MEX-PD: A National Network for the Epidemiological & Genetic Research of Parkinson's Disease.

Background: Parkinson's Disease (PD) has a complex etiology, involving genetic and environmental factors. Most of our current understanding of the disease comes from studies in populations with mostly European ancestry, representing challenges in generalizing findings to other populations with different genetic, social, and environmental contexts. There are scarce studies focused in Latin American populations. The Mexican population is genetically diverse because its admixture from Native American, European, and African ancestries, coupled with the unique environmental conditions, stressing the relevance of establishing genetic studies in this population. Thus, we have established the Mexican Parkinson's Research Network (MEX-PD), a consortium to research the clinical, genetical, environmental, and neurophysiological bases of the phenotypic diversity in Mexican PD patients. Objectives: Describing how MEX-PD was established, the methods and instruments and presenting the first results. Methods: Patients and controls were recruited from medical centers in 20 states of Mexico. Initial recruitment included neurological evaluation, cognitive assessment, and DNA collection. Results: MEX-PD has registered 302 controls and 262 PD patients with a mean age of diagnosis of 61 years (SD=10.86). There were 19.8% PD patients identified with early onset. Levodopa was the most common pharmacological treatment. Conclusions: MEX-PD contributes to understand PD nationally. The information gathered here will allow us to understand the prevalence of mental health, neurological symptoms, and cognitive function in the PD Mexican population and how genetical and environmental factors contributes to those outcomes. These will advocate for personalized treatments and improving quality of life in the Mexican population.

Adherence to treatment in Parkinson's disease: A multicenter exploratory study with patients from six Latin American countries.

BACKGROUND: Adherence to treatment in Parkinson's disease (PD) is compromised due to the need for multiple therapies, comorbidities related to aging, and the complexity of therapeutic schemes. In the present study, we aimed to explore adherence to treatment in groups of PD patients from six Latin-American (LA) countries and identify its associated demographic and clinical parameters. METHODS: A multicenter, cross-sectional, exploratory study was conducted from September 2016 to March 2017. Treatment adherence was assessed using the simplified medication adherence questionnaire (SMAQ), applied to patients and caregivers. Sociodemographic and clinical variables (MDS-UPDRS Part III-IV, MMSE, Beck Depression Inventory-II (BDI-II)) were recorded. RESULTS: Eight hundred patients from six LA countries were evaluated. Nonadherence was reported in 58.25% of the population, according to patients. The most frequent issues were forgetfulness and correct timing of doses. A high level of agreement in adherence prevalence and most SMAQ items were observed between patients and their caregivers. The nonadherent population had a significantly higher proportion of unemployment, free access to medication, troublesome dyskinesias and off-periods, lesser years of education, and worse motor, cognitive, and mood scores. In multiple logistic and linear regression analyses, MDS-UPDRS Part III, BDI-II, gender, free access to medication, treatment with dopamine agonists alone, years of education, excessive concerns about adverse effects, and beliefs about being well-treated remained significant contributors to adherence measures. CONCLUSION: Educational strategies, greater involvement of PD patients in decision-making, and consideration of their beliefs and values might be of great need to improve medication adherence in this PD population.

Determinants of self-efficacy in patients with Parkinson's disease.

BACKGROUND: Self-efficacy is the individual's assessment of his or hers ability to complete a specific task successfully and has been closely related to self-management and quality of life in several diseases. OBJECTIVE: To investigate self-efficacy in a population of Parkinson's disease (PD) patients in Mexico and study the factors that are associated with this measure. METHODS: We carried out a cross-sectional observational study involving patients with PD in an outpatient neurology clinic in Mexico, using the following instruments: Spanish version of the Chronic Disease Self-Efficacy Scale (CDSES), Quality of Life Questionnaire PDQ-8, Movement Disorders Society-Unified Parkinson's disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), and Non-Motor Symptom Scale (NMSS). Clinical and demographic variables were also recorded. RESULTS: We included 73 patients with a mean age of 65 years and most patients were male. Patients with lower CDSES scores (<7.75) had worse scores in MDS-UPDRS, NMSS, and PDQ-8 scales. CDSES scores were significantly correlated with MDS-UPDRS Part I (r=-0.497, p=<0.001), Part II (r= -0.271, p=0.020), Part III (r=-0.304, p=<0.001), PDQ-8 (r=-0.472, p=<0.001), and NMSS (r=-0.504, p=<0.001). Furthermore, when assessing the simultaneous effect of covariates associated with CDSES score, only Mood/Apathy domain of NMSS was significant (beta= -0.446, t= -3.807, p= 0.012). CONCLUSIONS: PD patients with lower self-efficacy scores had worse motor and non-motor symptomatology and quality of life. Mood/Apathy disorders were negatively associated with self-efficacy and contributed significantly to this measure.

Determinants of self-efficacy in patients with Parkinson's disease / Determinantes de autoeficacia en pacientes con enfermedad de Parkinson

ABSTRACT Background: Self-efficacy is the individual's assessment of his or hers ability to complete a specific task successfully and has been closely related to self-management and quality of life in several diseases. Objective: To investigate self-efficacy in a population of Parkinson's disease (PD) patients in Mexico and study the factors that are associated with this measure. Methods: We carried out a cross-sectional observational study involving patients with PD in an outpatient neurology clinic in Mexico, using the following instruments: Spanish version of the Chronic Disease Self-Efficacy Scale (CDSES), Quality of Life Questionnaire PDQ-8, Movement Disorders Society-Unified Parkinson's disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), and Non-Motor Symptom Scale (NMSS). Clinical and demographic variables were also recorded. Results: We included 73 patients with a mean age of 65 years and most patients were male. Patients with lower CDSES scores (<7.75) had worse scores in MDS-UPDRS, NMSS, and PDQ-8 scales. CDSES scores were significantly correlated with MDS-UPDRS Part I (r=-0.497, p=<0.001), Part II (r= -0.271, p=0.020), Part III (r=-0.304, p=<0.001), PDQ-8 (r=-0.472, p=<0.001), and NMSS (r=-0.504, p=<0.001). Furthermore, when assessing the simultaneous effect of covariates associated with CDSES score, only Mood/Apathy domain of NMSS was significant (beta= -0.446, t= -3.807, p= 0.012). Conclusions: PD patients with lower self-efficacy scores had worse motor and non-motor symptomatology and quality of life. Mood/Apathy disorders were negatively associated with self-efficacy and contributed significantly to this measure.

RESUMEN Antecedentes: La autoeficacia es la autoevaluación de un individuo sobre su capacidad para completar una tarea con éxito y se ha relacionado con automanejo y calidad de vida en otras enfermedades. Objetivo: Investigar la autoeficacia en una población de pacientes con enfermedad de Parkinson (EP) en México y estudiar factores asociados con esta medida. Métodos: Realizamos un estudio observacional transversal con pacientes con EP en una clínica de neurología en México. Se registraron datos demográficos y escalas que evalúan la función motora (MDS-UPDRS), no motora (NMSS) y cognitiva (MoCA), así como la calidad de vida (PDQ-8). Para valorar autoeficacia se utilizó la versión en español de la Escala de autoeficacia de enfermedades crónicas (CDSES). Resultados: Se incluyeron 73 pacientes, con una edad media de 65 años y la mayoría eran hombres. Pacientes con puntajes CDSES más bajos (<7.75) tuvieron peores puntajes en las escalas MDS-UPDRS, NMSS y PDQ-8. Las puntuaciones de CDSES se correlacionaron significativamente con la escala MDS-UPDRS Parte I (r=-0.497, p=<0.001), Parte II (r= -0.271, p=0.020), Parte III (r=-0.304, p=<0.001), PDQ-8 (r= -0.472, p=<0.001), y NMSS (r=-0.504, p=<0.001). Al evaluar el efecto simultáneo de covariables asociadas con la escala CDSES, solo el dominio estado de ánimo/apatía del NMSS resultó significativo (Beta = -0.449, t = -3.783, p = <0.001). Conclusiones: Los pacientes con menores puntajes de autoeficacia tienen peor calidad de vida y sintomatología motora y no motora. Los trastornos del estado de ánimo contribuyen negativamente a la autoeficacia.

Microalbuminuria as a potential biomarker for Parkinson's disease severity: A hypothesis.

Parkinson's disease (PD) is the second most common neurodegenerative condition characterized by motor and non-motor symptoms causing a great burden in patients' quality of life. PD has been associated with various metabolic factors such as diabetes, hypertension, and more recently chronic kidney disease where proteinuria has been associated with an increased risk. The presence of small amounts of albumin in urine, microalbuminuria, is a common biomarker for endothelial damage and a predictive factor for not only cardiovascular but also neurological dysfunction. Multiple studies have assessed potential biomarkers for PD progression with great heterogeneity, we hypothesize the use of microalbuminuria as a potential marker that correlates with PD severity and might represent a feasible and simple method of evaluating PD patients in clinical practice. Evidence supporting the present hypothesis comes from oxidative stress, insulin resistance, and endothelial dysfunction. Oxidative stress is a key element in PD pathogenesis; studies have shown lower antioxidant capacity as PD progresses. On the other side, insulin signaling plays an important role in neuronal growth and survival, with its resistance being associated with PD. Microalbuminuria has been associated with both processes; increased levels of oxidative stress markers and decreased insulin sensitivity, hence its screening in PD might reflect these common pathological mechanisms. Moreover, the low vitamin D levels observed in PD patients, which are correlated with endothelial dysfunction and disease severity, might contribute to microalbuminuria induction. More evidence on this vascular approach comes from white matter lesions (WML), observed in brain imaging, which have been significantly associated with motor and non-motor function in PD patients and are independently associated with microalbuminuria. In this manner, an oxidant and insulin resistant environment, along with low vitamin D levels in PD patients, which are associated with microalbuminuria, might contribute altogether to WML. As the latter are correlated with motor and non-motor function, microalbuminuria might thus give insight on PD status. Prospective cohort studies with an adequate sample size, follow-up, and a thorough battery of clinical tests for PD are needed to confirm this hypothesis.

Características clínicas del síndrome metabólico en pacientes con enfermedad de Parkinson / Clinical features of metabolic syndrome in patients with Parkinson's disease

INTRODUCCIÓN: Recientemente, se ha incrementado la atención hacia causas metabólicas de la pérdida de células dopaminérgicas en la enfermedad de Parkinson (EP), dada la intolerancia a la glucosa que pueden presentar estos pacientes. Un síndrome caracterizado por resistencia a la insulina es el síndrome metabólico. OBJETIVO: Determinar la prevalencia y las características clínicas del síndrome metabólico y sus componentes en pacientes con EP. PACIENTES Y MÉTODOS: Se analizaron variables de 99 pacientes con EP. Se registraron escalas que evalúan las funciones motora, no motora y cognitiva, los trastornos del sueño y la calidad de vida. El síndrome metabólico se diagnosticó según los criterios de la Organización Mundial de la Salud. RESULTADOS: La prevalencia de síndrome metabólico se notificó en un 8%. Al subdividir a los pacientes en función de los criterios positivos de síndrome metabólico, no se observaron diferencias significativas en las funciones motora y cognitiva, la calidad de vida ni los trastornos del sueño entre los grupos. No obstante, pacientes con síndrome metabólico mostraron peores puntuaciones en la escala de síntomas no motores en comparación con pacientes sin el síndrome, especialmente en cuanto a tracto gastrointestinal, estado de ánimo/apatía, función sexual, problemas perceptivos y misceláneos. No se observaron diferencias significativas en las características clínicas al agrupar a los pacientes sobre la base del componente único de síndrome metabólico presente. CONCLUSIÓN: El síndrome metabólico podría tener un efecto sobre la sintomatología no motora en la EP, ya que los pacientes con este síndrome mostraron peores puntuaciones en la escala de síntomas no motores

INTRODUCTION: Focus on the metabolic causes underlying dopaminergic cell loss in Parkinson's disease (PD) has increased lately. Glucose imbalances have been shown to be present in patients with PD. A syndrome characterized principally by insulin resistance and glucose dysregulations is metabolic syndrome. Scarce literature has evaluated the relation between these two diseases. AIM: To determine the prevalence and clinical features of metabolic syndrome and its components in patients with PD. PATIENTS AND METHODS: We analyzed data from 99 patients with PD diagnosis. Scales that evaluate motor, non-motor, and cognitive function, as well as sleep disorders and quality of life were registered. Metabolic syndrome was diagnosed according to the World Health Organization criteria. RESULTS: Metabolic syndrome was reported in 8% of the population. When subdividing patients based on positivity to metabolic syndrome criteria, no significant differences in motor and cognitive function, as well as quality of life and sleep disorders were observed between groups. However, patients with metabolic syndrome showed worse scores in Non-Motor Symptom Scale compared to patients without the syndrome, especially gastrointestinal, mood/apathy, sexual function, perceptual and miscellaneous symptoms. No significant differences in clinical correlates were observed when grouping patients based on which single metabolic syndrome component was present. CONCLUSION. Metabolic syndrome might have an effect on non-motor symptomatology in PD, as patients with metabolic syndrome showed worse scores in Non-Motor Symptom Scale

Comparison of the effect of whole-body vibration therapy versus conventional therapy on functional balance of patients with Parkinson's disease: adding a mixed group.

OBJECTIVE: Assess the effect of Whole-Body Vibration (WBV) therapy in functional balance status of Parkinson's disease (PD) patients and compare this to conventional and combined therapy. INTRODUCTION: PD patients experience a decreased mobility, inactivity, and loss of independence as consequence of disturbances in gait, posture, and balance. Rehabilitation therapy is a non-pharmacological way of improving functionality. One of the most studied modalities is WBV, with multiple studies showing improvement in motor function. However, results in this manner are inconsistent. METHODS: Forty-five patients were enrolled in a non-randomized controlled trial and divided into three groups. Group 1 received conventional therapy (thermotherapy, stretching, strengthening, coordination and balance). Group 2 received WBV therapy, and group 3 patients underwent a combined therapy protocol. A total of 20 sessions (3 per week) were conducted, assessing Berg Balance Scale (BBS) before initial and after final session. RESULTS: The 3 intervention groups showed significant improvement in BBS scores after concluding the 20-session trial compared to initial assessment. When comparing mean change in BBS score from initial to final assessment, the combined therapy group had a greater increase compared to conventional therapy, but no significant differences were observed comparing to WBV group. Mean change in BBS score showed no significant difference between conventional therapy and WBV therapy group. CONCLUSIONS: WBV therapy is a useful tool as co-adjuvant in conventional therapy. The combination of both therapies is a significant therapeutic alternative for the improvement of functional balance status in PD patients compared to conventional therapy alone.

Linking chronic kidney disease and Parkinson's disease: a literature review.

Chronic kidney disease (CKD) has been typically implicated in cardiovascular risk, considering the function the kidney has related to blood pressure, vitamin D, red blood cell metabolism, and electrolyte and acid-base regulation. However, neurological consequences are also attributed to this disease. Among these, recent large epidemiological studies have demonstrated an increased risk for Parkinson's disease (PD) in patients with CKD. Multiple studies have evaluated individually the association of blood pressure, vitamin D, and red blood cell dysmetabolism with PD, however, no study has reviewed the potential mechanisms related to these components in context of CKD and PD. In this review, we explored the association of CKD and PD and linked the components of the former to propose potential pathways explaining a future increased risk for PD, where renin-angiotensin system, oxidative stress, and inflammation have a main role. Potential preventive and therapeutic interventions based on these associations are also explored. More preclinical studies are needed to confirm the potential link of CKD conditions and future PD risk, whereas more interventional studies targeting this association are warranted to confirm their potential benefit in PD.

Does glitazone treatment have a role on the prevention of Parkinson's disease in adult diabetic population? A systematic review.

Lately, focus on the relation between Parkinson's disease (PD) and Diabetes has risen greatly, as neuroprotective properties have been attributed to insulin use. Several studies have assessed the effect of glitazones, an insulin-sensitizing agent, in diabetic population on PD future risk. However, reports on the effect of their use have been heterogeneous. We aimed to synthesize the available scientific evidence which assesses the effect of glitazone use in type 2 diabetes patients on PD incidence. A systematic review was performed on multiple electronic databases. Considered for inclusion were studies that assessed the incidence of PD in type 2 diabetes glitazone users. Two reviewers worked independently and in duplicate to assess all studies, extract information and assess the methodological quality in each included study. Four high quality retrospective cohorts fulfilled inclusion criteria. Comparison groups varied across studies. In each study, incidence of PD was lower in glitazone-exposed patients compared to their respective comparison group. Pooled analysis showed lesser risk of PD in ever versus never glitazone users (RR 0.75 [95% C.I. 0.67-0.85; p < .0001; I2 = 0]). Our pooled analysis showed lesser risk of PD in glitazone versus non glitazone users, however, we advise to take results with caution since results are non-adjusted to possible confounding variables, furthermore, different glitazone-exposure time, follow up and comparison groups are aspects that also need to be pointed out. More clinical research focused on glitazone use and its relation with PD is needed, as this could result in new potential treatment modalities.

The poor insane Ophelia: reconsidering Ophelia syndrome.

INTRODUCTION: The association between memory loss and Hodgkin's lymphoma has been given the eponym of Ophelia syndrome, in memory of Shakespeare's character in The Tragedy of Hamlet, Prince of Denmark. Nevertheless, there are differences between the disease and the character. OBJECTIVE: To review the origins and uses of the eponym through an original article by pathologist Ian Carr, its relation to the character Ophelia, and the related autoantibodies. METHODS: Historical narrative review. RESULTS: Besides an eloquent description in the original article, Carr presaged the presence of autoantibodies, before they had been thoroughly researched. Since then, five different autoantibodies (mGluR5, Hu, NMDAR, SOX, PCA2) have been associated with Hodgkin's disease. It is interesting to note the divergent outcomes of Shakespeare's character and the patient in the original description by Carr, the latter recovering to lead a normal life, and the former deceased. CONCLUSIONS: Although there is little relationship between the fictional character and the syndrome, both imply the unintentional trigger of self-harm (suicide in one case, autoimmunity in the other), thus remaining associated.

"Los libros y la noche", perspectiva neurológica de la ceguera de Jorge Luis Borges.

The works of Argentinian scholar Jorge Luis Borges (1899-1986) have captivated physicians. An assiduous reader, he was given, with magnificent irony, "books and the night". Borges suffered from chronic and irreversible blindness, which influenced much of his work and has been the subject of different literary and diagnostic analyses from the ophthalmological point of view. However, the characteristics of his visual impairment have escaped the neurological approach, which is why we reviewed his work looking for data suggesting a concomitant brain injury. On his autobiography, he recounts how, during an episode of septicemia, he suffered hallucinations and loss of speech; in addition, in some poems and essays he describes data that suggest "phantom chromatopsia", a lesion of cortical origin. After that accident, Borges survived with a radical change in literary style. Although a precise diagnosis is impossible, his literary work allows recognizing some elements in favor of concomitant brain involvement.

La obra del erudito argentino Jorge Luis Borges (1899-1986) ha cautivado a los médicos. Asiduo lector con magnífica ironía, le fueron dados "los libros y la noche". Borges padeció una ceguera crónica e irreversible que impulsó gran parte de su obra y ha sido objeto de distintos análisis literarios y diagnósticos desde el punto de vista oftalmológico. Sin embargo, las características de su ceguera han escapado al abordaje neurológico, por lo cual revisamos su obra en busca de datos que sugieran una lesión cerebral concomitante. En su autobiografía relata cómo durante un episodio de septicemia padeció alucinaciones y pérdida del habla; además, en algunos poemas y ensayos describe datos que sugieren "cromatopsia fantasma", lesión de origen cortical. Tras dicho accidente, Borges sobrevivió con un cambio radical en su estilo literario. Aunque un diagnóstico preciso es imposible, su obra literaria nos permite reconocer algunos elementos que sugieren involucramiento cerebral concomitante.

The poor insane Ophelia: reconsidering Ophelia syndrome / La pobre e insensata Ofelia: reconsiderando el síndrome de Ofelia

ABSTRACT The association between memory loss and Hodgkin's lymphoma has been given the eponym of Ophelia syndrome, in memory of Shakespeare's character in The Tragedy of Hamlet, Prince of Denmark. Nevertheless, there are differences between the disease and the character. Objective: To review the origins and uses of the eponym through an original article by pathologist Ian Carr, its relation to the character Ophelia, and the related autoantibodies. Methods: Historical narrative review. Results: Besides an eloquent description in the original article, Carr presaged the presence of autoantibodies, before they had been thoroughly researched. Since then, five different autoantibodies (mGluR5, Hu, NMDAR, SOX, PCA2) have been associated with Hodgkin's disease. It is interesting to note the divergent outcomes of Shakespeare's character and the patient in the original description by Carr, the latter recovering to lead a normal life, and the former deceased. Conclusions: Although there is little relationship between the fictional character and the syndrome, both imply the unintentional trigger of self-harm (suicide in one case, autoimmunity in the other), thus remaining associated.

RESUMO El síndrome de Ofelia describe la asociación entre pérdida de memoria y enfermedad de Hodgkin, en memoria del personaje de La Tragedia de Hamlet, Príncipe de Dinamarca, de William Shakespeare. Sin embargo, existen diferencias entre ambos. Objetivo: Revisar los orígenes y usos del epónimo a través del artículo original, su relación con el personaje y los autoanticuerpos relacionados. Métodos: Revisión narrativa histórica. Resultados: Además de una descripción elocuente, el artículo original prefigura los autoanticuerpos, cuando no se buscaban de rutina. Desde entonces, cinco distintos (mGluR5, Hu, NMDAR, SOX, PCA2) han sido asociados. Cabe destacar, que el desenlace del personaje y del paciente fueron diametralmente opuestos, el primero falleció y el segundo se recuperó, llevando una vida normal. Conclusiones: A pesar de la poca relación entre el personaje y el síndrome, ambos implican el desencadenamiento no intencional de daño auto-inflingido (suicidio en un caso, autoinmunidad en el otro), manteniendo así la adecuacía.

"The books and the night", neurological perspective on Jorge Luis Borges' blindness

The works of Argentinian scholar Jorge Luis Borges (1899-1986) have captivated physicians. An assiduous reader, he was given, with magnificent irony, "books and the night". Borges suffered from chronic and irreversible blindness, which influenced much of his work and has been the subject of different literary and diagnostic analyses from the ophthalmological point of view. However, the characteristics of his visual impairment have escaped the neurological approach, which is why we reviewed his work looking for data suggesting a concomitant brain injury. On his autobiography, he recounts how, during an episode of septicemia, he suffered hallucinations and loss of speech; in addition, in some poems and essays he describes data that suggest "phantom chromatopsia", a lesion of cortical origin. After that accident, Borges survived with a radical change in literary style. Although a precise diagnosis is impossible, his literary work allows recognizing some elements in favor of concomitant brain involvement.

The Parkinson's Disease Sleep Scale-2 (PDSS-2): Validation of the Spanish Version and Its Relationship With a Roommate-Based Version.

BACKGROUND: Because of the prevalence and impact of sleep disorders in Parkinson's disease (PD), valid instruments for their evaluation and monitoring are necessary. However, some nocturnal sleep disorders may go unnoticed by patients themselves. OBJECTIVES: To validate a pan-Spanish version of the Parkinson's Disease Sleep Scale Version 2 (PDSS-2) and to test the relationships between the PDSS-2 and a PDSS-2 roommate version. METHODS: PD patients (n = 399) from seven Spanish-speaking countries were included. In addition to the tested PDSS-2 scales, valid measures for sleep disorders and both motor and nonmotor manifestations were applied. Acceptability, dimensionality, reliability, precision, and construct validity were explored, as well as discrepancies and agreement between the PDSS-2 and the roommate version. RESULTS: PDSS-2 showed negligible floor and ceiling effects. Four factors (57% of the variance) were identified. Reliability parameters were satisfactory: alpha = 0.84; item homogeneity coefficient = 0.27; corrected item total correlation = 0.28 to 0.61; and test-retest reliability (average kappa = 0.70; intraclass correlation coefficient [ICC] = 0.83). The standard error of measurement was 5.84, and correlations with other scales assessing nocturnal sleep were high (rS = 0.62-0.56). In comparison to the patient-based total score, the by proxy total score showed no significant difference, high correlation (rS = 0.70), and acceptable agreement (ICC = 0.69), but there were discrepancies in two or more points in 18% of item scores. CONCLUSIONS: The Spanish version of the PDSS-2 has shown satisfactory clinimetric attributes. Acceptability and precision data are presented for the first time. The PDSS-2 roommate version could be useful to complement the patient-based evaluation, but additional studies are needed.