L-2 hydroxyglutaric aciduria: report of a Mexican-Mayan patient with the mutation c.569C>T and response to vitamin supplements and levocarnitine.

Background: L-2-hydroxyglutaric aciduria (L2HGA) is a rare inherited autosomal recessive neurometabolic disorder caused by pathogenic variants in the L2HGDH gene which encodes mitochondrial 2-hydroxyglutarate dehydrogenase. Here, we report a case of L2HGA in a Mexican-Mayan patient with a homozygous mutation at L2HGDH gene and clinical response to vitamin supplements and levocarnitine. Case report: A 17-year-old, right-handed female patient with long-term history of seizures, developmental delay and ataxia was referred to a movement disorders specialist for the evaluation of tremor. Her brain MRI showed typical findings of L2HGA. The diagnosis was corroborated with elevated levels of 2-hydroxyglutaric acid in urine and genetic test which revealed a homozygous genetic known variant c.569C>T in exon 5 of L2HGDH gene. She was treated with levocarnitine and vitamin supplements, showing improvement in tremor and gait. Discussion: To our knowledge this is the first report of a Mexican patient with L2HGA. This case adds information about a rare condition in a different ethnic group and supports the findings of other authors which encountered symptomatic improvement with the use of flavin adenine dinucleotide (and its precursor riboflavin), and levocarnitine. Highlights: We report the first case of Mexican-Mayan patient with L2HGA showing a missense homozygous mutation in L2HGDH gene, and improvement of symptoms with vitamin supplements and levocarnitine.

Latencia diagnóstica y percepción de síntomas prodrómicos en pacientes con enfermedad de Parkinson en Yucatán / Diagnostic latency and perception of prodromal symptoms in patients with Parkinson's disease in Yucatán

Resumen Objetivo: Determinar la latencia diagnóstica en la enfermedad de Parkinson (EP), así como su relación con variables clínicas y demográficas. Determinar la percepción de síntomas no motores: disfunción olfatoria, trastorno conductual del sueño MOR, depresión y estreñimiento, previos al diagnóstico de EP. Materiales y métodos: Estudio transversal realizado en Yucatán, México en sujetos con EP. Se analizó la asociación entre la latencia diagnóstica con variables clínicas y demográficas usando las pruebas estadísticas no paramétricas: U de Mann Whitney y Kruskal-Wallis. Resultados: Se incluyeron un total de 60 sujetos con una edad promedio de 66.7 años. El tiempo promedio transcurrido desde el inicio del primer síntoma motor hasta el diagnóstico fue de 20.8 meses. El tener antecedentes familiares de EP se asoció significativamente (p=0.031) con una latencia diagnóstica más prolongada en comparación con aquellos pacientes que no refirieron familiares con EP. En cualquier momento antes del diagnóstico de EP: el 36.6% de los pacientes percibieron estreñimiento, 15% depresión, 13.3% trastorno conductual del sueño MOR y 11.6% disfunción olfatoria, 51.7% no refirió ninguno. Conclusiones: La latencia diagnóstica promedio de un grupo de 60 pacientes con EP diagnosticados en Yucatán fue de 20.8 meses. La latencia diagnóstica no se asoció significativamente con el tipo de servicio médico de neurología que realizó en diagnóstico de EP (público o privado), ni con otras variables clínicas ni demográficas además del antecedente familiar de EP.

Abstract Objective: To determine the diagnostic latency in Parkinson's disease (PD), and its relationship with clinical and demographic variables. To determine the perception of non-motor symptoms: olfactory dysfunction, REM sleep behavior disorder, depression, and constipation, prior to the diagnosis of PD. Materials and methods: Cross-sectional study conducted in Yucatan, Mexico in subjects with PD. The association between diagnostic latency with clinical and demographic variables was analyzed using the non-parametric statistical tests: Mann Whitney U and Kruskal-Wallis. Results: A total of 60 subjects with a mean age of 66.7 years were included. The average time elapsed from the onset of the first sympoton to diagnosis was 20.8 months. A family history of PD was significantly associated (p=0.031) with a longer diagnostic latency compared to those patients who did not have relatives with PD. Before the diagnosis of PD: 36.6% of the patients perceived constipation, 15% depression, 13.3% REM sleep behavior disorder and 11.6% olfactory dysfunction, 51.7% did not report any. Conclusions: The mean diagnostic latency of a group of 60 patients with PD diagnosed in Yucatan was 20.8 months. Diagnostic latency was not significantly associated with the type of neurological medical service that performed the diagnosis (public or private), or with other clinical or demographic variables in addition to a family history of PD.

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.

Self-Perceived Pre-Motor Symptoms Load in Patients with Parkinson's Disease: A Retrospective Study.

BACKGROUND: Parkinson's disease is characterized by motor and non-motor clinical features. The latter may present as pre-motor symptoms several years before the motor onset. OBJECTIVE: To analyze the association between pre-motor symptoms load and its lead-time in relation to the motor onset and time to diagnosis. METHODS: A cross-sectional study was carried including subjects with Parkinson's disease from five different movement disorders clinics in Mexico. A structured questionnaire was applied to assess the presence of six self-perceived pre-motor symptoms (hyposmia, depression, anxiety, constipation, pain and sleep disorders). RESULTS: Overall frequency of pre-motor symptoms was 76.2% . Among the most prevalent symptoms were depression (38%), sleep disorders (37%) and anxiety (36.6%). The lead time to motor onset was greater for constipation (9.2 ± 17.89 years) and pain (8.66 ± 13.36 years). Patients with more than two pre-motor symptoms had a later age at motor onset when compared to patients without pre-motor symptoms (52.04 ± 13.11 vs 56.55 ± 12.97 years, p = 0.037). Late onset patients had a higher frequency of pre-motor symptoms (79% vs 65% in early onset, p = 0.002) and a higher load (1.75 ± 1.37 vs 1.44 ± 1.38, p = 0.033) in comparison to those with early onset. Female subjects reported a higher number of pre-motor symptoms (1.91 ± 1.43 versus 1.48 ± 1.29, p ≤ 0.001). PIGD patients reported a greater frequency of pain (8%) compared to tremor (1%, p = 0.0064) and bradykinetic-rigid (0.61%, p = 0.0061). Anxiety lead-time was greater in tremor-dominant (10.83 ± 15.77 years) compared to bradykinetic-rigid patients (3.48 ± 12.56, p = 0.014). CONCLUSIONS: Pre-motor symptoms load is associated to a later motor onset of PD. Pre-motor symptoms are more frequent in subjects with late onset Parkinson's disease. Female subjects report a higher number of pre-motor symptoms, depression and anxiety being the most common.

Impact of Neuropsychiatric Symptoms on the Quality of Life of Subjects with Parkinson's Disease.

BACKGROUND: Neuropsychiatric symptoms in Parkinson's disease (PD) are frequent. Impact of neuropsychiatric symptoms on quality of life has recently become a relevant topic of research due to its potential to develop targeted therapies to improve quality of life. OBJECTIVE: To determine the impact of neuropsychiatric symptoms in patients with PD using the Parkinson's Disease Questionnaire Short Form (PDQ-8). METHODS: Consecutive patients with PD were evaluated with the Scale for Evaluation of Neuropsychiatric Disorders in Parkinson's disease (SEND-PD) and PDQ-8 scales separately. Association between neuropsychiatric symptoms and quality of life was explored using, means comparisons, correlation coefficients and multiple regression models. RESULTS: A total of 492 patients were included for the study. Overall, 44.5% had psychotic symptoms, 76.5% had alterations on mood/apathy domains, and 27% had an impulse control disorder. All neuropsychiatric symptoms had an effect on the PDQ-8 with a moderate to large effect size. Correlation coefficients ranged from 0.17 to 0.63 between neuropsychiatric symptoms and quality of life (p <  0.001, in all cases). The regression model showed that mood/apathy alterations and impulse control disorders, along with MDS-UPDRS III accounted for 49.8% of variance in the PDQ-8 simplified index (F = 122.98; p <  0.001). Mood/apathy alterations showed the highest correlation coefficient (0.63, p <  0.001) and ß (0.53, p <  0.001). CONCLUSIONS: Both the presence and severity of neuropsychiatric symptoms, in particular mood/apathy alterations,had a significant impact on quality of life in subjects with PD.

Convergent validation of EQ-5D-5L in patients with Parkinson's disease.

INTRODUCTION: The European Quality of Life Questionnaire 5 level version (EQ-5D-5L) is a recently updated instrument to assess Health-Related Quality of Life (HRQoL) that has not been validated extensively. The main objective of this study was to evaluate the internal consistency and convergent validation of the EQ-5D-5L in a large sample of subjects with Parkinson's disease (PD). METHODS: A cross-sectional study was carried out. Consecutive Mexican subjects with PD were included. HRQoL was assessed using the EQ-5D-5L and the PDQ-8. Validity of the EQ-5D-5L was assessed determining its association with clinical ratings of disease severity, as well as correlation with PDQ-8. Additionally, performance was evaluated along predefined groups based on clinical and demographic data of known determinants of quality of life. RESULTS: A total of 585 patients were included for this study. A strong correlation was found between EQ-5D-5L index and PDQ-8 index (Spearman's correlation coefficient=-0.75; p<0.001). Correlation between EQ-5D-5L index and PDQ-8 index remained strong (-0.60 to -0.78; p values <0.001) through all predefined groups. EQ-5D-5L scored higher in those patients with dyskinesia, wearing off, freezing, postural instability, cognitive impairment or depressive mood (p values <0.001). CONCLUSION: The EQ-5D-5L is a valid instrument for evaluating HRQoL in PD, performing adequately irrespective of heterogeneous clinical and demographic characteristics, and showing to be sensitive to features of advanced disease and treatment complications.

Plasma cell tumor of the clivus: report of two cases.

BACKGROUND: Plasma cell tumor only rarely affects the cranium and may be found as an isolated lesion or as a part of multiple myeloma. In this review we present the clinical and radiological characteristics and analyze the evolution of two cases of this tumor located at the skull base, specifically in the clivus and sellar region. We also present a brief review of the literature. CLINICAL CASES: Case #1: The patient was a 66-year-old female with a solitary plasmacytoma of the bone (the isolated form of plasma cell tumor) that was totally removed. Case #2: The patient was a 61-year-old male with the diffuse form of this disease who was submitted to subtotal removal. In both patients, adjuvant treatment based on radiotherapy and chemotherapy was proposed; however, only one patient (Case #2) accepted adjuvant treatment and had a very favorable result. Most clinical symptoms disappeared and the patient is currently alive and with a very good quality of life (>3-year follow-up). The other patient (Case #1), despite the presence of the localized form of the disease, died 3 months after diagnosis. CONCLUSION: Early diagnosis and removal of as much of the tumor as possible, but mainly the opportune indication of adjuvant treatment with radiotherapy and chemotherapy, are the keys to management of these cases.