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Background: Headache is a prevalent and disabling non-respiratory symptom of COVID-19, posing a persistent challenge in post-COVID syndrome. This study aimed to determine the prevalence, phenotypes, risk factors and biomarkers associated with COVID-related headaches. Methods: A retrospective analysis of 634 hospitalized COVID-19 patients was conducted, with 295 participants being followed up 12-15 months post-discharge via telephone call. Initial laboratory workups, including complete blood count and various biochemical parameters, were compared between headache and non-headache groups. Results: One-third of hospitalized patients experienced headaches, predominantly younger individuals (p < 0.001) and women (p = 0.002). Non-dominant headaches were characterized as dull (56.9%) and holocranial (26.5%), while dominant headaches were unilateral (31.3%) with photophobia (34.3%) and nausea (56.3%). Persistent headaches were unilateral (40%) and pulsating (38%) with phonophobia (74%). Decreased CD4 T cells independently predicted COVID-associated headaches, with elevated IL-6 levels noted in the dominant-headache group (p = 0.040). Remarkably, 50% of patients reported persistent headaches 12-15 months post-infection. Dexamethasone administration significantly reduced the likelihood of long-COVID headaches (52% vs. 73%, p = 0.029). Conclusions: Headache was present in one-third of patients with heterogenous phenotypes: tension headache in the non-dominant group, and migraine in the dominant and persistent headache groups. Persistent headache remains a challenge, with dexamethasone showing potential in reducing its incidence, emphasizing the need for tailored approaches in managing long-COVID headaches.

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Pathogenic variants in LRRK2 are one of the most common genetic risk factors for Parkinson's disease (PD). Recently, the lesser-known p.L1795F variant was proposed as a strong genetic risk factor for PD, however, further families are currently lacking in literature. A multicentre young onset and familial PD cohort (n = 220) from 9 movement disorder centres across Central Europe within the CEGEMOD consortium was screened for rare LRRK2 variants using whole exome sequencing data. We identified 4 PD cases with heterozygous p.L1795F variant. All 4 cases were characterised by akinetic-rigid PD phenotype with early onset of severe motor fluctuations, 2 receiving LCIG therapy and 2 implanted with STN DBS; all 4 cases showed unsatisfactory effect of advanced therapies on motor fluctuations. Our data also suggest that p.L1795F may represent the most common currently known pathogenic LRRK2 variant in Central Europe compared to the more studied p.G2019S, being present in 1.81% of PD cases within the Central European cohort and 3.23% of familial PD cases. Together with the ongoing clinical trials for LRRK2 inhibitors, this finding emphasises the urgent need for more ethnic diversity in PD genetic research.

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Introduction: Bradykinesia is an essential diagnostic criterion for Parkinson's disease (PD) but is frequently observed in many non-parkinsonian movement disorders, complicating differential diagnosis, particularly in disorders featuring tremors. The presence of bradykinetic features in the subset of dystonic tremors (DT), either "pure" dystonic tremors or tremors associated with dystonia, remains currently unexplored. The aim of the current study was to evaluate upper limb bradykinesia in DT patients, comparing them with healthy controls (HC) and patients with PD by observing repetitive finger tapping (FT). Methods: The protocol consisted of two main parts. Initially, the kinematic recording of repetitive FT was performed using optical hand tracking system (Leap Motion Controller). The values of amplitude, amplitude decrement, frequency, frequency decrement, speed, acceleration and number of halts of FT were calculated. Subsequently, three independent movement disorder specialists from different movement disorders centres, blinded to the diagnosis, rated the presence of FT bradykinesia based on video recordings. Results: Thirty-six subjects participated in the study (12 DT, 12 HC and 12 early-stage PD). Kinematic analysis revealed no significant difference in the selected parameters of FT bradykinesia between DT patients and HC. In comparisons between DT and PD patients, PD patients exhibited bigger amplitude decrement and slower FT performance. In the blinded clinical assessment, bradykinesia was rated, on average, as being present in 41.6% of DT patients, 27.7% of HC, and 91.7% of PD patients. While overall inter-rater agreement was moderate, weak agreement was noted within the DT group. Discussion: Clinical ratings indicated signs of bradykinesia in almost half of DT patients. The objective kinematic analysis confirmed comparable parameters between DT and HC individuals, with more pronounced abnormalities in PD across various kinematic parameters. Interpretation of bradykinesia signs in tremor patients with DT should be approached cautiously and objective motion analysis might complement the diagnostic process and serve as a decision support system in the choice of clinical entities.

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Background: The long-term sequelae of coronavirus disease 2019 (COVID-19) significantly affects quality of life (QoL) in disease survivors. Delayed development of the adaptive immune response is associated with more severe disease and a worse prognosis in COVID-19. The effects of delayed immune response on COVID-19 sequelae and QoL are unknown. Methods: We conducted a prospective study to assess the relationship between the delayed antibody response in the acute phase of infection in naïve unvaccinated patients suffering from severe or critical COVID-19 and their QoL 12 months after hospital discharge. The 12-item Short Form Survey (SF-12) questionnaire was used for assessment of QoL. The SF-12 evaluates both mental and physical components of QoL, incorporating a mental component score (MCS-12) and a physical component score (PCS-12). A delayed antibody response was defined as testing negative for anti-spike SARS-CoV-2 antibodies at the time of hospital admission. Results: The study included 274 patients (154 men and 120 women). Of the enrolled patients, 144 had a delayed immune response. These patients had a significantly lower MCS-12 (p = 0.002), but PCS-12 (p = 0.397) was not significantly different at the 12-month follow-up compared to patients with positive anti-spike SARS-CoV-2 antibodies. The MCS-12 at the time of follow-up was negatively associated with delayed antibody response irrespective of possible confounders (p = 0.006; B = 3.609; ηp2 = 0.035; 95% CI = 1.069-6.150). An MSC-12 below 50 points at the time of follow-up was positively associated with delayed antibody response (p = 0.001; B = 1.092; OR = 2.979; 95% CI = 1.554-5.711). Conclusions: This study confirmed that, in patients with severe and critical COVID-19, a negative result for anti-spike SARS-CoV-2 antibodies at the time of hospital admission is associated with a lower mental component of QoL in unvaccinated patients naïve to COVID-19 one year after hospital discharge.

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INTRODUCTION: One of the most debilitating problems encountered by people with multiple sclerosis (MS) is the loss of balance and coordination. Our study aimed to comprehensively evaluate the effectiveness of one year of Tai-chi exercise in patients with MS using both subjective and objective methods, including posturography. METHODS: This was a single-group longitudinal one-year study performed from the 1st of January 2019 to the 1st of January 2020. The primary outcomes of interest were the Mini-Balance Evaluation Systems Test (Mini-BESTest) and static posturography measures as objective methods to detect subtle changes associated with postural control/balance impairment. Secondary outcomes were measures of depression, anxiety, cognitive performance, and quality of life. All objective and subjective parameters were assessed four times: at baseline, and after three, six and 12 months of regular Tai-chi training. The difference was calculated as a subtraction of baseline values from every timepoint value for each measurement. If the normality test was passed, parametric one-sample t-test was used, if failed, Wilcoxon signed ranks test was used to test the difference between the baseline and each timepoint. Alpha was set to 0.017 using Bonferroni correction for multiple comparisons. RESULTS: Out of 25 patients with MS enrolled, 15 women with MS (mean age 44.27 years) were included for statistical analyses after completing the 12-month program. After 12 months, significant improvements were found in all objective balance and gait tests: Mini-BESTest (p<0.001), static posturography measures (total area of the centre of foot pressure - TA; p = 0.015), 25 Feet Walk Test (25FWT; p = 0.001), anxiety (Beck Anxiety Inventory - BAI; p = 0.005) and cognition tests (Paced Auditory Serial Addition Test - PASAT; p = 0.003). Measures of depression (Beck Depression Inventory - BDI; p = 0.071), cognition (Symbol Digit Modalities Test - SDMT; p = 0.079), and health-related quality of life (European Quality of Life 5-Dimensions Questionnaire - EQ-5D-5L; p = 0.095) showed a trend of improvement but were not significant, which could be the result of a small sample and increased bias due the type II error. CONCLUSION: According to these preliminary results, this study indicates the possible beneficial effects of long-term Tai-chi training on patients with MS. Although these findings need to be confirmed by further studies with a larger sample of participants of both genders and require more rigorous randomized controlled trials (RCT) design, our findings support the recommendation of regular and long-term Tai-chi exercise in patients with MS. GOV IDENTIFIER (RETROSPECTIVELY REGISTERED): NCT05474209.

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Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare delayed complication of cranial radiotherapy, that may present decades after brain irradiation. Here we present a case of 41-year old patient with a history of grade 3 oligodendroglioma, epilepsy and migraine, 26 years after brain radiation therapy, who was admitted with right hemicranial headache, nausea, left homonymous hemianopsia, weakness of the left arm and left-sided hemihypesthesia. After considering alternate diagnoses, we ultimately diagnosed SMART syndrome. Despite its rare occurrence and unknown pathophysiology, there are more case reports of SMART syndrome reported due to advancements in oncology treatment and increasing patients' survival rates. Therefore, diagnosis of SMART syndrome should always be considered in patients with a history of cranial radiation presenting with focal neurologic deficits and migraine, especially with a change in pattern of their usual migraine attack.

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Combined central and peripheral demyelination (CCPD) is a rare autoimmune neurologic disease, characterized by immune-mediated damage of myelin sheath at central and peripheral levels of the nervous system. The current knowledge about this disorder is only limited, mainly due to the low incidence of the disease. According to previous studies, CCPD has a very heterogeneous course, insufficient therapeutic response, and an unfavorable prognosis. We report on the 37-year-old patient with a coincidence of demyelinating lesions in the brain fulfilling current McDonald's diagnostic criteria for multiple sclerosis, as well as the presence of an atypical variant of chronic inflammatory demyelinating polyneuropathy (CIDP) - multifocal acquired demyelinating sensory-motor neuropathy (MADSAM), as a subtype of combined central and peripheral demyelination (CCPD).

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A high burden of motor and non-motor parkinsonian symptoms is known to have a significant negative impact on the quality of life (QoL) of people with Parkinson's disease (PD). Effective control of these symptoms with therapies that enable patients to maintain a good QoL is therefore a key treatment goal in PD management. When symptom control can no longer be accomplished with oral or transdermal PD treatment regimens, device-aided therapies (DAT), namely levodopa and apomorphine infusion therapies, and deep brain stimulation, are valuable options to consider. DAT options may also help reduce pill burden and thereby improve compliance with treatment. Since PD therapy relies on symptomatic management, the efficacy and tolerability of any intervention is undoubtedly important, however the impact of different therapies on patient-related outcome measures, in particular health-related QoL, is also a critical consideration for those living with a chronic and disabling condition. This review discusses clinical evidence and ongoing research regarding the QoL benefits of levodopa and apomorphine infusion therapies from studies that have used validated QoL outcome measures. The data suggest that timing of these interventions is important to achieve optimal treatment effects, and that early initiation onto infusion therapies at the point when motor fluctuations emerge, and before patient QoL and functioning have significantly declined, may provide the best long-term outcomes. Healthcare professionals caring for people with PD should therefore discuss all available DAT options with them at an early stage in the course of their disease so they can make informed and timely choices that best suit them, their families and care network.

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Background: Bipolar disorder (BD) is a chronic and disabling affective disorder with significant morbidity and mortality. Despite the high rate of psychiatric and physical health comorbidity, little is known about the complex interrelationships between clinical features of bipolar illness and comorbid conditions. The present study sought to examine, quantify and characterize the cross-sectional associations of psychiatric and physical comorbidities with selected demographic and clinical characteristics of adults with BD. Methods: A nationwide multicenter cross-sectional observational epidemiological study conducted from October 2015 to March 2017 in Slovakia. Results: Out of 179 study participants [median age 49 years (interquartile range IQR 38-58); 57.5% females], 22.4% were free of comorbidity, 42.5% had both psychiatric and physical comorbidities, 53.6% at least one psychiatric comorbidity, and 66.5% at least one physical comorbidity. The most prevalent were the essential hypertension (33.5%), various psychoactive substance-related disorders (21.2%), specific personality disorders (14.6%), obesity (14.5%), and disorders of lipoprotein metabolism (14%). The presence of an at least one physical comorbidity, atypical symptoms of BD, and unemployed status were each associated with an at least one psychiatric comorbidity independent of sex, early onset of BD (age of onset <35 years), BD duration and pattern of BD illness progression (p < 0.001). The presence of various psychoactive substance-related disorders, BD duration, atypical symptoms of BD, unemployed status, pension, female sex, and not using antipsychotics were each associated with an at least one physical comorbidity independent of the pattern of BD illness progression (p < 0.001). In several other multiple regression models, the use of antipsychotics (in particular, olanzapine) was associated with a decreased probability of the essential hypertension and predicted the clinical phenotype of comorbidity-free BD (p < 0.05). Conclusion: This cross-national study has reported novel estimates and clinical correlates related to both the comorbidity-free phenotype and the factors associated with psychiatric and physical comorbidities in adults with BD in Slovakia. The findings provide new insights into understanding of the clinical presentation of BD that can inform clinical practice and further research to continue to investigate potential mechanisms of BD adverse outcomes and disease complications onset.

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INTRODUCTION: Neurodegeneration is likely to be present from the earliest stages of multiple sclerosis (MS). MS responds poorly to disease-modifying treatments (DMTs) and leads to irreversible brain volume loss (BVL), which is a reliable predictor of future physical and cognitive disability. Our study aimed to discover the relationship between BVL, disease activity, and DMTs in a cohort of patients with MS. MATERIAL AND METHODS: A total of 147 patients fulfilled our inclusion criteria. Relevant demographic and clinical data (age, gender, time of MS onset, time of treatment initiation, DMT characteristics, Expanded Disability Status Scale (EDSS), number of relapses in the last two years prior to MRI examination) were correlated with MRI findings. RESULTS: Patients with progressive MS had significantly lower total brain and grey matter volumes (p = 0.003; p < 0.001), and higher EDSS scores (p < 0.001), compared to relapsing-remitting patients matched by disease duration and age. There was no association between MRI atrophy and MRI activity (c2 = 0.013, p = 0.910). Total EDSS negatively correlated with the whole brain (rs = -0.368, p < 0.001) and grey matter volumes (rs = -0.308, p < 0.001), but was not associated with the number of relapses in the last two years (p = 0.278). Delay in DMT negatively correlated with whole brain (rs = -0.387, p < 0.001) and grey matter volumes (rs = -0.377, p < 0.001). Treatment delay was connected with a higher risk for lower brain volume (b = -3.973, p < 0.001), and also predicted a higher EDSS score (b = 0.067, p < 0.001). CONCLUSIONS: Brain volume loss is a major contributor to disability progression, independent of disease activity. Delay in DMT leads to higher BVL and increased disability. Brain atrophy assessment should be translated into daily clinical practice to monitor disease course and response to DMTs. The assessment of BVL itself should be considered a suitable marker for treatment escalation.

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The differential diagnosis of idiopathic normal pressure hydrocephalus (iNPH) and progressive supranuclear palsy (PSP) is difficult. The importance of proper diagnosis is particularly important for iNPH, which can be effectively treated with a ventriculoperitoneal (VP) shunt. In our case report, we present a unique case of a patient with overlapping symptoms and radiological findings of iNPH and PSP. Our patient underwent the VP shunt after a differential diagnostic evaluation which resulted in significant improvement in their clinical condition and quality of life, albeit for a short time.

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Objective: Strong evidence supports the benefits of exercise for healthy ageing, including reduced risk of neurodegenerative diseases. Recent studies suggested interorgan crosstalk as a key element of systemic adaptive response, however, the role of specific molecules in mediating exercise effects on the human brain are not fully understood. In the present study, we explored the exercise-related regulation of Growth Differentiation Factor 11 (GDF11) in cerebrospinal fluid (CSF) and blood. Methods: The samples of serum, plasma and CSF were obtained before and 60min after acute exercise (90min run) from twenty healthy young individuals. Additional serum and plasma samples were collected immediately after run. GDF11 protein content (immunoblotting), body composition (bioelectrical impedance), physical fitness (VO2max, cycle spiroergometry) and cognitive functions (standardized computerized tests, Cogstate) were evaluated. Results: Running decreased GDF11 protein content in CSF (-20.6%. p=0.046), while GDF11 in plasma and serum were not regulated. Two GDF11-specific antibodies of different origin were used to corroborate this result. Individuals with higher physical fitness displayed greater exercise-induced decrease of GDF11 in CSF than those with lower physical fitness (p=0.025). VO2max correlated positively with GDF11 in serum (r=0.63, p=0.020) as well as with the exercise-induced change in GDF11 levels in CSF (r=0.59, p=0.042). Indirect measure of blood-brain barrier permeability (i.e. CSF/serum albumin ratio) tended to positively correlate with CSF/serum GDF11 ratio (p=0.060). CSF levels of GDF11 correlated positively with cognitive functions, including working memory, both before and after run (p<0.05). Conclusion: Running-induced down-regulation of the GDF11 protein in the cerebrospinal fluid of healthy young individuals indicates the potential role of GDF11 in the exercise-induced cross-talk between periphery and the brain.

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Parkinson's disease (PD) affects the language processes, with a significant impact on the patients' daily communication. We aimed to describe specific alterations in the comprehension of syntactically complex sentences in patients with PD (PwPD) as compared to healthy controls (HC) and to identify the neural underpinnings of these deficits using a functional connectivity analysis of the striatum. A total of 20 patients PwPD and 15 HC participated in the fMRI study. We analyzed their performance of a Test of sentence comprehension (ToSC) adjusted for fMRI. A task-dependent functional connectivity analysis of the striatum was conducted using the psychophysiological interaction method (PPI). On the behavioral level, the PwPD scored significantly lower (mean ± sd: 77.3 ± 12.6) in the total ToSC score than the HC did (mean ± sd: 86.6 ± 8.0), p = 0.02, and the difference was also significant specifically for sentences with a non-canonical word order (PD-mean ± sd: 69.9 ± 14.1, HC-mean ± sd: 80.2 ± 11.5, p = 0.04). Using PPI, we found a statistically significant difference between the PwPD and the HC in connectivity from the right striatum to the supplementary motor area [SMA, (4 8 53)] for non-canonical sentences. This PPI connectivity was negatively correlated with the ToSC accuracy of non-canonical sentences in the PwPD. Our results showed disturbed sentence reading comprehension in the PwPD with altered task-dependent functional connectivity from the right striatum to the SMA, which supports the synchronization of the temporal and sequential aspects of language processing. The study revealed that subcortical-cortical networks (striatal-frontal loop) in PwPD are compromised, leading to impaired comprehension of syntactically complex sentences.

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OBJECTIVE: There are conflicting data regarding the relationship between Parkinson's disease (PD) and the atherosclerotic process. This study aimed to compare endothelial function in patients with PD and matched controls. In PD subjects, we searched for factors contributing to endothelial dysfunction as well. Traditional vascular risk factors, PD characteristics, and PD medication were considered. RESULTS: We prospectively enrolled 41 patients with PD and 41 controls matched for age, sex, body mass index, and vascular risk factors. Endothelial function (EF) was assessed using peripheral arterial tonometry (EndoPAT 2000 device) and expressed as reperfusion hyperemia index (RHI). Clinical characteristics including PD medication were recorded. RHI was non-significantly lower in the PD group than in controls (1.8 ± 0.5 vs. 1.9 ± 0.5, p = 0.478). In PD patients, in linear regression analysis, smoking (beta = -0.453, p = 0.008) and use of dopamine agonists (beta = -0.365, p = 0.030) were significant contributors in a model predicting RHI. Despite non-significant differences in endothelial dysfunction between PD patients and controls, our results suggest an association between smoking, dopamine agonists, and impaired EF in PD patients. The small sample size, as well as the absence of an extended search for traditional and non-traditional vascular risk factors, are the most important factors limiting the interpretation of the current results.

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BACKGROUND: Patients with Parkinson disease (PD) treated with levodopa/carbidopa intestinal gel (LCIG) have higher prevalence of hyperhomocysteinemia and peripheral nerves damage. OBJECTIVE: The aim of our study was to test the effect of catechol-O-methyl transferase inhibitor tolcapone-as an add-on therapy to LCIG in patients with PD-on homocysteine (HCY) metabolism and nerve conduction study (NCS) parameters. METHODS: We evaluated NCS and serum B12, folic acid, and homocysteine in 16 patients with advanced PD on LCIG. Quality of life (QoL) was also assessed. Six subjects were treated with tolcapone add-on therapy (and LCIG dose reduction), 5 with B vitamin supplementation, and 5 without additional treatment. RESULTS: The level of HCY increased among patients without treatment (4.95 ± 12.54), and decreased in the vitamin (-17.73 ± 11.82) and tolcapone groups (-8.81 ± 8.36). Patients with tolcapone demonstrated improvement in polyneuropathic symptoms and signs compared with patients treated with vitamins or those without additional treatment (-0.83, d = 0.961). Although the most robust improvement in NCS parameters were observed with tolcapone, the findings were inconsistent to prove the effect of any intervention. Only tolcapone treatment was associated with improvement in QoL (d = 1.089). CONCLUSION: Our study indicates potential of tolcapone add-on therapy in LCIG treated patients in control of homocysteine levels, and improvement of polyneuropathic symptoms, as well as QoL.

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Metabolomics has emerged as a powerful new tool in precision medicine. No studies have yet been published on the metabolomic changes in cerebrospinal fluid (CSF) produced by acute endurance exercise. CSF and plasma were collected from 19 young active adults (13 males and 6 females) before and 60 min after a 90-min monitored outdoor run. The median age, BMI, and VO2 max of subjects was 25 years (IQR 22-31), 23.2 kg/m2 (IQR 21.7-24.5), and 47 ml/kg/min (IQR 38-51), respectively. Targeted, broad-spectrum metabolomics was performed by liquid chromatography, tandem mass spectrometry (LC-MS/MS). In the CSF, purines and pyrimidines accounted for 32% of the metabolic impact after acute endurance exercise. Branch chain amino acids, amino acid neurotransmitters, fatty acid oxidation, phospholipids, and Krebs cycle metabolites traceable to mitochondrial function accounted for another 52% of the changes. A narrow but important channel of metabolic communication was identified between the brain and body by correlation network analysis. By comparing these results to previous work in experimental animal models, we found that over 80% of the changes in the CSF correlated with a cascade of mitochondrial and metabolic changes produced by ATP signaling. ATP is released as a co-neurotransmitter and neuromodulator at every synapse studied to date. By regulating brain mitochondrial function, ATP release was identified as an early step in the kinetic cascade of layered benefits produced by endurance exercise.

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OBJECTIVE: Co-morbidities in any disorder can complicate its diagnostic process, they require more complex clinical management and lead to worse health outcomes and increased healthcare costs. There are regional differences in the prevalence of specific co-morbidities in Parkinson's disease (PD), and data from middle Europe are lacking. The project COSMOS aimed to disclose the prevalence of co-morbidities among patients with PD in Slovakia. METHODS: In a national, multi-center, cross-sectional, observational study, neurologists gathered relevant demographical and clinical data aimed at all psychiatric and somatic co-morbidities. RESULTS: From overall 737 patients, 51.00 % had at least one psychiatric co-morbidity, the most prevalent were depressive episode/recurrent depressive disorder (26.05%), sleep disorders (23.20%), dementia (13.16%), and neurotic, stress-related, and somatoform disorders (11.53%). In addition, 92.9 % had at least one somatic co-morbidity, the most prevalent were hypertensive diseases (67.71%), ischemic heart diseases (42.74%), diseases of the musculoskeletal system, and connective tissue (39.21), and disorders of lipoprotein metabolism (33.24%). The number of psychiatric co-morbidities increased with PD progression; the prevalence of somatic comorbidities increased also with the age (p<0.001 in all cases). CONCLUSION: This study with a large cohort of PD patients confirmed a high prevalence of depression, dementia, sleep problems, and anxiety disorders, together with cardiovascular disorders, diseases of the musculoskeletal system, and metabolic syndrome. With PD progression, the number of both psychiatric and somatic co-morbidities is on the increase. If not treated properly, they lead to more complicated management. That's why it's essential to search for any co-morbidity to provide patients with early and adequate therapy to avoid further worsening of quality of life.

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Parkinson's disease (PD) is currently considered progressive neurodegeneration of both the central and peripheral nervous systems. Widespread neuropathological changes lead to a complex clinical presentation with typical motor (hypokinesia, tremor, and rigidity) and various nonmotor symptoms. Orthostatic hypotension is one of the most disabling nonmotor features contributing to increased morbidity and mortality and decreased quality of life (QoL). Our study aimed to disclose the effect of a continuous infusion of levodopa-carbidopa intestinal gel (LCIG) on symptoms of orthostatic hypotension. Nine patients indicated for LCIG and eight matched patients on optimized medical treatment (OMT) were examined with scales for orthostatic symptoms (SCOPA-AUT), nonmotor symptoms and motor fluctuations (MDS-UPDRS), and QoL (PDQ39) at both baseline and after six months. The scores of "light-headedness after standing" and "fainting" decreased in the LCIG group compared to the OMT group. Treatment with LCIG was associated with a significantly higher decrease in the score of "light-headedness after standing". Change in the PDQ39 correlated positively with fluctuation improvement and with change in the scores of both "light-headedness" and "fainting". LCIG treatment improved symptoms of orthostatic hypotension in patients with PD mainly by a reduction in motor complications. Decreased severity in both motor and nonmotor fluctuations was connected also with improved QoL. Continuous treatment with LCIG should be considered not only in the case of severe motor fluctuation but also in patients with nonmotor fluctuations responsive to dopaminergic treatment.

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Improvement of adherence to pharmacotherapy in patients with Parkinson's disease (PD) is a challenge in routine clinical practice. Our study was aimed at the effect of pillbox organizers with alarms improving adherence to pharmacotherapy and its impact on clinical outcomes. Forty nonadherent patients with PD being treated with ≥ 3 daily doses of levodopa and/or dopamine agonists were pseudorandomized and consecutively ranked to groups A (early-start intervention) and B (delayed-start intervention). We used the following validated diagnostic instruments: MMAS-8 (adherence), PDQ-8 (quality of life, QoL), GDS (depression), NMSS (non-motor symptoms), MDS-UPDRS III (motor involvement), MDS-UPDRS IV, and WOQ-9 (motor and non-motor fluctuations and dyskinesias). We proved a significantly improved rate of adherence with the use of pillbox organizers with alarms. Moreover, after only four weeks of using the pillbox organizer, we detected an improvement in QoL scores, motor involvement, motor-, and non-motor fluctuations. Our study showed that pillbox organizers with alarms are efficient in improving adherence to pharmacotherapy in PD. It also could contribute to better motor states, less severe fluctuations, and improved QoL.