RESUMO
Congenital hyperinsulinism is the most common cause of recurrent hypoglycemia in newborns and children. Early diagnosis and rapid management are essential to avoid hypoglycaemic brain injury and later neurological complications. Management of those patients involves biological evaluation, molecular genetics, imaging techniques and surgical advances. We report the case of a newborn with recurrent hypoglycemia due to congenital hyperinsulinism (CHI) caused by a new variant in the ABCC8 gene. Fluorine 18-L-3,4 Dihydroxyphenylalanine Positron Emission Tomography (18F-DOPA PET/CT scan) reported a focal lesion at the isthmus of the pancreas which has been removed by laparoscopic surgery with a complete recovery for the patient.
L'hyperinsulinisme congénital est la cause la plus fréquente d'hypoglycémies récidivantes chez le nouveau-né et l'enfant. Un diagnostic et une prise en charge précoces sont primordiaux pour éviter les conséquences potentielles sur le développement neurologique. Ces derniers reposent sur la conjonction d'éléments biologiques, génétiques et d'imagerie. Nous rapportons le cas d'un nouveau-né présentant des hypoglycémies récidivantes. La mise au point mettra en évidence un hyperinsulinisme congénital (CHI) lié à un variant non encore décrit au sein du gène ABCC8. L'imagerie par Fluorine 18-L-3,4 Dihydroxyphenylalanine Positron Emission Tomography/Computed Tomography-scanner (18F-DOPA PET/CT scan) a mis en évidence une forme focale de l'hyperinsulinisme justifiant une prise en charge chirurgicale amenant à une guérison complète et à l'arrêt de tout traitement médicamenteux.
Assuntos
Hiperinsulinismo Congênito , Laparoscopia , Criança , Humanos , Recém-Nascido , Lactente , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Hiperinsulinismo Congênito/diagnóstico por imagem , Hiperinsulinismo Congênito/genética , Hiperinsulinismo Congênito/patologia , Pâncreas/patologia , Pâncreas/cirurgia , Tomografia por Emissão de Pósitrons/métodosRESUMO
OBJECTIVES: Bone metastases (BM) may influence negatively the prognosis of midgut neuroendocrine tumors (NET). The diagnostic sensitivity of 18F-DOPA PET for midgut NET and associated metastases is high. This study aimed to assess the prognostic impact of BM detected by 18F-DOPA PET in metastatic midgut NET. METHODS: All patients with a metastatic midgut NET, who underwent a 18F-DOPA PET between June 2011 and June 2018, were included. BM were defined following imaging criteria and were classified as poly-BM or oligo-BM, according to their number (< 5 or ≥ 5, respectively). The variables associated with the presence of BM were evaluated by logistic regression. The factors associated with overall survival were explored by Cox regression models. RESULTS: Among 155 patients included, 46 had BM (29.7%). A carcinoid syndrome (OR 2.96, p = 0.009) and ≥ 3 extra-skeletal metastatic organs (OR 4.99, p = 0.002) were independently associated with the presence of BM. BM were mainly osteoblastic (78%), rarely symptomatic (8.9%), and had a short-term therapeutic impact for 3 patients (6.5%). The presence of BM (HR 2.67, p = 0.034), older age (HR 1.07, p = 0.016), and higher Ki67 (HR 1.09, p = 0.025) were independent prognostic factors. Unlike poly-BM (HR 1.92, p = 0.007), oligo-BM was not a poor prognosis factor (HR 0.77, p = 0.699) compared to the group without BM. CONCLUSION: 18F-DOPA PET frequently detects BM in patients with metastatic midgut NET. BM have a negative prognostic impact, especially poly-BM. Conversely, oligo-BM do not influence the prognosis and may not impact therapeutic decisions. KEY POINTS: ⢠18F-DOPA PET detected bone metastases in 46 (29.7%) of 155 patients with metastatic midgut neuroendocrine tumors. ⢠Bone metastases have a negative prognostic impact in metastatic midgut neuroendocrine tumors. ⢠Bone oligo-metastases (< 5) do not influence the prognosis and may not impact therapeutic decisions.
Assuntos
Di-Hidroxifenilalanina , Tumores Neuroendócrinos , Idoso , Di-Hidroxifenilalanina/análogos & derivados , Humanos , Tumores Neuroendócrinos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , PrognósticoRESUMO
Aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei are among the most consistent large-scale brain imaging findings in schizophrenia. A pathophysiological link between these two alterations is suggested by theoretical models based on striatal dopamine's topographic modulation of cortico-thalamic connectivity within cortico-basal-ganglia-thalamic circuits. We hypothesized that aberrant striatal dopamine links topographically with aberrant cortico-thalamic iFC, i.e. aberrant associative striatum dopamine is associated with aberrant iFC between the salience network and thalamus, and aberrant sensorimotor striatum dopamine with aberrant iFC between the auditory-sensorimotor network and thalamus. Nineteen patients with schizophrenia during remission of psychotic symptoms and 19 age- and sex-comparable control subjects underwent simultaneous fluorodihydroxyphenyl-l-alanine PET (18F-DOPA-PET) and resting state functional MRI (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure striatal dopamine synthesis capacity; correlation coefficients between rs-fMRI time series of cortical networks and thalamic regions of interest were used to measure iFC. In the salience network-centred system, patients had reduced associative striatum dopamine synthesis capacity, which correlated positively with decreased salience network-mediodorsal-thalamus iFC. This correlation was present in both patients and healthy controls. In the auditory-sensorimotor network-centred system, patients had reduced sensorimotor striatum dopamine synthesis capacity, which correlated positively with increased auditory-sensorimotor network-ventrolateral-thalamus iFC. This correlation was present in patients only. Results demonstrate that reduced striatal dopamine synthesis capacity links topographically with cortico-thalamic intrinsic dysconnectivity in schizophrenia. Data suggest that aberrant striatal dopamine and cortico-thalamic dysconnectivity are pathophysiologically related within dopamine-modulated cortico-basal ganglia-thalamic circuits in schizophrenia.
Assuntos
Córtex Cerebral/metabolismo , Corpo Estriado/metabolismo , Dopamina/metabolismo , Vias Neurais/metabolismo , Esquizofrenia/metabolismo , Tálamo/metabolismo , Adulto , Córtex Cerebral/diagnóstico por imagem , Corpo Estriado/diagnóstico por imagem , Di-Hidroxifenilalanina/análogos & derivados , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Esquizofrenia/diagnóstico por imagem , Tálamo/diagnóstico por imagemRESUMO
Hyperinsulinemic hypoglycemia (HH) is characterized by unregulated insulin release, leading to persistently low blood glucose concentrations with lack of alternative fuels, which increases the risk of neurological damage in these patients. It is the most common cause of persistent and recurrent hypoglycemia in the neonatal period. HH may be primary, Congenital HH (CHH), when it is associated with variants in a number of genes implicated in pancreatic development and function. Alterations in fifteen genes have been recognized to date, being some of the most recently identified mutations in genes HK1, PGM1, PMM2, CACNA1D, FOXA2 and EIF2S3. Alternatively, HH can be secondary when associated with syndromes, intra-uterine growth restriction, maternal diabetes, birth asphyxia, following gastrointestinal surgery, amongst other causes. CHH can be histologically characterized into three groups: diffuse, focal or atypical. Diffuse and focal forms can be determined by scanning using fluorine-18 dihydroxyphenylalanine-positron emission tomography. Newer and improved isotopes are currently in development to provide increased diagnostic accuracy in identifying lesions and performing successful surgical resection with the ultimate aim of curing the condition. Rapid diagnostics and innovative methods of management, including a wider range of treatment options, have resulted in a reduction in co-morbidities associated with HH with improved quality of life and long-term outcomes. Potential future developments in the management of this condition as well as pathways to transition of the care of these highly vulnerable children into adulthood will also be discussed.
Assuntos
Hiperinsulinismo Congênito/diagnóstico , Hiperinsulinismo Congênito/terapia , Adolescente , Criança , Pré-Escolar , Hiperinsulinismo Congênito/genética , Hiperinsulinismo Congênito/metabolismo , Humanos , LactenteRESUMO
While there is consistent evidence for increased presynaptic dopamine synthesis capacity in the striatum of patients with schizophrenia during psychosis, it is unclear whether this also holds for patients during psychotic remission. This study investigates whether striatal dopamine synthesis capacity is altered in patients with schizophrenia during symptomatic remission of positive symptoms, and whether potential alterations relate to symptoms other than positive, such as cognitive difficulties. Twenty-three patients with schizophrenia in symptomatic remission of positive symptoms according to Andreasen, and 24 healthy controls underwent 18F-DOPA-PET and behavioural-cognitive assessment. Imaging data were analysed with voxel-wise Patlak modelling with cerebellum as reference region, resulting in the influx constant kicer reflecting dopamine synthesis capacity. For the whole striatum and its subdivisions (i.e. limbic, associative, and sensorimotor), averaged regional kicer values were calculated, compared across groups, and correlated with behavioural-cognitive scores, including a mediation analysis. Patients had negative symptoms (Positive and Negative Syndrome Scale-negative 14.13 ± 5.91) and cognitive difficulties, i.e. they performed worse than controls in Trail-Making-Test-B (TMT-B; P = 0.01). Furthermore, kicer was reduced in patients for whole striatum (P = 0.004) and associative (P = 0.002) and sensorimotor subdivisions (P = 0.007). In patients, whole striatum kicer was negatively correlated with TMT-B (rho = -0.42, P = 0.04; i.e. the lower striatal kicer, the worse the cognitive performance). Mediation analysis showed that striatal kicer mediated the group difference in TMT-B. Results demonstrate that patients with schizophrenia in symptomatic remission of positive symptoms have decreased striatal dopamine synthesis capacity, which mediates the disorder's impact on cognitive difficulties. Data suggest that striatal dopamine dysfunction contributes to cognitive difficulties in schizophrenia.
Assuntos
Corpo Estriado/fisiopatologia , Dopamina/biossíntese , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Adulto , Idoso , Corpo Estriado/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neostriado/metabolismo , Neostriado/fisiopatologia , Tomografia por Emissão de Pósitrons/métodos , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/metabolismo , Esquizofrenia/metabolismoRESUMO
Hyperinsulinemic hypoglycaemia (HH) is the most frequent cause of persistent hypoglycaemia in neonates and infants. The most severe forms of HH are inherited and referred to as congenital hyperinsulinism (CHI). Diazoxide is the mainstay of treatment, with surgery being an option in appropriate cases. To describe the management and outcome of patients with CHI within our service. Children referred to or attending HH clinic between 2009 and 2017 were identified. Clinical course, genetics and interventions were documented. A total of 39 children were identified, and seven patients with secondary and syndromic HH were excluded. Most were born with an appropriate weight for gestational age (62.5%). Diazoxide was started in all patients; however, 7 did not respond and required octreotide/continuous feeding, with 6/7 requiring surgery. Genetic mutations were detected in 12/32 (37.5%). Hyperinsulinism resolved in conservatively treated patients within 12 months in 11/32 (34.3%) compared to 14/32 (43.7%) requiring more than 12 months of medication. A total of 7 patients underwent pancreatectomy.Conclusion: Although LGA and SGA are risk factors, most babies in our cohort are born AGA. A genetic mutation does not exclude medical remission; long-term conservative treatment of CHI is feasible as surgery does not guarantee complete remission.What is Known:â¢Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disorder that is the most common cause of permanent hypoglycaemia in infants and children.â¢Identification of genetic mutations and the use of 18F-DOPA PET scan when feasible lead to better outcomes.What is New:â¢The study describes clinical criteria, management and outcome of large number of patients with CHI in single tertiary centre.â¢Conservative treatment is feasible without the need for surgery, with HH resolving in over 30% within 12 months, irrespective of genetic mutation.
Assuntos
Hiperinsulinismo Congênito/terapia , Hiperinsulinismo Congênito/diagnóstico , Hiperinsulinismo Congênito/etiologia , Feminino , Marcadores Genéticos , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
Susceptibility to Parkinson's disease (PD) is believed to involve an interaction between genetic and environmental factors. The role of pesticides as a risk factor of PD and neurodegeneration remains controversial. An asymmetric decrease in ligand uptake on 18F-DOPA positron emission tomography (PET), especially in the dorsal putamen, is a sensitive marker of PD. The aim of this study was to examine the pattern of ligand uptake on 18F-DOPA PET in patients with PD exposed or not exposed to pesticides. The main sample included 26 Israeli patients with PD, 13 who were exposed to pesticides and 13 who were not, matched for age and disease duration. All underwent 18F-DOPA PET imaging, and an asymmetry index of ligand uptake between the ipsilateral and contralateral caudate, putamen, and whole striatum was calculated. No significant between-group differences were found in demographic variables, clinical asymmetry index (P = 0.15), or asymmetry index of ligand uptake in the putamen (P = 0.84), caudate (P = 0.78) and striatum (P = 0.45). Comparison of the 18F-DOPA results of the Israeli cohort with those of 17 non-pesticide-exposed patients with PD from Austria yielded no significant differences, further validating our findings. Our observations suggest that although exposure to pesticides might be a risk factor for PD, it does not have an effect on the asymmetry pattern in the nigrostriatal system over non-exposure. We assume that once the disease process is initiated in pesticide-exposed patients, the pathogenic mechanism does not differ from that of idiopathic PD.
Assuntos
Di-Hidroxifenilalanina/análogos & derivados , Exposição Ambiental/efeitos adversos , Neostriado/metabolismo , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Praguicidas/efeitos adversos , Tomografia por Emissão de Pósitrons , Idoso , Áustria , Estudos de Coortes , Di-Hidroxifenilalanina/farmacocinética , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Neostriado/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson Secundária/diagnóstico por imagem , Doença de Parkinson Secundária/etiologia , Doença de Parkinson Secundária/metabolismoRESUMO
PURPOSE: Medullary thyroid carcinoma (MTC) is characterized by a high rate of metastasis. In this study we evaluated the ability of [18F]DOPA PET/ceCT to stage MTC in patients with suspicious thyroid nodules and pathologically elevated serum calcitonin (Ctn) levels prior to total thyroidectomy and lymph node (LN) dissection. METHODS: A group of 32 patients with sonographically suspicious thyroid nodules and pathologically elevated basal Ctn (bCtn) and stimulated Ctn (sCtn) levels underwent DOPA PET/ceCT prior to surgery. Postoperative histology served as the standard of reference for ultrasonography and DOPA PET/ceCT region-based LN staging. Univariate and multivariate regression analyses as well as receiver operating characteristic analysis were used to evaluate the correlations between preoperative and histological parameters and postoperative tumour persistence or relapse. RESULTS: Primary MTC was histologically verified in all patients. Of the 32 patients, 28 showed increased DOPA decarboxylase activity in the primary tumour (sensitivity 88%, mean SUVmax 10.5). Undetected tumours were exclusively staged pT1a. The sensitivities of DOPA PET in the detection of central and lateral metastatic neck LN were 53% and 73%, in contrast to 20% and 39%, respectively, for neck ultrasonography. Preoperative bCtn and carcinoembryonic antigen levels as well as cN1b status and the number of involved neck regions on DOPA PET/ceCT were predictive of postoperative tumour persistence/relapse in the univariate regression analysis (P < 0.05). Only DOPA PET/ceCT cN1b status remained significant in the multivariate analysis (P = 0.016, relative risk 4.02). CONCLUSION: This study revealed that DOPA PET/ceCT has high sensitivity in the detection of primary MTC and superior sensitivity in the detection of LN metastases compared to ultrasonography. DOPA PET/ceCT identification of N1b status predicts postoperative tumour persistence. Thus, implementation of a DOPA-guided LN dissection might improve surgical success.
Assuntos
Carcinoma Neuroendócrino/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Adulto , Idoso , Carcinoma Neuroendócrino/patologia , Di-Hidroxifenilalanina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/patologiaRESUMO
Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on 123I-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging with 18F-FDG, 18F-DOPA and 68Ga-DOTA peptides. These PET/CT studies are increasingly employed in clinical practice. Indications, advantages and limitations are presented along with recommendations on study protocols, interpretation of findings and reporting results.
Assuntos
Diagnóstico por Imagem/métodos , Neuroblastoma/diagnóstico por imagem , Medicina Nuclear , Guias de Prática Clínica como Assunto , 3-Iodobenzilguanidina/metabolismo , 3-Iodobenzilguanidina/farmacocinética , Humanos , Neuroblastoma/metabolismo , Compostos Radiofarmacêuticos/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Distribuição TecidualRESUMO
Treatment-related changes can be difficult to differentiate from progressive glioma using MRI with contrast (CE). The purpose of this study is to compare the sensitivity and specificity of 18F-DOPA-PET and MRI in patients with recurrent glioma. Thirteen patients with MRI findings suspicious for recurrent glioma were prospectively enrolled and underwent 18F-DOPA-PET and MRI for neurosurgical planning. Stereotactic biopsies were obtained from regions of concordant and discordant PET and MRI CE, all within regions of T2/FLAIR signal hyperintensity. The sensitivity and specificity of 18F-DOPA-PET and CE were calculated based on histopathologic analysis. Receiver operating characteristic curve analysis revealed optimal tumor to normal (T/N) and SUVmax thresholds. In the 37 specimens obtained, 51% exhibited MRI contrast enhancement (M+) and 78% demonstrated 18F-DOPA-PET avidity (P+). Imaging characteristics included M-P- in 16%, M-P+ in 32%, M+P+ in 46% and M+P- in 5%. Histopathologic review of biopsies revealed grade II components in 16%, grade III in 43%, grade IV in 30% and no tumor in 11%. MRI CE sensitivity for recurrent tumor was 52% and specificity was 50%. PET sensitivity for tumor was 82% and specificity was 50%. A T/N threshold > 2.0 altered sensitivity to 76% and specificity to 100% and SUVmax > 1.36 improved sensitivity and specificity to 94 and 75%, respectively. 18F-DOPA-PET can provide increased sensitivity and specificity compared with MRI CE for visualizing the spatial distribution of recurrent gliomas. Future studies will incorporate 18F-DOPA-PET into re-irradiation target volume delineation for RT planning.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Glioma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Meios de Contraste , Di-Hidroxifenilalanina/análogos & derivados , Feminino , Glioma/metabolismo , Glioma/patologia , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/cirurgia , Compostos Radiofarmacêuticos , Terapia de Salvação , Sensibilidade e Especificidade , Adulto JovemRESUMO
Neuroendocrine tumors (NET) develop from the diffuse endocrine system. These are rare tumors that can affect diverse organs. We present here the case of a 42-year-old female patient in whom a NET of the breast was discovered that was likely not of mammary origin. The main challenge was finding the primary tumor using immunohistochemistry and specific medical imaging modalities for NET. The primary tumor was localized at the last ileal loop upstream of the Bauhin valve thanks to the use of 18F-DOPA-PET. Ileocaecal resection by laparoscopy was performed. A WHO grade 2 NET of the ileum measuring 2.2 cm × 1.5 cm was found that infiltrated the submucosa with six metastatic lymph nodes of the eight removed (6N+/8). This unusual clinical case is the first one of a digestive NET of the ileum-caecal junction by mammary metastasis.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias do Ceco/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Adulto , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/secundário , Neoplasias do Ceco/diagnóstico por imagem , Neoplasias do Ceco/patologia , Di-Hidroxifenilalanina/análogos & derivados , Feminino , Humanos , Metástase Neoplásica , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/secundário , Tomografia por Emissão de PósitronsRESUMO
PURPOSE: Congenital hyperinsulinism is a rare disease, and the newly developed 18 fluoro-L-dihydroxyphenylalanine-positron emission tomography (18F-DOPA PET) examination can detect hyperplastic lesions. Our purpose was to report the results of a nationwide survey on surgical treatment of congenital hyperinsulinism in Japan. METHODS: A questionnaire was sent to the 159 accredited and affiliated training institutes certified as pediatric surgical institutes by the Japanese Association of Pediatric Surgeons, asking if they had encountered patients who underwent surgical treatment for congenital hyperinsulinism after 18F-DOPA PET examination from 2000 to 2017. Six institutes answered that they had treated such cases, and the total number of cases was 14. RESULTS: 18F-DOPA PET examination detected the focal lesion in 12 of the 14 cases. 18F-DOPA PET examination could accurately determine the site of the hyperplastic lesion in the pancreas in 11 (91.7%) of the 12 cases. All cases underwent surgical resection of the hyperplastic lesion at under 2 years of age. CONCLUSION: Surgical resection of a focal hyperplastic lesion in the pancreas was a safe and effective treatment if the hyperplastic lesion was a focal lesion. However, it is necessary to check the exact distribution of the lesion by intraoperative pathologic examination of frozen sections.
Assuntos
Hiperinsulinismo Congênito/diagnóstico por imagem , Hiperinsulinismo Congênito/cirurgia , Di-Hidroxifenilalanina , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Japão , Masculino , Pâncreas/cirurgia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
PURPOSE: To assess the diagnostic performance of (18)F-DOPA PET/CT and fused (18)F-DOPA PET/MRI in detecting striatal involvement in children with gliomas. METHODS: This retrospective study included 28 paediatric patients referred to our institution for the presence of primary, residual or recurrent glioma (12 boys, 16 girls; mean age 10.7 years) and investigated with (18)F-DOPA PET/CT and brain MRI. Fused (18)F-DOPA PET/MR images were obtained and compared with PET/CT and MRI images. Accuracy, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for striatal involvement were calculated for each diagnostic tool. Univariate and multivariate logistic analyses were applied to evaluate the associations between (18)F-DOPA PET/CT and fused (18)F-DOPA PET/MRI diagnostic results and tumour uptake outside the striatum, grade, dimension and site of striatal involvement (ventral and/or dorsal). RESULTS: Accuracy, sensitivity, specificity, PPV, and NPV were 100 % for MRI, 93 %, 89 %, 100 %, 100 % and 82 % for (18)F-DOPA PET/MRI, and 75 %, 74 %, 78 %, 88 % and 58 % for (18)F-DOPA PET/CT, respectively. (18)F-DOPA PET/MRI showed a trend towards higher accuracy compared with (18)F-DOPA PET/CT (p = 0.06). MRI showed significantly higher accuracy compared with (18)F-DOPA PET/CT (p = 0.01), but there was no significant difference between MRI and (18)F-DOPA PET/MRI. Both univariate and multivariate logistic analyses showed a significant association (OR 8.0 and 7.7, respectively) between the tumour-to-normal striatal uptake (T/S) ratio and the diagnostic ability of (18)F-DOPA PET/CT (p = 0.03). A strong significant association was also found between involvement of the dorsal striatum and the (18)F-DOPA PET/CT results (p = 0.001), with a perfect prediction of involvement of the dorsal striatum by (18)F-DOPA PET/MRI. CONCLUSION: Physiological striatal (18)F-DOPA uptake does not appear to be a main limitation in the evaluation of basal ganglia involvement.(18)F-DOPA PET/CT correctly detected involvement of the dorsal striatum in lesions with a T/S ratio >1, but appeared to be less suitable for evaluation of the ventral striatum. The use of fused (18)F-DOPA PET/MRI further improves the accuracy and is essential for evaluation of the ventral striatum.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Di-Hidroxifenilalanina/análogos & derivados , Glioma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Imagem Multimodal , Neostriado/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adolescente , Criança , Pré-Escolar , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVES: Results of surgery for focal CHI in 30 children PATIENTS AND METHODS: All showed an ABCC8 or KCNJ11 mutation. After PET/CT in 29 children and PET/MRT in 1 case, frozen-section guided resection was performed, in left-sided cases by laparoscopy. Mean age at surgery was 11.7 months (2-49). RESULTS: In 28/30 children, the PET/CT or MRT correlated with histopathology. In two cases, a focal lesion was undectable; one of these was cured, one not. In total, 24 children showed lesions with sizes of 5-12 mm. All were cured instantly. In four children with huge lesions in the pancreatic head, pathological cells remained at the resection margins. One child was cured instantly, two children after a 2nd surgery, and one child was not cured, even after three surgeries. The overall cure rate was 93%. CONCLUSIONS: Imaging, surgical findings, histopathology and clinical outcome in surgery for focal CHI match in most, but not all cases.
Assuntos
Hiperinsulinismo Congênito/cirurgia , Criança , Pré-Escolar , Estudos de Coortes , Hiperinsulinismo Congênito/genética , Feminino , Alemanha , Humanos , Lactente , Masculino , Mutação , Canais de Potássio Corretores do Fluxo de Internalização/genética , Estudos Retrospectivos , Receptores de Sulfonilureias/genéticaRESUMO
Signal abnormalities of the substantia nigra and the olfactory tract detected either by diffusion tensor imaging, including measurements of mean diffusivity, a parameter of brain tissue integrity, and fractional anisotropy, a parameter of neuronal fibre integrity, or transcranial sonography, were recently reported in the early stages of Parkinson's disease. In this study, changes in the nigral and olfactory diffusion tensor signal, as well as nigral echogenicity, were correlated with clinical scales of motor disability, odour function and putaminal dopamine storage capacity measured with 6-[(18)F] fluorolevodopa positron emission tomography in early and advanced stages of Parkinson's disease. Diffusion tensor imaging, transcranial sonography and positron emission tomography were performed on 16 patients with Parkinson's disease (mean disease duration 3.7 ± 3.7 years, Hoehn and Yahr stage 1 to 4) and 14 age-matched healthy control subjects. Odour function was measured by the standardized Sniffin' Sticks Test. Mean putaminal 6-[(18)F] fluorolevodopa influx constant, mean nigral echogenicity, mean diffusivity and fractional anisotropy values of the substantia nigra and the olfactory tract were identified by region of interest analysis. When compared with the healthy control group, the Parkinson's disease group showed significant signal changes in the caudate and putamen by 6-[(18)F] fluorolevodopa positron emission tomography, in the substantia nigra by transcranial sonography, mean diffusivity and fractional anisotropy (P < 0.001, P < 0.01, P < 0.05, respectively) and in the olfactory tract by mean diffusivity (P < 0.05). Regional mean diffusivity values of the substantia nigra and the olfactory tract correlated significantly with putaminal 6-[(18)F] fluorolevodopa uptake (r = -0.52, P < 0.05 and r = -0.71, P < 0.01). Significant correlations were also found between nigral mean diffusivity values and the Unified Parkinson's Disease Rating Scale motor score (r = -0.48, P < 0.01) and between mean putaminal 6-[(18)F] fluorolevodopa uptake and the total odour score (r = 0.58; P < 0.05) as well as the Unified Parkinson's Disease Rating Scale motor score (r = -0.53, P < 0.05). This study reports a significant association between increased mean diffusivity signal and decreased 6-[(18)F] fluorolevodopa uptake, indicating that microstructural degradation of the substantia nigra and the olfactory tract parallels progression of putaminal dopaminergic dysfunction in Parkinson's disease. Since increases in nigral mean diffusivity signal also correlated with motor dysfunction, diffusion tensor imaging may serve as a surrogate marker for disease progression in future studies of putative disease modifying therapies.
Assuntos
Gânglios da Base/patologia , Dopamina/metabolismo , Neurônios Dopaminérgicos/patologia , Condutos Olfatórios/patologia , Doença de Parkinson/patologia , Substância Negra/patologia , Idoso , Anisotropia , Gânglios da Base/fisiopatologia , Corpo Estriado/fisiopatologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Condutos Olfatórios/metabolismo , Condutos Olfatórios/fisiopatologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Tomografia por Emissão de Pósitrons/métodos , Putamen/patologia , Putamen/fisiopatologia , Substância Negra/fisiopatologiaRESUMO
OBJECTIVES: To evaluate and present the data regarding clinical, laboratory, radiological and the results of molecular genetic analysis of patients with hyperinsulinemic hypoglycemia in our clinics. METHODS: A total of 9 patients with CHI followed at Istanbul Medipol University. Data related to gender, age at presentation, birth weight, gestational age, consanguinity, glucose and insulin levels at diagnosis, treatment modalities, response to treatment, the results of genetic analysis and radiological evaluation were gathered from the files. RESULTS: The oldest age at presentation was 6 months. KATP channel mutation was detected in 55% (n: 5). Diazoxide unresponsiveness was seen in 55% (n: 5). Octreotide was effective in 3 of them. 18F-DOPA PET performed in 4 diazoxide unresponsive patients revealed focal lesion in 3 of them. Spontaneous remission rate was 66% (n:6). All the patients with normal genetic result achieved spontaneous remission. Spontaneous remission was even noted in diazoxide unresponsive patients and in patients with focal lesion on 18F-DOPA PET. CONCLUSIONS: Clinical presentation of patients with congenital hypereinsulinism is heterogeneous. Spontaneous remission rate is quite high even in patients with severe clinical presentation. It is important to develop methods that can predict which patients will have spontaneous remission. Reporting the clinical and laboratory data of each patient is important and will help to guide the management of patients with hyperinsulinemic hypoglycemia.
Assuntos
Hiperinsulinismo Congênito , Canais de Potássio Corretores do Fluxo de Internalização , Humanos , Criança , Lactente , Canais de Potássio Corretores do Fluxo de Internalização/genética , Diazóxido/uso terapêutico , Remissão Espontânea , Receptores de Sulfonilureias/genética , Hiperinsulinismo Congênito/diagnóstico , Hiperinsulinismo Congênito/genética , Hiperinsulinismo Congênito/tratamento farmacológicoRESUMO
In congenital hyperinsulinemic hypoglycemia - the most common cause of persistent hypoglycemia in infancy - a focal lesion can be identified in 50% of the cases. With appropriate medical care based upon early diagnosis, these patients can be cured by the resection of the lesion rendering unnecessary long time medical care, and avoiding serious brain damage from recurrent hypoglycemic episodes. Genetic testing and 18F-fluoro-dihydroxyphenylalanine PET/CT imaging are essential for determining the best possible treatment. We report 2 cases of focal congenital hyperinsulinism - both male infants: 22 and 2 months of age - treated successfully with enucleation of the pancreas lesion (Semmelweis University, Budapest). Both patients had the pathognomonic mutation of the ABCC8 gene of the ATP-sensitive potassium channel. Radiologic imaging and histology confirmed the diagnosis, and after the operation, pharmacological treatment was terminated in both cases. During the follow-up period (5 and 1.5 years, respectively) they are euglycemic, with no morbidities attributed to the operation. We believe that these two operations for focal hyperinsulinism - diagnosed and localised by the above detailed genetic and specific radiological testing - were the first of their kind in Hungary. Based on the acquired experience, every necessary examination can be achieved in our country to improve patient care, reduce morbidity and medical costs. Orv Hetil. 2023; 164(47): 1877-1884.
Assuntos
Hiperinsulinismo Congênito , Hiperinsulinismo , Lactente , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos , Hiperinsulinismo Congênito/diagnóstico , Hiperinsulinismo Congênito/genética , Hiperinsulinismo Congênito/cirurgia , Pâncreas/patologia , Mutação , Hiperinsulinismo/patologiaRESUMO
Microdeletions at the 22q11.2 locus are associated with increased risk for schizophrenia. Recent work has demonstrated that antipsychotic naïve 22q11.2 carriers display elevated levels of dopamine synthesis capacity (DSC) as assessed by 18F-DOPA PET imaging. While this is consistent with a role for abnormal dopamine function in schizophrenia, it is unclear what molecular changes may be associated with this neuro-imaging endophenotype, and moreover, if these alterations occur independently of clinical presentation. We therefore conducted a pilot study in which we generated human induced pluripotent stem cells (hiPSCs) from two 22q11.2 deletion carriers with elevated DSC in vivo, but distinct clinical presentations. From these and neurotypical control lines we were able to robustly generate midbrain dopaminergic neurons (mDA-neurons). We then assessed whether genes associated with dopamine synthesis, metabolism or signaling show altered expression between genotypes and further between the 22q11.2 deletion lines. Our data showed alterations in expression of genes associated with dopamine metabolism and signaling that differed between the two 22q11.2 hiPSC lines with distinct clinical presentations. This reinforces the importance of considering clinical, genetic and molecular information, when possible, when choosing which donors to generate hiPSCs from, to carry out mechanistic studies.
RESUMO
Purpose: Neuroblastoma (NB) is childhood's most common extracranial solid malignancy. We have compared two imaging modalities, 131I-MIBG and 18F-DOPA PET/CT, to evaluate NB. Also, feasibility of the application of standardised scoring systems, SIOPEN and Curie scoring systems, in 18F-DOPA PET/CT was explored. Methods: Patients with histopathology-proven NB underwent 131I-MIBG (planar and SPECT/CT) and 18F-DOPA PET/CT scans, as per standard imaging protocols. Duration between scans ranged from 1 to 30 days (median = 8 days). Number of lesions in Curie and SIOPEN scoring systems applied on both modalities was compared. Results: Forty-six patients were included (M:F = 29:17) with a median age of 36 months. Both 131I-MIBG and 18F-DOPA scans were positive in 39 patients and negative in four patients. 18F-DOPA PET/CT was positive in additional three patients, in which 131I-MIBG was negative (p = 0.25). Overall, 18F-DOPA identified significantly greater number of lesions than 131I-MIBG, especially metastatic skeletal lesions (p < 0.05). Significant difference was observed between Curie scores in the two modalities, unlike SIOPEN scores. However, when the cut-off age of 18 months was taken, no significant difference was seen in either of the scoring systems in both the scans (p > 0.05). CS and SIOPEN scores were significantly higher in bone marrow-positive patients. Conclusion: 18F-DOPA PET/CT detected more lesions than 131I-MIBG but had little impact on staging of the disease. For evaluation of NB, both scans can be used interchangeably as per the availability. Furthermore, both SIOPEN and Curie scoring systems, standardised for MIBG, can also be used to semi-quantify disease extent in 18F-DOPA PET/CT. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-022-00762-6.
RESUMO
Surgery with curative intent can be offered to congenital hyperinsulinism (CHI) patients, provided that the lesion is focal. Radiolabeled exendin-4 specifically binds the glucagonlike peptide 1 receptor on pancreatic ß-cells. In this study, we compared the performance of 18F-DOPA PET/CT, the current standard imaging method for CHI, and PET/CT with the new tracer 68Ga-NODAGA-exendin-4 in the preoperative detection of focal CHI. Methods: Nineteen CHI patients underwent both 18F-DOPA PET/CT and 68Ga-NODAGA-exendin-4 PET/CT before surgery. The images were evaluated in 3 settings: a standard clinical reading, a masked expert reading, and a joint reading. The target (lesion)-to-nontarget (normal pancreas) ratio was determined using SUVmax Image quality was rated by pediatric surgeons in a questionnaire. Results: Fourteen of 19 patients having focal lesions underwent surgery. On the basis of clinical readings, the sensitivity of 68Ga-NODAGA-exendin-4 PET/CT (100%; 95% CI, 77%-100%) was higher than that of 18F-DOPA PET/CT (71%; 95% CI, 42%-92%). Interobserver agreement between readings was higher for 68Ga-NODAGA-exendin-4 than for 18F-DOPA PET/CT (Fleiss κ = 0.91 vs. 0.56). 68Ga-NODAGA-exendin-4 PET/CT provided significantly (P = 0.021) higher target-to-nontarget ratios (2.02 ± 0.65) than did 18F-DOPA PET/CT (1.40 ± 0.40). On a 5-point scale, pediatric surgeons rated 68Ga-NODAGA-exendin-4 PET/CT as superior to 18F-DOPA PET/CT. Conclusion: For the detection of focal CHI, 68Ga-NODAGA-exendin-4 PET/CT has higher clinical sensitivity and better interobserver correlation than 18F-DOPA PET/CT. Better contrast and image quality make 68Ga-NODAGA-exendin-4 PET/CT superior to 18F-DOPA PET/CT in surgeons' intraoperative quest for lesion localization.