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http://www.ksmf.org/arhimed/poglej.asp?id=70

Nevrofiziološka študija poteka in zdravljenja demenc
Avtor: Milica Kramberger, Anita Kušej
Mentor: prof. dr. Martin Janko
Somentor: assist. dr. Zvezdana Pirtošek


Uvod: Demenco lahko opredelimo kot sindrom, v katerem prevladuje globalni upad intelektualnih sposobnosti. Pri degenerativnih oblikah demence prihaja do znižanega nivoja acetilholina v možganih (7, 8, 10). Diagnoza je klinicna, temelji na anamnezi in heteroanamnezi, za izkljucitev sekundarnih oblik bolezni pa je pomemben nevrološki pregled, ustrezne laboratorijske preiskave in slikovne tehnike. V okviru nevrološkega pregleda obicajno opravimo še kratek preiskus spoznavnih sposobnosti (KPSS), po potrebi pa bolnika napotimo še k nevropsihologu ali na elektrofiziološke preiskave. Ena od elektrofizioloških metod so merjenja vidnih evociranih potencialov (VEP), s katerimi ocenjujemo delovanje vidnega sistema od mrežnice do asociacijskih predelov možganske skorje (12).
Kortikalne elektrofiziološke odzive odjemamo s površine glave nad vidnim predelom možganske skorje z elektrodami. Uporabljamo bliskovni dražljajaj s stroboskopom in slikovni dražljaj z vzorcem premikajoce se šahovnice. Poti nastanka odzivov sta pri obeh dražljajih razlicna; bliskovni odzivi izhajajo iz asociacijske skorje bogate z acetilholinom, slikovni pa iz primarne vidne skorje, kjer je malo acetilholina (27, 28, 29, 30).
Namen: Vprašalniki za oceno spoznavnih sposobnosti in nekatere elektrofiziološke metode so zapletene in od bolnika zahtevajo precej sodelovanja. V raziskavi smo želeli oceniti diagnosticno vrednost cimbolj preprostih metod (TRU, VEP), ki od bolnika zahtevajo manj sodelovanja, in jih primerjati z že uveljavljenim KPSS. Zanimalo nas je tudi, ali so bliskovni VEP, ki se generirajo v asociacijskih z acetilholinom bogatih predelih skorje, pri bolnikih bolj abnormni kot slikovni VEP, ki nastanejo v primarni vidni skorji, kjer je acetilholina malo. V prospektivnem delu študije pa smo želeli preveriti, ali zdravljenje z donepezilom, novim zdravilom, ki inhibira razgradnjo acetilholina, izboljšuje rezultate korelatov spoznavnih funkcij (KPSS, TRU, VEP) ali razpoloženje (depresijo).
Metode: V prospektivni raziskavi je sodelovalo 8 dementnih bolnikov in 7 zdravih preiskovancev primerljive starosti. Diagnozo demence smo postavili s klinicnim pregledom in v študijo vkljucili tiste bolnike, ki so na KPSS dosegli 23 tock ali manj (1). Sekundarne demence smo izkljucili z laboratorijskimi preiskavami, slikovnimi tehnikami in oceno depresivnosti. Pri preiskovancih smo izvedli TRU, VEP in elektroretinografijo (ERG).
Rezultati: Ugotovili smo statisticno znacilno razliko v rezultatih TRU med bolniki in zdravimi. Pred zacetkom zdravljenja z donepezilom so interval P1-P2, amplituda vala P1 in latenca P2 bliskovnega VEP med bolniki in zdravimi statisticno znacilni. Po zdravljenju ni vec statisticno znacilnih razlik med ocenjevanimi elektrofiziološkimi parametri.
Zakljucki: Diagnosticna vrednost preprostejših metod, kot so TRU in bVEP, je primerljiva s standardnimi, pa nekoliko zahtevnejšimi metodami, kot je npr. KPSS. Od elektrofizioloških metod so bolj obcutljive tiste, ki odražajo aktivnost asociacijskih predelov možganske skorje (npr. bliskovni, ne pa slikovni VEP). Trimesecno zdravljenje z donepezilom ne izboljša korelatov spoznavnih funkcij in razpoloženja, jih pa morda stabilizira


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[Abstract / English version]
Neurophysiological study of clinical course and treatment of dementia
Author: Milica Kramberger, Anita Kušej
Mentor: prof. dr. Martin Janko
Co-mentor: assist. dr. Zvezdana Pirtošek


Introduction: Dementia can be defined as a syndrom of global intellectual deterioration. Degenerative dementias are characterized by acetylcholine depletion (7, 8, 10). Diagnosis is a clinical one, based on the history obtained from the patient and the familly. In order to exclude secondary dementia, the complete examination has to be made and appropriate laboratory and imaging investigations performed. The Mini Mental Test (MMT) is an essential part of the examination. If necessary, neuropsychologist and electrophysiological investigation should be added. One of the diagnostic electrophysiological methods is the use of the visual evoked potentials (VEPs) (12).
Visual evoked potentials (VEP) verify the functional integrity of visual pathways from the retina to the associative cortex using a well defined sensory stimulus such as a shifting checkerboard pattern or a flash. The cortical response is seen as a change in the electrical field detected by scalp electrodes.
Components elicited by pattern reversal and flash stimuli are generated by two separate pathways. Flash related VEP pathway is characterized by a more prominent acetylcholine activity (27, 28, 29, 30), whereas the pattern VEPs are generated in the primary visual cortex with little acetylcholine.
Aims: Most of the questionnaires and electrophysiological methods can be quite sophisticated, demanding an active participation of the patient. In this study we wanted to assess the diagnostic value of simpler less effort demanding methods (CDT and VEP) and to compare them to the standard and much used MMT. We were further interested whether fVEPS generated in the acetylcholine-rich associative cortex are more abnormal compared to those generated in the acetylcholine-poor primary visual cortex (pVEP). The prospective part of the study assesed a possible effect of donepezil, a new acetylcholinergic drug on the correlates of the cognition (MMT, CTD, VEP) and mood (depression).
Methods: 8 patients with dementia and 7 healthy volunteers took part in our study. Diagnosis of dementia was made by clinical examination and supported by MMT value 23 or less. Biochemistry, imaging studies and test for depression were performed to exclude secondary dementia. Participans were also evaluated with CDT , VEP and electroretinography (ERG). Results: Our study showed a significant difference in results of MMT and CDT in patients and controls. P1 amplitude, P2 latency, P1-P2 interval of fVEP in patients and healthy controls before the use of donepezil were significantly different. According to the analysis of the second testing there are no significant differences in pre and post treatment results in patients.
Conclusions: Diagnostic value of simpler methods, such as CDT and fVEP is comparable to that of the more standard and complex ones, such as MMT. Among electrophysiological methods the most sensitive are those which reflect the activity of the associative corteces (e.g., fVEP, but not pVEP). Twelve-week treatement with donepezil does not improve correlates of cognitive functions and mood, however it may stabilise them.