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Journal of Neuroscience Methods Jan 2021Parkinson's disease (PD) is becoming a major public-health issue in an aging population. Available approaches to treat advanced PD still have limitations; new therapies... (Review)
Review
Parkinson's disease (PD) is becoming a major public-health issue in an aging population. Available approaches to treat advanced PD still have limitations; new therapies are needed. The non-invasive brain stimulation (NIBS) may offer a complementary approach to treat advanced PD by personalized stimulation. Although NIBS is not as effective as the gold-standard levodopa, recent randomized controlled trials show promising outcomes in the treatment of PD symptoms. Nevertheless, only a few NIBS-stimulation paradigms have shown to improve PD's symptoms. Current clinical recommendations based on the level of evidence are reported in Table 1 through Table 3. Furthermore, novel technological advances hold promise and may soon enable the non-invasive stimulation of deeper brain structures for longer periods.
Topics: Aged; Brain; Deep Brain Stimulation; Humans; Parkinson Disease; Stereotaxic Techniques
PubMed: 33017643
DOI: 10.1016/j.jneumeth.2020.108957 -
Frontiers in Neurology 2021To evaluate the diagnostic accuracy of PET with different radiotracers and parameters in differentiating between true glioma progression (TPR) and post...
To evaluate the diagnostic accuracy of PET with different radiotracers and parameters in differentiating between true glioma progression (TPR) and post treatment-related change (PTRC). Studies on using PET to differentiate between TPR and PTRC were screened from the PubMed and Embase databases. By following the PRISMA checklist, the quality assessment of included studies was performed, the true positive and negative values (TP and TN), false positive and negative values (FP and FN), and general characteristics of all the included studies were extracted. Results of PET consistent with reference standard were defined as TP or TN. The pooled sensitivity (Sen), specificity (Spe), and hierarchical summary receiver operating characteristic curves (HSROC) were generated to evaluate the diagnostic accuracy. The 33 included studies had 1,734 patients with 1,811 lesions suspected of glioma recurrence. Fifteen studies tested the accuracy of F-FET PET, 12 tested F-FDG PET, seven tested C-MET PET, and three tested F-DOPA PET. F-FET PET showed a pooled Sen and Spe of 0.88 (95% CI: 0.80, 0.93) and 0.78 (0.69, 0.85), respectively. In the subgroup analysis of FET-PET, diagnostic accuracy of high-grade gliomas (HGGs) was higher than that of mixed-grade gliomas ( = 0.04). F-FDG PET showed a pooled Sen and Spe of 0.78 (95% CI: 0.71, 0.83) and 0.87 (0.80, 0.92), the Spe of the HGGs group was lower than that of the low-grade gliomas group (0.82 vs. 0.90, = 0.02). C-MET PET had a pooled Sen and Spe of 0.92 (95% CI: 0.83, 0.96) and 0.78 (0.69, 0.86). F-DOPA PET had a pooled Sen and Spe of 0.85 (95% CI: 0.80, 0.89) and 0.70 (0.60, 0.79). FET-PET combined with MRI had a pooled Sen and Spe of 0.88 (95% CI: 0.78, 0.94) and 0.76 (0.57, 0.88). Multi-parameters analysis of FET-PET had pooled Sen and Spe values of 0.88 (95% CI: 0.81, 0.92) and 0.79 (0.63, 0.89). PET has a moderate diagnostic accuracy in differentiating between TPR and PTRC. The high Sen of amino acid PET and high Spe of FDG-PET suggest that the combination of commonly used FET-PET and FDG-PET may be more accurate and promising, especially for low-grade glioma.
PubMed: 34093419
DOI: 10.3389/fneur.2021.671867 -
Neurological Sciences : Official... Jul 2021Psychosis in Parkinson's disease (PD) is common and consists of hallucinations, illusions, and delusions. Among the latter, delusional jealousy, also named Othello... (Review)
Review
INTRODUCTION
Psychosis in Parkinson's disease (PD) is common and consists of hallucinations, illusions, and delusions. Among the latter, delusional jealousy, also named Othello syndrome (OS), might impair the quality of life of both patients and their partners. We aimed to perform a systematic review and report a series of PD patients presenting with OS.
METHODS
A systematic review research was performed in PubMed database, excluding non-English articles, single case reports, reviews and neuropathology articles, comments, and articles concerning OS associated with deep brain stimulation (DBS) and levodopa-carbidopa intestinal gel infusion. We also described eleven PD patients (9 M and 2 F) with OS, identified in a cohort of consecutive 153 patients, comparing them with eleven matched no OS (nOS) PD subjects taken from the same cohort.
RESULTS
We included eight articles (four case series and four cross-sectional studies). OS resulted more common among males than females. We did not find higher levodopa dose and levodopa equivalent dose for dopamine agonists and for all anti-parkinsonian drugs in our OS group. In our case series, OS patients showed visual hallucinations (p=0.001) and a trend to have depression (p=0.080) more frequently than nOS ones.
CONCLUSIONS
OS is not a rare disorder in PD, probably due not only to abnormal dopaminergic stimulation but also to serotonergic dysfunction in biologically predisposed subjects. Visual hallucinations and other concomitant psychiatric diseases, in particular depression, might represent a risk factor for the OS development.
Topics: Antiparkinson Agents; Cross-Sectional Studies; Delusions; Dopamine Agonists; Female; Humans; Levodopa; Male; Parkinson Disease; Quality of Life
PubMed: 33978871
DOI: 10.1007/s10072-021-05249-4 -
Advances in Therapy Jun 2021Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in... (Review)
Review
INTRODUCTION
Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in levodopa-responsive patients with advanced Parkinson's disease (PD) when other treatments have not given satisfactory results. Reduction in 'off'-time is a common primary endpoint in studies of LCIG, and it is important to assess the durability of this response. This systematic literature review was conducted to qualitatively summarise the data on the long-term effects of LCIG therapy on 'off'-time.
METHODS
Studies were identified by searching PubMed, EMBASE and Ovid on 30 September 2019. Studies were included if they reported on patients with PD, had a sample size of ≥ 10, LCIG was an active intervention and 'off'-time was reported for ≥ 12 months after initiation of LCIG treatment. Randomised clinical trials, retrospective and prospective observational studies, and other interventional studies were included for selection. Data were collected on: 'off'-time (at pre-specified time periods and the end of follow-up), study characteristics, Unified Parkinson's Disease Rating Scale (UPDRS) II, III and IV total scores, dyskinesia duration, quality of life scores, non-motor symptoms and safety outcomes.
RESULTS
Twenty-seven studies were included in this review. The improvement in 'off'-time observed shortly after initiating LCIG was maintained and was statistically significant at the end of follow-up in 24 of 27 studies. 'Off'-time was reduced from baseline to end of follow-up by 38-84% and was accompanied by a clinically meaningful improvement in quality of life. Stratified analysis of 'off'-time demonstrated mean relative reductions of 47-82% at 3-6 months and up to 83% reduction at 3-5 years of follow-up. Most studies reported significant improvements in activities of daily living and motor complications. Most frequent adverse events were related to the procedure or the device.
CONCLUSION
In one of the largest qualitative syntheses of published LCIG studies, LCIG treatment was observed to provide a durable effect in reducing 'off'-time.
INFOGRAPHIC
Video Abstract.
Topics: Activities of Daily Living; Antiparkinson Agents; Carbidopa; Drug Combinations; Gels; Humans; Levodopa; Observational Studies as Topic; Parkinson Disease; Quality of Life; Retrospective Studies
PubMed: 34018146
DOI: 10.1007/s12325-021-01747-1 -
Annals of Neurosciences Jan 2021In recent times, the US-FDA approved istradefylline and opicapone as an adjunct to levodopa/carbidopa for managing the "off" episodes in Parkinson's disease.
BACKGROUND
In recent times, the US-FDA approved istradefylline and opicapone as an adjunct to levodopa/carbidopa for managing the "off" episodes in Parkinson's disease.
PURPOSE
Current meta-analysis was performed to determine the safety and efficacy of these drugs in the management of "off" episodes and to recognize which among them would provide therapeutic benefits clinically.
METHODS
A thorough literature search was performed through the Cochrane Library, PubMed, and clinicaltrials.gov for a period from January 2003 to October 2020, with the following keywords: Istradefylline, KW-6002, opicapone, BIA 9-1067, and Parkinson's disease. Those randomized, double-blind placebo/active comparator-controlled trials that analyzed the efficacy and safety of istradefylline and opicapone and that were published in the English language were included. In this analysis, the outcomes focused on the least square mean change in "off" time and Unified Parkinson's Disability Rating Scale (UPDRS) III score from baseline to the end of the study, and the incidence of treatment-emergent adverse events (TEAEs) and dyskinesia.
RESULTS
Both drugs have shown significant reduction in "off" time duration (mean difference [MD] = -0.70; 95% CI [-1.11, -0.30]; < 0.001 for istradefylline and MD = -0.85; 95% CI [-1.09, -0.61]; < .001 for opicapone). Istradefylline showed significant improvement in UPDRS III (MD = -1.56; 95% CI [-2.71, -0.40]; < .008), but the same was not observed with opicapone (MD = -0.63; 95% CI [-1.42, -0.15]; < .12). The incidence of TEAEs and dyskinesia reportedly were higher in the intervention group rather than with the placebo, (risk ratio RR =1.11, 95% CI [1.02,1.20] for istradefylline and RR =1.12, 95% CI [1.00,1.25] for opicapone, and for dyskinesia particularly, the incidence was higher with opicapone as compared to istradefylline (RR = 3.47, 95% CI [2.17, 5.57], and RR = 1.77, 95% CI [1.29, 2.44], respectively).
CONCLUSIONS
Both drugs were comparable in efficacy; however, istradefylline seemed to be better in reducing the UPDRS III score. Although the incidence of TEAEs and dyskinesia were higher with both the drugs, the incidence of dyskinesia was more in the opicapone group.
PubMed: 34733056
DOI: 10.1177/09727531211046362 -
European Journal of Clinical... Jun 2021Tolcapone is an efficacious catechol-O-methyltransferase inhibitor for Parkinson's disease (PD). However, safety issues hampered its use in clinical practice. We aimed...
PURPOSE
Tolcapone is an efficacious catechol-O-methyltransferase inhibitor for Parkinson's disease (PD). However, safety issues hampered its use in clinical practice. We aimed to provide evidence of safety and efficacy of tolcapone by a systematic literature review to support clinicians' choices in the use of an enlarging PD therapeutic armamentarium.
METHODS
We searched PubMed for studies on PD patients treated with tolcapone, documenting the following outcomes: liver enzyme, adverse events (AEs), daily Off-time, levodopa daily dose, unified Parkinson's disease rating scale (UPDRS) part-III, quality of life (QoL), and non-motor symptoms. FAERS and EudraVigilance databases for suspected AEs were interrogated for potential additional cases of hepatotoxicity.
RESULTS
Thirty-two studies were included, for a total of 4780 patients treated with tolcapone. Pertaining safety, 0.9% of patients showed liver enzyme elevation > 2. Over 23 years, we found 7 cases of severe liver injury related to tolcapone, 3 of which were fatal. All fatal cases did not follow the guidelines for liver function monitoring. FAERS and EudraVigilance database search yielded 61 reports of suspected liver AEs possibly related to tolcapone. Pertaining efficacy, the median reduction of hours/day spent in Off was 2.1 (range 1-3.2), of levodopa was 108.9 mg (1-251.5), of "On" UPDRS-III was 3.6 points (1.1-6.5). Most studies reported a significant improvement of QoL and non-motor symptoms.
CONCLUSION
Literature data showed the absence of relevant safety concerns of tolcapone when strict adherence to hepatic function monitoring is respected. Given its high efficacy on motor fluctuations, tolcapone is probably an underutilized tool in the therapeutic PD armamentarium.
Topics: Antiparkinson Agents; Catechol O-Methyltransferase Inhibitors; Chemical and Drug Induced Liver Injury; Humans; Levodopa; Liver Function Tests; Parkinson Disease; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Tolcapone
PubMed: 33415500
DOI: 10.1007/s00228-020-03081-x -
Cureus Aug 2020Deep brain stimulation (DBS) is a rapidly evolving procedure with its application in multiple fields of neurology, but it is most prominent in Parkinson's disease (PD).... (Review)
Review
Deep brain stimulation (DBS) is a rapidly evolving procedure with its application in multiple fields of neurology, but it is most prominent in Parkinson's disease (PD). Through electrode implantation in different areas of the brain, it brings a favorable change to the motor symptoms to the magnitude that none of the medications have been able to, but the effect on cognition of the patients is still unknown. We did a comprehensive search through PubMed and Cochrane databases and conducted a systematic review by following the PRISMA guidelines. Inclusion criteria were studies conducted only in PD patients, after the year 2008. The studies published in languages other than English were excluded. Thirteen studies, including randomized and non-randomized controlled trials, observational studies, and meta-analysis, were analyzed in detail. The results showed a declining trend in verbal fluency and attention domains of cognition, while other functions remained unchanged. The decline was significant but not enough to impact the quality index in patients. DBS is associated with worse performance in verbal fluency and attention, and there is a further need for studies focusing on these domains with long-term follow-up. The overall cognitive profile was not affected significantly.
PubMed: 32923280
DOI: 10.7759/cureus.9688 -
Frontiers in Neurology 2022Parkinson's disease (PD) causes movement disorders [called motor symptoms (MS)], and motor dysfunction poses a great barrier to the quality of life. Although...
BACKGROUND
Parkinson's disease (PD) causes movement disorders [called motor symptoms (MS)], and motor dysfunction poses a great barrier to the quality of life. Although pharmacological therapy like levodopa can relieve the symptoms, it can also cause complications, such as psychosis, nausea, and dyskinesia. A therapy with more minor side effects is needed for PD. Therapeutic massages are the most commonly used forms of complementary and alternative medicine (CAM), but no systematic review and meta-analysis have focused on the efficacy of massage on PD.
OBJECTIVE
To evaluate the quality of evidence and efficacy of therapeutic massage for improving MS in PD.
METHODS
We independently searched four electronic databases, including Chinese National Knowledge Infrastructure (CNKI), MEDLINE/PubMed, Embase, and Cochrane Library, for randomized controlled trials (RCTs) about therapeutic massage and other available manual therapies improving MS in PD from January 1, 2012, to December 31, 2021 (recent 10 years). The main outcome measures were total effectiveness and the Unified Parkinson's Disease Rating Scale (UPDRS), including UPDRS total, II, and III. For the statistical analysis, the risk ratio, standard mean difference, and 95% confidence interval (CI) were used to calculate effect sizes between groups. To determine heterogeneity, statistical index was used.
RESULTS
A total of 363 PD participants in seven RCTs and one randomized pilot-control study were included in this meta-analysis. The total effectiveness showed that therapeutic massage was more effective than the intervention of the control group for improving MS [ratio risk (RR): 1.33, 95% CI (1.14-1.55), = 0.0002]. The UPDRS-III scores showed that massage improves motor function more than the control group [SMD = -0.46, 95% CI (-0.67, -0.24), < 0.00001]. But we found that massage performed no better than the control group in improving daily life activities [SMD = -0.15, 95% CI (-0.40, 0.10), = 0.23].
CONCLUSION
Therapeutic massage was effective in improving MS in PD. It is suggested to be an appropriate form of CAM in treating PD.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=323182, identifier: CRD42022323182.
PubMed: 36133798
DOI: 10.3389/fneur.2022.915232 -
Frontiers in Neurology 2023Available data suggest that there may be gender differences in the effect of STN-DBS in the treatment of Parkinson's disease (PD). The aim of this study was to review...
Gender discrepancies and differences in motor and non-motor symptoms, cognition, and psychological outcomes in the treatment of Parkinson's disease with subthalamic deep brain stimulation.
Available data suggest that there may be gender differences in the effect of STN-DBS in the treatment of Parkinson's disease (PD). The aim of this study was to review data on gender discrepancies and gender differences in clinical outcomes in PD patients treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). Included were original studies that specifically examined gender discrepancies or gender differences in PD patients with STN-DBS. Men receive more DBS than women, for various indications. The decision-making process for DBS in women compared to men is more influenced by personal preferences and external factors. Motor symptoms improve in both genders, but bradykinesia improves more in men. The postoperative reduction of the levodopa equivalent daily dose seems to be more pronounced in men. Men show more cognitive deterioration and less improvement than women after STN-DBS. Women show more depressive symptoms before surgery, but they improve similarly to men. Men show more improvement in impulsivity and less decrease in impulsive behaviour symptoms than women. Anxiety and personality traits remain unchanged in both genders. Voice quality improves more in men and deteriorates less often than in women. Men gain fat-free mass and fat mass, but women only gain fat mass. Regarding sexual function the evidence is inconsistent. More urinary symptoms improve in women than in men. Pain and restless leg syndrome seems to improve more in men. Regarding quality of life, the evidence seems to be inconsistent, and activities of daily living seems to improve in both genders. Better prospective controlled studies, focusing directly on gender differences in PD patients treated with STN-DBS, are needed to better explain gender differences in STN-DBS for PD.
PubMed: 38259647
DOI: 10.3389/fneur.2023.1257781 -
Brain and Behavior Aug 2023Secondary tumoral parkinsonism is a rare phenomenon that develops as a direct or indirect result of brain neoplasms or related conditions. (Review)
Review
Tumoral parkinsonism-Parkinsonism secondary to brain tumors, paraneoplastic syndromes, intracranial malformations, or oncological intervention, and the effect of dopaminergic treatment.
INTRODUCTION
Secondary tumoral parkinsonism is a rare phenomenon that develops as a direct or indirect result of brain neoplasms or related conditions.
OBJECTIVES
The first objective was to explore to what extent brain neoplasms, cavernomas, cysts, paraneoplastic syndromes (PNSs), and oncological treatment methods cause parkinsonism. The second objective was to investigate the effect of dopaminergic therapy on the symptomatology in patients with tumoral parkinsonism.
METHODS
A systematic literature review was conducted in the databases PubMed and Embase. Search terms like "secondary parkinsonism," "astrocytoma," and "cranial irradiation" were used. Articles fulfilling inclusion criteria were included in the review.
RESULTS
Out of 316 identified articles from the defined database search strategies, 56 were included in the detailed review. The studies, which were mostly case reports, provided research concerning tumoral parkinsonism and related conditions. It was found that various types of primary brain tumors, such as astrocytoma and meningioma, and more seldom brain metastases, can cause tumoral parkinsonism. Parkinsonism secondary to PNSs, cavernomas, cysts, as well as oncological treatments was reported. Twenty-five of the 56 included studies had tried initiating dopaminergic therapy, and of these 44% reported no, 48% low to moderate, and 8% excellent effect on motor symptomatology.
CONCLUSION
Brain neoplasms, PNSs, certain intracranial malformations, and oncological treatments can cause parkinsonism. Dopaminergic therapy has relatively benign side effects and may relieve motor and nonmotor symptomatology in patients with tumoral parkinsonism. Dopaminergic therapy, particularly levodopa, should therefore be considered in patients with tumoral parkinsonism.
Topics: Humans; Parkinsonian Disorders; Brain Neoplasms; Dopamine; Astrocytoma; Paraneoplastic Syndromes; Meningeal Neoplasms; Cysts
PubMed: 37433071
DOI: 10.1002/brb3.3151