482 research outputs found
Predictors of Response for “Off” Time Improvement With Levodopa-Carbidopa Intestinal Gel Treatment: An Analysis of the GLORIA Registry
No full textBackground: Levodopa-carbidopa intestinal gel (LCIG) is a long-term therapy for motor fluctuations in patients with advanced Parkinson's disease (PD). The aim of this analysis was to identify the baseline characteristics that predict “Off” time reduction in advanced PD patients treated with LCIG under routine clinical care in the GLORIA registry. Methods: Patients were followed under routine care for 24 months (M) with delivery of LCIG via percutaneous gastrojejunostomy. Analysis of covariance (ANCOVA) and logistic regression were performed to identify baseline characteristics that predict “Off” time reduction. Results: Compared to baseline, 86% (n/N = 131/152; mean ± SD baseline “Off” time: 3.4 ± 2.2 h) of M24 completers had ≥ 1 h reduction in “Off” time and 64% (n/N = 97/152; mean ± SD baseline “Off” time: 7.6 ± 2.9 h) had ≥ 3 h “Off” time reduction at M24. Most baseline characteristics were similar across responder subgroups; however, patients with ≥ 3 h “Off” time improvement had more “Off” time and less time with dyskinesia at baseline compared to patients with <3 h “Off” time reduction. Despite having less improvement in absolute “Off” h at M24, patients with <3 h “Off” time reduction experienced a 33% median reduction in “Off” time and a 44% median reduction in dyskinesia duration at M24, which was similar to the dyskinesia improvement observed among patients with ≥ 3 h “Off” time improvement (50% median reduction). Baseline “Off” time was both the best predictor of and the only significant factor associated with “Off” time improvement (P <0.0001). Conclusions: LCIG treatment led to clinically meaningful improvements in “Off” time in 86% of advanced PD patients and those with greater “Off” time are likely to experience the largest absolute reduction in hours “Off.
On "polysomnography reveals unexpectedly high rates of organic sleep disorders in patients with prediagnosed primary insomnia" (Sleep Breath 2011 doi 10.1007/s11325-011-0608-8)
No full textLetter to the EditorRaffaele Ferri, Viola Gschliesser, Birgit Frauscher, Werner Poewe, Birgit Hög
Levodopa in the treatment of Parkinson’s disease: an old drug still going strong
No full textWerner Poewe1, Angelo Antonini2, Jan CM Zijlmans3, Pierre R Burkhard4, François Vingerhoets51Department of Neurology, Medical University of Innsbruck, Austria; 2Parkinson Department, IRCCS San Camillo, Venice, and University of Padua, Italy; 3Department of Neurology, Amphia Hospital, Breda, The Netherlands; 4Department of Neurology, Faculty of Medicine and University Hospitals of Geneva, Switzerland; 5Neurodegenerative Disorders Unit, Neurology Department, CHUV, Lausanne, SwitzerlandAbstract: After more than 40 years of clinical use, levodopa (LD) remains the gold standard of symptomatic efficacy in the drug treatment of Parkinson’s disease (PD). Compared with other available dopaminergic therapies, dopamine replacement with LD is associated with the greatest improvement in motor function. Long-term treatment with LD is, however, often complicated by the development of various types of motor response oscillations over the day, as well as drug-induced dyskinesias. Motor fluctuations can be improved by the addition of drugs such as entacapone or monoamine oxidase inhibitors, which extend the half-life of levodopa or dopamine, respectively. However, dyskinesia control still represents a major challenge. As a result, many neurologists have become cautious when prescribing therapy with LD. This review summarizes the available evidence regarding the use of LD to treat PD and will also address the issue of LD delivery as a critical factor for the drug’s propensity to induce motor complications.Keywords: levodopa, motor fluctuations, dyskinesia, Parkinson’s diseas
Levodopa-Carbidopa Intestinal Gel Monotherapy: GLORIA Registry Demographics, Efficacy, and Safety
No full textBackground: Continuous delivery of levodopa-carbidopa intestinal gel (LCIG) provides stable plasma levodopa concentrations and reduces motor fluctuations in advanced Parkinson's disease (PD) patients. Objective: To compare the effectiveness and safety of LCIG monotherapy vs polytherapy in patients in the GLORIA registry. Methods: This was a post hoc analysis of a 24-month, multinational observational registry where advanced PD patients with persistent motor complications received LCIG (with adjunctive PD treatment, as necessary). Patients were categorized retrospectively into three stable treatment groups: LCIG monotherapy, LCIG in combination with oral levodopa only ('levodopa monotherapy' [including nighttime oral levodopa]), or LCIG in combination with any other antiparkinsonian medication ('LCIG polytherapy'). Results: Of 356 patients, 208 were on stable regimens (LCIG monotherapy n=80; levodopa monotherapy n=47; LCIG polytherapy n=81). Baseline characteristics were similar across groups. LCIG monotherapy showed significant improvements until month 18 in activities of daily living and quality of life, and until month 24 for Unified Parkinson's Disease Rating Scale (UPDRS) motor examination (p<0.05), 'Off' time (p<0.001), 'On' time with dyskinesia (p<0.01), and non-motor symptoms (p<0.01). More patients in the levodopa monotherapy and LCIG polytherapy groups experienced treatment-related adverse drug reactions (ADRs) including dyskinesias and serious ADRs than did patients in the LCIG monotherapy group. There were few polyneuropathy-related ADRs, of which one case of polyneuropathy led to discontinuation from the Levodopa monotherapy group. Conclusions: These data demonstrate that LCIG monotherapy is an effective treatment option in appropriate advanced PD patients; however, definitive baseline clinical predictors identifying patients who can discontinue concomitant oral therapy have not yet been defined
Elevated Levels of Methylmalonate and Homocysteine in Parkinson's Disease, Progressive Supranuclear Palsy and Amyotrophic Lateral Sclerosis
No full textBackground/Aims: Increasing evidence suggests that elevated levels of homocysteine (Hcy) and methylmalonate (MMA) may be involved in the pathogenesis of neurodegenerative diseases. Methods: The urine levels of MMA and serum levels of Hcy as well as folic acid and vitamin B 12 were measured in patients suffering from the distinct neurodegenerative diseases progressive supranuclear palsy (PSP), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), and compared to age-and gender-matched control subjects. Results: We found significantly elevated concentrations of Hcy (PD 15.1, PSP 15.8, ALS 13.9, control 11.2 mu mol/l) and MMA (PD 3.7, PSP 3.1, ALS 3.7, control 1.8 mg/g) in all patient groups in comparison with controls. Levels of Hcy and MMA did not differ significantly between the neurodegenerative diseases. Conclusion: Our findings might imply that Hcy and MMA are released as a consequence of neurodegeneration regardless of the underlying cause and serve as surrogate markers of neurodegeneration. Alternatively they might be directly implicated in the pathogenesis of these diseases. Since elevated levels of both Hcy and MMA are neurotoxic, further studies might investigate the effect of vitamin therapy on disease progression. Copyright (C) 2010 S. Karger AG, Base
Burden of non-motor symptoms in Parkinson's disease patients predicts improvement in quality of life during treatment with levodopa-carbidopa intestinal gel
No full textBackground and purpose GLORIA, a registry conducted with 375 advanced Parkinson's disease patients treated with levodopa‐carbidopa intestinal gel (LCIG) for 24 months in routine clinical care, demonstrated significant reductions from baseline in ‘off’ time and ‘on’ time with dyskinesia and improvements in the Non‐Motor Symptom Scale (NMSS) total and individual domain scores, and in Parkinson's Disease Questionnaire 8 item (PDQ‐8) total score. Methods Associations between baseline NMSS burden (NMSB), the multi‐domain NMSS total score and the PDQ‐8 total score were investigated for 233 patients. Baseline NMSB was assigned to five numerical categories defined by the NMSS total cutoff scores (0–20, 21–40, 41–60, 61–80 and >80). Pearson and Spearman correlations were calculated at month 24. Results The response of LCIG was assessed using validated criteria after 24 months. The proportion of patients decreasing ≥ 30 NMSS score points was 47% in the most affected NMSB category (NMSS total score > 80). A positive association was noted between baseline NMSB and NMSS total score (0.57, P < 0.0001), as well as between NMSS total score and PDQ‐8 total score (0.46, P < 0.0001). Associations between improvements of the NMSS domain sleep/fatigue and PDQ‐8 total score (0.32, P = 0.0001) as well as between the NMSS domain mood/cognition and PDQ‐8 total score (0.37, P < 0.0001) were also shown. Conclusions This analysis demonstrated positive associations between NMSS baseline burden and improvements of non‐motor symptoms. Improvements of non‐motor symptoms were associated with improved quality of life in advanced parkinsonian patients during a 2‐year treatment with LCIG and reflect the long‐term non‐motor efficacy of this treatment
Optimizing levodopa therapy, when and how? Perspectives on the importance of delivery and the potential for an early combination approach
No full textIntroduction: There is currently a resurgence of levodopa as the initial treatment of choice for most patients with Parkinson’s disease, albeit at lower doses than previously used. The addition of adjuvant treatments (including MAO-B inhibitors, COMT inhibitors and dopamine agonists) is an established strategy to reduce motor complications that develop with sustained levodopa therapy. Areas covered: In this narrative review, the authors discuss the evidence underpinning current levodopa optimization strategies, during early disease and once motor complications occur. To support the discussion, the authors performed a broad PubMed search with the terms ‘levodopa/L-dopa/L-Dopa, and Parkinson’s disease,’ restricted to clinical trials. There is now a wealth of evidence that improving levodopa delivery to the brain improves outcomes and we discuss how agents can be combined earlier in the course of disease to leverage the full potential of this strategy. Expert opinion: Levodopa remains the cornerstone of antiparkinsonian therapy. Several promising advances in formulation have been made and include novel extended-release oral drugs as well as non-oral delivery systems. However, evidence has long suggested that anti-parkinsonian medications may be better used in combination earlier in the disease, and consequently patients will benefit from low doses of several agents rather than ever larger levodopa doses
Rivastigmine versus placebo in hyperhomocysteinemic Parkinson's disease dementia patients. Aug 15;23(11):1532-40.PMID: 18581467
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