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Isolated cognitive relapses (ICRs) are transient deficits in cognitive performance that are not accompanied with other symptoms typical for multiple sclerosis (MS). They are often missed and can lead to long-term cognitive decline. Considering possible devastating consequences of cognitive impairment, especially in working adults, and high economic burden of MS, it is of great importance to establish whether ICRs are sufficient to start with high efficacy therapy. 42-year- old women with a recent diagnosis of relapsing-remitting multiple sclerosis developed significant impairment in almost all cognitive domains, with dominant difficulties in naming and low performance in phonemic fluency tasks, consistent with ICR. Her brain MRI showed new lesions affecting the anterior part of the thalamus and her condition partially improved on intravenous corticosteroid therapy. While waiting the disease-modifying therapy to begin, for what was now highly active MS, she developed subarachnoid haemorrhage which further narrowed the treatment options. This case illustrates the complexity of managing patients with MS and ICRs in at least three aspects. Firstly, the lack of uniform definition resulting in diagnostic delay of highly active MS and ICRs. Secondly, optimal treatment choices are often limited due to safety issues and reimbursement reasons. And thirdly, there is still an open question about the right treatment option for ICRs, so more research is needed.

In addition to amyloid β and tau protein pathology, Alzheimer's disease (AD) is characterized by dysregulation of the inflammatory response. The main objective of this study was to find out how the concentrations of immune mediators (cytokines and chemokines) differ between AD, patients with mild cognitive impairment (MCI), and healthy controls (HC) in two different types of samples, cerebrospinal fluid (CSF) and plasma. We also wanted to determine the cytokine profile for each group. Using the Bio-Plex Pro Human Cytokine 48-Plex Screening Panel, we determined the levels of 35 cytokines in CSF and 47 in plasma samples. Twenty-nine AD, 35 MCI, and 40 HC CSF and 102 AD, 37 MCI, and 10 HC plasma samples were analyzed. In the plasma samples, only 4 cytokines differed significantly between the groups (CTACK, IL-12 (p40), IL-4, IL1Rα), whereas analysis of the CSF samples revealed significantly different levels of 15 immune mediators (IL-1β, IL-1α, IL-3, IL-4, IL-7, IL-16, IL-17A, IL-18, IFN-γ, GRO-α, MIP-1β, CTACK, TNF-α, IL-2Rα, IP-10). Most of the mediators whose levels differed significantly were increased in the AD group ; only IP-10 had the highest levels in the MCI group. CSF analysis showed that the AD group was characterized by a pro-inflammatory profile and a higher rate of an adaptive immune response. Higher levels of predominantly pro-inflammatory cytokines (IL-1β, IL-18, MIG, EOTAXIN, MIP-1α, MIP-1β, TNF-β) were associated with higher levels of cognitive deficits. This study has shown that measurement of immune mediators in CSF, but not in plasma, may be a good strategy to track the immune response during disease progression and could be a promising tool for evaluating potential future immune and anti-inflammatory interventions.

Many recent studies confrmed importance of the NLRP3 and NLRP1 inflammasome activation in the pathogenesis of Alzheimer’s disease (AD). Apoptosis-associated speck-like protein (ASC) has a key role in assembling inflammasome complex as it couples danger signal sensors and procaspase-1. We aimed to compare CSF and plasma concentrations of ASC protein in AD, mild cognitive impairment (MCI), and cognitively normal controls, and to correlate them with subjects’ age, Mini Mental State Examination (MMSE) score, and core CSF biomarkers of AD (levels of Aβ1-42, total tau [t-tau], and tau phosphorylated at epitope 181 [p−tau181]). Concentrations of ASC were measured in 127 AD, 78 MCI, and 39 control CSF samples and 82 AD, 33 MCI, and 9 control plasma samples using ELISA. Compared to controls, the ASC levels in CSF were significantly higher in the AD and MCI group, whereas differences in plasma levels did not reach significance. CSF levels of ASC protein also positively correlated with the age of the subjects and the concentrations of t-tau and p-tau181. Therefore, we concluded that the ASC level in CSF, but not in plasma, could be a useful biomarker of both tau pathology and inflammasome activation in AD.

Introduction: Due to the growing number of older people with dementia worldwide, an increasing number of people will participate in their care, so do health professionals. The main goal of this research was to get an insight into the level of knowledge and attitudes towards dementia among medical students. Methods: This is a cross- sectional study. A total of 231 final-year medical students at the School of Medicine, University of Zagreb were recruited. The paper-and-pencil questionnaire included six categories of questions on demographic data (I.), success during medical studies (II.), personal interests (III.), personal attitudes towards dementia and experiences with people with dementia (IV.), two dementia knowledge exams (V.) and personal opinion on the prevalence of dementia in the undergraduate curriculum (VI.). Results: Students had relatively neutral attitudes towards working with people with dementia and a rather poor theoretical knowledge of dementia. The best theoretical knowledge was about the symptoms of dementia, and the weakest were in the field of differential diagnoses, epidemiology and pathogenesis of dementia. Every 11th final-year medical student had never had contact with a person with dementia. Medical students should spend more time with people with dementia during their medical education was predominant opinion. The higher grade point average in the study and the higher grade in Neurology were significantly correlated to the better result on the dementia knowledge exam. Conclusion: There is the need to broaden the current educational program in dementia from the earliest student days in order to increase knowledge and attitudes towards dementia.

Shima Mehrabian,1 Larissa Schwarzkopf,2 Stefanie Auer,3 Iva Holmerova,4 Milica G Kramberger,5 Marina Boban,6 Elka Stefanova,7 Catalina Tudose,8 Natalia Bachinskaya,9 Tibor Kovács,10 Petr Koranda,11 Todor Kunchev,1 Latchezar Traykov,1 Janine Diehl-Schmid,12 Katrina Milecka,12 Alexander Kurz12On behalf of the Danubian Network for Dementia Education Care (DANDEC) Consortium1UH “Alexandrovska”, Department of Neurology, Medical University Sofia, Sofia, Bulgaria; 2Helmholtz-Centre Munich, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Munich, Germany; 3Department for Clinical Neurosciences and Preventive Medicine, Danube University Krems, Krems, Austria; 4CELLO Faculty of Humanities, Charles University, Prague, the Czech Republic; 5University of Ljubljana, Department of Neurology, Ljubljana, Slovenia; 6University of Zagreb, Department of Cognitive Neurology, Zagreb, Croatia; 7School of Medicine, University of Belgrade, Neurology Clinic, Belgrade, Serbia; 8University of Medicine and Pharmacy Carol Davila, Department of Clinical Neurosciences, Bucharest, Romania; 9Acacdemy of Medical Sciences Kiev, Department of clinical physiology and pathology of the central nervous system, Kiev, the Ukraine; 10Department of Neurology, Semmelweis University, Budapest, Hungary; 11MEDIWARE corp., Prague, the Czech Republic; 12Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, GermanyCorrespondence: Alexander KurzCentre for Cognitive Disorders at the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar; Technische Universität München, Ismaninger Strasse 22Munich 81675, GermanyTel +49 894 140 4285Email a.kurz@tum.deBackground: Dementia is a particularly severe societal challenge in several countries of the Danube Region due to higher-than-average increment in population longevity, disproportionate increase of the old-age dependency ratio, and selective outward migration of health care professionals. A survey was conducted among dementia experts to obtain a deeper understanding of the dementia care structures and services in this geographical area, and to identify the educational needs of health care professionals, and the availability of assistive technology.Subjects and methods: A standardized questionnaire was sent out to 15 leading dementia experts/clinicians in 10 Danube Region countries inquiring about professional groups involved in dementia care, availability and reimbursement of services, inclusion of dementia in professional education and training, acceptability of Internet-based education, and availability of assistive technology. The authors are the survey respondents.Results: The majority of individuals with dementia receive care in the community rather than in institutions. The roles of medical specialties are disparate. General practitioners usually identify dementia symptoms while specialists contribute most to clinical diagnosis and treatment. Health care professionals, particularly those who work closely with patients and carers, have limited access to dementia-specific education and training. The greatest need for dementia-specific education is seen for general practitioners and nurses. An Internet-based education and skill-building program is considered to be equivalent to traditional face-to-face but offer advantages in terms of convenience of access. Assistive technology is available in countries of the Danube Region but is significantly underused.Conclusion: Dementia care in the Danube Region can be improved by an educational and skill-building program for health care professionals who work in the frontline of dementia care. Such a program should also attempt to enhance interdisciplinary and intersectorial collaboration, to intensify the interaction between primary care and specialists, and to promote the implementation of assistive technology.Keywords: dementia, Danube Region, expert survey, dementia care structures, education, assistive technology

The influence of cannabis use on the occurrence, clinical course and the treatment of the first psychotic episode (FEP) is well documented. However, the exact link is still not clearly established. The aim of this article is to review and report the noticed increase in the number of hospitalizations of young people with a clinical appearance of severe psychotic decompensation following cannabis consumption and to show the clinical challenges in treatment of the FEP. The case study describes the clinical course of a five selected patients with a diagnosis of the FEP and positive tetrahydrocannabinol (THC) urine test who were hospitalized in a similar pattern of events. They all have a history of cannabis consumption for at least 6 years in continuity and were presented with severe psychomotor agitation, disorganisation, confusion and aggression at admission. Although the chosen drug to treat all patients was atypical antipsychotic and benzodiazepines, the course of the disorder and the clinical response to therapy were noticeably different in each patient. The clinical presentation of FEP in cannabis users can be atypical and highly unpredictable from mild psychotic symptoms to severe substance intoxication delirium. In clinical practice clinicians treating new onset psychosis need to be watchful for cannabis and synthetic cannabinoids induced psychosis. Pharmacotherapeutic interventions include prompt and adequate use of the benzodiazepine, second-generation antipsychotic, and mood-stabilizers. Further research in the pharmacotherapy of cannabis-induced psychosis is required.

Objectives: To explore the influence of sex on the change of cerebral blood flow velocity (BFV) between resting state and during neurocognitive testing in patients with the first episode psychosis (FEP) compared to healthy controls. Background and Aims: Women and men diagnosed with schizophrenia differ and substantial sex-based differences have been observed. Patients suffering from schizophrenia have different intracranial hemodynamics compared to the health population. We aimed to explore association between sex and BFV in patients with FEP compared to healthy controls. Materials and Methods: We enrolled 46 patients with the FEP admitted at the Department of psychiatry, Zagreb University Hospital Centre, Croatia, during 2016-2017 and 41 healthy controls. The primary outcome was BFV in the middle cerebral arteries (MCAs) measured by Transcranial Doppler Ultrrasonograhy (TCD) in resting state and during the neurocognitive testing. Results and Conclusions: During neurocognitive testing, BFV in both MCAs increases in healthy control and decreases in FEP patients (p

Schizophrenia is one of the most demanding psychiatric disorders due to heterogeneity of clinical presentations and difficulties in posing diagnosis, prediciting prognosis and developing treatment plan treatment. Up to this date, possible biomarkers that could help to objectify the diagnosis and the course of treatment of schizophrenia are still not identified. In this project, we recruited a sample of 150 patients with first-episode of psychosis (of schizophrenia type) (FEP)and 100 healthy controls and assessed changes between the acute psychosis and subsequent remission among patients over an 18-month follow- up. The assessments included several methods performed through four work packages. In this report, we present the results of assessment with psychopathological scales, battery of neurocognitive tests and test for facial emotional recognition, as well as of salivatory cortisol measurement during a stress paradigm and cerebral blood perfusion in the resting state (with single photon emission computed tomography (SPECT)) and during stress conditions using the transcranial doppler ultrasound. Overall, we found multiple deficits in various functions including neurocognitive deficits, hypoperfusion in several brain areas in SPECT, as well as deficits in functional aspects (sensitivity to stress) that differentiated healthy controls from FEP. Some of these deficits were still present after 18- month follow-up. These results confirm that the deficits seen in schizophrenia are present from the first presentation of illness and some do not respond well to the treatment. This finding supports the concept of early detection and early intervention with multi-layered treatment approaches from the first-episode of psychosis.

Do početka 90-ih godina prevladavalo je uvriježeno mišljenje da su bolesnici s uznapredovalom jetrenom bolesti prirodno autoantikoagulirani i time zaštićeni od tromboembolijskih zbivanja. Međutim, novim saznanjima dugogodišnja je paradigma srušena. U bolesnika s cirozom jetre paralelno je reducirana sinteza prokoagulansa i endogenih antikoagulansa, dok je produkcija ekstrahepatalno sintetiziranih faktora, važnih za proces zgrušavanja i fi brinolize, očuvana. U stabilnoj jetrenoj bolesti sustav je „rebalansiran”, ali funkcionira u uskom rasponu homeostaze, što ga čini izuzetno fragilnim te ga i minimalni stres može uvesti u neželjeni ekstrem, trombozu ili krvarenje. Uz navedeno niz je drugih čimbenika koji prate jetrenu bolest, kao što su hemodinamske promjene, oštećenja drugih organa, ponajprije bubrega, te sklonost infekcijama, a koji pomiču ravnotežu prema sklonosti krvarenju ili pojačanom zgrušavanju. Konvencionalni laboratorijski testovi nisu prikladni za procjenu rizika od krvarenja u cirozi, rizični čimbenici za razvoj tromboze nisu nedvojbeno dokazani, a sigurnosni profi l antitrombotskih lijekova u cirozi nije precizno utvrđen jer su ti bolesnici uglavnom isključeni iz velikih kliničkih studija. Zbog svega navedenoga dijagnostički i terapijski pristup u ovom je kontekstu kompleksan te nalaže timski rad hematologa, hepatologa i u fazi operativnog liječenja anesteziologa. U ovome preglednom radu osvrnut ćemo se na mehanizme poremećaja hemostaze i fi brinolize u bolesnika s cirozom jetre, incidenciju tromboembolijskih zbivanja, laboratorijsku dijagnostiku te profi laktičke i terapijske opcije u okviru internističke skrbi.

U vremenu i ekonomskim okolnostima u kojima živimo, prijedlog nacrta Hrvatske strategije za borbu protiv Alzheimerove bolesti podastrt je stručnim društvima, udrugama građana i svim zainteresiranima, pozvanima na javnu raspravu koju smo otvorili na Okruglom stolu u Brelima tijekom CROCAD-14, a nastavili u Zagrebu na 6. psihijatrijskom kongresu. Smioni je to početak otvaranja dijaloga s dionicima Hrvatske Alzheimer alijanse i svim zainteresiranim grupacijama i pojedincima našega društva, kako bi se usvojila strategija temeljem koje će se moći otvoriti dijalog i s predlagateljima zakona i predstavnicima vlasti s ciljem implementacije strategije te ostvarivanja znatne koristi za osobe koje su oboljele od Alzheimerove demencije, odnosno za članove njihovih obitelji.

Hrvatska udruga za Alzheimerovu bolest (HUAB) do sada je, kao glavni organizator, uspješno organizirala ukupno šest kongresa o Alzheimerovoj bolesti (AB) od kojih su zadnja tri bila s međunarodnim sudjelovanjem. Prvi i drugi Kongres o AB održani su u Zagrebu (2004. i 2005. godine), treći 2006. na Brijunima bio je s međunarodnim sudjelovanjem. Tada je odlučeno da budući kongresi budu bienalni i s međunaro dnim sudjelovanjem, da službeni jezici budu hrvatski i engleski, te da streme tome da budu najznačajniji događaj na tom području u cijeloj državi pa i u regiji. U tome se i uspjelo, 2008. godine na Otoku Sv. Andrije kod Rovinja, 2010. u Zadru te sada 2012. u Primoštenu. Usprkos tome i sukladno s ovim aktivnostima, sagledava se potreba za redovitim lokalnim druženjima, kontinuiranom edukacijom, praktičnim tečajevima, razmjenom iskustava i kontaktima među budućim novoosnovanim Udrugama diljem Hrvatske, a koje bi bile učlanjene u HUAB kao krovnu organizaciju. Stoga je odlučeno da se uvede dodatna aktivnost u tzv. neparnim godištima i to počam od 2013. godine u obliku Konferencije o Alzheimerovoj bolesti i psihijatriji starije životne dobi, a koje bi zbog organizacijskih razloga bile organizirane uvijek u Zagrebu. Konferencija bi na neki način slijedila tradiciju Psihogerijatrijskih simpozija na Rabu, koje je HUAB svojevremeno organizirao, a posljednji je bio 2006. godine. Na taj način HUAB će povećati svoju aktivnost, svake godine organizirati će stručno/znanstveni skup i to tako da u neparnim godinama to bude lokalna konferencija u Zagrebu, i to u proljeće (najvjerojatnije ožujak), a u parnim godinama međunarodni kongres, na jesen (rujan ili listopad) uvijek na drugom mjestu u Hrvatskoj.

Alzheimerovu bolest (HUAB), od samog osnutka 1999. godine, pa do dana današnjeg, a također i u buduće, ima samo jednu osnovnu zadaću, a to je - pomoći osobama oboljelim od Alzheimerove bolesti (AB) i demencije, njihovim obiteljima i njegovateljima, boriti se protiv stigme, te educirati opću i ciljanu populaciju. Naša Udruga nema zaposlenika, pa stoga cjelokupnu radnu aktivnost provode volonteri. U našem Savjetovalištu imamo tjedne sastanke za obitelji oboljelih od demencije i sve druge zainteresirane. HUAB je izdao četiri brošure, brojne letke, sve u velikoj nakladi, a isti su distribuirani besplatno na javnim mjestima. Do sada naši članovi su nebrojeno puta govorili u medijima (TV, radio, tisak), organizirali smo brojna predavanja, sudjelovali na brojnim skupovima, konferencijama i kongresima koji su se bavili Alzheimerovom bolešću i drugim demencijama, a sve u svrhu podizanja svjesnosti o demenciji, a i da bi prezentirali svoj rad u vezi osoba oboljelih od AB i njihovih njegovatelja. Sada, u 2012. godini mi organiziramo 6. hrvatski kongres o AB s međunarodnim sudjelovanjem, ovaj puta u Primoštenu. HUAB organizira Kongrese svake dvije godine, tako da je jubilarni 5. kongres bio 2010. godine u Zadru i to je bio najveći skup o AB ikad održan u Hrvatskoj. Prije toga imali smo kongres na Otoku Sv. Andrije (2008. godine), na Brijunima (2006. godine) te u Zagrebu u dva navrata (2004. i 2003. godine). Osim ovoga HUAB je organizirao i tri Psihogerijatrijska simpozija na otoku Rabu, zadnji 2006. godine. HUAB je imao čast i priliku da se natječe za domaćinstvo Alzheimer Disease International (ADI) Konferencije za 2010. godinu, no konačna odluka donesena je u korist Grčke, pa se taj kongres održao u Solunu. Zadnjih osam godina obilježavamo Svjetski dan AB (21. rujna) u Zagrebu, na „Cvjetnom" i „Jelačić placu" - na dva najpopularnija trga u centru Grada. Organizirali smo humanitarna događanja pod nazivom „Ljetne večeri na Zrinjevcu", Ha kojima smo prikupljali dobrotvorne priloge za HUAB. Naša web stranica (www. alzheimer.hr) je ponovno obnovljena i vrlo je posjećena. Putem naše SOS-linije (+385 91 569 16 60), koja je non-stop otvorena (24/7/365) primamo svakodnevno pozive iz cijele Hrvatske, ali isto tako i iz Bosne i Hercegovine, a povremeno i iz drugih zemalja iz regije. Redovito odgovaramo na brojne upite upućene elektronskom poštom (alzheimer@ xnet.hr). Zadovoljni smo da je naš rad također i međunarodno priznat, pa smo tako već 2006. godine primljeni u punopravno članstvo međunarodne krovne asocijacije Alzheimer Disease International (ADI), a 2012. godine u punopravno članstvo Alzheimer Europe (AE). HUAB ima svoj ured u Zagrebu, u Vlaškoj 24a, što spada u staru jezgru centra Grada, a za lijep i adekvatan prostor zahvalni smo Gradu Zagrebu, koji nam je taj prostor dodijelio na korištenje.

Cilj rada bio je prospektivno ustanoviti frekvenciju i kliničke karakteristike vertiginoznih sindroma u okvirima sekundarne zdravstvene zaštite – na neurološkom odjelu opće bolnice tijekom jednogodišnjeg razdoblja sa 6 mjesečnim praćenjem. Studija je provedena na Odjelu za neurologiju Opće bolnice Varaždin, okružne bolnice koja se brine za populaciju Varaždinske županije od 180.000 stanovnika. Podaci su prospektivno prikupljani iz neurološke prakse bolničkog liječnika. Tijekom studije pregledano je 1670 bolesnika i od toga se 173 (10, 3%) žalilo na vertiginozne tegobe. Srednja dob bolesnika bila je 56 godina (raspon 16-89 godina) ; 113 (65, 3%) bolesnika bilo je ženskog spola. Od svih simptoma najzastupljeniji je benigni paroksizmalni položajni vertigo (BPPV) – 52 (30, 1%), zatim vestibularni neuritis u 29 (16, 8%) bolesnika i vertigo „ostale“ etiologije u 28 (16, 2%). Centralni uzroci vrtoglavice bili su prisutni u 17 (9, 8%) bolesnika. Autori zaključuju da je vrtoglavica perifernog uzroka, tj. BPPV, najčešći vertiginozni sindrom u sekundarnoj kliničkoj praksi. Budući da se postavljanjem dijagnoze BPPV- a omogućuje brzi i učinkoviti tretman bolesnikovih tegoba, bitno je prepoznati visoku učestalost toga poremećaja.

Importance of CSF biomarkers in differential diagnosis of dementia is being discussed

The aim was to determine prospectively the frequency and clinical characteristics of vertiginous syndromes in a neurology outpatient clinic of a community hospital during one-year period with 6-month follow up. The study was carried out at Department of Neurology, Varazdin General Hospital, in Varazdin County, Croatia, with a catchment population of 180, 000. Data were prospectively collected from one neurologist's practice during 12-month period with 6-month follow up (May 2007 - November 2008). During the study period, 1670 patients were examined and 173 (10.3%) of them complained of vertiginous symptoms (mean age 56, range 16-89 years ; 113 (65.3%) females). Benign paroxysmal positional vertigo was most common, recorded in 52 (30.1%) cases, followed by vestibular neuritis in 29 (16.8%) and other etiology in 28 (16.2%) cases. Central forms of vertigo were present in 17 (9.8%) patients. The authors conclude that vertigo of peripheral origin, i.e. benign paroxysmal positional vertigo, is the most common type of vertiginous syndromes encountered in this secondary neurological practice. Since this diagnosis allows for rapid and effective relief of patient symptoms, it is crucial that the neurologist is trained in recognizing and treating this neuro-otologic entity.

Alzheimer's disease (AD) and vascular cognitive impairment (VCI) are the two most common causes of dementia in older age groups. Due to inadequacy of current clinical diagnostic criteria in differential diagnosis of dementia, the identification of new biomarkers that would help establishing the diagnosis and primary cause of the dementia is therefore of great relevance. The aim of this study was to investigate the diagnostic accuracy of two potential CSF biomarkers, total tau protein (t-tau) and tau protein phosphorylated at threonine 181 (p-tau181) in the differential diagnosis of patients with AD and VCI. The concentrations of CSF biomarkers were measured in 29 AD patients, 12 VCI patients and 25 control subjects. The CSF concentrations of both markers were significantly higher in AD group compared to VCI (p>0.001) group and control subjects (p

First case of female patient with Hashimoto's encephalopathy, subtle cognitive decline and rumination syndrome that responded excellent on corticosteroid therapy.

Isolated ophthalmologic findings without history of head trauma or cranial bruit led to late diagnosis and irreversible changes in patient with indirect carotid-cavernous fistula.

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Alzheimerova bolest (AB) i frontotemporalna demencija (FTD) predstavljaju važan diferencijalno dijagnostički problem u svakodnevnoj kliničkoj praksi. Stoga postoji potreba pronalaska bioloških markera kojima bi se pospješila točnost postavljanja dijagnoze. Cilj je ove disertacije bio ocijeniti dijagnostičku važnost triju potencijalnih markera iz likvora: ukupnog tau proteina (t-tau), tau proteina fosforiliranog na treoninu 181 (p-tau181) i tau proteina fosforiliranog na serinu 199 (p-tau199) u diferencijalnoj dijagnozi bolesnika s AB i FTD podudarnih dobnih skupina. Koncentracije navedenih proteina iz likvora određene su u 25 bolesnika s FTD, 27 bolesnika s AB te 25 ispitanika kontrolne skupine. Vrijednosti t-tau, ptau181 i p-tau199 iz likvora su bile značajno veće u skupini bolesnika s AB nego u skupini bolesnika s FTD (p85%). Ipak, upotrebom kombinacije vrijednosti koncentracija t-tau i p-tau199 markera iz likvora postignuta je točna klasifikacija 22 od 25 bolesnika s FTD. Zaključeno je da nijedan od navedenih markera zasebno nije pokazao karakteristike „idealnog“ markera, ali je kombinacija ttau i p-tau199 detektirala zadovoljavajuće visoki postotak FTD bolesnika (88%).

Alzheimerova bolest (AB) i frontotemporalna demencija (FTD) predstavljaju važan diferencijalno dijagnostički problem u svakodnevnoj kliničkoj praksi. Stoga postoji potreba pronalaska bioloških markera kojima bi se pospješila točnost postavljanja dijagnoze. Cilj je ove disertacije bio ocijeniti dijagnostičku važnost triju potencijalnih markera iz likvora: ukupnog tau proteina (t-tau), tau proteina fosforiliranog na treoninu 181 (p-tau181) i tau proteina fosforiliranog na serinu 199 (p-tau199) u diferencijalnoj dijagnozi bolesnika s AB i FTD podudarnih dobnih skupina. Koncentracije navedenih proteina iz likvora određene su u 25 bolesnika s FTD, 27 bolesnika s AB te 25 ispitanika kontrolne skupine. Vrijednosti t-tau, ptau181 i p-tau199 iz likvora su bile značajno veće u skupini bolesnika s AB nego u skupini bolesnika s FTD (p85%). Ipak, upotrebom kombinacije vrijednosti koncentracija t-tau i p-tau199 markera iz likvora postignuta je točna klasifikacija 22 od 25 bolesnika s FTD. Zaključeno je da nijedan od navedenih markera zasebno nije pokazao karakteristike „idealnog“ markera, ali je kombinacija ttau i p-tau199 detektirala zadovoljavajuće visoki postotak FTD bolesnika (88%)., Alzheimer's disease (AD) and frontotemporal dementia (FTD) represent an important differential diagnostic problem in clinical practice. The identification for new biomarkers that would help establishing the diagnosis and primary cause of the dementia is therefore of great relevance. The aim of this study was to investigate the diagnostic accuracy of three potential CSF biomarkers, total tau protein (t-tau), tau protein phosphorylated at threonine 181 (p-tau181) and tau protein phosphorylated at serine 199 (p-tau199) in the differential diagnosis of AD and FTD patients in relatively young age groups. The concentrations of these three CSF biomarkers were measured in 25 FTD patients, 27 AD patients and 25 control subjects. The CSF concentrations of all three markers were significantly higher in AD than in FTD patients (p < 0.001) or control subjects (p < 0.001). No difference was observed in FTD patient group compared to controls, except for p-tau181 (p = 0.028). When sensitivity was set at 85% or higher, specificity in differentiation between FTD and AD patients reached 40,0% for t-tau, 37,5% for p-tau181 and 56,0% for p-tau199. Improvement of the diagnostic accuracy upon logistic regression analysis with t-tau and p-tau199 as independent variables showed that 22 out of 25 FTD patients could be correctly classified. In conclusion, none of the markers per se fulfilled the criteria for the „ideal“ marker (sensitivity and specificity higher than 85%). However, combination of t-tau and p-tau199 detected correctly 88% of FTD patients, thus largely satisfying practical requirements.

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common causes of dementia in old people. They remain difficult to differentiate in practice because of lack of sensitivity and specificity of current clinical diagnostic criteria. Recent molecular and cellular advancements indicate that the use of cerebrospinal fluid markers may improve early detection and differential diagnosis of AD. Our objective in this study was to determine diagnostic accuracy of three cerebrospinal (CSF) markers: total tau protein (t-tau), tau protein phosphorylated on threonine 181 (p-tau181) and tau protein phosphorylated on serine 199 (wp-tau199). Using commercially available ELISA kits concentrations of t-tau, p-tau181 and p-tau199 were analyzed in 12 patients with probable AD, 9 patients with VaD and 12 NC subjects. The median levels of all three markers were significantly higher in AD group versus VaD and NC groups. However, when the sensitivity levels were set to 85% or higher, only t-tau and p-tau199 satisfied consensus recommendations (specificity more than 75%) when differentiating AD from VaD. In conclusion, our preliminary data on a small group of selected subjects suggest that the CSF t-tau and p-tau199 levels are useful markers for differentiating AD from VaD.

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Major efforts are under way to define reliable biomarkers of Alzheimer’ s disease. Highly significant increases of hyperphosphorylated tau proteins in cerebrospinal fluid have been recently reported in Alzheimer’ s disease patients compared to controls by several independent groups, including ours. These findings support the notion that cerebrospinal fluid phosphorylated tau proteins may be very useful biomarkers in the early identification of Alzheimer’ s disease in patients with mild cognitive impairment.

Background: Alzheimer's disease (AD) is the most prevalent type of dementia. Although diagnostic markers for AD have been continuously improving, they still do not guarantee a definite diagnosis. However, it is safe to say that known biological markers from cerebrospinal fluid (CSF) can differentiate AD from other primary causes of dementia with high reliability and validity. As such, they were recently, together with structural and functional neuroimaging and genetic testing, included as an ancillary method in the clinical diagnostic criteria for AD. Objective: To assess the usability of CSF total tau protein (t-tau), tau protein phosphorylated at threonine 181 (p-tau-181) and beta-amyloid in a mixed population of patients with suspected dementia referred to a tertiary memory clinic. Patients and methods: Fifty-four consecutive patients with various primary causes of the dementia syndrome were included in the study. A retrospective diagnosis was established using the consensus criteria without prior knowledge of the CSF results. Lumbar puncture was performed as a part of the routine clinical workup. Levels of t-tau, p-tau-181 and beta-amyloid in CSF were measured using commercially available ELISA kits from Innogenetics, Ghent, Belgium and Biosource International, Camarillo, CA, USA. Results: Except for beta-amyloid, the overall sensitivity of the other two markers for diagnosis of AD was in range from 77 to 92%.

Malformations of cortical development (MCD) have been increasingly recognized as an important cause of intractable epilepsy. The aim of our study was to define epileptogenicity of MCDs by correlating MRI, EEG and semiology of epileptic attacks, and to determine the effect of MCD on drug resistant epilepsy. We also intended to reveal the utility of interictal single photo emission computed tomography (SPECT) in verification of MCD lesions and relative prevalence of different MCDs. Based on interictal EEG finding, semiology of the epileptic attacks and brain magnetic resonance imaging (MRI) "electroclinical epileptogenicity" of MCD was defined. Brain MRI revealed cortical dysplasia (CD) in nine patients, polymicrogyria in four patients, lissencephaly and schizencephaly in one patient each. Three patients had a combination of malformations. The localization of SPECT hypoperfusion corresponded to MCD lesion in ten (66.67%) patients. Electroclinically confirmed epileptogenicity of MCD overlapped with MR and interictal SPECT findings in fourteen (93.3%) and nine (60.0%) patients, respectively. Our study results demonstrated the MCD lesions to be highly epileptogenic and a frequent cause of intractability.

Poster se sastoji od kratkog tekstualnog dijela koji govori o epidemiologiji Alzheimerove bolesti u Republici Hrvatskoj i svijetu, te deset ilustracija glavnih ranih simptoma i znakova Alzheimerove bolesti na koje trebamo obratiti pozornost: 1. Poremećaj pamćenja, 2. Poteškoće u izvršavanju svakodnevnih aktivnosti, 3. Poteškoće govora, čitanja i pisanja, 4. Gubitak prostorne i vremenske orijentacije, 5. Pogrešne procjene i odluke, 6. Poremećaj apstraktnog mišljenja, 7. Učestalo gubljenje i zametanje stvari, 8. Promjene raspoloženja i ponašanja, 9. Promjene osobnosti i 10. Gubitak interesa za socijalne aktivnosti. Svaki simptom ili znak ilustriran je starijom muškom osobom koja promovira zdrave navike (pa smo mu dali nadimak "Zdravko"), a ispod ilustracije je još i pobliže opisan tekstualno.