Levodopa-Entacapone-Carbidopa Intestinal Gel in the Treatment of Advanced Parkinson's Disease: A Single Center Real-World Experience.

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.

Starting with 24-h levodopa carbidopa intestinal gel at initiation in a large cohort of advanced Parkinson's disease patients.

Continuous intra-jejunal infusion of levodopa-carbidopa intestinal gel (LCIG) is a long-term proven and effective treatment in advanced Parkinson's Disease (APD). Efficacy and safety of 16-h administration of LCIG has already been established. Additional benefits of 24-h LCIG administration have been reported in several case series and small clinical studies. The aim of this retrospective study was to compare the characteristics of patients who needed 24-h LCIG from the beginning of the DAT (device-aided treatment) with those who remained with the standard 16-h LCIG treatment and to identify particular motives if any. We initiated LCIG in 150 patients out of which in case of 62 patients (41,3%) due to unsatisfactory initial clinical benefits continuous 24-h LCIG was deemed necessary. Despite the subjective complaints and more severe clinical condition, at baseline evaluation we found statistically significant differences between 16-h LCIG cohort and 24-h LCIG cohort only in case of incidence of freezing (47% vs 65%, p = 0.03) and sudden off (32% vs 48%, p = 0.04). Wake hours/daytime LCIG does not always sufficiently improve the patient's quality of life in some patients due to persistent nighttime troublesome symptoms. Instead of labeling the patient as a non-responder, it is worth trying the 24-h LCIG dosage in a carefully selected group of patients, as there is currently no consensus on reliable criteria that serve the decision in these patients.

A Rare Case of Histopathologically Confirmed Creutzfeldt-Jakob Disease from Romania, Long Route to Diagnosis-Case Report and an Overview of the Romanian CJD Situation.

Creutzfeldt-Jacob disease is a progressive and ultimately fatal disease, representing one of the most common forms of prion diseases. It is a rare pathology presenting with various symptomatology, and the fact that a definite diagnosis can be obtained solely by neuropathological techniques makes it hard to recognize and diagnose. Here we present the clinical and neuropathological features of a 72-year-old woman, who originally presented in a county hospital, then, along with the disease progression, got transferred to a university center in Romania, where CJD-specific tests are rarely performed, and ultimately was diagnosed with the help of international collaboration. The purpose of this case report and review is to summarize the Romanian CJD situation until the present day, to place the Romanian CJD epidemiology in an Eastern European context, and to highlight the diagnostic options and possibilities for clinical practitioners. We would also like to draw attention to the need for a national surveillance system. By presenting the patient's route in Romania from the first presentation to diagnosis, we would like to emphasize the importance of interdisciplinary and international collaboration, by which we managed to cross the regional diagnostic boundaries and create a possible diagnostic pathway for future cases.

Ten-year trends of the characteristics in patients with advanced Parkinson's disease at the time of intestinal gel therapy introduction / Az intestinalis gél bevezetésekor rögzített jellemzok tízéves változásai elorehaladott Parkinson-kóros betegekben

Introduction: Parkinson's disease is a neurodegenerative disease, the symptoms of which can be treated reasonably well; however, therapeutic recommendations need to be refined based on the observations from everyday practice. Objective: We aimed to analyze the extent by which published expert recommendations were reflected in the manage-ment of patients with advanced Parkinson's disease, prior to the introduction of the intestinal gel. Method: Data from patients treated with levodopa-carbidopa intestinal gel were retrospectively examined. The period from 2011 to 2021 was divided into two five-year periods, prior and after the usage of the 5-2-1 rule in clinical decision-making. Results: Levodopa-carbidopa intestinal gel treatment was initiated in 150 patients during the study period. In the second five-year period, the mean age of the patients was lower and the time from diagnosis was shorter. Also, there were significantly fewer patients with peak-dose dyskinesias (p = 0.02), biphasic dyskinesias (p<0.001), and early morning akinesias (p = 0.02). Furthermore, in the last five years of the study, fewer patients were affected by delayed on (p = 0.03), no on (p = 0.02), and freezing (p = 0.01). The mean score measured on the Hoehn-Yahr scale was also lower in the second period, while the mean MMSE score was higher (p<0.001). Daily doses of levodopa were higher (p<0.01) in the second period, but with similar dosing frequency. Conclusion: Our retrospective analysis of trends during a ten-year period revealed that, in the second five-year period, levodopa-carbidopa intestinal gel was started in advanced Parkinson's disease patients with a significantly better physical and cognitive state. Compared to expert recommendations, our patients still had a more severe clinical pic -ture at the start of device-aided therapy, but acceptance of this invasive method has improved both for patients and for general practitioners and neurologists.

Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson's Disease: Observations and Dilemmas after 10 Years of Real-Life Experience.

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.

Management Challenges of Severe, Complex Dyskinesia. Data from a Large Cohort of Patients Treated with Levodopa-Carbidopa Intestinal Gel for Advanced Parkinson's Disease.

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.

Decision-making and duration to accept device-aided therapy in advanced Parkinson's disease / Döntési szempontok és az eszközös terápia elfogadásához szükséges ido elorehaladott Parkinson-kórban.

Összefoglaló. Bevezetés: Az elorehaladott Parkinson-kór bizonyos fázisában a motoros komplikációk már nem befolyásolhatók hatékonyan a hagyományos orális, illetve transdermalis gyógyszerekkel. Ilyenkor meg kell fontolni, komplex felmérési és döntési folyamatot követoen, az invazív eszközös terápiák bevezetését. Célkituzés: A döntéshozatal és a fontosabb klinikai paraméterek elemzése levodopa-karbidopa intestinalis géllel kezelt betegeinknél az elfogadás idotartamának függvényében. Módszer: Retrospektíven vizsgáltuk azon betegeink adatait, akiknél a marosvásárhelyi 2. Sz. Ideggyógyászati Klinikán 2011. június 1. és 2019. december 31. között vezettük be a levodopa-karbidopa intestinalis géllel történo terápiát. A kezelés elfogadásához szükséges idointervallum szerint két csoportot alkottunk: egy hónap vagy annál rövidebb, illetve egy hónapnál több ido az elso, célzott kivizsgálás és a tesztelés megkezdése között. Eredmények: A vizsgált idoszakban 163 betegnél teszteltük orrszondán a kezelés hatékonyságát, közülük 127 esetben történt meg a terápia véglegesítése. A döntéshozatal 56 betegnél egy hónap vagy annál rövidebb idot, míg 71 betegnél egy hónapnál több idot igényelt. A dyskinesisek átlagos idotartamának szempontjából szignifikáns különbséget találtunk a két csoport között (3,1 ± 0,7 vs. 2,8 ± 0,8 óra, p = 0,02). Az eszközös terápia bevezetése elotti levodopa-átlagadag 821,5 ± 246,6 mg volt, naponta átlagosan 5-ször adagolva. A kiegészíto terápiák alkalmazási arányai: a dopaminagonisták 80,3%-ban, a katechol-O-metiltranszferáz-gátlók 62,2%-ban, illetve a monoaminoxidáz-B-gátlók 68,5%-ban. Az átlagos off idotartam 4,7 ± 1,1 óra volt, és 85 betegünknél tapasztaltunk 2,9 ± 0,8 óra átlag-idotartamú dyskinesist. Következtetés: Hamarabb fogadják el az eszközös terápiát azok az elorehaladott Parkinson-kóros betegek, akiknek hosszabb idotartamú a napi dyskinesisük, illetve régebbi a betegségük. A terápiás irányelvek gyakorlatba ültetésekor figyelembe kell venni a helyi sajátosságokat: a kiegészíto gyógyszerekhez, illetve az eszközös terápiákhoz való hozzáférést. Orv Hetil. 2021; 162(21): 839-847. INTRODUCTION: In advanced stages of Parkinson's disease, motor complications cannot be effectively controlled with conventional therapies. In such cases, the complex assessment and decision-making process that leads to device-aided therapies should be considered. OBJECTIVE: To analyze the decision-making and key clinical parameters, as a function of duration of acceptance, patients treated with levodopa-carbidopa intestinal gel. METHOD: We retrospectively examined the data of patients who started levodopa-carbidopa intestinal gel therapy at the 2nd Department of Neurology Târgu Mures, between 1 June 2011 and 31 December 2019. Two groups were formed: less than one month and more than one month between the first targeted examination and the start of testing. RESULTS: Therapeutic efficiency was tested with nasal tube on 163 patients, out of whom 127 patients remained on treatment. Decision-making took one month or less for 56 patients and more than a month for 71 patients. Duration of dyskinesias was significantly different between the two groups (3.1 ± 0.7 vs 2.8 ± 0.8 hours, p = 0.02). Mean dose of levodopa prior to the introduction of device-aided therapy was 821.5 ± 246.6 mg, administered 5 times daily. Dopamine agonists were used in 80.3%, catechol-O-methyltransferase inhibitors in 62.2%, and monoamine oxidase-B inhibitors in 68.5% of cases. The mean off-time was 4.7±1.1 hours and data from 85 patients showed 2.9 ± 0.8 hours of dyskinesia. CONCLUSION: Device-aided therapy is adopted sooner by patients with advanced Parkinson's disease with longer disease duration and more dyskinesias. Local specificities, such as access to add-on medication and device-aided therapies, must be taken into account when implementing therapeutic guidelines. Orv Hetil. 2021; 162(21): 839-847.

Short-Term Amygdala Low-Frequency Stimulation Does not Influence Hippocampal Interneuron Changes Observed in the Pilocarpine Model of Epilepsy.

Temporal lobe epilepsy (TLE) is characterized by changes in interneuron numbers in the hippocampus. Deep brain stimulation (DBS) is an emerging tool to treat TLE seizures, although its mechanisms are not fully deciphered. We aimed to depict the effect of amygdala DBS on the density of the most common interneuron types in the CA1 hippocampal subfield in the lithium-pilocarpine model of epilepsy. Status epilepticus was induced in male Wistar rats. Eight weeks later, a stimulation electrode was implanted to the left basolateral amygdala of both pilocarpine-treated (Pilo, n = 14) and age-matched control rats (n = 12). Ten Pilo and 4 control animals received for 10 days 4 daily packages of 50 s 4 Hz regular stimulation trains. At the end of the stimulation period, interneurons were identified by immunolabeling for parvalbumin (PV), neuropeptide Y (NPY), and neuronal nitric oxide synthase (nNOS). Cell density was determined in the CA1 subfield of the hippocampus using confocal microscopy. We found that PV+ cell density was preserved in pilocarpine-treated rats, while the NPY+/nNOS+ cell density decreased significantly. The amygdala DBS did not significantly change the cell density in healthy or in epileptic animals. We conclude that DBS with low frequency applied for 10 days does not influence interneuron cell density changes in the hippocampus of epileptic rats.

Amygdala Low-Frequency Stimulation Reduces Pathological Phase-Amplitude Coupling in the Pilocarpine Model of Epilepsy.

Temporal-lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy and warrants the development of new therapies, such as deep-brain stimulation (DBS). DBS was applied to different brain regions for patients with epilepsy; however, the mechanisms of action are not fully understood. Therefore, we tried to characterize the effect of amygdala DBS on hippocampal electrical activity in the lithium-pilocarpine model in male Wistar rats. After status epilepticus (SE) induction, seizure patterns were determined based on continuous video recordings. Recording electrodes were inserted in the left and right hippocampus and a stimulating electrode in the left basolateral amygdala of both Pilo and age-matched control rats 10 weeks after SE. Daily stimulation protocol consisted of 4 × 50 s stimulation trains (4-Hz, regular interpulse interval) for 10 days. The hippocampal electroencephalogram was analyzed offline: interictal epileptiform discharge (IED) frequency, spectral analysis, and phase-amplitude coupling (PAC) between delta band and higher frequencies were measured. We found that the seizure rate and duration decreased (by 23% and 26.5%) and the decrease in seizure rate correlated negatively with the IED frequency. PAC was elevated in epileptic animals and DBS reduced the pathologically increased PAC and increased the average theta power (25.9% ± 1.1 vs. 30.3% ± 1.1; p < 0.01). Increasing theta power and reducing the PAC could be two possible mechanisms by which DBS may exhibit its antiepileptic effect in TLE; moreover, they could be used to monitor effectiveness of stimulation.

Levodopa-Carbidopa Intestinal Gel Infusion Therapy Discontinuation: A Ten-Year Retrospective Analysis of 204 Treated Patients.

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.

Role of Lacosamide in Preventing Pentylenetetrazole Kindling-Induced Alterations in the Expression of the Gamma-2 Subunit of the GABAA Receptor in Rats.

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.

[Dopamine agonists in Parkinson's disease therapy - 15 years of experience of the Neurological Clinics from Tîrgu Mureș. A cross-sectional study]. / A dopaminagonisták jelentosége a Parkinson-kór kezelésében a marosvásárhelyi ideggyógyászati klinikák 15 éves gyakorlatában - keresztmetszeti vizsgálat.

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 Tîrgu 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 agonist with the utmost courage to their maximum therapeutic potential.

Therapeutic strategies in the early stages of Parkinson's disease: a cross-sectional evaluation of 15 years' experience with a large cohort of Romanian patients.

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 Mures¸ 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.

[Characteristics of levodopa treatment in advanced Parkinson's disease in the experiences of the neurology clinics of Târgu Mureș, Romania]. / Az orális levodopakezelés jellegzetességei elorehaladott Parkinson-kórban a marosvásárhelyi neurológiai klinikák tapasztalatában.

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.

Profile Of Patients With Advanced Parkinson's disease Suitable For Device-Aided Therapies: Restrospective Data Of A Large Cohort Of Romanian Patients.

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.

[Diabetes, dementia, depression, distress]. / Diabetes, dementia, depresszió, distressz.

The number of people living with diabetes continues to rise. Therefore neurologists or other health care practitioners may be increasingly faced with comorbid neuropsychiatric disorders commonly presented by diabetic patients. More recently there has been an increasing research interest not only in the interactions between diabetes and the nervous system, the fine structure and functional changes of the brain, but also in the cognitive aspects of antidiabetic treatments. Patients with both types of diabetes mellitus may show signs of cognitive decline, and depression. Comorbid insomnia, anxiety, and distress may also occur. The bidirectional relationships between all these phenomena as well as their connection with diabetes can lead to further health and quality of life deterioration. Therefore it is important that all practitioners involved in the care of diabetic patients recognize the presence of comorbid neuropsychiatric disturbances early on during the healthcare process. Identifying higher risk patients and early screening could improve the prognosis of diabetes and may prevent complications.

Untangling the pathomechanisms of temporal lobe epilepsy--the promise of epileptic biomarkers and novel therapeutic approaches.

Epilepsy is one of the most common neurological diseases and it is characterized by the reoccurrence of seizures with variable severity and frequency. The burden of epilepsy, however, is more than having seizures, as the disease is frequently associated with comorbid cognitive and behavioral disorders. Diagnosis as well as treatment suffers both from the inadequate understanding of the underlying epileptogenic molecular, cellular and network mechanisms and the related lack of reliable biomarkers for the development, progression, or even the presence and severity of the epileptic condition. Here we summarize the recent advances in both clinical and experimental approach regarding epilepsy, which may create the premise for identification of clinically useful, reliable biomarkers. Identification of the basic pathomechanisms of epileptogenesis and epilepsy would potentially create new therapeutic approaches that could not only treat but also prevent and cure epilepsy. Current knowledge regarding the electrophysiological alterations as well as the underlying cellular and molecular mechanisms regarding temporal lobe epilepsy is also critically scrutinized.