Motor Complications In Patients Research Articles

Validity and reliability of the Italian version of the short Parkinson's evaluation scale (SPES/SCOPA)

BackgroundIn the medical and rehabilitative field, it is essential to employ tools such as evaluation scales and performance tests to assess the impact of Parkinson's disease on QoL of affected individuals. The Short Parkinson's Evaluation Scale (SPES) is a reliable and valid tool, applicable both in research and clinical practices, useful in assessing motor damage, activities of daily living, and motor complications in patients with Parkinson's disease. The aim of the study is to investigate validity and reliability of the Italian version of the SPES-SCOPA scale. MethodsTranslation and cultural adaptation were performed. Included patients had diagnosis of Parkinson's disease, no concurrent pathologies, MiniMental test score above 2 and signed informed consent; they were recruited at the Department of Human Neurosciences in Sapienza University of Rome, from February 2023 to November 2023. Test-retest reliability was evaluated through Intraclass Correlation Coefficient (ICC), internal consistency was assessed using Cronbach's Alpha and construct validity using Pearson's correlation between SPES-SCOPA and the gold standard PDQ-39. Results101 patients were recruited. Inter-rater evaluation was conducted on 62 patients, while 39 underwent an intra-rater assessment. The analysis showed statistically significant data with a Cronbach's Alpha value of 0.89 for the entire scale; test-retest reliability results are statistically significant for all subscales. Correlation between PDQ-39 domains and SPES/SCOPA subscales were statistically significant for most measurements. ConclusionThis research shows that the Italian version of SPES-SCOPA scale has excellent psychometric properties.

Altered gut microbiota in Parkinson's disease patients with motor complications

IntroductionParkinson's disease (PD) is associated with gut dysbiosis. However, whether gut dysbiosis can cause motor complications is unclear. MethodsSubjects were enrolled from four independent movement disorder centers in Japan. We performed 16S ribosomal RNA gene sequence analysis of gut microbiota. Relative abundance of gut microbiota and relationships between them and clinical characteristics were statistically analyzed. Analysis of co-variance (ANCOVA) was used to assess altered gut microbiota associated with wearing-off or dyskinesia. ResultsWe enrolled 223 patients with PD. Wearing-off was noted in 47.5% of patients and dyskinesia in 21.9%. We detected 98 genera of bacteria. Some changes in the gut microbiota were observed in patients with PD and motor complications. After Bonferroni correction, patients with wearing-off showed decreased relative abundance of Lachnospiraceae Blautia (p < 0.0001) and increased relative abundance of Lactobacillaceae Lactobacillus (p < 0.0001), but patients with dyskinesia no longer showed significant changes in the gut microbiota. Adjustment with two models of confounding factors followed by ANCOVA revealed that age (p < 0.0001), disease duration (p = 0.01), and wearing-off (p = 0.0004) were independent risks for the decreased relative abundance of Lachnospiraceae Blautia, and wearing-off (p = 0.009) was the only independent risk factor for the increased relative abundance of Lachnospiraceae Lactobacillus. ConclusionRelative abundance of Lachnospiraceae Blautia and Lactobacillaceae Lactobacillus was significantly decreased and increased, respectively, in the gut microbiota of PD patients with motor complications. This indicates that an altered gut microbiota is associated with the development of motor complications in patients with advanced PD.

Spotlight on the July 20 Issue

#### Notable in Neurology This Week This issue features an article that examines the long-term effects of deep brain stimulation of the subthalamic nucleus on motor complications in patients with Parkinson disease; another investigates how death by neurologic criteria protocols vary across pediatric hospitals in the United States. A featured Contemporary Issues in Practice, Education, & Research article reports on a program designed to help individuals who are underrepresented in biomedical research advance their careers. ### Reversible Cerebral Vasoconstriction Syndrome: Symptoms, Incidence, and Resource Utilization in a Population-Based US Cohort Reversible cerebral vasoconstriction syndrome (RCVS) …

Posterior Subthalamic Area, Pallidothalamic Tract, and Pedunculopontine Nucleus:Deep Brain Stimulation Targets for Parkinson's Disease and Essential Tremor

This article reviews the stereotactic targets in the posterior subthalamic area(PSA), fields H1/H2 of Forel(pallidothalamic tract), and the pedunculopontine nucleus(PPN)to complement the preceding articles on stereotactic and functional neurosurgery for movement disorders in the present issue of No Shinkei Geka. Two regions within the subthalamus, the PSA and fields H1/H2 of Forel, are the revisited stereotactic targets to treat movement disorders. Currently, the PSA is often utilized to treat essential tremor and various types of tremor. Fields H1/H2 of Forel are investigated as a target for magnetic resonance-guided focused ultrasound to treat motor symptoms and motor complications in patients with Parkinson's disease. For the past twenty years, the PPN has been investigated to treat refractory gait freezing and fall in patients with Parkinson's disease. These revisited and novel targets may be utilized as substitutes and complements for the present standard stereotactic targets.

Long-term Outcomes (15 Years) After Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease.

To evaluate the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) on motor complications in patients with Parkinson disease (PD) beyond 15 years after surgery. Data on motor complications, quality of life (QoL), activities of daily living, Unified Parkinson's Disease Rating Scale motor scores, dopaminergic treatment, stimulation measures, and side effects of STN-DBS were retrospectively retrieved and compared before surgery, at 1 year, and beyond 15 years after bilateral STN-DBS. Fifty-one patients with 17.06 ± 2.18 years STN-DBS follow-up were recruited. Compared to baseline, the time spent with dyskinesia and the time spent in the "off" state were reduced by 75% (p < 0.001) and by 58.7% (p < 0.001), respectively. Moreover, dopaminergic drugs were reduced by 50.6% (p < 0.001). Parkinson's Disease Quality of Life Questionnaire total score and the emotional function and social function domains improved 13.8% (p = 0.005), 13.6% (p = 0.01), and 29.9% (p < 0.001), respectively. Few and mostly manageable device-related adverse events were observed during the follow-up. STN-DBS is effective beyond 15 years from the intervention, notably with significant improvement in motor complications and stable reduction of dopaminergic drugs. Furthermore, despite the natural continuous progression of PD with worsening of levodopa-resistant motor and nonmotor symptoms over the years, patients undergoing STN-DBS could maintain an improvement in QoL. This study provides Class IV evidence that, for patients with PD, STN-DBS remains effective at treating motor complications 15 years after surgery.

Cerebrospinal fluid lactoperoxidase level is enhanced in idiopathic Parkinson’s disease, and correlates with levodopa equivalent daily dose

Lactoperoxidase (LPO) is proposed to play a role in the pathogenesis of Parkinson’s disease (PD). This enzyme has been reported to be enhanced in the cerebrospinal fluid (CSF) in parkinsonian patients. The objective was to look at the relationship of LPO in the CSF and serum with clinical features of idiopathic PD. LPO concentration was analyzed through ELISA techniques. Correlation of CSF or serum LPO and MDS-UPDRS, dopaminergic medication, and other clinical parameters was examined. The findings revealed that LPO concentration in the CSF, not serum, was found to be elevated in patients with PD relative to controls (p < 0.001). CSF LPO concentration negatively correlated with MDS-UPDRS part-IV score (p < .0001), a rating scale that allows evaluating motor complications. CSF LPO level inversely correlated with the dose intensity of the dopaminergic medication regimen, as evaluated with levodopa equivalent dose or LED (mg/day; p < .0001). LED value positively correlated with MDS-UPDRS part-IV score (p < .0001). To sum up, the findings indicate that CSF LPO is found to be elevated in the CSF of PD patients, and this enzyme holds promise as potential biomarker for diagnosis of PD. Increasing the dose intensity of the dopaminergic medication regimen attenuates the elevation in LPO levels in the CSF, and it facilitates the development of motor complications in patients. The pathophysiological mechanisms that seem to be responsible for LPO increase would include dopamine deficiency, oxidative stress, and less likely, microbial infection.

Delirium after Deep Brain Stimulation in Parkinson's Disease.

Deep brain stimulation is a primary treatment method that improves motor and motor complications in patients with advanced Parkinson's disease. Delirium is a common and serious complication following deep brain stimulation. However, the clinical attention toward this complication remains insufficient. Advanced age, cognitive decline, and the severity of the disease may all be risk factors for delirium. The presence of delirium may also affect cognitive function and disease prognosis. Neurotransmitters such as acetylcholine and dopamine may be involved in the occurrence of delirium. Furthermore, inflammation, the effects of microlesioning of local nuclei, and brain atrophy may also play roles in the onset of delirium. Nonpharmacological therapy appears to be the primary treatment for postoperative delirium in Parkinson's disease. The current article reviews the pathogenesis, epidemiology, prognosis, and treatment of delirium following deep brain stimulation in Parkinson's disease to help clinicians better understand this common complication and to prevent, identify, and treat it as soon as possible, as well as to provide more accurate treatment for patients.

Non-motor symptom burden is strongly correlated to motor complications in patients with Parkinson's disease.

The objective of this study was to analyze the relationship between motor complications and non-motor symptom (NMS) burden in a population of patients with Parkinson's disease (PD) and also in a subgroup of patients with early PD. Patients with PD from the COPPADIS cohort were included in this cross-sectional study. NMS burden was defined according to the Non-Motor Symptoms Scale (NMSS) total score. Unified Parkinson's Disease Rating Scale (UPDRS) part IV was used to establish motor complication types and their severity. Patients with ≤5years of symptoms from onset were included as patients with early PD. Of 690 patients with PD (62.6±8.9years old, 60.1% males), 33.9% and 18.1% presented motor fluctuations and dyskinesia, respectively. The NMS total score was higher in patients with motor fluctuations (59.2±43.1 vs. 38.3±33.1; P<0.0001) and dyskinesia (63.5±40.7 vs. 41.4±36.3; P<0.0001). In a multiple linear regression model and after adjustment for age, sex, disease duration, Hoehn & Yahr stage, UPDRS-III score and levodopa equivalent daily dose, UPDRS-IV score was significantly related to a higher NMSS total score (β=0.27; 95% confidence intervals, 2.81-5.61; P<0.0001), as it was in a logistic regression model on dichotomous NMSS total score (≤40, mild or moderate vs. >40, severe or very severe) (odds ratio, 1.31; 95% confidence intervals, 1.17-1.47; P<0.0001). In the subgroup of patients with early PD (n=396; mean disease duration 2.7±1.5years), motor fluctuations were frequent (18.1%) and similar results were obtained. Motor complications were frequent and were associated with a greater NMS burden in patients with PD even during the first 5years of disease duration.

What predicts quality of life after subthalamic deep brain stimulation in Parkinson's disease? A systematic review.

Subthalamic deep brain stimulation (STN DBS) is an effective therapy against medication-refractory motor complications in patients with Parkinson's disease. However, it remains difficult to predict which baseline patient characteristics are associated with quality of life (QoL) after surgery. The objective was to identify preoperative factors associated with QoL after STN DBS by systematically reviewing publications of sufficient methodological quality. Main databases were systematically searched up to March 2019 to identify studies that investigated factors associated with QoL after STN DBS in patients with idiopathic Parkinson's disease. In all, 869 studies were identified, of which 18 fulfilled the inclusion criteria. Higher QoL after DBS appears to be associated with a large preoperative difference between ON and OFF motor function in some studies, although there was no clear association of severity of motor function or motor complications with postoperative QoL. Lower severity of dyskinesias was associated with greater postoperative QoL improvement but has been insufficiently studied. Higher baseline QoL was suggestive of higher postoperative QoL. Four studies suggested that older age at surgery is associated with a lower improvement, although six other studies reported no association. No or limited evidence was found for cognitive impairment or psychiatric dysfunction. Various relative contraindications for STN DBS such as cognitive impairment and psychiatric dysfunction appear to be unrelated to postoperative QoL. However, the lack of clear correlations with disease-related variables suggests that QoL may be individually influenced by other factors, indicating that an ideal preoperative patient profile with regard to QoL improvement cannot be readily provided.

Improved self‐perceived performance for continence problems in patients with Parkinson's disease after deep brain stimulation

AbstractBackgroundDeep brain stimulation (DBS) is known to improve motor complications in patients with Parkinson's disease (PD); however, we lack information on how it changes self‐perceived performance for activities of daily living.AimWe assessed the degree of change in self‐perceived performance for activities of daily living after DBS.MethodWe applied the Canadian Occupational Performance Measure (COPM) in 21 patients with PD who underwent DBS before and 1 year after surgery and examined the relationship among the COPM score, motor and cognitive functions, and health‐related quality of life (HRQoL).ResultsPatients prioritized continence problems, gait, and household work. Self‐perceived performance satisfaction (5.46→8.38, P = 0.02) and execution (5.85→8.88, P = 0.01) for continence problems improved significantly after surgery. Self‐perceived performance satisfaction for gait tended to improve after surgery. Self‐perceived performance for household work did not change after surgery. Self‐perceived performance for continence problems negatively correlated with PD questionnaire (PDQ‐39; r = −0.827, P = 0.007) before surgery and Mini‐Mental State Examination (MMSE; r = −0.918, P = 0.028) after surgery.ConclusionThe self‐perceived performance for continence problems improved significantly after DBS and was associated with HRQoL before surgery and MMSE after surgery.

Urinary symptoms are correlated with quality of life after deep brain stimulation in Parkinson's disease.

AimsDeep brain stimulation (DBS) is known to dramatically improve motor complications in patients with Parkinson's disease (PD), but its effect on urinary symptoms and health‐related quality of life (HRQOL) remains unknown. We aimed to examine the relationship between urinary symptoms and HRQOL in patients with PD who underwent DBS.MethodsThe International Prostate Symptom Score (IPSS) and overactive bladder symptom score (OABSS) were determined to evaluate urinary symptoms in patients with PD who underwent DBS. Postoperative evaluations were performed at 3 months, 1 year, and 3 years postoperatively. We also performed a urodynamic study (UDS) in 13 patients with PD preoperatively and postoperatively. A follow‐up UDS was performed 2.0 ± 0.5 years postoperatively.ResultsThe preoperative urinary symptoms questionnaire was completed by 28 patients, of whom 14 completed the postoperative urinary symptoms questionnaire after 3 months, 18 after 1 year, and 10 after 3 years. The mean OABSS and IPSS did not change significantly at any follow‐up periods postoperatively. When assessing the relationship between urinary symptoms and HRQOL and motor functions, the OABSS and IPSS showed significant positive correlations with HRQOL at 3 months postoperatively. The OABSS and IPSS showed significant positive correlations with activities of daily living (ADL) during the off‐phase at 3 years postoperatively. All urodynamic parameters remained unchanged postoperatively.ConclusionsDeep brain stimulation did not significantly affect urinary dysfunctions in patients with PD. Urinary symptoms might partially contribute to HRQOL at 3 months postoperatively and ADL during the off‐phase at 3 years postoperatively.

Real life evaluation of safinamide effectiveness in Parkinson's disease.

In this retrospective study, we evaluated both efficacy and effectiveness of safinamide 50 and 100mg in the treatment of motor fluctuations and disabling dyskinesias in a cohort of patients with idiopathic Parkinson's disease (PD). Ninety-one PD patients were evaluated during the first year of commercialization of the drug, both prior to starting safinamide and at the last available follow-up. Evaluations were based on the Unified Parkinson's Disease Scale part III (UPDRS III), Hoehn & Yahr (HY), Unified Dyskinesia Rating Scale (UDysRS) walking and balance item 9 score, daily time spent in OFF and in ON with disabling dyskinesias (1week diary), mean daily dose of levodopa (LD), dopamine-agonists (DA), catechol-O-methyl transferase inhibitor (COMT-I), monoamine oxidase B inhibitor (MAOB-I), and their LD equivalent dose (LEDD). Eight patients withdrew safinamide within the first month for minor side effects. At the follow-up evaluation, after a mean time with safinamide of 7.5months ± 3.4, all patients showed a significant improvement of all the scale scores, except for HY, and of the daily dosages of the drugs and the LEDD. The same results were shown by PD patients treated with safinamide 50mg and patients who started safinamide without switching from a previous MAOBI. PD patients with safinamide 100mg and patients who started safinamide switching from a previous MAOBI significantly improved in time spent in OFF and LEDD. In conclusion, safinamide is safe and effective in improving motor complications in patients with idiopathic PD and can be considered a useful levodopa sparing strategy.

Metformin Inhibits the Development of L-DOPA-Induced Dyskinesia in a Murine Model of Parkinson's Disease.

Metformin is a medication that is widely prescribed for the management of type 2 diabetes. In addition to its anti-diabetic uses, metformin has been proposed as a therapeutically effective drug candidate in various central nervous system disorders, including Parkinson's disease (PD). PD is characterized by severe movement defects and is commonly treated with the dopamine (DA) precursor 3,4-dihydroxyphenyl-l-alanine (L-DOPA). However, prolonged use of L-DOPA can lead to the development of L-DOPA-induced dyskinesia (LID). Here, we hypothesized that metformin co-treatment would improve LID in the 6-hydroxydopamine (6-OHDA)-lesioned mouse model of PD. Metformin did not interfere the pharmacotherapeutic effects of L-DOPA in the cylinder test. Furthermore, metformin co-treatment with L-DOPA attenuated the development of LID in unilaterally 6-OHDA-lesioned mice. Metformin showed a long-lasting effect on axial, limb, and orofacial abnormal involuntary movement scores for up to 20days after treatment initiation. Interestingly, persistent enhancement of the mammalian target of rapamycin, dopamine D1 receptor, and extracellular signaling-regulated kinase 1/2 signaling was maintained in the DA-denervated striatum during metformin treatment. Metformin globally normalized the increased glycogen synthase kinase 3β activity induced by chronic treatment of L-DOPA in a manner associated with Akt activation in unilaterally 6-OHDA-lesioned mice. These findings suggest that metformin may have therapeutic potential for the suppression or management of L-DOPA-induced motor complications in patients with PD.

The Effects of Basic Gymnastic Trainings on Postural Stability in Children with Autism Spectrum Disorder

Introduction: Balance disorders are major motor complications in children with autism spectrum disorder (ASD). Physical exercise can improve motor complications in patients with this disorder. The aim of this study was to investigate the effect of basic gymnastics exercises on the postural stability in children with autism spectrum disorder. Materials and Methods: 20 boys with autism spectrum disorder participated in a controlled pre-post clinical trial study. Participants were divided in two 10-participant groups of case and control based on their scores in Gilliam Autism Rating Scale-II. The participants in the case group were trained with basic gymnastic exercises for 12 weeks (three sessions per week), each session lasted 45 minutes. The control group did not participate in any exercise during this time. Postural stability was measured using a force plate. Data were analyzed using multivariate ANOVA test while significant level was set at 0.05. Results: In post-test, less center of pressure oscillation was observed in the case group (657 ± 143 mm) compared to control group (1057 ± 311 mm) (P = 0.013). In the case group, the center of pressure oscillation was significantly reduced after gymnastic exercise (P = 0.001); but the changes were not significant in control group (P > 0.05). Conclusion: It seems that gymnastic training improves the postural stability through the reduction in the length of postural sway.

Effect of levodopa-carbidopa intestinal gel on resting tremors in patients with advanced Parkinson's disease.

Resting tremors occur in more than 70% of patients with advanced Parkinson’s disease (PD). PD patients with resting tremors are typically treated with oral dopaminergic therapy or non-dopaminergic agents. However, treatment response with these medications is inconsistent and often unsatisfactory. Levodopa-carbidopa intestinal gel (LCIG, also known in the United States as carbidopa-levodopa enteral suspension (CLES)), administered continuously by a portable pump via a percutaneous endoscopic gastrojejunostomy (PEG-J) tube, significantly improves motor complications in patients with advanced PD. This was a post hoc analysis of a large phase 3, 12-month, open-label study evaluating long-term safety and efficacy of LCIG via PEG-J tube (NCT00335153). Unified Parkinson’s Disease Rating Scale Part III Question 20 total scores at baseline, measuring resting tremors, were used to stratify patients into three subgroups (none, mild, or significant baseline resting tremors). Out of 354 enrolled patients, 286 had baseline and post-PEG-J assessments of resting tremors and were included in this analysis. At baseline the majority of patients (69%) had no resting tremors, whereas 13% had mild resting tremors, and 18% had significant resting tremors. A complete resolution in resting tremors after 12 months of LCIG treatment was reported for 78% and 70% of patients with mild and significant baseline resting tremors, respectively. Improvements in motor complications and quality of life occurred regardless of degree of baseline resting tremors. LCIG may provide more consistent and sustained improvements in resting tremors that were not well-controlled with optimized oral medication among patients with advanced PD.

Putaminal dopamine turnover in de novo Parkinson disease predicts later motor complications.

To investigate the predictive value of striatal dopamine turnover in patients with de novo Parkinson disease (PD) for the onset of later motor complications. This retrospective, observer-blinded cohort study followed up 31 patients with early PD who completed quantitative (18)F-dopa PET imaging to measure striatal (18)F-dopa uptake (Kocc) and effective distribution volume ratio (EDVR) as the inverse of dopamine turnover prior to antiparkinsonian treatment. The onset of wearing-off and dyskinesias was determined based on blinded clinical assessments and patient records. The predictive value of baseline PET measures for motor complications was evaluated using Cox proportional hazard models. During a mean follow-up time of 6.8 years, 18 (58.1%) patients developed wearing-off, 11 (35.5%) dyskinesia, and 20 (64.5%) any motor complication. Patients with dyskinesia and any motor complication showed lower baseline EDVR (higher dopamine turnover) in the putamen than those without dyskinesias and any motor complication, with differences most markedly present in the posterior putamen. Baseline EDVR in the whole and the posterior putamen predicted development of motor complications with an increasing risk with lower EDVR (higher dopamine turnover), whereas EDVR in other regions and Kocc did not correlate with motor complications. Correspondingly, Kaplan-Meier curves showed reduced survival from motor complications in patients with lower baseline EDVR (higher dopamine turnover) in the posterior putamen with ongoing levodopa treatment and disease duration. Elevated putaminal dopamine turnover in de novo PD is associated with an increased risk for later motor complications and comprises a disease-intrinsic predisposing factor for their development.

The modern pre-levodopa era of Parkinson's disease: insights into motor complications from sub-Saharan Africa.

During the past decade, a number of large drug trials suggested that the initiation of levodopa therapy should be delayed to reduce the risk of motor complications in patients with Parkinson's disease. However, the relative contribution of the cumulative exposure to levodopa and of disease progression to the pathophysiology of motor fluctuations and dyskinesias is still poorly understood. In this 4-year multicentre study, we investigated a large cohort of patients with Parkinson's disease in a sub-Saharan African country (Ghana), where access to medication is limited and the initiation of levodopa therapy often occurs many years after onset. The primary objective was to investigate whether the occurrence of motor complications is primarily related to the duration of levodopa therapy or to disease-related factors. Study design included a cross-sectional case-control analysis of data collected between December 2008 and November 2012, and a prospective study of patients followed-up for at least 6 months after the initiation of levodopa therapy. Ninety-one patients fulfilled criteria for clinical diagnosis of idiopathic Parkinson's disease (58 males, mean age at onset 60.6 ± 11.3 years). Demographic data were compared to those of 2282 consecutive Italian patients recruited during the same period, whereas nested matched subgroups were used to compare clinical variables. Demographic features, frequency and severity of motor and non-motor symptoms were comparable between the two populations, with the only exception of more frequent tremor-dominant presentation in Ghana. At baseline, the proportion of Ghanaian patients with motor fluctuations and dyskinesias was 56% and 14%, respectively. Although levodopa therapy was introduced later in Ghana (mean disease duration 4.2 ± 2.8 versus 2.4 ± 2.1 years, P < 0.001), disease duration at the occurrence of motor fluctuations and dyskinesias was similar in the two populations. In multivariate analysis, disease duration and levodopa daily dose (mg/kg of body weight) were associated with motor complications, while the disease duration at the initiation of levodopa was not. Prospective follow-up for a mean of 2.6 ± 1.3 years of a subgroup of 21 patients who were drug-naïve at baseline [median disease duration 4.5 (interquartile range, 2.3-5) years] revealed that the median time to development of motor fluctuations and dyskinesias after initiation of levodopa therapy was 6 months. We conclude that motor fluctuations and dyskinesias are not associated with the duration of levodopa therapy, but rather with longer disease duration and higher levodopa daily dose. Hence, the practice to withhold levodopa therapy with the objective of delaying the occurrence of motor complications is not justified.

Characteristics of motor complications in patients with Parkinson's/INS; disease in southern Tunisia (ST)

Characteristics of motor complications in patients with Parkinson's/INS; disease in southern Tunisia (ST)

Cognitive outcome and reliable change indices two years following bilateral subthalamic nucleus deep brain stimulation

Subthalamic nucleus deep brain stimulation (STN-DBS) is currently the treatment of choice for medication-resistant levodopa-related motor complications in patients with Parkinson’s disease (PD). While STN-DBS often results in meaningful motor improvements, consensus regarding long-term neuropsychological outcome continues to be debated. We assessed the cognitive outcomes of 19 STN-DBS patients compared to a group of 18 medically-managed PD patients on a comprehensive neuropsychological battery at baseline and two years post-surgery. Patients did not demonstrate changes in global cognitive functioning on screening measures. However, neuropsychological results revealed impairments in nonverbal recall, oral information processing speed, and lexical and semantic fluency in STN-DBS patients compared to PD controls 2 years post-surgery in these preliminary analyses. Additionally, reliable change indices revealed that approximately 50% of STN-DBS patients demonstrated significant declines in nonverbal memory and oral information processing speed compared to 25–30% of PD controls, and 26% of STN-DBS patients declined on lexical fluency compared to 11% of PD patients. Approximately 30% of both groups declined on semantic fluency. The number of STN-DBS patients who converted to dementia 2 years following surgery was not significantly different from the PD participants (32% versus 16%, respectively). Our results suggest that neuropsychological evaluations may identify possible mild cognitive changes following surgery.

Effects of piclozotan (SUN N4057), a partial serotonin 1A receptor agonist, on motor complications induced by repeated administration of levodopa in parkinsonian rats

Serotonin 1A receptor agonists have attracted much interest recently as potential therapeutic agents for levodopa-induced motor complications, such as dyskinesia and motor fluctuations. The effects of piclozotan (SUN N4057) on a rat model of advanced Parkinson's disease were investigated. Parkinsonian rats, unilaterally 6-hydroxydopamine-lesioned rats, were administered levodopa for 8 to 9 weeks. Based on the results of rotational behavior and forelimb hyperkinesia in Week 5, the rats were allocated to three treatment groups (saline and two dosing rates of piclozotan set at 0.018 and 0.036 mg/kg/h). Piclozotan was administered via continuous subcutaneous infusion using an osmotic pump for 3 to 4 weeks. At Week 7 of repeated levodopa dosing, the effects of piclozotan on levodopa-induced behavior were evaluated. In addition, extracellular levels of levodopa-derived dopamine in the striatum were measured using microdialysis in Weeks 8 to 9 after completion of the respective behavioral studies. Chronic treatment with levodopa-induced forelimb hyperkinesia and shortened the duration of rotational behavior. Piclozotan (0.018 and 0.036 mg/kg/h, plasma concentrations 5.3 ± 0.7 and 14.3 ± 2.9 ng/ml) reduced levodopa-induced forelimb hyperkinesia by 55% and 69%, respectively, at 1 h relative to the control. Piclozotan (0.036 mg/kg/h) significantly lengthened the duration of rotational behavior by 26% versus the control and attenuated the increase in striatal levodopa-derived extracellular dopamine levels. These findings suggest that piclozotan, a serotonin 1A agonist, can improve motor complications in patients with advanced Parkinson's disease.