Empathy relies on fronto-cingular and temporal networks that are selectively vulnerable in behavioral variant frontotemporal dementia (bvFTD). This study modeled when in the disease process empathy changes begin, and how they progress.
Four hundred thirty-one individuals with asymptomatic genetic FTD (n = 114), genetic and sporadic bvFTD (n = 317), and 163 asymptomatic non-carrier controls were enrolled. In sub-samples, we investigated empathy measured by the informant-based Interpersonal Reactivity Index (IRI) at each disease stage and over time (n = 91), and its correspondence to underlying atrophy (n = 51).
Empathic concern (estimate = 4.38, 95% confidence interval [CI] = 2.79, 5.97; p < 0.001) and perspective taking (estimate = 5.64, 95% CI = 3.81, 7.48; p < 0.001) scores declined between the asymptomatic and very mild symptomatic stages regardless of pathogenic variant status. More rapid loss of empathy corresponded with subcortical atrophy.
Loss of empathy is an early and progressive symptom of bvFTD that is measurable by IRI informant ratings and can be used to monitor behavior in neuropsychiatry practice and treatment trials.

Parkinson\'s disease (PD) is a multifaceted neurodegenerative disorder accompanied by mild cognitive impairment (MCI) as a crucial nonmotor manifestation. Event-related oscillations (EROs) are suggested to reflect cognitive status associated with subcortical structures in neurodegenerative conditions. In this study, 36 individuals with PD-MCI and 32 PD-CN were compared with 60 healthy control (HC) participants using visual EROs by measures of event-related spectral perturbation and inter-trial coherence, along with subcortical gray matter volumes based on the FIRST algorithm. Cross-correlations among electrophysiological, neuropsychological, and structural parameters were investigated exploratively. Both PD-MCI and PD-CN patients had diminished delta and alpha phase-locking than HC, however, electrophysiological abnormalities were more pronounced in PD-MCI over frontal, central, parietal, and temporal locations in almost all frequency bands, accompanied by bilateral thalamus, hippocampus, and right putamen atrophy. PD-CN had lower hippocampal volumes than HC, without exhibiting any subcortical differences from PD-MCI. Lastly, EROs showed low-to-high correlations with structural and neuropsychological measures. These findings may highlight the complex interplay between electrophysiological, neuropsychological, and structural parameters in detected abnormalities of PD-CN and PD-MCI.

BACKGROUND: Cerebellar involvement is not comprehensively studied from an MRI point of view in multiple sclerosis (MS). We aimed to quantify cerebellar damage and identify predictors of physical disability and cognitive dysfunction in MS patients, and to characterize patients with cerebellar disability.
METHODS: In this prospective study, 164 (89 relapsing-remitting and 75 progressive) MS patients and 53 healthy controls were enrolled. Subjects underwent 3T MRI with sequences for assessing lesions and atrophy in cerebellum, supratentorial brain, brainstem and cervical cord. Cerebellar peduncle diffusion-tensor metrics were also derived. Random forest models identified MRI predictors of Expanded Disability Status Scale (EDSS) score and cognition z-score. Hierarchical clustering was applied on MRI metrics in patients with cerebellar disability.
RESULTS: In MS patients, predictors of higher EDSS score (out-of-bag-R2 = 0.83) were: lower cord grey matter (GM) and global areas, brain volume, GM volume (GMV), cortical GMV, cerebellum lobules I-IV and vermis GMV; and higher cord GM and brainstem lesion volume (LV). Predictors of lower cognition z-score (out-of-bag-R2 = 0.25) were: higher supratentorial and superior cerebellar peduncle LV; and lower brain, thalamus and basal ganglia volumes, GMV, cerebellum lobule VIIIb and Crus II GMV. In patients with cerebellar disability, we found three clusters with homogenous MRI metrics: patients with high brain lesion volumes (including cerebellar peduncles), those with marked cerebellum GM atrophy and patients with severe cord damage.
CONCLUSIONS: Damage to cerebellum GM and connecting structures has a relevant role in explaining cognitive dysfunction and physical disability in MS. Data-driven MRI clustering might improve our knowledge of MRI-clinical correlations.

OBJECTIVE: To determine whether brain atrophy was present in patients with anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE) using qualitative and quantitative analyses of brain magnetic resonance imaging (MRI) and to explore clinical differences in patients with anti-NMDARE with or without brain atrophy.
METHODS: A retrospective observational study encompassing the serologic, cerebrospinal fluid, and brain MRI data of 23 patients with anti-NMDARE was conducted. Median patient age was 14 years (interquartile range [IQR], 12 years). The cohort included 15 children (<18 years old) and 8 adults (≥18 years old). There were 6 male and 17 female patients. Imaging analysis involved 2 expert readers\' observations of MRIs and automated volumetric quantification using NeuroQuant (CorTechs Labs, Inc.) software.
RESULTS: Of 23 pediatric and adult patients, 11 patients had 14 brain MRIs that were quantitatively analyzed. Quantitative NeuroQuant volumetric analysis showed atrophy in 9 of 14 MRIs for 7 of 11 patients compared to age-controlled normative data. In these 9 MRIs, atrophy was present in the temporal lobes (n = 9), cerebral cortex (n = 3), and cerebellum (n = 3). Qualitative analysis of 59 MRIs (23 patients) revealed volume loss in 6 patients: 5 with global cerebral and temporal lobe volume loss and 1 with temporal lobe volume loss. No patient showed cerebellar volume loss on qualitative analysis. Mean length of stay in the intensive care unit was not significantly different for patients with or without quantitative volume loss (3.5 [5.2] vs 27.4 [23.4] days; p = 0.08).
CONCLUSIONS: In this cohort of patients with anti-NMDARE, quantitative volumetric analysis showed brain atrophy, particularly affecting the temporal lobes, in 64% (7/11) of the patients. Qualitative analysis showed brain atrophy in 26% (6/23). These findings highlight the increased sensitivity of quantitative methods for volume loss detection. Larger studies are needed.

UNASSIGNED: In multiple sclerosis (MS), cortical, subcortical and infratentorial structural damage may have a differential contribution to clinical disability according to disease phases.
UNASSIGNED: To determine the relative contributions of cortical, deep (D) grey matter (GM), cerebellar and cervical cord damage to MS disability milestones.
UNASSIGNED: Multi-centre 3T brain and cervical cord T2- and three-dimensional (3D) T1-weighted images were acquired from 198 MS patients (139 relapsing-remitting (RR) MS, 59 progressive (P) MS) and 67 healthy controls. Brain/cord lesion burden, cortical thickness (CTh), DGM and cerebellar volumetry and cord cross-sectional area (CSA) were quantified. Random forest analyses identified predictors of expanded disability status scale (EDSS) disability milestones (EDSS = 3.0, 4.0 and 6.0).
UNASSIGNED: MS patients had widespread atrophy in all investigated compartments versus controls (p-range: ⩽0.001-0.05). Informative determinants of EDSS = 3.0 were cord CSA, brain lesion volume, frontal CTh and thalamic and cerebellar atrophy (out-of-bag (OOB) accuracy = 0.84, p-range: ⩽0.001-0.05). EDSS = 4.0 was mainly predicted by cerebellar and cord atrophy, frontal and sensorimotor CTh and cord lesion number (OOB accuracy = 0.84, p-range: ⩽0.001-0.04). Cervical cord CSA (p = 0.001) and cord lesion number (p = 0.003) predicted EDSS = 6.0 (OOB accuracy = 0.77).
UNASSIGNED: Brain lesion burden, cortical and thalamic atrophy were the main determinants of EDSS = 3.0 and 4.0, while cord damage played a major contribution to EDSS = 6.0.

To determine the association of molecular biomarkers with tumor growth in patients with high-grade gliomas (HGGs), the tumor growth rates and molecular biomarker status in 109 patients with HGGs were evaluated. Mean tumor diameter was assessed on at least two pre-surgical T2-weighted and contrast-enhancement T1-weighted magnetic resonance images (MRIs). Tumor growth rates were calculated based on tumor volume and diameter using various methods. The association of biomarkers with increased or decreased tumor growth was calculated using linear mixed-effects models. HGGs exhibited rapid growth rates, with an equivalent volume doubling time of 63.4 days and an equivalent velocity of diameter expansion of 51.6 mm/year. The WHO grade was an independent clinical factor of eVDEs. TERT promoter mutation C250T and MGMT promoter methylation was significantly associated with tumor growth in univariable analysis but not in multivariable analysis. Molecular groups of IDH1, TERT, and 1p/19q and IDH1 and MGMT were independently associated with tumor growth. In addition, tumor enhanced area had a faster growth rate than a tumor entity in incomplete enhanced HGGs (p = 0.006). Our findings provide crucial information for the prediction of preoperative tumor growth in HGGs, and aided in the decision making for aggressive resection and adjuvant treatment strategies.

BACKGROUND: Volume loss in the deep gray matter (DGM) has been reported in patients with multiple sclerosis (MS) already at early stages of the disease and is thought to progress throughout the disease course.
OBJECTIVE: To investigate the impact and predictive value of volume loss in DGM and thalamic subnuclei on disability worsening in patients MS over a 6-year follow-up period.
METHODS: Hundred and seventy-nine patients with RRMS (132 women; median Expanded Disability Status Scale, EDSS: 2.5) and 50 with SPMS (27 women; median EDSS: 4.5) were included in the study. Patients underwent annual EDSS assessments and annual MRI at 1.5 T. DGM/thalamic subnuclei volumes were identified on high-resolution T1-weighted. A hierarchical linear mixed model for each anatomical DGM area and each thalamic subnucleus was performed to investigate the associations with disability scores. Cox regression was used to estimate the predictive properties of volume loss in DGM and thalamic subnuclei on disease worsening.
RESULTS: In the whole sample and in RRMS, volumes of the thalamus and the striatum were associated with the EDSS; however, only thalamic volume loss was associated with EDSS change at follow-up. Regarding thalamic subnuclei, volume loss in the anterior nucleus, the pulvinar and the ventral anterior nucleus was associated with EDSS change in the whole cohort. A trend was observed for the ventral lateral nucleus. Volume loss in the anterior and ventral anterior nuclei was associated with EDSS change over time in patients with RRMS. Moreover, MS phenotype and annual rates of volume loss in the thalamus and ventral lateral nucleus were predictive of disability worsening.
CONCLUSIONS: These results highlight the relevance of volume loss in the thalamus as a key metric for predicting disability worsening as assessed by EDSS (in RRMS). Moreover, the volume loss in specific nuclei such as the ventral lateral nucleus seems to play a role in disability worsening.

Objective: To evaluate the degree to which recently proposed parameters measured via a prism adaptation task are correlated with changes in cerebellar structure, specifically gray matter volume (GMV), in patients with spinocerebellar degeneration (SCD). Methods: We performed whole-brain voxel-based morphometry (VBM) analysis on 3-dimensional T1-weighted images obtained from 23 patients with SCD [Spinocerebellar ataxia type 6 (SCA6), 31 (SCA31), 3/Machado-Joseph disease (SCA3/MJD), and sporadic cortical cerebellar atrophy (CCA)] and 21 sex- and age-matched healthy controls (HC group). We quantified a composite index representing adaptive motor learning abilities in a hand-reaching task with prism adaptation. After controlling for age, sex, and total intracranial volume, we analyzed group-wise differences in GMV and regional GMV correlations with the adaptive learning index. Results: Compared with the HC group, the SCD group showed reduced adaptive learning abilities and smaller GMV widely in the lobules IV-VIII in the bilateral cerebellar hemispheres. In the SCD group, the adaptive learning index was correlated with cerebellar hemispheric atrophy in the right lobule VI, the left Crus I. Additionally, GMV of the left supramarginal gyrus showed a correlation with the adaptive learning index in the SCD group, while the supramarginal region did not accompany reduction of GMV. Conclusions: This study indicated that a composite index derived from a prism adaptation task was correlated with GMV of the lateral cerebellum and the supramarginal gyrus in patients with SCD. This study should contribute to the development of objective biomarkers for disease severity and progression in SCD.

BACKGROUND: Recent studies have suggested the presence of a significant atrophy affecting the cerebellar cortex in Friedreich ataxia (FRDA) patients, an area of the brain long considered to be relatively spared by neurodegenerative phenomena. Cognitive deficits, which occur in FRDA patients, have been associated with cerebellar volume loss in other conditions. The aim of this study was to investigate the correlation between cerebellar volume and cognition in FRDA.
METHODS: Nineteen FRDA patients and 20 healthy controls (HC) were included in this study and evaluated via a neuropsychological examination. Cerebellar global and lobular volumes were computed using the Spatially Unbiased Infratentorial Toolbox (SUIT). Furthermore, a cerebellar voxel-based morphometry (VBM) analysis was also carried out. Correlations between MRI metrics and clinical data were tested via partial correlation analysis.
RESULTS: FRDA patients showed a significant reduction of the total cerebellar volume (p = 0.004), significantly affecting the Lobule IX (p = 0.001). At the VBM analysis, we found a cluster of significant reduced GM density encompassing the entire lobule IX (p = 0.003). When correlations were probed, we found a direct correlation between Lobule IX volume and impaired visuo-spatial functions (r = 0.58, p = 0.02), with a similar correlation that was found between the same altered function and results obtained at the VBM (r = 0.52; p = 0.03).
CONCLUSIONS: With two different image analysis techniques, we confirmed the presence of cerebellar volume loss in FRDA, mainly affecting the posterior lobe. In particular, Lobule IX atrophy correlated with worse visuo-spatial abilities, further expanding our knowledge about the physiopathology of cognitive impairment in FRDA.

UNASSIGNED: Cranial radiation therapy (CRT) may disrupt the corpus callosum (CC), which plays an important role in basic motor and cognitive functions. The aim of this prospective longitudinal study was to assess changes in CC mid-sagittal areas, CC volumes, and performance on neuropsychological (NP) tests related to the CC in children following CRT.
METHODS: Twelve pediatric patients were treated with CRT for primary brain malignancies. Thirteen age-matched healthy volunteers served as controls. Brain MRIs and NP assessment emphasizing motor dexterity, processing speed, visuomotor integration, and working memory (visual and verbal) were performed at baseline and at 6, 15, and 27 months following completion of CRT. Linear mixed effects (LME) analyses were used to evaluate patient NP performance and changes in regional CC volumes (genu, anterior body, mid-body, posterior body, and splenium) and mid-sagittal areas over time and with radiation doses, correcting for age at CRT start.
RESULTS: The mean age at CRT was 9.41 (range 1.2-15.7) years. The median prescription dose was 54 (range 18-59.4) Gy. LME analysis revealed a significant decrease in overall CC volumes over time (p < 0.00001), with no overall effect of radiation dose. Analysis of individual CC regions demonstrated a significant decrease in all regional volumes over time (p < 0.00001) in patients, with no effect of radiation dose. Only in the splenium was there a trend toward a dose-dependent effect (p = 0.093). Patients had significantly reduced NP performance across visits-most notably in motor dexterity and visual working memory (both p < 0.0001).
CONCLUSIONS: These prospective data demonstrate a significant decrease in CC regional volumes after CRT, with associated decline in neurocognitive function, most notably in manual dexterity, attention, and working memory. Further prospective study of larger cohorts of patients is needed to establish the relationship between CRT dose, neuroanatomical, and functional changes in the CC.