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.

Levodopa–entacapone–carbidopa intestinal gel (LECIG) infusion is a device-aided therapy (DAT) for advanced Parkinson’s disease (APD). ELEGANCE (NCT05043103) is a multinational observational study gathering real-world data on long-term efficacy, safety and patient-reported outcomes with LECIG. Here we report the experience of 69 patients (41

Background:Levodopa-carbidopa intestinal gel (LCIG) is an established treatment for patients with advanced Parkinson's disease (APD). Improvement of motor and non-motor symptoms, as well as the quality of life has been proven in clinical trials. Prospective long-term data in routine clinical practice are limited. Objective:To assess the effectiveness and safety of LCIG over a 36-month prospective follow-up in Romania, as part of the DUOGLOBE international non-interventional study. Methods:DUOGLOBE (DUOdopa/Duopa in Patients with APD - a GLobal OBservational Study Evaluating Long-Term Effectiveness; NCT02611713) was a long-term observational study in patients with APD receiving LCIG as part of their treatment strategy in routine clinical care. Prospective data up to 36 months from LCIG initiation were collected in the study. The primary objective assessed the change in OFF time from baseline to 36 months. Results:Of the total number of 195 patients enrolled worldwide, 51 patients were included in 6 movement disorder centers in Romania. In these patients, LCIG was initiated after a median disease duration of 8.1 years (1.6-19.7). The need for concomitant anti-PD medication decreased within one month after LCIG initiation and remained stable for up to 36 months. The OFF time was significantly reduced by LCIG treatment at all timepoints vs baseline (p<0.001) (mean change [standard deviation, SD] at final visit: -3.4 ± 2.8 hours). Improvement of dyskinesia was recorded at 36 months (mean change [SD] of the Unified Dyskinesia Rating Scale at final visit -9.0 [16.54], p=0.006). Improvements in non-motor symptoms and quality of life were consistent from Day 1 throughout the study. Safety was consistent with the well-established LCIG profile and with the global study results (serious adverse events [SAEs]): 49.0% of patients discontinued the therapy (27.5% due to SAEs). Conclusion:DUOGLOBE provides long-term data on routine practice in Romania and consistent LCIG benefits in patients with APD.

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.

Introduction: The management of sedation during percutaneous endoscopic gastrojejunostomy (PEG-J) placement in patients with advanced Parkinson’s disease (PD) is challenging due to the complex interactions between PD treatment, anesthetic agents, and the disease’s motor and non-motor symptoms. This study evaluates the effectiveness and safety of a target-controlled infusion (TCI) propofol protocol in the context of PEG-J placement in advanced PD patients. Materials and Methods: This prospective study included 169 patients diagnosed with advanced Parkinson’s disease (Hoehn and Yahr stages 4 and 5) who underwent PEG-J placement at Târgu Mureș County Emergency Clinical Hospital, Romania. Sedation was induced and maintained using TCI propofol, with additional benzodiazepines and short-acting opioids, while muscle relaxants were not used. Procedural success rates and adverse outcomes were assessed for 30 days post-procedure. Results: The sedation protocol demonstrated a high procedural success rate. No deaths were reported within 30 days post-procedure. Conclusion: This study highlights the feasibility and clinical applicability of a TCI propofol protocol for PEG-J placement in patients with advanced PD (stages 4 and 5). While no deaths were recorded within the 30-day follow-up, the sample size is insufficient to draw definitive conclusions regarding long-term safety.

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.

BACKGROUND:Levodopa-entacapone-carbidopa intestinal gel (LECIG) was introduced in 2018 as a device-aided therapy for advanced Parkinson's disease (PD). OBJECTIVES:The ELEGANCE study (NCT05043103) is gathering real-world data on long-term efficacy, safety and patient-reported outcomes with LECIG from 13 European countries. This article reports data from the planned interim analysis. METHODS:The study enrolled patients prescribed LECIG as part of routine clinical care. We evaluated patients at V1 before starting LECIG treatment (in seven patients V1 data were obtained retrospectively), and thereafter at V2 (3-6 months) or V3 (6-12 months). RESULTS:This analysis includes 167 patients from 37 centers. Three patients from this analysis set (1.8%) discontinued the study. Mean (±SD) daily OFF-time hours (MDS-UPDRS IV item 4.3) were substantially reduced by 3.47 ± 3.56 h at V2 (baseline: 5.15 ± 3.05; P < 0.0001). Similarly, MDS-UPDRS part IV total scores were reduced by 4.24 ± 4.08 at V2 (baseline: 10.77 ± 3.83); (P = 0.0001) and MDS-UPDRS part II scores by 3.63 ± 7.76 at V2 (baseline: 20.65 ± 8.17; P = 0.0004). PDSS-2 total scores were sustainably improved (reduction of 7.38 ± 10.72 at V2 [baseline: 25.21 ± 10.62]; P < 0.0001), as was the PDQ-8 summary index score indicating an improvement in quality of life (QoL) (reduction of 13.3 ± 19.05 at V2 [baseline: 46.34 ± 20.09]; P < 0.0001). For all parameters improvements were maintained at V3. Patient-reported satisfaction with the LECIG pump was high. Most adverse events were related to the procedure or the device. CONCLUSIONS:Routine use of LECIG for up to 12 months provided sustained control of motor symptoms, and was well tolerated with a positive impact on QoL and high patient satisfaction.

Introduction: In advanced Parkinson's disease, oral or transdermal dopaminergic treatment is not effective enough and have significant side effects, so it may be necessary to use device-aided therapies for continuous dopaminergic stimulation. Objective: Our aim was to compare the clinical parameters of patients with advanced Parkinson's disease treated with levodopa-entacapone-carbidopa intestinal gel before the start of the treatment and at the discharge from the hospital. Method: We retrospectively analyzed data from patients who started levodopa-entacapone-carbidopa intestinal gel treatment: the patients' general and neurological condition, previous treatment, medication side effects, and complications of Parkinson's disease. Results: Levodopa-entacapone-carbidopa intestinal gel treatment was initiated in 29 patients. The patients had an initial off state of 4.7 +/- 0.8 hours/day. 20 patients suffered from moderately severe peak-dose dyskinesia (2.8 +/- 1.2 hours/day) and 6 patients from severe dyskinesia (2.1 +/- 1.0 hours/day). After treatment, the duration of the off state decreased significantly. There was a similar trend for mild or moderate dyskinesias, while severe dyskinesias disappeared completely. The sudden off states that occurred in 7 patients, were not present at discharge. After treatment, the early morning akinesia only occurred in 8 out of the initial 24. Discussion: The introduction of levodopa-entacapone-carbidopa intestinal gel proved to be effective, although our patients started the treatment later than recommended, and with serious motor complications. The mild, transient side effects related to treatment were comparable to literature. No entacapone-naive patient experienced gastrointestinal side effects. Conclusion: The effect of levodopa-carbidopa-entacapone intestinal gel on improving motor complications is similar to that of levodopa-carbidopa intestinal gel, with the advantage of lower daily levodopa dose and a smaller device. Further studies and longer clinical experience are necessary to recommend which of the two types of levodopa-containing enteral gel is more advantageous in individual cases. Long-term safety is also an important aspect in this decision, in order to improve the patients' quality of life.

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.

Background: Levodopa–entacapone–carbidopa intestinal gel infusion (LECIG) is the latest device-aided therapy for advanced Parkinson's disease (APD), approved in Romania in 2021. We aimed to analyze the APD patients' profile initiated on LECIG treatment.

Continuous intra-jejunal infusion of levodopa-carbidopa intestinal gel (LCIG) is a long-term proven and effective treatment in advanced Parkinson’s Disease (APD). Efficacy and safety of 16-h administration of LCIG has already been established. Additional benefits of 24-h LCIG administration have been reported in several case series and small clinical studies. The aim of this retrospective study was to compare the characteristics of patients who needed 24-h LCIG from the beginning of the DAT (device-aided treatment) with those who remained with the standard 16-h LCIG treatment and to identify particular motives if any. We initiated LCIG in 150 patients out of which in case of 62 patients (41,3%) due to unsatisfactory initial clinical benefits continuous 24-h LCIG was deemed necessary. Despite the subjective complaints and more severe clinical condition, at baseline evaluation we found statistically significant differences between 16-h LCIG cohort and 24-h LCIG cohort only in case of incidence of freezing (47% vs 65%, p = 0.03) and sudden off (32% vs 48%, p = 0.04). Wake hours/daytime LCIG does not always sufficiently improve the patient's quality of life in some patients due to persistent nighttime troublesome symptoms. Instead of labeling the patient as a non-responder, it is worth trying the 24-h LCIG dosage in a carefully selected group of patients, as there is currently no consensus on reliable criteria that serve the decision in these patients.

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.

Background: For Parkinson disease (PD) patients who have been diagnosed with advanced disease that can no longer be effectively controlled with optimized oral or transdermal medications, a range of device-aided therapies (DAT) are available, comprising either deep brain stimulation or infusion therapies providing continuous dopaminergic stimulation. Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is the latest DAT for advanced PD (APD) that was approved in Romania in 2021. Study Question: What is the experience to date in real-world clinical practice in Romania regarding the efficacy and tolerability of LECIG in APD? Study Design: A retrospective evaluation of 74 APD patients treated with LECIG at 12 specialized APD centers in Romania. Measures and Outcomes: Demographic data and various clinical parameters were recorded, including Mini Mental State Evaluation score or Montreal Cognitive Assessment Test score. Levodopa-equivalent daily dose and the administered doses of levodopa and other PD medications were evaluated at baseline and after starting LECIG treatment. The efficacy of LECIG in reducing daily hours of off time, motor fluctuations, and dyskinesias were assessed. Any percutaneous endoscopic gastrojejunostomy system or device complications after starting LECIG treatment were noted. Results: At baseline, patients were taking oral levodopa for a mean of 5.3 times per day, with a high proportion also taking concomitant add-on therapies (dopamine agonists, 86%, monoamine oxidase type-B inhibitors, 53%; catechol-O-methyltransferase inhibitors, 64%). LECIG treatment significantly reduced daily off time versus baseline from 5.7 h/d to 1.7 hours per day (P < 0.01). Duration and severity of dyskinesias was also significantly reduced versus baseline, and improvements were observed in Hoehn and Yahr Scale scores. LECIG treatment also allowed a significant reduction in the use of concomitant oral medications. Conclusions: These findings suggest that LECIG treatment is an effective DAT option in APD that can simplify the treatment regimen.

A high burden of motor and non-motor parkinsonian symptoms is known to have a significant negative impact on the quality of life (QoL) of people with Parkinson's disease (PD). Effective control of these symptoms with therapies that enable patients to maintain a good QoL is therefore a key treatment goal in PD management. When symptom control can no longer be accomplished with oral or transdermal PD treatment regimens, device-aided therapies (DAT), namely levodopa and apomorphine infusion therapies, and deep brain stimulation, are valuable options to consider. DAT options may also help reduce pill burden and thereby improve compliance with treatment. Since PD therapy relies on symptomatic management, the efficacy and tolerability of any intervention is undoubtedly important, however the impact of different therapies on patient-related outcome measures, in particular health-related QoL, is also a critical consideration for those living with a chronic and disabling condition. This review discusses clinical evidence and ongoing research regarding the QoL benefits of levodopa and apomorphine infusion therapies from studies that have used validated QoL outcome measures. The data suggest that timing of these interventions is important to achieve optimal treatment effects, and that early initiation onto infusion therapies at the point when motor fluctuations emerge, and before patient QoL and functioning have significantly declined, may provide the best long-term outcomes. Healthcare professionals caring for people with PD should therefore discuss all available DAT options with them at an early stage in the course of their disease so they can make informed and timely choices that best suit them, their families and care network.

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.

INTRODUCTION:Patients with advanced Parkinson's disease (APD) commonly experience motor and nonmotor symptoms (NMS) associated with functional limitations and decreased quality of life. We compared motor and nonmotor outcomes in patients with APD receiving 24- versus 16-h levodopa-carbidopa intestinal gel (LCIG). METHODS:Data from COSMOS, a large, real-world, retrospective and cross-sectional, observational study on LCIG and comedication in APD were obtained from medical records and a single patient visit for patients receiving 24- and 16-h LCIG infusion. Changes from baseline were evaluated for motor symptoms, NMS, and clinical characteristics. Safety was also assessed. RESULTS:Data for 401 patients were included in this subanalysis. At the patient visit there were 35 patients on 24-h LCIG and 366 on 16-h LCIG. "Off" time and dyskinesia (duration and severity) were reduced in both groups. In both LCIG treatment groups, prevalence of most symptoms was reduced. There were significant differences in the change from baseline in severity and frequency of freezing of gait with 24-h LCIG versus 16-h LCIG (p = 0.011 and p = 0.038), severity of urinary symptoms (p = 0.006), and frequency of cognitive impairment (p = 0.014) with 24-h LCIG versus 16-h LCIG. Adverse events were similar for both treatment groups and considered tolerable. CONCLUSIONS:LCIG 24-h infusion may be a useful treatment option, when clinically justified, for select patients with APD. CLINICAL TRIAL NUMBER:NCT03362879.

Abstract Disulfiram is a drug commonly used in the treatment of chronic alcohol use disorder. It works by inhibiting the enzyme acetaldehyde dehydrogenase, causing highly unpleasant symptoms upon alcohol intake, which supports abstinence by deterring alcohol consumption. We present the case of a 31-year-old male with a long history of alcohol dependence, since the age of 14. The patient had no other comorbidities. His addiction problem determined him to pursue alcohol withdrawal and psychiatric treatment. He had been on disulfiram therapy for one year. The onset of his symptoms started three months prior to admission to our clinic; he developed progressive, symmetric lower limb weakness, which notably worsened during the two weeks prior to hospitalization. According to collateral history, this exacerbation coincided with significant alcohol consumption while on disulfiram treatment. Neurological Examination Findings revealed: no meningeal signs, right-sided hearing loss, stepping gait achievable only with partial assistance, flaccid paraparesis (MRC grade 4 in the lower limbs muscle groups), tongue tremor, upper limb postural tremor, and palpebral myoclonus, symmetrical deep tendon reflexes, decreased in the lower limbs, no pyramidal signs, pallhypesthesia of the legs with reduced vibratory sense in the distal lower limbs, lower limb muscle hypotrophy, no sphincter or erectile dysfunction, preserved coordination and orientation in time and space. Electromyography and electroneurography revealed bilateral active denervation in the lower limb muscles, consistent with progressive poly(radiculo)neuropathy. Laboratory tests, cranial CT, spinal MRI, and cerebrospinal fluid analysis showed no other pathological findings to explain the neuropathy. Disulfiram therapy was discontinued, and the patient was treated with neurotrophic medications and physical therapy, leading to a gradual resolution of his symptoms. Although peripheral neuropathy due to disulfiram is rarely reported in the literature, in this case, the combination of disulfiram treatment with concurrent alcohol use likely contributed to the acute exacerbation of peripheral nerve damage.