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.

Although Ca2+ ion plays an essential role in cellular physiology, calcium-binding proteins (CaBPs) were long used for mainly as immunohistochemical markers of specific cell types in different regions of the central nervous system. They are a heterogeneous and wide-ranging group of proteins. Their function was studied intensively in the last two decades and a tremendous amount of information was gathered about them. Girard et al. compiled a comprehensive list of the gene-expression profiles of the entire EF-hand gene superfamily in the murine brain. We selected from this database those CaBPs which are related to information processing and/or neuronal signalling, have a Ca2+-buffer activity, Ca2+-sensor activity, modulator of Ca2+-channel activity, or a yet unknown function. In this way we created a gene function-based selection of the CaBPs. We cross-referenced these findings with publicly available, high-quality RNA-sequencing and in situ hybridization databases (Human Protein Atlas (HPA), Brain RNA-seq database and Allen Brain Atlas integrated into the HPA) and created gene expression heat maps of the regional and cell type-specific expression levels of the selected CaBPs. This represents a useful tool to predict and investigate different expression patterns and functions of the less-known CaBPs of the central nervous system.

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.

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.

Background: Epilepsy remains challenging to treat still no etiologic treatment has been identified, however, some antiepileptic drugs (AEDs) are able to modify the pathogenesis of the disease. Lacosamide (LCM) has been shown to possess complex anticonvulsant and neuroprotective actions, being an enhancer of the slow inactivation of voltage-gated sodium channels, and it has the potential to prevent epileptogenesis. Recent evidence has shown that LCM indirectly improves the function of GABAA receptors. Receptors at most GABAergic synapses involve the gamma-2 subunit, which contributes to both phasic and tonic inhibition, and its presence assures benzodiazepine sensitivity. Moreover, mutant gamma-2 subunits were associated with generalized epilepsy syndromes. In animal models, the expression of the gamma-2 subunit of the gamma-aminobutyric acid A receptor (GABAAg2) was shown to be increased in pentylenetetrazole (PTZ)-induced chemical kindling in Wistar rats. Objective: This study hypothesized that LCM might affect the kindling process by influencing the expression of GABAA receptors in the hippocampus. Methods: The gene and protein expression levels of the GABAAg2 were studied using RT-qPCR and immunofluorescent staining. Results: It was found that LCM treatment (10 mg/kg i.p. daily for 57 days) reduced the maximal intensity of the PTZ-induced seizures but did not prevent kindling. On the other hand, LCM treatment reverted the increase of mRNA expression of GABAAg2 in the hippocampus and prevented the decrease of GABAAg2 protein in the hippocampal CA1 region. Conclusion: LCM could exhibit modulatory effects on the GABAergic system of the hippocampus that may be independent of the anticonvulsant action.