Adult Attention Deficit-Hyperactivity Disorder is associated with Lewy Body Disease and Cognitive Impairment: A prospective cohort Study With 15-year Follow-Up.

OBJECTIVES: Past reports have suggested that attention-deficit/hyperactivity disorder (ADHD) may be a risk factor for Lewy body disease (LBD). To confirm this relationship, we conducted the present study. DESIGN: A prospective observational cohort study with a follow-up to 15 years. SETTING: The subjects were recruited from cognitive neurology clinics, where they attended for a cognitive complaint or health check-up. PARTICIPANTS: Two groups of subjects: ADHD adults and healthy subjects. MEASUREMENTS: The risk of dementia and LBD was estimated with Kaplan-Meier analysis comparing for the presence or absence of ADHD with the log-rank test. Predictors of conversion were assessed through separate univariate and multivariate Cox regression analyses, adjusting for several variables. RESULTS: The baseline sample consisted of 161 subjects with ADHD and 109 without ADHD. At the end of the follow-up, 31 subjects developed dementia, 27 cases in the ADHD group and 4 in comparison group. Dementia with Lewy bodies (DLB) was the most frequent type (N:20) of which 19 corresponded to the ADHD group. The incidence of non-amnestic-MCI in the ADHD group was higher representing 67.1 % of these subjects (N:108), and 17.4% (N:19) of healthy cases. The hazard ratios for dementia and LBD in the multivariate adjusted model were 3.33 (95% CI 1.0915 to 10.1699) and 54.54 (95% CI 7.4849 to 397.5028), respectively in the ADHD group. CONCLUSIONS: This study showed that adult ADHD is independently associated with an increased risk of LBD, dementia, and na-MCI. Future studies should clarify this relationship to develop preventive measures for these patients.

Exposure to endogenous and exogenous sex hormones and reproductive history influence prognosis in women with ALS.

INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a higher incidence in men suggesting an influence of sex steroids. Our objective was to investigate past exposure to endogenous and synthetic steroids in female ALS patients and controls. METHODS: We administered a questionnaire to 158 postmenopausal women (75 ALS patients and 83 controls). We calculated reproductive time span (RTS), lifetime endogenous estrogen (LEE) and progesterone exposures (LPE), oral contraceptive pill (OCP) use, and reproductive history. RESULTS: ALS patients showed shorter LEE and LPE, a lower proportion of breast cancer, and 11% showed no history of pregnancies vs. 4% of controls. Odds ratios (ORs) showed that <17 y of LEE and a delayed menarche (>13 y) constitute risk factors for ALS [OR = 2.1 (95% confidence interval {CI}, 1.08-4.2); and OR = 2.4 (95% CI, 1.1-5.1) respectively]. According to Cox survival analysis, for each year the LEE increased over 17 y, it was independently associated with longer survival [hazard ratio (HR) = 0.37 (95% CI, 0.16-0.85)] after adjusting for smoking, age and site of onset. Multivariate regression analysis demonstrated that for each month using OCP for longer than 40 mo increased the risk of ALS [adjusted OR = 4.1 (95% CI, 1.2-13.8)]. DISCUSSION: Thus, longer exposure to endogenous female sex steroids increased survival and reduced ALS susceptibility. In contrast, longer exposure to synthetic sex steroids showed a negative impact by reducing the production of endogenous female sex steroids or due to crossover with other steroid receptors. Given the neuroprotective effects of sex steroids, we suggest that abnormalities of neuroendocrine components may alter motor function in women with ALS.

[Pre-pandemic melatonin treatment for sleep disorders and COVID-19 infection. A retrospective cross-sectional study]. / Tratamiento con melatonina pre-pandemia por trastornos del sueño e infección por COVID-19. Estudio de corte transversal, retrospectivo.

INTRODUCTION: Melatonin is a safe medication with multiple uses in sleep medicine for the treatment of circadian rhythm disorders, insomnia, and REM sleep behavior disorder. In view that melatonin has been recommended as an adjuvant treatment in COVID-19 pandemic mainly due to its anti-inflammatory properties, the objective of the present study was to evaluate the history of COVID-19 infection and the requirement of hospitalization in a group of adult patients previously treated with melatonin for various sleep disorders. MATERIAL AND METHODS: This is a retrospective cross-sectional study of data from a closed population of 110 adult patients at a University Hospital treated with melatonin for various sleep disorders, analyzed until the onset of COVID-19 pandemic. Demographic and melatonin-related variables (dose, treatment time) were analyzed and were reevaluated during the pandemic period, by scheduled tele-consultation regarding diagnosis, hospitalization requirements, variables related to COVID-19 infection prior to specific vaccination. Categorical variables were described as relative and absolute frequencies. RESULTS: N = 110 patients. Age range = 40- 96 years (mean = 71 years ± 9.9), older adults > 65 years: N =87 (79,1%). COVID-19 infection was recorded in 15 patients (13.5%) requiring hospitalization in 5 of those infected, only one of them with severe pneumonia. There were no deaths due to COVID-19. There were no differences between infected vs. uninfected in age (p = 0.74), body mass index (p = 0.65) or melatonin dose (p = 0.10).The melatonin dose range was 3-150 mg / day (mean = 46.33 ± 34.1), older adults receiving a mean dose of 50,3 ± 35,6.The 75.5% of the patients were treated for at least 12 months with melatonin. CONCLUSION: We found that 13.5% of patients previously treated with melatonin for various sleep disorders were infected by COVID-19, requiring hospitalization with subsequent medical discharge one third of them. According to national records the lethality rate in older adults in August 2020 was 10.5%. No patient treated with melatonin died for this cause in this sample. We did not find statistically significant differences in terms of indicated melatonin dose, age or body mass index, when comparing those infected with those not infected. The patients in general were mostly older adults, treated with a mean dose greater than 40 mg / day of melatonin for various sleep disorders, mainly for complaints of insomnia, for more than 12 months. The results are consistent with a possible preventive effect of melatonin in the COVID-19 pandemic.

[Argentine consensus on late-onset Pompe's disease]. / Consenso argentino sobre enfermedad de Pompe de inicio tardío.

Pompe's disease (PD) is an infrequent metabolic autosomic recessive disorder produced by the lack or deficiency of the acid alpha-glucosidase lysosomal enzyme in tissues of involved individuals. Delayed-onset PD is considered whenever symptoms onset start after one year of age. We present an update of the recommendations for the management of delayed-onset PD, taking as reference the guidelines from the Argentine Consensus for diagnosis, treatment and follow-up of PD published in 2013. The present consensus gathered several experts in PD in the areas of internal medicine, laboratory diagnosis, neuropathology, pulmonology, nutrition, neurology, metabolic and neuromuscular disorders as well as rehabilitation to perform an update of the literature of delayed-onset PD, with special attention on relevant information published within the last 4 years. The entire working group approved the final version of the consensus. Each participant provided a declaration of conflict of interest. As a result, it is an update of the previous Argentine PD Consensus with focus on the delayed-onset presentation of the disease. Being such infrequent disorder, available data were rather limited and thus, the recommendations represent expert opinions.

Incidence of Autoimmune Myasthenia Gravis in a Health Maintenance Organization in Buenos Aires, Argentina.

BACKGROUND: Different epidemiological studies, especially in Europe, have estimated the incidence density of myasthenia gravis (MG) to range between 1.7 and 21.3/1,000,000/person-year; however, data from regions such as Latin America are scarce. This study is aimed at estimating the incidence and prevalence of acquired MG in Buenos Aires, Argentina. METHODS: The study population comprised of affiliates of the Italian Hospital Medical Care Program, a prepaid health maintenance organization located in Buenos Aires. The evaluation method for case detection included a retrospective search from January 1, 2006, through December 31, 2012. RESULTS: Of the 60 cases identified, 36 (60%) were females. The median age at diagnosis was 69 years (IQR 51.5-79). The mean age at diagnosis was 63.3 years (SD ±20). A total of 28 patients (46.7%) had generalized MG and 32 had ocular MG (53.3%). Thirty five patients (58.3%) had acetylcholine receptor antibodies and 2 (3.3%) had muscle-specific receptor tyrosine kinase antibodies. The crude incidence density (ID) of MG was 61.33 per 1,000,000 person-years (95% CI 47.62-79.99). The adjusted ID for the Argentinean population was 38.8 per 1,000,000 person-years (95% CI 27.09-50.51) and for the Buenos Aires population was 47.49 (95% CI 34.73-60.25). CONCLUSIONS: The results obtained are similar to those published for other geographical areas.

[Presentations of transthyretin associated familial amyloid polyneuropathy in Argentina]. / Presentaciones de polineuropatía amiloidótica familiar asociada a transtiretina en la Argentina.

Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is a hereditary disease with variable geographical distribution. The aim of this study was to present our experience with TTR-FAP patients. We retrospectively analyzed nine cases belonging to different families. Diagnostic criteria were based on the combination of compatible clinical picture, histopathological findings and genetic confirmation. Five cases showed the classic presentation and other 4 the late onset variant. The p.Val30Met mutation in the TTR gene was found in 6 cases and p.Ala36Pro, p.Thr60Ala and p.Tyr114Cys in the remaining 3, respectively. The median age of symptom onset was 35 years (26-60 range). Mean time to diagnosis was 4.2 ± 1.5 years. Our patient series showed the heterogeneity in clinical presentation of TTR-FAP in a non-endemic region of South America.

Primary Central Nervous System Vasculitis Following Alemtuzumab Treatment for Multiple Sclerosis: A Case Report and Literature Review.

INTRODUCTION: Cerebral vasculitides are often devastating conditions that require immediate diagnosis and treatment. CASE REPORT: We report a pathologically proven clinical case of primary central nervous system vasculitis in a 50-year-old man with a diagnosis of relapsing-remitting multiple sclerosis after alemtuzumab therapy, which required additional immunosuppression to control this life-threatening condition. CONCLUSION: In patients presenting subacute neurological deterioration after alemtuzumab therapy, primary central nervous system vasculitis should be considered as a differential diagnosis among other autoimmune conditions.

Guillain-Barré Syndrome and COVID-19 Vaccine: A Multicenter Retrospective Study of 46 Cases.

ABSTRACT: In the context of the global vaccination campaign against COVID-19, several cases of postvaccinal Guillain-Barré syndrome (GBS) were reported. Whether a causal relationship exists between these events has yet to be established. We investigated the clinical and electromyographic characteristics of patients who developed GBS after COVID-19 vaccination and compare these with findings in patients with GBS, without a history of recent vaccination. We included 91 cases between March 2020 and March 2022, treated at 10 referral hospitals of Buenos Aires, Argentina. Of these, 46 had received vaccination against COVID-19 within the previous month. Although Medical Research Council sum-scores were similar in both groups (median 52 vs. 50; P = 0.4), cranial nerve involvement was significantly more frequent in the postvaccination group (59% vs. 38%; P = 0.02), as was bilateral facial paralysis (57% vs. 24%; P = 0.002). No differences were found in clinical or neurophysiological phenotypes, although 17 subjects presented the variant of bilateral facial palsy with paresthesias (11 vs. 6; P = 0.1); nor were significant differences observed in length of hospital stay or mortality rates. Future vaccine safety monitoring and epidemiology studies are essential to demonstrate any potential causal relationship between these events.

[Practice guideline for the treatment of familial amyloid polyneuropathy]. / Guía de práctica clínica de tratamiento de la polineuropatía amiloidótica familiar.

This clinical practice guideline for the treatment of familial amyloid polyneuropathy is based on the best available evidence of clinical effectiveness. A list of questions was generated with a PICO format focused on the effectiveness and safety of the treatment of familial amyloid polyneuropathy. The search was carried out in PubMed, Cochrane and Epistemonikos. The levels of evidence and grades of recommendation were based on the GRADE system. Recommendations were graded according to their direction and their strength and were evaluated with the GLIA tool for their implementation. In patients with familial amyloid polyneuropathy and stage I and II neuropathy, it is suggested: inotersen 300 mg subcutaneous weekly or patisirán 0.3 mg/kg intravenously once every 3 weeks, since they probably stabilize or slow the progression of neuropathy and worsening quality of life (moderate quality of evidence; strength of recommendation weak). In patients with familial amyloid polyneuropathy and stage I neuropathy, treatment with tafamidis 20 mg orally, once a day, is suggested, as it could slow the progression of neuropathy and worsen quality of life (low quality of evidence; strength of recommendation weak). In patients with familial amyloid polyneuropathy and symptomatic neuropathy and in the absence of other treatments with approved efficacy, treatment with oral diflunisal 250 mg twice daily is suggested, as it could prevent the progression of neuropathy (quality evidence low; strength of recommendation weak).

Esta guía de práctica clínica de tratamiento de la polineuropatía amiloidótica familiar se basa en la mejor evidencia disponible de efectividad clínica. Se generó un listado de preguntas con formato PICO centradas en efectividad y seguridad del tratamiento de polineuropatía amiloidótica familiar. Se realizó la búsqueda en PubMed, Cochrane y Epistemonikos. Los niveles de evidencia y los grados de recomendación se basaron en el sistema GRADE. Las recomendaciones se graduaron según dirección y fuerza y se evaluaron con la herramienta GLIA para su implementación. Resumen de recomendaciones: En pacientes con polineuropatía amiloidótica familiar y neuropatía estadio I y II, se sugiere el tratamiento con inotersen 300 mg subcutáneo semanal o patisirán 0.3 mg/kg endovenoso una vez cada 3 semanas, dado que, probablemente, estabilicen o enlentezcan el avance de la neuropatía y el empeoramiento de la calidad de vida (calidad de la evidencia moderada; fuerza de la recomendación débil). En pacientes con polineruropatía amiloidótica familiar y neuropatía estadio I, se sugiere el tratamiento con tafamidis 20 mg vía oral, una vez por día, ya que podría enlentecer el avance de la neuropatía y el empeoramiento en la calidad de vida (calidad de la evidencia baja; fuerza de la recomendación débil), y aquellos con polineuropatía amiloidótica familiar y neuropatía sintomática y en ausencia de otros tratamientos con eficacia aprobada, se sugiere el tratamiento con diflunisal 250 mg dos veces al día, vía oral, ya que podría evitar la progresión de la neuropatía (calidad de la evidencia baja; fuerza de la recomendación débil).

[Clinical Practice Guidelines for diagnosis of organic involvement of amyloidosis: Part 3/3 Year 2020] / Guía de Práctica Clínica para el diagnóstico de compromiso orgánico en amiloidosis: Parte 3/3 Año 2020.

Method: Use the PICO format to generate a series of questions, focusing on the specificity and sensitivity of the amyloidosis diagnostic test. PubMed searches were conducted in English and Spanish from July to August 2019. The level of evidence and recommendation are based on the GRADE system (http://www.gradeworkinggroup.org/index.htm). The recommendations are graded according to their direction (for or against) and strength (strong and weak). Finally, it is recommended to use GLIA tools to evaluate the obstacles and facilitators in implementation. Suggested explanation A strong suggestion indicates a high degree of trust in support or opposition to the intervention. When defining a strong recommendation, this guide uses the "recommended" language. The weaker recommendations indicate that the outcome of the intervention (favorable or unfavorable) is doubtful. In this case, if a weak recommendation is defined, the "recommendation" language is used. How to use these guidelines: Recommendations must be explained within the scope of special care in validated diagnostic studies conducted by specially trained doctors. It is not assumed to change the coexistence conditions of the disease process. Presumably, the attending physician has a high degree of suspicion of amyloidosis. It assumes that diagnostic research is conducted by well-trained doctors using a validated standardized method. This guide is intended for health care professionals and those involved in health care policies to help ensure that the necessary agreements have been reached to provide appropriate care. Summary of recommendations For patients with suspected amyloidosis, it is recommended: Measured value of creatinine be used as a preliminary assessment for the diagnosis of renal involvement in patients with suspected renal amyloidosis. 24-hour proteinuria be measured and characterized to diagnose renal involvement in patients with suspected renal amyloidosis. Immunohistochemical staining of skin biopsy for patients genetically diagnosed with ATTR, for early diagnosis of neuropathy. The signs or symptoms of these patients suggest the presence of fine fiber neuropathy. Skin biopsy and immunohistochemical staining for early diagnosis of neuropathy. These patients show signs or symptoms suggesting fine fiber neuropathy. Conduct nerve conduction studies on motor and sensory fibers to diagnose total fiber neuropathy in patients who are diagnosed or suspected of having amyloidosis. Test (Sudoscan) is recommended for the early diagnosis of peripheral autonomic neuropathy (even in asymptomatic patients) in patients with suspected autonomic neuropathy due to amyloidosis. Ewing's standard to measure heart rate variability to diagnose autonomic hypofunction in patients with autonomic neuropathy suspected of having amyloidosis. Measure orthostatic hypotension to diagnose early autonomic hypotension for patients with amyloidosis or systemic amyloidosis suspected of autonomic neuropathy. It is suggested: QST test to diagnose neuropathy early for patients genetically diagnosed with ATTR, if they show signs or symptoms suggesting fine fiber neuropathy Measure alkaline phosphatase to initially assess liver involvement in patients with amyloidosis.

Métodos: Se generó un listado de preguntas con el formato PICO centradas en la especificidad y sensibilidad de las pruebas diagnósticas en amiloidosis. Se realizó la búsqueda en PubMed durante julio-agosto del 2019, en inglés y español. Los niveles de evidencia y los grados de recomendación se basan en el sistema GRADE (http://www.gradeworkinggroup.org/index.htm). Las recomendaciones se graduaron según su dirección (a favor o en contra) y según fuerza (fuertes y débiles). Las recomendaciones finales fueron evaluadas con la herramienta GLIA para barreras y facilitadores en la implementación de éstas. Interpretación de recomendaciones: Las recomendaciones fuertes indican alta confianza, ya sea a favor o en contra, de una intervención. En esta guía se utiliza el lenguaje "se recomienda" cuando se define una recomendación fuerte. Las recomendaciones débiles indican que los resultados para una intervención, favorable o desfavorable, son dudosos. En este caso, se utiliza el lenguaje "se sugiere", cuando se define una recomendación débil.Cómo utilizar estas pautas: Las recomendaciones deben ser interpretadas en el contexto de la atención especializada, con estudios diagnósticos validados y realizados por médicos entrenados. Se asume que el médico tratante tiene alto nivel de sospecha de amiloidosis. No asume condiciones coexistentes que modifican el curso de la enfermedad. Asume que los estudios diagnósticos son realizados por médicos entrenados con métodos validados y estandarizados. Esta guía es relevante para los profesionales de la salud y los involucrados en las políticas sanitarias, para ayudar a asegurar que existan los acuerdos necesarios para brindar la atención adecuada. Resumen de recomendaciones En pacientes con sospecha de amiloidosis se recomienda: Medición de la creatinina como evaluación inicial para el diagnóstico del compromiso renal en el paciente con sospecha de amiloidosis renal. Medición y caracterización de la proteinuria de 24 hs para el diagnóstico de compromiso renal en pacientes con sospecha de amiloidosis renal. Biopsia de piel con tinción inmunohistoquímica para el diagnóstico precoz de neuropatía en pacientes con diagnóstico genético de ATTR, que presenten signos o síntomas sugestivos de neuropatía de fibra fina. Biopsia de piel con tinción inmunohistoquímica para el diagnóstico precoz de neuropatía en pacientes con sospecha de amiloidosis, que presenten signos o síntomas sugestivos de neuropatía de fibra fina. Estudios de conducción nerviosa evaluando fibras motoras y sensitivas para el diagnóstico de neuropatía de fibras gruesas en pacientes con diagnóstico o sospecha de amiloidosis. Prueba de QST para el diagnóstico precoz de neuropatía en pacientes con diagnóstico genético de ATTR, que presenten signos o síntomas sugestivos de neuropatía de fibras finas. Test de cuantificación sudorípara (Sudoscan) para diagnóstico precoz de neuropatía autonómica periférica (incluso en asintomáticos) en pacientes con sospecha de neuropatía autonómica por amiloidosis. Medición de la variabilidad de la frecuencia cardiaca con criterios de Ewing para el diagnóstico de disautonomía en pacientes con sospecha de neuropatía autonómica por amiloidosis. Medición de hipotensión ortostática con técnica adecuadamente estandarizada para el diagnóstico precoz de compromiso autonómico en el paciente con sospecha de neuropatía autonómica por amiloidosis o diagnóstico de amiloidosis sistémica Se sugiere: Prueba de QST para el diagnóstico precoz de neuropatía en pacientes con amiloidosis o sospecha de amiloidosis, que presenten signos o síntomas sugestivos de neuropatía de fibras finas. Medición de fosfatasa alcalina para evaluación inicial del compromiso hepático en el paciente con amiloidosis.

Clinical Practice Guidelines for diagnosis of amyloidosis: Part 1/3 Year 2020 / [Guía de Práctica Clínica para el diagnóstico de la amiloidosis: Parte 1/3. Año 2020]

Method: Use the PICO format to generate a series of questions, focusing on the specificity and sensitivity of the amyloidosis diagnostic test. PubMed searches were conducted in English and Spanish from July to August 2019. The level of evidence and recommendation are based on the GRADE system (http://www.gradeworkinggroup.org/index.htm). The recommendations are graded according to their direction (for or against) and strength (strong and weak). Finally, it is recommended to use GLIA tools to evaluate the obstacles and facilitators in implementation. Suggested explanation: A strong suggestion indicates a high degree of trust in support or opposition to the intervention. When defining a strong recommendation, this guide uses the "recommended" language. The weaker recommendations indicate that the outcome of the intervention (favorable or unfavorable) is doubtful. In this case, if a weak recommendation is defined, the "recommendation" language is used. How to use these guidelines: Recommendations must be explained within the scope of special care in validated diagnostic studies conducted by specially trained doctors. It is not assumed to change the coexistence conditions of the disease process. Presumably, the attending physician has a high degree of suspicion of amyloidosis. It assumes that diagnostic research is conducted by well-trained doctors using a validated standardized method. This guide is intended for health care professionals and those involved in health care policies to help ensure that the necessary agreements have been reached to provide appropriate care. Recommendations: For patients with suspected amyloidosis, it is recommended; Confirmation in the tissue by biopsy and Congo red staining with the characteristic green birefringence under polarized light is recommended.Confirmation by electron microscopy of the biopsy tissue is recommended. Protein typing by mass spectrometry is recommended. Protein typing by optical and / or electronic immunomicroscopy is recommended, as long as there are reliable antibodies. Measurement of serum free light chains is recommended for evaluation of a monoclonal plasma cell proliferative disorder. Serum and urinary immunofixation is recommended for evaluation of a monoclonal plasma cell proliferative disorder. Measurement of serum free light chains, plus serum and urinary immunofixation is recommended for the evaluation of a monoclonal plasma cell proliferative disorder. For patients suspected of having amyloidosis, it is suggested; Demonstration of a monoclonal plasma cell proliferative disorder by demonstration of clonal plasma cells by the most sensitive technique available in the bone marrow for the diagnosis of AL-type amyloidosis. Confirmation of ATTRv amyloidosis by DNA sequencing of the 4-exon amyloidogenic TTR gene in patients with suspected ATTRv amyloidosis.

Métodos: Se generó un listado de preguntas con el formato PICO centradas en la especificidad y sensibilidad de las pruebas diagnósticas en amiloidosis. Se realizó la búsqueda en PubMed durante julio-agosto del 2019, en inglés y español. Los niveles de evidencia y los grados de recomendación se basan en el sistema GRADE (http://www.gradeworkinggroup.org/index.htm). Las recomendaciones se graduaron según su dirección (a favor o en contra) y según fuerza (fuertes y débiles). Las recomendaciones finales fueron evaluadas con la herramienta GLIA para barreras y facilitadores en la implementación de éstas. Interpretación de recomendaciones: Las recomendaciones fuertes indican alta confianza, ya sea a favor o en contra, de una intervención. En esta guía se utiliza el lenguaje "se recomienda" cuando se define una recomendación fuerte. Las recomendaciones débiles indican que los resultados para una intervención, favorable o desfavorable, son dudosos. En este caso, se utiliza el lenguaje "se sugiere", cuando se define una recomendación débil. Como utilizar estas pautas: Las recomendaciones deben ser interpretadas en el contexto de la atención especializada, con estudios diagnósticos validados y realizados por médicos entrenados. No asume condiciones coexistentes que modificaran el curso de la enfermedad. Se asume que el médico tratante tiene alto nivel de sospecha de amiloidosis. Asume que los estudios diagnósticos son realizados por médicos entrenados con métodos validados y estandarizados. Esta guía es relevante para los profesionales de la salud y los involucrados en las políticas sanitarias, para ayudar a asegurar que existan los acuerdos necesarios para brindar la atención adecuada. Recomendaciones En pacientes con sospecha de amiloidosis se recomienda: La confirmación en el tejido mediante biopsia y tinción con rojo Congo con la característica birrefringencia verde bajo luz polarizada. La confirmación mediante microscopía electrónica en el tejido de biopsia. La tipificación de la proteína mediante espectrometría de masa. La tipificación de la proteína mediante inmunomicroscopía óptica y/o electrónica, en la medida que haya anticuerpos confiables. La medición de las cadenas livianas libres séricas para evaluación de un trastorno proliferativo de células plasmáticas monoclonales. La Inmunofijación sérica y urinaria para la evaluación de un trastorno proliferativo de células plasmáticas monoclonales. La medición de las cadenas livianas libres sérica, más la Inmunofijación sérica y urinaria para la evaluación de un trastorno proliferativo de células plasmáticas monoclonales. En pacientes con sospecha de amiloidosis se sugiere: Demostración de un trastorno proliferativo de células plasmáticas monoclonales mediante la demostración de plasmocitos clonales por la técnica más sensible disponible en la médula ósea para el diagnóstico de amiloidosis de tipo AL. La confirmación de amiloidosis ATTRv mediante secuenciación de ADN del gen TTR amiloidogénico de los 4 exones en pacientes con sospecha de amiloidosis por ATTRv.

Usefulness of diffusion tensor imaging in amyotrophic lateral sclerosis: potential biomarker and association with the cognitive profile.

METHODS: This was a case-control study conducted from December 1, 2012 to December 1, 2014. Clinical and demographic data were recorded. A neuropsychological test battery adapted to ALS patients was used. An MRI with DTI was performed in all patients and fractional anisotropy (FA) was analyzed in the white matter using the tract based spatial statistics program. RESULTS: Twenty-four patients with ALS (15 females, mean age 66.9 + -2.3) and 13 healthy controls (four females, average age 66.9 + - 2) were included. The DTI showed white matter damage in ALS patients vs. healthy controls (p < 0.001). DISCUSSION: In our preliminary study the alterations of white matter in DTI were significantly associated with cognitive impairment in patients with ALS.

Guía de práctica clínica de tratamiento de la polineuropatía amiloidótica familiar / Practice guideline for the treatment of familial amyloid polyneuropathy

Resumen Esta guía de práctica clínica de tratamiento de la polineuropatía amiloidótica familiar se basa en la mejor evidencia disponible de efectividad clínica. Se generó un listado de preguntas con formato PICO centradas en efectividad y seguridad del tratamiento de polineuropatía amiloidótica familiar. Se realizó la búsqueda en PubMed, Cochrane y Epistemonikos. Los niveles de evidencia y los grados de recomendación se basaron en el sistema GRADE. Las recomendaciones se graduaron según dirección y fuerza y se evaluaron con la herramienta GLIA para su implementación. Resumen de recomendaciones: En pacientes con polineuropatía amiloidótica familiar y neuropatía estadio I y II, se sugiere el tratamiento con inotersen 300 mg subcutáneo semanal o patisirán 0.3 mg/kg endovenoso una vez cada 3 semanas, dado que, probablemente, estabilicen o enlentezcan el avance de la neuropatía y el empeoramiento de la calidad de vida (calidad de la evidencia moderada; fuerza de la recomendación débil). En pacientes con polineruropatía amiloidótica familiar y neuropatía estadio I, se sugiere el tratamiento con tafamidis 20 mg vía oral, una vez por día, ya que podría enlentecer el avance de la neuropatía y el empeoramiento en la calidad de vida (calidad de la evidencia baja; fuerza de la recomendación débil), y aquellos con polineuropatía amiloidótica familiar y neuropatía sintomática y en ausencia de otros tratamientos con eficacia aprobada, se sugiere el tratamiento con diflunisal 250 mg dos veces al día, vía oral, ya que podría evitar la progresión de la neuropatía (calidad de la evidencia baja; fuerza de la recomendación débil).

Abstract. This clinical practice guideline for the treatment of familial amyloid polyneuropathy is based on the best available evi dence of clinical effectiveness. A list of questions was generated with a PICO format focused on the effectiveness and safety of the treatment of familial amyloid polyneuropathy. The search was carried out in PubMed, Cochrane and Epistemonikos. The levels of evidence and grades of recommendation were based on the GRADE system. Recommendations were graded according to their direction and their strength and were evaluated with the GLIA tool for their implementation. In patients with familial amyloid polyneuropathy and stage I and II neuropathy, it is suggested: inotersen 300 mg subcutaneous weekly or patisirán 0.3 mg/kg intravenously once every 3 weeks, since they probably stabilize or slow the progression of neuropathy and worsening quality of life (moderate qual ity of evidence; strength of recommendation weak). In patients with familial amyloid polyneuropathy and stage I neuropathy, treatment with tafamidis 20 mg orally, once a day, is suggested, as it could slow the progression of neuropathy and worsen quality of life (low quality of evidence; strength of recommendation weak). In patients with familial amyloid polyneuropathy and symptomatic neuropathy and in the absence of other treatments with approved efficacy, treatment with oral diflunisal 250 mg twice daily is suggested, as it could prevent the progres sion of neuropathy (quality evidence low; strength of recommendation weak).

Immune-mediated rippling muscle disease and myasthenia gravis.

Cases of acquired rippling muscle disease in association with myasthenia gravis have been reported. We present three patients with iRMD (immune-mediated rippling muscle disease) and AChR-antibody positive myasthenia gravis. None of them had thymus pathology. They presented exercise-induced muscle rippling combined with generalized myasthenia gravis. One of them had muscle biopsy showing a myopathic pattern and a patchy immunostaining with caveolin antibodies. They were successfully treated steroids and azathioprine. The immune nature of this association is supported by the response to immunotherapies and the positivity of AChR-antibodies.

Incidence and prevalence of amyotrophic lateral sclerosis in an HMO of Buenos Aires, Argentina.

The incidence of amyotrophic lateral sclerosis (ALS) ranges from 1.7 to 2.3 per 100,000 persons worldwide. Few epidemiological studies have been published in Latin America. The aim of this study was to estimate the incidence and prevalence of ALS in an HMO (Health Maintenance Organization) of Buenos Aires, capital city of Argentina. The population studied was affiliates of the Italian Hospital Medical Care Program, whose distribution across age and gender strata is similar to the population of Buenos Aires. Cases were detected from 1 January 2003 to 31 December 2010. Incidence density (ID) and prevalence for ALS were estimated for the whole period and at 31 December 2010, respectively. During the seven-year study period, the crude ID estimated was 3.17 per 100,000 person-years (95% CI 2.24-4.48) and the age-adjusted ID for the Buenos Aires population was 2.23 per 100,000 person-years (95% CI 1.45-3.01). Point prevalence at 31 December 2010 was 8.86 per 100,000 persons (95% CI 4.05-13.68). Mean age at diagnosis was 72.29 years (SD 8.5). In conclusion, estimated age-adjusted ID and prevalence of ALS were similar to the incidence and prevalence rates found in other geographical areas.

Consenso argentino sobre enfermedad de Pompe de inicio tardío / Argentine consensus on late-onset Pompe's disease

La enfermedad de Pompe (EP) es un desorden metabólico autosómico recesivo infrecuente, producido por la ausencia o deficiencia de la enzima lisosomal alfa-glucosidasa ácida en los tejidos de los individuos afectados. Se considera enfermedad de Pompe de inicio tardío (EPIT) en aquellos individuos de más de un año de edad al comienzo de los síntomas. El objetivo del presente consenso es el de actualizar las pautas y recomendaciones para un correcto tratamiento de los pacientes con EPIT, tomando como referencia los lineamientos del Consenso Argentino para el diagnóstico, seguimiento y tratamiento de la enfermedad de Pompe publicado en el año 2013. Se organizó un consenso que reunió profesionales con experiencia en la EP en las áreas de clínica médica, diagnóstico de laboratorio, neuropatología, neumonología, nutrición, neurología, enfermedades metabólicas, enfermedades neuromusculares y rehabilitación. Se realizó una actualización de la bibliografía sobre EPIT, con especial atención en las publicaciones relevantes de los últimos cuatro años. Los términos finales del documento fueron consensuados por todo el grupo de trabajo. Cada participante proporcionó su declaración de conflicto de intereses. El resultado es una actualización del último Consenso Argentino para la EP, con particular enfoque en su forma de comienzo tardío. Tratándose de una afección infrecuente, en la que los datos disponibles son limitados, las presentes recomendaciones deben ser consideradas como opinión de expertos.

Pompe's disease (PD) is an infrequent metabolic autosomic recessive disorder produced by the lack or deficiency of the acid alpha-glucosidase lysosomal enzyme in tissues of involved individuals. Delayed-onset PD is considered whenever symptoms onset start after one year of age. We present an update of the recommendations for the management of delayed-onset PD, taking as reference the guidelines from the Argentine Consensus for diagnosis, treatment and follow-up of PD published in 2013. The present consensus gathered several experts in PD in the areas of internal medicine, laboratory diagnosis, neuropathology, pulmonology, nutrition, neurology, metabolic and neuromuscular disorders as well as rehabilitation to perform an update of the literature of delayed-onset PD, with special attention on relevant information published within the last 4 years. The entire working group approved the final version of the consensus. Each participant provided a declaration of conflict of interest. As a result, it is an update of the previous Argentine PD Consensus with focus on the delayed-onset presentation of the disease. Being such infrequent disorder, available data were rather limited and thus, the recommendations represent expert opinions.

Usefulness of diffusion tensor imaging in amyotrophic lateral sclerosis: potential biomarker and association with the cognitive profile / Utilidad del tensor de difusión en esclerosis lateral amiotrofica: potencial biomarcador y asociación con el perfil cognitivo

ABSTRACT The objective of this preliminary study was to correlate diffusion tensor imaging (DTI) alterations with the cognitive profile of patients with amyotrophic lateral sclerosis (ALS). Methods This was a case-control study conducted from December 1, 2012 to December 1, 2014. Clinical and demographic data were recorded. A neuropsychological test battery adapted to ALS patients was used. An MRI with DTI was performed in all patients and fractional anisotropy (FA) was analyzed in the white matter using the tract based spatial statistics program. Results Twenty-four patients with ALS (15 females, mean age 66.9 + -2.3) and 13 healthy controls (four females, average age 66.9 + - 2) were included. The DTI showed white matter damage in ALS patients vs. healthy controls (p < 0.001). Discussion In our preliminary study the alterations of white matter in DTI were significantly associated with cognitive impairment in patients with ALS.

RESUMEN El objetivo del presente estudio preliminar fue correlacionar alteraciones del Tensor de Difusión (TD) con el perfil cognitivo de pacientes con Esclerosis Lateral Amiotrofica (ELA). Metodos Se realizó estudio casos-controles entre el 1 de Diciembre del 2012 hasta el 1 de Diciembre del 2014. Se registraron datos clínicos y demográficos. Se utilizó batería de tests neuropsicológicos adaptada a ELA. Se realizó RMN de cerebro con TD en todos los pacientes, la Fracción de Anisotropía (FA) se analizó en sustancia blanca, utilizando el programa Tract Based Spatial Statistics. Resultados Se incluyeron 24 pacientes con ELA (15 mujeres, edad media 66.9 + -2.3) y 13 controles sanos (4 mujeres, edad media 66.9 +-2). El TD mostró daño en sustancia blanca en los pacientes con ELA vs controles (p < 0.001). Discusión En nuestro estudio preliminar las alteraciones de sustancia blanca en TD se asociaron significativamente con alteraciones cognitivas en pacientes con ELA.