18F-FDG PET brain findings in disease-discordant monozygotic mosaic twins with Cri du Chat (5p-) syndrome.

We describe the first report on the genotype-phenotype patterns and [18F] fluoro-deoxygluycose (18F-FDG) Positron Emission Tomography (PET) findings in two disease-discordant monozygotic twins with Cri du Chat syndrome (CdcS) presenting deletion of 5p, 46, XY, del(5)(p14)/46, XY. One twin showed a severe phenotype; significant 18F-FDG PET hypometabolism (p=0.001) was revealed in the left and right hemispheres, thalamus, cerebellum, and midbrain, whereas hypermetabolism was detected in the left premotor cortex. The other twin presented a mild phenotype; significant hypometabolism was detected only in the right side (parahippoccampal gyrus and cerebellum). Further studies should investigate the causes of phenotypic discordance in twins with CdcS.

Testing the diagnostic accuracy of [18F]FDG-PET in discriminating spinal- and bulbar-onset amyotrophic lateral sclerosis.

PURPOSE: The role for [18F]FDG-PET in supporting amyotrophic lateral sclerosis (ALS) diagnosis is not fully established. In this study, we aim at evaluating [18F]FDG-PET hypo- and hyper-metabolism patterns in spinal- and bulbar-onset ALS cases, at the single-subject level, testing the diagnostic value in discriminating the two conditions, and the correlations with core clinical symptoms severity. METHODS: We included 95 probable-ALS patients with [18F]FDG-PET scan and clinical follow-up. [18F]FDG-PET images were analyzed with an optimized voxel-based-SPM method. The resulting single-subject SPM-t maps were used to: (a) assess brain regional hypo- and hyper-metabolism; (b) evaluate the accuracy of regional hypo- and hyper metabolism in discriminating spinal vs. bulbar-onset ALS; (c) perform correlation analysis with motor symptoms severity, as measured by ALS-FRS-R. RESULTS: Primary motor cortex showed the most frequent hypo-metabolism in both spinal-onset (∼57%) and bulbar-onset (∼64%) ALS; hyper-metabolism was prevalent in the cerebellum in both spinal-onset (∼56.5%) and bulbar-onset (∼55.7%) ALS, and in the occipital cortex in bulbar-onset (∼62.5%) ALS. Regional hypo- and hyper-metabolism yielded a very low accuracy (AUC < 0.63) in discriminating spinal- vs. bulbar-onset ALS, as obtained from single-subject SPM-t-maps. Severity of motor symptoms correlated with hypo-metabolism in sensorimotor cortex in spinal-onset ALS, and with cerebellar hyper-metabolism in bulbar-onset ALS. CONCLUSIONS: The high variability in regional hypo- and hyper-metabolism patterns, likely reflecting the heterogeneous pathology and clinical phenotypes, limits the diagnostic potential of [18F]FDG-PET in discriminating spinal and bulbar onset patients.

Interplay between spinal cord and cerebral cortex metabolism in amyotrophic lateral sclerosis.

We recently reported the potential of Hough transform in delineating spinal cord metabolism by 18F-fluorodeoxyglucose PET/CT scanning in amyotrophic lateral sclerosis. The present study aimed to verify the relationship between spinal cord and brain metabolism in 44 prospectively recruited patients affected by amyotrophic lateral sclerosis submitted to 18F-fluorodeoxyglucose brain and whole-body PET/CT. Patients were studied to highlight the presence of brain hypo- or hypermetabolism with respect to healthy controls, and multiple regression analysis was performed to evaluate the correlation between spinal cord and brain metabolism. Our results confirmed higher 18F-fluorodeoxyglucose uptake in both cervical and dorsal spinal cord in patients with amyotrophic lateral sclerosis with respect to controls. This finding was paralleled by the opposite pattern in the brain cortex that showed a generalized reduction in tracer uptake. This hypometabolism was particularly evident in wide regions of the frontal-dorsolateral cortex while it did not involve the midbrain. Bulbar and spinal disease onset was associated with similar degree of metabolic activation in the spinal cord. However, among spinal onset patients, upper limb presentation was associated with a more pronounced metabolic activation of cervical segment. Obtained data suggest a differential neuro-pathological state or temporal sequence in disease progression.

Metabolic spatial connectivity in amyotrophic lateral sclerosis as revealed by independent component analysis.

OBJECTIVES: Positron emission tomography (PET) and volume of interest (VOI) analysis have recently shown in amyotrophic lateral sclerosis (ALS) an accuracy of 93% in differentiating patients from controls. The aim of this study was to disclose by spatial independent component analysis (ICA) the brain networks involved in ALS pathological processes and evaluate their discriminative value in separating patients from controls. EXPERIMENTAL DESIGN: Two hundred fifty-nine ALS patients and 40 age- and sex-matched control subjects underwent brain 18F-2-fluoro-2-deoxy-D-glucose PET (FDG-PET). Spatial ICA of the preprocessed FDG-PET images was performed. Intensity values were converted to z-scores and binary masks were used as data-driven VOIs. The accuracy of this classifier was tested versus a validated system processing intensity signals in 27 brain meta-VOIs. A support vector machine was independently applied to both datasets and the 'leave-one-out' technique verified the general validity of results. PRINCIPAL OBSERVATIONS: The 8 components selected as pathophysiologically meaningful discriminated patients from controls with 99.0% accuracy, the discriminating value of bilateral cerebellum/midbrain alone representing 96.3%. Among the meta-VOIs, right temporal lobe alone reached an accuracy of 93.7%. CONCLUSIONS: Spatial ICA identified in a very large cohort of ALS patients distinct spatial networks showing a high discriminatory value, improving substantially on the previously obtained accuracy. The cerebellar/midbrain component accounted for the highest accuracy in separating ALS patients from controls. Spatial ICA and multivariate analysis perform better than univariate semi-quantification methods in identifying the neurodegenerative features of ALS and pave the way for inclusion of PET in clinical trials and early diagnosis.

A PET/CT approach to spinal cord metabolism in amyotrophic lateral sclerosis.

PURPOSE: In amyotrophic lateral sclerosis, functional alterations within the brain have been intensively assessed, while progression of lower motor neuron damage has scarcely been defined. The aim of the present study was to develop a computational method to systematically evaluate spinal cord metabolism as a tool to monitor disease mechanisms. METHODS: A new computational three-dimensional method to extract the spinal cord from (18)F-FDG PET/CT images was evaluated in 30 patients with spinal onset amyotrophic lateral sclerosis and 30 controls. The algorithm identified the skeleton on the CT images by using an extension of the Hough transform and then extracted the spinal canal and the spinal cord. In these regions, (18)F-FDG standardized uptake values were measured to estimate the metabolic activity of the spinal canal and cord. Measurements were performed in the cervical and dorsal spine and normalized to the corresponding value in the liver. RESULTS: Uptake of (18)F-FDG in the spinal cord was significantly higher in patients than in controls (p < 0.05). By contrast, no significant differences were observed in spinal cord and spinal canal volumes between the two groups. (18)F-FDG uptake was completely independent of age, gender, degree of functional impairment, disease duration and riluzole treatment. Kaplan-Meier analysis showed a higher mortality rate in patients with standardized uptake values above the fifth decile at the 3-year follow-up evaluation (log-rank test, p < 0.01). The independence of this value was confirmed by multivariate Cox analysis. CONCLUSION: Our computational three-dimensional method enabled the evaluation of spinal cord metabolism and volume and might represent a potential new window onto the pathophysiology of amyotrophic lateral sclerosis.

The metabolic signature of C9ORF72-related ALS: FDG PET comparison with nonmutated patients.

PURPOSE: Recently, a GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene, located on chromosome 9p21 has been demonstrated to be the commonest cause of familial amyotrophic lateral sclerosis (ALS) and to account for 5 to 10 % of apparently sporadic ALS. Relatively little is known about the brain metabolism profile of patients carrying the expansion. Our aim was to identify the [(18)F]FDG PET profile in ALS patients with the C9ORF72 expansion (C9ORF72-ALS). METHODS: Fifteen C9ORF72-ALS patients were compared with 12 patients with ALS and comorbid frontotemporal dementia (FTD) without the C9ORF72 expansion (ALS-FTD) and 30 cognitively normal patients with ALS without mutations of ALS-related genes (sALS). The three groups were then cross-matched to 40 neurologically normal controls. All patients underwent FDG PET within 4 months of diagnosis. RESULTS: The C9ORF72-ALS patients compared with the sALS patients showed significant hypometabolism in the anterior and posterior cingulate cortex, insula, caudate and thalamus, the left frontal and superior temporal cortex, and hypermetabolism in the midbrain, bilateral occipital cortex, globus pallidus and left inferior temporal cortex. The ALS-FTD patients compared with the sALS patients showed more limited hypometabolic areas, including the orbitofrontal, prefrontal, anterior cingulate and insular cortex, and hypermetabolic areas, including the bilateral occipital cortex, the left precentral and postcentral cortex and superior temporal gyrus. The C9ORF72-ALS patients compared with the ALS-FTD patients showed hypometabolism in the left temporal cortex. CONCLUSION: ALS patients with the C9ORF72 hexanucleotide repeat expansion had a more widespread central nervous system involvement than ALS patients without genetic mutations, with or without comorbid FTD, consistent with their more severe clinical picture.

Is %ΔSUVmax a useful indicator of survival in patients with advanced nonsmall-cell lung cancer?

PURPOSE: To investigate the impact of the maximum standardized uptake value (SUVmax), size of primary lung lesion, and %ΔSUVmax on outcome (overall survival (OS) and 2-year disease-free survival (2-year DFS)) of patients with advanced nonsmall-cell lung cancer (NSCLC). MATERIALS AND METHODS: 86 stage III-IV NSCLC patients underwent 18 F-FDGPET/CT, before and after chemotherapy, and were classified into subgroups according to the response criteria of the European Organization for Research and Treatment of Cancer. SUVmax values and tumor size with the best prognostic significance were searched. Correlation between the SUVmax value and the initial response to therapy (best response) and the relationship between %ΔSUVmax and OS were assessed. RESULTS: In patients in PD (20/86), the average pretreatment SUVmax was 11.8 ± 5.23, and the mean size of the primary lesion was 43.35 mm ± 16.63. In SD, PR, and CR patients (66/86), the average pretreatment SUVmax was 12.7 ± 8.05, and the mean size of the primary lesion was 41.6 mm ± 21.15. Correlation was identified only for %ΔSUVmax; patients with PD (ΔSUVmax > +25%) showed a worse OS than patients with ΔSUVmax < +25% (CR, PR, and SD) (P = 0.0235). CONCLUSIONS: In stage III-IV NSCLC, among the assessed factors, only %ΔSUVmax may be considered as a useful prognostic factor.

Prediction of 2 years-survival in patients with stage I and II non-small cell lung cancer utilizing (18)F-FDG PET/CT SUV quantification.

BACKGROUND: The purpose of the study was to evaluate the correlation between the maximum standardized uptake value (SUVmax), size of primary lung lesion, disease-free survival (DFS) and overall survival (OS) in patients with stage I and II non-small cell lung cancer (NSCLC) in 2 years follow-up. PATIENTS AND METHODS: Forty-nine patients with stage I-II NSCLC were included in this study. Pre-surgical 2-deoxy-2-[18F]fluoro-D-glucose positron-emission tomography ((18)F-FDG PET/CT) study was performed for all patients. The relationship between SUVmax, tumour size and clinical outcome was measured. The cut-off value for SUVmax and tumour size with the best prognostic significance, probability of DFS and the correlation between SUVmax and the response to therapy were calculated. RESULTS: There was a statistically significant correlation between SUVmax and DFS (p = 0.029). The optimal cut-offs were 9.00 for SUVmax (p = 0.0013) and 30mm for tumour size (p = 0.0028). Patients with SUVmax > 9 and primary lesion size > 30 mm had an expected 2years-DFS of 37.5%, while this rose to 90% if the tumour was <30 mm and/or SUVmax was <9. CONCLUSIONS: In stage I-II, SUVmax and tumour size might be helpful to identify the subgroup of patients with high chance for recurrence.

Brain positron emission tomography in idiopathic normal-pressure hydrocephalus: new 18 F-fluorodeoxyglucose pattern in a long-known syndrome.

AIM: Patients with idiopathic normal-pressure hydrocephalus (iNPH) can show a global reduction in cerebral glucose metabolism at [ 18 F]Fluorodeoxyglucose (FDG) PET. The presence of caudate hypometabolism has been identified as a potential biomarker in iNPH, yet there is limited evidence of hypermetabolic findings in patients with iNPH so far. METHODS: We retrieved retrospectively patients with iNPH and normal cognitive assessment, evaluated before surgery undergoing brain [ 18 F]FDG-PET. The 18 F-FDG-PET brain scans were compared to those of a control group of healthy subjects, matched for age and sex, by statistical parametric mapping (SPM) to identify areas of relative hypo- and hypermetabolism. Furthermore, the existence of a correlation between areas of hypo- and hypermetabolism in the patient group was tested. RESULTS: Seven iNPH patients (mean age 74 ±â€…6 years) were found in the hospital database. SPM group analysis revealed clusters of significant hypometabolism ( P  = 0.001) in the iNPH group in the dorsal striatum, involving caudate and putamen bilaterally. Clusters of significant hypermetabolism ( P  = 0.001) were revealed in the bilateral superior and precentral frontal gyrus (BA 4, 6). A significant inverse correlation between striatal hypometabolism and bilateral superior and precentral frontal gyrus hypermetabolism was revealed ( P  < 0.001 corrected for multiple comparisons). CONCLUSION: In this cohort, patients with iNPH showed subcortical hypometabolism, including bilateral dorsal striatum. To the best of our knowledge, this is the first report demonstrating a hypermetabolic pattern in the primary motor and premotor areas, and showing an inverse correlation between the striatum and motor cortex in patients with iNPH.

Brain hypermetabolism in amyotrophic lateral sclerosis: a FDG PET study in ALS of spinal and bulbar onset.

PURPOSE: To identify the neurobiological traits of amyotrophic lateral sclerosis (ALS) and to elucidate functional differences between ALS of spinal and bulbar onset. We hypothesized that glucose metabolism distribution might vary between groups. METHODS: The study groups comprised 32 patients with ALS of either bulbar (n = 13) or spinal (n = 19) onset and 22 subjects as controls. They were investigated by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (FDG PET), comparing the patient groups with each other and with the controls by statistical parametric mapping. RESULTS: Highly significant relative increases in glucose metabolism distribution were found in the group comprising all 32 ALS patients as compared with the controls in the bilateral amygdalae, midbrain, pons and cerebellum. Relative hypermetabolism was also found in patients with spinal onset as compared with the controls in the right midbrain. In patients with bulbar onset compared with the controls and with patients with spinal onset, large relatively hypometabolic areas were found in the bilateral frontal cortex, right insula, anterior cingulate, precuneus and inferior parietal lobe. Patients with spinal onset had significantly higher scores in a neuropsychological test assessing verbal fluency compared with patients with bulbar onset. CONCLUSION: This large FDG PET investigation provided unprecedented evidence of relatively increased metabolism in the amygdalae, midbrain and pons in ALS patients as compared with control subjects, possibly due to local activation of astrocytes and microglia. Highly significant relative decreases in metabolism were found in large frontal and parietal regions in the bulbar onset patients as compared with the spinal onset patients and the controls, suggesting a differential metabolic and neuropsychological state between the two conditions.

The role of 18F-FDG PET/CT in the metabolic characterization of lung nodules in pediatric patients with bone sarcoma.

BACKGROUND: The principal aim of this study was to identify the lowest nodule diameter and the SUV(max) capable of characterizing lung nodules in pediatric patients with bone sarcoma. PROCEDURE: Eighteen consecutive bone sarcoma patients (M/F = 11:7; mean age 14 years) with suspicious lung lesions at CT were enrolled. Overall, 63 lung nodules with a mean diameter of 3.35 mm (range 1.2-39.8 mm) were investigated. (18) F-FDG PET was performed according to standard procedure using a hybrid PET/CT system and results were compared with histology and/or clinical/radiological follow-up. For each lesion, we evaluated SUV(max) , SUV(ratio) to the mediastinal blood pool and maximum nodule diameter. RESULTS: Of the 63 nodules, 32 proved to be benign and 31 malignant. On a visual basis, (18) F-FDG PET had an accuracy of 88.9%, a sensitivity of 90.3%, a specificity of 87.5%, a PPV of 87.5%, and a NPV of 90.3%. ROC curve analysis of SUV(max) for all nodules showed a value around 1 (>1.09) to be capable of differentiating metastases from benign lesions: sensitivity and specificity were 90.3% and 93.8%, respectively (accuracy 92.1%). Similar analysis revealed a cut-off value around 1 (>0.83) for SUV(ratio) (sensitivity and specificity were 90.3% and 90.6%, respectively) and a cut-off value of ca. 6 mm (>5.8 mm) for nodule diameter (sensitivity and specificity of 90.3% and 81.3%, respectively). CONCLUSIONS: (18) F-FDG PET/CT is an accurate modality for the metabolic characterization of lung nodules in the pediatric population with bone sarcoma, and a SUV(max) (or SUV(ratio) ) >1 is capable of discriminating malignant from benign lesions.

18F-FDG-PET brain imaging may highlight brain metabolic alterations in dysautonomic syndrome after human papilloma virus vaccination.

AIM: The aim of this study was to evaluate brain glucose metabolism by means of [18F]-fluoro-deoxygluycose (F-FDG) PET in a group of patients presenting dysautonomic syndrome after human papilloma virus (HPV) immunization. METHODS: Medical records of patients, referred to the 'Second Opinion Medical Consulting Network' Medical Centre (Modena, Italy) diagnosed with dysautonomic syndrome were searched. Inclusion criteria were presence in the medical history of adverse drug reactions following HPV vaccine; a Montreal Cognitive Assessment score <25 and good quality of a F-FDG-PET brain scan performed within 12 months from the diagnosis of dysautonomic syndrome. F-FDG-PET images of patients (HPV-group) were compared to a control group, matched for age and sex, using statistical parametric mapping (SPM). RESULTS: The F-FDG-PET study was available for five female patients. The SPM-group analysis revealed significant hypometabolism (P < 0.05 false discovery rate corrected) in the right superior and medial temporal gyrus (Brodmann areas 22, 21) and insula (Brodmann area 13). At a threshold of P < 0.001 (uncorrected), further hypometabolic regions were revealed in the right superior temporal gyrus (Brodmann area 42) and caudate head and in the left superior temporal gyrus (Brodmann area 22), frontal subcallosal gyrus (Brodmann area 47) and insula (Brodmann area 13). Relative hypermetabolism (P = 0.001) was revealed in the right premotor cortex (Brodmann area 6). CONCLUSION: This study revealed the possibility of altered brain glucose metabolism in subjects with dysautonomic syndrome post-immunization with HPV vaccine. These results could reinforce the hypothesis of a causal relationship between HPV vaccine, or some component included in the vaccine and the development of clinical manifestations.

18F-FDG PET Identifies Altered Brain Metabolism in Patients with Cri du Chat Syndrome.

Cri du chat syndrome (CDCS) is a rare genetic disease that is caused by a deletion in the short arm of chromosome 5 (5p) and has a variable clinical spectrum. To our knowledge, no study in the literature has ever applied 18F-FDG PET/CT to investigate alterations in brain glucose metabolism in these subjects. The aims of this study were to detect differences in brain 18F-FDG metabolism in CDCS patients with different clinical presentations and identify possible brain metabolic phenotypes of this syndrome. Methods: Six patients (5 male and 1 female; age range, 10-27 y) with CDCS were assessed for the presence of cognitive and behavioral symptoms using a battery of neuropsychologic tests and then classified as having either a severe or a mild phenotype. The patients then underwent brain 18F-FDG PET/CT. The PET/CT findings were compared with an age- and sex-matched control group using statistical parametric mapping (SPM). Whether there was an association between different clinical phenotypes and 18F-FDG PET/CT findings was investigated. Results: Four patients had the severe phenotype, and 2 patients demonstrated the mild phenotype. SPM single-subject analysis, and a group analysis in comparison with the control cohort, revealed significant hypometabolism in the left temporal lobe (Brodmann areas [BAs] 20, 36, and 38), in the right frontal subcallosal gyrus (BA 34) and caudate body, and in the cerebellar tonsils (P < 0.001). Hypermetabolism (P = 0.001) was revealed in the right superior and precentral frontal gyrus (BA 6) in the patient group, compared with the control cohort. In SPM single-subject analysis, the hypermetabolic areas were detected only in patients with the severe phenotype. Conclusion: This study revealed different patterns of brain glucose metabolism in patients with the severe and mild phenotypes, compared with control subjects. In particular, abnormal hypermetabolism in the brain, as evaluated by18F-FDG PET/CT, seems to correlate with the severe CDCS phenotype.

Locked-in Syndrome and 18F-fluorodeoxyglucose-positron Emission Tomography/Computed Tomography: Observations from a Case of Basilar Artery Thrombosis.

We report the case of a 59-year-old male patient suffering from locked-in syndrome (LIS) following basilar artery thrombosis despite an attempt of thrombolysis. Neurological examination showed quadriplegia and aphonia and a state of coma requiring mechanical ventilation was diagnosed. The use of 18F-fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET) allowed to detect a normal 18F-FDG uptake in the main cerebral cortical areas and a significant reduction of 18F-FDG uptake in both cerebellar hemispheres, compatible with a functional deafferentation, helping confirming the clinical suspicion of LIS. The diagnosis of LIS, according to literature, is based on the clinical assessment and the utilization of scores as the Coma Recovery Scale-Revised. The standard neuroimaging techniques, although recognize the site of injury, are not able to differentiate the different conditions affecting a state of altered consciousness. Performing 18F-FDG-PET in patients with LIS might help addressing the correct diagnosis and prompting subsequent appropriate treatment, and therefore, ultimately improving the patient outcome. Therefore, 18F-FDG-PET should be taken into account in the early clinical assessment of doubtful cases.

Comparison among conventional and advanced MRI, 18F-FDG PET/CT, phenotype and genotype in glioblastoma.

Glioblastoma (GB) is a highly heterogeneous tumor. In order to identify in vivo the most malignant tumor areas, the extent of tumor infiltration and the sites giving origin to GB stem cells (GSCs), we combined positron emission tomography/computed tomography (PET/CT) and conventional and advanced magnetic resonance imaging (MRI) with histology, immunohistochemistry and molecular genetics. Prior to dura opening and tumor resection, forty-eight biopsy specimens [23 of contrast-enhancing (CE) and 25 of non-contrast enhancing (NE) regions] from 12 GB patients were obtained by a frameless image-guided stereotactic biopsy technique. The highest values of 2-[18F]-fluoro-2-deoxy-D-glucose maximum standardized uptake value (18F-FDG SUVmax), relative cerebral blood volume (rCBV), Choline/Creatine (Cho/Cr), Choline/N-acetylaspartate (Cho/NAA) and Lipids/Lactate (LL) ratio have been observed in the CE region. They corresponded to the most malignant tumor phenotype, to the greatest molecular spectrum and stem cell potential. On the contrary, apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in the CE region were very variable. 18F-FDG SUVmax, Cho/Cr and Cho/NAA ratio resulted the most suitable parameters to detect tumor infiltration. In edematous areas, reactive astrocytes and microglia/macrophages were influencing variables. Combined MRI and 18F-FDG PET/CT allowed to recognize the specific biological significance of the different identified areas of GB.

18F-FDG-PET correlates of cognitive impairment in ALS.

OBJECTIVE: To identify the metabolic signature of the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using 18F-2-fluoro-2-deoxy-d-glucose-PET (18F-FDG-PET). METHODS: A total of 170 ALS cases consecutively enrolled at the ALS Center of Turin underwent brain 18F-FDG-PET and were classified as displaying normal cognition (ALS-Cn; n = 94), full-blown frontotemporal dementia (ALS-FTD; n = 20), executive or nonexecutive cognitive impairment not fulfilling FTD criteria (ALS-Ci; n = 37), prevalent behavioral changes (n = 9), or nonclassifiable impairment (n = 10) according to neuropsychological testing. Group comparisons of 18F-FDG-PET pattern were carried out among the cognitive subgroups. RESULTS: We found a significantly reduced frontal and prefrontal metabolism in ALS-FTD as compared to ALS-Cn, while ALS-Ci showed an intermediate metabolic behavior in frontal cortex, being hypometabolic as compared to ALS-Cn, and relatively hypermetabolic as compared to ALS-FTD. Hypometabolism in frontal regions was associated in all comparisons to hypermetabolism in cerebellum, midbrain, and corticospinal tracts: the more severe the cognitive decline, the larger the size of the cluster and the statistical significance of 18F-FDG uptake differences. CONCLUSIONS: This study demonstrated in a large cohort of patients with ALS a continuum of frontal lobe metabolic impairment reflecting the clinical and anatomic continuum ranging from pure ALS, through ALS with intermediate cognitive deficits, to ALS-FTD, and showing that patients with intermediate cognitive impairment display a characteristic metabolic pattern. Since 18F-FDG-PET allows us to estimate the cerebral lesion load in vivo in neurodegenerative diseases, it might be helpful to investigate in ALS its association with neuropsychological testing along the disease course to disclose the early metabolic signature of possible cognitive impairment.

Uncommon 18F-FDG-PET/CT findings in patients affected by limbic encephalitis: hyper-hypometabolic pattern with double antibody positivity and migrating foci of hypermetabolism.

Autoimmune limbic encephalitis (LE) is a rare disorder; its diagnosis can be challenging. We report two uncommon cases of LE evaluated by brain 2-deoxy-2-[18F]fluoro-d-glucose ((18)F-FDG) positron emission tomography/computed tomography describing the metabolic imaging patterns, which were different from those observed in previous studies: the first one presented an unprecedented (18)F-FDG brain mixed pattern, involving also the midbrain, despite negative magnetic resonance imaging exams; the second one showed migrating foci of hypermetabolism, one of which turned into hypometabolism at a later examination.