-
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 -
Cureus Jul 2020Somatic symptom disorder (SSD) and antisocial personality disorder (APSD) are found at higher rates within families compared to the general population. Both disorders... (Review)
Review
Somatic symptom disorder (SSD) and antisocial personality disorder (APSD) are found at higher rates within families compared to the general population. Both disorders are characterized by low serotonin levels, which may be attributed to polymorphisms in the dopa decarboxylase (DDC) gene. The polymorphism rs11575542 of the gene leads to decreasing the efficiency of aromatic l-amino decarboxylase (AADC) and serotonin levels in a person. The polymorphism is also associated with the development of somatic symptoms and sensation-seeking behavior, a trait underlying APSD. Hence, the role of this polymorphism as an underlying feature that may predispose a person to develop APSD or SSD should be explored further in future studies.
PubMed: 32850196
DOI: 10.7759/cureus.9318 -
Tremor and Other Hyperkinetic Movements... Jul 2020Chorea consists of involuntary movements affecting the limbs, trunk, neck or face, that can move from one body part to another. Chorea is conceptualized as being...
BACKGROUND
Chorea consists of involuntary movements affecting the limbs, trunk, neck or face, that can move from one body part to another. Chorea is conceptualized as being "primary" when it is attributed to Huntington's disease (HD) or other genetic etiologies, or "secondary" when it is related to infectious, pharmacologic, metabolic, autoimmune disorders, or paraneoplastic syndromes. The mainstay of the secondary chorea management is treating the underlying causative disorder; here we review the literature regarding secondary chorea. We also discuss the management of several non-HD genetic diseases in which chorea can be a feature, where metabolic targets may be amenable to intervention and chorea reduction.
METHODS
A PubMed literature search was performed for articles relating to chorea and its medical and surgical management. We reviewed the articles and cross-references of pertinent articles to assess the current clinical practice, expert opinion, and evidence-based medicine to synthesize recommendations for the management of secondary chorea.
RESULTS
There are very few double-blind randomized controlled trials assessing chorea treatments regardless of etiology. Most recommendations are based on small open-label studies, case reports, and expert opinion.
DISCUSSION
Treatment of secondary chorea is currently based on expert opinion, clinical experience, and small case studies, with limited evidence-based medical data. When chorea is secondary to an underlying infection, medication, metabolic abnormality, autoimmune process, or paraneoplastic illness, the movements typically resolve following treatment of the underlying disease. Tardive dyskinesia is most rigorously studied secondary chorea with the best evidence-based medicine treatment guidelines recommending the use of pre-synaptic dopamine-depleting agents. Even though there is an insufficient pool of EBM, small clinical trials, case reports, and expert opinion are valuable for guiding treatment and improving the quality of life for patients with chorea.
HIGHLIGHTS
There is a dearth of well-controlled studies regarding the treatment of chorea. Expert opinion and clinical experiences are fundamental in guiding chorea management and determining successful treatment. In general, secondary chorea improves with treating the underlying medical abnormality; treatments include antibiotics, antivirals, immunosuppression, dopamine depleting agents, chelation, and supportive care.
Topics: Chorea; Humans; Tardive Dyskinesia
PubMed: 32775036
DOI: 10.5334/tohm.351 -
European Journal of Clinical... Dec 2020To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson's disease. (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson's disease.
METHODS
We performed a systematic literature search identifying randomized controlled trials investigating 4 dopamine agonists (cabergoline, pramipexole, ropinirole, rotigotine) and 3 MAO-B inhibitors (selegiline, rasagiline, safinamide) for Parkinson's disease. We extracted and pooled data from included clinical trials in a joint model allowing both direct and indirect comparison of the seven drugs. We considered dopamine agonists and MAO-B inhibitors given as monotherapy or in combination with levodopa. Selected endpoints were change in the Unified Parkinson's Disease Rating Scale (UPDRS) score, serious adverse events and withdrawals. We estimated the relative effectiveness of each dopamine agonist and MAO-B inhibitor versus comparator drug.
RESULTS
Altogether, 79 publications were included in the analysis. We found all the investigated drugs to be effective compared with placebo when given as monotherapy except safinamide. When considering combination treatment, the estimated relative effects of selegiline, pramipexole, ropinirole, rotigotine, cabergoline, rasagiline and safinamide were 2.316 (1.819, 2.951), 2.091 (1.889, 2.317), 2.037 (1.804, 2.294), 1.912 (1.716, 2.129), 1.664 (1.113, 2.418), 1.584 (1.379, 1.820) and 1.179 (1.031, 1.352), respectively, compared with joint placebo and levodopa treatment.
CONCLUSIONS
Dopamine agonists were found to be effective as treatment for Parkinson's disease, both when given as monotherapy and in combination with levodopa. Selegiline and rasagiline were also found to be effective for treating Parkinson's disease, and selegiline was the best option in combination with levodopa among all the drugs investigated.
Topics: Dopamine Agonists; Drug Therapy, Combination; Humans; Indans; Levodopa; Monoamine Oxidase Inhibitors; Parkinson Disease; Randomized Controlled Trials as Topic; Selegiline; Treatment Outcome
PubMed: 32710141
DOI: 10.1007/s00228-020-02961-6 -
Journal of Clinical Medicine Jul 2020Interest in an aetiopathogenic role for in neuropsychiatric diseases started with idiopathic parkinsonism (IP), where the cardinal signs can be assessed objectively.... (Review)
Review
Interest in an aetiopathogenic role for in neuropsychiatric diseases started with idiopathic parkinsonism (IP), where the cardinal signs can be assessed objectively. This systematic review, using an EMBASE database search, addresses Oxford Centre for Evidence-Based Medicine based questions on the inter-relationship of and IP, the benefits of eradicating in IP and the outcome of not treating. The search strategy was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines: 21 of 204 articles met the inclusion criteria. The results show that the assumption that any benefit of eradication results from improved levodopa bioavailability is unjustified. The inter-relationship between and IP is well-established. virulence markers (associated with autoimmunity and immune tolerance) influence the risk, severity and progression of IP. The birth cohort effect for virulence marker antibodies, seen in controls, is obliterated in IP, suggesting causality. Successful eradication in IP is disease-modifying (even in anti-parkinsonian treatment-naïve patients) but not preventive. Hypokinesia regresses with eradication and overall motor severity lessens. Eradication may influence gastrointestinal microbiota adversely, unlocking the next stage in the natural history, the development of rigidity. Failed eradication worsens hypokinesia, as does the presence/persistence of at molecular level only. Adequate prognostic assessment of the consequences of not treating , for IP, is prevented by a short follow-up. We conclude that is a pathophysiological driver of IP.
PubMed: 32650535
DOI: 10.3390/jcm9072159 -
F1000Research 2019Safinamide, a recently developed drug with several mechanisms of action has been investigated as an add-on therapy for Parkinson's disease patients suffering from motor... (Meta-Analysis)
Meta-Analysis
Safinamide, a recently developed drug with several mechanisms of action has been investigated as an add-on therapy for Parkinson's disease patients suffering from motor complications due to the usage of anti-Parkinson's medications such as levodopa and dopaminergic drugs. The aim of the study is to investigate the efficacy and safety of Safinamide as add-on therapy for Parkinson's disease patients. A computerized literature search was conducted of PubMed, EMBASE, ClinicalTrial.gov and Cochrane Library until August 2019. We selected relevant randomized controlled trials comparing safinamide groups to placebo groups. Relevant outcomes were pooled as mean difference (MD) and risk ratio (RR) using Review Manager 5.3. We found that the overall MD of changes in "off-time" and "on time without troublesome dyskinesia" favored the safinamide group over the placebo group (MD -0.72 h, 95% CI -0.89 to -0.56 and MD 0.71 h, 95% CI 0.52 to 0.90, respectively). Additionally, the overall MD of change in Unified Parkinson's Disease Rating Scale part three (UPDRS III) favored the safinamide group (MD -1.83, 95% CI -2.43 to -1.23). In case of adverse events, the pooled meta-analysis did not favor the safinamide group over the placebo group. In this study, we provide class I evidence about the potential role of safinamide as an add-on therapy for Parkinson's disease patients suffering from motor fluctuations. However, a few included studies did not mention the data of important outcomes. Also, we report high risk of bias in individual studies. Future randomized controlled trials with different doses are recommended to provide more evidence for the efficacy and safety of safinamide as a treatment for motor complications of anti-Parkinson's medications.
Topics: Alanine; Antiparkinson Agents; Benzylamines; Humans; Levodopa; Parkinson Disease; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 32431802
DOI: 10.12688/f1000research.21372.1 -
EXCLI Journal 2020The alleged effects of serotonergic agents in alleviating levodopa-induced dyskinesias (LIDs) in parkinsonian patients are debatable. To this end, we systematically... (Review)
Review
The alleged effects of serotonergic agents in alleviating levodopa-induced dyskinesias (LIDs) in parkinsonian patients are debatable. To this end, we systematically reviewed the serotonergic agents used for the treatment of LIDs in a 6-hydroxydopamine model of Parkinson's disease in rats. We searched MEDLINE via PubMed, Embase, Google Scholar, and Proquest for entries no later than March 2018, and restricted the search to publications on serotonergic agents used for the treatment of LIDs in hemiparkinsonian rats. The initial search yielded 447 citations, of which 49 articles and one conference paper met our inclusion criteria. The results revealed ten different categories of serotonergic agents, including but not limited to 5-HTR agonists, 5-HTR antagonists, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitor (SNRIs), and tricyclic antidepressants (TCAs), all of which improved LIDs without imposing considerable adverse effects. Although there is promising evidence regarding the role of these agents in relieving LIDs in hemiparkinsonian rats, further studies are needed for the enlightenment of hidden aspect of these molecules in terms of mechanisms and outcomes. Given this, improving the quality of the pre-clinical studies and designing appropriate clinical trials will help fill the bench-to-bedside gap.
PubMed: 32327954
DOI: 10.17179/excli2020-1024 -
Drug Design, Development and Therapy 2020Levodopa-carbidopa intestinal gel (LCIG) is a new type of administration that results in steadier levodopa plasma concentrations in advanced Parkinson's disease (PD)...
BACKGROUND
Levodopa-carbidopa intestinal gel (LCIG) is a new type of administration that results in steadier levodopa plasma concentrations in advanced Parkinson's disease (PD) patients and effectively reduces poor mobility and dyskinesia.
METHODS
Electronic databases were searched up to January 1, 2018. The inclusion criteria for this review were as follows: LCIG vs oral medication in advanced PD patients.
RESULTS
Five trials, with a total of 198 patients, met all the inclusion criteria. The quality score of these studies ranged from 3 to 5. Two clinical trials showed that compared with oral medication, LCIG had a better treatment effect on on-time with troublesome dyskinesia (TSD) ( = 0.02) and on-time without TSD ( < 0.00001) in advanced PD patients. In addition, four of the 5 studies showed that the LCIG may have better efficacy than oral medication for improving the scores of the UPDRS, and two studies found that LCIG demonstrated better efficacy for improving the PDQ-39 scores. The video recording results indicated a potential decline in both dyskinesia and the "off" state in LCIG-treated patients. The incidence of adverse events was not significantly different between the LCIG and oral medication groups.
CONCLUSION
Compared with oral treatment, LCIG exerts its effectiveness, mostly by reducing the time of on-time with TSD, increasing the time of on-time without TSD and scores of UPDRS and PDQ-39. It is suggesting that LCIG was likely to be a new type of administration used in clinical applications. However, due to methodological flaws, these findings should be viewed with caution, and more RCTs are needed in the field to complement our findings.
Topics: Administration, Oral; Antiparkinson Agents; Carbidopa; Drug Combinations; Gels; Humans; Levodopa; Parkinson Disease
PubMed: 32161444
DOI: 10.2147/DDDT.S229621 -
Frontiers in Neurology 2019Pregnancy in Parkinson's disease is a rare occurrence, and to date, clinical experience with its management is rather limited. In clinical practice, doubts concern...
Pregnancy in Parkinson's disease is a rare occurrence, and to date, clinical experience with its management is rather limited. In clinical practice, doubts concern mainly the impact of PD on gestation, labor, and delivery as well as the safety of dopaminergic drugs. We report the case of a 40-year-old woman with an 8-year history of PD. In the first trimester of her pregnancy, her motor status was similar to the pre-conceptional period. In gestation week 16, her motor status dramatically worsened and she complained of predictable "off" periods in the afternoon. For this reason, her dose of L-DOPA/carbidopa was increased up to 500/125 mg per day. At 39 gestational weeks, she gave birth to a healthy girl with an Apgar score of 9 by an uncomplicated cesarean delivery. The child was not breast fed to avoid exposure to antiparkinsonian drugs. The L-DOPA/carbidopa dosage remained constant during the postpartum period. We performed a systematic review of the literature using Ovid Medline, Scopus, and PubMed (including Cochrane database). We used the search terms "Parkinson disease" AND "pregnancy." We identified 20 studies of PD in pregnancy with a total of 37 pregnant women with PD. The most important available data concern the safety of L-DOPA therapy during pregnancy. There seems to be some risk of worsening of the condition or upcoming of new PD symptoms during or shortly after pregnancy. More data concerning the safety of antiparkinsonian drugs in PD treatment, as well as the effect of pregnancy on parkinsonian symptoms are needed. According to the current state of the art, L-DOPA therapy should be considered preferable to other drugs during pregnancy.
PubMed: 32140133
DOI: 10.3389/fneur.2019.01349 -
Movement Disorders Clinical Practice Feb 2020A good response to levodopa is a key feature of Parkinson's disease (PD), and a poor response suggests an alternative diagnosis, but the extent of variation in the...
BACKGROUND
A good response to levodopa is a key feature of Parkinson's disease (PD), and a poor response suggests an alternative diagnosis, but the extent of variation in the levodopa response in definite PD is not well defined.
LITERATURE REVIEW
A systematic review of articles reporting pathologically confirmed PD and levodopa responsiveness from 1971 to 2018 was performed using the medical subheadings "postmortem," "Parkinson's disease," "levodopa," and "l-dopa" in PubMed, Embase, and Latin American and Caribbean Health Sciences Literature (LILACS) databases.
CASES
A total of 12 articles described 445 PD cases: 61.7% male, age at disease onset 64.0 years (SD 9.6), age at death 77.1 years (SD 7.2). Levodopa responsiveness was reported in 399 cases (89.7%) either as a graded or a binary response. In the 280 cases (70.2%) describing a graded response, it was excellent in 37.5%, good in 45.7%, moderate in 12.1%, and poor in 4.6%. In the 119 cases describing a binary response (29.8%), 73.1% were levodopa responsive, and 26.9% were nonresponsive. Comorbid brain pathology was present in 137 of 235 cases assessed, being cerebrovascular in 46.0% and Alzheimer's disease in 37.2% of these, but its contribution to levodopa responsiveness was unclear.
CONCLUSIONS
The levodopa motor response varies in definite PD. Explanations other than diagnostic inaccuracy should be explored.
PubMed: 32071945
DOI: 10.1002/mdc3.12885