Association of ictal aphasia with hypoperfusion in language areas in temporal lobe epilepsy patients.

Ictal clinical phenomenology, including aphasia, is usually associated with increased regional cerebral perfusion. We present an unusual pattern of ictal cerebral perfusion in three patients with pharmacoresistant, lesional temporal lobe epilepsy and ictal/postictal aphasia studied with prolonged video-EEG, ictal, and interictal SPECT and MRI for pre-surgical evaluation. Subtraction of ictal-interictal SPECT images co-registered with MRI (SISCOM) showed ictal hyperperfusion in the temporal epileptogenic area in all patients. In addition, hypoperfusion of Broca's area in one case, Wernicke's area in other patient, and both areas in the remaining one were observed. Ictal aphasia in these patients may be explained by functional inhibition of a primary language area, driven by the epileptogenic network. This pattern can contribute to understand the pathophysiology of some ictal signs, with an impact on the evaluation of individual surgical risks.

Brain SPECT as a Biomarker of Neurodegeneration in Dementia in the Era of Molecular Imaging: Still a Valid Option?

Biomarkers are playing a progressively leading role in both clinical practice and scientific research in dementia. Although amyloid and tau biomarkers have gained ground in the clinical community in recent years, neurodegeneration biomarkers continue to play a key role due to their ability to identify different patterns of brain involvement that sign the transition between asymptomatic and symptomatic stages of the disease with high sensitivity and specificity. Both 18F-FDG positron emission tomography (PET) and perfusion single photon emission computed tomography (SPECT) have proved useful to reveal the functional alterations underlying various neurodegenerative diseases. Although the focus of nuclear neuroimaging has shifted to PET, the lower cost and wider availability of SPECT make it a still valid alternative for the study of patients with dementia. This review discusses the principles of both techniques, compares their diagnostic performance for the diagnosis of neurodegenerative diseases and highlights the role of SPECT to characterize patients from low- and middle-income countries, where special care of additional costs is particularly needed to meet the new recommendations for the diagnosis and characterization of patients with dementia.

Clinical Impact of PET With 18F-FDG and 11C-PIB in Patients With Dementia in a Developing Country.

Introduction: The objective of this study was to evaluate the clinical impact PET with 18F-FDG and 11C-PIB in patients with dementia in a developing country. Methodology: Retrospective study of the patients referred for the evaluation of dementia to the only PET center in Uruguay. A total of 248 patients were identified, from which 70 patients were included based on the availability of medical history and clinical follow-up. Main outcomes included change in diagnosis, diagnostic dilemma and AD treatment. We evaluated the association of clinical outcomes with PET concordance with baseline diagnosis, diagnostic dilemma, level of education, AD pathology/Non-AD pathology (AD/Non-AD), baseline diagnosis and 11C-PIB PET result. Results: Baseline clinical diagnosis was concordant with 18F-FDG and 11C-PIB PET results in 64.7 and 77.1% of the patients, respectively. Change in diagnosis after PET was identified in 30.0% of the patients and was associated with discordant 18F-FDG (p = 0.002) and 11C-PIB (p < 0.001) PET results, previous diagnostic dilemma (p = 0.005), low education (p = 0.027), Non-AD baseline diagnosis (p = 0.027), and negative 11C-PIB PET result (p < 0.001). Only the last variable remained significant in the multivariate analysis (adjusted p = 0.038). Diagnostic dilemma decreased after PET from 15.7 to 7.1% (p = 0.11) and was associated with Non-AD diagnosis (p = 0.002) and negative 11C-PIB PET result (p = 0.003). Change in AD treatment after PET occurred in 45.7% of the patients. Conclusion: 18F-FDG and 11C-PIB PET had a significant clinical impact in terms of change in diagnosis and treatment in patients with dementia in a developing country, similar to that reported in high-income countries.

Empathy deficits and their behavioral, neuroanatomical, and functional connectivity correlates in smoked cocaine users.

Reduced empathic abilities are frequently observed in drug abusers. These deficits may compromise interpersonal interactions and contribute to diminished social functioning. However, previous evidence regarding empathy and addiction is behaviorally unspecific and virtually null in terms of their brain structural or functional correlates. Moreover, no previous study has investigated how empathy is affected by drugs whose consumption is particularly characterized by counter-empathic behaviors. Here, we conducted the first assessment of neurocognitive correlates of empathy for pain in dependent users (predominantly men) of smoked cocaine (SC, coca paste, n = 37). We compared their performance in the empathy task with that of two groups matched in relevant demographic variables: 24 dependent users of insufflated cocaine hydrochloride (CC) and 21 healthy controls. In addition, we explored the structural anatomy and functional connectivity (FC) correlates of empathic impairments across groups. Our results showed that, compared to CC and controls, SC users exhibited a selective reduction of empathic concern for intentional harms. These impairments were associated with lower gray matter volumes in regions subserving social cognition (i.e., right inferior parietal lobule, supramarginal and angular gyri). Furthermore, reduced empathic concern correlated with FC within affective empathy and social cognition networks, which are also linked to cognitive changes reported in addiction (i.e., inferior frontal and orbital gyri, posterior insula, supplementary motor area, cingulate cortex). Our findings suggest that chronic consumption of SC may involve reduced empathic concern and relevant neuroanatomical and FC abnormalities, which, in turn, may result in social interaction dysfunction. These results can inform theoretical and applied developments in neuropsychopharmacology.

SPECT activation patterns in psychogenic non-epileptic seizures in temporal lobe epilepsy patients.

INTRODUCTION: The diagnosis of psychogenic non-epileptic seizures (PNES) can often be challenging. When video-electroencephalography (EEG) is not conclusive, single-photon emission computed tomography (SPECT) can be useful by quantifying changes in regional cerebral blood flow (rCBF). METHODS: We conducted a retrospective case-control study in adult patients with pharmacoresistant temporal lobe epilepsy (TLE). Those patients with an ictal SPECT obtained during an event finally diagnosed as PNES were included as cases (PNES+). The control group consisted of patients with TLE without PNES (PNES-). Clinical episodes were analysed and classified according to PNES subtypes. Subtraction ictal SPECT coregistered to MRI (SISCOM) analysis was performed for the detection of areas with significant changes in perfusion compared to individual interictal studies. Group comparisons in SPM12 included paired t-tests of ictal vs. interictal studies in each group of temporal lobe seizures and PNES events. RESULTS: Ten patients with TLE and PNES were included. We found no patterns of regional hyperperfusion typical of TLE seizures during the PNES events. In two of these cases, an ictal SPECT during a confirmed epileptic seizure was also obtained, showing antero-mesial temporal lobe hyperperfusion. Group comparisons between ictal and interictal SPECTs showed increased rCBF in the temporal lobe with reduced perfusion in the default mode network areas and cerebellum during temporal lobe seizures in PNES- patients and decreased perfusion restricted to the posterior parietal cortex without significant rCBF increases in PNES events. CONCLUSIONS: Ictal SPECT can be a helpful tool to characterize rCBF changes in PNES and for differential diagnosis with seizures in TLE patients.

Comparison of MRI, [18F]FDG PET/CT, and 99mTc-UBI 29-41 scintigraphy for postoperative spondylodiscitis-a prospective multicenter study.

PURPOSE: Postoperative infection still constitutes an important complication of spine surgery, and the optimal imaging modality for diagnosing postoperative spine infection has not yet been established. The aim of this prospective multicenter study was to assess the diagnostic performance of three imaging modalities in patients with suspected postoperative spine infection: MRI, [18F]FDG PET/CT, and SPECT/CT with 99mTc-UBI 29-41. METHODS: Patients had to undergo at least 2 out of the 3 imaging modalities investigated. Sixty-three patients enrolled fulfilled such criteria and were included in the final analysis: 15 patients underwent all 3 imaging modalities, while 48 patients underwent at least 2 imaging modalities (MRI + PET/CT, MRI + SPECT/CT, or PET/CT + SPECT/CT). Final diagnosis of postoperative spinal infection was based either on biopsy or on follow-up for at least 6 months. The MRI, PET/CT, and SPECT/CT scans were read blindly by experts at designated core laboratories. Spine surgery included metallic implants in 46/63 patients (73%); postoperative spine infection was diagnosed in 30/63 patients (48%). RESULTS: Significant discriminants between infection and no infection included fever (P = 0.041), discharge at the wound site (P < 0.0001), and elevated CRP (P = 0.042). There was no difference in the frequency of infection between patients who underwent surgery involving spinal implants versus those who did not. The diagnostic performances of MRI and [18F]FDG PET/CT analyzed as independent groups were equivalent, with values of the area under the ROC curve equal to 0.78 (95% CI: 0.64-0.92) and 0.80 (95% CI: 0.64-0.98), respectively. SPECT/CT with 99mTc-UBI 29-41 yielded either unacceptably low sensitivity (44%) or unacceptably low specificity (41%) when adopting more or less stringent interpretation criteria. The best diagnostic performance was observed when combining the results of MRI with those of [18F]FDG PET/CT, with an area under the ROC curve equal to 0.938 (95% CI: 0.80-1.00). CONCLUSION: [18F]FDG PET/CT and MRI both possess equally satisfactory diagnostic performance in patients with suspected postoperative spine infection, the best diagnostic performance being obtained by combining MRI with [18F]FDG PET/CT. The diagnostic performance of SPECT/CT with 99mTc-UBI 29-41 was suboptimal in the postoperative clinical setting explored with the present study.

Efectos de la estimulación endocárdica prolongada sobre la sincronía mecánica ventricular izquierda. Ensayo piloto aplicando análisis de fase por tomografía computada por emisión de fotón único gatillada. Estimulación prolongada y disincronía mecánica / Effects of prolonged endocardial stimulation on left ventricular mechanical synchrony. A pilot study applying gated-SPECT phase analysis. Endocardial stimulation and dyssynchrony

Resumen: Objetivo: Evaluar la disincronía mecánica ventricular izquierda (DMVI) asociada a la estimulación endocárdica prolongada del ventrículo derecho mediante el ensayo piloto de una nueva técnica de imagen en Uruguay. Métodos: Se estudiaron 12 pacientes con marcapasos implantados al menos hace un año utilizando SPECT gatillada con 99mTc-MIBI y análisis de fase en reposo. Se registraron variables clínicas, duración del QRS, tasa, modo y sitio de estimulación ventricular, presencia y extensión de infarto e isquemia, volúmenes cavitarios y FEVI en reposo. Utilizando V-Sync de Emory Cardiac Toolbox se obtuvieron desviación estándar y ancho de banda de fase en reposo (grados), comparando los individuos con FEVI ≥ y < 50% con una población control. Resultados: Los pacientes de la serie con estimulación endocárdica prolongada en el ventrículo derecho exhibieron marcada DMVI. Los pacientes con FEVI moderada/severamente disminuida (con diámetros cavitarios mayores, estimulación septal, infarto extenso o isquemia significativa) exhibieron mayor disincronía que aquellos con FEVI conservada/levemente disminuida (ancho de banda = 144.33o vs. 77.41o, p < 0.05; desviación estándar = 46.67o vs. 26.81o, p < 0.05). Conclusiones: En la cardiopatía isquémica la elevada tasa de estimulación endocárdica crónica se asocia con marcada DMVI, aun cuando la función sistólica esté conservada. El análisis de fase podría ser una herramienta válida para evaluar la disincronía asociada al infarto en pacientes con marcapasos, y aportar a la indicación oportuna del pasaje (upgrading) al modo de estimulación biventricular.

Abstract: Objetive: To evaluate left ventricular mechanical dyssynchrony (LVMD) associated with prolonged right ventricular pacing through an innovative imaging technique as a pilot study in Uruguay. Methods: A 99mTc-MIBI gated-SPECT and phase analysis was performed in 12 patients with pace-makers implanted at least one year before scintigraphy, due to advanced atrioventricular block. Clinical data, QRS duration, rate, mode and site of pacing in right ventricle, chamber diameters, presence and extension of myocardial scar and ischaemia, as well as LVEF at rest, were recorded. Using V-Sync of Emory Cardiac Toolbox, a standard deviation (PSD) and band-width (PBW) from rest phase histogram was obtained and these indexes were compared with controls in the subgroups of patients with LVEF ≥ 50% and < 50%. Results: Patients with prolonged RV endocardial pacing exhibited marked LVMD. More severe dyssynchrony was found in patients with impaired LVEF than in patients with preserved LVEF (PSD: 46.67o vs. 26.81o, P < .05; PBW: 144.33o vs. 77.41o, P < .05). Higher left ventricle diameters, extensive infarct, or significant ischaemia were found in patients with impaired LVEF. Conclusions: Chronic right ventricular pacing was invariably associated with LVMD, even when systolic function was preserved. Phase analysis could be a potentially useful technique to evaluate LMVD associated with myocardial scar in patients with pacemakers, and to decide promptly the upgrading to biventricular pacing.

Tasa de angiografías coronarias sin lesiones ("en blanco") de indicación electiva tras estudios funcionales / Rate of coronary angiography without lesions ("blank") of elective indication after functional studies

Antecedentes: aunque la cineangiocoronariografía (CACG) sigue siendo el "patrón oro" diagnóstico en la enfermedad coronaria, la optimización de sus indicaciones electivas obliga a revisar sistemáticamente los resultados de los estudios funcionales de detección de isquemia. Objetivo: analizar la tasa de angiografías sin obstrucciones coronarias epicárdicas ("en blanco") de indicación electiva tras estudios funcionales. Material y método: se realizó un estudio observacional analítico y transversal, analizando las CACG electivas realizadas en 2011-2014 en el servicio de hemodinamia público del país. Se registraron variables clínicas, indicación y resultados de la interpretación angiográfica en los pacientes que fueron estudiados previamente mediante pruebas no invasivas para detección de isquemia. La ausencia de estenosis coronaria significativa fue definida como la presencia de estenosis luminal <50%. Se excluyeron las indicaciones electivas por preoperatorio de valvulopatías, disfunción sistólica severa y arritmias ventriculares, y los pacientes con antecedentes de intervencionismo coronario percutáneo o cirugía de bypass coronario. Resultados: se incluyeron los resultados de las CACG electivas en 219 pacientes con pruebas funcionales previas. La tasa de CACG "en blanco" fue de 35,62%. Las variables asociadas con la presencia de lesiones coronarias angiográficas fueron: el sexo masculino (OR=2,22, IC 95%: 1,26-3,92), la edad ³65 años (OR=2,09, IC 95%: 1,19-3,69), la diabetes (OR=2,94, IC 95%: 1,52-45,65) y un resultado funcional de moderado/alto riesgo (OR=22,99, IC 95%: 2,90-181,80). En contraposición, un resultado funcional normal/de bajo riesgo se asoció con la ausencia de lesiones angiográficas (OR=0,04, IC 95%: 0,005-0,34). La población de pacientes estudiados previamente mediante ecocardiografía de estrés fue poco representativa (5,02%). Conclusiones: en un centro universitario público de referencia la tasa de angiografías coronarias electivas "en blanco" es acorde con lo reportado en los grandes estudios multicéntricos.

Background: although coronary angiography is still the "gold standard" diagnostic of coronary artery disease, a systematic review of its elective indications after noninvasive (functional) tests is needed. Objective: to analyze through functional tests the rate of nonobstructive ("blank") elective coronary angiography (CA) in patients previously studied through noninvasive (functional) tests. Methods: we performed an observational analytic and cross-sectional study analyzing elective CA performed in 2011-2014 in a nationwide public hemodynamic service. Clinical data indications and results of angiographic interpretation were recorded in the subjects previously studied through noninvasive (functional) tests. Elective indications corresponding to preoperative evaluation of valvular disease, severe systolic dysfunction, ventricular arrhytmias, previous history of angioplasty or coronary artery bypass surgery were excluded. We defined the absence of significant coronary stenosis as those lesions determining a luminal stenosis <50%. Results: we analyzed the results of 219 functional tests. The rate of CA without significant coronary stenosis was 35,62%. Male gender (OR=2,22, IC 95%: 1,26-3,92), age >65 years (OR=2,09, IC 95%:1,19-3,69), diabetes (OR=2,94, IC 95%: 1.52-45,65) and a moderate/high risk functional test outcome (OR=22,99, IC 95%: 2,90-181,80) were positively associated with angiographic lesions. In contrast, a normal/low risk functional outcome was associated with the absence of coronary stenosis (OR=0,04, IC 95%: 0,005-0,34). The sample of patients studied through stress-ECHO was not representative (5,02%). Conclusions: in a nationwide public university center, the rate of "blank" elective coronary angiography after functional tests is similar to large international multicenter studies.

Unusual Dipyridamole-induced Aberrant Conduction in the Absence of Myocardial Ischemia.

We report two patients referred to 2 day stress-rest single photon emission computed tomography for diagnosis of ischemia who elicited a transient left bundle branch block during dipyridamole intravenous infusion. The conduction disturbance disappeared after aminophyline infusion and became permanent during follow-up. Possible mechanisms underlying this unusual phenomenon in the absence of myocardial ischemia are discussed.

[Ischemic T wave distortion associated with vasodilator-stress myocardial perfusion imaging]. / Distorsión morfológica isquémica de la onda T en la centellografía de perfusión miocárdica con estrés vasodilatador.

The protocols using vasodilators to induce ischemia on myocardial perfusion scintigraphy have shown a high diagnostic accuracy and a very low incidence of serious complications. However, the physiological significance and diagnostic value of various electrocardiographic changes associated with vasodilator stress has not been deeply evaluated beyond the ST-segment. Five clinical cases presenting morphological distortion of the T-wave in electrocardiographic chest leads associated with varying degrees of perfusion defects are described, discussing potential contributions of these changes to the diagnosis and quantification of myocardial ischemia in imaging studies using vasodilator stress.

Distorsión morfológica isquémica de la onda T en la centellografía de perfusión miocárdica con estrés vasodilatador / Ischemic T wave distortion associated with vasodilator-stress myocardial perfusion imaging

Los protocolos que utilizan vasodilatadores para inducir isquemia en la centellografía de perfusión miocárdica han demostrado una exactitud diagnóstica elevada e incidencia muy baja de complicaciones graves. Sin embargo, el significado fisiológico y valor diagnóstico de diversas alteraciones electrocardiográficas asociadas al estrés vasodilatador ha sido escasamente evaluado más allá del segmento ST. Describimos cinco pacientes que presentan distorsión morfológica de la onda T en derivaciones electrocardiográficas torácicas asociada a diversos defectos de perfusión, discutiendo los potenciales aportes de estos cambios al diagnóstico y cuantificación de la isquemia miocárdica en los estudios de imagen que utilizan estrés con vasodilatadores.

The protocols using vasodilators to induce ischemia on myocardial perfusion scintigraphy have shown a high diagnostic accuracy and a very low incidence of serious complications. However, the physiological significance and diagnostic value of various electrocardiographic changes associated with vasodilator stress has not been deeply evaluated beyond the ST-segment. Five clinical cases presenting morphological distortion of the T-wave in electrocardiographic chest leads associated with varying degrees of perfusion defects are described, discussing potential contributions of these changes to the diagnosis and quantification of myocardial ischemia in imaging studies using vasodilator stress.

Atrial Arrhythmias and Scintigraphic "D-shape" Sign in Pulmonary Artery Hypertension.

Pulmonary hypertension significantly changes biventricular anatomy and physiology, frequently evolving to clinical deterioration and right ventricular failure. The case of a woman developing atrial arrhythmias complicating dipyridamole stress in concomitance with scintigraphic "D-shaped" left ventricle is briefly reported. Although rare, our finding may suggest that nonselective vasodilators should be used with caution in this clinical setting.

[Effects of prolonged endocardial stimulation on left ventricular mechanical synchrony. A pilot study applying gated-SPECT phase analysis. Endocardial stimulation and dyssynchrony]. / Efectos de la estimulación endocárdica prolongada sobre la sincronía mecánica ventricular izquierda. Ensayo piloto aplicando análisis de fase por tomografía computada por emisión de fotón único gatillada. Estimulación prolongada y disincronía mecánica.

OBJETIVE: To evaluate left ventricular mechanical dyssynchrony (LVMD) associated with prolonged right ventricular pacing through an innovative imaging technique as a pilot study in Uruguay. METHODS: A 99mTc-MIBI gated-SPECT and phase analysis was performed in 12 patients with pace-makers implanted at least one year before scintigraphy, due to advanced atrioventricular block. Clinical data, QRS duration, rate, mode and site of pacing in right ventricle, chamber diameters, presence and extension of myocardial scar and ischaemia, as well as LVEF at rest, were recorded. Using V-Sync of Emory Cardiac Toolbox, a standard deviation (PSD) and bandwidth (PBW) from rest phase histogram was obtained and these indexes were compared with controls in the subgroups of patients with LVEF≥50% and <50%. RESULTS: Patients with prolonged RV endocardial pacing exhibited marked LVMD. More severe dyssynchrony was found in patients with impaired LVEF than in patients with preserved LVEF (PSD: 46.67o vs. 26.81o, P<.05; PBW: 144.33o vs. 77.41o, P<.05). Higher left ventricle diameters, extensive infarct, or significant ischaemia were found in patients with impaired LVEF. CONCLUSIONS: Chronic right ventricular pacing was invariably associated with LVMD, even when systolic function was preserved. Phase analysis could be a potentially useful technique to evaluate LMVD associated with myocardial scar in patients with pacemakers, and to decide promptly the upgrading to biventricular pacing.

[Left ventricular dyssynchrony in prolonged septal stimulation]. / Disincronía ventricular izquierda en la estimulación septal prolongada.

Pacemaker stimulation is associated with unpredictable severe cardiac events. We evaluated left ventricular mechanical dyssynchrony (LVMD) during prolonged septal right ventricular pacing. We performed 99mTc-MIBI gated-SPECT and phase analysis in 6 patients with pacemakers implanted at least one year before scintigraphy due to advanced atrioventricular block. Using V-Sync of Emory Cardiac Toolbox we obtained phase bandwidth (PBW) and standard deviation (PSD) from rest phase histogram. Clinical variables, QRS duration, rate and mode of pacing in septal right ventricle wall, chamber diameters, presence and extension of myocardial scar and ischemia and rest LVEF were recorded. Prolonged septal endocardial pacing is associated with marked LVMD, even when systolic function was preserved. More severe dyssynchrony was found in patients with impaired LVEF, higher left ventricle diameters, extensive infarct or severe ischemia than in patients with preserved LVEF (PBW: 177.3o vs. 88.3o; PSD: 53.1o vs. 33.8o). In the patients with ischemic heart disease and pacemaker, gated-SPECT phase analysis is a valid and potentially useful technique to evaluate LMVD associated with myocardial scar and to decide the upgrading to biventricular pacing mode.

Disincronía ventricular izquierda en la estimulación septal prolongada / Left ventricular dyssynchrony in prolonged septal stimulation

La estimulación por marcapasos se asocia con eventos adversos graves. En la siguiente serie de casos se evaluó la disincronía mecánica intraventricular izquierda (DMVI) en la estimulación endocárdica prolongada del ventrículo derecho a nivel septal. Se estudiaron 6 personas con marcapasos implantados no antes de un año utilizando SPECT gatillado con 99mTc-MIBI y análisis de fase en reposo. Se registraron variables clínicas, duración del QRS, tasa y modo de estimulación ventricular, presencia y extensión de isquemia y/o infarto, volúmenes cavitarios y FEVI en reposo. Utilizando V-Sync de Emory Cardiac Toolbox se obtuvieron el ancho de banda (AB) y el desvío estándar de fase (DEF) en reposo (grados), comparándolos con una población control. La estimulación endocárdica prolongada en el septum ventricular derecho se asoció con marcada DMVI, aun cuando la función sistólica estaba conservada. Aquellos con FEVI moderada/gravemente disminuida (caracterizados por diámetros cavitarios mayores, infarto o isquemia grave) exhibieron mayor disincronía que aquellos con FEVI conservada/levemente disminuida (AB: 177.3o vs. 88.3o; DEF: 53.1o vs. 33.8o). En los casos con cardiopatía isquémica portadores de marcapasos, el AF es una herramienta válida de potencial utilidad para evaluar la disincronía asociada al infarto y, eventualmente, aportar a la decisión oportuna del pasaje al modo de estimulación biventricular.

Pacemaker stimulation is associated with unpredictable severe cardiac events. We evaluated left ventricular mechanical dyssynchrony (LVMD) during prolonged septal right ventricular pacing. We performed 99mTc-MIBI gated-SPECT and phase analysis in 6 patients with pacemakers implanted at least one year before scintigraphy due to advanced atrioventricular block. Using V-Sync of Emory Cardiac Toolbox we obtained phase bandwidth (PBW) and standard deviation (PSD) from rest phase histogram. Clinical variables, QRS duration, rate and mode of pacing in septal right ventricle wall, chamber diameters, presence and extension of myocardial scar and ischemia and rest LVEF were recorded. Prolonged septal endocardial pacing is associated with marked LVMD, even when systolic function was preserved. More severe dyssynchrony was found in patients with impaired LVEF, higher left ventricle diameters, extensive infarct or severe ischemia than in patients with preserved LVEF (PBW: 177.3o vs. 88.3o; PSD: 53.1o vs. 33.8o). In the patients with ischemic heart disease and pacemaker, gated-SPECT phase analysis is a valid and potentially useful technique to evaluate LMVD associated with myocardial scar and to decide the upgrading to biventricular pacing mode.

Human Mesenchymal Stromal Cells Improve Cardiac Perfusion in an Ovine Immunocompetent Animal Model.

BACKGROUND: Mesenchymal stromal cells (MSCs) hold considerable promise in the treatment of ischemic heart disease. Most preclinical studies of MSCs for acute myocardial infarction (AMI) have been performed either in syngeneic animal models or with human cells in xenogeneic immunodeficient animals. A preferable pre-clinical model, however, would involve human MSCs in an immunocompetent animal. METHODS: AMI was generated in adult sheep by inducing ischemia reperfusion of the second diagonal branch. Sheep (n = 10) were randomized to receive an intravenous injection of human MSCs (1 × 10(6) cells/kg) or phosphate buffered saline. Cardiac function and remodeling were evaluated with echocardiography. Perfusion scintigraphy was used to identify sustained myocardial ischemia. Interaction between human MSCs and ovine lymphocytes was assessed by a mixed lymphocyte response (MLR). RESULTS: Sheep receiving human MSCs showed significant improvement in myocardial perfusion at 1 month compared with baseline measurements. There was no change in ventricular dimensions in either group after 1 month of AMI. No adverse events or symptoms were observed in the sheep receiving human MSCs. The MLR was negative. CONCLUSION: The immunocompetent ovine AMI model demonstrates the clinical safety and efficacy of human MSCs. The human cells do not appear to be immunogenic, further suggesting that immunocompetent sheep may serve as a suitable pre-clinical large animal model for testing human MSCs.

Ischemia-induced model of diastolic dysfunction in sheep.

BACKGROUND: Ischemic heart failure with normal ejection fraction (HFNEF) is an increasingly recognized entity that carries similar morbidity and mortality than low ejection fraction heart failure. Animal models of diastolic dysfunction mimicking this condition are lacking and are essential for the development of therapeutic strategies. METHODS AND RESULTS: Eight Corriedale sheep, 18 ± 5 months old, were included in the study. Basal echocardiography and myocardial perfusion evaluation (SPECT) was performed. Acute myocardial infarction (AMI) was made by occlusion (90 min) and reperfusion of the second diagonal branch of the anterior descending coronary artery. Two months after AMI, echocardiography and SPECT evaluation were performed prior to sacrifice. Basal and 2 months echocardiography showed similar fractional shortening and ventricular dimensions in each animal except for an increase in left atrial diameter. No mitral regurgitation was evidenced. SPECT imaging and pathology confirmed infarction in the apical, apico-anterior, and apico-septal segments. CONCLUSION: A novel model of ischemia-induced diastolic dysfunction with preserved ventricular thickness and ejection fraction is described. This model opens the possibility of testing therapeutic options for patients with this condition.

El consumo crónico de clorhidrato y/o pasta base de cocaína asocia envejecimiento arterial prematuro y aumento del riesgo cardiovascular / Chronic consumption of hydrochloride and / or cocaine base paste associates premature arterial aging and increased cardiovascular risk

Introducción: el consumo de cocaína en forma de clorhidrato (CC), y especialmente de su pasta base (PBC), es un problema sanitario mayor, entre otros factores, por su incidencia, repercusión y franja etaria a la que involucra. Múltiples efectos cardiovasculares han sido descritos en asociación con el consumo de CC, pero el impacto a corto/mediano plazo del uso crónico de CC y PBC en el sistema arterial en sujetos jóvenes no se ha estudiado. Objetivo: determinar la prevalencia de cambios (alteraciones) arteriales estructurales y/o funcionales en jóvenes consumidores de cocaína o sus derivados. Material y método: se incluyeron 29 sujetos (27 hombres; edad media/rango: 29/20-35 años) con criterios toxicológicos de dependencia a cocaína, más de dos años de consumo, y abstinencia menor a un mes. Se realizó evaluación clínica y paraclínica para cuantificar el riesgo cardiovascular global (escore de riesgo de Framingham [EF] para enfermedad cardiovascular a diez años). Los estudios incluyeron determinación de: 1) presencia de placas de ateroma carotídeas y espesor íntima-media carotídeo (EIMC; ecografía modo-B color y software específico). 2) Rigidez aórtica regional (mediante velocidad de la onda del pulso, [VOP]). 3) Presión de pulso aórtica central (tonometría de aplanamiento). 4) Índice tobillo-brazo (oscilometría). 5) Reactividad vascular, función endotelial, por vasodilatación mediada por flujo (DMF; ecografía modo-B y software específico). Se determinó la edad vascular (EV) mediante análisis multiparamétrico. El envejecimiento arterial precoz (EAP) se definió como la diferencia entre la EV y la edad cronológica. Los datos obtenidos se compararon con valores de normalidad (sujetos control). Resultados: de los 29 pacientes, 10 fueron consumidores de CC, 3 de PBC y 16 de ambas sustancias. El 90% eran fumadores de cigarrillos (promedio de consumo: 14,4 cigarrillos/día). Si bien ningún paciente presentó VOP >10 m/s (punto de normalidad aceptado por la Sociedad Europea de Cardiología), 63,6% tuvo niveles de VOP entre el percentil (p)50 y el p90 de la población control de referencia, y 13,6% por encima del p90 de la misma población, indicando que el 77,2% de los mismos presentaron VOP >p50. Respecto del EIMC, un 8% de los pacientes estudiados tuvo niveles > 0,9 mm, y 69% niveles por encima del p95 de la población de referencia, para sexo y edad.. El análisis de la función endotelial mostró que 13,6% de los pacientes no presentó dilatación arterial (DMF £ 0%) y 36% presentó DMF £ 5%. Finalmente, el 33% de los pacientes presentó niveles de presión de pulso aórtica por encima del nivel umbral (p95), para sexo y edad. La EA fue de 37,1 ± 8,4 años, indicando la existencia de un EAP de 8,1 ± 6,2 años (rango: 3-24 años). Conclusión: los usuarios de cocaína mostraron cambios subclínicos perjudiciales a nivel arterial que se asocian a mayor riesgo cardiovascular. Sus parámetros arteriales presentaron niveles compatibles con los existentes en una población control con una edad de 8,1 ± 6,2 años mayor que la estudiada, indicando que los consumidores de CC y PBC podrían presentar "envejecimiento arterial precoz".

Introduction: cocaine consumption, in particular cocaine base paste, is a major health problem, among other factors, its incidence, impact, and the age group involved. Multiple cardiovascular effects have been described in association with cocaine use but the impact in the short/medium-term chronic use of hydrochloride cocaine and cocaine base paste in the arterial system in young subjects has not been studied.Objective: to determine the prevalence of changes (alterations) arterial structural and/or functional in young cocaine or its derivatives users Method: 29 subjects (age: 20-35 years; 27 men) with toxicological criteria for cocaine dependence, over 2 years old and less than one month withdrawal were included. Clinical and paraclinical evaluation was conducted to quantify the global cardio-vascular risk (10-years Framingham Risk Score for cardiovascular disease). The studies included determination of: 1) presence of carotid atheromatous plaques and carotid intima-media thickness (CIMT; color and B-mode ultra sound and specific software), 2) assessment of regional aortic stiffness by pulse wave velocity (PWV), 3) evaluation of central aortic pulse pressure by applanation tonometry, 4) ankle-brachial index, by oscillometry and 5) vascular reactivity (endothelial function) by flow mediated dilatation (FMD) with B-mode ultra sound and specific software. The vascular age (VA) was calculated by multiparametric analysis. The arterial aging (AA) was defined as the difference between the VA and chronological age. The obtained data were compared with normal values (control subjects). Results: 29 patients were evaluated, 10 patients were users of hydrochloride cocaine, 3 cocaine base paste and 16 of both substances. 90% of patients were smokers (mean consumption: 14.4 cigarettes/day). Although no patient had PWV values above 10 m/s, 63,6% had levels of PWV between p50 and p90 and 13,6% above the p90, indicating that 77% of them presented by PWV over p50. Regarding the CIMT, 8% of the patients studied had levels above 0,9 mm, and 69% higher than p75 levels to age and sex. The endothelial function analysis showed that 13,6% of patients had no arterial dilation (FMD £ 0%) and 36% presented a £ 5% FMD. Finally, 33% of patients had levels of aortic pulse pressure above the threshold level (p95 of the reference control group) for gender and age. The AA was 37.1±8.4 years, indicating the existence of early arterial aging 8.1±6.2 years (range 3-24 years). Conclusion: cocaine users showed adverse subclinical level changes of the structure and function of the arteries which is associated with increased cardiovascular risk. The levels obtained for different arterial parameters evaluated were consistent with those in a control population with an age 8.1±6.2 years older than the study, indicating that users of hydrochloride cocaine and cocaine base paste might present "early arterial aging."

Integrated software for the detection of epileptogenic zones in refractory epilepsy.

In this paper we present an integrated software designed to help nuclear medicine physicians in the detection of epileptogenic zones (EZ) by means of ictal-interictal SPECT and MR images. This tool was designed to be flexible, friendly and efficient. A novel detection method was included (A-contrario) along with the classical detection method (Subtraction analysis). The software's performance was evaluated with two separate sets of validation studies: visual interpretation of 12 patient images by an experimented observer and objective analysis of virtual brain phantom experiments by proposed numerical observers. Our results support the potential use of the proposed software to help nuclear medicine physicians in the detection of EZ in clinical practice.