Metaiodobenzylguanidine Scintigraphy Research Articles

Imaging of Nonmalignant Adrenal Lesions in Children.

The adrenal glands in children can be affected by a variety of benign lesions. The diagnosis of adrenal lesions can be challenging, but assessment of morphologic changes in correlation with the clinical presentation can lead to an accurate diagnosis. These lesions can be classified by their cause: congenital (eg, discoid adrenal gland, horseshoe adrenal gland, and epithelial cysts), vascular and/or traumatic (eg, adrenal hemorrhage), infectious (eg, granulomatous diseases), enzyme deficiency disorders (eg, congenital adrenal hyperplasia [CAH] and Wolman disease), benign neoplasms (eg, pheochromocytomas, ganglioneuromas, adrenal adenomas, and myelolipomas), and adrenal mass mimics (eg, extralobar sequestration and extramedullary hematopoiesis). Multimodality cross-sectional imaging helps to define the origin, extent, and relationship of these lesions to adjacent structures, as well as to guide treatment management. The anatomic and functional imaging modalities used to evaluate pediatric adrenal lesions include ultrasonography, computed tomography (CT), magnetic resonance imaging, and iodine 123 metaiodobenzylguanidine scintigraphy. Identifying the imaging features of nonmalignant adrenal lesions is helpful to distinguish these lesions from malignant adrenal neoplasms. Identifying characteristic imaging findings (eg, enlarged adrenal glands, with cerebriform surface, and stippled echogenicity in CAH; a T2-hyperintense mass with avid contrast enhancement in pheochromocytoma; low CT attenuation [<10 HU] and signal intensity drop on opposed-phase chemical shift images in adenoma; and enhancing suprarenal mass supplied by a systemic feeding artery in extralobar sequestration) can aid in making the correct diagnosis. In addition, clinical features (eg, ambiguous genitalia in CAH and hypertension in pheochromocytoma) can also guide the radiologist toward the correct diagnosis. ©RSNA, 2017.

Thyrotoxic and pheochromocytoma multisystem crisis: a case report

BackgroundThyrotoxic crisis and pheochromocytoma multisystem crisis are rare, life-threatening, emergency endocrine diseases with various clinical manifestations. Here we report a case of a patient who simultaneously developed thyrotoxic crisis and pheochromocytoma multisystem crisis and required intensive cardiovascular management.Case presentationA 60-year-old Asian man experienced nausea and vomiting, and subsequently developed dyspnea and cold sweats while farming. His serum free thyroxine, free triiodothyronine, and thyrotropin receptor antibody levels were elevated at 2.9 ng/dL, 7.2 pg/dL, and 4.7 IU/L, respectively. Serum thyrotropin levels were suppressed at less than 0.01 μIU/mL. Thyroid echography demonstrated no thyroid swelling (23 × 43 mm).A whole body computed tomography was performed for systemic evaluation. This revealed exophthalmos and a mass of size 57 × 64 mm in the anterior pararenal space. Based on these findings, we made an initial diagnosis of thyrotoxic crisis secondary to exacerbation of Grave’s hyperthyroidism. Treatment was begun with an iodine agent at a dose of 36 mg/day, thiamazole at a dose of 30 mg/day, and hydrocortisone at a dose of 300 mg daily for 3 consecutive days. To control tachycardia, continuous intravenously administered propranolol and diltiazem infusions were given. At the same time, small doses of doxazosin and carvedilol were used for both alpha and beta adrenergic blockade. On hospital day 5, his blood pressure and serum catecholamine concentrations (adrenalin 42,365 pg/mL, dopamine 6409 pg/mL, noradrenalin 72,212 pg/mL) were still high despite higher beta blocker and calcium channel blocker doses. These findings contributed to the diagnosis of pheochromocytoma multisystem crisis with simultaneous thyrotoxic crisis. We increased the doses of doxazosin and carvedilol, which stabilized his hemodynamic status. On hospital day 16, metaiodobenzylguanidine scintigraphy showed high accumulation in the right adrenal gland tumor. After retroperitoneal laparoscopic adrenalectomy on hospital day 33, his condition stabilized. He was discharged on hospital day 58.ConclusionsSince he required more intensive cardiovascular management for thyrotoxic crisis, beta blockade was increased under intensive care unit monitoring even though initial alpha blockade is recommended in pheochromocytoma. When these crises occur simultaneously, cardiovascular management can be very challenging.

Progressão da desnervação simpática cardíaca avaliada por cintigrafia com MIBG‐I123 na polineuropatia amiloidótica familiar e o impacto da transplantação hepática

IntroductionFamilial amyloid polyneuropathy (FAP) is a rare disease caused by systemic deposition of amyloidogenic variants of the transthyretin (TTR) protein. The TTR‐V30M mutation is caused by the substitution of valine by methionine at position 30 and mainly affects the peripheral and autonomic nervous systems. Cardiovascular manifestations are common and are due to autonomic denervation and to amyloid deposition in the heart. Cardiac sympathetic denervation detected by iodine‐123 labeled metaiodobenzylguanidine (MIBG) is an important prognostic marker in TTR‐V30M FAP. Liver transplantation, widely used to halt neurological involvement, appears to have a varying effect on the progression of amyloid cardiomyopathy. Its effect on the progression of cardiac denervation remains unknown. MethodsIn this observational study, patients with the TTR‐V30M mutation underwent annual cardiac assessment and serial MIBG imaging with quantification of the late heart‐to‐mediastinum (H/M) ratio. ResultsWe studied 232 patients (median age 40 years, 54.7% female, 37.9% asymptomatic at the time of inclusion) who were followed for a median of 4.5 years and underwent a total of 558 MIBG scans. During follow‐up, 47 patients (20.3%) died. MIBG scintigraphy at inclusion was a strong predictor of prognosis, with the risk of death increasing by 27.8% for each one‐tenth reduction in the late H/M ratio. The late H/M ratio decreased with age (0.082/year, p<0.001), but progression of cardiac denervation was so slow that annual repetition of MIBG imaging did not increase its prognostic accuracy. During follow‐up, 70 symptomatic patients underwent liver transplantation. The late H/M ratio decreased by 0.19/year until transplantation but no statistically significant differences were detected after the procedure. ConclusionsCardiac denervation is common during the progression of TTR‐V30M FAP and quantification of the late H/M ratio on MIBG scintigraphy is valuable for prognostic stratification of these patients. Liver transplantation stabilizes cardiac denervation, without recovery or further deterioration in cardiac MIBG uptake after the procedure.

Progression of myocardial sympathetic denervation assessed by 123I-MIBG imaging in familial amyloid polyneuropathy and the effect of liver transplantation

IntroductionFamilial amyloid polyneuropathy (FAP) is a rare disease caused by systemic deposition of amyloidogenic variants of the transthyretin (TTR) protein. The TTR-V30M mutation is caused by the substitution of valine by methionine at position 30 and mainly affects the peripheral and autonomic nervous systems. Cardiovascular manifestations are common and are due to autonomic denervation and to amyloid deposition in the heart. Cardiac sympathetic denervation detected by iodine-123 labeled metaiodobenzylguanidine (MIBG) is an important prognostic marker in TTR-V30 M FAP. Liver transplantation, widely used to halt neurological involvement, appears to have a varying effect on the progression of amyloid cardiomyopathy. Its effect on the progression of cardiac denervation remains unknown. MethodsIn this observational study, patients with the TTR-V30 M mutation underwent annual cardiac assessment and serial MIBG imaging with quantification of the late heart-to-mediastinum (H/M) ratio. ResultsWe studied 232 patients (median age 40 years, 54.7% female, 37.9% asymptomatic at the time of inclusion) who were followed for a median of 4.5 years and underwent a total of 558 MIBG scans. During follow-up, 47 patients (20.3%) died. MIBG scintigraphy at inclusion was a strong predictor of prognosis, with the risk of death increasing by 27.8% for each one-tenth reduction in the late H/M ratio. The late H/M ratio decreased with age (0.082/year, p<0.001), but progression of cardiac denervation was so slow that annual repetition of MIBG imaging did not increase its prognostic accuracy. During follow-up, 70 symptomatic patients underwent liver transplantation. The late H/M ratio decreased by 0.19/year until transplantation but no statistically significant differences were detected after the procedure. ConclusionsCardiac denervation is common during the progression of TTR-V30 M FAP and quantification of the late H/M ratio on MIBG scintigraphy is valuable for prognostic stratification of these patients. Liver transplantation stabilizes cardiac denervation, without recovery or further deterioration in cardiac MIBG uptake after the procedure.

Significant correlation between renal 123I-metaiodobenzylguanidine scintigraphy and muscle sympathetic nerve activity in patients with primary hypertension

BackgroundIodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy is used as a noninvasive imaging method for assessing cardiac sympathetic nerve activity. We tested the hypothesis that renal 123I-MIBG imaging is correlated with muscle sympathetic nerve activity (MSNA) in patients with primary hypertension. MethodsThirty-one consecutive patients with primary hypertension were included. Multiunit MSNA was recorded from the peroneal nerve to evaluate direct efferent sympathetic nerve activity. Planar renal and cardiac 123I-MIBG images were acquired. Early and delayed kidney-to-mediastinum ratio (K/M), early and delayed heart-to-mediastinum ratio (H/M), and washout rates (WR) were calculated. ResultsIn 27 of 31 patients, blood pressure was controlled on antihypertensive medication. Mean systolic and diastolic blood pressures were 118 ± 18 and 67 ± 15 mmHg, respectively. Although early and late K/M and H/M were not significantly correlated with MSNA, both cardiac and average renal WR were significantly correlated with MSNA (r = 0.45, P = .0035 and r = 0.68, P < .001, respectively). Right and left renal WR were similarly correlated with MSNA. Renal WR was significantly higher than cardiac WR (43.2% vs 25.8%, P < .001) in these patients with hypertension. ConclusionsRenal 123I-MIBG WR was significantly associated with multiunit MSNA. Renal 123I-MIBG imaging offers a noninvasive clinical methodology for assessing renal sympathetic nerve function.

Pheochromocytomatosis Treated By Radio-Guided Surgery

ABSTRACT Objective: Pheochromocytomatosis is a rare cause of recurrent pheochromocytoma due to seeding of tumor cells at the time of adrenalectomy. The diagnosis can be difficult and a high degree of suspicion is required pre-operatively. We present the case of a 57-year-old woman with a long history of symptoms suggestive of recurrent pheochromocytoma that evaded diagnosis for many years. Methods: We describe the clinical course, diagnosis, and management. We also present a comprehensive review of the current literature. Results: Pheochromocytomatosis in our patient presented as multiple recurrent episodes of tachycardia and hypertension 15 years after left adrenalectomy for pheochromocytoma. Diagnosis was evaded until complete hormonal evaluation confirmed biochemical evidence of catecholamine overproduction. Imaging revealed two sites of recurrence. Management included alpha-blockade followed by radio-guided surgery using 123I-labeled metaiodobenzylguanidine scintigraphy and a gamma probe. At surgery, ...

Iodine-123 metaiodobenzylguanidine scintigraphy for the assessment of cardiac sympathetic innervation and the relationship with cardiac autonomic function in healthy adults using standardized methods.

Global iodine-123 metaiodobenzylguanidine (I-MIBG) uptake is predictive of cardiovascular events and mortality in patients with heart failure. Normal variations in global and regional uptake, however, are not well defined and few studies have addressed the functional relevance of I-MIBG uptake and distribution in healthy individuals. We performed I-MIBG scintigraphy and cardiac autonomic function testing using the standardized methodology in 15 healthy individuals (mean age 54.6±5.3 years, male : female 10 : 5) with no evidence of previous myocardial infarction or ischaemic heart disease. Early heart to mediastinum ratio (HMR) was 1.67±0.13, late HMR was 1.73±0.16 and washout rate was 19.09±7.63% (4.20-31.30). Regional analysis showed reduced tracer uptake at the apex, base and inferior wall in all individuals. Early and late HMR correlated negatively with RFa (r=-0.603; P=0.05 and r=-0.644; P=0.033) and expiration and inspiration ratio (r=-0.616; P=0.043 and r=-0.676; P=0.022) and positively with LFa/RFa (r=0.711; P=0.014 and r=0.784; P=0.004). Washout rate correlated only with RFa (r=0.642; P=0.033). Healthy adults show a heterogeneous pattern of cardiac innervation with reduced regional uptake of I-MIBG. Furthermore, HMR correlates with indices of cardiac sympathetic function, suggesting that it might not only be a useful prognostic marker but may also provide insight into the functional integrity of the cardiac autonomic nervous system.

Abstract 12766: Cardiac Sympathetic Nerve System Activity Evaluated by Cardiac I-123 Metaiodobenzylguanidine Scintigraphy in Heart Failure Patients With Preserved or Reduced Ejection Fraction

Introduction: Heart failure with preserved ejection fraction (HFpEF) is the predominant form of heart failure. However, there is no proven therapy for HFpEF. In contrast, significant benefits of beta-blockers that inhibit cardiac nerve system activity have been established in patients with heart failure with reduced ejection fraction (HFrEF). The purpose of this study is to compare cardiac sympathetic nerve system activity in patients with HFpEF versus HFrEF. Methods: The I-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to evaluate cardiac sympathetic nerve system activity in 48 heart failure patients (age 77.0±10.6 years; male 52.1%). We compared the early and delayed heart/mediastinum (H/M) ratio and the washout rate (WR) in patients with HFpEF (left ventricular ejection fraction; LVEF≥50%, n=20) and HFrEF (LVEF&lt;50%, n=28). Results: There were no differences in age and sex between two groups. LVEF was significantly higher in patients with HFpEF than in those with HFrEF (62.5±11.7 vs 31.7±9.1%, p&lt;0.001). Plasma BNP level was significantly lower in patients with HFpEF than in those with HFrEF (205.1 [IQR, 155.0-430.5] vs 369.0 [IQR, 196.6-662.1] pg/mL, p=0.04). Plasma norepinephrine level was not different between HFpEF patients and HFrEF patients (428.5 [IQR, 210.5-676.3] vs 392.5 [IQR, 307.2-535.8] pg/mL, p=0.93). No significant differences were found in the early H/M ratio (2.17±0.46 vs 2.10±0.32, p=0.53) and in the delayed H/M ratio (1.94±0.53 vs 1.80±0.35, p=0.91) between HFpEF patients and HFrEF patients. The WR was also similar in HFpEF patients and HFrEF patients (37.9±17.0 vs 46.3±16.4%, p=0.09). The use of beta-blockers was significantly lower in patients with HFpEF than in those with HFrEF (35.0 vs 71.4%, p=0.01). Conclusions: Although the use of beta-blockers was lower in patients with HFpEF as compared to in those with HFrEF, cardiac sympathetic nerve system activity was elevated to a similar extent between patients with HFpEF and HFrEF. These findings suggest that cardiac sympathetic nerve system is a promising therapeutic target in patients with HFpEF.

Ikerpárban előforduló örökletes phaeochromocytoma

Phaeochromocytoma is a tumor of the catecholamine-producing cells of the adrenal gland. Extraadrenal phaeochromocytomas are frequently called paragangliomas. The majority of phaeochromocytomas are sporadic, however, about 25-30% are caused by genetic mutation. These tumor are frequently referred as hereditary phaeochromocytomas/paragangliomas. Their incidence increases continuously which can be attributed to availability of genetic examination and to the discovery of novel genes. The 47-year-old female patient underwent abdominal computed tomography which revealed bilateral adrenal gland enlargement. Abdominal magnetic resonance imaging, the 131-I- metaiodobenzylguanidine scintigraphy, urinary catecholamines and serum chomogranin A measurements confirmed the diagnosis of bilateral phaeochromocytomas. The genetically identical twin sister of the patient was also diagnosed with hormonally active bilateral phaechromocytoma, suggesting the genetic origin of phaeochromocytoma. Mutation screening confirmed a germline mutation of the transmembrane protein 127 tumorsupressor gene in both patients. Both patients underwent cortical-sparing adrenalectomy. The adrenal gland with the larger tumor was totally resected, while in the opposite side only the tumor was resected and a small part of the cortex was saved. After the operation urinary catecholamines and serum chromogranin A returned to normal in both patients. Adrenocortical deficiency was absent in the first patient, but her sister developed adrenal insufficiency requiring glucocorticoid replacement. To the best of the authors' knowledge phaeochromocytoma affecting twins has never been described earlier. Genetic examination performed in siblings confirmed the presence of the mutant gene through four generations. Orv. Hetil., 2016, 157(33), 1326-1330.

Initial Experience with Renal Denervation for the Treatment of Resistant Hypertension - The Utility of Novel Anesthetics and Metaiodobenzylguanidine Scintigraphy (MIBG).

Background:The Symplicity-HTN 3 trial failed to show significant difference in blood pressure (BP) lowering between patients undergoing catheter-based renal denervation (RDN) and the sham-procedure arm of the study. However, there is still optimism about the role of RDN in the treatment of resistant hypertension, because identification of patients with increased sympathetic activity thus being good RDN responders, improvements in the RDN procedure and new technology RDN catheters are all expected to lead to better RDN results. We present our initial experience with RDN for the treatment of resistant hypertension, and the utility of novel anesthetics and cardiac 123I-metaiodobenzylguanidine scintigraphy (123I-MIBG).Methods and Results:Seven patients with resistant hypertension underwent RDN and were followed up for 6 months. MIBG was performed before RDN, in order to estimate sympathetic activity and predict the response to RDN. All patients were sedated with dexmedetomidine and remifentanil during RDN. All patients tolerated the procedure well, were hemodynamically stable and their peri-procedural pain was effectively controlled. A median of 7.6 ± 2.1 and 6 ± 1.4 ablations were delivered in the right and left renal artery respectively, making an average of 6.8 burns per artery. No peri-procedural or late complications - adverse events (local or systematic) occurred. At 6 months, mean reduction in office BP was -26.0/-16.3 mmHg (p=0.004/p=0.02), while mean reduction in ambulatory BP was -12.3/-9.2 mmHg (p=0.118/p=0.045). One patient (14.3%) was a non-responder. None of the cardiac 123I-MIBG imaging indexes(early and late heart-to-mediastinum (H/M) count density ratio, washout rate (WR) of the tracer from the myocardium) were different between responders and non-responders.Conclusion:Patients with resistant hypertension who underwent RDN in our department had a significant reduction in BP 6 months after the intervention. 123I-MIBG was not useful in predicting RDN response. Dexmedetomidine and remifentanil provided sufficient patient comfort during the procedure, allowing an adequate number of ablations per renal artery to be performed, and this could probably lead to improved RDN results.

Advantages and disadvantages of nuclear medicine techniques used in the diagnosis of patients with neuroblastoma (a review)

About the 50 % of patients with neuroblastoma (NB) suffered from generalized form of disease at the moment of diagnosis establishing. So, the correct staging with the usage of methods of radiation diagnosis and nuclear medicine is very important in this setting. Meta-iodobenzyl guanidine (MIBG) is an analogue of noradrenalin so this is the ideal tumortropic drug for visualization of cells expresses carriers of noradrenalin. Main problems of method of MIBG scintigraphy are the limited spatial resolution, low sensitivity during the diagnosis of small-sized tumours, presence of NB without MIBG accumulation, duration of scanning and necessity of several scanning protocols. Positron-emission tomography with consequent radiopharmaceuticals can be good alternative way in comparison with routine scintigraphy with MIBG to help in case of doubtful and contradictory results.

Usefulness of Cardiac MetaIodobenzylguanidine Imaging to Improve Prognostic Power of the Model for End-Stage Liver Disease Scoring System in Patients With Mild-to-Moderate Chronic Heart Failure

Liver dysfunction has a prognostic impact on the outcomes of patients with advanced heart failure (HF). The model for end-stage liver disease (MELD) score is a robust system for rating liver dysfunction, and a high score has been shown to be associated with a poor prognosis in ambulatory patients with HF. In addition, cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with chronic HF (CHF). However, the long-term predictive value of combining the MELD score and cardiac MIBG imaging in patients with CHF has not been elucidated. To prospectively investigate whether cardiac MIBG imaging provides additional prognostic value to the MELD score in patients with mild-to-moderate CHF, we studied 109 CHF outpatients (New York Heart Association: 2.0 ± 0.6) with left ventricular ejection fraction <40%. At enrollment, an MELD score was obtained, and the heart-to-mediastinal ratio on delayed imaging and MIBG washout rate (WR) were measured using cardiac MIBG scintigraphy. During a follow-up period of 7.5 ± 4.2years, 36 of 109 patients experienced cardiac death (CD). On multivariate Cox analysis, MELD score and WR were significantly independently associated with CD, although heart-to-mediastinal ratio showed an association with CD only on univariate Cox analysis. Patients with abnormal WR (>27%) had a significantly greater risk of CD than those with normal WR in both those with high MELD scores (≥10; hazard ratio 4.0 [1.2 to 13.6]) and with low MELD scores (<10; hazard ratio 6.4 [1.7 to 23.2]). In conclusion, cardiac MIBG imaging would provide additional prognostic information to the MELD score in patients with mild-to-moderate CHF.

V11-02 BILATERAL ADRENALECTOMY AND MULTIPLE TUMORECTOMY IN VON HIPPEL–LINDAU DESEASE

You have accessJournal of UrologyAdrenal/Single Port Surgery/LESS/NOTES1 Apr 2016V11-02 BILATERAL ADRENALECTOMY AND MULTIPLE TUMORECTOMY IN VON HIPPEL–LINDAU DESEASE Juan Antonio Peña, Joan Palou, Andrés Kanashiro, Luis Miguel Sierra, Ivan Schwartzmann, and Humberto Villavicencio Juan Antonio PeñaJuan Antonio Peña More articles by this author , Joan PalouJoan Palou More articles by this author , Andrés KanashiroAndrés Kanashiro More articles by this author , Luis Miguel SierraLuis Miguel Sierra More articles by this author , Ivan SchwartzmannIvan Schwartzmann More articles by this author , and Humberto VillavicencioHumberto Villavicencio More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1819AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The von Hippel - Lindau disease is an autosomal dominant disease that courses with multifocal renal cell carcinoma in 65% of the affected individuals. The risk of developing pheochromocytomas in these patients reaches 20%. METHODS We present the case of a 50 year old man, obese with past history of hypertension; diagnosed by MRI performed prior to bariatric surgery, with a bilateral adrenal tumor (Left 7x7cm and right 5x4cm) and a double right renal tumor (posterior middle valve 3x2cm and lower pole 1.5cm). Given the high plasma and urinary levels of norepinephrine and the positive metaiodobenzylguanidine scintigraphy (MYBG), diagnosis of bilateral pheochromocytoma was confirmed. Simultaneous left nephron sparing surgery and adrenalectomy by retroperitoneoscopy approach after trasnperitoneal left adrenalectomy were proposed. RESULTS Following an alpha and beta-adrenergic blockade, a left transperitoneal laparoscopic adrenalectomy was performed without incident. (120 minutes - Estimated blood loss: 150 cc). One month later a retroperitoneal right adrenalectomy with off-clamp tumorectomy of the two right kidney tumors was undertaken. The pathology showed bilateral pheochromocytoma; while the right kidney tumorectomy report clear cell carcinoma, Fuhrman I, pT1a, with negative surgical margin in both tumours. The genetic studies confirmed VHL disease. The patient remained normotensive without medical treatment. CONCLUSIONS Simultaneous laparoscopic nephron sparing surgery and adrenalectomy is a suitable option for patients with Von Hippel-Lindau Disease affected by synchronic pheocromocytomas and renal tumors. Trans and Retroperitoneal approaches are both safe and effective procedures presenting low morbidity, and may both be used as an alternative, depending on the position of the renal tumors. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1003 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Juan Antonio Peña More articles by this author Joan Palou More articles by this author Andrés Kanashiro More articles by this author Luis Miguel Sierra More articles by this author Ivan Schwartzmann More articles by this author Humberto Villavicencio More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

24-Hour Ambulatory Blood Pressure Monitoring in SWEDDs Patients With Parkinsonism.

Patients diagnosed with Parkinson's disease (PD) on clinics who subsequently turn out to have normal dopamine transporter images have been referred to as scans without evidence of dopaminergic deficits (SWEDDs) patients. Cardiovascular autonomic dysfunction has frequently been reported in PD. In this study, we determined the similarities and differences in cardiac autonomic dysfunction between SWEDDs and PD patients. This study investigated whether 24-hour ambulatory blood pressure monitoring (24-hour ABPM) can help identify possible cases with SWEDDs. We enrolled 28 SWEDDs patients, 46 patients with PD, and 30 healthy controls. To evaluate cardiac autonomic function, 24-hour ABPM was performed on all subjects. Cardiac metaiodobenzylguanidine (MIBG) scintigraphy was performed on the SWEDDs and PD subjects. The percentage nocturnal decline in blood pressure differed significantly among SWEDDs patients, PD patients, and controls (p<0.05). In addition to the abnormal nocturnal BP, regulation (nondipping and reverse dipping) was significantly higher in SWEDDs and PD subjects than in the control subjects (p<0.05). There was no significant correlation between the % nocturnal blood pressure reduction and parameters of cardiac MIBG uptake ratio. However, orthostatic hypotension was significant correlated with the nocturnal blood pressure dip (%), nocturnal blood pressure patterns, and the cardiac MIBG uptake ratio (early and late) in combined SWEDDs and PD subjects. Pathologic nocturnal blood pressure regulation and nocturnal hypertension, known characteristics of PD, are also present in SWEDDs. Moreover, cardiac sympathetic denervation should not be attributed to cardiac autonomic dysfunction in SWEDDs patients. As with PD patients, the SWEDDs patients studied here tended to have cardiac autonomic dysfunction.

A longitudinal study of a family with adult-onset autosomal dominant leukodystrophy: Clinical, autonomic and neuropsychological findings.

Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare progressive neurological disorder caused by Lamin B1 duplication (LMNB1). Our aim was to investigate longitudinally the pattern of the autonomic dysfunction and the degree of neuropsychological involvement. Three related ADLD patients and one asymptomatic carrier of LMNB1 duplication underwent a standardized evaluation of autonomic nervous system, including cardiovascular reflexes, pharmacological testing, microneurography, skin biopsy, Metaiodobenzylguanidine scintigraphy and a complete neuropsychological battery. An early neurogenic orthostatic hypotension was detected in all patients and confirmed by a low rise in noradrenaline levels on Tilt Test. However infusion of noradrenaline resulted in normal blood pressure rise as well as the infusion of clonidine. At the insulin tolerance test the increase in adrenaline resulted pathological in two out three patients. Microneurography failed to detect muscle sympathetic nerve activity bursts. Skin biopsy revealed a poor adrenergic innervation, while cardiac sympathetic nerves were normal. None of ADLD patients showed a global cognitive deficit but a selective impairment in the executive functions. Autonomic disorder in ADLD involves selectively the postganglionic sympathetic system including the sympatho-adrenal response. Cognitive involvement consisting in an early impairment of executive tasks that might precede brain MR abnormalities.

Biomarkers Differentiating Dementia withLewy Bodies from Other Dementias: AMeta-Analysis.

Several nuclear imaging and cerebrospinal fluid (CSF) biomarkers are under investigation, aimed at facilitating the differential diagnosis of dementias. To quantitatively synthesize data on test performance in differentiating dementia with Lewy bodies (DLB) from other dementias. We searched PubMed (January 2000- March 2015) for English-language publications that assessed a selected set of five imaging and three CSF biomarkers for this purpose. We meta-analyzed measures of agreement between biomarker results and clinical diagnosis. Forty-five publications were eligible. The majority of evidence was based on studies that enrolled representative disease populations. For differentiating between DLB and Alzheimer's disease (AD) or other dementias, metaiodobenzylguanidine scintigraphy and dopamine transporter (DAT) single photon emission computed tomography (SPECT) showed, respectively, excellent (summary kappa = 0.85; 95% confidence interval [95% CI], 0.74-0.96) and good (summary kappa = 0.71; 95% CI, 0.43-0.99) agreement. Metaiodobenzylguanidine scintigraphy appeared superior to fluorodeoxyglucose- positron emission tomography (summary kappa = 0.53; 95% CI, 0.36-0.69) and cerebral blood flow SPECT (summary kappa = 0.40; 95% CI, 0.33-0.47). For differentiating DLB from AD, CSF t-tau levels (summary kappa = 0.68; 95% CI, 0.55-0.82) performed comparably to metaiodobenzylguanidine scintigraphy and DAT SPECT. Sparse direct comparative evidence failed to corroborate these indirect comparisons. Metaiodobenzylguanidine scintigraphy and DAT SPECT are highly concordant with clinical diagnosis in differentiating DLB from other dementias. However, given the limitations in the study design, the applicability of these results to real-world differential diagnosis remains unclear. Prospective studies targeting patients with atypical presentations that adopt gold standard tests would reliably estimate the true test performance of these promising biomarkers.

Neuroblastoma: From Diagnosis to Treatment

Neuroblastoma (NB) is the most common extracranial solid tumor in children. It affects mostly pre-teen age, and in almost 50% of the cases the disease is already metastatic at initial diagnosis. NB originates from neuroectodermal cells of the neural crest that migrate during the embryonic life, giving rise to the sympathetic ganglia and adrenal medulla. For this reason, over 90% of patients with NB show high levels of catecholamines in the serum and urine. Typically, symptoms at presentation reflect the location and the extent of the disease, as well as the secretory status of the tumor. The diagnosis of NB is based on a multidisciplinary workup including clinical and laboratory data, tumor histology, bone marrow biopsy, and instrumental investigations. A significant role in the diagnostic and therapeutic process of NB is nowadays played by metaiodobenzylguanidine (MIBG) scintigraphy, considered as standard for the initial staging, detection of recurrence and disease monitoring. According to age, disease stage, tumor histology, N - MYC gene amplification, or chromosomal aberrations, NB can be classified into four different risk groups, reflecting different prognosis and leading to different therapeutic options. The treatment of NB is based on a variegate approach ranging from pure monitoring in very low-risk patients, to curative surgery or combined surgery and chemotherapy in low-intermediate risk, to very aggressive multi-agent regimens for high risk patients.

Role of Pre-operative Meta-Iodo Benzyl Guanidine (MIBG) in Biochemically Proven and Anatomically Localized Adrenal Pheochromocytoma

Background: Radio labeled metaiodobenzylguanidine scintigraphy (MIBG) is used for used to image pheochromocytomas. While computed tomography (CECT) or magnetic resonance imaging (MRI) usually localizes the tumor, MIBG is often obtained to rule out multifocal and metastatic disease and to corroborate anatomic imaging with functional data. Since the utility of routine MIBG is questionable in the pre-operative setting, the aim of this retrospective analysis was to look at this issue. Methods: All patients of pheochromocytoma who underwent MIBG scintigraphy at our institute between 2003 and 2013 were identified retrospectively. The findings of CECT, MIBG, operative findings and histopathological results were reviewed and compared. Results: A total of 29 patients underwent MIBG scintigraphy for the pre-operative evaluation of pheochromocytoma for variable reasons. All patients had raised 24 hr. urinary fractionated metanephrine or nor-metanephrine. Four patients with >5 cm tumors had negative MIBG uptake and 4 patients with unilateral tumors showed bilateral uptake. MIBG did not identify any additional foci of disease or alter the surgical management in any patient but added to the confusion regarding optimum management in patients with bilateral uptake. Conclusion: The routine use of pre-operative MIBG scintigraphy is not useful in patients with biochemically confirmed and localized apparently sporadic adrenal pheochromocytoma. Its use should be limited to the subset of patients with equivocal biochemical disease, familial disease, negative cross sectional imaging or those with recurrent or metastatic disease.

68Gallium-DOTANOC positron emission tomography/computed tomography scintigraphy for an unusual case of malignant pheochromocytoma: Findings and review of literature

Functional imaging is an important step in the diagnostic approach of patients with pheochromocytoma (PCC). Metaiodobenzylguanidine (MIBG) scintigraphy (single-photon emission computed tomography) is currently the most widely used functional imaging modality for evaluating a case of PCC. However, it has some limitations and poor sensitivity, especially in cases of malignant PCC (MPCC). Positron emission tomography (PET) scanning with gallium-68 (68Ga)-DOTA-coupled somatostatin analogs is the newer upcoming modality with some superiority over MIBG scan. We present a case of MPCC with unusual invasion and metastasis positive on DOTANOC PET scan along with relevant review of literature.

Effect of Nebivolol on MIBG Parameters and Exercise in Heart Failure with Normal Ejection Fraction.

BackgroundMore than 50% of the patients with heart failure have normal ejection fraction (HFNEF). Iodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy and cardiopulmonary exercise test (CPET) are prognostic markers in HFNEF. Nebivolol is a beta-blocker with vasodilating properties.ObjectivesTo evaluate the impact of nebivolol therapy on CPET and123I-MIBG scintigraphic parameters in patients with HFNEF.MethodsTwenty-five patients underwent 123I-MIBG scintigraphy to determine the washout rate and early and late heart-to-mediastinum ratios. During the CPET, we analyzed the systolic blood pressure (SBP) response, heart rate (HR) during effort and recovery (HRR), and oxygen uptake (VO2). After the initial evaluation, we divided our cohort into control and intervention groups. We then started nebivolol and repeated the tests after 3 months.ResultsAfter treatment, the intervention group showed improvement in rest SBP (149 mmHg [143.5-171 mmHg] versus 135 mmHg [125-151 mmHg, p = 0.016]), rest HR (78 bpm [65.5-84 bpm] versus 64.5 bpm [57.5-75.5 bpm, p = 0.028]), peak SBP (235 mmHg [216.5-249 mmHg] versus 198 mmHg [191-220.5 mmHg], p = 0.001), peak HR (124.5 bpm [115-142 bpm] versus 115 bpm [103.7-124 bpm], p= 0.043), HRR on the 1st minute (6.5 bpm [4.75-12.75 bpm] versus 14.5 bpm [6.7-22 bpm], p = 0.025) and HRR on the 2nd minute (15.5 bpm [13-21.75 bpm] versus 23.5 bpm [16-31.7 bpm], p = 0.005), but no change in peak VO2 and 123I-MIBG scintigraphic parameters.ConclusionDespite a better control in SBP, HR during rest and exercise, and improvement in HRR, nebivolol failed to show a positive effect on peak VO2 and 123I-MIBG scintigraphic parameters. The lack of effect on adrenergic activity may be the cause of the lack of effect on functional capacity.