BACKGROUND: Conventional oral levodopa therapy for the treatment of Parkinson\'s disease can be associated with variations in plasma concentrations. Levodopa infusion strategies might provide more consistent drug delivery and fewer motor fluctuations. We aimed to assess the safety and efficacy of a continuous 24 h/day subcutaneous infusion of ND0612 (a levodopa-carbidopa solution) compared with oral immediate-release levodopa-carbidopa for the treatment of motor fluctuations in people with Parkinson\'s disease.
METHODS: We conducted a phase 3, randomised, double-blind, double-dummy, active-controlled, multicentre trial at 117 academic and community neurology sites in 16 countries, including in Europe, Israel, and the USA. Eligible participants were men and women aged 30 years or older with a diagnosis of Parkinson\'s disease (Hoehn and Yahr stage ≤3 in the on state) who experienced at least 2·5 h/day of off time. Participants underwent an open-label run-in phase (<12 weeks), during which time optimal regimens were established for both oral immediate-release levodopa-carbidopa and for 24 h/day subcutaneous ND0612 infusion (levodopa-carbidopa 60·0/7·5 mg/mL), with supplemental oral levodopa-carbidopa if needed. Participants were then randomly assigned (1:1) to 12 weeks of double-blind treatment with their optimised regimen of either subcutaneous ND0612 or oral levodopa-carbidopa, with matching oral or subcutaneous placebo given as required to maintain blinding. Randomisation was done via an interactive web response system, stratified by region, using a permuted block schedule. Participants, study partners, treating investigators, study site personnel, and the sponsor were masked to treatment group allocation. The primary efficacy endpoint was the change from baseline (ie, time of randomisation, when all patients were receiving an optimised open-label ND0612 regimen) to end of the double-blind phase in total daily on time without troublesome dyskinesia, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT04006210, and is complete.
RESULTS: Between Sept 30, 2019, and April 8, 2022, 381 participants were enrolled, of whom 259 (68%) were randomly assigned, 128 (49%) to subcutaneous ND0612 and 131 (51%) to oral levodopa-carbidopa. 243 (94%) participants completed the study. Treatment with subcutaneous ND0612 provided an additional 1·72 h (95% CI 1·08 to 2·36) of on time without troublesome dyskinesia compared with oral levodopa-carbidopa (change from baseline of -0·48 h [-0·94 to -0·02] with subcutaneous ND0612 vs -2·20 h [-2·65 to -1·74] with oral levodopa-carbidopa; p<0·0001). Significant treatment differences favouring subcutaneous ND0612 were also found in the first four of nine prespecified hierarchical outcomes of daily off time (-1·40 h [95% CI -1·99 to -0·80]), Movement Disorders Society-Unified Parkinson\'s Disease Rating Scale part II scores (-3·05 [-4·28 to -1·81]), Patients Global Impression of Change (odds ratio [OR] 5·31 [2·67 to 10·58]), and Clinical Global Impression of Improvement (OR 7·23 [3·57 to 14·64]). Hierarchical testing ended after the fourth secondary endpoint. Adverse events were reported by 287 (89%) of 322 participants during open-label ND0612 optimisation, and by 103 (80%) of 128 in the ND0612 group and 97 (74%) of 131 in the oral levodopa-carbidopa group during the double-blind phase. The most common adverse events were infusion-site reactions (266 [83%] participants during open-label ND0612, and 73 [57%] in the ND0612 group vs 56 [43%] in the oral levodopa-carbidopa group during the double-blind phase), most of which were mild. Serious adverse events in four participants in the ND0612 group were related to study treatment (infusion-site cellulitis [n=2], infusion-site abscess and infusion-site ulcer [n=1]; and paraesthesia and peripheral sensorimotor neuropathy [n=1]). One participant in the ND0612 group died during the double-blind phase, but the death was not related to study treatment (fall leading to traumatic brain injury).
CONCLUSIONS: Results of this phase 3 study showed that subcutaneous ND0612 used in combination with oral immediate-release levodopa-carbidopa increased on time without troublesome dyskinesia and reduced off time, with a favourable benefit-risk profile. ND0612 might offer a safe and efficacious subcutaneous levodopa infusion approach to managing motor fluctuations in people with Parkinson\'s disease. The ongoing open-label extension phase will provide further information on the long-term efficacy and safety of treatment.
BACKGROUND: NeuroDerm.

OBJECTIVE: Overactive bladder (OAB) and dyskinesia are frequent complications in patients with Parkinson\'s disease (PD). However, the correlation between OAB and dyskinesia has been insufficiently explored. The purpose of this study was to examine the relationship between dyskinesia, OAB, and clinical characteristics among individuals with PD.
METHODS: 1338 PD patients were included in the present study. Demographic features were compared between patients with or without dyskinesia and OAB symptoms. Logistic regression was conducted on dyskinesia to screen clinically relevant factors. Overactive Bladder Symptom Score (OABSS) was further used to stratify the association between the severity of OAB and the occurrence of dyskinesia.
RESULTS: This study indicates that both dyskinesia and OAB are significantly related to disease severity and cognitive status. PD patients with dyskinesia and OAB having higher UPDRS scores (p < 0.001), H-Y scores (p < 0.001), NMSQ (p < 0.001) and MoCA scores (p < 0.001), and lower MMSE scores (p < 0.001) are identified. The multivariate logistic regression confirms that disease duration (p = 0.041), LEDD (p < 0.001), UPDRSII (p < 0.001), MoCA (p = 0.024), urgency (p < 0.001), frequency (p < 0.001), and nocturia (p = 0.002) are independent risk factors for dyskinesia. Trend analysis indicates that the risk of dyskinesia significantly increases when patients exhibit moderate to severe OAB symptoms (OABSS > 5) (p < 0.001). No significant interactions were found between OABSS and age, gender, disease duration, LEDD, and NMSQ scores in different subgroups, indicating that dyskinesia is more pronounced in patients with OABSS > 5.
CONCLUSIONS: This study provides compelling evidence supporting the strong correlation between OAB and dyskinesia in PD patients, emphasizing the presence of shared pathogenic mechanisms between these two conditions. Our findings underscore the importance of considering both OAB and dyskinesia in the clinical management of PD, investigating the intricate connections between OAB and dyskinesia could unveil valuable insights into the complex pathophysiology of PD and potentially identify novel therapeutic targets for more effective PD treatment strategies.

Subacromial pain syndrome (SPS) is a common cause of shoulder pain, and is associated with functional limitation, workdays lost, disability, and poor quality of life.
Our purpose was to investigate the effects of scapular stabilization exercises in patients with SPS.
Sixty-four patients with SPS who also exhibit observable scapular dyskinesis defined by the scapular dyskinesis test were recruited and randomized to scapular stabilization exercise training group or to control group. All participants received the same rehabilitation protocol including glenohumeral and scapular mobilization, pendulum exercises, shoulder stretching, range of motion exercises, strengthening, and proprioceptive exercises. Patients in the scapular stabilization exercise training group performed additional scapular stabilization exercises. The presence of scapular dyskinesis, shoulder pain severity, motion, muscle strength, scapular upward rotation, and shoulder disability were assessed before and after the four-week rehabilitation program.
The scapular stabilization exercise training group had better improvement in scapular dyskinesis, pain, muscle strength, and shoulder disability compared to the control group (p < 0.05). However, there was no statistically significant time-group interaction regarding shoulder motion and scapular upward rotation (p > 0.05).
Scapular stabilization exercises added to the shoulder mobilization, stretching, and strengthening are effective in improving scapular dyskinesis, reducing pain, increasing muscle strength and shoulder function in patients with SPS accompanied by scapular dyskinesis.

BACKGROUND: The DYSCOVER study was a phase 3b, open-label, randomized trial (NCT02799381) that evaluated levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) in patients with Parkinson\'s disease (PD) and a high burden of dyskinesia at baseline (defined as Unified Dyskinesia Rating Scale [UDysRS] total score ≥ 30). At week 12, patients receiving LCIG versus OMT experienced significant improvements in dyskinesia, pain, and health-related outcomes. The objective of this analysis was to examine correlations between dyskinesia, pain, and health-related outcomes in PD.
METHODS: This post hoc analysis assessed correlations between UDysRS, King\'s Parkinson\'s Disease Pain Scale (KPPS), 8-item Parkinson\'s Disease Questionnaire (PDQ-8), Unified Parkinson\'s Disease Rating Scale part II, Clinical Global Impression of Severity (CGI-S) or Change (CGI-C), and \"On\" time without troublesome dyskinesia at baseline and after 12 weeks of LCIG or OMT. Correlations were assessed by Pearson correlation coefficients (categorization: weak, r = 0.20-0.39; moderate, r = 0.40-0.59; strong, r ≥ 0.60).
RESULTS: Among 61 patients, moderate-to-strong positive and significant correlations were observed between UDysRS and KPPS scores (baseline, r = 0.47; week 12 change from baseline [CFB], r = 0.63; all p < 0.001). UDysRS and KPPS scores had moderate-to-strong positive and highly significant correlations with PDQ-8 scores (baseline, r = 0.45 and 0.46, respectively; CFB, r = 0.54 and 0.64, respectively; all p < 0.001). Moderate positive and significant correlations were observed between UDysRS and CGI-S/CGI-C scores (baseline, r = 0.41; CFB, r = 0.47; all p < 0.001).
CONCLUSIONS: In patients with high dyskinesia burden, positive correlations were observed between dyskinesia, pain, and health-related quality of life (HRQoL) at baseline. Improvements in dyskinesia and pain were associated with improvements in HRQoL, demonstrating the clinical burden of troublesome dyskinesia.
BACKGROUND: Clinicaltrials.gov identifier NCT02799381.

BACKGROUND Non-ketotic hyperglycemic hemichorea-hemiballism (HCHB) is a rare complication of diabetes, which is mainly described in case reports. This condition occurs more commonly in older women and is known to be associated with T1 hyperintensity basal ganglia lesions on magnetic resonance imaging (MRI). The pathophysiology of non-ketotic hyperglycemic HCHB is not well defined, although a combination of regional metabolic failure and ischemia due to hyperglycemia is suspected to occur. Treatment entails tight blood glucose control, although antipsychotic medications such as risperidone may be helpful in refractory cases. CASE REPORT We describe a case of a middle-aged man with long-standing type 2 diabetes who experienced 3 weeks of progressive unilateral arm, leg, and face choreiform movements. Laboratory testing performed just prior to symptom onset was notable for a hemoglobin A1C of >15% and a serum blood glucose of 566 mg/dl. MRI revealed diffuse T1 hyperintensity in the left lentiform nucleus. Our patient\'s insulin regimen was adjusted, resulting in improvement in average serum glucose (A1C of 9.4%). However, his symptoms did not improve significantly. A trial of benzodiazepine was attempted, without success. When risperidone was started, the patient experienced resolution of symptoms. Recurrence of non-ketotic hyperglycemic HCHB while off risperidone has not occurred to date. CONCLUSIONS Non-ketotic hyperglycemic HCHB is a rare but important diagnosis to consider in patients with hyperglycemia and new-onset choreiform movements. Patients with long-standing type 2 diabetes may be affected, especially when glycemic control worsens. When tight blood glucose control does not resolve symptoms, a short course of antipsychotic agents may provide relief.

With the benefit of using next-generation sequencing (NGS), our aim was to examine the prevalence of known monogenic causes in early-onset Parkinson\'s disease (EOPD) patients in Thailand. The association between clinical features, such as levodopa-induced dyskinesia (LID), and genotypes were also explored.
NGS studies were carried out for EOPD patients in the Tertiary-referral center for Parkinson\'s disease and movement disorders. EOPD patients who had LID symptoms were enrolled in this study (n = 47). We defined EOPD as a patient with onset of PD at or below 50 years of age. LID was defined as hyperkinetic movements including chorea, ballism, dystonia, myoclonus, or any combination of these movements resulting from levodopa therapy, which could be peak-dose, off-period, or diphasic dyskinesias.
Pathogenic variants were identified in 17% (8/47) of the Thai EOPD patients, of which 10.6% (5/47) were heterozygous GBA variants (c.1448T>C in 3 patients and c.115+1G>A in 2 patients), 4.3% (2/47) homozygous PINK1 variants (c.1474C>T) and 2.1% (1/47) a PRKN mutation (homozygous deletion of exon 7). The LID onset was earlier in patients with GBA mutations compared to those without (34.8±23.4 vs 106.2±59.5 months after starting levodopa, respectively, p = 0.001). LID onset within the first 30 months of the disease was also found to be independently associated with the GBA mutation (odds ratio [95% confidence interval] = 25.00 [2.12-295.06], p = 0.011).
Our study highlights the high prevalence of GBA pathogenic variants in Thai patients with EOPD and the independent association of these variants with the earlier onset of LID. This emphasizes the importance of genetic testing in this population.

GBA variants increase the risk of developing Parkinson disease (PD) and influence its outcome. Deep brain stimulation (DBS) is a recognised therapeutic option for advanced PD. Data on DBS long-term outcome in GBA carriers are scarce.
To elucidate the impact of GBA variants on long-term DBS outcome in a large Italian cohort.
We retrospectively recruited a multicentric Italian DBS-PD cohort and assessed: (1) GBA prevalence; (2) pre-DBS clinical features; and (3) outcomes of motor, cognitive and other non-motor features up to 5 years post-DBS.
We included 365 patients with PD, of whom 73 (20%) carried GBA variants. 5-year follow-up data were available for 173 PD, including 32 mutated subjects. GBA-PD had an earlier onset and were younger at DBS than non-GBA-PD. They also had shorter disease duration, higher occurrence of dyskinesias and orthostatic hypotension symptoms.At post-DBS, both groups showed marked motor improvement, a significant reduction of fluctuations, dyskinesias and impulsive-compulsive disorders (ICD) and low occurrence of most complications. Only cognitive scores worsened significantly faster in GBA-PD after 3 years. Overt dementia was diagnosed in 11% non-GBA-PD and 25% GBA-PD at 5-year follow-up.
Evaluation of long-term impact of GBA variants in a large Italian DBS-PD cohort supported the role of DBS surgery as a valid therapeutic strategy in GBA-PD, with long-term benefit on motor performance and ICD. Despite the selective worsening of cognitive scores since 3 years post-DBS, the majority of GBA-PD had not developed dementia at 5-year follow-up.

BACKGROUND: Scapular dyskinesis (SD) is defined as an altered position of the scapula or altered motion patterns and their relationship with shoulder pain (SP) is still under debate. The modified scapular assistance test (mSAT) modifies scapular kinematics and is used to determine the impact of scapular dyskinesis in shoulder pain. However, data about the relationship between SD and the result of mSAT is scarce.
OBJECTIVE: The aim of this study is to establish the frequency of positive mSAT in patients with SP and compare the prevalence in those with and without SD. As a secondary objective, we compare changes in pain intensity during the mSAT in patients with a positive test between those with and without SD.
METHODS: Cross-sectional study.
METHODS: Adult patients with a diagnosis of SP and with pain ≥2 during anterior flexion were included. The mSAT, scapular dyskinesis test (SDT), and shoulder function were assessed.
RESULTS: The study was conducted between August 2018 and May 2022 and included 70 patients. The prevalence of SDT was 54.29%. No statistically significant associations were detected when assessing the relation between the presence of mSAT and SDT (p-value 0.83). When comparing pain response during the mSAT in patients with a positive test, no differences were seen between patients with SD and patients without SD (p-value 0.26).
CONCLUSIONS: The prevalence of positive mSAT results was equal between individuals with and without SD. These findings suggest that the presence or absence of SD in individuals with SP was independent of the mSAT result. The mSAT should not be used solely for the assessment of SD in clinical practice nor be influenced by the SDT result. More research is needed to determine if the result of this test could inform prognosis and guide treatment choices.

BACKGROUND: Kinesio taping (KT) is one of the treatment methods used on patients with shoulder impingement syndrome (SIS). There are different results regarding its effectiveness in the literature.
OBJECTIVE: To investigate the effects of scapular KT combined with a conventional physiotherapy program on scapular dyskinesia, shoulder pain, upper extremity function, and well-being in patients with SIS.
METHODS: The study was conducted with 60 outpatients diagnosed with SIS, aged 40-65 years. The patients were divided into two groups: KT [conventional physiotherapy program + scapular KT (targets scapular retraction and is applied along the inferior-medial edge of the scapula, starting from the processus coracoids), n= 30] and control [conventional physiotherapy program, n= 30]. In before- and after-treatment evaluations, the Lateral Scapular Slide Test (LSST) for scapular dyskinesia, a Visual Analogue Scale (VAS) for shoulder pain, and the Disabilities of the Arm, Shoulder, and Hand (DASH) for upper extremity function were used. In addition, at the end of treatment, a Kinesio taping Satisfaction Survey, created by the researchers, was filled out by the KT group for the assessment of well-being.
RESULTS: The interaction effect of Group*Time was not statistically significant in all outcome measures (p> 0.05). However, the main effect of both group and time was statistically significant in the DASH-Function/Symptom, VAS-Rest, VAS-Activity, and VAS-Night (p< 0.05). Moreover, only the main effect of time was statistically significant in LSST-1 and LSST-3 (p< 0.05). In the KT group, the satisfaction level was 8.50 ± 1.69 and the recommendation level was 8.72 ± 1.81.
CONCLUSIONS: Both conventional physiotherapy programs and additional scapular KT improved scapular dyskinesia, reduced pain, and increased the upper extremity function. Adding scapular KT to treatment did not change the results, but it had positive psychological effects and yielded a high satisfaction rate.

Previous studies have suggested an association between Impulsive Compulsive Behaviour (ICB) and dyskinesia in Parkinson\'s disease (PD). However, none of these studies have employed an objective home-based measure of dyskinesia.
To evaluate in advanced PD the relationship between ICB and dyskinesia, objectively measured with a wearable device.
In this cross-sectional study, ICB and other neuropsychiatric symptoms were assessed by means of structured clinical interview and specific screening instruments. Presence and severity of motor fluctuations and dyskinesia were rated with patient\'s and clinician\'s based rating instruments. Motor fluctuations and dyskinesia were also measured at home for 5-days using a validated wearable devise, the Parkinson\'s KinetiGraph™(PKG).
We included 89 subjects with PD (29 females, 62 ± 7 years, disease duration 10.3 ± 4.5), of whom 36 (40%) had ICB. Patients with and without ICB did not differ by presence and severity of dyskinesia measured by clinical scales and PKG. There was no association between the presence of ICB and dyskinesia in the whole sample.
Our data suggest that ICB and dyskinesia are common but unrelated disorders in advanced PD.