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ObjectivesNormative brain volume reports (NBVRs) are becoming more and more available for the workup of dementia patients in clinical routine. However, it is yet unknown how this information can be used in the radiological decision-making process. The present study investigates the diagnostic value of NBVRs for detection and differential diagnosis of distinct regional brain atrophy in several dementing neurodegenerative disorders.MethodsNBVRs were obtained for 81 consecutive patients with distinct dementing neurodegenerative diseases and 13 healthy controls (HC). Forty Alzheimer’s disease (AD; 18 with dementia, 22 with mild cognitive impairment (MCI), 11 posterior cortical atrophy (PCA)), 20 frontotemporal dementia (FTD), and ten semantic dementia (SD) cases were analyzed, and reports were tested qualitatively for the representation of atrophy patterns. Gold standard diagnoses were based on the patients’ clinical course, FDG-PET imaging, and/or cerebrospinal fluid (CSF) biomarkers following established diagnostic criteria. Diagnostic accuracy of pattern representations was calculated.ResultsNBVRs improved the correct identification of patients vs. healthy controls based on structural MRI for rater 1 (p < 0.001) whereas the amount of correct classifications was rather unchanged for rater 2. Correct differential diagnosis of dementing neurodegenerative disorders was significantly improved for both rater 1 (p = 0.001) and rater 2 (p = 0.022). Furthermore, interrater reliability was improved from moderate to excellent for both detection and differential diagnosis of neurodegenerative diseases (κ = 0.556/0.894 and κ = 0.403/0.850, respectively).ConclusionNBVRs deliver valuable and observer-independent information, which can improve differential diagnosis of neurodegenerative diseases.Key Points• Normative brain volume reports increase detection of neurodegenerative atrophy patterns compared to visual reading alone.• Differential diagnosis of regionally distinct atrophy patterns is improved.• Agreement between radiologists is significantly improved from moderate to excellent when using normative brain volume reports.

The objective is to estimate average global and regional percentage brain volume loss per year (BVL/year) of the physiologically ageing brain. Two independent, cross-sectional single scanner cohorts of healthy subjects were included. The first cohort ( n  = 248) was acquired at the Medical Prevention Center (MPCH) in Hamburg, Germany. The second cohort ( n  = 316) was taken from the Open Access Series of Imaging Studies (OASIS). Brain parenchyma (BP), grey matter (GM), white matter (WM), corpus callosum (CC), and thalamus volumes were calculated. A non-parametric technique was applied to fit the resulting age–volume data. For each age, the BVL/year was derived from the age–volume curves. The resulting BVL/year curves were compared between the two cohorts. For the MPCH cohort, the BVL/year curve of the BP was an increasing function starting from 0.20% at the age of 35 years increasing to 0.52% at 70 years (corresponding values for GM ranged from 0.32 to 0.55%, WM from 0.02 to 0.47%, CC from 0.07 to 0.48%, and thalamus from 0.25 to 0.54%). Mean absolute difference between BVL/year trajectories across the age range of 35–70 years was 0.02% for BP, 0.04% for GM, 0.04% for WM, 0.11% for CC, and 0.02% for the thalamus. Physiological BVL/year rates were remarkably consistent between the two cohorts and independent from the scanner applied. Average BVL/year was clearly age and compartment dependent. These results need to be taken into account when defining cut-off values for pathological annual brain volume loss in disease models, such as multiple sclerosis.

Background Neurofibromatosis 1 (NF1) is a rare autosomal dominant disease characterized by increased Schwann cell proliferation in peripheral nerves. Several small studies of brain morphology in children with NF1 have found increased total brain volume, total white matter volume and/or corpus callosum area. Some studies (mostly in children with NF1) also attempted to correlate changes in brain morphology and volume with cognitive or behavioural abnormalities, although the findings were inconsistent. We aimed to characterize alterations in brain volumes by three-dimensional (3D) MRI in adults with NF1 in major intracranial sub-regions. We also aimed to assess the effect of age on these volumes and correlated brain white matter and grey matter volumes with neuropsychometric findings in adults with NF1. Methods We obtained brain volume measurements using 3D magnetic resonance imaging for 351 adults with NF1 and, as a comparison group, 43 adults with neurofibromatosis 2 (NF2) or Schwannomatosis. We assessed a subset of 19 adults with NF1 for clinical severity of NF1 features and neurological problems and conducted psychometric testing for attention deficiencies and intelligence quotient. We compared brain volumes between NF1 patients and controls and correlated volumetric measurements to clinical and psychometric features in the NF1 patients. Results Total brain volume and total and regional white matter volumes were all significantly increased in adults with NF1. Grey matter volume decreased faster with age in adults with NF1 than in controls. Greater total brain volume and white matter volume were correlated with lower attention deficits and higher intelligence quotients in adults with NF1. Conclusion Our findings are consistent with the hypothesis that dysregulation of brain myelin production is a cardinal manifestation of NF1 and that these white matter changes may be functionally important in affected adults.

PurposeIncreased blood glucose level (BGL) has been reported to cause alterations of FDG uptake in the brain that mimic Alzheimer’s disease (AD), even within the \"acceptable\" range ≤ 160 mg/dl. The aim of this study was (i) to confirm this in a large sample of well-characterized normal control (NC) subjects, and (ii) to analyze its impact on the prediction of AD dementia (ADD) in mild cognitive impairment (MCI).MethodsThe study included NCs from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) that were cognitively stable for ≥36 months after PET (n = 87, 74.2 ± 5.3 y), and ADNI MCIs with ≥36 months follow-up if not progressed to ADD earlier (n = 323, 71.1 ± 7.1 y). Seventy-three of the MCIs had progressed to ADD within 36 months. In the NCs, parenchyma-scaled FDG uptake was tested for clusters of correlation with BGL on the family-wise, error-corrected 5% level. In the MCIs, ROC analysis was used to assess the power of FDG uptake in a predefined AD-typical region for prediction of ADD. ROC analysis was repeated after correcting mean FDG uptake in the AD-typical region for BGL based on linear regression in the NCs.ResultsIn the NCs, BGL (59–149 mg/dl) was negatively correlated with FDG uptake in a cluster comprising the occipital cortex and precuneus but sparing the posterior cingulate, independent of amyloid-β and ApoE4 status. In the MCIs, FDG uptake in the AD-typical region provided an area of 0.804 under the ROC curve for prediction of ADD. Correcting FDG uptake in the AD-typical region for BGL (55–189 mg/dl) did not change predictive performance (area = 0.808, p = 0.311).ConclusionsIncreasing BGL is associated with relative reduction of FDG uptake in the posterior cortex even in the \"acceptable\" range ≤ 160 mg/dl. The BGL-associated pattern is similar to the typical AD pattern, but not identical. BGL-associated variability of regional FDG uptake has no relevant impact on the power of FDG PET for prediction of MCI-to-ADD progression.

Objective Neurofibromatosis 1 (NF1) is a rare autosomal dominant disease that causes the dysregulated growth of Schwann cells. Most reported studies of brain morphology in NF1 patients have included only children, and clinical implications of the observed changes later in life remain unclear. In this study, we used MRI to characterize brain morphology in adults with NF1. Methods Planar (2D) MRI measurements of 29 intracranial structures were compared in 389 adults with NF1 and 112 age- and sex-matched unaffected control subjects. The 2D measurements were correlated with volumetric (3D) brain measurements in 99 of the adults with NF1 to help interpret the 2D findings. A subset (n = 70) of these NF1 patients also received psychometric testing for attention deficits and IQ and was assessed for clinical severity of NF1 features and neurological problems. Correlation analysis was performed between the MRI measurements and clinical and psychometric features of these patients. Results Four of nine corpus callosum measurements were significantly greater in adults with NF1 than in sex- and age-matched controls. All seven brainstem measurements were significantly greater in adults with NF1 than in controls. Increased corpus callosum and brainstem 2D morphology were correlated with increased total white matter volume among the NF1 patients. No robust correlations were observed between the 2D size of these structures and clinical or neuropsychometric assessments. Conclusion Our findings are consistent with the hypothesis that dysregulation of brain myelin production is an important manifestation of NF1 in adults.

Brain MRI white matter hyperintensities (WMHs) are common in elderly subjects. Their impact on cognition, however, appears highly variable. Complementing conventional scoring of WMH load (volume and location) by quantitative characterization of the shape irregularity of WMHs might improve the understanding of the relationship between WMH load and cognitive performance. Here we propose the “confluency sum score” (COSU) as a marker of the total shape irregularity of WMHs in the brain. The study included two independent patient samples: 87 cognitively impaired geriatric inpatients from a prospective neuroimaging study (iDSS) and 198 subjects from the National Alzheimer’s Coordinating Center (NACC) database (132 with, 66 w/o cognitive impairment). After automatic segmentation and clustering of the WMHs on FLAIR (LST toolbox, SPM8), the confluency of the i-th contiguous WMH cluster was computed as confluency i  = [1/(36π)∙surface i 3 /volume i 2 ] 1/3 –1. The COSU was obtained by summing the confluency over all WMH clusters. COSU was tested for correlation with CERAD-plus subscores. Correlation analysis was restricted to subjects with at least moderate WMH load (≥ 13.5 ml; iDSS / NACC: n  = 52 / 80). In the iDSS sample, among the 12 CERAD-plus subtests the trail making test A (TMT-A) was most strongly correlated with the COSU (Spearman rho = −0.345, p  = 0.027). TMT-A performance was not associated with total WMH volume (rho = 0.147, p  = 0.358). This finding was confirmed in the NACC sample (rho = −0.261, p  = 0.023 versus rho = −0.040, p  = 0.732). Cognitive performance in specific domains including mental speed and fluid abilities seems to be more strongly associated with the shape irregularity of white matter MRI hyperintensities than with their volume.

Review of Fausta Antonucci & Anna Tedesco, eds., La «Comedia nueva» e le scene italiane nel Seicento: trame, drammaturgie, contesti a confronto, Olschki (Biblioteca dell’ «Archivum Romanicum» Serie I: Storia, Letteratura, Paleografia, vol. 461), Florencia, 2016, 340 pp. ISBN: 9788822264756. Reseña de Fausta Antonucci y Anna Tedesco, eds., La «Comedia nueva» e le scene italiane nel Seicento: trame, drammaturgie, contesti a confronto, Olschki (Biblioteca dell’«Archivum Romanicum» Serie I: Storia, Letteratura, Paleografia, vol. 461), Florencia, 2016, 340 pp. ISBN: 9788822264756.

We examine the criteria adopted by the European Commission for assessing EU member states’ compliance with the “fiscal discipline” principles, with a focus on the role played by the output gap. This indicator, due to inertia and uncertainty inherent in its determination, is unable to correctly inform stabilization policies. The empirical literature reveals that the estimation techniques currently in use face serious difficulties in grasping the NAIRU during cyclical fluctuations, especially when these are of considerable strength and duration. There is a systematic tendency to interpret the evolution of real variables as the result of changes in productive capacity, with a distortion in the European Commission’s assessments of the adequacy of member states’ fiscal policies to economic conditions. Significant fiscal retrenchment was imposed, sometimes causing heavy consequences on productive capacity and productivity dynamics, and therefore on growth.

We present the clinical case of a 54 years old man who accessed for dyspnea and severe anemia. After being transfused, he underwent to gastroscopy, which showed an erosive gastritis with large hiatal hernia. The hernia was surgically reduced with laparoscopic hiatoplastic and Nissen-Rossetti fundoplication. In conclusion, dyspnea is not merely a medical competence but also a surgical one.

Devo ringraziare il nostro Presidente Gian Mario Bravo per avere affettuosamente voluto affidare anche a me, che per motivi di forza maggiore non avevo potuto presenziare al Convegno bolognese di neppure un anno fa, insieme all'amico Silvio Suppa, il ruolo di presentatrice di questo volume dei suoi Atti, curato in maniera impeccabile e a tempo di record da Raffaella Gherardi e da Saffo Testoni. Reprinted by permission of Casa Editrice Leo S. Olschki