Human Embryonic Stem Cell-Derived Immature Midbrain Dopaminergic Neurons Transplanted in Parkinsonian Monkeys.

Human embryonic stem cells (hESCs) differentiate into specialized cells, including midbrain dopaminergic neurons (DANs), and Non-human primates (NHPs) injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine develop some alterations observed in Parkinson's disease (PD) patients. Here, we obtained well-characterized DANs from hESCs and transplanted them into two parkinsonian monkeys to assess their behavioral and imaging changes. DANs from hESCs expressed dopaminergic markers, generated action potentials, and released dopamine (DA) in vitro. These neurons were transplanted bilaterally into the putamen of parkinsonian NHPs, and using magnetic resonance imaging techniques, we calculated the fractional anisotropy (FA) and mean diffusivity (MD), both employed for the first time for these purposes, to detect in vivo axonal and cellular density changes in the brain. Likewise, positron-emission tomography scans were performed to evaluate grafted DANs. Histological analyses identified grafted DANs, which were quantified stereologically. After grafting, animals showed signs of partially improved motor behavior in some of the HALLWAY motor tasks. Improvement in motor evaluations was inversely correlated with increases in bilateral FA. MD did not correlate with behavior but presented a negative correlation with FA. We also found higher 11C-DTBZ binding in positron-emission tomography scans associated with grafts. Higher DA levels measured by microdialysis after stimulation with a high-potassium solution or amphetamine were present in grafted animals after ten months, which has not been previously reported. Postmortem analysis of NHP brains showed that transplanted DANs survived in the putamen long-term, without developing tumors, in immunosuppressed animals. Although these results need to be confirmed with larger groups of NHPs, our molecular, behavioral, biochemical, and imaging findings support the integration and survival of human DANs in this pre-clinical PD model.

Experiencia con la enfermedad de Creutzfeldt-Jakob de un único centro de referencia en México. Análisis de una serie de casos / Experience with Creutzfeldt-Jakob disease in a single referral center in Mexico. Case series

Resumen Introducción: La enfermedad de Creutzfeldt-Jakob (ECJ) es una enfermedad del sistema nervioso central rápidamente progresiva y mortal causada por priones. Objetivo: Presentar las principales características clínicas y paraclínicas de pacientes con probable ECJ en un centro de referencia de América Latina. Métodos: Estudio retrospectivo de pacientes diagnosticados con demencia rápidamente progresiva entre 2014 y 2019. Se incluyeron características clínicas, demográficas, del electroencefalograma, imágenes por resonancia magnética, proteína 14-3-3 y tomografía por emisión de positrones (PET), cuando estaba disponible. Resultados: Veinticuatro pacientes cumplieron con los criterios de ECJ esporádica (75 % mujeres), la edad media fue de 59.29 ± 11.67 años, la duración de la enfermedad desde el inicio de los síntomas hasta el ingreso hospitalario fue de 7.41 ± 6.54 meses y las primeras manifestaciones más comunes fueron las alteraciones del comportamiento (41.7 %). Los complejos de ondas delta prevalecieron en el electroencefalograma (54.2 %), la hiperintensidad cortical en la resonancia magnética (83.3 %) y el hipometabolismo frontal en la PET (37.5 %). En el análisis del líquido cefalorraquídeo, siete casos mostraron proteína tau total positiva; cinco, proteína 14-3-3 positiva; y tres, proteína tau hiperfosforilada positiva. Conclusiones: Existe importante heterogeneidad clínica en cuanto a los síntomas iniciales. Los hallazgos de las pruebas auxiliares coincidieron con los de otras series.

Abstract Introduction: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal central nervous system disease caused by prions. Objective: To present the main clinical and paraclinical characteristics of patients with probable CJD in a referral center of Latin America. Methods: Retrospective study of patients diagnosed with rapidly progressive dementia between 2014 and 2019. Clinical, demographic, electroencephalogram, magnetic resonance imaging, and 14-3-3 protein characteristics were included, as well as positron-emission tomography (PET) data when available. Results: Twenty-four patients met the criteria for sporadic CJD (75% were women). Mean age was 59.29 ± 11.67 years, while mean disease duration from symptom onset to hospital admission was 7.41 ± 6.54 months. The most common first symptom was behavioral changes (41.7%). Delta wave complexes prevailed (54.2%) on electroencephalogram, cortical hyperintensity (83.3%) on magnetic resonance and frontal hypometabolism (37.5%) on PET. Seven cases showed positive total Tau; five, positive 14-3-3 protein; and three, positive phosphorylated tau on cerebrospinal fluid analysis. Conclusions: There is significant clinical heterogeneity regarding initial symptoms. Auxiliary test findings were consistent with those of other series.

Experience with Creutzfeldt-Jakob disease in a single referral center in Mexico. Case series.

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal central nervous system disease caused by prions. OBJECTIVE: To present the main clinical and paraclinical characteristics of patients with probable CJD in a referral center of Latin America. METHODS: Retrospective study of patients diagnosed with rapidly progressive dementia between 2014 and 2019. Clinical, demographic, electroencephalogram, magnetic resonance imaging, and 14-3-3 protein characteristics were included, as well as positron-emission tomography (PET) data when available. RESULTS: Twenty-four patients met the criteria for sporadic CJD (75% were women). Mean age was 59.29 ± 11.67 years, while mean disease duration from symptom onset to hospital admission was 7.41 ± 6.54 months. The most common first symptom was behavioral changes (41.7%). Delta wave complexes prevailed (54.2%) on electroencephalogram, cortical hyperintensity (83.3%) on magnetic resonance and frontal hypometabolism (37.5%) on PET. Seven cases showed positive total Tau; five, positive 14-3-3 protein; and three, positive phosphorylated tau on cerebrospinal fluid analysis. CONCLUSIONS: There is significant clinical heterogeneity regarding initial symptoms. Auxiliary test findings were consistent with those of other series.

INTRODUCCIÓN: La enfermedad de Creutzfeldt-Jakob (ECJ) es una enfermedad del sistema nervioso central rápidamente progresiva y mortal causada por priones. OBJETIVO: Presentar las principales características clínicas y paraclínicas de pacientes con probable ECJ en un centro de referencia de América Latina. MÉTODOS: Estudio retrospectivo de pacientes diagnosticados con demencia rápidamente progresiva entre 2014 y 2019. Se incluyeron características clínicas, demográficas, del electroencefalograma, imágenes por resonancia magnética, proteína 14-3-3 y tomografía por emisión de positrones (PET), cuando estaba disponible. RESULTADOS: Veinticuatro pacientes cumplieron con los criterios de ECJ esporádica (75 % mujeres), la edad media fue de 59.29 ± 11.67 años, la duración de la enfermedad desde el inicio de los síntomas hasta el ingreso hospitalario fue de 7.41 ± 6.54 meses y las primeras manifestaciones más comunes fueron las alteraciones del comportamiento (41.7 %). Los complejos de ondas delta prevalecieron en el electroencefalograma (54.2 %), la hiperintensidad cortical en la resonancia magnética (83.3 %) y el hipometabolismo frontal en la PET (37.5 %). En el análisis del líquido cefalorraquídeo, siete casos mostraron proteína tau total positiva; cinco, proteína 14-3-3 positiva; y tres, proteína tau hiperfosforilada positiva. CONCLUSIONES: Existe importante heterogeneidad clínica en cuanto a los síntomas iniciales. Los hallazgos de las pruebas auxiliares coincidieron con los de otras series.

FDG-PET in Cotard syndrome before and after treatment: can functional brain imaging support a two-factor hypothesis of nihilistic delusions?

Introduction: Cotard syndrome is a neuropsychiatric entity recognised by the presence of nihilistic delusions. Although different models have been proposed for the development of monothematic delusions, including Cotard syndrome, functional neuroanatomical models are lacking.Methods: A case report of a 19-year old male with autoimmune encephalitis and Cotard syndrome, in whom Positron Emission Tomography (18F-FDG-PET) scans were performed before and after successful treatment with electroconvulsive therapy (ECT), is presented. Literature review on brain imaging is provided to discuss a functional neuroanatomical model of Cotard syndrome, in accordance with the two-factor theory of delusions.Results: The patient's 18F-FDG-PET showed marked insular and prefrontal metabolic abnormalities. Except for insular hypometabolism, metabolic abnormalities improved after ECT. Previously reported structural neuroimaging studies in Cotard syndrome showed a predominance of right hemisphere lesions, in which frontal lobes were more frequently involved, followed by parietal and temporal lesions. Functional neuroimaging studies reported abnormalities in frontoparietal circuits as well as midline structures included in the "default mode network".Conclusions: Abnormalities in the functioning of the insular cortex and the prefrontal cortex could be related to the development of nihilistic delusions when a two-factor theory of delusions is considered.

Diagnostic Utility of [11C]DTBZ Positron Emission Tomography In Clinically Uncertain Parkinsonism: Experience of a Single Tertiary Center.

BACKGROUND: The use of single-photon emission computed tomography and positron emission tomography (PET) has proven to be helpful in differentiating Parkinson's disease (PD) from other movement disorders with a sensitivity of up to 95%. OBJECTIVE: The objective of this study was to determine the accuracy of [11C]DTBZ PET imaging in patients with clinically uncertain parkinsonism from a tertiary referral center in Mexico City. MATERIALS AND METHODS: Patients who underwent [11C]DTBZ PET brain scan due to clinically uncertain parkinsonism where divided into two groups: PD or non-PD. A scan was considered positive when visual assessment revealed a decrease in [11C]DTBZ uptake typical for PD; a scan was considered negative when visual assessment showed no decrease in [11C]DTBZ uptake or showed a decrease in tracer uptake in a non-PD pattern. Sensitivity, specificity, and positive and negative predictive values were calculated using a 2 × 2 table, with a 95% confidence interval. RESULTS: A total of 39 patients were included in the study. 14 PET studies were deemed positive and 25 PET studies were deemed negative; 12 true positives and 23 true negatives were found. This yielded a sensitivity of 92.9% (95% CI, 66.1-99.8), specificity of 92% (95% CI, 74-99), PPV of 86.7% (95% CI, 63.1-96.1), and NPV of 95.8% (95% CI, 79.1-98.4). CONCLUSIONS: The [11C]DTBZ PET has an excellent accuracy for differentiating idiopathic PD from other disorders.

[Usefulness of positron tomography (PET) in lung cancer]. / Utilidad de la tomografía por emisión de positrones (PET) en el cáncer pulmonar.

Lung carcinoma is one on the leading causes of death from cancer in all parts of the world. The frequency of this tumor is increasing; at present, accounts for approximately 25% of all cancer deaths. The majority of lung cancers are initially detected on chest radiographs, but many benign lesions have radiologic characteristics similar to malignant lesions. Computed tomography (CT) is most frequently used to provide additional anatomic and morphologic information on lesions, but it is limited in distinguishing between benign and malignant abnormalities. Fluorodeoxyglucose-Positron emission tomography (PET-FDG) imaging provides physiologic and metabolic information that characterizes lesions indeterminate by CT, is used clinically to-differentiate benign from malignant focal pulmonary abnormalities, to stage mediastinal and extrathoracic metastases, and to identify recurrence. It is the gold standard that define the therapeutic strategy.

Utilidad de la tomografía por emisión de positrones (PET) en el cáncer pulmonar / Usefulness of Positron Tomograhy (PET) in Lung Cancer

El cáncer de pulmón es una de las principales causas de mortalidad en el mundo. Actualmente representa 25% de lamortalidad de todas las muertes por cáncer y suincidencia se encuentra en aumento. La mayoría de los cánceres pulmonares se detectan inicialmente en radiografías de tórax pero las características de las lesiones benignas son similares a las malignas. La tomografía computada (TC) es el estudio más frecuentemente utilizado para recabar información anatómica y morfológica acerca de las lesiones, pero es limitado para distinguir entre las lesiones malignas y benignas. La tomografía por emisión depositrones (PET) con fluorodeoxiglucosa (FDG) provee imágenes con información metabólica y fisiológica que caracteriza a las lesiones que son indeterminadas en TC y se utiliza en la clínica para diferenciar alteraciones pulmonares focales malignas de las benignas, así como, estadificar metástasis mediastinales y extratorácicas e identificar su recurrencia, haciéndolo el estudio de elección para la estrategia terapéutica.

Lung carcinoma is one on the leading causes of death from cancer in all parts of the world. The frequency of this tumor is increasing; at present, accounts for approximately 25% of all cancer deaths. The majority of lung cancers are initially detected on chest radiographs, but many benign lesions have radiologic characteristics similar to malignant lesions. Computed tomography (CT) is most frequently used to provide additional anatomic and morphologic information on lesions, but it is limited in distinguishing between benign and malignant abnormalities. Fluorodeoxyglucose-Positron emission tomography (PET-FDG) imaging provides physiologic and metabolic information that characterizes lesions indeterminate by CT, is used clinically to differentiate benign from malignant focal pulmonary abnormalities, to stage mediastinal and extrathoracic metastases, and to identify recurrence. Lt is the gold standard that define the therapeutic strategy.

[Principles and applications of positron emission tomography (PET) in cardiology. PET in Mexico: a reality]. / Principios y aplicaciones de la tomografía por emisión de positrones (PET) en la cardiología. PET en México: una realidad.

Positron emission tomography (PET) offers the unique capability of measuring non-invasive by the regional myocardial substrate flow and the biochemical reaction index in millimol per minute per gram of myocardial tissue. PET also allows for the assessment or quantification of regional myocardial blood flow, cardiac metabolism, ventricular function, myocardial viability, as well as autonomous nervous system, research and evaluating of dilated myocardiopathy and of ventricular hypertrophy. PET's success is based on the radioisotopes properties, their very short half-life allows for the administration of large doses.

Principios y aplicaciones de la tomografía por emisión de positrones (PET) en la cardiologÝa. PET en MÚxico: una realidad / Principles and applications of positron emission tomography (PET) in cardiology. PET in Mexico: a reality

Positron emission tomography (PET) offers the unique capability of measuring non-invasive by the regional myocardial substrate flow and the biochemical reaction index in millimol per minute per gram of myocardial tissue. PET also allows for the assessment or quantification of regional myocardial blood flow, cardiac metabolism, ventricular function, myocardial viability, as well as autonomous nervous system, research and evaluating of dilated myocardiopathy and of ventricular hypertrophy. PET's success is based on the radioisotopes properties, their very short half-life allows for the administration of large doses.