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Movement Disorders : Official Journal... Jul 2021This Movement Disorder Society Genetic mutation database Systematic Review focuses on monogenic atypical parkinsonism with mutations in the ATP13A2, DCTN1, DNAJC6,...
This Movement Disorder Society Genetic mutation database Systematic Review focuses on monogenic atypical parkinsonism with mutations in the ATP13A2, DCTN1, DNAJC6, FBXO7, SYNJ1, and VPS13C genes. We screened 673 citations and extracted genotypic and phenotypic data for 140 patients (73 families) from 77 publications. In an exploratory fashion, we applied an automated classification procedure via an ensemble of bootstrap-aggregated ("bagged") decision trees to distinguish these 6 forms of monogenic atypical parkinsonism and found a high accuracy of 86.5% (95%CI, 86.3%-86.7%) based on the following 10 clinical variables: age at onset, spasticity and pyramidal signs, hypoventilation, decreased body weight, minimyoclonus, vertical gaze palsy, autonomic symptoms, other nonmotor symptoms, levodopa response quantification, and cognitive decline. Comparing monogenic atypical with monogenic typical parkinsonism using 2063 data sets from Movement Disorder Society Genetic mutation database on patients with SNCA, LRRK2, VPS35, Parkin, PINK1, and DJ-1 mutations, the age at onset was earlier in monogenic atypical parkinsonism (24 vs 40 years; P = 1.2647 × 10) and levodopa response less favorable than in patients with monogenic typical presentations (49% vs 93%). In addition, we compared monogenic to nonmonogenic atypical parkinsonism using data from 362 patients with progressive supranuclear gaze palsy, corticobasal degeneration, multiple system atrophy, or frontotemporal lobar degeneration. Although these conditions share many clinical features with the monogenic atypical forms, they can typically be distinguished based on their later median age at onset (64 years; IQR, 57-70 years). In conclusion, age at onset, presence of specific signs, and degree of levodopa response inform differential diagnostic considerations and genetic testing indications in atypical forms of parkinsonism. © 2021 International Parkinson and Movement Disorder Society.
Topics: Genotype; Humans; Levodopa; Parkinson Disease; Parkinsonian Disorders; Phenotype
PubMed: 34396589
DOI: 10.1002/mds.28517 -
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 Alzheimer's Disease : JAD 2017There is uncertainty about the efficacy and tolerability of zonisamide for Parkinson's disease (PD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is uncertainty about the efficacy and tolerability of zonisamide for Parkinson's disease (PD).
OBJECTIVE
We performed a meta-analysis of zonisamide treatment in PD patients who received antiparkinson drugs such as levodopa.
METHODS
The primary outcome measures were the Unified Parkinson's Disease Rating Scale (UPDRS) Part III scores, wearing-off time, and discontinuation rate due to all causes. Secondary outcome measures were UPDRS total and subscale scores; discontinuation rates due to adverse events, inefficacy, and death; and individual adverse events.
RESULTS
Four randomized placebo-controlled trials including 1,068 PD patients were analyzed. All studies were conducted in Japan. UPDRS Part III scores were significantly lower with zonisamide than with placebo (weighted mean difference [WMD], -2.56; 95% confidence interval [CI]; -4.20 to -0.92; p = 0.002). Further, zonisamide significantly decreased the wearing-off time compared with placebo (standardized mean difference, -0.24; 95% CI, -0.39 to -0.09; p = 0.001). Discontinuation rates due to all causes were similar between the zonisamide and placebo groups (risk ratio, 1.29; 95% CI, 0.90 to 1.84; p = 0.16). While zonisamide also decreased both UPDRS Part II (off-time) and UPDRS total scores compared to placebo (UPDRS Part II [off-time] scores: WMD, -0.79; UPDRS total scores: WMD, -2.51), there were no significant differences in other secondary outcomes between the two groups.
CONCLUSIONS
Our results suggested that zonisamide combination therapy was beneficial in treating motor symptoms in PD patients receiving antiparkinson drugs and was well tolerated in Japanese patients. Future studies in populations other than the Japanese are needed.
Topics: Antioxidants; Antiparkinson Agents; Drug Therapy, Combination; Humans; Isoxazoles; Parkinson Disease; Randomized Controlled Trials as Topic; Zonisamide
PubMed: 28157097
DOI: 10.3233/JAD-161068 -
Aesthetic Plastic Surgery Feb 2023Gestational gigantomastia (GG) is an uncommon pregnancy condition, and the underlying cause of GG has yet to be determined. Medical management and surgery are two... (Review)
Review
BACKGROUND
Gestational gigantomastia (GG) is an uncommon pregnancy condition, and the underlying cause of GG has yet to be determined. Medical management and surgery are two treatment options for GG, and breast reduction or mastectomy with delayed reconstruction is the only available surgical option. We have conducted this systematic review to summarize and critically analyze all the GG data in the literature.
METHODS
The preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines were adhered to in reporting this article. A systematic search was conducted in February 2022 for published case reports and case series on GG using the PubMed, MEDLINE, and Cochrane databases. The following keywords were used: macromastia, gestational gigantomastia, and gestational.
RESULTS
A total of 639 articles were searched, and only 66 case reports published between 1962 and 2022 were included. The mean patient's age at presentation was 28.79 years old. The majority of the patients were in their first trimester (n = 23, 47%). The main complaint was rapid bilateral breast enlargement (n = 54, 80.59%). Bromocriptine was the most common medical management used (n = 19/35, 54.28%). Bilateral breast reduction was the most common surgery (n = 24/48, 50%). Most patients had uneventful recovery (n = 40/54, 74.07%).
CONCLUSION
Gigantomastia is a difficult condition, in terms of its management. We have found that surgery is the gold-standard among all the cases reported; while Bromocriptine was the most commonly administered medical therapy. This systematic review provides a guideline for plastic surgeons to better facilitate their care of these patients.
LEVEL OF EVIDENCE III
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Topics: Female; Pregnancy; Humans; Adult; Mastectomy; Bromocriptine; Breast Neoplasms; Treatment Outcome; Mammaplasty
PubMed: 35941388
DOI: 10.1007/s00266-022-03003-5 -
Journal of Geriatric Psychiatry and... Sep 2023The current comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) in treating Parkinson's Disease Psychosis (PDP) are not entirely understood. (Meta-Analysis)
Meta-Analysis
Comparative Efficacy, Safety, and Acceptability of Pimavanserin and Other Atypical Antipsychotics for Parkinson's Disease Psychosis: Systematic Review and Network Meta-Analysis.
BACKGROUND
The current comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) in treating Parkinson's Disease Psychosis (PDP) are not entirely understood.
OBJECTIVE
To evaluate comparative efficacy, safety, and acceptability of AAPs in patients with PDP.
METHODS
We conducted a systematic review and a network meta-analysis to compare the efficacy, safety, and acceptability of pimavanserin, quetiapine, olanzapine, clozapine, ziprasidone, and risperidone. We estimated relative standardized mean differences (SMDs) for continuous outcomes and odds ratios (OR) for binary outcomes, with their respective 95% confidence intervals (CIs).
RESULTS
We included 19 unique studies evaluating AAPs in a total of 1,242 persons with PDP. Based on Clinical Global Impression Scale for Severity, pimavanserin (SMD, -4.81; 95% CI, -5.39, -4.24) and clozapine (SMD, -4.25; 95% CI, -5.24, -3.26) significantly improved symptoms compared with placebo. Also, compared to placebo, pimavanserin (OR, 1.16; 95% CI, 1.07, 1.24) significantly improved psychotic symptoms based on Scale for Assessment of Positive Symptoms for Parkinson's Disease Psychosis/Hallucinations and Delusions scores. In comparison to placebo, clozapine (SMD, -0.69; 95% CI, -1.35, -0.02), pimavanserin (SMD, -0.01; 95% CI, -0.56, 0.53), and quetiapine (SMD, 0.00; 95% CI, -0.68, 0.69) did not impair motor function per Unified Parkinson's Disease Rating scale. Based on Mini-Mental State Examination scale, quetiapine (SMD, 0.60; 95% CI, 0.07, 1.14) significantly impaired cognition compared to placebo.
CONCLUSIONS
In patients with PDP, pimavanserin and clozapine demonstrated significant improvement in psychosis without affecting motor function. With quetiapine being associated with a significant decline in cognition and despite not impairing motor function, our findings suggest that it should be avoided in patients with PDP and reduced cognitive abilities.
Topics: Humans; Antipsychotic Agents; Parkinson Disease; Clozapine; Quetiapine Fumarate; Network Meta-Analysis; Psychotic Disorders
PubMed: 36720473
DOI: 10.1177/08919887231154933 -
Journal of Affective Disorders Jun 2022To date, there is limited evidence on the antidepressant effects of memantine in patients with major mental diseases. We conducted a systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Review
The efficacy and tolerability of memantine for depressive symptoms in major mental diseases: A systematic review and updated meta-analysis of double-blind randomized controlled trials.
OBJECTIVE
To date, there is limited evidence on the antidepressant effects of memantine in patients with major mental diseases. We conducted a systematic review and meta-analysis to assess the efficacy of memantine in such populations.
METHODS
A literature search was performed for randomized controlled trials (RCTs) from the date of their inception until September 28, 2021, using PubMed, Medline, Embase, and the Cochrane Library. Changes in depression scores were the primary outcome. The response rate and remission rate to the treatment were secondary outcomes. We also assessed the dropout rate for tolerance.
RESULTS
Eleven double-blind RCTs were included with 899 participants. Memantine significantly reduced depressive symptom scores compared with the control group (k = 11, n = 899, Hedges' g = -0.17, 95% confidence interval [CI] = -0.30 to -0.04, p = 0.009) with a small effect size. For secondary outcomes, memantine did not show a significant effect on response rate nor remission rate. In the subgroup analysis, memantine significantly reduced depressive symptom scores in patients with mood disorders (k = 8, n = 673, Hedges' g = -0.17, 95% CI = -0.32 to -0.01, p = 0.035) with a small effect size, but not in patients with schizophrenia.
CONCLUSION
The present meta-analysis indicates that memantine effectively alleviates depressive symptoms in patients with mood disorders with a small effect size. Furthermore, memantine is well-tolerated and acceptable.
Topics: Antidepressive Agents; Depression; Humans; Memantine; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 35331821
DOI: 10.1016/j.jad.2022.03.047 -
Medicina (Kaunas, Lithuania) Feb 2023: So far, there is little evidence of the ambient effect on motor and non-motor symptoms of Parkinson's Disease (PD). This systematic review aimed to determine the... (Review)
Review
: So far, there is little evidence of the ambient effect on motor and non-motor symptoms of Parkinson's Disease (PD). This systematic review aimed to determine the association between ambiental factors and the progression of PD. A systematic literature search of PubMed, Cochrane, Embase, and Web of Science was conducted up to 21 December 2021 according the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. : Eight articles were used in the analyses. Long-term exposure to fine particles (particulate matter ≤ 2.5 μm; PM) was positively associated with disease aggravation in two studies. Short-term PM exposure was positively associated with disease aggravation in three studies. Significant associations were found between PD aggravation and NO, SO, CO, nitrate and organic matter (OM) concentrations in two studies. Associations were more pronounced, without reaching statistical significance however, in women, patients over 65 years old and cold temperatures. A 1% increase in temperature was associated with a significant 0.18% increase in Levodopa Equivalent Dose (LED). Ultraviolet light and humidity were not significantly associated with an increase in LED. There was no difference in hallucination severity with changing seasons. There was no evidence for seasonal fluctuation in Unified Parkinson's Disease Rating Scale (UPDRS) scores. : There is a link between air pollutants and temperature for PD progression, but this has yet to be proven. More longitudinal studies are warranted to confirm these findings.
Topics: Humans; Female; Aged; Parkinson Disease; Levodopa; Air Pollutants; Particulate Matter; Disease Progression
PubMed: 36837495
DOI: 10.3390/medicina59020294 -
Behavioural Neurology 2022Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare congenital autosomal recessive metabolic disorder caused by pathogenic homozygous or compound... (Review)
Review
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare congenital autosomal recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene. Adeno-associated viral vector-mediated gene transfer of the human AADC gene into the putamina has become available. This systematic review on PubMed, Scopus databases, and other sources is aimed at describing the AADC whole phenotypic spectrum in order to facilitate its early diagnosis. Literature reviews, original articles, retrospective and comparative studies, large case series, case reports, and short communications were considered. A database was set up using Microsoft Excel to collect clinical, molecular, biochemical, and therapeutic data. By analysing 261 patients from 41 papers with molecular and/or biochemical diagnosis of AADC deficiency for which individuality could be determined with certainty, we found symptom onset to occur in the first 6 months of life in 93% of cases. Hypotonia and developmental delay are cardinal signs, reported as present in 73.9% and 72% of cases, respectively. Oculogyric crises were seen in 67% of patients while hypokinesia in 42% and ptosis in 26%. Dysautonomic features have been revealed in 53% and gastrointestinal symptoms in 19% of cases. With 37% and 30% of patients reported being affected by sleep and behavioural disorders, it seems to be commoner than previously acknowledged. Although reporting bias cannot be excluded, there is still a need for comprehensive clinical descriptions of symptoms at onset and during follow-up. In fact, our review suggests that most of the neurological and extraneurological symptoms and signs reported, although quite frequent in this condition, are not pathognomonic, and therefore, ADCC deficiency can remain an underdiscovered disorder.
Topics: Humans; Dopa Decarboxylase; Retrospective Studies; Amino Acid Metabolism, Inborn Errors; Amino Acids
PubMed: 36268467
DOI: 10.1155/2022/2210555 -
The Cochrane Database of Systematic... Feb 2014Patients with hepatic encephalopathy may present with extrapyramidal symptoms and changes in basal ganglia. These changes are similar to those seen in patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with hepatic encephalopathy may present with extrapyramidal symptoms and changes in basal ganglia. These changes are similar to those seen in patients with Parkinson's disease. Dopamine agents (such as bromocriptine and levodopa, used for patients with Parkinson's disease) have therefore been assessed as a potential treatment for patients with hepatic encephalopathy.
OBJECTIVES
To evaluate the beneficial and harmful effects of dopamine agents versus placebo or no intervention for patients with hepatic encephalopathy.
SEARCH METHODS
Trials were identified through the Cochrane Hepato-Biliary Group Controlled Trials Register (January 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 12 of 12, 2013), MEDLINE (1946 to January 2014), EMBASE (1974 to January 2014), and Science Citation Index-Expanded (1900 to January 2014). Manual searches in reference lists, conference proceedings, and online trial registers were also performed.
SELECTION CRITERIA
Randomised trials were included, irrespective of publication status or language. The primary analyses included data from randomised trials using a parallel-group design or the first period of cross-over trials. Paired data from cross-over trials were included in sensitivity analyses.
DATA COLLECTION AND ANALYSIS
Three review authors extracted data independently. Random-effects meta-analyses were performed as the result of an expected clinical heterogeneity. Fixed-effect meta-analyses, meta-regression analyses, subgroup analyses, and sensitivity analyses were performed to evaluate sources of heterogeneity and bias (systematic errors). Trial sequential analysis was used to control the risk of play of chance (random errors).
MAIN RESULTS
Five trials that randomly assigned 144 participants with overt hepatic encephalopathy that were published during 1979 to 1982 were included. Three trials assessed levodopa, and two trials assessed bromocriptine. The mean daily dose was 4 grams for levodopa and 15 grams for bromocriptine. The median duration of treatment was 14 days (range seven to 56 days). None of the trials followed participants after the end of treatment. Only one trial reported adequate bias control; the remaining four trials were considered to have high risk of bias. Random-effects model meta-analyses showed that dopamine agents had no beneficial or detrimental effect on hepatic encephalopathy in the primary analyses (15/80 (19%) versus 14/80 (18%); odds ratio (OR) 2.99, 95% confidence interval (CI) 0.09 to 100.55; two trials) or when paired data from cross-over trials were included (OR 1.04, 95% CI 0.75 to 1.43). Clear evidence of intertrial heterogeneity was identified both in the primary analysis (I(2) = 65%) and when paired data from cross-over trials were included (I(2) = 40%).Dopamine agents had no beneficial or harmful effect on mortality (42/144 (29%) versus 38/144 (26%); OR 1.11, 95% CI 0.35 to 3.54; five trials). Trial sequential analyses demonstrated that we lacked information to refute or recommend the interventions for all outcomes. Dopamine agonists did not seem to increase the risk of adverse events.
AUTHORS' CONCLUSIONS
This review found no evidence to recommend or refute the use of dopamine agents for hepatic encephalopathy. More randomised placebo-controlled clinical trials without risks of systematic errors and risks of random errors seem necessary to permit firm decisions on dopamine agents for patients with hepatic encephalopathy.
Topics: Bromocriptine; Dopamine Agonists; Hepatic Encephalopathy; Humans; Levodopa; Randomized Controlled Trials as Topic
PubMed: 24515383
DOI: 10.1002/14651858.CD003047.pub3 -
General Hospital Psychiatry 2024This network meta-analysis assessed the efficacy, tolerability, and acceptability of second-generation antipsychotics (SGAs) for Parkinson's disease psychosis (PDP). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This network meta-analysis assessed the efficacy, tolerability, and acceptability of second-generation antipsychotics (SGAs) for Parkinson's disease psychosis (PDP).
METHODS
We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials investigating SGAs for PDP up to October 26, 2023.
RESULTS
We included 16 trials (N = 1252) investigating clozapine, melperone, olanzapine, pimavanserin, quetiapine, ulotaront, and placebo. In comparisons between SGAs and placebo, the findings were: i) Standardized mean differences, 95% confidence intervals (SMDs, 95%CIs), for psychotic-symptom reduction revealed the first rank of clozapine (-1.31, -1.73 to -0.89), the second rank of pimavanserin, with significant inferiority of quetiapine (SMD = 0.47, 0.02 to 0.92); ii) Mean differences (MDs, 95%CIs) for abnormal movement, as assessed by the Unified Parkinson's Disease Rating Scale - Part III, indicated that clozapine had the least motor side effects (-0.92, -2.75 to 0.91); iii) Risk ratios (RRs, 95% CIs) for adverse-effect dropout rates were lowest for melperone (1.02, 0.20 to 5.24); and iv) RRs (95% CIs) for all-cause dropout rates were lowest for clozapine (0.73, 0.42 to 1.25).
CONCLUSIONS
For patients with PDP, clozapine may substantially reduce psychotic symptoms with minimal abnormal movement, high acceptability, and moderate overall tolerability. Pimavanserin, not quetiapine, could be an alternative.
Topics: Humans; Antipsychotic Agents; Butyrophenones; Clozapine; Dyskinesias; Network Meta-Analysis; Parkinson Disease; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Urea
PubMed: 38412585
DOI: 10.1016/j.genhosppsych.2024.02.008