Introduction: Inflammation is a unifying driver of pathologies from joint degeneration to neurodegenerative disorders. Age-associated diseases like osteoarthritis (OA) and Alzheimer's disease (AD) pose immense public health challenges, contributing to disability and reduced quality of life. Traditionally viewed as distinct, OA involves cartilage degradation and chronic pain, while AD is marked by neurodegeneration and memory loss. Growing evidence highlights inflammation as a systemic phenomenon underlying both diseases. Damage-associated molecular patterns (DAMPs), released during extracellular matrix (ECM) remodeling, trigger innate immune responses, linking peripheral tissue injury to neurodegeneration. This study investigates shared inflammatory mechanisms between enzymatically triggered transcriptomic changes in chondrocytes and neuroinflammatory processes in AD. Methods: Chondrocytes were isolated from chicken articular cartilage using collagenase digestion (16 hours) or cryogrinding. Differentially expressed genes (DEGs) were identified using stringent thresholds (adjusted p-value < 0.05, log2FoldChange [LFC] > 2). The transcriptomic profiles of digested chondrocytes were compared to publicly available AD datasets from the Gene Expression Omnibus (GEO). Functional enrichment and STRING-based interactome analyses identified overlapping molecular pathways and interaction networks driving inflammation. Results: Enzymatic digestion induced upregulation of inflammatory cytokines (IL-6, LFC = 12.09; IL-8, LFC = 11.43) and pathways linked to inflammasome activation and ECM remodeling. Comparative analysis revealed significant overlaps with AD datasets, including DAMP-mediated Toll-like receptor activation, cytokine signaling, and integrin pathways. Protein-protein interaction networks highlighted inflammasome activation and immune regulation as central nodes, with interleukins (IL-6, IL-8) and purinergic signaling (P2RX7) emerging as key hubs, supporting a systemic inflammatory axis connecting cartilage to neural degeneration. Conclusion: This study uncovers a molecular connection between ECM disruption and neuroinflammation, identifying DAMP-mediated pathways as unifying mechanisms across cartilage and neural degeneration. These findings redefine systemic inflammation's role in degenerative diseases and present novel molecular targets for disrupting shared inflammatory networks. The results open avenues for precision therapies targeting inflammation's dual role in musculoskeletal and neurological health. 

Témavezető: Dr. László Ducza és Dr. Roland Ádám Takács

INTRODUCTION Neuroleptics are essential in the treatment of psychotic disorders. Antipsychotics are often associated with a range of side effects that may vary based on the pharmacological agent used. In everyday practice in inpatients, antipsychotics often used in combination with benzodiazepines (BZD). BZDs have many drawbacks like dependence, cognitive impairment, and risk of falls, although it may lessen the risk of extrapyramidal side effects. AIM This study aimed to investigate the side effect profiles antipsychotics, with a particular focus on extrapyramidal symptoms. In this work we examine the antipsychotic therapy and the concomitantly administered BZD relationship on the emergence of extrapyramidal side effects. Secondary aim was to shed light on the full side effect profile of the antipsychotics used in standard care at UD CC Department of Psychiatry and Psychotherapy. METHOD This observational study examined a cohort of 104 psychiatric patients, aged between 18 and 75 years, who were receiving antipsychotic treatment. Participants were categorised into two groups based on their BZD medication: one group received low dose or no BZD, while the other group received higher doses. Threshold was 1.25 mg clonazepam dose equivalent daily; it was the arithmetic mean of the amount of medication. Statistical analyses were performed using chi-square (χ²) tests and Fisher’s exact tests to discern correlations between BZD dosages and the severity or frequency of EPS. RESULTS Cross tabulation revealed low BZD dosages are 1.388 times more likely to have side effects than high BZD dosages with wider 95% CI and a significance level P = 0.4391. Similarly, patients over the age of 60 are 2.4 times more likely to have side effects than patients younger than 60 with wider 95% CI and a significance level P = 0.0517. However, patients over the age of 40 are 2.596 times more likely to have side effects than patients under 40 with narrow 95% CI and significance level P = 0.0238. Additionally, women are 2.23 times more likely to have side effects than men, with a wide 95% CI and a significance level P = 0.0387 CONCLUSION The results suggest while the odds ratio for EPS is higher in the low BZD group showing greater chances of developing EPS, the effect in this sample is not statistically significant. Importantly, the protective benefits of high dose BZD against EPS outweigh its associated risks, underscoring its potential advantage in managing EPS risk.

Témavezető: Dr. Morvai Szabolcs

Introduction: It is well established that sleep deprivation (SD) is associated with a higher incidence of cerebrovascular and cardiovascular diseases, as well as impaired cognition and neurodegenerative changes, but little is known about the effects of SD on cerebral blood flow. Method: In this study, 25 healthy subjects (between ages 21 to 38 years) were included. Examinations were performed before (control) and after 24 hours of SD, under controlled conditions. The goal was to measure changes in baseline cerebral blood flow velocities and flow velocity responses to visual stimulus, in the posterior cerebral artery (PCA), and hypercapnia, in the middle cerebral artery (MCA). Transcranial doppler ultrasound was used to monitor the pulsatility index (PI), and peak-systolic (PSV), and time averaged mean (TAMV) blood flow velocities. Visually evoked potentials (VEP), P100 wave latency and amplitude, were measured over the bilateral visual cortices, and stimulation was achieved via a high- contrast, black-and-white checkerboard pattern-reversal stimulation, with a 2 Hz reversal frequency. Hypercapnia was induced by breath-holding for a period of 30 seconds, and the associated vascular changes were expressed as the breath-holding index (BHI, percent increase of flow velocity divided by the breath holding period). Results: When baseline PCA flow velocity parameters were compared, a statistically insignificant trend toward higher flow velocities (p=0.16 for PSV; p=0.08 for TAMV) and lower PI (p=0.06) after SD could be smaller after SD (p<0.01), and likewise, the PSV and TAMV relative flow velocity increases were smaller after SD than in the control period, at the PCA (p<0.05 for both). After SD, the latency of the VEP P100 wave increased (before SD 108.93±3.90 ms vs. after SD 111.98 ± 4.46 ms, p<0.01), but the amplitude of the VEP P100 wave did not change significantly. MCA BHIs were lower after SD (before SD 1.63 ± 0.47 %/s vs. after SD 1.42 ± 0.43 %/s, p=0.023). Conclusion: Our data suggested that SD results in cerebral vasodilation and thus reduces vascular compliance. These effects of SD were not due to a reduced neuronal activity, but rather likely due to reduced vascular changes.

Témavezető: Krisztina Szonja Rab-Bábel és László Oláh

Abstract Background: Ischemic stroke (IS) is amongst the leading causes of death and disability. Hemorrhagic transformation (HT), a potentially severe complication of the disease itself or its treatment, worsens the outcome and increase mortality. Several investigations aimed to determine easily accessible and cost-effective biomarkers that would predict HT. Among these, the different hematologic indices are to be highlighted. Methods: Over a span of 10 years, a total of 1,426 acute IS patients undervent intravenous thrombolysis at the Department of Neurology, University of Debrecen. Body and brain autopsies – as gold standard for the determination of HT - were conducted on 98 out of the 167 deceased patients. Among them, HT was present in 46, and was absent in 52 cases and the complete blood counts (CBC) determined upon admission were available for all individuals except for 2 in the HT group. We calculated various ratios such as RDW to platelet (RPR), platelet to lymphocyte (PLR), neutrophil to lymphocyte (NLR), lymphocyte to monocyte (LMR), eosinophil to lymphocyte (ELR), white blood cell to platelet (WPR) neutrophil to platelet (NPR), lymphocyte to platelet (LPR), eosinophil to platelet (EPR) and systemic immune inflammation index (neutrophil x platelet / lyphocyte). Results: Platelet count was significantly lower in HT positive vs. HT negative patients before thrombolysis (p: 0.0080). Out of the calculated indices, PLR (p: 0.2391), NLR (p: 0.8520), LMR (p: 0.8437), systemic immune inflammation index (p: 0.3733), ELR (p: 0.8473), showed no statistical significance. RPR (p: 0.0063), WPR (p: 0.0068), NPR (p: 0.0159), LPR (p﹤0.0001) and EPR (p﹤0.0001) showed statistically significant correlation with the incidence of HT. Receiver operating characteristic curve (ROC) analysis was performed to determine optimal cutoffs of LPR and EPR as predictors of HT, these were 0.0307 and 0.0031, respectively. The sensitivity proved to be 100% for both ratios while the specificity was 95.45% (AUC (95%CI)= 0.9969) and 84.21% (AUC (95% CI)= 0.9608) for LPR and EPR, respectively. Conclusions: According to our study, low platelet count and the platelet ratios may predict HT and unfavorable clinical outcome. Therefore, along with proper management of clinical conditions like hypertension, diabetes, these factors should be considered during secondary stroke prevention measures, mainly the choice and timing of antithrombotic treatment to reduce the risk of HT.

Témavezető: Dr. Kitti Kovacs

Background: Progressive multifocal leukoencephalopathy (PML) is a rare but potentially life-threatening demyelinating disease resulting from reactivation of John Cunningham virus (JCV), primarily in immunocompromised individuals. It is a rare but serious complication, it can also develop during treatment with natalizumab, an α4-integrin antagonist monoclonal antibody, in patients with relapsing-remitting multiple sclerosis (RRMS). Therefore, when monitoring disease progression in RRMS patients receiving natalizumab, serum JCV index values and magnetic resonance imaging (MRI) findings suggestive of PML should also be considered when assessing the safety and efficacy of therapy. Method: This retrospective study analyzed data from 11 RRMS patients treated with natalizumab, including one deceased. Parameters studied included demographics, comorbidities, previous disease- modifying therapies and their side effects, and details of natalizumab treatment (duration, dosing, frequency, side effects). Baseline and follow-up JCV index values, Expanded Disability Status Scale (EDSS) scores (0-10), clinical evaluations, MRI findings and relapse history were also reviewed. Results: In our cohort of 11 patients (3 male, 8 female), the mean age at diagnosis of RRMS was 25.5 (20-43) years. The average duration from MS diagnosis to first natalizumab treatment was 11.5 (0-22) years. Patients experienced an average of 2.72 relapses before starting natalizumab treatment and an average of 0.1 relapses after treatment. The mean JCV index before natalizumab therapy was 0.56 (seronegative to 0.86), and afterwards it was 0.64 (seronegative to 1.2). Two patients experienced JCV seroconversion from negative to positive after initiation of natalizumab therapy. The mean EDSS score was 4.2 (1-8.0) before therapy and 4.0 (1-7.5) after therapy, while the median score was 5.0 and 4.0. Regarding MRI findings, 1 patient showed increased demyelination, while no patients had radiological evidence of PML. Conclusion: The reduction in relapse rate and the modest improvement in EDSS scores indicate the therapeutic efficacy of natalizumab. The JCV index remained relatively stable, but seroconversion from negative to positive occurred in 2 patients. Although one patient showed increased demyelination, MRI findings and clinical course did not indicate the development of PML. These results highlight the need for continued monitoring of JCV serology and demyelination status during natalizumab therapy.

Témavezető: Dr. Piros Pálma

Introduction: Carotid atherosclerosis is a major cause of ischemic stroke, influenced by several risk factors like hypertension, hyperlipidemia, smoking, diabetes, and obesity, which contribute to vascular dysfunction and plaque progression. While hemostasis in atherosclerosis has been studied, the relationship between carotid atherosclerosis and thrombin generation markers remains unclear. This study aimed to investigate the association between carotid atherosclerosis, peripheral atherosclerosis and hemostatic markers. Patients and Methods: In a pilot study, 30 patients from the Department of Neurology who had no acute thrombotic disease at inclusion were enrolled, and all were monitored for carotid atherosclerosis. Demographic data, comorbidities and medications were recorded. Routine laboratory tests and thrombin generation markers were assessed. Carotid stenosis was evaluated using Doppler ultrasonography, and patients were classified into mild (1–49%) and advanced (50–100%) stenosis groups. Ankle-brachial index (ABI) measurements were conducted to assess peripheral atherosclerosis. Results: No significant association was found between thrombin generation markers and carotid stenosis severity. ABI values were significantly lower in patients with advanced stenosis compared to those with mild stenosis (left ABI p=0.039; right ABI p=0.001). In the mild stenosis group, a significant inverse correlation was observed between triglyceride levels and CRP (r=-0.5581, p=0.0328). Across the entire cohort, peak thrombin level (r=0.3753, p=0.0410) and endogenous thrombin potential (ETP) (r=0.3802, p=0.0382) showed a significant positive correlation with CRP. Moreover, time to peak showed significant positive correlations with triglyceride levels in both the advanced stenosis group (r=0.653, p=0.008) and the entire cohort (r=0.501, p=0.005). Conclusion: These findings suggest thrombin generation markers do not correlate with carotid atherosclerosis severity, implying that localized carotid pathology does not directly affect systemic thrombin generation. ABI values, reflecting systemic atherosclerotic burden, are significantly associated with advanced carotid stenosis, highlighting their utility as a complementary tool in evaluating carotid atherosclerosis. The observed correlations reflect a complex interplay between lipid metabolism, inflammation and coagulation in patients with atherosclerosis.

Témavezető: Dr. Szegedi István és Linda Lóczi

Az ischemias stroke világszerte a vezető halálokok közé tartozik. A reperfúziós terápiát klinikánkon a kétezres évek elején vezettük be. 2007-től a Neurológiai Klinika az Auguszta Tömbben működik, ahol korszerű intenzív osztály, csőposta révén gyors laborvizsgálati lehetőség és ugyanazon épületen belül belgyógyászat, kardiológia, idegsebészet működik, valamint teljes képalkotó diagnosztika. Célkitűzés: tükröződik-e klinikai és patológiai vizsgálatokban a javuló diagnosztikus és terápiás feltételrendszer. Összehasonlítottuk: nem, életkor, ápolási napok száma, iv. thrombolysis, vérzéses transzformáció, pneumonia, thromboticus szövődmények, tumorok gyakorisága a reperfúziós éra előtt (1989-99) és után (2007-17). Zárójelentéseket és boncjegyzőkönyveket dolgoztunk fel, STATA-val elemeztük az adatokat. 89-99 között 477, 07-17 között 439 elhunytat boncoltak, ebből 89-99 között 44,9% volt a nők aránya, 07-17 között 50,1%. A 07-17-es populáció szignifikánsan idősebb volt (p=0,003). 89-99 között nem volt reperfúzió, míg 07-17 között az elhunytak 41,6%-a kapott kezelést. A 89-99 periódusban a boncolások 18%-ban volt vérzéses transzformáció, míg 07-17 között 38,5%-ban (p<0,001). A klinikai fázisban 89-99 között nem volt kimutatott vérzéses transzformáció, míg 07-17 között 33,1%-ot igazoltak (p<0,001). Thromboticus szövődmény a boncolás során 89-99 között 39,8%-ban, 07-17 között 11,6%-ban volt (p<0,001), ebből a klinikai fázisban 89-99-ben 60%-ot, 07-17-ben 34%-ot észleltek. 89-99 között 75,4%-ban 2007-17 között 67,9%-ban diagnosztizáltak pneumoniat a boncolás során (p=0,012), a klinikai fázisban 89-99 között 77,8%, 07-17-ben 86,4% volt ismert. A boncolás 89-99 között 8,6%-ban, 07-17 között 12,3%-ban talált extraneuralis tumort. Összefoglalva a későbbi periódusban szignifikánsan több nőbeteget veszítettünk el, a betegek idősebbek voltak. A reperfúziós kezelés szignifikánsan növelte a vérzéses transzformáció arányát, amit a klinikai fázisban és a boncolás során is észleltünk, s ez a beválogatási kritériumok további finomítására hívja fel a figyelmet. Pneumonia gyakorisága lényegesen nem csökkent, ami antibiotikum rezisztencia fokozódásának veszélyét jelezheti. Csökkent a thromboembolias szövődmények száma, vélhetően a modern antithromboticus kezelésnek (LMWH) köszönhetően. Ugyanakkor a javuló diagnosztikai körülmények ellenére a tumorok nagyobb százaléka maradt felderítetlen a klinikai fázisban, ami a diagnosztikus algoritmus áttekintését teszi szükségessé.

Témavezető: Dr. Bencs Viktor és Prof. Dr. Csiba László

Bevezetés: A szorongás világszerte a pszichiátriai kórképek között az egyik leggyakrabban előforduló állapot. A tünetek súlyosbodásával megemelkednek a komorbiditások, funkcióromlás jelentkezik. Mindez jelentős terhet ró a közegészségügyre és gazdaságra. A gyermekkori nemkívánatos események a felnőttkori szorongásos rendellenességek kockázati tényezőinek tekinthetők. Az ily módon érintett felnőttek körében fellelhető elkerülő megküzdési mechanizmusok – például szerhasználat – korrelálnak a szorongásos tünetekkel. A szorongásos zavarok kockázata nő az ártalmas gyermekkori események – különösen a bántalmazás, elhanyagolás, családon belüli erőszak - számával. Szintén kutatások igazolták a kedvezőtlen gyermekkori események, a szorongás és az öngyilkossági hajlam kapcsolatát. Módszer: Munkánk során a Debreceni Egyetem Klinikai Központ Pszichiátriai és Pszichoterápiás Klinikáján 2023 októbere és 2024 decembere közt vizsgáltuk az ambuláns gyógyszeres, az ambuláns illetve osztályos pszichoterápiás ellátásban részesült pácienseket. Demográfiai sajátosságai mellett felmértük a kedvezőtlen gyermekkori élmények számát, típusát az Adverse Childhood Experiences (ACE), a szorongásuk szintjét és fajtáját a Generalized Anxiety Disorder (GAD-7) és a State-Trait Anxiety Inventory (STAI) kérdőív által. Célkitűzés: Célunk volt a kapott eredmények alapján az összefüggések keresése a szorongásos tünetek és a kedvezőtlen gyermekkori élmények között. Eredmények: 130 beteg adatait dolgoztuk fel, közülük 42 ambuláns gyógyszeres, 40 ambuláns pszichoterápiás és 48 pszichoterápiás osztályos kezelésben részesült. Korrelációs vizsgálatunk alapján az ACE kérdőív összpontszáma a STAI-T-vel mutatta a legerősebb összefüggést, közepeset a GAD-7-tel, míg STAI-S-sel a leggyengébbet (Spearman ρ rendre: 0.326; 0.234; 0.127). A lineáris regressziós modellünk azt mutatta, hogy mindhárom kérdőívünk pontszámait csupán egyetlen ACE-10 tétel jósolta be megbízhatóan, ez pedig a 9-es volt: családon belüli pszichiátriai betegség, öngyilkossági kísérlet. Következtetések: Kutatásunk alátámasztja az ártalmas gyermekkori események és a felnőttkori szorongás közti kapcsolatot, melyek közül a vonásszorongással mutatja a legnagyobb összefüggést. Eredményeink azt sugallják, hogy a családon belüli pszichiátriai betegség és/vagy öngyilkossági kísérlet magas kockázatot jelenthet a később megjelenő szorongásra és öngyilkossági kísérletekre, ezért fontosnak tartjuk ezek szűrését, követését a családokban.

Témavezető: Dr. Garbóczy Szabolcs

Bevezetés. Az akut iszkémiás stroke (AIS) intravénás trombolízis kezelés célja a keringésből kizárt agyterület vérellátásának gyors helyreállítása rekombináns szöveti plazminogén aktivátor (i.v. rt-PA) révén. A kezelés az esetek mintegy felében nem hatásos, továbbá a betegek egy részében potenciálisan fatális hemorrhagiás transzformáció (HT) alakulhat ki, melynek genetikai rizikótényezői nem ismertek. Célkitűzés. Egypontos nukleotid-polimorfizmusok (SNP) azonosítása a hemosztázis természetes inhibitorainak génjeiben, melyek befolyásolhatják a trombolízis kimenetelét. Betegek és módszerek. Prospektív, obszervációs eset-kontroll tanulmányunkban i.v. rt-PA-val kezelt AIS betegek DNS mintáit vizsgáltuk. A DE Neurológia Klinikával kollaborációban létrehozott biobankunkban (2011-2020) tárolt mintákból a protein C, protein S, endotheliális protein C receptor és antitrombin génjeiben (PROC, PROS1, PROCR, SERPINC1) 12 gyakori polimorfizmust vizsgáltunk (PROC: IVS1-1641 G>A, IVS-1654 C>T, IVS1-1476 A>T, IVS7+111 G>T, 3’UTR C>T; PROCR: p.Ser219Gly, 5’UTR C>T, 5’UTR G>A; SERPINC1: IVS+141 G>A, p.Ala384Pro; PROS1: IVS11+54 T>C, p.Ser501Ala Herleen) primer extenzió és fragmentanalízis elvén működő SNaPshot Multiplex módszerrel. A HT jelenlétének megítélése a lízist követő másnapi (~24h) kontroll CT felvételek alapján történt. A 7. napi NIHSS ≥4 ponttal való csökkenését kedvező rövidtávú kimenetelnek tekintettük. Eredmények. Összesen 112 trombolízissel kezelt AIS beteg DNS mintáját vizsgáltuk: 22 HT-t szenvedett beteghez kontrollként 42 kedvező ill. 48 kedvezőtlen/stagnáló kimenetelű beteget választottunk, a kontrollokat kor, nem és felvételkori NIHSS szerint illesztve. A vizsgált SNP-k közül kizárólag a PROC IVS1-1641 G>A allélfrekvenciája tért el a csoportokban. A PROC IVS1-1641 G>A variáns allél szignifikánsan gyakoribb volt a HT betegekben, a HT kialakulásának esélyét heterozigóta formában 4,7-szeresre, homozigóta formában 6-szorosra emelve a vad típushoz képest (p=0,0289). A PROC IVS1-1476 A>T, PROS1 IVS11+54 T>C és SEPRINC1 IVS1+141G>A SNP-k variáns alléljai szignifikánsan gyakrabban fordultak elő a teljes kohorszban a referens európai populációhoz képest. Konklúzió. Eredményeink alapján a PROC IVS1-1641 G>A polimorfizmus összefüggésben állhat a trombolízist követő HT kialakulásával. A PROC IVS1-1476A>T, PROS1 IVS11+54T>C és SEPRINC1 IVS1+141G>A SNP-k gyakoribb előfordulása az általunk vizsgált kohorszban felveti e polimorfizmusok szerepét az AIS kialakulásában.

Témavezető: Dr. Bagoly Zsuzsa és Dr. Hodossy-Takács Rebeka

Epilepsy is a neurological disorder frequently monitored by video-EEG, which generates extensive footage of patient behavior. Manual analysis of such recordings can be time-consuming and prone to oversight, potentially missing subtle facial movements linked to seizure onset or progression. Growing clinical interest in quantitative approaches highlights the need for automated systems that can rapidly and accurately detect significant facial patterns from large-scale video data. The primary aim of this study was to develop a software pipeline capable of automatically identifying and tracking facial landmarks in video-EEG recordings. By focusing on key facial features such as facial expressions, facial symmetry, and mouth openness, the goal was to investigate the potential of these metrics to signal the onset and characterize the evolution of seizures. A dataset encompassing more than 2,000 hours of patient video-EEG, annotated for 192 seizures, served as the basis for this work. The pipeline was programmed in Python and incorporated Google Media Pipe’s Face Landmark Detection Solution to extract 3D facial coordinates. Additional preprocessing included trimming video segments around seizure events, isolating the patient’s face through cropping, and calculating custom symmetry scores and mouth openness indicators. Blendshape heatmaps provided a visual overview of changes in facial expressions before, during, and after seizures. The creation of this pipeline enabled the efficient processing of large video datasets and demonstrated reliable landmark detection under favorable lighting and minimal occlusions. Preliminary analyses revealed notable shifts in mouth openness and facial symmetry during the ictal phase compared to baseline, suggesting potential for early seizure detection. Blendshape variations also appeared to capture characteristic facial expression patterns, although low-quality footage occasionally posed challenges for robust landmark tracking. These findings underscore the promise of integrating automated facial feature analysis with conventional EEG data to enhance seizure diagnosis and management. Further refinements to the pipeline and expansion of the dataset could improve detection accuracy and support more personalized therapeutic interventions.

Témavezető: Dr. Csiki Zoltán és Prof. Dr. Björn Krüger