Try a new search

Format these results:

Searched for:



Total Results:


The impact of supine hypertension on target organ damage and survival in patients with synucleinopathies and neurogenic orthostatic hypotension

Palma, Jose-Alberto; Redel-Traub, Gabriel; Porciuncula, Angelo; Samaniego-Toro, Daniela; Millar Vernetti, Patricio; Lui, Yvonne W; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio
INTRODUCTION/BACKGROUND:In addition to neurogenic orthostatic hypotension (nOH), patients with synucleinopathies frequently have hypertension when supine. The long-term consequences of both abnormalities are difficult to disentangle. We aimed to determine if supine hypertension is associated with target organ damage and worse survival in patients with nOH. METHODS:Patients with nOH due to multiple system atrophy (MSA), Parkinson disease (PD), or pure autonomic failure (PAF) were classified into those with or without supine hypertension (systolic BP of at least 140 mmHg or diastolic BP of at least 90 mmHg). Organ damage was assessed by measuring cerebral white matter hyperintensities (WMH), left ventricular hypertrophy (LVH), and renal function. We prospectively followed patients for 30 months (range: 12-66 months) and recorded incident cardiovascular events and all-cause mortality. RESULTS:Fifty-seven patients (35 with probable MSA, 14 with PD and 8 with PAF) completed all evaluations. In addition to nOH (average fall 35 ± 21/17 ± 14 mmHg, systolic/diastolic, mean ± SD), 38 patients (67%) had supine hypertension (systolic BP > 140 mmHg). Compared to those without hypertension, patients with hypertension had higher blood urea nitrogen levels (P = 0.005), lower estimated glomerular filtration rate (P = 0.008), higher prevalence of LVH (P = 0.040), and higher WMH volume (P = 0.019). Longitudinal follow-up of patients for over 2 years (27.1 ± 14.5 months) showed that supine hypertension was independently associated with earlier incidence of cardiovascular events and death (HR = 0.25; P = 0.039). CONCLUSIONS:Supine hypertension in patients with nOH was associated with an increased risk for target organ damage, cardiovascular events, and premature death. Defining management strategies and safe blood pressure ranges in patients with nOH remains an important research question.
PMID: 32516630
ISSN: 1873-5126
CID: 4475012

Design and validation of a new instrument to assess fear of falling in Parkinson's disease

Terroba-Chambi, Cinthia; Bruno, Veronica; Millar-Vernetti, Patricio; Bruce, David; Brockman, Simone; Merello, Marcelo; Starkstein, Sergio
BACKGROUND:Fear of falling may be significantly associated with falls in Parkinson's disease (PD) and may have a negative impact on quality of life. Nevertheless, there are no valid and reliable tools to examine this condition in PD. The objective of this study was to design and determine the psychometric attributes of an instrument to assess fear of falling in PD. METHODS:A prospective 1-year, 2-phase study was conducted to validate the Fear of Falling Scale, a self-assessed instrument for assessing fear of falling in PD. During phase 1, we designed a scale to measure the severity of fear of falling and determine its baseline psychometric characteristics, whereas phase 2 was a 1-year follow-up study to assess the frequency of falls and other clinical factors linked to fear of falling. Convergent and discriminant validity were assessed against the Fear of Falling Measure and the Starkstein Apathy Scale, respectively. RESULTS:The Fear of Falling Scale showed high internal consistency, test-retest reliability, and strong convergent and discriminant validity. There was a significant association between fear of falling score and the presence of both generalized anxiety disorder and major depression, poor balance-related motor ability, increased nonmotor symptoms of PD, more severe impairments in activities of daily living, and increased motor fluctuations. Finally, generalized anxiety disorder was a significant predictor of number of falls during a 12-month follow-up period. CONCLUSIONS:The Fear of Falling Scale is a valid and reliable instrument to assess fear of falling in PD. Fear of falling in PD is associated with specific psychiatric and motor disorders and is significantly related to the performance of balance-related motor functions. © 2019 International Parkinson and Movement Disorder Society.
PMID: 31442364
ISSN: 1531-8257
CID: 4839922

The Role of Poly(ADP-ribose) in α-Synuclein Neurodegeneration: Another Piece of the Puzzle for α-Synucleinopathies

Millar Vernetti, Patricio
PMID: 30949549
ISSN: 2330-1619
CID: 4839912

Genetic Dystonia-ataxia Syndromes: Clinical Spectrum, Diagnostic Approach, and Treatment Options

Rossi, Malco; Balint, Bettina; Millar Vernetti, Patricio; Bhatia, Kailash P; Merello, Marcelo
Background/UNASSIGNED:Dystonia and ataxia are manifestations of numerous disorders, and indeed, an ever-expanding spectrum of genes causing diseases that encompass dystonia and ataxia are discovered with the advances of genetic techniques. In recent years, a pathophysiological link between both clinical features and the role of the cerebellum in the genesis of dystonia, in some cases, has been proposed. In clinical practice, the genetic diagnosis of dystonia-ataxia syndromes is a major issue for genetic counseling, prognosis and, occasionally, specific treatment. Methods/UNASSIGNED:For this pragmatic and educational review, we conducted a comprehensive and structured literature search in Pubmed, OMIM, and GeneReviews using the key words "dystonia" and "ataxia" to identify those genetic diseases that may combine dystonia with ataxia. Results/UNASSIGNED:There are a plethora of genetic diseases causing dystonia and ataxia. We propose a series of clinico-radiological algorithms to guide their differential diagnosis depending on the age of onset, additional neurological or systemic features, and imaging findings. We suggest a sequential diagnostic approach to dystonia-ataxia syndromes. We briefly highlight the pathophysiological links between dystonia and ataxia and conclude with a review of specific treatment implications. Conclusions/UNASSIGNED:The clinical approach presented in this review is intended to improve the diagnostic success of clinicians when faced with patients with dystonia-ataxia syndromes.
PMID: 30363394
ISSN: 2330-1619
CID: 4839902

A multifactorial study on nutritional status, binge eating and physical activity as main factors directly influencing body weight in Parkinson's disease

Bril, Andrea; Perez-Lloret, Santiago; Rossi, Malco; Fariña, Sofía; Morisset, Pierre; Sorrentino, Laura; Iglesias, Micaela; Medina Escobar, Alex; Millar Vernetti, Patricio; Cerquetti, Daniel; Merello, Marcelo
Weight lossisa multifactorial disorder commonly affecting Parkinson's disease patients. The aim of this study was to investigate the relationship between body weight, nutritional status, physical activity, and Parkinson's disease-related factors. A total of 114 consecutive Parkinson's disease patients without dietary restrictions were evaluated prospectively with respect to: nutritional status (Mini Nutritional Assessment), physical activity level (Yale Physical Activity Survey), MDS-UPDRS score, olfactory function, depression, cognitive functionand impulse-control disorders, among other variables. Structural equation modeling was used to build multivariate models and to calculate standardized regression weights (srw) for pairs of variables, which are homologous to correlation coefficients, taking into account the effects of all other variables in the model. Sixty (53%) patients were males. Mean age was 66.1 ± 9.8 years and mean disease duration was 8.3 ± 5.6 years. Longer disease duration was negatively related to nutritional status (srw = -0.25; p = 0.01). UPDRS II + III score was associated with reduced cognitive function (srw = -0.39; p = 0.01), which was positivelyrelated to nutritional status (srw = 0.23; p = 0.01). Finally, nutritional status was positively related to body weight (srw = 0.22, p < 0.01). Binge eating and physical activity were also directly and positively related to body weight (srw = 0.32; p = 0.001 and srw = 0.23; p = 0.001). Nutritional status, binge eating and physical activity were directly and independently related to body weight in our sample of Parkinson's disease patients. Therefore, physicians should actively explore nutritional status and binge eating in Parkinson's disease patients to avoid alterations in body weight regulation. Effects of physical activity should be further explored.
PMID: 28649617
ISSN: 2373-8057
CID: 4839892

Motor features in Parkinson's disease with normal olfactory function

Rossi, Malco; Escobar, Alex Medina; Bril, Andrea; Millar Vernetti, Patricio; De Palo, Juan Ignacio; Cerquetti, Daniel; Merello, Marcelo
BACKGROUND:Normosmic Parkinson's disease (PD) might be a unique clinical phenotype with a more benign course when compared with hyposmic PD. OBJECTIVE:The objective of this study was to evaluate motor features and the acute levodopa response according to olfactory function. METHODS:A total of 169 de novo PD patients that underwent olfactory testing and acute levodopa challenge for clinical prediction of sustained long-term dopaminergic response were evaluated. RESULTS:The overall frequency of normosmia was 33%. Normosmic PD patients scored nonsignificantly different to hyposmic/anosmic patients on motor scale and on degree of improvement with levodopa. Motor scores at follow-up were comparable among groups. CONCLUSIONS:Normal olfactory function is common in early PD and was not associated with a different motor phenotype when compared with PD patients with olfactory dysfunction. © 2016 International Parkinson and Movement Disorder Society.
PMID: 27277396
ISSN: 1531-8257
CID: 4839882

Comparison of Olfactory Identification Patterns among Parkinson's Disease Patients from Different Countries

Millar Vernetti, Patricio; Rossi, Malco; Cerquetti, Daniel; Perez Lloret, Santiago; Merello, Marcelo
Olfactory function assessment is an important screening tool and also may differentiate Parkinson's disease (PD) patients from other parkinsonisms, including nondegenerative ones, such as, normal pressure hydrocephalus, vascular, drug induced, or infectious parkinsonism. Several authors in different countries have reported various sets of odors that best differentiate between these conditions. It is debated if distinctive patterns of "restrictive" or "selective" hyposmia in PD may be affected by cultural aspects. To compare the olfactory identification function in PD across different countries, we analyzed Sniffin' Sticks identification task results between 112 PD patients from Argentina and previously reported data of PD patients from Brazil (106 patients), the Netherlands (400 patients), Germany (40 patients), China (110 patients), and Sri Lanka (89 patients). Categorical principal component analysis (CATPCA) was performed to find components reflecting groups of odors similarly perceived across subjects. CATPCA analysis found 2 components for each group which shared 10 out of 16 odors amongst each other. We found that only the shared items of component 2 (orange, mint, banana, garlic, coffee, cloves, and fish) showed uniform results across all of the included countries, whereas variations in component 1 (licorice, turpentine, and apple) were attributed mostly to differences across control groups.
PMID: 26512070
ISSN: 1464-3553
CID: 4839872

Olfactory Dysfunction Evaluation Is Not Affected by Comorbid Depression in Parkinson's Disease

Rossi, Malco; Perez-Lloret, Santiago; Millar Vernetti, Patricio; Drucaroff, Lucas; Costanzo, Elsa; Ballesteros, Diego; Bril, Andrea; Cerquetti, Daniel; Guinjoan, Salvador; Merello, Marcelo
BACKGROUND:Olfactory function assessment is an important screening tool for Parkinson's disease (PD) diagnosis. It is debated whether olfaction is affected by comorbid depression. We assessed the relationship between depression and olfaction in PD and determined whether depression may limit the usefulness of olfactory testing for PD diagnosis. METHODS:Olfaction was evaluated using the Sniffin' Sticks test and the Hyposmia Rating Scale in four groups of subjects: PD patients without depression (n = 30); PD patients with major depression (PDD; n = 30); major depressive disorder (MDD) patients (n = 29); and healthy controls (HCs; n = 30). RESULTS:No differences were found between PD and PDD patients for total Sniffin' Sticks test, threshold, discrimination or identification scores, or in Hyposmia Rating Scale, although both groups differed from HCs and MDD patients (P < 0.05), which, in turn, showed similar olfactory scores. CONCLUSIONS:Lack of differences in olfactory impairment between PD and PDD suggest that depression may not contribute to olfactory dysfunction in PD.
PMID: 26096632
ISSN: 1531-8257
CID: 4839862

Autosomal dominant cerebellar ataxias: a systematic review of clinical features

Rossi, M; Perez-Lloret, S; Doldan, L; Cerquetti, D; Balej, J; Millar Vernetti, P; Hawkes, H; Cammarota, A; Merello, M
BACKGROUND AND PURPOSE/OBJECTIVE:To assess, through systematic review, distinctive or common clinical signs of autosomal dominant cerebellar ataxias (ADCAs), also referred to as spinocerebellar ataxias (SCAs) in genetic nomenclature. METHODS:This was a structured search of electronic databases up to September 2012 conducted by two independent reviewers. Publications containing proportions or descriptions of ADCA clinical features written in several languages were selected. Gray literature was included and a back-search was conducted of retrieved publication reference lists. Initial selection was based on title and abstract screening, followed by full-text reading of potentially relevant publications. Clinical findings and demographic data from genetically confirmed patients were extracted. Data were analyzed using the chi-squared test and controlled for alpha-error inflation by applying the Holms step-down procedure. RESULTS:In all, 1062 publications reviewing 12 141 patients (52% male) from 30 SCAs were analyzed. Mean age at onset was 35 ± 11 years. Onset symptoms in 3945 patients revealed gait ataxia as the most frequent sign (68%), whereas overall non-ataxia symptom frequency was 50%. Some ADCAs often presented non-ataxia symptoms at onset, such as SCA7 (visual impairment), SCA14 (myoclonus) and SCA17 (parkinsonism). Therefore a categorization into two groups was established: pure ataxia and mainly non-ataxia forms. During overall disease course, dysarthria (90%) and saccadic eye movement alterations (69%) were the most prevalent non-ataxia findings. Some ADCAs were clinically restricted to cerebellar dysfunction, whilst others presented additional features. CONCLUSIONS:Autosomal dominant cerebellar ataxias encompass a broad spectrum of clinical features with high prevalence of non-ataxia symptoms. Certain features distinguish different genetic subtypes. A new algorithm for ADCA classification at disease onset is proposed.
PMID: 24765663
ISSN: 1468-1331
CID: 4839852

Validation of a new scale to assess olfactory dysfunction in patients with Parkinson's disease

Millar Vernetti, Patricio; Perez Lloret, Santiago; Rossi, Malco; Cerquetti, Daniel; Merello, Marcelo
UNLABELLED:BAKCKGROUND: Olfactory dysfunction is present in up to 90% of Parkinson's disease (PD) patients. It is usually evaluated by means of objective standardized tests; however no self-administered scales have been developed for olfactory dysfunction bedside assessment. We present validation of a new scale to assess this symptom in PD patients. METHODS:Seventy-five PD patients and 25 control subjects were evaluated using a Hyposmia Rating Scale developed in-house, combined with the extended Sniffin' Sticks test. RESULTS:Total score of the 6-item Hyposmia Rating Scale showed significant correlation with threshold, discrimination, identification and total Sniffin' Sticks test scores (r = 0.53; r = 0.60; r = 0.57; r = 0.65 respectively, p < 0.001 for all values). Area under the curve of the receiver operating curve for the ability of Hyposmia Rating Scale to discriminate patients with Sniffin' Sticks test total scores below or above the cut-off point was 80 ± 6% (p < 0.001). Considering Sniffin' Sticks test as the gold standard method for olfactory dysfunction detection, an affirmative response to a single screening question about smelling ability problems showed 35% sensitivity (95%CI = 23-47%) and 100% specificity. The best cut-off point for Hyposmia Rating Scale was 22.5 with a sensitivity of 70% (60-81%) and a specificity of 85% (65-100%). CONCLUSION/CONCLUSIONS:The Hyposmia Rating Scale here presented may offer a simple, cost-effective, time-saving and reliable approach to evaluate olfactory dysfunction in PD patients.
PMID: 22227345
ISSN: 1873-5126
CID: 4839842