Anexa 5

Recomandri EFNS privind sindromul picioarelor nelini tite i sindromul micrii periodice a membrelor n somn
L. Vignatellia, M. Billiardb, P. Clarenbachc, D. Garcia-Borreguerod, D. Kayna e, V. Lie!iene", C. #ren $alderg i P. Montagnaa
a

Departamentul de tiine Neurologice, coala Medical Universitatea din Bologna, Italia; bFacultatea de Medicin, Spitalul Gui de C auliac, Montpellier, Fran a; cClinica Neurologic, !" #o annes$ %ran&en aus, Biele'eld, Germania; dDepartamentul de Neurologie, Fundaia #imene( Dia(, Unitatea Dereglri ale Somnului, Universitatea )utonom din Madrid, Madrid, Spania; eFacultatea de Medicin Cerra pasa, Unitatea Dereglri ale Somnului, Universitatea Istanbul, Istanbul, *urcia; 'Facultatea de Medicin, Universitatea din %aunas, %aunas, +ituania; i gDepartamentul de Neuro'i(iologie Clinic, Universitatea din Goettingen, Goettingen, Germania

Cuvinte cheie% Ben&odia&e'ine, do'a(inergice, indicaii ale (edica(entelor, !indro(ul (i)c*rii 'eriodice a (e(brelor +n !o(n, !indro(ul 'icioarelor nelini tite ,n -../, a "o!t con!tituit un Gru' de Lucru 0123 'entru a !tabili reco(and*ri 'ri4ind (anage(entul 3indro(ului Picioarelor 2elini tite 56L37 i al 3indro(ului (i)c*rii 'eriodice a (e(brelor +n !o(n 5PLMD7. Du'* deter(inarea obiecti4elor de (anage(ent i a !trategiei de cercetare 'entru 6L3 i PLMD 'ri(are i !ecundare, !-a de!"*urat o anali&* a literaturii tiini"ice 'ublicate '8n* +n -..9, 'entru cla!ele de (edica(ente i 'rocedurile "olo!ite +n trata(ent 5(edica(ente ce ac:ionea&* la ni4elul adrenorece'torilor, (edica(ente antie'ile'tice, ben&odia'ine;hi'notice, ageni do'a(inergici, o'ioi&i, alte trata(ente7. 3-au con!ultat ghidurile anterioare. Au "o!t anali&ate toate !tudiile lu8nd +n con!iderare cla!ele de e4iden * i !-au "or(ulat reco(and*ri +n con"or(itate cu criteriile 0123 -..9 'entru cla!i"icare. 3-a con!tatat c* (edicaia do'a(inergic* are cele (ai bune do4e&i de e"icien * +n 6L3 'ri(ar. 0"ectele ad4er!e ra'ortate au "o!t de obicei u)oare i re4er!ibile<e"ectul de a('li"icare a "o!t o caracteri!tic* a agen ilor do'a(inergici. 2u au "o!t di!'onibile !tudii controlate 'entru 6L3 la co'ii i 6L3 +n ti('ul !arcinii. Pot "i o"erite ur(*toarele reco(and*ri de ni4el A 'entru 6L3 'ri(ar% cabergolina, gaba'entinul, 'ergolidul, ro'inirole, le4odo'a i rotigotina ad(ini!trat* tran!der(ic 5ulti(ele dou* 'entru u& 'e ter(en !curt7 !unt e"iciente +n a(eliorarea !i('to(elor. 0!tradiolul tran!der(al e!te ine"icient +n PLMD.
1

'ro'u! 9 criterii (ini(ale de diagno!tic Context 3indro(ul Picioarelor 2elinitite 56L37 a "o!t identi"icat 'ri(a dat* de =illi! >?@ i anali&at in "or(* co('let* (onogra"ic* de c*tre 0 bo( >-@. ,n con!ecin:*, e!te de a!e(enea nu(it i A!indro(ul 0 bo(A. 6L3 (ai e!te cuno!cut i ca Aanxieta! tibiaru(A i coloc4ial e!te denu(it in literatura de li(ba engle&a Aleg Bitter!A. 6L3 are un du'licat (otor i('ortant !ub "or(a (ic*rilor !o(nA recurente bru)te nu(ite anterior A(icarea A(ic*ri 'eriodice ale (e(brelor +n 5PLM3, denu(it i Anocturnal (yoclonu!A clinic 'entru 6L3 >9@ re4i&uite +n -../ >5@% 5i7 ne4oia i('erioa!* de a (ica 'icioarele, de obicei +n!oit* !au cau&at* de o !en&aie ne'l*cut* !au necon"ortabil* la ni4elul 'icioarelor< 5ii7 ne4oia de (icare !au !en&aiile ne'l*cute +nce' !au !e +nr*ut*e!c +n ti('ul 'erioadei de odihn* !au inacti4itate cu( ar "i !tatul +ntin! !au !tatul +n )e&ut< 5iii7 ne4oia de (icare !au !en&aiile ne'l*cute !unt 'arial !au total a(eliorate de (icare, cu( ar "i 'li(barea !au +ntinderea, cel 'uin c8t ti(' acti4itatea continu*< 5i47 ne4oia de (icare !au !en&aiile ne'l*cute !e +nr*ut*e!c !eara !au noa'tea (ai (ult dec8t &iua, !au a'ar doar !eara !au noa'tea. 3e4eritatea e!te (*!urat* 'e 3cala internaional* de e4aluare 6L3, care conine ?. +ntreb*ri 'entru e4aluarea !e4erit*:ii bolii >D@. 6ecent, a "o!t 4alidat* o 3cal* de e4aluare a calit*:ii 4ie:ii la 'acien:ii cu 6L3>E@. 6L3 'oate "i 'ri(ar !au !ecundar >F@. 6L3 'ri(ar re're&int* de!eori o boal* "a(ilial*. 6L3 'oate "i i !ecundar !arcinii, !au unor condi:ii 'atologice ca neuro'atiile 'eri"erice, (ielo'atiile, ure(ia, artrita reu(atoid*, de 3tudiu al C('licarea o'ioidelor
2

'eriodic* a 'icioarelor +n !o(nA7. Dei PLM3 'oate !* a'ar* inde'endent de 6L3 ca o de!co'erire incidental* 'oli!o(nogra"ic*, Cla!i"icarea Cnternaional* a Deregl*rilor 3o(nului recunoate PLMD datorit* 'oten:ialului !*u i('act a!u'ra calit*ii !o(nului i datorit* "a'tului c* 'oate "i o !ur!* a !o(nolenei exce!i4e +n ti('ul &ilei, (ai ale! c8nd PLM3 e!te a!ociat cu tre&irea din !o(n 5PLM3-A7 >/@. 3e4eritatea PLM3;PLMD e!te e4aluat* cu aButorul indexulului PLM3 5PLM3 C% PLM3 Gru'ul 'er or* de +nregi!trare 'oli!o(nogra"ic*7. Cnternaional 3indro(ului Picioarelor 2elinitite a

boala di!"unciei endogene i

Par in!on, !i!te(ului !i!te(ului

de"iciena de "ier, ADGD la co'ii.

do'a(inergic +n 6L3 e!te ba&at* +n 'rinci'al 'e e"ectele "a4orabile ale inter4eniilor "ar(acologice. Do4e&ile cu 'ri4ire la de"ectul do'a(inergic central !unt +nc* contro4er!ate. 6olul "ierului )i al de'o&itelor de "ier +n "i&io'atologia !indro(ului e!te deri4at din !tudiile (etaboli!(ului "ierului +n 6L3. 3co'ul trata(entului +n 6L3 i PLMD e!te de a controla !i('to(ele. 3co'ul ace!tui ghid e!te de a exa(ina cele (ai bune do4e&i di!'onibile de!'re e"iciena "iec*rui trata(ent +n ace!te a"ec:iuni. Obiective Pentru a deter(ina e"iciena i e"ectul (eninut al (edica(entelor i 'rocedurilor "i&ice +n trata(entul 6L3 i PLMD, au "o!t te!tate ur(*toarele i'ote&e% ?. Hrice (edica(ent e!te (ai e"icient dec8t li'!a total* de trata(ent !au trata(ent cu 'lacebo% a. b. -. /. +n abolirea !au reducerea a'ariiei 6L3 i PLM3< +n +(bun*t*irea calit*ii 4ieii. H cla!* !au o (olecul* e!te (ai Hrice 'rocedur* "i&ic* e!te (ai

b. 4.

+n +(bun*t*irea calit*ii 4ieii. 0"ectele !ecundare ale cla!ei

!au (oleculelor i ale trata(entelor "i&ice care !-au do4edit a "i e"iciente, nu de'*e!c e"ectele tera'eutice. Metode i strategii de cercetare 3-a c*utat cea (ai rele4ant* do4ad* di!'onibil* 'entru a aborda "iecare +ntrebare, cu o !che(* de cla!i"icare a ti'urilor de !tudii +n con"or(itate cu docu(entul 0123 re"eritor la ghiduri 5Cla!a C '8n* la Cla!a CV de e4iden:*, >I@7. Dac* cea (ai +nalt* cla!* de e4iden:* nu a "o!t !u"icient* !au nece!ita actuali&area literaturii, !-a extin! cercetarea literaturii la cla!a adiacent* in"erioar*. Au "o!t luai +n calcul 'acienii cu 6L3 i;!au PLMD, cu orice alt* co(orbiditate i (edicaie a!ociate. 'entru Criteriile Au ex'licite "o!t de diagno!tic ale 6L3 nu au "o!t nece!are includere. inclu!e tera'iile cu orice "el de (edica(ente 5orice do&aB, orice regi(7 i cu orice "el de 'roceduri "i&ice. 3-au ur(*toarele cele ce luat +n de con!iderare (edica(ente% a!u'ra (edica(entele do'a(inergici cla!e

ac:ionea&*

bun* dec8t alta. e"icient* dec8t li'!a trata(entului !au trata(entul cu 'lacebo% a. +n abolirea !au reducerea
3

adrenorece'torilor, antie'ile'tice, agenii 5le4odo'a,

ben&odia&e'inele;hi'noticele,

do'a(inergice deri4ate din ergot !au nederi4ate din ergot7, o'ioidele, alte

a'ariiei 6L3 i PLM3

trata(ente. Durata trata(entului +n "iecare !tudiu a "o!t +('*rit* +n ter(en !curt 5J/. &ile7 !au ter(en lung 5K/. &ile7. Pentru 6L3, re&ultatele ur(*rite au "o!t din ur(*toarele do(enii% ?. 'rin 2. Pare!te&ii;di!e!te&ii, !au durere !cale;che!tionare Cndexuri !ubiecti4e ale 5'rin !i('l* ra'ortare !ubiecti4* !au 4alidate7. 'oli!o(nogra"ice di!"unciei !o(nului 5indexul (ediu PLM3-C +n !o(n, (edia PLM3-A, e"iciena !o(nului, latena !o(nului, acti4itatea actigra"ic* +n !o(n7. 3. 4. Calitatea 4ieii. 6eacii ad4er!e% !e(ni"icati4 e"ectul +n de

9.

Abandon tera'eutic.

,n !trategia de identi"icare a !tudiilor, !au generat ter(eni de c*utare 'entru c*utarea +n ur(*toarele ba&e de date electronice 54e&i #abel 3? 'e !ite7% Biblioteca Cochrane, Biblioteca 2aional* a Medicinei M0DLC20 5din ?IDD7, 0MBA30 5din ?IF.7, CC2AGL 5din ?IF-7. Ghidurile exi!tente au "o!t de a!e(enea c*utate i anali&ate. Au "o!t re4*&ute toate re"erinele '8n* la !"8ritul anului -..9 'entru a identi"ica 'otenialele !tudii de inclu!, i !-a de!"*urat extragerea datelor. Pentru "iecare +ntrebare cheie !-a creat un tabel de e4iden*, enu(er8nd de!ign-ul i cla!i"icarea (etodologic* a "iec*rui !tudiu. Pentru de "or(ularea 4olu(ul reco(and*rilor e4idenelor, ghid,

a('li"icare, de"init ca A!i('to(e 6L3 a('li"icate du'*a(ia&a !au !eara +nainte de luarea ur(*toarei do&ei de noa'teA, a "o!t cla!i"icat 'rintre e"ectele ad4er!e, la ulti(a actuali&are. 5. D. Abandon tera'eutic. 6ata 'acienilor care au ale! !*

a'licabilitatea,

generalitatea, con!i!tena i i('actul clinic au "o!t re&u(ate de "iecare (e(bru al Gru'ului de Lucru. Cla!ele de e4idene au cu i "o!t Ghidul ni4elurile atribuite 0123 de +n al reco(andare con"or(itate

continue trata(entul du'* "inali&area !tudiului. Pentru PLMD, re&ultatele ur(*rite au a'ar:inut ur(*toarelor do(enii% ?. -. /. Cndexurile 'oli!o(nogra"ice ale Calitatea 4ieii. 6eacii ad4er!e.
4

Gru'ului de Lucru >I@. De&acordurile !au re&ol4at 'rin di!cuii. La "inal, "iecare (e(bru al gru'ului a trebuit !* declare Re ultate un 'otenial con"lict de intere!e, dac* exi!ta 4reunul.

di!"unciei !o(nului.

3tudiile de cla!* C '8n* la CCC !unt ra'ortate aici i !e "ace re"erire la ele +n #abelul 3- 5'e !ite7. 3tudiile de cla!* CV au "o!t luate de a!e(enea +n con!iderare, dar nu !e "ace re"erire la ele dec8t +n #abelul 3/ 5'e !ite7. Medicamente ce ac!ionea asupra adrenoreceptorilor ?5 ra'oarte au "*cut re"erire la "olo!irea (edica(entelor ce ac:ione&* a!u'ra adrenorece'torilor 5clonidin*, "enoxiben&a(in*,'ro'ranolol,tali'exol7. ,n 6L3 'ri(ar, +ntr-un !tudiu de cla!* CC >?.@, clonidina 5do&* (edie .,5 (g cu -h +naintea debutului !i('to(elor7 ad(ini!trat* ti(' de --/ !*'t*(8ni a a(eliorat 'are!te&iile i nelinitea (otorie 5?,D i ?,E 'uncte re!'ecti4, 'e o !cal* ne4alidat*7 i latena !o(nului 5/5,5 (in7, dar PLM3-C, PLM3-A, actigra"ia i e"icien:a !o(nului au r*(a! ne!chi(bate. 0"ectele ad4er!e ale clonidinei 5u!c*ciunea gurii, tulbur*rile cogniti4e, con!ti'aia,

e"iciena !o(nului i a redu! PLM3-C i PLM3-A. ,n 6L3 !ecundar, exi!t* cla!* CCC >?-@ do4e&i de c*rora con"or(

ad(ini!trarea de dou* ori 'e &i a .,.E5 (g clonidin*, 'entru o 'erioad* de trei &ile, la 'acien:i cu ure(ie cronic*, a du! la reducerea; +n I din atenuarea ?. ca&uri !i('to(elor

co('arati4 cu unul din ?. 'acien i tratai cu 'lacebo. ,ecomandri Clonidina e!te 'robabil e"icient* +n reducerea !i('to(elor i a latenei !o(nului +n 6L3 'ri(ar 'e ter(en !curt 5ni4el B7. Clonidina a a4ut (ai (ulte e"ecte ad4er!e care au "o!t tolerate 5u!c*ciunea gurii, tulbur*ri cogniti4e, !c*derea libidoului, !en&atia de L'lutireM, !o(nolen*, ce"alee7 5ni4el B7. 2u exi!t* !u"iciente do4e&i 'entru a e(ite o reco(andare re"eritoare la tali'exol,'ro'ranolol, "enoxiben&a(in* i la clonidin* +n 6L3 !ecundar. Medicamente antiepileptice -- de ra'oarte au 4i&at utili&area (edica(entelor 5gaba'entin, antie'ile'tice carba(a&e'in*,

libidoul !c*&ut, !en&atia de L'lutireM, !o(nolena, ce"aleea7 nu au du! la renun*ri. 0xi!t* do4e&i de cla!* CCC >??@ con"or( c*rora tali'exolul 5agoni!t at8t al rece'torilor do'a(inergici Dc8t i al autorece'torilor adrenergici -7 +n do&* de .,9-.,F (g ad(ini!trat la culcare, a +(bun*t*it !i('to(ele i

la(otrigin*, to'ira(at, 4al'roat7. ,n 6L3 'ri(ar exi!t* do4e&i de cla!* CC >?/@ dintr-un !tudiu 'e ter(en lung 55 !*'t*(8ni7 con"or( c*rora carba(a&e'ina +n do&* de ?..-/.. (g 5do&* (edie -/D (g7 ad(ini!trat* la
5

culcare

!c*&ut

"rec4ena

,ntr-un !tudiu de cla!* CC 'e -. de 'acieni >-.@, ad(ini!trarea de 4al'roat cu eliberare 'relungit*, +ntr-o do&* (edie de D.. (g, 4er!u! 'lacebo a redu! !e(ni"icati4 inten!itatea !i('to(elor 6L3 cu ?,E 'uncte, +n con"or(itate cu o !cal* ne4alidat*, i durata !i('to(elor 'entru e"ect o 6L3 cu I-,/ de "o!t (in;-9 h, dar nu a redu! )i PLM3-C i PL3M-A, "rec4ent ,n 6L3 'erioad* a ur(*rire de / !*'t*(8ni. Cel (ai ad4er! la !o(nolen:a. !ecundar 'acienii he(odiali&a:i, exi!t* e4idene de cla!* CC >-?@ con"or( c*rora gaba'entinul, ad(ini!trat intr-o do&* de -..;/.. (g du'* "iecare edin* de he(odiali&*, 4er!u! 'lacebo a redu! !i('to(ele 6L3 cu -,F 'uncte, 'entru o 'erioad* de ur(*rire de D !*'t*(8ni. Doi 'acieni au renunat i din cau&a datorate !o(nolenei letargiei

!i('to(elor 6L3 reduc8nd atacurile de la o (edie de -,I la ?,5 'e !*'t*(8n*. 0"ectele ad4er!e ra'ortate ca Ane"iind i('ortanteA au a'*rut la /9 din F9 de 'acieni 4er!u! -. din I. 'acieni tratai cu 'lacebo. 0xi!t* do4e&i de cla!* CC >?9@ de!'re e"ectul bene"ic al carba(a&e'inei co('arati4 cu 'lacebo, dar "*r* a !e "i calculat !e(ni"icaia !tati!tic*. 0xi!t* do4e&i de cla!* C >?5@ con"or( c*rora gaba'entinul ad(ini!trat +n do&* de ?F.. (g 'e &i 5o trei(e din do&a total* la ora ?- i dou* trei(i la ora -.7 4er!u! 'lacebo a redu! !i('to(ele 6L3 cu F,9 'uncte con"or( 3calei de Cla!i"icare 6L3, a +(bun*t*it e"iciena !o(nului cu I,FN i a redu! PLM3-C cu I,F e'i!oade, 'entru o 'erioad* de ur(*rire de D !*'t*(8ni. 0"ectele ad4er!e au "o!t (ai "rec4ente la 'acien:ii trata:i cu gaba'entin 59FN 4! -.,FN7 i au inclu! !tare de r*u general, e"ectele !o(nolen* 2ici nu ad4er!e i a !i('to(e dintre du! la ga!trointe!tinale. unul

gaba'entinului. ,ntr-un !tudiu de cla!* CCC >--@, !ubiecilor cu 6L3 !ecundar i abu& de heroin*, +n 'rogra( de detoxi"icare ra'id*, c*rora li !-a ad(ini!trat gaba'entin +n do&* de ?-.. (g, li !-au redu! !i('to(ele cu - 'uncte 'e o !cal* ne4alidat*, la ? h du'* ad(ini!trare. ,ecomandri Gaba'entinul,
6

+ntreru'erea trata(entului. 3tudii de cla!* CCC cu gaba'entin >?D-?I@ au ra'ortat o +(bun*t*ire a !i('to(elor 6L3 'e ter(en lung 5D-?F luni7 cu e"ecte ad4er!e (inore !'orirea 5a(eeal*, e"ectelor !o(nolen:*,

+n

do&*

de

F..-

alcoolului i ce"alee7.

?F..(g;&i 'oate "i con!iderat e"icient

+n 6L3 'ri(ar 5ni4el A7 i 'robabil e"icient !unt /..(g +n 6L3 !ecundar i cu du'* he(odiali&* 5ni4el B7. 0"ectele ad4er!e bl8nde i re4er!ibile. eliberare Carba(a&e'ina, +n do&* de ?..4al'roatul 'relungit*, +n do&* de D..(g;&i, 'ot "i con!iderate ca 'robabil e"iciente +n 6L3 'ri(ar 5ni4el B7. 2u exi!t* do4e&i !u"iciente 'entru a "ace reco(and*ri de!'re to'ira(at i la(otrigin* i de!'re utili&area (edica(entelor antie'ile'tice +n PLMD. "en odia epine # hipnotice /D de ra'oarte au !tudiat e"icacitatea ben&odia&e'inelor;hi'noticelor 5al'ra&ola(, clona&e'a(, dia&e'a(, nitra&e'a(, oxa&e'a(, te(a&e'a(, tria&ola( i &ol'ide(7. Pentru 6L3 'ri(ar, exi!t* do4e&i con"lictuale de cla!* CC >-/,-9@ con"or( c*rora clona&e'a(ul, +n do&* de .,5-(g, a redu!;eli(inat !au nu !e(ni"icati4 'are!te&iile;di!e!te&iile

>-/@, ?(g de clona&e'a( ad(ini!trat +nainte de culcare a +(bun*t* it !ubiecti4 calitatea !o(nului. 0"ectele ad4er!e au "o!t ab!ente +ntr-un !tudiu de cla!* CC dar, +n alt !tudiu de cla!* CC, cu clona&e'a( +n do&* de .,5-- (g, ad(ini!trat +n 'atru 'ri&e +n ti('ul &ilei, !o(nolena &ilnic* !-a ra'ortat la / 'acieni 5din D7 4er!u! unul tratat cu 'lacebo >-9@. Pentru PLMD, exi!t* do4e&i de cla!* CC con"or( c*rora clona&e'a(ul ? (g nu a "o!t (ai e"icient dec8t te(a&e'a(ul /. (g >-D@ iar clona&e'a(ul .,5-?,5 (g nu a "o!t (ai e"icient dec8t tera'ia cogniti4-co('orta(ental* >-E@. Mai (ulte !tudii de cla!* CCC au ar*tat c* clona&e'a(ul .,5--(g ad(ini!trat la culcare a (icorat PLM3-C i uneori PLM3-A >-D,-F-/?@. 0"ectele ad4er!e la ad(ini!trarea de clona&e'a( .,5(g la culcare au "o!t anxietate cre!cut*, duc8nd la renunare la unul din D 'acieni 'acien:i, 5>-E@, !tudiu cla!* CC7 )i !au a(eeal* din ?. la unul 'acieni !o(nolen*

co('arati4 cu 'lacebo 5di!cre'ana e!te legat* 'robabil de (odul di"erit de ad(ini!trare% +nainte de culcare 4er!u! 9 do&e;+n ti('ul &ilei7. ,n ceea ce 'ri4ete indicii 'oli!o(nogra"ici, nu(ai o +(bun*t*ire de ?9N a e"icienei !o(nului a "o!t ra'ortat* +ntr-un !tudiu de cla!* CCC 'e ter(en !curt cu ?(g de clona&e'a( ad(ini!trat +nainte de
7

renun:8nd 5>-I@, te!t cla!a CCC7. 0xi!t* dou* !tudii de cla!* CC con"or( c*rora tria&ola(ul 5.,?-5-.,5. (g7 a +(bun*t*it e"iciena !o(nului i a redu! !o(nolena diurn*, "*r* e"ect a!u'ra PLM3, la ur(*rirea 'e ter(en !curt >/-,//@. 0xi!t* te!te !ingulare de cla!* CCC care arat* c* te(a&e'a(ul

culcare >-5@. ,ntr-un !tudiu de cla!* CC

5/. (g7 >-D@ i nitra&e'a(ul 5-,5-?. (g7 >/9@ au +(bun*t*it e"iciena !o(nului, latena !o(nului i PLM3-C. ,ecomandri Clona&e'a(ul 'robabil e"icient trebuie +n con!iderat +(bun*t*irea

'erioad* de ur(*rire de 9 !*'t*(8ni, le4odo'a; ben!era&id*, ad(ini!trat* +n do&* unic* la culcare 5do&a (edie% ?5I;9.(g7 4er!u! 'lacebo a +(bun*t*it calitatea !o(nului cu .,E 'uncte 'e o !cal* de la ? la 5, a redu! latena !o(nului cu -D (inute, a +(bun*t*it calitatea 4ieii i a redu! PLM3-C cu -E,F e4eni(ente;or*. Ace!t !tudiu nu a a4ut dre't obiecti4 a(eliorarea !i('to(elor 6L3. 0xi!t* !tudii de cla!* CC >-.,/D-9?@ care arat* c* 'e ter(en !curt 5? noa'te;9 !*'t7 le4odo'a, ad(ini!trat* +n do&* unic* la culcare 5?..--.. (g7, cu !au "*r* o do&* !u'li(entar* de ?.. (g ad(ini!trat* la / ore du'* culcare, a redu! (oderat !i('to(ele 6L3, cu .,5 'uncte 'e o !cal* de 9 'uncte, cu ?,I 'uncte 'e o !cal* de ?. 'uncte, i cu -I,/ 'uncte 'e o 3cal* Vi&ual* Analoag* 5VA37. 2u a (ai "o!t de(on!trat acelai lucru +ntr-un alt !tudiu. ,ntr-un !tudiu de cla!* CC 'e 'acieni cu 6L3 !-au cu co('arat eliberare le4odo'a;ben!era&id*

!i('to(elor +n 6L3 'ri(ar c8nd e!te ad(ini!trat +n do&* de ?(g la culcare, )i 'robabil ine"icient c8nd e!te ad(ini!trat +n 9 do&e 'e 'arcur!ul &ilei 5ni4el B7. ,n PLMD, clona&e'a(ul 5.,5-(g;&i7 e!te 'robabil e"icient +n a(eliorarea PLM3-C i PLM3-A 5ni4el B7 iar tria&ola(ul 5.,?-5-.,5.(g;&i7 e!te 'robabil e"icient +n a(eliorarea e"icienei !o(nului i 'robabil ine"icient +n reducerea PLM3 5ni4el B7. 0"ectele ad4er!e ale ben&odia&e'inelor 5!edare (atinal*, !o(nolen* tulbur*ri diurn* de i (e(orie, !l*biciune

(u!cular*7 au "o!t de obicei bl8nde, de'endente de do&* i re4er!ibile. 2u exi!t* do4e&i !u"iciente 'entru reco(and*ri re"eritoare la al'ra&ola(, nitra&e'a(, te(a&e'a( i &ol'ide(. De a!e(enea nu 'ot "i +n "*cute de!'re 6L3 reco(and*ri ben&odia&e'ine;hi'notice !ecundar. $geni dopaminergici %evodopa 5- de ra'oarte !-au concentrat 'e utili&area le4odo'ei. 0xi!t* do4e&i de cla!* C >/5@ c* +n 6L3 'ri(ar, 'e o
8

i(ediat* 5do&e de la ?..;-5 la -..;5. (g7 cu le4odo'a; ben!era&id* cu eliberare 'relungit* i(ediat* cu 5do&* ?..;-5 'lu! eliberare (g7, le4odo'a;ben!era&id*

ad(ini!trate la culcare. Al doilea regi( a redu! !i('to(ele 6L3 +n a doua Bu(*tate a no'ii, a +(bun*t*:it

!ubiecti4 calitatea !o(nului i a redu! latena ace!tuia >9.@. 0"ecte ad4er!e ra'ortate de (aBoritatea !tudiilor au "o!t diareea, greaa, a di!'e'!ia, controlului, 6L3 a "o!t !caderea ce"aleea. globala ,nr*ut*irea

=al er et al. >9-@, !-a +(bun*t* it doar indexul PLM3 nu i !i('to(ele 6L3. Pentru PLMD, exi!t* !tudii de cla!* CC cu le4odo'a 5'lu! ben!era&id* !au carbido'a< -.. (g la culcare !au ?.. (g de 5 ori 'e &i7 4er!u! 'lacebo +n PLMD, cu !au "*r* 6L3 >9/@, PLMD cu narcole'!ie >99@ i PLMD la 'acienii cu le&iuni !'inale co('lete >95@% PLM3-C i PLM3-A !-au redu!. ,ecomandri ,n 6L3 'ri(ar, 'e ter(en !curt, le4odo'a a "o!t e"icient* +n reducerea !i('to(elor calit*ii 6L3, +n a(eliorarea !o(nului, +n a(eliorarea reducerea PLM3

!l*biciunea (u!cular*, !o(nolen:a i ra'ortat* la - din /E de 'acien:i i la 9 din -. de 'acieni, !au la ?D,E--D,EN dintre 'acieni. Pe ter(en lung 5---9 luni7, +n !tudii de!chi!e de cla!* CCC, le4odo'a !-a do4edit +nc* Ae"icient*A la E.,-N din 'acien:i, -I-/?N din 'acieni "iind !ati!"*cui de tera'ie, a a(eliorat !i('to(ele 6L3 cu D,.-D,5 'uncte 'e o !cal* de E 'uncte i a redu! latena 'erce'ut* a !o(nului cu ?/? (inute. 6enun*rile au "o!t nu(eroa!e, /.E.N +n ace!te !erii, iar agra4area !i('to(atologiei a 4ariat +ntre ?F,DN i F-N. Pentru 6L3 !ecundar, la ur(*rirea 'e ter(en !curt, dou* !tudii de cla!* CC >/F,9-@ au e4aluat le4odo'a 5'lu! ben!era&id* !au carbido'a7 +ntr-o do&* unic* la culcare 5?..--.. (g7 4er!u! 'lacebo, la 'acienii cu ure(ie. ,ntr-un !tudiu, !i('to(ele 6L3 !-au redu! 5+(bun*t*:ire cu .,I 'uncte 'e o !cal* de la . la ?.7. De a!ee(enea, PLM3-C i PLM3-A !-au redu! iar calitatea 4ie ii !-a +(bun*t*:it. #otui, +n !tudiul lui
9

calit*:ii 4ieii i +n

5ni4el A7. 0"ectele ad4er!e au "o!t (inore dar (ai "rec4ente dec8t la 'lacebo 5ni4el A7. Pe ter(en lung, le4odo'a a "o!t 'robabil e"icient*, dar /.OE.N din 'acieni au renunat din cau&a e"ectelor ad4er!e !au li'!ei e"icienei -.-F-N necuno!cut trata(entului. 5ni4el dintre dintre ,n C7. Agra4area tratai, o'rirea !ecundar !i('to(atologiei !-a 'rodu! 'robabil la 'acienii ei, 6L3 la conduc8nd 'entru un nu(*r +nc*

ure(iei, 'e ter(en !curt, le4odo'a a "o!t 'robabil e"icient* +n reducerea !i('to(elor, a(elior8nd calitatea 4ie ii i reduc8nd PLM3-C i PLM3-A 5ni4el B7. ,n PLMD, 'e ter(en !curt, le4odo'a a "o!t 'robabil e"icient* +n

+(bun*t*:irea PLM3-C i PLM3-A 5ni4el B7. &eriva!ii de Ergotamin /I de ra'oarte au !tudiat utili&area deri4atelor cabergolin*, tergurid7. ,ntr-un !tudiu de cla!* CCC, dihidroergocri'tina +n do&* de ?.-9. (g a redu! !ubiecti4 !i('to(ele 6L3 'ri(ar< !-a +(bun*t*it de a!e(enea calitatea !o(nului >9D@. ,ntr-un !tudiu de cla!* CC >9E@ bro(ocri'tina, +n do&* de E,5 (g, a adu! +(bun*t* iri 'ariale !ubiecti4e ale !en&a:iei de nelini te i ale 'are!te&iilor la 5 din D 'acien i, "*r* e"ecte ad4er!e !e(ni"icati4e. Pentru cabergolin* 5.,5, ? i - (g o dat* 'e &i7, un !tudiu de cla!* C 'e FD 'acien i >9F@ a ar*tat o !chi(bare de la !ituaia iniial* de, re!'ecti4, -?/,?, -?/,5 i -?5,E 'uncte 'e 3cala Cnterna:ional* 6L3, co('arati4 cu -/,/ la 'lacebo, 'entru o 'erioad* de ur(*rire de 5 !*'t*(8ni. Di!'ari:ia !i('to(elor !-a ob!e4at gru'ului la ce /D,9N a dintre 'acien:ii (g de 'ri(it ergota(in* li!urid, 'ergolid 5 i

CCC7. ,n ca&ul trata(entului 'e ter(en lung, e"ectele ad4er!e au du! la renun:area a ?? 'acien:i din F5< 3-a ob!er4at agra4area !i('to(elor la ??N 'acieni. Pentru 'ergolid, exi!t* D !tudii 'e ter(en !curt i 5 'e ter(en lung. ,ntr-un !tudiu de cla!* C 5nu(*r total 'acieni ?..7 'ergolidul, +n do&e de .,.5-?,5 (g, cu o do&* (edie de .,9-.,55 (g;&i, a a(eliorat !e(ni"icati4 !e4eritatea 6L3, a a(eliorat !e(ni"icati4 calitatea !o(nului i a di(inuat !e(ni"icati4 PLM3-C i PLM3A >5.@. 6ata re!'ondenilor 5A(ult +(bun*t*itA +(bun*t*itA !au 'e A"oarte (ult a 3cala Global*

dihidroergocri'tin*,

bro(ocri'tin*,

C('re!iilor Pacientului7 la D !*'t*(8ni a "o!t DFN +n gru'ul ce a 'ri(it 'ergolid 4er!u! ?5N +n gru'ul ce a 'ri(it 'lacebo. Continuarea ad(ini!tr*rii trata(entului &ilnic, intr-o do&* (edie de .,5- (g;&i, 'e o 'erioad* de ?- luni, a du! la !c*derea !e(ni"icati4* a PLM3-C i PLM3-A 5cla!* CCC7. 0"ectele ad4er!e au "o!t ra'ortate de 9.-E.N dintre 'acieni ca "iind bl8nde% grea*, ce"alee, conge!tie na&al*, orto!tatic*, a(eeal*, controlate hi'oten!iune uor +ntr-un

cabergolin* co('arati4 cu 9,9N dintre cei ce au 'ri(it 'lacebo. Pe ter(en lung 5? an7 trata(entul cu do&e (edii de -,/ (g;&i !au ?,5 (g;&i ti(' de -D !*'t*(8ni >9I@ a r*(a! e"icient 5cla!a
10

!tudiu cu do('eridone -.(g. 2u !-au ob!er4at "eno(ene de rebound !au agra4*ri ale !i('to(elor +n !tudiile de cla!* C i CC. Pn !tudiu co('arati4 de cla!* CC, ce a !tudiat e"icien:a 'ergolid-

ului 4! le4odo'a >5?@, a ar*tat un re&ultat (ai bun al trata(entului cu 'ergolid% 'ergolid .,?-5 (g &ilnic a atenuat co('let !i('to(atologia la F-N dintre 'acieni co('arati4 cu IN +n ca&ul ad(ini!tr*rii de le4odo'a -5. (g< (ai (ult, 'ergolidul a du! la o !c*dere cu EIN a PLM3-C "a* de o !c*dere cu 95N ob:inut* cu le4odo'a. #erguride .,-5-.,5 (g;&i a +(bun*t* it !i('to(ele 6L3 +ntr-un !tudiu de cla!* CCC. ,n 6L3 !ecundar ure(iei, la 'acien:i he(odiali&a:i, 'ergolide .,.5-.,-5 (g ad(ini!trat 'e ter(en !curt 5?. no' i7 nu a (odi"icat (o(entul debutului !o(nului, nu(*rul tre&irilor i actigra"ia 'entru PLM3. ,ntr-un !tudiu de cla!* CC !-au ob!er4at a(elior*ri !ubiecti4e ale calit*ii !o(nului i ale !i('to(elor 6L3 la 5 din F 'acieni, dar re&ultatele nu au "o!t 4alidate 'rin anali&* !tati!tic* 4er!u! 'lacebo >5-@. 0"ectele ad4er!e au "o!t greaa la un !ubiect i co(aruri la un altul. 0xi!t* do4e&i de cla!* CC c* +n PLMD din narcole'!ie >5/@ bro(ocri'tina 5E,5 (g7 a "o!t e"icient*. ,ecomandri ,n 6L3 'ri(ar, !-a !tabilit c* 'ergolidul e!te e"icient la do&e (edii de .,9-.,55 (g;&i 5ni4el A7 i e!te 'o!ibil e"icient 'e ter(en lung 5ni4el C7. PLM3-C i
11

PLM3-A !-au +(bun*t*it i ele du'* ad(ini!trarea de 'ergolid. Cabergolina e!te e"icient* la do&e de .,5--(g;&i 5ni4el A7 i 'o!ibil e"icient* 'e ter(en lung 5ni4el C7. Bro(ocri'tina E,5 (g 'oate "i reco(andat* ca 'robabil e"icient* 5ni4el B7. ,n 6L3 !ecundar a!ocia he(odiali&ei cronice, 'ergolidul ad(ini!trat 5ni4el B7. 'e ,n ter(en PLMD !curt a!ociat e!te cu e!te 'robabil ine"icient la do&a de .,-5(g;&i narcole'!ie, bro(ocri'tina

'robabil e"icient* 5ni4el B7. Cele (ai "rec4ente e"ecte ad4er!e ale agoni)tilor do'a(inergici deri4a:i din ergota(in* 5grea*, ce"alee, conge!tie na&al*, a(eeal* i hi'oten!iune orto!tatic*7 au "o!t controlate de do('eridone. ,n !tudiile de cla!* C nu !-a e4aluat agra4area do4e&i !i('to(atologiei 'entru 'ri4ire a la du'* "ace ad(ini!trarea de 'ergolid. 2u exi!t* !u"iciente cu reco(and*ri

dihidroergocri'tin*, li!urid i tergurid.

$goniti dopaminergici non'ergot deriva!i /I ra'oarte au !tudiat utili&area nonalc*tuirii agoni)tilor rotigotine7. do'a(inergici La (o(entul

ergota(inici 5'ra(i'exole, ro'inirole, ace!tui docu(ent, ro'inirole era cel

(ai !tudiat (edica(ent 'entru 6L3 +n !tudiile de cla!* C. Pentru 6L3 'ri(ar, +ntr-un te!t de cla!* C 'e -F9 'acieni >59@, trata(entul cu ro'inirole, +n do&* (edie e"ecti4* de ?,I (g;&ilnic, a du! la o reducere !e(ni"icati4* 'e 3cala Cnternaional* 6L3 5??,.9 'uncte 4!. F,./ la 'lacebo7 iar calitatea 4ieii !-a a(eliorat du'* ?- !*'t*(8ni. 3-au obinut re&ultate !i(ilare +n alte dou* !tudii de cla!* C, unul 'e -DD de 'acieni trata:i cu ro'inirole +n do&* (edie e"ecti4* de ?,5 (g;&ilnic 5??,'uncte reducere 'e 3cala Cnternaional* 6L3 4!. F,E cu 'lacebo7 >55@ i un altul 'e -- de 'acien i trata:i cu ro'inirole +n do&* (edie de 9,D (g;&ilnic >5D@. 0"ectele ad4er!e bl8nde i tran&itorii au inclu!% greaa, ce"aleea, obo!eala i a(eeala. ,n ce 'ri4ete indicii 'oli!o(nogra"ici ai +ntreru'erii !o(nului, +ntr-un !tudiu de cla!* C cu 'oli!o(nogra"ie >5E@, ro'inirole +n do&* (edie de ?,F (g;&ilnic a a(eliorat !e(ni"icati4 PLM3-C 5cu ED,-N 4!. ?9N 'lacebo7, PLM3-A i latena !o(nului. 0"ectele ad4er!e au "o!t ce"aleea 'o!ibil i din greaa, cau&a )i (ai 'uin de "rec4ent a(eeala. Agra4area 6L3, e"ectului a('li"icare, !-a ob!er4at la 9 din 5I 5EN7 'acieni. ,n ceea ce 'ri4e)te 'ra(i'exol-ul, un !tudiu de cla!* CC 5.,E5-?,5 (g cu o
12

or* +nainte de culcare7 'e ?. 'acien i >5F@ 6L3 a i de(on!trat a(elior*ri 0"ectele reducerea ale !e(ni"icati4* a !corurilor !ubiecti4e i('ortante ad4er!e PLM3-C. din 5greaa, la 9.N<

con!ti'aia, 'ierderea a'etitului la I.N 'acieni< a(eeal* obo!eal* diurn* la /.N7 au "o!t ra'ortate ca bl8nde i tran&itorii, dar greaa 'er!i!tent* !-a ob!er4at la //N dintre 'acien:i la do&a de ?,5 (g;&i. #rata(entul +ndelungat cu 'ra(i'exol !-a do4edit e"icient +n !tudiile de cla!* CCC. 6otigotina 5'atch cu eliberare continu* tran!der(al* - ?,?-5, -,-5 i 9,5 (g;&i7 a a(eliorat !i('to(ele 6L3 5cu ?.,5?5,E 'uncte !curt co('arati4 'e D/ de cu F la 'lacebo7 +ntr-un !tudiu de cla!* C 'e ter(en 'acieni, !e(ni"icati4 la do&a de 9,5 (g;&i >5I@. 0"ectele ad4er!e i tolerabilitatea 'ielii au "o!t !i(ilare cu 'lacebo. Pentru c* ace!te date !-au obinut du'* ? !*'t*(8n* de !tudiu, r8(8ne de 4*&ut care Pentru e!te 6L3 e"iciena rotigotinei ure(iei, 'e la ter(en (ediu i lung. !ecundar 'acien:ii he(odiali&a:i, exi!t* un !tudiu de cla!* CC 'e ?? 'acien i +n care ro'inirole ?,95 (g;&i a a(eliorat !i('to(ele (ai bine ca le4odo'a ?I.(g;&i >D.@. ,ecomandri

,n 6L3 'ri(ar, ro'inirole +n do&* de ?,5-9,D (g;&i are un ni4el de e"icien* A. 6otigotina, !ub "or(* de 'atch cu eliberare tran!der(al*, e!te e"icient* 'e ter(en !curt e!te 5ni4el 'robabil A7 iar 'ra(i'exole e"icient

au "o!t con!ti'aia uoar* la - din ?? 'acien:i i letargie +n ti('ul &ilei la ? din ?? 'acieni. Pentru PLMD, exi!t* do4e&i de cla!* CC >9/@ con"or( c*rora 'ro'oxi"enul 'e ter(en !curt, +n do&e de ?..--.. (g, ad(ini!trat la culcare, nu a +(bun*t*it latena !o(nului, e"iciena ace!tuia i PLM3-C, dar a redu! PLM3-A cu -F,D e4eni(ente;or* 4er!u! 'lacebo. 0"ectele ad4er!e au "o!t de're!ia uoar*, a(eeala, greaa i unul din D 'acieni a renunat din cau&a urticariei i tu(e"ac:iei linguale. ,ecomandri Pentru 6L3 'ri(ar, oxicodona +n do&* (edie de ??,9 (g 'oate "i con!iderat* 'robabil e"icient* +n a(eliorarea !i('to(elor 6L3 i PLM3-C, PLM3-A i e"icienei !o(nului 'e ter(en !curt 5ni4el B7. 0"ectele ad4er!e 5!edarea bl8nd* i rare di!"unc:ii re!'iratorii nocturne atunci c8nd e!te utili&at* +ndelungat7 au "o!t +n general bl8nde i re4er!ibile, 'roble(e legate de de'enden* 'ut8nd "i ob!er4ate "oarte rar. Pentru PLMD, 'ro'oxi"enul 'e ter(en !curt e!te 'robabil ine"icient +n +(bun*t*:irea calit*ii !o(nului i a PLM3-C 5ni4el B7. 2u exi!t* 'robe !u"iciente 'entru a "ace reco(and*ri re"eritoare la (or"in*, tra(adol, codein* i dihidrocodein*, tilidin* i (etadon* i de!'re o cale intratecal*
13

5ni4el B7. ,n 6L3 !ecundar ure(iei, ro'inirole e!te 'robabil e"icient 5ni4el B7. 0"ectele ad4er!e au "o!t acelea co(une tuturor agenilor do'a(inergici. 0"ectul de a('li"icare nu a "o!t bine !tudiat 'entru niciunul dintre ace!te (edica(ente i a "o!t ra'ortat* de EN din 'acien ii trata:i cu ro'inirole 5cla!a C de e4iden:*7. 2u exi!t* 'robe !u"iciente 'entru a "ace reco(and*ri re"eritoare la utili&area agoni)tilor Opioi ii -- de ra'oarte au !tudiat utili&area o'ioi&ilor 5codein* i dihidrocodein*, dextro(etor"an, oxicodon, (etadon*, (or"in*, i 'ro'oxi"en, tilidin* do'a(inergici non-ergot deri4a:i +n PLMD.

tra(adol7. Pentr 6L3 'ri(ar exi!t* do4e&i de cla!* CC >D?@ con"or( c*rora oxicodonul 'e ter(en !curt +ntr-o do&* (edie de ??,9 (g;&i a generat o +(bun*t*ire cu 5-N a !i('to(elor 6L3 con"or( !calelor !ubiecti4e. ,n ace!t !tudiu, oxicodonul a redu! (ult PLM3-C 5cu /9N7 i PLM3-A 5cu -/N7, 'e l8ng* +(bun*t*irea e"icien:ei !o(nului 5cu -5N7. 0"ectele ad4er!e

de

ad(ini!trare.

2u

exi!t*

'robe

e"icienei !o(nului !au di(inuarea PLM3-C +n !tudii de cla!* CCC ce au e4aluat e"icacitatea dextranului de "ier, ad(ini!trat intra4eno! +n do&* unic* de ?... (g >D/@, oxidului de (agne&iu ?-,9 ((oli >D9@ i a(antadinei ?../..(g;&i >D5@. Pentru 6L3 !ecundar ure(iei, exi!t* do4e&i de cla!* CC >DD@ 'entru 6L3 la a(eliorarea !i('to(elor

!u"iciente 'entru a "ace o reco(andare re"eritoare la utili&area o'ioi&ilor +n 6L3 !ecundar. $lte tratamente F- de ra'oarte au !tudiat utili&area altor trata(ente. 3ubiecte ale ace!tor !tudii "i&ici, relaxare 4ita(inele;(ineralele, i antide're!i4ele. cu +n au !ti(ulare boala "o!t de au "o!t% inter4eniile ce non'roduc hor(onii Cnter4en iile cerebral* Par in!on, a!e(enea "ar(acologice cogniti4e !au cu agen:i (edica(entele (u!cular*,

ad(ini!trarea intra4enoa!* de ?... (g de dextran de "ier< e"iciena a !c*&ut la 9 !*'t*(8ni du'* trata(ent. ,ntr-un !tudiu de cla!* CCC, tran!'lantul de rinichi a du! la di!'ari:ia !i('to(elor 6L3 'e ter(en !curt la toi cei ?? 'acieni, i la 9 din ?? 'e ter(en lung >DE@. ,n PLMD, un !tudiu de cla!* C cu e!tradiol ad(ini!trat tran!der(al !ub "or(* de gel, +n do&* de -,5g;&i 5!au 5.Qg;-9 h 'entru 'acienii cu 48r!ta 'e!te 55 ani7 nu a ar*tat nici un e"ect a!u'ra PLM3-C i PLM3-A la / luni >DF@. 3tudii de cla!* CC au ar*tat c*, +n PLMD a!ociat narcole'!iei >DI@ (oda"inilul +n do&* de -..-99. (g;&i )i o )edin:* de he(odiali&* nocturn* >E.@ au "o!t ine"iciente. ,n PLMD a!ociat in!o(niei, un !tudiu de cla!* CC ba&at 'e tera'ie cogniti4co('orta(ental* 5educaia !o(nului, controlul !ti(ulilor, re!tricia la !o(n7 nu a g*!it nici o di"eren * "a:* de
14

5e!trogeni, (elatonin*, eritro'oietin*7 chirurgicale 'ro"und* de rinichi

!clerotera'ia 4enoa!* i tran!'lantul di!'onibile. Pentru 6L3 'ri(ar, un !tudiu de cla!* CC cu ad(ini!trare de !ul"at de "ier, /-5 (g +n "or(* lichid*, 'er o!, ti(' de ?!*'t*(8ni 5+n 'aralel cu alte trata(ente7 nu a ar*tat nici un e"ect !e(ni"icati4 a!u'ra !i('to(elor 6L3 !au calit*ii !o(nului< E din -F de 'acieni au renunat i e"ecte ad4er!e rele4ante au "o!t greaa, con!ti'aia, colorarea dinilor, !caune +nchi!e la culoare, "racturi 4ertebrale i +nr*ut*irea 6L3 >D-@. ,ntr-un !tudiu de cla!* CC nu !-a ob!er4at nici un e"ect al 4ibraiilor a(eliorarea >-/@. 3-au ra'ortat 6L3, a !e4erit*ii

clona&e'a( .,5-?,5 (g;&i >-E@. Mai (ulte !tudii de cla!* CCC ba&ate 'e a'licarea unei 're!iuni 'o&iti4e na&ale continue la 'acienii PLM3-C a!cociat "ie cu a a'nee r*(a! din ob!tructi4* de !o(n au du! la re&ultate con"lictuale% ,n PLMD ne!chi(bat, "ie a cre!cut, "ie a !c*&ut. in!o(niei de're!ie, tra&odonul +n do&* de ?.. (g nu a (odi"icat calitatea !o(nului !au PLM3-C, !au di('otri4* a redu! PLM3-C cu ?.,F 5dou* !tudii de cla!* CCC 'e durata unei noa':i >E?,E-@7. ,n !tudii de cla!* CCC, 5-HG-tri'to"anul +n do&* de 5.. (g nu a (odi"icat PLM3C;PLM3-A >E/@, +n ti(' ce a'o(or"ina, +n do&* unic* de .,5 (g ad(ini!trat* "ie !ubcutanat "ie tran!der(ic >E9,E5@ i exerciiile "i&ice la 'acienii cu PLMD cu le&iuni !'inale co('lete >ED-EF@ au redu! PLM3-C. ,ecomandri ,n 6L3 'ri(ar, at8t !ul"atul de "ier c8t i 4ibraiile !unt 'robabil ine"iciente 5ni4el B7. 2u exi!t* do4e&i !u"iciente 'entru a "ace reco(and*ri re"eritoare la ad(ini!trarea dextranului de "ier intra4eno!, oxidului de (agne&iu i a(antadinei. ,n 6L3 !ecundar ure(iei, dextranul de "ier, ?... (g +n do&* unic* +ntra4enoa!*, e!te 'robabil e"icient 'e ter(en !curt 5R ? lun*7 5ni4el B7. ,n PLMD, !-a !tabilit c* e!tradiolul tran!der(al e!te ine"icient
15

5ni4el A7 iar (oda"inilul i o )edin:* de he(odiali&* nocturn* !unt 'robabil ine"iciente, +n ti(' ce tera'ia cogniti4co('orta(ental* nu e!te di"erit* "a:* de clona&e'a( 5ni4el B7. 5-HGtri'to"anul i tra&odona !unt 'o!ibil ine"iciente iar a'o(or"ina i exerciiul "i&ic 5+n (ielo'atie7 !unt e"iciente 5ni4el C7. 'o!ibil

&iscuii ,nainte de a "urni&a co(entariile "inale, dori( !* !ublinie( "a'tul c* agen ii do'a(inergici !unt la (o(entul actual cele (ai bine !tudiate (edica(ente datorit* intere!ului cre!cut al co('aniilor "ar(aceutice de a ob:ine indicaii o"iciale de trata(ent +n 6L3. #otui, cu( !-a e"ectuat nu(ai un nu(*r (ic de !tudii de!'re co('u)ii non-do'a(inergici, iar unele au ar*tat e"ecte !'er*( tera'eutice c* at8t 'ro(i*toare, c8t i indu!tia

cercet*torii 4or "ace e"orturi 'entru a de&4olta noi alternati4e de trata(ent. ,n ace!t !en!, li'!a !tudiilor controlate 'entru (ulte cla!e de (edica(ente nu trebuie do4e&i 'ri4it* ca generatoare de de negati4e ine"icien*.

Punctele !labe cel (ai de! ob!er4ate ale !u!-(enionatelor !tudii controlate !unt de"ecte ale 'rocedurilor de rando(i&are, ab!ena obiecti4ului

'ri(ar (*!ur*

'rede"init, a

"olo!irea

'e!te 'ri(are

nu(ai 'entru utili&are de !curt* durat* '8n* acu( 5ni4el A7. Dintre (edica(entele +n 6L3 'ri(ar 5ni4el A7. Alte do'a(inergice i 5'ra(i'exol, 4al'roatul, bro(ocri'tin*7 antie'ile'tice,

obiecti4elor

ne4alidate !au !urogate +n loc de obiecti4e rele4ante clinic )i orientate c*tre 'acient 5ex. rata re(i!iunii, calitatea 4ieii7. A!t"el de 'roble(e !unt co(une +n general, dar nu nu(ai, 'entru !tudiile anterioare anului -.... 6ecent 4alidatele !cale interna:ionale ale !e4erit*:ii bolii )i ale calit*:ii 4ie:ii +n ca&uri !'eci"ice de boal* >D,E@ 4or re're&enta in!tru(ente 4aloroa!e 'entru a 'roiecta noi !tudii cu obiecti4e 'ri(are rele4ante clinic. Mai (ult, e"ectul de a('li"icare nu a "o!t e4aluat adec4at +n ca&ul (ultor (edica(ente 5at8t do'a(inergice c8t i nondo'a(inergice7 i !e !'er* c*, cu c8t (ai !'eci"ice i (ai de +ncredere !unt in!tru(entele +n cur! de de&4oltare, cu at8t (ai (ult ele 4or 'er(ite o e4aluare (ai bun* at8t al e"icacit*:ii 'e ter(en lung i c8t i a('li"icare. Recomandri Pentru 6L3 'ri(ar, ro'inirol-ul ad(ini!trat +n do&e (edii de ?,5-9,D (g;&i i 'ergolidul ad(ini!trat +n do&e de .,9-.,55 (g;&i au ni4el A con"ir(at de e"icien* +n atenuarea 'are!te&iilor i nelinitii i (otorii. rotigotina !unt e"iciente, Cabergolina, ad(ini!trat* de dou*
16

gaba'entinul trebuie con!iderat e"icient

carba(a&e'ina, clonidina i oxicodonul !unt con!iderate a "i 'robabil e"iciente 5ni4el B7, +n ti(' ce clona&e'a(ul e!te 'robabil e"icient 5atunci c8nd e!te ad(ini!trat +n do&* de ? (g la culcare7 i 'robabil ine"icient 5atunci c8nd e!te ad(ini!trat +n 9 do&e;&i7, +n "uncie de orarul de do&elor 5ni4el B7. 3ul"atul de "ier i 4ibraiile !unt 'robabil ine"iciente 5ni4el B7. Pe ter(en lung, le4odo'a e!te 'o!ibil e"icient* 5ni4el C7. Pentru le4odo'a, 6L3 !ecundar ?,95 -..-/.. ure(iei, (g;&i, i (g;&i ro'inirol-ul

gaba'entinul

dextranul de "ier ?... (g i.4. !unt 'obabil e"iciente, ulti(ul atunci c8nd e!te utili&at 'e ter(en !curt 5ni4el B7. Pentru PLMD, e!tradiolul tran!der(ic e!te inei"icient 5ni4el A7. Clona&e'a(ul i le4odo'a !unt 'robabil e"iciente +n ti(' ce 'ro'oxi"enul, tria&ola(ul, (oda"inilul i he(odiali&* de o noa'te !unt 'robabil ine"iciente 5ni4el B7. Bro(ocri'tina e!te 'robabil e"icient* +n PLMD a!ociat narcole'!iei 5ni4el B7. 5HG-tri'to"anul i tra&odona !unt 'o!ibil

al e"ectului de

le4odo'a a!e(enea

tran!der(al

con!iderate ulti(ele

ine"iciente iar a'o(or"ina i exerciiul "i&ic 'o!ibil e"iciente 5ni4el C7. ,n "iind ce 'ri4ete bl8nde i e"ectele ad4er!e, la +n ale ace!tea au "o!t ra'ortate +n general ca re4er!ibile ,n +ntreru'erea (aBoritatea e"ectele uurin:* trata(entului !tudiilor. 'eri"erice

do'a(inergici ar trebui !* "ie e4alua:i clinic cardiologic la inter4ale de /-D luni )i dac* exi!t* 4reo !u!'iciune trebuie e4alua:i "ibro&a ecocardiogra"ic. cardio'ul(onar*, ca #otui, e"ect

!ecundar al deri4atelor ergot a "o!t de!cri!* 'rea recent 'entru a 'utea "i anali&at* rele4ant, +n "uncie de di"eri:ii co('u)i. Co('araia di"erene 'robe agenii reco(andai ghidurilor de ,n de contradictorii raiona(ent, ghidurile, !unt 'entru deBa 'ublicate >EI-F?@ de(on!trea&* (inore 'arial legate de di"eritele !eturi de utili&ate. toate elec:ie do'a(inergici

'articular,

!ecundare de

do'a(inergicelor au "o!t atenuate cu do('eridon. Pentru acea!t* cla!* de (edica(ente, e"ectul de a('li"icare re're&int* un e"ect ad4er! !u'*r*tor< dei e!te ra'ortat +n !'ecial la le4odo'a, e!te greu de obinut date co('arati4e de +ncredere, (ai ale! +n a!b!ena unei !cale de a('li"icare. 6ecent, intere!ul 'entru deri4a:ii gra4e de ergota(in* a cre!cut i datorit* de!co'eririi (ai (ultor de"ecte cardiace (ulti4al4ulare i 'ericarditei +n Boala con!tricti4e Par in!on "ibro&ei la

trata(entul 6L3. H'ioi&ii au o indica:ie +nc* di!cutabil* +n 're&entul docu(ent, iar 'entru !u'li(entele cu "ier a( g*!it nu(ai !tudii "a4orabile de cla!* CC 5'e ter(en !curt7 !au chiar do4e&i de ine"icien*. 1ierul a "o!t (ai e"icient la 'aciene cu de"icit de "ier. Din ne"ericire, !unt di!'onibile doar do4e&i 'ariale 'entru 6L3 !ecundar, a'roa'e toate "iind legate de 6L3 !ecundar ure(iei i de PLMD. 2u 'ot "i "*cute reco(and*ri 'entru 6L3 +n ti('ul !arcinii !au la co'ii, unde !unt nece!are !tudii de calitate. ,n !"8rit, e!te util !* !ublinie( "a'tul c* ace!te indicaii ca nu trebuie toate con!iderate
17

'leuro'ul(onare du'* u&ul +ndelungat 5ra'ortate cabergolin*, 'ergolid i bro(ocri'tin*7. Do&ele &ilnice +n ace!te ca&uri au "o!t egale !au (ai (ari de 9 (g 'entru 'ergolid 'entru (ai (ulte luni. 6egre!ia !'ontan* ecocardiogra"ic* a in!u"icienei 4al4ulare, +('reun* cu +(bun*t*irea (arcat* clinic*, !-a ra'ortat du'* o'rirea deri4atelor ergot +n anu(ite ca&uri. 3-a !ugerat c* do&ele (ari ar trebui e4itate i c* 'acienii trata:i cu agoni)ti

e'ui&8nd

(etodele de trata(ent al 6L3 !au

PLMD. ,n "unc:ie de 'articularit*:ile "iec*rui r*(8ne 'acient, raiona(ent a "inal re"eritor la ti'ul de +ngriBire nece!ar* +ntotdeauna latitudinea (edicului curant. Recomandri (inale de nivel $ Pentru 6L3 'ri(ar% 6L3. Gaba'entinul 5do&* F..?F..(g;&i7 reduce !corurile 6L3 i +(bun*t*:e)te PLM3-C. (edie Le4odo'a;ben!era&ida ?5I;9. (g 5do&* la ad(ini!trat* e"iciena !o(nului i Cabergolina 5.,5--(g o dat* 'e &i7 aBut* la +(bun*t*irea !corurilor

Pentru PLMD% 0!tradiolul ad(ini!trat tran!der(ic e!te ine"icient. Con(licte de interese Dr. Billiard a bene"iciat de o educaie (edical* continu* din 'artea Glaxo3(ithKline. Dr. Clarenbach a "o!t i('licat +ntr-un !tudiu cu 3ch$ar& Phar(a iar Dr. Montagna +n !tudii cu Glaxo3(ithKline, 3ch$ar& Phar(a i a 'ri(it onorarii de con!ultant din 'artea Boehringer-Cngelhei(. Dr. #ren $alder a 'ri(it grant-uri; !u'ort de cercetare din 'artea con!ultant Cngelhei(, di!cur!urile educationale Glaxo3(ithKline, e!te 'entru Boehringeri Glaxo3(ithKline la din

2o4arti!, i a 'ri(it onorariu 'entru !i('o&ioanele 'artea

culcare7 a(eliorea&* !i('to(ele 6L3, calitatea !o(nului, latena ace!tuia, PLM3-C i calitatea 4ieii. (g;&i7 Pergolidul 5do&e (edii .,9-.,55 e!te e"icient i +n +n reducerea a(eliorarea 6L3

Glaxo3(ithKline, Go""(an La 6oche i P"i&er. Dr. Garcia-Borreguero a 'ri(it grant-uri de cercetare din 'artea P"i&er i e!te con!ultant 'entru P"i&er, Glaxo3(ithKline, 3ch$ar& Phar(a i Boehringer-Cngelhei(. Mulumiri Dori( !* (ulu(i( 'entru aButorul doa(nei A. La""i +n tehnoredactarea (anu!cri!ului i doa(nei 3. Mu&&i 'entru aButorul cu bibliogra"ia. 3u!inut de MP63#, D.N grant. Material suplimentar

!e4erit*ii

!ubiecti4* a calit*ii !o(nului. 6o'inirole 5do&e (edii ?,5-9,D (g;&i7 e!te e"icient +n a(eliorarea !corurilor !calare 6L3, a calit*ii 4ieii, )i +n +(bun*t*:irea latenei !o(nului i a PLM3-C;PLM3-A. (g7 6otigotine, i "olo!it* 'e ad(ini!trar* ter(en !curt tran!der(ic !ub "or(* de 'atch 59,5 a(eliorea&* !i('to(ele 6L3.
18

Pr(*torul (aterial !u'li(entar 'oate "i g*!it la% htt'%;;$$$.blac $ell!ynergy.co(;toc;e ne;?/;?. #abel 3?% 3trategia de cercetare 'entru identi"icarea !tudiilor. #abel 3-% 3tudii de Cla!* C, CC i CCC #abel 3/% 3tudii de Cla!* CV. "ibliogra(ie ?. =illi! #. #he London Practice o" Phy!ice, London%#ho(a! ?!t Ba!!ett edn. and

=illia( Croo e, ?DF5% 9.9. -. 0 bo( KA. 6e!tle!! leg!. Acta Medica 3candina4ica ?I95< ?5F% 5S?-/. /. A(erican Medicine. (o4e(ent Cnternational Coding Acade(y 9. =alter! A3. Acade(y o" 3lee' li(b di!order. Cla!!i"ication Manual, o" #o$ard #he a o" -nd 3lee' better Periodic

3lee' Di!order!. Diagno!tic and edn.=e!tche!ter, CL% A(erican Medicine,-..5% ?F-S?FD. de"inition o" the re!tle!! leg! !yndro(e. Grou'. Cnternational Di!order! 6e!tle!! Leg! 3yndro(e 3tudy Mo4e(ent ?II5< ?.% D/9SD9-.

5. Allen 6P, Picchietti D, Gening =A, #ren $alder C, =alter! A3, Mont'lai!ir T. 6e!tle!! leg! !yndro(e% diagno!tic criteria, !'ecial con!ideration!, and e'ide(iology. A re'ort "ro( the re!tle!! leg! !yndro(e diagno!i! and e'ide(iology $or !ho' at the 2ational Cn!titute! o" Gealth. 3lee' Medicine -../< 9% ?.?S??I. D. =alter! A3, LeBrocU C, Dhar A, et al. Cnternational 6e!tle!! Leg! 3yndro(e 3tudy Grou'. Validation o" the Cnternational 6e!tle!! Leg! 3yndro(e 3tudy Grou' rating !cale "or re!tle!! leg! !yndro(e. 3lee' Medicine -../< 9% ?-?S?/-. E. At in!on MT, Allen 6P, Du Chane T, Murray C, Ku!hida C, 6oth #. 6L3 Vuality o" Li"e Con!ortiu(. Validation o" the 6e!tle!! Leg! 3yndro(e Vuality o" Li"e Cn!tru(ent 56L3-VLC7% "inding! o" a con!ortiu( o" national ex'ert! and the 6L3 1oundation. Vuality Li"e 6e!earch -..9< ?/% DEISDI/. F. A(erican Acade(y o" 3lee' Medicine. 6e!tle!! leg! !yndro(e. Cnternational Cla!!i"ication o" 3lee' Di!order!. Diagno!tic and Coding Manual, -nd edn. =e!tche!ter, CL% A(erican Acade(y o" 3lee' Medicine, -..5% ?EFS?F?. I. Brai nin M, Barne! M, Baron TC, et al. Guidance "or the 're'aration o" neurological (anage(ent guideline! by 0123 !cienti"ic ta! "orce! S re4i!ed reco((endation! -..9. 0uro'ean Tournal o" 2eurology -..9< ??% 5EES5F?. ?.. =agner ML, =alter! A3, Cole(an 6G, Gening =A, Gra!ing K, Cho ro4erty 3. 6ando(i&ed, doubleblind, 'lacebo-controlled !tudy o" clonidine in re!tle!! leg! !yndro(e. 3lee' ?IID< ?I% 5-S5F. ??. Cnoue W, Mitani G, 2anba K, Ka$ahara 6. #reat(ent o" 'eriodic leg
19

(o4e(ent di!order and re!tle!! leg !yndro(e $ith tali'exole. P!ychiatry and Clinical 2euro!cience! ?III< 5/% -F/S-F5. ?-. Au!!er$in ler M, 3ch(idt P. 0r"olgreiche Behandlung de! re!tle!! leg!-3yndro(! bei chroni!cher 2ierenin!u""i&ien& (it Clonidin. 3ch$ei&eri!che Medi&ini!che =ochen!chri"t. Tournal 3ui!!e de Medecine ?IFI< ??I%?F9S?FD. ?/. #el!tad =, 3oren!en H, Lar!en 3, Lille4old P0, 3ten!rud P, Gan!en 6. #reat(ent o" the re!tle!! leg! !yndro(e $ith carba(a&e'ine% a double blind !tudy. Briti!h Medical Tournal 5Clinical 6e!earch 0dition7 ?IF9< -FF% 999S99D. ?9. Lund4all H, Abo( P0, Gol( 6. Carba(a&e'ine in re!tle!! leg!. A controlled 'ilot !tudy. 0uro'ean Tournal o" Clinical Phar(acology ?IF/< -5% /-/S/-9. ?5. Garcia-Borreguero D, Larro!a H, de la Lla4e W, Verger K, Ma!ra(on X, Gernande& G. #reat(ent o" re!tle!! leg! !yndro(e $ith gaba'entin% a double-blind, cro!!o4er !tudy. 2eurology -..-< 5I% ?5E/S?5EI. ?D. Mellic GA, Mellic LB. Manage(ent o" re!tle!! leg! !yndro(e $ith gaba'entin 52eurontin7. 3lee' ?IID< ?I%--9S--D. ?E. Ga''e 3, Klo!ch G, 3aletu B, Yeitlho"er T. #reat(ent o" idio'athic re!tle!! leg! !yndro(e 56L37 $ith gaba'entin. 2eurology -..?< 5E% ?E?ES?E?I. ?F. Ga''e 3, 3auter C, Klo!ch G, 3aletu B, Yeitlho"er T. Gaba'entin 4er!u! ro'inirole in the treat(ent o" idio'athic re!tle!! leg! !yndro(e. 2euro'!ychobiology -../< 9F% F-SFD. ?I. Adler CG. #reat(ent o" re!tle!! leg! !yndro(e $ith gaba'entin. Clinical 2euro'har(acology ?IIE< -.% ?9FS?5?. -.. 0i!en!ehr C, 0hrenberg BL, 6ogge3olti 3, 2oachtar 3. #reat(ent o" idio'athic re!tle!! leg! !yndro(e
20

56L37 $ith !lo$-relea!e 4al'roic acid co('ared $ith !lo$-relea!e le4odo'a;ben!era&id. Tournal o" 2eurology -..9< -5?% 5EIS5F/. -?. #hor' ML, Morri! CD, Bagby 3P. A cro!!o4er !tudy o" gaba'entin in treat(ent o" re!tle!! leg! !yndro(e a(ong hae(odialy!i! 'atient!. A(erican Tournal o" Kidney Di!ea!e! -..?< /F% ?.9S?.F. --. 1reye 0, Le4y TV, Partec e L. P!e o" gaba'entin "or attenuation o" !y('to(! "ollo$ing ra'id o'iate detoxi"ication 56HD7 S correlation $ith neuro'hy!iological 'ara(eter!. 2euro'hy!iologie CliniUue -..9< /9% F?SFI. -/. Montagna P, 3a!!oli-de-Bianchi L, Yucconi M, Cirignotta 1, Lugare!i 0. Clona&e'a( and 4ibration in re!tle!! leg! !yndro(e. Acta 2eurologica 3candina4ica ?IF9< DI%9-FS9/.. -9. Boghen D, La(othe L, 0lie 6, Godbout 6, Mont'lai!ir T. #he treat(ent o" the re!tle!! leg! !yndro(e $ith clona&e'a(% a 'ro!'ecti4e controlled !tudy. Canadian Tournal o" 2eurological 3cience! ?IFD< ?/% -95S-9E. -5. 3aletu M, Anderer P, 3aletuYyhlar& G, et al. 6e!tle!! leg! !yndro(e 56L37 and 'eriodic li(b (o4e(ent di!order 5PLMD7% acute 'lacebo-controlled !lee' laboratory !tudie! $ith clona&e'a(. 0uro'ean 2euro'!ycho'har(acology -..?a< ??% ?5/S?D?. -D. Mitler MM, Bro$(an CP, Menn 3T, GuBa4arty K, #i((! 6M. 2octurnal (yoclonu!% treat(ent e""icacy o" clona&e'a( and te(a&e'a(. 3lee' ?IFD< I% /F5S/I-. -E. 0dinger TD, 1in! AC, 3ulli4an 6T, Mar!h G6, Dailey D3, Woung M. Co('ari!on o" cogniti4e-beha4ioral thera'y and clona&e'a( "or treating 'eriodic li(b (o4e(ent di!order. 3lee' ?IID< ?I% 99-S999. -F. Hhanna 2, Peled 6, 6ubin AG, Yo(er T, La4ie P.

Periodic leg (o4e(ent! in !lee'% e""ect o" clona&e'a( treat(ent. 2eurology ?IF5< /5% 9.FS9??. -I. Peled 6, La4ie P. Double-blind e4aluation o" clona&e'a( on 'eriodic leg (o4e(ent! in !lee'. Tournal o" 2eurology, 2euro!urgery, and P!ychiatry ?IFE< 5.% ?DEIS?DF?. /.. Cna(i W, Goriguchi T, 2i!hi(at!u H, et al. A 'oly!o(nogra'hic !tudy on 'eriodic li(b (o4e(ent! in 'atient! $ith re!tle!! leg! !yndro(e and neurole'tic-induced a athi!ia. Giro!hi(a Tournal o" Medical 3cience! ?IIE< 9D% ?//S?9?. /?. Aren! 6, =right B, 0lliott T, et al. Periodic li(b (o4e(ent in !lee' in children $ith =illia(! !yndro(e. Tournal o" Pediatric! ?IIF< ?//% DE.S DE9. /-. Doghra(Bi K, Bro$(an CP, Gaddy T6, =al!h TK. #ria&ola( di(ini!he! dayti(e !lee'ine!! and !lee' "rag(entation in 'atient! $ith 'eriodic leg (o4e(ent! in !lee'. Tournal o" Clinical P!ycho'har(acology ?II?< ??% -F9S -I.. //. Bonnet MG, Arand DL. Chronic u!e o" tria&ola( in 'atient! $ith 'eriodic leg (o4e(ent!, "rag(ented !lee' and dayti(e !lee'ine!!. Aging ?II?< /% /?/S/-9. /9. Moldo"! y G, #ulli! C, Vuance G, Lue 1A. 2itra&e'a( "or 'eriodic (o4e(ent! in !lee' 5!lee'-related (yoclonu!7. Canadian Tournal o" 2eurological 3cience! ?IFD<?/% 5-S59. /5. Bene! G, Kurella B, Ku((er T, Ka&en$adel T, 3el&er 6, Kohnen 6. 6a'id on!et o" action o" le4odo'a in re!tle!! leg! !yndro(e% a double-blind, rando(i&ed, (ulticenter, cro!!o4er trial. 3lee' ?III< --% ?.E/S?.F?. /D. A 'inar 3. 6e!tle!! leg! !yndro(e treat(ent $ith do'a(inergic drug!. Clinical 2euro'har(acology ?IFE< ?.%DISEI. /E. Brodeur C, Mont'lai!ir T, Godbout 6, Marinier 6. #reat(ent o" re!tle!!
21

leg! !yndro(e and 'eriodic (o4e(ent! during !lee' $ith L-do'a% a double-blind, controlled !tudy. 2eurology ?IFF< /F% ?F95S?F9F. /F. #ren $alder C, 3tia!ny K, Poll(acher #, et al. L-do'a thera'y o" ure(ic and idio'athic re!tle!! leg! !yndro(e%a double-blind, cro!!o4er trial. 3lee' ?II5< ?F% DF?SDFF. /I. Mont'lai!ir T, Boucher 3, Go!!elin A, Poirier G, La4igne G. Per!i!tence o" re'etiti4e 00G arou!al! 5K-al'ha co('lexe!7 in 6L3 'atient! treated $ith L-DHPA. 3lee' ?IID< ?I% ?IDS ?II. 9.. Collado-3eidel V, Ka&en$adel T, =etter #C, et al. A controlled !tudy o" additional !r-L-do'a in Ldo'are!'on!i4e re!tle!! leg! !yndro(e $ith late-night !y('to(!. 2eurology ?III< 5-% -F5S-I.. 9?. 3aletu M, Anderer P, Gogl B, et al. Acute double-blind, 'lacebo-controlled !lee' laboratory and clinical "ollo$u' !tudie! $ith a co(bination treat(ent o" rr-L-do'a and !r-L-do'a in re!tle!! leg! !yndro(e. Tournal o" 2eural #ran!(i!!ion -../< ??.% D??SD-D. 9-. =al er 3L, 1ine A, Kryger MG. LDHPA;carbido'a "or nocturnal (o4e(ent di!order! in ure(ia. 3lee' ?IID< ?I%-?9S-?F. 9/. Ka'lan P=, Allen 6P, Buchhol& D=, =alter! TK. A double-blind, 'lacebo-controlled !tudy o" the treat(ent o" 'eriodic li(b (o4e(ent! in !lee' u!ing carbido'a;le4odo'a and 'ro'oxy'hene. 3lee' ?II/< ?D% E?ES E-/. 99. Boi4in DB, Mont'lai!ir T, Poirier G. #he e""ect! o" Ldo'a on 'eriodic leg (o4e(ent! and !lee' organi&ation in narcole'!y. Clinical 2euro'har(acology ?IFI< ?-%//IS /95. 95. de Mello M#, Poyare! DL, #u"i 3. #reat(ent o" 'eriodic leg (o4e(ent! $ith a do'a(inergic agoni!t in !ubBect! $ith total !'inal cord le!ion!. 3'inal Cord ?III< /E% D/9SD/E.

9D. #ergau 1, =i!cher 3, =ol" C, Paulu! =. #reat(ent o" re!tle!! leg! !yndro(e $ith the do'a(ine agoni!t al'hadihydroergocry'tine. Mo4e(ent Di!order! -..?< ?D% E/?SE/5. 9E. =alter! A3, Gening =A, Ka4ey 2, Cho ro4erty 3, Gidro-1ran 3. A double-blind rando(i&ed cro!!o4er trial o" bro(ocri'tine and 'lacebo in re!tle!! leg! !yndro(e. Annal! o" 2eurology ?IFF< -9% 955S95F. 9F. 3tia!ny-Kol!ter K, Bene! G, Peglau C, et al. 0""ecti4e cabergoline treat(ent in idio'athic re!tle!! leg! !yndro(e. 2eurology -..9< D/% --E-S--EI. 9I. Bene! G, Geinrich C6, Peberall MA, Kohnen 6. Longter( !a"ety and e""icacy o" cabergoline "or the treat(ent o" idio'athic re!tle!! leg! !yndro(e% re!ult! "ro( an o'en-label D-(onth clinical trial. 3lee' -..9< -E% DE9SDF-. 5.. #ren $alder C, Gunde(er GP, Lledo A, et al. 0""icacy o" 'ergolide in treat(ent o" re!tle!! leg! !yndro(e% #he P0A6L3 3tudy. 2eurology -..9< D-% ?/I?S?/IE. 5?. 3taedt T, =a!!(uth 1, Yie(ann P, GaBa G, 6uther 0, 3to''e G. Pergolide% treat(ent o" choice in re!tle!! leg! !yndro(e 56L37 and nocturnal (yoclonu! !yndro(e 52M37. A double-blind rando(i&ed cro!!o4er trial o" 'ergolide 4er!u! L-Do'a. Tournal o" 2eural #ran!(i!!ion ?IIE< ?.9% 9D?S9DF. 5-. Pieta T, Millar #, Yacharia! T, 1ine A, Kryger M. 0""ect o" 'ergolide on re!tle!! leg! and leg (o4e(ent! in !lee' in ure(ic 'atient!. 3lee' ?IIF< -?% D?ESD--. 5/. Boi4in DB, Lorrain D, Mont'lai!ir T. 0""ect! o" bro(ocri'tine on 'eriodic li(b (o4e(ent! in hu(an narcole'!y. 2eurology ?II/< 9/% -?/9S-?/D. 59. #ren $alder C, Garcia-Borreguero D, Montagna P, et al. 6o'inirole in the treat(ent o" re!tle!! leg! !yndro(e%re!ult! "ro( the #60A# 6L3
22

? !tudy, a ?- $ee , rando(i!ed, 'lacebo controlled !tudy in ?. 0uro'ean countrie!. Tournal o" 2eurology, 2euro!urgery and P!ychiatry -..9a< E5% I-SIE. 55. =alter! A3, Hndo =, Drey lu"t #, Grun!tein 6, Lee D, 3ethi K, #60A# 6L3 - 3tudy Grou'. 6o'inirole i! e""ecti4e in the treat(ent o" re!tle!! leg! !yndro(e. #60A# 6L3 -% a ?-$ee , double-blind, rando(i&ed, 'arallel-grou', 'lacebo-controlled !tudy. Mo4e(ent Di!order! -..9< ?I% ?9?9S?9-/. 5D. Adler CG, Gau!er 6A, 3ethi K, et al. 6o'inirole "or re!tle!! leg! !yndro(e% a 'lacebo-controlled cro!!o4er trial. 2eurology -..9< D-% ?9.5S?9.E. 5E. Allen 6, Bec er PM, Bogan 6, et al. 6o'inirole decrea!e! 'eriodic leg (o4e(ent! and i('ro4e! !lee' 'ara(eter! in 'atient! $ith re!tle!! leg! !yndro(e. 3lee' -..9< -E% I.ESI?9. 5F. Mont'lai!ir T, 2icola! A, Dene!le 6, Go(e&-Mancilla B. 6e!tle!! leg! !yndro(e i('ro4ed by 'ra(i'exole% a double-blind rando(i&ed trial. 2eurology ?III< 5-% I/FS I9/. 5I. 3tia!ny-Kol!ter K, Kohen 6, 3choll(ayer 0, Moller TC, Hertel =G, 6otigotine 3' DDD 3tudy Grou'. Patch a''lication o" the do'a(ine agoni!t rotigotine to 'atient! $ith (oderate to ad4anced !tage! o" re!tle!! leg! !yndro(e% a double-blind, 'lacebocontrolled 'ilot !tudy. Mo4e(ent Di!order! -..9< ?I% ?9/-S?9/F. D.. Pellecchia M#, Vitale C, 3abatini M, et al. 6o'inirole a! a treat(ent o" re!tle!! leg! !yndro(e in 'atient! on chronic he(odialy!i!% an o'en rando(i&ed cro!!o4er trial 4er!u! le4odo'a !u!tained relea!e. Clinical 2euro'har(acology -..9< -E% ?EFS ?F?. D?. =alter! A3, =agner ML, Gening =A, et al. 3ucce!!"ul treat(ent o" the idio'athic re!tle!! leg! !yndro(e in a

rando(i&ed double-blind trial o" oxycodone 4er!u! 'lacebo. 3lee' ?II/< ?D% /-ES//-. D-. Da4i! BT, 6aB'ut A, 6aB'ut ML, Aul 0A, 0ichhorn G6. A rando(i&ed, double-blind 'lacebo-controlled trial o" iron in re!tle!! leg! !yndro(e. 0uro'ean 2eurology -...< 9/% E.SE5. D/. 0arley CT, Gec ler D, Allen 6P. #he treat(ent o" re!tle!! leg! !yndro(e $ith intra4enou! iron dextran. 3lee' Medicine -..9< 5% -/?S -/5. D9. Gornya M, Voderhol&er P, Gohagen 1, Berger M, 6ie(ann D. Magne!iu( thera'y "or 'eriodic leg (o4e(ent!-related in!o(nia and re!tle!! leg! !yndro(e% an o'en 'ilot !tudy. 3lee' ?IIF< -?% 5.?S5.5. D5. 04idente VG, Adler CG, Ca4ine!! T2, Gent& TG, G$inn-Gardy K. A(antadine i! bene"icial in re!tle!! leg! !yndro(e. Mo4e(ent Di!order! -...< ?5% /-9S /-E. DD. 3loand TA, 3helly MA, 1eigin A, Bern!tein P, Mon 6D. A double-blind, 'lacebo-controlled trial o" intra4enou! iron dextran thera'y in 'atient! $ith 036D and re!tle!! leg !yndro(e. A(erican Tournal o" Kidney Di!ea!e! -..9< 9/% DD/SDE.. DE. =in el(ann T, 3tautner A, 3a(tleben =, #ren $alder C. Longter( cour!e o" re!tle!! leg! !yndro(e in dialy!i! 'atient! a"ter idney tran!'lantation. Mo4e(ent Di!order! -..-< ?E% ?.E-S?.ED. DF. Polo-Kantola P, 6auhala 0, 0r ola 6, CrBala K, Polo H. 0!trogen re'lace(ent thera'y and nocturnal 'eriodic li(b (o4e(ent!% a rando(i&ed controlled trial. Hb!tetric! and Gynecology -..?< IE% 59FS559. DI. Broughton 6T, 1le(ing TA0, George C1P, et al. 6ando(i&ed, double-blind, 'lacebocontrolled cro!!o4er trial o" (oda"inil in the treat(ent o" exce!!i4e dayti(e
23

!lee'ine!! in narcole'!y. 2eurology ?IIE< 9I% 999S95?. E.. Ganly PT, Gabor TW, Chan C, Pierrato! A. Dayti(e !lee'ine!! in 'atient! $ith C61% i('act o" nocturnal he(odialy!i!. A(erican Tournal o" Kidney Di!ea!e! -../< 9?% 9./S9?.. E?. 3aletu-Yyhlar& GM, Abu-Ba r MG, Anderer P, et al. Cn!o(nia related to dy!thy(ia% 'oly!o(nogra'hic and '!ycho(etric% co('ari!on $ith nor(al control! and acute thera'eutic trial! $ith tra&odone. 2euro'!ychobiology -..?< 99% ?/IS?9I. E-. 3aletu-Yyhlar& GM, Abu-Ba r MG, Anderer P, et al. Cn!o(nia in de're!!ion% di""erence! in obBecti4e and !ubBecti4e !lee' and a$a ening Uuality to nor(al control! and acute e""ect! o" tra&odone. Progre!! in 2euro-P!ycho'har(acology and Biological P!ychiatry -..-< -D%-9IS -D.. E/. Guille(inault C, Mondini 3, Mont'lai!ir T, Mancu!o T, Coba! o D, De(ent =C. Periodic leg (o4e(ent, Ldo'a, 5-hydroxytry'to'han, and Ltry'to'han. 3lee' ?IFE< ?.% /I/S/IE. E9. Priano L, Albani G, Brio!chi A, et al. 2octurnal ano(alou! (o4e(ent reduction and !lee' (icro!tructure analy!i! in 'ar in!onian 'atient! during ?-night tran!der(al a'o(or'hine treat(ent. 2eurological 3cience! -../< -9% -.ES-.F. E5. Gaba-6ubio T, 3taner L, Cornette 1, et al. Acute lo$ !ingle do!e o" a'o(or'hine reduce! 'eriodic li(b (o4e(ent! but ha! no !igni"icant e""ect on !lee' arou!al!% a 'reli(inary re'ort. 2euro'hy!iologie CliniUue -../< //% ?F.S?F9. ED. de Mello M#, Lauro 1AA, 3il4a AC, #u"i 3. Cncidence o" 'eriodic leg (o4e(ent! and o" the re!tle!! leg! !yndro(e during !lee' "ollo$ing acute 'hy!ical acti4ity in !'inal cord inBury !ubBect!. 3'inal Cord ?IID< /9% -I9S -ID.

EE. de Mello M#, 3il4a AC, 6ueda AD, Poyare! D, #u"i 3. Correlation bet$een K co('lex, 'eriodic leg (o4e(ent! 5PLM7, and (yoclonu! during !lee' in 'ara'legic adult! be"ore and a"ter an acute 'hy!ical acti4ity. 3'inal Cord ?IIE< /5% -9FS -5-. EF. de Mello M#, 3il4a AC, 0!te4e! AM, #u"i 3. 6eduction o" 'eriodic leg (o4e(ent in indi4idual! $ith 'ara'legia "ollo$ing aerobic 'hy!ical exerci!e. 3'inal Cord -..-< 9.%D9DS D9I. EI. Che!!on AL, Tr, =i!e M, Da4ila D, et al. Practice 'ara(eter! "or the treat(ent o" re!tle!! leg! !yndro(e and 'eriodic li(b (o4e(ent di!order. An A(erican Acade(y o" 3lee' Medicine 6e'ort. 3tandard! o" Practice Co((ittee o" the A(erican Acade(y o" 3lee' Medicine. 3lee' ?III< --% ID?SIIF. F.. Gening =A, Allen 6, 0arley C, Ku!hida C, Picchietti D, 3ilber M. #he treat(ent o" re!tle!! leg! !yndro(e and 'eriodic li(b (o4e(ent di!order. An A(erican Acade(y o" 3lee' Medicine 6e4ie$. 3lee' ?III< --% IE.SIII. F?. Gening =A, Allen 6P, 0arley CT, Picchietti DL, 3ilber MG. An u'date on the do'a(inergic treat(ent o" re!tle!! leg! !yndro(e and 'eriodic li(b (o4e(ent di!order. 3lee' -..9< -E% 5D.S5F/. F-. Garcia-Borreguero D, Larro!a H, Verger K, Ma!ra(on X, Gernande& G. 0""ect! o" gaba'entin on re!tle!! leg! !yndro(e acco('anied by nocturnal 'ain% re!ult! o" a double-blind, cro!!o4er !tudy $ith 'oly!o(nogra'hic control in -9 'atient!. 0uro'ean Tournal o" 2eurology -..-< I% 9IS5.. F/. Lar!en 3, #el!tad =, 3oren!en H, #ho( 0, 3ten!rud P, 2yberg-Gan!en 6. Carba(a&e'ine thera'y in re!tle!! leg!. Di!cri(ination bet$een re!'onder! and nonre!'onder!. Acta
24

Medica 3candina4ica ?IF5< -?F% --/S --E. F9. Yucconi M, Coccagna G, Petronelli 6, Gerardi 6, Mondini 3, Cirignotta 1. 2octurnal (yoclonu! in re!tle!! leg! !yndro(e e""ect o" carba(a&e'ine treat(ent. 1unctional 2eurology ?IFI< 9% -D/S -E?. F5. Pere&-Bra4o A. Ptilidad del to'ira(ato en el trata(iento del !indro(e de 'ierna! inUuieta!. Acta! 0!'anola! de P!iUuiatria -..9< /-% ?/-S?/E. FD. Goriguchi T, Cna(i W, 3a!a i A, 2i!hi(at!u H, 3u ega$a #. Periodic leg (o4e(ent! in !lee' $ith re!tle!! leg! !yndro(e% e""ect o" clona&e'a( treat(ent. #he Ta'ane!e Tournal o" P!ychiatry and 2eurology ?II-< 9D% E-ESE/-. FE. =etter #C, #ren $alder C, 3tia!ny K, et al. Behandlung de! idio'athi!chen und ura(i!chen 6e!tle!!-leg!-3yndro( (it L-Do'a S 0ine do''elblinde Cro!!-o4er-3tudie. =iener Medi&ini!che =ochen!chri"t ?II5< ?95% 5-5S5-E. FF. Collado-3eidel V. #reat(ent o" the re!tle!! leg! !yndro(e $ith a co(bination o" !tandard and !u!tained relea!e le4odo'a;ben!era&ide 5Mado'ar De'ot7% a double-blind controlled !tudy. Phar(aco'!ychiatry ?IIE< /.% ?5F. FI. #ren $alder C, 3eidel VC, Ka&en$adel T, et al. #reat(ent o" the re!tle!! leg! !yndro(e $ith a co(bination o" !tandard and !u!tained-relea!e le4odo'a;ben!era&ide 5Mado'ar De'ot5677% a double-blind controlled !tudy. Tournal o" the 2eurological 3cience! ?IIE< ?5.% 3-.9. I.. Mont'lai!ir T, Godbout 6, Poirier G, Bedard MA. 6e!tle!! leg! !yndro(e and 'eriodic (o4e(ent! in !lee'%'hy!io'athology and treat(ent $ith L-do'a. Clinical 2euro'har(acology ?IFD< I% 95DS9D/.

I?. 4on 3cheele C. Le4odo'a in re!tle!! leg!. Lancet ?IFD< -%9-DS9-E. I-. Bec er PM, Ta(ie!on AH, Bro$n =D. Do'a(inergic agent! in re!tle!! leg! !yndro(e and 'eriodic li(b (o4e(ent! o" !lee'% re!'on!e and co('lication! o" extended treat(ent in 9I ca!e!. 3lee' ?II/< ?D% E?/SE?D. I/. Guille(inault C, Cetel M, Phili' P. Do'a(inergic treat(ent o" re!tle!! leg! and rebound 'heno(enon. 2eurology ?II/< 9/% 995. I9. Allen 6P, 0arley CT. Aug(entation o" the re!tle!! leg! !yndro(e $ith carbido'a;le4odo'a. 3lee' ?IID< ?I% -.5S-?/. I5. 0arley CT, Allen 6P. Pergolide and carbido'a;le4odo'a treat(ent o" the re!tle!! leg! !yndro(e and 'eriodic leg (o4e(ent! in !lee' in a con!ecuti4e !erie! o" 'atient!. 3lee' ?IID< ?I% F.?SF?.. ID. #ren $alder C, Collado-3eidel V, Ka&en$adel T, et al. Hne-year treat(ent $ith !tandard and !u!tainedrelea!e le4odo'a% a''ro'riate longter( treat(ent o" re!tle!! leg! !yndro(eZ Mo4e(ent Di!order! -../< ?F% ??F9S??FI. IE. Garcia-Borreguero D, 3errano C, Larro!a H, To!e-Grani&o T. Circadian e""ect! o" do'a(inergic treat(ent in re!tle!! leg! !yndro(e. 3lee' Medicine -..9< 5%9?/S9-.. IF. 3tia!ny-Kol!ter K, Magerl =, Hertel =G, Moller TC, #reede 6D. 3tatic (echanical hy'eralge!ia $ithout dyna(ic tactile allodynia in 'atient! $ith re!tle!! leg! !yndro(e. Brain -..9< ?-E% EE/SEF-. II. 3tia!ny K, Moller TC, Boden!chat& 6, et al. 6otigotine CD3 in the treat(ent o" (oderate to ad4anced !tage! o" re!tle!! leg! !yndro(e% a double-blind 'lacebo-controlled !tudy. Mo4e(ent Di!order! -..-< ?E% 3-9?. ?... 3tia!ny K, Pberall M, Hertel =G. Cabergoline in re!tle!! leg! !yndro(e 56L37 S a double-blind 'lacebocontrolled (ulticenter do!e-"inding trial.
25

0uro'ean Tournal o" 2eurology -..-< I% 5.. ?.?. 3tia!ny-Kol!ter K, Hertel =G. Lo$-do!e 'ra(i'exole in the (anage(ent o" re!tle!! leg! !yndro(e. An o'en label trial. 2euro'!ychobiology -..9< 5.% D5SE.. ?.-. 3tia!ny K, 6obbec e T, 3chuler P, Hertel =G. #reat(ent o" idio'athic re!tle!! leg! !yndro(e 56L37 $ith the D--agoni!t cabergoline S an o'en clinical trial. 3lee' -...< -/% /9IS/59. ?./. 3tia!ny K. Clinical data on re!tle!! leg! !yndro(e% a do!e-"inding !tudy $ith cabergoline. 0uro'ean 2eurology -..?< 9D53u''l. ?7% -9S-D. ?.9. 3tia!ny K. Gandling the 'roble( o" aug(entation in re!tle!! leg! !yndro(e 56L37. 0uro'ean Tournal o" 2eurology -..?< F% ?5. ?.5. Yucconi M, Hldani A, Ca!trono4o C, 1erini-3tra(bi L. Cabergoline i! an e""ecti4e !ingle-drug treat(ent "or re!tle!! leg! !yndro(e% clinical and actigra'hic e4aluation. 3lee' -../< -D% F?5SF?F. ?.D. #ren $alder C, Brandenburg P, Gunde(er GP, et al. A rando(i&ed long-ter( 'lacebo-controlled (ulticenter trial o" 'ergolide in the treat(ent o" re!tle!! leg! !yndro(e $ith central e4aluation o" 'oly!o(nogra'hic data. 2eurology -..?< 5D% A5SAD. ?.E. #ren $alder C, Brandenburg P, Gunde(er GP, Lledo A, Vuail D, 3$ieca T. A long-ter( controlled (ulticenter trial o" 'ergolide in the treat(ent o" re!tle!! leg! !yndro(e $ith central e4aluation o" 'oly!o(nogra'hic data. Tournal o" the 2eurological 3cience! -..?< ?FE% 39/-. ?.F. Gunde(er GP, #ren $alder C, Lledo A, et al. #he !a"ety o" 'ergolide in the treat(ent o" re!tle!! leg! !yndro(e 56L37% re!ult! o" a rando(i&ed long-ter( (ulticenter trial o" 'ergolide in the treat(ent o" 6L3. 2eurology -..?< 5D% A-..

?.I. =etter #C, 3tia!ny K, =in el(ann T, et al. A rando(i&ed controlled !tudy o" 'ergolide in 'atient! $ith re!tle!! leg! !yndro(e. 2eurology ?III< 5-% I99SI5.. ??.. #agaya G, =etter #C, =in el(ann T, et al. Pergolide re!tore! !lee' (aintenance but i('air! !lee' 00G !ynchroni&ation in 'atient! $ith re!tle!! leg! !yndro(e. 3lee' Medicine -..-< /% 9IS59. ???. 3taedt T, GunerBager G, 6uther 0, 3to''e G. Pergolide% treat(ent o" choice in 6e!tle!! Leg! 3yndro(e 56L37 and 2octurnal Myoclonu! 3yndro(e 52M37. Longter( "ollo$ u' on 'ergolide. 3hort co((unication. Tournal o" 2eural #ran!(i!!ion ?IIF< ?.5% -D5S-DF. ??-. 0arley CT, Wa""ee TB, Allen 6P. 6ando(i&ed, doubleblind, 'lacebocontrolled trial o" 'ergolide in re!tle!! leg! !yndro(e. 2eurology ?IIF< 5?% ?5IIS?D.-. ??/. 3tia!ny K, =etter #C, =in el(ann T, et al. Long-ter( e""ect! o" 'ergolide in the treat(ent o" re!tle!! leg! !yndro(e. 2eurology -..?< 5D% ?/IIS?9.-. ??9. Bene! G, Dei!!ler A, Clarenbach P, 6odenbec A, GaBa G. Li!uride in the (anage(ent o" re!tle!! leg! !yndro(e. Mo4e(ent Di!order! -...< ?5% 3?/9S3?/5. ??5. 3on a K, Pretl M, Kranda K. Manage(ent o" re!tle!! leg! !yndro(e by the 'artial D--agoni!t terguride. 3lee' Medicine -../< 9% 955S95E. ??D. 0!ti4ill 0, de la 1uente V. P!o de ro'inirol co(o trata(iento del !indro(e de 'ierna! inUuieta!. 6e4i!ta de 2eurologia ?III< -F% ID-SID/. ??E. 0!ti4ill 0, de la 1uente V. 0"icacia del ro'inirol co(o trata(iento del in!o(nio cronico !ecundario al !indro(e de 'ierna! inUuieta!% dato! 'oli!o(nogra"ico!. 6e4i!ta de 2eurologia ?III< -I% F.5SF.E.
26

??F. Hndo =. 6o'inirole "or re!tle!! leg! !yndro(e. Mo4e(ent Di!order! ?III< ?9% ?/FS?9.. ??I. 3aletu B, Gruber G, 3aletu M, et al. 3lee' laboratory !tudie! in re!tle!! leg! !yndro(e 'atient! a! co('ared $ith nor(al! and acute e""ect! o" ro'inirole. ?. 1inding! on obBecti4e and !ubBecti4e !lee' and a$a ening Uuality. 2euro'!ychobiology -...< 9?% ?F?S?FI. ?-.. 3aletu M, Anderer P, 3aletu B, et al. 3lee' laboratory !tudie! in re!tle!! leg! !yndro(e 'atient! a! co('ared $ith nor(al! and acute e""ect! o" ro'inirole. -. 1inding! on 'eriodic leg (o4e(ent!, arou!al! and re!'iratory 4ariable!. 2euro'!ychobiology -...< 9?% ?I.S?II. ?-?. =att! 6L, 1ree(an A, 6ye DB, Bli$i!e DL, Krule$ic& 3. 6o'inirole "or re!tle!! leg! !yndro(e. Mo4e(ent Di!order! -...< ?5% 3?/9. ?--. 1ree(an A, 6ye DB, Bli$i!e D, Cha ra4orty 3, Krule$ic& 3, =att! 6L. 6o'inirole "or re!tle!! leg! !yndro(e 56L37% an o'en label and double blind 'lacebo-controlled !tudy. 2eurology -..?< 5D% A5. ?-/. Ah(ed C. 6o'inirole in re!tle!! leg !yndro(e. Mi!!ouri Medicine -..-< II% 5..S5.?. ?-9. Mont'lai!ir T, 2icola! A, Dene!le 6, Go(e&-Mancilla B. Pra(i'exole alle4iate! !en!ory and (otor !y('to(! o" re!tle!! leg! !yndro(e. 2eurology ?IIF< 5?% /??S/?-. ?-5. Bec er PM, Hndo =, 3haron D. 0ncouraging initial re!'on!e o" re!tle!! leg! !yndro(e to 'ra(i'exole. 2eurology ?IIF< 5?% ?--?S?--/. ?-D. Lin 3C, Ka'lan T, Burger CD, 1redric !on PA. 0""ect o" 'ra(i'exole in treat(ent o" re!i!tant re!tle!! leg! !yndro(e. Mayo Clinic Proceeding! ?IIF< E/% 9IES5... ?-E. Mont'lai!ir T, Dene!le 6, Petit D. Pra(i'exole in the treat(ent o" re!tle!! leg! !yndro(e% a "ollo$-u'

!tudy. 0uro'ean Tournal o" 2eurology -...< E53u''l. ?7% -ES/?. ?-F. 3aletu M, Anderer P, 3aletuYyhlar& G, Gauer C, 3aletu B. Acute 'lacebo-controlled !lee' laboratory !tudie! and clinical "ollo$-u' $ith 'ra(i'exole in re!tle!! leg! !yndro(e. 0uro'ean Archi4e! o" P!ychiatry and Clinical 2euro!cience -..-< -5-% ?F5S ?I9. ?-I. Manconi M, Ca!etta C, Go4oni V, Ce!ni 0, 1erini-3tra(bi L, Granieri 0. Pra(i'exole in re!tle!! leg! !yndro(e. 04aluation by !ugge!ted i((obili&ation te!t. Tournal o" 2eurology -../< -5.% ?9I9S?9I5. ?/.. Gening =, =alter! A3, =agner ML, et al. 3ucce!!"ul oxycodone thera'y "or the re!tle!! leg! !yndro(e% a double-blind !tudy. Canadian Tournal o" 2eurological 3cience! ?II/< -.% 3-?-. ?/?. Lauer(a G, Mar ula T. #reat(ent o" re!tle!! leg! !yndro(e $ith tra(adol% an o'en !tudy. Tournal o" Clinical P!ychiatry ?III< D.% -9?S -99. ?/-. 4an DiB TG, Bollen 0L, 3loot$eg T, 4an der Meer CM, Durian 1=, Y$inder(an AG. Geen 4er!chil in $er &aa(heid tu!!en hydro inine en 'lacebo biB het [re!tle!! leg![!yndroo(. 2ederland! #iBd!chri"t 4oor Genee! unde ?II?< ?/5% E5ISED/. ?//. Au!!er$in ler M, 3ch(idt P. Clonidine i! e""ecti4e in the treat(ent o" [re!tle!! leg[ !yndro(e in chronic urae(ic 'atient!. 2e'hrology, Dialy!i!, #ran!'lantation ?IFF< /%5/.. ?/9. Au!!er$in ler M, 3ch(idt P. Clonidine i! e""ecti4e in the treat(ent o" [re!tle!! leg[ !yndro(e in chronic urae(ia 'atient!. 2e'hrology, Dialy!i!, #ran!'lantation ?IFI< 9%?9I. ?/5. Mico& adioglu G, H&de(ir 12, Kut A, 3e&er 3, 3aatci P, Gaberal M. Gaba'entin 4er!u! le4odo'a "or the treat(ent o" re!tle!! leg! !yndro(e in he(odialy!i! 'atient!%an o'en-label
27

!tudy. 6enal 1ailure -..9< -D% /I/S /IE. ?/D. Gal4e&-Ti(ene& 2, Khan #. 6o'inirole and re!tle!! leg! !yndro(e. Mo4e(ent Di!order! ?III< ?9% FI.S FI-. ?/E. Miranda M, 1abre! L, Kagi M, et al. #rata(iento del !indro(e de 'ierna! inUuieta! en 'aciente! ure(ico! en diali!i! con 'ra(i'exole% re!ultado! 'reli(inare!. 6e4i!ta Medica de Chile -../< ?/?% E..SE.?. ?/F. Miranda M, Kagi M, 1abre! L, et al. Pra(i'exole "or the treat(ent o" ure(ic re!tle!! leg! in 'atient! undergoing he(odialy!i!. 2eurology -..9< D-% F/?SF/-. ?/I. Gol(an AT, 2ei(an 6A, 0ttlinger 60. Preli(inary e""icacy o" the do'a(ine agoni!t, 'ra(i'exole, "or "ibro(yalgia%the "ir!t, o'en label, (ulticenter ex'erience. Tournal o" Mu!culo! eletal Pain -..9< ?-% DISE9. ?9.. H\Kee""e 3#, Ga4in K, La4an T2. Cron !tatu! and re!tle!! leg! !yndro(e in the elderly. Age and Ageing ?II9< -/% -..S-./. ?9?. 04idente VG. Piribedil "or re!tle!! leg! !yndro(e% a 'ilot !tudy. Mo4e(ent Di!order! -..?< ?D% 5EIS 5F?. ?9-. 0hrenberg BL, 0i!en!ehr C, Corbett K0, Cro$ley P1, =alter! A3. Val'roate "or !lee' con!olidation in 'eriodic li(b (o4e(ent di!order. Tournal o" Clinical P!ycho'har(acology -...< -.% 5E9S 5EF. ?9/. 2i!hi(at!u H, Goriguchi T, Cna(i W, 3u ega$a #, 3a!a i A. Periodic li(b (o4e(ent di!order in neurole'ticinduced a athi!ia. Kobe Tournal o" Medical 3cience! ?IIE< 9/% ?DIS?EE. ?99. 6oehr! #, Yoric 1, =ittig 6, 6oth #. 0""icacy o" a reduced tria&ola( do!e in elderly in!o(niac!. 2eurobiology o" Aging ?IF5< D% -I/S-ID. ?95. Bonnet MG, Arand DL. #he u!e o" tria&ola( in older 'atient! $ith 'eriodic

leg (o4e(ent!, "rag(ented !lee', and dayti(e !lee'ine!!. Tournal o" Gerontology ?II.< 95%M?/ISM?99. ?9D. Ka'lan P=, Allen 6P, Buchhol& D=, =alter! TK. Double-blind co('ari!on o" L-do'a 4er!u! 'ro'oxy'hene in 'atient! $ith 'eriodic li(b (o4e(ent! in !lee'. 0lectroence'halogra'hy and Clinical 2euro'hy!iology ?II?< EI% /-P. ?9E. Bedard MA, Mont'lai!ir T, Godbout 6. 0""ect o" Ldo'a on 'eriodic (o4e(ent! in !lee' in narcole'!y. 0uro'ean 2eurology ?IFE< -E% /5S/F. ?9F. de Mello M#, 0!te4e! AM, #u"i 3. Co('ari!on bet$een do'a(inergic agent! and 'hy!ical exerci!e a! treat(ent "or 'eriodic li(b (o4e(ent! in 'atient! $ith !'inal cord inBury. 3'inal Cord -..9< 9-% -?FS--?. ?9I. Boi4in DB, Mont'lai!ir T, La(bert C. 0""ect! o" bro(ocri'tine in hu(an narcole'!y. Clinical 2euro'har(acology ?II/< ?D% ?-.S?-D. ?5.. Gogl B, 6othdach A, =etter #C, #ren $alder C. #he e""ect o" cabergoline on !lee', 'eriodic leg (o4e(ent! in !lee', and early (orning (otor "unction in 'atient! $ith Par in!on\! di!ea!e. 2euro'!ycho'har(acology -../< -F%?FDDS?FE.. ?5?. 3aletu M, Anderer P, 3aletu B, et al. 3lee' laboratory !tudie! in 'eriodic li(b (o4e(ent di!order 5PLMD7 'atient! a! co('ared $ith nor(al! and acute e""ect! o" ro'inirole. Gu(an P!ycho'har(acology -..?< ?D% ?EES ?FE. ?5-. 1antini ML, Gagnon T, 1ili'ini D, Mont'lai!ir T. #he e""ect! o" 'ra(i'exole in 60M !lee' beha4ior di!order. 2eurology -../< D?% ?9?FS ?9-.. ?5/. Buy!!e DT, 6eynold! C1, CCC, Goch CC, et al. Longitudinal e""ect! o" nortri'tyline on 00G !lee' and the li elihood o" recurrence in elderly de're!!ed 'atient!.
28

2euro'!ycho'har(acology ?IID< ?9% -9/S-5-. ?59. 2o"&inger 0A, 1a!ic& a A, Ber(an 3, #ha!e M0. Bu'ro'ion 36 reduce! 'eriodic li(b (o4e(ent! a!!ociated $ith arou!al! "ro( !lee' in de're!!ed 'atient! $ith 'eriodic li(b (o4e(ent di!order. Tournal o" Clinical P!ychiatry -...< D?% F5FSFD-. ?55. Gre$al M, Ga$a 6, 3ha'iro C. #reat(ent o" 'eriodic li(b (o4e(ent! in !lee' $ith !elegiline GCl. Mo4e(ent Di!order! -..-< ?E% /IFS9.?. ?5D. Wa(a!hiro W, Kryger MG. Acute e""ect o" na!al CPAP on 'eriodic li(b (o4e(ent! a!!ociated $ith breathing di!order! during !lee'. 3lee' ?II9< ?E% ?E-S?E5. ?5E. Briell(ann 63, Mathi! T, Ba!!etti C, Gugger M, Ge!! C=. Pattern! o" (u!cle acti4ity in leg! in !lee' a'nea 'atient! be"ore and during nCPAP thera'y. 0uro'ean 2eurology ?IIE< /F% ??/S??F. ?5F. Kotterba 3, Clarenbach P, Bo((el =, 6a!che K. Periodic leg (o4e(ent! in 'atient! $ith ob!tructi4e !lee' a'nea !yndro(e during nCPAP thera'y. 3o(nologie -...< 9% I/SI5. ?5I. 3cholle 3, 3cholle GC, Y$ac a G. Periodic leg (o4e(ent! and !lee'di!ordered breathing in children. 3o(nologie -..?< 5% ?5/S?5F. ?D.. Baran A3, 6ichert AC, Dougla!! AB, May =, An!arin K. Change in 'eriodic li(b (o4e(ent index during treat(ent o" ob!tructi4e !lee' a'nea $ith continuou! 'o!iti4e air$ay 're!!ure. 3lee' -../< -D% E?ESE-.. ?D?. Guille(inault C, 1lagg =. 0""ect o" baclo"en on !lee'related 'eriodic leg (o4e(ent!. Annal! o" 2eurology ?IF9< ?5% -/9S-/I. ?D-. Bedard MA, Mont'lai!ir T, Godbout 6, La'ierre H. 2octurnal ga((a-hydroxybutyrate. 0""ect on 'eriodic leg (o4e(ent! and !lee' organi&ation o" narcole'tic 'atient!. Clinical 2euro'har(acology ?IFI< ?-% -IS/D.

?D/. Ko4ace4ic-6i!tano4ic 6, Cart$right 6D, Lloyd 3. 2on'har(acologic treat(ent o" 'eriodic leg (o4e(ent! in !lee'. Archi4e! o" Phy!ical Medicine and 6ehabilitation ?II?< E-% /F5S/FI. ?D9. La4ie P, 2ahir M, Lorber M, 3char" W. 2on!teroidal antiin"la((atory drug thera'y in rheu(atoid arthriti! 'atient!% lac o" a!!ociation bet$een clinical i('ro4e(ent and e""ect! on !lee'. Arthriti! and 6heu(ati!( ?II?< /9% D55SD5I. ?D5. Ben& 6L, Pre!!(an M6, Go4ic 0#, Peter!on DD. A 'reli(inary !tudy o" the e""ect! o" correction o" ane(ia $ith reco(binant hu(an erythro'oietin thera'y on !lee', !lee' di!order!, and dayti(e !lee'ine!! in he(odialy!i! 'atient! 5the 3L00PH !tudy7. A(erican Tournal o" Kidney Di!ea!e! ?III< /9% ?.FIS?.I5. ?DD. Kun& D, Be! 1. 0xogenou! (elatonin in 'eriodic li(b (o4e(ent di!order% an o'en clinical trial and a hy'othe!i!. 3lee' -..?< -9% ?F/S?FE. ?DE. Ca('o! G, #u"i 3, Bittencourt L, Gaidar M, Baracat 0C. Proge!ton reduce! 'eriodic leg (o4e(ent! in (eno'au!e. Cli(acteric -..-< 5% ?5E 5ab!tract7. ?DF. 3aletu A, Grit!ch 1, MailathPo orny G, Gruber G, Anderer P, 3aletu B. HbBe ti4ierung der #hera'iee""i&ien& eine! neuartigen (andibularen Protru!ion!behel"! "ur 3chnarchen und !chla"be&ogene At(ung!!torungen (ittel! Poly!o(nogra'hie. =iener Klini!che =ochen!chri"t -..-< ??9% F.ESF?5. ?DI. Michal!en A, 3chlegel 1, 6odenbec A, et al. 0""ect! o" !hortter( (odi"ied "a!ting on !lee' 'attern! and dayti(e 4igilance in non-obe!e !ubBect!% re!ult! o" a 'ilot !tudy. Annal! o" 2utrition and Metaboli!( -../< 9E% ?I9S-... ?E.. 3i(a aBornboon 2, Go&al D, Vla!ic V, Mac C, 3haron D, McGinley
29

BM. Periodic li(b (o4e(ent! in !lee' and iron !tatu! in children. 3lee' -../< -D% E/5SE/F. ?E?. Cicolin A, Lo'iano L, Yibetti M, et al. 0""ect! o" dee' brain !ti(ulation o" the !ubthala(ic nucleu! on !lee' architecture in 'ar in!onian 'atient!. 3lee' Medicine -..9< 5% -.ES-?.. ?E-. Brenning 6. 0nantaldehyde! and "uraldehyde! in (oli(ina cruru( nocturna including re!tle!! leg!. A co('arati4e trial $ith carbacholine, ino!itolnicotinate, and 'lacebo. 2ordi! Medicin ?IDI< F?% 5-FS5/9. ?E/.Chri!tian!en C. Me!iono!itolhexani otinat 5Gexanicit7 og 'entaerytritoltetrani otinat 5Bu"on7 4ed re!tle!! leg!. Pge! ri"t "or Laeger ?IE.< ?/-% ?9E5S?9ED. ?E9. Gurli(ann 1. 6e!tle!! leg! and cra('i in the night. Double blind !tudy $ith circonyl in 'atient! $ith de"ecti4e 'eri'heric arterial circulation. 3ch$ei&eri!che 6und!chau "ur Medi&in Praxi! ?IE9< D/% ?I9S?I5. ?E5. 2o!eda A, 2ou4elle M, LanUuart T6, et al. Gigh leg (otor acti4ity in !lee' a'nea hy'o'nea 'atient!% e""icacy o" clona&e'a( co(bined $ith na!al CPAP on 'oly!o(nogra'hic 4ariable!. 6e!'iratory Medicine -..-< ID% DI/SDII. ?ED. 3oren!en H, #el!tad =. Carba(a&e'in 5#egretol7 4ed re!tle!! leg! !yndro(. #id!! ri"t "or den 2or! e Laege"orening ?IF9< ?.9% -.I/S-.I5. ?EE. Gand$er er T-VT, Pal(er 61. Clonidine in the treat(ent o" re!tle!! leg !yndro(e. 2e$ 0ngland Tournal o" Medicine ?IF5< /?/% ?--FS?--I. ?EF. Ba("ord C6, 3andy 6. 1ailure o" clonidine to a(eliorate the !y('to(! o" re!tle!! leg! !yndro(e. 3lee' ?IFE< ?.% /IFS/II. ?EI. Yoe A, =agner ML, =alter! A3. Gigh-do!e clonidine in a ca!e o" re!tle!! leg! !yndro(e. Annal! o" Phar(acothera'y ?II9< -F% FEFSFF?. ?F.. 6ie(ann D, Gann G, Dre!!ing G. 6e!tle!! leg! !yndro(e and 'eriodic

leg (o4e(ent! in !lee'. #= 2eurologie P!ychiatrie ?II5< I% ?I5?. ?F?. Merren MD. Gaba'entin "or treat(ent o" 'ain and tre(or% a large ca!e !erie!. 3outhern Medical Tournal ?IIF< I?% E/ISE99. ?F-. Morgan LK. 6e!tle!! li(b!% a co((only o4erloo ed !y('to( controlled by Valiu(. Medical Tournal o" Au!tralia ?IDE< -% 5FIS5I9. ?F/. Matthe$! =B. #reat(ent o" the re!tle!! leg! !yndro(e $ith clona&e'a(. Briti!h Medical Tournal ?IEI< ?% E5?. ?F9. Boghen D. 3ucce!!"ul treat(ent o" re!tle!! leg! $ith clona&e'a(. Annal! o" 2eurology ?IF.< F% /9?. ?F5. Mont'lai!ir T, Godbout 6, Boghen D, DeCha('lain T, Woung 32, La'ierre G. 1a(ilial re!tle!! leg! $ith 'eriodic (o4e(ent! in !lee'% electro'hy!iologic, bioche(ical, and 'har(acologic !tudy. 2eurology ?IF5< /5% ?/.S?/9. ?FD. #olle"!on G, 0rd(an C. #ria&ola( in the re!tle!! leg! !yndro(e. Tournal o" Clinical P!ycho'har(acology ?IF5< 5% /D?S/D-. ?FE. 3char" MB, Bro$n L, Gir!cho$it& T. Po!!ible e""icacy o" al'ra&ola( in re!tle!! leg !yndro(e. #he Gill!ide Tournal o" Clinical P!ychiatry ?IFD< F% -?9S--/. ?FF. 3chenc CG, Maho$ald M=. Long-ter(, nightly ben&odia&e'ine treat(ent o" inBuriou! 'ara!o(nia! and other di!order! o" di!ru'ted nocturnal !lee' in ?E. adult!. A(erican Tournal o" Medicine ?IID< ?..% ///S//E. ?FI. 3tautner A, 3tia!ny-Kol!ter K, Collado-3eidel V, Bucher 31, Hertel =G, #ren $alder C. Co('ari!on o" idio'athic and ure(ic re!tle!! leg! !yndro(e% re!ult! o" data ba!e o" ?/9 'atient!. Mo4e(ent Di!order! ?IID< ??%3IF. ?I.. Be&erra ML, Martine& TV. Yol'ide( in re!tle!! leg! !yndro(e. 0uro'ean 2eurology -..-< 9F% ?F.S ?F?.
30

?I?. A 'inar 3. #reat(ent o" re!tle!! leg! !yndro(e $ith le4odo'a 'lu! ben!era&ide. Archi4e! o" 2eurology ?IF-< /I% E/I. ?I-. 4on 3cheele C, Ke('i V. Longter( e""ect o" do'a(inergic drug! in re!tle!! leg!. A --year "ollo$-u'. Archi4e! o" 2eurology ?II.< 9E% ?--/S ?--9. ?I/. Lauer(a G. 2octurnal $andering cau!ed by re!tle!! leg! and !hortacting ben&odia&e'ine!. Acta P!ychiatrica 3candina4ica ?II?< F/% 9I-S9I/. ?I9. Hech!ner M. Cdio'athic re!tle!! leg! !yndro(e% co(bination thera'y $ith le4odo'a and ro'inirole. A tuelle 2eurologie ?IIF< -5% ?I.S?I-. ?I5. Ku(ar VG, Bhatia M, #ri'athi M, 3ri4a!ta4a AK, Tain 3. 6e!tle!! leg! !yndro(e% diagno!i! and treat(ent. Tournal o" the A!!ociation o" Phy!ician! o" Cndia -../< 5?%EF-SEF/. ?ID. 3ilber MG, 3he'ard T-=T, =i!bey TA. Pergolide in the (anage(ent o" re!tle!! leg! !yndro(e% an extended !tudy. 3lee' ?IIE< -.% FEFSFF-. ?IE. 2oel 3, Korri G, Vanderheyden T0. Lo$ do!age o" 'ergolide in the treat(ent o" re!tle!! leg! !yndro(e. Acta 2eurologica Belgica ?IIF< IF% 5-S5/. ?IF. =in el(ann T, =etter #C, 3tia!ny K, Hertel =G, #ren $alder C. #reat(ent o" re!tle!! leg !yndro(e $ith 'ergolide S an o'en clinical trial. Mo4e(ent Di!order! ?IIF< ?/% 5DDS 5DI. ?II. Bene! G. Cdio'athi!che! 6e!tle!!-leg!-3yndro(% Behandlung (it Li!urid. 2er4enheil unde -..?< -.% ??IS?--. -... Dano"" 3K, Gra!!o M0, #erry PB, 1lynn TA. Pleuro'ul(onary di!ea!e due to 'ergolide u!e "or re!tle!! leg! !yndro(e. Che!t -..?< ?-.% /?/S/?D. -.?. Ba!!etti C, Cla4adet!cher 3, Gugger M, Ge!! C=. Pergolidea!!ociated !lee' attac ! in a 'atient

$ith re!tle!! leg! !yndro(e. 3lee' Medicine -..-< /% -E5S-EE. -.-. 3tia!ny K, Moller TC, Hertel =G. 3a"ety o" 'ra(i'exole in 'atient! $ith re!tle!! leg! !yndro(e. 2eurology -...< 55% ?5FIS?5I.. -./. 1erini-3tra(bi L. 6e!tle!! leg! !yndro(e aug(entation and 'ra(i'exole treat(ent. 3lee' Medicine -..-< /% 3-/S3-5. -.9. #ei4e GA, de Vuadro! A, Barro! 1C, =ernec LC. 3indro(e da! 'erna! inUuieta! co( heranca auto!!o(ica do(inante 'iorada 'elo u!o de (irta&a'ina% relato de ca!o. ArUui4o! de 2euro-P!iUuiatria -..-< D.% ?.-5S?.-I. -.5. 3ilber MG, Giri!h M, C&urieta 6. Pra(i'exole in the (anage(ent o" re!tle!! leg! !yndro(e% an extended !tudy. 3lee' -../< -D% F?ISF-?. -.D. =in el(an T=, Tohn!ton L. Aug(entation and tolerance $ith longter( 'ra(i'exole treat(ent o" re!tle!! leg! !yndro(e 56L37. 3lee' Medicine -..9< 5% IS?9. -.E. #r&e'ac& P#, Violette 0T, 3ateia MT. 6e!'on!e to o'ioid! in three 'atient! $ith re!tle!! leg! !yndro(e. A(erican Tournal o" P!ychiatry ?IF9< ?9?% II/SII5. -.F. Gening =A, =alter! A, Ka4ey 2, Gidro-1ran 3, Cote L, 1ahn 3. Dy! ine!ia! $hile a$a e and 'eriodic (o4e(ent! in !lee' in re!tle!! leg! !yndro(e% treat(ent $ith o'ioid!. 2eurology ?IFD< /D% ?/D/S?/DD. -.I. =alter! A, Gening =, Cote L, 1ahn 3. Do(inantly inherited re!tle!! leg! $ith (yoclonu! and 'eriodic (o4e(ent! o" !lee'% a !yndro(e related to the endogenou! o'iate!Z Ad4ance! in 2eurology ?IFD< 9/% /.IS /?I. -?.. 3andy 6, Bernic C, Lee 3M, 3tern LY, Cacono 6P, Ba("ord C6. Ldo'a in ure(ic 'atient! $ith the re!tle!! leg! !yndro(e. Cnternational Tournal o" 2euro!cience ?IFE< /5% -//S-/5.
31

-??. 3andy 6, Ba("ord C6, Gill(an MA. H'iate! in the re!tle!! leg! !yndro(e. Cnternational Tournal o" 2euro!cience ?IFE< /D% IIS?.9. -?-. Mont'lai!ir T, Lorrain D, Godbout 6. 6e!tle!! leg! !yndro(e and 'eriodic leg (o4e(ent! in !lee'% the 'ri(ary role o" do'a(inergic (echani!(. 0uro'ean 2eurology ?II?< /?% 9?S9/. -?/. Vahedi G, Kuchle M, #ren $alder C, Kren& CT. Peridurale Mor'hiu(an$endung bei 6e!tle!!Leg!-3tatu!. Ana!the!iologie, Cnten!i4(edi&in, 2ot"all(edi&in, 3ch(er&thera'ie ?II9< -I% /DFS/E.. -?9. =alter! A3, =in el(ann T, #ren $alder C, et al. Longter( "ollo$u' on re!tle!! leg! !yndro(e 'atient! treated $ith o'ioid!. Mo4e(ent Di!order! -..?< ?D% ??.5S??.I. -?5. Ta ob!!on B, 6uuth K. 3ucce!!"ul treat(ent o" re!tle!! leg! !yndro(e $ith an i('lanted 'u(' "or intrathecal drug deli4ery. Acta Anae!the!iologica 3candina4ica -..-< 9D% ??9S??E. -?D. Ayre! 3T, Mihan 6. Leg cra('! 5!y!tre((a7 and re!tle!! leg! !yndro(e. 6e!'on!e to 4ita(in 0 5toco'herol7. Cali"ornia Medicine ?IDI< ???% FESI?. -?E. Blattler =, Muhle(ann M. 6e!tle!! leg! und nachtliche Bein ra('"e S Verge!!ene! &ur Diagno!e S 2eue! &ur #hera'ie. 3ch$ei&eri!che Medi&ini!che =ochen!chri"t. Tournal 3ui!!e de Medecine ?IF-< ??-% ??5S??E. -?F. Mounti"ield TA. 6e!tle!! leg !yndro(e relie4ed by ce!!ation o" !(o ing. CMAT ?IF5< ?//% 9-DS9-E. -?I. Ga GC. 6egional intra4enou! analge!ia "or re!tle!! leg! !yndro(e. Pain Clinic ?IFF< -% ?-?S?-/. --.. 3andy 6, K$o-on-Wuen P1, Ba("ord C6. #he e""ect! o" baclo"en in the re!tle!! leg! !yndro(e% e4idence "or endogenou! o'ioid in4ol4e(ent. Tournal o" Clinical

P!ycho'har(acology ?IFF< F% 99.S 99?. --?. Di((itt 3B, 6iley GT. 3electi4e !erotonin rece'tor u'ta e inhibitor! can reduce re!tle!! leg! !y('to(!. Archi4e! o" Cnternal Medicine -...< ?D.% E?-. ---. Gu T. Acu'uncture treat(ent o" re!tle!! leg !yndro(e. Tournal o" #raditional Chine!e Medicine -..?< -?% /?-S/?D. --/. Ka'ur 2, 1ried(an 6. Hral eta(ine% a 'ro(i!ing treat(ent "or re!tle!! leg! !yndro(e. Ane!the!ia and Analge!ia -..-< I9% ?55FS?55I. --9. Lin Y. Go$ to treat re!tle!! leg !yndro(e $ith traditional Chine!e (edicineZ Tournal o" #raditional Chine!e Medicine -../< -/% /.DS/.E. --5. 3trang 66. #he !y('to( o" re!tle!! leg!. Medical Tournal o" Au!tralia ?IDE< ?% ?-??S?-?/. --D. Li'in! i T1, Yuben o G3, Barreira P, Cohen BM. Pro'ranolol in the treat(ent o" neurole'tic-induced a athi!ia. Lancet ?IF/< -% DF5SDFD. --E. Dero( 0, 0linc =, Buylaert =, 4an der 3traeten M. =hich betabloc er "or the re!tle!! legZ Lancet ?IF9< ?%F5E. --F. Gin!berg G2. Pro'ranolol in the treat(ent o" re!tle!! leg! !yndro(e induced by i(i'ra(ine $ithdra$al. A(erican Tournal o" P!ychiatry ?IFD< ?9/% I/F. --I. Ba!tani B, =e!ter4elt 1B. 0""ecti4ene!! o" clonidine in alle4iating the !y('to(! o" re!tle!! leg!. A(erican Tournal o" Kidney Di!ea!e! ?IFE< ?.% /-D. -/.. Ca4atorta 1, Vagge 6, 3olari P, Vueirolo C. 6i!ultati 'reli(inari con clonidina nella !indro(e delle ga(be !en&a ri'o!o in due 'a&ienti ure(ici e(odiali&&ati. Miner4a Prologica e 2e"rologica ?IFE< /I% I/. -/?. 2o4elli G, Mediati 6D, Ca!ali 6, Paler(o P. #reat(ent o" re!tle!! leg!
32

!yndro(e $ith gaba'entin. Pain Clinic -...< ?-% D?SD/. -/-. 6ead DT, 1ee!t #G, 2a!!i( MA. Clona&e'a(% e""ecti4e treat(ent "or re!tle!! leg! !yndro(e in urae(ia. Briti!h Medical Tournal 5Clinical 6e!earch 0dition7 ?IF?< -F/% FF5SFFD. -//. 3al4i 1, Montagna P, Pla!(ati 6, et al. 6e!tle!! leg! !yndro(e and nocturnal (yoclonu!% initial clinical (ani"e!tation o" "a(ilial a(yloid 'olyneuro'athy. Tournal o" 2eurology, 2euro!urgery and P!ychiatry ?II.< 5/% 5--S5-5. -/9. Goriguchi T, Wa(a!hita G, Mi&uno 3, et al. 2octurnal eating;drin ing !yndro(e and neurole'tic-induced re!tle!! leg! !yndro(e. Cnternational Clinical P!ycho'har(acology ?III< ?9% //S/D. -/5. Bruno 6L. Abnor(al (o4e(ent! in !lee' a! a 'o!t-'olio !eUuelae. A(erican Tournal o" Phy!ical Medicine and 6ehabilitation ?IIF< EE% //IS/99. -/D. =alter! A3, Mandelbau( D0, Le$in D3, Kugler 3, 0ngland 3T, Miller M. Do'a(inergic thera'y in children $ith re!tle!! leg!;'eriodic li(b (o4e(ent! in !lee' and ADGD. Do'a(inergic #hera'y 3tudy Grou'. Pediatric 2eurology -...< --% ?F-S ?FD. -/E. 3hari" AA. 0ntaca'one in re!tle!! leg! !yndro(e. Mo4e(ent Di!order! -..-< ?E% 9-?. -/F. 3cherbau( 2, 3tu'er B, Bonnet P, Ga!t'ar M. #ran!ient re!tle!! leg!-li e !yndro(e a! a co('lication o" o'iate $ithdra$al. Phar(aco'!ychiatry -../< /D% E.SE-. -/I. Li'in! i T1, 3allee 16, Tac !on C, 3ethura(an G. Do'a(ine agoni!t treat(ent o" #ourette di!order in children% re!ult! o" an o'en-label trial o" 'ergolide. Mo4e(ent Di!order! ?IIE< ?-% 9.-S9.E. -9.. Bro$n LK, Ge""ner T0, Hbben! 0A. #ran!4er!e (yeliti! a!!ociated $ith re!tle!! leg! !yndro(e and 'eriodic (o4e(ent! o" !lee'

re!'on!i4e to an oral do'a(inergic agent but not to intrathecal baclo"en. 3lee' -...< -/% 5I?S5I9. -9?. Ganna PA, Ku(ar 3, =alter! A3. 6e!tle!! leg! !y('to(! in a 'atient $ith abo4e nee a('utation!% a ca!e o" 'hanto( re!tle!! leg!. Clinical 2euro'har(acology -..9< -E% FESFI. -9-. 0!ti4ill 0, 1uente-Panell V, 3egarra-C!ern 1, Albare!-#endero T. 3indro(e de 'ierna! inUuieta! en un 'aciente con a('utacion de a(ba! 'ierna!. 6e4i!ta de 2eurologia -..9< /I% 5/DS5/F. -9/. Lauer(a G, Mar ula T, Gy4onen G, Kyyronen K. Cdio'athic re!tle!! leg! !yndro(e and '!ycho!e!. 2ordic Tournal o" P!ychiatry ?IIE< 5?% -.5. -99. Burn! K0. P!e o" tra(adol to control re!tle!! leg! !yndro(e a"ter ortho'edic !urgery. Go!'ital Phar(acy -...< /5% DE/. -95. 1reye 0, Le4y T. Acute ab!tinence !yndro(e "ollo$ing abru't ce!!ation o" long-ter( u!e o" tra(adol 5Pltra(7% a ca!e !tudy. 0uro'ean Tournal o" Pain -...< 9% /.ES/??. -9D. 2ordlander 2B. #hera'y in re!tle!! leg!. Acta Medica 3candina4ica ?I5/< ?95% 95/S95E. -9E. Po' in 6T. Hr'henadrine citrate 52or"lex7 "or the treat(ent o" re!tle!! leg! and related !yndro(e!. Tournal o" the A(erican Geriatric! 3ociety ?IE?< ?I% EDSEI. -9F. Morgan LK. Letter% 6e!tle!! leg!% 'reci'itated by beta bloc er!, relie4ed by or'henadrine. Medical Tournal o" Au!tralia ?IE5< -% E5/. -9I. Bote& MC, 1ontaine 1, Bote& #, Bache4alier T. 1olatere!'on!i4e neurological and (ental di!order!% re'ort o" ?D ca!e!. 2euro'!ychological correlate! o" co('uteri&ed tran!axial to(ogra'hy and radionuclide ci!ternogra'hy in "olic acid de"iciencie!. 0uro'ean 2eurology ?IEE< ?D% -/.S-9D. -5.. Bote& MC, Cadotte M, Beaulieu 6, Pichette LP, Pi!on C. 2eurologic
33

di!order! re!'on!i4e to "olic acid thera'y. Canadian Medical A!!ociation Tournal ?IED< ??5% -?ES--/. -5?. Wat&idi! G, Kout!ico! D, Agroyanni! B, Pa'a!te'hanidi! C, Ple(eno! M, Delatola Y. Biotin in the (anage(ent o" ure(ic neurologic di!order!. 2e'hron ?IF9< /D%?F/S?FD. -5-. 3andy 6. L-#ry'to'han in the treat(ent o" re!tle!! leg! !yndro(e. A(erican Tournal o" P!ychiatry ?IFD< ?9/%559S555. -5/. Wa!uda #, 2i!hi(ura A, Kat!u i W, #!uBi W. 6e!tle!! leg! !yndro(e treated !ucce!!"ully by idney tran!'lantation S a ca!e re'ort. Clinical #ran!'lant! ?IFD< ?-% ?/F. -59. 3andy 6, Cacono 6P, Ba("ord C6. 3'inal cord (echani!(! in a(itri'tyline re!'on!i4e re!tle!! leg! !yndro(e in Par in!on\! di!ea!e. Cnternational Tournal o" 2euro!cience ?IFF< /F% ?-?S?-9. -55. Kerr PG, 4an Ba el C, Da$born TK. A!!e!!(ent o" the !y('to(atic bene"it o" cool dialy!ate. 2e'hron ?IFI< 5-% ?DDS?DI. -5D. H\Kee""e 3#, 2oel T, La4an T2. 6e!tle!! leg! !yndro(e in the elderly. Po!tgraduate Medical Tournal ?II/< DI%E.?SE./. -5E. Kanter AG. #he e""ect o" !clerothera'y on re!tle!! leg! !yndro(e. Der(atologic 3urgery ?II5< -?% /-FS//-. -5F. 6euter C, 0lli! CM, 6ay-Chaudhuri K. 2octurnal !ubcutaneou! a'o(or'hine in"u!ion in Par in!on\! di!ea!e and re!tle!! leg! !yndro(e. Acta 2eurologica 3candina4ica ?III< ?..% ?D/S?DE. -5I. 6ye DB, DeLong M6. A(elioration o" !en!ory li(b di!co("ort o" re!tle!! leg! !yndro(e by 'allidoto(y. Annal! o" 2eurology ?III< 9D% F..SF.?. -D.. C!hi&u #, Hhyagi W, 1uruya G, et al. A 'atient $ith re!tle!! leg! !yndro(e;'eriodic li(b (o4e(ent !ucce!!"ully treated by $earing a

lu(bar cor!et. 6in!ho 3hin eiga u. Clinical 2eurology -..?< 9?% 9/FS99?. -D?. Kryger MG, Hta e K, 1oer!ter T. Lo$ body !tore! o" iron and re!tle!! leg! !yndro(e% a correctable cau!e o" in!o(nia in adole!cent! and teenager!. 3lee' Medicine -..-< /% ?-ES?/-. -D-. 3ilber MG, 6ichard!on T=. Multi'le blood donation! a!!ociated $ith iron de"iciency in 'atient! $ith re!tle!! leg! !yndro(e. Mayo Clinic Proceeding! -../< EF% 5-S59. -D/. McLean AT. #he u!e o" the do'a(ine-rece'tor 'artial agoni!t ari'i'ra&ole in the treat(ent o" re!tle!! leg! !yndro(e. 3lee' -..9< -E% ?.--. -D9. =are TC, Blu(o"" 6, Pittard T#. Peri'heral 4a!ocon!triction in 'atient! $ith !lee' related 'eriodic leg (o4e(ent!. 3lee' ?IFF< ??% ?F-S?FD. -D5. La!che$! i 1, 3anner B, Koner(ann M, Kreu&er C, Gor!ten!(eyer D, 3tur( A. Au!ge'ragte Gy'er!o(nie einer ?/Bahrigen bei 'eriodic leg (o4e(ent. Pneu(ologie ?IIE< /53u''l. 5?7% E-5S E-F. -DD. 3taedt T, 3to''e G, 6ie(ann G, GaBa G, 6uther 0, 6iederer P. La(otrigine in the treat(ent o" nocturnal (yoclonu! !yndro(e 52M37% t$o ca!e re'ort!. Tournal o" 2eural #ran!(i!!ion ?IID< ?./% /55S/D?. -DE. H!htory MA, ViBayan 2. Clona&e'a( treat(ent o" in!o(nia due to !lee' (yoclonu!. Archi4e! o" 2eurology ?IF.< /E% ??IS?-.. -DF. 6ou!!eau TT, Debati!!e D1. 0tude cliniUue et 'olygra'hiUue de deux ob!er4ation! de nocturnal (yoclonu! !en!ible! au clona&e'a(. Acta 2eurologica Belgica ?IF5< F5% /?FS/-D. -DI. Guille(inault C, Cro$e C, Vuera3al4a MA, Mile! L, Partinen M. Periodic leg (o4e(ent, !lee' "rag(entation and central !lee' a'noea in t$o ca!e!% reduction $ith
34

clona&e'a(. 0uro'ean 6e!'iratory Tournal ?IFF< ?% ED-SED5. -E.. 6o(ano #T. Phar(acothera'y. Pre!ence o" nocturnal (yoclonu! in 'atient! $ith "ibro(yalgia !yndro(e. A(erican Tournal o" Pain Manage(ent ?III< I% F5. -E?. Male -Ah(adi P. Bu'ro'ion, 'eriodic li(b (o4e(ent di!order, and ADGD. Tournal o" the A(erican Acade(y o" Child and Adole!cent P!ychiatry ?III< /F% D/ESD/F. -E-. Leonhardt M, Abele M, Kloc gether #, Dichgan! T, =eller M. Pathological ya$ning 5cha!(7 a!!ociated $ith 'eriodic leg (o4e(ent! in !lee'% cure by le4odo'a. Tournal o" 2eurology ?III< -9D% D-?S D--. -E/. Picchietti DL, =alter! A3. Moderate to !e4ere 'eriodic li(b (o4e(ent di!order in childhood and adole!cence. 3lee' ?III< --% -IES /... -E9. 6odrigue! 62, 3il4a AA. 3onolencia diurna exce!!i4a 'o!trau(ati!(o de cranio% a!!ociacao co( (o4i(ento! 'eriodico! de 'erna! e di!turbio de co('orta(ento do !ono 60M% relato de ca!o. ArUui4o! de 2euro-P!iUuiatria -..-< D.% D5DSDD.. -E5. 3anta(aria T, Cran&o A, #olo!a 0. De4elo'(ent o" re!tle!! leg! !yndro(e a"ter do'a(inergic treat(ent in a 'atient $ith 'eriodic leg (o4e(ent! in !lee'. 3lee' Medicine -../< 9% ?5/S?55. -ED. Ka4ey 2, =alter! A3, Gening =, Gidro-1ran 3. H'ioid treat(ent o" 'eriodic (o4e(ent! in !lee' in 'atient! $ithout re!tle!! leg!. 2euro'e'tide! ?IFF< ??%?F?S?F9. -EE. Ancoli-C!rael 3, 3ei"ert A6, Le(on M. #her(al bio"eedbac and 'eriodic (o4e(ent! in !lee'% 'atient! !ubBecti4e re'ort! and a ca!e !tudy. Bio"eedbac and 3el" 6egulation ?IFD< ??% ?EES?FF.

-EF. Ganly P, Yuberi 2. Periodic leg (o4e(ent! during !lee' be"ore and a"ter heart tran!'lantation. 3lee' ?II-< ?5%9FIS9I-. -EI. Lee M3, Choi WC, Lee 3G, Lee 3B. 3lee'-related 'eriodic leg in4ol4e(ent! a!!ociated $ith !'inal cord le!ion!. Mo4e(ent Di!order! ?IID< ??% E?ISE--. -F.. Paradi!o G, Khan 1, Chen 6. 0""ect! o" a'o(or'hine on "lexor re"lex and 'eriodic li(b (o4e(ent. Mo4e(ent Di!order! -..-< ?E% 5I9S 5IE. -F?. Gulden T. Le4odo'a in the treat(ent o" re!tle!! leg! !yndro(e. 1ort!chritte der Medi&in ?II9< ??-% D?S D-. -F-. Gain C. De4elo'(ent o" o'ioid de'endence in a not diagno!ed re!tle!! leg! !yndro(e. P!ychiatri!che Praxi! -..-< -I% /-?S/-/. -F/. Goriguchi T, Cna(i W, Miyo!hi 2, Ka i(oto W. 6e!tle!! leg! !yndro(e in "our 'ar in!onian 'atient! treated $ith a(antadine. 6in!ho 3hin eiga u. Clinical 2eurology ?IF5< -5% ?5/S?5D. -F9. Ka!tin AT, Kullander 3, Borglin 20, et al. 0xtra'ig(entary e""ect! o" (elanocyte-!ti(ulating hor(one in a(enorrhoeic $o(en. Lancet ?IDF< ?% ?..ES?.?.. -F5. 2a!!r DG. Paradoxical re!'on!e to nitra&e'a( in a 'atient $ith hy'er!o(nia !econdary to nocturnal (yoclonu!. Tournal o" Clinical P!ycho'har(acology ?IFD< D% ?-?S ?--. -FD. Petiau C, Ya(agni M, #raut(ann D, 3"or&a 0, Krieger T. Periodic (o4e(ent! during !lee' !yndro(e. Tournal de (edecine de 3tra!bourg ?II5< -D% ?DDS?DI. -FE. 3at&ger-Gar!ch P. Current !tudie!% thera'y $ith Ldo'a;ben!era&ide relie4e! excruciating !y('to(! in re!tle!! leg !yndro(e. A]r&tliche Praxi! 2eurologie P!ychiatrie ?IIF< ??% 9..
35

-FF. 3ch$ar& T, #ren $alder C. 6e!tle!! leg! !yndro(e%treat(ent $ith L-do'a or L-do'a !lo$ relea!e 're'aration!. A tuelle 2eurologie ?IID< -/% -DS-I. -FI. 3taedt T, 3to''e G, Kogler A, et al. 2achtliche! Myo lonie-3yndro( 52M37 und 6e!tle!!-Leg!-3yndro( 56L37 S Pber!icht und 1allbe!chreibung. 1ort!chritte der 2eurologie-P!ychiatrie ?II9< D-% FFS I/. -I.. 3tia!ny K. 6e!tle!! leg! !yndro(e% !o(eti(e! are hot and cold !ho$er! !u""icient. A] r&tliche Praxi! 2eurologie P!ychiatrie ?III< /% /FS9.. -I?. #ren $alder C. Dy! ine!ia on do'a(inergic thera'y "or re!tle!! leg! !yndro(eZ Cnterni!ti!che Praxi! -../< 9/% IIS?... -I-. Va! i4! yB M. Vli4 hy'ere(i&uBici 4odolecby na !yndro( ne lidnych nohou. 1y!iatric y a 6eu(atologic y Ve!tni ?IE/< 5?% /.FS/.I.