61 F/79 F/7 M/8 F/6 M/ in 9/9 9/8 9/7 11/11 1/1 1/1 1/1 1/8 16/1 16/8 18/18 18/18 19/19 19/1 /16 1/18 1/1 1/ 1/19 1/15 1/1 / /18 / / /19 5/5 5/1 6/6 6/ 7/1 7/7 8/6 8/8 8/7 8/ NA NA o o -bg -bg NA -bg -bg-o -bg-o -bg-o -bg-t -bg -bg -T -bg-o -bg -bg-o-pf-t- -bg-o- -bg-o-pf- -bg-o-t- -bg -bg-o- -bg-o-pf-t- -bg NA -bg o- o -bg-t- The Adams scoe (ange -8) was assessed at the patient's fist neuological evaluation (1) and afte months (). M = male; F = female; D = deep; S = supeficial; - = absent; + = pesent; = ight; = left; = white matte; bg = basal ganglia; o = olandic cotex; T = tempoal cotex; pf = pefontal cotex; = paietal cotex; NA = images not available. esults Clinical featues Detailed clinical data ae shown in Table 1. The scoe obtained using the Adams' scale at enty fo the evaluation of the moto deficit was 19.6±6. (ange 7-8). Thee was no significant coelation between the seveity of moto deficit and the patient's sex o age, o with the time elapsed since stoke. The moto deficit was associated with visuo-spatial neglect in 11 patients, with aphasia in 15, and with deep and/o supeficial sensoy loss in 6. The pesence of eithe neglect o deep sensoy loss was associated with a moe sevee moto deficit ( =.5 and., espectively, by Mann- Whitney U test). Afte months, the Adams' scoe was significantly lowe than at the fist evaluation ( =.1 by Wilcoxon signed-ank test). The extent of moto ecovey was 1± 1%. Howeve, in 18 patients no moto impovement was obseved at the second evaluation when compaed with the fist; in the emaining 19, the extent of moto ecovey anged fom % to 5%. The goup with no moto impovement did not contain patients with significantly moe sevee moto deficit at enty o a significant highe popotion of cases with sensoy distubances, aphasia o neglect than the goup of patients who impoved. Howeve, the time elapsed between stoke and the fist Adams' evaluation was significantly longe in patients without any moto impovement (.8±1.5 vesus.8±1. months, <.1 by Mann-Whitney U test). The extent of moto ecovey, in fact, coelated significantly (negatively) with the time elapsed since stoke ( = -.6; <.5). on 5 July 18

4 185. antano et al. Table Coelation between Adams' scoe and CBF at enty in 7 stoke patients egion CBF asymmety Nomalized CBF Damaged hemisphee Undamaged hemisphee Ceebellum Thalamus entifom nucleus Caudate nucleus imay moto cotex emoto cotex SMA efontal cotex Supeio paietal cotex Infeio paietal cotex *.1.*.5* *.1.1*.1* * Ceebal pefusion calculated both as egional asymmety (1 - dlu), whee (d/u) is the atio of CBF in the damaged and undamaged hemisphee and nomalized CBF. *Significant coelation. Since the evaluation of the degee of moto ecovey may be affected by a 'ceiling' effect when consideing patients with a mild moto deficit at enty, we decided to analyse ou data again, excluding patients who showed an Adams ( ) scoe of <1. A scoe <1 on the Adams' scale is indicative of a mild moto impaiement which means such patients have a good degee of autonomy in daily activities. This futhe analysis, pefomed on 8 patients with a modeate to sevee moto deficit at enty (Adams ( ) scoe ange 16-8), showed the same esults, the time since stoke being the only clinical vaiable which coelated significantly (negatively) with the degee of moto ecovey ( = -.95, =.). CT/MI findings The volume of the ischaemic lesion vaied geatly (ange cm ). The lesion was located on the ight side in 18 patients and on the left in 19. Two patients, fo whom neuoadiological images wee not available, wee evaluated by means of witten epots. Infacts wee puely subcotical in 18 cases, and also affected the ceebal cotex in the emaining 17 cases. Detailed neuoadiological findings ae also shown in Table 1. The volume and the side of the ischaemic lesion did not influence the seveity of the moto deficit. atients with pue subcotical infacts did not show significant diffeences in moto deficit seveity when compaed with patients pesenting lesions also affecting the ceebal cotex (Adams ( ): 18±6. vesus 1 ±5.6). Howeve, a significant diffeence in moto deficit seveity was obseved when patients with damage to the ceebal cotex wee divided accoding to whethe only the moto aeas wee affected o whethe the damage extended to the paietal lobe. While patients with damage limited to the moto aeas {n = 7) had values [Adams m : 17.±6] which wee simila to those of patients with subcotical infacts, patients with paietal involvement (n = 8) had significantly highe values ( =.; Adams (l) :.7±.). The lesions affecting the paietal cotex wee not significantly lage than cotical lesions spaing the paietal lobe. A significant association was found between the damage to the paietal lobe and both visuo-spatial neglect and deep sensoy loss ( =.1 and.1, espectively, by x )- No patient had a lesion puely of the paietal cotex, and in seven out of eight patients the olandic aea was also damaged. A two-facto ANOVA of the effects of a 'olandic lesion' and a 'paietal lesion' on Adams',,) scoes showed that the lesion in the paietal cotex, but not in the olandic one, had a significant effect [F(l) = 6.16, =.1] without any inteaction between the two factos. The volume and the side of the ischaemic lesion did not influence the evolution of the moto deficit eithe. No significant diffeences in the degee of moto ecovey wee obseved between patients with pue subcotical lesions and patients with damage to the ceebal cotex. The coexistance of damage to the paietal cotex did not influence the possibility of futhe ecovey in the following months. This finding was consistent even if the analysis was esticted to the 8 patients with a modeate to sevee moto deficit at enty. CBF findings In the entie goup of 7 patients, the mean values of nomalized CBF in the 1 ceebal aeas of the damaged hemisphee wee significantly lowe than the coesponding values in the undamaged hemisphee ( <.5 by Wilcoxon test) and than contol values ( <.1 by Mann-Whitney U test). esults of egession analysis between Adams' scoes and SET findings ae shown in Table : significant negative coelations wee found with CBF values in the SMA and paietal aeas of the damaged hemisphee, and in the pimay moto cotex of the undamaged hemisphee. Figues 1 and show the highly significant negative coelations between the CBF atios (damaged/undamaged on 5 July 18

5 Moto ecovey afte stoke 185 Fig. 1. Simple negative egession between moto deficit, as assessed by the Adams' scale at enty, and CBF atios in the infeio paietal lobule (I) (damaged/undamaged hemisphee) of 7 stoke patients. Cosses indicate patients with stuctual damage to the paietal lobe. The hatched aea epesents the 95% confidence intevals of the mean of CBF atios in the infeio paietal lobule in contols. O 8. CO as u. m o ;.'; ;!!# 1 15, scoes 8 iifjiiiiiliiiliiiiiiiiiiiitiiiii : = ::::. <-:-:-:<-:-:-9:-:^^>- : : : > : : : < : : > : : : : : 5 8 Fig. Simple negative egession between moto deficit, as assessed by the Adams' scale at enty, and nomalized CBF values in the pimay moto cotex (MC) of the undamaged hemisphee of 7 stoke patients. The hatched aea epesents the 95% confidence intevals of the mean of nomalized CBF values in the pimay moto cotex in contols. hemisphee) in the infeio paietal lobule and the nomalized CBF in the undamaged pimay moto cotex and moto deficit seveity. Stepwise egessions of nomalized CBF in these two egions with all the othe 19 egions of both hemisphees showed significant positive associations between the infeio paietal lobule of the damaged hemisphee and the ipsilateal pemoto aea (coefficient =.66±.117, <.1) and contalateal infeio paietal cotex ( =.7+.5, <.) and between the pimay moto cotex of the undamaged hemisphee and the ipsilateal supeio paietal cotex ((} =.56±.1, <.1). The extent of moto ecovey in the goup of 7 patients (taken as a whole) did not coelate with the values of ceebal pefusion in the 1 bain aeas analysed. Howeve, when we excluded patients with a mild moto deficit at enty fom the analysis, the CBF values fom the thalamus, lentifom nucleus, caudate nucleus and pemoto cotex of the undamaged hemisphee wee found to coelate significantly (positively) with the moto impovement. The esults of linea egession between the degee of moto ecovey and the nomalized CBF values (in the 8 patients with an Adams' scoe of >1) ae shown in Table. Figue shows the highly significant positive coelation between the CBF in the caudate nucleus of the undamaged hemisphee and the degee of moto ecovey. None of the many vaiables analysed, i.e. moto deficit seveity, time elapsed since stoke, volume, side and location (cotical o subcotical) of the infact, stuctual damage to the cotical moto o paietal aeas, was significantly associated with low CBF values in the caudate nucleus of the undamaged hemisphee. Stepwise egession of nomalized CBF in the caudate nucleus of the undamaged hemisphee with all the othe 19 egions of both hemisphees showed a significant positive association with CBF levels in the ipsilateal thalamus ( =.9 ±.7, <.1) and pefontal cotex (p =.757±.19, <.1). Discussion The pocesses undelying moto function ecovey ae not yet completely known. It is possible to use ET activation studies to show which ceebal aeas ae involved in movement execution in patients who have ecoveed fom moto stoke (Chollet et al., 1991; Weille et al., 199; Weille et al., 199). Howeve, the question emains whethe some patients, in whom the impovement of moto function is absent o patial, have any stuctual o functional bain alteation which may be incompatible with ecovey. Fom a clinical point of view, the possibility of identifying those patients who can benefit fom ehabilitation in the late phase of stoke is elevant to the costs of hospitalization and ehabilitation theapy (Feigenson et al., 1978; Oste et al., 199; Smuawska et al., 199). At the pesent time, thee ae no data to guide selection of stoke patients fo specific inteventions (Wade, 199). Clinical featues The age of the patient, consideed to be a good pognostic indicato in the acute phase of stoke (Fioelli et al., 1995), was not found to be associated with eithe the seveity o the impovement of the moto deficit in ou patients who on 5 July 18

6 185. antano et al. Table Coelations between moto impovement and CBF at enty, in 8 stoke patients with modeate to sevee moto deficit at enty (Adams' scoe >1) egion CBF asymmety Nomalized CBF Damaged hemisphee Undamaged hemisphee Ceebellum Thalamus entifom nucleus Caudate nucleus imay moto cotex emoto cotex SMA efontal cotex Supeio paietal cotex Infeio paietal cotex *.5*.1*..5* Ceebal pefusion calculated both as egional asymmety and nomalized CBF. 'Significant coelation. 1.1 I 1. CD CO ".9 <D CD O.8.7 mm : : : : : : : : : : : : : : : : : : : : : : :! : : : : iiiiiiiiiiiii 1 Moto impovement (%) : : : : : : * 5 6 Fig. Simple positive egession between moto impovement and nomalized CBF values in the caudate nucleus (CN) of the undamaged hemisphee in 8 stoke patients with a modeate to sevee hemipaesis at enty (Adams' scoe >I). The hatched aea epesents the 95% confidence intevals of the mean of nomalized CBF values in the caudate nucleus in contols. wee studied in the late phase of stoke; ou obsevation is in ageement with othe studies (Hiee/ al., 198; Schenkman et al., 198). Ou study suggests that in patients still pesenting a moto deficit -7 months afte stoke, the possibility of moto ecovey in the months following the enolment in the study, is independent of the seveity of the esidual moto deficit but is significantly negatively coelated with the time elapsed since stoke. This finding futhe suppots the need to stat ehabilitation in stoke patients as soon as possible, and also suggests that little o no impovement can be expected afte months; this is in keeping with studies indicating that moto ecovey has eached its final level 8-1 weeks afte a stoke (Andews et al., 1981; Skillbeck et al., 198). Clinical studies suggest that the concomitant pesence of visuo-spatial deficits have an influence on outcome (Kotila et al., 198; Fomisano et al., 199). This finding was confimed by the pesent study in which patients with a pesistent visuospatial neglect and/o deep sensoy loss showed a moe sevee moto deficit at enty. Moto impovement in nine out of 11 patients with neglect was eithe absent o minimal (<1%). These findings, togethe with the close association with paietal damage, suggests that the lack of infomation on the left-side inta- and extapesonal space and/o the oientation and position of the body pats in the space can constitute a futhe obstacle to the eoganization of movement. This intepetation is suppoted by expeimental evidence that sensoy inputs ae integated in the posteio paietal association cotex of the monkey with behavioal acts in the immediate extapesonal space (Mountcastle et al., 1975). Mophological findings We found that the volume, side and location (cotical o subcotical) of the lesion did not coelate with eithe the seveity o delayed impovement of moto function. The elationship between CT findings and clinical ecovey has been peviously studied. Kotila et al. (198) epoted that in thei seies of 15 stoke patients, the outcome at and 1 months did not diffe between patients with left and ight hemispheic lesions. In ecent studies, no association between cotical o subcotical site, o lesion size, and clinical outcome was obseved (Schenkman et al., 198; Domeick and eding, 1995). In a clinical study on ecovey of function afte lesions esticted to the ight hemisphee, Hie et al. (198) found that ecovey fom constuctional apaxia and visuo-spatial neglect was moe apid in patients without injuy to the fontal lobe, wheeas patients without injuy to the paietal lobe ecoveed moe quickly fom extinction and leg weakness. These authos concluded that the spaing of on 5 July 18

7 Moto ecovey afte stoke 1855 anatomical stuctues adjacent to the site of injuy is impotant in the ecovey fom cetain deficits, wheeas damage to them may delay the emegence of compensatoy mechanisms. Similaly, ou esults indicate that damage to the paietal lobe is associated with a moe sevee moto deficit -7 months afte stoke, which would be expected in patients with a poo ecovey in the fist phase of stoke. aietal damage did not, howeve, peclude the possibility of a delayed impovement in moto function, obseved in fou out of eight patients with an infact also affecting the paietal cotex. Functional findings In ou attempt to identify othe factos of impotance in pedicting the possibility of moto ecovey in the chonic phase of stoke, we also analysed SET-CBF findings. We obseved that patients with moto deficit following stoke had many ceebal aeas which wee hypopefused even if spaed by the stuctual lesion, as peviously demonstated by emission tomogaphy studies in stoke patients (Baon et al., 1986; antano et al., 1986; Mette et al., 1987; eani et al., 1988). Howeve, only the CBF in the SMA and paietal aeas in the damaged hemisphee, and in the pimay moto cotex in the undamaged hemisphee, wee significantly coelated (negatively) with the seveity of the moto deficit. Moeove, the undamaged hemisphee seems to play an impotant ole in moto ecovey, as is suggested by the fact that the CBF in the thalamus, caudate nucleus, lentifom nucleus and pemoto cotex was significantly positively coelated with the impovement obseved duing the month peiod of study. In the damaged hemisphee, the pimay moto and pemoto cotices wee pobably functionally compomised in all the patients by lesions in diffeent sites, as shown by CT/M images. Consequently, the additional impaiment of othe stuctues, such as the SMA and the paietal lobe, assumes a special ole in the pesistence of a sevee moto deficit. The impotance of the SMA in moto ecovey is suppoted by studies showing its ole in the moto system both in a hieachic and paallel oganization, though effeents both to the pimay moto cotex (Stick, 1988) and diectly to the spinal cod (Bibe et al., 1978; Fies et al., 199). Moeove, the functional involvement of the SMA, which has been demonstated in the eoganization of cotical moto aeas afte damage of the pimay moto cotex (Aizawa et al., 1991), may explain the negative coelation between CBF in the SMA and moto deficit seveity. Fibe connections between moto aeas and paietal association aeas ae well documented (Godshalk et al., 198; etndes and andya, 198; Cavada and Goldman-akic, 1989). Ou stepwise analysis seems to assign paticula impotance to the connections between the infeio paietal lobule and the ipsilateal pemoto cotex, in ageement with expeimental esults indicating that the acuate pemoto aea in macaques eceives inputs fom paietal aea 7 (Stick, 1988). This aea, equivalent to the human infeio paietal lobule (Mountcastle et al., 1975), has been shown to paticipate in the contol of visually guided am movements (ynch et al., 1977). In 1 patients who ecoveed fom thei stiato-capsula moto stoke, Weille et al. (199) found that CBF at est was deceased in many aeas of the damaged hemisphee and inceased in some aeas of the undamaged hemisphee when compaed with nomals. The existence of these abnomal CBF pattens at est, howeve, was not clealy associated with moto deficit since all thei patients had ecoveed well and could move thei peviously paetic hand at the time of the ET studies. The movement of the ecoveed hand induced a significant CBF incease in many aeas of both ceebal hemisphees, some of which, such as the lowe paietal cotex of the damaged hemisphee, had nomal CBF at est. It is inteesting to compae the ole of the infeio paietal lobule in ou study with that in the study of Weille et al. (199); they found that CBF in this aea in patients who had ecoveed was nomal at est, but inceased duing the movements of the ecoveed hand. We found, in patients who had not ecoveed, a low CBF at est in the infeio paietal lobule. It could be agued that the infeio paietal lobule plays an essential ole in the impovement of moto function in the fist months afte stoke, while its stuctual and/o functional involvement may be associated with the pesistence of a sevee moto deficit. In ou data the blood flow in the paietal aeas of the undamaged hemisphee was not coelated with eithe the seveity o the degee of impovement of the moto deficit, indicating that the CBF at est in this egion is not pedictive of moto ecovey, despite the fact that this same aea was found to be activated duing the movement of the peviously paetic hand by Weille et al. (199). Ou esults ae quite diffeent fom those obtained by Seitz et al. (199), who found that the depession of glucose metabolism in the putamen of the lesioned hemisphee and in the contalateal ceebellum was significantly coelated with moto impaiment in 8 patients with a fist-eve hemipaetic stoke. In ou pevious wok (antano et al., 1995), we found that hypopefusion in these stuctues was associated with the pesistence of muscula flaccidity afte stoke, egadless of the moto deficit seveity. In the pesent wok, both the lentifom nucleus and ceebellum showed low CBF levels not significantly associated with eithe a moe sevee hemipaesis o a less maked moto impovement. These data ae in accodance with those epoted by the Caen ET goup on the elationship between ceebella hypometabolism and stoke outcome (Seati et al., 199). They found that in the acute phase (within 5- h of onset) the ceebella metabolism and the neuological outcome (o ecovey at day 6) wee neithe stongly no consistently coelated; they wee coelated in the subacute phase (1-56 days late), but this finding became non-significant when the effect of lesion size was taken into account. on 5 July 18

8 1856. antano et al. Ou data also point to a link between the functional activity of the undamaged hemisphee and moto function. The CBF levels in the pimay moto cotex of the undamaged hemisphee coelated negatively with the seveity of the moto deficit, while CBF in the deep gey stuctues, i.e. the thalamus, caudate and lentifom nuclei, and the pemoto cotex coelated positively with the moto impovement afte months. The ole of the ipsilateal cotico-spinal pathways in the ecovey pocesses has aleady been suggested by expeimental (Bucy et al., 1966), clinical (Glees, 198) and emission tomogaphy (Chollet et al., 1991; Weille et al., 199; Sabatini et al., 199) studies. The possibility of delayed moto impovement seems to be elated to the functional activity of deep gey stuctues, paticulaly the caudate nucleus and its conical pojections to the fontal lobe. It is inteesting to note that these aeas, i.e. the caudate nucleus, pemoto and pefontal cotices of the undamaged hemisphee, wee also found to be activated duing movement execution in patients who made an ealy complete ecovey (Weille et al., 199). The caudate nucleus and the associative fontal cotex, which ae linked by well-defined anatomical connections (Goldman and Nauta, 1977; Yeteian and Hasen, 1978; Alexande et al., 1986), might epesent a functional cognitive netwok whose functional integity is necessay in both ealy spontaneous and delayed ehabilitation-induced moto ecovey afte stoke. This concept is futhe suppoted by the fact that stiatal dysfunction in humans appeas to affect aspects of mood, motivation, attention, leaning and behavioual pogamming (Cummings and Benson, 198). The eason fo the eduction of CBF in the caudate nucleus of the undamaged hemisphee in some patients, howeve, emains pooly undestood. Ou wok may povide useful infomation on bain alteations associated with moto deficit in the late phase of stoke, when some impovement in moto function is still possible. Many points, howeve, need to be elucidated and futhe studies ae necessay, especially in selected goups of patients in whom a bette moto ecovey is obseved. Acknowledgements The authos thank ofesso Cesae Fieschi fo his continuous suppot, ofesso Giogio Benadi and D uigi Amadio fo thei valuable help in oganizing the wok and D Maco Fioelli fo his useful suggestions on the statistical appoach to data analysis. This wok was suppoted by gants fom CN (No. 9.7.CT) and Clinica Santa ucia ICCS. efeences Adams J. Meado KJ, Sethi KD. Gotta JC. Thomson DS. Gaded neuologic scale fo use in acute hemispheic stoke teatment potocols. Stoke 1987; 18: Ahlsio B, Bitton M, Muay V, Theoell T. Disablement and quality of life afte stoke. Stoke 198: 15: Aizawa H, Inase M, Mushiake H. Shima K. Tanji J. eoganization of activity in the supplementay moto aea associated with moto leaning and functional ecovey. Exp Bain es 1991; 8: Alexande GE, Deong M, Stick. aallel oganization of functionally segegated cicuits linking basal ganglia and cotex. Ann ev Neuosci 1986: 9: Andews K, Bocklehust JC, ichads B, aycock J. The ate of ecovey fom stoke and its measuement. Int ehabil Med 1981: : Baon JC, D'Antona, antano, Sedau M. Samson Y, Bousse MG. Effects of thalamic stoke on enegy metabolism of the ceebal cotex. Bain 1986; Bibe M, Kneisley W, a Vail JH. Cotical neuons pojecting to the cevical and lumba enlagements of the spinal cod in young and adult hesus monkeys. Exp Neuol 1978, 59: Bucy C, adpli, Ehlich A. Destuction of the pyamidal tact in the monkey: the effects of bilateal section of the ceebal peduncles. J Neuosug 1966; 5: 1-. Cavada C, Goldman-akic S. osteio paietal cotex in hesus monkey: II. Evidence fo segegated coticocotical netwoks linking sensoy and limbic aeas with the fontal lobe. J Comp Neuol 1989; 87: ^5. Chollet F, Di ieo V, Wise JS, Books DJ, Dolan J, Fackowiak SJ. The functional anatomy of moto ecovey afte stoke in humans' a study with positon emission tomogaphy. Ann Neuol 1991; 9: Cummings J, Benson DF. Subcotical dementia. eview of an emeging concept [eview]. Ach Neuol 198; Damasio H, Damasio A. esion analysis in neuopsychology. New Yok: Oxfod Univesity ess, Di ieo V, Chollet FM, MacCathy. enzi G. Fackowiak SJ. Moto ecovey afte acute ischaemic stoke: a metabolic study. J Neuol Neuosug sychiaty 199; 55: Domeick AW, eding MJ. Functional outcome fo patients with hemipaesis, hemihypesthesia, and hemianopsia. Does lesion location matte? Stoke 1995; 6: -6. Duncan W, Goldstein B, Matcha D, Divine GW. Feussne J. Measuement of moto ecovey afte stoke. Outcome assessment and sample size equiements. Stoke 199: : Feigenson JS, Feigenson WD, Gitlow HS, McCathy M. Geenbeg SD. Outcome and cost fo stoke patients in academic and community hospitals: compaison of two goups efeed to a egional ehabilitation cente. JAMA 1978: : Fioelli M, Alpeovitch A, Agentino C. Sacchetti M. Toni D. Sette G, et al. ediction of long-tem outcome in the ealy hous following acute ischemic stoke. Italian Acute Stoke Study Goup. Ach Neuol 1995: 5: 5-5. Fomisano, Babanti. Cataci T. De Vuono G. Calisse. azzano C. olonged muscula flaccidity: fequency and association with unilateal spatial neglect afte stoke. Acta Neuol Scand 199: 88: 1-5. Fies W, Danek A, Scheidtmann K, Hambuge C. Moto ecoves' following capsula stoke. Bain 199,116: on 5 July 18

9 Moto ecovey afte stoke 1857 Glees. Functional ceebal eoganization following hemispheectomy in man and small expeimental lesions in pimates. In: Bach-y-ita, edito. ecovey of function: theoetical consideations fo bain injuy ehabilitation. Ben: Hans Hube, 198: Godschalk M, emon N, Kuypes HGJM, onday HK. Conical affeents and effeents of monkey postacuate aea: an anatomical and electophysiological study. Exp Bain es 198; 56: 1-. Goldman S, Nauta WJH. An inticately pattened pefonto-caudate pojection in the hesus monkey. J Comp Neuol 1977; 7: Goldstein B, Davis JN. estoative neuology: dugs and ecovey following stoke. [eview]. Stoke 199; 1: Gesham GE, Fitzpatick TE, Wolf A, McNamaa M, Kannel WB, Dawbe T. esidual disability in suvivos of stoke the Famingham study. J Engl J Med 1975; 9: Gesham GE, hillips TF, Wolf A, McNamaa M, Kannel WB, Dawbe T. Epidemiologic pofile of long-tem stoke disability: the Famingham study. Ach hys Med ehabil 1979; 6: Hie DB, Mondlock J. Caplan. ecovey of behavioal abnomalities afte ight hemisphee stoke. Neuology 198; : 5-5. Kotila M, Waltimo O, Niemi M, aaksonen, empinen M. The pofile of ecovey fom stoke and factos influencing outcome. Stoke 198; 15:19^*. enzi G, Fackowiak S, Jones T. Ceebal oxygen metabolism and blood flow in human ceebal ischemic infaction. J Ceeb Blood Flow Metab 198; : 1-5. ynch JC, Mountcastle VB, Talbot WH, Yin TCT. aietal lobe mechanisms fo diected visual attention. J Neuophysiol 1977: : Mette EJ, Kemple D, Jackson CA, Hanson W, iege WH, Camas, et al. Ceebella glucose metabolism in chonic aphasia. Neuology 1987; 7: Mountcastle VB. ynch JC, Geogopoulos A, Sakata H, Acuna C. osteio paietal association cotex of the monkey: command functions fo opeations within extapesonal space. J Neuophysiol 1975; 8: Oste G, Huse DM, acey MJ, Epstein AM. Cost-effectiveness of ticlopidine in peventing stoke in high-isk patients [see comments!. Stoke 199; 5: Comment in: Stoke 199; 5: antano, Baon JC, Samson Y, Bousse MG, Deouesne C, Coma D. Cossed ceebella diaschisis: futhe studies. Bain 1986; 19: antano, Fomisano, icci M, Babanti, Fioelli M, Sabatini U, et al. olonged musculaflaccidityin stoke patients is associated with cossed ceebella diaschisis. Ceebovasc Dis 199: : 8-5. antano, Fomisano, icci M, Di ieo V, Sabatini U, Babanti, et al. olonged muscula flaccidity afte stoke: mophological and functional bain alteations. Bain 1995; 118: eani D, Di ieo V, ucignani G, Giladi MC, antano, ossetti C, et al. emote effects of subcotical ceebovascula lesions: a SECT ceebal pefusion study. J Ceeb Blood Flow Metab 1988; 8: etides M. andya DN. ojections to the fontal cotex fom the posteio paietal egion in the hesus monkey. J Comp Neuol 198; 8: Sabatini U, Tom D, antano, Bughitta G. adovani A, Bozzao, et al. Moto ecovey afte ealy bain damage: a case of bain plasticity. Stoke 199; 5: Schenkman M, Butle B, Naese MA, Kleefield J. Ceebal hemisphee asymmety in CT and functional ecovey fom hemiplegia. Neuology 198; : 7-7. Seitz J, Schlaug G. Kleinschmidt A, Kno U, Nobeling B, Wiwa A, et al. emote depessions of ceebal metabolism in hemipaetic stoke: topogaphy and elation to moto and somatosensoy functions. Hum Bain Map 199; 1: Seati C, Machal G, ioux, Viade F, etit-taboue' MC, ochon, et al. Contalateal ceebella hypometabolism: a pedicto fo stoke outcome? J Neuol Neuosug sychiaty 199: 57: Skilbeck CE, Wade DT, Hewe, Wood VA. ecovey afte stoke. J Neuol Neuosug sychiaty 198; 6: 5-8. Smuawska T, Alexandov AV, Bladin CF, Nois JW. Cost of acute stoke cae in Toonto, Canada. Stoke 199: 5: Stallones A, Dyken M, Fang HCH, Heyman A. Seltse. Stamle J. Epidemiology fo stoke facilities planning. Stoke 197: : Stick. Anatomical oganization of multiple moto aeas in the fontal lobe: implications fo ecovey of function. [eview]. Adv Neuol 1988; 7: 9-1. Twitchell TE. The estoation of moto function hemiplegia in man. Bain 1951; 7: -8. following Van Buskik C. etun of moto function in hemiplegia. Neuology 195; : Wade DT. Stoke: ehabilitation and long-tem cae. eview]. ancet 199; 9: Weille C, Chollet F, Fiston KJ. Wise JS. Fackowiak SJ. Functional eoganization of the bain in ecovey fom stiatocapsula infaction in man. Ann Neuol 199; 1: 6-7. Weille C, amsay SC, Wise JS. Fnston KJ, Fackowiak SJ. Individual pattens of functional eoganization in the human ceebal cotex afte capsula infaction. Ann Neuol 199; : Yeteian EH, Van Hoesen CW. Cotico-stiate pojection in the hesus monkey: the oganization of cetain cotico-caudate connections. Bain es 1978; 19: -6. eceived Apil, evised July 15, Accepted August 6, 1996 on 5 July 18

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