Safety and effectiveness of levodopa-carbidopa intestinal gel for advanced Parkinson's disease: A large single-center study

BackgroundTreatment with levodopa-carbidopa intestinal gel (LCIG) can effectively relieve motor and non-motor symptoms in advanced Parkinson's disease (PD). However, adverse events (AEs) are frequent.ObjectiveTo describe AEs associated with LCIG treatment and the main reasons for treatment discontinuation. We also looked for factors that were potentially predictive of serious AEs and assessed the effectiveness of and satisfaction with LCIG.MethodWe retrospectively analyzed data on AEs in patients treated with LCIG at a French university medical center. For patients still receiving treatment at last follow-up, effectiveness was assessed according to the Clinical Global Impression (CGI) scale and the Movement Disorders Society – Unified Parkinson's Disease Rating Scale motor score.ResultsOf the 63 patients treated with LCIG for a mean (range) of 19 months (8–47), 57 (90%) experienced at least one AE (340 AEs in total). Most of the AEs (in 69.8% of the patients) were related to percutaneous endoscopic gastrostomy with a jejunal tube (PEG-J) or affected the gastrointestinal tract (granuloma, leakage, or a local infection). Device-related AEs (such as PEG-J removal and device occlusion) were frequent (in 63.5% of patients). Forty-three patients (68%) required at least one additional endoscopic procedure. Dopatherapy-related AEs occurred in 30 patients (48%). Most of the AEs occurred long after treatment initiations, and only a small proportion led to discontinuation. On the CGI scale, 53 patients (84.4%) considered that their condition had improved during LCIG treatment.ConclusionDespite the high frequency of AEs, patients with advanced PD gain clinical benefit from treatment with LCIG. This treatment requires a competent, multidisciplinary team on site.     

Levodopa-carbidopa intestinal gel (LCIG) treatment in routine care of patients with advanced Parkinson’s disease: An open-label prospective observational study of effectiveness,tolerability and healthcare costs

BackgroundContinuous infusion of levodopa-carbidopa intestinal gel (LCIG) can effectively manage motor and non-motor complications in advanced Parkinson’s disease (PD). Healthcare costs, quality of life (QoL), effectiveness, and tolerability were assessed in routine care treatment with LCIG.MethodsThe seventy-seven patients enrolled in this prospective, open-label, 3-year study in routine medical care were LCIG-naïve (N = 37), or had previous LCIG treatment for <2 (N = 22), or ≥2 (N = 18) years. Healthcare costs were collected monthly. PD symptoms and QoL were assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS), 39-item Parkinson’s Disease Questionnaire (PDQ-39), and EuroQoL 5-Dimension Visual Analog Scale (EQ-5D VAS); LCIG dose, safety, and tolerability were monitored.ResultsMean monthly costs per patient (€8226 ± 5952) were similar across cohorts, remained steady during 3-year follow-up, and increased with PD severity and QoL impairment. In LCIG-naïve patients, significant improvements compared to baseline were observed on the UPDRS total score and PDQ-39 summary index score through 18 months (n = 24; UPDRS, p = 0.033; PDQ-39, p = 0.049). Symptom control was maintained during 3-year follow-up in LCIG-experienced cohorts. Small changes in mean daily LCIG dose were observed. Adverse events were common and generally related to the device, procedure, levodopa, or laboratory evaluations.ConclusionsCosts in LCIG-treated patients were stable over 3 years. LCIG treatment led to significant improvements in motor function and QoL over 18 months in LCIG-naïve patients and no worsening was observed in LCIG-experienced patients over 3 years despite natural PD progression over time. The long-term safety was consistent with the established LCIG profile.     

Long-term safety,discontinuation and mortality in an Italian cohort with advanced Parkinson’s disease on levodopa/carbidopa intestinal gel infusion

Introduction

Levodopa/carbidopa intestinal gel (LCIG) is an effective treatment in patients with advanced Parkinson’s disease (PD) with consolidated evidence of clinical efficacy. However, only few studies have assessed long-term safety, causes of discontinuation, mortality, and relative predictors.

Methods

We conducted a retrospective analysis of 79 PD patients treated with LCIG between 2005 and 2020 in two Italian Neurological Centers, recording all adverse events (AEs), including weight loss (WL). Kaplan–Meier curve was used to estimate the time to discontinuation and survival. Cox proportional hazard model was employed to identify predictors of discontinuation and mortality, while Pearson’s correlation was used to analyze predictors of WL.

Results

The average follow-up was 47.7 ± 40.5 months and the median survival from disease onset was 25 years. There were three cases of polyradiculoneuropathy Guillain–Barre syndrome-like, all occurred in the early years of LCIG treatment. Twenty-five patients died (32%), 18 on LCIG (including one suicide) and seven after discontinuation. The mean WL was 3.62 ± 7.5 kg, which correlated with levodopa dose at baseline (p = 0.002), levodopa equivalent daily dose (LEDD) baseline (p = 0.017) and off-duration (p = 0.0014), but not dyskinesia. Peristomal complications emerged as a negative predictor of discontinuation (p = 0.008).

Conclusions

LCIG has a relatively satisfactory long-term safety profile and efficacy and a relatively low rate of discontinuation. Peristomal complications may represent a predictor of longer duration of therapy. According to the mortality analysis, LCIG patients show a long lifespan. Delaying the initiation of LCIG does not affect the sustainability of LCIG therapy.

     

Diphasic dyskinesias during levodopa-carbidopa intestinal gel (LCIG) infusion in Parkinson's disease

ObjectivesLevodopa-carbidopa intestinal gel infusion (LCIG) is indicated in patients with advanced levodopa-responsive Parkinson's disease (PD) for the treatment of motor fluctuations and dyskinesias. Here we describe 4 PD patients who developed disabling diphasic dyskinesias after LCIG initiation.MethodsThe clinical data of 33 PD patients consecutively treated with LCIG therapy were obtained through direct clinical observation and detailed review of medical records.ResultsWithin 10 days, after LCIG introduction, we identified 4 subjects (12.1%) with persistent and disabling diphasic dyskinesia (DD). We tried to manage these symptoms by increasing morning LCIG flow and adding “extended-release” formulations of dopamine-agonists and levodopa/carbidopa during bedtime. Within 1 month, all patients presented a gradual reduction in the duration and severity of DD.ConclusionsTo our knowledge, this is the first report describing the occurrence of DD in a small cohort of advanced PD patients after LCIG initiation. We wish to draw the attention of clinicians to the risk of developing disabling DD in PD patients switched to the LCIG monotherapy.     

Beyond 10 years of levodopa intestinal infusion experience: Analysis of mortality and its predictors

IntroductionAlthough levodopa/carbidopa intestinal infusion (LCIG) proved a sustained efficacy on Parkinson's disease (PD) motor fluctuations, there is a lack of studies on mortality of LCIG patients. In this study, we aimed at analyzing mortality and its predictors in a cohort of 105 PD patients treated with LCIG for over 10 years.MethodsThe death rate, death causes, mortality predictors, and serious adverse events (SAEs) were analyzed. A Cox regression model was used to estimate the influence of several demographic and clinical factors on mortality, and a binary logistic regression to evaluate the association between SAEs number and mortality. Kaplan-Meier and Log-rank test was used for a survival comparison between patients with an early drop-out (within 3 years since LCIG start) and patients continuing LCIG.ResultsNinety-eight advanced PD patients treated with LCIG were included. During follow-up, 34.7% of patients died at a mean age of 74.7 years, with a mean survival time of 4.6 years since LCIG start and 18 years since PD onset. The only predictor of mortality identified was the Mini Mental State Examination score at LCIG start (p:0.034). A total of 222 SAEs occurred in 87.9% of LCIG patients. The number of SAEs did not correlate with the mortality of LCIG patients (p:0.370). No survival difference exists between early drop-out patients and those continuing LCIG (p:0.341).ConclusionOur findings do not indicate an association between SAEs or LCIG treatment duration and mortality and highlight the importance of cognitive alterations as a mortality predictor of LCIG patients.     

Which patients discontinue? Issues on Levodopa/carbidopa intestinal gel treatment: Italian multicentre survey of 905 patients with long-term follow-up

ObjectivesTo report the results of a national survey aimed at quantifying the current level of diffusion of Levodopa/carbidopa intestinal gel (LCIG) in Italy.MethodsSixty Parkinson's Disease (PD) specialists in Italy were invited to complete a survey covering issues on clinical and practical aspects of LCIG therapy.ResultsClinical features of 905 patients were collected retrospectively. The majority of centres reported the use of a multidisciplinary team, biochemistry testing, neurophysiological and neuropsychological tests before and after treatment, in addition to caregivers' training and patient's follow as outpatients. Most centres (60%) used internal guidelines for patient selection. The overall rate of adverse events was 55.1%. Weight loss, chronic polyneuropathy and stoma infection were the most frequently reported. 40% of centres used replacement therapy with Vitamin B12 and Folic acid from the start of LCIG and continued this for the duration of treatment. The rate of discontinuation was of 25.7% overall, with 9.5% of cases occurring in the first year. The main causes of withdrawal were device-related complications, disease progression (comorbidity, severe dementia) and caregiver and/or patient dissatisfaction.ConclusionsIn Italy LCIG infusion is managed in a uniform manner at a clinical, practical and organizational level even though the selection criteria are not standardized through the country. The high percentage of patients remaining on treatment in the short- and long-term follow-up confirms effectiveness of treatment, careful follow-up, and appropriate patient and caregivers training.     

Melatonin secretion in patients with Parkinson's disease receiving different-dose levodopa therapy

ObjectiveMelatonin is involved in the regulation of sleep and circadian biological rhythmicity; decreased melatonin secretion has been associated with circadian disruptions. Previous studies evaluating melatonin levels between patients with Parkinson's disease (PD) and controls without PD have found conflicting results; however, large-scale studies have not been performed. Our aim is to compare endogenous melatonin levels between patients with Parkinson's disease (PD) and non-PD older adults.MethodsIn this cross-sectional study on 201 outpatients with PD and 380 community-dwelling older Japanese adults (controls), urinary 6-sulfatoxymelatonin excretion was measured to estimate endogenous melatonin levels.ResultsUrinary 6-sulfatoxymelatonin excretion (UME) did not significantly differ overall between PD patients and non-PD controls, even after adjusting for age, gender, medications, sleep habits, and seasons. Among PD patients, a clear and robust dose–response association was found between levodopa equivalent dose and UME, independent of potential confounding factors, including Parkinson's disease severity. Compared with the lowest levodopa equivalent dose quartile group (mean levodopa equivalent dose, 132 mg/day), the highest group (mean levodopa equivalent dose, 973 mg/day) exhibited a 68% increase in UME (17.8 vs. 30.0 ng/mg cre, respectively). In addition, compared with the non-PD controls, PD patients receiving a lower levodopa equivalent dose displayed decreased UME and those receiving higher levodopa equivalent dose displayed increased UME.ConclusionOur study suggests that melatonin levels in PD patients receiving average levodopa doses are comparable with those in older adults, even after considering confounding factors. This association was modulated by daily levodopa dose in PD patients.     

Fasting state is one of the factors associated with plasma levodopa fluctuations during levodopa‒carbidopa intestinal gel treatment

IntroductionSome patients with Parkinson's disease (PD) undergoing levodopa‒carbidopa intestinal gel (LCIG) treatment experience motor fluctuations in the afternoon. The migrating motor complex, a specific periodic migrating contraction pattern occurring in the stomach and small intestine during the fasting state, can affect drug absorption. We aimed to compare the pharmacokinetic parameters between two conditions (with and without lunch) and assessed the influence of the fasting state on the levodopa pharmacokinetics in LCIG treatment.MethodsWe evaluated the levodopa pharmacokinetics from 12:00 p.m. to 6:00 p.m. in 10 LCIG-treated PD patients in the presence and absence of lunch.ResultsThe maintenance dose of LCIG correlated strongly with the mean plasma concentration of levodopa in the absence (r = 0.94, coefficient of determination (R²) = 0.89, p < 0.001) or presence of lunch (r = 0.96, R² = 0.93, p < 0.001). Comparison of the pharmacokinetic parameters revealed that the coefficient of variation was significantly greater in the condition without lunch than in the condition with lunch (p = 0.004): 16.73% (4.88%) without lunch and 9.22% (3.80%) with lunch. There were no significant differences in the mean plasma concentration of levodopa (p = 0.49) and area under the plasma concentration‒time curve (p = 0.27) between the two conditions.ConclusionsPlasma concentrations of levodopa fluctuated more in patients undergoing LCIG treatment without than with lunch. Our results indicate that a small amount of food intake may be a better corrective approach for worsening of symptoms in the fasting state rather than additional levodopa.     

Risk and prognostic factors for pneumonia and choking amongst Parkinson’s disease patients with dysphagia

ObjectiveTo evaluate the time to hospitalisation and baseline factors associated with pneumonia/choking in Parkinson’s Disease (PD) patients.BackgroundAlthough dysphagia and pneumonia are common problems in PD, scarce research has been performed.MethodsA total of 194 PD patients who underwent a VFS evaluation were retrospectively selected. The mode of feeding and admissions for pneumonia/choking were analyzed. Baseline clinical and demographic variables were compared between feeding groups. Kaplan-Meier survival analysis was performed to estimate time to pneumonia/choking. Clinical variables significantly associated with pneumonia/choking free survival were identified using Cox regression.ResultsHospitalisation for pneumonia/choking occurred in 89 out of 194 patients, with the highest admission rate in rejected enteral feeding group (66.7%), followed by enteral feeding (61.8%) and oral feeding (38.8%) groups. The estimates of median time to event were 11, 14, and 47 months for rejected enteral feeding, enteral and oral feeding groups respectively (log-rank test p < 0.001). The rejected enteral feeding group had the highest risk of pneumonia/choking (HR 4.61, 95%CI:2.33–9.08, p < 0.001), followed by enteral feeding group (HR 2.29, 95%CI:1.25–4.19, p = 0.007), when compared to oral feeding group after adjusting for possible confounders. A stepwise Cox regression showed that the rejected enteral feeding (HR 4.89, 95%CI:2.19–10.88, p < 0.001), enteral mode of feeding (HR 2.43, 95%CI:1.11–5.32, p = 0.026), and Charlson weighted index of co-morbidity (HR 1.27, 95%CI:1.03–1.58, p = 0.028) were independently associated with higher hazard of pneumonia/choking.ConclusionsCompliance to feeding recommendations is important to reduce the risk of hospitalisation for pneumonia/choking. The recommended mode of feeding and comorbidity index was significantly associated with pneumonia/choking risk.     

Levodopa‐carbidopa intestinal gel in advanced Parkinson's disease: Final 12‐month,open‐label results

Motor complications in Parkinson's disease (PD) are associated with long‐term oral levodopa treatment and linked to pulsatile dopaminergic stimulation. l ‐dopa‐carbidopa intestinal gel (LCIG) is delivered continuously by percutaneous endoscopic gastrojejunostomy tube (PEG‐J), which reduces l‐ dopa‐plasma–level fluctuations and can translate to reduced motor complications. We present final results of the largest international, prospective, 54‐week, open‐label LCIG study. PD patients with severe motor fluctuations (>3 h/day “off” time) despite optimized therapy received LCIG monotherapy. Additional PD medications were allowed >28 days post‐LCIG initiation. Safety was the primary endpoint measured through adverse events (AEs), device complications, and number of completers. Secondary endpoints included diary‐assessed off time, “on” time with/without troublesome dyskinesia, UPDRS, and health‐related quality‐of‐life (HRQoL) outcomes. Of 354 enrolled patients, 324 (91.5%) received PEG‐J and 272 (76.8%) completed the study. Most AEs were mild/moderate and transient; complication of device insertion (34.9%) was the most common. Twenty‐seven (7.6%) patients withdrew because of AEs. Serious AEs occurred in 105 (32.4%), most commonly complication of device insertion (6.5%). Mean daily off time decreased by 4.4 h/65.6% (P < 0.001). On time without troublesome dyskinesia increased by 4.8 h/62.9% (P < 0.001); on time with troublesome dyskinesia decreased by 0.4 h/22.5% (P = 0.023). Improvements persisted from week 4 through study completion. UPDRS and HRQoL outcomes were also improved throughout. In the advanced PD population, LCIG's safety profile consisted primarily of AEs associated with the device/procedure, l‐ dopa/carbidopa, and advanced PD. LCIG was generally well tolerated and demonstrated clinically significant improvements in motor function, daily activities, and HRQoL sustained over 54 weeks. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.     

Body mass index variations in patients with Parkinson's disease treated with levodopa-carbidopa intestinal gel infusion: A case control study versus standard of care and subthalamic nucleus deep brain stimulation

BackgroundLevodopa-carbidopa intestinal gel (LCIG) is an advanced therapy for patients with Parkinson Disease (PD). Weight loss has been pointed out as an adverse event of LCIG infusion.Aims of the studyTo compare weight changes between three groups of PD patients: patients treated with LCIG, patients within the first year of subthalamic deep brain stimulation (STN-DBS) and patients treated exclusively with oral treatment during 1 year of follow up.MethodsPatients treated with LCIG were retrospectively matched by age, gender, disease duration and Hoehn and Yahr to patients undergoing STN-DBS and to patients both receiving the standard of care treatment and unwilling advanced therapies (SOC). Clinical features and weight were collected at baseline, and 12 months after introducing the treatment (LCIG and STN-DBS groups) or for one year of treatment (SOC).ResultsEighteen patients were included in each group. They had no differences in clinical and demographic features, except for cognitive impairment. There was a mean weight (−5.8 kg ±6.8) and BMI (−2.1 kg/m² ± 2.6) reduction in the LCIG group after 12 months, while there was a slight weight loss in the SOC (−1.4 kg ±3.1) and a weight increase in the STN-DBS group (5.4 kg ±4.7). Differences of weight were statistically different between, LCIG and STN-DBS (P < 0.001), LCIG and SOC (P = 0.002) and STN-DBS and SOC (P < 0.001).ConclusionsThe study shows a significant weight reduction after starting LCIG infusion compared to the other groups. Weight loss should be closely monitored in patients treated with LCIG.     

La gastrostomía endoscópica percutánea en pacientes diagnosticados de esclerosis lateral amiotrófica: mortalidad y complicaciones

IntroductionAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes severe dysphagia and weight loss. Percutaneous endoscopic gastrostomy (PEG) is currently the technique of choice for the enteral nutrition of these patients.ObjectivesTo analyse mortality and complications in a series of patients diagnosed with ALS who underwent PEG, and to evaluate factors related to patient survival after the procedure.Material and methodsWe performed a prospective, observational study including all patients diagnosed with ALS and treated by our hospital's Gastroenterology Department in the period 1997-2013. We studied mortality, complications, and clinical and biochemical parameters, and correlated these with the survival rate.ResultsThe study included a total of 57 patients, of whom 49 were ultimately treated with PEG. ALS onset was bulbar in 30 patients and spinal in 19. Mortality during the procedure and at 30 days was 2% (n = 1). Six patients (12.2%) experienced major complications; 17 (34.7%) experienced less serious complications which were easily resolved with conservative treatment. No significant differences were observed in forced vital capacity, albumin level, or age between patients with (n = 6) and without (n = 43) major complications.ConclusionsPEG is an effective, relatively safe procedure for the enteral nutrition of patients with ALS, although not without morbidity and mortality. Neither forced vital capacity nor the form of presentation of ALS were associated with morbidity in PEG.     

Levodopa/carbidopa intestinal gel can improve both motor and non-motor experiences of daily living in Parkinson’s disease: An open-label study

BackgroundLevodopa/carbidopa intestinal gel therapy (LCIG) can efficiently improve several motor and non-motor symptoms of advanced Parkinson's disease (PD). The recently developed Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) improved the original UPDRS making it a more robust tool to evaluate therapeutic changes. However, previous studies have not used the MDS-UPDRS and the Unified Dyskinesia Rating Scale (UDysRS) to assess the efficacy of LCIG.ObjectivesOur aim was to determine if the MDS-UPDRS and UDysRS could detect improvement in the experiences of daily living following 1-year LCIG treatment.MethodsIn this prospective, multicenter, open-label study, 34 consecutive patients undergoing LCIG treatment were enrolled. Patients were examined twice: prior to LCIG initiation and 12 months later. Impact of PD-related symptoms and dyskinesia was assessed by the MDS-UPDRS and UDysRS.ResultsNon-motor Experiences of Daily Living part of MDS-UPDRS improved from 20 (median, interquartile-range, IQR:14–23) to 16 points (median, IQR:12–20, p = 0.044) and the Motor Experiences of Daily Living ameliorated from 24 (median, IQR:20–29) to 18 points (median, IQR:13–25, p = 0.025). Health-related quality of life, measured by PDQ-39, also improved from 35.4 (median, IQR:26.9–50.3) to 27.0 (median, IQR:21.3–31.4) points (p = 0.003). The total score of UDysRS decreased from 47 (median, IQR:36–54) to 34 (median, IQR:21–45) points (p = 0.003).ConclusionsAs far as the authors are aware of, our paper is the first to evaluate the impact of LCIG on dyskinesia by the means of UDysRS. Changes in MDS-UPDRS and UDysRS confirm that LCIG treatment can efficiently improve experiences of daily living in advanced PD.     

Circadian activity rhythm in Parkinson's disease: findings from the PHASE study

ObjectiveCircadian disruptions in Parkinson's disease (PD) are characterized as amplitude reduction rather than as phase shift; however, large-scale studies evaluating circadian rhythms between PD patients and non-PD older adults have not been performed. The present study aimed to compare the circadian activity rhythm (CAR) between PD patients and non-PD older adults.MethodsIn this cross-sectional study on 157 PD outpatients and 1111 community-dwelling older adults (controls), physical activity was measured using actigraphy at 1-min intervals over 6 days in PD patients and 2 days in non-PD older adults. Data were base-10 log-transformed and regretted to the sigmoidally transformed cosine curve.ResultsThe mean amplitude (log counts/min) and acrophase were 1.85 (SD, 0.52) and 14:19 (SD, 1:15), respectively, in the controls (n = 1111); 1.42 (0.48) and 14:24 (1:20), respectively, in the early-stage (Hoehn–Yahr I and II) PD patients (n = 95); and 1.23 (0.54) and 13:41 (1:56), respectively, in the late-stage (Hoehn–Yahr III–V) PD patients (n = 62). Multivariable analysis revealed significantly lower amplitude in the early-stage and late-stage PD groups than in the controls. The acrophase significantly advanced in the late-stage PD group than in the controls. With the advancement of PD stage, amplitude and peak significantly decreased; trough increased; acrophase and active offset advanced; and robustness weakened.ConclusionsCompared with non-PD older adults, PD patients exhibited a phase advance in CAR, along with amplitude reduction. With an advanced stage of PD, a phase advance in CAR also occurred, along with amplitude reduction and weakened robustness.     

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

IntroductionThis 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.MethodsMotor 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.ResultsOverall, 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%).ConclusionsLCIG 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.     

Advanced therapies in Parkinson’s disease: Long-term retrospective study

BackgroundLevodopa/carbidopa intestinal gel infusion (LCIG) and subthalamic nucleus deep brain stimulation (STN-DBS) are approved therapies for advanced Parkinson’s disease (PD) whose long-term comparability remains unclear.MethodsWe reviewed the 5-year data on activities of daily living (ADL) and motor complications (OFF time, dyskinesia duration, and dyskinesia severity), as measured by the Unified Parkinson Disease Rating Scale (UPDRS) section-II and section-IV (items 39, 32, and 33, respectively) in 60 PD patients exposed to STN-DBS (n = 20), LCIG (n = 20), and oral medical therapy (OMT) (n = 20) at similar baseline disability and cognitive state.ResultsSTN-DBS and LCIG showed a similar magnitude of deterioration in ADL (+6.1 vs. +5.7 UPDRS-II; p = 0.709), but lesser than with OMT (+13.7 UPDRS-II; p = 0.005). OFF time also improved to the same extent in STN-DBS and LCIG (−62% vs. −54.5%; p = 0.830), while worsened with OMT (+78.6%; p < 0.001). STN-DBS and LCIG yielded greater improvement on dyskinesia compared to OMT (dyskinesia duration: −66.1% vs. −9.0% vs. +24.2% [p = 0.001]; dyskinesia severity: −68.8% vs. −18.0% vs. +16.2% [p = 0.002]), with relative superiority of STN-DBS over LCIG (p = 0.004 for duration; p = 0.014 for severity). The annualized rate of complication was lower in STN-DBS vs. LCIG (0.13 vs. 0.68; p < 0.001) but not different between STN-DBS and OMT (0.13 vs. 0.10; p = 0.795).ConclusionsSTN-DBS and LCIG showed comparable efficacy in ADL and OFF time, superior to OMT. STN-DBS yielded greater improvement in dyskinesia and lower long-term rate of complications than LCIG.     

Severity of depression and anxiety are predictors of response to antidepressant treatment in Parkinson's disease

BackgroundAntidepressants have appeared to be more effective than placebo treatment in treating depressive syndromes in patients with Parkinson's disease (PD).ObjectiveTo identify factors that predict improvement in depressive symptoms during antidepressant treatment in depressed PD patients.MethodsA secondary analysis was performed on the dataset of the Randomized Placebo-controlled Study of Antidepressants in PD (SAD-PD), in which 76 patients received active treatment with either paroxetine or venlafaxine extended release (XR), and 39 patients received placebo treatment. Backward stepwise regression analyses were conducted with change in 24-item Hamilton Depression Rating Scale (HAMD-24) score between assessments at baseline and week 12 as the main outcome measure, and sex, age, baseline HAMD-24 score, Unified Parkinson's Disease Rating Scale section III (UPDRS-III) score, Mini-Mental State Examination (MMSE), and the Clinical Anxiety Scale (CAS) as independent variables.ResultsIn both the active treatment and placebo groups, higher baseline HAMD-24 score and lower UPDRS-III score were associated with greater reduction in HAMD-24 score. Higher anxiety scores predicted less response in the active treatment group. Higher MMSE scores predicted greater response only in the placebo-treated group. Sex and age were no predictors of response.ConclusionsHigher pre-treatment depression scores and lower pre-treatment anxiety scores are the two most important predictors for improvement during antidepressant treatment in depressed PD patients, which is in line with those found in treatment studies of depressed non-PD patients. Furthermore, our results indicate the requirement for different or more intensive treatment for depressed PD patients with more severe anxiety symptoms.     

Improvement of impulse control disorders associated with levodopa–carbidopa intestinal gel treatment in advanced Parkinson’s disease

Impulse control behaviors are a frequent comorbidity for patients with Parkinson’s disease (PD). The objective of the present study was to evaluate the effectiveness levodopa–carbidopa intestinal gel (LCIG) therapy on impulse control disorders (ICDs) in patients with advanced PD. We conducted a multicenter, observational, and prospective (6 months follow-up) study that included consecutive PD patients assigned to LCIG through routine medical practice. Patients completed visits at baseline, 1, 3, and 6 months after percutaneous endoscopic gastrostomy procedure. The following outcomes were evaluated: presence and severity of ICDs and other neuropsychiatric disorders, sleep disturbances, patients’ quality of life, and caregivers’ burden. Sixty-two patients were included at baseline: mean age 72.2 years (SD ± 7.0), 42% women. Median duration of PD symptoms was 13.5 years (IQR 5.5–21.5) and median time with motor fluctuations was 5.0 years (IQR 1.0–9.0). Treatment with LCIG infusion was associated with progressive and significant improvements in ICDs symptoms over the study period (64.4% reduction in the Questionnaire for Impulsive–Compulsive Disorders in Parkinson’s disease—Rating Scale score). Psychotic and other neuropsychiatric symptoms were also significantly reduced, and patients’ sleep quality and psychosocial function improved. Caregivers’ burden remained unchanged. There was a significant improvement in the daily “Off” time [7.4 h (SD ± 4.0) vs 1.5 h (SD ± 1.8); p < 0.0001] at the end of follow-up, whereas duration of dyskinesias was not affected. ICDs significantly improved after 6-month LCIG treatment in a group of PD patients with mild-to-moderate neuropsychiatric disturbances.     

Temperament,character and personality disorders

ObjectiveTo study, whether temperament and character remain stable over time and whether they differ between patients with and without personality disorder (PD) and between patients with specific PDs.MethodsPatients with (n = 225) or without (n = 285) PD from Jorvi Bipolar Study, Vantaa Depression Study (VDS) and Vantaa Primary Care Depression Study were interviewed at baseline and at 18 months, and in the VDS also at 5 years. A general population comparison group (n = 264) was surveyed by mail.ResultsCompared with non-PD patients, PD patients scored lower on self-directedness and cooperativeness. Cluster B and C PDs associated with high Novelty Seeking and Harm Avoidance, respectively. In logistic regression models, sensitivity and specificity of Temperament and Character Inventory (TCI) dimensions for presence of any PD were 53% and 75%, and for specific PDs from 11% to 41% and from 92% to 100%, respectively. The 18-month test-retest correlations of TCI-R dimensions ranged from 0.58 to 0.82.ConclusionsMedium-term temporal stability of TCI in a clinical population appears good. Character scores differ markedly between PD and non-PD patients, whereas temperament scores differ only somewhat between the specific PDs. However, the TCI dimensions capture only a portion of the differences between PD and non-PD patients.     

Parkinson's disease patients may have higher rates of Covid-19 mortality in Iran

BackgroundParkinson's disease (PD) patients may be at increased risk of Covid-19 mortality due to the nature of their disease or underlying conditions.MethodThe information of 12,909 Covid-19 patients who were hospitalized during the last eleven months were collected from the data depository of two referral university hospitals. Eighty-seven of these patients were diagnosed with PD, and thirty-one of these PD patients died because of Covid-19. 2132 other deaths occurred in these centers, related to Covid-19 of non-PD patients. Fisher exact test, Chi-square test, and Principle component analysis were used for statistical analysis.ResultsThe mortality among PD patients and other hospitalized patients was 35.6% and 19.8%, respectively, and the difference between the mortality of these two groups was found to be statistically significant (p-value<0.01). The mean age of PD patients who passed away was 77.06 ± 7.46, and it was not significantly different from that of alive PD patients (p-value>0.05). Alzheimer's disease as an underlying condition was more frequent in deceased PD patients in comparison to survived PD patients, and this difference was found to be statistically significant (p-value<0.01).ConclusionPD patients possess a higher rate of Covid-19 mortality in comparison with other patients hospitalized for Covid-19. PD pathophysiology, advanced age, underlying conditions, and health systems’ efficacy may play an essential role in such an outcome.