GILLES DE LATOURETTE-OV ,SINDROM I MOGUCSPEKTARKOMORBIDITETA

Milica Pejovi: Milovancevic 1

Dragan Marinkovic 2

Miroslava jasovic-Gasic 2

Vesna Matovic:

I Institut za mentalno zdravlje, BeogradInstitut za psihijatriju, KCS, Beograd

Kratak sadriaj: Gilles de la Tourette-ov sindrom je je­dan od najboljih modela za neuropsihijatrijski po­remecaj - neophodan most izmedu psihijatrije i neu­rologije. Bogata simptomatologija klinicke ekspresijese deli na motorne, vokaine i bihejvioralne manife­tacije. U proucavanju spektra komorbiditeta TS saostalim porernecajima u svetskoj literaturi spominjuse sledeci porernecaji: opsesivno kompulzivni pore­mecaj, porernecaj paznje sa hiperkineticnoscu, pore­mecaji raspolozenja (bipolarni porernecaj i major de­presivni poremecaj) i poremecaji iz shizofrenog kru­gao Ovaj rad ima za ciIj da pokaze mogucnosti ko­morbiditeta TS sa odredenim klinickim entitetima.Prikazan je slucaj pacijenta kod koga se Gill de laTourett-ov javio u komorbiditetu sa shiofreniform­nim porernecajem. Zajednicke karakteristike shizo­frenije i TS su sledece: obsesivno kompuIsivni simp­tomi, poremecaji pokreta po tipu motornih streotip­ija i porernecaji dopaminergickog sistema u eNS.Zajednicko ovim poremecajima je i terapijski pristup- Iekovi izbora su neuroleptici. Pokazani su i raziozizbog cega u u slucajevirna TS sa produktivnom psi­hoticnom simptomatoIogijom istu smatramo kaoshizofreniformni porernecaj (shizofreniformne mani­festacije u skiopu TS iii komorbiditetno), a ne kaokomorbiditet TS i shizofrenije kao entiteta, Smatralismo znacajnim da podsetimo i podvucerno da brojniklinicki entiteti idu zajedno jedan sa drugim i da senjihove klinicke slike prekiapaju, nadopunjuju i me­saju sto je vazno u holistickom pristupu tretmanurazlicitih entiteta.

Kljuene reci: Tourette-ov sindrom, shizofreniformniporemecaj, komorbiditiet.

Uvod

Tikovi su nevoljni, brzi, repetitivni, stere­otipni pokreti individualne misicne grupe.Lakse ih je prepoznati nego precizno di­jagnostikovati. Tikovi se kategorisu u od­nosu na godinu javljanja, duzinu trajanja,ozbiljnost simptoma i prisustva motornihi/ili vokalnih tikova (1, 2, 3).

Gilles de la Tourette-ov sindrom je jedanod najboljih modela za neuropsihijatrijskiporemeca] - neophodan most izmedu psi­hijatrije i neurologije.

Jedan od prvih opisa motornih tikova, eho­lalije i koprolalije je dao francuski neurolog19-og veka Jean-Marc Itard (32). Njegova

pacijentkinja francuska noblesa Marquisede Dampierre je sa 7 godina ispoljila mo­tome tikove a ubrzo zatim i nevoljne voka­lizacije u vidu vriskanja i krikova gusenja,Nekoliko godina kasnije ispoljila je kopro­laliju. Ove poteskoce je imala do svoje smr-ti u 85-oj godini zivota. Nekih 50 godinakasnije Gilles de la Tourette je saopstio ne- l'koliko svojih slucajeva sa slicnom simpto- ~

matologijom (ukljucujuci i Marquise de 8Darnpierre u njenim kasnijim godinama) ~

cime je i definisan ovaj entitet (33). Vodeci N

evropski neurolog tog vremena jean Martin ~Charcot, Tourette-ov supervizor u bolnici o

zSalpetriere u Parizu, je 1880. godine dodao '-L.l

ime svog ucenika ovom sindromu i odvojioovaj entitet od Sydenharn-ove horeje. 109

• slozeni vokalni tikovi: izgovaranje smi­saonih reci ili fraza (»covece«, »kao stoznate«, »U redu, u redu"; rituali- ponav-

Tourette-ov sindrom (TS) javlja se izrnedu2. i 15. godine zivota (srednja godina poja­ve sindroma je 7.) i odlikuje se prisustvommultiplih, brzih, stereotipnih i nevoljnihmisicnih i vokalnih tikova. Prema Asoci­jaciji za Tourett-ov sindrom (TSA) osnova­ne 1972. godine porernecaj se javlja pre 21godine zivota a najcesce izmedu 5. - 18. Udefinisanju se povremeno srecu dva proble­ma: pojava redih slucajeva i posle 21. go­dine zivota i »nevoljnost«, jer pacijenti po­nekad opisuju tikove kao voljne radnje u ci­lju smanjenja napetosti. Prevalenca sindro­rna je 0,3(0,8) - 0,5 (4,5) u populaciji od1000 (3, 4).

KLINICKA SLIKA GILLES DE LATOURETTE-ovog SINDROMA

Bogata simptomatologija klinicke ekspre­sije se deli na motorne, vokalne i bihejvi­oralne manifetacije.

Motorne manifestacije

• jednostavni motorni tikovi: brzi i besmi­sleni (treptanje, grimasiranje, pipkanjenosa, pucenje, klacenje glave, ruku, tela,pokreti prstiju i dr.)

• slozeni motorni tikovi: mogu biti sporijiili mogu sadrzavati stereotipnu seriju po­kreta (dodirivanje objekata, sebe iii dru­gih, okretanje, »distonican« polozaj tela,grickanje usana iii ruke, pokreti pisanja,ljubljenja i dr.; Kopropraksija - dodiriva­nje genitalija i drugi nepristojni gestovi ­»Giving the finger«: Ehopraksija- imitira­nje gestova i pokreta drugih).

Vokalne manifestacijeag • jednostavni vokalni tikovi: besmisleni2 zvuci (kasljucanje, mljackanje, podrigiva-N nje, smrkanje, pravljenje glasova kao:E »eee«, »uh«, »oh« i dr.)~ozu.l

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ljanje fraza iii necega vise od 3 puta: go­vorne atipicnosti - neobican ritam, ton,akcenat, glasan i veoma brz govor; Ko­prolalija- obsene, agresivne i druge soci­jalno neprihvatljive reci i fraze; Ehola­lija- ponavljanje glasova, reci ili delovareci drugih osoba; Palilalija- ponavljenjesopstvenih reci iii delova reci)

Bihejvioralne manifestacije

Opsesije, kompulzije, emocionalna labil­nost, iritabilnost, impulzivnost, agresiv­nost i samopovredivanje, razlicite pores­koce ucenja, i poteskoce u socijalnim kon­taktima, povlacenje.

Tok klinicke slike varira (simptomi seusloznjavaju, smiruju i postepeno menja­ju), tikovi se mogu redukovati iii potpunokontrolisati za kratko vreme (koncentra­cijom iii preokupaciojom drugim poslom)sto dovodi do narastanja tenzije a time iponovne potrebe za tikovima. Simptomiuvek nestaju tokom spavanja ili orgazma,a sam TS je hronicnog toka i traje celogzivota (1, 5).

Potvrdujuci ali ne i osnovni za dijagnozusu sledeci simptomi: koprolalija, kopro­praksija, eholalija, ehopraksija, palilalija(palikoprolalija) i palipraksija (7, 8, 9).Cesto udruzeni sa TS ali ne i odlucujuci zadijagnozu su rani hiperkinetski poreme­caj, kao i porernecaj paznje sa hiperkine­ticnim porernecajem (6); zatim, nespecifi­cni EEG nalaz; »soft sighns« u okviru stan­dardnog neuroloskog pregleda i subtilniznaci organske disfunkcije u okviru stan­dardnog psiholoskog testiranja (10).

KOMORBEDITET GILLES DE LATOURETTE-ovog SINDROMA

Komorbiditet se definise kao postojanjejednog iii vise porernecaja u isto vreme.Obicno se ne spominje da li su ovi pore­rnecaji nastali u isto vreme ili u sekven-

cionalnom redu. U proucavanju spektrakomorbiditeta TS sa ostalim poremeca­jima u svetskoj literaturi spominju se sle­deci porernecaji: opsesivno kompulzivniporernecaj (u daljem tekstu OKP) (1, 5, 6,7, 16) porernecaj paznje sa hiperkinetic­noscu (prema anglo-saksonskoj literaturiattention deficit hyperactivity disorderADHD) (1,6,7,8), poremecaji raspolozenja(bipolarni porernecaj i major depresivni po­remecaj) (10,14) i poremecaji iz shizofre­nog kruga (11,12,13). Ovaj rad ima za ciljda pokaze mogucnosti komorbiditeta TS saodredenim klinickim entitetima.

Etiologija TS se moze proucavati sa viseaspekta: genetskog, sredinsko-genetskog,preko uloge pol nih hormona, psihofarrna­ka, endogenih opijata i proucavanjem imu­noloskih faktora (1, 2, 26). Neuroimidzingmetodama pokazan je i neurobioloski sup­strat TS (17, 18, 19). U odnosu na rad ko­jim se bavimo proucavacemo detaljnije oneetioloske cinioce koji su bitni u objasnjenjukomorbiditeta ovog klinickog sindroma idrugih entiteta.

Studije blizanaca, adoptivne studije i stu­dije segregacione analize podrzavaju genet­ski aspekt etiologije TS. U vecini porodicaTS i hronicni tik poremecaji izgleda pratiautozomno dominantni model nasiediva­nja, sa razlicitim stepenima penetracije. Zamuski pol penetracija je gotovo kompletnakada se ukljuce svi tik porernecaji. Zazen ski pol penetracija raste sa 56% za tikporernecaje na 70% kada je ukljucen iopsesivno kompulzivni porerneca] (OKP)kao tip fenotipske ekspresije gena za TS (4,21, 25). Ova opservacija kao i porodicnaudruzenost OKP i TS postavila je teoriju daje OKP klinicki varijetet genetskog defekta(defekata) TS (1, 3, 5, 6, 30). Time smopredstavili i prvi najcesci komorbiditet iz­medu Tourettovog sindroma i opsesivnokompulzivnog poremecaja.

Studije blizanaca su pokazale da je konkor­danca TS kod monozigotnih blizanaca sta­tisticki znacajno visa nego kod kod dizigot­nih blizanaca. Najvisi rizik od oboljevanjaimaju sinovi majki obolelih od TS. U priIoggenetske osnove TS ukazuje visoki proce­netat komorbiditeta izmedu ADHD (pore­mecaj paznje sa hiperkineticnoscu) i TS sajedne strane i OKP i TS sa druge strane. Zaoba pomenuta klinicka entiteta postojejasni dokazi za genetsku etiologiju poreme­caja te 50% slucajeva sa TS se javlja u ko­omorbiditetu sa ADHD (5); u slucaju OKP40% pacijenata sa TS ima i OKP (5, 6, 7,20). Tako, poremecaj paznje sa hiperkine­ticnoscu predstavlja drugi najcesci komor­biditet Tourettovog sindroma.

Antagonisti dopamina kao sto su haloperi­dol, pimozid i flufenazin dovode do sman­jivanja ekspresije tikova u TS iz cega proi­zlazi hipoteza da povecano oslobadanjeDA, hipersentzitivnost DA receptora iiialteracija u striatalnom DA metabolizmumoze predstavljati neurohemijski supstratTS (5). Ispitivanjem efekata psihofararna­ka na ekspresiju TS ide u priIog hipotezi 0

disregulaciji u presinaptickoj DA funkcijiu TS. Na osnovu izlozenog mozerno pred­postaviti da svi poremecaji kod kojih mozedoci do disregulacije u dopaminskom sis­temu mogu biti u komorbiditetu sa To­urettov-im poremecajern (kao najpoznati­je pomenucemo shizofreniju, bolesti izshizofrenog kruga i s1.)

S druge strane, abnormalnosti u adrener-l'

gickom sistemu, koja se koriguje adrener- r<'l

8'gickim agonistima (klonidin) smanjuje os- globadanje NA u eNS i time konsekutivno ~

N

smanjuje aktivnost i u DA sistemu (18, 29, N

31). U odnosu na noradrenergicki sistem :@

komorbiditet Tourettovog sindroma i pore- ~mecaja raspolozenja (pre svega bipolarnih ~poremecaja i major depresivnih epizoda)moze pronaci svoje znacenje i mesto. 111

Farrnakoloske sup stance koje antagonizu­ju endogene opijate (naltrexon) smanjujuekspresiju tikova i povoljno resavaju pro­blem u odrzavanju paznje u TS (koji jezbog ranije pomenutih veza u komorbidi­tetu sa ADHD cesto prisutan u pacijenatasa TS) i time dokazuje i ulogu endogenihopijata u etiologiji TS (26).

Neurobioloski susptrat TS moze se poka­zati i neuroimidzing metodama (PET,SPECT) ciji nalaz u TS se opisuju kao:subtilne strukturne anomalije u predelubazalnih ganglija (redukcija volumena ba­zalnih ganglija) , redukcija volumena des­nog nco caudatusa, devijacije u normalnojcerebralnoj simetriji komora i nedostatakpeptida dinorfina u projekcionim vlakni­rna od strijatuma do globus-a palidusa(16, 17, 18, 23).

U odnosu na TS postoji siroka lepeza kli­nickih entiteta i sindorma koji se moguuzeti u razmataranje priIikom postavljanjadiferencijalne dijagnoze. Atetoidni tip ce­rebelerane paralize, dystonia musculorumdeformans, encephalitis lethargica, Halle­vorden-Spatz-ova bolest, Hungtintonovahorea, dr. tikovi koji se javljaju u detinjstvu,kao i habitualni spazmi, spasticni tortiko­lis, Status dysmyelinatus, Sydenhamovahorea, Wilsonova bolest i Lesh-Nyhan bo­lest su oni klinicki sindromi koji se razma­traju u diferencijalnoj dijagnozi. Treba do­dati svakako i direktan efekat specificnihsupstanci, pervazivne razvojne porernecaje,OKp, shizofreniju i epilepsiju (1, 3).

Neleceni TS predstavlja hronicno i dozivo-<;I<

~ tno oboljenje sa povremenim remisijama i8' egzarcerbracijama u svom klinickom toku.o~ Ono sto je svakako od velike znacajnosti

kako za razumevanje ovog porernecaja tako~ i za terapiju je da TS izaziva veliku emoci­g onalnu patnju pacijenta te da je stoga vazno~ proceniti nivo te emocionalne trpnje i sho-

dno tome modelirati terapijske postupke.

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Terapija

Tretman TS obuhvata primenu psihofar­maka kao i primenu odredenih oblika psi­hoterapije (pre svega bihejvioralne terapij­ske procedure). Opste prihvacen stay je daje psihoterapija manje efikasan metod le­cenja, pogotovo bez dodatne farmakote­rapije.

U farrnakoloskom tretmanu TS primenju­ju se sledece grupe medikamenta (28, 29,30, 31):

• neuroleptici: haloperidol- i to u nizirnterapijskim dozama nego sto je to po­trebno za bolesti iz shizofrenog kruga:incijalna doza je 0,25-0,5 mg a maksi­malna terapijska doza za TS je 3-4 mg!dnevno, efikasan u 80% sluqeva: pimo­zid - inicijalna doza je 1-2mg dnevno,doza odrzavanja je 0,2mg/kg IT; levo­promazin, hlorpromazin, promazin- se­dativni neuroleptici - u situacijama izra­zene iritabilnosti, agresivnosti, diskon­trole impulsa, agitacije.

• NA agonisti: klonidin- pozitivan terapij­ski odogovor je u 40-70% slucajeva.

• antidepresivi: i to SSRI (selektivni inhi­bitori preuzimanja serotonina) kao mo­noterapija ili u kombinaciji sa neurolep­ticima iii bupropion, antidepresiv ami­noketonske grupe.

• benzodiazepini: posebno je klonazepamkoristan u anksiolizi, liziranju opsesiv­nih i kompulzivnih manifestacija i pore­rnecaja spavanja.

Prikaz sluiaja

O. B. 33 godine, iz Beograda, hemijski teh­nicar, neozenjen, radi na poslovima kont­role kvaliteta proizvoda.

B. je roden iz rnajcine trece trudnoce, na­kon 7 godina lecenje steriliteta u rnajcinoj34. godini. Prve dye trudnoce su zavrsenespontanim abortusom u 2. mesecu. U pr­vom trimestru trudnoce je uzimala hor­monsku terapiju (testosteron i pronizon),

kompleksnih motornih tikova vrata, trupai leve ruke koji su kombinovani sa kaslju­canjem koji su datirali unazad 1 mesec.Objektivno osim opisanih tikova ostalinalaz je bio uredan. Kratkotrajno je treti­ran Haldolom i Orap forte (bez uvida uduzinu lecenja kao i primenjene doze).Uradena su i dopunska ispitivanja: 24 ca­sovni EEG holter, fenfluraminski test, ne­uropsiholosko testiranje kao i psiholoskotestiranje. Na Institutu za medicinu radaje uradena ekspertiza radi ispitivanja od­nosa izrazenih tikova i rada sa organskimrastvaracima. Zakljucak ekspertize je: Exs­positio solv. Org.; Sy Gilles de la Tourettei Neurosis. Indikovano da ne radi sa neu­rotoksicnim noksama; sposoban za drugeposlove.

Iz oskudne medicinske dokumentacije saz­najemo da je 1995. godine B. obavio NMRendokranijuma po predlogu neurologa;nalaz je opisan u prilog postojanja kortikoi subkortikalnih reduktivne promene uzumerenu redukciju cerebralnog parenhi­rna.

Aprila 1998. godine »ekosplodiralo je treceoko i vise normalan covek nije mogao daprezivi to stanje«. Sa pojavom »ezoterrnic­nog termina trece oko« pojavilo se udara­nje po cakrama (prema hindu religiji cakresu mesta izbijanja energije unutrasnjihorgana na covekovom telu tj. kozi) od ko­jih je bukvalno dobijao modrice, a kasnijei zadebljanja koze vidljiva golim okom.Prvi pokret je bio pokret leve ruke, fleksi-

'<t'rane u laktu kojom se udarao u predelu ~

leve slabine. Nakon toga je istom rukom u gistom polozaju poceo da se udara u pre- gdelu grudi (te udarce naziva »predator- ~

skim udarcima«). Noktima je vise puta ce­pao svoju majicu.

52~CJz

Pojavili su se glasovi, unutrasnji glasovi iii UJ

»u stvari jedan glas koji je imao sposob-nost metamorfoze« koji je imao sposob- 113

a celu trudnocu je odrzavala kod kuce, ug­lavnom lezeci. U 7. mesecu je prokrvarila,ali je krvarenje spontano stalo i od tada jeneprekidno lezala. Porodaj je bio u 9. lu­narnom mesecu: karlicna prezentacija, pro­longiran, pupcanik oko vrata tri puta oba­vijen. Zbog tezeg stepena zutice u poro­dilistu su ostali 10 dana duze.

U 8. godini zivota su mu se pojavili tikovi,koji su spontano prestali za godinu dana.Tikovi su bili u predelu usta - kao gric­kanje zeca (Rabbit sy). Nisu se obratili zapomoc strucnim sluzbama. Nakon toga sevise nisu pojavljivali do pocetka bolesti.

U vise navrata hospitalizovan u okviru ne­uroloskih i psihijatrijskih sluzbi.

Ovom prilikom na psihijatrijski tretmanprimljen zbog tikova, psihickog zamora,nesanice, gubitka apetita, prisustva »bro­jnih sugestija« u vidu glasova koji su munaredivali kako i sta da cini u odredenimsituacijama, prisustvo strahova bez real­nih pokazatelja za iste i povremeno nekon­trolisano i impulsivno ponasanje.

Bolest pocinje 1989., u pacijentovoj 23.godini zivota, pojavom trzaja levog rame­na koji su se provocirali napetoscu, Zatimse javljaju spazmi koje opisuje kao kocenjeruku pri radu, a nesto kasnije se i kaslju­canje, povremeno gubici daha i s1.

Uporedo sa pojavom nevoljnih radnji poja­vila se i intenzivna napetost u svim soci­jalnim okruzenjirna - povukao se iz drust­va: do tada druzeljubiv i veseo mladic po­stao je prznica, gundalo, osobenjak i sa­motnjak. Pravdao se da su mu svi dosadni,da je sve oko njega isto, da ne moze vise daslusa kafanske isprazne price i ostalo. Tadase pojavilo klacenje celog tela, narocito usedecern polozaju sto je konacno i samogB. pokrenulo da potrazi pornoc od lekara.

Tada je usledila prva hospitalizacija naInstitutu za neurologiju. Primljen je zbog

NN

nost »da menja zvucnost i uduvava suge­stiju u glavu iii stomak« od cega je on sub­jektivno osecao da mu »puca glava« iii kaomucninu u stomaku i gadenje prema hra­ni. Imao je osecaj kao da su mu slusalicena usima ida od buke tih glasova ne mozenista da cuje. Zbog pojave unutrasnjih gla­soya samoinicijativno je poceo da uzimaenormne kolicine vitamina B.

Tri meseca pred prijem poceo je da inten­zivno upotrebljava uzasno ruzne reci maj­ci, a znao je da izade na terasu i da na sayglas psuje kornsije, njihovu decu i ostale.Mesec dana pred prijem na psihijatrijskoodeljenje komsije su ga prijavile milicijizbog buke koju je izazvao u stanu urlajucina majku, sa terase i razbacujuci stvari pokuci.

Somatski nalaz pri prijemu: uredan;

Neuroloski nalaz pri prijemu: na kranijal­nim nervima obostrano troma i jedva pri­metna reakcija zenice na svetlost (simetri­cno), Pri protruziji jezika nevoljni pokretikoji imponuju kao horeaticni (diskinezije)u miru se potpuno kupiraju. Ostali nalazuredan osim blage hipertrofije levog ster­nocleidomastoideusa.

Psihicki status na prijemu: Neurednog izapustenog spoljasnjeg izgleda sa upadlji­vim, brojnim i cestim motornim i vokal­nim tikvima. Prisutni su sledeci tikovi:slozeni motorni tikovi u vidu pokreta he­mibalizma u predelu desnog ramena, za­tim sitni pokreti prstima leve ruke sa do­dirivanjem predela brkova i brade, kao i

<t' vokalni prosti tikovi u vidu zakasljavanjarJ, odnosno stucanja, Komunikacija se lako§' uspostavlja, odrzava uz podpitanja, neo2!- produbljuje spontano. Govori tesko ra-

zumljivim glasom - reci su mu cesto sli­~ vene, nazalni govor upadljiv, podrazumeva~ zavrsetak recenice, te ih vrlo cesto ne za­orE vrsava. Reakciono vreme odgovora nije pro-

duzeno.

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Svesnost ocuvana, pravilno orjentisan usvim modalitetima. Prisutni su manifestnifenomeni depresonalizacije i derealizacijekoje ne mogu jasno da se izdiferenciraju uodnosu na perceptivne fenomena.

Prisutni su auditivni perceptivni fenomenisa karakteristikama imperativnosti, repe­-titivnosti i nametanja u vidu »unutrasnjihi spoljasnjih glasova ili jednog glasa kojiima sposobnost metarmofoze, telepatije isugestije«,

Misaoni tok povremeno prekida bez jasnihrazloga, ali ne po tipu misaonog bloka, veekao da se podrazumeva nastavak. Povre­meno prisutna bujica ideja koja ima izgledlogoreje kao i nekonfluentnost misli. Pri­sutne paranoidne sumanute ideje haluci­natornog i intuitivnog mehanizma nastan­ka sa elementima ksenopatije a po temiideje odnosa, telepatije, sugestije.

Ne evidentiraju se kvantitativni poreme­caji pamcenja, a per anamnesis navodideja vu i jamais vu fenomene, koji ne mo­gu da se izdiferenciraju u odnosu na pro­duktivne psihopatoloske fenomene.

Fond znanja iznad proseka, ocuvana spo­sobnost apstraktnog misljenja, sa naruse­nim mehanizmima zakljucivanja pogotovovezanim za sopstvenu bolest i stanje.

Negativno polarisana hipertimija kao od­raz dugotrajnog prisustva opisane simpto­matologije (tikova). Anksiozan narocitopri intenziviranju pokreta. Prisutna inici­jalna i tranzitorna insomnija uz poremecajciklusa spavanja i budnosti i skracenjaukupne kolicine spavanja. Pad libidinalnihnagona. Negira suicidalne ideje. Kritican,sa delimicnim uvidom u svoje stanje, rela­tivno motivisan za lecenje. Vrednosni sis­tern nije narusen, dosledno se pridrzavadrustvenih normi do stepena ugrozavanjasopstvene licnosti, Socijalno adaptiranomoralno misljenje.

115

ZakljucakPored dobro poznatih klinickih entitetakoji se najcesce javljaju u komorbiditetu saTS (OKP i ADHD) ovim radom smo zelelida podsetimo i pokazemo komorbiditet TSsa oboljenjima iz shizofrenog kruga.

Zajednicke karakteristike shizofrenije i TSsu sledece: obsesivno kompulsivni simp­tomi, poremecaji pokreta po tipu motor­nih streotipija i porernecaji dopaminer­gickog sistema u CNS. Zajednicko ovimporemecajima je i terapijski pristup - le­kovi izbora su neuroleptici.

Medutim, ovako pojednostavljen pristup idalje ostavlja dilemu 0 mogucem komor­biditetu shizofrenije i TS i to iz vise razlo­gao Pre svega, genetska transmisija TS jeprakticno autozomno dominantnog tip a(kod shizofrenije nije definisana ali u sva­kom slucaju nije kao kod TS). Kod TS pri­mena incizivnih, selektivnih antidopami­nergika, za razliku od shizofrenije, je umalim dozama, sto upucuje na ukljuce­nost sasvim razlicitih doparninergickihmehanizama u etiopatogenezi, posebno usvetlu slozenog meduodnosa dopamins­kog i serotoninskog sistema. Sumirani se­rotoninski efekti na dopaminski sistem suinhibitorni (34). Pretpostavljena hipose­rotonergija (najcesce vezivana za OKP iafektivne poremecaje), potkrepljena pozi­tivnim efektom SSRI u lecenju TS (kon­traindikovani kod produktivnih formi shi­zofrenije) ide u prilog tezi 0 presinaptickojdopaminskoj disregulaciji. U tom slucajuje aplikovanje vecih doza (postsinapticka !blokada) selektivnih antidopaminergika §(02 blokatori - incizivni neuroleptici) &kontraproduktivna, sto je i klinicki najce- ~

see slucaj. ~

Stoga smo misljenja da u slucajevima TS ~zsa produktivnom psihoticnom simptoma- w

tologijom istu smatramo kao shizofreni­formni poremecaj (shizofreniformne ma-

Na osnovu ICD 10 kriterijuma kao i DSMIV postavljena je dijagnoza: Gilles de laTourette-ov sindrom i Shizofrenifomni po­rernecaj i ordinirana terapija: Nozinan, tbl.a 25 mg 1+1+2, Haldol, tbl a a 2 mg1+ 1+0, Rivotril 1+ 1+ 2 mg i Bensedin,amp a 20 mg p.p.

Sprovedena su sledeca dopunska ispitiva­nja laboratorija, pregled krvi i urina na ba­kar (Cu), EEG, neurooftarnoloski pregled,psiholosko testiranje.

Rezultat psiholoskog testiranja zakljucujeda se radi 0 osobi prosecnog nivoa intelek­tualnog funkcionisanja, ali primarno ne­zrelog kognitivnog aparata (organski de­ficit), a sekundarno sa snizenjem intelek­tualne efikasnosti po psihoticnom tipu(dominira visoka anksioznost).

Kao dominantno podrucje problema seizdvaja afektivitet, koji je lose kontrolisani modulisan i vrsi upliv na misljenje, kojepostaje dezorganizovano i inkonzistentno.

U odnosu na skromne potencijale i kapa­citete licnosti prikazani pacijent ima viso­ke aspiracije, sto konstantno stvara osecajneuspesnosti i manje vrednosti. To doziv­ljava kao stres (unutrasnji), sto mu uma­njuje efikasnost u funkcionisanju i cini gaimpulsivnim i sklonim dezorganizaciji.

Misljenje mu lako postaje dezorganizova­no, a karakterisu ga perceptivne netacno­sti, sto vodi do problema u testiranju real­nosti.

Tok bolesti: Ubrzo nakon primene malihdoza neuroleptika doslo do poboljsanja uklnickoj slici (za 7. dana) redukcija motor­nih tikova, nestajanje perceptivnih pore­rnecaja, poboljsanja spavanja.

Subjektivno se osecao bolje, nema unu­trasnje glasove ali i dalje veruje u njihovopostojanje.

116

nifestacije u sklopu TS ili komorbiditet­no), a ne kao komorbiditet TS i shizofre­nije kao entiteta.

Shizofreniformni porernecaj ima gotovoidenticnu klinicku sliku sa shizofrenijom,ali simptomi traju najmanje I mesec, a naj­duze 6 meseci (kod shizofrenije je naj­manje 6 meseci potrebno da budu prisut­ni neophodni dijagnosticki kirterijumi dabi se postavila dijagnoza) i prognoza pore­mecaja je znatno povoljnija u odnosu nashizofreniju. Osnovni pozitivni prognos­ticki znaci su: nagao pocetak bolesti (stoje prikazano i ovim slucajem), zatim slabi­je naznacen stepen kognitivnog ostecenja

(sto je potvrdeno psiholoskim testira­njem), dobro premorbidno funkcionisanje(sto kod naseg pacijenta nije bio slucaj sobzirom na postojanje TS) kao i odsustvodefekta afektiviteta. Prisustvo afektivnesimptomatologije se u prikazanom slucajuposmatra kao pozitivan prognosticki znak.

Smatrali smo znacajnim da podsetimo ipodvucerno da brojni klinicki entiteti iduzajedno jedan sa drugim i da se njihoveklinicke slike preklapaju, nadopunjuju imesaju. S toga je znacajno da se zadrzi kli­nicka senzitivnost i radoznalost u cilju stobolje i kompletnije pomoci nasim pacijen­tima.

GILLES DE LATOURETTE SYNDROMEAND POSSIBLESPECTAR OFCOMORBIDITY

Milica Pejovic Milovancevic 1

Dragan Marinkovic 2

Miroslava jasovic-Gaiit»Vesna Matovic 2

] Institute of Mental Health, BelgradeInstitute of Psychiatry,Clinical Centre of Serbia, Belgrade

Summary: Gilles de la Tourette syndrome is one ofthe best model for neuropsychiatric disorders ­essential transit among psychiatry and neurology.Abundant clinical symptology is divided on motor,vocal and behavioral manifestation. The most fre­quently comorbidity with TS have the following dis­orders: obsessive compulsive disorder, attentiondeficit and hyperactivity disorder, mood disorders(bipolar disorder and major depression) and psy­chotic disorders. The purpose of this article is toshow possible comorbidity between TS and other cli­nical entities. METHOD We present the case reportwith Gill de la Tourett syndrome in cornorbidity withschizophreniform disorder. RESULT The commoncharacteristics between schizophrenia and TS are:obsessive-compulsive symptoms, movement distur­bance such as motor stereotypes and disturbance ofdopaminergic transmission in central nervous sys­tem. Those two disorders have similar terapeuticalprocedure - the first choice medicaments are neu­roleptics. We also analyze the reasons why we whenchallenged TS with psychotic features analyze thecommon picture as a shizophreniform disorderrather then as comorbidity between TS and schizo­phrenia. CONCLUSION We find important to re­mind that many clinical entities overlap betweeneach other in clinical signs and that holistic approachin treatment should be always followed.

Key words: Tourette syndrome, shizophreniform di­sorder, comorbidity.

Introduction

Tics are involuntary, rapid, repetitive andstereotyped movements of individual mu­scle groups. They are more easily recog­nized than precisely defined. Tics disordersare generally categorized to age of onset,duration of symptoms, severity of symp­toms and the presence of vocal and/ormotor tics (l, 2, 3).

Gilles de la Tourett syndrome is one of thebest model for neuropsychiatric disorders- indispensable bond between psychiatryand neurology.

One of the first explanation of motor tics,echolalila and coprolalila is given by theFrench neurologist from nineteen centuries

Jean-Marc Itard (32). His patient, the Fre­nch nobles Marquise de Dampierre in herseven manifested the motor tics and soonafter the involuntary vocalization in formof southing. Few years lately she got copro­lalia. She suffered from this disturbancesuntil her death in eightyfive. Fifty yearslately Gilles de la Tourette presented few ~

I

cases with similar simptomatology (includ- r<)

Sing the Marquise de Dampierre's case in gher lattes) and defined the new clinical ~

N

entity (33). The leading European neurolo- N

gist in that time, Jean Martin Charcot, ~Tourett's supervisor in Salpetriere Hospital ~in Paris, 1880 added the name of his stu- ~dent to mentioned syndrome and separa-ted this entity from Sydenham chorea. 117

Tourette syndrome (TS) appears between2 and 15 (the median age at onset is 7years) and the main characteristics aremultiple, rapid, stereotyped and involun­tary motor and vocal tics. According to theTourette Syndrome Association, whichwas established in 1972, this clinical enti­ty develops before 21, most commonly be­tween 5-18 age. There are two basic prob­lems in definition of syndrome: the casesthat appear after 21 and the »willingness«,because some patient explain their move­ments as the way to decrease the tension.The prevalence is 0.3(0.8) - 0.5 (4.5) per1000 population (3,4).

CLINICAL FEATURES OFGILLES DE LA TOURETTESYNDROME

Reach symptomatology of clinical expres­sion is divided at motor, vocal and beha­vioral manifestation.

Motor manifestations

simple motor tics: rapid and unreasonable(eye blinking, facial grimacing, nose tou­ching, neck jerking, shoulder shrugging,coughing, deep knee bends, hopping)complex motor tics: they could be retard­ed or they can consist of stereotypical seri­al of motor tics (touching the objects, selfor others, twisting, »distonical« posture ofbody, grooming behaviors, jumping, touc­hing, stamping and smelling at objects,etc. Corpopraxia - touching of genitalia

l' and other obscene gestures-sfliving ther<')

0' finger«: Echopraxia - the imitation ofoo other gestures and movements).!::!-NN

:@ Vocal manifestations

~ simple vocal tics: purposeless sounds (co­@ ughs, clicks, grunts, barks, sniffs, snorts,

yelps)

118

complex vocal tics: telling the words orphrases with sense, repeating words orphrases more then three times, vocalabnormalities: unusual rhythm, tone,accent, Coprolalia-the uttering of obsceni­ties; Echolalia - repetition of phonemes,words or the part's of words; Palilalia­involuntary repetition of a patient's ownphrases or words.

Behavioral manifestation

Obsessions, compulsions, emotionallabil­ity, irritability, impulsiveness, aggressive­ness and self-injures, learning disabilitiesand social withdrawal are some of behav­ioral manifestations.

The course of clinical expression change(symptoms could exacerbated, attenuatedor change), and tics could be suppressed orcontrolled for the short time period (usingpatient concentration or being occupied byother job). This suppression of tics lead totension expansion and again appearance oftics. Symptoms usually disappear duringsleep or orgasm, but TS has chronicle cour­se and it is life long disorder (1, 5).

Confirmatory but not the basic symptomsfor the diagnosis are: coprolalia, copropra­xia, echopraxia, echolalia, palilalia (palico­prolalia) and palipraxia (7, 8, 9). Usuallyassociated but not confirmatory for thediagnosis are: early hyperkinetic disorderas well as attention deficit hyperactivitydisorder (6); unspecific EEG; soft signsduring neurological examination and sub­tle signs of organic dysfunction duringpsychological examination (10).

COMORBIDITY OF GILLES DELA TOURETTE SYNDROME

Comorbidity is tacitly defined as one ormore psychiatric conditions existing at thesame ,time. However, no mention is made

whether these disorders emerge specifi­cally at the same time or in sequentialorder. In analyzing the comorbidity spec­ter due to Gilles de la Tourette syndromein the literature following disorders arerecognized: Obsessive-compulsive disor­der (OCD) (I, 5, 6, 7, 16) attention deficitand hyperactivity disorder (ADHD) (I, 6,7, 8), mood disorders (bipolar disorderand major depression) (10, 14) and otherpsychotic disorders (11, 12, 13). The pur­pose of the following article is to analyzethe possibilities of comorbidity betweenTS and other clinical entities.

Etiology of TS could be investigated fromdifferent perspectives: genetic, environ­mental-genetic, the role of gender hor­mones, psychopharamcs, endogen opiatesand by examination of imunoligical factors(1, 2, 26). In vivo neuroimaging studieshave provided some clues about neurobio­logical substrate of TS (I7, 18, 19). Wewould analyze those etiological factorsthat are important in understanding thecomorbidity between TS and other clinicalentities.

Twin studies, adoption studies and segre­gation analysis studies have all support agenetic etiology for Tourette's disorder. Inmost families, TS and chronic tic disordersseem to follow an autosomal dominantpattern of inheritance, with varying de­grees of penetrance. For males, penetranceis nearly complete when all tic disordersare included. For females, penetrance in­creases from 56% for tic disorders to 70%when OCD is included as a part of the phe­notypic expression of the TS gene(s) (4,21, 25). This observation and the familialassociation of OCD and TS have led to thetheory that OCD is a clinical variant in theexpression of the TS genetic defectts) (I, 3,5, 6, 30). This assumption also representthe first and most common comorbidity ofTS and OCD.

Twin studies have reported concordancerates statistically significant more for TSin monozigot twins compared with dizy­gotic twins. The sons of mothers with To­urette's disorder seem to be at the highestrisk for the disorder. According to thegenetic factor in the etiology ofTS there ishigh percent of comorbidity betweenADHD and TS at one side and OCD andTS on the other. For both mentioned clin­ical entities there are clear evidences forgenetic etiology and in that sense 50% ofTS patients have also ADHD (5); in thecase of OCD 40% of patients with TS havealso OCD (5, 6, 7, 20). ADHD is the sec­ond most frequent comorbidity due to aTourette syndrome.

Pharmacological agents that antagonizedopamine - haloperidol, pimozide and flu­phenazine suppress tics in TS and leads tothe hypothesis that increase release of do­pamine (DA), hypersensitivity of DA oralteration in striatum DA metabolismcould present the nerochemical substrateof TS (5). Exploration of the effects thatpsychopharmacs have at TS expressionlead to the hypothesis about disregulationin presynapthic DA function as one of thefactor in the etiology of TS. We can as­sume that every disorders that have dis­regulation in DA metabolism could be inconceivable comorbidity with TS.

On the other hand, abnormalities in thenoradrenergic systems have been impli­cated in some cases by the reduction of l'tics with clonidin. This adrenrgic agonist ("()

areduce the release of norepinephrin in the gcentral nervous system and thus may !::!.

N

reduce activity in the dopaminergic sys- N

tern (I8, 29, 31). According to this system S§comorbidity between TS and mood disor- ~ders (first of all bipolar disorder and major ~depression) could find its place in furtheranalysis. 119

Endogenous opiates may be involved in ticdisorders and obsessive-compulsive disor­der. Some evidence indicates that pharma­cological agents that antagonize endoge­nous opiates, for example naltrexon redu­ces tics and attention deficit's in Tou­rette's disorder patients (26).

Neurobiological substrate of TS could beprovidede in vivo by analyzing the neuro­imaging studies (PEl: SPECT). Focusingmainly on the basal ganglia, such studieshave found preliminary evidence of subtlestructura; abnormalities in this region.There are: reductions in regional basalganglia volumes, statistically significantreduction in right caudate nucleus vol­ume, and more consistent deviations innormal cerebral asymmetries of ventriclesand basal ganglia (16, 17, 18, 23).

TS must be differentiated from other dis­ordered movements and the neurologicaldiseases of which they are characteristics.They are cerebral palsy atetoid type, dys­tonia musculorum deformans, encephali­tis lethargica, Hallevorden-Spatz disorder,Hungtinton chorea, and other tics disor­der that could appear in childhood as wellas habitual spasms, spastic torticolis,Status dysmyelinatus, Sydenham's chorea,Wilson's disease and Lesh-Nyhan's dis­ease. We should also mention the directeffect of a substance, pervasive disorders,OCD, schizophrenia and epilepsy as possi­ble differential diagnosis (1, 3).

Untreated TS is usually a chronic, lifelongdisease with relative remissions and exac-

1" erbation's in its course. Severely affectedr-<)

8 people may have serious emotional prob-8 lems and it is important to understand the~N level of suffer of this patients in workingN

~ with them as well as in pharmacological~ treatment.ozU.l

120

'ITeatment

Pharmacological treatments are mosteffective for TS but some patients may notrequire medication and psychotherapymay help them in coping with the disor­der's symptoms (the first choice psycho­therapy is behavioral therapy. Psychothe­rapies are usually ineffective as a primarytreatment modality.

In pharmacological treatment the follow­ing medications could be used in TS (8,29, 30, 31):

neuroleptics: haloperidol - in less thera­peutical doses comparing to that doses weare use in schizophrenia treatment: theinitial daily dosage is usually between0,25-0,5 mg and the maximal effectivedosage is often in then range of 3-4 mg aday. Up to 80% of patients have a favo­rable response; pimozide - the initialdosage is 1-2mg daily in divided doses,and most patients are maintained at 10mg a day (0.2 mg/kg a day); levopro­mazine, hlorpromazine, promazine - seda­tive neuroleptics - are often use in thosecase where irritability, aggressiveness, agi­tation and weak impulse control are pro­minent symptoms.

NA antagonist: clonidine - 40-70% ofpatients benefited from the medicationantidepressants: SSRI (serotonin-specificreuptake inhibitor) have been useed aloneor in combination with antipsychotics orwith bupropion, an antidepressant of theaminoketone class.

Benzodiazepines: especially clonazepam isuseful in as an anxiolityc, and for the ob­sessive and compulsive manifestation andsleep disturbances.

121

His first hospitalization was at Institutefor neurology. He was hospitalized beca­use of existence out of complex motor ticsof neck, chests and left arm which werecombined with coughing that persisted amonth. Objectively, except the mentionedsymptoms the whole mental and physicalstate was regular. He was treated for shorttime with haloperidol and Orap forte, butthere are no evidences for how long andwith what doses. He also committed someextra medical procedures: EEG holter,phenphulraime test, neuropsychologicaltest and psychological test. At Institute forworking medicine he took the expertisetest to explore the influence of organicsolvents on the appearance of tics. Theconclusion is: Exspositio solv. Org.; SyGilles de la Tourette et Neurosis. It wassuggested to stop working with organic !solvents but he was capable for other jobs. §'

o~From poor medical documentation we fo-N

und that during 1995. B. conducted the N

NMR of endocranium after his neurologist ::gsuggested that: the report consists of cor- ~

Ztical and subcortical reductive changes UJ

with moderate reduction of cerebral vol­ume at all.

described as stiffening the hand while wor­king, and soon after he started to coughwith occasionally breath taking.

At the same time he started to feel inten­sive tension in all social situations - hewithdrawal from the friends: he wasknown as very friendly and happy person,but when illness started he became grum­bler, complainer, crank and secluded. Hejustify himself that friends are boring, thateverything is same around him for a yearsand that he cannot stand anymore simpleand boring stories. In that time he startedto loaf the whole body, especially in sittingposition ant that was the final reasonwhich moves B. to ask for the medical help.

Case report

O. B. 33 years old, form Belgrade, chemi­cal technician, unmarried, working onproductions' quality control in one firm.

B. is born form third mother pregnancy,after 7 years of sterility treatment inmother's 34. First two pregnancies endedas miscarriage in second month. In firsttrimester of pregnancy patient's motherwas taken hormonal therapy, and duringpregnancy she was at home, not working,mostly in bed. In seventh month of preg­nancy mother had an uterus bleeding,which spontaneously stopped in few dayslately. After this episode she was lying inthe bed until the delivery. The deliverywas at the time, in 9. month: pelivicalpresentation, prolonged, umbilicus wasaround the baby neck. Baby had strongerneonatal icterus then usually, so both ofthem stayed a little bit longer in hospitalthan was expected.

The first tics appear in his 8 and theyspontaneously stopped in a year. They we­re located around the mouth - Rabbit syn­drome. He and his parents did not askedfor a help any professional services. Untilthe new relapse, that we here present, hedid not have any episode with tics.

He was hospitalized several times at diffe­rent neurological and psychiatric services.

This time he was accepted at psychiatricdepartment because of tics, psychical ex­haustion, insomnia, loss of appetite, pres­ence of »many suggestion« in the form ofvoices which command him what to do incertain situations, presence of fears with­out logical reasons and periodical uncon­trolled impulsive behavior.

The present illness started at 1989, in pa­tient's 23, with appearance of left shoulderjerk which were been provoked by tension.After this he gained spasms which were

In April 1998, »the third eye exploded andnormal man could not survive the presentcondition«. With appearance of »the eso­teric term third eye« he started to kickhimself at »Ischackre« (according to theHindu religion tschackre are place at theskin where energy form the internal organis presented) and many bruises and laterskin callosity were indications easily rec­ognized by regular checking. First movewas the one with left arm, which was ban­ded in elbow and with whom he was kic­king in the left part of the chest.

He also started to experience the differentkind of voices or »one voice which has thecapability of metamorphosis and couldblow the suggestion in my head or sto­rnach«. Because of that he has the feelingthat his head would explode or has somestomach nausea and disgust toward thefood. He also had a feeling that he had theearphones and that noise produced bythem made impossible to hear anything.He started to treat himself by taking theenormous quantity of vitamin B.

Three months before the hospitalizationhe started to use obscene words usually inhis mother presence, and he also startedto use them at the balcony usually direct­ed to his first door neighbors. Once, theneighbors alarmed the police because ofnoise.

Somatic state: no evidences of any distur­bances.

Neurological state: at cranial nervous at"1 both sides slow reaction on light. Whiler<)

o protrusion of the tong he had some stern­oo oc1eidomastoideusa. No evidences of any~N other disturbances.N

~ Psychical state: Untidily and uncared ap­g pearance, with presence of many tics, mo­~ tor and vocal. He has: complex motor tics

in left shoulder region in form of cherni-

122

balism; in the region of left hand he hassmall movements in form of touching themoustache and bear, as well as simple vo­cal tics in form of coughing or hiccuping.Communication could be easily started,maintained with extra questions, but co­uld not be deepened spontaneously. Hespeaks with hardly recognized voice ­words are confluent, he has nasal speech,and usually does not finish the sentence.The reaction time for answering is notprolongate.

Conscious sustained, adequately orientedin all modalities. He has depersonalizationand dereralization phenomena whichcould not be clearly distinguished fromperceptive phenomena.

He had auditory perceptive phenomenawith characteristics of imperative, repeti­tive and forced voices in form »internaland external voices or one voice which hadcapability of metamorphosis, telepathyand suggestion«,

Thinking process in form has blocking pe­riod when patient has abrupt interruptionin train of thinking before a thought or ideais finished. Form time to time there wereevidence of loosening of association, logor­rhea or incoherence. In content of thoughthe had paranoid delusions which originateby hallucinations or intuition with ele­ments of xenophobia; delusions of referen­ce, telephatia and suggestion.

There were no evidence of qualitative me­mory disturbance, but per anamnesis hementioned deja vu and jame vu phenome­na, which could not be well differentiatedfrom productive psychopathological phe­nomena.

He had well developed education level, hisabstract thinking was preserved but hehad problems in deduction especially inthose areas close to his illness and presentcondition.

He had depression, probaly as a resultlong lasting tics. He had irritable moodespecially it is easily provoked to tics. Hehad inicial and transitory insomnia withdisturbance of sleeping process with shor­tening of totoal hours spent at sleep. Hehad diminished libido and he deny suici­dal ideation. He was partial indulgence inhis condition and was relatively motivatedfor the treatment.

According to ICDIO criteria as well asDSMIV criteria he got the following diag­nosis: Gilles de la Tourett syndrome andschizophreniform disorder and he wastreated with following medications:levopromazine (Nozinan), tbl. a 25 mg1+1+2, haloperidol (Haldol), tbl. a 2 mg1+ 1+ 0, clonazepam (Rivotril), tbl. 1+1+2 mg and (diazepam), amp a 20 mgp.p.

We took following extra diagnostical pro­cedures: blood and urine analysis, EEG,neuroophtamoliogical examination andpsychological testing.

Results of psychological tests concludedthat our patient was average intellectualfunctioning, with primary immaturity ofcognitive functioning and secondary, dueto an illness and psychotic decompesa­tion, intellectual deprivation especially itsefficacy (he also had high anxiety).

As a main problem of his functionig isaffective area which is poorely controlledand was modulated disorgasnized andinconssitent thinking processes.

This patient had high personal aspirationbut because of his dissabilities he had per­sonal feeling of law valusness and capabi­lities. Because of that he had constant in­ternal stres which enabled him in efficaslyfuncitionig and made him immpulsive anddisorganized.

His thinking easilly became disorganizedand is charactarized by perceptive incorec

and lead him to the problems of realitytesting.

Course of illness: Soon after application ofsmall doses of neuroleptics he improved(less than seven days) and had less motortics, diminishing of perceptive disturbanceand less sleeping problems.

Subjectively he felt better, with no internalvoices but he still believed that those voic­es had excited.

Conclusion

With this article we wanted to remind andrepresent the comorbidity between TS andschizophrenia like disorders beside wellknown comorbidity between TS on oneside and OCD and ADHD on the other.

Common characteristics between schizo­phrenia and TS are: obsessive-compulsivesymptoms, movement disturbances inform of stereotypes and disturbance in DAsystem in the central nervous system. Mu­tual to this two entities is also the treat­ment procedure-the first choice medica­ments are neuroleptics.

But, this simplistic attitude still open thedilemma about the reason for comorbiditybetween schizophrenia and TS because ofmany reasons. First of all, genetical trans­mission in TS is almost always autosomaldominant type (in case of schizophrenia isnot jet clearly defined). In TS we use inci­sive, selective neuroleptics in smallerdoses than in schizophrenia which could l'lead to the conclusion that some other DA r<")Ssystem differed from those involved in g

~schizophrenia etiopathogenins are invol- N

ved in TS's etiology. Looking form the DA- N

serotonergic system which has its place in ~complicated etiology of schizophrenia we 0zcould also analyze the effects of this rela- u.l

tion in etiology of TS. The serotonineffects at DA systems are inhibitory (34). 123

-e-I,....,

0'oo~NN

124

Suggested hyperserotonaemia (usuallyconnected to oeD and mood disorders)and positive effect of SSRI in treatment ofTS conform to presynapthic DA disregula­tion. In that case, application of selectiveantidopaminergics in higher doses (D2blockers - incisive neuroleptics) is unde­sired, which is always the case in clinicalpractice.

Because of that we reflect that in cases ofTS with productive symptomatology thesame situation we considered as shizo­phreniform disorder (scnizophreniform'manifestations in TS or comorbidity) andnot as comorbidity between TS and schiz­ophrenia as the entity.

Schizophreniform disorder is identical toschizophrenia except that its symptoms

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