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Abstract Background/Objectives Several studies have shown a relationship between vitamin D and migraine, including the association between decreased serum 25‐hydroxyvitamin D in patients with migraine and the positive effects of vitamin D supplementations in the therapy of this disease. Two single‐nucleotide variants (SNVs) vitamin D receptor (VDR) gene, VDR rs2228570, and VDR rs731236 have shown an association with migraine risk in a previous case–control association study, while an exome sequencing study identified a rare variant in GC vitamin D binding protein gene. This study aims to look for the association between several common variants in these two genes and the risk for migraine. Methods We genotyped 290 patients diagnosed with migraine and 300 age‐matched controls using specific TaqMan assays for VDR rs2228570, VDR rs731236, VDR rs7975232, VDR rs739837, VDR rs78783628, GC rs7041, and GC rs4588 SNVs. Results We did not find an association between these SNVs and the risk for migraine. None of these SNVs were related to the positivity of a family history of migraine or with the presence of aura. The VDR rs731236A allele showed a significant association with the triggering of migraine attacks by ethanol (Pc = 0.007). Conclusions In summary, the results of the current study suggest a lack of association between common SNVs in the VDR and GC gene and the risk of developing migraine. The possible relationship between VDR rs731236 and the triggering of migraine episodes with ethanol deserves future studies.

Introduction In recent years, multiple studies have aimed to develop and validate portable technological devices capable of monitoring the motor complications of Parkinson’s disease patients (Parkinson’s Holter). The effectiveness of these monitoring devices for improving clinical control is not known.Methods and analysis This is a single-blind, cluster-randomised controlled clinical trial. Neurologists from Spanish health centres will be randomly assigned to one of three study arms (1:1:1): (a) therapeutic adjustment using information from a Parkinson’s Holter that will be worn by their patients for 7 days, (b) therapeutic adjustment using information from a diary of motor fluctuations that will be completed by their patients for 7 days and (c) therapeutic adjustment using clinical information collected during consultation. It is expected that 162 consecutive patients will be included over a period of 6 months.The primary outcome is the efficiency of the Parkinson’s Holter compared with traditional clinical practice in terms of Off time reduction with respect to the baseline (recorded through a diary of motor fluctuations, which will be completed by all patients). As secondary outcomes, changes in variables related to other motor complications (dyskinesia and freezing of gait), quality of life, autonomy in activities of daily living, adherence to the monitoring system and number of doctor–patient contacts will be analysed. The noninferiority of the Parkinson’s Holter against the diary of motor fluctuations in terms of Off time reduction will be studied as the exploratory objective.Ethics and dissemination approval for this study has been obtained from the Hospital Universitari de Bellvitge Ethics Committee. The results of this study will inform the practical utility of the objective information provided by a Parkinson’s Holter and, therefore, the convenience of adopting this technology in clinical practice and in future clinical trials. We expect public dissemination of the results in 2022.Trial registration NCT04176302; https://clinicaltrials.gov/show/NCT04176302

Because nitric oxide and endothelial dysfunction could play a role in the pathogenesis of idiopathic restless legs syndrome (RLS), as was suggested by some preliminary data, we investigated the possible association between the rs2070744 variants in the endothelial nitric oxide synthase (eNOS or NOS3) gene (chromosome 7q36.1) and the risk for RLS in a Caucasian Spanish population. We assessed the frequencies of NOS3 single nucleotide polymorphisms (SNPs) rs2070744, rs1799983, and rs79467411 genotypes and allelic variants in 273 patients with idiopathic RLS and 325 healthy controls using a TaqMan-based qPCR assay. We also analyzed the possible influence of genotype frequency on age at onset of RLS symptoms, gender, family history of RLS, and response to drugs commonly used in the treatment of RLS such as dopaminergic drugs, clonazepam, and GABAergic drugs. The frequencies of genotypes and allelic variants were not associated with the risk for RLS and were not influenced by gender, age, and positive family history of RLS. We identified weak statistical associations of the SNP rs1799983 with the response to dopamine agonists (Pc = 0.018 for the rs1799983 G/T genotype) and of the SNP rs79467411 with the response to clonazepam (Pc = 0.018 for the rs79467411 G allele), although these findings should be cautiously interpreted and require further confirmation. These associations aside, our findings suggest that common NOS3 SNPs are not associated with the risk for idiopathic RLS in Caucasian Spanish people.

Increased brain and serum zinc levels in patients with idiopathic restless legs syndrome (idiopathic RLS or iRLS) were described when compared with controls, suggesting a possible role of zinc in the pathogenesis of this disease. However, serum magnesium, calcium, manganese, iron, and copper levels of RLS patients were similar to controls, suggesting a specific impairment of zinc-dependent metabolism in RLS. The aim of this study is to assess the serum concentrations of trace elements involved in oxidative stress or causing peripheral nerve toxicity in a large series of patients with iRLS and controls. We determined serum levels of iron, copper, manganese, zinc, magnesium, selenium, calcium, aluminium, lead, cadmium, arsenic and mercury in 100 patients diagnosed with iRLS and in 110 age- and sex-matched controls using Inductively Coupled Plasma Mass Spectrometry. Serum copper, magnesium, selenium, and calcium concentrations were significantly higher in RLS patients than in controls. These differences were observed both in men and women. There were no major correlations between serum trace metal concentrations and age at onset of RLS or RLS severity, nor was there any association with a family history of RLS or drug response. This study shows an association between increased serum concentrations of copper, magnesium, selenium, and calcium with RLS in a Spanish Caucasian population and does not confirm the previously reported increase in serum zinc concentrations in patients suffering from this disease, suggesting that the different accuracy of the analytical methods used could have influenced the inconsistent results found in the literature.

Background/Objectives: Several studies have shown a relationship between vitamin D and migraine, including the association between decreased serum 25‐hydroxyvitamin D in patients with migraine and the positive effects of vitamin D supplementations in the therapy of this disease. Two single‐nucleotide variants (SNVs) vitamin D receptor (VDR) gene, VDR rs2228570, and VDR rs731236 have shown an association with migraine risk in a previous case–control association study, while an exome sequencing study identified a rare variant in GC vitamin D binding protein gene. This study aims to look for the association between several common variants in these two genes and the risk for migraine. Methods: We genotyped 290 patients diagnosed with migraine and 300 age‐matched controls using specific TaqMan assays for VDR rs2228570, VDR rs731236, VDR rs7975232, VDR rs739837, VDR rs78783628, GC rs7041, and GC rs4588 SNVs. Results: We did not find an association between these SNVs and the risk for migraine. None of these SNVs were related to the positivity of a family history of migraine or with the presence of aura. The VDR rs731236A allele showed a significant association with the triggering of migraine attacks by ethanol (Pc = 0.007). Conclusions: In summary, the results of the current study suggest a lack of association between common SNVs in the VDR and GC gene and the risk of developing migraine. The possible relationship between VDR rs731236 and the triggering of migraine episodes with ethanol deserves future studies. [ABSTRACT FROM AUTHOR]

Several papers have been published suggesting a probable role of inflammatory factors in the etiopathogenesis of migraine. In this study, we investigated the possible association between common variants in the LAG3/CD4 genes (both genes, which are closely related, encode proteins involved in inflammatory and autoimmune responses) in the risk of migraine in a cohort of Caucasian Spanish participants. For this purpose, the frequencies of CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants, using a specific TaqMan-based qPCR assay, were assessed in 290 patients diagnosed with migraine and in 300 healthy controls. The relationship of these variables with several clinical features of migraine was also analyzed. The frequencies of the analyzed LAG3/CD4 genotypes did not differ significantly between the two study groups and were not related to the sex, age at onset of migraine, family history of migraine, presence or absence of aura, or the triggering effect of ethanol on migraine episodes. These results suggest a lack of association between common variants in the LAG3/CD4 genes and the risk of developing migraine in the Caucasian Spanish population. [ABSTRACT FROM AUTHOR]

According to several studies, inflammatory factors could be related to the pathogenesis of idiopathic restless legs syndrome (RLS). In addition, RLS and Parkinson's disease (PD) have shown a possible relationship, and recent studies have shown an association between CD4 rs1922452 and CD4 rs951818 single nucleotide variants (SNVs) and the risk for PD. For these reasons, we investigated the possible association between common variants in the LAG3/CD4 genes (which encoded proteins involved in inflammatory and autoimmune responses) and the risk for RLS in a Caucasian Spanish population. We assessed the frequencies of CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants in 285 patients with idiopathic RLS and 350 healthy controls using a specific TaqMan-based qPCR assay. We also analyzed the possible influence of the genotypes' frequencies on several variables, including age at onset of RLS, gender, family history of RLS, and response to drugs commonly used in the treatment of RLS. We found a lack of association between the frequencies of genotypes and allelic variants of the 3 SNVs studied and the risk of RLS, and a weak though significant association between the CD4 rs1922452 GG genotype and an older age at onset of RLS. With the exception of this association, our findings suggest that common SNVs in the CD4/LAG3 genes are not associated with the risk of developing idiopathic RLS in Caucasian Spanish people. [ABSTRACT FROM AUTHOR]

Background/objectives: Histamine has shown a possible role in the etiopathogenesis of migraine. It has been reported an association between some polymorphisms in the diamine oxidase (DAO) gene and migraine, especially in women. Two studies addressing DAO activity in migraine patients showed conflicting results. We investigated the possible relationship of serum DAO activity and histamine levels and 3 polymorphisms in the DAO gene with the risk for migraine. Methods: We studied the frequencies of DAO rs10156191, rs1049742 and rs1049793 genotypes and allelic variants in 298 migraine patients and 360 healthy controls (using a TaqMan‐based qPCR assay), and serum DAO activity and histamine levels in a subset of 99 migraine patients and 115 controls with strict exclusion criteria, and analysed the relationship of these variables with several clinical features of migraine. Results: The frequencies of the DAO genotypes and allelic variants analysed were similar in migraine patients and controls. Serum DAO activity was significantly higher in migraine patients (Vmax/Km 4.24 ± 2.93 vs. 3.60 ± 7.64, p < 0.001), especially in females (Vmax/Km 4.63 ± 2.96 vs. 3.18 ± 2.32, p < 0.0001), while serum histamine was similar in both study groups. Conclusion: Serum DAO activity was increased in patients with migraine, especially in females, while serum histamine levels were normal. None of the studied polymorphisms was associated with the risk for migraine. [ABSTRACT FROM AUTHOR]

Background: For specialists in charge of Parkinson's disease (PD), one of the most time-consuming tasks of the consultations is the assessment of symptoms and motor fluctuations. This task is complex and is usually based on the information provided by the patients themselves, which in most cases is complex and biased. In recent times, different tools have appeared on the market that allow automatic ambulatory monitoring. The MoMoPa-EC clinical trial (NCT04176302) investigates the effect of one of these tools—Sense4Care's STAT-ON—can have on routine clinical practice. In this sub-analysis the agreement between the Hauser diaries and the STAT-ON sensor is analyzed. Methods: Eighty four patients from MoMoPa-EC cohort were included in this sub-analysis. The intraclass correlation coefficient was calculated between the patient diary entries and the sensor data. Results: The intraclass correlation coefficient of both methods was 0.57 (95% CI: 0.3–0.73) for the OFF time (%), 0.48 (95% CI: 0.17–0.68) for the time in ON (%), and 0.65 (95% CI%: 0.44–0.78) for the time with dyskinesias (%). Furthermore, the Spearman correlations with the UPDRS scale have been analyzed for different parameters of the two methods. The maximum correlation found was −0.63 (p < 0.001) between Mean Fluidity (one of the variables offered by the STAT-dON) and factor 1 of the UPDRS. Conclusion: This sub-analysis shows a moderate concordance between the two tools, it is clearly appreciated that the correlation between the different UPDRS indices is better with the STAT-ON than with the Hauser diary. Trial Registration: https://clinicaltrials.gov/show/NCT04176302 (NCT04176302). [ABSTRACT FROM AUTHOR]

The impact of apathy on health-related quality of life (HRQOL) in recently diagnosed Parkinson's disease (PD) has not been systematically investigated. The objective of this cross-sectional survey (ANIMO study) was to examine the contribution of apathy to HRQOL in a Spanish sample of recently diagnosed PD patients. PD patients, diagnosed within 2 years of inclusion, were recruited at 102 outpatient clinics in 82 communities throughout Spain. Apathy was quantified using the Lille Apathy Rating Scale and HRQOL with the EuroQol-5D questionnaire. A mean EuroQol-5D index score of 0.89 obtained from population references in Spain was used as the cutoff for this study. The relationship between apathy and the dichotomized EuroQol-5D index score (<0.89 [lower HRQOL] vs ≥0.89 [reference]) was examined using multiple logistic regression analysis, adjusting for sociodemographic and clinical variables. We consecutively recruited 557 patients (60.3% men) with a mean age of 68.8 ± 9.7 years. Apathy was diagnosed in 291 (52.2%) and was related to problems in each of the EuroQoL dimensions. Apathetic PD patients showed EuroQol-5D index scores significantly lower than those without apathy (0.64 vs 0.83). In an adjusted model, apathetic PD patients were 2.49 times more likely to have lower HRQOL than nonapathetic patients (odds ratio, 2.49; 95% confidence interval, 1.49-4.15, P < 0.01). Apathy is very common in those with recently diagnosed PD and is one of the major clinical determinants of HRQOL in this disease. It should be one of the primary concerns among clinicians who provide treatment to individuals affected by PD. © 2011 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Objective: Little is known about apathy in the early stages of Parkinson's disease (PD). We determined the clinical correlates of apathy in a large representative sample of patients recently diagnosed with PD (ANIMO study). Methods: PD patients, diagnosed within 2 years of inclusion, were recruited in 102 outpatient clinics situated in 82 populations throughout Spain. Apathy was quantified using the Lille Apathy Rating Scale (LARS). Clinical comparisons and correlations were performed using nonparametric tests. Regression analyses were used to test the association of clinical variables with apathy. Results: We recruited 557 PD patients (60.3% men) with a mean age of 68.8 ± 9.7 years, and UPDRS motor score of 21.1 ± 10.8. Apathy only was diagnosed in 186 (33.4%), and apathy and depression in 215 patients (38.6%). Patients with higher comorbidity (OR = 1.10, 95% CI 1.01-1.20, p = 0.001), motor impairment (OR = 1.07, 95% CI 1.03-1.10, p < 0.0001), and lower education (OR = 2.16, 95% CI 1.21-3.85, p = 0.009) had higher odds of having apathy, in contrast to patients living in a rural environment (OR = 0.35, 95% CI 0.32-0.85, p = 0.01), and left predominant PD motor laterality (OR = 0.34, 95% CI 0.13-0.88, p = 0.01). LARS scores were significantly correlated with UPDRS motor scores (rs = 0.44, p < 0.001), predominantly with axial score (rs = 0.43, p < 0.001). Conclusions: In PD, apathy is a very common and disabling nonmotor symptom separable from depression. Patients living in a rural environment, with lower comorbidity and motor impairment, higher education background, and left predominant PD motor laterality are at lower risk of suffering from apathy. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Increased brain and serum zinc levels in patients with idiopathic restless legs syndrome (idiopathic RLS or iRLS) were described when compared with controls, suggesting a possible role of zinc in the pathogenesis of this disease. However, serum magnesium, calcium, manganese, iron, and copper levels of RLS patients were similar to controls, suggesting a specific impairment of zinc-dependent metabolism in RLS. The aim of this study is to assess the serum concentrations of trace elements involved in oxidative stress or causing peripheral nerve toxicity in a large series of patients with iRLS and controls. We determined serum levels of iron, copper, manganese, zinc, magnesium, selenium, calcium, aluminium, lead, cadmium, arsenic and mercury in 100 patients diagnosed with iRLS and in 110 age- and sex-matched controls using Inductively Coupled Plasma Mass Spectrometry. Serum copper, magnesium, selenium, and calcium concentrations were significantly higher in RLS patients than in controls. These differences were observed both in men and women. There were no major correlations between serum trace metal concentrations and age at onset of RLS or RLS severity, nor was there any association with a family history of RLS or drug response. This study shows an association between increased serum concentrations of copper, magnesium, selenium, and calcium with RLS in a Spanish Caucasian population and does not confirm the previously reported increase in serum zinc concentrations in patients suffering from this disease, suggesting that the different accuracy of the analytical methods used could have influenced the inconsistent results found in the literature. [ABSTRACT FROM AUTHOR]

Because nitric oxide and endothelial dysfunction could play a role in the pathogenesis of idiopathic restless legs syndrome (RLS), as was suggested by some preliminary data, we investigated the possible association between the rs2070744 variants in the endothelial nitric oxide synthase (eNOS or NOS3) gene (chromosome 7q36.1) and the risk for RLS in a Caucasian Spanish population. We assessed the frequencies of NOS3 single nucleotide polymorphisms (SNPs) rs2070744, rs1799983, and rs79467411 genotypes and allelic variants in 273 patients with idiopathic RLS and 325 healthy controls using a TaqMan -based qPCR assay. We also analyzed the possible influence of genotype frequency on age at onset of RLS symptoms, gender, family history of RLS, and response to drugs commonly used in the treatment of RLS such as dopaminergic drugs, clonazepam, and GABAergic drugs. The frequencies of genotypes and allelic variants were not associated with the risk for RLS and were not influenced by gender, age, and positive family history of RLS. We identified weak statistical associations of the SNP rs1799983 with the response to dopamine agonists (Pc = 0.018 for the rs1799983 G/T genotype) and of the SNP rs79467411 with the response to clonazepam (Pc = 0.018 for the rs79467411 G allele), although these findings should be cautiously interpreted and require further confirmation. These associations aside, our findings suggest that common NOS3 SNPs are not associated with the risk for idiopathic RLS in Caucasian Spanish people. [ABSTRACT FROM AUTHOR]