Demenca z Lewyjevimi telesci Klinična slika in diagnostični kriteriji Lewy body dementia Clinical picture and diagnostic Criteria
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1 Demenca z Lewyjevimi telesci Klinična slika in diagnostični kriteriji Lewy body dementia Clinical picture and diagnostic Criteria Izvleček Demenca z Lewyjevimi telesci je bolezen, ki jo uvrščamo med sinukleinopatije oziroma tiste bolezni, pri katerih gre za patološko odlaganje sinukleina. Demenca z Lewyjevimi telesci je drugi najpogostejši vzrok nastopa demence pri starejših. Klinična slika demence z Lewyjevimi telesci lahko zajema v poljudni kombinaciji kognitivni upad, raznolike psihiatrične simptome, ekstrapiramidne znake, motnje spanja in okvaro avtonomnega živčevja. Zaradi očitne heterogenosti klinične slike je stroka potrebovala vrsto let za izdelavo kliničnih diagnostičnih kriterijev slednji so danes zadostni za uspešno postavitev klinične diagnoze demence z Lewyjevimi telesci v večini primerov. Abstract Dementia with Lewy bodies belongs to synucleinopathies since its pathological hallmark is considered to be the aberrant accumulation of synuclein. Dementia with Lewy bodies represents the second most common cause of dementia among the elderly. Clinically, dementia with Lewy bodies encompasses a random combination of cognitive, psychiatric, extrapyramidal, sleep and autonomic dysfunctions. As a result of this clear clinical heterogeneity the experts needed several years to develop suffi cient clinical diagnostic criteria these are today succeful in clinically diagnosing dementia with Lewy bodies in a vast majority of cases. Demenca z Lewyjevimi telesci je med pogostejšimi boleznimi, ki povzročajo demenco, verjetno zadnja, ki smo spoznali, navkljub temu da je F. Lewy pod mentorstvom A. Alzheimerja opisal patološko kopičenje njemu neznane snovi kot telesca znotraj živčnih celic v substantii nigri umrlega s Parkinsonovo boleznijo že leta Prvi opis demence z Lewyjevimi telesci je verjetno podal že J.-M. Charcot, saj se v nasprotju z J. Parkinsonom pri njegovih bolnikih s Parkinsonovo boleznijo omenja zgodnji kognitivni upad, in to več kot 100 let pred Lewyjevim odkritjem kopičenja njemu neznane snovi znotraj živčnih celic. Po tem odkritju je ponovno sledilo zatišje, in sicer do
2 60. let prejšnjega stoletja, ko je več zdravnikov in znanstvenikov iz Japonske v več objavah poročalo o prisotnosti Lewyjevih telesc pri umrlih bolnikih z demenco, halucinacijami in parkinsonizmom. V 80. letih prejšnjega stoletja so prikazali ubikvitin znotraj Lewyjevih telesc, v istem obdobju je bil odkrit sinuklein, katerega transkript se je značilno proizvajal le v obdobju učenja petja ptičev. Sledita opisa beljakovine, imenovane neamiloidna komponenta senilnih leh, in tik za tem prikaz Lewyjevih telesc pri Alzheimerjevi bolezni, kar je botrovalo objavi morebitne Lewyjeve oblike Alzheimerjeve bolezni. V 90. letih prejšnjega stoletja je bilo ugotovljeno, da je sinuklein glavna patološko kopičena beljakovina znotraj Lewyjevih telesc in da so mutacije gena za sinuklein zadostni vzrok za razvoj nekaterih dednih oblik Parkinsonove bolezni. V istem obdobju so bili objavljeni prvi klinični diagnostični kriteriji za postavitev diagnoze demence z Lewyjevimi telesci, ti kriteriji poudarjajo predvsem kombinacijo kognitivnega upada, halucinacij in parkinsonizma (1). V zadnjem desetletju so raziskave Lewyjevih telesc ugotovile, da je beljakovina neamiloidne komponente senilnih leh sinkulein, da je ob Parkinsonovi bolezni in demenci Lewyjevih telesc tudi multipla sistemska atrofi ja sinukleinopatija, objavljeni so bili že četrti klinični diagnostični kriteriji za postavitev diagnoze demence z Lewyjevimi telesci. Danes vemo, da je demenca z Lewyjevimi telesci drugi najpogostejši vzrok razvoja demence pri starejših od 65 let, pri mlajših je ta bolezen mnogo redkejša. Klinično se demenca z Lewyjevimi telesci kaže v poljudni kombinaciji kognitivnega upada, ekstrapiramidnih znakov, motenj spanja in okvare avtonomnega živčevja. Glavne značilnosti kognitivnega upada pri demenci z Lewyjevimi telesci so nihanja pozornosti in izvršilnih sposobnosti, pogosto je prisotna abulija oziroma apatija, govor je adinamičen, prisotne so»blokade«govora, izrazito in pogosto zgodaj v razvoju bolezni so prizadete vidnoprostorske sposobnosti, ki obsegajo predvsem raznolike vidne agnozije, oškodovane so tudi spominske sposobnosti, vendar v manjšem obsegu in kasneje kot pri Alzheimerjevi bolezni. Med psihiatričnimi simptomi napogosteje srečamo privide, slednje zasledimo pri približno polovici vseh z demenco z Lewyjevimi telesci, ravno tako pri približno polovici ob samem pričetku klinične manifestacije same bolezni. Prividi so značilno zelo živi, vsebinsko gre najpogosteje za ljudi ali živali, do prividov so bolniki z demenco z Lewyjevimi telesci značilno kritični, prividi jih značilno ne vznemirijo (2, 3). Do polovice bolnikov z demenco z Lewyjevimi telesci ima tudi prisluhe, redkeje,
3 pa vendarle, bolniki z demenco z Lewyjevimi telesci opisujejo tudi olfaktorne in taktilne halucinacije. Pogosto gre za več raznolikih doživljanj v smislu halucinacij kot takih. Pri demenci z Lewyjevimi telesci so značilne tudi blodnje, pogosto gre za blodnje kraje, preganjanja, pogosti so Capgrasov, Fregolijev in tudi drugi sindromi (4). Izmed drugih psihiatričnih simptomov pogosto srečamo tudi anksioznost in depresijo, nemir in nanašalnost sta bolj redka kot pri drugih pogostejših boleznih, ki vodijo v demenco po 65. letu starosti. Med ekstrapiramidnimi znaki izstopa hipomimija, tremor je najpogosteje posturalni in simetričen, bradikineza in hipokineza, rigidno povišan mišični tonus, pogosto bolj aksialno, stoja in hoja sta značilno parkinsonski, posturalni refl eksi so moteni (5, 6). Ne redko je opaziti mioklonus. Motnje spanja pogosto nastopijo leta pred dejanskim razvojem klinične slike, značilne za demenco z Lewyjevimi telesci. Med pogostejšimi motnjami spanja najdemo motnjo REM-spanja in prekomerno dnevno zaspanost, ki najverjetneje zrcali nihanja splošnega pozornostnega sitema. Dodatno so pri demenci z Lewyjevimi telesci opisane tudi obstruktivna in centralna apnea v spanju, sindrom nemirnih nog, periodični gibi v spanju in insomnia. Med znaki okvare avtonomnega živčevja prednjači ortostatska hipotenzija, sledijo pogoste nepojasnjene sinkope, impotenca, inkontinenca in konstipacija. Klinični diagnostični kriteriji demence z Lewyjevimi telesci izpostavljajo predvsem demenco, pod drugo točko nihanja pozornosti, privide in ekstrapiramidne znake ter kot tretje REM-motnjo spanja, preobčutljivost na antipsihotike in zmanjšan privzem dopaminskega transporterja v bazalnih jedrih s PET (7, 8). Diagnozo verjetne demence z Lewyjevimi telesci postavimo, če ima preiskovanec demenco, dve od treh značilnosti, opisanih pod drugo točko, oziroma demenco ter eno značilnost, opisano pod drugo in eno pod tretjo točko. V vseh drugih primerih ob sumu na demenco z Lewyjevimi telesci govorimo o možni demenci z Lewyjevimi telesci. Podobno kot pri Alzheimerjevi bolezni postavimo dokončno diagnozo demence z Lewyjevimi telesci zgolj v primerih, ko je tako klinična kot histopatološka slika značilna za demenco z Lewyjevimi telesci. Dodatno obstaja vrsta simptomov oziroma znakov, značilnih za demenco z Lewyjevimi telesci, ki pa niso zadostno proučeni, da bi jih lahko vključili v klinične diagnostične kriterije. Na kratko, med slednje vključujemo pogoste padce oziroma sinkope, disavtonomijo, druge vrste halucinacij, blodnje, depresijo, ohranjenost struktur medialnega senčnega režnja s slikovnimi metodami, temensko-zatilno hipoperfuzijo s SPECT/PET
4 in patološko MIBG-scintigrafi jo srca. V pomoč pri diagnostični obravnavi nam je slikovna diagnostika, na izvidih MRI glave je velikokrat poudarjeno, da atrofi je hipokampusa oziroma struktur medialnega senčnega režnja ni, čeprav je videti difuzno atrofi jo možganovine, SPECT/PET prikaže hipoperfuzijo temensko-zatilnega predela, DATScan pa zmanjšan privzem dopaminskega transporterja v bazalnih jedrih s PET (9). Zaključek Po več kot 100 letih raziskav postaja klinični fenotip demence z Lewyjevimi telesci vedno bolj jasen. Posledično postaja tudi klinična diagnostična obravnava demence z Lewyjevimi telesci vedno bolj enostavna. V prihodnjih letih lahko pričakujemo še bolj enovito razumevanje tako klinične slike kot kliničnih diagnostičnih kriterijev, kar bo vsekakor prispevalo k boljšemu zdravljenju predvsem po zaslugi vedno boljšega razumevanja mehanizma nastanka demence z Lewyjevimi telesci, ki ga bo omogočilo dobro poznavanje tako kliničnega kot patološkega fenotipa. Literatura 1. McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology Nov; 47(5): Ballard C, McKeith I, Harrison R, O Brien J, Thompson P, Lowery K, et al. A detailed phenomenological comparison of complex visual hallucinations in dementia with Lewy bodies and Alzheimer s disease. Int Psychogeriatr Dec; 9(4): Mosimann UP, Rowan EN, Partington CE, Collerton D, Littlewood E, O Brien JT, et al. Characteristics of visual hallucinations in Parkinson disease dementia and dementia with lewy bodies. Am J Geriatr Psychiatry Feb; 14(2): Ballard CG, O Brien JT, Swann AG, Thompson P, Neill D, McKeith IG. The natural history of psychosis and depression in dementia with Lewy bodies and Alzheimer s disease: persistence and new cases over 1 year of follow-up. J Clin Psychiatry Jan; 62(1): Burn DJ. Cortical Lewy body disease and Parkinson s disease dementia. Curr Opin Neurol Dec; 19(6): Burn DJ, Rowan EN, Allan LM, Molloy S, O Brien JT, McKeith IG. Motor subtype and cognitive decline in Parkinson s disease, Parkinson s disease with dementia, and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry May; 77(5): McKeith IG, Dickson DW, Lowe J, Emre M, O Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium.
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