Constipation is a prevalent and clinically significant non-motor symptom in Parkinson’s disease (PD), affecting up to 90 https://drks.de/search/en/trial/DRKS00027061/details ). Many people with Parkinson’s disease experience constipation, which can be distressing and greatly affect daily life. Constipation may appear years before movement problems and is thought to be linked to changes in gut bacteria and reduced production of beneficial substances called short-chain fatty acids. In this clinical study, we investigated whether dietary supplementation with short-chain fatty acids, the prebiotic 2-fucosyllactose, or a combination of both could improve constipation in people with Parkinson’s disease, and 72 participants received one of these supplements for 6 months. We found that supplementation with 2-fucosyllactose improved constipation symptoms, while the combination of 2-fucosyllactose and short-chain fatty acids led to the greatest and most consistent improvements, with participants reporting better stool consistency, fewer problematic bowel movements, and an improved constipation-related quality of life. Physical activity levels did not change during the study, indicating that the observed benefits were likely related to the supplements themselves. These findings suggest that targeting the gut using specific dietary supplements may offer a safe and effective way to relieve constipation in people with Parkinson’s disease, although further studies are needed to evaluate the long-term safety of these supplements, the sustainability of symptom relief, the long-term benefits, and possible effects on disease progression.

A patient-tailored therapy of the heterogeneous, neuropsychiatric disorder of Parkinson’s disease (PD) aims to improve dopamine sensitive motor symptoms and associated non-motor features. A repeated, individual adaptation of dopamine substituting compounds is required throughout the disease course due to the progress of neurodegeneration. Therapeutic drug monitoring of dopamine substituting drugs may be an essential tool to optimize drug applications. We suggest plasma determination of levodopa as an initial step. The complex pharmacology of levodopa is influenced by its short elimination half-life and the gastric emptying velocity. Both considerably contribute to the observed variability of plasma concentrations of levodopa and its metabolite 3-O-methyldopa. These amino acids compete with other aromatic amino acids as well as branched chain amino acids on the limited transport capacity in the gastrointestinal tract and the blood brain barrier. However, not much is known about plasma concentrations of levodopa and other drugs/drug combinations in PD. Some examples may illustrate this lack of knowledge: Levodopa measurements may allow further insights in the phenomenon of inappropriate levodopa response. They may result from missing compliance, interactions e.g. with treatments for other mainly age-related disorders, like hypertension, diabetes, hyperlipidaemia, rheumatism or by patients themselves independently taken herbal medicines. Indeed, uncontrolled combination of compounds for accompanying disorders as given above with PD drugs might increase the risk of side effects. Determination of other drugs used to treat PD in plasma such as dopamine receptor agonists, amantadine and inhibitors of catechol-O-methyltransferase or monoamine oxidase B may refine and improve the value of calculations of levodopa equivalents. How COMT-Is change levodopa plasma concentrations? How other dopaminergic and non-dopaminergic drugs influence levodopa levels? Also, delivery of drugs as well as single and repeated dosing and continuous levodopa administrations with a possible accumulation of levodopa, pharmacokinetic behaviour of generic and branded compounds appear to have a marked influence on efficacy of drug treatment and side effect profile. Their increase over time may reflect progression of PD to a certain degree. Therapeutic drug monitoring in PD is considered to improve the therapeutic efficacy in the course of this devastating neurologic disorder and therefore is able to contribute to the patients’ precision medicine. State-of-the-art clinical studies are urgently needed to demonstrate the usefulness of TDM for optimizing the treatment of PD.

Purpose: Multiple sclerosis (MS) is a neurological disorder affecting almost 2.8 million people globally, approximately 80-85% of whom have the relapsing-remitting form of the disease (RRMS). There are several autoinjectors available for the administration of injectable disease- modifying therapies for the treatment of MS. The objective of the current study was to gain an understanding of factors related to patients' and nurses' autoinjector preferences, and to evaluate two autoinjectors for glatiramer acetate (MyJECTTM and CSYNCTM) against those preferences. Patients and Methods: Patients with RRMS and nurses experienced in training patients with an autoinjector were recruited from 12 health centers in Germany. Surveys were administered to patients and nurses and their answers to 13 questions over five categories (participants' characteristics, important autoinjector attributes, autoinjector performance, satisfaction with the autoinjector devices and demographics) were scored, where appropriate, using a 5-point Likert scale. Results: A total of 15 patients and 15 nurses were included in the study. Overall, the top four most important attributes, for both nurses and patients, were ease of handling, ability to use independently, ease of gripping the autoinjector and ease of self-injection. MyJECTTM received a mean score of at least 4.5 (out of 5) on more attributes than CSYNCTM and satisfaction with both autoinjectors was high. Conclusion: Nurses and patients with RRMS were highly satisfied with both the MyJECTTM and CSYNCTM autoinjectors, with scores suggesting that MyJECTTM performs better on the attributes they identified as most important. All patients currently using the MyJECTTM were likely or highly likely to recommend it to another patient with RRMS.

INTRODUCTION:Parkinson's disease is a chronic neurodegenerative disease entity characterized by heterogeneity of symptoms and progression. Levodopa is an efficacious and well tolerated dopamine substituting drug for its therapy. Its O-methylation and generation of 3-O-methyldopa is enhanced by levodopa/dopa decarboxylase inhibitor formulations. Additional inhibition of catechol-O-methyltransferase is the relevant add on therapy for levodopa application. This pharmacologic approach increases the plasma appearance of levodopa and reduces 3-O-methyldopa synthesis. Available marketed compounds are entacapone, tolcapone and opicapone. Data on their effects on levodopa pharmacokinetics in patients are rare. AREAS COVERED:This review describes the impact of this add-on therapy on the pharmacokinetic profile of levodopa and 3-O-methyldopa in plasma. The rationale was to perform a comparison with data from previously published pharmacokinetic trials with a standardized one time intake of levodopa/carbidopa without and with the available catechol-O-methyltransferase inhibitors. EXPERT OPINION:Results of this analysis identified opicapone as the most efficacious inhibitor of catechol-O-methyltransferase in terms of changes of levodopa plasma concentrations. Opicapone induced higher levodopa plasma levels compared with the ones following application of levodopa/carbidopa alone or combined with entacapone or tolcapone. Co-administration of opicapone with its once daily intake regimen may support the efficacy of subcutaneous and intrajejunal levodopa infusions.

Aim of this review is to discuss the value of current ongoing research initiatives in Parkinson’s disease from the clinicians’ point of view. The repeat, recent failures on progress slowing reflect the drifting apart between initially promising experimental and then disappointing clinical outcomes in the translational trials with well selected Parkinson’s disease patients. A similar development concerns the emerging gap between novel developed drugs with improved pharmacokinetic behaviour and their limited use in the clinical practice following approval. Restricted regional different worldwide availability and direct, respectively indirect budget limitations for neurologists in private practice are essential hurdles. They prevent the widespread prescription of these compounds. As a result return of investment for the pharmaceutical industry becomes more and more uncertain. The interest for research on novel treatment approaches for the amelioration of motor and non motor symptoms declines. Clinicians crucially scrutinize the claim for an optimum patient care by payers and regulators.

ABSTRACT Introduction Pathogenic mutations of the abundant leucine-rich repeat kinase 2 gene support the onset of familial and sporadic forms of Parkinson’s disease. These genetic variants catalyze kinase activity by substrate phosphorylation. They promote the nigrostriatal neurodegenerative process, i.e. characterized by Lewy body formation. Areas covered This narrative review discusses leucine-rich repeat kinase 2 inhibitors as therapeutic concept for beneficial disease modification following a literature search. Expert opinion Leucine-rich repeat kinase 2 gene function contributes to the onset of microglia inflammation, cellular, and mitochondrial dysfunction. Leucine-rich repeat kinase 2 inhibition with oral application of DNL151, respectively DNL201, and intrathecal administration of the antisense oligonucleotide BIIB094 in a single and multiple ascending dose study was safe and well tolerated. Approval of Leucine-rich repeat kinase 2 inhibitors in case of positive clinical study outcomes will introduce personalized medicine for beneficial modification of progression as the most unmet need for treatment of patients with Parkinson’s disease. In addition to the currently, preponderantly performed clinical rating with established scales, further clinical trial endpoints, such as dosing of dopamine substitution, may be considered in study designs to demonstrate therapeutic effects on the progression of Parkinson’s disease. Plain Language Summary Certain mutations of the abundant leucine-rich repeat kinase 2 gene contribute to the onset of inherited and sporadic forms of idiopathic Parkinson’s disease. These genetic variants enhance the gene related kinase activity and promote nigrostriatal neurodegeneration with features like inflammation of microglia, cellular, and mitochondrial dysfunction. Inhibition of leucine-rich repeat kinase 2 activity was efficacious, safe, and well tolerated in experimental investigations and in the still ongoing clinical study program. Approval of this therapeutic concept after future positive clinical study outcomes is the introduction of personalized medicine based on molecular mechanisms and targets in Parkinson’s disease. Beneficial modification of progression is the most unmet need for the therapy of patients with Parkinson’s disease.

Dopamine agonists are an important component of Parkinson's therapy. When weighing up the various therapy options, therapy with levodopa has recently been increasingly preferred due to its stronger efficacy and the ostensibly lower rate of side effects. The advantage of the lower incidence of motor complications during therapy with dopamine agonists was neglected. The occurrence of side effects can be explained by the different receptor affinity to the individual dopaminergic and non-dopaminergic receptors of the individual dopamine agonists. However, the different affinity to individual receptors also explains the different effect on individual Parkinson symptoms and can, therefore, contribute to a targeted use of the different dopamine agonists. Since comparative studies on the differential effect of dopamine agonists have only been conducted for individual substances, empirical knowledge of the differential effect is of great importance. Therefore, the guidelines for the treatment of Parkinson's disease do not consider the differential effect of the dopamine agonists. The historical consideration of dopamine agonists within Parkinson's therapy deserves special attention to be able to classify the current discussion about the significance of dopamine agonists.

Introduction: Concomitant drug use is common among opioid-dependent patients in maintenance therapy. Attention deficit hyperactivity disorder (ADHD), a common comorbidity among opioid users, is associated with a higher risk of concomitant drug use. Earlier studies showed that methylphenidate (MPH) can reduce cocaine consumption among patients with ADHD. The use of MPH as an agonist-replacement or maintenance therapy in cocaine-dependent patients without ADHD is also common in Switzerland, despite a lack of supporting evidence. The aim of this study was to assess concomitant cocaine, amphetamine, MDMA, MPH, and heroin use among patients in opioid maintenance therapy either with or without comorbid ADHD. We expected stimulant consumption to be higher in patients with cocaine dependence and comorbid ADHD and that use of MPH would not lead to a reduction in cocaine consumption in patients without ADHD. We therefore evaluated correlations between use of MPH and cocaine consumption and between MPH consumption and cocaine craving within the two groups. Methods: This cross-sectional study included 94 opioid-dependent patients in maintenance therapy in an outpatient department of the Psychiatric Hospital of Zurich. The patients were divided into two groups based on comorbid ADHD; a group with ADHD (N = 27) and a group without ADHD (N = 67). Drug use was assessed using 3-month hair analysis. Results: We did not find significant differences in the number of patients using cocaine, amphetamine, MDMA, or heroin between groups with or without ADHD. With respect to cocaine use, 85.2 percent of patients in the ADHD group and 73.1 percent in the non-ADHD group were users. The non-ADHD group showed a significant positive correlation between the concentration of MPH and cocaine in hair samples (p < 0.05), and a positive correlation between cocaine craving and the concentration of MPH in hair samples (p = 0.065). These two trends were not evident in the ADHD group. Conclusion: Among patients without ADHD, use of MPH correlates with higher cocaine consumption and craving. Conversely, no significant correlation was found between MPH and cocaine use in patients with ADHD. Our study adds to the evidence that MPH confers negative effects in cocaine users without ADHD and should thus have no place in the treatment of these patients.

Parkinson's disease (PD) is the second most chronic neurodegenerative disorder worldwide. Deficit of monoamines, particularly dopamine, causes an individually varying compilation of motor and non-motor features. Constraint of presynaptic uptake extends monoamine stay in the synaptic cleft. This review discusses possible benefits of dopamine reuptake inhibition for the treatment of PD. Translation of this pharmacologic principle into positive clinical study results failed to date. Past clinical trial designs did not consider a mandatory, concomitant stable inhibition of glial monoamine turnover, i.e. with monoamine oxidase B inhibitors. These studies focused on improvement of motor behavior and levodopa associated motor complications, which are fluctuations of motor and non-motor behavior. Future clinical investigations in early, levodopa- and dopamine agonist naïve patients shall also aim on alleviation of non-motor symptoms, like fatigue, apathy or cognitive slowing. Oral levodopa/dopa decarboxylase inhibitor application is inevitably necessary with advance of PD. Monoamine reuptake (MRT) inhibition improves the efficacy of levodopa, the blood brain barrier crossing metabolic precursor of dopamine. The pulsatile brain delivery pattern of orally administered levodopa containing formulations results in synaptic dopamine variability. Ups and downs of dopamine counteract the physiologic principle of continuous neurotransmission, particularly in nigrostriatal, respectively mesocorticolimbic pathways, both of which regulate motor respectively non-motor behavior. Thus synaptic dopamine pulsatility overwhelms the existing buffering capacity. Onset of motor and non-motor complications occurs. Future MRT inhibitor studies shall focus on a stabilizing and preventive effect on levodopa related fluctuations of motor and non-motor behavior. Their long-term study designs in advanced levodopa treated patients shall allow a cautious adaptation of oral l-dopa therapy combined with a mandatory inhibition of glial monoamine turnover. Then the evidence for a preventive and beneficial, symptomatic effect of MRT inhibition on motor and non-motor complications will become more likely.

A rare condition is temporary but recurrent onset of involuntary motion sequences in the abdominal region. They demands for an extensive diagnostic workup. Therapeutic options are limited. The successful treatment of this spinal myoclonus or abdominal involuntary movements resembling syndrome prompted this report.

BACKGROUND:Vitamin D has a steroid- and an anabolic-resembling chemical structure. Vitamin D is essential for many processes in the human body after hydroxylation.AIMS OF THE STUDY:To investigate the impact of 25-hydroxy-vitamin D plasma concentrations on the blood parameters number of erythrocytes, hematocrit, mean corpuscular hemoglobin and mean corpuscular volume.METHODS:Serial assessments were done in 290 patients with multiple sclerosis and repeated after a mean interval of 245 days. A recommendation for vitamin D supplementation was given in case of a concentration lower than 20 ng/mL combined with a prescription of a formulation containing vitamin D but not vitamin K.RESULTS:There was a fall of vitamin D in 119 subjects and a rise in 164, while no change appeared in 7 participants. When vitamin D values went down between both assessments moments, the computed increase of mean corpuscular haemoglobin was significantly lower compared with the rise of mean corpuscular haemoglobin associated with a vitamin D elevation. When vitamin D declined, the computed fall of mean corpuscular volume fall was significantly lower compared with the decrease of mean corpuscular volume, when vitamin D rose. Positive correlations were found between differences of vitamin D and mean corpuscular haemoglobin, respectively mean corpuscular volume. Inverse relations appeared between disparities of vitamin D and erythrocytes, respectively haematocrit.CONCLUSIONS:The elevation of vitamin D plasma levels provides enhanced preconditions for a better tissue oxygenation on a cellular level.

Amantadine is an old, antiviral compound, which moderately improves motor behavior in Parkinson's disease. Its current resurgence results from an innovative, delayed uptake and extended release amantadine hydrochloride capsule, given at bedtime once daily. It is the only approved compound for reduction of involuntary movements, so called dyskinesia, in fluctuating orally levodopa treated patients. It additionally ameliorates 'off'-intervals characterized by impaired motor behavior. These beneficial effects result from higher and more continuous brain delivery of amantadine. Future clinical research is warranted on preventive effects of this amantadine capsule combined with enzyme blockers of central monoamine oxidase B and peripheral catechol-O-methyltransferase on motor complications in orally levodopa treated patients, as all these pharmacological principles support the concept of continuous dopamine substitution.

Motor behaviour in patients with Parkinson’s disease is determined with instrumental tests and rating procedures. Results mirror impairment of an individual patient. Objectives were to determine the associations between two kinds of motion series and rating scores in previously untreated 64 patients and to compare outcomes to controls. The line tracing task asks to follow a given path. It measures the needed interval, the number and duration of contacts to the path. The aiming procedure asks to hit contact plates with a pencil and determines the needed time period and the number of accurate, respectively, missed key strokes. Both tests differed between patients and controls. The line tracing task was more sensitive. The line tracing task asks for a complex motion series performance with more cognitive load. The aiming task prompts for a conduction of preponderant simple, repetitive movement series. Only initially, a complex process of aiming is necessary. Performance of complex motion sequences better differs between patients with Parkinson’s disease and controls than conduction of simple, repetitive movement series.