Szabolcs Szatmári

Background: Advanced Parkinson’s disease (aPD) is characterized by motor fluctuations, unpredictable oral absorption, and severe dyskinesias. Levodopa–entacapone–carbidopa intestinal gel (LECIG) is designed to provide dopaminergic stimulation and optimize levodopa bioavailability. We evaluated 18-month clinical outcomes, motor stabilization, disease burden, and oral medication simplification in a real-world cohort transitioning to LECIG. Methods: This retrospective longitudinal study included 41 patients with medication-refractory aPD. Patients underwent nasojejunal titration (mean 5.58 ± 1.50 days), followed by percutaneous endoscopic gastrojejunostomy. Assessments were performed at baseline, initiation, and 6, 12, and 18 months. Primary endpoints were daily OFF time, dyskinesia duration, and non-linear fluctuations. Disease burden was analyzed using Linear Mixed-Effects Models and medication changes using McNemar tests and paired t-tests. Results: Patients (56.1% male; mean age 65.39 ± 8.32 years; disease duration 10.46 ± 4.23 years) demonstrated significant and sustained clinical improvements. For the 38 patients evaluable at 18 months, daily OFF time decreased from 4.67 ± 0.79 h to 1.34 ± 0.40 at initiation and 1.55 ± 0.69 at 18 months (p < 0.0001; 66.8% reduction). Severe peak-dose dyskinesia was absent after initiation (2.17 ± 1.00 to 0.00 h/day; p < 0.001), whereas early morning akinesia decreased from 78.0% to 36.6% and freezing of gait from 56.1% to 31.6%. Total Clinical Burden Score decreased from 9.33 to 3.49 (−62.6%). Dopamine agonist use decreased from 80.5% to 42.1% at 18 months (McNemar p < 0.0001), while adjunct medications decreased from 1.73 to 1.39/patient (p = 0.0284). Adverse events were predominantly mild-to-moderate. No patient discontinued therapy because of an adverse event or hardware failure; one patient discontinued LECIG by personal choice. Two additional patients died from sudden cardiac arrest during follow-up, both considered unrelated to LECIG therapy or pump hardware. At 18 months, 38 of 41 patients remained evaluable. Conclusions: In this observational cohort, LECIG initiation was followed by sustained reductions in motor complications, OFF time, and clinical burden over 18 months. Treatment was also associated with a reduction in dopamine agonist use and overall adjunctive medication burden. The favorable tolerability and low discontinuation rate observed support further evaluation of LECIG as an advanced treatment pathway. However, pre-switch LEDD calculations may support initial pump programming but should not be considered definitive predictors of individualized maintenance settings; inpatient clinical titration remains necessary.

Background/Objectives: Advanced Parkinson’s disease is characterized by severe motor fluctuations and disabling dyskinesias that often become refractory to conventional oral dopaminergic therapies. Methods: This study aimed to evaluate the clinical efficacy of levodopa–entacapone–carbidopa intestinal gel (LECIG) in 50 patients initiated during a four-year period at a tertiary movement disorders center. Motor outcomes were analyzed using Wilcoxon signed-rank and McNemar’s tests, while multivariable logistic regression was employed to identify predictors of improvement. Results: LECIG initiation significantly reduced mean daily OFF time from 4.63 ± 0.75 to 1.62 ± 1.97 h (p < 0.0001) and total dyskinesia duration by 65% (p < 0.0001). Furthermore, the prevalence of early morning akinesia decreased from 80% to 26%, and delayed ON phenomena were completely eliminated (p < 0.0001). Subgroup analyses indicated that patients with troublesome dyskinesia (≥1 h/day) achieved significantly greater reductions in involuntary movements compared to those with lower baseline dyskinesia levels (p = 0.013). Conclusions: These findings suggest that LECIG provides a meaningful and sustained stabilization of motor complications, highlighting its role as a valuable device-aided therapy in managing advanced Parkinson’s disease.

Calcium-binding proteins (CaBPs) are known to modulate neuronal excitability and calcium signaling, and they may play a role in the imbalances of excitation and inhibition of temporal lobe epilepsy (TLE). While parvalbumin and calretinin are well-characterized CaBPs, N-Terminal EF-Hand Calcium-Binding Protein 1 (NECAB1) remains understudied in epilepsy, despite its association with neurodegenerative conditions. In this study, we used fluorescent immunolabeling to determine the distribution of NECAB1, as well as its co-expression with parvalbumin and calretinin, in brain regions associated with the epileptic circuitry using a kainic acid-induced TLE model. Additionally, we examined the impact of levetiracetam and brivaracetam on NECAB1 expression. In our study, NECAB1-positive cells were prominently localized to the paraventricular nucleus of the thalamus (PVT), endopiriform nucleus (EPN), and amygdala in healthy brain regions involved in epileptic circuitry. A NECAB1–calretinin co-expressing subpopulation was detected in the amygdala, PVT, and hippocampus but was nearly absent in the EPN. In chronic epilepsy, NECAB1 expression was significantly upregulated in the PVT and bilaterally in the amygdala. These findings suggest that NECAB1 upregulation may compensate for epileptic hyperexcitability, potentially contributing to circuit remodeling via thalamocortical regulation and interneuron diversity. Levetiracetam and brivaracetam treatments partially reduced the NECAB1 density increase in TLE, indicating a modulatory effect on NECAB1 expression.

In addition to the classically accepted pathophysiological features of Alzheimer’s disease (AD), increasing attention is paid to the role of the insulin-resistant state of the central nervous system. Glucagon-like peptide-1 receptor (GLP-1R) agonism demonstrated neuroprotective consequences by mitigating neuroinflammation and oxidative damage. The present review aims to offer a comprehensive overview of the neuroprotective properties of GLP-1R agonists (GLP-1RAs), with a particular focus on experimental animal models of AD. Ameliorated amyloid-β plaque and neurofibrillary tangle formation and deposition following exenatide, liraglutide, and lixisenatide treatment was confirmed in several models. The GLP-1RAs studied alleviated central insulin resistance, as evidenced by the decreased serine phosphorylation of insulin receptor substrate 1 (IRS-1) and restored downstream phosphoinositide 3-kinase/RAC serine/threonine–protein kinase (PI3K/Akt) signaling. Furthermore, the GLP-1RAs influenced multiple mitogen-activated protein kinases (extracellular signal-regulated kinase: ERK; c-Jun N-terminal kinase: JNK, p38) positively and suppressed glycogen synthase kinase 3 (GSK-3β) hyperactivation. A lower proportion of reactive microglia and astrocytes was associated with better neuronal preservation following their administration. Finally, restoration of cognitive functions, particularly spatial memory, was also observed for semaglutide and dulaglutide. GLP-1RAs, therefore, hold promising disease-modifying potential in the management of AD.

Bevezetés: Előrehaladott Parkinson-kórban az oralisan, illetve transdermalisan adagolt dopaminerg szerek már nem elég hatékonyak, és jelentős mellékhatással bírnak, ezért szükség lehet a folyamatos dopaminerg stimuláció elvén alapuló eszközös terápiák valamelyikére. Célkitűzés: Célunk volt összehasonlítani a levodopa-entakapon-karbidopa intestinalis géllel kezelt, előrehaladott Parkinson-kóros betegeink klinikai paramétereit a kezelés megkezdése előtt és közvetlenül a klinikáról való elbocsátáskor. Módszer: Retrospektíven elemeztük azokat az azonos szempontok alapján nyert adatokat, amelyek a kezelésben részesülő betegekre vonatkoztak, figyelembe véve a betegek általános és neurológiai állapotát és annak ingadozásait, az előzetes kezelési sémákat, a gyógyszerelés mellékhatásait és a Parkinson-kór szövődményeit. Eredmények: Két év alatt 29 betegnél vezettük be a levodopa-entakapon-karbidopa intestinalis gél kezelést, ezt megelőzően átlagosan 4,7 ± 0,8 órás off állapot mellett 20 betegnél tapasztaltunk átlagosan 2,8 ± 1,2 órás közepesen súlyos csúcsdózis-dyskinesist, illetve 6 esetben 2,1 ± 1,0 órás súlyos dyskinesist. A kezelés elindítása után az off állapot időtartama szignifikánsan csökkent. Hasonló volt a tendencia az enyhe vagy középsúlyos dyskinesisek esetében, ugyanakkor a súlyos dyskinesisek teljes mértékben megszűntek. Szintén nem tapasztaltuk hazabocsátáskor a 7 betegnél korábban jelentkező hirtelen off állapotokat. A 24 esetben jelentkező kora hajnali akineticus állapotot a végső felméréskor már csak 8 beteg jelezte. Megbeszélés: Habár a Parkinson-kóros betegek megkésve, a megengedettnél súlyosabb motoros komplikációkkal kezdték el a kezelést, a levodopa-entakapon-karbidopa intestinalis gél bevezetése hatékonynak bizonyult. A vizsgált periódus alatt észlelt enyhe, múló mellékhatások az irodalomban jelzett szinten voltak. Egyetlen entakaponnaiv betegben sem jelentkeztek gastrointestinalis mellékhatások. Következtetés: A levodopa-entakapon-karbidopa intestinalis gél motoros komplikációkat javító hatása a levodopa-karbidopa intestinalis gélhez hasonló mértékű, a napi kisebb levodopaadag és a kisebb méretű adagolószerkezet előnyeivel. További vizsgálatok és több klinikai tapasztalat összegzése szükséges annak eldöntésére, hogy a levodopát tartalmazó két enteralis géltípus közül melyik előnyösebb az egyénre szabott kezelési stratégia keretében. A hosszú távú biztonságos alkalmazás és a motoros komplikációk hatékony enyhítése egyaránt fontos szempont ebben a döntésben, a beteg életminőségének javítása érdekében. Orv Hetil. 2025; 166(3): 90–97.

Levodopa–entacapone–carbidopa intestinal gel infusion is a relatively new treatment option for advanced Parkinson’s disease. We aimed to describe and analyze the characteristics of de novo levodopa–entacapone–carbidopa intestinal gel therapy in 20 consecutive patients with advanced Parkinson’s disease. We assessed the profile of motor complications by evaluating the following: motor fluctuations, dyskinesias, and the freezing phenomenon at baseline (before the testing period) and before discharge. The treatment significantly reduced the duration of daily hours spent in off time compared with baseline pre-treatment values from a mean of 4.8 ± 0.9 h/day to a mean of 1.4 ± 0.5 h per day (p < 0.001). The duration and severity of peak-dose dyskinesia were also significantly reduced compared with baseline values. Out of the 10 patients who reported freezing, 8 did not present this complication at the pre-discharge assessment. Significant improvements were observed in Hoehn and Yahr scale scores in both the on and off states. The levodopa–entacapone–carbidopa intestinal gel therapy was well tolerated during the follow-up period immediately after initiation. Despite a relatively severe stage of the disease, all patients experienced a significant improvement in motor fluctuations, dyskinesias, and the freezing phenomenon.

Creutzfeldt–Jacob disease is a progressive and ultimately fatal disease, representing one of the most common forms of prion diseases. It is a rare pathology presenting with various symptomatology, and the fact that a definite diagnosis can be obtained solely by neuropathological techniques makes it hard to recognize and diagnose. Here we present the clinical and neuropathological features of a 72-year-old woman, who originally presented in a county hospital, then, along with the disease progression, got transferred to a university center in Romania, where CJD-specific tests are rarely performed, and ultimately was diagnosed with the help of international collaboration. The purpose of this case report and review is to summarize the Romanian CJD situation until the present day, to place the Romanian CJD epidemiology in an Eastern European context, and to highlight the diagnostic options and possibilities for clinical practitioners. We would also like to draw attention to the need for a national surveillance system. By presenting the patient’s route in Romania from the first presentation to diagnosis, we would like to emphasize the importance of interdisciplinary and international collaboration, by which we managed to cross the regional diagnostic boundaries and create a possible diagnostic pathway for future cases.

Bevezetés: A Parkinson-kór olyan neurodegeneratív kórkép, melynek tüneti kezelése hatékonyan megoldható, bár a terápiás ajánlások gyakran szorulnak finomításokra a gyarapodó tapasztalatok birtokában. Célkitűzés: Azt kívántuk elemezni, hogy előrehaladott Parkinson-kóros betegeinknél az időközben megjelent szakértői ajánlások hogyan tükröződtek az intestinalis gél bevezetését megelőző időszakban. Módszer: Retrospektíven vizsgáltuk azokat az azonos szempontok alapján nyert adatokat, amelyek levodopa-karbidopa intestinalis gél kezelésben részesülő betegekre vonatkoztak. A 2011 és 2021 közötti periódust két ötévesre osztottuk fel, mivel az első öt év után fogadták el a klinikai döntéshozatalban az „5-2-1-es szabályt”. Eredmények: A vizsgált időszakban 150 betegnél kezdtük el a levodopa-karbidopa intestinalis gél kezelést. A második periódusban a betegek átlagéletkora alacsonyabb, a diagnózis óta eltelt idő rövidebb volt. Csúcsdózis dyskinesisei (p = 0,02), bifázisos dyskinesisei (pKövetkeztetés: Tízéves időszakot vizsgálva azt tapasztaltuk, hogy a második öt évben szignifikánsan jobb fizikális és kognitív állapotban került sor az előrehaladott Parkinson-kóros betegeknél a levodopa-karbidopa intestinalis gél bevezetésére. A szakértői ajánlásokhoz viszonyítva még mindig súlyosabb klinikai képet tapasztalunk az eszközös kezelés elkezdésekor, de ennek az invazív módszernek már javult az elfogadása mind a betegek, mind az őket alapszinten ellátó családorvosok és területi neurológusok részéről. Orv Hetil. 2022; 163(30): 1189–1195.

Advanced Parkinson’s disease (APD) cannot be treated efficiently using the classical medications however, in recent decades invasive therapeutical methods were implemented and confirmed as effective. One of these methods makes it possible to continue the levodopa (LD) supplementation as a gel administered directly into the upper intestine. However, there are a number of unanswered questions regarding this method. Therefore, we retrospectively analyzed a 10-year period of selected patients that were treated with levodopa/carbidopa intestinal gel (LCIG). We included all APD patients with motor fluctuations and dyskinesia at presentation. LCIG treatment was started in 150 patients: on average these patients received LD for 10.6 ± 4.4 years with a frequency of 5.2 ± 1.0/day until the introduction of LCIG. The estimated and the real LCIG dose differed significantly (mean: 1309 ± 321 mg vs. 1877 ± 769 mg). The mean duration of LCIG administration was 19.8 ± 3.6 h, but in a number of 62 patients we had to administer it for 24 h, to maximize the therapeutic benefit. A carefully and individually adjusted LCIG treatment improves the quality of life of APD patients, but questions remain unresolved even after treating a large number of patients. It is important to share the ideas and observations based on the real-life experience related to the optimal timing, the appropriate dose and duration of administration of the LCIG.

Background: In the advanced stages of Parkinson’s disease (APD), complex forms of dyskinesia may severely impair the patient’s quality of life. Objective: In the present study, we aimed to analyze the evolution under LCIG therapy of the most important motor fluctuations and complex disabling dyskinesias, including diphasic dyskinesia. Methods: In this retrospective study, we analyzed the characteristics of patients with APD who had at least 30 min of diphasic dyskinesia (DID) in 3 consecutive days, were considered responders and were treated with LCIG in our clinic. Patients were evaluated before and after PEG and at 6, 12 and 18 months, when the changes in the therapy were recorded, and they completed a 7-point Global Patient Impression of Improvement (PGI-I) scale. Results: Forty patients fulfilled the inclusion criteria—out of which, 34 performed all visits. There was a substantial difference between the calculated and real LCIG (1232 ± 337 mg vs. 1823 ± 728 mg). The motor fluctuations and most dyskinesias improved significantly after starting LCIG, but an increasing number of patients needed longer daily administrations of LCIG (24 instead of 16 h). Conclusions: Patients with APD with complex dyskinesias must be tested in dedicated hospitals, and they need a special therapeutic approach. The properly adapted LCIG treatment regarding the dose and time of administration completed with well-selected add-on medication should offer improvement for patients who want to or can only choose this DAT vs. others.