Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients With Synucleinopathies.

Importance: Finding a reliable diagnostic biomarker for the disorders collectively known as synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA], and pure autonomic failure [PAF]) is an urgent unmet need. Immunohistochemical detection of cutaneous phosphorylated α-synuclein may be a sensitive and specific clinical test for the diagnosis of synucleinopathies. Objective: To evaluate the positivity rate of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF. Design, Setting, and Participants: This blinded, 30-site, cross-sectional study of academic and community-based neurology practices conducted from February 2021 through March 2023 included patients aged 40 to 99 years with a clinical diagnosis of PD, DLB, MSA, or PAF based on clinical consensus criteria and confirmed by an expert review panel and control participants aged 40 to 99 years with no history of examination findings or symptoms suggestive of a synucleinopathy or neurodegenerative disease. All participants completed detailed neurologic examinations and disease-specific questionnaires and underwent skin biopsy for detection of phosphorylated α-synuclein. An expert review panel blinded to pathologic data determined the final participant diagnosis. Exposure: Skin biopsy for detection of phosphorylated α-synuclein. Main Outcomes: Rates of detection of cutaneous α-synuclein in patients with PD, MSA, DLB, and PAF and controls without synucleinopathy. Results: Of 428 enrolled participants, 343 were included in the primary analysis (mean [SD] age, 69.5 [9.1] years; 175 [51.0%] male); 223 met the consensus criteria for a synucleinopathy and 120 met criteria as controls after expert panel review. The proportions of individuals with cutaneous phosphorylated α-synuclein detected by skin biopsy were 92.7% (89 of 96) with PD, 98.2% (54 of 55) with MSA, 96.0% (48 of 50) with DLB, and 100% (22 of 22) with PAF; 3.3% (4 of 120) of controls had cutaneous phosphorylated α-synuclein detected. Conclusions and Relevance: In this cross-sectional study, a high proportion of individuals meeting clinical consensus criteria for PD, DLB, MSA, and PAF had phosphorylated α-synuclein detected by skin biopsy. Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of phosphorylated α-synuclein in clinical care.

Continuous subcutaneous foslevodopa/foscarbidopa infusion for the treatment of motor fluctuations in Parkinson's disease: Considerations for initiation and maintenance.

Background: As Parkinson's disease (PD) advances, management is challenged by an increasingly variable and inconsistent response to oral dopaminergic therapy, requiring special considerations by the provider. Continuous 24 h/day subcutaneous infusion of foslevodopa/foscarbidopa (LDp/CDp) provides steady dopaminergic stimulation that can reduce symptom fluctuation. Objective: Our aim is to review the initiation, optimization, and maintenance of LDp/CDp therapy, identify possible challenges, and share potential mitigations. Methods: Review available LDp/CDp clinical trial data for practical considerations regarding the management of patients during LDp/CDp therapy initiation, optimization, and maintenance based on investigator clinical trial experience. Results: LDp/CDp initiation, optimization, and maintenance can be done without hospitalization in the clinic setting. Continuous 24 h/day LDp/CDp infusion can offer more precise symptom control than oral medications, showing improvements in motor fluctuations during both daytime and nighttime hours. Challenges include infusion-site adverse events for which early detection and prompt management may be required, as well as systemic adverse events (eg, hallucinations) that may require adjustment of the infusion rate or other interventions. A learning curve should be anticipated with initiation of therapy, and expectation setting with patients and care partners is key to successful initiation and maintenance of therapy. Conclusion: Continuous subcutaneous infusion of LDp/CDp represents a promising therapeutic option for individuals with PD. Individualized dose optimization during both daytime and nighttime hours, coupled with patient education, and early recognition of certain adverse events (plus their appropriate management) are required for the success of this minimally invasive and highly efficacious therapy.

Cost-Effectiveness of Carbidopa-Levodopa Enteral Suspension for Advanced Parkinson's Disease in the United States.

BACKGROUND: Carbidopa/levodopa enteral suspension (CLES) is indicated for the treatment of advanced Parkinson's disease (aPD) with severe motor fluctuations. OBJECTIVE: To determine the cost, quality-adjusted life years (QALY), and cost-effectiveness of CLES compared to the standard-of-care (SoC) for aPD patients in the United States (US), using real-world data. METHODS: A published Markov model, comprising of 25 health states and a death state, (defined by a combination of the Hoehn and Yahr scale and waking time spent in OFF-time) was adapted to estimate the benefits for CLES versus oral SoC over a patient's lifetime in the US healthcare setting. Clinical inputs were based on a clinical trial and a registry study; utility inputs were sourced from the Adelphi-Disease Specific Programmes. RESULTS: CLES compared to SoC was associated with incremental costs ($1,031,791 vs. $1,025,180) and QALY gain (4.61 vs. 3.76), resulting in an incremental cost-effectiveness ratio of $7711/QALY. CONCLUSION: CLES is a cost-effective treatment for aPD patients with medication resistant motor fluctuations. © 2023 AbbVie, Inc and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Comparative Effectiveness of Carbidopa/Levodopa Enteral Suspension and Deep Brain Stimulation on Pill Burden Reduction in Medicare Fee-for-Service Patients with Advanced Parkinson's Disease.

INTRODUCTION: Complex polypharmacy regimens to manage persistent motor fluctuations result in significant pill burden for patients with advanced Parkinson's disease (APD). This study evaluated the effectiveness of carbidopa/levodopa enteral suspension (CLES) and deep brain stimulation (DBS) on reducing pill burden in APD patients. METHODS: We utilized 100% Medicare fee-for-service claims from 2014 to 2018 linked to CLES Patient Support Program (PSP) data. CLES initiators (CLES-I) were propensity matched 1:1 with patients enrolled in PSP who did not initiate treatment (CLES-NI) (N = 188) or undergo DBS, and 1:3 with patients who received DBS (N = 204, N = 612). Average daily pill burden and levodopa equivalent daily dosage (LEDD) were measured at baseline, 0-6 months and 7-12 months follow-up. RESULTS: CLES-I and CLES-NI had higher pill burden than DBS patients at baseline. However, at 6 months post-treatment, CLES-I had significantly fewer pills/day than CLES-NI (4.7 versus 11.4, p < 0.05) and DBS (4.8 versus 7.4, p < 0.05). A significant reduction in pill burden was observed at 0-6 months (46.3%) and 7-12 months (68.3%) follow-up for CLES-I (p < 0.001) versus increased burden for CLES-NI (+10.5%, p < 0.05 and +8.2%, p > 0.05) and insignificant reductions for DBS (-3.9% and -6.1%, p > 0.05). Mean adjusted pill burden showed 57.3% fewer pills at 0-6 months and 74.1% at 7-12 months among CLES-I compared with CLES-NI, and 49.6% and 70.1% reduction compared with DBS. CLES-I showed a decrease in LEDD at 7-12 months compared with baseline (935 to 237 mg) and to CLES-NI (237 mg versus 1112 mg) and DBS patients (236 mg versus 594 mg). CONCLUSION: CLES led to a significant reduction in pill burden and oral LEDD compared with CLES-NI and DBS patients. Pill burden reduction could be considered a treatment goal for patients with APD challenged by complex polypharmacy regimens that interfere with activities of daily living and quality of life.

Management of uncontrollable motor movements in patients with advanced Parkinson's disease rely on oral levodopa-based treatments. Non-motor symptoms such as depression and anxiety are managed with additional oral medications. Over time, higher and more frequent dosing of oral medications is required, resulting in complex medication regimens that impact quality of life and adherence.A real-world study of 10,752 Parkinson's disease patients between 2014 and 2018 evaluated the effectiveness of two device-aided therapies to reduce pill burden, carbidopa/levodopa enteral suspension and deep brain stimulation. Carbidopa/levodopa suspension treatment involves continuous delivery of levodopa to the intestines through a surgical port attached to a portable pump. Brain stimulation involves surgery to attach metal wires to the brain to send electrical pulses via an implanted stimulator.As Parkinson's disease predominately affects the elderly, we compared Medicare patients on carbidopa/levodopa suspension to a matched control group receiving no suspension and to those receiving brain stimulation. Average pill burden/day was measured prior to receiving a device-aided treatment (baseline) and at 0­6 months and 7­12 months post-treatment (follow-up).The top graph shows that by 6-months post-treatment, patients on carbidopa/levodopa suspension required fewer pills than those without suspension (4.7 versus 11.4), with further pill reduction at 12 months (3.5 versus 11.1). The bottom graph shows that by 6 months, patients on carbidopa/levodopa suspension required fewer pills than patients treated with brain stimulation (4.8 versus 7.4), with further reduction at 12 months (3.6 versus 7.0). The reduction in oral pill burden suggests that the carbidopa/levodopa suspension may present an opportunity to simplify treatment regimens.

Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson's disease: a randomised, double-blind, active-controlled, phase 3 trial.

BACKGROUND: Levodopa is the most effective symptomatic therapy for Parkinson's disease, but patients with advanced Parkinson's disease develop motor fluctuations with chronic oral levodopa therapy. Foslevodopa-foscarbidopa is a soluble formulation of levodopa and carbidopa prodrugs that is delivered as a 24-h/day continuous subcutaneous infusion, and we aimed to assess the safety and efficacy of this formulation in patients with advanced Parkinson's disease. METHODS: A 12-week randomised, double-blind, double-dummy, active-controlled study was done at 65 academic and community study centres in the USA and Australia. Patients with levodopa-responsive advanced Parkinson's disease inadequately controlled on current therapy, including at least 2·5 h of average daily off time, were randomly assigned (1:1) to continuous subcutaneous infusion of foslevodopa-foscarbidopa plus oral placebo or to oral immediate-release levodopa-carbidopa plus continuous subcutaneous infusion of placebo solution. Randomisation was stratified by site by means of a permutated-block schedule with a block size of two. The participants, treating investigators, study site personnel, and sponsor were masked to treatment group allocation. The primary and first key secondary endpoint in the hierarchical testing strategy were change from baseline to week 12 in on time without troublesome dyskinesia and off time, respectively; both endpoints were evaluated by an intention-to-treat analysis applying a mixed model for repeated measures analysis. Safety and tolerability were assessed throughout the study. The study is completed and is listed on ClinicalTrials.gov, NCT04380142. FINDINGS: Between Oct 19, 2020, and Sept 29, 2021, of 270 participants screened and 174 enrolled, 141 were randomly assigned and received continuous subcutaneous infusion of foslevodopa-foscarbidopa plus oral placebo capsules (n=74) or oral encapsulated immediate-release levodopa-carbidopa plus continuous subcutaneous infusion of placebo solution (n=67). Compared with levodopa-carbidopa, foslevodopa-foscarbidopa showed a significantly greater increase in on time without troublesome dyskinesia (model-based mean [SE] 2·72 [0·52] vs 0·97 [0·50] h; difference 1·75 h, 95% CI 0·46 to 3·05; p=0·0083) and a significantly greater reduction in off time (-2·75 [0·50] vs -0·96 [0·49] h; difference -1·79 h, -3·03 to -0·54; p=0·0054). Hierarchical testing ended after the first secondary endpoint. Adverse events were reported in 63 (85%) of 74 patients in the foslevodopa-foscarbidopa group versus 42 (63%) of 67 in the levodopa-carbidopa group, and incidences of serious adverse events were similar between the groups (six [8%] of 74 vs four [6%] of 67, respectively). The most frequent adverse events in the foslevodopa-foscarbidopa group were infusion site adverse events (erythema 20 [27%]), pain 19 [26%]), cellulitis (14 [19%]), and oedema (nine [12%]), most of which were non-serious and mild-moderate in severity. The only system organ class that had more than one serious adverse event in the foslevodopa-foscarbidopa group was infections and infestations (catheter site cellulitis [one [1%]] and infusion site cellulitis [one [1%]). Adverse events led to premature discontinuation of study drug in 16 (22%) of 74 participants in the foslevodopa-foscarbidopa group versus one (1%) of 67 participants in the oral levodopa-carbidopa group. INTERPRETATION: Foslevodopa-foscarbidopa improved motor fluctuations, with benefits in both on time without troublesome dyskinesia and off time. Foslevodopa-foscarbidopa has a favourable benefit-risk profile and represents a potential non-surgical alternative for patients with advanced Parkinson's disease. FUNDING: AbbVie.

Comparative Effectiveness of Carbidopa-Levodopa Enteral Suspension and Deep Brain Stimulation on Parkinson's Disease-Related Pill Burden Reduction in Advanced Parkinson's Disease: A Retrospective Real-World Cohort Study.

INTRODUCTION: In advanced Parkinson's disease (PD), a high pill burden is associated with poor compliance, reduced control of symptoms, and decreased quality of life. We assessed the impact of carbidopa-levodopa enteral suspension (CLES) and deep brain stimulation (DBS) on PD-related pill burden. METHODS: A retrospective cohort analysis was conducted in the IBM MarketScan and Medicare Supplemental databases. Patients with advanced PD, taking only PD medications, and initiating CLES or DBS between 9 January 2015 and 31 July 2019 were identified. CLES patients were matched to DBS patients in a 1:3 ratio based on a propensity score to balance patient characteristics. Pill burden was measured as a 30-day average number of PD-related pills per day and was captured monthly. Pill-free status was evaluated as the percentage of patients receiving CLES or DBS monotherapy. Descriptive statistics were used to compare pill counts and assess the proportion of patients on monotherapy at 6 and 12 months after initiating CLES or DBS. RESULTS: The cohorts included 34 CLES patients matched to 97 DBS patients. A significant reduction in PD-related pill burden was observed at 6 months after initiation of CLES or DBS (∆CLES: -5.62, p < 0.0001; ∆DBS: -1.48, p = 0.0022). PD-related pill burden reduction in CLES patients was significantly greater than in matched DBS patients at 6 months (∆: -4.14, p < 0.0001), which was sustained at 12 months after initiation. At 12 months, nearly three times more CLES patients were pill free than DBS patients (29.41% and 10.31%, respectively, p = 0.0123). CONCLUSIONS: Device-aided therapies such as CLES and DBS are effective in significantly reducing PD-related pill burden. Patients treated with CLES were more likely to achieve pill-free status than patients receiving DBS.

Does the 5-2-1 criteria identify patients with advanced Parkinson's disease? Real-world screening accuracy and burden of 5-2-1-positive patients in 7 countries.

BACKGROUND: The burden of Parkinson's disease (PD) worsens with disease progression. However, the lack of objective and uniform disease classification challenges our understanding of the incremental burden in patients with advanced Parkinson's disease (APD) and suboptimal medication control. The 5-2-1 criteria was proposed by clinical consensus to identify patients with advancing PD. Our objective was to evaluate the screening accuracy and incremental clinical burden, healthcare resource utilization (HCRU), and humanistic burden in PD patients meeting the 5-2-1 screening criteria. METHODS: Data were drawn from the Adelphi Parkinson's Disease Specific Program (DSP™), a multi-country point-in-time survey (2017-2020). People with PD who were naive to device-aided therapy and on oral PD therapy were included. Patients meeting the 5-2-1 screening criteria had one or more of the three clinical indicators of APD: (i) ≥5 doses of oral levodopa/day, OR (ii) "off" symptoms for ≥2 h of waking day, OR (iii) ≥1 h of troublesome dyskinesia. Clinician assessment of PD stage was used as the reference in this study. Clinical screening accuracy of the 5-2-1 criteria was assessed using area under the curve and multivariable logistic regression models. Incremental clinical, HCRU, and humanistic burden were assessed by known-group comparisons between 5 and 2-1-positive and negative patients. RESULTS: From the analytic sample (n = 4714), 33% of patients met the 5-2-1 screening criteria. Among physician-classified APD patients, 78.6% were 5-2-1 positive. Concordance between clinician judgment and 5-2-1 screening criteria was > 75%. 5-2-1-positive patients were nearly 7-times more likely to be classified as APD by physician judgment. Compared with the 5-2-1-negative group, 5-2-1-positive patients had significantly higher clinical, HCRU, and humanistic burden across all measures. In particular, 5-2-1-positive patients had 3.8-times more falls, 3.6-times higher annual hospitalization rate, and 3.4-times greater dissatisfaction with PD treatment. 5-2-1-positive patients also had significantly lower quality of life and worse caregiver burden. CONCLUSIONS: 5-2-1 criteria demonstrated potential as a screening tool for identifying people with APD with considerable clinical, humanistic, and HCRU burden. The 5-2-1 screening criteria is an objective and reliable tool that may aid the timely identification and treatment optimization of patients inadequately controlled on oral PD medications.

Psychometric Properties of Clinical Indicators for Identification and Management of Advanced Parkinson's Disease: Real-World Evidence From G7 Countries.

INTRODUCTION: Standardized and validated criteria to define advanced Parkinson's disease (PD) or identify patient eligibility for device-aided therapy are needed. This study assessed the psychometric properties of clinical indicators of advanced PD and eligibility for device-aided therapy in a large population. METHODS: This retrospective analysis of the Adelphi Parkinson's Disease Specific Programme collected data from device-aided therapy-naïve people with PD in G7 countries. We assessed the presence of 15 clinical indicators of advancing PD and seven indicators of eligibility for device-aided therapy in patients classified with advanced PD or as eligible for device-aided therapy by the treating physician. Accuracy was assessed using area under the curve (AUC) and multivariable logistic regression models. Construct validity was examined via known-group comparisons of disease severity and burden among patients with and without each clinical indicator. RESULTS: Of 4714 PD patients, 14.9% were classified with advanced PD and 17.5% as eligible for device-aided therapy by physician judgment. The presence of each clinical indicator was 1.9- to 7.3-fold more likely in patients classified with advanced PD. Similarly, the presence of device-aided therapy eligibility indicators was 1.8- to 5.5-fold more likely in patients considered eligible for device-aided therapy. All indicators demonstrated high clinical screening accuracy for identifying advanced PD (AUC range 0.84-0.89) and patients eligible for device-aided therapy (AUC range 0.73-0.80). The Unified Parkinson's Disease Rating Scale (UPDRS) score, cognitive function, quality of life, and caregiver burden were significantly worse in indicator-positive patients. CONCLUSION: Specific clinical indicators of advanced PD and eligibility for device-aided therapy demonstrated excellent psychometric properties in a large sample, and thus may provide an objective and reliable approach for patient identification and treatment optimization.

Advanced Parkinson's disease (PD) refers to the stage of disease when motor complications are difficult to manage with standard therapy. Patients reaching this stage of the disease may benefit from a treatment change from pills to the so-called device-aided therapies. However, there is currently no unanimous definition of advanced PD, which makes it challenging to identify suitable candidates for device-aided therapies. There is urgent need to define specific features (or 'clinical indicators') to support healthcare professionals and patients in the identification of advanced PD as well as to define suitability for device-aided therapy. This study aimed to assess the accuracy of 15 clinical indicators and seven device-aided therapy eligibility criteria using information from a large database of 4714 patients in G7 countries. Physicians classified 14.9% of patients as having advanced PD and 17.5% were judged to be eligible for device-aided therapy. Each clinical indicator or device-aided therapy eligibility indicator was detected more frequently in patients classified as having advanced PD and in patients considered eligible for device-aided therapy, respectively. All indicators had high accuracy for identifying advanced PD and device-aided therapy-eligibility. These previously identified clinical indicators of advanced PD and device-aided therapy eligibility may provide an objective and reliable approach for patient screening and treatment optimization.

24-Hour Levodopa-Carbidopa Intestinal Gel: Clinical Experience and Practical Recommendations.

Infusion of levodopa-carbidopa intestinal gel (LCIG; also designated carbidopa-levodopa enteral suspension) for 16 hours is a standard treatment for patients with advanced Parkinson's disease, and clinical observations suggest that 24-hour LCIG infusion may further reduce symptoms. This review provides practical advice on the management of patients transitioning to 24-hour LCIG infusion. We review available clinical data for 24-hour infusion and discuss adjustments to dosing, recommendations for monitoring, and management of patient concerns, based on our clinical experience. Data from multiple studies suggest that LCIG may improve non-motor symptoms. Although few studies have examined 24-hour LCIG infusion, available data indicate that certain patients may benefit from around-the-clock treatment. Studies of 24-hour LCIG infusion are limited by small sample sizes and open-label study designs, which may hamper translation to clinical practice. In our experience, we have found that patients may benefit from 24-hour infusion when reductions in nocturnal symptoms and improvements to quality of sleep are needed. Levodopa-unresponsive freezing of gait or poorly controlled troublesome dyskinesias may also indicate a patient may benefit from 24-hour infusion. Dose adjustments, especially of the nocturnal rate, are typically necessary and, as with 16-hour infusion, patients should be monitored for autonomic dysfunction; overnight wearing off symptoms; weight changes; fluctuations in plasma levels of vitamins B6/B12, folate, and homocysteine; changes in sleep patterns; or worsening of hallucinations, delusions, and/or nightmares. Available data and our clinical experience suggest that 24-hour LCIG may be warranted among selected patients who have poorly controlled nocturnal fluctuations or early morning "off" symptoms.

Prospective Home-use Study on Non-invasive Neuromodulation Therapy for Essential Tremor.

Highlights: This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients. Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use. Methods: This was a prospective, open-label, post-clearance, single-arm study with 263 patients enrolled across 26 sites. Patients were instructed to use the therapy twice daily for three months. Pre-specified co-primary endpoints were improvements on clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (BF-ADL) dominant hand scores. Other endpoints included improvement in the tremor power detected by an accelerometer on the therapeutic device, Clinical and Patient Global Impression scores (CGI-I, PGI-I), and Quality of Life in Essential Tremor (QUEST) survey. Results: 205 patients completed the study. The co-primary endpoints were met (p≪0.0001), with 62% (TETRAS) and 68% (BF-ADL) of 'severe' or 'moderate' patients improving to 'mild' or 'slight'. Clinicians (CGI-I) reported improvement in 68% of patients, 60% (PGI-I) of patients reported improvement, and QUEST improved (p = 0.0019). Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced ≥50% improvement in tremor power. Device-related adverse events (e.g., wrist discomfort, skin irritation, pain) occurred in 18% of patients. No device-related serious adverse events were reported. Discussion: This study suggests that non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction in many essential tremor patients.

The Everyday Cognition Scale in Parkinson's disease.

This brief report describes caregiver ratings on the Everyday Cognition (ECog) scale, a psychometrically robust measure of cognitively driven daily activities that was initially designed for other neurodegenerative conditions, in individuals with Parkinson's disease (PD). In 49 individuals with PD, those with suspected PD dementia had more difficulties across ECog domains than those with normal cognition or mild cognitive impairment. Results from multiple regression analyses revealed that activities captured by the ECog were related to measured cognitive ability, over and above disease duration and demographic factors. The lack of floor and ceiling effects speaks to the potential utility of the instrument in practice and research regarding this population. Preliminary data support the utility of the ECog as a marker of functional impact of cognitive problems in PD, though further research will be required to validate the instrument in this population.

Factor structure of the Montreal Cognitive Assessment items in a sample with early Parkinson's disease.

INTRODUCTION: The Montreal Cognitive Assessment (MoCA) is a frequently utilized cognitive screening tool that has attractive clinical attributes when utilized in individuals with Parkinson's disease. However, the construct validity of this instrument has not been well-characterized in Parkinson's samples. The purpose of this study is to explore the underlying factor structure of the MoCA in individuals with early stage Parkinson's disease. METHOD: Item responses from the MoCA in 357 individuals with Parkinson's disease from the Parkinson's Progression Markers Initiative were analyzed first for frequency of errors and polychoric inter item correlations. This correlation matrix was then analyzed with exploratory factor analysis. RESULTS: Omitting items with ceiling effects, three factors emerged which explained the majority of the variance. These factors were reflective of executive dysfunction, memory, and verbal attention. Scores on the MoCA and all of its subscales were significantly different between individuals with Parkinson's disease-no cognitive impairment and those who met criteria for mild cognitive impairment. CONCLUSIONS: In keeping with prior studies in Parkinson's disease, executive dysfunction seems to underpin performance of many items of the MoCA. Implications of this finding both in terms of optimizing the MoCA for use in this population and further steps to validate the constructs behind the MoCA are discussed.

Placement of the AbbVie PEG-J tube for the treatment of Parkinson's disease in the interventional radiology suite.

The primary treatment for Parkinson's disease is dopaminergic stimulation. Although levodopa has historically been administered orally, maintaining a predictable plasma concentration of the drug is challenging. As a result, enteral administration of carbidopa/levodopa (Duopa) has emerged as a promising tool in the treatment of the disease. This requires placement of an enteric catheter, two of which have been approved by the Food and Drug Administration for delivery of Duopa. The approved tubes are placed using the "peroral" or "pull" technique, a method traditionally requiring endoscopy. This technical note describes placement of the AbbVie PEG-J tube by means of the peroral route while utilizing only sonographic and fluoroscopic guidance. After placing an orogastric tube and achieving percutaneous access to the stomach under fluoroscopic visualization, a snare catheter is advanced through the percutaneous access into the stomach. The orogastric tube is engaged with the snare and retracted, bringing the attached snare with it to the mouth. The AbbVie PEG tube is attached to the snare, pulled back down the esophagus and into the stomach before being retracted through the percutaneous access to the skin. Finally, the AbbVie J tube is advanced through the gastrostomy tube into the proximal jejunum and attached with the provided connectors. As demonstrated, the AbbVie PEG-J tube can be placed safely and effectively using a percutaneous image-guided technique without the use of an endoscope.

Caregiver burden in patients with Parkinson disease undergoing deep brain stimulation: an exploratory analysis.

BACKGROUND: Little is known about caregiver burden in Parkinson disease (PD) patients undergoing brain stimulation (DBS) surgery. OBJECTIVE: The aim of this exploratory analysis was to evaluate whether caregiver burden improves after bilateral subthalamic nucleus (STN) DBS for PD patients and identify baseline factors associated with caregiver burden. METHODS: We analyzed the motor, cognitive and behavioral data of 12 PD patients (9 men/3 women) who underwent bilateral STN DBS and whose caregivers completed the Caregiver Burden Inventory (CBI) both before and approximately 6 months after bilateral STN DBS. RESULTS: Total CBI score did not change from baseline (17.8 ± 10.7) to the 6 month evaluation (18.7 ± 13.1), despite a 29% improvement in the MDS-UPDRS motor score (baseline 40.3 ± 12.1 compared to 28.7 ± 8.4 at 6 months, p = 0.01). Change in total CBI score did not correlate with change in MDS-UPDRS Parts I-IV or MoCA from baseline to 6 months. In post-hoc analyses looking at baseline characteristics that may correlate with caregiver burden, only the disinhibition subscore on the Frontal Systems Behavioral Scale correlated positively with the baseline total CBI score (ρ = 0.763, p = 0.004). CONCLUSION: Caregiver burden for PD patients (as measured by the CBI) does not change 6 months after bilateral STN DBS, despite significant improvement in motor function. Only baseline behavioral problems, specifically disinhibition, correlated with higher baseline caregiver burden. Clinicians may need to better counsel patients on expectations for caregiver burden after DBS.

Intracranial atherosclerosis is associated with progression of neurological deficit in subcortical stroke.

BACKGROUND: Progression of neurological deficit (PND) is a frequent complication of acute subcortical ischemic stroke (SCS). The role of intracranial atherosclerosis (IAS) in PND is controversial. Our goal was to evaluate IAS on admission, as predictor of PND in SCS patients. METHODS: SCS patients were identified from our prospective database from 2004 to 2008. Clinical and laboratory data were collected from charts, and radiographic data from original radiographs. The proximal intracranial arteries were graded as patent, irregular, stenotic, or occlusion. IAS was defined as irregularity or stenosis. PND was defined as a change in the National Institutes of Health Stroke Scale >1 point. RESULTS: Two hundred and two SCS patients were identified. In 14%, PND occurred at a median of 2 days from onset. Univariate analysis by infarct location showed the following to be associated with PND: for anterior circulation infarcts (centrum semiovale/basal ganglia), M1 atherosclerosis (p = 0.042); for posterior circulation infarcts, vertebral artery atherosclerosis (p = 0.018). For both groups, we found a non-significant association with age (p = 0.2) and HbA1c levels (p = 0.095). No association was found with admission glucose levels. Multivariate analysis showed the following association with PND: for anterior circulation infarcts, M1 atherosclerosis (OR 4.7; 95% CI 1.2-18.8; p = 0.03); for pontine infarcts, vertebral artery atherosclerosis (OR 5.8; 95% CI 1.1-29.4; p = 0.033). There was an increase in PND likelihood with an increasing number of atherosclerotic vessels. DISCUSSION: In our cohort of SCS patients, PND was associated with IAS of the responsible vessels. These results suggest a role for IAS in the pathogenesis of PNF in SCS patients.