20 research outputs found
Overnight unilateral withdrawal of thalamic deep brain stimulation to identify reversibility of gait disturbances
BACKGROUND: Gait disturbances are frequent side effects related to chronic thalamic deep brain stimulation (DBS) that may persist beyond cessation of stimulation. OBJECTIVE: We investigate the temporal dynamics and clinical effects of an overnight unilateral withdrawal of DBS on gait disturbances. METHODS: 10 essential tremor (ET) patients with gait disturbances following thalamic DBS underwent clinical and kinematic gait assessment ON DBS, after instant and after an overnight unilateral withdrawal of DBS of the hemisphere corresponding to the non-dominant hand. The effect of stimulation withdrawal on gait performance was quantitatively assessed using clinical rating and inertial sensors and compared to gait kinematics from 10 additional patients with ET but without subjective gait impairment. DBS leads were reconstructed and active contacts were visualized in relation to surrounding axonal pathways and nuclei. RESULTS: Patients with gait deterioration following DBS exhibited greater excursion of sagittal trunk movements and greater variability of stride length and shank range of motion compared to ET patients without DBS and without subjective gait impairment. Overnight but not instant withdrawal of unilateral DBS resulted in significant reduction of SARA axial subscore and stride length variability, while tremor control of the dominant hand was preserved. Cerebellothalamic, striatopallidofugal and corticospinal fibers were in direct vicinity of transiently deactivated contacts. CONCLUSION: Non-dominant unilateral cessation of VIM DBS may serve as a therapeutic option as well as a diagnostic tool to detect stimulation-induced gait disturbances that is applicable in ambulatory settings due to preserved functionality of the dominant hand
Continuous Subcutaneous Foslevodopa/Foscarbidopa in Parkinsonâs Disease: Safety and Efficacy Results From a 12-Month, Single-Arm, Open-Label, Phase 3 Study
\ua9 2023, The Author(s). Introduction: Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinsonâs disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD. Methods: Male and female patients with levodopa-responsive PD and â„ 2.5 hours of âOffâ time/day received 24-hour/day foslevodopa/foscarbidopa CSCI at individually optimized therapeutic doses (approximately 700â4250 mg of LD per 24 hours) for 52 weeks. The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in normalized âOffâ and âOnâ time, percentage of patients reporting morning akinesia, Movement Disorder Society Unified Parkinsonâs Disease Rating Scale (MDS-UPDRS), Parkinsonâs Disease Sleep Scaleâ2 (PDSS-2), 39-item Parkinsonâs Disease Questionnaire (PDQ-39), and EuroQol 5-dimension questionnaire (EQ-5D-5L). Results: Of 244 enrolled patients, 107 discontinued, and 137 completed treatment. Infusion site events were the most common adverse events (AEs). AEs were mostly nonserious (25.8% of patients reported serious AEs) and mild/moderate in severity. At week 52, âOnâ time without troublesome dyskinesia and âOffâ time were improved from baseline (mean [standard deviation (SD)] change in normalized âOnâ time without troublesome dyskinesia, 3.8 [3.3] hours; normalized âOffâ time, â3.5 [3.1] hours). The percentage of patients experiencing morning akinesia dropped from 77.7% at baseline to 27.8% at week 52. Sleep quality (PDSS-2) and quality of life (PDQ-39 and EQ-5D-5L) also improved. Conclusion: Foslevodopa/foscarbidopa has the potential to provide a safe and efficacious, individualized, 24-hour/day, nonsurgical alternative for patients with PD. Trial Registration Number: ClinicalTrials.gov identifier NCT03781167
The nosological significance of Folie Ă Deux: a review of the literature
BACKGROUND: Folie Ă Deux is a rare syndrome that has attracted much clinical attention. There is increasing doubt over the essence of the condition and the validity of the original description, such that it remains an elusive entity difficult to define. METHOD: We conducted a systematic review of the literature of all cases reporting the phenomenon of Folie Ă Deux, from the years 1993â2005. RESULTS: 64 cases were identified of which 42 met the inclusion criteria. The diagnoses in the primary and secondary were more heterogeneous than current diagnostic criteria suggest. There exists a high degree of similarity between the primary and secondary in terms of susceptibility to psychiatric illness, family and past psychiatric history, than previously thought. CONCLUSION: Folie Ă Deux can occur in many situations outside the confines of the current classification systems and is not as rare as believed, and should alert the clinician to unrecognized psychiatric problems in the secondary
The comorbidity and co-medication profile of patients with progressive supranuclear palsy
Background: Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients. Objectives: To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease. Methods: Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drugâdrug interactions were evaluated using AiDKlinikÂź. Results: In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drugâdrug interactions was higher in PSP patients, especially severe and moderate interactions. Conclusions: PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients
Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: The OPTIPARK open-label study
BACKGROUND: The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. METHODS: OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinsonâs disease and motor fluctuations were treated with opicapone 50âmg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinicianâs Global Impression of Change (CGI-C) after 3âmonths. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinsonâs Disease Rating Scale (UPDRS), Parkinsonâs Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). RESULTS: Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3âmonths of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3âmonths, respectively (full analysis set). At 6âmonths, for UK subgroup only (nâ=â95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3âmonths showed statistically significant improvements in activities of daily living during OFF (meanâ±âSD change from baseline: ââ3.0â±â4.6, pâ<â0.0001) and motor scores during ON (ââ4.6â±â8.1, pâ<â0.0001). The meanâ±âSD improvements of ââ3.4â±â12.8 points for PDQ-8 and -6.8â±â19.7 points for NMSS were statistically significant versus baseline (both pâ<â0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. CONCLUSIONS: Opicapone 50âmg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. TRIAL REGISTRATION: Registered in July 2016 at clinicaltrials.gov (NCT02847442)
The comorbidity and co-medication profile of patients with progressive supranuclear palsy
Background
Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients.
Objectives
To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease.
Methods
Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drugâdrug interactions were evaluated using AiDKlinikÂź.
Results
In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drugâdrug interactions was higher in PSP patients, especially severe and moderate interactions.
Conclusions
PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients
The comorbidity profiles and medication issues of patients with multiple system atrophy: a systematic cross-sectional analysis
Background
Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patientsâ safety and management.
Objectives
To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients.
Methods
Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinikÂź.
Results
The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue.
Conclusions
MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients
PHOTOGRAMMETRIC MISSION PLANNER FOR RPAS
This paper presents a development of an open-source flight planning tool for Remotely Piloted Aircraft Systems (RPAS) that is dedicated to high-precision photogrammetric mapping. This tool contains planning functions that are usually available in professional mapping systems for manned aircrafts as well as new features related to GPS signal masking in complex (e.g. mountainous) terrain. The application is based on the open-source Java SDK (Software Development Kit) World Wind from NASA that contains the main geospatial components facilitating the development itself. Besides standard planning functions known from other mission planners, we mainly focus on additional features dealing with safety and accuracy, such as GPS quality assessment. The need for the development came as a response for unifying mission planning across different platforms (e.g. rotary or fixed wing) operating over terrain of different complexity. A special attention is given to the user interface, that is intuitive to use and cost-effective with respect to computer resources
Subjective Visual Vertical in PD Patients with Lateral Trunk Flexion
Lateral trunk flexion (LTF) is a common phenomenon in patients with Parkinsonâs disease (PD) and has recently been associated with peripheral vestibular dysfunction. Since deviation of the subjective visual vertical (SVV) is a well-recognized feature of disorders involving vestibular processing, we analyzed SVV angles in 30 PD patients with and without LTF to assess the possible role of vestibular dysfunction in the pathogenesis of LTF in PD. Quantification of SVV was obtained using a simple bedside test. PD patients with LTF had significantly greater SVV angles as compared to PD patients without LTF (median: 4.3° [range: 0.1â17.7], n=21, versus 0.8° [0.1â1.9], n=9; p<0.001). 14 of 21 patients with LTF showed pathological SVV, while all 9 patients without LTF had normal SVV. Abnormal SVV was more frequent when LTF was reversible in the supine position compared to fixed LTF. In a subgroup of PD patients with LTF, pathological SVV suggests vestibular dysbalance, which might be involved in the pathophysiological mechanisms underlying LTF
Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones
Statins [3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors] exert cholesterol-independent pleiotropic effects that include anti-thrombotic, anti-inflammatory, and anti-oxidative properties. Here, we examined direct protective effects of atorvastatin on neurones in different cell damage models in vitro. Primary cortical neurones were pre-treated with atorvastatin and then exposed to (i) glutamate, (ii) oxygen-glucose deprivation or (iii) several apoptosis-inducing compounds. Atorvastatin significantly protected from glutamate-induced excitotoxicity as evidenced by propidium iodide staining, nuclear morphology, release of lactate dehydrogenase, and mitochondrial tetrazolium metabolism, but not from oxygen-glucose deprivation or apoptotic cell death. This anti-excitototoxic effect was evident with 2-4 days pre-treatment but not with daily administration or shorter-term pre-treatment. The protective properties occurred independently of 3-hydroxy-3-methylglutaryl- CoA reductase inhibition because co-treatment with mevalonate or other isoprenoids did not reverse or attenuate neuroprotection. Atorvastatin attenuated the glutamate-induced increase of intracellular calcium, which was associated with a modulation of NMDA receptor function. Taken together, atorvastatin exerts specific anti-excitotoxic effects independent of 3-hydroxy-3-methylglutaryl-CoA reductase inhibition, which has potential therapeutic implications