Usefulness of Heart Rate Variability to Identify the Risk of Falling in Huntington’s Disease

Objective: To evaluate the relationship between the HRV and the risk of falling in HD patients.Background: Huntington’s disease (HD) patients have a high prevalence of falls, on the other hand, autonomic nervous system dysfunction has been reported from early stages of the disease. However, there is lack of evidence regarding the relationship between heart rate variability (HRV) and falls in this population....Fil: Terroba Chambi, Cinthia Jennifer. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vigo, Daniel E.. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; ArgentinaFil: Merello, Marcelo Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaInternational Congress of the Parkinson's Disease and Movement DisordersNizaFranciaInternational Parkinson and Movement Disorder Societ

Pain in monogenic Parkinson’s disease: a comprehensive review

Pain, a challenging symptom experienced by individuals diagnosed with Parkinson’s disease (PD), still lacks a comprehensive understanding of its underlying pathophysiological mechanisms. A systematic investigation of its prevalence and impact on the quality of life in patients affected by monogenic forms of PD has yet to be undertaken. This comprehensive review aims to provide an overview of the association between pain and monogenic forms of PD, specifically focusing on pathogenic variants in SNCA, PRKN, PINK1, PARK7, LRRK2, GBA1, VPS35, ATP13A2, DNAJC6, FBXO7, and SYNJ1. Sixty-three articles discussing pain associated with monogenic PD were identified and analyzed. The included studies exhibited significant heterogeneity in design, sample size, and pain outcome measures. Nonetheless, the findings of this review suggest that patients with monogenic PD may experience specific types of pain depending on the pathogenic variant present, distinguishing them from non-carriers. For instance, individuals with SNCA pathogenic variants have reported painful dystonia, lower extremity pain, dorsal pain, and upper back pain. However, these observations are primarily based on case reports with unclear prevalence. Painful lower limb dystonia and lower back pain are prominent symptoms in PRKN carriers. A continual correlation has been noted between LRRK2 mutations and the emergence of pain, though the conflicting research outcomes pose challenges in reaching definitive conclusions. Individuals with PINK1 mutation carriers also frequently report experiencing pain. Pain has been frequently reported as an initial symptom and the most troublesome one in GBA1-PD patients compared to those with idiopathic PD. The evidence regarding pain in ATP13A2, PARK7, VPS35, DNAJC6, FBXO7, and SYNJ1pathogenic variants is limited and insufficient. The potential linkage between genetic profiles and pain outcomes holds promising clinical implications, allowing for the potential stratification of patients in clinical trials and the development of personalized treatments for pain in monogenic PD. In conclusion, this review underscores the need for further research to unravel the intricate relationship between pain and monogenic forms of PD. Standardized methodologies, larger sample sizes, and longitudinal studies are essential to elucidate the underlying mechanisms and develop targeted therapeutic interventions for pain management in individuals with monogenic PD

Miedo a las caídas en las enfermedades neurodegenerativas de los ganglios basales : rol de la disfunción cognitiva, conductual y autonómica en la asociación entre la percepción de riesgo y el miedo a las caídas

Resumen: Los pacientes con enfermedades neurodegenerativas de los ganglios basales (ENGB), constituyen un grupo de especial interés en el estudio del miedo a las caídas (FoF, por sus siglas en inglés), debido a que presentan un mayor riesgo de caídas (RoF, por sus siglas en inglés) desde etapas tempranas del proceso neurodegenerativo. A pesar del conocido impacto negativo que el FoF impone sobre la funcionalidad y calidad de vida de estos pacientes, la investigación sobre sus causas es limitada, y está enfocada, principalmente, en los aspectos motores sobre los no motores. Existen pocos o ningún instrumento de medición específico y validado para su diagnóstico, y la evaluación simultánea de la percepción del riesgo de caídas (PRoF, por sus siglas en inglés) no ha sido incorporada. El objetivo de esta tesis es examinar el FoF, la PRoF y sus correlatos clínicos en la Enfermedad de Parkinson (EP), la Atrofia multisistémica (AMS), la Parálisis Supranuclear Progresiva (PSP), y la Enfermedad de Huntington (EH). Se aborda el estudio del FoF, como el nivel de preocupación por las caídas y la PRoF, a través de un enfoque multidimensional que busca establecer el valor clínico de la asociación entre disfunción cognitiva y autonómica en la génesis del FoF y de la PRoF, y validar una escala específica, para evaluar el FoF en la EP. La primera parte, resume y revisa la literatura existente disponible al comienzo de este proyecto de investigación, sobre el rol de los ganglios basales en la génesis de algunos síntomas motores y no motores, clásicamente vinculados al FoF. Se revisa también la conceptualización de dos constructos: el FoF y la PRoF, así como la descripción de las estrategias de medición de ambos. Con el propósito de caracterizar el FoF y la PRoF en cuatro ENGB, se diseñaron dos estudios exploratorios de cohorte prospectiva y se reclutaron 86 y 95 pacientes respectivamente (figura 12); un grupo equivalente de 22 sujetos control, sin antecedentes familiares de enfermedades neurodegenerativas, para el estudio 1. En el primer estudio, se administró una batería de pruebas sobre el RoF; pruebas neuropsicológicas, con énfasis en las funciones ejecutivas, y, en paralelo, se realizaron estudios de función autonómica durante el reto ortostático, a partir de la evaluación de la variabilidad de la frecuencia cardíaca (VFC), con el fin de detectar posibles factores asociados en el desarrollo de FoF y de la PRoF; el establecimiento de asociaciones temporales entre las caídas y el FoF, y caracterizar la asociación entre el RoF y la PRoF en los cuatro grupos de pacientes. A partir de los dominios evaluados, se construyeron modelos de predicción del FoF y de la PRoF. Se encontró una alta prevalencia de FoF y de PRoF en la población estudiada, con un incremento global temporal de los niveles del FoF. El FoF se asoció a una mayor severidad de la enfermedad motora en la EH y la EP; al congelamiento de la marcha (FoG) en la EP, y a ansiedad y depresión en la PSP. Por otro lado, la PRoF se asoció a una mayor duración de la enfermedad motora; a mayor ansiedad y menor VFC en la EH; a mayor edad y disfunción ejecutiva en la EP; a alteraciones de la VFC en la AMS y a disfunción cognitiva global y ejecutiva en la PSP. Un rendimiento ejecutivo disminuido y disfunción autonómica con predominio parasimpático fueron relevantes en los sujetos con RoF que no perciben que están en riesgo; lo que refuerza la hipótesis de que las alteraciones del procesamiento cognitivo y autonómico juegan un rol determinante en el proceso de evaluación global de riesgos, pero no del desarrollo del FoF. Por otro lado, se encontró que las caídas recurrentes son un factor de riesgo importante en el FoF, pero no en la PRoF. Finalmente, la ansiedad resultó ser el factor de riesgo más significativo, tanto para el desarrollo del FoF, como para la PRoF; incluso, en ausencia de caídas, lo cual insta a un mejor entendimiento de los neurocircuitos comunes disfuncionales, en la comorbilidad psiquiátrica de este grupo específico de pacientes. El segundo estudio, estuvo dirigido a diseñar y validar una escala específica (“Fear of falling Scale”, FFS) para la evaluación del FoF utilizando el paradigma de la EP y su aplicación en el modelo de esta enfermedad. Se identificó al trastorno de ansiedad generalizada (TAG) como un predictor importante del FoF, lo cual tiene implicancias clínicas relevantes, para una mejor conceptualización del FoF en la EP. Se demostró que la FFS tiene fuertes atributos psicométricos y que su corta duración y la simplicidad de su uso hacen de este instrumento una herramienta útil, para evaluar el FoF en la EP.Abstract: Patients with neurodegenerative diseases of the basal ganglia (ENGB) constitute a group of particular interest in the study of fear of falling (FoF) because they present an increased risk of falling (RoF) from the early stages of the neurodegenerative process. Despite the known negative impact that FoF imposes on these patients' functionality and quality of life, research on its causes is limited and is mainly focused on motor over non-motor aspects. There are few or no specific and validated measurement instruments for its diagnosis, and the simultaneous assessment of fall risk perception (PRoF) has not been incorporated. This thesis aims to examine FoF, PRoF, and their clinical correlates in Parkinson's Disease (PD), Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP), and Huntington's Disease (HD). The study of FoF, such as the level of concern for falls and PRoF, is addressed through a multidimensional approach that seeks to establish the clinical value of the association between cognitive and autonomic dysfunction in the genesis of FoF and PRoF and to validate a specific scale to assess FoF in PD. The first part summarizes and reviews the existing literature available at the beginning of this research project on the role of the basal ganglia in the genesis of some motor and non-motor symptoms classically linked to FoF. The conceptualization of two constructs: FoF and PRoF, and the description of measurement strategies for both are also reviewed. In order to characterize FoF and PRoF in four ENGB, two exploratory prospective cohort studies were designed. Eighty-six and 95 patients were recruited, respectively (figure 12), along with an equivalent group of 22 control subjects with no family history of neurodegenerative diseases, for study 1. In the first study, a battery of tests on RoF was administered; neuropsychological tests, with emphasis on executive functions, and in parallel, studies of autonomic function during the orthostatic challenge were performed, from the assessment of heart rate variability (HRV), in order to detect possible associated factors in the development of FoF and PRoF; the establishment of temporal associations between falls and FoF, and to characterize the association between RoF and PRoF in the four groups of patients. From the domains assessed, prediction models of FoF and PRoF were constructed. A high prevalence of FoF and PRoF was found in the studied population, with an overall temporal increase in FoF levels. FoF was associated with increased severity of motor disease in HD and PD, freezing of gait (FoG) in PD, and anxiety and depression in PSP. On the other hand, PRoF was associated with a longer duration of motor disease, greater anxiety and lower HRV in HD, older age, and executive dysfunction in PD, impaired HRV in MSA, and global cognitive and executive dysfunction in PSP. Reduced executive performance and parasympathetic-dominant autonomic dysfunction were relevant in subjects with RoF who do not perceive that they are at risk, reinforcing the hypothesis that cognitive and autonomic processing impairments play a determinant role in the global risk assessment process, but not in the development of FoF. On the other hand, recurrent falls were a significant risk factor in FoF but not in PRoF. Finally, anxiety was found to be the most significant risk factor for both the development of FoF and PRoF, even in the absence of falls, which calls for a better understanding of the common dysfunctional neurocircuitry in the psychiatric comorbidity of this specific group of patients. The second study aimed to design and validate a specific scale ("Fear of falling Scale", FFS) for the assessment of FoF using the PD paradigm and its application in the PD model. Generalized anxiety disorder (GAD) was an essential predictor of FoF, which has relevant clinical implications for better conceptualizing FoF in PD. It was demonstrated that the FFS has strong psychometric attributes and that its short duration and simplicity of use make this instrument a valuable tool for assessing FoF in PD

Heart Rate Variability and Cognitive Impairment in Parkinson’s Disease

Objective: To evaluate the association between the heart rate variability (HRV) and cognitive impairment in PD patients.Background: Emerging evidence suggests an association between cognitive impairment and autonomic dysfunction in Parkinson?s disease (PD). However, there is lack of information between the relationship of HRV and changes in cognition in this population.Method: Nineteen consecutive PD patients without dementia in Hoehn & Yahr stage 2.1±0.2 mean (SD) enrolled in a prospective study of Fear of Falling and falls were assessed by short-term HRV analysis and blood pressure measures during postural changes. EKG were recorded during 5 minutes in resting (RS) and standing (SS) states. Time domain (Mean RR, SDNN, RMSSD), frequency domain (VLF, LF, HF, LF/HF) and non-linear (DFA α1, DFA α2, SampEn) parameters were calculated. Data in RS and SS and its difference (DS) were analyzed. Cognitive performance was evaluated by MoCA, Frontal Assessment battery [FAB], Trail making test [TMT-B], Digit symbol modality test [DSMT], phonemic fluency and Stroop word-color test [SCWT].Results: Eleven patients (57%) were classified as mild cognitive impairment (PD-MCI) by MoCA. The mean (SD) of age and illness duration were 70.9 ± 6.5 and 8.1 ± 4.7 years respectively. There was no difference in age, gender, illness duration, blood pressure, LED or any MDS-UPDRS scores between groups with or without MCI; MCI-group showed significantly higher LF/HF-SS ratio (p=0.032), lower RMSSD-DS (p=0.003) and lower SampEn-DS (p=0.032) than non-MCI group. The poorer performance in multiple cognitive domain tests was significantly associated with HRV indexes: the phonemic fluency scores with reduced overall HRV (RMSSD-SS p=0.016; SDNN-RS p=0.039; SDNN-SS p=0.016); decreased baroreflex function (LF-SS p=0.029; HF-RS p=0.017; HF-SS p=0.037) and SampEn-SS p=0.049); MoCA test was associated to lower RMSSD-DS (p=0.003) and higher DFA α2-SS (p=0.044); SWCT was associated to higher values of DFA α2-SS (p=0.026) and DFA α2-DS (p=0.024). No significant differences were found between groups with or without MCI or any independent cognitive test and blood pressure measures during postural changes.Conclusion: Reduced HRV reflecting decreased parasympathetic activity independently of orthostatic hypotension is significantly associated with PD-MCI. Considering the high rate of conversion of PD-MCI to PDD its role as predictive biomarker should be explored in future studies.Fil: Terroba Chambi, Cinthia Jennifer. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vigo, Daniel Eduardo. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Merello, Marcelo Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina2019 International CongressNizaFranciaInternational Parkinson and Movement Disorder Societ

Heart rate variability and mild cognitive impairment in parkinson’s disease

Abstract: Heart rate variability (HRV) is an index of autonomic control of the heart.1 Evidence suggests loss of sympathetic innervation of the heart takes place in early stages of Parkinson’s disease (PD) and is independent of orthostatic hypotension.2,3 Information about the relationship between HRV and mild cognitive impairment in PD (PD-MCI) is scarce.4 We assessed the association between short-term HRV and MCI in participants of a larger observational crosssectional study of fear of falling. The local ethics committee approved the study, and patients provided written informed consent. Patients without dementia with idiopathic PD and stable medication regimen were included, excluding those with cardiac, liver, or kidney diseases and medications (eg, betareceptor blockers) that affect HRV. Patients were examined during ON state

Heart rate variability and falls in Huntington’s disease

Purpose: Persons with Huntington's disease (HD) have a high incidence of falls. Autonomic nervous system dysfunction has been reported even in early stages of this disease. To date, there has been no analysis of the relationship between heart rate variability (HRV) and falls in this patient population. The aim of the study reported here was to evaluate the relationship between HRV and falls in persons with HD. Methods: Huntington's disease patients enrolled in a prospective study on fear of falling and falls were assessed using short-term HRV analyses and blood pressure measures in both the resting and standing states. Time–frequency domains and nonlinear parameters were calculated. Data on falls, the risk of falling (RoF) and disease-specific scales were collected at baseline and at the end of the 6-month follow-up. Results: Of the 24 HD patients who were invited to participate in the study, 20 completed the baseline analysis and 18 completed the 6-month follow-up. At baseline, seven (35%) HD patients reported at least one fall (single fallers) and 13 (65%) reported ≥ 2 falls (recurrent fallers) in the previous 12 months. At baseline, recurrent fallers had lower RMSSD (root mean square of successive RR interval differences) in the resting state (RMSSD-resting), higher LF/HF (low/high frequency) ratio in both states and higher DFA-α1 parameter (detrended fluctuation analyses over the short term) in both states. This association was similar at the 6-month follow-up for recurrent fallers, who showed lower RMSSD-resting and higher LF/HF ratio in the standing state (LF/HF-standing) than single fallers. Significant correlations were found between the number of falls, RMSSD-resting and LF/HF-standing. No differences were found between recurrent and single fallers for any blood pressure measures. Conclusions: The observed HRV pattern is consistent with a higher sympathetic prevalence associated with a higher RoF. Reduced parasympathetic HRV values in this patient population predict being a recurrent faller at 6 months of follow-up, independently of orthostatic phenomena.Fil: Terroba Chambi, Cinthia Jennifer. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Bruno, Veronica. University of Calgary; CanadáFil: Vigo, Daniel Eduardo. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Merello, Marcelo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentin

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

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.Fil: Terroba Chambi, Cinthia Jennifer. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bruno, Veronica. University of Calgary; CanadáFil: Millar Vernetti, Patricio Alejandro. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Bruce, David. University of Western Australia; AustraliaFil: Brockman, Simone. University of Western Australia; AustraliaFil: Merello, Marcelo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Starkstein, Sergio. University of Western Australia; Australi

Diagnostic Value of Combined Acute Levodopa Challenge and Olfactory Testing to Predict Parkinson's Disease

Background: The diagnosis of Parkinson's disease (PD) can be challenging early in the diseasecourse, when motor features are subtle. The objective of this study was to explore the diagnostic value ofcombining acute levodopa challenge and olfactory testing to predict PD.Methods: Data from 210 patients with a recent onset of parkinsonism who had at least 2 years of follow-upand underwent acute levodopa challenge for the clinical prediction of long-term dopaminergic response andhad olfactory testing with Sniffin? Sticks Test were evaluated. Single and combined diagnostic measures wereanalyzed.Results: After 2 years of follow-up, a PD diagnosis was confirmed in 157 patients who fulfilled United KingdomParkinson?s Disease Society Brain Bank criteria and was ruled out in 53. Sensitivity and specificity of acutelevodopa challenge to predict PD diagnosis were 0.71 and 0.94, respectively. Sensitivity and specificity ofolfactory tests were calculated according to the total olfactory score for hyposmia (0.61 and 0.77respectively), the hyposmia identification subscore (0.63 and 0.74, respectively), and the anosmia score (0.40and 0.85, respectively). The best combination identified was response to acute levodopa challenge togetherwith hyposmia according to the total olfactory score (sensitivity, 0.90; specificity, 0.74; positive predictivevalue, 0.91; negative predictive value, 0.72; accuracy, 0.86).Conclusion: The combination of response to acute levodopa challenge with hyposmia according to the totalolfactory score improved sensitivity for the early diagnosis of PD.Fil: Terroba Chambi, Cinthia Jennifer. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rossi, Malco Damián. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bril, Andrea. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Vernetti, Patricio Millar. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Cerquetti, Daniel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Cammarota, Angel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Merello, Marcelo Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Open-Access Electronic Diary for Motor Fluctuation and Dyskinesia Evaluation in Parkinson Disease: Comparison with Paper Diary

Objective To determine the utility of an electronic diary for registering motor fluctuations and dyskinesia in Parkinson disease (PD). Methods Free, open-access touch screen software suitable for Android 4.4 or higher, with medication alarms, adjustable intervals, and medication dose settings was developed to evaluate ON-OFF periods and dyskinesia. Prospective evaluation included a first phase conducted to make adjustments concerning motor limitations when using the tablet, as well as for proper motor complication identification, and a second phase of 3 days of use at home with a prior diary training session comparing a modified paper version of Core Assessment Program for Surgical Interventional Therapies in PD and the electronic diary. Results All patients correctly identified ON-OFF periods and dyskinesia. Rater/patient matching ON-OFF fluctuations ranged between 94% and 100% for evaluations of different motor states. Dyskinesia matching percentage was 100% for patients with dyskinesia interfering with activities of daily living and 88% for those who reported no-interference. No significant differences between paper and electronic diaries were identified when reporting ON-OFF motor states or in the number of errors when filling the diaries. Conclusions This electronic motor diary proved to be reliable for ON-OFF state and dyskinesia identification and classification. However, no advantage to paper diary has been observed in terms of number of erroneous entries. Based on these results, to improve home motor fluctuations, detection efforts should be directed toward the development of automatic wearable devices rather than digital versions of current available ON-OFF diaries.Fil: Terroba Chambi, Cinthia Jennifer. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Bruno, Veronica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Medina Escobar, Alex. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Nanni, Federico. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Cerquetti, Daniel Fabián. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Rossi, Malco Damián. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Merello, Marcelo Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin