Parsonage-Turner Syndrome following COVID-19 Vaccination: A Systematic Review.

BACKGROUND: Parsonage-Turner syndrome (PTS) is an inflammatory condition of the brachial plexus, with more than half of patients presenting a trigger, such as infection or vaccination. Our objective was to synthesize the clinical and paraclinical features, therapeutic responses, and outcomes of PTS post-COVID-19 vaccination. METHODS: We systematically reviewed two databases (LitCOVID and the WHO database on COVID-19) up to January 2024 following a published protocol (OSF registries). RESULTS: We included 59 cases. PTS occurred more frequently in males (61.1% mRNA group, 83.3% viral vector group). Patients in the mRNA group were younger (41.7% between 41 and 50 years vs. 38.9% between 61 and 70 years). Most cases had sudden pain within two weeks. Unilateral PTS was present in 94.4% of mRNA and all viral vector-vaccinated cases. Symptoms included pain (97.1% and 92.3%, respectively), usually followed within two weeks by motor deficits (97.2% and 94.1%, respectively), amyotrophy (30% and 81.8%, respectively), paresthesia (50% and 27.3%, respectively), and sensory loss (33.3% and 38.5%, respectively). Viral vector vaccine recipients had nerve involvement outside the brachial plexus. Ancillary investigations revealed CSF albuminocytological dissociation (33.3% and 100%, respectively) and ipsilateral axillary lymphadenopathy. Two PTS cases worsened after the second mRNA dose, and another recurred after influenza vaccination. One patient well tolerated the second dose of the viral vector vaccine, but symptoms reemerged in another. CONCLUSIONS: Current evidence suggests PTS may occur after all COVID-19 vaccine types, with some subgroup differences. Also, PTS might recur with subsequent similar or unrelated vaccines.

Levodopa-Carbidopa-Entacapone Intestinal Gel in Advanced Parkinson Disease: A Multicenter Real-Life Experience.

BACKGROUND: For Parkinson disease (PD) patients who have been diagnosed with advanced disease that can no longer be effectively controlled with optimized oral or transdermal medications, a range of device-aided therapies (DAT) are available, comprising either deep brain stimulation or infusion therapies providing continuous dopaminergic stimulation. Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is the latest DAT for advanced PD (APD) that was approved in Romania in 2021. STUDY QUESTION: What is the experience to date in real-world clinical practice in Romania regarding the efficacy and tolerability of LECIG in APD? STUDY DESIGN: A retrospective evaluation of 74 APD patients treated with LECIG at 12 specialized APD centers in Romania. MEASURES AND OUTCOMES: Demographic data and various clinical parameters were recorded, including Mini Mental State Evaluation score or Montreal Cognitive Assessment Test score. Levodopa-equivalent daily dose and the administered doses of levodopa and other PD medications were evaluated at baseline and after starting LECIG treatment. The efficacy of LECIG in reducing daily hours of off time, motor fluctuations, and dyskinesias were assessed. Any percutaneous endoscopic gastrojejunostomy system or device complications after starting LECIG treatment were noted. RESULTS: At baseline, patients were taking oral levodopa for a mean of 5.3 times per day, with a high proportion also taking concomitant add-on therapies (dopamine agonists, 86%, monoamine oxidase type-B inhibitors, 53%; catechol-O-methyltransferase inhibitors, 64%). LECIG treatment significantly reduced daily off time versus baseline from 5.7 h/d to 1.7 hours per day ( P < 0.01). Duration and severity of dyskinesias was also significantly reduced versus baseline, and improvements were observed in Hoehn and Yahr Scale scores. LECIG treatment also allowed a significant reduction in the use of concomitant oral medications. CONCLUSIONS: These findings suggest that LECIG treatment is an effective DAT option in APD that can simplify the treatment regimen.

Chorea following SARS-CoV-2 infection and vaccination: a systematic review of reported cases.

OBJECTIVES: Chorea following SARS-CoV-2 infection and vaccination, has been increasingly recognized. We aimed to synthesize clinical and paraclinical characteristics, treatment responses, and outcomes of this neurologic complication. METHODS: We systematically reviewed LitCOVID, the World Health Organization database on COVID-19, and MedRxiv up to March 2023, following a published protocol. RESULTS: We included 14 chorea cases in patients with SARS-CoV-2 infection and eight following COVID-19 vaccination. Acute or subacute chorea preceded COVID-19 symptoms within 1-3 days or developed up to 3 months after infection. Frequently it was generalized (85.7%), with associated neurological manifestations (encephalopathy 35.7%; other movement disorders 7.1%). After vaccination, chorea had a sudden onset (87.5%) within 2 weeks (75%); 87.5% of cases presented hemichorea, with hemiballismus (37.5%) or other movement disorders; 12.5% presented additional neurological findings. Cerebrospinal fluid was normal in 50% of infected individuals but abnormal in all vaccinated cases. Brain magnetic resonance imaging detected normal basal ganglia in 51.7% of infection cases and 87.5% following vaccination. CONCLUSION: In SARS-CoV-2 infection, chorea may present several pathogenic mechanisms: autoimmune response to infection, direct infection-related injury, or an infection-related complication (i.e., acute disseminated encephalomyelitis, cerebral venous sinus thrombosis, hyperglycemia); also, previous Sydenham chorea may relapse. After COVID-19 vaccination, chorea could be due to an autoimmune reaction or other mechanisms (vaccine-induced hyperglycemia, stroke).

Levodopa Carbidopa Intestinal Gel in Advanced Parkinson's Disease: DUOGLOBE Final 3-Year Results.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) improves motor and non-motor symptoms in patients with advanced Parkinson's disease (aPD). OBJECTIVE: To present the final 36-month efficacy and safety results from DUOGLOBE (DUOdopa/Duopa in Patients with Advanced Parkinson's Disease - a GLobal OBservational Study Evaluating Long-Term Effectiveness; NCT02611713). METHODS: DUOGLOBE was an international, prospective, long-term, real-world, observational study of patients with aPD initiating LCIG in routine clinical care. The primary endpoint was change in patient-reported "Off" time to Month 36. Safety was assessed by monitoring serious adverse events (SAEs). RESULTS: Significant improvements in "Off" time were maintained over 3 years (mean [SD]: -3.3 hours [3.7]; p < 0.001). There were significant improvements to Month 36 in total scores of the Unified Dyskinesia Rating Scale (-5.9 [23.7]; p = 0.044), Non-Motor Symptoms Scale (-14.3 [40.5]; p = 0.002), Parkinson's Disease Sleep Scale-2 (-5.8 [12.9]; p < 0.001), and Epworth Sleepiness Scale (-1.8 [6.0]; p = 0.008). Health-related quality of life and caregiver burden significantly improved through Months 24 and 30, respectively (Month 24, 8-item Parkinson's Disease Questionnaire Summary Index, -6.0 [22.5]; p = 0.006; Month 30, Modified Caregiver Strain Index, -2.3 [7.6]; p = 0.026). Safety was consistent with the well-established LCIG profile (SAEs: 54.9% of patients; discontinuations: 54.4%; discontinuations due to an adverse event: 27.2%). Of 106 study discontinuations, 32 patients (30.2%) continued LCIG outside the study. CONCLUSION: DUOGLOBE demonstrates real-world, long-term, reductions in motor and non-motor symptoms in patients with aPD treated with LCIG.

Parsonage-Turner Syndrome Following SARS-CoV-2 Infection: A Systematic Review.

Parsonage-Turner syndrome (PTS) is an inflammatory disorder of the brachial plexus. Hypothesized underlying causes focus on immune-mediated processes, as more than half of patients present some antecedent event or possible predisposing condition, such as infection, vaccination, exercise, or surgery. Recently, PTS was reported following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to investigate data on PTS triggered by SARS-CoV-2 infection to provide an extensive perspective on this pathology and to reveal what other, more specific, research questions can be further addressed. In addition, we aimed to highlight research gaps requiring further attention. We systematically reviewed two databases (LitCOVID and the World Health Organization database on COVID-19) to January 2023. We found 26 cases of PTS in patients with previous SARS-CoV-2 infection. The clinical and paraclinical spectrum was heterogeneous, ranging from classical PTS to pure sensory neuropathy, extended neuropathy, spinal accessory nerve involvement, and diaphragmatic palsy. Also, two familial cases were reported. Among them, 93.8% of patients had severe pain, 80.8% were reported to present a motor deficit, and 53.8% of patients presented muscle wasting. Paresthesia was noted in 46.2% of PTS individuals and a sensory loss was reported in 34.6% of patients. The present systematic review highlights the necessity of having a high index of suspicion of PTS in patients with previous SARS-CoV-2 infection, as the clinical manifestations can be variable. Also, there is a need for a standardized approach to investigation and reporting on PTS. Future studies should aim for a comprehensive assessment of patients. Factors including the baseline characteristics of the patients, evolution, and treatments should be consistently assessed across studies. In addition, a thorough differential diagnosis should be employed.

Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: long-term results from COSMOS.

BACKGROUND: While immediate benefits of levodopa-carbidopa intestinal gel (LCIG) are evident in patients with Parkinson's disease (PD), long-term LCIG effects require further study. OBJECTIVES: We explored long-term LCIG on motor symptoms, nonmotor symptoms (NMS), and LCIG treatment settings in patients with advanced PD (APD). METHODS: Data were obtained (medical records and patient visit) from COSMOS, a multinational, retrospective, cross-sectional post-marketing observational study in patients with APD. Patients were stratified into 5 groups based on LCIG treatment duration at the patient visit, from 1-2 to > 5 years LCIG. Between-group differences were assessed for changes from baseline in LCIG settings, motor symptoms, NMS, add-on medications, and safety. RESULTS: Out of 387 patients, the number of patients per LCIG group was: > 1- ≤ 2 years LCIG (n = 156); > 2- ≤ 3 years LCIG (n = 80); > 3- ≤ 4 years LCIG (n = 61); > 4- ≤ 5 years LCIG (n = 30); > 5 years LCIG (n = 60). Baseline values were similar; data reported are changes from the baseline. There were reductions in "off" time, dyskinesia duration, and severity across LCIG groups. Prevalence, severity, and frequency of many individual motor symptoms and some NMS were reduced amongst all LCIG groups, with few differences between groups. Doses for LCIG, LEDD and LEDD for add-on medications were similar across groups both at LCIG initiation and patient visit. Adverse events were similar across all LCIG groups and consistent with the established safety profile of LCIG. CONCLUSIONS: LCIG may provide sustained, long-term symptom control, while potentially avoiding increases in add-on medication dosages. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03362879. Number and date: P16-831, November 30, 2017.

Assessment and Diagnosis of HIV-Associated Dementia.

The modern combined antiretroviral treatment (cART) for human immunodeficiency virus (HIV) infection has substantially lowered the incidence of HIV-associated dementia (HAD). The dominant clinical features include deficits in cognitive processing speed, concentration, attention, and memory. As people living with HIV become older, with high rates of comorbidities and concomitant treatments, the prevalence and complexity of cognitive impairment are expected to increase. Currently, the management of HAD and milder forms of HAND is grounded on the best clinical practice, as there is no specific, evidence-based, proven intervention for managing cognitive impairment. The present article acknowledges the multifactorial nature of the cognitive impairments found in HIV patients, outlining the current concepts in the field of HAD. Major areas of interest include neuropsychological testing and neuroimaging to evaluate CNS status, focusing on greater reliability in the exclusion of associated diseases and allowing for earlier diagnosis. Additionally, we considered the evidence for neurological involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the impact of the coronavirus (COVID-19) pandemic, with wider consequences to population health than can be attributed to the virus itself. The indirect effects of COVID-19, including the increased adoption of telehealth, decreased access to community resources, and social isolation, represent a significant health burden, disproportionately affecting older adults with dementia who have limited social networks and increased functional dependence on the community and health system. This synopsis reviews these aspects in greater detail, identifying key gaps and opportunities for researchers and clinicians; we provide an overview of the current concepts in the field of HAD, with suggestions for diagnosing and managing this important neurological complication, which is intended to be applicable across diverse populations, in line with clinical observations, and closely representative of HIV brain pathology.

Quality of acute stroke care in Romania: Achievements and gaps between 2017 and 2022.

Romania has one of the highest incidences of stroke and one of the highest mortality rates in Europe. The mortality rate due to treatable causes is also very high and is associated with the lowest public spending on healthcare in the European Union. Nonetheless, significant achievements in acute stroke care have been made in Romania in the last 5 years, most notably the increase of the national thrombolysis rate from 0.8% to 5.4%. Numerous educational workshops and constant communication with the stroke centers led to a solid and active stroke network. Due to the joint efforts of this stroke network and the ESO-EAST project, the quality of stroke care has significantly improved. However, Romania still faces many problems: a major lack of specialists in interventional neuroradiology and consequently a low number of stroke patients treated by thrombectomy and carotid revascularization procedures, a low number of neuro-rehabilitation centers and a country-wide lack of neurologists.

Conservative versus aggressive antiplatelet strategy for emergent carotid stenting during stroke thrombectomy.

BACKGROUND: There is no consensus regarding optimal antiplatelet regimen for emergent carotid stenting during stroke thrombectomy. We aimed to assess the safety and efficacy of an aggressive periprocedural antiplatelet strategy focused on preserving stent patency, in comparison with conservative antiplatelet strategy consisting of aspirin monotherapy. MATERIALS AND METHODS: Retrospective review of a prospectively collected database in a comprehensive stroke center, including all cases of emergent carotid stenting for tandem lesions stroke between 01.03.2012-01.06.2021. Aggressive antiplatelet strategy consisted of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel loading doses, with added intravenous (IV) tirofiban if in-stent thrombosis was observed during thrombectomy. Clinical and radiological outcomes were compared between conservative and aggressive antiplatelet treatment groups using inverse probability of treatment weighting (IPTW) analysis based on propensity scores. RESULTS: We included 132 cases (76.5% atheroma, 22.7% dissection, 0.7% carotid web). Forty-five patients (34%) cases received conservative antiplatelet therapy. The remaining 87 (65.9%) received aggressive antiplatelet therapy: 66 (75.8%) treated with DAPT, 21 (24.1%) with DAPT and tirofiban. Periprocedural heparin was avoided in all cases. In adjusted analysis of the weighted samples, aggressive antiplatelet strategy was associated with improved carotid stent patency (aOR 0.23, 95% CI 0.07-0.80, p = 0.021), higher proportion of moderate clinical outcome (mRS ≤ 3, aOR 2.72, 95% CI 1.01-7.30, p = 0.04), with no significant differences in mortality and hemorrhagic transformation (HT) rates. CONCLUSIONS: In this retrospective study, aggressive periprocedural antiplatelet strategy led to improved stent patency and clinical outcomes, without increased HT. Further prospective randomized research is warranted to identify the optimal combination of antiplatelet agents for emergent carotid stenting in the setting of acute stroke.

Emerging Trends in Complications Associated with SARS-CoV-2 Infection.

The coronavirus disease 2019 (COVID-19) pandemic has presented a remarkable challenge to global health, sparking a surge in research aimed at understanding the multifaceted impacts of the virus [...].

Wernicke Encephalopathy Presenting with Dysphagia: A Case Report and Systematic Literature Review.

Wernicke encephalopathy (WE) is a well-known neurological condition caused by thiamine (vitamin B1) deficiency that occurs in both alcoholic and non-alcoholic populations. We aimed to report a case of a patient with WE who presented with dysphagia and dysphonia and later developed typical symptoms of thiamine deficiency and to conduct a systematic review of the literature on this rare presentation of WE. We searched two databases (PubMed and Scopus) and included publications up to November 2022. We found 12 cases of WE and dysphagia, aged between 12 and 81 years; swallowing problems presented at the onset in nine patients (including the current case report). Our findings suggest that thiamine deficiency should be suspected in patients with dysphagia of unknown cause, even in the absence of alcohol abuse. In contrast to most WE patients, the majority of patients included in this review presented with dysphagia at the onset of their disease, even in the absence of the classic triad of cognitive impairment, ataxia, and oculomotor abnormalities, indicating that there could be varying susceptibilities to clinical manifestations of thiamine deficiency in different brain regions.

Subarachnoid Hemorrhage in Patients with SARS-CoV-2 Infection: Protocol for A Scoping Review.

Subarachnoid hemorrhage (SAH) is a life-threatening condition associated with high mortality and substantial long-term morbidity. The SARS-CoV-2 virus is a new pathogen that causes a disease with variable clinical manifestations. Although the Coronavirus disease 2019 (COVID-19) is associated with hypercoagulopathy, patients may also present with cerebral hemorrhage, including SAH. The present paper reports a protocol for a scoping review that is aimed to provide a comprehensive report on existing literature by examining data on SAH associated with SARS-CoV-2 infection. Our objective is to evaluate the epidemiology, clinical, laboratory, and neuroimaging features of SAH in patients with COVID-19 and to explore the etiology and possible interventions in this pathology. Using appropriate search terms, we will search LitCOVID, the WHO database on COVID-19, and MedRxiv. The inclusion criteria are pre-defined. We will extract the data of eligible studies in standardized forms and will report the results in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We will provide information for clinicians, healthcare providers, and public health specialists.

Montreal Cognitive Assessment for Evaluating Cognitive Impairment in Subarachnoid Hemorrhage: A Systematic Review.

Subarachnoid hemorrhage (SAH) is a severe condition with high mortality and extensive long-term morbidity. Although research has focused mainly on physical signs and disability for decades, in recent years, it has been increasingly recognized that cognitive and psychological impairments may be present in many patients with SAH, negatively impacting their quality of life. We performed a systematic review aiming to provide a comprehensive report on the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) test for evaluating the presence of cognitive impairment in patients with SAH. Using appropriate search terms, we searched five databases (PubMed, Scopus, PsychINFO, Web of Sciences, and Latin American and Caribbean Health Sciences Literature) up to January 2022. Two cross-sectional studies investigated the accuracy of MoCA in SAH patients in the subacute and chronic phase. We appraised the quality of the included studies using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) criteria. The MoCA test provides information about general cognitive functioning disturbances. However, a lower threshold than the original cutoff might be needed as it improves diagnostic accuracy, lowering the false positive rates. Further research is necessary for an evidence-based decision to use the MoCA in SAH patients.

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.

Outcomes Impacting Quality of Life in Advanced Parkinson's Disease Patients Treated with Levodopa-Carbidopa Intestinal Gel.

BACKGROUND: It is believed that motor symptoms, including dyskinesia, and non-motor symptoms impact health-related quality of life (HRQoL) in patients with Parkinson's disease (PD), and that improvements in these metrics are correlated. OBJECTIVE: Investigate the relationship between HRQoL and measures of PD severity and treatment efficacy, including motor and non-motor symptoms. METHODS: This was a planned investigation of an international, prospective, single-arm, post-marketing observational study of the long-term effectiveness of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. Pearson correlation coefficients (PCC) were calculated for baseline and change from baseline at 12 months between HRQoL and motor and non-motor symptoms. RESULTS: A total of 195 patients were included. At baseline, HRQoL was moderately positively correlated with Activities of Daily Living (UPDRS II, PCC = 0.44), non-motor symptoms (0.48), and measures of sleep (0.50 and 0.40); all p < 0.001. After 12 months of treatment with LCIG, improvements in HRQoL were moderately positively correlated with improvement from baseline in non-motor symptoms (PCC = 0.42), sleep (0.54), and daytime sleepiness (0.40; all p < 0.001), and weakly correlated with improvement in dyskinesia signs and symptoms (PCC = 0.23; p = 0.011). Improvement in HRQoL was not correlated with improvements in OFF time or dyskinesia time. CONCLUSION: Both at baseline and for change from baseline at 12 months, HRQoL was correlated with baseline and change from baseline in dyskinesia, Activities of Daily Living, and non-motor symptoms, including sleep; but not with baseline or change in OFF time.

Montreal cognitive assessment for evaluating cognitive impairment in Huntington's disease: a systematic review.

OBJECTIVE: This study aims to systematically review evidence of the accuracy of the Montreal Cognitive Assessment (MoCA) for evaluating the presence of cognitive impairment in patients with Huntington's disease (HD) and to outline the quality and quantity of research evidence available about the use of the MoCA in this population. METHODS: We conducted a systematic literature review, searching four databases from inception until April 2020. RESULTS: We identified 26 studies that met the inclusion criteria: two case-control studies comparing the MoCA to a battery of tests, three studies comparing MoCA to Mini-Mental State Examination, two studies estimating the prevalence of cognitive impairment in individuals with HD and 19 studies or clinical trials in which the MoCA was used as an instrument for the cognitive assessment of participants with HD. We found no cross-sectional studies in which participants received the index test (MoCA) and a reference standard diagnostic assessment composed of an extensive neuropsychological battery. The publication period ranged from 2010 to 2020. CONCLUSIONS: In patients with HD, the MoCA provides information about disturbances in general cognitive function. Even if the MoCA demonstrated good sensitivity and specificity when used at the recommended threshold score of 26, further cross-sectional studies are required to examine the optimum cutoff score for detecting cognitive impairments in patients with HD. Moreover, more studies are necessary to determine whether the MoCA adequately assesses cognitive status in individuals with HD.

Advanced Parkinson's Disease Treatment Simplification and Long-Term Outcomes with Levodopa Carbidopa Intestinal Gel: COSMOS Romanian Subanalysis.

The aim of the COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS) was to assess the use of levodopa/carbidopa intestinal gel (LCIG) as monotherapy in patients with advanced Parkinson's disease (APD) in routine clinical practice. COSMOS was an international observational study with one cross-sectional visit and retrospective data collection. In Romania, 95 adult patients with APD on LCIG treatment for at least 12 months were enrolled and stratified according to their LCIG therapy after 12 months: monotherapy (without any add-on PD medication), monotherapy with night PD medication and LCIG + add-on medication. Compared to the moment of LCIG initiation, the percentage of patients on monotherapy increased at three months after LCIG initiation and remained constant up to 12 months, when 30.5% of the patients were on LCIG monotherapy and 11.6% were on monotherapy with night medication. "Off" time and "On" time with dyskinesia decreased from LCIG initiation to patient visit in all groups. LCIG monotherapy with or without night medication may provide a simplified treatment option for selected APD patients, with long-term efficacy similar to that of LCIG plus add-on medication.

DUOGLOBE: One-Year Outcomes in a Real-World Study of Levodopa Carbidopa Intestinal Gel for Parkinson's Disease.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is an established treatment for improving motor and some non-motor symptoms (NMS) in patients with advanced Parkinson's disease (PD). Prospective long-term data in routine clinical practice are limited. OBJECTIVE: Assess LCIG effectiveness and safety in patients with advanced PD after 12 months during real-world routine clinical practice. METHODS: Duodopa/Duopa in patients with advanced Parkinson's disease-a global observational study evaluating long-term effectiveness (DUOGLOBE) (NCT02611713) is an ongoing, prospective, multinational, observational study of LCIG-naïve patients treated as part of routine clinical practice; 3 years of follow-up are planned. The primary outcome is the change in patient-reported off time. Other assessments include the Unified Dyskinesia Rating Scale (UDysRS), Non-Motor Symptoms Scale (NMSS), Parkinson's Disease Sleep scale (PDSS-2), Epworth Sleepiness Scale (ESS), health-related quality of life (HR-QoL), caregiver burden, and serious adverse events (SAEs). Outcomes from baseline to month (M) 12 are presented. RESULTS: In this 12-month follow-up, patients (N = 195) had baseline characteristics similar to other LCIG studies. Significant improvements (mean change to M12) were observed in off time (-3.9 ± 3.6 hr/day, P < 0.001), dyskinesia assessed using the UDysRS (-9.6 ± 22.5, P < 0.001), NMSS (-23.1 ± 41.4, P < 0.001), sleep and sleepiness symptoms on the PDSS-2 (-6.5 ± 12.2, P < 0.001) and ESS (-1.0 ± 5.7, P < 0.05), HR-QoL (-9.0 ± 21.6, P < 0.001), and caregiver burden (-1.9 ± 6.7, P = 0.008). Overall, 40.5% (n = 79) of patients experienced SAEs; fall (n = 6; 3.1%) and urinary tract infection (n = 6; 3.1%) were SAEs reported in ≥3% of patients. CONCLUSIONS: These 12-month outcome data show sustained, long-term improvements and support the real-world effectiveness of LCIG in patients with advanced PD. Safety was consistent with previous studies.

Plasma hsa-mir-19b is a potential LevoDopa therapy marker.

Parkinson's disease (PD) is the second most common neurodegenerative disorder among the elderly, the diagnostic and prognostic of which is based mostly on clinical signs. LevoDopa replacement is the gold standard therapy for PD, as it ameliorates the motor symptoms. However, it does not affect the progression of the disease and its long-term use triggers severe complications. There are no bona fide biomarkers for monitoring the patients' response to LevoDopa and predicting the efficacy of levodopa treatment. Here, we have combined qPCR microRNA array screening with analysis of validated miRs in naïve versus Levodopa-treated PD patients. We have identified plasma miR-19b as a possible biomarker for LevoDopa therapy and validated this result in human differentiated dopaminergic neurons exposed to LevoDopa. In silico analysis suggests that the LevoDopa-induced miR-19b regulates ubiquitin-mediated proteolysis.