Intrajejunal Levodopa Infusion Research Articles

Parkinson's disease and vitamins: a focus on vitamin B12.

Parkinson's disease (PD) has been linked to a vast array of vitamins among which vitamin B12 (Vit B12) is the most relevant and often investigated specially in the context of intrajejunal levodopa infusion therapy. Vit B12 deficiency, itself, has been reported to cause acute parkinsonism. Nevertheless, concrete mechanisms through which B12 deficiency interacts with PD in terms of pathophysiology, clinical manifestation and progression remains unclear. Recent studies have suggested that Vit B12 deficiency along with the induced hyperhomocysteinemia are correlated with specific PD phenotypes characterized with early postural instability and falls and more rapid motor progression, cognitive impairment, visual hallucinations and autonomic dysfunction. Specific clinical features such as polyneuropathy have also been linked to Vit B12 deficiency specifically in context of intrajejunal levodopa therapy. In this review, we explore the link between Vit B12 and PD in terms of physiopathology regarding dysfunctional neural pathways, neuropathological processes as well as reviewing the major clinical traits of Vit B12 deficiency in PD and Levodopa-mediated neuropathy. Finally, we provide an overview of the therapeutic effect of Vit B12 supplementation in PD and posit a practical guideline for Vit B12 testing and supplementation.

Can Continuous Levodopa Delivery Be Achieved in the Absence of Intrajejunal Levodopa Infusion? Implications for India and Underserved Countries.

Can Continuous Levodopa Delivery Be Achieved in the Absence of Intrajejunal Levodopa Infusion? Implications for India and Underserved Countries.

Intrajejunal Levodopa Infusion for Parkinson’s Disease over 11 years: A Canadian Experience (P13-11.014)

<h3>Objective:</h3> To analyze long-term experience in the clinical management of Parkinson’s disease (PD) patients with intrajejunal levodopa infusion (ILI) therapy over 11 years. <h3>Background:</h3> ILI therapy is a safe and effective drug delivery method for advanced Parkinson’s disease with proven short-term efficacy and safety profile. Limited data is available regarding long-term benefits and complications. ILI is done at the University of Alberta Hospital in a multidisciplinary clinic including neurology, gastroenterology, psychiatry, PT, OT, and specialized nursing. <h3>Design/Methods:</h3> Retrospective chart review was done for patients with PD who underwent ILI from 2011 to 2022. Data collected included dosing, UPDRS-III motor scores, OFF times, hours with dyskinesias, MoCA scores, complications, discontinuation reasons, and nursing time requirements. <h3>Results:</h3> Thirty-three patients received ILI therapy with a mean follow up of <i>3.25 ± 2.09</i> years. Over 11 years, <i>6 (18.1%)</i> patients discontinued treatment due to side effects or lack of efficacy, <i>2 (6.06%)</i> transitioned to DBS therapy, and <i>11 (33.3%)</i> died of causes unrelated to ILI infusion. One patient died from haematemesis related to a coiled PEG-J tube. UPDRS-III score showed relative reduction by <i>16.3%</i> from baseline (<i>mean 33</i>) maintained for 4 years <i>(mean 28)</i>. Mean daily OFF time improved from baseline (mean <i>7.1± 3.13 hours</i>) up to 5 years (mean <i>3.3± 2.31 hours</i>; −<i>73.07%; p - 0.048</i>). Dyskinesias remained stable. Nursing time averaged 22 hours per patient per year after PEG-J insertion and titration. Most common complications were PEG-J tube dislodgement and pump malfunction in <i>18 (54.5%</i>) patients over the study period. <h3>Conclusions:</h3> Patients on ILI had improved motor scores, reduced OFF-times, and stable dyskinesias over 5-year follow-up. Most common complication was PEG-J dislodgement; serious complications were uncommon. Nursing time requirements necessitate ILI trained nurses. <b>Disclosure:</b> Dr. VEKHANDE has nothing to disclose. Dr. Hamed has nothing to disclose. Ms. Tremain has nothing to disclose. Mrs. Mah has nothing to disclose. Dr. Shetty has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Suchowersky has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Syneos/Alexion. The institution of Dr. Suchowersky has received research support from Roche. The institution of Dr. Suchowersky has received research support from Wave LifeSciences. The institution of Dr. Suchowersky has received research support from CHDI. Dr. Suchowersky has received publishing royalties from a publication relating to health care. Dr. Suchowersky has received publishing royalties from a publication relating to health care.

Long-term effects of intrajejunal levodopa infusion on sleep in people with advanced Parkinson's disease.

Sleep disturbances are commonly encountered in people with advanced Parkinson's disease (PD). In these stages, levodopa-carbidopa intestinal gel (LCIG) is recommended for improving motor symptoms, some non-motor dysfunctions, and quality of life in these patients. This study aimed to assess the effects of LCIG on sleep in PD in a longitudinal study. An open-label observational study in patients with advanced PD undergoing LCIG treatment was carried out. In total, 10 consecutive advanced people with PD were evaluated at the baseline and after 6 months and 1 year, respectively, of LCIG infusion. Sleep parameters were assessed with several validated scales. We assessed the evolution of sleep parameters under LCIG infusion over time and the effects on sleep quality. Significant improvement following LCIG was observed in PSQI total score (p = 0.007), SCOPA-SLEEP total score (p = 0.008), SCOPA-NS subscale (p = 0.007), and AIS total score (p = 0.001) at 6 months and 1 year, compared to the baseline. The PSQI total score at 6 months correlated significantly with the Parkinson's Disease Sleep Scale, version 2 (PDSS-2) "disturbed sleep" item at 6 months (p = 0.28; R = 0.688), while the PSQI total score at 12 months significantly correlated with the PDSS-2 total score at 1 year (p = 0.025, R = 0.697) and with the AIS total score at 1 year (p = 0.015, R = 0.739). LCIG infusion demonstrated beneficial effects on sleep parameters and sleep quality, which were constant over time for up to 12 months.

Real-life benefits of intrajejunal levodopa infusion therapy in four patients with the parkinsonian variant of progressive supranuclear palsy: A 1-year follow-up data report.

BackgroundProgressive supranuclear palsy (PSP) is a progressive neurodegenerative condition presenting with different clinical endophenotypes. The parkinsonian variant of PSP (PSP‐P) is characterised by early but fading responsiveness to high‐dose levodopa therapy; however, high‐dose oral therapy is often associated with intolerance due to dopaminergic side effects and so doses may have to be capped despite clinical benefits. Evidence from animal models and real‐life registries suggest far higher doses of levodopa can be tolerated if given in a continuous drug delivery (CDD) manner. We investigated tolerance and possible clinical benefits in patients with PSP‐P still responsive to levodopa after initiating CDD in the form of intrajejunal levodopa infusion (IJLI) therapy as part of a compassionate usage program (CU).MethodsThis is an observational clinical data report from the IJLI implementation program undertaken in regional tertiary referral Parkinson's centres in India and at King's College Hospital London, Dubai as part of a CU. Four patients with PSP‐P receiving IJLI as a part of a CU underwent evaluations of liver and renal function, motor and nonmotor function, quality of life, sleep dysfunction, fatigue, anxiety and depression, and cognitive impairment at baseline and 6 and 12 months post‐IJLI initiation.ResultsIn total, three out of four patients successfully completed 12 months of treatment (6 months in one patient). All four patients showed good tolerability to IJLI even at higher doses (1400 and 1960 mg at 6 and 12 months, respectively) when compared to oral levodopa (812.5 ± 103 levodopa equivalent daily dose [LEDD]) and presented with overall persistent improvements in motor and nonmotor scores and quality‐of‐life scores at 6 and 12 months post‐IJLI. All patients showed improvement in estimated glomerular filtration rate (43.50 ml/min/1.73 m2 to 67.5 ml/min/1.73 m2 and 79.5 ml/min/1.73 m2 at 6 and 12 months, respectively).ConclusionsIJLI led to persistent beneficial effects on motor and some nonmotor aspects in patients with PSP‐P at up to 12 months after treatment with associated improvement in overall renal function.

First Two-Year Observational Exploratory Real Life Clinical Phenotyping, and Societal Impact Study of Parkinson's Disease in Emiratis and Expatriate Population of United Arab Emirates 2019-2021: The EmPark Study.

Background: Phenotypic differences in Parkinson’s Disease (PD) among locals (Emiratis) and Expatriates (Expats) living in United Arab Emirates have not been described and could be important to unravel local aspects of clinical heterogenicity of PD pointing towards genetic and epigenetic variations. Objective: To investigate the range and nature of motor and nonmotor clinical presentations of PD and its impact on time to diagnosis, local service provisions, and quality of life in Emiratis and Expats in UAE, as well as address the presence of current unmet needs on relation to care and etiopathogenesis of PD related to possible genetic and epigenetic factors. Methods: a cross-sectional one point in time prospective, observational real-life study of 171 patients recruited from PD and Neurology clinics across United Arab Emirates from 2019–2021. Primary outcomes were sociodemographic data, motor and nonmotor symptoms (NMS), including cognition and sleep, and quality of life (QOL) assessments, Results: A total of 171 PD patients (52 Emiratis 119 Expats) were included with mean age (Emiratis 48.5 (13.1) Expats 64.15 (13.1)) and mean disease duration (Emiratis 4.8 (3.2) Expats 6.1 (2.9)). In the Emiratis, there was a significant mean delay in initiating treatment after diagnosis (Emiratis 1.2 (0.9) Expats 1.6 (1.1)), while from a clinical phenotyping aspect, there is a high percentage of akinesia 25 (48.1) or tremor dominant (22 (42.3)) phenotypes as opposed to mixed subtype 67 (56.3) in Expat cohorts; double tremor dominant, especially Emirati females (25%), had a predominant lower limb onset PD. Both Emirati (27.9 (24.0)) and Expat 29.4 (15.6) showed moderate NMS burden and the NMS profile is dominated by Sleep, Fatigue, Mood, Emotional well-being 3.0 (1.1) and Social Stigma 3.5 (0.9) aspects of PDQ8 SI measurements are predicted worse QOL in Emiratis, while lack of social support 2.3 (1.3) impaired QOL in Expat population. Awareness for advanced therapies was low and only 25% of Emiratis were aware of deep brain surgery (DBS), compared to 69% Expats. Only 2% of Emiratis, compared to 32% of Expats, heard of Apomorphine infusion (CSAI), and no (0%) Emiratis were aware of intrajejunal levodopa infusion (IJLI), compared to 13% of expats. Conclusion: Our pilot data suggest clinical phenotypic differences in presentation of PD in Emiratis population of UAE compared to expats. Worryingly, the data also show delayed treatment initiation, as well as widespread lack of knowledge of advanced therapies in the Emirati population.

Device-Assisted and Neuromodulatory Therapies for Parkinson's Disease: A Network Meta-Analysis.

Device-assisted and neuromodulatory therapies are the standard of care for Parkinson's disease (PD) with disabling motor complications. We aimed to compare and rank the currently available advanced therapies for PD on patient relevant outcomes. We searched various databases for randomized controlled trials that studied subthalamic nucleus deep brain stimulation (STN-DBS), globus pallidus interna (GPi) DBS, pallidotomy, subthalamotomy, continuous subcutaneous apomorphine infusion (CSAI), or intrajejunal levodopa infusion (IJLI), in patients with PD and motor complications. Primary outcome was the quality of life (QOL) at 6 months. Secondary outcomes included Unified Parkinson's Disease Rating Scale III and II, ON time, OFF time, levodopa equivalent daily doses, and adverse events (AE). Data were pooled using a Bayesian network meta-analysis, summarized as mean difference (MD) with 95% credibility intervals (CrI) and visualized in forest plots/league tables. Surface under the cumulative ranking curve plots determined the ranking probability. We identified 6745 citations and included 26 trials. STN-DBS (MD, -8.0; 95% CrI, -11, -5.8), GPi-DBS (MD, -7.1; 95% CrI, -11, -2.9), and IJLI (MD, -7.0; 95% CrI, -12, -1.8) led to better QOL than medical therapy alone, without significant differences among them. STN-DBS had the highest probability of being ranked the best treatment for QOL (79.6%), followed by IJLI (63.5%) and GPi-DBS (62.8%). In advanced PD, STN-DBS alleviates more patient and clinician relevant outcomes, followed by GPi-DBS and IJLI. In resource limited settings, unilateral pallidotomy may improve motor symptoms and activities of daily living, although overall QOL may not be improved. © 2022 International Parkinson and Movement Disorder Society.

Tolerability of overnight rotigotine transdermal patch combined with intrajejunal levodopa infusion at 1 year: a 24-h treatment option in Parkinson’s disease

BackgroundTwenty-four-hour treatment options could provide a continuous drug delivery strategy in advanced Parkinson’s disease and can ameliorate motor and non-motor complications. Use of levodopa infusion is often limited to 12–16 h/day due to its cost. Adjunctive overnight rotigotine transdermal patch is a continuous drug delivery option successfully used in clinical practice coupled with apomorphine infusion. However, real-life data addressing the tolerability of transdermal dopamine agonist therapy with concomitant use of intrajejunal levodopa infusion in advanced Parkinson’s disease are not available.ObjectiveTo evaluate the tolerability and beneficial effects of combined therapy with overnight rotigotine transdermal patch and intrajejunal levodopa infusion over a follow-up period of 12 months in advanced Parkinson’s disease.MethodIn this retrospective data analysis, data before and after the initiation of the continuous drug delivery combined therapy using overnight rotigotine transdermal patch and intrajejunal levodopa infusion were collected from the ongoing non-motor-international-longitudinal study (NILS) and local clinical practice at King’s College Hospital (London, United Kingdom). 12 advanced Parkinson’s disease patients on intrajejunal levodopa therapy who were additionally treated with overnight rotigotine transdermal patch (mean dose 5.67 ± 4.19 mg) are included. Tolerability over a 12-month period was assessed. In addition, changes in motor symptoms (SCales for Outcomes in Parkinson's disease, SCOPA-Motor), non-motor symptoms (Non-Motor Symptoms Scale, NMSS) and quality of life (Parkinson's disease Questionnaire-8, PDQ-8) before and 12-month after continuous drug delivery combined therapy initiation are evaluated.ResultsTolerability was 100% irrespective of age, disease duration, stages of disease. (Treatment with overnight rotigotine transdermal patch that was maintained for a minimum of 6 months was considered “tolerated”, primary tolerability). In addition, we noted a significant reduction of the NMSS total score (p = 0.009) and the NMSS domain 3 score (mood and apathy domain) (p = 0.028), although the latter did not remain statistically significant after correction for multiple testing (p2 = 0.252) at 12 months.ConclusionCombination of intrajejunal levodopa infusion with overnight rotigotine transdermal patch is well tolerated and extend the beneficial effects of infusion with excellent tolerability; and also improved aspects of mood and apathy sustained at 12 months in advanced Parkinson’s disease.

Apomorphine infusion for improving sleep in Parkinson's disease

Apomorphine infusion for improving sleep in Parkinson's disease

Combined and Sequential Treatment with Deep Brain Stimulation and Continuous Intrajejunal Levodopa Infusion for Parkinson's Disease.

(1) Background: Deep brain stimulation (DBS) and continuous intrajejunal levodopa infusion (CLI) are efficacious treatments of medication related motor response fluctuations in advanced Parkinson’s disease (PD). Literature regarding the use of both advanced treatments within one patient is scarce. (2) Methods: We present a retrospective single center case series and a review of the literature. Patients with PD who were treated with both DBS and CLI in our tertiary referral center between 2005 and 2020 were identified and medical records were assessed. Additionally, literature on patients treated with both therapies was systematically searched for in Medline and Embase. (3) Results: Nineteen patients were included. Medication related motor response fluctuations were a major indication for the second therapy in all but one. Of nine patients initially treated with DBS, five reported improvement with CLI. Seven of ten patients initially treated with CLI experienced benefits from DBS. The systematic literature search resulted in fifteen previous publications comprising 66 patients. Of the 59 patients, for whom the effect of the second treatment was known, 57 improved. (4) Conclusions: PD patients, who have persisting medication related motor response fluctuations, despite DBS or CLI treatment, may benefit from an additional or alternative treatment with either CLI or DBS.

Addition of Tolcapone in Intrajejunal Levodopa Infusion Therapy Requires a Pronounced Dose Reduction.

Addition of Tolcapone in Intrajejunal Levodopa Infusion Therapy Requires a Pronounced Dose Reduction.

Protocol of a randomized open label multicentre trial comparing continuous intrajejunal levodopa infusion with deep brain stimulation in Parkinson\u2019s disease - the INfusion VErsus STimulation (INVEST) study

BackgroundBoth Deep Brain Stimulation (DBS) and Continuous intrajejunal Levodopa Infusion (CLI) are effective therapies for the treatment of Parkinson’s disease (PD). To our knowledge, no direct head-to-head comparison of DBS and CLI has been performed, whilst the costs probably differ significantly. In the INfusion VErsus STimulation (INVEST) study, costs and effectiveness of DBS and CLI are compared in a randomized controlled trial (RCT) in patients with PD, to study whether higher costs of one of the therapies are justified by superiority of that treatment.MethodsA prospective open label multicentre RCT is being performed, with ancillary patient preference observational arms. Patients with PD who, despite optimal pharmacological treatment, have severe response fluctuations, bradykinesia, dyskinesias, or painful dystonia are eligible for inclusion. A total of 66 patients will be randomized. There is no minimal inclusion in the patient preference arms. The primary health economic outcomes are costs per unit on the Parkinson’s Disease Questionnaire-39 (PDQ-39) and costs per unit Quality-Adjusted Life Year (QALY) at 12 months. The main clinical outcome is patient-reported quality of life measured with the PDQ-39 at 12 months. Patients will additionally be followed during 36 months after initiation of the study treatment.DiscussionThe INVEST trial directly compares the costs and effectiveness of the advanced therapies DBS and CLI.Trial registrationDutch Trial Register identifier 4753, registered November 3rd, 2014; EudraCT number 2014–001501-32, Clinicaltrials.gov: NCT02480803.

Pain in Parkinson's disease: new concepts in pathogenesis and treatment.

In this review, we discuss the most recent evidence on mechanisms underlying pathological nociceptive processing in Parkinson's disease patients, as well as novel treatment strategies. In Parkinson's disease, specific neurodegenerative changes may cause alterations in nociceptive processing at multiple levels. Optimization of dopaminergic therapies should always be the first step in the management of Parkinson's disease pain. Reportedly, rotigotine transdermal patch, a monoamine oxidase type B inhibitor safinamide (as an add-on therapy to levodopa), subcutaneous apomorphine and intrajejunal levodopa infusion therapy may have a beneficial effect on pain sensations in Parkinson's disease patients. Among the nondopaminergic pharmacological therapies, prolonged-release oxycodone/naloxone and duloxetine may be effective in the treatment of chronic pain in Parkinson's disease. Botulinum toxin (BTX) injections should be considered for the treatment of dystonic Parkinson's disease pain. Deep brain stimulation (DBS) may lead to pain relief with a long-lasting effect in Parkinson's disease patients. Physiotherapy and physical activity in general are essential for Parkinson's disease patients suffering from pain. Pain in Parkinson's disease is not simply a consequence of motor complainants. The management of Parkinson's disease-related pain implicates maintenance of stable levels of dopaminergic drugs. Nondopaminergic pharmacological therapies (prolonged-release oxycodone/naloxone, duloxetine, BTX) and nonpharmacological interventions (DBS, physiotherapie) may also be beneficial in treatment of Parkinson's disease pain.

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

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). 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. 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. 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.

Intrajejunal levodopa infusion therapy for Parkinson’s disease: practical and pragmatic tips for successful maintenance of therapy

ABSTRACTIntroduction: Intrajejunal levodopa infusion (IJLI) therapy is one of the most influential therapies in moderate to late stage Parkinson’s disease with documented effects on motor and nonmotor symptoms and quality of life. The process of initiation and maintenance of therapy however, remains a challenge particularly in the long term.Areas covered: The authors reviewed ‘evidence base’ for pathways and advice given to patients pre and post IJLI initiation. The authors found lack of patient, carer and clinician led ‘real life’ advisory documents which need to be given to patients on IJLI.Expert commentary: Experience from centers engaged in IJLI therapy as well as feedback from carers and patients on IJLI suggest wide variability of practical advice given to patients. This is important as such tips could avoid termination of treatment or serious adverse events in some cases. In this review the authors provide a collection of pragmatic and practical tips for patients initiated on IJLI, both related to the short and long term and which we believe is a key unmet need. The paper is illustrated with two case reports.

A comparison of deep brain stimulation and continuous intrajejunal levodopa infusion in advanced Parkinson’s disease: The INVEST study

A comparison of deep brain stimulation and continuous intrajejunal levodopa infusion in advanced Parkinson’s disease: The INVEST study

Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson's disease--Clinical practice recommendations.

Extensive published evidence supports the use of subcutaneously-administered apomorphine as an effective therapy for Parkinson's disease (PD) but to date no consensus recommendations have been available to guide healthcare professionals in the optimal application of apomorphine therapy in clinical practice. This document outlines best-practice recommendations for selecting appropriate candidates for apomorphine intermittent injection (the pen-injection formulation) or apomorphine continuous infusion (the pump formulation), for initiating patients onto therapy and for managing their ongoing treatment. Apomorphine is a suitable therapeutic option for PD patients who experience troublesome 'off' periods despite optimized treatment with oral PD medications. Due to its speed of onset, apomorphine injection is particularly suited to those patients requiring rapid, reliable relief of both unpredictable and predictable 'off' periods, those who require reliable and fast relief when anticipating an 'off', those with levodopa absorption or gastric emptying problems resulting in delayed or failed 'on', or for rapid relief of early morning dystonia or akinesia. Apomorphine infusion(1) is suited for patients whose 'off' periods can no longer be adequately controlled by standard oral PD treatment or for those in whom rescue doses of apomorphine injection are effective but either needed too frequently (more than 4-6 times per day), or are associated with increasing dyskinesia. In addition to treating motor fluctuations, there is evidence that apomorphine infusion may be effective for the management of specific non-motor symptoms of PD associated with 'off' periods. Apomorphine infusion is less invasive than other non-oral treatment options for advancing disease, intrajejunal levodopa infusion and deep-brain stimulation.

Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson's disease: Consensus from an international survey and discussion program.

Navigate PD was an educational program established to supplement existing guidelines and provide recommendations on the management of Parkinson's disease (PD) refractory to oral/transdermal therapies. It involved 103 experts from 13 countries overseen by an International Steering Committee (ISC) of 13 movement disorder specialists. The ISC identified 71 clinical questions important for device-aided management of PD. Fifty-six experts responded to a web-based survey, rating 15 questions as 'critically important;' these were refined to 10 questions by the ISC to be addressed through available evidence and expert opinion. Draft guidance was presented at international/national meetings and revised based on feedback. Key take-home points are: • Patients requiring levodopa >5 times daily who have severe, troublesome 'off' periods (>1-2h/day) despite optimal oral/transdermal levodopa or non-levodopa-based therapies should be referred for specialist assessment even if disease duration is <4 years. • Cognitive decline related to non-motor fluctuations is an indication for device-aided therapies. If cognitive impairment is mild, use deep brain stimulation (DBS) with caution. For patients who have cognitive impairment or dementia, intrajejunal levodopa infusion is considered as both therapeutic and palliative in some countries. Falls are linked to cognitive decline and are likely to become more frequent with device-aided therapies. • Insufficient control of motor complications (or drug-resistant tremor in the case of DBS) are indications for device-aided therapies. Levodopa-carbidopa intestinal gel infusions or subcutaneous apomorphine pump may be considered for patients aged >70 years who have mild or moderate cognitive impairment, severe depression or other contraindications to DBS.

Infusion Therapies and Development of Impulse Control Disorders in Advanced Parkinson Disease: Clinical Experience After 3 Years' Follow-up.

In Parkinson disease (PD), compulsive behaviors, cumulatively termed impulse control disorders (ICDs), are known to develop in patients receiving dopamine-replacement therapy with oral dopamine agonists being particularly implicated. However, the effects of continuous infusion therapies have not been explored. We report data from a 3-year clinical observational screening of our active cohort of patients receiving apomorphine (Apo) infusion and intrajejunal levodopa infusion (IJLI) for development or attenuation of ICDs. Forty-one patients (24 male/17 female, mean age 61.9 ± 10.9 years; PD duration 14.2 ± 4.5 years) on Apo (mean dose 106 ± 24 mg; mean duration of infusion 16 h/d) and 19 patients (13 male/6 female, mean age 58.6 ± 8.2 years; PD duration 16.2 ± 5.7 years) on IJLI (mean dose 1990 ± 807 mg; mean duration of infusion 16 h/d) were screened and observed prospectively for development of nonmotor symptoms and ICD at 3 monthly follow-ups for up to 3 years. In Apo group, 4 patients had preexisting ICD, and in 1 patient, ICD (binge eating) completely resolved after being started on Apo. In 3 others, ICDs continue but attenuated after Apo. However, 7 new cases of ICDs developed in the Apo group, but in only 1 (2.4%), Apo had to be discontinued. Furthermore, in 3 with binge eating, the ICDs resolved after 2 months with Apo infusion being continued. In the IJLI group, 8 patients with active ICDs showed attenuation of the behavior after IJLI initiation. At 3 years, 2 of these patients continue to have ICD. No new ICDs have developed. Strategies utilizing continuous drug delivery appear to have a relatively low risk of development of ICD. Apomorphine and IJLI can be used in cases with ICD if clinically indicated, with IJLI therapy possibly emerging as the most advantageous in this setting.

Twenty Years of Apomorphine Therapy – How Does it Compare with Levodopa?

Apomorphine administered subcutaneously has provided clinicians with an effective option for the rapid resolution of the symptoms of Parkinson’s disease (PD) for over a quarter of a century. It is available for use either as an intermittent injection or a continuous infusion, depending on the severity of the patient’s symptoms. This satellite symposium, held during the 18th International Congress of Parkinson’s Disease and Movement Disorders in Stockholm, Sweden, from 8–12 June 2014, and chaired by Professor Andrew Lees, set out to review the extensive clinical experience of subcutaneous apomorphine in the management of PD accumulated over the past 25 years. It also aimed to explore why it continues to play such a valuable therapeutic role in this setting. The presenters highlighted key clinical data demonstrating why apomorphine is an effective choice for the management of both motor and non-motor symptoms in PD. Results from the limited number of comparative studies of apomorphine continuous infusion with other therapies for complex PD suggest that it has a robust motor effect, resulting in a reduction of OFF periods comparable to that achieved with more invasive options such as intrajejunal levodopa infusion or deep brain stimulation. In a large European study, apomorphine infusion has been shown to provide similar improvements in health-related quality of life to intrajejunal levodopa infusion but with a superior side-effect profile. In addition, apomorphine infusion has demonstrated beneficial non-motor effects in PD patients and reports suggest it is associated with low rates of impulse control disorders (ICDs). The motor fluctuations that occur over time in PD patients treated with oral levodopa present a management challenge as the disease progresses. Many PD patients experience these OFF periods despite optimised oral therapy and the use of multiple medications. They are due to both end-of-dose wearing OFF and delayed time to ON (TTO). A prolonged TTO is common in PD patients who have gastroparesis (delayed gastric emptying) whereby the levodopa dose is delayed exiting the stomach and is slow in reaching its site of absorption in the small intestine. Alternative non-oral formulations that avoid the gastrointestinal route, such as subcutaneous apomorphine intermittent injection, have therefore been investigated for the relief of motor fluctuations in this setting. Interim results from the ongoing Apokyn for Motor IMProvement of Morning AKinesia Trial (AM IMPAKT) study have shown that subcutaneous apomorphine injection is a valuable treatment option in PD patients with morning akinesia. This is due to a delayed onset of levodopa dose as it produces a rapid and reliable TTO, with 95 % of patients achieving at least a 20-minute reduction in TTO and an average reduction of 40 minutes. Patients also experienced improvements in Unified Parkinson’s Disease Rating Scale (UPDRS) motor score and Hoehn and Yahr stage, as well as measures of quality of life and global impression of severity.