Parkinson-kóros betegek betegségteher felmérése Magyarországon

Szerte Európában az öregedő társadalom problémájával nézünk szembe. Ezzel függ össze a növekvő Parkinson-esetszám (Magyarországon megközelítőleg 20 000 beteg él ezzel a betegséggel), és az egyre nagyobb igény az idősödéssel összefüggő egészségügyi kiadásokra. Egyre fontosabb szerephez jut a költségtudatos egészségügyi gondoskodás. A betegségteher felmérések ezt igyekszenek alátámasztani. Keresztmetszeti kérdőíves vizsgálatot végeztünk a SE Neurológiai Klinika Parkinson-kórral élő betegein, életminőséget (EQ-5D és PDQ-39 kérdőívekkel) és a betegség költségeit (indirekt és direkt) vizsgálva. Az eredmények szerint a betegséggel összefüggő költségek jelentősek, 3 509 310 Ft/beteg/év, és a betegség jelentős életminőség csökkenést okoz. Tanulmányunkban a 2008 őszén elkezdett kutatást szeretnénk bemutatni, ismertetni a módszertant és az eredményeket, összevetve nemzetközi adatokkal

Levodopa/carbidopa intesztinális gél alkalmazása előrehaladott Parkinson-kórban.

Parkinson's disease is the second most common neurodegenerative disorder around the world. Levodopa has remained the "gold standard" of the therapy even several decades after its introduction. Chronic levodopa treatment is associated with the development of motor complications in most patients. Advanced Parkinson's disease is characterized by these complications: motor and non-motor fluctuation and disturbing dyskinesia. Continuous dopaminergic stimulation might reduce these complications. In advanced Parkinson's disease levodopa is still effective. In the treatment of this stage there are several advanced or device-aided therapies: apomorphine pump, deep brain stimulation and levodopa/carbidopa intestinal gel. Levodopa/carbidopa intestinal gel is an aqueous gel that can be delivered to the jejunum via a percutaneous gastrojejunostomy tube which is connected to an infusion pump dosing the levodopa gel continuously to the place of absorption. Levodopa/carbidopa gel infusion can be used as monotherapy, can be tested, can be used individually and this therapy is reversible. Several clinical trials demonstrated that levodopa/carbidopa intestinal gel therapy is of long-term benefit, improves the quality of life of the patients and can reduce motor fluctuation and dyskinesia

Disturbed post-movement beta synchronization in Wilson's disease with neurological manifestation

We analyzed the changes of post-movement beta synchronization (PMBS) of the electroencephalogram (EEG) in Wilson's disease with neurological manifestation. Our aim was to determine if PMBS in Wilson's disease is altered in a different way than in Parkinson's disease or in essential tremor. Our purpose was to find out whether the analysis of PMBS could help the diagnosis in ambiguous cases. Ten patients with neurological manifestation of Wilson's disease and ten controls performed self-paced movements with the dominant hand during EEG acquisition. Five electrodes above the sensorimotor cortex were selected for evaluation (C3, C1, Cz, C2, C4) as contralateral (C); contralateral medial (CM); medial (M); ipsilateral medial (IM); ipsilateral (I) relative to the dominant hand. Power and latency of PMBS were calculated by time resolved power spectral analysis with multitaper method. PMBS power in the C electrode position was significantly lower in patients than in controls, its contralateral preponderance disappeared in the patient group. In every location, latency of PMBS was significantly longer in the Wilson group compared to controls. More altered PMBS could be measured in patients with both basal ganglia and cerebellar involvements. Since decreased power of PMBS was observed in Parkinson's disease and increased latency in essential tremor, the combined change of PMBS can indicate pathology of different neural circuits and may help the diagnosis in challenging cases

GBA-associated Parkinson’s disease in Hungary: clinical features and genetic insights

Introduction: Parkinson’s disease (PD) has a complex genetic background involving both rare and common genetic variants. Although a small percentage of cases show a clear Mendelian inheritance pattern, it is much more relevant to identify patients who present with a complex genetic profile of risk variants with different severity. The ß-glucocerebrosidase coding gene (GBA1) is recognized as the most frequent genetic risk factor for PD and Lewy body dementia, irrespective of reduction of the enzyme activity due to genetic variants. Methods: In a selected cohort of 190 Hungarian patients with clinical signs of PD and suspected genetic risk, we performed the genetic testing of the GBA1 gene. As other genetic hits can modify clinical features, we also screened for additional rare variants in other neurodegenerative genes and assessed the APOE-ε genotype of the patients. Results: In our cohort, we identified 29 GBA1 rare variant (RV) carriers. Out of the six different detected RVs, the highly debated E365K and T408M variants are composed of the majority of them (22 out of 32). Three patients carried two GBA1 variants, and an additional three patients carried rare variants in other neurodegenerative genes (SMPD1, SPG11, and SNCA). We did not observe differences in age at onset or other clinical features of the patients carrying two GBA1 variants or patients carrying heterozygous APOE-ε4 allele. Conclusion: We need further studies to better understand the drivers of clinical differences in these patients, as this could have important therapeutic implications. © 2023, The Author(s)

Quality of Life and Costs in Parkinson's Disease: A Cross Sectional Study in Hungary.

BACKGROUND: Patient reported outcomes and costs of illness are useful to capture some of the multiple effects of a disease and its treatments. Our aim was to assess quality of life (QoL) and costs of Parkinson's disease (PD) in Hungary, and to analyze their associations. METHODS: A cross-sectional questionnaire survey was conducted in one neurology university clinic. Clinical characteristics, PD related resource utilizations and productivity loss in the past 12 months were recorded; the Hoehn&Yahr (HY) scale, PDQ-39 and EQ-5D questionnaires were applied. Cost calculation was performed from the societal perspective. RESULTS: 110 patients (34.5% female) were involved with mean age of 63.3 (SD = 11.3) and disease duration of 8.2 (SD = 5.8) years. PDQ-39 summary score was 48.1 (SD = 13.4). The average EQ-5D score was 0.59 (SD = 0.28), and was significantly lower than the population norm in age-groups 45-74. The correlation was significant between EQ-5D and PDQ-39 (-0.47, p = 0.000), the HY scale and EQ-5D (-0.3416, p = 0.0008) and PDQ-39 (0.3419, p = 0.0006) scores. The total mean cost was euro6030.2 (SD = 6163.0)/patient/year (direct medical 35.7%, direct non-medical 29.4%, indirect cost 34.9%). A one year increase in disease duration and 0.1 decrease of the EQ-5D utility score increase the yearly costs by 8 to 10%, and 7.8%, respectively. The effect of the PDQ-39 score on total cost was not significant. CONCLUSIONS: Disease severity and public health importance of PD are clearly demonstrated by the magnitude of QoL loss. PD-related costs are substantial, but are much lower in Hungary than in Western European countries. Disease duration and EQ-5D score are significant proxy of costs

Cutaneous Autonomic Pilomotor Testing to Unveil the Role of Neuropathy Progression in Early Parkinson’s Disease (CAPTURE PD): Protocol for a Multicenter Study

BackgroundIn Parkinson’s disease (PD), alpha-synuclein accumulation in cutaneous autonomic pilomotor and sudomotor nerve fibers has been linked to autonomic nervous system disturbances even in the early stages of the disease. This study aims to assess the association between alpha-synuclein-mediated structural autonomic nerve fiber damage and function in PD, elucidate the role of neuropathy progression during the early disease stages, and test reproducibility and external validity of pilomotor function assessment using quantitative pilomotor axon-reflex test and sudomotor function via quantitative direct and indirect test of sudomotor function.Methods/designA prospective controlled study will be conducted at four study sites in Europe and the USA. Fifty-two male and female patients with idiopathic PD (Hoehn and Yahr 1–2) and 52 age- and sex-matched healthy controls will be recruited. Axon-reflex-mediated pilomotor erection will be induced by iontophoresis of phenylephrine on the dorsal forearm. Silicone impressions of the response will be obtained, scanned, and quantified for pilomotor muscle impressions by number, impression size, and area of axon-reflex spread. Axon-reflex-mediated sweating following acetylcholine iontophoresis will be quantified for number and size of droplets and axon-reflex spread. Sympathetic skin responses, autonomic and motor symptoms will be evaluated. Tests will be performed at baseline, after 2 weeks, 1, 2, and 3 years. Skin biopsies will be obtained at baseline and after 3 years and will be analyzed for nerve fiber density and alpha-synuclein accumulation.DiscussionWe anticipate that progression of autonomic nerve dysfunction assessed via pilomotor and sudomotor axon-reflex tests is related to progression of autonomic symptom severity and alpha-synuclein deposition. Potential applications of the techniques include interventional studies evaluating disease-modifying approaches and clinical assessment of autonomic dysfunction in patients with PD.Clinical trail registrationTRN NCT03043768

The effect of dopamine agonists on adaptive and aberrant salience in Parkinson's disease

Clinical evidence suggests that after initiation of dopaminergic medications some patients with Parkinson's disease (PD) develop psychotic symptoms, such as hallucinations and delusions. Here, we tested the hypothesis that the neurocognitive basis of this phenomenon can be defined as the formation of arbitrary and illusory associations between conditioned stimuli and reward signals, called aberrant salience. Young, never-medicated PD patients and matched controls were assessed on a speeded reaction time task in which the probe stimulus was preceded by conditioned stimuli that could signal monetary reward by color or shape. The patients and controls were re-evaluated after 12 weeks during which the patients received a dopamine agonist (pramipexole or ropinirole). Results indicated that dopamine agonists increased both adaptive and aberrant salience in PD patients, that is, formation of real and illusory associations between conditioned stimuli and reward, respectively. This effect was present when associations were assessed by means of faster responding after conditioned stimuli signaling reward (implicit salience) and overt rating of stimulus-reward links (explicit salience). However, unusual feelings and experiences, which are subclinical manifestations of psychotic-like symptoms, were specifically related to irrelevant and illusory stimulus-reward associations (aberrant salience) in PD patients receiving dopamine agonists. The learning of relevant and real stimulus-reward associations (adaptive salience) was not related to unusual experiences. These results suggest that dopamine agonists may increase psychotic-like experiences in young patients with PD, possibly by facilitating dopaminergic transmission in the ventral striatum, which results in aberrant associations between conditioned stimuli and reward