Background: Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease. In the advanced stages, the continuous delivery of levodopa (LD) as levodopa-carbidopa intestinal gel (LCIG) has demonstrated significant improvement of motor and nonmotor complications and improvement of the patients’ quality of life (QoL). Despite the growing global experience with this treatment, anumber of unsolved practical issues remain, and currently, the data on the reasons that can lead to the discontinuation of LCIG are scarce. Objective: In the present study, we aimed to analyze the causes that led to the discontinuation of LCIG therapy. Methods: In this retrospective study, after 10 years of experience with LCIG as a therapeutic option in advanced PD, we analyzed the data of all dropout cases among the 204 patients that initiated LCIG therapy in two Romanian centers. Results: Of the 204 patients enrolled, 43 patients dropped out. Disease duration until LCIG infusion was significantly longer (11.67± 4.98 vs 9.44± 3.44) and the overall clinical picture more sever (both regarding motor symptoms and cognitive decline) in dropout patients (compared to patients who continued treatment). The dropout patients also presented significant differences regarding the incidence of polyneuropathy (32.5% vs 11.18%). The main cause of discontinuation was death. Conclusion: The causes of discontinuation from LCIG therapy in Romanian patients are similar to those from other centers; however, the rate of dropouts is somewhat lower. The clinician’s experience in selecting and treating the patients in advanced stages of PD can increase therapeutic adherence. Also, the presence of a well-trained caregiver along with the availability of a proper aftercare system is mandatory for maintaining the long-term benefits of the therapy and the overall best outcome possible. Targeted prospective studies are needed to confirm whether a more severe stage of the disease and cognitive impairment at the time of initiation, respectively, the association of polyneuropathy can be considered as predictive factors for dropout.

Introduction: In patients older than 70 years there is no valid alternative to progressively introduced substitution therapy. The antiparkinsonian drugs introduced in the last decade to treat Parkinson’s disease, especially in its early phases, promised a comparable efficacy in reducing symptoms to levodopa. In younger patients and/or patients with mild symptoms we hoped to delay the motor complications by postponing the start of levodopa therapy. While these assumptions may not be true for all patients, probably the most important current challenge is the optimal starting moment of levodopa therapy. The aim of the study was to analyze the therapeutical choices during the early phase of Parkinson’s disease in the Neurological Departments of Târgu Mureş County Hospital. Materials and methods: We examined data obtained from hospitalized Parkinson’s disease patients during a 15-year period. According to the duration of the disease we split the patients into two groups, patients with Parkinson’s disease for less than or equal to 5 years and patients with disease duration longer than 5 years, and then analyzed only the former group. Results: During the examined period, 2,379 patients with Parkinson’s disease were hospitalized, and 1,237 patients had a disease duration shorter than 5 years. In this group, 18 patients had monoamine oxidase inhibitor monotherapy. Also, 665 patients received dopamine agonists, in 120 cases as monotherapy and in 83 patients associated with monoamine oxidase inhibitors. In 521 patients we found only levodopa treatment. A further 481 patients received combined therapy (levodopa with dopamine agonists and/or monoamine oxidase inhibitors). Conclusion: Treatment strategies for the early stages of Parkinson’s disease in our group were comparable to results from other studies. However, the authors feel that neurologists should use levodopa-sparing drugs with greater courage. Furthermore, if the clinical context is appropriate, physicians should combine substitution therapy with other antiparkinsonian drugs in order to reduce levodopa doses.

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.

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 and purpose - There is relatively few data regarding the usage of dopaminagonists for the treatment of Parkinson's disease; furthermore, there are no publications regarding Central- and Eastern-European countries. The aim of the study was to evaluate the use of dopamine agonists as a therapeutic option amongst Parkinson's disease patients admitted to the Neurological Clinics of Tirgu Mures during the last 15 years. Methods - In our study we investigated the data of all Parkinson's patients treated at our clinics between the 1st of January 2003 and the 31st of December 2017. We analyzed the particularities of dopamine agonists' usage based on the therapeutic recommendations from the final report of these patients. Regarding time since the diagnosis, we divided the patients in two groups: less than or equal to 5 years and more than 5 years. Results - During the studied period a total of 2379 patients with Parkinson's disease were treated at the Clinics. From the 1237 patients with disease duration under 5 years 665 received dopamine agonists: 120 as monotherapy, 83 together with monoamine oxidase inhibitors and in 234 cases associated with levodopa. The remaining 228 patients were treated with a triple combination of levodopa, dopamine agonists and monoamine oxidase inhibitors. In patients suffering from Parkinson's disease for more than 5 years, in 364 cases out of 653 a dopamine agonist was part of the therapy. Conclusion - The usage of dopamine agonists was similar to the data presented in other studies. We consider that clinicians treating the disease should, with the necessary prudence, use the available and recommended dopamine agofiist with the utmost-courage.to their maximum therapeutic potential.

Absztrakt: Bevezetés: A Parkinson-kór előrehaladásával jelentkező motoros, illetve nem motoros komplikációk jelentősen rontják a Parkinson-kóros betegek életminőségét, behatárolják a terápiás lehetőségeket. Nincs egyértelműen meghatározva az „előrehaladott” Parkinson-kór, sem az invazív terápiák bevezetésének optimális pillanata. Kevés irodalmi adat vonatkozik arra, hogy a mindennapi klinikai gyakorlatban alkalmazott levodopaadagok felső határai hogyan alakulnak előrehaladott Parkinson-kórban, illetve az egyes eszközös terápiák elérhetősége hogyan befolyásolja ezeket. Célkitűzés: A szubsztitúciós terápia elemzése előrehaladott Parkinson-kórban. Módszer: Retrospektív tanulmányunkban 2011. június 1. és 2017. május 31. között minden olyan, Parkinson-kórral kezelt beteget megvizsgáltunk, aki legalább napi 2 óra off állapotról számolt be, dyskinesisekkel vagy ezek nélkül, és legalább napi négyszer kapott különböző kombinációkban levodopát. Elemeztük a levodopaterápia sajátosságait az eszközös, illetve a további konzervatív kezelésre javasolt betegcsoportoknál. Eredmények: Előrehaladott Parkinson-kórt állapítottunk meg 311 betegnél, közülük 125-nél véltük indokoltnak valamilyen eszközös terápia elkezdését, míg 42-nél a levodopa dózisának emelését. Az eszközös kezelésre javasolt betegcsoport és a konzervatív kezelést folytató betegcsoport között különbségek voltak a betegség fennállása, a levodopa átlagadagja és adagolási frekvenciája tekintetében. A 107 levodopa-karbidopa intestinalis gélre tesztelt betegnél az adagolási frekvencia és a levodopa-átlagadagok magasabbak voltak. Következtetés: A vizsgált periódusban előrehaladott Parkinson-kórban az irodalmi adatokhoz viszonyítva kisebb levodopaadagokat találtunk, a kombináció adjuváns terápiával viszont gyakoribb. Előrehaladott Parkinson-kórban érdemes az eszközös terápiát mérlegelni, ha a napi átlagos levodopaadag legalább 750–1000 mg, minimum ötszöri adagolásra elosztva, és kombinált terápia ellenére az életminőséget jelentősen csökkentő motoros komplikációk jelentkeznek. Ezeket a betegeket erre szakosodott központokban multidiszciplináris csapat közreműködésével kell tesztelni, és a legjobb döntést meghozni a további teendőket illetően. Orv Hetil. 2019; 160(17): 662–669. Introduction: The motor and non-motor complications of Parkinson’s disease impair the patients’ quality of life and limit therapeutical options. There are no clear criteria for ‘advanced’ Parkinson’s disease or for the optimal moment for invasive therapies. There is little evidence regarding the upper limits of levodopa doses, and how these may be influenced by the availability of device-aided therapies. Aim: To analyze substitution therapy in patients with advanced Parkinson’s disease. Method: In our retrospective study, we analyzed the data from all patients with advanced Parkinson’s disease hospitalized between 1st June 2011 and 31st May 2017, receiving combined levodopa treatment at least 4×/day, reporting a minimum of 2 hours off periods, with or without dyskinesia. We analyzed levodopa therapy for patients who were recommended either device-aided or conservative therapy. Results: Out of 311 patients with advanced Parkinson’s disease, for 125 we proposed device-aided therapies whereas in 42 patients we increased the levodopa dose. The average levodopa doses and the administration rate were higher for the 107 patients tested for levodopa-carbidopa intestinal gel. Disease duration, mean levodopa doses and frequency of dosing were all higher in patients proposed for device-aided therapies versus patients with continued conservative treatment. Conclusion: Our patients were on lower levodopa doses (compared to literature), but the combinations were used more often. Device-aided therapies should be considered in patients with severe motor complications who receive at least 750–1000 mg levodopa daily, divided minimum 5×/day. These patients need to be tested in specialized centers by multidisciplinary teams in order to make the best decision for further action. Orv Hetil. 2019; 160(17): 662–669.