Central nervous system manganese induced lesions and clinical consequences in patients with hereditary hemorrhagic telangiectasia

Abstract Background Around 47–74% of patients with hereditary hemorrhagic telangiectasia (HHT) have hepatic vascular malformations (HVMs); magnetic resonance images (MRI) of the central nervous system (CNS) might show in T1 sequences a hyper-intensity signal in different areas, mainly in the basal ganglia (BG) as consequence of manganese (Mn) deposits as observed in cirrhotic patients. These patients might suffer from different neuropsychiatric disorders (hepatic encephalopathy). In HHT patients, even in the presence of hepatic shunts, hepatocellular function is usually preserved. Additionally, Mn shares iron absorption mechanisms, transferrin and CNS transferrin receptors. In iron deficiency conditions, the Mn may harbor transferrin and access BG. The objectives were to describe frequency of BG Mn deposit-induced lesions (BGMnIL) in HHT patients, its relationship with iron deficiency anemia (IDA) and HVMs. Finally, explore the association between neuropsychological and motor consequences. We performed a cross-sectional study. We determined HHT patients with or without BG-MnIL by the MRI screening of the CNS. We included all patients with lesions and a random sample of those without lesions. All patients underwent standardized and validated neuropsychological assessment to evaluate BG actions. Results were analyzed with multiple logistic regression, adjusting for potential confounders. Results Among 307 participants from a cohort included in the Institutional HHT Registry, 179 patients had MRI performed and Curaçao Criteria ≥3. The prevalence of BG-MnIL was 34.6% (95%CI 27.69-42.09). While neuropsychological symptoms were present in all patients, BG-MnIL patients performed poorly in three of the neuropsychological tests (serial dotting, line tracing time, number connection test A). HVMs frequency in BG-MnIL was 95.1%, versus 71.4% in those without lesions (p < 0.001). IDA frequency was 90.3% versus 54% (p < 0.001). When IDA is present, estimated risk for BG-MnIL is remarkably high (OR 7.73, 95%CI 2.23–26.73). After adjustment for possible confounders (gender, age, presence of HVMs), IDA was still associated with increased risk of BG-MnIL (adjusted OR 6.32, 95% CI 2.32–17.20; p < 0.001). Conclusions Physicians should assess BG-MnIL in HHT patients in CNS-MRI. IDA and HVMs present increased risk of lesions. Patients with BG-MnIL have neuropsychological impairment, and they might benefit from sparing IDA, or undergoing future therapeutic options. Trial registration NCT01761981 . Registered January 3rd 2013

Alzheimer's disease: Clinical practice guideline

El Grupo de Trabajo de Neurología de la Conducta y Neurociencias Cognitivas de la Sociedad Neurológica Argentina publicó en 2006 la primera Guía de práctica clínica sobre la enfermedad de Alzheimer para su aplicación en nuestro medio y, eventualmente, en el resto de los países hispanoparlantes del Cono Sur. La Guía que hoy publicamos, mediante la revisión y actualización del estado actual del conocimiento sobre la enfermedad de Alzheimer y su manejo clínico y neurológico, provee a los profesionales los estándares surgidos de la medicina basada en la evidencia para una adecuada implementación de las conductas diagnósticas y terapéuticas a su alcance en nuestro medio.In 2006, the Argentine Neurological Society Research Group on Behavioral Neurology and Cognitive Neurosciences published the first Clinical Practice Guideline on Alzheimer's Disease to be consulted in Argentina and eventually in other countries in Latin America. The present Guideline is a review of the state of the art concerning the 2010 knowledge on the management of this disease. It provides physicians with the usual standards provided by evidence based medicine in order to reach the most adequate diagnostic and therapeutic measures at hand in our countries.Fil: Allegri, Ricardo Francisco. Sociedad Neurológica Argentina; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Instituto de Neurociencias - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Neurociencias; ArgentinaFil: Arizaga, Raúl Luciano. Sociedad Neurológica Argentina; ArgentinaFil: Bavec, Claudia V.. Sociedad Neurológica Argentina; ArgentinaFil: Colli, Liliana P.. Sociedad Neurológica Argentina; ArgentinaFil: Demey, Ignacio. Sociedad Neurológica Argentina; ArgentinaFil: Fernández, María C.. Sociedad Neurológica Argentina; ArgentinaFil: Frontera, Silvina A.. Sociedad Neurológica Argentina; ArgentinaFil: Garau, María L.. Sociedad Neurológica Argentina; ArgentinaFil: Jiménez, Julio J.. Sociedad Neurológica Argentina; ArgentinaFil: Golimstok, Angel. Sociedad Neurológica Argentina; ArgentinaFil: Kremer, Janus. Sociedad Neurológica Argentina; ArgentinaFil: Labos, Edith. Sociedad Neurológica Argentina; ArgentinaFil: Mangone, Carlos Antonio. Sociedad Neurológica Argentina; ArgentinaFil: Ollari, Juan A.. Sociedad Neurológica Argentina; ArgentinaFil: Rojas, Zenón Galeno. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Sociedad Neurológica Argentina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Salmini, Omar. Sociedad Neurológica Argentina; ArgentinaFil: Ure, Jorge A.. Sociedad Neurológica Argentina; ArgentinaFil: Zuin, Daniel R.. Sociedad Neurológica Argentina; Argentin

Additional file 1: of Central nervous system manganese induced lesions and clinical consequences in patients with hereditary hemorrhagic telangiectasia

The Psychometric Hepatic Encephalopathy Score (PHES) is a “paper and pencil” screening test battery, designed for the diagnosis of minimal hepatic encephalopathy [20, 37]. This validated tool includes the following five tests: the line tracing test (LTT) with two scores for the same test: time and numbers of errors -motor speed and accuracy-, the serial dotting test (SDT) -motor speed-, the digit symbol test (DST) -associative learning; graphomotor speed, cognitive processing speed, visual perception, working memory-, the number connection test A (NCT-A) -psychomotor speed; visual scanning efficiency, sequencing, attention, concentration- and the number connection test B (NCT-B) -attention set shifting ability, psychomotor speed, visual scanning efficiency, sequencing, attention, concentration- all test are represented in Fig. 6 [38]. These tests examine motor speed and accuracy, visual perception, visuospatial orientation, visual construction, concentration, attention and to a lesser extent memory [22]. (DOCX 15 kb)

Clinical practice guideline. Fitness to drive in cognitive impairment and dementia

El deterioro de las funciones cognitivas puede afectar a las habilidades de conducción vehicular representando un riesgo de salud pública al incrementar los accidentes de tránsito. El deterioro cognitivo leve y las demencias se caracterizan por presentar alteraciones cognitivas que afectan, en mayor o menor grado, a las actividades instrumentales de la vida diaria e influyen en la conducción segura. El Grupo de Trabajo de Neurología de la Conducta y Neurociencias Cognitivas de la Sociedad Neurológica Argentina ha elaborado esta Guía de práctica clínica para facilitar a los profesionales médicos la evaluación de pacientes en quienes se sospecha deterioro cognitivo o demencia y para detectar y prevenir eventuales conductas de riesgo.Cognitive impairment may compromise driving skills and represent a public health risk by increasing traffic accidents. Mild Cognitive Impairment and Dementia are characterized by cognitive impairment affecting to a greater or lesser degree the instrumental activities of daily living and fitness to drive. The Argentine Neurologic Society Working Group on Behavioural Neurology and Cognitive Neurosciences has prepared this clinical practice guideline to help physicians evaluate patients suspected to present cognitive impairment or dementia and detect and prevent risky behaviors.Fil: Allegri, Ricardo Francisco. Sociedad Neurológica Argentina. Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Arizaga, Raúl Luciano. Sociedad Neurológica Argentina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bavec, Claudia Veronica. Sociedad Neurológica Argentina; ArgentinaFil: Barreto, María Dolores. Sociedad Neurológica Argentina; ArgentinaFil: Brusco, Luis Ignacio. Sociedad Neurológica Argentina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Colli, Liliana Patricia. Sociedad Neurológica Argentina; ArgentinaFil: Demey, Ignacio. Sociedad Neurológica Argentina; ArgentinaFil: Fernandez, Maria Cecilia. Sociedad Neurológica Argentina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Frontera, Silvana A.. Sociedad Neurológica Argentina; ArgentinaFil: Garau, Maria Laura. Sociedad Neurológica Argentina; ArgentinaFil: Gimenez, Julio Jorge. Sociedad Neurológica Argentina; ArgentinaFil: Golimstok, Angel. Sociedad Neurológica Argentina; ArgentinaFil: Kremer, Janus. Sociedad Neurológica Argentina; ArgentinaFil: Labos, Luisa Edit. Sociedad Neurológica Argentina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Leis, Adriana Mónica. Sociedad Neurológica Argentina; ArgentinaFil: Lopez Llano, María Luz. Sociedad Neurológica Argentina; ArgentinaFil: Mangone, Carlos Alberto. Sociedad Neurológica Argentina; ArgentinaFil: Ollari, Juan Alberto. Sociedad Neurológica Argentina; ArgentinaFil: Rojas, Zenón Galeno. Sociedad Neurológica Argentina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Russo, María Julieta. Sociedad Neurológica Argentina; ArgentinaFil: Serrano, Mariela Cecilia. Sociedad Neurológica Argentina; ArgentinaFil: Somale, Maria Veronica. Sociedad Neurológica Argentina; ArgentinaFil: D. Souza, Leandro. Sociedad Neurológica Argentina; ArgentinaFil: Ure, Jorge Alberto. Sociedad Neurológica Argentina; ArgentinaFil: Zuin, Daniel Raul. Sociedad Neurológica Argentina; Argentin

Mendelian and sporadic FTD: disease risk and avenues from genetics to disease pathways through in silico modelling.

Frontotemporal dementia (FTD) is regarded as the second most common form of young-onset dementia after Alzheimer's disease (AD).FTD is a complex neurodegenerative condition characterised by heterogeneous clinical, pathological and genetic features. No efficient measures for early diagnosis and therapy are available.Familial (Mendelian) forms of disease have been studied over the past 20 years. Conversely, the genetics of sporadic forms of FTD (up to 70% of all cases) is understudied and still poorly understood. All this taken together suggests that more powerful and in-depth studies to tackle missing heritability and define the genetic architecture of sporadic FTD, with particular focus on the different subtypes (i.e. clinical and pathological diagnoses), are warranted.In parallel, it will be critical to translate the genetic findings into functional understanding of disease, i.e. moving from the identification of risk genes to the definition of risk pathways. It will be necessary to implement a paradigm shift - from reductionist to holistic approaches - to better interpret genetics and assist functional studies aimed at modelling and validating such risk pathways.In this chapter, we focus on the heterogeneous features of FTD touching upon its complex genetic landscape and discuss how novel approaches (e.g. computationally driven systems biology) promise to revolutionise the translation of genetic information into functional understanding of disease pathogenesis