Neurosyphilis Mimicking Behavioral Variant of Frontotemporal Dementia in a 59-Year-Old Man.

We present the case of a man exhibiting a clinical phenotype of behavioral variant of frontotemporal dementia (bvFTD). The man had developed psychiatric disturbances with verbal aggressiveness over a few months, followed by cognitive and frontal behavioral disorders, fulfilling the clinical criteria for bvFTD. Atrophy and hypometabolism in frontotemporal regions were consistent with the diagnosis. However, serum-screening exams for syphilis infection were positive, and CSF analysis, despite a negative Venereal Disease Research Laboratory Test, suggested the diagnosis of neurosyphilis. After specific antibiotic therapy, the man's behavioral abnormalities and cognitive deficits notably improved, confirming neurosyphilis as the cause of the clinical phenotype. The cognitive deficits completely recovered 1 year post therapy and remained stable for 2 years. After ∼2½ years from the first treatment, the man's behavioral disorders mildly worsened, at which time we re-evaluated him. His cognition was stable, and a positive Venereal Disease Research Laboratory Test confirmed the diagnosis of neurosyphilis. With this case, we demonstrated that in some instances, neurosyphilis can mimic frontotemporal dementia. As a cause of treatable dementia, it should be considered in the differential diagnosis of bvFTD, particularly when psychiatric symptoms and a rapid cognitive decline are noted, even in the presence of brain atrophy and/or hypometabolism.

Psychiatric Disorders in Alzheimer Disease With the Presenilin-1 L226F Mutation.

The presenilin-1 (PSEN1) L226F mutation has been linked to very early onset of prominent behavioral and psychiatric disturbances followed by cognitive decline within a few years. We report a novel case of early-onset Alzheimer disease that was originally diagnosed as psychotic depression in a patient with this gene mutation. We also compare our patient's clinical data to those of other cases of this mutation that have been described in the literature. Because atypical behavioral and psychiatric disturbances in young (<40 years) individuals can herald Alzheimer disease, a tight collaboration between psychiatrists and neurologists is crucial for an early diagnosis.

Impact of non-specific normal databases on perfusion quantification of low-dose myocardial SPECT studies.

AIM: To evaluate the impact of non-specific normal databases on the percent summed rest score (SR%) and stress score (SS%) from simulated low-dose SPECT studies by shortening the acquisition time/projection. METHODS: Forty normal-weight and 40 overweight/obese patients underwent myocardial studies with a conventional gamma-camera (BrightView, Philips) using three different acquisition times/projection: 30, 15, and 8 s (100%-counts, 50%-counts, and 25%-counts scan, respectively) and reconstructed using the iterative algorithm with resolution recovery (IRR) AstonishTM (Philips). Three sets of normal databases were used: (1) full-counts IRR; (2) half-counts IRR; and (3) full-counts traditional reconstruction algorithm database (TRAD). The impact of these databases and the acquired count statistics on the SR% and SS% was assessed by ANOVA analysis and Tukey test (P < 0.05). RESULTS: Significantly higher SR% and SS% values (> 40%) were found for the full-counts TRAD databases respect to the IRR databases. For overweight/obese patients, significantly higher SS% values for 25%-counts scans (+19%) are confirmed compared to those of 50%-counts scan, independently of using the half-counts or the full-counts IRR databases. CONCLUSIONS: AstonishTM requires the adoption of the own specific normal databases in order to prevent very high overestimation of both stress and rest perfusion scores. Conversely, the count statistics of the normal databases seems not to influence the quantification scores.

68Ga-PSMA-PET: added value and future applications in comparison to the current use of choline-PET and mpMRI in the workup of prostate cancer.

Positron emission tomography (PET) has been commonly and successfully used, in combination with computed tomography (CT) and more recently magnetic resonance (MRI), in the workup of intermediate or high-risk prostate cancer (PCa). Nowadays, new specific receptor targeted PET tracers in prostate cancer imaging have been introduced; one of the most used is 68Ga-PSMA, that evaluates the expression of prostate-specific membrane antigen (PSMA). This tracer has been rapidly taken into account for its better sensitivity and specificity compared to lipid metabolism tracers, such as 11C/18F labelled fluorocholine. Besides, in the era of theranostics, this tracer is having a useful application not only for imaging but also for therapeutic purposes. The aim of this review article is, in the first part, to give an overview of the main indications and future development of 68Ga-PSMA imaging, using PET/CT or PET/MRI, according to the clinical course of the disease and in view of the current use of multiparametric MRI (mpMRI) and choline PET in the management of PCa. In the second part, a brief overview of the promising 18F-labelled PSMA tracers and the current use of PSMA radionuclide therapy will be provided.

Comparative analysis of iterative reconstruction algorithms with resolution recovery and time of flight modeling for 18F-FDG cardiac PET: A multi-center phantom study.

BACKGROUND: The purpose of this study was to evaluate the image quality in cardiac 18F-FDG PET using the time of flight (TOF) and/or point spread function (PSF) modeling in the iterative reconstruction (IR). METHODS: Three scanners and an anthropomorphic cardiac phantom with an insert simulating a transmural defect (TD) were used. Two sets of scans (with/without TD) were acquired, and four reconstruction schemes were considered: (1) IR; (2) IR + PSF, (3) IR + TOF, and (4) IR + TOF + PSF. LV wall thickness (FWHM), contrast between LV wall and inner chamber (C IC), and TD contrast in LV wall (C TD) were evaluated. RESULTS: Tests of the reconstruction protocols showed a decrease in FWHM from IR (13 mm) to IR + PSF (11 mm); an increase in the C IC from IR (65%) to IR + PSF (71%) and from IR + TOF (72%) to IR + TOF + PSF (77%); and an increase in the C TD from IR + PSF (72%) to IR + TOF (75%) and to IR + TOF + PSF (77%). Tests of the scanner/software combinations showed a decrease in FWHM from Gemini_TF (13 mm) to Biograph_mCT (12 mm) and to Discovery_690 (11 mm); an increase in the C IC from Gemini_TF (65%) to Biograph_mCT (73%) and to Discovery_690 (75%); and an increase in the C TD from Gemini_TF/Biograph_mCT (72%) to Discovery_690 (77%). CONCLUSION: The introduction of TOF and PSF increases image quality in cardiac 18F-FDG PET. The scanner/software combinations exhibit different performances, which should be taken into consideration when making cross comparisons.

Comparative analysis of cadmium-zincum-telluride cameras dedicated to myocardial perfusion SPECT: A phantom study.

BACKGROUND: This investigation used image data generated by an anthropomorphic phantom with a cardiac insert for a comparison between two solid state cameras: D-SPECT and D530c. METHODS: For each camera, two sets (with and without a simulated transmural defect (TD)) of scans were acquired starting from the in vivo standard count statistics in the left ventricle (LV). Other two acquisitions corresponding to 150% and 50% of the reference count statistics were acquired. Five performance indices related to spatial resolution, contrast, and contrast-to-noise ratio (CNR) were analyzed. RESULTS: D-SPECT showed a lower LV wall thickness and an inferior sharpness than D530c. No significant differences were found in terms of contrast between LV wall and the inner cavity, TD contrast or CNR. No significant differences were observed in CNR when moving from the reference level of count statistics down to 50% or up to 150% of the counts acquired on the LV. CONCLUSIONS: Our results show that D-SPECT and D530c have different performances. The lack of differences in the image performance indices along the range of count statistics explored, indicates that there is the possibility for a further reduction in the injected activity and/or the acquisition time, for both systems.

Comparative analysis of iterative reconstruction algorithms with resolution recovery for cardiac SPECT studies. A multi-center phantom study.

BACKGROUND: This investigation used image data generated by a physical phantom over a wide range of count statistics to evaluate the effectiveness of several of the newer commercially available SPECT reconstruction iterative algorithms (IRR) in improving perfusion defect contrast and spatial resolution, while controlling image noise. METHODS: A cardiac phantom was imaged using four different gamma cameras over a wide range of counts statistics (from 6 to 0.8 Mcounts). Images were reconstructed with FBP, OSEM, and the IRR available on site. IRR were applied without corrections (IRR NC), with attenuation correction (IRR AC), scatter correction (IRR SC), and attenuation + scatter corrections (IRR SCAC). Four image performance indices related to spatial resolution, contrast, and image noise were analyzed. RESULTS: IRR NC always determined significant improvements in all indices in comparison to FBP or OSEM. Improvements were emphasized with IRR SC and IRR SCAC. Count reduction from 6 to 1.5 Mcounts did not impair the performances of any of the considered indices. CONCLUSIONS: This is the first study comparing the relative performance of different, commercially available, IRR software, over a wide range of count statistics; the additional effect of scatter and attenuation corrections, alone or in combination, was also evaluated. Our results confirm that IRR algorithms produce substantial benefits with respect to conventional FBP or OSEM reconstruction methods, as assessed through different figures of merit, in particular when SC and/or SCAC are also included.

Association between peripheral T-Lymphocyte activation and impaired bone mineral density in HIV-infected patients.

BACKGROUND: HIV-infected patients display an increased and early incidence of osteopenia/osteoporosis. We investigated whether bone metabolism disorders in HIV-infected patients are related to immune hyperactivation and premature immune senescence. METHODS: Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA): low BMD (LBMD) was defined as T-score or z-score < -1. CD4+/CD8+ phenotype (CD38/HLA-DR, CD127, CD28/CD57), and circulating IL-7, TNF-α, RANKL, OPG were measured. The variables with p < .05 were evaluated by multivariate logistic regression. RESULTS: 78 patients were enrolled: 55 were LBMD. LBMD patients showed increased activated HDLADR + CD4+ and CD8+ (p = .03 and p = .002, respectively). Interestingly, no differences in senescent CD28-CD57 + CD4+/CD8+ T-cells were observed between groups. However, LBMD patients displayed a decreased CD4 + CD28- phenotype (p = .04) at the advantage of the CD28+ pool (p = .03), possibly reflecting heightened apoptosis of highly differentiated CD28-negative cells.Activated HLADR + CD4+/CD8+ and CD28 + CD4+ cells were independently associated with impaired BMD (AOR = 1.08 for each additional HLADR + CD4+ percentage higher; CI 95%,1.01-1.15; p = .02; AOR = 1.07 for each additional HLADR + CD8+ percentage higher; CI 95%,1.01-1.11; p = .01; AOR = 1.06 for each additional CD28 + CD4+ percentage higher; CI 95%,1.0-1.13; p = .05). CONCLUSIONS: Heightened T-cell activation in HIV-infected patients independently predicts BMD disorders, suggesting a critical role of immune activation in the pathogenesis of osteopenia/osteoporosis, even in patients achieving full viral suppression with HAART.

Overview of presurgical assessment and surgical treatment of epilepsy from the Italian League Against Epilepsy.

The Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) presents an overview of the techniques and methodologies of presurgical evaluation and of the surgical treatment of epilepsies. This overview is the result of the experience developed in the past years in the major Italian centers where programs of epilepsy surgery have been established, and it has the aim of offering a quick and easy reference tool for those involved in the treatment of patients with epilepsy. The sharing of different experiences has the additional aim of conforming and disseminating the employed techniques as well as the methods of selection and evaluation of patients. The synthetic coverage of the main issues concerning the presurgical workup and the available surgical options will hopefully provide a framework that may integrate and develop the contributions of every single center, in one of the more complex, challenging, and dynamic areas of neurological sciences.

Validation of a new protocol for ¹8F-FDG infusion using an automatic combined dispenser and injector system.

PURPOSE: In nuclear medicine, radiopharmaceuticals are usually administered in unit doses partitioned from multi-dose vials. The partitioning typically takes place in a radiopharmacy, depending on local practice. Automatic, as opposed to manual, partitioning and administration should reduce radiation exposure of the personnel involved, improve the accuracy of the administration and mitigate contamination. This study set out to verify and validate the (18)F-fluorodeoxyglucose (FDG) administration procedure performed using Intego (MEDRAD, Inc., Warrendale, PA, USA), a combined dispenser and injector system. We considered maintenance of sterility and the system's potential to improve, with respect to the manual procedure, the accuracy of net administered (18)F-FDG radioactivity in patients and the radiation protection of operators. METHODS: A media-fill procedure was used to assess whether sterility is maintained during use of the Intego system. Simulating a typical working day's setup and use of the system, we investigated the accuracy of the net administered (18)F-FDG activity obtained with Intego versus the manual dose delivery system. We also measured personnel radiation exposure during use of Intego and during manual administration and recorded and compared environmental doses in the two conditions. RESULTS: The radiopharmaceutical remained sterile in all the tests performed. The accuracy of the net (18)F-FDG activity delivered to the patients was found to be within 3 % points, as required by European Association of Nuclear Medicine (EANM) guidelines on (18)F-FDG imaging procedures. With Intego, the residual radioactivity in the tubing was 0.20 MBq, corresponding to approximately 0.07 % of the mean activity delivered. With manual injection, the residual radioactivity in the syringe averaged 7.37 MBq, corresponding to a mean error of 2.9 % in the delivered dose. During the injection step of the positron emission tomography (PET) procedure, whole-body and extremity radiation exposures were significantly reduced with Intego by 38 and by 94 %, respectively, compared to the levels associated with manual administration (p < 0.05). CONCLUSION: Integoaccurately partitions and administers sterile doses of (18)F-FDG from multi-dose vials. Compared with standard manual (18)F-FDG administration, the new procedure with an automatic dispensing and injection system greatly reduces the extremity dose to the operator involved in the administration of the radiopharmaceutical.

Increased Sensitivity of Computed Tomography Scan for Neoplastic Tissues Using the Extracellular Vesicle Formulation of the Contrast Agent Iohexol.

Computed tomography (CT) is a diagnostic medical imaging modality commonly used to detect disease and injury. Contrast agents containing iodine, such as iohexol, are frequently used in CT examinations to more clearly differentiate anatomic structures and to detect and characterize abnormalities, including tumors. However, these contrast agents do not have a specific tropism for cancer cells, so the ability to detect tumors is severely limited by the degree of vascularization of the tumor itself. Identifying delivery systems allowing enrichment of contrast agents at the tumor site would increase the sensitivity of detection of tumors and metastases, potentially in organs that are normally inaccessible to contrast agents, such as the CNS. Recent work from our laboratory has identified cancer patient-derived extracellular vesicles (PDEVs) as effective delivery vehicles for targeting diagnostic drugs to patients' tumors. Based on this premise, we explored the possibility of introducing iohexol into PDEVs for targeted delivery to neoplastic tissue. Here, we provide preclinical proof-of-principle for the tumor-targeting ability of iohexol-loaded PDEVs, which resulted in an impressive accumulation of the contrast agent selectively into the neoplastic tissue, significantly improving the ability of the contrast agent to delineate tumor boundaries.

The ideal marker for measuring GFR: what are we looking for?

INTRODUCTION: The most accurate way of assessing kidney function is the measurement of the glomerular filtration rate (GFR). Since, we do not have good formulae to estimate GFR in elderly, in this study we  evaluate the accuracy of the most commonly used formulas for the estimation of GFR in comparison with direct measurement in elderly. MATERIALS AND METHODS: 85 patients (51 males and 34 females), with an average age of 76.2 ± 4.4 years, 42% already diagnosed with chronic kidney disease (CKD) were investigated. Two plasma samples were collected between  60-90 and 165-195 minutes after injection of 99mTc-DTPA, and the GFR was calculated applying Charles D. Russell's two-sample method. RESULTS: When comparing the GFR values obtained from the various formulae by creatinine levels with the GFR values obtained by measuring 99mTc-DTPA residue, the following concordance values emerged: (1) MDRD: 57.5 ± 9.59 %; (2) Cockroft-Gault: 48.33 ± 24.93; (3) CKD-EPI: 49.40 ± 26.30; (4) BIS1: 58 ± 6.79. CONCLUSION: Our data shows a greater concordance between the GFR values calculated with the Russell's method and the estimated values of GFR when the latter are calculated using the MDRD or BIS1 formulae.

Identifying the epileptogenic zone by four non-invasive imaging techniques versus stereo-EEG in MRI-negative pre-surgery epilepsy patients.

OBJECTIVE: We evaluated four imaging techniques, i.e. Electroencephalography (EEG)-functional Magnetic Resonance Imaging (MRI) (EEG-fMRI), High-resolution EEG (HR-EEG), Magnetoencephalography (MEG) and 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (PET), for the identification of the epileptogenic zone (EZ) in 41 patients with negative MRI, candidate to neurosurgery. METHODS: For each technique, results were compared to the Stereo-EEG. Diagnostic measures were calculated with respect to the post-surgical outcome, either for all the patients (39/41, two patients excluded) and for the subgroup of patients with the EZ involving more than one lobe (20/41). RESULTS: When considered individually, each functional technique showed accuracy values ranging 54,6%-63,2%, having PET, MEG and HR-EEG higher sensitivity, and EEG-fMRI higher specificity. In patients with multilobar epileptogenic zone, functional techniques achieved the best accuracies (up to 80%) when three techniques, including EEG-fMRI, were considered together. CONCLUSIONS: The study highlights the accuracy of a combination of functional imaging techniques in the identification of EZ in MRI negative focal epilepsy. The best diagnostic yield was obtained if the combination of PET, MEG (or HR-EEG as alternative), EEG-fMRI were considered together. SIGNIFICANCE: The functional imaging techniques may improve the presurgical workup of MRI negative focal epilepsy, if epileptogenic zone involves more than one lobe.

Impact of low-dose SPECT imaging on normal databases and myocardial perfusion scores.

PURPOSE: We have recently demonstrated that iterative reconstruction algorithms with resolution recovery require the adoption of specific normal databases (NDBs) for perfusion SPECT quantification. This work was aimed at investigating the impact of patient low-dose imaging on NDBs and percent summed rest (SR%) and stress (SS%) scores. METHODS: Assuming that count statistics of shorter acquisition time may simulate that of lower patient dose, three simultaneous scans were acquired (BrightView, Philips) with different acquisition-time/projection: 30, 15 and 8 s (from 100% to 25% of the reference). Fifty-two normal patients with low likelihood of coronary artery disease were enrolled and three homemade NDBs were then generated and compared (Astonish™ algorithm with default parameters): 100%-HM-NDBs, 50%-HM-NDBs and 25%-HM-NDBs. SR% and SS% were subsequently calculated for another group of 38 patients (normal/abnormal = 5/33). SR% and SS% values of 100%-HM-NDBs were compared with those obtained with the NDBs available on the workstation. Moreover, the impact of the study count statistics on perfusion scores was evaluated using the count-specific NDBs. RESULTS: Significantly higher standard-deviation values were found for 25%-HM-NDBs compared to the other HM-NDBs (p < 0.02). Significantly higher SS% were also found for the 100%-HM-NDBs compared to the workstation NDBs (95%CI: 0.15-2.11%). Moreover, a post-hoc test showed significantly lower SR% and SS% for 25%-count statistics compared to 100%-HM-NDBs (p < 0.03). CONCLUSIONS: NDBs and perfusion scores depend significantly on study count-statistics. A 50% reduction in patient dose is ultimately the limit for Astonish™ (with the default parameters) in order to prevent a significant variation in myocardial perfusion quantification.

Predictive value of high titer of GAD65 antibodies in a case of limbic encephalitis.

We report the case of a 42-year-old woman who presented with vertigo and migraine and rapidly developed cognitive decline and seizures. Both serum and cerebro-spinal fluid samples showed high titer of anti-glutamic acid decarboxylase (anti-GAD65) antibodies (998,881 IU/ml and 54,687 IU/ml respectively). Limbic encephalitis was diagnosed and high dose steroids treatment started. During one-year follow-up, without further immunomodulatory therapy, the patient became seizure free, and cognitive functions returned to normal. Serum anti-GAD65 antibodies titer decreased significantly but remained elevated (192,680 IU/ml). We discuss the prognostic and pathogenic value of high titer anti-GAD65 antibodies and its variations in a case of autoimmune limbic encephalitis.

Frontotemporal Dementia and Chorea Associated with a Compound Heterozygous TREM2 Mutation.

Frontotemporal dementia (FTD) is clinically characterized by behavioral changes, language impairment, and executive dysfunction. FTD usually belongs to the frontotemporal lobar degeneration (FTLD) disease group, and its familial forms are dominantly inherited and linked to a group of genes relevant to frontal and temporal brain pathology, such as MAPT, GRN, C9ORF72, TARDBP, CHMP2B, VCP, and FUS. However, FTD can also be associated with different clinical or pathological phenotypes caused by mutations in other genes, whose heredity can be dominant or recessive. In this work we report on a familial case of FTD characterized by behavioral changes and aphasia, very early onset and very long duration, choreic movements, and white matter lesions at magnetic resonance imaging. We performed a wide-range genetic analysis, using a next generation sequencing approach, to evaluate a number of genes involved in neurodegeneration. We found a previously unreported compound heterozygous mutation in TREM2, that is commonly associated with the recessively inherited Nasu-Hakola disease. We discuss the differential diagnosis to be taken into account in cases of FTD presenting with atypical features.