Repositorio Institucional Fleni
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Combination therapy of apo-transferrin and thyroid hormones enhances remyelination
No full textThe current study presents two different approaches with a view to elucidating the interaction between thyroid hormones (TH) and apo-transferrin (aTf) and their role in myelination and remyelination. First, in vitro assays were conducted to determine the single and combined effects of aTf and triiodothyronine (T3) on oligodendroglial cell lineage proliferation and oligodendrocyte (OLG) maturation in primary cultures. Results revealed higher proliferation rates upon single aTf treatment but Control values upon T3 and aTf + T3 treatments. In addition, both aTf and T3 accelerated OLG maturation, with the greatest effects being exerted by combined aTf + T3 administration in terms of both myelin basic protein (MBP) expression and morphological complexity. Second, in vivo assays were carried out to establish single and combined effects of aTf and T3, as well as TH receptor (THR) inhibitor I-850, on remyelination following a CPZ-induced demyelination protocol. Results showed an increase in myelin deposition and the number of mature remyelinating OLG upon single treatments, but a synergic effect upon combined aTf + T3 treatment which was prevented by THR inhibition. It may be thus concluded that combined treatment yielded the most beneficial effects on OLG maturation parameters in vitro and remyelinating capacity in vivo when compared to single treatments. These findings may help explore the development of new target molecules in the treatment of demyelinating diseases
A novel mutation in PSEN1 (p.Arg41Ser) in an Argentinian woman with early onset Parkinsonism
No full textIntroduction: Mutations in presenilin-1 (PSEN1) account for the majority of cases of familial autosomal dominant early-onset Alzheimer's disease (AD) as well as in sporadic forms. Atypical presentations are reported including extrapyramidal signs. In the last years, a pleiotropic effect of some PSEN1 variants has been reported in Parkinson's disease (PD).
Objective: to report a new PSEN1 mutation characterized by early-onset Parkinsonism (EOPD) without dementia or classical AD biomarkers phenotype.
Patient and methods: An Argentinian 46 years old woman was diagnosed with EOPD at 35 years old with no family history of neurodegenerative disorders. Her medical history included iron deficiency and anemia since childhood. A brain MRI showed moderate frontal atrophy. 18FDG-PET and PiB-PET as well as CSF biomarkers were inconclusive for AD. Two neuropsychological examinations were compatible with a mild non amnestic cognitive impairment. Whole blood DNA was extracted and whole exome sequencing and analysis was performed.
Results and conclusion: A heterozygous novel missense PSEN1 mutation (position 14:73637540, A > T, pArg41Ser) was identified as a likely causative mutation in this patient. To the best of our knowledge, this case is the first PSEN1 mutation with a l-dopa responsive Parkinsonism lacking distinctive classical AD biomarkers. This case opens a new window to explore the pathophysiological link among PSEN1 and EOPDs and contributes to increase the phenotypes of PSEN1 variants.Fil: Sevlever, Gustavo Emilio. Fleni. Departamento de Neuropatología y Biología Molecular. Laboratorio de Enfermedades Neurodegenerativas (LEN); Argentina.Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría. Centro de Memoria y Envejecimiento; Argentina.Fil: Gatto, Emilia M. Sanatorio de la Trinidad Mitre. Departamento de Neurología; Argentina.Fil: Rojas, Galeno J. Sanatorio de la Trinidad Mitre. Unidad de Neurociencias Cognitivas; Argentina.Fil: Nemirovsky, Sergio I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales (IQUIBICEN). Instituto de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Da Prat, Gustavo. Instituto de Neurociencias Buenos Aires (INEBA); Argentina.Fil: Persi, Gabriel. Sanatorio de la Trinidad Mitre. Departamento de Neurología; Argentina.Fil: Cesarini, Martin. Instituto de Neurociencias Buenos Aires (INEBA); Argentina.Fil: Etcheverry, Jose L. Instituto de Neurociencias Buenos Aires (INEBA); Argentina.Fil: Gonzalez Rojas, Natalia. Instituto de Neurociencias Buenos Aires (INEBA); Argentina.Fil: Parisi, Virginia. Sanatorio de la Trinidad Mitre. Departamento de Neurología; Argentina.Fil: Cordoba, Marta. SInstituto de Neurociencias Buenos Aires (INEBA); Argentina.Fil: Turjanski, Adrian G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales (IQUIBICEN). Instituto de Química Biológica; Argentin
Iron Metabolism in Oligodendrocytes and Astrocytes, Implications for Myelination and Remyelination
No full textIron is a key nutrient for normal central nervous system (CNS) development and function; thus, iron deficiency as well as iron excess may result in harmful effects in the CNS. Oligodendrocytes and astrocytes are crucial players in brain iron equilibrium. However, the mechanisms of iron uptake, storage, and efflux in oligodendrocytes and astrocytes during CNS development or under pathological situations such as demyelination are not completely understood. In the CNS, iron is directly required for myelin production as a cofactor for enzymes involved in ATP, cholesterol and lipid synthesis, and oligodendrocytes are the cells with the highest iron levels in the brain which is linked to their elevated metabolic needs associated with the process of myelination. Unlike oligodendrocytes, astrocytes do not have a high metabolic requirement for iron. However, these cells are in close contact with blood vessel and have a strong iron transport capacity. In several pathological situations, changes in iron homoeostasis result in altered cellular iron distribution and accumulation and oxidative stress. In inflammatory demyelinating diseases such as multiple sclerosis, reactive astrocytes accumulate iron and upregulate iron efflux and influx molecules, which suggest that they are outfitted to take up and safely recycle iron. In this review, we will discuss the participation of oligodendrocytes and astrocytes in CNS iron homeostasis. Understanding the molecular mechanisms of iron uptake, storage, and efflux in oligodendrocytes and astrocytes is necessary for planning effective strategies for iron management during CNS development as well as for the treatment of demyelinating diseases.Fil: Correale, Jorge. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina.Fil: Cheli, Veronica T. The State University of New York, University at Buffalo. Hunter James Kelly Research Institute. Jacobs School of Medicine and Biomedical Sciences. Department of Pharmacology and Toxicology; Estados Unidos.Fil: Paez, Pablo M. The State University of New York, University at Buffalo. Hunter James Kelly Research Institute. Jacobs School of Medicine and Biomedical Sciences. Department of Pharmacology and Toxicology; Estados Unidos.Fil: Pasquini, Juana María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Instituto de Química y Fisicoquímica Biológicas; Argentina
Pituicytoma Associated with Acromegaly and Cushing Disease
No full textBackground: Pituicytoma is a rare neoplasm arising in the sellar region (World Health Organization grade I). Clinically, pituicytomas mimic nonfunctioning pituitary macroadenomas and are occasionally incidentally discovered at autopsy. Pituitary adenomas can occur with other sellar pathologies, and the term "collision sellar lesions" has been coined for this rare entity. There have only been a few reports of the coexistence of pituicytoma and pituitary adenoma. We present 2 cases of pituicytoma coexisting with acromegaly and Cushing disease.
Case description: Case 1: A 29-year-old woman had acromegaly. The macroadenoma was partially removed in her first surgery; thus an endonasal reoperation was required for debulking and posterior radiosurgery. Pituicytoma coexisting with somatotropinoma was diagnosed on pathologic examination. Case 2: A 33-year-old woman had adrenocorticotropic hormone-dependent Cushing disease. She underwent endonasal resection. Undetectable postoperative cortisol levels provided evidence that the underlying adrenocorticotropic hormone source was successfully removed. On the basis of morphologic features and the immunohistochemical profile, pituicytoma was diagnosed on pathologic examination. Pituitary adenoma was not confirmed histologically in this patient.
Conclusions: Only 117 cases of pituicytoma have been reported since it was first described in 1955. Before our report, only 5 cases of patients with pituicytoma coexisting with pituitary adenoma had been described. The coexistence of these 2 entities may not just be a mere coincidence but may be due to a yet unknown pathophysiologic link or common progenitor lineage of both lesions. Association between pituicytoma and pituitary adenoma is increasingly being reported.Fil: Marcó Del Pont, Francisco. Fleni. Departamento de Neurocirugía; Argentina.Fil: Villalonga, Juan Francisco. Universidad Nacional de Tucumán. Facultad de Medicina. LINT; Argentina.Fil: Ries Centeno, Tomás. Fleni. Departamento de Neurocirugía; Argentina.Fil: Arakaki, Naomi. Fleni. Departamento de Neuropatología y Biología Molecular; Argentina.Fil: Katz, Débora Adela. Fleni. Departamento de Neurología. Servicio de Neuroendocrinología; Argentina.Fil: Cervio, Andrés Eduardo. Fleni. Departamento de Neurocirugía; Argentina
Femoral intraneural ganglion cyst: the first confirmed case report
No full textBackground: Ganglion cysts affecting nerve are rare causes of neuropathy. The formation of intraneural ganglion cysts, once controversial, has recently been clarified. We describe the first modern description of a femoral intraneural ganglion cyst at the hip region.
Methods: A patient presented with a 1 year history of radiating pain, quadriceps weakness and anteromedial leg numbness was found to have a femoral intraneural cyst with a hip joint connection on MRI.
Results: Surgical disconnection of the articular branch led to improvement of the neuropathy and resolution of the cyst on postoperative MRI.
Conclusions: The unifying articular (synovial) theory describes the joint origin of intraneural cysts, even when they occur in unusual locations, and their propagation into the parent nerve. Knowledge of this theory can improve outcomes; surgery needs to address the joint origin or capsulolabral defect lest recurrence ensue.Fil: Cejas, Claudia Patricia. Fleni. Departamento de Diagnóstico por Imágenes; Argentina.Fil: Lovaglio, Ana C. Universidad de Buenos Aires. División de Neurocirugía. Programa de Cirugía de Nervios y Plexos; Argentina.Fil: Mansilla, Beatríz. Hospital Central de la Defensa Gómez Ulla. Departamento de Neurocirugía; España.Fil: Spinner, Robert J. Mayo Clinic. Department of Neurologic Surgery; Estados Unidos.Fil: Socolovsky, Mariano. Fleni. Departamento de Neurocirugía; Argentina. Universidad de Buenos Aires. División de Neurocirugía. Programa de Cirugía de Nervios y Plexos; Argentina
Effect of assisted reproductive technology on multiple sclerosis relapses: Case series and meta-analysis
No full textBACKGROUND:
Five case series reported increased relapse risk after assisted reproductive technologies (ART) in women with multiple sclerosis (MS), but small numbers and heterogeneous study design limit broader conclusions.
OBJECTIVE:
To evaluate the risk of relapses after ART in an independent case series and in aggregated analyses of existing studies.
METHODS:
We compared annualized relapse rate (ARR) in the 3 months after, and 12 months before, ART in (1) an unpublished cohort (Boston: prospectively collected relapses; 22 ART cycles), (2i) data pooled from Boston and five published studies (164 cycles), and (2ii) a meta-analysis of all case series published by 2017 (220 cycles; PRISMA and MOOSE guidelines).
RESULTS:
In the Boston cohort, mean ARR was not higher after ART than before (mean: 0.18 ± 0.85 vs 0.27 ± 0.55, p = 0.58). In the pooled analyses, ARR was significantly higher after ART for all clinical scenarios, including varying ART protocols (p ⩽ 0.01 for each). The meta-analysis confirmed an increased ARR after ART (mean difference (MD) = 0.92, 95% confidence interval (CI) = [0.33, 1.51], p = 0.01).
CONCLUSION:
These pooled data support an increase in ARR following ART. Reasons for local variation in ARR after ART, and consideration of MS treatments during conception attempts, will be pursued.Fil: Bove, Riley. University of California. Weill Institute for the Neurosciences. Department of Neurology; Estados Unidos. Harvard Medical School. Brigham and Women's Hospital; Estados Unidos.Fil: Rankin, Kelsey. University of California. Weill Institute for the Neurosciences. Department of Neurology; Estados UnidosFil: Lin, Chris. University of California. Weill Institute for the Neurosciences. Department of Neurology; Estados Unidos.Fil: Zhao, Chao. University of California. Weill Institute for the Neurosciences. Department of Neurology; Estados Unidos.Fil: Correale, Jorge. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; ArgentinaFil: Hellwig, Kerstin. Ruhr-University Bochum. St. Josef Hospital; Alemania.Fil: Michel, Laure. Centre de Recherche en Transplantation et Immunologie; Francia. Centre Hospitalier Universitaire de Nantes. Service de Neurologie; Francia.Fil: Laplaud, David A. Centre de Recherche en Transplantation et Immunologie. Francia. Centre Hospitalier Universitaire de Nantes. Service de Neurologie; Francia.Fil: Chitnis, Tanuja. Harvard Medical School. Brigham and Women's Hospital; Estados Unido
Aspectos clínicos y demográficos de los pacientes con esclerosis múltiple secundaria progresiva en Argentina
No full textEl objetivo del estudio fue evaluar los aspectos clínicos y demográficos de los pacientes con esclerosis múltiple (EM) secundaria progresiva (EMSP) en los pacientes incluidos en el Registro Argentino de EM (RelevarEM, número de registro de Clinical Trials 03375177). RelevarEM es un registro longitudinal, estrictamente observacional, de pacientes con EM y trastornos del espectro de neuromielitis óptica. Los aspectos clínicos y demográficos fueron descriptos en pacientes con EMSP respecto a aquellos con EM recaída en remisión (EMRR). Se incluyeron 1723 pacientes con EM (1605, 93.2% EMRR y 118, 6.8%, EMSP). En el grupo con EMSP la mediana de edad fue de 53 (intervalo inter-cuartil [IIQ] 47-62) años, 67% eran mujeres, mediana de tiempo de evolución de enfermedad 19.5 (IIQ 14-26) años, EDSS (expanded disability status scale), 6.5 y 48.3% estaban en tratamiento para su EM. Solo el 23.7% con EMSP estaban trabajando activamente y el 86% tenía certificado de discapacidad. Un 35.6% con EMSP presentaron nuevas lesiones en resonancia magnética y 5% tuvo recaídas clínicas en los 12 meses previos al análisis, mostrando una actividad de la enfermedad significativamente menor respecto a la forma EMRR (p < 0.01).Fil: Gaitán, María Inés. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina.Fil: Marrodán, Mariano. Fleni. Departamento de Neurología; Argentina.Fil: Negrotto, Laura. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina.Fil: Ysrraelit, Maria. Fleni. Departamento de Neurología. Servicio de Neuroinmunología y Enfermedades Desmielinizantes; Argentina.Fil: Miguez, Jimena. Hospital Italiano de Buenos Aires. Servicio de Neurología; Argentina.Fil: Alonso Serena, Marina. Hospital Italiano de Buenos Aires. Sección de Epidemiología; Argentina.Fil: Pappolla, Agustín. Hospital Italiano de Buenos Aires. Servicio de Neurología; Argentina.Fil: Patrucco, Liliana. Hospital Italiano de Buenos Aires. Servicio de Neurología; Argentina.Fil: Cristiano, Edgardo. Centro de Esclerosis Múltiple de Buenos Aires; Argentina.Fil: Vrech, Carlos. Sanatorio Allende. Departamento de Enfermedades Desmielinizantes; Argentina.Fil: Rojas, Juan I. Centro de Esclerosis Múltiple de Buenos Aires; Argentina
Baseline characteristics of patients with heart failure with preserved ejection fraction in the EMPEROR-Preserved trial
No full textAims: EMPEROR-Preserved is an ongoing trial evaluating the effect of empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF). This report describes the baseline characteristics of the EMPEROR-Preserved cohort and compares them with patients enrolled in prior HFpEF trials.
Methods and results: EMPEROR-Preserved is a phase III randomized, international, double-blind, parallel-group, placebo-controlled trial in which 5988 symptomatic HFpEF patients [left ventricular ejection fraction (LVEF) >40%] with and without type 2 diabetes mellitus (T2DM) have been enrolled. Patients were required to have elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations (i.e. >300 pg/mL in patients without and >900 pg/mL in patients with atrial fibrillation) along with evidence of structural changes in the heart or documented history of heart failure hospitalization. Among patients enrolled from various regions (45% Europe, 11% Asia, 25% Latin America, 12% North America), the mean age was 72 ± 9 years, 45% were women. Almost all patients had New York Heart Association class II or III symptoms (99.6%), and 23% had prior heart failure hospitalization within 12 months. Thirty-three percent of the patients had baseline LVEF of 41-50%. The mean LVEF (54 ± 9%) was slightly lower while the median NT-proBNP [974 (499-1731) pg/mL] was higher compared with previous HFpEF trials. Presence of comorbidities such as diabetes (49%) and chronic kidney disease (50%) were common. The majority of the patients were on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (80%) and beta-blockers (86%), and 37% of patients were on mineralocorticoid receptor antagonists.
Conclusion: When compared with prior trials in HFpEF, the EMPEROR-Preserved cohort has a somewhat higher burden of comorbidities, lower LVEF, higher median NT-proBNP and greater use of mineralocorticoid receptor antagonists at baseline. Results of the EMPEROR-Preserved trial will be available in 2021.Fil: Perrone, Sergio Victor. Fleni. Departamento de Neurología. Servicio de Cardiología; Argentina.Fil: Anker, Stefan D. Berlin-Brandenburg Center for Regenerative Therapies. Department of Cardiology; Alemania. German Centre for Cardiovascular Research (DZHK); Alemania. Charité Universitätsmedizin Berlin; Alemania.Fil: Butler, Javed. University of Mississippi School of Medicine; Estados Unidos.Fil: Filippatos, Gerasimos. National and Kapodistrian University of Athens School of Medicine; Grecia.Fil: Khan, Muhammad Shahzeb. University of Mississippi School of Medicine; Estados Unidos.Fil: Ferreira, João Pedro. Université de Lorraine, Inserm INI-CRCT; Francia.Fil: Bocchi, Edimar. São Paulo University Medical School; Brasil.Fil: Böhm, Michael. Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes; Alemania.Fil: Brunner-La Rocca, Hans Pieter. Maastricht University Medical Center; Países Bajos.Fil: Choi, Dong-Ju. Seoul National University Bundang Hospital; Corea.Fil: Chopra, Vijay. Medanta Medicity to Max Superspeciality Hospital; India.Fil: Chuquiure, Eduardo. Instituto Nacional de Cardiología Ignacio Chavez; México.Fil: Giannetti, Nadia. Centre Universitaire de Sante McGill; Canadá.Fil: Gomez-Mesa, Juan Esteban. Fundación Valle del Lili; Colombia.Fil: Janssens, Stefan. University Hospitals Leuven; Brasil.Fil: Januzzi, James L. Massachusetts General Hospital. Harvard Medical School; Estados Unidos.Fil: Gonzalez-Juanatey, Jose R. Complejo Hospitalario Universitario de Santiago; España.Fil: Merkely, Bela. Semmelweis University; Hungría.Fil: Nicholls, Stephen J. Victorian Heart Institute, Monash University; Australia.Fil: Piña, Ileana L. Wayne State University; Estados Unidos
Demographic and clinical characteristics of individuals with traumatic spinal cord injury in Argentina from 2015 to 2019: a multicenter study
No full textStudy design: Descriptive and ambispective study.
Objectives: To describe the demographics, clinical characteristics, and etiologies of traumatic spinal cord injury (TSCI) in a metropolitan region of Argentina.
Setting: Five inpatient rehabilitation centers in Buenos Aires, Argentina.
Methods: We included all patients with acute TSCI who required hospital treatment at five rehabilitation facilities between 2015 and 2019. We collected data using portions of the International Spinal Cord Injury (SCI) Core Data Set.
Results: We registered 186 individuals as having TSCI. The males were 77% of the total sample. The mean age was 36 (SD ± 15.7) years. The distribution between paraplegia and tetraplegia was 50.3% and 49.7%, respectively. TSCI was complete in 57.3%. Including patients with motor complete SCI, the percentage reached 71.9% of the sample. Vehicular collisions were the leading cause of TSCI (47.3%), followed by falls (21.5%) and assaults (16.1%).
Conclusions: We collected data about demographics, clinical characteristics, and aetiologies of TSCI for the first time in Argentina. The predominant demographic profile of the individuals with TSCI was of young males with complete SCI. We found the most important cause of TSCI was vehicular collisions. Implementation of road safety strategies in this target population might decrease the incidence of TSCI.Fil: Olmos, Lisandro Emilio. Fleni. Centro de Rehabilitación Adultos CR; Argentina.Fil: Gatti, Marcelo A. Fleni. Centro de Rehabilitación Adultos CR. Servicio de Kinesiología; Argentina.Fil: Rivas, María Elisa. Fleni. Centro de Rehabilitación Adultos CR. Servicio de Kinesiología; Argentina.Fil: Broggi, María Silvina. Fleni. Centro de Rehabilitación Adultos CR. Servicio de Kinesiología; Argentina.Fil: Sampayo, María P. Santa Catalina, Neurorehabilitación Clínica; Argentina.Fil: Rolandelli, Analis. Remeo Center; Argentina.Fil: Yannone, Santiago. ALPI; Argentina.Fil: Gorman, Peter. University of Maryland School of Medicine; Estados Unidos
Diagnosis of Rapidly Progressive Dementia in a Referral Center in Argentina
No full textINTRODUCTION:
Rapidly progressive dementia (RPD) is a broadly defined clinical syndrome. Our aim was to describe clinical and ancillary study findings in patients with RPD and evaluate their diagnostic performance for the identification of nonchronic neurodegenerative rapidly progressive dementia (ncnRPD).
METHODS:
We reviewed clinical records and ancillary methods of patients evaluated for RPD at our institution in Buenos Aires, Argentina from 2011 to 2017. We compared findings between chronic neurodegenerative RPD and ncnRPD and evaluated the diagnostic metrics using receiver operating characteristic curves.
RESULTS:
We included 104 patients with RPD, 29 of whom were chronic neurodegenerative RPD and 75 of whom were ncnRPD. The 6-month time to dementia cutpoint had a sensitivity of 89% and specificity of 100% for ncnRPD, with an area under the receiver operating characteristic curve of 0.965 (95% confidence interval=0.935-0.99; P<0.001). A decision tree that included time to dementia, brain magnetic resonance imaging, and cerebrospinal fluid analysis identified ncnRPD patients with a sensitivity of 100%, specificity of 79%, positive predictive value of 93%, and negative predictive value of 100% overall.
DISCUSSION:
RPD is a clinical syndrome that comprises different diagnoses, many of them for treatable diseases. Using the time to dementia, brain magnetic resonance imaging, and cerebrospinal fluid analysis when triaging these patients could help identify those diseases that need to be studied more aggressively.Fil: Acosta, Julián Nicolás. Fleni. Departamento de Neurología; Argentina.Fil: Ricciardi, Mario Emiliano. Fleni. Departamento de Neurología; Argentina.Fil: Alessandro, Lucas. Fleni. Departamento de Neurología; ArgentinaFil: Carnevale, Martín Diego. Fleni. Departamento de Diagnóstico por Imágenes; Argentina.Fil: Farez, Mauricio Franco. Fleni. Centro de Epidemiología, Bioestadística y Salud Pública; ArgentinaFil: Nagel, Vanesa. Fleni. Departamento de Neurología; ArgentinaFil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina