Quantitative trunk sway analysis under challenging gait conditions in early and untreated Parkinson's disease.

INTRODUCTION: Even experienced clinicians may encounter difficulties in making a definitive diagnosis in the early motor stages of Parkinson's disease (PD). We investigated whether quantitative biomechanical trunk sway analysis could support the diagnosis of PD early on. METHODS: We quantified trunk sway performance using body-worn sensors during a test battery of six challenging gait conditions in a cohort of 17 early and untreated PD patients (with evidence of reduced tracer uptake in the basal ganglia on dopamine transporter scans) and 17 age- and sex-matched healthy controls (HCs). RESULTS: Compared to HC, the PD group (Hoehn & Yahr ≤ 2, Unified Parkinson's Disease Rating Scale motor score: mean 13.7 ± 3.5 points) showed significant trunk rigidity in five challenging gait tasks (decreased medio-lateral direction and sway angle area). Post hoc receiver operating characteristic analysis of the significant parameters revealed excellent discrimination with high sensitivity and specificity. CONCLUSION: In the early and untreated motor stages of PD, patients exhibit significant trunk rigidity during challenging gait tasks. Trunk sway motion recorded with body-worn sensors might be a useful tool to disclose a sometimes hard-to-trace cardinal motor sign of PD and support an early clinical diagnosis.

Hepatic brucellosis detected by 18F-FDG PET/CT.

A 52-year old woman with fever of unknown origin underwent fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scan for further evaluation. A clinical history of cervical cancer (CIS) operated 20 years ago was documented. Two foci in the right lobe of the slightly enlarged liver presented increased 18F-FDG uptake. Visceral brucellosis was diagnosed via blood culture. The patient received anti-brucella therapy and recovered rapidly, the liver lesions diminished on control CT.

Serotonin 1A receptor density measured by F18-Mefway PET/CT in mesiotemporal cortex and raphe does not discriminate therapeutic response in patients with major depressive episode.

BACKGROUND: More than 50% of patients with major depressive episode (MDE) fail to respond to initial treatment with first line pharmacological therapy. Altered receptor and serotonin transporter function are considered to be associated with mental disorders. Our investigation aimed on the density of the HT1A receptor in mesiotemporal cortex (MTC) and raphe measured by F18-Mefway in patients with MDD. METHODS: Patients with untreated clinically suspected major depressive episode were recruited from June 2012 to May 2014. 49 patients were included into the study: 36 patients (73%) were identified as responders, whereas 13 (27%) were non-responders. Gender distribution was 26 men (56%) and 23 women (44%). For treatment, only a standard medication of a selective serotonin reuptake inhibitor (SSRI) with escitalopram in a range of 10-20 mg/day was permitted. Responders were defined by improvement of the MADRS>50%. Visually MTC had the highest uptake of F18-Mefway among all brain regions, an asymmetry could not be observed in any patient. An elliptical region was drawn over the amygdala and hippocampus area and a small circular region was drawn over the raphe nuclei. All data were calculated related to (unspecific) cerebellar uptake. RESULTS: The quotient of the right MTC was 5.00 [4.33; 5.50] in all patients, in responders 5.00 [4.00; 5.75] and in non-responders 5.00 [4.50; 5.50] (P=0.56). The quotient of the left MTC presented with a median level of 4.50 [4.50; 5.50] in all persons. The responders had 4.50 [4.50; 5.75] which was not statistically significant to the data of the non-responders with 5.00 [4.50; 5.50] at P=0.64. The raphe had a median quotient of 2.50 [2.00; 3.00] in all and the cohort of responders, whereas non-responders had 2.50 [2.00; 2.50] (P=0.61). Also the absolute values of SUV in the three brain regions were not statistically different between the cohorts. Additionally, we did not find any sex-related differences in our patient group. CONCLUSIONS: Serotonin 1A receptor density can be assessed efficiently by F18-Mefway and PET-CT in patients with MDE. The method can be estimated as a possible tool for clinical and academic investigation, marked tracer uptake can constantly be observed at MTC and the raphe. Anyhow, under conditions of real life in patient care, it is not possible to distinguish patients with a good prognosis who will respond to standard SSRI therapy from non-responders who would benefit from a different therapeutic approach starting earlier.

(18)F-fluorodeoxyglucose and (18)F-flumazenil positron emission tomography in patients with refractory epilepsy.

BACKGROUND: Epilepsy is a neurological disorder characterized by epileptic seizures as a result of excessive neuronal activity in the brain. Approximately 65 million people worldwide suffer from epilepsy; 20-40% of them are refractory to medication therapy. Early detection of disease is crucial in the management of patients with epilepsy. Correct localization of the ictal onset zone is associated with a better surgical outcome. The modern non-invasive techniques used for structural-functional localization of the seizure focus includes electroencephalography (EEG) monitoring, magnetic resonance imaging (MRI), single photon emission tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT). PET/CT can predict surgical outcome in patients with refractory epilepsy. The aim of the article is to review the current role of routinely used tracer 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) as well as non routinely used (18)F-Flumazenil ((18)F-FMZ) tracers PET/CT in patients with refractory epilepsy. CONCLUSIONS: Functional information delivered by PET and the morphologic information delivered by CT or MRI are essential in presurgical evaluation of epilepsy. Nowadays (18)F-FDG PET/CT is a routinely performed imaging modality in localization of the ictal onset zone in patients with refractory epilepsy who are unresponsive to medication therapy. Unfortunately, (18)F-FDG is not an ideal PET tracer regarding the management of patients with epilepsy: areas of glucose hypometabolism do not correlate precisely with the proven degree of change within hippocampal sclerosis, as observed by histopathology or MRI. Benzodiazepine-receptor imaging is a promising alternative in nuclear medicine imaging of epileptogenic focus. The use of (11)C-FMZ in clinical practice has been limited by its short half-life and necessitating an on-site cyclotron for production. Therefore, (18)F-FMZ might be established as one of the tracers of choice for patients with refractory epilepsy because of better sensitivity and anatomical resolution.

Multiparametric Analysis Combining DSC-MR Perfusion and [18F]FET-PET is Superior to a Single Parameter Approach for Differentiation of Progressive Glioma from Radiation Necrosis.

PURPOSE: Perfusion-weighted (PWI) magnetic resonance imaging (MRI) and O­(2-[18F]fluoroethyl-)-l-tyrosine ([18F]FET) positron emission tomography (PET) are both useful for discrimination of progressive disease (PD) from radiation necrosis (RN) in patients with gliomas. Previous literature showed that the combined use of FET-PET and MRI-PWI is advantageous; hhowever the increased diagnostic performances were only modest compared to the use of a single modality. Hence, the goal of this study was to further explore the benefit of combining MRI-PWI and [18F]FET-PET for differentiation of PD from RN. Secondarily, we evaluated the usefulness of cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TTP) as previous studies mainly examined cerebral blood volume (CBV). METHODS: In this single center study, we retrospectively identified patients with WHO grades II-IV gliomas with suspected tumor recurrence, presenting with ambiguous findings on structural MRI. For differentiation of PD from RN we used both MRI-PWI and [18F]FET-PET. Dynamic susceptibility contrast MRI-PWI provided normalized parameters derived from perfusion maps (r(relative)CBV, rCBF, rMTT, rTTP). Static [18F]FET-PET parameters including mean and maximum tumor to brain ratios (TBRmean, TBRmax) were calculated. Based on histopathology and radioclinical follow-up we diagnosed PD in 27 and RN in 10 cases. Using the receiver operating characteristic (ROC) analysis, area under the curve (AUC) values were calculated for single and multiparametric models. The performances of single and multiparametric approaches were assessed with analysis of variance and cross-validation. RESULTS: After application of inclusion and exclusion criteria, we included 37 patients in this study. Regarding the in-sample based approach, in single parameter analysis rTBRmean (AUC = 0.91, p < 0.001), rTBRmax (AUC = 0.89, p < 0.001), rTTP (AUC = 0.87, p < 0.001) and rCBVmean (AUC = 0.84, p < 0.001) were efficacious for discrimination of PD from RN. The rCBFmean and rMTT did not reach statistical significance. A classification model consisting of TBRmean, rCBVmean and rTTP achieved an AUC of 0.98 (p < 0.001), outperforming the use of rTBRmean alone, which was the single parametric approach with the highest AUC. Analysis of variance confirmed the superiority of the multiparametric approach over the single parameter one (p = 0.002). While cross-validation attributed the highest AUC value to the model consisting of TBRmean and rCBVmean, it also suggested that the addition of rTTP resulted in the highest accuracy. Overall, multiparametric models performed better than single parameter ones. CONCLUSION: A multiparametric MRI-PWI and [18F]FET-PET model consisting of TBRmean, rCBVmean and PWI rTTP significantly outperformed the use of rTBRmean alone, which was the best single parameter approach. Secondarily, we firstly report the potential usefulness of PWI rTTP for discrimination of PD from RN in patients with glioma; however, for validation of our findings the prospective studies with larger patient samples are necessary.

Pitfall in follow-up imaging of pancreatic neuroendocrine tumor by somatostatin receptor PET.

56-year old woman was operated of a pancreatic NET in May 2011. Abdominal pain had led to imaging and consecutively the finding of cholecystolithiasis and the tumor. The gall bladder, left hemi-pancreas, regional lymph nodes and the (unintentional injured) spleen were resected. At routine control examination in October 2012 CT presented three contract enhancing intra-abdominal lesions with a diameter of 2-3.5 cm. Consecutively 68Ga-DOTA-NOC PET-CT showed high tracer uptake (SUV 10-12) at these lesions. Therefore a relapse of the neuro-endocrine tumor was suspected. After reoperation in December 2012 histology did not reveal any sign of neuroendocrine tumor but identified spleen tissue most probably caused by splenosis accidentally seeded at the first operation. Physiologically the spleen is highly avid at 68Ga-DOTATOC PET, but splenosis presents with less standard uptake value. In our case the described lesions presented with an SUV quite comparable to that of neuroendocrine tumor tissue.

18F-Fluoroethyl-L Tyrosine Positron Emission Tomography Radiomics in the Differentiation of Treatment-Related Changes from Disease Progression in Patients with Glioblastoma.

The follow-up of glioma patients after therapeutic intervention remains a challenging topic, as therapy-related changes can emulate true progression in contrast-enhanced magnetic resonance imaging. 18F-fluoroethyl-tyrosine (18F-FET) is a radiopharmaceutical that accumulates in glioma cells due to an increased expression of L-amino acid transporters and, contrary to gadolinium, does not depend on blood-brain barrier disruption to reach tumoral cells. It has demonstrated a high diagnostic value in the differentiation of tumoral viability and pseudoprogression or any other therapy-related changes, especially when combining traditional visual analysis with modern radiomics. In this review, we aim to cover the potential role of 18F-FET positron emission tomography in everyday clinical practice when applied to the follow-up of patients after the first therapeutical intervention, early response evaluation, and the differential diagnosis between therapy-related changes and progression.

Visceral Hepatic Leishmaniasis in a Melanoma Patient in FDG-PET.

BACKGROUND: Leishmaniasis is caused by protozoans that depend on female phlebotomine sandflies as vectors. The natural habitat of these sandflies is changing due to climatic changes, affecting the immunocompromised population, as more patients get immunocompromised due to cancer therapy in the present time. CASE REPORT: We report the case of a 72-year-old patient with melanoma in whom we found visceral leishmaniasis mimicking hepatic metastasis in routine FDG-PET/CT. The patient was hospitalised due to fever and pancytopenia in the general hospital Steyr. The diagnosis was made by biopsy of the iliac crest with cytological study and polymerase chain reaction. After treatment with amphotericin B, the patient recovered and tests became negative, including FDG-PET/CT. Because of climate change and the increasing use of immunomodulatory medication, our awareness of such findings should grow. CONCLUSION: New pitfalls in diagnosis and surveillance of cancer patients because of altered environmental conditions and immunocompromised patients have to be taken into account.

Somatostatin Receptor Subtype Expression in Patients with Acromegaly and Complicated Clinical Course.

Somatostatin analogues are considered to be the first line of treatment in acromegaly. Somatostatin analogues of the first generation mainly target the somatostatin receptor (SSTR) subtype 2 and have been proven efficient in the majority of patients with acromegaly. Pasireotide was the first somatostatin analogue also substantially targeting the SSTR subtype 5. An efficient drug for Cushing's disease tailored to suboptimal-responding patients with acromegaly then became available. We immunohistochemically investigated SSTR subtypes expression in pituitary adenomas from operated acromegaly patients with clinical relapse and a complicated clinical course. Patients received pasireotide in the course of their disease. The predictive value of SSTR subtypes immunhistochemical analysis for the therapeutic response is discussed.

Pembrolizumab-Induced Thyroiditis Shows PD-L1Expressing Histiocytes and Infiltrating T Cells in Thyroid Tissue - A Case Report.

Context: Immune-related adverse events frequently take place after initiation of immune checkpoint inhibitors (ICI) therapy. The thyroid gland is the endocrine organ most commonly affected by ICI therapy, the pathological mechanism is still poorly understood. Case Description: A 60-year old Upper Austrian male melanoma patient under pembrolizumab therapy received thyroidectomy because of a suspicious FDG avid thyroid nodule. Histopathology showed a pattern comparable with thyroiditis de Quervain. The inflammatory process consisted predominantly of T lymphocytes with a dominance of CD4+ T helper cells. In addition CD68+ histiocytes co-expressing PD-L1 were observed. Conclusion: Clusters of perifollicular histiocytes expressing PD-L1 were observed in this case of pembrolizumab induced thyroiditis - probably induced by the former ICI therapy. This finding might indicate the initial target for the breakdown of self tolerance. In context with other data the immunological process seems to be driven by CD3+ lymphocytes infiltrating the thyroid.

Giant silent corticotrope pituitary adenoma in a patient with complicated clinical course.

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Lack of association between cortical amyloid deposition and glucose metabolism in early stage Alzheimer´s disease patients.

BACKGROUND: Beta amyloid (Aß) causes synaptic dysfunction leading to neuronal death. It is still controversial if the magnitude of Aß deposition correlates with the degree of cognitive impairment. Diagnostic imaging may lead to a better understanding the role of Aß in development of cognitive deficits. The aim of the present study was to investigate if Aß deposition in the corresponding brain region of early stage Alzheimer´s disease (AD) patients, directly correlates to neuronal dysfunction and cognitive impairment indicated by reduced glucose metabolism. PATIENTS AND METHODS: In 30 patients with a clinical phenotype of AD and amyloid positive brain imaging, 2-[18F] fluoro-2-deoxy-d-glucose (FDG) PET/CT was performed. We extracted the average [18F] flutemetamol (Vizamyl) uptake for each of the 16 regions of interest in both hemispheres and computed the standardized uptake value ratio (SUVR) by dividing the Vimazyl intensities by the mean signal of positive and negative control regions. Data were analysed using the R environment for statistical computing and graphics. RESULTS: Any negative correlation between Aß deposition and glucose metabolism in 32 dementia related and corresponding brain regions in AD patients was not found. None of the correlation coefficient values were statistically significant different from zero based on two-sided p- value. CONCLUSIONS: Regional Aß deposition did not correlate negatively with local glucose metabolism in early stage AD patients. Our findings support the role of Aß as a valid biomarker, but does not permit to conclude that Aß is a direct cause for an aberrant brain glucose metabolism and neuronal dysfunction.

Is there a place for FET PET in the initial evaluation of brain lesions with unknown significance?

PURPOSE: The aim of this study was to evaluate the clinical value of the use of O-(2-[(18)F]fluoroethyl)-L: -tyrosine (FET) positron emission tomography (PET)/computed tomography (CT) in patients of a neurological clinic for evaluation of brain lesions newly diagnosed by magnetic resonance imaging (MRI). METHODS: We evaluated 88 patients (44 women and 44 men) with a mean age of 50 +/- 19 years who were sent consecutively for evaluation of an intracerebral mass or lesion observed by MRI from 2006 to 2008. Hospitalization was necessary due to neurological clinical symptoms. Images were obtained by PET/CT 30 min after i.v. injection of 185 MBq FET. Coregistration with MRI was done by HERMES workstation. RESULTS: FET uptake above the cortical level was observed in 60 patients. Neurosurgery was performed in 60 patients (51 with FET-positive imaging); 36 high-grade and 19 low-grade tumours were verified histologically. The sensitivity of FET PET for high-grade tumours (WHO III-IV) was 94% in this setting. Among the low-grade brain tumours (WHO I-II) 13 of 19 were FET positive, which indicates a sensitivity of 68%. Five of ten (50%) astrocytomas I and II could not be visualized by FET. Histological data were not provided for 28 of 88 patients, so the diagnostic approach is based upon longitudinal observation. Radiological and/or clinical control was done at a median of 7 months later. Three patients (all FET positive) died a few months after the examination because of rapid progression of the malignant brain tumour. A malignant entity could be excluded in the other 25 patients. Considering the whole cohort of 88 patients, 43 patients with malignant tumour could be identified, including high-grade glioma, intracerebral lymphoma (n = 1) and metastasis (n = 3). The sensitivity of FET PET for detecting a malignant tumour entity was 93%. We observed two false-positive cases with postischaemic lesions. Remarkably, the two patients with cerebral gliomatosis were false-negative on FET PET imaging. The negative predictive value for a malignant entity was calculated to be 89%. CONCLUSION: Our results indicate a high sensitivity of FET PET for detecting high-grade glioma in patients with neurological symptoms and recently observed brain lesions by MRI. In the setting of evaluating new brain lesions of unknown significance via FET PET a negative image can encourage a wait and see strategy-of course in accordance with the clinical picture and morphological imaging.

Serum leptin is correlated to high turnover in osteoporosis.

OBJECTIVE: Clinical data have suggested that obesity protects against osteoporosis. Leptin, mainly secreted by white adipose tissue, might be involved by mediating an effect on bone metabolism. This study was conducted to investigate a possible relationship of leptin and bone turn-over in postmenopausal women with osteoporosis. METHODS: We measured bone mineral density (BMD), serum leptin levels and markers of bone metabolism, including osteocalcin and cross-laps in 44 patients with osteoporosis. The main group consisted of 32 postmenopausal women. RESULTS: Mean serum leptin was 13.1 microg/L and showed no statistically significant difference to the levels measured in a collective of normal persons adjusted for age and BMI. When related to serum cross-laps as markers of bone resorption, a positive correlation (p<0.05) was observed, whereas no correlation with osteocalcin could be seen. CONCLUSIONS: A dual control of bone formation by leptin is assumed: This involves local mechanisms acting on osteoblasts and a central inhibitory effect on bone metabolism via a hypothalamic relay. Our data indicate that the net effect of circulating leptin may cause bone loss and is significantly related to high-turnover serum bone markers, at least in postmenopausal women with osteoporosis.

Lymphocyte imbalance in vitiligo patients indicated by elevated CD4+/CD8+ T-cell ratio.

Vitiligo is a disorder of pigmentation associated with an autoimmune-mediated loss of melanocytes from the epidermis. Humoral immunity and the involvement of cellular immunity have been investigated in the pathogenesis of vitiligo. We evaluated the role of pro-inflammatory cytokines and lymphocyte fractions in peripheral blood in a cohort of Austrian patients with vitiligo. Morning blood samples from 40 patients with vitiligo were collected. Twenty-one patients had active and 19 had stable vitiligo disease. All patients were suffering from non-segmental vitiligo at different stages of the disease. Sixteen persons presented with an additional autoimmune thyroid disease. To evaluate a possible involvement of proinflammatory cytokines in vitiligo we measured sTNF-RI (soluble tumour necrosis factor receptor I), IL-6 and additionally CIC (circulating immune complexes). We compared these findings to the data from matched normal persons. To investigate the mechanisms of cellular immunity, peripheral blood cell count and lymphocyte subtype analysis by flow cytometry were done. sTNF-RI, IL-6 and CIC serum levels were in the normal range. In the patient group median sTNF-RI level was 1.5 ng/ml and median CIC level was 35.2 microg/ml, and no statistically significant differences to the control group were observed. Median IL-6 level in vitiligo patients was 2.7 pg/ml and in the normal range-but higher than the median level of 0.5 pg/ml observed in normal persons (p < 0.001). Absolute and relative counts of lymphocyte subtypes were normal. The ratio of CD4+/CD8+ T-cells had an elevated median value of 2.6 [quartiles 2.0; 3.1]. 61% of the vitiligo patients had a ratio higher than 2.4, which was the normal cut-off point. In most vitiligo patients the balance of cytotoxic/suppressor and helper/inducer T-cells in peripheral blood is disturbed which might lead to a predominance of T-cell subtypes in the intracutaneous site of autoimmune melanocyte loss.

68Ga/64Cu PSMA Bio-Distribution in Prostate Cancer Patients: Potential Pitfalls for Different Tracers.

BACKGROUND: 68Ga-PSMA is a widely useful PET/CT tracer for prostate cancer imaging. Being a transmembrane protein acting as a glutamate carboxypeptidase enzyme, PSMA is highly expressed in prostate cancer cells. PSMA can also be labeled with 64Cu, offering a longer half-life and different resolution imaging. Several studies documented bio-distribution and pitfalls of 68Ga-PSMA as well as of 64Cu- PSMA. No data are reported on differences between these two variants of PSMA. Our aim was to evaluate physiological distribution of these two tracers and to analyze false positive cases. METHODS: We examined tracer bio-distribution in prostate cancer patients with negative 68Ga-PSMA PET/CT (n=20) and negative 64Ga-PSMA PET/CT (n=10). A diagnostic pitfall for each tracer was documented. RESULT: Bio-distribution of both tracers was similar, with some differences due to renal excretion of 68Ga- PSMA and biliary excretion of 64Cu-PSMA. 68Ga-PSMA uptake was observed in sarcoidosis while 64Cu- PSMA uptake was recorded in pneumonitis. DISCUSSION: Both tracers may present similar bio-distribution in the human body, with similar uptake in exocrine glands and high intestinal uptake. Similarly to other tracers, false positive cases cannot be excluded in clinical practice. CONCLUSION: The knowledge of difference in bio-distribution between two tracers may help in interpretation of PET data. Diagnostic pitfalls can be documented, due to the possibility of PSMA uptake in inflammation. Our results are preliminary to future studies comparing diagnostic accuracies of 68Ga-PSMA and 64Cu-PSMA.

Multitracer study in Heidenhain variant of Creutzfeldt-Jakob disease: mismatch pattern of cerebral hypometabolism and perfusion imaging.

Creutzfeldt-Jakob disease (CJD) is a subacute spongiform encephalopathy. This fatal prion disease is characterized by rapidly progressive dementia with a variety of neurological disorders. Diagnostic methods provided by nuclear medicine might be helpful for evaluation of patients with probable CJD as additional diagnostic tools to MRI and cerebro-spinal fluid evaluation. The experience with FDG-PET and brain perfusion SPECT is presented.

[SPECT and FDG-PET in diagnostics of neurolues]. / SPECT und FDG-PET in der Diagnostik der Neurolues.

Syphilis is a recurrent treponematosis of acute and chronic evolution. In general it is either sexually or congenitally transmitted. Primary syphilis appears as a single and painless lesion. Secondary syphilis may manifest years later, the secondary bacteremic stage is accompanied by generalized mucocutaneous lesions. Tertiary disease can be disseminated to bones and virtually any organ, involving principally the ascending aorta and the central nervous system. Nuclear medicine provides diagnostic methods in case of skeletal manifestations by bone scan - identifying periostitis and osteomyelitis. Hepatic gummas can be imaged by 99m-Tc-colloid liver scintigraphy. In neurosyphilis brain perfusion SPECT enables imaging of cerebral involvement by small vessel endarteritis resulting from syphilitic vascular disease. 18-FDG PET is also useful to evaluate neurosyphilis, a reduction of brain glucose consumption is observed. The technique adequately enables imaging of therapeutic response and might be superior to morphologic imaging. We present our experiences with these nuclear medicine methods in patients with neurolues. The incidence of neurolues is estimated at 2 per 100.000 inhabitants worldwide, migration processes might bring a re-emergence of this disease to Austria and other developed countries of the EU. Scintigraphic methods should be kept in mind for diagnostic evaluation of neurosyphilis.