BACKGROUND:Levodopa-entacapone-carbidopa intestinal gel (LECIG) was introduced on the Swedish market in 2019. The therapy is aimed at patients with Parkinson's disease (PD) with fluctuations and dyskinesias. Long-term efficacy and safety data are lacking. OBJECTIVE:To investigate the efficacy, tolerability, and safety of LECIG in regular clinical practice for Parkinson's disease in Sweden. METHODS:Real-world data were collected from the Swedish registry for Parkinson's disease (ParkReg) for all patients reported to receive LECIG during the period from 2019 until 31 August 2022. RESULTS:A total of 150 patients were identified. Sixty-one (41%) of 150 patients were females. At the start of treatment, the median age was 73 years (range: 43-86). The median duration since motor symptoms onset was 17 years (IQR: 9). Fifty (33%) of 150 patients switched from another device-assisted therapy, mostly LCIG (39 patients). Reported complications were mainly related to PEG-J tube and stoma (30%). Twenty (13.3%) of 150 patients discontinued LECIG and 11 (7.3%) patients died while on LECIG. The Parkinson KinetiGraph scores for bradykinesia, dyskinesia, fluctuations, tremor, and immobility for 53 patients during LECIG showed good therapy control. The median (IQR) p-Hcy during LECIG was 12 (4.6) μmol/L (n = 44). The median (IQR) PDQ-8 summary index during LECIG was 31 (17) (n = 52). The median (IQR) EQ5D during LECIG was 0.62 (0.32) (n = 41). CONCLUSIONS:Data from ParkReg covering 150 patients over 3 years show LECIG to be an effective and safe device-aided therapy for advanced PD. However, the long-term efficacy and tolerability of LECIG need to be further investigated.

Memory decline is a central cognitive symptom in Parkinson’s Disease (PD). While task-fMRI studies link hippocampal activity (AHA) to poorer memory and olfactory performance, this relationship during rest remains understudied. The objectives of this study are to examine differences in resting-state hippocampal networks, explore the occurrence of reduced AHA within these networks, and investigate its impact on memory and olfaction in PD. Thirty-nine PD patients awaiting evaluation for device-aided Parkinson therapy and 46 healthy controls (HC) underwent resting-state fMRI (rs-fMRI). PD patients also completed a memory and olfactory assessment. Co-activation pattern (CAP) analysis was performed on the rs-fMRI data. Our results demonstrated reduced activity in two hippocampal networks in PD: Network 1, incorporating the visual cortex, cerebellum, superior parietal lobule, and precuneus, and Network 5, incorporating parts of the central executive network. PD subgroups with reduced AHA in Network 1 and 5 performed significantly worse on tests of auditory-verbal short-term, long-term and recognition memory, as well as odor identification. In conclusion, within specific resting-state hippocampal networks, reduced AHA in PD is linked to poorer auditory-verbal memory and odor identification.

Odor recognition memory (ORM) combines olfaction and episodic memory, both linked to dementia and impaired in Parkinson’s Disease (PD). Measuring ORM may indicate early PD dementia and aid in selecting device-aided Parkinson therapy. This study investigates ORM capacity and hippocampal dynamic functional connectivity in PD. Thirty-one PD participants and 31 healthy controls (HC) underwent functional MRI during an ORM task. Co-activation pattern analysis identified active hippocampal networks. The PD group showed impaired ORM and a sequence of four activated hippocampal networks. The fourth network, involving the dorsal Attention Network (dAN), had fewer and shorter expressions during correct ORM responses in PD compared with HC. Hippocampal functional asymmetry was observed in HC but not in PD. These findings suggest that impaired ORM in PD is linked to reduced hippocampal functional asymmetry. Future research should explore differences in functional dynamics of odor memory-related brain regions in PD patients with and without cognitive decline.

Introduction:Recent studies suggest that the dopamine agonist (DA) rotigotine improves sleep among Parkinson disease (PD) patients. Parkinson's KinetiGraph (PKG) offers a home-based alternative for evaluating sleep. We investigated the effect of rotigotine on sleep in PD patients with PKG and questionnaires. Secondarily, the effects of rotigotine on daytime sleepiness, motor symptoms, quality of life and correlations between PKG variables and rating scale results were investigated. Method:Thirty-two PD patients with sleep disturbances (Clinical Global Impression-Severity (CGI-S) ≥ 3) were included in this observational study. Before start of treatment and during stable dose with rotigotine patients were assessed with Parkinson's disease sleep scale 2 (PDSS-2), Epworth Sleepiness Scale (ESS), Parkinson's disease quality of life questionnaire (PDQ-8), European Quality of life five dimensions (EQ-5D-5L) questionnaires and PKG recordings (24 h/day for 6 days). Clinicians evaluated sleep using CGI scales, and PD severity using Clinical Impression of Severity Index for Parkinson's Disease (CISI-PD). Results:Rotigotine did not significantly improve total PDSS-2 or PKG nighttime scores in the entire group, but PDSS-2 improved among patients with PDSS-2 ≥ 18 at baseline and for DA-naïve patients (p = 0.009 and p = 0.013). Treatment improved percent time tremor (PTT; p < 0.001), percent time immobile during daytime (PTID; p < 0.001), CISI-PD (p < 0.001), PDQ-8 (p = 0.014), and EQ-5D-5L (p = 0.002). No significant correlations were found between PTID and ESS-total (ρ = -0.046, p = 0.718) or between combined sleep score (CSS) and PDSS-2 total (ρ = -0.065, p = 0.612). Conclusion:Rotigotine improved sleep in patients with a baseline PDSS-2 ≥ 18 and in DA-naïve patients, but not in the whole study group. Additionally, rotigotine seemed to improve motor function and quality of life. PTID improved with treatment. Whether the improved PTID reflects a positive impact on daytime sleepiness or just improved mobility and to what extent PKG nighttime scores accurately represent sleep variables remains to be investigated in further studies.

Background: It has been suggested that carbidopa at high blood concentrations may counter the therapeutic effect of levodopa in Parkinson's disease by entering the brain and blocking central levodopa conversion to dopamine. We previously demonstrated equivalent plasma levodopa concentration in patients with Parkinson's disease during 16 h of (1) intravenous carbidopa/levodopa (DIZ101) infusion, (2) subcutaneous carbidopa/levodopa (DIZ102) infusion or (3) intestinal carbidopa/levodopa gel infusion. Plasma levels of carbidopa were however approximately four times higher with DIZ101 and DIZ102 than with LCIG, and higher than those usually observed with oral levodopa/carbidopa. Objectives: To investigate if high carbidopa blood concentrations obtained with parenteral levodopa/carbidopa (ratio 8:1) counter the effect of levodopa on motor symptoms. Methods: Eighteen patients with advanced Parkinson's disease were administered DIZ101, DIZ102, and intestinal levodopa/carbidopa gel for 16 h on different days in randomized order. Video recordings of a subset of the motor examination in the Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated by raters blinded for treatment and time. Motor function was also measured using a wrist-worn device monitoring bradykinesia, dyskinesia, and tremor (Parkinson KinetiGraph). Results: There was no tendency for poorer levodopa effect with DIZ101 or DIZ102 as compared to LCIG. Conclusion: Although DIZ101 or DIZ102 causes approximately four times higher plasma carbidopa levels than LCIG, patients responded equally well to all treatments. The results do not indicate that high plasma carbidopa levels hamper the motor efficacy of levodopa.

Introduction. Parkinson's disease (PD) is a neurodegenerative disease with motor and nonmotor symptoms. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives. To explore how COVID-19 affects motor, nonmotor, and general health aspects of PD and to map how PD patients perceive their change in symptoms since falling ill with COVID-19. Method. The study was descriptive, case-controlled, and based on both registry and questionnaire data. At baseline, the controls were matched on age, sex, and disease severity. Information on the severity of the disease, nonmotor symptoms, motor symptoms, and general health was retrieved from the Swedish Registry for PD. Registry data from a COVID-19 group (n=45) and a control group (n=73), as well as questionnaires from a COVID-19 group (n=24) and a control group (n=42), were compared. Results. We did not find that SARS-CoV-2 infection affects any major aspect of nonmotor symptoms, motor symptoms, general health, and perception of change in PD patients' post-COVID-19. Compared to controls, the COVID-19 group reported a more positive subjective experience of pain and quality of life and a perception of change post-COVID-19 regarding general motor function, sleep quality, and mood (all p<0.05). Conclusion. Although SARS-CoV-2 infection does not seem to affect PD symptoms in any major respect, the subjective experience of several aspects of life in PD patients might be slightly improved post-COVID-19 compared to a control group. The findings warrant further investigations due to the small sample size and possible survivorship bias.

Introduction: Whilst awake craniotomy has been widely used historically in epilepsy surgery, the safety and efficacy of this approach in epilepsy surgery has been sparsely investigated in controlled studies. The objective of this study is to investigate the safety and efficacy of awake resection in epilepsy surgery and focuses on the possibility to widen surgical indications with awake surgery. Methods: Fifteen patients operated with awake epilepsy surgery were compared to 30 matched controls undergoing conventional/asleep epilepsy surgery. The groups were compared with regard to neurological complications, seizure control and location of resection. Results: Regarding seizure control, 86% of patients in the awake group reached Engel grade 1-2 compared to 73% in the control group, operated with conventional/asleep surgery, not a statistically significant difference. Neither was there a statistical significant difference regarding postoperative neurological complications. However, there was a significant difference in location of the resection when comparing the two groups. Of the 15 patients operated with awake intraoperative mapping, four had previously been considered as non-operable by epilepsy surgery centres, due to vicinity to eloquent brain regions and predicted risk of post-operative neurological deficits. Discussion: The results show that awake epilepsy surgery yields similar level of seizure control when compared to conventional asleep surgery, with maintained safety in regard to neurological complications. Furthermore, the results indicate that awake craniotomy in epilepsy surgery is feasible and possible in patients otherwise regarded as inoperable with epileptigenic zone in proximity to eloquent brain structures.

Background and Objectives Intestinal levodopa/carbidopa gel infusion (LCIG) is superior to oral treatment in advanced Parkinson disease. The primary objective of this trial was to investigate whether continuous subcutaneous or intravenous infusion with a continuously buffered acidic levodopa/carbidopa solution yields steady-state plasma concentrations of levodopa that are equivalent in magnitude, and noninferior in variability, to those obtained with LCIG in patients with advanced Parkinson disease. Methods A concentrated acidic levodopa/carbidopa (8:1) solution buffered continuously and administered intravenously (DIZ101) or subcutaneously (DIZ102) was compared with an approved LCIG in a randomized, 3-period crossover, open-label, multicenter trial. Formulations were infused for 16 hours to patients with Parkinson disease who were using LCIG as their regular treatment. Patients were recruited from several university neurology clinics but came to the same phase I unit for treatment. Pharmacokinetic variables and safety including dermal tolerance are reported. The primary outcomes were bioequivalence and noninferior variability of DIZ101 and DIZ102 vs LCIG with respect to levodopa plasma concentrations. Results With dosing adjusted to estimated bioavailability, DIZ101 and DIZ102 produced levodopa plasma levels within standard bioequivalence limits compared with LCIG in the 18 participants who received all treatments. Although the levodopa bioavailability for DIZ102 was complete, it was 80% for LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of DIZ102 as with LCIG and remained stable throughout the infusions. Owing to poor uptake of LCIG, carbidopa levels in plasma were higher with DIZ101 and DIZ102 than with the former. All individuals receiving any of the treatments (n = 20) were included in the evaluation of safety and tolerability. Reactions at the infusion sites were mild and transient. Discussion It is feasible to rapidly achieve high and stable levodopa concentrations by means of continuous buffering of a subcutaneously administered acidic levodopa/carbidopa-containing solution. Trial Registration Information ClinicalTrials.gov identifier: NCT03419806. Registration first posted on February 5, 2018, first patient enrolled on February 16, 2018.

Olfactory impairment is a central non-motor symptom in Parkinson's disease (PD). Previous studies have demonstrated that olfactory dysfunction is associated with mental illness and impaired cognition. The frequently investigated olfactory functions are odor detection, discrimination, and identification. However, few studies have focused on odor recognition memory (ORM). ORM tasks involves episodic memory which therefore can facilitate the detection of dementia among patients with PD and consequently adjust their treatment. Thus, the aim of this systematic review is to summarize the existing research on ORM in PD. Databases and reference lists were used for data collection. Studies were included in the review if they met the eligibility criteria derived from the PICOS-framework. Quality evaluation of the studies was based on the STROBE-statement. Six studies with small samples were included in the analysis which demonstrated the scarce research on the subject. The studies targeting ORM were heterogenous and involved two main tasks: odor recognition and odor matching. The synthesis of the data demonstrated that PD patients performed significantly lower than controls on both tasks, especially on odor matching task. Only the odor recognition task exhibited a difference between patients with PD vs. Alzheimer's disease (AD). PD patients performed significantly better than AD patients. The findings based on the available limited data support the notion that odor recognition task can be of importance in identifying Parkinson's disease dementia (PDD). To investigate this hypothesis, future research needs to include larger samples of PD, PDD and AD patients executing the same odor recognition task.

Continuous subcutaneous (s.c.) apomorphine infusion is an effective therapy for Parkinson’s disease (PD), but a limitation is the formation of troublesome s.c. nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal experiences have suggested that shifting from one of these (Apo-Go PumpFill®; apoGPF) to another (Apomorphine PharmSwed®; apoPS) may influence the occurrence and severity of s.c. nodules. We, therefore, followed 15 people with advanced PD (median PD-duration, 15 years; median “off”-phase Hoehn and Yahr, IV) on apoGPF and with troublesome s.c. nodules who were switched to apoPS. Data were collected at baseline, at the time of switching, and at a median of 1, 2.5, and 7.3 months post-switch. Total nodule numbers (P < 0.001), size (P < 0.001), consistency (P < 0.001), skin changes (P = 0.058), and pain (P ≤ 0.032) improved over the observation period. PD severity and dyskinesias tended to improve and increase, respectively. Apomorphine doses were stable, but levodopa doses increased by 100 mg/day. Patient-reported apomorphine efficacy tended to increase and all participants remained on apoPS throughout the observation period; with the main patient-reported reason being improved nodules. These observations suggest that patients with s.c. nodules caused by apoGPF may benefit from switching to apoPS in terms of s.c. nodule occurrence and severity. Alternatively, observed benefits may have been due to the switch itself. As nodule formation is a limiting factor in apomorphine treatment, a controlled prospective study comparing local tolerance with different formulations is warranted.

Background IRL752 is a novel small-molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex. Objective The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson's disease and dementia. Methods Patients with Parkinson's disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28 days. The study drug was given as an adjunct treatment to the patients' regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days. Results A total of 32 patients were randomized to treatment, and 29 patients completed the 4-week treatment. Adverse events were generally mild and transient and were mostly reported during the dose titration phase. There were 2 serious adverse events, and none of them were related to the experimental treatment. The average dose achieved in the stable dose phase was 600 mg daily, yielding a 2-hour postdose plasma concentration of about 4 mu M on day 28. Exploratory assessment of secondary outcomes indicated efficacy for symptoms and signs known to be poorly responsive to levodopa. Conclusions IRL752 appears to be safe and well tolerated for a 4-week treatment in patients with Parkinson's disease and dementia. (c) 2020 International Parkinson and Movement Disorder Society

Parkinson's disease is the second most common neurodegenerative disease. Lewy bodies with alpha-synuclein as the major component and loss of dopaminergic nerve cells in substantia nigra are neuropathological features. The diagnosis of Parkinson's disease is based on the occurrence of bradykinesia, rigidity and resting tremor. The disease is also associated with several non-motor symptoms. The therapy is mainly based on pharmacological treatment to increase dopamine signaling and neurosurgical deep brain stimulation. The symptoms and signs of the progressive disease change over time, requiring treatment adjustments. Patients should be followed by a physician, nurse and a multidisciplinary team with expertise in Parkinson's disease.

Objective: To evaluate a group-based music intervention in patients with Parkinson’s disease. Design: Parallel group randomized controlled trial with qualitative triangulation. Setting: Neurorehabilitation in primary care. Subjects: Forty-six patients with Parkinson’s disease were randomized into intervention group (n = 26), which received training with the music-based intervention, and control group (n = 20) without training. Interventions: The intervention was delivered twice weekly for 12 weeks. Main measures: Primary outcome was Timed-Up-and-Go subtracting serial 7’s (dual-task ability). Secondary outcomes were cognition, balance, concerns about falling, freezing of gait, and quality of life. All outcomes were evaluated at baseline, post-intervention, and three months post-intervention. Focus groups and individual interviews were conducted with the intervention group and with the delivering physiotherapists. Results: No between-group differences were observed for dual-task ability. Between-group differences were observed for Falls Efficacy Scale (mean difference (MD) = 6.5 points; 95% confidence interval (CI) = 3.0 to 10.0, P = 0.001) and for Parkinson Disease Questionnaire-39 items (MD = 8.3; 95% CI = 2.7 to 13.8, P = 0.005) when compared to the control group post-intervention, but these were not maintained at three months post-intervention. Three themes were derived from the interviews: Expectations versus Results, Perspectives on Treatment Contents, and Key Factors for Success. Conclusion: Patient-reported outcomes and interviews suggest that the group-based music intervention adds value to mood, alertness, and quality of life in patients with Parkinson’s disease. The study does not support the efficacy in producing immediate or lasting gains in dual-tasking, cognition, balance, or freezing of gait.

Background. Parkinson’s disease is a neurodegenerative condition with both physical and mental consequences that affect many aspects of everyday life. Persons with Parkinson’s disease and their care partners want guidance from healthcare services in order to develop skills to adjust to life with a long-term condition. The Swedish National Parkinson School is a dyadic self-management programme to support both persons with Parkinson’s disease and care partners. Objective. To assess the outcomes of the Swedish National Parkinson School as reported by participants. Design. A quasi-experimental case-control study in clinical care using self-reported questionnaires. Participants. Swedish National Parkinson School was offered by health care professionals working in clinical care. Participants in the programme were also asked to participate in the study. A matched control group was recruited for a comparison of findings. In total, 92 persons with Parkinson’s disease and 55 care partners were included. Settings. Five Swedish geriatric and neurologic outpatient clinics. Method. Data were collected during 2015–2017, before and after participation in the National Parkinson School or before and after seven weeks of standard care. Outcomes were assessed using generic and Parkinson’s specific questionnaires. Descriptive statistics were used to describe baseline characteristics. Mann–Whitney U and Chi2 tests were used to test for between-group differences and within-group differences were tested by the Wilcoxon signed-ranks test. Results. Improvements regarding health status, constructive attitudes and approaches, and skill and technique acquisition were found after the intervention among persons with Parkinson’s disease. No changes were found among care partners. Conclusion. The findings indicate that the Swedish National Parkinson School may improve health status and self-management among persons with Parkinson’s disease, but further studies are needed to better understand the effects of the programme.

Persons with Parkinson's disease and their care partners want support from health care to develop the skills to handle everyday life with the long-term condition. Earlier findings indicate that participants of the self-management program Swedish National Parkinson School experience several benefits of the program. The purpose of this qualitative observational study was to explore if participants had implemented the strategies of self-monitoring included in the program and use them to communicate health care status and needs in clinical encounters. Data were collected 3 to 15 months after participation in the program and analyzed using constant comparative analysis. Three categories were evident: "Self-observation in everyday life," "Self-care activities to promote health," and "Managing emotional impact of Parkinson's Disease." Categories were linked together in a core category that highlight the use of self-management strategies described by participants during clinical encounters. Results confirmed that persons with Parkinson's disease and care partners use the techniques of self-observation in their everyday lives. Observations of effects in clinical care can be a valuable approach to evaluate the outcomes educational interventions and their benefits for individuals and health care.

Parkinson's disease is the second most common neurodegenerative disease. Lewy bodies with alpha-synuclein as the major component and loss of dopaminergic nerve cells in substantia nigra are neuropathological features. The diagnosis of Parkinson's disease is based on the occurrence of bradykinesia, rigidity and resting tremor. The disease is also associated with several non-motor symptoms. The therapy is mainly based on pharmacological treatment to increase dopamine signaling and neurosurgical deep brain stimulation. The symptoms and signs of the progressive disease change over time, requiring treatment adjustments. Patients should be followed by a physician, nurse and a multidisciplinary team with expertise in Parkinson's disease.

Olfactory dysfunction is an early manifestation of Parkinson's disease (PD). The present study aimed to illustrate potential differences between PD patients and healthy controls in terms of neural activity and functional connectivity within the olfactory brain network. Twenty PD patients and twenty healthy controls were examined with olfactory fMRI and resting-state fMRI. Data analysis of olfactory fMRI included data-driven tensorial independent component (ICA) and task-driven general linear model (GLM) analyses. Data analysis of resting-state fMRI included probabilistic ICA based on temporal concatenation and functional connectivity analysis within the olfactory network. ICA of olfactory fMRI identified an olfactory network consisting of the posterior piriform cortex, insula, right orbitofrontal cortex and thalamus. Recruitment of this network was less significant for PD patients. GLM analysis revealed significantly lower activity in the insula bilaterally and the right orbitofrontal cortex in PD compared to healthy controls but no significant differences in the olfactory cortex itself. Analysis of resting-state fMRI did not reveal any differences in the functional connectivity within the olfactory, default mode, salience or central executive networks between the two groups. In conclusion, olfactory dysfunction in PD is associated with less significant recruitment of the olfactory brain network. ICA could demonstrate differences in both the olfactory cortex and its main projections, compared to GLM that revealed differences only on the latter. Resting-state fMRI did not reveal any significant differences in functional connectivity within the olfactory, default mode, salience and central executive networks in this cohort.

AIMS AND OBJECTIVE:To identify and describe experiences valuable for managing daily life after participation in the NPS self-management intervention. The second part was to explore the applicability of the Self- and family management framework by Grey and colleagues for persons with Parkinson's Disease and their relatives.BACKGROUND:The impact of PD is evident on the lives of both patients and relatives. The National Parkinson School (NPS) is a Swedish self-management programme designed for patients and relatives, aiming at teaching strategies helpful for the ability of self-management, in order to promote life satisfaction.DESIGN:Qualitative explorative with inductive and deductive analysis.METHODS:Five group discussions with NPS participants were audio-recorded. Verbatim transcriptions were analysed inductively with thematic analysis according to Braun and Clarke, and the findings were then applied deductively to the existing model for patients with chronic disease.RESULTS:Through the first step of inductive analysis, three themes capturing the meaning, value and experience of being a participant at the NPS were identified: exchanging experiences and feeling support, adjustment and acceptance of PD for managing daily life and promoting life satisfaction. The deductive analysis applied the inductive findings to the Self- and family management framework of chronically ill to explore the fit to persons with PD and relatives attending the NPS programme.CONCLUSIONS:The NPS programme is a promising approach for helping persons with PD and their relatives to achieve better self-management of disease and improved life satisfaction. Further evaluations of programme outcomes in clinical practice are warranted.RELEVANCE OF CLINICAL PRACTICE:Self-management programmes like the NPS is a promising approach in facilitating a positive mindset and outlook on life and gain knowledge to understand, adapt and handle chronic disease, such as PD, better.

In this study we investigated the association between SNPs in the S100B gene and Parkinson’s disease (PD) in two independent Swedish cohorts. The SNP rs9722 has previously been shown to be associated with higher S100B concentrations in serum and frontal cortex in humans. S100B is widely expressed in the central nervous system and has many functions such as regulating calcium homeostasis, inflammatory processes, cytoskeleton assembly/disassembly, protein phosphorylation and degradation, and cell proliferation and differentiation. Several of these functions have been suggested to be of importance for the pathophysiology of PD.