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Advances in Nutrition (Bethesda, Md.) Dec 2021Although levodopa remains the most effective drug for symptomatic management of Parkinson's Disease (PD), treatment during advanced disease stages may raise...
Although levodopa remains the most effective drug for symptomatic management of Parkinson's Disease (PD), treatment during advanced disease stages may raise unpredictable motor fluctuations and other complications. Counteracting these complications with other pharmacological therapies may prompt a vicious circle of side effects, and here, nutritional therapy may have great potential. Knowledge about the role of diet in PD is emerging and multiple studies have investigated nutritional support specifically with respect to levodopa therapy. With this systematic review, we aim to give a comprehensive overview of dietary approaches to optimize levodopa treatment in PD. A systematic search was performed using the databases of PubMed and Scopus between January 1985 and September 2020. Nutritional interventions with the rationale to optimize levodopa therapy in human PD patients were eligible for this study and their quality was assessed with the Cochrane risk-of-bias tool. In total, we included 22 papers that addressed the effects of dietary proteins (n = 10), vitamins (n = 7), fiber (n = 2), soybeans (n = 1), caffeine (n = 1), and ketogenic diets (n = 1) on levodopa therapy. Interventions with protein redistribution diets (PRDs), dietary fiber, vitamin C, and caffeine improved levodopa absorption, thereby enhancing clinical response and reducing motor fluctuations. Furthermore, supplementation of vitamin B-12, vitamin B-6, and folic acid successfully reduced high homocysteine concentrations that emerged from levodopa metabolism and promoted many metabolic and clinical complications, such as neuropathology and osteoporosis. In conclusion, dietary interventions have the potential to optimize levodopa efficacy and control side effects. Nutrition that improves levodopa absorption, including PRDs, fiber, vitamin C, and caffeine, is specifically recommended when fluctuating clinical responses appear. Supplements of vitamin B-12, vitamin B-6, and folic acid are advised along with levodopa initiation to attenuate hyperhomocysteinemia, and importantly, their potential to treat consequent metabolic and clinical complications warrants future research.
Topics: Antiparkinson Agents; Diet; Humans; Levodopa; Parkinson Disease; Vitamin B 12
PubMed: 34113965
DOI: 10.1093/advances/nmab060 -
Movement Disorders Clinical Practice Feb 2019Clinical, neurophysiological, and pathological evidence suggest an association between Parkinson's disease (PD) and peripheral neuropathy (PNP), with a possible... (Review)
Review
BACKGROUND
Clinical, neurophysiological, and pathological evidence suggest an association between Parkinson's disease (PD) and peripheral neuropathy (PNP), with a possible causative role of levodopa metabolic products, such as homocysteine and methylmalonic acid.
METHODS
We conducted a systematic review of studies reporting cases of PNP in l-dopa-treated PD patients indexed in PubMed between January 1990 and March 2018.
RESULTS
We identified 38 articles reporting cases of PNP in PD patients treated with oral l-dopa or with l-dopa/carbidopa intestinal gel infusion (LCIG). Prevalence of PNP was 30.2% in the former group and 42.1% in the latter. Oral l-dopa was mostly associated with slowly progressive PNP, whereas LCIG showed an acute or subacute onset in 35.7% of cases. In both groups, there was an association between PNP and higher l-dopa doses, as well as with the following biochemical alterations: increased homocysteine; reduced vitamin B12; increased methylmalonic acid; and reduced vitamin B6. A skin biopsy was performed in 181 patients, showing signs of small fibers neuropathy in 169 (93.4%). Positive, yet preliminary, results were observed in patients receiving periodic vitamin supplementation.
CONCLUSIONS
Over one third of PD patients in treatment with l-dopa may develop PNP, with a significantly higher prevalence of acute and subacute forms in those receiving LCIG. Pathogenic mechanisms remain unclear, but possibly related to a complex interplay between peripheral neurodegenerative processes and l-dopa neurotoxic metabolites. Prospective, randomized, clinical trials are required to identify factors associated with the onset and progression of PD-associated PNP and clarify the protective role of B-group vitamin supplementation.
PubMed: 30838307
DOI: 10.1002/mdc3.12688 -
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 -
Movement Disorders : Official Journal... Feb 2022Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive... (Review)
Review
BACKGROUND
Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive dystonia (DRD). Diagnosis and treatment are often delayed due to high between- and within-group variability.
OBJECTIVES
Comprehensively analyzed individual genotype, phenotype, treatment response, and biochemistry information.
METHODS
734 DRD patients and 151 asymptomatic GCH1 mutation carriers were included using an MDSGene systematic literature review and an automated classification approach to distinguish between different forms of monogenic DRDs.
RESULTS
Whereas dystonia, L-Dopa responsiveness, early age at onset, and diurnal fluctuations were identified as red flags, parkinsonism without dystonia was rarely reported (11%) and combined with dystonia in only 18% of patients. While sex was equally distributed in autosomal recessive DRD, there was female predominance in autosomal dominant DYT/PARK-GCH1 patients accompanied by a lower median age at onset and more dystonia in females compared to males. Accordingly, the majority of asymptomatic heterozygous GCH1 mutation carriers (>8 years of age) were males. Multiple other subgroup-specific characteristics were identified, showing high accuracy in the automated classification approach: Seizures and microcephaly were mostly seen in DYT/PARK-PTS, autonomic symptoms appeared commonly in DYT/PARK-TH and DYT/PARK-PTS, and sleep disorders and oculogyric crises in DYT/PARK-SPR. Biochemically, homovanillic acid and 5-hydroxyindoleacetic acid in CSF were reduced in most DRDs, but neopterin and biopterin were increased only in DYT/PARK-PTS and DYT/PARK-SPR. Hyperphenylalaninemia was seen in DYT/PARK-PTS, DYT/PARK-QDPR, and rarely reported in autosomal recessive DYT/PARK-GCH1.
CONCLUSIONS
Our indicators will help to specify diagnosis and accelerate start of treatment. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Dystonia; Dystonic Disorders; Female; GTP Cyclohydrolase; Genotype; Humans; Male; Phenotype
PubMed: 34908184
DOI: 10.1002/mds.28874 -
Neuroscience and Biobehavioral Reviews Apr 2023Freezing of gait (FOG) is a common and disabling symptom in people with Parkinson's Disease (PwPD). Although cognition is thought to be worse in PwPD who freeze, a... (Meta-Analysis)
Meta-Analysis Review
Freezing of gait (FOG) is a common and disabling symptom in people with Parkinson's Disease (PwPD). Although cognition is thought to be worse in PwPD who freeze, a comprehensive analysis of this relationship will inform future research and clinical care. This systematic review and meta-analysis compared cognition between PwPD who do and do not exhibit FOG across a range of cognitive domains and assessed the impact of disease severity and medication status on this relationship. 145 papers (n = 9010 participants) were included in the analysis, with 144 and 138 articles meeting the criteria to assess moderating effects of disease severity and medication status, respectively. PwPD who freeze exhibited worse cognition than PwPD without FOG across global cognition, executive function/attention, language, memory, and visuospatial domains. Greater disease severity and "ON" levodopa medication status moderated the FOG status-cognition relationship in global cognitive performance but not in other cognitive domains. This meta-analysis confirmed that cognition is worse in PwPD with FOG and highlights the importance of disease severity and medication status in this relationship.
Topics: Humans; Parkinson Disease; Gait Disorders, Neurologic; Cognition; Levodopa; Gait
PubMed: 36738813
DOI: 10.1016/j.neubiorev.2023.105068 -
Brain Sciences Mar 2023Although the distinction between vascular parkinsonism (VP) and idiopathic Parkinson's disease (IPD) is widely described, it is not uncommon to find parkinsonisms with... (Review)
Review
BACKGROUND AND AIMS
Although the distinction between vascular parkinsonism (VP) and idiopathic Parkinson's disease (IPD) is widely described, it is not uncommon to find parkinsonisms with overlapping clinical and neuroimaging features even in response to levodopa treatment. In addition, several treatments have been described as possible adjuvants in VP. This study aims to update and analyze the different treatments and their efficacy in VP.
METHODS
A literature search was performed in PubMed, Scopus and Web of Science for studies published in the last 15 years until April 2022. A systematic review was performed. No meta-analysis was performed as no new studies on response to levodopa in VP were found since the last systematic review and meta-analysis in 2017, and insufficient studies on other treatments were located to conduct it in another treatment subgroup.
RESULTS
Databases and other sources yielded 59 publications after eliminating duplicates, and a total of 12 original studies were finally included in the systematic review. The treatments evaluated included levodopa, vitamin D, repetitive transcranial magnetic stimulation (rTMS) and intracerebral transcatheter laser photobiomodulation therapy (PBMT). The response to levodopa was lower in patients with VP with respect to IPD. Despite this, there has been described a subgroup of patients with good response, it being possible to identify them by means of neuroimaging techniques and the olfactory identification test. Other therapies showed encouraging results in studies with some risk of bias.
CONCLUSIONS
The response of VP to different therapeutic strategies is modest. However, there is evidence that a subgroup of patients can be identified as more responsive to L-dopa based on clinical and neuroimaging criteria. This subgroup should be treated with L-dopa at appropriate doses. New therapies such as vitamin D, rTMS and PBMT warrant further studies to demonstrate their efficacy.
PubMed: 36979299
DOI: 10.3390/brainsci13030489 -
Parkinsonism & Related Disorders May 2016This review on micrographia aims to draw the clinician's attention to non-Parkinsonian etiologies, provide clues to differential diagnosis, and summarize current... (Review)
Review
INTRODUCTION
This review on micrographia aims to draw the clinician's attention to non-Parkinsonian etiologies, provide clues to differential diagnosis, and summarize current knowledge on the phenomenology, etiology, and mechanisms underlying micrographia.
METHODS
A systematic review of the existing literature was performed.
RESULTS
Micrographia, namely small sized handwriting has long been attributed to Parkinson's disease. However, it has often been observed as part of the clinical picture of additional neurodegenerative disorders, sometimes antedating the motor signs, or following focal basal ganglia lesions without any accompanying parkinsonism, suggesting that bradykinesia and rigidity are not sine-qua-non for the development of this phenomenon. Therefore, micrographia in a patient with no signs of parkinsonism may prompt the clinician to perform imaging in order to exclude a focal basal ganglia lesion. Dopaminergic etiology in this and other cases is doubtful, since levodopa ameliorates letter stroke size only partially, and only in some patients. Parkinsonian handwriting is often characterized by lack of fluency, slowness, and less frequently by micrographia. Deviations from kinematic laws of motion that govern normal movement, including the lack of movement smoothness and inability to scale movement amplitude to the desired size, may reflect impairments in motion planning, possible loss of automaticity and reduced movement vigor.
CONCLUSIONS
The etiology, neuroanatomy, mechanisms and models of micrographia are discussed. Dysfunction of the basal ganglia circuitry induced by neurodegeneration or disruption by focal damage give rise to micrographia.
Topics: Agraphia; Basal Ganglia; Handwriting; Humans; Hypokinesia; Nerve Net; Parkinson Disease
PubMed: 26997656
DOI: 10.1016/j.parkreldis.2016.03.003 -
Journal of Geriatric Psychiatry and... Sep 2022Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue.
METHODS
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available.
RESULTS
Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81-6.46]), (OR 1.39 [95% CI:0.97-1.98]).
CONCLUSIONS
Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH.
Topics: Antiparkinson Agents; Dopamine Agonists; Humans; Hypotension, Orthostatic; Levodopa; Monoamine Oxidase; Parkinson Disease
PubMed: 34964392
DOI: 10.1177/08919887211060017 -
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 -
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