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Movement Disorders : Official Journal... Nov 2018We conducted a systematic review and meta-analysis aimed at establishing robust prevalence estimates and identifying clinical correlates of fatigue in PD. From 2,459... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic review and meta-analysis aimed at establishing robust prevalence estimates and identifying clinical correlates of fatigue in PD. From 2,459 titles and abstracts, we selected 44 relevant studies (n = 7427 patients). Overall, the meta-analysis showed a prevalence of fatigue of 50% in PD. This prevalence estimate, however, was significantly moderated by study heterogeneity in measurement scales and cut-off thresholds. In contrast, demographic features, disease severity, cognitive impairment, and depression did not moderate prevalence estimates. Moreover, fatigue prevalence did not differ between de novo and treated PD patients. Compared to nonfatigued patients, fatigued patients had sligthly higher age (1.44 years), disease duration (0.93 years), l-dopa equivalent daily dose (50.89 units), UPDRS-III (4.99 points), and H & Y (0.33 points), as well as risk of comorbid depression (risk ratio = 1.89) and had a little lower MMSE score (-0.66 points). Fatigue was moderately associated with apathy (Hedges' g = 0.55), anxiety (Hedges' g = 0.67), daytime somnolence (Hedges' g = 0.43), sleep disturbances (Hedges' g = 0.66), and poorer quality of life (Hedges' g = 1.23). Our analyses suggest that fatigue is a frequent, independent nonmotor symptom in PD appearing early and persisting throughout the disease course, and that establishing uniform diagnostic criteria for PD-related fatigue is critical. In addition, several nonmotor symptoms appear to be associated with fatigue and negatively impact quality of life. Pharmacological and nonpharmacological interventions targeting fatigue and associated symptoms may improve quality of life in patients with PD. © 2018 International Parkinson and Movement Disorder Society.
Topics: Age Factors; Fatigue; Humans; Mood Disorders; Parkinson Disease; Quality of Health Care; Quality of Life
PubMed: 30264539
DOI: 10.1002/mds.27461 -
CNS Drugs Dec 2022Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced... (Meta-Analysis)
Meta-Analysis
Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis.
INTRODUCTION
Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson's disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD.
METHODS
A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson's Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson's Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness.
RESULTS
A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5-70.9 years, duration of PD was 9.1-15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL.
CONCLUSIONS
This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.
Topics: Humans; Middle Aged; Aged; Carbidopa; Levodopa; Quality of Life; Network Meta-Analysis; Parkinson Disease; Apomorphine
PubMed: 36414908
DOI: 10.1007/s40263-022-00963-9 -
Journal of Neural Transmission (Vienna,... Oct 2022Anecdotal references, preclinical, and non-randomized studies support the therapeutic potential of cannabinoids for movement disorders (MD). To create an evidenced-based... (Review)
Review
Anecdotal references, preclinical, and non-randomized studies support the therapeutic potential of cannabinoids for movement disorders (MD). To create an evidenced-based point of view for patients and physicians, we performed a systematic review of randomized controlled trials (RCT) on the use of cannabinoids in MD. The seven RCTs found on PD used different cannabis formulations. No improvement of motor symptoms was shown in any of the two RCTs with this as primary outcome (PO), but in the nabilone group, an improvement in quality of life was documented. Of the three RCTs having levodopa-induced dyskinesia as PO, only one using nabilone showed a reduction. Anxiety and anxiety-induced tremor could be reduced in the cannabidiol group as well as anxiety and sleeping problems in the nabilone group in another RCT. In two RCTs with Tourette syndrome, an improvement in tics was revealed. From three RCTs on Huntington's disease only one found symptoms relief using nabilone. No reduction of dystonia could be shown in the two included RCTs. The limited number of available but small and inhomogeneous RCTs precludes reliable conclusions. Therefore, more and smartly designed RCTs are urgently needed.
Topics: Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Hallucinogens; Humans; Randomized Controlled Trials as Topic; Tourette Syndrome
PubMed: 35859051
DOI: 10.1007/s00702-022-02529-x -
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 -
The Cochrane Database of Systematic... Jun 2016Restless legs syndrome (RLS) is a distressing and common neurological disorder that may have a huge impact in the quality of life of those with frequent and intense... (Review)
Review
BACKGROUND
Restless legs syndrome (RLS) is a distressing and common neurological disorder that may have a huge impact in the quality of life of those with frequent and intense symptoms. Patients complain of unpleasant sensations in the legs, at or before bedtime, and feel an urge to move the legs, which improves with movement, such as walking. Symptoms start with the patient at rest (e.g. sitting or lying down), and follow a circadian pattern, increasing during the evening or at night. Many pharmacological intervention are available for RLS, including drugs used to treat Parkinson's disease (L-Dopa and dopaminergic agonists), epilepsy (anticonvulsants), anxiety (benzodiazepines), and pain (opioids). Dopaminergic drugs are those most frequently used for treatment of RLS, but some patients do not respond effectively and require other medication. Opioids, a class of medications used to treat severe pain, seem to be effective in treating RLS symptoms, and are recommended for patients with severe symptoms, because RLS and pain appear to share the same mechanism in the central nervous system. All available drugs are associated to some degree with side effects, which can impede treatment. Opioids are associated with adverse events such as constipation, tolerance, and dependence. This justifies the conduct of a systematic review to ascertain whether opioids are safe and effective for treatment of RLS.
OBJECTIVES
To asses the effects of opioids compared to placebo treatment for restless legs syndrome in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled trials, CENTRAL 2016, issue 4 and MEDLINE, EMBASE, and LILACS up to April 2016, using a search strategy adapted by Cochraneto identify randomised clinical trials. We checked the references of each study and established personal communication with other authors to identify any additional studies. We considered publications in all languages.
SELECTION CRITERIA
Randomised controlled clinical trials of opioid treatment in adults with idiopathic RLS.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened articles, independently extracted data into a standard form, and assessed for risk of bias. If necessary, they discussed discrepancies with a third researcher to resolve any doubts.
MAIN RESULTS
We included one randomised clinical trial (N = 304 randomised; 204 completed; 276 analysed) that evaluated opioids (prolonged release oxycodone/naloxone) versus placebo. After 12 weeks, RSL symptoms had improved more in the drug group than in the placebo group (using the IRLSSS: MD -7.0; 95% CI -9.69 to -4.31 and the CGI: MD -1.11; 95% CI -1.49 to -0.73). More patients in the drug group than in the placebo group were drug responders (using the IRLSSS: RR 1.82; 95% CI 1.37 to 2.42 and the CGI: RR1.92; 95% ICI 1.49 to 2.48). The proportion of remitters was greater in the drug group than in the placebo group (using the IRLSSS: RR 2.14; 95% CI 1.45 to 3.16). Quality of life scores also improved more in the drug group than in the placebo group (MD -0.73; 95% CI -1.1 to -0.36). Quality of sleep was improved more in the drug group measured by sleep adequacy (MD -0.74; 95% CI -1.15 to -0.33), and sleep quantity (MD 0.89; 95% CI 0.52 to 1.26).There was no difference between groups for daytime somnolence, trouble staying awake during the day, or naps during the day. More adverse events were reported in the drug group (RR 1.22; 95% CI 1.07 to 1.39). The major adverse events were gastrointestinal problems, fatigue, and headache.
AUTHORS' CONCLUSIONS
Opioids seem to be effective for treating RLS symptoms, but there are no definitive data regarding the important problem of safety. This conclusion is based on only one study with a high dropout rate (moderate quality evidence).
Topics: Analgesics, Opioid; Disorders of Excessive Somnolence; Humans; Naloxone; Oxycodone; Randomized Controlled Trials as Topic; Restless Legs Syndrome
PubMed: 27355187
DOI: 10.1002/14651858.CD006941.pub2 -
Movement Disorders Clinical Practice 2016Dopa-responsive dystonia (DRD) and DRD-plus are inherited metabolic disorders of the dopamine synthetic pathway that have considerable clinical, biochemical, and genetic... (Review)
Review
BACKGROUND
Dopa-responsive dystonia (DRD) and DRD-plus are inherited metabolic disorders of the dopamine synthetic pathway that have considerable clinical, biochemical, and genetic heterogeneity. Dopamine is the main deficient neurotransmitter; however, a deficiency in norepinephrine and serotonin can coexist, depending on the gene and its degree of defect. Therefore, even though levodopa is the mainstay of therapy, response to levodopa can be suboptimal and, thus, other drugs are tried.
METHODS AND RESULTS
The authors searched for reports of DRD and DRD-plus and reviewed the drugs used, their response and side effects, and neurologic outcomes, including motor and cognition. Based on the current results, a recommended treatment plan is presented according to the type of enzyme defect in patients with DRD and DRD-plus.
CONCLUSIONS
It is important to recognize the features of DRD and DRD-plus, because many of them have a good clinical response to the appropriate treatment. The aim of this review is to help guide clinicians with planning treatment for patients with DRD and DRD-plus.
PubMed: 30363598
DOI: 10.1002/mdc3.12361 -
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 -
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 -
RSC Advances Jun 2021Tyrosinase is a multifunctional glycosylated and copper-containing oxidase that is highly prevalent in plants and animals and plays a pivotal role in catalyzing the two... (Review)
Review
Tyrosinase is a multifunctional glycosylated and copper-containing oxidase that is highly prevalent in plants and animals and plays a pivotal role in catalyzing the two key steps of melanogenesis: tyrosine's hydroxylation to dihydroxyphenylalanine (DOPA), and oxidation of the latter species to dopaquinone. Melanin guards against the destructive effects of ultraviolet radiation which is known to produce considerable pathological disorders such as skin cancer, among others. Moreover, the overproduction of melanin can create aesthetic problems along with serious disorders linked to hyperpigmented spots or patches on skin. Several skin-whitening products which reduce melanogenesis activity and alleviate hyperpigmentation are commercially available. A few of them, particularly those obtained from natural sources and that incorporate a phenolic scaffold, have been exploited in the cosmetic industry. In this context, synthetic tyrosinase inhibitors (TIs) with elevated efficacy and fewer side effects are direly needed in the pharmaceutical and cosmetic industries owing to their protective effect against pigmentation and dermatological disorders. Furthermore, the biological significance of the chromone skeleton and its associated medicinal and bioactive properties has drawn immense interest and inspired many researchers to design and develop novel anti-tyrosinase agents based on the flavonoid core (2-arylchromone). This review article is oriented to provide an insight and a deeper understanding of the tyrosinase inhibitory activity of an array of natural and bioinspired phenolic compounds with special emphasis on flavonoids to demonstrate how the position of ring substituents and their interaction with tyrosinase could be correlated with their effectiveness or lack thereof against inhibiting the enzyme.
PubMed: 35480807
DOI: 10.1039/d1ra03196a -
Journal of Neural Transmission (Vienna,... Sep 2022The trajectory of the use of dopamine replacement therapy (DRT) in Parkinson's disease (PD) is variable and doses may need to be increased, but also tapered. The plan... (Review)
Review
The trajectory of the use of dopamine replacement therapy (DRT) in Parkinson's disease (PD) is variable and doses may need to be increased, but also tapered. The plan for dose adjustment is usually done as per drug information recommendations from the licensing bodies, but there are no clear guidelines with regards to the best practice regarding the tapering off schedule given sudden dose reductions of drugs such as dopamine agonists may have serious adverse consequences. A systematic literature search was, therefore, performed to derive recommendations and the data show that there are no controlled studies or evidence-based recommendations how to taper or discontinue PD medication in a systematic manner. Most of the data were available on the dopamine agonist withdrawal syndrome (DAWS) and we found only two instructions on how to reduce pramipexole and rotigotine published by the EMA. We suggest that based on the available data, levodopa, dopamine agonists (DA), and amantadine should not be discontinued abruptly. Abrupt or sudden reduction of DA or amantadine in particular can lead to severe life-threatening withdrawal symptoms. Tapering off levodopa, COMT inhibitors, and MAO-B inhibitors may worsen motor and non-motor symptoms. Based on our clinical experience, we have proposed how to reduce PD medication and this work will form the basis of a future Delphi panel to define the recommendations in a consensus.
Topics: Amantadine; Dopamine; Dopamine Agonists; Humans; Levodopa; Parkinson Disease; Substance Withdrawal Syndrome
PubMed: 34324057
DOI: 10.1007/s00702-021-02389-x