Advanced Parkinson's Disease Research Articles

Are 5-2-1 Delphi criteria and MANAGE-PD useful screening tools for general neurologists for qualification to device-aided therapies in advanced Parkinson's Disease?

We sought to compare MANAGE-PD and 5-2-1 Delphi criteria which are two commonly used and approved screening tools in Parkinson's Disease, in order to highlight their strengths and limitations. Timely intervention with device-aided therapies is vital as it enables improving motor symptoms, lowering the dosage and side-effects of dopaminergic treatment, and improving patients' and caregivers' quality of life. Various screening tools have been created to help clinicians find the best candidates for device-aided therapies (DAT) for advanced Parkinson's Disease. In this study, we aimed to compare the 5-2-1 Delphi criteria to MANAGE-PD to determine how they could be used specifically to maximise their potential. All of the patients (260) included in this study were DAT-naive, > 18 years of age, diagnosed with Parkinson's Disease, and had been referred to the Department of Neurology for qualification for advanced therapies over a 4-year period (2019-2022). They were subjected to both 5-2-1 Delphi criteria and MANAGE-PD tools and divided into subgroups based on the results of the screening. The data of patients was then statistically analysed. In the study group, 51 patients (19.5%) met all three of the 5-2-1 criteria, and 123 (47.1%) patients were categorised as '3' in MANAGE-PD, meaning that they may benefit from DAT. Finally, at the local centre level, 64 (24.5%) patients were qualified for DAT. 22 (34.4%) patients who were qualified for DAT by a clinician did not meet the 5-2-1 criteria. The 5-2-1 scheme based on the data from this study was characterised by a 92.5% specificity level and 65.1% sensitivity level compared to 69.5% specificity and 98.4% sensitivity level of MANAGE-PD. We found that MANAGE-PD has a better screening potential of DAT admission than 5-2-1 criteria. While both tools are reliable and valuable in daily practice, our study suggests that some patients may be omitted when using only less complicated tools such as 5-2-1 during the assessment.

Nasojejunal Tube Placement for Levodopa-carbidopa Intestinal Gel Treatment by Neurologists in Patients with Advanced Parkinson's Disease: A Retrospective Observational Study.

Introduction Short-term levodopa-carbidopa intestinal gel (LCIG) treatment using nasojejunal (NJ) tubes (NJ-LCIG test) is recommended for patients with advanced Parkinson's disease to ensure compatibility with this treatment system prior to permanent percutaneous endoscopic gastrojejunostomy. However, there have been no studies on NJ tube insertion by neurologists or on possible differences in treatment efficacy based on the NJ tube insertion method or tube tip position. We therefore investigated the effects of LCIG with NJ tube placement performed by a neurologist. Methods This retrospective observational study included 13 patients with advanced Parkinson's disease and NJ tube placement between March 1, 2020, and October 31, 2023. A neurologist performed all NJ tube placements, and the daily off-time and dyskinesia time before and after NJ tube placement were compared. We also investigated the effects of differences in the NJ tube tip site. Results NJ tubes were placed using either a combination of X-ray fluoroscopy-guided insertion and gastric motility methods (23.1%) or X-ray fluoroscopy-guided insertion alone (76.9%). All tubes were successfully placed in the descending duodenum (15.4%), ascending duodenum (23.1%), or jejunum (61.5%). The off time decreased significantly after the NJ-LCIG test (pre-NJ-LCIG test, 6.6 h [5.1-8.1] vs. post-NJ-LCIG test, 2.0 h [0.8-3.5], p<0.01). There was no difference in effectiveness based on the site of NJ tube tip placement. Conclusion Our results suggest that neurologists can place NJ tubes and that the NJ-LCIG test can also improve off-time, regardless of the placement site.

Validity and Reliability of the Korean Versions of the 9- and 19-Item Wearing-Off Questionnaires in Parkinson's Disease.

The wearing-off (WO) phenomenon is the most common motor complication in advanced Parkinson's disease (PD), but its identification remains challenging. The 9- and 19-item Wearing-off Questionnaires (WOQ-9 and WOQ-19) are self-assessment tools for motor and nonmotor symptoms that are widely used for WO screening. We produced Korean versions of the WOQ-19 and WOQ-9 (K-WOQ-19 and K-WOQ-9) and investigated their validity and reliability. We used the translation-back translation method to produce K-WOQ-19 and K-WOQ-9, which were self-administered by 124 patients with PD. We conducted in-depth 10-minute interviews for confirming the presence of the WO phenomenon, and then stratified the participants into groups with and without WO. Diagnostic accuracy was assessed byanalyzing receiver operating characteristic curves. Concurrent validity was assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) andthe Hoehn and Yahr stage with Spearman's rank correlation analysis. Reliability was assessedbased on test-retest Cohen's kappa (κ) values and intraclass correlation coefficients (ICCs). The optimal cutoff scores on the K-WOQ-19 and K-WOQ-9 for WO screening were 4 and 2, respectively. The test-retest ICCs of K-WOQ-19 and K-WOQ-9 were 0.943 and 0.938, respectively. Nineteen of the combined 20 items in K-WOQ-19 and K-WOQ-9 showed moderate-to-substantial agreement (κ=0.412-0.771, p<0.001). The scores on the translated scales were significantly correlated with MDS-UPDRS IV scores. K-WOQ-19 and K-WOQ-9 are reliable and valid tools for detecting WO, with optimal cutoff scores of 4 and 2, respectively.

Force Control Issues in Upper and Lower Limbs in Parkinson's Disease and Freezing of Gait.

Parkinson's Disease (PD) has been found to cause force control deficits in upper and lower limbs. About 50% of patients with advanced PD develop a debilitating symptom called freezing of gait (FOG), which has been linked to force control problems in the lower limbs, and some may only have a limited response to the gold standard pharmaceutical therapy, levodopa, resulting in partially levodopa-responsive FOG (PLR-FOG). There has been limited research on investigating upper-limb force control in people with PD with PLR-FOG, and without FOG. In this pilot study, force control was explored using an upper-and-lower-limb haptics-enabled robot in a reaching task while people with PD with and without PLR-FOG were on their levodopa medication. A healthy control group was used for reference, and each cohort completed the task at three different levels of assistance provided by the robot. Similar significant proportional force control deficits were found in the upper and lower limbs in patients with PLR-FOG versus those without FOG. Some aspects of force control were found to be retained, including an ability to increase or decrease force in response to changes in resistance while completing a reaching task. Overall, these results suggest there are force control deficits in both the upper and lower limbs in people with PLR-FOG.

Motor and process skills of people with parkinson's disease compared to healthy older adults. A cross-sectional study.

Both Parkinson's disease (PD) and the process of ageing are associated with functional limitations. The aim of this study was to determine the differences in motor and process skills between individuals with PD and healthy older adults, as well as to observe how disease progression affects motor and process skills performance in PD patients. A cross-sectional study was conducted. The Assessment of Motor and Process Skills (AMPS) measure was employed in order to analyze the differences in the motor and process skills of daily tasks in people with PD and healthy older adults age- and sex-matched. Part III of the Unified Parkinson Disease Rating Scale (UPDRS), the Hoehn and Yahr (HY) scale and the Schwab & England scale was administered to determine the severity of the disease. Seventy participants (49 patients with PD and 21 healthy older adults) were recruited for this study. Our results showed that even at moderate stages of the disease, both motor and process skills were found deteriorated in PD patients more than older healthy older adults (p < 0.001). As PD progresses, motor and process skills present significantly deterioration. PD leads to a greater deterioration in motor and process skills compared to healthy older adults. As disease stages advance according to the HY scale, performance in motor and process skills deteriorates significantly between moderate and advanced PD stages. According to the AMPS scale, PD patients show no impairment of processing skills up to HY IV, but motor impairment at HY stages II, III and IV.

Prediction of pyramidal tract side effect threshold by intra-operative electromyography in subthalamic nucleus deep brain stimulation for patients with Parkinson's disease under general anaesthesia.

In DBS for patients with PD, STN is the most common DBS target with the sweet point located dorsal ipsilaterally adjacent to the pyramidal tract. During awake DBS lead implantation, macrostimulation is performed to test the clinical effects and side effects especially the pyramidal tract side effect (PTSE) threshold. A too low PTSE threshold will compromise the therapeutic stimulation window. When DBS lead implantation is performed under general anaesthesia (GA), there is a lack of real time feedback regarding the PTSE. In this study, we evaluated the macrostimulation-induced PTSE by electromyography (EMG) during DBS surgery under GA. Our aim is to investigate the prediction of post-operative programming PTSE threshold using EMG-based PTSE threshold, and its potential application to guide intra-operative lead implantation. 44 patients with advanced PD received STN DBS under GA were studied. Intra-operative macrostimulation via EMG was assessed from the contralateral upper limb. EMG signal activation was defined as the amplitude doubling or greater than the base line. In the first programming session at one month post-operation, the PTSE threshold was documented. All patients were followed up for one year to assess clinical outcome. All 44 cases (88 sides) demonstrated activations of limb EMG via increasing amplitude of macrostimulation the contralateral STN under GA. Revision tracts were explored in 7 patients due to a low EMG activation threshold (<= 2.5 mA). The mean intraoperative EMG-based PTSE threshold was 4.3 mA (SD 1.2 mA, Range 2.0-8.0 mA), programming PTSE threshold was 3.7 mA (SD 0.8 mA, Range 2.0-6.5 mA). Linear regression showed that EMG-based PTSE threshold was a statistically significant predictor variable for the programming PTSE threshold (p value <0.001). At one year, the mean improvement of UPDRS Part III score at medication-off/DBS-on was 54.0% (SD 12.7%) and the levodopa equivalent dose (LED) reduction was 59.5% (SD 23.5%). During STN DBS lead implantation under GA, PTSE threshold can be tested by EMG through macrostimulation. It can provide real-time information on the laterality of the trajectory and serves as reference to guide intra-operative DBS lead placement.

Longitudinal Neuropsychological Assessment of Symptomatic Edema after Subthalamic Nucleus Deep Brain Stimulation Surgery: A Case Series Study.

Severe non-infectious or non-haemorrhagic brain edema surrounding the electrode represents a rare complication of subthalamic nucleus deep brain stimulation (STN-DBS) surgery. The aim of this study is to report three patients with advanced Parkinson's Disease (PD) who developed symptomatic brain edema after STN-DBS surgery treated with intravenous steroids with a specific profile of reversible cognitive alterations. Patients were both assessed with a comprehensive neuropsychological battery including attention, memory, visuo-spatial and executive tasks. They were also briefly assessed for emotional and behavioural alterations, and for possible limitations in the activities of daily living. Normative data for an Italian population were available for all neuropsychological tests. The patients were firstly assessed before the surgery (baseline) as soon as they became symptomatic for the post-surgery edema and a few more times in follow-up up to ten months. In all patients we observed the resolution of cognitive deficits within six months after surgery with the corresponding reabsorption of edema at brain CT scans. The appearance of post-DBS edema is a fairly frequent and clinically benign event. However, in some rare cases it can be very marked and lead to important clinical-albeit transient-disturbances. These events can compromise, at least from a psychological point of view, the delicate path of patients who undergo DBS and can prolong the post-operative hospital stay. In this setting it could be helpful to perform a brain CT scan in 2-3 days with the aim of detecting the early appearance of edema and treating it before it can constitute a relevant clinical problem.

Triggers for freezing of gait in individuals with Parkinson's disease: a systematic review.

Freezing of Gait (FOG) is a motor symptom frequently observed in advanced Parkinson's disease. However, due to its paroxysmal nature and diverse presentation, assessing FOG in a clinical setting can be challenging. Before FOG can be fully investigated, it is critical that a reliable experimental setting is established in which FOG can be evoked in a standardized manner, but the efficacy of various gait tasks and triggers for eliciting FOG remains unclear. This study aimed to conduct a systematic review of the existing literature and evaluate the available evidence for the relationship between specific motor tasks, triggers, and FOG episodes in individuals with Parkinson's disease (PwPD). We conducted a literature search on four online databases (PubMed, Web of Science, EMBASE, and Cochrane Library) using the keywords "Parkinson's disease," "Freezing of Gait", "triggers" and "tasks". A total of 128 articles met the inclusion criteria and were included in our analysis. The review found that a wide range of gait tasks were employed in studies assessing FOG among PD patients. However, three tasks (turning, dual tasking, and straight walking) emerged as the most frequently used. Turning (28%) appears to be the most effective trigger for eliciting FOG in PwPD, followed by walking through a doorway (14%) and dual tasking (10%). This review thereby supports the utilisation of turning, especially a 360-degree turn, as a reliable trigger for FOG in PwPD. This finding could be beneficial to clinicians conducting clinical evaluations and researchers aiming to assess FOG in a laboratory environment.

Transcranial direct current stimulation improves motor function in rats with 6-hydroxydopamine-induced Parkinsonism

Transcranial direct current stimulation (tDCS) is increasingly being used for Parkinson's disease (PD); however, the evaluation of its clinical impact remains complex owing to the heterogeneity of patients and treatments. Therefore, we used a unilateral 6-hydroxydopamine-induced PD rat model to investigate whether anodal tDCS of the primary motor cortex (M1) alleviates PD motor deficits. Before tDCS treatment, unilateral PD rats preferentially used the forelimb ipsilateral to the lesion in the exploratory cylinder test and showed reduced locomotor activity in the open field test. In addition, PD-related clumsy forelimb movements during treadmill walking were detected using deep learning-based video analysis (DeepLabCut). When the 5-day tDCS treatment began, the forelimb-use asymmetry was ameliorated gradually, and locomotor activity increased to pre-lesion levels. tDCS treatment also normalized unnatural forelimb movement during walking and restored a balanced gait. However, these therapeutic effects were rapidly lost or gradually disappeared when the tDCS treatment was terminated. Histological analysis at the end of the experiment revealed that the animals had moderately advanced PD, with 40–50% of dopamine neurons and fibers preserved on the injured side compared with those on the intact side. Although it remains a challenge to elucidate the neural mechanisms of the transient improvement in motor function induced by tDCS, the results of this study provide evidence that tDCS of the M1 produces positive behavioral outcomes in PD animals and provides the basis for further clinical research examining the application of tDCS in patients with PD.

Levodopa-Entacapone-Carbidopa Intestinal Gel Treatment in Advanced Parkinson's Disease: A Single-Center Study of 30 Patients.

Levodopa-entacapone-carbidopa intestinal gel (LECIG) is a novel device assisted treatment option for advanced Parkinson's disease (PD). It has been available in Finland since 2020. There is paucity of scientific studies considering LECIG treatment in clinical practice. Objectives of this study were to evaluate the changes in medication, adverse events and early discontinuations of LECIG treatment in real life clinical practice. The records of 30 consecutive patients, who received LECIG between years 2020 and 2022 in Helsinki University Hospital, were retrospectively analyzed. Data considering changes in medication, discontinuations, and adverse events during the first six months of LECIG treatment was collected. Mean levodopa equivalent daily dose (LEDD) rose significantly between baseline before LECIG and six months with treatment (1230 mg vs. 1570 mg, P = 0.001). Three patients were discarded during nasojejunal tube test phase and seven discontinued the treatment during six-month follow-up. Most common reasons for discontinuation were difficulty in finding suitable infusion rate and neuropsychiatric problems. Safety issues encountered were similar to those reported with levodopa-carbidopa intestinal gel (LCIG) treatment. One case of rhabdomyolysis due to severe dyskinesia during LECIG treatment was observed. Patients were satisfied with the small size of the pump system. LEDD seems to increase during the first months of LECIG treatment. When compared to studies on LCIG, safety profile of LECIG appears similar, but early discontinuation rate is higher than expected. However, long-term studies are lacking. Only clear advantage to LCIG appears to be the smaller LECIG pump size.

Different associated factors of subjective cognitive complaints in patients with early and advanced Parkinson's disease.

Subjective cognitive complaints (SCCs), defined as cognitive decline reported by subjects or their informants, are common in the early stage of Parkinson's disease (PD). Previous studies have shown a significant association between SCCs and non-motor features as well as objective cognitive decline in PD patients. However, the discrepancy in SCC prevalence and SCC-related factors between patients with early PD and those with advanced PD remains poorly understood. We recruited a total of 114 and 69 early PD patients and advanced PD patients, respectively. Univariate and multivariate logistic regression analyses were performed for early PD and advanced PD patients. The prevalence of SCCs in the early PD and advanced PD groups was 60.5 and 68.1%, respectively. In the early PD group, the presence of SCCs in early PD participants was significantly associated with a higher nonmotor symptoms questionnaire (NMSQ) score (OR = 1.05, 95% CI = 1.00-1.10, p = 0.040). SCCs in the advanced PD group were related to lower attention scores (OR = 0.24, 95% CI = 0.05-0.90, p = 0.043) and lower visuospatial/executive abilities scores (OR = 0.18, 95% CI = 0.04-0.86, p = 0.032). The prevalence and SCC-related factors are distinct in early PD and advanced PD. These findings suggest that SCCs in PD patients with different disease statuses appear to have different related factors that may depend on different disease severities.

EE351 Using Social Return on Investment to Capture the Broader Impact of Medicines: Advanced Parkinson's Disease Example

EE351 Using Social Return on Investment to Capture the Broader Impact of Medicines: Advanced Parkinson's Disease Example

Investigating two pore potassium channel THIK‐1 expression in Alzheimer’s disease

AbstractBackgroundThe neuroinflammatory response, particularly the activation of the NLRP3 pathway, has been suggested as one of the key mechanisms of the pathological process in neurodegenerative diseases. Tandem pore domain halothane‐inhibited K+ channel 1 (THIK‐1) provides an upstream regulation of this neuroinflammatory response by modulating intracellular K+. While in vitro and in vivo model systems provide strong support for these mechanisms, unequivocal evidence from neurodegenerative disorders has been lacking.MethodThis research project investigated gene expression of markers in the THIK‐1/NLRP3 pathway by studying post‐mortem brain tissue of animal model representing Alzheimer’s disease (AD). In addition, THIK‐1 gene and protein expression in human post‐mortem brains of AD and Parkinson’s disease (PD) was investigated. Furthermore, DNA methylation of THIK‐1 gene in human post‐mortem brains of AD was analysed to explore a potential underlying mechanism of the changes of THIK‐1 gene expression.ResultA rat model of AD pathogenesis by intrahippocampal Aβ oligomer injection showed substantial up regulation of THIK‐1, glial activation markers, NLRP3 inflammasome components and IL‐1β. Changes in cortical gene expression for THIK‐1 support an inflammatory glial cell activation in both advanced AD and PD with dementia, not observed in the substantia nigra of the latter group. The increase in THIK‐1 expression was also supported by down‐regulation in DNA methylation of its corresponding gene in AD.ConclusionThe association between THIK‐1 expression and pathology changes observed in this study indicate a THIK‐1‐induced activation of this glial subtype in AD and PD. Therefore, specific blocks of the microglial THIK‐1 K+ channels at the early stage of AD and PD provides a potential therapeutic target.

Synthesis of an Advanced Pd–Rh Bimetallic Three-Way Catalyst by Adjusting the Distribution of Noble Metals

Synthesis of an Advanced Pd–Rh Bimetallic Three-Way Catalyst by Adjusting the Distribution of Noble Metals

Parkinson’s Disease Non-Motor Subtypes Classification in a Group of Slovenian Patients: Actuarial vs. Data-Driven Approach

Background and purpose: The aim of this study was to examine the risk factors, prodromal symptoms, non-motor symptoms (NMS), and motor symptoms (MS) in different Parkinson’s disease (PD) non-motor subtypes, classified using newly established criteria and a data-driven approach. Methods: A total of 168 patients with idiopathic PD underwent comprehensive NMS and MS examinations. NMS were assessed by the Non-Motor Symptom Scale (NMSS), Montreal Cognitive Assessment (MoCA), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), Epworth Sleepiness Scale (ESS), Starkstein Apathy Scale (SAS) and Fatigue Severity Scale (FSS). Motor subtypes were classified based on Stebbins’ method. Patients were classified into groups of three NMS subtypes (cortical, limbic, and brainstem) based on the newly designed inclusion criteria. Further, data-driven clustering was performed as an alternative, statistical learning-based classification approach. The two classification approaches were compared for consistency. Results: We identified 38 (22.6%) patients with the cortical subtype, 48 (28.6%) with the limbic, and 82 (48.8%) patients with the brainstem NMS PD subtype. Using a data-driven approach, we identified five different clusters. Three corresponded to the cortical, limbic, and brainstem subtypes, while the two additional clusters may have represented patients with early and advanced PD. Pearson chi-square test of independence revealed that a priori classification and cluster membership were significantly related to one another with a large effect size (χ2(8) = 175.001, p &lt; 0.001, Cramer’s V = 0.722). The demographic and clinical profiles differed between NMS subtypes and clusters. Conclusion: Using the actuarial and clustering approach, marked differences between individual NMS subtypes were found. The newly established criteria have potential as a simplified tool for future clinical research of NMS subtypes of Parkinson’s disease.

Multiculturalism and reported cognitive change in Parkinson's disease.

Subjective cognitive decline (SCD) and how much cognitive decline impacts one's ability to perform instrumental activities of daily living (iADLs) are necessary elements of neuropsychological assessment when diagnosing mild cognitive impairment (MCI) and dementia. Though limited, the literature suggests that culture and self-appraisal of cognitive abilities are related. However, it is unclear if differences exist in the subjective elements of neuropsychological assessments between patients born in Anglosphere countries (Canada, the USA, and the UK) versus immigrants born elsewhere (International Group). We conducted a retrospective chart review of advanced Parkinson's disease (PD) patients (n = 764). Reports of SCD and iADL difficulties were extracted from neuropsychological reports and coded by two independent raters. We also examined responses on self- and family-rated questionnaires of executive functioning and iADL difficulties. Anglosphere and International patients did not differ on overall, memory, or attention SCD, or overall iADL difficulties based on interviews. Anglosphere patients reported more executive and language SCD during the interview but International care-partners reported more current executive dysfunction on a questionnaire. International patients and care-partners reported more iADL difficulties on a questionnaire, which they ascribed to motor (not cognitive) symptoms. The effects on questionnaires were small and persisted after accounting for depression severity ratings. There were no consistent group differences in the number or pervasiveness of SCD or iADL difficulties reported by Anglosphere versus International groups. Immigration status has limited effect on these subjective elements and they should be given significant weight when diagnosing cognitive dysfunction in PD.

Serum BLMH and CKM as Potential Biomarkers for Predicting Therapeutic Effects of Deep Brain Stimulation in Parkinson's Disease: A Proteomics Study.

Deep brain stimulation (DBS) is recommended for the treatment of advanced Parkinson's disease (PD), though individual reactions may be different. There are currently no clinically available biomarkers for predicting the responses of PD patients to DBS before surgery. This study aimed to determine serum biomarkers to predict DBS responses in PD. We profiled differentially expressed proteins (DEPs) in serum samples and identified potential biomarkers to predict the therapeutic responses to DBS in PD patients. Ten serum samples were selected from PD patients to identify DEPs via mass spectrometry proteomics; these were then verified by enzyme-linked immunosorbent assay in another 21 serum samples of PD patients. The present study identified 14 DEPs (10 downregulated and four upregulated DEPs) with significantly different levels between non-responders and responders. Most of the DEPs were related to amino acid metabolism and protein modification pathways. Bleomycin hydrolase (BLMH) and creatine kinase M-type (CKM) were found to be significantly downregulated in the responders. Additionally, subsequent logistic regression and receiver operating characteristic analyses were performed to determine the diagnostic performance of candidate proteins. The identified DEPs show potential as biomarkers for the accurate evaluation of DBS therapeutic responses before surgery. Furthermore, assessment of serum BLMH and CKM may be particularly useful for predicting the therapeutic responses to DBS in PD patients.

A video-atlas of levodopa-induced dyskinesia in Parkinson's disease: terminology matters.

Dyskinesia is a common complication of long-term levodopa therapy in patients with Parkinson's disease (PD), which often worsens the quality of life. It is usually dose-dependent and emerges possibly due to pulsatile stimulation of dopamine receptors. Delineating the pattern of dyskinesia is crucial for determining the most effective therapeutic approach, a task that often presents challenges for numerous neurologists. This article comprehensively describes various patterns of dyskinesia in PD patients and features video demonstration of some of the common forms of dyskinesia. We have used a real case scenario as an example to lead the discussion on the phenomenology, distinguishing features, and management of various types of dyskinesia. A comprehensive literature search was conducted in PubMed using "dyskinesia" as a keyword. The prototype case with videos highlights the differentiating features of dyskinesia along with the treatment strategies. A wide range of descriptive rubrics have been used for certain dyskinesia which are described in detail in this article. The newer types of dyskinesia associated with continuous dopaminergic stimulation in patients with advanced PD and their implications have been described. As there are distinct ways of managing various types of dyskinesia, understanding the phenomenology and chronology of dyskinesia is vital for the optimal management of dyskinetic PD patients. We suggest that dyskinesia should be classified broadly into peak-dose dyskinesia (PDD), biphasic dyskinesia (BD), and OFF-period dystonia. The occurrence of low-dose dyskinesia and complex dyskinesia of continuous dopaminergic treatments should be known to specialists and will require additional studies.

Sensory neuropathy complicated with de novo diabetes mellitus during levodopa‐carbidopa intestinal gel infusion in a patient with Parkinson's disease: A case report

AbstractLevodopa‐carbidopa intestinal gel therapy (LCIG), an effective treatment for advanced Parkinson's disease, can cause peripheral neuropathy. We present a 39‐year‐old man with LCIG‐related neuropathy with de novo diabetes mellitus (DM), decreased vitamin B6 and folate levels, and elevated homocysteine levels that developed over 2 years of LCIG treatment. Physicians should assess levels of levodopa metabolism‐associated vitamins and monitor risk factors of peripheral neuropathy, such as DM, before and after LCIG initiation.

Applicability of clinical genetic testing for deep brain stimulation treatment in monogenic Parkinson's disease and monogenic dystonia: a multidisciplinary team perspective.

In this perspective article, we highlight the possible applicability of genetic testing in Parkinson's disease and dystonia patients treated with deep brain stimulation (DBS). DBS, a neuromodulatory technique employing electrical stimulation, has historically targeted motor symptoms in advanced PD and dystonia, yet its precise mechanisms remain elusive. Genetic insights have emerged as potential determinants of DBS efficacy. Known PD genes such as GBA, SNCA, LRRK2, and PRKN are most studied, even though further studies are required to make firm conclusions. Variable outcomes depending on genotype is present in genetic dystonia, as DYT-TOR1A, NBIA/DYTPANK2, DYT-SCGE and X-linked dystonia-parkinsonism have demonstrated promising outcomes following GPi-DBS, while varying outcomes have been documented in DYT-THAP1. We present two clinical vignettes that illustrate the applicability of genetics in clinical practice, with one PD patient with compound GBA mutations and one GNAL dystonia patient. Integrating genetic testing into clinical practice is pivotal, particularly with advancements in next-generation sequencing. However, there is a clear need for further research, especially in rarer monogenic forms. Our perspective is that applying genetics in PD and dystonia is possible today, and despite challenges, it has the potential to refine patient selection and enhance treatment outcomes.