Raffaele Palladino

Cognitive impairment at diagnosis predicts 10-year multiple sclerosis progression:

Background: Cognitive impairment occurs from the early phases of multiple sclerosis (MS), and more frequently affects secondary progressive (SP) subjects than relapsing–remitting (RR). Objective: To investigate relationships between cognitive dysfunctions in newly diagnosed RRMS, and long-term MS-related outcomes. Methods: The present 10-year retrospective longitudinal study included 155 RRMS subjects, tested with the Rao Brief Repeatable Battery at MS diagnosis. The reaching of Expanded Disability Status Scale (EDSS) 4.0, and the SP conversion were recorded. Results: 67 subjects (43.2%) reached EDSS 4.0, and 34 subjects (21.9%) converted to SP during a follow-up period of 10.0±1.8 years. Subjects with cognitive impairment at diagnosis had a rate of reaching EDSS 4.0 more than three times greater (p<0.001; HR=3.183), and a rate of SP conversion more than two times greater, as compared to cognitively preserved subjects (p=0.008; HR=2.535). In particular, better scores in the Selective Reminding Test-Delayed Recall and in the Symbol Digit Modalities Test at baseline were associated with lower SP conversion rates during the follow-up period (p=0.018; HR=0.835; and p=0.001; HR=0.941, respectively). Conclusion: Cognitive impairment, with particular involvement of processing speed and memory, predicts disability progression and SP conversion in newly diagnosed RRMS, highlighting the importance of cognitive assessment from the beginning of MS.

A Four-Year Longitudinal Study on Restless Legs Syndrome in Parkinson Disease.

STUDY OBJECTIVES Restless legs syndrome (RLS) prevalence estimates range from 0% to 52% in Parkinson disease (PD), but the causal relationship between the two disorders is still debated. The present study aims to evaluate RLS prevalence in de novo PD subjects, its incidence during the first 4 years from diagnosis, and possible relationships with clinical, laboratory, and neuroradiological data. METHODS One hundred nine newly diagnosed, drug-naïve PD subjects were evaluated at the time of PD diagnosis, and after 2- and 4-years. RLS diagnosis was performed with the RLS Diagnostic Index at each visit. Motor features, additional non-motor symptoms (NMS), and concomitant dopaminergic and nondopaminergic treatments were also gathered. Moreover, at baseline, 65 subjects were randomly selected to undergo a FP-CIT SPECT to study dopamine transporter availability. RESULTS RLS prevalence rose from 4.6% at baseline evaluation to 6.5% after 2 years and to 16.3% after 4 years (P = 0.007). A multinomial logistic stepwise regression model selected NMS Questionnaire items more likely to be associated with RLS at diagnosis (insomnia, OR = 15.555; P = 0.040) and with occurrence of RLS during follow-up (dizziness, OR = 1.153; P = 0.022; and daytime sleepiness; OR = 9.557; P = 0.001), as compared to patients without RLS. Older age was more likely associated to increased RLS occurrence during follow-up in a random effect logistic regression model (OR = 1.187; P = 0.036). A multinomial logistic stepwise model found increased dopaminergic transporter availability of affected caudate and putamen to be more likely associated with RLS presence at diagnosis (n = 5; OR = 75.711; P = 0.077), and RLS occurrence during follow-up (n = 16; OR = 12.004; P = 0.059), respectively, as compared to patients without RLS (n = 88). CONCLUSIONS RLS is present since PD diagnosis, and increases in prevalence during the course of PD. PD subjects with RLS have higher age at PD onset, more preserved dopaminergic pathways, and worse sleep and cardiovascular disturbances.

The Framingham cardiovascular risk score in multiple sclerosis.

Cardiovascular risk factors can increase the risk of multiple sclerosis (MS) and modify its course. However, such factors possibly interact, determining a global cardiovascular risk. Our aim was to compare the global cardiovascular risk of subjects with and without MS with the simplified 10‐year Framingham General Cardiovascular Disease Risk Score (FR) and to evaluate its importance on MS‐related outcomes.

Presence and progression of non‐motor symptoms in relation to uric acid in de novo Parkinson's disease

Uric acid (UA) has been studied extensively as a valuable biomarker of Parkinsons disease (PD), but its relationship with non‐motor symptoms (NMS) in de novo PD has been poorly investigated. Our aim was to evaluate the usefulness of baseline serum UA as a marker of NMS progression in newly diagnosed PD.

Associations between multimorbidity, healthcare utilisation and health status: evidence from 16 European countries.

BACKGROUND with ageing populations and increasing exposure to risk factors for chronic diseases, the prevalence of chronic disease multimorbidity is rising globally. There is little evidence on the determinants of multimorbidity and its impact on healthcare utilisation and health status in Europe. METHODS we used cross-sectional data from the Survey of Health, Ageing and Retirement in Europe (SHARE) in 2011-12, which included nationally representative samples of persons aged 50 and older from 16 European nations. Negative binomial and logistic regression models were used to assess the association between number of chronic diseases and healthcare utilisation, self-perceived health, depression and reduction of functional capacity. RESULTS overall, 37.3% of participants reported multimorbidity; the lowest prevalence was in Switzerland (24.7%), the highest in Hungary (51.0%). The likelihood of having multimorbidity increased substantially with age. Number of chronic conditions was associated with greater healthcare utilisation in both primary (regression coefficient for medical doctor visits = 0.29, 95% CI = 0.27-0.30) and secondary setting (adjusted odds ratio (AOR) for having any hospitalisation in the last year = 1.49, 95% CI = 1.42-1.55) in all countries analysed. Number of chronic diseases was associated with fair/poor health status (AOR 2.13, 95% CI = 2.03-2.24), being depressed (AOR 1.48, 95% CI = 1.42-1.54) and reduced functional capacity (AOR 2.12, 95% CI = 2.02-2.22). CONCLUSION multimorbidity is associated with greater healthcare utilisation, worse self-reported health status, depression and reduced functional capacity in European countries. European health systems should prioritise improving the management of patients with multimorbidity to improve their health status and increase healthcare efficiency.

Uric acid relates to dopamine transporter availability in Parkinson's disease

Diagnosing Parkinsons disease (PD) and tracking its progression may require the combination of reliable biomarkers. Among them, both serum uric acid (UA) and dopamine transporter (DaT) binding deserve more investigations.

Clinical clusters and dopaminergic dysfunction in de-novo Parkinson disease.

BACKGROUND The heterogeneity of PD suggests the existence of different subtypes. While some motor clusters have been consistently identified, little is known about non-motor PD subtypes and motor-non-motor interplay. Research in this regard has produced somewhat contradictory results, which might be biased by the inclusion of treated patients. PATIENTS AND METHODS We performed a non-hierarchical cluster analysis using both motor and non-motor data on 398 newly diagnosed untreated PD patients enrolled in the Parkinsons Progressive Marker Initiative (PPMI) study. We further evaluated whether dopaminergic dysfunction, as measured by (123)[I]-FP-CIT SPECT scan, could explain, at least partially, the observed difference between the clusters. RESULTS Three clusters were identified. Group 1 was characterized by the lowest motor and non-motor burden, whereas group 2 and 3 had similar motor disability, but different non-motor involvement, especially with regards to apathy and hallucinations. (123)[I]-FP-CIT binding values paralleled motor disability burden among the 3 clusters, but further multivariate analyses also revealed a negative correlation with depression. DISCUSSION Our results confirm the motor as well as non-motor heterogeneity of PD, suggesting the existence of 3 different subtypes. Dopaminergic dysfunction only marginally explains the non-motor variability of PD. Identification of such clusters can have important implications for generating novel pathophysiological hypotheses and therapeutic strategies.

Google Trends: new evidence for seasonality of multiple sclerosis

People with multiple sclerosis (MS) frequently use search engines, such as Google, to look for terms related to their disease, and its possible causes and symptoms.1 ,2 The large number of searches conducted through Google creates trend data, and can be analysed with Google Trends, a publicly available tool that compares the volume of Internet search queries in different areas and periods.3 Therefore, Google Trends can provide indirect estimates of the burden of diseases and symptoms, and, accordingly, has been used for surveillance studies.3 For instance, Google Trends can precede traditional control systems in detecting seasonal or annual outbreaks of infectious (ie, influenza, scarlet fever, HIV) and non-infectious diseases (ie, cancer, epilepsy) presenting specific patterns in different parts of the world.3 Nevertheless, Google Trends for MS have positively been associated with disease prevalence in an Italian study.2 Different clinical and epidemiological studies have been conducted on seasonality of MS, and focused on relapses, fatigue and MRI. Overall, disease activity has been associated with specific seasonal patterns in both, Northern and Southern hemispheres, possibly in relation to sun exposure.4 ,5 Therefore, the present 10-year retrospective web-based research investigated the seasonality of Google Trends search volumes for ‘multiple sclerosis’ and for MS-related search terms, in the Northern and Southern hemispheres. Search terms, considered on Google Trends separately, were: ‘multiple sclerosis’ (requiring the exact phrase to be present in the search field), ‘relapse’ and ‘fatigue’ (http://www.google.com/trends with …

Quitting smoking: An early non-motor feature of Parkinson's disease?

INTRODUCTION Epidemiological studies report a 60-70% reduced risk of Parkinsons disease (PD) in smokers as compared to non-smokers. However, relationships between former smoking and PD have been poorly investigated. METHODS We recruited 116 de novo PD subjects, and investigated current, former and never smoking, and reasons for smoking cessation among former smokers. Two hundred and thirty-two controls were matched by Propensity Score. RESULTS PD subjects and controls were found to be current smokers (7.7 vs. 39.6%), former smokers (43.9 vs. 6.5%) and never smokers (48.2 vs. 53.9%). Logistic regression showed that current smokers were less likely to have PD (p < 0.001; OR: 0.22; 95% CI: 0.10-0.46), while former smokers were more likely to have PD (p < 0.001; OR: 7.6; 95% CI: 4.09-15.75), as compared to never smokers. Fifty-one PD patients reported quitting smoking before PD diagnosis (mean time since cessation 9.4 ± 7.3 years). Most important reasons to quit smoking in PD group were illness different from PD (26 subjects, 51.0%), knowledge of the harmful effects of smoking (24 subjects, 47.0%), and physicians advice (1 subject, 2.0%). CONCLUSION The reduced prevalence of current smokers among PD subjects as compared to healthy controls is consistent with previous findings, suggesting a possible neuroprotective effect of smoking. However, it could be due, at least in part, to the increased prevalence of former smokers among PD patients, that were more prone to quit smoking as compared to healthy controls. We suggest that smoking cessation could be an early preclinical condition occurring in PD.

Uric acid: a potential biomarker of multiple sclerosis and of its disability

Abstract Background: Uric acid (UA) is a strong natural scavenger of reactive oxygen and nitrogen species, with evidence of possible use in the treatment of animal models of multiple sclerosis (MS). Consequently, serum UA has gained much attention as a possible biomarker of MS. We aim to investigate differences in serum UA levels between MS subjects and controls and evaluate possible relationships of UA with MS clinical features. Methods: We recruited relapsing-remitting and secondary progressive MS subjects and healthy controls and measured their serum UA levels. We excluded subjects presenting concomitant conditions affecting UA levels. Results: MS subjects (n=362) and controls (n=181) were recruited by propensity score matching (PSM). Statistical analyses were corrected for age, gender, and renal function. MS subjects presented significantly lower serum UA levels than controls (analysis of variance, p=0.014, adjusted r2=0.3036). Linear regression analysis showed a relationship between UA levels and disease duration (p<0.001, adjusted r2=0.3158, coefficient –0.00039), time from diagnosis (p<0.001, adjusted r2=0.3100, coefficient –0.0012), and Expanded Disability Status Scale (EDSS) (p<0.001, adjusted r2=0.3230, coefficient –0.1). Conclusions: Our findings support the importance of serum UA as a biomarker of MS disability and progression. Further studies with longitudinal design should be specifically designed to evaluate the importance of UA in the different stages of MS and in relation to distinct therapeutic strategies.