Background: There is insufficient data in the literature regarding the real-life, daily clinical practice evaluation of patients with advanced Parkinson’s disease (APD). We are not sure what is the upper limit of dopaminergic medication, especially the levodopa (LD) dosage, and how it is influenced by access and suitability to the various add-on and device-aided therapies (DAT). Objective: This retrospective study explored the profile of APD patients that were considered and systematically evaluated regarding the suitability for DAT. Methods: We analyzed the data from 311 consecutive patients with APD hospitalized between 2011 and 2017 that 1) described at least 2 hrs/day off periods divided into at least two instances/day (except early morning akinesia), 2) were in stage 3 or above on the Hoehn and Yahr scale, 3) were with or without dyskinesia, and 4) received at least four levodopa doses/day combined with adjuvant therapy. Results: Of the 311 patients enrolled initially, 286 patients showed up for the second visit, of which in 125 cases we assessed that DAT would be necessary. Finally, 107 patients were tested in our clinic to confirm the efficacy of LCIG. Patients selected for DAT had significantly longer off periods, more frequent dyskinesia, early morning akinesia, and freezing despite having significantly higher LD doses than those with an improved conservative therapy. Conclusion: Patients with APD can have a variety of symptoms, and because symptoms and therapeutical efficacy can be manifested in many different combinations, it is not possible to decide using a single, rigid set of criteria which APD patient is eligible for DAT. Nevertheless, treating physicians should refer APD patients to a specialized movement disorder center when patients with an average daily dose of LD of at least 750–1000 mg and maximal complementary therapies present daily motor complications that significantly reduce the quality of life.

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.

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.

Absztrakt: Bevezetés: A Parkinson-kór kezelési stratégiájában a szelektív monoaminoxidáz-B-gátlóknak a betegség minden stádiumában jól meghatározott helyük van. Enyhe esetekben, főleg fiatal betegeknél, a szubsztitúciós terápia késleltetésének egyik hatékony eszközeként számolhatunk velük; előrehaladott Parkinson-kórban, a motoros komplikációk ellátásában, a levodopaterápia kiegészítői. Célkitűzés: Annak felmérése, hogy a marosvásárhelyi ideggyógyászati klinikákon alkalmazott terápiás stratégiákban mekkora szerep jut a szelektív monoaminoxidáz-B-gátlóknak. Módszer: Retrospektív tanulmányunkban 2003. január 1. és 2016. december 31. között a klinikákon vizsgált összes Parkinson-kóros beteg adatait elemeztük. A 2194 beteg zárójelentésében rögzített terápiás ajánlások alapján tanulmányoztuk a monoaminoxidáz-B-gátlók alkalmazásának sajátosságait. A Parkinson-kór megállapítása óta eltelt idő szerint öt éve, illetve több mint öt éve tartó betegségcsoportokat alkottunk. Eredmények: A vizsgált időszakban az öt éve vagy ennél rövidebb ideje diagnosztizált csoportban 1183 betegből 243 esetben szerepelt a kezelési stratégiában monoaminoxidáz-B-gátló: 12 esetben monoterápia, 52 esetben dopaminagonistával, illetve 61 esetben levodopával kombinálva. A többi 118 betegnél levodopa és dopaminagonista kombinációjához társítva kerültek alkalmazásra a monoaminoxidáz-B-gátlók. A több mint öt éve ismert 582 esetből 195-nél egészítették ki a terápiás stratégiát monoaminoxidáz-B-gátlóval (10 esetben szelegilin, 185 esetben rasagilin). Nem volt felhasználható adat a betegség kezdetét illetően 429 esetben (ezek közül öt esetben szelegilint, illetve 93 esetben rasagilint alkalmaztak). Következtetés: A vizsgált periódusban a monoaminoxidáz-B-gátlók alkalmazásának aránya hasonló az irodalomban talált adatokhoz. A betegséggel foglalkozó szakorvosoknak nagyobb bátorsággal kellene alkalmazniuk a rendelkezésre álló és az ajánlásokban szereplő készítményeket, jobban kihasználni a különböző gyógyszertársítások előnyeit, különösen, ha ez nem terheli anyagilag a beteget. Orv Hetil. 2017; 158(51): 2023–2028. Introduction: Selective monoamine oxidase B inhibitors have an accurate place in therapeutical strategy of Parkinsons’s disease. In the early stages of the disease, especially in younger patients with milder symptoms, the introduction of levodopa substitution could be efficacious in delaying; in advanced stages they are mainly used to treat motor complications, as an adjunct to levodopa. Aim: The evaluation of therapeutical strategies used in the neurology clinics of Tirgu Mures County Emergency Clinical Hospital in order to define the role of monoamine oxidase B inhibitors. Method: This retrospective study includes all records of patients with Parkinson’s disease hospitalized between 1 January 2003 and 31 December 2016. From the 2194 reports we used data focusing on the therapeutic recommendations. Regarding disease duration, we divided the patients in two groups: less than or equal to 5 years and more than 5 years. Results: From the 1183 patients in first group, 243 received monoamine oxidase inhibitors: 12 as monotherapy, 52 together with dopamine agonists, in 61 cases combined with levodopa. In 118 cases monoamine oxidase inhibitors were combined with levodopa and dopamine agonists. From 582 cases whith Parkinson’s disease for more than 5 years, 195 received monoamine oxidase B inhibitors (selegiline: 10 cases, rasagiline: 185 cases). In 429 cases we did not find accurate data regarding disease duration (selegiline: 5 cases, rasagiline: 93 cases). Conclusion: The use of monoamine oxidase B inhibitors was similar to those found in literature. The treating physicians should utilise more confidently the available therapeutical combinations. Orv Hetil. 2017; 158(51): 2023–2028.

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.

The aim of the COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS) was to assess the use of levodopa/carbidopa intestinal gel (LCIG) as monotherapy in patients with advanced Parkinson’s disease (APD) in routine clinical practice. COSMOS was an international observational study with one cross-sectional visit and retrospective data collection. In Romania, 95 adult patients with APD on LCIG treatment for at least 12 months were enrolled and stratified according to their LCIG therapy after 12 months: monotherapy (without any add-on PD medication), monotherapy with night PD medication and LCIG + add-on medication. Compared to the moment of LCIG initiation, the percentage of patients on monotherapy increased at three months after LCIG initiation and remained constant up to 12 months, when 30.5% of the patients were on LCIG monotherapy and 11.6% were on monotherapy with night medication. “Off” time and “On” time with dyskinesia decreased from LCIG initiation to patient visit in all groups. LCIG monotherapy with or without night medication may provide a simplified treatment option for selected APD patients, with long-term efficacy similar to that of LCIG plus add-on medication.