Antiparkinsonian Drugs Research Articles

Prospects of successful treatment of Parkinson's disease using apomorphine

Abstract. Optimising the treatment of idiopathic Parkinson's disease is a complex, multifaceted and continuous process that directly affects quality of life. The main position of this examination is the need for individualised therapy that provides optimal motor function with the least negative consequences. Apomorphine, a dopamine agonist used as rescue therapy for patients with motor fluctuations with a potentially positive effect on non-motor symptoms, is the only antiparkinsonian drug whose ability to control motor symptoms is equivalent to that of levodopa. Subcutaneous injection is the most effective and affordable way to correct dopaminergic insufficiency in Parkinson's disease. The data of multi-centre studies presented in the review confirm the high efficiency, adequate tolerability, and prospects of using apomorphine in the complex pathogenetic therapy of the disease. This review provides historical background and summarises the structure, mechanism of action, pharmacodynamics, indications, contraindications, and side effects of subcutaneous apomorphine injections in the advanced stages of Parkinson's disease. Keywords: Parkinson's disease; apomorphine; pharmacokinetics; mechanism of action; clinical trials; indications: and contraindications

Efficacy of Safinamide and Gender Differences During Routine Clinical Practice.

Background: There is increasing evidence of gender differences in the epidemiology and clinical manifestation of both motor and non-motor symptoms of Parkinson's disease (PD). Nevertheless, few data are available on gender differences in the response to antiparkinsonian drugs. Safinamide is a multimodal drug with positive effects on motor and non-motor fluctuations that might improve patients' care and quality of life.Objective: To analyze gender differences on clinical effects of safinamide in PD patients treated in real-life conditions during the SYNAPSES trial.Methods: SYNAPSES was a multinational, multicenter, observational study. At baseline, patients with PD diagnosis received safinamide as an add-on to levodopa and were followed up for 12 months, with visits performed every 4 months. A new statistical analysis was performed to describe the efficacy of safinamide in men and women on motor complications, motor symptoms, and adverse events.Results: Six hundred and sixteen (38%) out of 1,610 patients enrolled in the SYNAPSES study were women and 994 (62%) men. Safinamide improved motor symptoms and motor complications (fluctuations and dyskinesia) in both genders, with a good safety profile and without requiring any change in the concomitant dopaminergic therapy. Clinically significant improvements, according to the criteria developed by Shulman et al., were seen in 46% of male and female patients for the UPDRS motor score and 43.5% of men vs. 39.1% of women for the UPDRS total score.Conclusions: Safinamide was effective in improving motor fluctuations and dyskinesia and proved to be safe in both male and female patients with PD. Further prospective studies, specifically addressing potential gender differences in response to PD therapies, are needed to develop tailored management strategies.

Melanochrome-based colorimetric assay for quantitative detection of levodopa in co-presence of carbidopa and its application to relevant anti-Parkinson drugs.

In this paper is reported the selective detection and quantification of levodopa in co-presence of carbidopa. The method took advantage of the spontaneous oxidation and color development of levodopa at basic pH here driven by alkaline earth cations and co-solvent in solution. We have shown for the first time the generation and stabilization of the purple melanochrome from levodopa, by using magnesium acetate and dimethyl sulfoxide, which was here exploited for the development of a quantitative colorimetric assay for the active principle ingredient in commercial drugs for the treatment of Parkinson's disease. The calibration curves of levodopa in the two tablet formulations, containing carbidopa as decarboxylase inhibitor, showed a common linear trend between 10 mg L-1 and 40 mg L-1 with levodopa alone or in combination with carbidopa in standard solutions, with very good reproducibility (CVav%, 3.3% for both brand and generic drug) and very good sensitivity, with limit of quantification about 0.6 mg L-1 in any case. The colorimetric method here developed is very simple and effective, appearing as a rapid and low-cost alternative to other methodologies, involving large and expensive instrumentations, for drug estimation and quality control of pharmaceutical formulations.

Prospects for successful treatment of Parkinson’s disease with the use of apomorphine

Optimizing the treatment of idiopathic Parkinson’s disease is a complex, multifaceted and continuous process that directly affects quality of life. The main position of this review is the need for individualized therapy that provides optimal motor function with the least negative consequences. Apomorphine, a dopamine agonist used as emergency therapy for patients with motor fluctuations with a potential positive effect on non-motor symptoms, is the only antiparkinsonian drug whose ability to control motor symptoms is equivalent to that of levodopa. Subcutaneous administration as a periodic injection is the most effective and affordable way to correct dopaminergic insufficiency in Parkinson’s disease. The data of multicenter studies presented in the review confirm the high efficiency, adequate tolerability and prospects of apomorphine use in comprehensive pathogenetic therapy of the disease. This review contains the historical reference and generalizes structure, the mechanism of action, pharmacodyna-mics, indications, contraindications and side effects in subcutaneous injections of apomorphine at the advanced stages of a clinical course of Parkinson’s disease.

Prevalence of oropharyngeal dysphagia in geriatric patients and real-life associations with diseases and drugs

Risk factors for oropharyngeal dysphagia (OD) in elderly patients are mainly central nervous system (CNS) and structural organic diseases or presbyphagia. We analysed the OD prevalence and association of OD with multimorbidity and polypharmacy using real-life data to complete this spectrum, with a focus on further and iatrogenic risk. This was a cross-sectional retrospective study based on a random sample of 200 patients admitted to a geriatric hospital. Data analysis included diagnoses, the detailed list of drugs, and an intense clinical investigation of swallowing according to Stanschus to screen for OD in each patient. The mean patient age was 84 ± 6.5 years. The prevalence of OD was 29.0%, without an effect of age, but a higher rate was found in men and in nursing home residents and an elevated risk of pneumonia. OD risk was slight in diabetes mellitus and COPD, and pronounced in CNS diseases. A relevant OD association was found, even after adjusting for CNS diseases, with antipsychotics, benzodiazepines, anti-Parkinson drugs, antidepressants, and antiepileptics. Further risk of OD was found with beta-blockers, alpha-blockers, opioids, antiemetics, antivertiginosa or antihistamines, metoclopramide, domperidone, anticholinergics, loop diuretics, urologics, and ophthalmics. From real-life data in patients with and without CNS diseases, we identified drug groups associated with a risk of aggravating/inducing OD. Restrictive indications for these drugs may be a preventative contribution, requiring implementation in dysphagia guidelines and an integrative dysphagia risk scale that considers all associated and cumulative medication risks in addition to diseases.

Switching from blonanserin oral tablets/powders to transdermal patches alleviates extrapyramidal symptoms in patients with schizophrenia: A 52-week open-label study

Blonanserin is a second-generation antipsychotic for the treatment of schizophrenia. Blonanserin has two different routes of administration: oral tablets/powder and transdermal patches. The aim of this study was to investigate as a post-hoc analysis of an original study whether switching from blonanserin tablets/powders to transdermal patches would reduce extrapyramidal symptoms (EPS) and/or the dose of antiparkinsonian drugs for the stabilization of blood pharmacokinetics in patients with schizophrenia. Patients with schizophrenia (n = 155) were enrolled in either cohort 1 or 2. In cohort 1 (n = 97), patients received 40–80 mg/day blonanserin transdermal patches for one year after taking 8–16 mg/day blonanserin tablets for 6 weeks, and the dose of patches was determined based on the dose of the tablets. In cohort 2 (n = 58), all patients started with 40 mg/day blonanserin patches and then received 40–80 mg/day for a year after taking blonanserin tablets/powders. Changes from the start of transdermal patch treatment in EPS and the dose of antiparkinsonian drugs at 3, 6, and 12 months were assessed using the Drug-Induced EPS Scale (DIEPSS) and biperiden equivalents of total antiparkinsonian drugs (BPD-eq), respectively. Among 155 patients, only four patients in cohort 1 discontinued owing to EPS during a patch period. Significant improvements from the start of patch treatment in the DIEPSS total score at any point were observed (mean change±SD): −0.44 ± 1.50 (p = 0.013), −0.07 ± 1.78 (p = 0.73), and − 0.14 ± 1.37 (p = 0.44) in cohort 1 and − 0.16 ± 1.32 (p = 0.40), −0.74 ± 1.92 (p = 0.020), and − 0.81 ± 2.22 (p = 0.047) in cohort 2 at 3, 6, and 12 months, respectively. In contrast, there were no significant changes from the start of patch treatment in BPD-eq at any month (p > 0.05). Transdermal patches of blonanserin are a more effective route of administration to diminish EPS than oral tablets/powder.

Impulse control disorders in Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterised by typical motor symptoms and a range of non-motor symptoms, among which impulse control disorders, defined by an inability to resist temptations, impulses or urges, despite them being potentially harmful to the patient or caregivers, are gaining an increasing research interest. The most common compulsive activities include pathological gambling, hyper-sexuality, compulsive buying, and binge eating. The prevalence of impulse control disorders varies greatly depending on the country where the study was conducted, probably due to cultural and socioeconomic factors or the research methods used. Non-ergotamine dopamine agonists, and to a lesser extent highdose L-dopa and other antiparkinsonian drugs, are considered to be major risk factors for the development of impulse control disorders. Young age of patients, male gender, and early age of disease onset also increase the risk of developing this type of disorder. A probable cause of impulse control disorders is a state of dopaminergic overstimulation within the mesolimbic pathway and frontal-striatal circuit. The management of impulse control disorders is particularly challenging in view of the possible worsening of motor symptoms. The primary strategy remains dose reduction, discontinuation or switching from a dopamine agonist to another drug. If this type of intervention has failed, it is advisable to add atypical antipsychotics or antiepileptic drugs. Because of the low detection rate of impulse control disorders and their potentially devastating impact on patients’ personal and family lives, every clinician managing patients with Parkinson’s disease should be particularly vigilant for the presence of such disorders.

Systematic enhancement of L-DOPA and Secondary metabolites from Mucuna imbricata: Implication of precursors and elicitors in Callus culture

The bioprocess methodology for the enhanced production of phytochemicals using plant cultures predominantly depends on the elicitors and precursors. The drug L-DOPA (anti-Parkinson's drug) (L-3, 4-dihydroxyphenylalanine) has been chiefly isolated from the popular medicinal plant species Mucuna. The present study has been carried out to enhance the production of L-DOPA and other secondary metabolites in the presence of the optimized concentration of growth promoters, elicitors and precursor's in vitro callus culture of Mucuna imbricata. Results revealed that there is a positive influence of Methyl Jasmonate (MJC) and Salicylic Acid (SAC) on the accumulation of L-DOPA and other secondary metabolites (Nutritional and anti-nutritional factors), which enhances their production by more than two folds. The highest accumulation of L-DOPA was noticed in the elicitation of 1 mM MJC (4.3 ± 0.4 %) followed by 1 mM SAC (3.4 ± 0.08 %) on 45th and 30th days respectively. Results also illustrated a significant increase of callus biomass (dry and moist weight) as well as total phenolics, flavonoids and antioxidants values in the elicited callus from day 30th to day 45th of explant inoculation which indicates a synergistic interaction of auxin, cytokinins with elicitors and precursors respectively. Additionally, results revealed that improved accumulation of carbohydrates was positively correlated with an increase in L-DOPA content in the elicited callus. Hence the protocol formulated delivers an effective alternative for mass production of L-DOPA from callus culture with improved metabolite content.

The antiparkinsonian drug safinamide is not harmful for the human retina. A neurophysiological study

Safinamide is a selective MAO-B inhibitor, indicated for the treatment of Parkinson's disease (PD). The European patient information leaflet warns about the “Potential for retinal degeneration in patients with presence/prior history of retinal disease: Safinamide should not be administered to patients with ophthalmological history that would put them at increased risk for potential retinal effects”. The available literature, however, misses any data concerning this potential retinal toxicity. This prompted us to implement a neurophysiological study concerning a possible drug-related retinal damage.

Changes in personality associated with deep brain stimulation in Parkinson's disease

Subthalamic deep brain stimulation (STN-DBS) is an effective treatment option in Parkinson's disease (PD), producing robust motor improvements in the motor symptoms and allowing the reduction of antiparkinsonian drugs dosage. There is, however, increasing evidence that STN-DBS may be associated with a higher incidence of adverse changes in behavior when compared to other stimulation sites (1). To date, no study has investigated the effect of the amount of total electrical energy delivered (TEED) on behavioral adverse changes. To characterize this issue, we assessed personality traits correlated with TEED in twenty PD patients before and 12 months after the start of neurostimulation.

Czy preparaty lewodopy z karbidopą oraz lewodopy z benserazydem są klinicznie równoważne?

Parkinson’s disease is the only neurodegenerative disease that can be effectively treated symptomatically. Treatment of motor symptoms is based primarily on the use of drugs that increase the activity of the nigrostriatal dopaminergic system and compensate for dopamine deficiency. Levodopa remains the gold standard of dopaminergic therapy. It is the most effective and best tolerated anti-parkinsonian drug, it causes the fewest side effects, also in the elderly patients. Oral preparations of levodopa additionally contain one of the aromatic L-amino acid decarboxylase inhibitors: benserazide or carbidopa. Inhibitors have a beneficial effect on the bioavailability of levodopa in the central nervous system, its clinical efficacy and tolerability. In practice, according to common opinion, the preparations of levodopa with carbidopa and levodopa with benserazide are clinically equivalent and can be used interchangeably. The case of a 69-year-old patient treated for 6 years for Parkinson’s disease is presented. The patient presented motor symptoms of advanced Parkinson’s disease: wearing-off motor fluctuations and peak dose dyskinesia. The was treated with levodopa in a dose of 5 × 200 mg (preparation of levodopa with benserazide) as a monotherapy. Due to the worsening availability of the drug used so far in pharmacies, it was changed to a preparation containing levodopa and carbidopa, while maintaining the same dose of levodopa. During the next visit, the patient reported that the change of the formulation had a beneficial effect in the form of a slight but significant reduction in the incidence and severity of peak dose dyskinesia. Pharmacokinetic studies showed that the mean maximum concentration of levodopa after administration of levodopa + benserazide was significantly higher than after administration of levodopa + carbidopa. The preparation containing benserazide caused a rapid increase and then a rapid decrease of the lewodopa plasma concentration. When levodopa was combined with carbidopa, the concentration of levodopa increased and decreased slowly. The results of these pharmacokinetic studies may explain the patient’s observation of the amelioration of peak dose dyskinesia after switching from a levodopa + benserazide formulation to a levodopa + carbidopa combination.

Antiparkinsonian activity of new N-methyl-D-aspartate receptor ligands in the arecoline hyperkinesis test

Introduction. Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in the population of older patients. Even though long-term combination therapy helps to cope with the main manifestations of PD. It inevitably leads to the appearance of such side effects as drowsiness, hallucinations, dyskinesia, and many others. [12]. Therefore, the search for effective antiparkinsonian drugs devoid of the above-mentioned adverse reactions remains an urgent task of modern neuropharmacology.The explored substances are derivatives of imidazole-4,5-dicarboxylic acid. These compounds belong to a fundamentally new class of N-methyl-D-aspartate ligands (NMDA) that are not channel blockers. Their pharmacological effect is realized due to interaction with the NMDA receptor recognition site, which, along with high efficiency, allows us to assume their higher safety, compared to previously existing channel blockers from the NMDA ligand group.Objective. Studing of the antiparkinsonian activity of new ligands of the glutamate NMDA-receptor complex-1,2-substituted imidazole-4,5-dicarboxylic acids on an experimental model of arecoline hyperkinesis.Materials and methods. Imidazole-dicarboxylic acid derivatives (IEM2258, IEM2248, IEM2247, and IEM1574) were injected into the lateral ventricles of the mouse brain 10 minutes before arecoline in a volume of 5 µl at doses of 0.1-0.5 µmol, then the latent period, intensity, and duration of tremor were recorded. Amantadine was used as a comparison drug.Results. Preliminary administration of the studied examined substances led to a significant decrease in the intensity and duration of arecoline tremor. The highest inhibitory activity with respect to the intensity and duration of the experimental tremor was demonstrated with the introduction of the compound IEM-2247 (at a dose of 0.1-0.5 mmol, the duration of the latent period of the tremor was 1.7-2.3 times longer than the control one, respectively, the duration of the tremor decreased by 1.5 - 2.5 times).Conclusions. The dose-dependent antiparkinsonian activity of imidazole-dicarboxylic acid derivatives is shown, indicating the prospects for the development of these substances and the further search for effective and safe antiparkinsonian agents among the compounds of this class.

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice

Background and purposeThe aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. MethodsWe conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. ResultsClinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years±8.43 and H&Y stage was 3 [2–4]. Mean dose of levodopa used was 703.75mg±233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. ConclusionsOur real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.

Selected Molecular Targets for Antiepileptogenesis.

The term epileptogenesis defines the usually durable process of converting normal brain into an epileptic one. The resistance of a significant proportion of patients with epilepsy to the available pharmacotherapy prompted the concept of a causative treatment option consisting in stopping or modifying the progress of epileptogenesis. Most antiepileptic drugs possess only a weak or no antiepileptogenic potential at all, but a few of them appear promising in this regard; these include, for example, eslicarbazepine (a sodium and T-type channel blocker), lamotrigine (a sodium channel blocker and glutamate antagonist) or levetiracetam (a ligand of synaptic vehicle protein SV2A). Among the approved non-antiepileptic drugs, antiepileptogenic potential seems to reside in losartan (a blocker of angiotensin II type 1 receptors), biperiden (an antiparkinsonian drug), nonsteroidal anti-inflammatory drugs, antioxidative drugs and minocycline (a second-generation tetracycline with anti-inflammatory and antioxidant properties). Among other possible antiepileptogenic compounds, antisense nucleotides have been considered, among these an antagomir targeting microRNA-134. The drugs and agents mentioned above have been evaluated in post-status epilepticus models of epileptogenesis, so their preventive efficacy must be verified. Limited clinical data indicate that biperiden in patients with brain injuries is well-tolerated and seems to reduce the incidence of post-traumatic epilepsy. Exceptionally, in this regard, our own original data presented here point to c-Fos as an early seizure duration, but not seizure intensity-related, marker of early epileptogenesis. Further research of reliable markers of early epileptogenesis is definitely needed to improve the process of designing adequate antiepileptogenic therapies.

Real World Pharmacological First Treatment Patterns of Patients With Parkinson Disease and Disease Duration: A Large-Scale Cohort Study Using an Health Maintenance Organization Database.

Real-world data were used to describe first antiparkinsonian drug (FAPD) prescription patterns among Parkinson disease (PD) patients and to evaluate disease duration until levodopa (l-DOPA) treatment and until death, as related to FAPD, by age group. The community-based cohort (2000-2012) included 6243 patients, members of an Israeli Health Maintenance Organizations. Time from FAPD purchase to 2 end points (l-DOPA purchase and death) was calculated. Cox regressions were used to estimate adjusted heart rate (HR) to either end point as related to FAPD type, by age group. During a mean follow-up of 4.8 ± 3.2 years, one third of the cohort died. The percent of l-DOPA use as a start drug increased with age, whereas the percent of dopamine agonists (DAs) and monoamine oxidase inhibitor B inhibitor (MAO-BI) decreased with age. Younger women were treated more often with DA as a start drug compared with younger men. In ages of younger than 50 years, time to l-DOPA start in the initial DA-group was 4 times longer than in the initial MAO-BI group (HR, 0.23; 95% confidence interval, 0.08-0.43; 1/0.23, 4.35). All age groups exhibited a similar survival time trend associated with initial drug type. An age-pooled HR with initial l-DOPA-group as a reference group yielded that survival time was 2.4 times longer for the initial DA group (HR, 0.41; 95% confidence interval, 0.31-0.55; 1/0.41, 2.44), 1.9 times and 1.4 times for initial MAO-BI or amantadine, respectively. First antiparkinsonian drug choice might be associated with time until l-DOPA initiation but may represent disease severity at the time of prescription, thus also affecting survival time as well. Real-world data illustrated that this choice is also age and sex dependent.

Hypersexuality Complication of Dopamine Agonists: Pramipexole or Ropinirole

Antiparkinsonian drugs especially dopamine agonists have many side effects. Dopamine agonists have been linked with compulsive inappropriate behaviours such as gambling, compulsive shopping, hobbyism, other repetitive or purposeless behaviours such as punding, compulsive eating and hypersexuality. However pathological hypersexuality has rarely surfaced in routine Parkinson’s disease practice. We present clinical findings of a seventy-three year old male Parkinson’s disease patient with diagnosis of hypersexuality as a side effect of pramipexole. After pramipexole was withdrawn, dopamine agonist was changed to ropinirole and full remission was observed. Prevalence of psychiatric disorders in patients suffering from Parkinson’s disease varies from 12 to 90%. Hypersexuality is a common impulse control disorder seen in Parkinson’s disease and noted in these patients taking a variety of dopaminergic agents; including levodopa, dopamine agonists or MAO inhibitors. In our patient, pramipexole caused hypersexuality unexpectedly. Since this case constitutes interesting findings in two different points, one is hypersexuality with pramipexole, the other is no hypersexuality with use of ropinirole after pramipexole withdrawal, it is chosen to be presented here.

Antipsychotic polypharmacy in adult patients diagnosed with schizophrenia: A retrospective study.

Antipsychotic polypharmacy (APP) is a common practice in the treatment of schizophrenia. In this study, we aimed to identify the prevalence of APP in our department, as well as the trends associated with co-prescribing antipsychotics. We collected data from the medical records of all 193 inpatients diagnosed with schizophrenia who were admitted to Prof. Dr. Alexandru Obregia Clinical Psychiatry Hospital (Bucharest, Romania), Department 9, during January 2019-December 2019. Demographic characteristics of the patients, clinical diagnosis, psychiatric admission type and duration of hospitalization were examined. Data regarding the antipsychotic regimen at discharge and other psychotropic drugs used were collected. A total of 69 (35.75%) patients received more than 2 antipsychotics upon discharge. Patients treated with APP did not differ in regards to sex, age, education level, employment status, marital status, living situation, type of admission from those receiving antipsychotic monotherapy (APM). Prolonged hospitalization was found to be an independent predictor of APP (P=0.014). Most of the combinations used in our unit included clozapine (47.8%), and the most frequently used treatment in the APP group was the combination of paliperidone and clozapine (14.5%). In the APP group, 30 (43.5%) patients included in their regimen was a long-acting intramuscular antipsychotic. There was no significant difference in terms of the use of mood stabilizers, antiparkinsonian drugs or anxiolytics between the APP and the APM group; yet, a higher prevalence of antidepressant use, although not statistically significant (P=0.067), in the APP group compared to the APM group, was observed. The use of APP as a long-term regimen is a common practice in our department, as it is worldwide. There is a great need for randomized-control trials and evidence-based studies in order to define the safest and most effective combinations of antipsychotics and also the characteristics of patients that may benefit from these combinations.

Ropinirole involved in a fatal case: blood and urinary concentrations.

Ropinirole is an antiparkinsonian drug and has recently been suggested to be effective in amyotrophic lateral sclerosis. It is expected that ropinirole prescriptions will increase in the nearfuture. However, the fatal concentration in blood is unclear at this time. Therefore, we report a fatal case involving ropinirole intoxication and discuss the fatal concentrations with reference to several autopsy cases involving ropinirole. Ropinirole was quantified in femoral vein blood, cardiac blood, and urine from five autopsy cases in which ropinirole was detected by drug screening in our laboratory. One is a ropinirole intoxication case (this report) and the others were non-intoxication cases. Their ropinirole concentrations were compared and discussed. The ropinirole concentration in this case was 100ng/mL in femoral blood, 160ng/mL in cardiac blood, and 1840ng/mL in urine. The ropinirole concentrations in the four non-ropinirole poisoning cases were 7-35ng/mL (mean: 24ng/mL) in femoral blood, 13-100ng/mL (mean: 60ng/mL) in cardiac blood, and 140-1090ng/mL (mean: 640ng/mL) in urine. Cardiac/peripheral ratios were in the range of 1.6-2.1 (mean 1.8). There were no obvious signs of overdose, and the high cardiac/peripheral blood ratio suggested that postmortem redistribution may have occurred, but the peripheralblood ropiniroleconcentration (100 ng/mL)was obviously higher than that reported in theprevious fatalcase of ropinirole poisoning (64ng/mL). Based on these results, the cause of death in this case was considered to be shock and fatal arrhythmia due to ropinirole poisoning. This case provides important data on postmortem blood and urinary levels of ropinirole poisoning.

Surgical treatments for Parkinson’s disease

Parkinson’s disease (PD) is a progressive, incurable degenerative disease of the central nervous system, leading to a significant limitation of the functional state of patients. Modern medicine has several methods of medical and surgical treatment for this pathology. In the review, all stages of the surgical treatment of PD are considered, starting with the descriptions of the resection of the precentral gyrus of historical interest to stereotaxic lesions by various methods of exposure and electrical stimulation of the deep brain structures. The indications for each of the methods, their advantages and disadvantages, the principles of patient selection are presented. Indications for neurosurgical treatment are determined taking into account the international CAPSIT-PD criteria. Stereotactic lesions lead to irreversible changes in the medulla, therefore their widespread use is limited. Stimulation with deep electrodes has advantages in disease progression due to the possibility of changing the stimulation parameters and the possibility of a bilateral effect on motor symptoms. Surgical treatment of PD does not mean the cancelling of drug therapy, but it can reduce the dose of anti-Parkinsonian drugs and reduce their side effects. The best result can be achieved with timely operation and correct selection of patients by a multidisciplinary medical team with considering the characteristics of the course of the disease, the possibility of long-term postoperative observation of the patient and correction of stimulation parameters.

Mortality of People with Parkinson's Disease in a Large UK-Based Cohort Study: Time Trends and Relationship to Disease Duration.

BackgroundParkinson’s disease (PD) is associated with increased mortality, but little is known about changes over time, and relationship to disease progression.ObjectivesTo explore how PD mortality rates have changed over time and their relationship to disease duration and demographics using a large population-based cohort in the UK.MethodsWe included individuals aged 50+ years with a first recording of PD diagnosis and at least two prescriptions of any antiparkinsonian drug actively registered within a general practice from 2006 to 2016 and up to six frequency-matched controls from The Health Improvement Network (THIN) database. We estimated adjusted mortality rates using multivariable Poisson regression.ResultsA total of 10,104 people with a diagnosis of PD and 55,664 people without PD were included. Overall, PD was associated with slightly increased mortality compared to non-PD controls (adjusted mortality rate ratio: 1.14; 95% CI: 1.03 to 1.19). Adjusted mortality rates per 1000 person-years at risk for people with PD approximately doubled in the 5 years following diagnosis from 43 (95% CI: 38 to 48) to 75 (95% CI: 64 to 85). Following adjustments for age, gender, and time since diagnosis, mortality rates between 2007 and 2016 declined more slowly for people with PD (2% per year; 95% CI: 0%–4%) compared to people without PD (5% per year; 95% CI: 3%–6%).ConclusionsWhilst mortality in PD is only slightly increased overall, it gradually increases with advancing disease. There has been a decline in mortality in PD over time, but this decrease was less pronounced than that in the general population.