RESUMEN
Bone marrow metastases-noted in 6% of patients with rhabdomyosarcoma-have been linked to very poor outcomes. Bilateral bone marrow sampling from iliac crests has been the gold standard for bone marrow examination in rhabdomyosarcoma, but sampling errors due to patchy bone marrow involvement may limit its sensitivity. Here, we report the case of a 6-year-old boy with embryonal rhabdomyosarcoma of the skull base and multiple 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG)-avid bone marrow metastases visualized by positron emission tomography and computed tomography (2-[18F]FDG PET/CT). His bone marrow aspirates were tumor-free. This case illustrates the diagnostic value of 2-[18F]FDG PET/CT in the detection of bone marrow metastases in rhabdomyosarcoma patients, which may re-shape the definition of bone marrow disease and, ultimately, alter disease staging and risk stratification.
Asunto(s)
Neoplasias de la Médula Ósea , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Humanos , Masculino , Niño , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Médula Ósea/diagnóstico por imagen , Neoplasias de la Médula Ósea/patología , Rabdomiosarcoma/diagnóstico por imagen , Rabdomiosarcoma/patologíaRESUMEN
Background: Anaplastic thyroid carcinoma (ATC) and metastatic poorly differentiated thyroid carcinomas (PDTCs) are rare aggressive malignancies with poor overall survival (OS) despite extensive multimodal therapy. These tumors are highly proliferative, with frequently increased tumor mutational burden (TMB) compared with differentiated thyroid carcinomas, and elevated programmed death ligand 1 (PD-L1) levels. These tumor properties implicate responsiveness to antiangiogenic and antiproliferative multikinase inhibitors such as lenvatinib, and immune checkpoint inhibitors such as pembrolizumab. Patients and Methods: In a retrospective study, we analyzed six patients with metastatic ATC and two patients with PDTC, who received a combination therapy of lenvatinib and pembrolizumab. Lenvatinib was started at 14-24 mg daily and combined with pembrolizumab at a fixed dose of 200 mg every three weeks. Maximum treatment duration with this combination was 40 months, and 3 of 6 ATC patients are still on therapy. Patient tumors were characterized by whole-exome sequencing and PD-L1 expression levels (tumor proportion score [TPS] 1-90%). Results: Best overall response (BOR) within ATCs was 66% complete remissions (4/6 CR), 16% stable disease (1/6 SD), and 16% progressive disease (1/6 PD). BOR within PDTCs was partial remission (PR 2/2). The median progression-free survival was 17.75 months for all patients, and 16.5 months for ATCs, with treatment durations ranging from 1 to 40 months (1, 4, 11, 15, 19, 25, 27, and 40 months). Grade III/IV toxicities developed in 4 of 8 patients, requiring dose reduction/discontinuation of lenvatinib. The median OS was 18.5 months, with three ATC patients being still alive without relapse (40, 27, and 19 months) despite metastatic disease at the time of treatment initiation (UICC and stage IVC). All patients with long-term (>2 years) or complete responses (CRs) had either increased TMB or a PD-L1 TPS >50%. Conclusions: Our results implicate that the combination of lenvatinib and pembrolizumab might be safe and effective in patients with ATC/PDTC and can result in complete and long-term remissions. The combination treatment is now being systematically examined in a phase II clinical trial (Anaplastic Thyroid Carcinoma Lenvatinib Pembrolizumab [ATLEP]) in ATC/PDTC patients.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Quinolinas/uso terapéutico , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Carcinoma Anaplásico de Tiroides/mortalidad , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Resultado del TratamientoRESUMEN
ABSTRACT: A 58-year-old man with progressive dyspnea and recurrent extensive left-sided pleural effusion underwent pulmonary ventilation/perfusion SPECT/CT, which showed a pronounced mismatched perfusion deficit of the entire, normally ventilated left lung. As unilateral perfusion deficits of an entire lobe are generally not due to pulmonary embolism, further CT angiography and cardiac MRI were conducted. These examinations revealed high-grade left pulmonary vein stenosis (PVS) caused by pulmonary vein isolation performed for atrial fibrillation 3 and 4 years earlier. Thus, in addition to, for example, neoplastic processes or pulmonary congenital vascular abnormalities, PVS must be considered as a differential diagnosis and possible pitfall in ventilation/perfusion SPECT/CT in dyspneic patients with prior pulmonary vein isolation.
Asunto(s)
Imagen de Perfusión/efectos adversos , Embolia Pulmonar/diagnóstico por imagen , Ventilación Pulmonar , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/efectos adversos , Estenosis de Vena Pulmonar/etiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The purpose of this analysis was primarily to analyze biochemical-recurrence free survival (BRFS) after positron emission tomography (PET)-guided salvage radiotherapy (sRT) in a large cohort, and to further compare BRFS after PSMA vs. choline PET/ computer tomography (CT)-based sRT. This retrospective analysis is based on 421 patients referred for PSMA or choline PET/CT after radical prostatectomy due to biochemically recurrent or persistent disease. BRFS (PSA: 0.2 ng/mL) was defined as the study endpoint. Cox regression analyses were performed to assess the impact of different clinical parameters on BRFS. Additionally, propensity score matching was performed to adjust patient cohorts (PSMA vs. choline PET/CT-based sRT). The median follow-up time was 30 months. BRFS at three years after sRT was 58%. In the multivariate analysis, only PSA before PET imaging and PSA before sRT were significantly associated with BRFS (p < 0.05). After propensity score matching, 272 patients were further analyzed; there was no significant difference in three-year BRFS between patients with PSMA PET-based vs. choline PET-based sRT (55% vs. 63%, p = 0.197). The present analysis confirmed the overall high BRFS rates after PET-based sRT and the strong prognostic effect of PSA level prior to sRT. PSMA PET-based sRT did not have superior BRFS rates when compared with choline PET-based sRT.
RESUMEN
BACKGROUND: Amyloid-ß (Aß) PET is an established predictor of conversion from mild cognitive impairment (MCI) to Alzheimer's dementia (AD). We compared three PET (including an approach based on voxel-wise Cox regression) and one cerebrospinal fluid (CSF) outcome measures in their predictive power. METHODS: Datasets were retrieved from the ADNI database. In a training dataset (N = 159), voxel-wise Cox regression and principal component analyses were used to identify conversion-related regions (Cox-VOI and AD conversion-related pattern (ADCRP), respectively). In a test dataset (N = 129), the predictive value of mean normalized 18F-florbetapir uptake (SUVR) in AD-typical brain regions (composite SUVR) or the Cox-VOI and the pattern expression score (PES) of ADCRP and CSF Aß42/Aß40 as predictors were compared by Cox models (corrected for age and sex). RESULTS: All four Aß measures were significant predictors (p < 0.001). Prediction accuracies (Harrell's c) showed step-wise significant increases from Cox-SUVR (c = 0.71; HR = 1.84 per Z-score increase), composite SUVR (c = 0.73; HR = 2.18), CSF Aß42/Aß40 (c = 0.75; HR = 3.89) to PES (c = 0.77; HR = 2.71). CONCLUSION: The PES of ADCRP is the most predictive Aß PET outcome measure, comparable to CSF Aß42/Aß40, with a slight but statistically significant advantage.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/diagnóstico por imagen , Péptidos beta-Amiloides , Biomarcadores , Disfunción Cognitiva/diagnóstico por imagen , Humanos , Tomografía de Emisión de PositronesRESUMEN
The present work provides an overview of the various nuclear medicine methods in the diagnosis of neurodegenerative parkinsonian syndromes and their respective evidence and is intended to enable practical decision-making aids in the application and interpretation of the methods and findings. The value of the procedures differs considerably in relation to the two relevant diagnostic questions. On the one hand, it is the question of whether there is a neurodegenerative parkinsonian syndrome at all, and on the other hand the question of which one. While the DAT-SPECT is undisputedly the method of choice for answering the first question (taking certain parameters into account), this method is not suitable for answering the second question. To categorise parkinsonian syndromes into idiopathic (i.âe. Parkinson´s disease) or atypical, various procedures are used in everyday clinical practice including MIBG scintigraphy, and FDG-PET. We explain why FDG-PET currently is not only the most suitable of these methods to differentiate an idiopathic parkinsonian syndrome, from an atypical Parkinson's syndrome, but also enables sufficiently valid to distinguish the various atypical neurodegenerative Parkinson's syndromes (i.âe. MSA, PSP and CBD) from each other and therefore should be reimbursed by health insurances.
Asunto(s)
Trastornos Parkinsonianos/clasificación , Trastornos Parkinsonianos/diagnóstico , Diagnóstico Diferencial , Humanos , Enfermedad de Parkinson/diagnóstico , Tomografía de Emisión de Positrones , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
AIM: The value of 18F-fluorodeoxyglucose (FDG) PET for the prognosis of conversion from mild cognitive impairment (MCI) to Alzheimer's dementia (AD) is controversial. In the present work, the identification of cerebral metabolic patterns with significant prognostic value for conversion of MCI patients to AD is investigated with voxel-based Cox regression, which in contrast to common categorical comparisons also utilizes time information. METHODS: FDG PET data of 544 MCI patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were randomly split into two equally-sized datasets (training and test). Within a median follow-up duration of 47â¯months (95% CI: 46-48â¯months) 181 patients developed AD. In the training dataset, voxel-wise Cox regressions were used to identify regions associated with conversion of MCI to AD. These were compared to regions identified by a classical group comparison (analysis of covariance (ANCOVA) with statistical parametric mapping (SPM) 8) between converters and non-converters (both adjusted for apolipoprotein E (APOE) genotype, mini-mental state examination (MMSE) score, age, sex and education). In the test dataset, normalized FDG uptake within significant brain regions from voxel-wise Cox- and ANCOVA analyses (Cox- and ANCOVA- regions of interest (ROI), respectively) and clinical variables APOE status, MMSE score and education were tested in different Cox models (adjusted for age, sex) including: (1) only clinical variables, (2) only normalized FDG uptake in ANCOVA-ROI, (3) only normalized FDG uptake from Cox-ROI, (4) clinical variables plus FDG uptake in ANCOVA-ROI, (5) clinical variables plus FDG uptake from Cox-ROI. RESULTS: Conversion-related regions with relative hypometabolism comprised parts of the temporo-parietal and posterior cingulate cortex/precuneus for voxel-wise ANCOVA, plus frontal regions for voxel-wise Cox regression (both pâ¯<â¯.01, false discovery rate (FDR) corrected). The clinical-only model (1) and the models based on normalized FDG uptake from Cox-ROI only (2) and ANCOVA-ROI only (3) all significantly predicted conversion to AD (Wald Test (WT): pâ¯<â¯.001). The clinical model (1) was significantly improved by adding imaging information in model (4) (Akaike information criterion (AIC) relative likelihood (RL) (1) vs (4): RLâ¯<â¯0.018). There were no significant differences between models (2) and (3), as well as (4) and (5). CONCLUSIONS: Voxel-wise Cox regression identifies conversion-related patterns of cerebral glucose metabolism, but is not superior to classical group contrasts in this regard. With imaging information from both FDG PET patterns, the prediction of conversion to AD was improved.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Progresión de la Enfermedad , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones/tendencias , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Disfunción Cognitiva/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , PronósticoRESUMEN
BACKGROUND AND PURPOSE: GTV definition for re-irradiation treatment planning in recurrent glioblastoma (rGBM) is usually based on contrast-enhanced MRI (GdT1w-MRI) and, for an increased specificity, on amino acid PET. Diffusion-weighted (DWI) MRI and ADC maps can reveal regions of high cellularity as surrogate for active tumor. The objective of this study was to compare the localization and quality of diffusion restriction foci (GTV-ADClow) with FET-PET (GTV-PET) and GdT1w-MRI (GTV-GdT1w-MRI). MATERIAL AND METHODS: We prospectively evaluated 41 patients, who received a fractionated stereotactic re-irradiation for rGBM. GTV-PET was generated automatically (tumor-to-background ratio 1.7-1.8) and manually customized. GTV-ADClow was manually defined based on DWI data (3D diffusion gradients, bâ¯=â¯0, 1000â¯s/mm2) and parametric ADC maps. The localization of recurrence was correlated with initial GdT1w-MRI and PET data. RESULTS: In 30/41 patients, DWI-MRI showed areas with restricted diffusion (mean ADC-value 0.74⯱â¯0.22â¯mm2/s). 66% of GTVs-ADClow were located outside the GdT1w-MRI volume and 76% outside increased FET uptake regions. Furthermore, GTVs-ADClow were only partially included in the high dose volume and received in mean 82% of the reference dose. An adjusted volume including GdT1w-MRI, PET-positive and restricted diffusion areas would imply a GTV increase of 48%. GTV-PET and GdT1w-MRI correlated better with the localization of re-recurrence in comparison to GTV-ADClow. CONCLUSION: Unexpectedly, GTV-ADClow overlapped only partially with FET-PET and GdT1w-MRI in rGBM. Moreover, GTV-ADClow correlated poorly with later rGBM-recurrences. Seeing as a restricted diffusion is known to correlate with hypercellularity, this imaging discrepancy could only be further explained in histopathological studies.
Asunto(s)
Neoplasias Encefálicas/radioterapia , Imagen de Difusión por Resonancia Magnética/métodos , Glioblastoma/radioterapia , Tomografía de Emisión de Positrones/métodos , Radiocirugia , Reirradiación , Carga Tumoral , Adulto , Anciano , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Femenino , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Estudios Prospectivos , Tirosina/análogos & derivadosRESUMEN
177Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of 177Lu-PSMA-617 in a large cohort of patients. METHODS: One hundred forty-five patients (median age, 73 y; range, 43-88 y) with mCRPC were treated with 177Lu-PSMA-617 in 12 therapy centers between February 2014 and July 2015 with 1-4 therapy cycles and an activity range of 2-8 GBq per cycle. Toxicity was categorized by the common toxicity criteria for adverse events (version 4.0) on the basis of serial blood tests and the attending physician's report. The primary endpoint for efficacy was biochemical response as defined by a prostate-specific antigen decline ≥ 50% from baseline to at least 2 wk after the start of RLT. RESULTS: A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response in 99 patients as well as data for physician-reported and laboratory-based toxicity in 145 and 121 patients, respectively, were available. The median follow-up was 16 wk (range, 2-30 wk). Nineteen patients died during the observation period. Grade 3-4 hematotoxicity occurred in 18 patients: 10%, 4%, and 3% of the patients experienced anemia, thrombocytopenia, and leukopenia, respectively. Xerostomia occurred in 8%. The overall biochemical response rate was 45% after all therapy cycles, whereas 40% of patients already responded after a single cycle. Elevated alkaline phosphatase and the presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response. CONCLUSION: The present retrospective multicenter study of 177Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third-line systemic therapies in mCRPC patients. Future phase II/III studies are warranted to elucidate the survival benefit of this new therapy in patients with mCRPC.
Asunto(s)
Dipéptidos/uso terapéutico , Enfermedades Hematológicas/epidemiología , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/radioterapia , Traumatismos por Radiación/epidemiología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Causalidad , Comorbilidad , Alemania/epidemiología , Enfermedades Hematológicas/prevención & control , Humanos , Lutecio , Masculino , Persona de Mediana Edad , Prevalencia , Antígeno Prostático Específico , Traumatismos por Radiación/prevención & control , Radiofármacos/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
AIM: In radioiodine therapy (RIT) of benign thyroid-disorders empirical half-lives (HLemp) may be used to calculate therapeutic dose. In this study the effective half-life (HLf as well as potential influence factors were retrospectively determined in order to better estimate HLemp. METHODS: Data from patients undergoing RIT from 01/09 to 04/14 were analysed (empirically estimated HLeff stratified by metabolic state and diagnosis). Inclusion criteria were: Benign thyroid-disorders, singular capsule administration and ≥ 6 dosimetry time-points (i. e. > 72 h inpatient stay). The effects of metabolic state, previous thy- reostatic medication and sex on HLeff were assessed by non-parametric ANOVA. The effects of target-volume and patient-age were assessed by regression analysis and nonparametric correlation (Spearman). RESULTS: Data of 1,498 patients were analyzed: Graves' Disease (GD), n = 286; multinodular goiter/disseminated autonomy (AMG/DA), n = 751; autonomous thyroid nodules (ATN), n = 421; euthyroid goiter (EG), n = 40. Mean HLeff (days ± SD) was 5.4 ± 1.5 in GD, 6.6 ± 1.2 in AMG/DA, 5.5 ± 1.6 in ATN and 6.9 ± 0.7 in EG. HLeff differed by metabolic state in GD, AMG/DA, and ATN, whereas neither thyreos- tatic medication nor sex were relevant. Moreover, target-volume (all diagnoses) and age (ATN and GD only) were associated with HLeft although the effect was small (R2 < 3.8%). CONCLUSION: When using standard HLeff for RIT, diagnosis and metabolic state should be considered for dose-calculations in RIT. Despite partial significance, the effects of target-volume and patient-age are small and a correction of HLeff, for these factors doesn't appear to be necessary in a routine setting.
Asunto(s)
Radioisótopos de Yodo/uso terapéutico , Enfermedades de la Tiroides/radioterapia , Anciano , Femenino , Humanos , Radioisótopos de Yodo/farmacocinética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades de la Tiroides/metabolismoRESUMEN
PURPOSE: We present a novel method for treatment of locally recurrent prostate cancer (PCa) following radiation therapy: focal, multimodal image guided high-dose-rate (HDR) brachytherapy. MATERIAL AND METHODS: We treated two patients with recurrent PCa after primary (#1) or adjuvant (#2) external beam radiation therapy. Multiparametric magnetic resonance imaging (mpMRI), choline, positron emission tomography combined with computed tomography (PET/CT), or prostate-specific membrane antigen (PSMA)-PET combined with CT identified a single intraprostatic lesion. Positron emission tomography or magnetic resonance imaging - transrectal ultrasound (MRI-TRUS) fusion guided transperineal biopsy confirmed PCa within each target lesion. We defined a PET and mpMRI based gross tumor volume (GTV). A 5 mm isotropic margin was applied additionally to each lesion to generate a planning target volume (PTV), which accounts for technical fusion inaccuracies. A D90 of 18 Gy was intended in one fraction to each PTV using ultrasound guided HDR brachytherapy. RESULTS: Six month follow-up showed adequate prostate specific antygen (PSA) decline in both patients (ΔPSA 83% in patient 1 and ΔPSA 59.3% in patient 2). Follow-up 3-tesla MRI revealed regressive disease in both patients and PSMA-PET/CT showed no evidence of active disease in patient #1. No acute or late toxicities occurred. CONCLUSIONS: Single fraction, focal, multimodal image guided salvage HDR brachytherapy for recurrent prostate cancer is a feasible therapy for selected patients with single lesions. This approach has to be evaluated in larger clinical trials.
RESUMEN
PURPOSE: We performed a voxel-wise comparison of (68)Ga-HBED-CC-PSMA PET/CT with prostate histopathology to evaluate the performance of (68)Ga-HBED-CC-PSMA for the detection and delineation of primary prostate cancer (PCa). METHODOLOGY: Nine patients with histopathological proven primary PCa underwent (68)Ga-HBED-CC-PSMA PET/CT followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and histopathologically prepared. Histopathological information was matched to ex-vivo CT. PCa volume (PCa-histo) and non-PCa tissue in the prostate (NPCa-histo) were processed to obtain a PCa-model, which was adjusted to PET-resolution (histo-PET). Each histo-PET was coregistered to in-vivo PSMA-PET/CT data. RESULTS: Analysis of spatial overlap between histo-PET and PSMA PET revealed highly significant correlations (p < 10(-5)) in nine patients and moderate to high coefficients of determination (R²) from 42 to 82 % with an average of 60 ± 14 % in eight patients (in one patient R(2) = 7 %). Mean SUVmean in PCa-histo and NPCa-histo was 5.6 ± 6.1 and 3.3 ± 2.5 (p = 0.012). Voxel-wise receiver-operating characteristic (ROC) analyses comparing the prediction by PSMA-PET with the non-smoothed tumor distribution from histopathology yielded an average area under the curve of 0.83 ± 0.12. Absolute and relative SUV (normalized to SUVmax) thresholds for achieving at least 90 % sensitivity were 3.19 ± 3.35 and 0.28 ± 0.09, respectively. CONCLUSIONS: Voxel-wise analyses revealed good correlations of (68)Ga-HBED-CC-PSMA PET/CT and histopathology in eight out of nine patients. Thus, PSMA-PET allows a reliable detection and delineation of PCa as basis for PET-guided focal therapies.
Asunto(s)
Histocitoquímica/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/diagnóstico , Antígenos de Superficie/administración & dosificación , Ácido Edético/administración & dosificación , Ácido Edético/análogos & derivados , Glutamato Carboxipeptidasa II/administración & dosificación , Humanos , Masculino , Radioisótopos/administración & dosificaciónRESUMEN
BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis was first described in 2005 in association with ovarian teratoma. The diagnostic workup of this common autoimmune encephalitis includes cerebrospinal fluid analysis, electroencephalography, magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (FDG-PET). In addition to standard diagnostics, we performed metabolic investigations using proton magnet resonance spectroscopy ((1)H-MRS). CASE PRESENTATION: We describe the case of a non-limbic anti-NMDAR encephalitis with a long course of disease (21 months). Laboratory diagnostics showed antibodies against NMDAR; an MRI revealed unspecific findings. (1)H-MRS indicated a hypoglutamatergic state in the left prefrontal cortex associated with a left hemispherical hypometabolism on FDG-PET. Despite the long course of disease, immunosuppressive therapy with methylprednisolone and azathioprine led to almost complete remission of clinical symptoms. Clinical improvement developed in parallel with remarkable normalization of cerebral glucose metabolism on FDG-PET. CONCLUSION: This case of long-lasting extra-limbic anti-NMDAR encephalitis is of high clinical relevance. First, it illustrates that a very good outcome is possible even if adequate therapy is started only 21 months after the onset of severe symptoms. Second, it provides valuable insights into the pathophysiology of such anti-NMDAR encephalitis; these insights prove that anti-NMDAR encephalitis is linked not only to hyperglutamatergic signals but also to hypoglutamatergic states. These findings, contradictory at first glance, can be integrated within the model of excitatory/inhibitory imbalance and local area network inhibition.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/metabolismo , Glucemia/metabolismo , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , Autoanticuerpos/metabolismo , Azatioprina/uso terapéutico , Quimioterapia Combinada , Electroencefalografía , Femenino , Humanos , Inmunosupresores/uso terapéutico , Imagen por Resonancia Magnética , Metilprednisolona/uso terapéutico , Imagen Multimodal/métodos , Fármacos Neuroprotectores/uso terapéutico , Tomografía de Emisión de Positrones/métodos , Receptores de N-Metil-D-Aspartato/inmunología , Resultado del TratamientoRESUMEN
BACKGROUND: Autoimmune and inflammatory mechanisms in psychotic disorders have attracted increasing scientific attention in recent years. In this regard, we performed routine cerebrospinal fluid (CSF) basic diagnostics and CSF/serum analyses for antibodies directed against neuronal intracellular and surface antigens in psychotic patients. In this context, the patient presented in this paper was diagnosed. CASE PRESENTATION: We present the case of a 20-year-old female patient with a first episode of a drug-induced psychotic syndrome but without neurological deficits. Further investigations showed a reproducible low-titre positive anti-Yo reactivity in the CSF and serum with two independent immunoblot assays. Magnetic resonance imaging showed frontoparietal and cerebellar atrophy. On [(18)F]fluorodeoxyglucose positron emission tomography, a mild cerebellar hypometabolism was found. No underlying tumor was detected. CONCLUSION: Despite the presence of anti-Yo reactivity, the diagnostic criteria for a paraneoplastic neurological syndrome were not fulfilled. Previously published data indicate the possible association between low-titer antibodies against intracellular localized, onconeural antigens, and psychotic disorders. Large prospective studies that investigate the prevalence and clinical significance of antibodies against intracellular onconeural antigens in psychiatry are needed.
Asunto(s)
Proteínas del Tejido Nervioso , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Psicosis Inducidas por Sustancias/diagnóstico , Atrofia , Cerebelo/metabolismo , Cerebelo/patología , Diagnóstico Diferencial , Femenino , Fluorodesoxiglucosa F18 , Lóbulo Frontal/metabolismo , Lóbulo Frontal/patología , Humanos , Imagen por Resonancia Magnética/métodos , Proteínas del Tejido Nervioso/sangre , Proteínas del Tejido Nervioso/líquido cefalorraquídeo , Lóbulo Parietal/metabolismo , Lóbulo Parietal/patología , Tomografía de Emisión de Positrones/métodos , Psicosis Inducidas por Sustancias/inmunología , Radiofármacos , Adulto JovenRESUMEN
PURPOSE: Progressive supranuclear palsy (PSP) is characterized by a symmetric hypokinetic syndrome with early falls and vertical supranuclear gaze palsy. However, clinically asymmetric manifestations occur, resembling idiopathic Parkinson disease or corticobasal degeneration. The aim of this study was to determine the neuronal correlates of patients suffering from PSP with a lateralized disease manifestation (hemi-PSP) in comparison to patients with symmetric clinical presentation (symPSP) and corticobasal degeneration. METHODS: Twenty-three patients with PSP and 8 patients with corticobasal degeneration according to standard diagnostic criteria underwent F-fluorodeoxyglucose (FDG) PET scans to assess disease-specific patterns of regional cerebral glucose metabolism reflecting neuronal activity. Group differences were analyzed by statistical parametric mapping and region-of-interest analyses. RESULTS: Clinically, 14 patients presented with symPSP while 9 patients were considered as hemi-PSP. Patients with symPSP or hemi-PSP showed similar bilateral medial frontal hypometabolism compared to corticobasal degeneration patients. In contrast, corticobasal degeneration patients exhibited a prominent parietal hypometabolism compared to both symPSP and hemi-PSP patients. SymPSP patients showed no significant hypometabolism compared to hemi-PSP, whereas hemi-PSP patients presented with significant hypometabolism of the motor thalamus, middle cingulate gyrus, and sensorimotor cortex contralateral to the most affected body side compared to symPSP patients. CONCLUSIONS: The present study demonstrates that a more pronounced and asymmetric involvement of cortical and subcortical motor areas is associated with a lateralized disease manifestation of PSP. Furthermore, these findings strongly suggest that FDG PET imaging may assist the challenging clinical differentiation between hemi-PSP and corticobasal degeneration by depicting disease-specific patterns of regional cerebral glucose metabolism.
Asunto(s)
Neuronas/patología , Parálisis Supranuclear Progresiva/patología , Anciano , Anciano de 80 o más Años , Mapeo Encefálico , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Neuronas/diagnóstico por imagen , Tomografía de Emisión de Positrones , Pronóstico , Parálisis Supranuclear Progresiva/diagnóstico por imagen , Parálisis Supranuclear Progresiva/fisiopatología , Parálisis Supranuclear Progresiva/terapiaRESUMEN
PURPOSE: The aim of the study was the comparison of C-11 methionine (MET) and C-11 choline (CHO) in the positron emission tomography (PET) imaging of brain metastases in correlation to the histopathology findings in stereotactic biopsy. METHODS: In all, 8 patients underwent MET and CHO PET and magnetic resonance imaging, in 7 of these, the metastases were previously treated by radiation therapy. Histopathologic diagnosis was made for each patient by frame-based stereotactic serial biopsy. Standardized uptake values of tumor uptake and lesion-to-normal brain tissue ratios (LNRs) of the lesions were determined. LNRs for each tracer were compared with the histopathology findings and follow-up. RESULTS: In 6 patients, biopsy revealed viable metastases, 1 patient suffered from tumor recurrence in follow-up and 1 patient was tumor free in biopsy and follow-up. In the last mentioned patient, LNR was the lowest determined in all patients for CHO, but not for MET. Mean standardized uptake values of the lesions were in median 1.8 for MET and 1.1 for CHO, median LNRs were 1.5 for MET and 6.6 for CHO. LNRs for CHO were significant higher than those for MET (P = 0.007). CONCLUSIONS: In the direct comparison to the well-established amino acid tracer MET, CHO seems to be promising for the imaging of brain metastases because of significantly higher LNRs in tumor tissue compared with MET without evidence for a lower specificity of CHO uptake.