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Competing Interests: Declaration of competing interest H B–S: none. AM: none.

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., Competing Interests: Declarations of competing interest Gurleen Vilkhu: Nothing to declare, Clarisse Goas: Nothing to declare, Jacob Miller: Nothing to declare, Scott M. Kelly: Nothing to declare, Kelsey J. McDonald: Nothing to declare, Anna J. Tsai: Nothing to declare, Alok Dviwedi: Dr. Dwivedi has received grant funding from the NIH and CPRIT and he is a director of the Biostatistics and Epidemiology Consulting Lab (BECL), TTUHSC El Paso, and holds an adjunct associate professor appointment at the University of Cincinnati Department of Neurology and Rehabilitation Medicine., Brian D. Dalm: Nothing to declare, Aristide Merola: Received speaker honoraria from Abbott and Boston Scientific, advisory board compensation from Abbott, Abbvie, Boston Scientific, and Lundbeck, and compensation as Chief Editor from Frontiers in Neurology Experimental Therapeutics., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Optimal placement of Deep Brain Stimulation (DBS) lead is critical to ensure an adequate therapeutic benefit and minimize stimulation-induced side effects., Methods: We reviewed data from 2004 to 2018 of all cases of essential tremor treated with thalamic DBS at the University of Cincinnati. All procedures were performed with the patient awake. Change in parallel trajectory was classified as major repositioning, whereas a change in depth of electrode classified as minor repositioning. The following data were compared between groups (no vs. minor vs. major repositioning): age at surgery, sex, AC-PC length, third ventricle width, cerebral atrophy, small vessel disease burden, and intraoperative tremor control. Univariate and multivariate analyses were conducted to identify factors associated with intraoperative repositioning., Results: Of the 127 encounters with essential tremor, 71 required repositioning (33 major and 38 minor). Comparing procedures with major, minor, and no repositioning, mean number of changes per procedure (4 vs. 1.2 vs 0; p < 0.001) and AC-PC length (26 vs. 27 vs. 27.2 mm; p = 0.021) differed between the three groups. Older age at surgery (OR 1.04, p = 0.042), left side (OR 2.56, p = 0.04) and decrease in AC-PC length (OR 1.33, p = 0.026) were associated with greater odds of any (minor or major) repositioning. A decrease in AC-PC length was associated with greater odds of major repositioning (OR 1.37, p = 0.009)., Conclusion: Intraoperative functional testing may be critical to ensure the accuracy of thalamic DBS targeting based on neuroimaging data, particularly in patients with reduced AC-PC length., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Pisa syndrome is a disabling, medication-resistant, postural abnormality that may affect 7-10% of patients with Parkinson's disease. In this study, we sought to assess the efficacy of botulinum toxin injections in Parkinson's disease-associated Pisa syndrome using a Magnetic Resonance Imaging-, Ultrasonography-, and Electromyography-guided combined approach., Methods: We conducted a pilot study to evaluate the efficacy of botulinum toxin type-A injection in paraspinal and non-paraspinal axial muscles after a Magnetic Resonance Imaging and ultrasound-guided electromyography evaluation. Inclusion criteria were Pisa syndrome, idiopathic Parkinson's disease, and stable dopaminergic medications. Exclusion criteria were previous treatment with botulinum toxin, history of major spine surgery, and severe orthopedic diseases. As primary endpoint, we measured the rate of patients improving by at least 5° in the lateral trunk flexion 2 months after therapy. Secondary endpoints were the extent of lateral trunk flexion improvement, and changes in PS-associated pain/discomfort, measured by the Visual Analogue Scale., Results: Out the 15 patients initially enrolled, 13 completed the follow-up assessment, while 2 joined a rehabilitation program and were excluded from the analyses. The rate of responders was 84.6% (n = 11/13), with 40% average reduction in trunk bending. Pain/discomfort improved in all patients, with 52.2% amelioration at the Visual Analogue Scale. The procedure was well tolerated in all cases, without side effects or complications., Conclusion: A combined imaging and EMG botulinum toxin approach to Pisa syndrome may yield a success rate greater than 80% in Parkinson's disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: We sought to assess the effect of subthalamic deep brain stimulation (STN DBS) on Parkinson's disease (PD)-associated postural abnormalities., Methods: A computerized analysis of posture was used to quantify the thoracolumbar, thoracic, and cervical-occipital ventral angles, as well as the thoracolumbar and cervical-occipital lateral angles from the video-repository of three specialized movement disorder centers (n = 158 patients). Data was extracted from frames from video-recordings in the pre-surgical medication-ON (dopaminergic therapy) and post-surgical stimulation-ON/medication-ON states (STN DBS plus dopaminergic therapy). The sum of the five postural angles (global postural angle) was used to compare pre-vs. post-surgical trunk posture alterations. A multivariate analysis was used to examine the association between changes in the postural angles and demographic or clinical variables., Results: There was a 6.7% amelioration in the global postural angle between the pre- and post-surgical assessments (p = 0.031). Motor response to and pre-surgical dosage of levodopa, male gender, and shorter PD duration were identified as predictors for posture improvement after STN DBS. Cases meeting criteria for lower (n = 2) or upper (n = 1) camptocormia respectively improved by 48.1% in the ventral thoracolumbar angle (from 36.4 ± 0.0° to 18.9 ± 4.2°) and 13.8% in the ventral thoracic angle (from 49.1° to 42.3°). Cases meeting criteria for Pisa syndrome (n = 2) improved by 67.5% in the lateral thoracolumbar angle (from 16.9 ± 2.0° to 5.5 ± 4.7°)., Conclusions: STN DBS has a relatively small but significant effect on PD-associated postural abnormalities, potentially enhancing the effect of dopaminergic medications alone., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: We sought to evaluate if the presence of abnormal circadian loss of nocturnal blood pressure dipping (reverse dipping) is associated with cardiovascular dysautonomia, a major source of morbidity in Parkinson disease., Methods: Consecutive Parkinson disease patients were enrolled in this cross-sectional study between January 2015 and June 2017. All subjects underwent same-day autonomic testing and 24-h ambulatory blood pressure monitoring. Cardiovascular dysautonomia was defined by the presence of at least one moderate or severe cardiovagal and adrenergic test abnormality., Results: We recruited 114 PD patients (79 males; mean age 64 ± 10 years; disease duration 6 ± 4 years). Cardiovascular dysautonomia was present in 32% (36/114). The blood pressure patterns were normal dipping in 28.9% (n = 33), extreme dipping in 6.1% (n = 7), reduced dipping in 32.5% (n = 37), and reverse dipping in 32.5% (n = 37). Reverse dipping was disproportionately prevalent in subjects with cardiovascular dysautonomia (69% vs 15%, p < 0.001). The diagnostic accuracy of reverse dipping in discriminating cardiovascular dysautonomia (AUC 0.791, specificity 84%, sensitivity 69%) was higher than that of bedside blood pressure ascertainment of neurogenic orthostatic hypotension (0.681, 66%, 69%) and supine hypertension (0.641, 78%, 50%)., Conclusions: Reverse nocturnal blood pressure dipping is a marker of cardiovascular dysautonomia in Parkinson disease, which can be screened for with ease and affordability using ambulatory blood pressure monitoring., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Orthostatic hypotension (OH) represents a frequent yet overlooked source of disability in Parkinson disease (PD). In particular, its impact on health care utilization has been insufficiently examined. We sought to determine the differential health care utilization in PD patients with (PDOH+) and without OH (PDOH-)., Methods: We quantified the emergency room (ER) visits, hospitalizations, outpatient clinic evaluations, phone calls, and e-mails from PD patients on whom supine and orthostatic blood pressure (BP) measurements were obtained during routine clinical practice between June 2013 and July 2016. Comparative costs between PDOH+ and PDOH- were adjusted for age, disease duration, motor severity, levodopa equivalent daily dose, and Montreal Cognitive Assessment., Results: From a total of 317 PD patients, 29.3% were classified as PDOH+ (n = 93) and 70.6% as PDOH- (n = 224) over 30.2 ± 11.0 months, in which there were 247 hospitalizations, 170 ER visits, 2386 outpatient evaluations, and 4747 telephone calls/e-mails. After-adjusting for relevant covariates, PDOH+ was associated with more hospitalization days (+285%; p = 0.041), ER visits (+152%; p = 0.045), and telephone calls/e-mails than PDOH- (+142%; p = 0.009). The overall health care-related cost in PDOH+ was 2.5-fold higher than for PDOH- ($25,205 ± $6546 vs. $9831 ± $4167/person/year; p = 0.037)., Conclusion: OH increases health care utilization in PD independently from age, disease duration, motor severity, dopaminergic treatment, and cognitive function., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: We sought to review the landscape of past, present, and future use of technology-based outcome measures (TOMs) in clinical trials of neurodegenerative disorders., Methods: We systematically reviewed PubMed and ClinicalTrials.gov for published and ongoing clinical trials in neurodegenerative disorders employing TOMs. In addition, medical directors of selected pharmaceutical companies were surveyed on their companies' ongoing efforts and future plans to integrate TOMs in clinical trials as primary, secondary, or exploratory endpoints., Results: We identified 164 published clinical trials indexed in PubMed that used TOMs as outcome measures in Parkinson disease (n = 132) or other neurodegenerative disorders (n = 32). The ClinicalTrials.gov search yielded 42 clinical trials using TOMs, representing 2.7% of ongoing trials. Sensor-based technology accounted for over 75% of TOMs applied. Gait and physical activity were the most common targeted domains. Within the next 5 years, 83% of surveyed pharmaceutical companies engaged in neurodegenerative disorders plan to deploy TOMs in clinical trials., Conclusion: Although promising, TOMs are underutilized in clinical trials of neurodegenerative disorders. Validating relevant endpoints, standardizing measures and procedures, establishing a single platform for integration of data and algorithms from different devices, and facilitating regulatory approvals should advance TOMs integration into clinical trials., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Orthostatic hypotension (OH) may frequently be asymptomatic in patients with Parkinson's disease (PD). However, the relationship between symptomatic/asymptomatic status and functional disability remains unclear., Methods: Using orthostatic blood pressure (BP) measurements and the Orthostatic Hypotension Symptom Assessment (OHSA) questionnaire, 121 consecutive PD patients without history of chronic hypertension and not taking alpha-adrenergic antagonists for bladder disorders were classified according to (1) OH symptomatic status, based on presence/absence of orthostatic symptoms (symptomatic OH: OHSA item 1 ≥ 1), and (2) OH severity, based on the magnitude of BP fall on the lying-to-standing test: OH- (<20/10 mmHg); moderate OH+ (≥20/10 mmHg but < 30/15 mmHg); and severe OH+ (≥30/15 mmHg). The primary endpoints were the activities of daily living/instrumental activities of daily living (ADL/iADL) and the Ambulatory Capacity Measure (ACM). Secondary endpoints included PD quality of life (PDQ-8) and prevalence of falls., Results: The overall prevalence of OH+ was 30.6% (37/121 patients), with 62.2% symptomatic (23/37) and 37.8% asymptomatic (14/37). Symptomatic and asymptomatic OH + patients had similar impairments in ADL/iADL and ACM, significantly worse than OH- (p ≤ 0.035). There was a trend for worse ADL/iADL and ACM scores in severe OH + compared to moderate OH+, but both were worse than OH- (p ≤ 0.048). Symptomatic and asymptomatic OH + showed similar impairment in PDQ-8 and higher prevalence of falls compared to OH-., Conclusions: Asymptomatic OH+ was associated with similar impairments in ADL/iADL and ACM than symptomatic OH+. These findings support screening for OH in PD patients regardless of postural lightheadedness., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Levodopa/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., Methods: We 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., Results: STN-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)., Conclusions: STN-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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Our purpose was to determine whether the use of catechol-O-methyltransferase-inhibitors (ICOMT) can reduce the risk of developing levodopa (LD)-induced neuropathy in Parkinson's disease (PD) patients., Methods: A multicentre study of 197 PD patients was performed. 144 were exposed to LD for more than three years (LELD group); 53 simultaneously assumed Entacapone for at least eighteen months (LELD&#95;ICOMT group)., Results: The prevalence of neuropathy in LELD patients was 19.4% whereas it was 5.7% in LELD&#95;ICOMT group with a significant difference (p = 0.025). In LELD&#95;ICOMT cohort the daily LD dose and serum VB12 levels were significantly higher (p < 0.0001), the serum Hcy levels were significantly lower (p = 0.001) compared to LELD group., Conclusion: Our results suggest that ICOMT could have a protective effect on the development of LD-induced neuropathy. Their action probably occurs through the metabolic rebalancing of the one-carbon-pathway cycle and is independent of the PD duration and severity and the duration of LD intake., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Subthalamic nucleus deep brain stimulation (STN-DBS) has been recently compared to a possible "second therapeutic honeymoon" for Parkinson's disease, as it might prevent the development of severe motor complications and lessen the social adjustment associated to disease progression. This study aims to evaluate whether an early surgical treatment could result in better long-term outcomes, comparing the follow-up evolution of 203 parkinsonian patients, treated at different stages of the disease course., Methods: The retrospective allocation to Early- or Late-Stimulated groups was performed in accordance to disease severity at the time of surgery and motor fluctuations duration. Then, the two groups clinical outcomes were compared after more than 8 years of follow-up by means of the Unified Parkinson's Disease Rating Scale, reporting the overall disability experienced by patients during the entire observational period., Results: Subjects receiving an earlier STN-DBS showed a sustained improvement in the activities of daily living and motor complications, never reaching the severe levels of disability reported by Late-Stimulated patients at the time of surgical selection. After ≥8 years of follow-up the Early-Stimulated group still reported a 28.7% lower impairment in activities of daily living and 43.8% lower duration of waking day spent in OFF compared to their pre-surgical basal scores., Conclusion: Although the limitation of a retrospective study design should be considered in the interpretation of data, our findings suggest that an earlier STN-DBS treatment might result in a more precocious stabilization of motor complications, with beneficial effects on the patient's social and professional life autonomy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) represents a valid therapeutic option for advanced Parkinson's disease (PD), leading to a significant amelioration of motor fluctuations and levodopa-induced involuntary movements (IM). This study address the issue of whether stimulation frequency may influence the control of IM in STN-DBS treated patients, comparing the effects of 80 Hz and 130 Hz STN-DBS frequencies in 10 parkinsonian patients with residual IM (dyskinesia in 6 cases and dystonia in 4 cases)., Methods: Patients were evaluated by means of the Rush Dyskinesias Rating Scale (blinded-video analysis) and Unified Parkinson's Disease Rating Scale at 4 different time-points: baseline, shortly after the switch of stimulation frequency from 130 Hz to 80 Hz, after 1 month and 12 months of chronic 80 Hz stimulation., Results: IM improved in most subjects after the switch of stimulation frequency: dyskinesias improved in 6/6 subjects and dystonic features in 3/4 subjects after one month of 80 Hz stimulation. However, the 130 Hz STN stimulation was restored in 4 subjects during the following months, because of a gradual worsening of parkinsonian symptoms. A sustained efficacy on motor features and IM was observed with 80 Hz stimulation frequency in the remaining patients., Conclusions: In this limited cohort of STN-DBS patients, we observed an improvement of residual IM after the switch of stimulation frequency from 130 Hz to 80 Hz. However, a moderate worsening of parkinsonian symptoms was observed in a portion of patients, requiring to return at 130 Hz STN-DBS., (Copyright © 2013 Elsevier Ltd. All rights reserved.)