Diego Santos-García

Bio: Diego Santos-García is an academic researcher from Yahoo!. The author has contributed to research in topics: Parkinson's disease & Medicine. The author has an hindex of 16, co-authored 68 publications receiving 817 citations. Previous affiliations of Diego Santos-García include University of Santiago de Compostela.

Impact of non-motor symptoms on health-related and perceived quality of life in Parkinson's disease.

Abstract: Objective To investigate the impact of non-motor symptoms on health-related and perceived quality of life in Parkinson's disease (PD). Methods One hundred and fifty PD patients (57.3% males; 70.9 ± 8.6 years old) were included in this cross-sectional, monocenter, evaluation study. Multiple linear regression methods were used to evaluate the direct impact of non-motor symptoms (as assessed by the Non-Motor Symptoms Scale [NMSS]) on 1) the 39-item PD Quality of Life Questionnaire Summary Index score (PDQ-39SI), and 2) a subjective assessment of perceived quality of life (PQ-10), after adjusting for age, sex, mood (Beck Depression Inventory), disability (SchwabE for PQ-10, p = 0.017). PD-specific motor dysfunction had a larger negative impact on health-related quality of life (PDQ-39SI) than non-motor symptoms (2.8% vs 0.7%). In contrast, the negative impact of non-motor symptoms on perceived quality of life (PQ-10) was larger than that found for PD-specific motor dysfunction (2.8% vs 0.9%). While the model for PDQ-39SI provided an adequate fit (adjusted R-squared, 0.83), a substantial proportion of the PQ-10 variance remained unexplained (adjusted R-squared, 0.48). Conclusions Non-motor symptoms have a direct negative impact on health-related and perceived quality of life in PD. Perceived quality of life is not adequately explained by motor and non-motor manifestations of the disease.

The effects of treadmill or overground walking training program on gait in Parkinson's disease.

Abstract: Background Gait impairment in Parkinson's disease (PD) patients is characterized by the inability to generate appropriate stride length. Treadmill training has been proposed as a therapeutic tool for PD patients. However, it remains unknown whether treadmill training effects are different from overground walking training. Thus, our goal was to explore the effects of two training programs, walking on a treadmill and walking overground, in PD patients. Methods 22 PD patients were randomly assigned to a treadmill or overground training group. The training program consisted of 5 weeks (3 sessions/week). Before and after the program we evaluated gait kinematics during walking at preferred and maximal speed; Timed Up and Go (TUG); static posturography and knee extensors strength. Gait parameters were reevaluated in the treadmill training group one month after the cessation of the training. Results Preferred speed walking improved in both groups after the training program. The treadmill training program, but not the overground, led to an improvement in the stride length at the preferred and maximal walking speed in the PD patients. In addition, the treadmill training group showed improvement of the TUG and static posturography tests. The improvement in gait parameters was maintained one month after the cessation of the treadmill training. Conclusions This study provides evidence of a specific therapeutic effect of treadmill training on Parkinsonian gait and balance. Walking on a treadmill may be used as an easy, effective and accessible way to improve the stride length and balance in PD patients.

Factors contributing to caregivers' stress and burden in Parkinson's disease

Abstract: Background and objective To analyze the main determinants of burden and stress in caregivers of Spanish Parkinson's disease (PD) patients. Methods One-hundred and twenty-one non-demented patients with PD (57.9% males; 70.9 ± 8.2 years old) were included in this cross-sectional, monocenter, evaluation study. Caregivers (n = 121; 71.9% females; 60.2 ± 15 years old) were assessed using the Zarit Caregiver Burden Inventory (ZCBI) and Caregiver Strain Index (CSI). Multiple linear regression methods were used to evaluate factors contributing to caregivers' stress and burden: (i) PD motor dysfunction (ON-state Hoehn & Yahr/Unified Parkinson's Disease Rating Scale [UPDRS] part III and motor complications [UPDRS part IV]); (ii) Mood (Beck Depression Inventory [BDI]); (iii) Non-motor symptoms (Non-Motor Symptoms Scale [NMSS]); (iv) Disability (Schwab & England Activities of Daily Living Scale [ADLS]); and (v) Socio-demographic and other disease-related variables. Results Zarit Caregiver Burden Inventory and CSI mean scores were 16 ± 13.9 and 2.1 ± 2.3, respectively. High correlation was found between ZCBI and CSI (r = 0.819; P 40) was present in 9.1% of caregivers; 5.8% had high levels of stress (CSI ≥ 7). Moderate to strong correlations were observed between patient-related variables (Hoehn&Yahr, UPDRS-III, UPDRS-IV, BDI, NMSS, and ADLS) and ZCBI and CSI (P < 0.0001). Linear regression methods showed that ADLS had the strongest influence on ZCBI and CSI, followed by BDI on ZCBI. Conclusions Disability (ADLS) and mood (BDI) of patients with PD are the main factors contributing to burden and stress in caregivers.

COPPADIS-2015 (COhort of Patients with PArkinson’s DIsease in Spain, 2015), a global –clinical evaluations, serum biomarkers, genetic studies and neuroimaging– prospective, multicenter, non-interventional, long-term study on Parkinson’s disease progression

Abstract: Parkinson’s disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms that can affect independence, social adjustment and the quality of life (QoL) of both patients and caregivers. Studies designed to find diagnostic and/or progression biomarkers of PD are needed. We describe here the study protocol of COPPADIS-2015 (COhort of Patients with PArkinson’s DIsease in Spain, 2015), an integral PD project based on four aspects/concepts: 1) PD as a global disease (motor and non-motor symptoms); 2) QoL and caregiver issues; 3) Biomarkers; 4) Disease progression. Observational, descriptive, non-interventional, 5-year follow-up, national (Spain), multicenter (45 centers from 15 autonomous communities), evaluation study. Specific goals: (1) detailed study (clinical evaluations, serum biomarkers, genetic studies and neuroimaging) of a population of PD patients from different areas of Spain, (2) comparison with a control group and (3) follow-up for 5 years. COPPADIS-2015 has been specifically designed to assess 17 proposed objectives. Study population: approximately 800 non-dementia PD patients, 600 principal caregivers and 400 control subjects. Study evaluations: (1) baseline includes motor assessment (e.g., Unified Parkinson’s Disease Rating Scale part III), non-motor symptoms (e.g., Non-Motor Symptoms Scale), cognition (e.g., Parkinson’s Disease Cognitive Rating Scale), mood and neuropsychiatric symptoms (e.g., Neuropsychiatric Inventory), disability, QoL (e.g., 39-item Parkinson’s disease Quality of Life Questionnaire Summary-Index) and caregiver status (e.g., Zarit Caregiver Burden Inventory); (2) follow-up includes annual (patients) or biannual (caregivers and controls) evaluations. Serum biomarkers (S-100b protein, TNF-α, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid, homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain MRI (volumetry, tractography and MTAi [Medial Temporal Atrophy Index]), at baseline and at the end of follow-up, and genetic studies (DNA and RNA) at baseline will be performed in a subgroup of subjects (300 PD patients and 100 control subjects). Study periods: (1) recruitment period, from November, 2015 to February, 2017 (basal assessment); (2) follow-up period, 5 years; (3) closing date of clinical follow-up, May, 2022. Funding: Public/Private. COPPADIS-2015 is a challenging initiative. This project will provide important information on the natural history of PD and the value of various biomarkers.

Polyneuropathy while on duodenal levodopa infusion in Parkinson’s disease patients: we must be alert

Abstract: Some reports have emerged describing the occurrence of Guillain-Barre syndrome and polyneuropathy related to vitamin B(12) deficiency in some patients with Parkinson's disease (PD) treated with continuous duodenal levodopa infusion. We describe five PD patients who developed axonal polyneuropathy and vitamin B(12) deficiency while on treatment with duodenal levodopa infusion, review other cases reported in the literature, discuss potential etiologic factors, and suggest a possible algorithm for the management and prevention of this complication. One case of Guillain-Barre syndrome and at least 12 cases of polyneuropathy related to vitamin B(12) deficiency have been reported in PD patients treated with duodenal levodopa infusion. Levodopa gel infusion may induce a decrease in vitamin B(12) levels, leading to peripheral neuropathy. Additional pathogenetic mechanisms include alterations related to the metabolism of L: -dopa, abnormal L: -dopa absorption, and direct neurotoxicity of L: -dopa at high doses. Vitamin B(12) supplementation may need to be considered in PD patients on duodenal levodopa infusion therapy. Vitamin B(12) deficiency in patients on duodenal levodopa infusion therapy may be more frequent than the published data suggest. We must be alert.

MDS Clinical Diagnostic Criteria for Parkinson's Disease (S19.001)

Abstract: Objective To present the International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease. Background Although several diagnostic criteria for Parkinson9s disease have been proposed, none have been officially adopted by an official Parkinson society. Moreover, the commonest-used criteria, the UK brain bank, were created more than 25 years ago. In recognition of the lack of standard criteria, the MDS initiated a task force to design new diagnostic criteria for clinical Parkinson9s disease. Methods/Results The MDS-PD Criteria are intended for use in clinical research, but may also be used to guide clinical diagnosis. The benchmark is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise. Although motor abnormalities remain central, there is increasing recognition of non-motor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the MDS-PD Criteria retain motor parkinsonism as the core disease feature, defined as bradykinesia plus rest tremor and/or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies upon three categories of diagnostic features; absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of PD diagnosis). Two levels of certainty are delineated: Clinically-established PD (maximizing specificity at the expense of reduced sensitivity), and Probable PD (which balances sensitivity and specificity). Conclusion The MDS criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, criteria will need continuous revision to accommodate these advances. Disclosure: Dr. Postuma has received personal compensation for activities with Roche Diagnostics Corporation and Biotie Therapies. Dr. Berg has received research support from Michael J. Fox Foundation, the Bundesministerium fur Bildung und Forschung (BMBF), the German Parkinson Association and Novartis GmbH.

An Essay on the Shaking Palsy

Abstract: PREFACE The advantages which have been derived from the caution with which hypothetical statements are admitted, are in no instance more obvious than in those sciences which more particularly belong to the healing art. It therefore is necessary, that some conciliatory explanation should be offered for the present publication: in which, it is acknowledged, that mere conjecture takes the place of experiment; and, that analogy is the substitute for anatomical examination, the only sure foundation for pathological knowledge. When, however, the nature of the subject, and the circumstances under which it has been here taken up, are considered, it is hoped that the offering of the following pages to the attention of the medical public, will not be severely censured. The disease, respecting which the present inquiry is made, is of a nature highly afflictive. Notwithstanding which, it has not yet obtained a place in the classification of nosologists; some have regarded its characteristic symptoms as distinct and different diseases, and others have given its name to diseases differing essentially from it; whilst the unhappy sufferer has considered it as an evil, from the domination of which he had no prospect of escape. The disease is of long duration: to connect, therefore, the symptoms which occur in its later stages with those which mark its commencement, requires a continuance of observation of the same case, or at least a correct history of its symptoms, even for several years. Of both these advantages the writer has had the opportunities of availing himself, and has hence been led particularly to observe several other cases in which the disease existed in different stages of its progress. By these repeated observations, he hoped that he had been led to a probable conjecture as to the nature of the malady, and that analogy had suggested such means as might be productive of relief, and perhaps even of cure, if employed before the disease had been too long established. He therefore considered it to be a duty to submit his opinions to the examination of others, even in their present state of immaturity and imperfection. To delay their publication did not, indeed, appear to be warrantable. The disease had escaped particular notice; and the task of ascertaining its nature and cause by anatomical investigation, did not seem likely to be taken up by those who, from their abilities and opportunities, were most likely to accomplish it. That these friends to humanity and medical science, who have already unveiled to us many of the morbid processes by which health and life is abridged, might be excited to extend their researches to this malady, was much desired; and it was hoped, that this might be procured by the publication of these remarks. Should the necessary information be thus obtained, the writer will repine at no censurewhich the precipitate publication of mere conjectural suggestions may incur: but shall think himself fully rewarded by having excited the attention of those, who may point out the most appropriate means of relieving a tedious and most distressing malady.

Cognitive decline in Parkinson disease

Abstract: Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition - or even reversal to normal cognition - is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*e4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results.

The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society.

Abstract: While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for a clinical endpoint. In order to be considered as a surrogate endpoint of cardiovascular events, a biomarker should satisfy several criteria, such as proof of concept, prospective validation, incremental value, clinical utility, clinical outcomes, cost-effectiveness, ease of use, methodological consensus, and reference values. We scrutinized the role of peripheral (i.e. not related to coronary circulation) noninvasive vascular biomarkers for primary and secondary cardiovascular disease prevention. Most of the biomarkers examined fit within the concept of early vascular aging. Biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity; biomarkers that fulfill some, but not all of the criteria are brachial ankle pulse wave velocity, central haemodynamics/wave reflections and C-reactive protein; biomarkers that do no not at present fulfill essential criteria are flow-mediated dilation, endothelial peripheral arterial tonometry, oxidized LDL and dysfunctional HDL. Nevertheless, it is still unclear whether a specific vascular biomarker is overly superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required.