Utility of 18F-FDG-PET/CT in patients suspected of paraneoplastic neurological syndrome: importance of risk classification

Purpose. To assess the diagnostic impact of 18F-FDG-PET/CT in patients suspected of paraneoplastic neurological syndrome (PNS) based on our own pre-test risk classification (PRC). Methods. A multicenter retrospective longitudinal study was conducted from 2006 to 2014. We designed a seven-point scoring system using the clinical syndrome characteristics [classical (CS) and non-classical syndromes (NCS)] and its location (central, peripheral, in the neuromuscular junction or combined), onconeural antibodies and tumor markers. Patients were classified as low (score 0-2), intermediate (3-4) and high (5-7) pre-test risk of PNS. FDG-PET/CT was classified as negative or positive. Final diagnosis according Graus’ criteria (definite, possible or no PNS) was established. Relations between clinical and metabolic variables with the final diagnosis were studied. Results. 73 patients were included, with a follow-up time of 33 months. Eleven (15 %) patients were finally diagnosed with neoplasm (8 invasive cancers). Ultimately, 13 (18 %) and 24 (33 %) subjects were diagnosed as definite or possible PNS. All the patients with final diagnosis of neoplasm had a CS (p = 0.005). PET/CT was helpful to diagnose 6/8 (75 %) invasive cancers. PET/CT findings were associated with the final diagnosis of neoplasm (p = 0.003) and the diagnosis of PNS attending to Graus’ criteria (p = 0.019). PRC showed significant association with the final diagnosis of neoplasm and PET/CT results. A majority of patients (10/11) diagnosed of neoplasm had intermediate/high-risk. Conclusions. Our PRC seems to be a valid tool to select candidates for PET/CT imaging in this setting. PET/CT detected malignancy in a significant proportion of patients with invasive cancer (AU)

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Utility of 18F-FDG-PET/CT in patients suspected of paraneoplastic neurological syndrome: importance of risk classification.

PURPOSE: To assess the diagnostic impact of 18F-FDG-PET/CT in patients suspected of paraneoplastic neurological syndrome (PNS) based on our own pre-test risk classification (PRC). METHODS: A multicenter retrospective longitudinal study was conducted from 2006 to 2014. We designed a seven-point scoring system using the clinical syndrome characteristics [classical (CS) and non-classical syndromes (NCS)] and its location (central, peripheral, in the neuromuscular junction or combined), onconeural antibodies and tumor markers. Patients were classified as low (score 0-2), intermediate (3-4) and high (5-7) pre-test risk of PNS. FDG-PET/CT was classified as negative or positive. Final diagnosis according Graus' criteria (definite, possible or no PNS) was established. Relations between clinical and metabolic variables with the final diagnosis were studied. RESULTS: 73 patients were included, with a follow-up time of 33 months. Eleven (15 %) patients were finally diagnosed with neoplasm (8 invasive cancers). Ultimately, 13 (18 %) and 24 (33 %) subjects were diagnosed as definite or possible PNS. All the patients with final diagnosis of neoplasm had a CS (p = 0.005). PET/CT was helpful to diagnose 6/8 (75 %) invasive cancers. PET/CT findings were associated with the final diagnosis of neoplasm (p = 0.003) and the diagnosis of PNS attending to Graus' criteria (p = 0.019). PRC showed significant association with the final diagnosis of neoplasm and PET/CT results. A majority of patients (10/11) diagnosed of neoplasm had intermediate/high-risk. CONCLUSIONS: Our PRC seems to be a valid tool to select candidates for PET/CT imaging in this setting. PET/CT detected malignancy in a significant proportion of patients with invasive cancer.

PET/TC con 18F-FDG en la valoración de pacientes con sospecha de síndrome paraneoplásico neurológico / 18F-FDG PET/CT in the evaluation of patients suspected of paraneoplastic neurological syndrome

Objetivo. Definir el impacto diagnóstico de la PET/TC con 18F-FDG en función de las características clínicas del síndrome paraneoplásico neurológico (SPN). Material y métodos. Estudio retrospectivo multicéntrico y longitudinal de pacientes con sospecha de SPN. El cuadro clínico se clasificó en síndrome clásico (SC) o no clásico (SNC). Tras el seguimiento se estableció el diagnóstico de SPN definitivo o posible. Los cuadros que no encajaron en ninguna de las categorías previas se catalogaron como no clasificables. Se analizó el estado de los anticuerpos onconeuronales. La PET/TC se clasificó en positiva o negativa para la detección de malignidad. Se determinó la relación entre los hallazgos PET/TC y el diagnóstico final. Se analizaron las diferencias entre variables (Chi cuadrado de Pearson) y la relación entre el resultado de la PET/TC y el diagnóstico definitivo. Resultados. Se analizaron 64 pacientes. El 30% de los cuadros clínicos se catalogaron como SC y el 42% como SNC. Tras el seguimiento el 20% se clasificó en SPN posible y el 16% en definitivo. El 13% de los pacientes tenía anticuerpos onconeuronales positivos. El hecho de poseer un SPN definitivo se relacionó con un resultado positivo de la PET/TC (p = 0,08). Se demostró relación significativa entre la positividad de los anticuerpos y el diagnóstico final de proceso neoplásico (p = 0,04). La PET/TC fue eficaz en la correcta localización tumoral en 5/7 casos con cáncer invasivo. Conclusiones. La PET-TC mostró un mayor porcentaje de resultados positivos en pacientes con diagnóstico de SPN definitivo. A pesar de la baja prevalencia de malignidad en nuestra serie, la PET/TC detectó malignidad en una significativa proporción de pacientes con cáncer invasivo (AU)

Objective. This study aimed to determine the diagnostic impact of 18F-FDG PET/CT based on the clinical features of paraneoplastic neurological syndrome (PNS). Material and methods. Multicenter retrospective and longitudinal study of patients with suspicion of PNS. The clinical picture was classified into classic (CS) and non-classic syndrome (NCS). After the follow-up, the definitive or possible diagnosis of PNS was established. The pictures that did not match any of the previous criteria were categorized as non-classifiable. The state of the onco-neural antibodies was studied. The PET/CT was classified as positive or negative for the detection of malignancy. The relationship between PET/CT findings and the final diagnosis was determined. The differences between variables (Pearson test X2) and the relationship between the results of the PET/CT and the final diagnosis were analyzed. Results. A total of 64 patients were analyzed, classifying 30% as CS and 42% as NCS. After the follow-up, 20% and 16% of subjects were diagnosed as possible and definitive PNS, respectively. Positive onco-neural antibodies were found in 13% of the patients. A definitive diagnosis of PNS was associated with a positive PET/CT (P = .08). A significant relation between antibodies expression and final diagnosis of neoplasia (P = .04) was demonstrated. The PET/CT correctly localized malignancy in 5/7 cases of invasive cancer. Conclusions. The PET/CT showed a higher percentage of positive results in patients with definitive diagnosis of PNS. Despite the low prevalence of malignancy in our series, the PET/CT detected malignancy in a significant proportion of patients with invasive cancer (AU)

[(18)F-FDG PET/CT in the evaluation of patients suspected of paraneoplastic neurological syndrome]. / PET/TC con (18)F-FDG en la valoración de pacientes con sospecha de síndrome paraneoplásico neurológico.

OBJECTIVE: This study aimed to determine the diagnostic impact of (18)F-FDG PET/CT based on the clinical features of paraneoplastic neurological syndrome (PNS). MATERIAL AND METHODS: Multicenter retrospective and longitudinal study of patients with suspicion of PNS. The clinical picture was classified into classic (CS) and non-classic syndrome (NCS). After the follow-up, the definitive or possible diagnosis of PNS was established. The pictures that did not match any of the previous criteria were categorized as non-classifiable. The state of the onco-neural antibodies was studied. The PET/CT was classified as positive or negative for the detection of malignancy. The relationship between PET/CT findings and the final diagnosis was determined. The differences between variables (Pearson test X(2)) and the relationship between the results of the PET/CT and the final diagnosis were analyzed. RESULTS: A total of 64 patients were analyzed, classifying 30% as CS and 42% as NCS. After the follow-up, 20% and 16% of subjects were diagnosed as possible and definitive PNS, respectively. Positive onco-neural antibodies were found in 13% of the patients. A definitive diagnosis of PNS was associated with a positive PET/CT (P=.08). A significant relation between antibodies expression and final diagnosis of neoplasia (P=.04) was demonstrated. The PET/CT correctly localized malignancy in 5/7 cases of invasive cancer. CONCLUSIONS: The PET/CT showed a higher percentage of positive results in patients with definitive diagnosis of PNS. Despite the low prevalence of malignancy in our series, the PET/CT detected malignancy in a significant proportion of patients with invasive cancer.

Change of the melanocortin system caused by bilateral subthalamic nucleus stimulation in Parkinson's disease.

OBJECTIVES - Determine whether bilateral subthalamic nucleus stimulation (STN-DBS) in Parkinson's disease (PD) is associated with an increase in neuropeptide Y (NPY) and/or resistance to inhibition by leptin in relation to post-surgery weight gain. MATERIALS AND METHODS - This prospective study included 20 patients who underwent bilateral STN-DBS and 17 who refused surgery. Data were obtained at baseline, 3 and 6 months on neurological and nutritional status, including determination of body mass index (BMI) and serum NPY and leptin levels. RESULTS - NPY and leptin levels changed over time, with a distinct pattern. The BMI increase at 6 months was greater in the surgical group (5.5 ± 6.3% vs 0.5 ± 3.5%; P = 0.035). Medical group exhibited a reduction in leptin level (-2.0 ± 4.3 ng/ml) and a consequent increase in NPY level (72.4 ± 58.7 pmol/ml). However, STN-DBS patients showed an increase in leptin (3.1 ± 5.0 ng/ml; P = 0.001 vs medical group) and also in NPY (12.1 ± 53.6 pmol/ml; P = 0.022 vs medical group) levels, which suggests resistance to inhibition by leptin. Rise in NPY level correlated with higher stimulation voltages. CONCLUSIONS - Bilateral STN-DBS causes disruption of the melanocortin system, probably related to diffusion of the electric current to the hypothalamus. This mechanism may in part explain the weight gain of patients with PD after surgery.

[Diagnostic value of cardiac 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy in Lewy body disorders]. / Valor diagnóstico de la gammagrafía cardíaca con 123I-metaiodobenzilguanidina en las enfermedades con cuerpos de Lewy.

INTRODUCTION: Lewy body disorders such as Parkinson's disease (PD) and Lewy body dementia (LBD) are associated with cardiac sympathetic denervation, which can be visualized on 123I-MIBG scintigraphy. Our objectives were to study the diagnostic value of this technique in Lewy body disorders and its relationship with PD clinical variables. PATIENTS AND METHODS: We studied 90 patients: 51 with PD, 19 with LBD, 9 with multiple system atrophy (MSA) and 11 controls. Scintigraphy images were qualitatively evaluated and early and delayed heart-to-mediastinum ratios (HMR) were calculated. The main confounding factors (ischemic heart disease, diabetes, hypertension and drugs) were controlled by multivariate linear regression analysis. We investigated correlations between scintigraphy variables and PD variables. RESULTS: The delayed HMR, which showed better discriminative ability was 2.03 +/- 0.32 in controls, 1.37 +/- 0.30 in PD (p<0.001 vs controls), 1.47+/-0.45 in LBD (p=0.001 vs controls) and 1.69+/-0.28 in MSA (p=0.02 vs controls; p=0.004 vs PD). This ratio was influenced by PD/LBD diagnosis (beta= -0.638; p<0.001) and to a lesser degree, by ischemic heart disease (beta= -0.244; p=0.028). Optimal cut-off value between PD/LBD and controls was 1.71 (83% sensitivity and 82% specificity). Within the PD group, those with a family history of PD/LB showed higher delayed HMR values (1.65+/-0.34 vs 1.30+/-0.24 without history; p<0.001) and proportion with normal scintigraphy (56% vs 5%; p=0.001). CONCLUSIONS: Cardiac 123I-MIBG scintigraphy is useful in the diagnosis of Lewy body disorders, although its value in PD is conditioned by having a family history of PD.

Valor diagnóstico de la gammagrafíacardíaca con 123I-metaiodobenzilguanidinaen las enfermedades con cuerpos de Lewy / Diagnostic value of cardiac 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy in Lewy body disorders

Introducción. Enfermedades con cuerpos de Lewy (ECL), como laenfermedad de Parkinson (EP) y la demencia con cuerpos de Lewy(DCL), asocian una denervación simpática cardíaca que puede evidenciarsemediante gammagrafía con 123I-metaiodobenzilguanidina(123I-MIBG). Nuestros objetivos fueron estudiar su valor diagnósticoen las ECL y su relación con variables clínicas de la EP.Pacientes y métodos. Estudiamos 90 pacientes: 51 con EP, 19 conDCL, 9 con atrofia multisistémica (AMS) y 11 controles. Se realizó valoracióncualitativa de la gammagrafía y se calcularon los índices corazón/mediastino (ICM) precoz y tardío. Los principales factores deconfusión (cardiopatía isquémica, diabetes, hipertensión y fármacos)se controlaron mediante regresión lineal multivariante. Efectuamoscorrelaciones entre las variables gammagráficas y del grupo con EP.Resultados. El ICM tardío, con mayor capacidad discriminativa,fue 2,03±0,32 en los controles, 1,37±0,30 en EP (p<0,001 vs controles),1,47±0,45 en DCL (p=0,001 vs controles) y 1,69±0,28 enAMS (p=0,02 vs controles; p=0,004 vs EP). En este índice influía eldiagnóstico de ECL (ß=–0,638; p<0,001) y en menor grado la cardiopatíaisquémica (ß=–0,244; p=0,028). Identificamos el valor 1,71como mejor punto de corte entre ECL y controles (sensibilidad 83%y especificidad 82%). Dentro del grupo con EP, aquellos con antecedentesfamiliares de EP mostraron mayores ICM tardío (1,65±0,34 vs1,30±0,24 sin antecedentes; p<0,001) y proporción de gammagrafíasnormales (56% vs 5%; p=0,001).Conclusiones. La gammagrafía cardíaca con 123I-MIBG es útilen el diagnóstico de ECL, si bien, en la EP su valor está condicionadopor el hecho de tener historia familiar de la enfermedad (AU)

Introduction. Lewy body disorders such as Parkinson’s disease(PD) and Lewy body dementia (LBD) are associated withcardiac sympathetic denervation, which can be visualized on123I-MIBG scintigraphy. Our objectives were to study the diagnosticvalue of this technique in Lewy body disorders and its relationshipwith PD clinical variables.Patients and methods. We studied 90 patients: 51 with PD,19 with LBD, 9 with multiple system atrophy (MSA) and 11 controls.Scintigraphy images were qualitatively evaluated and earlyand delayed heart-to-mediastinum ratios (HMR) were calculated.The main confounding factors (ischemic heart disease, diabetes,hypertension and drugs) were controlled by multivariate linearregression analysis. We investigated correlations between scintigraphyvariables and PD variables.Results. The delayed HMR, which showed better discriminativeability was 2.03 ± 0.32 in controls, 1.37 ± 0.30 in PD(p<0.001 vs controls), 1.47±0.45 in LBD (p=0.001 vs controls) and1.69±0.28 in MSA (p=0.02 vs controls; p=0.004 vs PD). This ratiowas influenced by PD/LBD diagnosis (ß=–0.638; p<0.001)and to a lesser degree, by ischemic heart disease (ß = –0.244;p=0.028). Optimal cut-off value between PD/LBD and controlswas 1.71 (83% sensitivity and 82% specificity). Within the PDgroup, those with a family history of PD/LB showed higher delayedHMR values (1.65±0.34 vs 1.30±0.24 without history; p<0.001)and proportion with normal scintigraphy (56% vs 5%; p=0.001).Conclusions. Cardiac 123I-MIBG scintigraphy is useful in thediagnosis of Lewy body disorders, although its value in PD isconditioned by having a family history of PD (AU)