Search

BACKGROUND: Behavioral and neuropsychological functions are frequent longterm sequelae of severe traumatic brain injury (TBI). Neuropeptides, such as nerve growth factor (NGF), can enhance neurogenesis and improve cognitive functions after TBI, playing a pivotal role in neuroplasticity. A limited number of studies documented the safety and efficacy of intranasal NGF administration in children with severe TBI. CASE REPORT: A fourteen-year-old boy with a diffuse axonal injury secondary to severe TBI was treated with human-recombinant NGF administration. This patient underwent treatment with intranasal hr-NGF administration at a total dose of 50 gamma/kg, three times a day for seven consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. NGF administration improved radiologic functional assessment evaluated with positron emission tomography scan (PET) and single photon emission computed tomography (SPECT), with an important improvement in clinical conditions. Significant improvements were also observed, mainly in cognitive processes, memory, the planning of a communication strategy, execution skills, attention, and verbal expression. No side effects were reported. CONCLUSIONS: Additional studies are required to gain a deeper insight into this neurotrophin's neuroprotective function, but our findings reveal a potential efficacy of intranasal hr-NGF administration in enhancing cognitive and clinical outcomes among children with diffuse axonal injury after severe TBI. [ABSTRACT FROM AUTHOR]

Abstract Background To evaluate the metabolic changes on 18 F-fluoro-2-deoxyglucose positron emission tomography integrated with computed tomography (18 F-FDG PET-CT) performed before, during and after concurrent chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC); to correlate the metabolic response with the delivered radiation dose and with the clinical outcome. Methods Twenty-five NSCLC patients candidates for concurrent chemo-radiotherapy underwent 18 F-FDG PET-CT before treatment (pre-RT PET-CT), during the third week (during-RT PET-CT) of chemo-radiotherapy, and 4 weeks from the end of chemo-radiotherapy (post-RT PET-CT). The parameters evaluated were: the maximum standardized uptake value (SUVmax) of the primary tumor, the SUVmax of the lymph nodes, and the Metabolic Tumor Volume (MTV). Results SUVmax of the tumor and MTV significantly (p=0.0001, p=0.002, respectively) decreased earlier during the third week of chemo-radiotherapy, with a further reduction 4 weeks from the end of treatment (p Conclusions In patients with locally advanced NSCLC, 18 F-FDG PET-CT performed during and after treatment allows early metabolic modifications to be detected, and for this SUVmax is the more sensitive parameter. Further studies are needed to investigate the correlation between the metabolic modifications during therapy and the clinical outcome in order to optimize the therapeutic strategy. Since the metabolic activity during chemo-radiotherapy correlates with the cumulative dose of fractionated radiotherapy delivered at the moment of the scan, special attention should be paid to methodological aspects, such as the radiation dose reached at the time of PET.

The role of dopamine in the pathophysiology of gambling disorder (GD) remains incompletely understood, with disparate research findings concerning presynaptic and postsynaptic structures and dopaminergic synthesis. The aim of this study was to investigate potential correlations between striatal dopamine transporter (DAT) lateralization and asymmetry index, as assessed by 123 I-FP-CIT SPECT, and temperamental traits, as measured by Cloninger's Temperament and Character Inventory (TCI), in GD subjects. Significant associations were found between DAT binding asymmetries in the caudate and putamen and the temperamental dimensions of harm avoidance and novelty seeking. Specifically, high novelty seeking scores correlated with increased DAT binding in the left caudate relative to the right, whereas higher harm avoidance scores corresponded to increased DAT binding in the right putamen relative to the left. These observations potentially imply that the asymmetry in DAT expression in the basal ganglia could be an outcome of hemispheric asymmetry in emotional processing and behavioural guidance. In summary, our study provides evidence supporting the relationship between DAT asymmetries, temperamental dimensions and GD. Future investigations could be directed towards examining postsynaptic receptors to gain a more comprehensive understanding of dopamine's influence within the basal ganglia circuit in disordered gambling. If confirmed in larger cohorts, these findings could have substantial implications for the tailoring of individualized neuromodulation therapies in the treatment of behavioural addictions., Competing Interests: Declarations G.M. has been a consultant and a speaker and has received research grants from Angelini, Doc Generici, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Servier, and Recordati. J. E. G. has received research grants from Janssen, Boehringer Ingelheim, and Biohaven Pharmaceuticals. He receives yearly compensation from Springer Publishing for acting as Editor-in Chief of the Journal of Gambling Studies and has received royalties from Oxford University Press, American Psychiatric Publishing, Inc., Norton Press, and McGraw Hill. The other Authors have nothing to declare., (© 2024. The Author(s).)

Introduction: Dopaminergic transmission impairment has been identified as one of the main neurobiological correlates of both depression and clinical symptoms commonly associated with its spectrum such as anhedonia and psychomotor retardation., Objectives: We examined the relationship between dopaminergic deficit in the striatum, as measured by 123 I-FP-CIT SPECT imaging, and specific psychopathological dimensions in patients with major depressive disorder., Methods: To our knowledge this is the first study with a sample of >120 subjects. After check for inclusion and exclusion criteria, 121 (67 females, 54 males) patients were chosen retrospectively from an extensive 1106 patients database of 123I-FP-CIT SPECT scans obtained at the Nuclear Medicine Unit of Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome. These individuals had undergone striatal dopamine transporter (DAT) assessments based on the recommendation of their referring clinicians, who were either neurologists or psychiatrists. At the time of SPECT imaging, each participant underwent psychiatric and psychometric evaluations. We used the following psychometric scales: Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Snaith Hamilton Pleasure Scale, and Depression Retardation Rating Scale., Results: We found a negative correlation between levels of depression (p = 0.007), anxiety (p = 0.035), anhedonia (p = 0.028) and psychomotor retardation (p = 0.014) and DAT availability in the left putamen. We further stratified the sample and found that DAT availability in the left putamen was lower in seriously depressed patients (p = 0.027) and in patients with significant psychomotor retardation (p = 0.048)., Conclusion: To our knowledge this is the first study to have such a high number of sample. Our study reveals a pivotal role of dopaminergic dysfunction in patients with major depressive disorder. Elevated levels of depression, anxiety, anhedonia, and psychomotor retardation appear to be associated with reduced DAT availability specifically in the left putamen., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Prion diseases are rare, rapidly progressive, and fatal incurable degenerative brain disorders caused by the misfolding of a normal protein called PrPC into an abnormal protein called PrPSc. Their highly variable clinical presentation mimics various degenerative and non-degenerative brain disorders, making diagnosis a significant challenge for neurologists. Currently, definitive diagnosis relies on post-mortem examination of nervous tissue to detect the pathogenic prion protein. The current diagnostic criteria are limited. While structural magnetic resonance imaging (MRI) remains the gold standard imaging modality for Creutzfeldt-Jakob disease (CJD) diagnosis, positron emission tomography (PET) using 18 fluorine-fluorodeoxyglucose ( 18 F-FDG) and other radiotracers have demonstrated promising potential in the diagnostic assessment of prion disease. In this context, a comprehensive and updated review exclusively focused on PET imaging in prion diseases is still lacking. We review the current value of PET imaging with 18 F-FDG and non-FDG tracers in the diagnostic management of prion diseases. From the collected data, 18 F-FDG PET mainly reveals cortical and subcortical hypometabolic areas in prion disease, although fails to identify typical pattern or laterality abnormalities to differentiate between genetic and sporadic prion diseases. Although the rarity of prion diseases limits the establishment of a definitive hypometabolism pattern, this review reveals some more prevalent 18 F-FDG patterns associated with each disease subtype. Interestingly, in both sporadic and genetic prion diseases, the hippocampus does not show significant glucose metabolism alterations, appearing as a useful sign in the differential diagnosis with other neurodegenerative disease. In genetic prion disease forms, PET abnormality precedes clinical manifestation. Discordant diagnostic value for amyloid tracers among different prion disease subtypes was observed, needing further investigation. PET has emerged as a potential valuable tool in the diagnostic armamentarium for CJD. Its ability to visualize functional and metabolic brain changes provides complementary information to structural MRI, aiding in the early detection and confirmation of CJD., (© 2024. The Author(s), under exclusive licence to World Molecular Imaging Society.)

New Psychoactive Substances (NPS) are modifying the drug scenario worldwide and have become a public health concern because of their toxicological profiles and their harmful physical/psychological effects. 3-Methoxy-Phencyclidine (3-MeO-PCP), a non-competitive antagonist of glutamate N-methyl-D-aspartate (NMDA) receptors, belongs to the phencyclidine-like subfamily of arylcyclohexylamines and has gained attention for its toxic, sometimes fatal, effects. Despite several cases of intoxication and death reported in the literature, little is known about substance-induced psychotic disorders (SIP) and potential cognitive impairment following 3-MeO-PCP intake. This literature review aimed to summarize available evidence about 3-MeO-PCP mechanisms of action and physical and psychotropic effects and to spread preliminary findings about persistent psychotic symptoms and impaired cognitive functioning. Additionally, the case of an SIP is reported in a 29-year-old man with small oral intakes of 3-MeO-PCP over two weeks until a high dose ingestion. Psychometric and neuropsychological assessment and brain [ 18 F]-fluorodeoxyglucose positron emission tomography integrated with computed tomography were used to support clinical description. Identifying and addressing the characteristic clinical features and neural substrates of NPS-induced psychoses might help clinicians with a more precise differentiation from other psychotic disorders. Although further studies are required, phenotyping the cognitive profile of NPS users might provide targets for tailored therapeutic approaches.

Introduction: 18 F-Fluoro-deoxyglucose-positron emission tomography (FDG-PET) is a supportive biomarker in dementia with Lewy bodies (DLB) diagnosis and its advanced analysis methods, including radiomics and machine learning (ML), were developed recently. The aim of this study was to evaluate the FDG-PET diagnostic performance in predicting a DLB versus Alzheimer's disease (AD) diagnosis., Methods: FDG-PET scans were visually and semi-quantitatively analyzed in 61 patients. Radiomics and ML analyses were performed, building five ML models: (1) clinical features; (2) visual and semi-quantitative PET features; (3) radiomic features; (4) all PET features; and (5) overall features., Results: At follow-up, 34 patients had DLB and 27 had AD. At visual analysis, DLB PET signs were significantly more frequent in DLB, having the highest diagnostic accuracy (86.9%). At semi-quantitative analysis, the right precuneus, superior parietal, lateral occipital, and primary visual cortices showed significantly reduced uptake in DLB. The ML model 2 had the highest diagnostic accuracy (84.3%)., Discussion: FDG-PET is a valuable tool in DLB diagnosis, having visual and semi-quantitative analyses with the highest diagnostic accuracy at ML analyses., Competing Interests: All authors report no conflicts of interest., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Severe traumatic brain injury (TBI) is one of the most dramatic events in pediatric age and, despite advanced neuro-intensive care, the survival rate of these patients remains low. Children suffering from severe TBI show long-term sequelae, more pronounced in behavioral, neurological and neuropsychological functions leading to, in the most severe cases, an unresponsive wakefulness syndrome (UWS). Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. In experimental animal models, human- recombinant Nerve Growth Factor (hr-NGF) promotes neural recovery supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated processes. Only a few studies reported the efficacy of intranasal hr-NGF administration in children with post- traumatic UWS., Methods: Children with the diagnosis of post-traumatic UWS were enrolled. These patients underwent a treatment with intranasal hr-NGF administration, at a total dose of 50 gamma/kg, three times a day for 7 consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. Neuroradiogical evaluation by Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG), and Power Spectral Density (PSD) was determined before the treatment and one month after the end. Neurological assessment was also deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale., Results: Three children with post-traumatic UWS were treated. hr-NGF administration improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary movements, facial mimicry, attention and verbal comprehension, ability to cry, cough reflex, oral motility, and feeding capacity, with a significant improvement of their neurological scores. No side effects were reported., Conclusion: These promising results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from severe TBI and in patients with better baseline neurological conditions, to explore more thoroughly the benefits of this new approach on neuronal function recovery after traumatic brain damage., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Out-of-hospital cardiac arrest (OHCA) is one of the most dramatic events in pediatric age and, despite advanced neurointensive care, the survival rate remains low. Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. Nerve Growth Factor (NGF) is a neurotrophin potentially able to counteract many of the deleterious effects triggered by OHCA. Transcranial Direct Current Stimulation (tDCS) has been reported to be neuroprotective in many neurological diseases, such as motor deficit and cognitive impairment. Children with the diagnosis of chronic vegetative state after OHCA were enrolled. These patients underwent a combined treatment of intranasal administration of human recombinant NGF (hr-NGF), at a total dose of 50 gamma/kg, and tDCS, in which current intensity was increased from zero to 2 mA from the first 5 s of stimulation and maintained constant for 20 min. The treatment schedule was performed twice, at one month distance each. Neuroradiogical evaluation with Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG) and Power Spectral Density of the brain (PSD) was determined before the treatment and one month after the end. Neurological assessment was deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale., Results: Three children with a chronic vegetative state secondary to OHCA were treated. The combined treatment with hr-NGF and tDCS improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary finger movements, improved facial mimicry and reaction to painful stimuli. No side effects were reported., Conclusions: These promising preliminary results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from OHCA and in patients with better baseline neurological conditions, in order to explore more thoroughly the benefits of this new approach on neuronal function recovery after OHCA., (© 2023. The Author(s).)

We describe 3 children with new-onset neurocognitive problems after coronavirus disease 2019 (COVID-19), that showed, at the brain [18F]-fluorodeoxyglucose positron emission tomography/computed tomography, hypometabolism in the left orbito-frontal region. The voxel-wise analysis confirmed a cluster of hypometabolic voxels in this region with a peak at -18/46/-4mm (179 voxels, T-Score 8.1). These findings may explain neurocognitive symptoms that some children develop after COVID-19 and require further investigations., Competing Interests: This study is part of a larger study funded by Pfizer non-competitive grant, granted to. D.B. for the definition of long-term outcomes of SARS-CoV-2 infection in children. The funder had no role in the development of the project nor in the interpretation of results. Other authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The benefit of surgery and maintenance treatment with PARP inhibitors (PARPi) has been clearly demonstrated in ovarian cancer. Also, the efficacy and safety of stereotactic body radiotherapy has been shown in patients with metastatic, persistent, and recurrent disease. The aim of this study is to evaluate the management of oligometastatic progression during PARPi maintenance treatment., Methods: This is an observational, retrospective, single-arm study conducted from June 2017 to December 2020 in patients with recurrent ovarian cancer with oligometastatic progression under PARPi maintenance treatment and receiving surgery or stereotactic body radiotherapy for such recurrence. PARPi treatment was continued until further progression of the disease. The primary objective of the study was the median prolongation of the treatment-free interval-p (without platinum) after local treatment., Results: A total of 186 patients with ovarian cancer were treated with PARPi at recurrence. Of these, 30 (16%) developed oligometastatic progression. The median age was 49.5 years (range 35-73). Olaparib, niraparib and rucaparib were administered to 33%, 60%, and 7% of patients, respectively. The median prolongation of the treatment-free interval-p of patients treated with surgery or stereotactic body radiotherapy was 6 and 10 months, respectively (p=0.53). The median treatment-free interval-p of patients treated with surgery or stereotactic body radiotherapy at the time of oligometastatic progression was 32 and 29 months, respectively (p=0.44). At the time of this publication, 50% of patients are still on treatment with PARPi following progression., Conclusions: Patients with recurrent ovarian cancer who have oligometastic progression during PARPi maintenance may continue to benefit from PARPi if combined with local treatment., Competing Interests: Competing interests: CM reports fees for advisory work from GSK, AstraZeneca, Pharmamar, and Clovis outside the submitted work. GS reports consulting fees or speaker fees from TESARO Bio Italy Srl, Clovis Oncology Italy Srl, Johnson & Johnson, AstraZeneca/MSD, Covidien AG, a Medtronic company, and from Baxter Healthcare SA outside the submitted work. AF reports consulting fees or speaker fees from Pharmamar, Johnson & Johnson, AstraZeneca/MSD and MSD Italia Srl outside the submitted work., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate whether the COVID-19 pandemic and national lockdown had an impact on the extent of cancer disease at FDG PET/CT staging as surrogate marker., Methods: Retrospective observational study including cancer patients submitted to FDG PET/CT staging from June 1 to October 31, 2020, and June 1 to October 31, 2019, respectively. Data regarding primary tumour, nodal (N) status and number of involved nodal stations, and presence and number of distant metastases (M) were collected. Each scan was classified in limited vs advanced status. Data were aggregated across the study population and tumour type. Bi-weekly frequencies of the observed events were analysed., Results: Six hundred eleven patients were included (240 in 2019 vs 371 in 2020, respectively). A significant increase of advanced disease patients (rate 1.56, P < 0.001), N + or M + patients (rate 1.84 and 2.09, respectively, P < 0.001), and patients with a greater number of involved N stations or M (rate 2.01 and 2.06, respectively, P < 0.001) were found in 2020 compared with data of 2019. Analysis by tumour type showed a significant increase of advanced disease in lymphoma and lung cancer in 2020 compared with 2019 (P < 0.001). In addition, a significant increase of nodal involvement was found in lung, gastro-intestinal, and breast cancers, as well as in lymphoma patients (P < 0.02). A significant increase of distant metastases was found in lung cancers (P = 0.002)., Conclusion: Cancer patients with advanced disease at FDG PET/CT staging increased in 2020 compared with 2019, following the national lockdown due to the COVID-19 pandemic, 1.5-fold with a significant increase of patients with N or M involvement. Targeted health interventions are needed to mitigate the effects of the pandemic on patient outcome., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: We declare no competing interests. The patient provided informed consent to publish this case.

Abstract: Diffuse 18F-FDG skeletal uptake due to chemotherapy-induced bone marrow activation is well documented, whereas it has never been reported with 18F-fluorocholine. We described a patient with pelvic recurrence of prostate cancer at 18F-fluorocholine PET/CT. A second PET/CT after docetaxel showed minimal residual activity in pelvis, but it revealed diffuse, intense 18F-fluorocholine skeletal uptake. Considering biochemical and metabolic response and absence of morphologically suspected bone lesions, skeletal hyperactivity was interpreted as chemotherapy-related bone marrow rebound rather than diffuse metastatic involvement, as confirmed by its resolution after treatment ended. The occurrence of such 18F-fluorocholine pattern should be considered to avoid imaging misinterpretation., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The prognostic evaluation of glioma recurrence patients is important in the therapeutic management. We investigated the prognostic value of 11 C-methionine PET-CT (MET-PET) dynamic and semiquantitative parameters in patients with suspected glioma recurrence., Methods: Sixty-seven consecutive patients who underwent MET-PET for suspected glioma recurrence at MR were retrospectively included. Twenty-one patients underwent static MET-PET; 46/67 underwent dynamic MET-PET. In all patients, SUVmax, SUVmean and tumour-to-background ratio (T/B) were calculated. From dynamic acquisition, the shape and slope of time-activity curves, time-to-peak and its SUVmax (SUVmax TTP ) were extrapolated. The prognostic value of PET parameters on progression-free (PFS) and overall survival (OS) was evaluated using Kaplan-Meier survival estimates and Cox regression., Results: The overall median follow-up was 19 months from MET-PET. Recurrence patients (38/67) had higher SUVmax ( p = 0.001), SUVmean ( p = 0.002) and T/B ( p < 0.001); deceased patients (16/67) showed higher SUVmax ( p = 0.03), SUVmean ( p = 0.03) and T/B ( p = 0.006). All static parameters were associated with PFS (all p < 0.001); T/B was associated with OS ( p = 0.031). Regarding kinetic analyses, recurrence (27/46) and deceased (14/46) patients had higher SUVmax TTP ( p = 0.02, p = 0.01, respectively). SUVmax TTP was the only dynamic parameter associated with PFS ( p = 0.02) and OS ( p = 0.006). At univariate analysis, SUVmax, SUVmean, T/B and SUVmax TTP were predictive for PFS (all p < 0.05); SUVmax TTP was predictive for OS ( p = 0.02). At multivariate analysis, SUVmax TTP remained significant for PFS ( p = 0.03)., Conclusion: Semiquantitative parameters and SUVmax TTP were associated with clinical outcomes in patients with suspected glioma recurrence. Dynamic PET-CT acquisition, with static and kinetic parameters, can be a valuable non-invasive prognostic marker, identifying patients with worse prognosis who require personalised therapy.

Background: Major depressive disorder (MDD) has different clinical presentations and is associated with neurobiological alterations. Hopelessness, anhedonia, and dissociation represent some of the most pervasive psychopathological symptoms that often lead to suicidal thoughts, attempts, and actions. To further research on the concept of depression endophenotypes, this study aimed to assess the possible relationships between hopelessness and other clinical and biological correlates (i.e., striatal dopaminergic dysfunction) in depressed patients. Methods: We recruited 51 subjects with MDD. All subjects underwent 123 I-FP-CIT SPECT to assess striatal dopamine transporter (DAT) availability and a psychometric evaluation using the psychometric scale to assess depressive, anxious, dissociative, and hopelessness symptoms aside from suicidal ideation. Result: An inverse correlation between the hopelessness score and dopamine transporter availability in all basal ganglia was bilaterally found. (Right Putamen, r = -0.445, p < 0.01; Left Putamen, r = -0.454, p < 0.01; Right Caudate, r = -0.398, p < 0.01; Left Caudate, r = -0.467, p < 0.01) Moreover, a positive correlation was also found between hopelessness and dissociative symptoms. Conclusions: These results provide important evidence on the neurobiological and clinical correlates of different psychopathological symptoms of depression with potential implications in terms of devising more effective treatment programs.

Although the involvement of dopamine in gambling disorder (GD) has long been hypothesized, its precise role remains unclear. The action of dopamine in the synapses is regulated by the dopamine transporter (DAT). We hereinafter present significant differences between a sample of 15 treatment-seeking GD subjects and 17 healthy controls in terms of striatal DAT availability, and we explore its association with reward-based decision making. We performed 123 I-FP-CIT Single-photon emission computed tomography (SPECT) and correlated DAT binding ratios in the bilateral caudate and putamen with gambling symptoms (G-SAS, PG-YBOCS) and behaviors, as well as other psychometric variables (anhedonia and impulsivity). Gambling disorder (GD) subjects were also administered a computerized version of the Iowa gambling task (IGT) to assess reward-based decision making. We found reduced DAT availability in GD subjects compared with healthy controls (-13.30% in right caudate, -11.11% in right putamen, -11.44% in left caudate, and -11.46% in the left putamen). We also found that striatal DAT availability was inversely correlated with days spent gambling and IGT performance in GD subjects. These results provide evidence for a presynaptic dopaminergic dysfunction in striatal regions of GD subjects. Functional DAT down-regulation possibly sustains the transition towards compulsive gambling addiction, characterized both by hyperdopaminergic and hypodopaminergic states in the context of a sensitized dopaminergic system., (© 2018 Society for the Study of Addiction.)

Repetitive Transcranial Magnetic Stimulation (rTMS) shows the potential to modulate local brain activity, thus resulting in a modulatory action on neurocircuitries implicated in the pathophysiology of Gambling Disorder (GD). We report the case of a GD patient treated with two weeks of high frequency (15 Hz) rTMS over the dorsolateral prefrontal cortex (DLPFC). At baseline and after rTMS treatment the patient underwent a SPECT examination with (123)I-FP-CIT tracer, to test changes in dopamine transporter (DAT) availability. The patient was followed up for six months, to explore safety and clinical correlates of a weekly high frequency rTMS maintenance treatment. Over the six-month follow-up the patient reported no episodes of gambling relapse. Also, the patient did not report craving for gambling or gambling-related symptoms. After two weeks of left DLPFC-rTMS treatment, we found a decrease in DAT availability in striatal regions, that represents a putative neurobiological substrate of dopaminergic pathways modulation. This study suggests that high frequency DLPFC-rTMS deserves further investigations in larger samples, using controlled study designs, to assess its real potential as a treatment for GD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Alcohol use disorders (AUDs) are one of the leading causes of mortality and morbidity worldwide. In spite of significant advances in understanding the neural underpinnings of AUDs, therapeutic options remain limited. Recent studies have highlighted the potential of repetitive transcranial magnetic stimulation (rTMS) as an innovative, safe, and cost-effective treatment for AUDs. Here, we summarize the fundamental principles of rTMS and its putative mechanisms of action via neurocircuitries related to alcohol addiction. We will also discuss advantages and limitations of rTMS, and argue that Hebbian plasticity and connectivity changes, as well as state-dependency, play a role in shaping some of the long-term effects of rTMS. Visual imaging studies will be linked to recent clinical pilot studies describing the effect of rTMS on alcohol craving and intake, pinpointing new advances, and highlighting conceptual gaps to be filled by future controlled studies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The present study aimed at assessing if the ability to predict progression from amnesic Mild Cognitive Impairment (aMCI) to dementia is improved by considering the presence at the baseline of Single Photon Emission Computed Tomography (SPECT) perfusion abnormalities in addition to a defect of long term memory. The Episodic Memory Score (EMS), a global index which integrates results obtained in subtests of the Rey's Verbal Learning Test and the Rey-Osterrieth Figure recall, were taken into account to evaluate defects of long term memory. The study sample consisted of 42 subjects affected by aMCI, who were followed-up during a two-year period. At the final follow-up 15 subjects progressed to AD. The EMS predicted progression from aMCI to dementia with a high level of sensitivity and a lower level of specificity, but the association of neuropsychological (EMS) and SPECT data (hypoperfusion in the Posterior Cingulate Cortex) increased the accuracy in predicting conversion from aMCI to AD. The association of results obtained by aMCI patients on memory tests and perfusion SPECT may improve the accuracy in detecting subjects who will progress to dementia. The use of currently available and low-cost investigations could be advantageous in terms of public health policies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Accelerometry is a reliable tool for gauging the occurrence, amplitude and frequency of tremor. However, there is no consensus on criteria for accelerometric diagnosis of tremor syndromes. We enrolled 20 patients with essential tremor (ET), 20 with dystonic tremor (DT), and 20 with classic parkinsonian tremor (PD-T), all meeting accepted clinical criteria. All the patients underwent dopamine transporter imaging (by means of single-photon emission computed tomography) and triaxial accelerometric tremor analysis. The latter revealed groupwise differences in tremor frequency, peak dispersion, spectral coherence, unilaterality and resting vs action tremor amplitude. From the above, five diagnostic criteria were extrapolated for each condition. Receiver operating characteristic curves, depicting criteriabased scoring of each tremor type, showed negligible declines in specificity for scores ≥4 in patients with ET or DT and scores ≥3 in patients with PD-T, thus providing a simple scoring method (accelerometrically derived) for differential diagnosis of the principal tremor syndromes.

Repetitive Transcranial Magnetic Stimulation (rTMS) of the dorsolateral prefrontal cortex may affect neuro-adaptations associated with alcohol use disorder (AUD), potentially influencing craving and alcohol intake. We investigated alcohol intake and dopamine transporter (DAT) availability by Single Photon Emission Computed Tomography (SPECT) in the striatum of AUD patients before and after deep rTMS. Fourteen patients underwent baseline clinical and SPECT assessment. Eleven out of fourteen patients were randomized into two groups for the REAL (n.5) or SHAM (n.6) treatment. Clinical and SPECT evaluations were then carried out after four weeks of rTMS sessions (T1). At baseline, AUD patients showed higher striatal DAT availability than healthy control subjects (HC). Patients receiving the REAL stimulation revealed a reduction in DAT availability at T1, whereas the SHAM-treated group did not. In addition, patients receiving the REAL stimulation had a decrease in alcohol intake. The results of this longitudinal pilot study may suggest a modulatory effect of deep rTMS on dopaminergic terminals and a potential clinical efficacy in reducing alcohol intake in AUD patients. Further investigations are required to confirm these preliminary data., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

Background: Nerve growth factor (NGF) promotes neural recovery after experimental traumatic brain injury (TBI) supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated protein Doublecortin (DCX). Only a few studies reported NGF administration in paediatric patients with severe TBI., Methods: A four-year-old boy in a persistent unresponsive wakefulness syndrome (UWS) was treated with intranasal murine NGF administration 6 months after severe TBI. The patient received four cycles of intranasal NGF (0.1 mg/kg, twice a day for 10 consecutive days)., Results: NGF administration improved functional [Positron Emission Tomography/Computed Tomography (PET/CT); Single photon emission/Computed Tomography (SPECT/CT) and Magnetic Resonance Imaging (MRI)] assessment, electrophysiological [Electroencephalogram (EEG) and Visual Evoked Potential (VEP)] studies and clinical conditions. He showed improvements in voluntary movements, facial mimicry, phonation, attention and verbal comprehension, ability to cry, cough reflex, oral motility, feeding capacity, and bowel and urinary functions. After NGF administration, raised levels of both NGF and DCX were found in the cerebrospinal fluid of the patient. No side effects were reported., Conclusions: Although further studies are needed for better understanding the neuroprotective role of this neurotrophin, intranasal NGF administration appears to be a promising and safe rescuing strategy treatment in children with neurological impairment after TBI.

Purpose: Ovarian cancer is the eighth most common malignancy among women and has a high mortality rate. Prognostic factors able to drive an effective therapy are essential. (18)F-Fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has been investigated in patients with epithelial ovarian cancer and showed promise in diagnosing, staging, detecting recurrent lesions and monitoring treatment response. Conversely, its prognostic role remains unclear. We aimed at assessing the prognostic value of (18)F-FDG PET/CT performed in the restaging process in a multicentre study., Methods: We evaluated 168 patients affected by ovarian carcinoma, who underwent a restaging (18)F-FDG PET/CT. The presence of local recurrences, lymph node involvement and distant metastasis was recorded as well as lesion dimensions, maximum and mean standardized uptake values (SUVmax and SUVmean, respectively). Progression-free survival (PFS) and overall survival (OS) at 3 and 4 years were computed by using Kaplan-Meier curves. Increased odds ratio was assessed using Cox regression analysis testing all lesion parameters measured by PET/CT., Results: PFS was significantly longer in patients with a negative than a positive restaging PET/CT study (3- and 4-year PFS 64 and 53% vs 23 and 12%, respectively; p < 0.001). Similarly, a negative study was associated with a significantly higher OS rate after 4 years of follow-up (67 vs 25% in negative and positive groups, respectively; p < 0.001). Lymph node or distant involvement were also independently associated with an increased risk of disease progression [hazard ratio (HR) 1.6 and 2.2, respectively; p = 0.003]. Moreover, PET/CT showed an incremental prognostic value compared to the International Federation of Gynecology and Obstetrics (FIGO) staging system. In the analysis of patient subsets, individuals with the same FIGO stage I-II but with negative PET had a significantly better 4-year OS than patients with low FIGO stage but positive PET. This implies that patients with the same FIGO stage can be further prognostically stratified using PET (p = 0.01). At receiver-operating characteristic (ROC) analysis, no thresholds for semiquantitative parameters were predictive of a worse outcome., Conclusion: (18)F-FDG PET/CT has an important prognostic value in assessing the risk of disease progression and mortality rate. An efficacious therapy planning might therefore effectively rely on (18)F-FDG PET/CT findings. Semiquantitative data were not proven to be an effective tool to predict disease progression.

Autoimmune limbic encephalitis (LE) is a rare disorder affecting the medial temporal lobe of the brain. Although brain Magnetic Resonance (MR) has been widely evaluated and is currently considered essential in the suspicion of LE, Positron Emission Tomography/Computed Tomography (PET/CT) has been demonstrated to be useful also in the evaluation of brain inflammatory diseases such as encephalitis. We therefore aim to review the current literature about the role of PET/CT in the evaluation of patients affected by LE., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background/aims: Dopamine is an important neurotransmitter involved in the pathophysiology of depression and anhedonia. Dopamine transporters (DAT) may play a crucial role in the pathophysiology of dopaminergic transmission. We investigated the relationship between striatal DAT availability and depression, pointing out possible correlations with anhedonia and treatment outcomes., Methods: Ten depressed patients with anhedonia, 10 depressed patients without anhedonia and 20 healthy controls underwent single photon emission computed tomography using (123)I-FP-CIT [(123)I-N-ω-fluoropropyl-carbomethoxy-3β-(4-iodophenyl)tropane]. Psychometric measures included the Snaith-Hamilton Pleasure Scale and the Hamilton Depression Rating Scale. A further assessment of DAT availability was performed in the 10 patients with marked anhedonia after a 3-month pharmacological treatment., Results: Depressed patients with and without anhedonia showed significantly lower (123)I-FP-CIT binding ratios in the bilateral striatum, caudate and putamen. No significant changes were detected after treatment in the 10 patients with marked anhedonia. When considering clinical outcomes, subjects with remission of depression showed a significant reduction of (123)I-FP-CIT binding ratios in all regions at baseline, but after treatment no differences were found any longer., Conclusions: We suppose that a hypofunction of the striatal dopaminergic system may be a 'state' feature of a depressive condition as a whole rather than anhedonia itself. On the other hand, some anhedonic features mainly represent an enduring trait that persists independently of mood state., (© 2015 S. Karger AG, Basel.)

Purpose: Psychiatric symptoms frequently occur in patients with movement disorders. They are not a mere reaction to chronic disability, but most likely due to a combination of psychosocial factors and biochemical dysfunction underlying the movement disorder. We assessed dopamine transporter (DAT) availability by means of (123)I-FP-CIT SPECT, and motor and psychiatric features in patients with Parkinson's disease, primary dystonia and essential tremor, exploring the association between SPECT findings and symptom severity., Methods: Enrolled in the study were 21 patients with Parkinson's disease, 14 patients with primary dystonia and 15 patients with essential tremor. The severity of depression symptoms was assessed using the Hamilton depression rating scale, anxiety levels using the Hamilton anxiety rating scale and hedonic tone impairment using the Snaith-Hamilton pleasure scale. Specific (123)I-FP-CIT binding in the caudate and putamen was calculated based on ROI analysis. The control group included 17 healthy subjects., Results: As expected, DAT availability was significantly decreased in patients with Parkinson's disease, whereas in essential tremor and dystonia patients it did not differ from that observed in the control group. In Parkinson's disease patients, an inverse correlation between severity of depression symptoms and DAT availability in the left caudate was found (r = -0.63, p = 0.002). In essential tremor patients, levels of anxiety symptoms were inversely correlated with DAT availability in the left caudate (r = -0.69, p = 0.004). In dystonia patients, the severities of both anxiety and depression symptoms were inversely associated with DAT availability in the left putamen (r = -0.71, p = 0.004, and r = -0.75, p = 0.002, respectively). There were no correlations between psychometric scores and (123)I-FP-CIT uptake ratios in healthy subjects., Conclusion: We found association between presynaptic dopaminergic function and affective symptoms in different movement disorders. Interestingly, the inverse correlation was present in each group of patients, supporting the fascinating perspective that common subcortical substrates may be involved in both anxiety and depression dimensions and movement disorders.

Rationale and Objectives: The aim of this study was to perform a meta-analysis of published data about the diagnostic performance of (18)F-dihydroxyphenylalanine (DOPA) positron emission tomography (PET) or PET/computed tomography (CT) in detecting recurrent medullary thyroid carcinoma (MTC)., Materials and Methods: A comprehensive literature search of studies indexed in the PubMed/MEDLINE, Scopus, and Embase databases through January 2012 and regarding (18)F-DOPA PET or PET/CT in patients with suspected recurrent MTC was carried out. Pooled detection rates (DR) in per patient and per lesion analyses were calculated. A subanalysis considering serum levels of calcitonin and carcinoembryonic antigen, device used, and carbidopa pretreatment was also performed., Results: Eight studies including 146 patients with suspected recurrent MTC were included. The DRs of (18)F-DOPA PET and PET/CT in per patient and per lesion analyses were 66% and 71%, respectively. DRs significantly increased in patients with serum calcitonin ≥1000 ng/L (86%) and calcitonin doubling times <24 months (86%)., Conclusions: Fluorine-18-DOPA PET and PET/CT may be useful functional imaging methods in detecting recurrent MTC. The DR of recurrent MTC using these imaging methods increases in patients with higher calcitonin levels and lower calcitonin doubling times., (Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to assess striatal dopamine transporter availability in patients with advanced Parkinson's disease (PD) before and after 13 months of unilateral extradural motor cortex stimulation (EMCS) with [123I]N-ω-fluoropropyl-2-β-carbo-methoxy-3-β-(4-iodophenyl)nortropane single photon emission computed tomography (123I-FP-CIT SPECT)., Methods: Six PD patients (five women and one man, aged 63.2 ± 5.6 years) underwent 123I-FP-CIT SPECT and clinical evaluation [Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Quality of Life Scale (PDQL)] preoperatively, 8 and 13 months after EMCS. Striatum-to-occipital cortex, caudate-to-occipital cortex and putamen-to-occipital cortex 123I-FP-CIT uptake ratios were calculated using the region of interest method., Results: Total and part III UPDRS scores significantly decreased at 8 and 13 months after stimulation (P=0.02 and 0.04, respectively); UPDRS part II and PDQL scores improved after 13 months (P=0.02 and 0.04, respectively). No significant differences in 123I-FP-CIT uptake ratios between baseline and follow-up were found in the examined regions. However, a progressive reduction in 123I-FP-CIT uptake ratios in the striatum contralateral to the implant was found. In contrast, no further decrease in 123I-FP-CIT uptake ratios was detected in the striatum ipsilateral to the implant. There were no correlations between changes in 123I-FP-CIT uptake ratios with disease duration, changes in medication dosage and motor UPDRS scores., Conclusion: Despite a small but highly selected sample of advanced PD patients, our results showed that no further dopamine transporter reduction occurred in the striatum ipsilateral to the implant side. This finding could lead to the hypothesis that EMCS might elicit a 'neuroprotective' effect, as suggested by significant clinical benefits.

Background: To evaluate the metabolic changes on ¹⁸F-fluoro-2-deoxyglucose positron emission tomography integrated with computed tomography (¹⁸ F-FDG PET-CT) performed before, during and after concurrent chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC); to correlate the metabolic response with the delivered radiation dose and with the clinical outcome., Methods: Twenty-five NSCLC patients candidates for concurrent chemo-radiotherapy underwent ¹⁸F-FDG PET-CT before treatment (pre-RT PET-CT), during the third week (during-RT PET-CT) of chemo-radiotherapy, and 4 weeks from the end of chemo-radiotherapy (post-RT PET-CT). The parameters evaluated were: the maximum standardized uptake value (SUVmax) of the primary tumor, the SUVmax of the lymph nodes, and the Metabolic Tumor Volume (MTV)., Results: SUVmax of the tumor and MTV significantly (p=0.0001, p=0.002, respectively) decreased earlier during the third week of chemo-radiotherapy, with a further reduction 4 weeks from the end of treatment (p<0.0000, p<0.0002, respectively). SUVmax of lymph nodes showed a trend towards a reduction during chemo-radiotherapy (p=0.06) and decreased significantly (p=0.0006) at the end of treatment. There was a significant correlation (r=0.53, p=0.001) between SUVmax of the tumor measured at during-RT PET-CT and the total dose of radiotherapy reached at the moment of the scan. Disease progression free survival was significantly (p=0.01) longer in patients with complete metabolic response measured at post-RT PET-CT., Conclusions: In patients with locally advanced NSCLC, ¹⁸F-FDG PET-CT performed during and after treatment allows early metabolic modifications to be detected, and for this SUVmax is the more sensitive parameter. Further studies are needed to investigate the correlation between the metabolic modifications during therapy and the clinical outcome in order to optimize the therapeutic strategy. Since the metabolic activity during chemo-radiotherapy correlates with the cumulative dose of fractionated radiotherapy delivered at the moment of the scan, special attention should be paid to methodological aspects, such as the radiation dose reached at the time of PET.

Purpose: The aim of this study was to systematically review and conduct a meta-analysis of published data about the diagnostic performance of (18)F-dihydroxyphenylalanine (DOPA) positron emission tomography (PET) in patients with paraganglioma (PG)., Methods: A comprehensive computer literature search of studies published through 30 June 2011 regarding (18)F-DOPA PET or PET/computed tomography (PET/CT) in patients with PG was performed in PubMed/MEDLINE, Embase and Scopus databases. Pooled sensitivity and specificity of (18)F-DOPA PET or PET/CT in patients with PG on a per patient- and on a per lesion-based analysis were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of (18)F-DOPA PET or PET/CT in patients with PG. Furthermore, a sub-analysis taking into account the different genetic mutations in PG patients was also performed., Results: Eleven studies comprising 275 patients with suspected PG were included in this meta-analysis. The pooled sensitivity of (18)F-DOPA PET and PET/CT in detecting PG was 91% [95% confidence interval (CI) 87-94%] on a per patient-based analysis and 79% (95% CI 76-81%) on a per lesion-based analysis. The pooled specificity of (18)F-DOPA PET and PET/CT in detecting PG was 95% (95% CI 86-99%) on a per patient-based analysis and 95% (95% CI 84-99%) on a per lesion-based analysis. The area under the ROC curve was 0.95 on a per patient- and 0.94 on a per lesion-based analysis. Heterogeneity between the studies about sensitivity of (18)F-DOPA PET or PET/CT was found. A significant increase in sensitivity of (18)F-DOPA PET or PET/CT was observed when a sub-analysis excluding patients with succinate dehydrogenase subunit B (SDHB) gene mutations was performed., Conclusion: In patients with suspected PG (18)F-DOPA PET or PET/CT demonstrated high sensitivity and specificity. (18)F-DOPA PET or PET/CT are accurate methods in this setting. Nevertheless, possible sources of false-negative results should be kept in mind. Furthermore, SDHB gene mutations could influence (18)F-DOPA PET or PET/CT diagnostic performance.

Objective: Differential diagnosis between Parkinson's disease (PD) and other Parkinsonism using clinical criteria or imaging methods is often difficult. The purpose of this study is to systematically review and meta-analyze published data about the diagnostic performance of myocardial innervation imaging using (123)I-metaiodobenzylguanidine (MIBG) scintigraphy in differential diagnosis between PD and other Parkinsonism., Methods: A comprehensive computer literature search of studies published through March 2011 regarding MIBG scintigraphy in patients with PD and other Parkinsonism was performed in PubMed/MEDLINE and Embase databases. Only studies in which MIBG scintigraphy was performed for differential diagnosis between PD and other Parkinsonism were selected. Pooled sensitivity, pooled specificity and area under the ROC curve were calculated to measure the accuracy of MIBG scintigraphy in differential diagnosis between PD and other Parkinsonism., Results: Nineteen studies comprising 1,972 patients (1,076 patients with PD, 117 patients with other Lewy body diseases and 779 patients with other diseases) were included in this meta-analysis. The pooled sensitivity of MIBG scintigraphy in detecting PD was 88% (95% CI 86-90%); the pooled specificity of MIBG scintigraphy in discriminating between PD and other Parkinsonism was 85% (95% CI 81-88%). The area under the ROC curve was 0.93., Conclusions: In patients with clinically suspected PD, myocardial innervation imaging demonstrated high sensitivity and specificity. MIBG scintigraphy is an accurate test in this setting. Nevertheless, possible causes of false-negative and false-positive results should be kept in mind when interpreting the scintigraphic results.

Background and Purpose: This study was designed to review the diagnostic performance of iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy in differential diagnosis between Parkinson's disease (PD) and multiple-system atrophy (MSA)., Methods: A comprehensive computer literature search of studies published through March 2011 regarding MIBG scintigraphy in patients with PD and MSA was performed in PubMed/MEDLINE and Embase databases. Only studies in which MIBG scintigraphy was performed for differential diagnosis between PD and MSA were selected. Pooled sensitivity and specificity of MIBG scintigraphy were presented with a 95% confidence interval (CI). The area under the ROC curve was calculated to measure the accuracy of MIBG scintigraphy in differential diagnosis between PD and MSA., Results: Ultimately, we identified 12 studies comprising a total of 1226 patients (593 patients with PD, 117 patients with other Lewy body disease, 129 patients with MSA, and 387 patients with other diseases). The pooled sensitivity of MIBG scintigraphy to detect PD was 89% (95% CI: 86-91%); the pooled specificity of MIBG scintigraphy to discriminate between PD and MSA was 77% (95% CI: 68-84%). The area under the ROC curve was 0.93., Conclusions: MIBG scintigraphy is an accurate test for PD detection and differential diagnosis between PD and MSA; this method shows high sensitivity and adequate specificity in this field. Nevertheless, possible causes of false negative and false positive findings should be considered when interpreting the scintigraphic results., (Copyright © 2011 Elsevier B.V. All rights reserved.)