Publications by authors named "Per Odin"

87 Publications

Cost-Effectiveness of Device-Aided Therapies in Parkinson's Disease: A Structured Review.

J Parkinsons Dis 2020 Dec 27. Epub 2020 Dec 27.

Institute of Psychiatry, Psychology & Neuroscience, Department of Basic & Clinical Neuroscience, King's College London, London, United Kingdom.

Background: Despite optimal dopaminergic treatment most patients in moderate to advanced stages of Parkinson's disease (PD) experience progressively increasing disabilities, necessitating a shift from oral medication to device-aided therapies, including deep brain stimulation (DBS), intrajejunal levodopa-carbidopa infusion (IJLI), and continuous subcutaneous apomorphine infusion (CSAI). However, these therapies are costly, limiting their implementation.

Objectives: To perform a systematic review on cost-effectiveness analyses for device-aided therapies in PD.

Methods: References were identified by performing a systematic search in the PubMed and Web of Science databases in accordance with the PRISMA statement. In the absence of universal cost-effectiveness definitions, the gross domestic product per capita (GDP) in the country where a study was performed was used as a cut-off for cost-effectiveness based on cost per quality adjusted life year (QALY) gained.

Results: In total 30 studies were retrieved. All device-aided therapies improved quality of life compared to best medical treatment, with improvements in QALYs between 0.88 and 1.26 in the studies with long temporal horizons. For DBS, nearly all studies showed that cost per QALY was below the GDP threshold. For infusion therapies only three studies showed a cost per QALY below this threshold, with several studies with long temporal horizons showing costs below or near the GDP threshold.

Conclusion: Of the device-aided therapies, DBS can be considered cost-effective, but the majority of infusion therapy studies showed that these were less cost-effective. However, long-term use of the infusion therapies appears to improve their cost-effectiveness and in addition, several strategies are underway to reduce these high costs.
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http://dx.doi.org/10.3233/JPD-202348DOI Listing
December 2020

Caregiver Burden in Late-Stage Parkinsonism and Its Associations.

J Geriatr Psychiatry Neurol 2020 Oct 23:891988720968263. Epub 2020 Oct 23.

UCL Queen Square Institute of Neurology, 61554University College London, United Kingdom.

Background: Patients in the late stages of parkinsonism are highly dependent on others in their self-care and activities of daily living. However, few studies have assessed the physical, psychological and social consequences of caring for a person with late-stage parkinsonism.

Patients And Methods: Five hundred and six patients and their caregivers from the Care of Late Stage Parkinsonism (CLaSP) study were included. Patients' motor and non-motor symptoms were assessed using the UPDRS and Non-motor symptom scale (NMSS), Neuropsychiatric inventory (NPI-12), and caregivers' health status using the EQ-5D-3 L. Caregiver burden was assessed by the Zarit Burden Interview (ZBI).

Results: The majority of caregivers were the spouse or life partner (71.2%), and were living with the patient at home (67%). Approximately half of caregivers reported anxiety/depression and pain/discomfort (45% and 59% respectively). The factors most strongly associated with caregiver burden were patients' neuropsychiatric features on the total NPI score (r = 0.38, < 0.0001), total NMSS score (r = 0.28, < 0.0001), caring for male patients and patients living at home. Being the spouse, the hours per day assisting and supervising the patient as well as caregivers' EQ-5D mood and pain scores were also associated with higher ZBI scores (all < 0.001).

Conclusion: The care of patients with late stage parkinsonism is associated with significant caregiver burden, particularly when patients manifest many neuropsychiatric and non-motor features and when caring for a male patient at home.
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http://dx.doi.org/10.1177/0891988720968263DOI Listing
October 2020

Longitudinal prediction of falls and near falls frequencies in Parkinson's disease: a prospective cohort study.

J Neurol 2021 Mar 24;268(3):997-1005. Epub 2020 Sep 24.

Division of Neurology, Department of Clinical Sciences Lund, Restorative Parkinson Unit, Lund University, Lund, Sweden.

Introduction And Objective: Several prediction models for falls/near falls in Parkinson's disease (PD) have been proposed. However, longitudinal predictors of frequency of falls/near falls are poorly investigated. Therefore, we aimed to identify short- and long-term predictors of the number of falls/near falls in PD.

Methods: A prospective cohort of 58 persons with PD was assessed at baseline (mean age and PD duration, 65 and 3.2 years, respectively) and 3.5 years later. Potential predictors were history of falls and near falls, comfortable gait speed, freezing of gate, dyskinesia, retropulsion, tandem gait (TG), pain, and cognition (Mini-Mental State Exam, MMSE). After each assessment, the participants registered a number of falls/near falls during the following 6 months. Multivariate Poisson regression was used to identify short- and long-term predictors of a number of falls/near falls.

Results: Baseline median (q1-q3) motor (UPDRS) and MMSE scores were 10 (6.75-14) and 28.5 (27-29), respectively. History of falls was the only significant short-time predictor [incidence rate ratio (IRR), 15.17] for the number of falls/near falls during 6 months following baseline. Abnormal TG (IRR, 3.77) and lower MMSE scores (IRR, 1.17) were short-term predictors 3.5 years later. Abnormal TG (IRR, 7.79) and lower MMSE scores (IRR, 1.49) at baseline were long-term predictors of the number of falls/near falls 3.5 years later.

Conclusion: Abnormal TG and MMSE scores predict the number of falls/near falls in short and long term, and may be indicative of disease progression. Our observations provide important additions to the evidence base for clinical fall prediction in PD.
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http://dx.doi.org/10.1007/s00415-020-10234-6DOI Listing
March 2021

The Non-Motor Symptoms Scale in Parkinson's disease: Validation and use.

Acta Neurol Scand 2021 Jan 29;143(1):3-12. Epub 2020 Sep 29.

Department of Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

The Non-Motor Symptoms Scale (NMSS) was developed and validated in 2007 as the first instrument for the comprehensive assessment of a range of non-motor symptoms in Parkinson's disease (PD). Thirteen years have elapsed since its introduction and extensive international validation with good psychometric attributes has been carried out. Here, we review the validation data of the NMSS and its cross-validity with other scales, and describe the key evidence derived from use of the NMSS in clinical studies. To date, over 100 clinical studies and trials have made use of it as an outcome measure, showing consistent and strong correlations between NMSS burden and health-related quality of life measures. Moreover, the scale has shown to be capable of detecting longitudinal changes in non-motor symptoms, where studies have shown differential changes over time of several of the NMSS domains. The scale has become a key outcome in several randomized clinical trials. Highlighting the prevalence and importance of non-motor symptoms to quality of life in patients with PD, the development of NMSS has also been useful in signposting clinical and biomarker based research addressing non-motor symptoms in PD.
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http://dx.doi.org/10.1111/ane.13336DOI Listing
January 2021

Characteristics of Patients with Late-Stage Parkinsonism Who are Nursing Home Residents Compared with those Living at Home.

J Am Med Dir Assoc 2021 Feb 25;22(2):440-445.e2. Epub 2020 Jul 25.

UCL Queen Square Institute of Neurology, University College London, London, UK. Electronic address:

Objectives: To determine clinical characteristics and treatment complications of patients with late-stage Parkinsonism living in nursing homes compared with those living at home.

Design: Cross-sectional analysis.

Setting And Participants: This study is an analysis of 692 patients with late stage Parkinsonism recruited to an in-depth international study, Care of Late-Stage Parkinsonism (CLaSP).

Measures: Sociodemographic characteristics were compared between patients who were living in a nursing home (n = 194) and those living at home (n = 498). Clinical assessments included the Unified Parkinson's Disease Rating Scale (UPDRS), the nonmotor symptom scale, the neuropsychiatric inventory, and a structured interview of patients and carers. Predictors of nursing home status were determined in a multivariate analysis.

Results: Nursing home placement was strongly associated with more severe cognitive impairment, worse UPDRS motor scores and disability, and with being unmarried and older. Although nursing home residents had significantly higher axial scores, falls were less common. Despite similar levodopa equivalence doses, they had less dyskinesia. Nonmotor symptom burden, particularly delusion, hallucination, and depression scores were higher in nursing home residents, and they were more frequently on psychotropic medication. They had lower rates of dopamine agonist use and lower rates of impulse control disorders. In multivariate analysis, being unmarried, presence of cognitive impairment, worse disease severity as assessed on the UPDRS parts II and III, severity of delusions, and lower rate of dyskinesia were associated with nursing home placement.

Conclusions And Implications: These clinical characteristics suggest that in patients with Parkinsonsim who are nursing home residents, presence of cognitive impairment and delusions particularly add to the higher overall symptom burden, and more often require specific treatments, including clozapine. Despite similar levodopa equivalent daily dose, motor severity is higher, and dyskinesias, indicative of a response to levodopa, are less common. Falls, however, also occur less commonly, and dopamine agonists are less frequently used, with lower rates of impulse control disorder.
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http://dx.doi.org/10.1016/j.jamda.2020.06.025DOI Listing
February 2021

Lack of Accredited Clinical Training in Movement Disorders in Europe, Egypt, and Tunisia.

J Parkinsons Dis 2020 ;10(4):1833-1843

Instituto de Medicina Molecular, Lisbon, Portugal.

Background: Little information is available on the official postgraduate and subspecialty training programs in movement disorders (MD) in Europe and North Africa.

Objective: To survey the accessible MD clinical training in these regions.

Methods: We designed a survey on clinical training in MD in different medical fields, at postgraduate and specialized levels. We assessed the characteristics of the participants and the facilities for MD care in their respective countries. We examined whether there are structured, or even accredited postgraduate, or subspecialty MD training programs in neurology, neurosurgery, internal medicine, geriatrics, neuroradiology, neuropediatrics, and general practice. Participants also shared their suggestions and needs.

Results: The survey was completed in 31/49 countries. Structured postgraduate MD programs in neurology exist in 20 countries; structured neurology subspecialty training exists in 14 countries and is being developed in two additional countries. Certified neurology subspecialty training was reported to exist in 7 countries. Recommended reading lists, printed books, and other materials are the most popular educational tools, while courses, lectures, webinars, and case presentations are the most popular learning formats. Mandatory activities and skills to be certified were not defined in 15/31 countries. Most participants expressed their need for a mandatory postgraduate MD program and for certified MD sub-specialization programs in neurology.

Conclusion: Certified postgraduate and subspecialty training exists only in a minority of European countries and was not found in the surveyed Egypt and Tunisia. MD training should be improved in many countries.
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http://dx.doi.org/10.3233/JPD-202000DOI Listing
January 2020

The Prevalence and Determinants of Neuropsychiatric Symptoms in Late-Stage Parkinsonism.

Mov Disord Clin Pract 2020 Jul 21;7(5):531-542. Epub 2020 May 21.

University College London, Queen Square Institute of Neurology, University College London London United Kingdom.

Background: Late-stage parkinsonism and Parkinson's disease (PD) are insufficiently studied population. Although neuropsychiatric symptoms (eg, psychosis, depression, anxiety, behavioral problems) are frequently present, their prevalence and clinical predictors remain unknown.

Objective: To determine the prevalence and predictors of neuropsychiatric symptoms in late-stage PD.

Methods: We conducted a multinational study of patients with PD with ≥7 years disease duration and either a Hoehn and Yahr stage ≥4 or a Schwab and England score ≤ 50% in the stage. Neuropsychiatric symptoms were assessed through interviews with carers using the Neuropsychiatric Inventory, with a frequency × severity score ≥ 4, indicating clinically relevant symptoms. The determinants analyzed were demographic characteristics, medication, and motor and nonmotor symptoms. Univariate and multivariate logistic analyses were performed on predictors of clinically relevant neuropsychiatric symptoms.

Results: A total of 625 patients were recruited in whom the Neuropsychiatric Inventory could be completed. In 92.2% (576/625) of the patients, at least 1 neuropsychiatric symptom was present, and 75.5% (472/625) had ≥1 clinically relevant symptom. The most common clinically relevant symptoms were apathy (n = 242; 38.9%), depression (n = 213; 34.5%), and anxiety (n = 148; 23.8%). The multivariate analysis revealed unique sets of predictors for each symptom, particularly the presence of other neuropsychiatric features, cognitive impairment, daytime sleepiness.

Conclusion: Neuropsychiatric symptoms are common in late-stage PD. The strongest predictors are the presence of other neuropsychiatric symptoms. Clinicians involved in the care for patients with late-stage PD should be aware of these symptoms in this specific disease group and proactively explore other psychiatric comorbidities once a neuropsychiatric symptom is recognized.
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http://dx.doi.org/10.1002/mdc3.12968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328429PMC
July 2020

Optimizing Treatment in Undertreated Late-Stage Parkinsonism: A Pragmatic Randomized Trial.

J Parkinsons Dis 2020 ;10(3):1171-1184

UCL Queen Square Institute of Neurology, University College London, Royal Free Campus, Rowland Hill Street, London, UK.

Background: Treatment of patients with late-stage parkinsonism is often sub-optimal.

Objective: To test the effectiveness of recommendations by a movement disorder specialist with expertise in late-stage parkinsonism.

Methods: Ninety-one patients with late-stage parkinsonism considered undertreated were included in apragmatic a pragmatic multi-center randomized-controlled trial with six-month follow-up. The intervention group received a letter with treatment recommendations to their primary clinician based on an extensive clinical assessment. Controls received care as usual. The primary outcome was the Unified Parkinson Disease Rating Scale (UPDRS)part-II (Activities of Daily Living). Other outcomes included quality-of-life (PDQ-8), mental health (UPDRS-I), motor function (UPDRS-III), treatment complications (UPDRS-IV), cognition (Mini-mental-state-examination), non-motor symptoms (Non-Motor-Symptoms-scale), health status (EQ-5D-5L) and levodopa-equivalent-daily-dose (LEDD). We also assessed adherence to recommendations. In addition to intention-to-treat analyses, a per-protocol analysis was conducted.

Results: Sample size calculation required 288 patients, but only 91 patients could be included. Treating physicians followed recommendations fully in 16 (28%) and partially in 21 (36%) patients. The intention-to-treat analysis showed no difference in primary outcome (between-group difference = -1.2, p = 0.45), but there was greater improvement for PDQ-8 in the intervention group (between-group difference = -3.7, p = 0.02). The per-protocol analysis confirmed these findings, and showed less deterioration in UPDRS-part I, greater improvement on UPDRS-total score and greater increase in LEDD in the intervention group.

Conclusions: The findings suggest that therapeutic gains may be reached even in this vulnerable group of patients with late-stage parkinsonism, but also emphasize that specialist recommendations need to be accompanied by better strategies to implement these to further improve outcomes.
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http://dx.doi.org/10.3233/JPD-202033DOI Listing
January 2020

Levodopa infusion in Parkinson's disease: Individual quality of life.

Acta Neurol Scand 2020 Sep 22;142(3):248-254. Epub 2020 May 22.

Department of Neurology, Hospital Bremerhaven Reinkenheide, Bremerhaven, Germany.

Objectives: Parkinson's disease (PD) features both motor and non-motor symptoms that substantially impact quality of life (QoL). Levodopa-carbidopa intestinal gel (LCIG) reduces motor complications and improves some non-motor symptoms in advanced PD (APD). Change in patients' health-related quality of life (hrQoL) is a common endpoint in PD trials and has become an important factor in judging overall effect of LCIG. However, hrQoL is considered to be only one dimension of QoL. The primary aim of this prospective observational study was to observe the effects of LCIG on individual quality of life (iQoL) in PD and caregivers. The secondary aim was to investigate its effects on patients' motor and non-motor symptoms as well as effects on caregiver burden.

Materials & Methods: Utilizing the Schedule for the Evaluation of Individual Quality of Life-Questionnaire (SEIQoL-Q) and the Personal Wellbeing Index-Adult (PWI-A), twelve patients with advanced PD and their caregivers were followed for six months after initiation of LCIG treatment.

Results: At the final follow-up, improvements of iQoL for patients (median SEIQoL index improvement 0.16, P < .05) and caregivers (median SEIQoL index improvement 0.20, P < .05) were seen together with improvements of motor and non-motor symptoms. There were no significant improvements of hrQoL.

Conclusions: The study results indicate that LCIG improves iQoL in PD in addition to the improvement of motor and non-motor symptoms. Furthermore, this study signals that LCIG may also contribute to improvement of iQoL in caregivers.
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http://dx.doi.org/10.1111/ane.13260DOI Listing
September 2020

Management of Advanced Therapies in Parkinson's Disease Patients in Times of Humanitarian Crisis: The COVID-19 Experience.

Mov Disord Clin Pract 2020 May 4;7(4):361-372. Epub 2020 May 4.

Movement Disorders Section Fleni Buenos Aires Argentina.

Background: Although the COVID-19 pandemic is affecting a relatively small proportion of the global population, its effects have already reached everyone. The pandemic has the potential to differentially disadvantage chronically ill patients, including those with Parkinson's disease (PD). The first health care reaction has been to limit access to clinics and neurology wards to preserve fragile patients with PD from being infected. In some regions, the shortage of medical staff has also forced movement disorders neurologists to provide care for patients with COVID-19.

Objective: To share the experience of various movement disorder neurologists operating in different world regions and provide a common approach to patients with PD, with a focus on those already on advanced therapies, which may serve as guidance in the current pandemic and for emergency situations that we may face in the future.

Conclusion: Most of us were unprepared to deal with this condition given that in many health care systems, telemedicine has been only marginally available or only limited to email or telephone contacts. In addition, to ensure sufficient access to intensive care unit beds, most elective procedures (including deep brain stimulation or the initiation of infusion therapies) have been postponed. We all hope there will soon be a time when we will return to more regular hospital schedules. However, we should consider this crisis as an opportunity to change our approach and encourage our hospitals and health care systems to facilitate the remote management of chronic neurological patients, including those with advanced PD.
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http://dx.doi.org/10.1002/mdc3.12965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197306PMC
May 2020

A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia.

Mov Disord 2020 06 21;35(6):1046-1054. Epub 2020 Mar 21.

Section of Neurology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

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 μM 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. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28020DOI Listing
June 2020

[Parkinson's disease - heterogeneous and complex in its clinical presentation].

Lakartidningen 2020 03 9;117. Epub 2020 Mar 9.

Karolinska Universitetssjukhuset - Tema Neuro Stockholm, Sweden - Stockholm, Sweden.

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.
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March 2020

Everyday Occupations and Other Factors in Relation to Mental Well-Being among Persons with Advanced Parkinson's Disease.

Occup Ther Health Care 2020 Jan 26;34(1):1-18. Epub 2019 Nov 26.

Department of Health Sciences, Mental Health, Activity and Participation (MAP), Lund University, Lund, Sweden.

This cross-sectional study investigated performed activities and the level of satisfaction with everyday occupations among people (n = 67) with advanced Parkinson's disease (PD), and how these factors and experiences of social relationships were related to mental well-being. Managing one's hygiene and physical exercises were activities that the majority still performed, whereas few were engaged in work or other productive occupations. Perceived health problems and satisfaction with everyday occupations were important factors for mental well-being since satisfaction with everyday occupations may be an important focus for occupational therapists and other health professionals when supporting mental well-being among persons with advanced PD.
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http://dx.doi.org/10.1080/07380577.2019.1692269DOI Listing
January 2020

Low prevalence of known pathogenic mutations in dominant PD genes: A Swedish multicenter study.

Parkinsonism Relat Disord 2019 09 31;66:158-165. Epub 2019 Jul 31.

Lund University, Department of Experimental Medical Science, Lund, Sweden.

Objective: To determine the frequency of mutations known to cause autosomal dominant Parkinson disease (PD) in a series with more than 10% of Sweden's estimated number of PD patients.

Methods: The Swedish Parkinson Disease Genetics Network was formed as a national multicenter consortium of clinical researchers who together have access to DNA from a total of 2,206 PD patients; 85.4% were from population-based studies. Samples were analyzed centrally for known pathogenic mutations in SNCA (duplications/triplications, p.Ala30Pro, p.Ala53Thr) and LRRK2 (p.Asn1437His, p.Arg1441His, p.Tyr1699Cys, p.Gly2019Ser, p.Ile2020Thr). We compared the frequency of these mutations in Swedish patients with published PD series and the gnomAD database.

Results: A family history of PD in first- and/or second-degree relatives was reported by 21.6% of participants. Twelve patients (0.54%) carried LRRK2 p.(Gly2019Ser) mutations, one patient (0.045%) an SNCA duplication. The frequency of LRRK2 p.(Gly2019Ser) carriers was 0.11% in a matched Swedish control cohort and a similar 0.098% in total gnomAD, but there was a marked difference between ethnicities in gnomAD, with 42-fold higher frequency among Ashkenazi Jews than all others combined.

Conclusions: In relative terms, the LRRK2 p.(Gly2019Ser) variant is the most frequent mutation among Swedish or international PD patients, and in gnomAD. SNCA duplications were the second most common of the mutations examined. In absolute terms, however, these known pathogenic variants in dominant PD genes are generally very rare and can only explain a minute fraction of familial aggregation of PD. Additional genetic and environmental mechanisms may explain the frequent co-occurrence of PD in close relatives.
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http://dx.doi.org/10.1016/j.parkreldis.2019.07.032DOI Listing
September 2019

Satisfaction with Care in Late Stage Parkinson's Disease.

Parkinsons Dis 2019 9;2019:2593547. Epub 2019 Jun 9.

Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Neurology, Lund, Sweden.

In late stage Parkinson's disease (PD) (i.e., Hoehn and Yahr (HY) stages IV-V), both motor and nonmotor symptoms (NMS) are pronounced, and the patients become increasingly dependent on help in their daily life. Consequently, there is an increasing demand on health-care and social care resources for these patients and support for their informal caregivers. The aim of this study was to assess satisfaction with care in late stage PD patients and to identify factors associated with satisfaction with care. Moreover, to assess their informal caregivers' satisfaction with support and to identify factors associated with caregivers' satisfaction with support. Factors potentially associated with satisfaction with care/support were assessed in 107 late stage PD patients and their informal caregivers (=76) and entered into multivariable logistic regression analyses. Fifty-eight (59%) of the patients and 45 (59%) of the informal caregivers reported satisfaction with their overall care/support. Patients satisfied with their care reported higher independence in activities of daily living (ADL) (Katz ADL index; =0.044), less depressive symptoms (Geriatric Depression Scale, GDS-30; =0.005), and higher individual quality of life (QoL) (Schedule for the Evaluation of Individual Quality of Life Questionnaire, SEIQoL-Q; =0.036). Multivariable logistic regression analyses identified depressive symptoms (=0.015) and independence in ADL (=0.025) as independently associated with satisfaction with care. For informal caregivers, the analyses identified patients' HY stage (=0.005) and caregivers' QoL (Alzheimer's Carers Quality of Life Inventory, ACQLI; =0.012) as independently associated with satisfaction with caregiver support. The results indicate that an effective both pharmacological and nonpharmacological PD therapy is important, to adequately treat motor and NMS (e.g., depressive symptoms) in order to improve depressive symptoms and patient independence in ADL. This may benefit not only the patients, but also their informal caregivers.
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http://dx.doi.org/10.1155/2019/2593547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590557PMC
June 2019

Disease stage dependency of motor and non-motor fluctuations in Parkinson's disease.

J Neural Transm (Vienna) 2019 07 19;126(7):841-851. Epub 2019 Jun 19.

Division of Neurology, Department of Clinical Sciences, Lund University, 22185, Lund, Sweden.

Recent data suggested a decrease in non-motor fluctuations in late-stage Parkinson's disease (PD), but systematic data on non-motor fluctuations over the whole disease course are mainly lacking. We performed a meta-analysis of two studies with very similar cross-sectional cohort designs, namely the German multicenter Non Motor Fluctuation in PD study and the Swedish part of the European multicenter study Care for Late Stage Parkinsonism. We included only patients with documented motor fluctuations in the analyses. Disease stage was estimated using the Hoehn and Yahr score, motor symptoms using the Unified PD Rating Scale part III motor score and non-motor symptom (NMS) fluctuations using the modified version of the NMS scale assessing a broad range of NMS in motor On and Off state. We included 101 patients (55% men; median age: 71 (interquartile range, IQR 65-78) years with Hoehn and Yahr stages ranging from 1 to 5 [median (IQR) 3.0 (2.0-4.0); distribution of patients in Hoehn and Yahr stages was n = 42 (42%) in stages 2/3 and n = 48 (48%) in stages 4/5]. We found a clear dependency of non-motor burden on Hoehn and Yahr stage with increasing symptom severity, but decreasing fluctuation amplitudes for motor and NMS (difference of symptom severity between On and Off state) with disease stage progression. Indeed, in Hoehn and Yahr stage 5, we did not detect significant NMS fluctuations. Multivariate regression with major demographic and clinical covariates confirmed these results. In conclusion, NMS fluctuations showed a similar disease stage dependency as observed for motor fluctuations with decreasing fluctuation amplitude with disease progression.
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http://dx.doi.org/10.1007/s00702-019-02033-9DOI Listing
July 2019

Relationship of Nocturnal Sleep Dysfunction and Pain Subtypes in Parkinson's Disease.

Mov Disord Clin Pract 2019 Jan 8;6(1):57-64. Epub 2018 Nov 8.

Institute of Psychiatry, Psychology, & Neuroscience at King's College and King's College Hospital NHS Foundation Trust London United Kingdom.

Background: Little research has been conducted regarding the relationship between sleep disorders and different pain types in Parkinson's disease (PD).

Objective: To explore the influence of the various pain subtypes experienced by PD patients on sleep.

Methods: Three hundred consecutive PD patients were assessed with the PD Sleep Scale-Version 2 (PDSS-2), King's PD Pain Scale (KPPS), King's PD Pain Questionnaire (KPPQ), Visual Analog Scales for Pain (VAS-Pain), and Hospital Anxiety and Depression Scale.

Results: According to the PDSS-2, 99.3% of our sample suffered from at least one sleep issue. Those who reported experiencing any modality of pain suffered significantly more from sleep disorders than those who did not (all,  < 0.003). The PDSS-2 showed moderate-to-high correlations with the KPPS (r = 0.57), KPPQ (0.57), and VAS-Pain (0.35). When PDSS-2 items 10 to 12 (pain-related) were excluded, the correlation values decreased to 0.50, 0.51, and 0.28, respectively, while these items showed moderate-to-high correlations with KPPS (0.56), KPPQ (0.54), and VAS-Pain (0.42). Among the variables analyzed, multiple linear regression models suggested that KPPS and KPPQ were the most relevant predictors of sleep disorders (as per the PDSS-2), although following exclusion of PDSS-2 pain items, depression was the relevant predictor. Depression and anxiety were the most relevant predictors in the analysis involving the VAS-Pain. Regression analysis, considering only the KPPS domains, showed that nocturnal and musculoskeletal pains were the best predictors of overall nocturnal sleep disorder.

Conclusions: Pain showed a moderate association with nocturnal sleep dysfunction in PD. Some pain subtypes had a greater effect on sleep than others.
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http://dx.doi.org/10.1002/mdc3.12694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335509PMC
January 2019

EuroInf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson's disease.

Mov Disord 2019 03 4;34(3):353-365. Epub 2019 Feb 4.

National Parkinson Foundation International Centre of Excellence, King's College Hospital, London, United Kingdom.

Objective: Real-life observational report of clinical efficacy of bilateral subthalamic stimulation (STN-DBS), apomorphine (APO), and intrajejunal levodopa infusion (IJLI) on quality of life, motor, and nonmotor symptoms (NMS) in Parkinson's disease (PD).

Methods: In this prospective, multicenter, international, real-life cohort observation study of 173 PD patients undergoing STN-DBS (n = 101), IJLI (n = 33), or APO (n = 39) were followed-up using PDQuestionnaire-8, NMSScale (NMSS), Unified PD Rating Scale (UPDRS)-III, UPDRS-IV, and levodopa equivalent daily dose (LEDD) before and 6 months after intervention. Outcome changes were analyzed with Wilcoxon signed-rank or paired t test when parametric tests were applicable. Multiple comparisons were corrected (multiple treatments/scales). Effect strengths were quantified with relative changes, effect size, and number needed to treat. Analyses were computed before and after propensity score matching, balancing demographic and clinical characteristics.

Results: In all groups, PDQuestionnaire-8, UPDRS-IV, and NMSS total scores improved significantly at follow-up. Levodopa equivalent daily dose was significantly reduced after STN-DBS. Explorative NMSS domain analyses resulted in distinct profiles: STN-DBS improved urinary/sexual functions, mood/cognition, sleep/fatigue, and the miscellaneous domain. IJLI improved the 3 latter domains and gastrointestinal symptoms. APO improved mood/cognition, perceptual problems/hallucinations, attention/memory, and the miscellaneous domain. Overall, STN-DBS and IJLI seemed favorable for NMSS total score, and APO favorable for neuropsychological/neuropsychiatric NMS and PDQuestionnaire-8 outcome.

Conclusions: This is the first comparison of quality of life, nonmotor. and motor outcomes in PD patients undergoing STN-DBS, IJLI, and APO in a real-life cohort. Distinct effect profiles were identified for each treatment option. Our results highlight the importance of holistic nonmotor and motor symptoms assessments to personalize treatment choices. © 2019 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27626DOI Listing
March 2019

Continuous Drug Delivery Aiming Continuous Dopaminergic Stimulation in Parkinson's Disease.

J Parkinsons Dis 2018 ;8(s1):S65-S72

University of Lund, Faculty of Medicine, Lund, Sweden.

Continuous dopaminergic stimulation in Parkinson's disease (PD) has several advantages over pulsatile, non-continuous, stimulation. These therapies currently consist of pump-based and transcutaneous therapies and are based on a more constant delivery of the dopaminergic drug resulting in continuous dopaminergic stimulation and a more stable treatment effect. Several clinical and experimental observations have shown that continuous stimulation of dopaminergic receptors induces fewer complications, such as dyskinesia, compared to pulsatile stimulation. Currently available non-oral pharmacological continuous therapies in PD include the transdermal Rotigotine (RTG) patch, infusion therapies with Apomorphine and Intrajejunal Levodopa (IJLI) and the Rivastigmine patch. Here we aim to provide a concise review of these current therapies and discuss ongoing and future developments of continuous non-oral pharmacological dopaminergic therapies in PD.
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http://dx.doi.org/10.3233/JPD-181476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311379PMC
October 2019

Reduced workforce participation 5 years prior to first Parkinson's disease sick-leave.

NPJ Parkinsons Dis 2018 12;4:36. Epub 2018 Dec 12.

1Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden.

The importance of understanding the prodromal phase of Parkinson's disease (PD) by systematic recording of prediagnostic symptoms and reductions in body functions has been highlighted. The aim of this study was to investigate whether persons later diagnosed with PD exhibit increased physician-certified sickness absence 1, 2, and 5 years prior to a first sick-leave episode attributed to PD. A case-control study was performed to analyze data from all nontrivial (exceeding 14 days) sick-leave episodes in Sweden between 2008 and 2014. The 537 incident PD sick-leave episodes were identified as PD sick-leave cases and compared to 537 sick-leave controls identified by matching age, sex, and date of the first day of the sick-leave episode. The total sickness absence and sickness absence due to musculoskeletal diagnoses were found to be increased among the PD sick-leave cases from 5 years prior to the first sick-leave episode ascribed to PD when compared to the controls. No differences between PD sick-leave cases and sick-leave controls were found with regard to mental and behavioral diagnoses. We conclude that the capacity to participate in working life is reduced already at the early prediagnostic stages of PD. This finding can be used as a basis for further research into the process of identifying individuals at risk for developing PD, particularly in combination with further investigation into biochemical, genetic, and imaging biomarkers.
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http://dx.doi.org/10.1038/s41531-018-0072-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290795PMC
December 2018

Study protocol: Care of Late-Stage Parkinsonism (CLaSP): a longitudinal cohort study.

BMC Neurol 2018 Nov 5;18(1):185. Epub 2018 Nov 5.

UCL Institute of Neurology, University College London, Royal Free Campus, Rowland Hill street, NW3 2PF, London, UK.

Background: Parkinson's disease (PD) is a chronic progressive disorder leading to increasing disability. While the symptoms and needs of patients in the early stages of their disease are well characterized, little information is available on patients in the late stage of the disease.

Methods/design: The Care of Late-Stage Parkinsonism (CLaSP) study is a longitudinal, multicenter, prospective cohort study to assess the needs and provision of care for patients with late stage Parkinsonism and their carers in six European countries (UK, France, Germany, Netherlands, Portugal, Sweden). In addition, it will compare the effectiveness of different health and social care systems. Patients with Parkinsonism with Hoehn and Yahr stage ≥IV in the "On"-state or Schwab and England stage 50% or less are evaluated at baseline and three follow-up time-points. Standardised questionnaires and tests are applied for detailed clinical, neuropsychological, behavioural and health-economic assessments. A qualitative study explores the health care needs and experiences of patients and carers, and an interventional sub-study evaluates the impact of specialist recommendations on their outcomes.

Discussion: Through the combined assessment of a range of quantitative measures and qualitative assessments of patients with late stage parkinsonism, this study will provide for the first time comprehensive and in-depth information on the clinical presentation, needs and health care provision in this population in Europe, and lay the foundation for improved outcomes in these patients.

Trial Registration: The protocol was registered at ClinicalTrials.gov as NCT02333175 on 07/01/2015.
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http://dx.doi.org/10.1186/s12883-018-1184-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217790PMC
November 2018

Dopaminergic Effect on Non-Motor Symptoms in Late Stage Parkinson's Disease.

J Parkinsons Dis 2018 ;8(3):409-420

Background: Non-motor symptoms (NMS) are common in late stage Parkinson's disease (PD), as the frequency and severity of most of these symptoms increase with advancing disease.

Objective: To assess effect of dopaminergic therapy on NMS in late stage PD and to investigate relationships between dopaminergic effect on NMS and on motor function.

Method: Thirty PD patients in Hoehn and Yahr (HY) stages IV and V in "on" were included. Dopaminergic effect on non-motor symptomatology was assessed by the modified version of the Non-Motor Symptoms Scale (NMSS) in the "off" and the "on" state during a standardized L-dopa test, in parallel also assessing motor function.

Results: NMS were common and many of the symptoms occurred in >80% of the individuals. The highest NMSS scores were seen within the NMSS domains 3: mood/apathy and 7: urinary in both the "off" and the "on" state. There was a statistically significant (p < 0.001) improvement in the modified NMSS total score (median) from 79 in "off" to 64 in "on". There were statistically significant differences between the "off" and the "on" state for domains 2: sleep/fatigue, 3: mood/apathy, 5: attention/memory, 6: gastrointestinal and 7: urinary. The differences in the NMSS score between the "off" and the "on" state were in general larger for motor responders than for motor non-responders. In motor non-responders, differences of the NMSS score between the "off" and the "on" state were found for the total score, domain 3: mood/apathy and its item 11-flat moods.

Conclusion: There is an effect of dopaminergic medication on NMS in late stage PD, to some extent also for those with a non-significant response on motor function during L-dopa test. It is therefore of importance to optimize dopaminergic therapy in order to give the most effective symptomatic treatment possible.
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http://dx.doi.org/10.3233/JPD-181380DOI Listing
October 2019

Developing consensus among movement disorder specialists on clinical indicators for identification and management of advanced Parkinson's disease: a multi-country Delphi-panel approach.

Curr Med Res Opin 2018 12 20;34(12):2063-2073. Epub 2018 Aug 20.

e Department of Neurology , Lund University, Skåne University Hospital , Lund Sweden.

Background: Lack of a global consensus on the definition of advanced Parkinson's disease (APD) and considerations for timing of device-aided therapies may result in heterogeneity in care.

Objectives: To reach consensus among movement disorder specialists regarding key patient characteristics indicating transition to APD and guiding appropriate use of device-aided therapies in the management of PD symptoms.

Methods: A Delphi-panel approach was utilized to synthesize opinions of movement disorder specialists and build consensus.

Results: A panel was comprised of movement disorder specialists from 10 European countries with extensive experience of treating PD patients (mean =24.8 ± 7.2 years). Consensus on indicators of suspected APD and eligibility for device-aided therapies were based on motor symptoms, non-motor symptoms, and functional impairments. Key indicators of APD included: (i) motor-moderate troublesome motor fluctuations, ≥1 h of troublesome dyskinesia/day, ≥2 h "off" symptoms/day, and ≥5-times oral levodopa doses/day; (ii) non-motor-mild dementia, and non-transitory troublesome hallucinations; (iii) functional impairment-repeated falls despite optimal treatment, and difficulty with activities of daily living. Patients with good levodopa response, good cognition, and <70 years of age were deemed as good candidates for all three device-aided therapies. Patients with troublesome dyskinesia were considered good candidates for both levodopa-carbidopa intestinal gel and Deep Brain Stimulation (DBS). PD patients with levodopa-resistant tremor were considered good candidates for DBS.

Conclusion: Identifying patients progressing to APD and suitable for device-aided therapies will enable general neurologists to assess the need for referral to movement disorder specialists and improve the quality of care and patient outcomes.
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http://dx.doi.org/10.1080/03007995.2018.1502165DOI Listing
December 2018

Viewpoint and practical recommendations from a movement disorder specialist panel on objective measurement in the clinical management of Parkinson's disease.

NPJ Parkinsons Dis 2018 10;4:14. Epub 2018 May 10.

14Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Motor aspects of Parkinson's disease, such as fluctuations and dyskinesia, can be reliably evaluated using a variety of "wearable" technologies, but practical guidance on objective measurement (OM) and the optimum use of these devices is lacking. Therefore, as a first step, a panel of movement disorder specialists met to provide guidance on how OM could be assessed and incorporated into clinical guidelines. A key aspect of the incorporation of OM into the management of Parkinson's disease (PD) is defining cutoff values that separate "controlled" from "uncontrolled" symptoms that can be modified by therapy and that relate to an outcome that is relevant to the person with PD (such as quality of life). Defining cutoffs by consensus, which can be subsequently tested and refined, is the first step to optimizing OM in the management of PD. OM should be used by all clinicians that treat people with PD but the least experienced may find the most value, but this requires guidance from experts to allow non-experts to apply guidelines. While evidence is gained for devices that produce OM, expert opinion is needed to supplement the evidence base.
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http://dx.doi.org/10.1038/s41531-018-0051-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945844PMC
May 2018

Levodopa Effect and Motor Function in Late Stage Parkinson's Disease.

J Parkinsons Dis 2018 ;8(1):59-70

Department of Clinical Sciences Lund, Neurology, Faculty of Medicine, Lund University, Lund, Sweden.

Background: It is unclear to which degree Levodopa (L-dopa) remains effective also in the late stage of Parkinson's disease (PD) and to which degree motor fluctuations and dyskinesias remain a problem.

Objective: To assess responsiveness of motor symptomatology to L-dopa in a group of patients with late stage PD. Moreover, to investigate the extent to which motor fluctuations and dyskinesias occur.

Methods: Thirty PD patients in Hoehn and Yahr (HY) stages IV and V in "on" were included. L-dopa responsiveness was assessed with a standardized L-dopa test in the defined "off" and defined "on" states. Motor function was assessed by the Unified PD Rating Scale (UPDRS) III and timed tests. Motor fluctuations and dyskinesias were assessed by the UPDRS IV. The participants were further monitored for 10 days with a mobile movement-analyses-system, the Parkinson's Kinetigraph (PKG). The median (q1-q3) L-dopa equivalent daily dose (LEDD) was 799 (536-973) mg.

Results: The UPDRS III score improved with ≥15% in 15 (50%) and with ≥30% in six (20%) participants during the L-dopa test. The median (q1-q3) UPDRS III score in "off" was 46 (37-53) and in "on" 36 (28-46). Twenty-one (70%) of the participants reported either predictable or unpredictable "off" fluctuations (items 36-37). The prevalence of dyskinesias (item 32, duration of dyskinesias ≥1) was 47%. The PKG indicated that dyskinesias primarily were mild and that a majority had a pronounced "off" symptomatology, spending a large proportion of the day either asleep or very inactive.

Conclusions: Half of a group of patients with late stage PD had an L-dopa response of ≥15% on the UPDRS III. According to the UPDRS IV, a majority of the patients had motor fluctuations and about half had dyskinesias, although the PKG results suggested that these were not very severe.
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http://dx.doi.org/10.3233/JPD-171181DOI Listing
October 2019

Systematic evaluation of levodopa-carbidopa intestinal gel patient-responder characteristics.

NPJ Parkinsons Dis 2018 24;4. Epub 2018 Jan 24.

4AbbVie Inc., North Chicago, IL USA.

Levodopa-carbidopa intestinal gel (LCIG, carbidopa-levodopa enteral suspension in the United States) is a treatment option for advanced Parkinson's disease (PD) patients with motor fluctuations. The objective of this investigation was to identify the baseline characteristics predictive of treatment response, measured by improvement in motor symptom severity, in advanced PD patients treated with LCIG during a 54-week, open-label phase 3 study. Patients with ≥1 h improvement from baseline in "Off" time were categorized as "Responders"; whereas those with <1 h improvement, any worsening, or no post-baseline assessment were "Non-Responders". A subgroup of Responders with ≥3 h improvement in "Off" time was also examined; this subgroup was identified as "Robust Responders". Baseline demographics and disease characteristics were analyzed and their predictive relationship to change from baseline in normalized "Off" time was assessed. Out of the 324 patients included in the analysis, 272 (84.0%) were categorized as Responders and 52 (16.0%) were Non-Responders. A majority of patients (65.7%) had ≥3 h improvement in "Off" time. In general, baseline characteristics were similar between Non-responders, Responders, and the subgroup of Robust Responders. A conditional tree-structured regression analysis identified baseline "Off" time as the only factor that had significant effect on Responder and Robust Responder status. The safety profile of LCIG was similar between patient groups. Overall, this analysis showed that 84% of LCIG-treated advanced PD patients had ≥1 h improvement in "Off" time and the number-needed-to-treat to observe one patient responder was 1.19 patients. Notably, Responders and Robust Responders to LCIG were observed across the range of baseline demographics and clinical characteristics examined.
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http://dx.doi.org/10.1038/s41531-017-0040-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784118PMC
January 2018

Can suitable candidates for levodopa/carbidopa intestinal gel therapy be identified using current evidence?

eNeurologicalSci 2017 Sep 2;8:44-53. Epub 2017 Jul 2.

Hospital Santa Creu i Sant Pau, Ciberned, Universitat Autònoma de Barcelona, Universitat Oberta de Catalunya, Barcelona, Spain.

Advanced Parkinson's disease (APD) is characterized by increased functional disability, caused by motor complications, the presence of axial symptoms, and emergent disease- and drug-related non-motor symptoms. One of the advanced therapies available is intrajejunal infusion of levodopa/carbidopa intestinal gel (LCIG); however, patient selection for this treatment is sometimes difficult, particularly because of overlapping indications with other alternatives. In recent years, strong evidence has supported the use of LCIG in treating motor fluctuations associated with APD, and several clinical studies provide emerging evidence for additional benefits of LCIG treatment in certain patients. This article provides an overview of the published literature on the benefits, limitations, and drawbacks of LCIG in relation to PD symptoms, the psychosocial impact of the disease, and the quality of life of patients, with the aim of determining candidates for whom treatment with LCIG would be beneficial. According to current evidence, patients with APD (defined as inability to achieve optimal control of the disease with conventional oral treatment), a relatively well-preserved cognitive-behavioral status, and good family/caregiver would count as suitable candidates for LCIG treatment. Contraindications in the opinion of the authors are severe dementia and active psychosis.
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http://dx.doi.org/10.1016/j.ensci.2017.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730910PMC
September 2017

Levodopa-carbidopa intestinal gel in advanced Parkinson's: Final results of the GLORIA registry.

Parkinsonism Relat Disord 2017 Dec 22;45:13-20. Epub 2017 Sep 22.

Lund University, Lund, Sweden.

Introduction: This registry evaluated the 24-month safety and efficacy of levodopa-carbidopa intestinal gel (LCIG) treatment in advanced Parkinson's disease (PD) patients under routine clinical care.

Methods: Motor fluctuations, dyskinesia, non-motor symptoms, quality of life, and safety were evaluated. Observations were fully prospective for treatment-naïve patients (60% of patients) and partially retrospective for patients with ≤12 months of pre-treatment with LCIG (40% of patients). Hours of "On" and "Off" time were assessed with a modified version of the Unified Parkinson's Disease Rating Scale part IV items 32 and 39.

Results: Overall, 375 patients were enrolled by 75 movement disorder centers in 18 countries and 258 patients completed the registry. At 24 months LCIG treatment led to significant reductions from baseline in "Off" time (hours/day) (mean ± SD = -4.1 ± 3.5, P < 0.001), "On" time with dyskinesia (hours/day) (-1.1 ± 4.8, P = 0.006), Non-Motor Symptom Scale total (-16.7 ± 43.2, P < 0.001) and individual domains scores, and Parkinson's Disease Questionnaire-8 item total score (-7.1 ± 21.0, P < 0.001). Adverse events deemed to have a possible/probable causal relationship to treatment drug/device were reported in 194 (54%) patients; the most frequently reported were decreased weight (6.7%), device related infections (5.9%), device dislocations (4.8%), device issues (4.8%), and polyneuropathy (4.5%).

Conclusions: LCIG treatment led to sustained improvements in motor fluctuations, non-motor symptoms particularly sleep/fatigue, mood/cognition and gastrointestinal domains, as well as quality of life in advanced PD patients over 24 months. Safety events were consistent with the established safety profile of LCIG.
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http://dx.doi.org/10.1016/j.parkreldis.2017.09.018DOI Listing
December 2017

Infusional Therapies, Continuous Dopaminergic Stimulation, and Nonmotor Symptoms.

Int Rev Neurobiol 2017 24;134:1019-1044. Epub 2017 Jul 24.

Lund University, Faculty of Medicine, Lund, Sweden.

Pump-based Parkinson (PD) therapies, including subcutaneous apomorphine infusion (CSA) and levodopa-carbidopa intestinal gel (LCIG), presently constitute the most effective pharmacological treatments available for advanced PD. These therapies are based on a more constant delivery of the dopaminergic drug resulting in a more continuous dopaminergic stimulation and a more stable treatment effect. This can be detected as reduction of time in off, reduction of dyskinesia frequency and severity, as well as increase of time in on without troublesome dyskinesias. A number of open-label studies now suggest that also the nonmotor PD symptomatology can improve under CSA and LCIG therapy. The most consistent improvements are seen concerning sleep, mood, and apathy, gastrointestinal symptoms, and urological symptoms. But also cardiovascular symptoms, perception, attention, and sexual function might show beneficial effects when moving from conventional therapies to pump treatment. Further there might be negative influences on some parts of the nonmotor symptomatology through side effects of CSA and LCIG therapy. In this chapter, we review the present knowledge about these aspects of the pump-based therapies. This information might be valuable when deciding on advanced therapy for individual patients.
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http://dx.doi.org/10.1016/bs.irn.2017.05.036DOI Listing
April 2018