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Movement Disorders : Official Journal... Jul 2023To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in...
BACKGROUND
To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed.
OBJECTIVES
To update LED conversion formulae based on a systematic review.
METHODS
The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency.
RESULTS
The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon.
CONCLUSIONS
The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Humans; Levodopa; Parkinson Disease; Antiparkinson Agents; Treatment Outcome
PubMed: 37147135
DOI: 10.1002/mds.29410 -
Journal of the Neurological Sciences Jul 2023The prevalences of polyneuropathy and epilepsy are higher in people living with Parkinson's disease (PwPD) when compared to older adults. Vitamin B6 is widely available... (Review)
Review
The prevalences of polyneuropathy and epilepsy are higher in people living with Parkinson's disease (PwPD) when compared to older adults. Vitamin B6 is widely available and affordable. PwPD are at higher risk of having abnormal serum levels of vitamin B6, which are associated with polyneuropathy and epilepsy that are potentially preventable and treatable. Potential contributors to abnormal B6 levels in PwPD include age, dietary habits, vitamin supplement misuse, gastrointestinal dysfunction and complex interactions with levodopa. The literature on the potential consequences of abnormal B6 levels in PwPD is limited by a small number of observational studies focused on polyneuropathy and epilepsy. Abnormal B6 levels have been reported in 60 of 145 PwPD (41.4% relative frequency). Low B6 levels were reported in 52 PwPD and high B6 levels were reported in 8 PwPD. There were 14 PwPD, polyneuropathy and low B6. There were 4 PwPD, polyneuropathy and high B6. There were 4 PwPD, epilepsy and low B6. Vitamin B6 level was low in 44.6% of PwPD receiving levodopa-carbidopa intestinal gel and in 30.1% of PwPD receiving oral levodopa-carbidopa. In almost all studies reporting low B6 in PwPD receiving oral levodopa-carbidopa, the dose of levodopa was ≥1000 mg/day. Rigorous epidemiological studies will clarify the prevalence, natural history and clinical relevance of abnormal serum levels of vitamin B6 in PwPD. These studies should account for diet, vitamin supplement use, gastrointestinal dysfunction, concurrent levels of vitamin B12, folate, homocysteine and methylmalonic acid, formulations and dosages of levodopa and other medications commonly used in PwPD.
Topics: Humans; Aged; Levodopa; Parkinson Disease; Carbidopa; Antiparkinson Agents; Vitamin B 6; Polyneuropathies; Vitamin B 12; Epilepsy; Vitamins
PubMed: 37210937
DOI: 10.1016/j.jns.2023.120690 -
Movement Disorders Clinical Practice Oct 2023In Parkinson's disease (PD), impulsivity as a personality trait may be linked to the risk of developing impulse control disorders (ICDs) during dopaminergic therapy.... (Review)
Review
BACKGROUND
In Parkinson's disease (PD), impulsivity as a personality trait may be linked to the risk of developing impulse control disorders (ICDs) during dopaminergic therapy. However, studies evaluating differences in trait impulsivity between patients with PD and healthy controls or between patients with PD with and without ICDs reported partly inconsistent findings.
OBJECTIVES
We conducted a systematic review and meta-analysis (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) of studies comparing Barratt Impulsiveness Scale (BIS-11) scores between patients with PD and healthy controls and between patients with PD with and without ICDs.
METHODS
Eligible studies were identified through a systematic search in 3 databases. Mean differences with 95% confidence intervals (CIs) for BIS-11 total and subscale scores were separately calculated for studies comparing patients with PD and healthy controls and patients with PD with and without ICDs. Meta-regressions were performed to explore sources of heterogeneity (percentage of men, age, disease duration, and levodopa equivalent daily dose).
RESULTS
A total of 40 studies were included in the quantitative analyses. BIS-11 total scores were significantly higher in patients with PD compared with healthy controls (mean difference 2.43; 95% CI, 1.03, 3.83), and in patients with PD with active ICDs compared with patients without ICDs (6.62; 95% CI, 5.01, 8.23). No significant moderators emerged by meta-regression analyses.
CONCLUSIONS
The present meta-analysis supports that impulsivity, as a personality trait, may characterize patients with PD, even in the absence of ICDs. Moreover, these data corroborate findings of clinical studies reporting higher levels of trait impulsivity in PD patients with ICDs compared with patients without ICDs.
PubMed: 37868926
DOI: 10.1002/mdc3.13839 -
Frontiers in Aging Neuroscience 2023Parkinson's disease (PD) is recognized as the second most prevalent progressive neurodegenerative disease among the elderly. However, the relationship between PD and...
BACKGROUND
Parkinson's disease (PD) is recognized as the second most prevalent progressive neurodegenerative disease among the elderly. However, the relationship between PD and plasma homocysteine (Hcy), vitamin B12, and folate has yielded inconsistent results in previous studies. Hence, in order to address this ambiguity, we conducted a meta-analysis to summarize the existing evidence.
METHODS
Suitable studies published prior to May 2023 were identified by searching PubMed, EMBASE, Medline, Ovid, and Web of Science. The methodological quality of eligible studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Meta-analysis and publication bias were then performed using R version 4.3.1.
RESULTS
The results of our meta-analysis, consisting of case-control and cross-sectional studies, showed that PD patients had lower folate and vitamin B12 levels (SMD [95%CI]: -0.30[-0.39, -0.22], < 0.001 for Vitamin B12; SMD [95%CI]: -0.20 [-0.28, -0.13], < 0.001 for folate), but a significant higher Hcy level (SMD [95%CI]: 0.86 [0.59, 1.14], < 0.001) than healthy people. Meanwhile, PD was significantly related to hyperhomocysteinemia (SMD [95%]: 2.02 [1.26, 2.78], < 0.001) rather than plasma Hcy below 15 μmol/L (SMD [95%]: -0.31 [-0.62, 0.00], = 0.05). Subgroup analysis revealed associations between the Hcy level of PD patients and region ( = 0.03), age ( = 0.03), levodopa therapy ( = 0.03), Hoehn and Yahr stage ( < 0.001), and cognitive impairment ( < 0.001). However, gender ( = 0.38) and sample size ( = 0.49) were not associated.
CONCLUSION
Hcy, vitamin B12, and folic acid potentially predict the onset and development of PD. Additionally, multiple factors were linked to Hcy levels in PD patients. Further studies are needed to comprehend their roles in PD.
PubMed: 37941998
DOI: 10.3389/fnagi.2023.1254824 -
European Journal of Neurology Aug 2023Tremor is often perceived as severely disabling by patients with idiopathic Parkinson's disease (iPD) and yet ranges among the most difficult symptoms to treat. To date,... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Tremor is often perceived as severely disabling by patients with idiopathic Parkinson's disease (iPD) and yet ranges among the most difficult symptoms to treat. To date, no comprehensive analysis of non-lesional therapies to manage tremor in iPD exists to base recommendations upon. We therefore present a systematic literature review and meta-analysis assessing the efficacy/effectiveness and safety of non-lesional treatments for tremor in iPD.
METHODS
Three electronic databases were searched using a combination of title/abstract keywords complemented by hand-searching of reference lists. A random-effects meta-analysis of standardized mean change scores was conducted where appropriate.
RESULTS
Some 114 studies met inclusion criteria involving 8045 patients. The meta-analysis revealed an overall reduction of standardized mean change scores by (-0.93 [CI: -1.42; -0.43], p < 0.001) by 14 different dopaminergic and non-dopaminergic classes of agents. No significant differences were identified between direct comparisons. Subgroup analysis comparing dopamine receptor agonists resulted in superior effects of pramipexole and rotigotine compared with ropinirole. There was little cumulative evidence to support the use of individual non-pharmacological interventions for tremor, except for electrical stimulation.
CONCLUSIONS
The results of this meta-analysis suggest a large but nonspecific effect of established pharmacological therapies on tremor in iPD. Based on high-quality studies, there is sufficient evidence to support that levodopa, dopamine receptor agonists, and monoamine oxidase inhibitors provide tremor relief in most patients, while evidence supporting other treatments is less well established. Sufficient evidence to draw conclusions on effects of non-lesional treatments in cases with refractory tremor is lacking.
Topics: Humans; Parkinson Disease; Dopamine Agonists; Antiparkinson Agents; Tremor; Levodopa
PubMed: 37154268
DOI: 10.1111/ene.15823 -
Eye (London, England) Jun 2024Traumatic optic neuropathy is classically described in up to 8% of patients with traumatic brain injury (TBI), but subclinical or undiagnosed optic nerve damage is much... (Review)
Review
BACKGROUND
Traumatic optic neuropathy is classically described in up to 8% of patients with traumatic brain injury (TBI), but subclinical or undiagnosed optic nerve damage is much more common. When more sensitive testing is performed, at least half of patients with moderate to severe TBI demonstrate visual field defects or optic atrophy on examination with optical coherence tomography. Acute optic nerve compression and ischaemia in orbital compartment syndrome require urgent surgical and medical intervention to lower the intraocular pressure and diminish the risk of permanent optic nerve dysfunction. Other manifestations of traumatic optic neuropathy have more variable treatments in international practice.
METHODS
We conducted a systematic review of traumatic optic neuropathy treatments in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement.
RESULTS
We included three randomised controlled trials of intravenous methylprednisolone (IVMP), erythropoietin, and levodopa-carbidopa combination, with no evidence of benefit for any treatment. In addition, large studies in TBI have found strong evidence of increased mortality in patients treated with megadose IVMP.
CONCLUSIONS
There is therefore no evidence of benefit for any medical treatment and strong evidence of harm from IVMP. There is also no evidence of benefit for optic canal decompression for traumatic optic neuropathy. Orbital compartment syndrome is a separate entity that requires both medical and surgical interventions to prevent visual loss.
PubMed: 38862644
DOI: 10.1038/s41433-024-03129-7 -
Journal of Translational Medicine Sep 2023Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson's disease (PD) for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson's disease (PD) for decades. However, despite promising preclinical results, clinical trials on cell-therapy for PD reported mixed outcomes and a thorough synthesis of these findings is lacking. We performed a systematic review and meta-analysis to evaluate cell-therapy for PD patients.
METHODS
We systematically identified all clinical trials investigating cell- or tissue-based therapies for PD published before July 2023. Out of those, studies reporting transplantation of homogenous cells (containing one cell type) were included in meta-analysis. The mean difference or standardized mean difference in quantitative neurological scale scores before and after cell-therapy was analyzed to evaluate treatment effects.
RESULTS
The systematic literature search revealed 106 articles. Eleven studies reporting data from 11 independent trials (210 patients) were eligible for meta-analysis. Disease severity and motor function evaluation indicated beneficial effects of homogenous cell-therapy in the 'off' state at 3-, 6-, 12-, or 24-month follow-ups, and for motor function even after 36 months. Most of the patients were levodopa responders (61.6-100% in different follow-ups). Cell-therapy was also effective in improving the daily living activities in the 'off' state of PD patients. Cells from diverse sources were used and multiple transplantation modes were applied. Autografts did not improve functional outcomes, while allografts exhibited beneficial effects. Encouragingly, both transplantation into basal ganglia and to areas outside the basal ganglia were effective to reduce disease severity. Some trials reported adverse events potentially related to the surgical procedure. One confirmed and four possible cases of graft-induced dyskinesia were reported in two trials included in this meta-analysis.
CONCLUSIONS
This meta-analysis provides preliminary evidence for the beneficial effects of homogenous cell-therapy for PD, potentially to the levodopa responders. Allogeneic cells were superior to autologous cells, and the effective transplantation sites are not limited to the basal ganglia. PROSPERO registration number: CRD42022369760.
Topics: Humans; Parkinson Disease; Levodopa; Transplantation, Autologous; Transplantation, Homologous; Allogeneic Cells
PubMed: 37679754
DOI: 10.1186/s12967-023-04484-x -
European Journal of Neurology Dec 2023The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European... (Review)
Review
BACKGROUND
The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European Reference Network of Rare Neurological Disorders funded by the European Commission conducted a systematic review to assess drug treatment of chorea in NKX2-1-RD, aiming to provide clinical recommendations for its management.
METHODS
A systematic pairwise review using various databases, including MEDLINE, Embase, Cochrane, CINAHL, and PsycInfo, was conducted. The review included patients diagnosed with chorea and NKX2-1-RD genetic diagnosis, drug therapy as intervention, no comparator, and outcomes of chorea improvement and adverse events. The methodological quality of the studies was assessed, and the study protocol was registered in PROSPERO.
RESULTS
Of the 1417 studies examined, 28 studies met the selection criteria, consisting of 68 patients. The studies reported 22 different treatments for chorea, including carbidopa/levodopa, tetrabenazine, clonazepam, methylphenidate, carbamazepine, topiramate, trihexyphenidyl, haloperidol, propranolol, risperidone, and valproate. No clinical improvements were observed with carbidopa/levodopa, tetrabenazine, or clonazepam, and various adverse effects were reported. However, most patients treated with methylphenidate experienced improvements in chorea and reported only a few negative effects. The quality of evidence was determined to be low.
CONCLUSIONS
The management of chorea in individuals with NKX2-1-RD presents significant heterogeneity and lack of clarity. While the available evidence suggests that methylphenidate may be effective in improving chorea symptoms, the findings should be interpreted with caution due to the limitations of the studies reviewed. Nonetheless, more rigorous and comprehensive studies are necessary to provide sufficient evidence for clinical recommendations.
Topics: Humans; Chorea; Tetrabenazine; Levodopa; Carbidopa; Clonazepam; Methylphenidate
PubMed: 37694681
DOI: 10.1111/ene.16038 -
Clinical Neurology and Neurosurgery Apr 2024Levodopa treatment requires the addition of other drugs, such as catechol-O-methyl transferase (COMT) inhibitors, to alleviate motor fluctuations in advanced parkinson's... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Levodopa treatment requires the addition of other drugs, such as catechol-O-methyl transferase (COMT) inhibitors, to alleviate motor fluctuations in advanced parkinson's disease (PD). However, the optimal strategy, including the type and dose of COMT inhibitors remains unknown. This systematic review and network meta-analysis aimed to assess the efficacy and safety of different COMT inhibitors and for treating PD patients.
METHODS
PubMed, Embase, Cochrane Library and Web of Science were screened up to November 20, 2022. Randomized controlled trials (RCTs) of COMT inhibitors (entacapone, opicapone, tolcapone) for PD patients were included. Eligible outcomes were total ON-time, rate of ON-time >1 h, total daily dose of levodopa therapy, mean change from baseline to final follow up in Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, adverse events and dyskinesia. Network meta-analyses integrated direct and indirect evidence with placebo as a common comparator.
RESULTS
We identified 18 studies with 7564 patients. Opicapone, entacapone, and tolcapone could increase total ON-time when compared with placebo. However, opicapone (25 mg, MD 4.0, 95%CrI: 1.1-7.5) and opicapone (50 mg, MD 5.1, 95%CrI: 2.2-8.7) statistically significant increase the total ON-time. opicapone and entacapone could increase the rate of ON-time >1 h when compared with placebo. Only opicapone (5 mg) showed no statistically significant with placebo (OR 1.4, 95%CrI: 0.74-2.4). We found that opicapone (50 mg, SURCA, 0.796) is the best option compared with other treatments. TOL (200 mg) was ranked highest in the rank probability test for total daily dose of levodopa therapy, followed by OPI (50 mg), TOL (400 mg) and TOL (100 mg) in order. SUCRA rankings identified TOL (200 mg) as the most likely therapy for increasing adverse events (SUCRA 27.19%), followed by TOL (400 mg, SUCRA 27.20%) and OPI (5 mg, SUCRA 30.81%). The SUCRA probabilities were 91.6%, 75.2%, 67.9%, 59.3%, 45.6%, 41.1%, 35.1%, 24.6% and 9.4% for PLA, TOL (400 mg), ENT (100 mg), ENT (200 mg), OPI (5 mg), TOL (100 mg), OPI (25 mg), OPI (50 mg), and TOL (200 mg) respectively.
CONCLUSION
In conclusion, opicapone (50 mg) may be a better choice for treatment PD when compared with other COMT inhibitors.
Topics: Humans; Parkinson Disease; Levodopa; Antiparkinson Agents; Tolcapone; Network Meta-Analysis; Catechol O-Methyltransferase Inhibitors; Catechols; Transferases; Randomized Controlled Trials as Topic; Nitriles
PubMed: 38437773
DOI: 10.1016/j.clineuro.2024.108189 -
Movement Disorders : Official Journal... Jan 2024Subjective cognitive complaints (SCCs) in Parkinson's disease (PD) are reported frequently, but their prevalence and association with changes on objective testing are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Subjective cognitive complaints (SCCs) in Parkinson's disease (PD) are reported frequently, but their prevalence and association with changes on objective testing are not fully known.
OBJECTIVE
We aimed to determine the prevalence, clinical correlates, and predictive value of SCCs in PD.
METHODS
We conducted a systematic review and meta-analysis. From 204 abstracts, we selected 31 studies (n = 3441 patients), and from these, identified the prevalence, clinical features, associations with neuropsychiatric symptoms, and predictive values of SCCs in PD.
RESULTS
The meta-analysis showed an SCC prevalence of 36%. This prevalence, however, was significantly moderated by study heterogeneity regarding female sex, disease severity, levodopa equivalent daily dosage, exclusion from the overall sample of patients with objective cognitive impairment, and measurement instrument. SCC prevalence did not differ between de novo and treated PD patients. SCCs were weakly and negligibly associated with cognitive changes on objective testing in cross-sectional studies. However, in cognitively healthy patients, SCCs had a risk ratio of 2.71 for later cognitive decline over a mean follow-up of 3.16 years. Moreover, SCCs were moderately related to co-occurring symptoms of depression, anxiety, or apathy and were more strongly related to these neuropsychiatric symptoms than objective cognitive functioning.
CONCLUSION
Our analyses suggest that SCCs in patients with and without objective cognitive impairment are frequent, occurring in more than one third of PD patients. Establishing uniform measurement instruments for identifying PD-related SCCs is critical to understand their implications. Even in cases lacking evidence of objective cognitive impairment and where SCCs might reflect underlying neuropsychiatric symptoms, the possibility of later cognitive deterioration should not be excluded. Therefore, SCCs in PD patients warrant close monitoring for opportunities for targeted and effective interventions. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Humans; Female; Parkinson Disease; Cross-Sectional Studies; Cognition Disorders; Cognitive Dysfunction; Cognition
PubMed: 38173220
DOI: 10.1002/mds.29649