Antiparkinsonian Medication Research Articles

82 Timely Prescribing of Regular Medications in General Surgery

Abstract Aim It’s crucial that regular medications are prescribed in a timely manner for hospital inpatients. Missed or delayed doses of critical medications (insulin, anti-parkinsonian medication, antiepileptics and steroids) can compromise patient safety. This audit, with two closed-loop cycles, aimed to improve prescribing on surgical wards. Method Data was gathered from >48 adult non-elective general surgery patients pre- and post-intervention with four outcomes measured, listed in results. Data was re-collected after one month and the cycle repeated one year later. Interventions: Results Average time for prescribing regular medications improved from 13hrs to 11.2hrs in the first cycle and 22.5hrs to 13.1hrs in the second cycle. Percentage of patients with critical medications prescribed on admission improved by 50% in the first cycle and remained at 100% pre- and post-intervention in the second cycle. Percentage of patients who missed medication due to delayed prescribing reduced by 11% in the first cycle and 16% in the second cycle. Percentage of patients who had regular medications prescribed before pharmacy medicines reconciliation improved by 9% in the first cycle and 28% in the second cycle. Conclusions In both cycles, all measurements experienced improvements. Largest improvements were in the 2nd cycle with the addition of educational posters. SCR access improves ability to prescribe regular medications. Educational posters act as effective visual aids. Both can be recommended.

Assessment of Repetitive and Compulsive Behaviors Induced by Pramipexole in Rats: Effect of Alpha-Synuclein-Induced Nigrostriatal Degeneration.

Treatment with dopamine agonists in Parkinson’s disease (PD) is associated with debilitating neuropsychiatric side-effects characterized by impulsive and compulsive behaviors. The vulnerability to develop such impairments is thought to involve interactions between individual vulnerability traits, types of antiparkinsonian medications, and the neurodegenerative process. We investigated the effect of the dopamine D3/D2 agonist pramipexole (PPX) and selective nigrostriatal degeneration achieved by viral-mediated expression of alpha-synuclein on the expression of repetitive and compulsive-like behaviors in rats. In a task assessing spontaneous food hoarding behavior, PPX increased the time spent interacting with food pellets at the expense of hoarding. This disruption of hoarding behavior was identical in sham and lesioned rats. In an operant post-training signal attenuation task, the combination of nigrostriatal lesion and PPX decreased the number of completed trials and increased the number of uncompleted trials. The lesion led to an increased compulsive behavior after signal attenuation, and PPX shifted the overall behavioral output towards an increased proportion of compulsive lever-presses. Given the magnitude of the behavioral effects and the lack of strong interaction between PPX and nigral degeneration, these results suggest that extra-nigral pathology may be critical to increase the vulnerability to develop compulsive behaviors following treatment with D3/D2 agonists.

Adherence to Medication among Parkinson's Disease Patients Using the Adherence to Refills and Medications Scale.

Objectives Adherence to medication is an important factor that can influence Parkinson's disease (PD) control. We aimed to explore patients' adherence to antiparkinsonian medication and determine factors that might affect adherence to medications among PD patients. Methods A cross-sectional, exploratory survey of PD patients treated with at least one antiparkinsonian drug and with a total score of MoCA (Montreal Cognitive Assessment) ≥26 was conducted. The final sample included 112 PD patients. A patient's adherence was assessed through ARMS (Adherence to Refills and Medications Scale). ARMS scores higher than 12 were assumed lower adherence. In addition, each patient underwent neurological examination, assessment of depression, anxiety, and evaluation of the presence of PD nonmotor symptoms. Results The mean ARDS value in our cohort was 14.9 ± 2.5. Most PD patients (74.1%) reported lower adherence to their medication. Participants in the lower adherence group were younger at PD onset, had significantly higher UPDRS (Unified PD Rating Scale) scores, as well as UPDRS III and UPDRS IV subscores, HARS (Hamilton Anxiety Rating Scale), and NMSQuest (Non-Motor Symptoms Questionnaire for PD) scores compared to the fully adherent group (p=0.013, p=0.017, p=0.041, p=0.043, and p=0.023, respectively). Among nonmotor PD symptoms, the presence of cardiovascular, apathy/attention-deficit/memory disorders, hallucinations/delusions, and problems regarding changes in weight, diplopia, or sweating were associated with lower adherence. Multivariate regression analysis revealed depression as the strongest independent predictor of lower adherence. Conclusion Depressed PD patients compared to PD patients without clinical depression had a three times higher risk for lower adherence to pharmacotherapy. Recognition and adequate treatment of depression might result in improved adherence.

Antiparkinsonian Drug Reduction After Directional Versus Omnidirectional Bilateral Subthalamic Deep Brain Stimulation

BackgroundSeveral pilot trials and the Clinical Evaluation of the Infinity Deep Brain Stimulation System (PROGRESS) study have found that directional stimulation can provide a wider therapeutic window and lower therapeutic current strength than omnidirectional stimulation. ObjectiveWe conducted a single-center, open-label, registry-based, comparative trial to test the hypothesis that directional stimulation can be associated with a greater reduction in the total daily dose of antiparkinsonian medications (ApMeds) than omnidirectional stimulation. Materials and MethodsA total of 52 patients with directional and 57 subjects with omnidirectional bilateral subthalamic deep brain stimulation (STN-DBS) were enrolled. Preoperatively and 12 months postoperatively, the dose of different ApMeds, the number of tablets used daily, the severity of motor and nonmotor symptoms using the Movement Disorder Society–sponsored Unified Parkinson Disease Rating Scale, and the health-related quality of life (HRQoL) using the 39-item Parkinson’s Disease Questionnaire (PDQ-39) were assessed. ResultsAccording to the changes in the levodopa equivalent daily dose, directional STN-DBS led to a 13% greater reduction in the total daily dose of ApMed. The 10.3% greater reduction in the dose of levodopa was the main contributor to this difference. The number of different ApMed types also could be decreased in a greater manner with directional stimulation. The improvement in the severity of motor and nonmotor symptoms was comparable; however, we detected a 15.8% greater improvement in the global HRQoL among patients with directional stimulation according to the changes in the summary index of the PDQ-39. The total electrical energy delivered per second was comparable between the groups at 12-month postoperative visit, whereas the amplitude of stimulation was significantly lower and the impedance was significantly higher with directional leads. ConclusionsDirectional programming can further increase the reduction in the total daily dose of ApMed after STN-DBS. In addition, directional stimulation can have additional beneficial effects on the global HRQoL. The greater reduction of ApMed doses did not require more energy-consuming stimulation with directional stimulation.

Electromyographic measures of asymmetric muscle control of swallowing in Parkinson's disease.

During the early stages, Parkinson's disease (PD) is well recognized as an asymmetric disease with unilateral onset of resting tremor with varying degrees of rigidity, and bradykinesia. However, it remains unknown if other impairments, such as swallowing impairment (i.e., dysphagia), also present asymmetrically. The primary aim of this study was to examine muscle activity associated with swallow on the most affected side (MAS) and least affected side (LAS) in persons with PD. A secondary aim was to explore the relationship between differences in muscle activity associated with swallow and subjective reports of swallowing impairment and disease severity. Function of muscles associated with swallowing was assessed using surface electromyography placed over the right and left submental and laryngeal regions during three swallows for a THIN and THICK condition. The Swallowing Quality of Life (SWAL-QOL) questionnaire and the Unified Parkinson's Disease Rating Scale (UPDRS) were collected as measures of subjective swallow impairment and disease severity, respectively. Thirty-five participants diagnosed with idiopathic PD and on a stable antiparkinsonian medication regimen completed this study. Results revealed no significant mean difference in muscle activity during swallow between the more and less affected side. For the laryngeal muscle region, a significant difference in coefficient of variation between the MAS and LAS was revealed for peak amplitude for the THIN swallow condition. For the laryngeal muscle region, a significant association was revealed between muscle activity and disease severity but not subjective reports of swallowing impairment. Superficially it appears that swallowing impairment present symmetrical during the early stages of PD, however, our variability data indicates otherwise. These results will be used to inform future studies in specific types of swallowing impairment (i.e., oral dysphagia, pharyngeal dysphagia, and esophageal dysphagia), disease progression, and overall asymmetry.

Anticholinergic Medication Burden in Parkinson's Disease Outpatients.

Individuals with Parkinson's disease (PD) may be especially vulnerable to future cognitive decline from anticholinergic medications. To characterize anticholinergic medication burden, determine the co-occurrence of anticholinergic and cholinesterase inhibitors, and to assess the correlations among anticholinergic burden scales in PD outpatients. We studied 670 PD outpatients enrolled in a clinic registry between 2012 and 2020. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden Scale (ACB), Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Drug Burden Index-Anticholinergic component (DBI-Ach). Correlations between scales were assessed with weighted kappa coefficients. Between 31.5 to 46.3% of PD patients were taking medications with anticholinergic properties. Among the scales applied, the ACB produced the highest prevalence of medications with anticholinergic properties (46.3%). Considering only medications with definite anticholinergic activity (scores of 2 or 3 on ACB, ADS, or ARS), the most common anticholinergic drug classes were antiparkinsonian (8.2%), antipsychotic (6.4%), and urological (3.3%) medications. Cholinesterase inhibitors and medications with anticholinergic properties were co-prescribed to 5.4% of the total cohort. The most highly correlated scales were ACB and ADS (κ= 0.71), ACB and ARS (κ= 0.67), and ADS and ARS (κ= 0.55). A high proportion of PD patients (20%) were either taking antiparkinsonian, urological, or antipsychotic anticholinergic medications or were co-prescribed anticholinergic medications and cholinesterase inhibitors. By virtue of its detection of a high prevalence of anticholinergic medication usage and its high correlation with other scales, our data support use of the ACB scale to assess anticholinergic burden in PD patients.

Difference in rural and urban Medicare prescription pattern for Parkinson’s disease in Hawai‘i

BackgroundMedical management of Parkinson’s Disease (PD) is becoming complex. Increasing evidence suggests that patients have better outcomes when they are managed by neurologists. However, access to neurologists can be limited in rural areas. Analysis of prescription pattern can provide insight into access gap rural patients face. MethodsThis retrospective observational study used National Medicare Provider Utilization and Payment Data: Part D Prescriber Public Use Files from 2013 to 2018. Query was made for levodopa, dopamine agonists and other antiparkinsonian medications. The data elements obtained included drug name, number of prescribers, prescriber specialty, number of claims, number of standardized 30-day Part D prescriptions, and number of Medicare beneficiaries in the state of Hawai‘i. Individual prescribing providers were categorized as urban or rural based on their cities of practice. Prescription patterns of urban and rural providers in Hawai‘i as well as difference in provider specialty were compared, using standardized 30-day prescriptions as the primary measure of utilization. ResultsPractice patterns differed between rural and urban areas. In rural Hawai‘i, Rytary, Rotigoitne and selegiline were rarely prescribed. Levodopa percentage was higher in urban Hawai‘i. In urban Hawai‘i, 74.4% of the prescriptions were provided by movement disorders and general neurologists. In rural Hawai'i, 25.1% of the prescriptions were written by neurologists and 74.9% by general practitioners. ConclusionsIn the state of Hawai‘i, there is an urban–rural access gap to neurologists as evidenced by Medicare prescription pattern. Further study is needed to understand the reasons for rural–urban differences in prescription patterns and their impact on outcomes.

Catatonia in Parkinson disease due to withdrawal of antiparkinsonian medications: a case report

Catatonia in Parkinson disease due to withdrawal of antiparkinsonian medications: a case report

Orthostatic Hypotension and Antiparkinsonian Drugs: A Systematic Review and Meta-analysis.

BackgroundOrthostatic hypotension (OH) is multifactorial in Parkinson’s disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue.MethodsWe conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available.ResultsTwenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81–6.46]), (OR 1.39 [95% CI:0.97–1.98]).ConclusionsMost studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH.

Frequency-Specific Effects of Galvanic Vestibular Stimulation on Response-Time Performance in Parkinson's Disease.

Background: Galvanic vestibular stimulation (GVS) is being increasingly explored as a non-invasive brain stimulation technique to treat symptoms in Parkinson's disease (PD). To date, behavioral GVS effects in PD have been explored with only two stimulus types, direct current and random noise (RN). The interaction between GVS effects and anti-parkinsonian medication is unknown. In the present study, we designed multisine (ms) stimuli and investigated the effects of ms and RN GVS on motor response time. In comparison to the RN stimulus, the ms stimuli contained sinusoidal components only at a set of desired frequencies and the phases were optimized to improve participants' comfort. We hypothesized GVS motor effects were a function of stimulation frequency, and specifically, that band-limited ms-GVS would result in better motor performance than conventionally used broadband RN-GVS.Materials and Methods: Eighteen PD patients (PDMOFF/PDMON: off-/on-levodopa medication) and 20 healthy controls (HC) performed a simple reaction time task while receiving sub-threshold GVS. Each participant underwent nine stimulation conditions: off-stimulation, RN (4–200 Hz), ms-θ (4–8 Hz), ms-α (8–13 Hz), ms-β (13–30 Hz), ms-γ (30–50 Hz), ms-h1 (50–100 Hz), ms-h2 (100–150 Hz), and ms-h3 (150–200 Hz).Results: The ms-γ resulted in shorter response time (RPT) in both PDMOFF and HC groups compared with the RN. In addition, the RPT of the PDMOFF group decreased during the ms-β while the RPT of the HC group decreased during the ms-α, ms-h1, ms-h2, and ms-h3. There was considerable inter-subject variability in the optimum stimulus type, although the frequency range tended to fall within 8–100 Hz. Levodopa medication significantly reduced the baseline RPT of the PD patients. In contrast to the off-medication state, GVS did not significantly change RPT of the PD patients in the on-medication state.Conclusions: Using band-limited ms-GVS, we demonstrated that the GVS frequency for the best RPT varied considerably across participants and was >30 Hz for half of the PDMOFF patients. Moreover, dopaminergic medication was found to influence GVS effects in PD patients. Our results indicate the common “one-size-fits-all” RN approach is suboptimal for PD, and therefore personalized stimuli aiming to address this variability is warranted to improve GVS effects.

Facing the Challenges of Understanding and Managing Behavior and Psychiatric Issues

Facing the Challenges of Understanding and Managing Behavior and Psychiatric Issues

Effectiveness of Long-Term Physiotherapy in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Background:Long-term physiotherapy is acknowledged to be crucial to manage motor symptoms for Parkinson’s disease (PD) patients, but its effectiveness is not well understood.Objective:This systematic review and meta-analysis aimed to assess the evidence regarding the effectiveness of long-term physiotherapy to improve motor symptoms and reduce antiparkinsonian medication dose in PD patients.Methods:Pubmed, Cochrane, PEDro, and CINAHL were searched for randomized controlled trials before August 31, 2020 that investigated the effectiveness of physiotherapy for 6 months or longer on motor symptoms and levodopa-equivalent dose (LED) in PD patients with Hoehn and Yahr stage 1– 3. We performed random effects meta-analyses for long-term physiotherapy versus no/control intervention and estimated standard mean differences with 95% confidence intervals (CIs). Levels of evidence were rated by the Grading of Recommendation Assessment, Development and Evaluation approach.Results:From 2,940 studies, 10 studies involving 663 PD patients were assessed. Long-term physiotherapy had favorable effects on motor symptoms in off medication state [– 0.65, 95% CI – 1.04 to – 0.26, p = 0.001] and LED [– 0.49, 95% CI – 0.89to – 0.09, p = 0.02]. Subgroup analyses demonstrated favorable effects on motor symptoms in off medication state by aerobic exercise [– 0.42, 95% CI – 0.64 to – 0.20, p < 0.001] and LED by multidisciplinary rehabilitation of primarily physiotherapy [– 1.00, 95% CI – 1.44 to – 0.56, p < 0.001]. Quality of evidence for aerobic exercise and multidisciplinary rehabilitation were low and very low.Conclusion:This review provided evidence that long-term physiotherapy has beneficial impact on motor symptoms and antiparkinsonian medication dose in PD patients and could motivate implementation of long-term physiotherapy.

A retrospective study evaluating the use of anti-Parkinsonian medications in patients with advanced Parkinson's disease treated with Levodopa-Carbidopa Intestinal Gel and deep brain stimulation

Patients using deep brain stimulation (DBS) with adjunctive oral therapy may require additional therapies like levodopa-carbidopa intestinal gel (LCIG), known as CLES in the United States. We examine use of oral/transdermal anti-parkinsonian medications in advanced Parkinson's disease (APD) patients with history of or current treatment with DBS, receiving LCIG.

Altered White-Matter Functional Networks in Patients With Conduct Disorder

Drooling is a common symptom in Parkinson’s disease (PD). This study used resting-state functional MRI (fMRI) to evaluate the brain connectivity of cortico-striatal circuits in PD patients with drooling.We enrolled 30 early-stage drug-naïve PD patients and 30 matched normal controls. Among the PD patients, 15 patients were classified as “droolers” with the presence of drooling and 15 patients as “non-droolers” with the absence of drooling. All participants underwent resting-state fMRI scans on a 3-T MR system, focusing on the functional connectivity of striatum subregions.Compared with PD patients without drooling, PD patients with drooling showed the significantly reduced functional connectivity of putamen within bilateral sensorimotor cortices, superior and inferior parietal lobules and areas in the right occipital and temporal lobes. No increased functional connectivity was found between the two PD subgroups. In addition, compared with healthy controls, both PD subgroups showed the functional connectivity alterations in cortico-striatal loops. The decreased functional connectivity was prominent in the most affected posterior putamen, and the increased functional connectivity was evident only in the relatively unaffected anterior striatum and caudate.By studying a cohort of early-stage drug-naïve PD patients, we eliminated the potential confounding effects of antiparkinson medication on the functional integration of neural networks. We demonstrated decreased connectivity within cortico-striatal networks in PD patients with drooling. These findings might be helpful for promoting the further understanding of neural system effects underlying drooling in PD. Our result is preliminary and further investigation is needed.

Bilateral Subthalamic Nucleus Deep Brain Stimulation Improves Gastric Emptying Time in Parkinson Disease

It is well-established that deep brain stimulation (DBS) can improve motor function in those with Parkinson disease (PD); however, its effects on gastrointestinal disorders remain unclear. From January 2019 to December 2020, 26 patients with PD who had undergone subthalamic nucleus (STN) DBS were included in our study. The evaluated items included the pre- and postoperative dose of levodopa, Unified Parkinson's Disease Rating Scale, part III, scores with and without medication and stimulation, and gastric emptying time (expressed as the peak time of carbon-13C dioxide excretion in the 13C-acetate breath test). Sex-, age-, and body weight-matched controls were recruited to test the gastric emptying time in healthy individuals. All the patients benefited from DBS. The Unified Parkinson's Disease Rating Scale, part III, scores had decreased from 48.5 ± 13.77 to 25.23 ± 8.59 without medication and 31.23 ± 11.4 to 13.92 ± 5.27 with medication. The levodopa equivalent dose had decreased from 1009.8 ± 291 mg to 707.65 ± 193.79 mg. The gastric emptying time was significantly prolonged in the patients with PD before DBS compared with the healthy control group (29.23 ± 6.58 minutes) and had improved to 35.19 ± 10.14 minutes with medication and 38.07 ± 11.17 minutes without medication after 3 months of STN stimulation. At 6 months postoperatively, the gastric emptying time was 32.3 ± 10.02 minutes without medication and 33.84 ± 10.79 minutes with medication. A delayed gastric emptying time is associated with greater PD severity. Antiparkinsonian medications did not affect gastric emptying in patients with PD. STN DBS can improve both movement function and gastrointestinal motility in patients with PD in the long term. The exact mechanism by which DBS improves gastric emptying requires further exploration.

Balance between competing spectral states in subthalamic nucleus is linked to motor impairment in Parkinson's disease.

Exaggerated local field potential bursts of activity at frequencies in the low beta band are a well-established phenomenon in the subthalamic nucleus of patients with Parkinson’s disease. However, such activity is only moderately correlated with motor impairment. Here we test the hypothesis that beta bursts are just one of several dynamic states in the subthalamic nucleus local field potential in Parkinson’s disease, and that together these different states predict motor impairment with high fidelity.Local field potentials were recorded in 32 patients (64 hemispheres) undergoing deep brain stimulation surgery targeting the subthalamic nucleus. Recordings were performed following overnight withdrawal of anti-parkinsonian medication, and after administration of levodopa. Local field potentials were analysed using hidden Markov modelling to identify transient spectral states with frequencies under 40 Hz.Findings in the low beta frequency band were similar to those previously reported; levodopa reduced occurrence rate and duration of low beta states, and the greater the reductions, the greater the improvement in motor impairment. However, additional local field potential states were distinguished in the theta, alpha and high beta bands, and these behaved in an opposite manner. They were increased in occurrence rate and duration by levodopa, and the greater the increases, the greater the improvement in motor impairment. In addition, levodopa favoured the transition of low beta states to other spectral states. When all local field potential states and corresponding features were considered in a multivariate model it was possible to predict 50% of the variance in patients’ hemibody impairment OFF medication, and in the change in hemibody impairment following levodopa. This only improved slightly if signal amplitude or gamma band features were also included in the multivariate model. In addition, it compares with a prediction of only 16% of the variance when using beta bursts alone.We conclude that multiple spectral states in the subthalamic nucleus local field potential have a bearing on motor impairment, and that levodopa-induced shifts in the balance between these states can predict clinical change with high fidelity. This is important in suggesting that some states might be upregulated to improve parkinsonism and in suggesting how local field potential feedback can be made more informative in closed-loop deep brain stimulation systems.

Idiopathic Parkinson's Disease at the End of Life: A Retrospective Evaluation of Symptom Prevalence, Pharmacological Symptom Management and Transdermal Rotigotine Dosing.

Distressing symptoms are prevalent in patients with idiopathic Parkinson's disease, yet little is known about symptom burden and subsequent pharmacological management at the end of life. Additionally, when oral administration of antiparkinsonian medications is no longer possible in dying patients, it is becoming common place to initiate transdermal rotigotine, despite a paucity of evidence to guide dosing. To assess: (1) symptom prevalence from the use of anticipatory medicines in patients with idiopathic Parkinson's disease, (2) the prescribing of antiparkinsonian medication at the end of life; and (3) the accuracy of conversion from oral antiparkinsonian medicines to transdermal rotigotine and any associations between rotigotine dosing and end-of-life symptoms. A retrospective case review was performed. One hundred consecutive patients with idiopathic Parkinson's disease who died during an inpatient admission at a UK teaching hospital were assessed. The most prevalent terminal symptoms were excess respiratory secretions (58%), pain (52%), agitation (51%) and fever (23%). The majority of patients were converted to transdermal rotigotine (90%). Patients converted to a higher than equivalent dose of rotigotine were more likely to be agitated (p<0.05), whilst those converted to a lower than equivalent dose were less likely to develop excess respiratory secretions (p<0.05). The prevalence of pain did not differ according to rotigotine dosing. This study highlights for the first time use of anticipatory medications at the end of life in patients with idiopathic Parkinson's disease and the prevalence of terminal symptoms. It also demonstrates the widespread use of rotigotine patches, and that lower than equivalent doses may be better tolerated.

Methamphetamine-induced dopaminergic neurotoxicity as a model of Parkinson’s disease

Parkinson's disease (PD) is a progressive neurodegenerative disease with a high prevalence, approximately 1 % in the elderly population. Numerous studies have demonstrated that methamphetamine (MA) intoxication caused the neurological deficits and nigrostriatal damage seen in Parkinsonian conditions, and subsequent rodent studies have found that neurotoxic binge administration of MA reproduced PD-like features, in terms of its symptomatology and pathology. Several anti-Parkinsonian medications have been shown to attenuate the motor impairments and dopaminergic damage induced by MA. In addition, it has been recognized that mitochondrial dysfunction, oxidative stress, pro-apoptosis, proteasomal/autophagic impairment, and neuroinflammation play important roles in inducing MA neurotoxicity. Importantly, MA neurotoxicity has been shown to share a common mechanism of dopaminergic toxicity with that of PD pathogenesis. This review describes the major findings on the neuropathological features and underlying neurotoxic mechanisms induced by MA and compares them with Parkinsonian pathogenesis. Taken together, it is suggested that neurotoxic binge-type administration of MA in rodents is a valid animal model for PD that may provide knowledge on the neuropathogenesis of PD.

The SleepFit Tablet Application for Home-Based Clinical Data Collection in Parkinson Disease: User-Centric Development and Usability Study.

BackgroundParkinson disease (PD) is a common, multifaceted neurodegenerative disorder profoundly impacting patients' autonomy and quality of life. Assessment in real-life conditions of subjective symptoms and objective metrics of mobility and nonmotor symptoms such as sleep disturbance is strongly advocated. This information would critically guide the adaptation of antiparkinsonian medications and nonpharmacological interventions. Moreover, since the spread of the COVID-19 pandemic, health care practices are being reshaped toward a more home-based care. New technologies could play a pivotal role in this new approach to clinical care. Nevertheless, devices and information technology tools might be unhandy for PD patients, thus dramatically limiting their widespread employment.ObjectiveThe goals of the research were development and usability evaluation of an application, SleepFit, for ecological momentary assessment of objective and subjective clinical metrics at PD patients’ homes, and as a remote tool for researchers to monitor patients and integrate and manage data.MethodsAn iterative and user-centric strategy was employed for the development of SleepFit. The core structure of SleepFit consists of (1) an electronic finger-tapping test; (2) motor, sleepiness, and emotional subjective scales; and (3) a sleep diary. Applicable design, ergonomic, and navigation principles have been applied while tailoring the application to the specific patient population. Three progressively enhanced versions of the application (alpha, v1.0, v2.0) were tested by a total of 56 patients with PD who were asked to perform multiple home assessments 4 times per day for 2 weeks. Patient compliance was calculated as the proportion of completed tasks out of the total number of expected tasks. Satisfaction on the latest version (v2.0) was evaluated as potential willingness to use SleepFit again after the end of the study.ResultsFrom alpha to v1.0, SleepFit was improved in graphics, ergonomics, and navigation, with automated flows guiding the patients in performing tasks throughout the 24 hours, and real-time data collection and consultation were made possible thanks to a remote web portal. In v2.0, the kiosk-mode feature restricts the use of the tablet to the SleepFit application only, thus preventing users from accidentally exiting the application. A total of 52 (4 dropouts) patients were included in the analyses. Overall compliance (all versions) was 88.89% (5707/6420). SleepFit was progressively enhanced and compliance increased from 87.86% (2070/2356) to 89.92% (2899/3224; P=.04). Among the patients who used v2.0, 96% (25/26) declared they would use SleepFit again.ConclusionsSleepFit can be considered a state-of-the-art home-based system that increases compliance in PD patients, ensures high-quality data collection, and works as a handy tool for remote monitoring and data management in clinical research. Thanks to its user-friendliness and modular structure, it could be employed in other clinical studies with minimum adaptation efforts.Trial RegistrationClinicalTrials.gov NCT02723396; https://clinicaltrials.gov/ct2/show/NCT02723396

ATP13A2 levels in serum and cerebrospinal fluid in patients with idiopathic Parkinson's disease

BackgroundThe enzyme ATP13A2 holds promise as biomarker in Parkinson's disease (PD). No study has examined the content of ATP13A2 in serum and cerebrospinal fluid (CSF) in idiopathic PD cohorts, or how ATP13A2 relates to the clinical features of the disease. MethodsATP13A2 concentration was evaluated with ELISA and immunoblotting. Correlations of serum and CSF ATP13A2 with clinical parameters were examined. The antiparkinsonian medication regimen was expressed as levodopa equivalent dose (LED, mg/day). ResultsSerum ATP13A2 concentration was similar in patients and controls, and it correlated with LED and MDS-UPDRS part-IV score (p < .0001), a scale which allows evaluating motor complications. LED also correlated with MDS-UPDRS part-IV score (p < .0001). Serum ATP13A2 concentration and LED were higher in patients with motor complications than in patients without motor complications (p < .0001). The ratio of serum ATP13A2 concentration versus LED was calculated, and mean value was similar in patients with or without motor complications. ATP13A2 concentration in the CSF was undetectable in many subjects because the ELISA assay was hampered by its detection limit. Immunoblotting indicated that CSF ATP13A2 content was higher in patients relative to controls (p = .0002), and no clinical correlations were found. ConclusionsIncreasing LED enhanced serum ATP13A2 concentration and facilitated the development of motor complications. There is a direct relationship between serum ATP13A2 level and the dose intensity of the antiparkinsonian dopaminergic medication. The associations between serum ATP13A2 and LED suggest that serum ATP13A2 content might be a marker of dopamine replacement therapy.