Hypokinetic dysarthria (HD) is a difficult-to-treat symptom affecting quality of life in patients with Parkinson's disease (PD). Levodopa may partially alleviate some symptoms of HD in PD, but the neural correlates of these effects are not fully understood. The aim of our study was to identify neural mechanisms by which levodopa affects articulation and prosody in patients with PD. Altogether 20 PD patients participated in a task fMRI study (overt sentence reading). Using a single dose of levodopa after an overnight withdrawal of dopaminergic medication, levodopa-induced BOLD signal changes within the articulatory pathway (in regions of interest; ROIs) were studied. We also correlated levodopa-induced BOLD signal changes with the changes in acoustic parameters of speech. We observed no significant changes in acoustic parameters due to acute levodopa administration. After levodopa administration as compared to the OFF dopaminergic condition, patients showed task-induced BOLD signal decreases in the left ventral thalamus (p = 0.0033). The changes in thalamic activation were associated with changes in pitch variation (R = 0.67, p = 0.006), while the changes in caudate nucleus activation were related to changes in the second formant variability which evaluates precise articulation (R = 0.70, p = 0.003). The results are in line with the notion that levodopa does not have a major impact on HD in PD, but it may induce neural changes within the basal ganglia circuitries that are related to changes in speech prosody and articulation.
- MeSH
- antiparkinsonika škodlivé účinky MeSH
- dysartrie etiologie komplikace MeSH
- kvalita života MeSH
- levodopa * škodlivé účinky MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- Parkinsonova nemoc * komplikace diagnostické zobrazování farmakoterapie MeSH
- poruchy řeči diagnostické zobrazování etiologie MeSH
- řeč fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Po více než 50 let od zahájení klinického použití levodopy nebyl k dispozici minimálně invazivní způsob podání, který by umožnil udržení stabilní hladiny v těle pacienta. To se nyní změnilo díky fosforylované levodopě, tzv. foslevodopě, kterou lze kvůli zvýšené rozpustnosti ve vodě podávat podkožně pomocí připojené pumpy. Díky subkutánnímu podání se očekává značné rozšíření tohoto léčebného postupu do klinické praxe. Autoři v článku shrnují aspekty vývoje uvedeného léku a shrnují dostupné praktické klinické informace.
More than 50 years since the first clinical use of levodopa there has been no mini-invasive way of administration which would maintain a stable level of levodopa in patients ́s body. This has now changed with phosphorylated levodopa, co called phospholevodopa which is soluble in water and therefore can be injected subcutaneously using a pumps. Owing to the subcutaneous application this therapeutic method is expected to spread into clinical practice. The authors summarise the aspects of the development and clinical information of the drug.
- MeSH
- antiparkinsonika farmakologie terapeutické užití MeSH
- inhibitory dekarboxylasy aromatických aminokyselin farmakologie terapeutické užití MeSH
- levodopa farmakologie terapeutické užití MeSH
- lidé MeSH
- Parkinsonova nemoc * farmakoterapie patologie MeSH
- příznaky a symptomy MeSH
- rehabilitace metody MeSH
- Check Tag
- lidé MeSH
Cieľom štúdie bolo poukázať na prínos nových invazívnych terapeutických postupov v liečbe pokročilých štádií Parkinsonovej choroby (PCh) v porovnaní s klasickou perorálnou farmakoterapiou. Výsledky boli získané zo súboru 43 pacientov s PCh, z ktorých 39 % podstúpilo klasickú terapiu pozostávajúcu z perorálnych antiparkinsoník, 23 % pacientov užívalo intestinálny gél obsahujúci levodopou (Duodopa), 19 % pacientov malo indikovanú apomorfínovú subkutánnu pumpu a 19 % pacientov podstúpilo hĺbkovú mozgovú stimuláciu (DBS). Väčšina pacientov mala pokročilejšie štádiá PCh, štádium 4 podľa Hoehnovej a Yahra (1967). Výsledky práce ukazujú zlepšenie stavu po nasadení nového terapeutického postupu u väčšiny pacientov v porovnaní s klasickou terapiou. Pozitívny vplyv bol zaznamenaný aj v zníženej potrebe užívania liekov per os, kde bol zaznamenaný signifikantný pokles pri všetkých nových terapeutických postupoch. Taktiež bol zaznamenaný pozitívny účinok v redukcii off stavov u pacientov. V prípade Duodopy a DBS došlo k skráteniu off periódy o 50 % a pri apomorfínovej pumpe o 40 %. Pacienti tiež hlásili zlepšenie niektorých symptómov ochorenia ako tremor či rigidita, zatiaľ čo dyskinézy naďalej predstavujú výzvu. Na základe získaných výsledkov sa môže konštatovať, že nové terapeutické postupy pri PCh umožnia zvládnuť symptómy typické pre pokročilé štádia ochorenia, ktoré by bez týchto postupov viedli k invalidite, čo je hlavným dôvodom ich indikácie. U pacientov s pomalšou progresiou ochorenia v skorých štádiách je klasická forma terapie perorálnymi antiparkinsonikami stále zlatým štandardom. Dôvodom je nielen ich relatívna účinnosť, ale aj lepšia ekonomická dostupnosť, nakoľko nové postupy sú spojené s vysokými finančnými nákladmi a v rámci verejného zdravotného poistenia môžu byť v Slovenskej republike použité len na základe rozhodnutia revízneho lekára.
The aim of the study was to point out the contribution of new invasive therapeutic procedures in the treatment of advanced stages of Parkinson’s disease (PD) in comparison with classical oral pharmacotherapy. Data originated from a group of 43 patients with PD, 39% (17) with classic treatment, 23% (10) with intestinal gel of methyl ester levodopa (Duodopa), 19% (8) of patients were using subcutaneous delivery of apomorphine (APO) and the same quantity of patients had undergone deep brain stimulation (DBS). Majority of patients had advanced stages of PD, stage 4, by standards of Hoehn and Yahr scale (Hoehn and Yahr, 1967). Research observed improvement in majority of patients with novel treatments. A positive effect was also noted in the reduced need for oral therapy, where there was a significant decrease in all new therapies. Benefits were observed in the amount of antiparkinsonic drugs taken per os, where we observed reduction in all new therapies. A positive effect of the new therapeutic approaches in reducing “off” periods in patients has also been noted. In the case of Duodopa and DBS, the ”off” period was shortened up to 50% and in the apomorphine pump up to 40%. Patients also reported reduction of some symptoms like rigidity, tremor and bradykinesis while dyskinesis still remains suba challenge. On the basis of the obtained results, it can be concluded that new therapeutic procedures for PCh will make it possible to manage symptoms typical of advanced stages of the disease, which without these procedures would lead to disability, which is the main reason for their indication. However, in early stages, well responding patients or in slow progressing disease oral antiparkinsonics are remaining as golden standard of treatment. This is not just due to good response but also because these classic drug formulations are significantly less expensive. In Slovakia, novel treatments are accessible through healthcare insurance only after secondary revision by insurance company doctors.
- Klíčová slova
- Duodopa, apomorfínová pumpa,
- MeSH
- apomorfin aplikace a dávkování terapeutické užití MeSH
- fixní kombinace léků MeSH
- hluboká mozková stimulace metody MeSH
- implantabilní infuzní pumpy MeSH
- karbidopa farmakologie terapeutické užití MeSH
- klinická studie jako téma MeSH
- levodopa farmakologie terapeutické užití MeSH
- lidé MeSH
- Parkinsonova nemoc * terapie MeSH
- Check Tag
- lidé MeSH
BACKGROUND: While immediate benefits of levodopa-carbidopa intestinal gel (LCIG) are evident in patients with Parkinson's disease (PD), long-term LCIG effects require further study. OBJECTIVES: We explored long-term LCIG on motor symptoms, nonmotor symptoms (NMS), and LCIG treatment settings in patients with advanced PD (APD). METHODS: Data were obtained (medical records and patient visit) from COSMOS, a multinational, retrospective, cross-sectional post-marketing observational study in patients with APD. Patients were stratified into 5 groups based on LCIG treatment duration at the patient visit, from 1-2 to > 5 years LCIG. Between-group differences were assessed for changes from baseline in LCIG settings, motor symptoms, NMS, add-on medications, and safety. RESULTS: Out of 387 patients, the number of patients per LCIG group was: > 1- ≤ 2 years LCIG (n = 156); > 2- ≤ 3 years LCIG (n = 80); > 3- ≤ 4 years LCIG (n = 61); > 4- ≤ 5 years LCIG (n = 30); > 5 years LCIG (n = 60). Baseline values were similar; data reported are changes from the baseline. There were reductions in "off" time, dyskinesia duration, and severity across LCIG groups. Prevalence, severity, and frequency of many individual motor symptoms and some NMS were reduced amongst all LCIG groups, with few differences between groups. Doses for LCIG, LEDD and LEDD for add-on medications were similar across groups both at LCIG initiation and patient visit. Adverse events were similar across all LCIG groups and consistent with the established safety profile of LCIG. CONCLUSIONS: LCIG may provide sustained, long-term symptom control, while potentially avoiding increases in add-on medication dosages. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03362879. Number and date: P16-831, November 30, 2017.
- MeSH
- antiparkinsonika škodlivé účinky MeSH
- fixní kombinace léků MeSH
- gely terapeutické užití MeSH
- karbidopa * MeSH
- levodopa terapeutické užití MeSH
- lidé MeSH
- Parkinsonova nemoc * farmakoterapie MeSH
- průřezové studie MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
Parkinsonova nemoc je chronické, nevyléčitelné a invalidizující neurodegenerativní onemocnění, kdy se v mozku netvoří dostatek neurotransmiteru dopaminu. V České republice se týká několika desítek tisíc lidí zejména po padesátém roce života, kdy tito pacienti mají v různé míře vyjádřeny potíže motorické a nemotorické. Pro pacienty s rozvinutou Parkinsonovou nemocí je životně důležitý přísun správně dávkovaného dopaminu v tabletách nebo výjimečně jiná léčba. Bez léčby anebo zejména při náhlém výpadku léčby může dojít až k úmrtí. Kazuistika s dobrým koncem popisuje raritní případ původně personálem LDN považovaný za střevní helmintózu provázený vážným zhoršením zdravotního stavu u lucidní pacientky parkinsoničky s překvapivým rozuzlením. Pro autora slouží pro příště i jako ponaučení, že je třeba znát alespoň základy konstrukce a funkce moderních léčebných možností i přes to, že se s nimi lékař mimo kliniku setká jen několikrát za život a že se tyto jeví dosud jako zcela bezproblémové a bezobslužné.
Parkinson disease is a long-term degenerative, incurable and invaliding disorder of the central nervous system showing the deficient production of neurotransmitter dopamine in the brain. In the Czech Republic the disease affects several ten thousands of people, especially those aged fifty or more. The patients suffer from various symptoms, both motor and non-motor. It is important to supply the patients in a developed stage of the disease with the right doses of dopamine in tablets or, exceptionally, a different treatment. Where no treatment is given or a treatment is suddenly disrupted, a death may occur. The following well-ending case history describes a rare case considered by the hospital for long term sickness personnel to be intestinal helminthiases accompanied by a serious worsening of the health condition in a lucid female patient with Parkinson disease. The case had a surprising outcome. The case history also shows that it is necessary to be knowledgeable in the constructions and functions of the medicala dvices although one meets such medical advices outside clinics only a few times in his/her life and that such constructions and functions seem to be totally trouble-free and fully automated.
- MeSH
- chybná diagnóza MeSH
- helmintóza MeSH
- jejunostomie MeSH
- levodopa aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc * farmakoterapie MeSH
- selhání zařízení MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- antiparkinsonika aplikace a dávkování farmakologie klasifikace MeSH
- diferenciální diagnóza MeSH
- levodopa aplikace a dávkování farmakologie klasifikace MeSH
- lidé MeSH
- Parkinsonova nemoc * dějiny diagnóza epidemiologie etiologie farmakoterapie terapie MeSH
- rizikové faktory MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- Klíčová slova
- LECIGIMON,
- MeSH
- antiparkinsonika terapeutické užití MeSH
- gastrointestinální intubace metody MeSH
- gely MeSH
- karbidopa aplikace a dávkování farmakokinetika MeSH
- katecholy aplikace a dávkování farmakokinetika MeSH
- kombinovaná farmakoterapie MeSH
- levodopa aplikace a dávkování farmakokinetika MeSH
- lidé MeSH
- nitrily aplikace a dávkování farmakokinetika MeSH
- Parkinsonova nemoc farmakoterapie patofyziologie MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants. CONCLUSIONS: In participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks. (Funded by the European Union Horizon 2020 program; FAIRPARK-II ClinicalTrials.gov number, NCT02655315.).
- MeSH
- antiparkinsonika * aplikace a dávkování škodlivé účinky farmakologie terapeutické užití MeSH
- aplikace orální MeSH
- chelátory železa * aplikace a dávkování škodlivé účinky farmakologie terapeutické užití MeSH
- deferipron * aplikace a dávkování škodlivé účinky farmakologie terapeutické užití MeSH
- dopaminové látky aplikace a dávkování škodlivé účinky farmakologie terapeutické užití MeSH
- dvojitá slepá metoda MeSH
- levodopa terapeutické užití MeSH
- lidé MeSH
- mozek - chemie MeSH
- mozek diagnostické zobrazování MeSH
- neutropenie chemicky indukované MeSH
- Parkinsonova nemoc * farmakoterapie metabolismus patofyziologie MeSH
- progrese nemoci MeSH
- substantia nigra * chemie diagnostické zobrazování účinky léků metabolismus MeSH
- železo * analýza metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Dopamine depletion in the axons of Parkinson's disease (PD) patients precedes depletion in cell bodies thus proposing that macroscopic connectivity can be used to understand disease mechanism. A novel multivariate functional connectivity analysis, based on high order coherence among four fMRI BOLD signals was applied on resting-state fMRI data of controls and PD patients (OFF and ON medication states) and unidirectional multiple-region pathways in the sensorimotor system were identified. Pathways were classified as "preserved" (unaffected by the disease), "damaged" (not observed in patients) and "corrected" (observed in controls and in PD-ON state). The majority of all pathways were feedforward, most of them with the pattern "S1→M1→SMA." Of these pathways, 67% were "damaged," 28% "preserved," and 5% "corrected." Prefrontal cortex (PFC) afferent and efferent pathways that corresponded to goal directed and habitual activities corresponded to recurrent circuits. Eighty-one percent of habitual afferent had internal cue (i.e., M1→S1→), of them 79% were "damaged" and the rest "preserved." All goal-directed afferent had external cue (i.e., S1→M1→) with third "damaged," third "preserved," and third "corrected." Corrected pathways were initiated in the dorsolateral PFC. Reduced connectivity of the SMA and PFC resulted from reduced sensorimotor afferent to these regions. Reduced sensorimotor internal cues to the PFC resulted with reduced habitual processes. Levodopa effects were for pathways that started in region reach with dopamine receptors. This methodology can enrich understudying of PD mechanisms in other (e.g., the default mode network) systems.
- MeSH
- levodopa MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mapování mozku MeSH
- nervové dráhy MeSH
- odpočinek MeSH
- Parkinsonova nemoc * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
