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.

Long-term results of carbidopa/levodopa enteral suspension across the day in advanced Parkinson's disease: Post-hoc analyses from a large 54-week trial.

Introduction: Carbidopa/levodopa enteral suspension (CLES) previously demonstrated reduction in total daily OFF from baseline by over 4 hours in advanced Parkinson's disease patients across 54 weeks. Evidence on CLES's long-term effectiveness on patterns of motor-symptom control throughout the day remains limited. Methods: We present post-hoc analyses of a large, open-label study of CLES monotherapy (N = 289). Diary data recorded patients' motor states at 30-minute intervals over 3 days at baseline and weeks 4, 12, 24, 36, and 54. Adjusted generalized linear mixed models assessed changes from baseline at each timepoint for four outcome measures: time to ON without troublesome dyskinesia (ON-woTD) after waking, motor-symptom control as measured by motor states' durations throughout the day, number of motor-state transitions, and presence of extreme fluctuations (OFF to ON with TD). Results: Patients demonstrated short-term (wk4) and sustained (wk54) improvement in all outcomes compared to baseline. At weeks 4 and 54, patients were more likely to reach ON-woTD over the course of their day (HR: 1.86 and 2.51, both P < 0.0001). Across 4-hour intervals throughout the day, patients also experienced increases in ON-woTD (wk4: 58-65 min; wk54: 60-78 min; all P < 0.0001) and reductions in OFF (wk4: 50-61 min; wk54: 56-68 min; all P < 0.0001). At weeks 4 and 54, patients' motor-state transitions were reduced by about half (IRR: 0.53 and 0.49, both P < 0.0001), and fewer patients experienced extreme fluctuations (OR: 0.22 and 0.15, both P < 0.0001). Conclusion: CLES monotherapy was associated with significant long-term reductions in motor-state fluctuations, faster time to ON-woTD upon awakening, and increased symptom control throughout the day.

Functional Movement Disorders and Deep Brain Stimulation: A Multi-Center Study.

Background: Functional movement disorders (FMD) are a commonly under-recognized diagnosis in patients with underlying neurodegenerative diseases. FMD have been observed in patients undergoing deep brain stimulation (DBS) for Parkinson's disease (PD) and other movement disorders. The prevalence of coexisting FMD among movement disorder-related DBS patients is unknown, and it may occur more often than previously recognized. Methods: We retrospectively assessed the relative prevalence and clinical characteristics of FMD occurring post-DBS, in PD and dystonia patients (FMD+, n = 29). We compared this cohort with age at surgery-, sex-, and diagnosis-matched subjects without FMD post-DBS (FMD-, n = 29). Results: Both the FMD prevalence (0.2%-2.1%) and the number of cases/DBS procedures/year varied across centers (0.15-3.65). A total of nine of 29 FMD+ cases reported worse outcomes following DBS. Although FMD+ and FMD- manifested similar features, FMD+ showed higher psychiatric comorbidity. Conclusions: DBS may be complicated by the development of FMD in a subset of patients, particularly those with pre-morbid psychiatric conditions.

Clinician vs. imaging-based subthalamic nucleus deep brain stimulation programming.

INTRODUCTION: We sought to explore whether electrode visualization tools (EVT) can accurately predict the selection of optimal Deep Brain Stimulation (DBS) electrode contacts. METHODS: Twelve patients with Parkinson's disease (PD) undergoing STN-DBS at The Ohio State University were enrolled in a prospective analysis to evaluate the accuracy of EVT-based vs. standard DBS programming. EVTs were generated by the Surgical Information Sciences (SIS) system to develop a 3D model showing the implanted lead location relative to the STN. Then, imaging-based data were compared to the results of a standard monopolar review to evaluate concordance with clinical data and time spent selecting useable, non-useable, and borderline electrode contacts. RESULTS: A total of 18 DBS leads (n = 68 electrode contacts) were analyzed. The concordance between EVT and standard clinical programming expressed as the kappa coefficient was 0.65 (82.35% raw agreement) for non-useable, 0.52 for useable (64.71% raw agreement), and 0.52 for borderline (58.82% raw agreement). The average time spent determining whether an electrode contact was useable, non-useable, or borderline was 1.46 ± 0.76 min with EVT vs. 61.25 ± 17.47 with standard monopolar review. Eight different categories of side effects were identified, with facial pulling and speech difficulties being observed with the most frequency. The type of side effect observed was accurately predicted using EVT 90% of the time. CONCLUSIONS: This study demonstrates that next-generation EVT-based programming can be implemented into STN-DBS programming workflows with a considerable saving of time and effort spent in testing combinations of stimulation settings, particularly for the identification of non-useable electrode contacts.

Pallidal deep brain stimulation for tardive dystonia: meta-analysis of clinical outcomes.

INTRODUCTION: Tardive dystonia (TD) is a disabling complication of pharmacological therapy with dopaminergic receptor antagonists, usually resistant to oral medications. Several reports have shown that deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) might be effective in TD, but the overall level of evidence remains limited to case reports or small case series. OBJECTIVES: We sought to summarize the collective evidence in support of GPi-DBS for TD using a meta-analytic approach. METHODS: We searched PubMed for human studies reporting tardive dystonia cases treated with GPi-DBS that reported the validated Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) as outcome measure. Data extracted were reviewed for risk of bias. Then, through linear mixed effects modeling of the percent improvement seen on an individual level, we estimated the average improvement effect varying by study. RESULTS: The searching strategy resulted in a total of n = 78 studies, which were screened for eligibility criteria resulting in the inclusion of n = 14 studies, yielding 134 TD patients for the final analyses. The overall estimate improvement in the BFMDRS after GPi-DBS was 66.88 ± 11.96%. The review of individual case reports indicated rare worsening (n = 4) or lack of improvement (n = 3) following GPi-DBS. CONCLUSIONS: Bilateral GPi-DBS can be an effective therapeutic option for severe cases of TD resistant to oral pharmacological therapies, even though rare cases of symptom worsening or lack of improvement have also been reported.

Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis.

INTRODUCTION: Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson's disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD. METHODS: A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson's Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson's Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness. RESULTS: A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5-70.9 years, duration of PD was 9.1-15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL. CONCLUSIONS: This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.

Benefits and Risks of a Staged-Bilateral VIM Versus Unilateral VIM DBS for Essential Tremor.

Background: Despite over 30 years of clinical experience, high-quality studies on the efficacy of bilateral versus unilateral deep brain stimulation (DBS) of the ventral intermediate (VIM) nucleus of the thalamus for medically refractory essential tremor (ET) remain limited. Objectives: To compare benefits and risks of bilateral versus unilateral VIM DBS using the largest ET DBS clinical trial dataset available to date. Methods: Participants from the US St. Jude/Abbott pivotal ET DBS trial who underwent staged-bilateral VIM implantation constituted the primary cohort in this sub-analysis. Their assessments "on" DBS at six months after second-side VIM DBS implantation were compared to the assessments six months after unilateral implantation. Two control cohorts of participants with unilateral implantation only were also used for between-group comparisons. Results: The primary cohort consisted of n = 38 ET patients (22M/16F; age of 65.3 ± 9.5 years). The second side VIM-DBS resulted in a 29.6% additional improvement in the total motor CRST score (P < 0.001), with a 64.1% CRST improvement in the contralateral side (P < 0.001). An added improvement was observed in the axial tremor score (21.4%, P = 0.005), and CRST part B (24.8%, P < 0.001) score. Rate of adverse events was slightly higher after bilateral stimulation. Conclusions: In the largest ET DBS study to date, staged-bilateral VIM DBS was a highly effective treatment for ET with bilateral implantation resulting in greater reduction in total motor tremor scores when compared to unilateral stimulation alone.

Burden of caregiving for cardiovascular dysautonomia in Parkinson's disease.

PURPOSE: We sought to estimate the impact of cardiovascular autonomic neuropathy (cAN) on informal caregivers of patients with Parkinson's disease (PD), defined as individuals providing regular care to a friend, partner, or family member with PD, and to evaluate the mutual relationship between caregiver burden and patient health-related quality of life (HRQoL). METHODS: We enrolled 36 consecutive patients with PD and their informal caregivers. Patients underwent a detailed motor, autonomic, cognitive, and functional assessment. Caregivers were assessed using the Zarit Burden Interview (ZBI). Differences in caregiver burden, expressed by the ZBI score, and strength of association between caregiver burden, cAN, and HRQoL were assessed using analysis of covariance (ANCOVA), logistic regression, and linear regression analyses. Analyses were adjusted for patients' age, PD duration, and motor and cognitive disability, as well as caregivers' age. RESULTS: Moderate-severe caregiver burden was reported in 41.7% of PDcAN+ versus 8.7% of PDcAN- (p < 0.001). The ZBI score was increased in PDcAN+ versus PDcAN- (31.5 ± 3.4 versus 15.2 ± 2.3; p < 0.001), with tenfold higher odds (p = 0.012) of moderate-severe caregiver burden in PDcAN+, even after adjusting for potential confounders. The ZBI score correlated with cAN severity (p = 0.005), global autonomic impairment (p = 0.012), and HRQoL impairment (p < 0.001). CONCLUSION: These results highlight the significant impact of cAN on PD caregivers and the need for targeted interventions addressing this frequently overlooked and insufficiently treated source of nonmotor disability in PD.

Are smartphones and machine learning enough to diagnose tremor?

BACKGROUND: Patients with essential tremor (ET), Parkinson's disease (PD) and dystonic tremor (DT) can be difficult to classify and often share similar characteristics. OBJECTIVES: To use ubiquitous smartphone accelerometers with and without clinical features to automate tremor classification using supervised machine learning, and to use unsupervised learning to evaluate if natural clusterings of patients correspond to assigned clinical diagnoses. METHODS: A supervised machine learning classifier was trained to classify 78 tremor patients using leave-one-out cross-validation to estimate performance on unseen accelerometer data. An independent cohort of 27 patients were also studied. Next, we focused on a subset of 48 patients with both smartphone-based tremor measurements and detailed clinical assessment metrics and compared two separate machine learning classifiers trained on these data. RESULTS: The classifier yielded a total accuracy of 74.4% and F1-score of 0.74 for a trinary classification with an area under the curve of 0.904, average F1-score of 0.94, specificity of 97% and sensitivity of 84% in classifying PD from ET or DT. The algorithm classified ET from non-ET with 88% accuracy, but only classified DT from non-DT with 29% accuracy. A poorer performance was found in the independent cohort. Classifiers trained on accelerometer and clinical data respectively obtained similar results. CONCLUSIONS: Machine learning classifiers achieved a high accuracy of PD, however moderate accuracy of ET, and poor accuracy of DT classification. This underscores the difficulty of using AI to classify some tremors due to lack of specificity in clinical and neuropathological features, reinforcing that they may represent overlapping syndromes.

Differential impact of individual autonomic domains on clinical outcomes in Parkinson's disease.

INTRODUCTION: While autonomic failure is a well-known prognostic factor for more aggressive disease progression in Parkinson's disease (PD), with a three- to sevenfold higher risk of dementia and death within 10 years after the diagnosis, the individual impact of cardiovascular, gastrointestinal, urogenital, thermoregulatory, and pupillomotor autonomic domains on PD clinical outcomes remains unclear. OBJECTIVES: We sought to determine the 5-year risk of developing dementia, falls, postural instability, dysarthria, and dysphagia in PD patients with and without autonomic impairment at baseline and to assess the joint and individual association of each autonomic domain on these key functional outcomes. In addition, we aimed to determine the impact of each autonomic domain on activities of daily living (ADLs) and health-related quality of life (HRQoL). METHODS: We enrolled 65 consecutive PD patients in a 5-year cohort study involving standardized evaluations of autonomic symptoms, orthostatic hypotension, and motor and non-motor features, including cognitive function. Associations were estimated as odds ratio and adjusted for PD duration, age, and baseline motor impairment. RESULTS: Cardiovascular dysautonomia was associated with a sevenfold higher risk of developing dementia (95%CI: 1.154-50.436; p = 0.035) and a fivefold higher risk of falls (95%CI: 1.099-18.949; p = 0.039), as well as significantly higher impairment in ADLs (p = 0.042) and HRQoL (p = 0.031). No relevant associations were found between the other autonomic domains and these outcomes. CONCLUSIONS: Cardiovascular dysautonomia, but not other domains, showed an association with worse 5-year clinical outcomes in PD. Our data suggest a specific role for cardiovascular autonomic dysregulation in the pathogenic mechanisms of PD progression.

Droxidopa reduces postural sway in Parkinson disease patients with orthostatic hypotension.

We evaluate the effect of droxidopa on gait and balance measures in nine patients with Parkinson's disease and neurogenic orthostatic hypotension. Computerized gait/balance analysis showed a significant effect of droxidopa in reducing postural sway. Future studies may determine if such effect translates into improvement in postural reflexes and falls.

Reliable cognitive change following unilateral deep brain stimulation in essential tremor.

Objective: This retrospective analysis assessed regression-based reliable change (RC) of cognition in a sample of essential tremor (ET) patients who underwent unilateral deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM-DBS).Method: Thirty patients (mean age at pre-evaluation = 70.4 ± 6.3 years) underwent neuropsychological evaluation pre- and post-unilateral VIM-DBS placement (mean time between pre and post-evaluation = 13.1 ± 4.0 months). Paired samples t-tests and RC analyses were employed.Results: No significant within-group differences were observed when cognitive scores were compared between evaluations. The vast majority of patients demonstrated stability across pre-and post-surgical evaluations (i.e. 29 out of 30); however, those with high-risk co-morbid medical conditions may be vulnerable to post-surgical cognitive decline as indicated by RC measures.Conclusions: The use of regression-based RC indices to assess individual cognitive changes between pre and post-surgical evaluations control for systematic and measurement errors that can occur over repeated evaluations, and may be able to identify cognitive changes that evade detection in traditional within-group comparisons.

Necessity and feasibility of remote tele-programming of deep brain stimulation systems in Parkinson's disease.

INTRODUCTION: Outcomes after deep brain stimulation (DBS) therapy are dependent on good surgical placement in the target nucleus and optimized stimulation parameters through multiple programming sessions. This often requires frequent travel to a specialized DBS center, which presents a challenge for those with limited access. Recently, the FDA approved a remote tele-programming solution for DBS. To determine if remote tele-programming of DBS systems is beneficial and useful for Parkinson's Disease (PD) patients, Parkinson's Foundation hosted a survey in collaboration with Abbott Labs. METHODS: The survey was conducted to assess the need for telemedicine among PD patients with DBS and the usability of the telehealth interface for DBS teleprogramming. The survey included two validated instruments: The Effective Accessibility and Accommodation survey (EAA) and the Telehealth Usability Questionnaire (TUQ). RESULTS: 47 patients completed the EAA and 41 completed the TUQ. Results from the EAA revealed more than a third of PD patients cannot easily get to a clinic for various reasons, and more than a quarter reported difficulty contacting their clinic for advice. Results from the TUQ revealed overall satisfaction with the DBS remote programming telehealth interface and care provided. The majority of respondents reported that remote tele-programming visits are similar in quality to in-person visits. CONCLUSION: This study provides support for the use of telehealth and tele-programming for DBS management in PD patients. The ability to use remote technologies for care will increase access to DBS and mitigate the disparities that currently prevent access to care.

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.

Vitamins and Infusion of Levodopa-Carbidopa Intestinal Gel.

Levodopa-carbidopa intestinal gel infusion (LCIG) is an established therapy for advanced Parkinson disease (PD), resulting in a significant improvement of quality of life. With increased LCIG adoption worldwide, potential complications due to abnormal vitamin absorption or metabolism have been reported in these patients. Neurologists are unfamiliar with vitamins physiology and pathophysiological mechanisms in case of their deficiency. Unfortunately, clinical and laboratory guidelines related to vitamin monitoring and supplementation in the context of treatment with LCIG are not available. We herein summarize the current knowledge on three vitamins that are reduced with LCIG therapy reporting on their physiology, laboratory testing, and clinical impact of their deficiency/excess. In addition, we proposed an opinion-based recommendation for clinicians treating LCIG patients. Patients and caregivers should be informed about the risk of vitamin deficiency. Vitamin B12, homocysteine, and methylmalonic acid (MMA) should be tested before starting LCIG, six months after and once/year thereafter. Vitamin B6 and folate testing is not universally available but it should be considered if homocysteine is elevated but MMA and/or total vitamin B12 are normal. Prophylaxis of vitamin deficiency should be started as soon as LCIG is implemented, possibly even before. Dietary recommendations are enough in most patients although a subgroup of patients is at higher risk and should receive Vitamin B12 regularly and cycles of B6. Finally, once diagnosed a vitamin deficiency should be readily treated and accompanied by clinical and laboratory monitoring. Resistant cases should receive non-oral routes of administration and possibly discontinue LCIG, even temporarily.

An Update on Gene Therapy Approaches for Parkinson's Disease: Restoration of Dopaminergic Function.

At present there is a significant unmet need for clinically available treatments for Parkinson's disease (PD) patients to stably restore balance to dopamine network function, leaving patients with inadequate management of symptoms as the disease progresses. Gene therapy is an attractive approach to impart a durable effect on neuronal function through introduction of genetic material to reestablish dopamine levels and/or functionally recover dopaminergic signaling by improving neuronal health. Ongoing clinical gene therapy trials in PD are focused on enzymatic enhancement of dopamine production and/or the restoration of the nigrostriatal pathway to improve dopaminergic network function. In this review, we discuss data from current gene therapy trials for PD and recent advances in study design and surgical approaches.

New Frontiers for Deep Brain Stimulation: Directionality, Sensing Technologies, Remote Programming, Robotic Stereotactic Assistance, Asleep Procedures, and Connectomics.

Over the last few years, while expanding its clinical indications from movement disorders to epilepsy and psychiatry, the field of deep brain stimulation (DBS) has seen significant innovations. Hardware developments have introduced directional leads to stimulate specific brain targets and sensing electrodes to determine optimal settings via feedback from local field potentials. In addition, variable-frequency stimulation and asynchronous high-frequency pulse trains have introduced new programming paradigms to efficiently desynchronize pathological neural circuitry and regulate dysfunctional brain networks not responsive to conventional settings. Overall, these innovations have provided clinicians with more anatomically accurate programming and closed-looped feedback to identify optimal strategies for neuromodulation. Simultaneously, software developments have simplified programming algorithms, introduced platforms for DBS remote management via telemedicine, and tools for estimating the volume of tissue activated within and outside the DBS targets. Finally, the surgical accuracy has improved thanks to intraoperative magnetic resonance or computerized tomography guidance, network-based imaging for DBS planning and targeting, and robotic-assisted surgery for ultra-accurate, millimetric lead placement. These technological and imaging advances have collectively optimized DBS outcomes and allowed "asleep" DBS procedures. Still, the short- and long-term outcomes of different implantable devices, surgical techniques, and asleep vs. awake procedures remain to be clarified. This expert review summarizes and critically discusses these recent innovations and their potential impact on the DBS field.

Association of Orthostatic Hypotension With Cerebral Atrophy in Patients With Lewy Body Disorders.

OBJECTIVE: To evaluate whether orthostatic hypotension (OH) or supine hypertension (SH) is associated with brain atrophy and white matter hyperintensities (WMH), we analyzed clinical and radiologic data from a large multicenter consortium of patients with Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: Supine and orthostatic blood pressure (BP) and structural MRI data were extracted from patients with PD and DLB evaluated at 8 tertiary-referral centers in the United States, Canada, Italy, and Japan. OH was defined as a systolic/diastolic BP fall ≥20/10 mm Hg within 3 minutes of standing from the supine position (severe ≥30/15 mm Hg) and SH as a BP ≥140/90 mm Hg with normal sitting BP. Diagnosis-, age-, sex-, and disease duration-adjusted differences in global and regional cerebral atrophy and WMH were appraised with validated semiquantitative rating scales. RESULTS: A total of 384 patients (310 with PD, 74 with DLB) met eligibility criteria, of whom 44.3% (n = 170) had OH, including 24.7% (n = 42) with severe OH and 41.7% (n = 71) with SH. OH was associated with global brain atrophy (p = 0.004) and regional atrophy involving the anterior-temporal (p = 0.001) and mediotemporal (p = 0.001) regions, greater in severe vs nonsevere OH (p = 0.001). The WMH burden was similar in those with and without OH (p = 0.49). SH was not associated with brain atrophy (p = 0.59) or WMH (p = 0.72). CONCLUSIONS: OH, but not SH, was associated with cerebral atrophy in Lewy body disorders, with prominent temporal region involvement. Neither OH nor SH was associated with WMH.