Levodopa Equivalent Daily Dose Research Articles

Characteristics of fatigue in Parkinson's disease: A longitudinal cohort study.

To assess the prevalence, evolution, clinical characteristics, correlates and predictors of fatigue as well as to investigate the influence of comorbid fatigue on the longitudinal changes in motor and non-motor symptoms over a 2-year longitudinal follow-up period in a large cohort of patients with Parkinson's disease (PD). A total of 2,100 PD patients were enrolled from the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC), and their motor and non-motor symptoms were assessed biennially using comprehensive scales, including the 16-item Parkinson Fatigue Scale (PFS-16). Each PD patient was categorized as PD with or without fatigue on the basis of a cut-off mean PFS-16 score of 3.3. The prevalence of fatigue in our cohort was 36.8%. Compared to PD patients without fatigue, PD patients with fatigue were more likely to be older, have a longer disease duration, and higher baseline levodopa equivalent daily dose (all p < 0.05). Moreover, PD patients with fatigue showed more severe motor and non-motor phenotypes than those without fatigue. Overall, high total Unified Parkinson's Disease Rating Scale (UPDRS) score (odds ratio [OR] = 1.016, 95% confidence interval [CI]: 1.009-1.024), Non-Motor Symptoms Scale score (OR = 1.022, 95% CI: 1.015-1.029), postural instability and gait difficulty (PIGD) subtype (OR = 1.586, 95% CI: 1.211-2.079), presence of excessive daytime sleepiness (EDS; OR = 1.343, 95% CI: 1.083-1.666), and wearing-off (OR = 1.282, 95% CI: 1.023-1.607) were significantly associated with fatigue in PD patients (all p < 0.05). High total UPDRS score at baseline (OR = 1.014, 95% CI: 1.002-1.027, p = 0.028) increased the risk of developing fatigue during follow-up. Although significant, the odds ratios were low and confidence intervals were narrow. Analysis of disease progression showed significant group differences in motor and non-motor symptoms. In comparison with the never-fatigue group, the persistent-fatigue group showed significantly greater progression in motor, autonomic dysfunction, sleep, depression and cognitive symptoms (all p < 0.05). Increased disease severity, presence of the PIGD subtype, EDS, and wearing-off were associated with fatigue in PD patients. Significant subgroup-level differences were observed in the progression of motor and non-motor symptoms across different fatigue subgroups of PD patients.

Central retinal microvasculature damage is associated with orthostatic hypotension in Parkinson’s disease

Orthostatic hypotension (OH) is a common non-motor symptom in Parkinson’s disease (PD). OH can cause cerebral and retinal hypoperfusion and is associated with microvascular damage in PD. Optical coherence tomography angiography (OCTA) is a non-invasive technology that can be used to visualize the retinal microvasculature and detect microvascular damage in PD. In the present study, 51 PD patients (OH+, n = 20, 37 eyes; OH−, n = 32, 61 eyes) and 51 healthy controls (100 eyes) were evaluated. The Unified Parkinson’s Disease Rating Scale III, Hoehn and Yahr scale, Montreal Cognitive Assessment, levodopa equivalent daily dose, and vascular risk factors, including hypertension, diabetes, and dyslipidemia, were investigated. PD patients underwent a head-up tilt (HUT) test. The PD patients had a lower superficial retinal capillary plexus (SRCP) density in the central region than control patients. The PDOH+ group had lower vessel density in the SRCP of the central region compared with the control group and lower vessel density in the DRCP of the central region than the PDOH− and control groups. The changes in systolic and diastolic blood pressure during the HUT test in PD patients showed a negative correlation with the vessel density in the DRCP central region. The presence of OH was a critical factor associated with central microvasculature damage in PD. These findings indicate that OCTA can be a useful and non-invasive tool for detecting microvasculature damage in PD patients.

Timely referral for device-aided therapy in Parkinson's disease. Development of a screening tool

BackgroundTimely referral of Parkinson's disease (PD) patients to specialized centers for treatment with device-aided therapies (DAT) is suboptimal. ObjectiveTo develop a screening tool for timely referral for DAT in PD and to compare the tool with the published 5-2-1 criteria. MethodsA cross-sectional, observational study was performed in 8 hospitals in the catchment area of a specialized movement disorder center in the Northern part of the Netherlands. The target population comprised PD patients not yet on DAT visiting the outpatient clinic of participating hospitals. The primary outcome was apparent eligibility for referral for DAT based on consensus by a panel of 5 experts in the field of DAT. Multivariable logistic regression modelling was used to develop a screening tool for eligibility for referral for DAT. Potential predictors were patient and disease characteristics as observed by attending neurologists. ResultsIn total, 259 consecutive PD patients were included, of whom 17 were deemed eligible for referral for DAT (point prevalence: 6.6%). Presence of response fluctuations and troublesome dyskinesias were the strongest independent predictors of being considered eligible. Both variables were included in the final model, as well as levodopa equivalent daily dose. Decision curve analysis revealed the new model outperforms the 5-2-1 criteria. A simple chart was constructed to provide guidance for referral. Discrimination of this simplified scoring system proved excellent (AUC after bootstrapping: 0.97). ConclusionsAwaiting external validation, the developed screening tool already appears promising for timely referral and subsequent treatment with DAT in patients with PD.

Non-motor effects of deep brain stimulation in Parkinson's disease motor subtypes

IntroductionDeep brain stimulation (DBS) is a well-established treatment for patients with Parkinson's disease (PD) improving quality of life, motor, and non-motor symptoms. However, non-motor effects in PD subtypes are understudied. We hypothesized that patients with ‘postural instability and gait difficulty’ (PIGD) experience more beneficial non-motor effects than ‘tremor-dominant’ patients undergoing DBS for PD. MethodsIn this prospective, observational, international multicentre study with a 6-month follow-up, we assessed the Non-Motor Symptom Scale (NMSS) as primary and the following secondary outcomes: Unified PD Rating Scale-motor examination (UPDRS-III), Scales for Outcomes in PD (SCOPA)-activities of daily living (ADL) and -motor complications, PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose (LEDD). We analysed within-group longitudinal changes with Wilcoxon signed-rank test and Benjamini-Hochberg correction for multiple comparisons. Additionally, we explored outcome between-group differences of motor subtypes with Mann-Whitney U-tests. ResultsIn 82 PIGD and 33 tremor-dominant patients included in this study, baseline NMSS total scores were worse in PIGD patients, both groups experienced postoperative improvements of the NMSS sleep/fatigue domain, and between-group differences in postoperative outcomes were favourable in the PIGD group for the NMSS total and miscellaneous domain scores. ConclusionsThis study provides evidence of a favourable outcome of total non-motor burden in PIGD compared to tremor-dominant patients undergoing DBS for PD. These differences of clinical efficacy on non-motor aspects should be considered when advising and monitoring patients with PD undergoing DBS.

Sex Differences in Motor and Non-Motor Symptoms among Spanish Patients with Parkinson's Disease.

Sex plays a role in Parkinson's disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD. PD patients who were recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis were conducted. Univariate analyses and general linear model repeated measure were used. At baseline, data from 681 PD patients (mean age 62.54 ± 8.93) fit the criteria for analysis. Of them, 410 (60.2%) were males and 271 (39.8%) females. There were no differences between the groups in mean age (62.36 ± 8.73 vs. 62.8 ± 9.24; p = 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11; p = 0.259). Symptoms such as depression (p < 0.0001), fatigue (p < 0.0001), and pain (p < 0.00001) were more frequent and/or severe in females, whereas other symptoms such as hypomimia (p < 0.0001), speech problems (p < 0.0001), rigidity (p < 0.0001), and hypersexuality (p < 0.0001) were more noted in males. Women received a lower levodopa equivalent daily dose (p = 0.002). Perception of quality of life was generally worse in females (PDQ-39, p = 0.002; EUROHIS-QOL8, p = 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males (p = 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females (p = 0.001). The present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed.

Identifying the therapeutic zone in globus pallidus deep brain stimulation for Parkinson's disease.

The globus pallidus internus (GPI) has been demonstrated to be an effective surgical target for deep brain stimulation (DBS) treatment in patients with medication-refractory Parkinson's disease (PD). The ability of neurosurgeons to define the area of greatest therapeutic benefit within the globus pallidus (GP) may improve clinical outcomes in these patients. The objective of this study was to determine the best DBS therapeutic implantation site within the GP for effective treatment in PD patients. The authors performed a retrospective review of 56 patients who underwent bilateral GP DBS implantation at their institution during the period from January 2015 to January 2020. Each implanted contact was anatomically localized. Patients were followed for stimulation programming for at least 6 months. The authors reviewed preoperative and 6-month postsurgery clinical outcomes based on data from the Unified Parkinson's Disease Rating Scale Part III (UPDRS III), dyskinesia scores, and levodopa equivalent daily dose (LEDD). Of the 112 leads implanted, the therapeutic cathode was most frequently located in the lamina between the GPI external segment (GPIe) and the GP externus (GPE) (n = 40). Other common locations included the GPE (n = 24), the GPIe (n = 15), and the lamina between the GPI internal segment (GPIi) and the GPIe (n = 14). In the majority of patients (73%) a monopolar programming configuration was used. At 6 months postsurgery, UPDRS III off medications (OFF) and on stimulation (ON) scores significantly improved (z = -4.02, p < 0.001), as did postsurgery dyskinesia ON scores (z = -4.08, p < 0.001) and postsurgery LEDD (z = -4.7, p < 0.001). Though the ventral GP (pallidotomy target) has been a commonly used target for GP DBS, a more dorsolateral target may be more effective for neuromodulation strategies. The assessment of therapeutic contact locations performed in this study showed that the lamina between GPI and GPE used in most patients is the optimal central stimulation target. This information should improve preoperative GP targeting.

Both Motor and Non-Motor Fluctuations Matter in the Clinical Management of Patients with Parkinson's Disease: An Exploratory Study.

Non-motor symptoms (NMS) characterize the Parkinson's disease (PD) clinical picture, and as well as motor fluctuations, PD patients can also experience NMS fluctuations (NMF). The aim of this observational study was to investigate the presence of NMS and NMF in patients with PD using the recently validated Non-Motor Fluctuation Assessment questionnaire (NoMoFa) and to evaluate their associations with disease characteristics and motor impairment. Patients with PD were consecutively recruited, and NMS, NMF, motor impairment, motor fluctuations, levodopa-equivalent daily dose, and motor performance were evaluated. One-third of the 25 patients included in the study (10 females, 15 males, mean age: 69.9 ± 10.3) showed NMF, and patients with NMF presented a higher number of NMS (p < 0.01). Static NMS and NoMoFa total score were positively associated with motor performance assessed with the Global Mobility Task (p < 0.01 and p < 0.001), and the latter was also correlated with motor impairment (p < 0.05) but not with motor fluctuations. Overall, this study shows evidence that NMF are frequently reported by mild-to-moderate PD patients and associated with an increased number of NMS. The relationship between NoMoFa total score and motor functioning highlights the importance of understanding the clinical role of NMS and NMF in the management of PD patients.

Are the EEG microstates correlated with motor and non-motor parameters in patients with Parkinson's disease?

ObjectivesThis study compared electroencephalography microstates (EEG-MS) of patients with Parkinson's disease (PD) to healthy controls and correlated EEG-MS with motor and non-motor aspects of PD. MethodsThis cross-sectional exploratory study was conducted with patients with PD (n = 10) and healthy controls (n = 10) matched by sex and age. We recorded EEG-MS using 32 channels during eyes‐closed and eyes‐open conditions and analyzed the four classic EEG-MS maps (A, B, C, D). Clinical information (e.g., disease duration, medications, levodopa equivalent daily dose), motor (Movement Disorder Society - Unified Parkinson Disease Rating Scale II and III, Timed Up and Go simple and dual-task, and Mini-Balance Evaluation Systems Test) and non-motor aspects (Mini-Mental State Exam [MMSE], verbal fluency, Hospital Anxiety and Depression Scale, and Parkinson's Disease Questionnaire-39 [PDQ-39]) were assessed in the PD group. Mann-Whitney U test was used to compare groups, and Spearman's correlation coefficient to analyze the correlations between coverage of EEG-MS and clinical aspects of PD. ResultsThe PD group showed a shorter duration of EEG-MS C in the eyes-closed condition than the control group. We observed correlations (rho = 0.64 to 0.82) between EEG-MS B, C, and D and non-motor aspects of PD (MMSE, verbal fluency, PDQ-39, and levodopa equivalent daily dose). ConclusionAlterations in EEG-MS and correlations between topographies and cognitive aspects, quality of life, and medication dose indicate that EEG could be used as a PD biomarker. Future studies should investigate these associations using a longitudinal design.

Assessing the risks of treatment in Parkinson disease psychosis: An in-depth analysis.

Parkinson disease (PD) psychosis (PDP) is a disabling non-motor symptom. Pharmacologic treatment is limited to pimavanserin, quetiapine, and clozapine, which do not worsen parkinsonism. A Food and Drug Administration black box warning exists for antipsychotics, suggesting increased mortality in elderly patients with dementia. However, the reasons for higher mortality are unknown. Expanding on prior work exploring mortality in treated PDP patients, we conducted a retrospective comparison to understand the links between treatment regimen, clinical characteristics, and negative outcomes. Electronic medical record data extraction included clinically diagnosed PD patients between 4/29/16-4/29/19 and excluded patients with primary psychiatric diagnoses or atypical parkinsonism. Mortality and clinical characteristics during the study period were compared between untreated patients and those receiving pimavanserin, quetiapine, or both agents (combination). Mortality analyses were adjusted for age, sex, levodopa equivalent daily dose (LEDD), and dementia. The pimavanserin group (n = 34) had lower mortality than the untreated group (n = 66) (odds ratio = 0.171, 95% confidence interval: 0.025-0.676, p = 0.026). The untreated group had similar mortality compared to the quetiapine (n = 147) and combination (n = 68) groups. All treated groups had a higher LEDD compared to the untreated group, but no other differences in demographics, hospitalizations, medical comorbidities, medications, or laboratory values were found between the untreated and treated groups. PDP patients receiving pimavanserin had lower mortality than untreated patients. We found no other clear differences in clinical characteristics to explain the mortality risk. Prospective randomized trials are needed to definitively identify the optimal PDP treatment regimen and associated risks.

Characteristics of behavioural addiction in Parkinson’s disease patients with self-reported impulse control disorder and controls matched for levodopa equivalent dose: a matched case–control study

Impulse control disorders (ICD) in Parkinson’s disease (PD) frequently occur, not always as a direct consequence of dopaminergic medication. This study investigated premorbid personality traits and behavioural characteristics in non-demented PD patients with self-reported symptoms of ICD (PD-srICD). From a total of 200 non-demented PD patients who filled out questionnaires assessing symptoms and severity of ICD, those were classified as PD-srICD (n = 32) who reported current occurrence of at least one compulsive behaviour (gambling, sexual behaviour, buying behaviour, or eating). As a control group, 32 patients with no self-reported ICD symptoms were matched for levodopa equivalent daily dose. The demographic, clinical, and premorbid personality profiles were compared between both groups. Frequency of psychological characteristics indicating substance use disorder was evaluated in patients with PD-srICD. Patients with PD-srICD were more frequently male, younger at examination, had earlier PD onset, more depression, higher non-motor burden, less quality of life (p < 0.05, respectively), and more frequently reported premorbid sensation seeking/novelty orientation (p = 0.03) and joyful experience of stress (p = 0.04) than patients in the control group. Of patients with PD-srICD, 90.6% reported at least one behavioural characteristic of substance use disorder, most frequently positive expectations following ICD behaviour and illusional beliefs about its behavioural control. Signs of addiction were common among patients with PD-srICD. Therefore, the profile of psychological characteristics in patients with PD-srICD resembled that of patients with substance use disorder. It can be concluded that dopamine replacement therapy (DRT) alone does not account for PD-srICD and that thorough psychological diagnostics are recommended.

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.

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. We utilized 100% Medicarefee-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, 0-6months and 7-12months follow-up. CLES-I and CLES-NI had higher pill burden than DBS patients at baseline. However, at 6months 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 0-6months (46.3%) and 7-12months (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 0-6months and 74.1% at 7-12months 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 7-12months compared with baseline (935 to237mg) and to CLES-NI (237mg versus 1112mg) and DBS patients (236mg versus 594mg). 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.

An Institutional Experience of Directional Deep Brain Stimulation and a Review of the Literature

IntroductionDirectional deep brain stimulation (dDBS) has been suggested to have a similar therapeutic effect when compared with the traditional omnidirectional DBS, but with an improved therapeutic window that yields optimized clinical effect owing to the ability to better direct, or “steer,” electric current. We present our single-center, retrospective analysis of our experience in the use of dDBS in patients with movement disorders and provide a review of the literature. Materials and MethodsWe identified all patients with Parkinson disease (PD) and essential tremor (ET) who received a dDBS system between 2018 and 2022 and retrospectively examined characteristics of their longitudinal treatment. A total of 70 leads were identified across 42 patients (28 PD, 14 ET). ResultsThree types of systems were implemented (single-segment activation, 45.2% of patients; multiple independent current control, 50.0%; and local field potential sensing-enabled, 4.7%). The subthalamic nucleus or globus pallidus internus was targeted in PD, and the ventral intermediate nucleus of the thalamus in ET. Across the entire cohort (n = 70 leads), at initial programming, 54.2% of leads (n = 38) were programmed using directional stimulation. At the most recent reprogramming, 58.6% of leads (n = 41) implemented directionality. In patients with PD, the average decrease in levodopa-equivalent daily dose at six months after implantation was 35.4% ± 39.2%. Despite the ability to steer current to relieve stimulation-induced side effects, ten leads in six patients required surgical revision owing to electrode malposition. ConclusionsWe show wide adaptability and implementation of directional stimulation, adding to the growing compendium of real-world uses of dDBS therapy. We used directionality to improve clinical response in both patients with PD and patients with ET and found that its programming flexibility was used at high rates long after implantation and initial programming. In patients with PD, dDBS led to a significant reduction in dopaminergic medication, suggesting sustained clinical improvement. Nonetheless, accurate surgical placement remains necessary to ensure optimal clinical outcomes.

1218 GREY MATTER VOLUME AND NEUROTRANSMITTER RECEPTORS ABNORMALITIES IN PARKINSON’S DISEASE PSYCHOSIS: A META-ANALYSIS

Abstract Introduction Recent evidence suggests extensive grey matter abnormalities in Parkinson’s Disease Psychosis (PDP), as well as dysfunction of dopaminergic and serotonergic receptors. However, findings remain unclear. This meta-analysis aimed to identify neuroanatomical correlates of PDP and to examine the relationship between grey matter and key candidate receptors. Method Peak coordinates were extracted from structural magnetic resonance imaging (MRI) studies (identified through systematic searches on PubMed, Web of Science, and Embase) for PDP patients and Parkinson's Disease patients without psychosis (PDnP) and were analysed using Seed-based d mapping with permutation of subject images (SDM-PSI). Gene expression data for dopaminergic (D1/D2) and serotonergic (5-HT2a/5-HT1a) receptors were extracted from the Allen Human Brain Atlas, probe-to-gene re-annotation data were downloaded from Arnatkevic̆iūtė et al. (Neuroimage, 2019;189:353-67) and parcellated on 78 regions of the Desikan-Killiany brain atlas. Effect-size estimates, extracted from the SDM-PSI analysis for these 78 regions as a measure of grey matter in PDP patients, were entered in multiple regression models. Results 10 studies were included in the meta-analysis (PDP, n= 211; mean age = 69.01 years, 52.1% males; PDnP, n = 298, mean age = 67.34 years, 41.9 % males). Reduction in grey matter was observed in parieto-temporo-occipital regions in PDP patients (uncorrected, p &amp;lt; 0.05). When controlling for PD medications, expressed in Levodopa equivalent daily dose (LEDD), results remained significant (uncorrected, p &amp;lt; 0.05). 5-HT2a and 5-HT1a gene receptor expressions were associated with estimates of grey matter volume (5-HT2a, b=-0.20, p=0.01, adjusted for LEDD, b=-0.18, p=0.03; 5-HT1a, b=0.11, p=0.02, adjusted for LEDD, b=0.12, p=0.01). Conclusion We observed lower cortical volume in parieto-temporo-occipital areas, which are involved in information processing, integration, and attention in PDP compared to PDnP patients. We also reported an association between regional brain expression of serotonergic receptors and grey matter volume suggesting a role of serotonin in PDP.

The mortality of patients with Parkinson's disease with deep brain stimulation.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in improving motor function in patients with Parkinson's disease (PD). This study aimed to investigate mortality associated with bilateral STN DBS in patients with PD and to assess the factors associated with mortality and causes of death after DBS. We reviewed the medical records of 257 patients with PD who underwent bilateral STN DBS at the Movement Disorder Center at Seoul National University Hospital between March 2005 and November 2018. Patients were evaluated preoperatively, at 3, 6, and 12 months after surgery and annually thereafter. The cause and date of death were obtained from interviews with caregivers or from medical certificates at the last follow-up. Of the 257 patients with PD, 48 patients (18.7%) died, with a median time of death of 11.2 years after surgery. Pneumonia was the most common cause of death. Older age of disease onset, preoperative falling score while on medication, and higher preoperative total levodopa equivalent daily dose were associated with a higher risk of mortality in time-dependent Cox regression analysis. These results confirm the mortality outcome of STN DBS in patients with advanced PD.

Social Cognition in Parkinson's Disease: A Case-Control Study.

Social cognition is the study of how people make sense of themselves and others. Impairment in several domains of social cognition is increasingly being recognized in Parkinson's disease (PD). We aimed to study multiple domains of social cognition in Indian PD patients using a culturally appropriate, validated instrument. We recruited 52 individuals with PD and 31 healthy volunteers (HV) and used the Social Cognition Rating Tools in Indian Setting (SOCRATIS) tool to assess theory of mind (ToM), attributional biases and social cue perception. Quality of life (QoL) was assessed using the PDQOL scale. Baseline characteristics were comparable between PD and HV. The mean (SD) FOT index (first order ToM index) was 0.86(0.18) in PD and 0.99(0.07) in HV [P < 0.001]. The PD group showed higher Externalizing Bias [EB, 4.42(3.91)], compared to HV [1.58(3.22), P=0.001]. The mean (SD) Faux Pas Composite Index (FPCI ALT) was 0.69(0.09) in PD and 0.78(0.13) in HV [P < 0.001]. Social cognition indices were not associated with QoL in PD. Clinical parameters-age, gender, HAM-D, MOCA, education, levodopa equivalent daily dose of medication, number of PD drugs and trihexyphenidyl use did not predict social cognition. PD patients were less successful than age, gender matched controls in understanding social situations and other's thought processes and had higher tendency to attribute undesirable events to external causes. Deficits in social cognition did not impair the quality of life.

Efficacy of Deep Brain Stimulation for Camptocormia in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Camptocormia is one of the most common postural disorders of Parkinson's disease (PD) which has limited treatment options. In this review, we summarize the efficacy of deep brain stimulation (DBS) for camptocormia in PD. The PubMed (https://pubmed.ncbi.nlm.nih.gov/) and EMBASE databases (https://www.embase.com/) were searched for the terms "Parkinson Disease" and "camptocormia" in combination with "deep brain stimulation". We then explored the efficacy of DBS for camptocormia by statistical analysis of the bending angle, the Unified Parkinson's Disease Rating Scale III (UPDRS-III) and L-dopa equivalent daily dose (LEDD), and by evaluating the prognosis after DBS. Twenty articles that reported results for 152 patients were included in this review. These comprised 136 patients from 16 studies who underwent subthalamic nucleus deep brain stimulation (STN-DBS), and 13 patients from 3 studies who underwent globus pallidus internus deep brain stimulation (GPi-DBS). One study used both STN-DBS (2 patients) and GPi-DBS (one patient). After 3-21 months of follow-up, the mean bending angle during the Off-period was significantly reduced compared to pre-DBS (31.5 ± 21.4 vs. 53.6 ± 22.7, respectively; p < 0.0001). For the STN-DBS trials, the mean post-operative bending angles during both Off- and On-periods were significantly reduced compared to pre-operative (32.1 ± 22.7 vs. 55.4 ± 24.1, p = 0.0003; and 33.1 ± 21.5 vs. 43.7 ± 20.6, p = 0.0003, respectively). For GPi-DBS, the mean bending angle post-DBS during the Off-period was considerably lower than pre-DBS (28.5 ± 10.7 vs. 42.9 ± 9.9, p < 0.001). The decrease in bending angle after DBS was negatively correlated with the duration of camptocormia (R = - 0.433, p = 0.013), whereas positively associated with the pre-bending angle (R = 0.352, p = 0.03). DBS is an effective treatment for camptocormia in PD. Patients in the early stage of camptocormia with more significant bending angle may benefit more from DBS.

Deep brain stimulation for Parkinson's disease: A case for patient empowerment

Deep brain stimulation for Parkinson's disease: A case for patient empowerment

Stimulation of the Presupplementary Motor Area Cluster of the Subthalamic Nucleus Predicts More Consistent Clinical Outcomes.

The development of diffusion tensor imaging and tractography has raised increasing interest in the functional targeting of deep brain stimulation of the subthalamic nucleus (STN) in Parkinson disease. To study, using deterministic tractography, the functional subdivisions of the STN and hyperdirect white matter connections located between the STN and the medial frontal cortex, especially the presupplementary motor area (preSMA), SMA, primary motor area (M1), and dorsolateral premotor cortex, and to study retrospectively whether this information correlates with clinical outcome. Twenty-two patients with Parkinson disease who underwent STN deep brain stimulation were analyzed. Using 3 T MR images, the medial frontal cortex was manually segmented into preSMA, SMA, M1, and dorsolateral premotor cortex, which were then used to determine the functional subdivisions of the lateral border of the STN. The intersectional quantities of the volume of activated tissue (VAT) and the hyperdirect white matter connections were calculated. The results were combined with clinical data including unilateral 12-month postoperative motor outcome and levodopa equivalent daily dose. Stimulated clusters of the STN were connected mostly to the cortical SMA and preSMA regions. Patients with primarily preSMA cluster stimulation (presmaVAT% ≥ 50%) had good responses to the treatment with unilateral motor improvement over 40% and levodopa equivalent daily dose reduction over 60%. Larger VAT was not found to correlate with better patient outcomes. Our study is the first to suggest that stimulating, predominantly, the STN cluster where preSMA hyperdirect pathways are located, could be predictive of more consistent treatment results.

Correlation of response to subthalamic deep brain stimulation in Parkinson’s disease patients with striatal dopamine transporter density on 99mtc-TRODAT-1 SPECT

ABSTRACT Background Deep brain stimulation (DBS) is a surgical approach with electrical stimulation of certain parts of the brain, which reduce Parkinson’s disease (PD) symptoms. Since the loss of dopaminergic neurons in the substantia nigra is the main pathophysiology of PD, we aimed to evaluate the association of response to DBS with preoperative dopamine transporter density (DAT) and its postoperative changes in PD patients who underwent the bilateral implantation of the electrodes in the subthalamic nucleus (STN). Method A prospective evaluation of Parkinson’s disease patients who underwent STN-DBS for 2 years was done. 99mTc-TRODAT-1 single-photon emission computed tomography (SPECT) scan and assessment of PD using unified Parkinson’s disease rating scale (UPDRS) III were performed in both pre- and post-operation states. The correlation of response to DBS after 6 months was assessed with baseline findings and postoperative changes of 99mTc-TRODAT-1 SPECT parameters. Results Compared to the preoperative state, UPDRS III scores and Levodopa equivalent daily dose (LEDD) were significantly decreased after DBS. However, in 17 patients who underwent both pre-and post-operative 99mTc-TRODAT-1 SPECT, no significant change was seen in any quantitative parameters, including right and left striatal-binding ratio (SBR) as well as striatal asymmetry index (SAI). No significant correlation was also found between the percent of UPDRS III change after DBS and values of preoperative SBRs. The percentage of LEDD reduction also showed no significant correlation with the preoperative state of 99 m-TRODAT-1 SPECT. Conclusion Our results showed that the mechanism of DBS action is not accompanied by short-term compensation of DAT in basal ganglia in severely advanced PD

Neural correlates of impulsive compulsive behaviors in Parkinson’s disease: A Japanese retrospective study

BackgroundImpulsive compulsive behaviors (ICBs) often disturb patients with Parkinson’s Disease (PD), of which impulse control disorder (ICD) and dopamine dysregulation syndrome (DDS) are two major subsets. The nucleus accumbens (NAcc) is involved in ICB; however, it remains unclear how the NAcc affects cortical function and defines the different behavioral characteristics of ICD and DDS. ObjectivesTo identify the cortico-striatal network primarily involved in ICB and the differences in these networks between patients with ICD and DDS using structural and resting-state functional magnetic resonance imaging. MethodsPatients with PD were recruited using data from a previous cohort study and divided into those with ICB (ICB group) and without ICB (non-ICB group) using the Japanese version of the Questionnaire for Impulsive Compulsive Disorders in Parkinson’s Disease (J-QUIP). From these two groups, we extracted 37 pairs matched for age, sex, disease duration, and levodopa equivalent daily dose of dopamine agonists. Patients with ICB were further classified as having ICD or DDS based on the J-QUIP subscore. General linear models were used to compare gray matter volume and functional connectivity (FC) of the NAcc, caudate, and putamen between the ICB and non-ICB groups and between patients with ICD and those with DDS. ResultsWe found no significant differences in gray matter volumebetween the ICB and non-ICB groups or between patients with ICD and those with DDS. Compared with the non-ICB group, the FC of the right NAcc in the ICB group was lower in the bilateral ventromedial prefrontal cortex and higher in the left middle occipital gyrus. Furthermore, patients with DDS showed higher FC between the right putamen and left superior temporal gyrus and higher FC between the left caudate and bilateral middle occipital gyrus than patients with ICD. In contrast, patients with ICD exhibited higher FC between the left NAcc and the right posterior cingulate cortex than patients with DDS. ConclusionsThe functionally altered network between the right NAcc and ventromedial prefrontal cortex was associated with ICB in PD. In addition, the surrounding cortico-striatal networks may differentiate the behavioral characteristics of patients with ICD and those with DDS.