Challenges managing myasthenia gravis: an international perspective

There have been increasing breakthroughs in the diagnosis and treatment of myasthenia gravis over the past decades. However, most published research in myasthenia is conducted in developed regions, such as the US, Canada and Europe. The challenges faced in these regions may be different from other areas of the world, often with fewer resources, such as fewer neurologists, limited or no access to specialised testing for myasthenia, and limited access to some interventions. During the 14th International Conference for Myasthenia Gravis and Myasthenic Disorders, we organized a panel of neurologists and researchers who work with people living with myasthenia in different world regions. The goal was to stimulate discussion around common challenges as well as those that are specific for given areas. Ultimately, we aimed to develop networks of clinicians caring for people living with myasthenia gravis around the world, to improve patient care. We present a summary of challenges using a case format by region, and a discussion around common threads and potential next steps

Adverse Outcome of Early Recurrent Ischemic Stroke Secondary to Atrial Fibrillation after Repeated Systemic Thrombolysis

Background. Recurrent ischemic stroke is associated with adverse neurological outcome in patients with atrial fibrillation. There is very scarce information regarding the neurological outcome of atrial fibrillation patients undergoing repeated systemic thrombolysis after early recurrent ischemic stroke. Clinical Case and Discussion. We describe a case of a 76-year-old woman with known paroxysmal atrial fibrillation who was admitted because of an acute right middle cerebral artery ischemic stroke and who underwent repeated systemic thrombolysis within 110 hours. The patient underwent systemic thrombolysis after the first ischemic stroke with almost complete neurological recovery. On the fourth day after treatment, an acute left middle cerebral artery ischemic stroke was diagnosed and she was treated with full-dose intravenous recombinant tissue plasminogen activator. A hemorrhagic transformation of the left middle cerebral artery infarction was noted on follow-up cranial computed tomographic scans. The patient did not recover from the second cerebrovascular event and died 25 days after admission. Conclusion. To the best of our knowledge, this is the second case reporting the adverse neurological outcome of a patient with diagnosis of atrial fibrillation undergoing repeated systemic thrombolysis after early recurrent ischemic stroke. Our report represents a contribution to the scarce available evidence suggesting that repeated systemic thrombolysis for recurrent ischemic stroke should be avoided

Case Report Adverse Outcome of Early Recurrent Ischemic Stroke Secondary to Atrial Fibrillation after Repeated Systemic Thrombolysis

Background. Recurrent ischemic stroke is associated with adverse neurological outcome in patients with atrial fibrillation. There is very scarce information regarding the neurological outcome of atrial fibrillation patients undergoing repeated systemic thrombolysis after early recurrent ischemic stroke. Clinical Case and Discussion. We describe a case of a 76-year-old woman with known paroxysmal atrial fibrillation who was admitted because of an acute right middle cerebral artery ischemic stroke and who underwent repeated systemic thrombolysis within 110 hours. The patient underwent systemic thrombolysis after the first ischemic stroke with almost complete neurological recovery. On the fourth day after treatment, an acute left middle cerebral artery ischemic stroke was diagnosed and she was treated with full-dose intravenous recombinant tissue plasminogen activator. A hemorrhagic transformation of the left middle cerebral artery infarction was noted on follow-up cranial computed tomographic scans. The patient did not recover from the second cerebrovascular event and died 25 days after admission. Conclusion. To the best of our knowledge, this is the second case reporting the adverse neurological outcome of a patient with diagnosis of atrial fibrillation undergoing repeated systemic thrombolysis after early recurrent ischemic stroke. Our report represents a contribution to the scarce available evidence suggesting that repeated systemic thrombolysis for recurrent ischemic stroke should be avoided

Multicentric epidemiological study in amyotrophic lateral sclerosis in the Autonomous City of Buenos Aires

Introduction: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease of unknown cause, characterized by the simultaneous involvement of the upper and lower motor neurons. Epidemiological studies have estimated its annual incidence between 0.31 and 3.2 and its prevalence between 0.8 and 8.5 cases per 100,000 inhabitants. The epidemiological information in our country is limited to specialized centers. The present study presents the results of an epidemiological study in ELA performed in the Autonomous City of Buenos Aires (CABA). Methods: A multicentric retrospective study was conducted. Patients with defined and probable ALS according to the El Escorial Criteria, evaluated between January 1, 2012 and December 31, 2013, who lived in the CABA at the onset of symptoms, were included. The calculation of the incidence was based on the 2010 census. Results: We included 103 patients (55 men), with a mean age of 64 years. The onset of symptoms was in the lower limbs at 39%, upper extremities at 25% and bulbar at 26%. The initial symptom was weakness in 58% and dysarthria in 20%; 9% had dementia associated with ALS. The mean time to diagnosis was 14.5 months. Thirty new cases/patients were diagnosed between 01/06/2012 and 01/06/2013, with an incidence rate of 1.04 per 100,000 inhabitants. Conclusions: The epidemiological characteristics of ALS in CABA are similar to those reported in the universal literature. Further studies are needed to determine if these findings are applicable to the rest of the Argentine population.Introduction: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease of unknown cause, characterized by the simultaneous involvement of the upper and lower motor neurons. Epidemiological studies have estimated its annual incidence between 0.31 and 3.2 and its prevalence between 0.8 and 8.5 cases per 100,000 inhabitants. The epidemiological information in our country is limited to specialized centers. The present study presents the results of an epidemiological study in ELA performed in the Autonomous City of Buenos Aires (CABA). Methods: A multicentric retrospective study was conducted. Patients with defined and probable ALS according to the El Escorial Criteria, evaluated between January 1, 2012 and December 31, 2013, who lived in the CABA at the onset of symptoms, were included. The calculation of the incidence was based on the 2010 census. Results: We included 103 patients (55 men), with a mean age of 64 years. The onset of symptoms was in the lower limbs at 39%, upper extremities at 25% and bulbar at 26%. The initial symptom was weakness in 58% and dysarthria in 20%; 9% had dementia associated with ALS. The mean time to diagnosis was 14.5 months. Thirty new cases/patients were diagnosed between 01/06/2012 and 01/06/2013, with an incidence rate of 1.04 per 100,000 inhabitants. Conclusions: The epidemiological characteristics of ALS in CABA are similar to those reported in the universal literature. Further studies are needed to determine if these findings are applicable to the rest of the Argentine population.Fil: Pérez Akly, Manuel. Sociedad Neurológica; ArgentinaFil: Schiava, Marianela. Unidad Asistencial Doctor César Milstein; ArgentinaFil: Melcom, Mario. Fundación para la Investigación en Neuroepidemiología; ArgentinaFil: Rodríguez, Gabriel. Sociedad Neurológica; ArgentinaFil: Gargiulo Monachelli, Gisella Mariana. Sociedad Neurológica; ArgentinaFil: Bettini, Mariela. Sociedad Neurológica; ArgentinaFil: Reisin, Ricardo. Sociedad Neurológica; ArgentinaFil: Bendersky, Mariana. Sociedad Neurológica; ArgentinaFil: Barroso, Fabio. Sociedad Neurológica; ArgentinaFil: Brand, Patricio. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; ArgentinaFil: de Ambrosi, Bruno. Sociedad Neurológica; ArgentinaFil: Di Egidio, Marianna. Sociedad Neurológica; ArgentinaFil: Fiorotto, Luis. Sociedad Neurológica; ArgentinaFil: Jáuregui, Agustín. Sociedad Neurológica; ArgentinaFil: Landriscina, Paula. Sociedad Neurológica; ArgentinaFil: Marchesoni, Cintia. Sociedad Neurológica; ArgentinaFil: Mazia, Claudio. Sociedad Neurológica; ArgentinaFil: Rey, Roberto. Sociedad Neurológica; ArgentinaFil: Rugiero, Marcelo. Sociedad Neurológica; ArgentinaFil: Salutto, Valeria Luján. Sociedad Neurológica; ArgentinaFil: Tillard, Belén. Sociedad Neurológica; ArgentinaFil: Fulgenzi, Ernesto. Sociedad Neurológica; Argentin

Usefulness of the identification of antibodies in peripheral neuropathies, neuronopathies and ganglionopathies: review

Introducción: En los últimos anos ˜ la identificación de anticuerpos y gammapatías monoclonales ha permitido comprender la fisiopatología y favorecer el diagnóstico y tratamiento de una multiplicidad de neuropatías inmunomediadas. Objetivo: Describir los anticuerpos de mayor relevancia clínica en las neuropatías, ganglionopatías y neuronopatías inmunomediadas caracterizando en cada caso su valor fisiopatológico o diagnóstico, así como la sensibilidad y especificidad de los métodos utilizados para su determinación. Desarrollo: Se analizarán los anticuerpos identificados en 1) síndrome de Guillain-Barré; 2) polineuropatía inflamatoria desmielinizante crónica (PDIC), 3) neuropatía motora con bloqueo multifocal (NMM); 4) CANOMAD (neuropatía atáxica crónica, oftalmoplejía, proteína IgM monoclonal, aglutininas frías y anticuerpos disialosil); 5) ganglionopatías y neuronopatías y la utilidad de identificar las gammapatías monoclonales. Conclusiones: Los anticuerpos y las gammapatías monoclonales son herramientas que han permitido mejorar el diagnóstico y la comprensión fisiopatológica de las neuropatías inmunomediadas y algunas criptogénicas, así como orientar el tratamiento más adecuado.Introduction: Over the last several years the identification of both antineural antibodies and monoclonal gammopathies allowed a better understanding of pathophysiology and improvement in the diagnosis and treatment of many different immune mediated neuropathies. Objective: To describe the antineural antibodies of greater clinical utility in the diagnosis of immune mediated neuropathies and neuronopathies. In each case we underline their value in either the pathophysiology or diagnosis of these disorders as well as the sensitivity and specificity of the diagnostic techniques currently in use. Development: We will review the antibodies identified in 1) Guillain-Barré syndrome; 2) Chronic inflammatory demyelinating polyneuropathy (CIDP); 3) Multifocal motor neuropathy (MMN); 4) Chronic Ataxic Neuropathy Ophthalmoplegia M-protein Agglutination Disialosyl antibodies syndrome (CANOMAD); 5) Ganglionopathies and Neuropathies and the value of identifying monoclonal gammopathies. Conclusions: The antibodies and monoclonal gammopathies are useful tools in both the diagnosis and understanding of the mechanisms involved in immune mediated and cryptogenic neuropathies and orienting treatment.Fil: Reisin, Ricardo C.. Hospital Británico de Buenos Aires; ArgentinaFil: Salutto, Valeria Luján. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Aguirre, Florencia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos; ArgentinaFil: Alvarez, Valeria. Hospital Italiano. Departamento de Medicina. Servicio de Neurologia.; ArgentinaFil: Barroso, Fabio. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Bendersky, Mariana. Hospital Italiano. Departamento de Medicina. Servicio de Neurologia.; ArgentinaFil: Berardo, Andrés. Columbia University; Estados UnidosFil: Bettini, Mariela. Hospital Italiano; ArgentinaFil: Borrelli, Mariano M.. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Chaves, Marcelo. Hospital San Martín de Paraná; ArgentinaFil: Cisneros, Elisa M.. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Conti, Eugenia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Crespo, José M.. Hospital Británico de Buenos Aires; ArgentinaFil: di Egidio, Mariana. Hospital Enrique Tornú; ArgentinaFil: Figueredo, María Alejandra. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal de Agudos San Roque de Gonnet; ArgentinaFil: Gargiulo Monachelli, Gisella Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Jáuregui, Agustín. Universidad Favaloro; ArgentinaFil: Landriscina, Paula. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: León Cejas, Luciana. Hospital Británico de Buenos Aires; ArgentinaFil: Martínez Perea, María del Carmen. Hospital Rivadavia; ArgentinaFil: Pirra, Laura. Universidad Favaloro; ArgentinaFil: Pivetta, Paola. Complejo Medico Policial Bartolome Churruca Andres Visca; ArgentinaFil: Quarracino, Cecilia. Complejo Medico Policial Bartolome Churruca Andres Visca; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rattagan, María Lucía. Hospital Italiano; ArgentinaFil: Rey, Roberto. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal General de Agudos Presidente Peron; ArgentinaFil: Rodriguez, Alejandro. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: Rodriguez, Gabriel E.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Rugiero, Marcelo. Hospital Italiano; ArgentinaFil: Tillard, Belen. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Zuberhbuler, Paz. Hospital Alvarez; Argentin

Argentine consensus on late-onset Pompe's disease

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 opinion

Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS) : 14-year update

Background: Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods: Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results: This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions: This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier: NCT00628745