High-dose glucocorticoids in COVID-19 patients with acute encephalopathy: clinical and imaging findings in a retrospective cohort study.

OBJECTIVES: Acute encephalopathy (AE) has been described as a severe complication of COVID-19. Inflammation has been suggested as a pathogenic mechanism, with high-dose glucocorticoids (GC) showing a beneficial effect. Here, we retrospectively analyzed the clinical and radiological features in a group of COVID-19 AE patients who received GC treatment (GT) and in a non-treated (NT) group. METHOD: Thirty-six patients with COVID-19 AE (mean age 72.6 ± 11 years; 86.11% men) were evaluated for GC treatment. Twelve patients (mean age 73.6 ± 4.5 years; 66.67% men) received GC, whereas 24 patients who showed signs of spontaneous remission were not treated with GC (mean age 70.1 ± 8.6 years; 95.83% men). Differences in clinical characteristics and correlations with imaging features were explored. RESULTS: The GT group showed signs of vulnerability, with a longer hospitalization (p = 0.009) and AE duration (p = 0.012) and a higher hypertensive arteriopathy (HTNA) score (p = 0.022), when compared to NT group. At hospital discharge, the two groups were comparable in terms of clinical outcome (modified Rankin scale; p = 0.666) or mortality (p = 0.607). In our whole group analyses, AE severity was positively correlated with periventricular white matter hyperintensities (p = 0.011), deep enlarged perivascular spaces (p = 0.039) and HTNA score (p = 0.014). CONCLUSION: This study suggests that, despite signs of radiological vulnerability and AE severity, patients treated by high-dose GC showed similar outcome at discharge, with respect to NT patients. Imaging features of cerebral small vessel disease correlated with AE severity, supporting the hypothesis that brain structural vulnerability can impact AE in COVID-19.

Characterizing upper extremity fine motor function in the presence of white matter hyperintensities: A 7 T MRI cross-sectional study in older adults.

BACKGROUND: White matter hyperintensities (WMH) are a prevalent radiographic finding in the aging brain studies. Research on WMH association with motor impairment is mostly focused on the lower-extremity function and further investigation on the upper-extremity is needed. How different degrees of WMH burden impact the network of activation recruited during upper limb motor performance could provide further insight on the complex mechanisms of WMH pathophysiology and its interaction with aging and neurological disease processes. METHODS: 40 healthy elderly subjects without a neurological/psychiatric diagnosis were included in the study (16F, mean age 69.3 years). All subjects underwent ultra-high field 7 T MRI including structural and finger tapping task-fMRI. First, we quantified the WMH lesion load and its spatial distribution. Secondly, we performed a data-driven stratification of the subjects according to their periventricular and deep WMH burdens. Thirdly, we investigated the distribution of neural recruitment and the corresponding activity assessed through BOLD signal changes among different brain regions for groups of subjects. We clustered the degree of WMH based on location, numbers, and volume into three categories; ranging from mild, moderate, and severe. Finally, we explored how the spatial distribution of WMH, and activity elicited during task-fMRI relate to motor function, measured with the 9-Hole Peg Test. RESULTS: Within our population, we found three subgroups of subjects, partitioned according to their periventricular and deep WMH lesion load. We found decreased activity in several frontal and cingulate cortex areas in subjects with a severe WMH burden. No statistically significant associations were found when performing the brain-behavior statistical analysis for structural or functional data. CONCLUSION: WMH burden has an effect on brain activity during fine motor control and the activity changes are associated with varying degrees of the total burden and distributions of WMH lesions. Collectively, our results shed new light on the potential impact of WMH on motor function in the context of aging and neurodegeneration.

Obstructive sleep apnea: a major risk factor for COVID-19 encephalopathy?

BACKGROUND: This study evaluates the impact of high risk of obstructive sleep apnea (OSA) on coronavirus disease 2019 (COVID-19) acute encephalopathy (AE). METHODS: Between 3/1/2020 and 11/1/2021, 97 consecutive patients were evaluated at the Geneva University Hospitals with a neurological diagnosis of COVID-19 AE. They were divided in two groups depending on the presence or absence of high risk for OSA based on the modified NOSAS score (mNOSAS, respectively ≥ 8 and < 8). We compared patients' characteristics (clinical, biological, brain MRI, EEG, pulmonary CT). The severity of COVID-19 AE relied on the RASS and CAM scores. RESULTS: Most COVID-19 AE patients presented with a high mNOSAS, suggesting high risk of OSA (> 80%). Patients with a high mNOSAS had a more severe form of COVID-19 AE (84.8% versus 27.8%), longer mean duration of COVID-19 AE (27.9 versus 16.9 days), higher mRS at discharge (≥ 3 in 58.2% versus 16.7%), and increased prevalence of brain vessels enhancement (98.1% versus 20.0%). High risk of OSA was associated with a 14 fold increased risk of developing a severe COVID-19 AE (OR = 14.52). DISCUSSION: These observations suggest an association between high risk of OSA and COVID-19 AE severity. High risk of OSA could be a predisposing factor leading to severe COVID-19 AE and consecutive long-term sequalae.

The role of disconnection in explaining disability in multiple sclerosis.

BACKGROUND: In multiple sclerosis, the correlation between white matter lesion volumes (LV) and expanded disability status scale (EDSS) is at best moderate, leading to the "clinico-radiological paradox", influenced by many factors, including the lack of information on the spatial localisation of each lesion on synthetic metrics such as LV. We used a probabilistic approach to provide the volume of WM tracts that may be disconnected by lesions and to evaluate its correlation with EDSS. METHODS: Forty-five patients (aged 37.4 ± 6.8 years, mean ± standard deviation; 30 females; 29 relapsing-remitting, 16 progressive) underwent 3-T magnetic resonance imaging. Both LV and the volume of the tracts crossing the lesioned regions (disconnectome volume, DV) were calculated using BCBtoolkit and correlated with EDSS. RESULTS: T1-weighted LV and DV significantly correlated with EDSS (p ≤ 0.006 r ≥ 0.413) as it was for T2-weighted LV and T2-weighted DV (p ≤ 0.004 r ≥ 0.430), but only T1-weighetd and T2-weighted DVs were EDSS significant predictors (p ≤ 0.001). The correlations of T1-weighted and T2-weighted LV with EDSS were significantly mediated by DV, while no effect of LV on the EDSS-DV correlation was observed. CONCLUSION: The volume of disconnected WM bundles mediates the LV-EDSS correlation, representing the lonely EDSS predictor.

CSF tap test in idiopathic normal pressure hydrocephalus: still a necessary prognostic test?

OBJECTIVE: To assess whether gait, neuropsychological, and multimodal MRI parameters predict short-term symptom reversal after cerebrospinal fluid (CSF) tap test in idiopathic normal pressure hydrocephalus (iNPH). METHODS: Thirty patients (79.3 ± 5.9 years, 12 women) with a diagnosis of probable iNPH and 46 healthy controls (74.7 ± 5.4 years, 35 women) underwent comprehensive neuropsychological, quantitative gait, and multimodal MRI assessments of brain morphology, periventricular white-matter microstructure, cortical and subcortical blood perfusion, default mode network function, and white-matter lesion load. Responders were defined as an improvement of at least 10% in walking speed or timed up and go test 24 h after tap test. Univariate and multivariable tap test outcome prediction models were evaluated with logistic regression and linear support vector machine classification. RESULTS: Sixteen patients (53%) respondedpositively to tap test. None of the gait, neuropsychological, or neuroimaging parameters considered separately predicted outcome. A multivariable classifier achieved modest out-of-sample outcome prediction accuracy of 70% (p = .028); gait parameters, white-matter lesion load and periventricular microstructure were the main contributors. CONCLUSIONS: Our negative findings show that short-term symptom reversal after tap test cannot be predicted from single gait, neuropsychological, or MRI parameters, thus supporting the use of tap test as prognostic procedure. However, multivariable approaches integrating non-invasive multimodal data are informative of outcome and may be included in patient-screening procedures. Their value in predicting shunting outcome should be further explored, particularly in relation to gait and white-matter parameters.

The Biological Substrate of the Motoric Cognitive Risk Syndrome: A Pilot Study Using Amyloid-/Tau-PET and MR Imaging.

We conducted a cross-sectional pilot study to explore the biological substrate of the Motoric Cognitive Risk (MCR) syndrome in a Memory Clinic cohort, using a multimodal imaging approach. Twenty participants were recruited and classified as MCR+/-. Amyloid- and tau-PET uptakes, temporal atrophy, white matter hyperintensities, lateral ventricular volume (LVV), and diffusion tensor parameters were compared between groups. No significant differences were found in imaging features related to Alzheimer's disease or gross vascular damage. MCR+ patients had increased LVV and altered diffusion parameters in the superior corona radiata. Ventricular enlargement and microstructural damage of the surrounding white matter tracts could contribute to MCR pathophysiology.

Altered anterior default mode network dynamics in progressive multiple sclerosis.

BACKGROUND: Modifications in brain function remain relatively unexplored in progressive multiple sclerosis (PMS), despite their potential to provide new insights into the pathophysiology of the disease at this stage. OBJECTIVES: To characterize the dynamics of functional networks at rest in patients with PMS, and the relation with clinical disability. METHODS: Thirty-two patients with PMS underwent clinical and cognitive assessment. The dynamic properties of functional networks, retrieved from transient brain activity, were obtained from patients and 25 healthy controls (HCs). Sixteen HCs and 19 patients underwent a 1-year follow-up (FU) clinical and imaging assessment. Differences in the dynamic metrics between groups, their longitudinal changes, and the correlation with clinical disability were explored. RESULTS: PMS patients, compared to HCs, showed a reduced dynamic functional activation of the anterior default mode network (aDMN) and a decrease in its opposite-signed co-activation with the executive control network (ECN), at baseline and FU. Processing speed and visuo-spatial memory negatively correlated to aDMN dynamic activity. The anti-couplings between aDMN and auditory/sensory-motor network, temporal-pole/amygdala, or salience networks were differently associated with separate cognitive domains. CONCLUSION: Patients with PMS presented an altered aDMN functional recruitment and anti-correlation with ECN. The aDMN dynamic functional activity and interaction with other networks explained cognitive disability.

The Two-Way Route between Delirium Disorder and Dementia: Insights from COVID-19.

BACKGROUND: Delirium disorder is a frequent neurological complication of SARS-CoV-2 infection and associated with increased disease severity and mortality. Cognitive impairment is a major risk factor for developing delirium disorder during COVID-19, which, in turn, increases the risk of subsequent neurological complications and cognitive decline. SUMMARY: The bidirectional connection between delirium disorder and dementia likely resides at multiple levels, and its pathophysiological mechanisms during COVID-19 include endothelial damage, blood-brain barrier dysfunction, and local inflammation, with activation of microglia and astrocytes. Here, we describe the putative pathogenic pathways underlying delirium disorder during COVID-19 and highlight how they cross with the ones leading to neurodegenerative dementia. KEY MESSAGES: The analysis of the two-sided link can offer useful insights for confronting with long-term neurological consequences of COVID-19 and framing future prevention and early treatment strategies.

Alzheimer's Disease Biomarkers in Idiopathic Normal Pressure Hydrocephalus: Linking Functional Connectivity and Clinical Outcome.

BACKGROUND: Alzheimer's disease (AD) pathology impacts the response to treatment in patients with idiopathic normal pressure hydrocephalus (iNPH), possibly through changes in resting-state functional connectivity (rs-FC). OBJECTIVE: To explore the relationship between cerebrospinal fluid biomarkers of AD and the default mode network (DMN)/hippocampal rs-FC in iNPH patients, based on their outcome after cerebrospinal fluid tap test (CSFTT), and in patients with AD. METHODS: Twenty-six iNPH patients (mean age: 79.9±5.9 years; 12 females) underwent MRI and clinical assessment before and after CSFTT and were classified as responders (Resp) or not (NResp), based on the improvement at the timed up and go test and walking speed. Eleven AD patients (mean age: 70.91±5.2 years; 5 females), matched to iNPH for cognitive status, were also included. DMN and hippocampal rs-FC was related to amyloid-ß42 and phosphorylated tau (pTau) levels. RESULTS: Lower amyloid-ß42 levels were associated with reduced inter- and intra-network rs-FC in NResp, and the interaction between amyloid-ß42 and rs-FC was a predictor of outcome after CSFTT. The rs-FC between DMN and salience networks positively correlated to amyloid-ß42 levels in both NResp and AD patients. The increase in the inter-network rs-FC after CSFTT was associated with higher pTau and lower amyloid-ß42 levels in NResp, and to lower pTau levels in Resp. CONCLUSION: Amyloid-ß42 and pTau impact on rs-FC and its changes after CSFTT in iNPH patients. The interaction between AD biomarkers and rs-FC might explain the responder status in iNPH.

A Multimodal Imaging Approach Demonstrates Reduced Midbrain Functional Network Connectivity Is Associated With Freezing of Gait in Parkinson's Disease.

Background: The pathophysiological mechanisms underlying freezing of gait (FOG) are poorly defined. MRI studies in FOG showed a distinct pattern of cortical atrophy and decreased functional connectivity (FC) within motor and cognitive networks. Furthermore, reduced rs-FC within midbrain, frontal, and temporal areas has been also described. This study investigated the patterns of whole-brain FC alterations within midbrain inter-connected regions in PD-FOG patients, and whether these patterns are linked to midbrain structural damage using a multi-modal imaging approach, combing structural and functional imaging techniques. Methods: Thirty three PD patients (16 PD-FOG, 17 PD noFOG), and 21 sex- and age-matched healthy controls (HCs) were prospectively enrolled. All subjects underwent MRI scan at 1.5T, whereas only PD patients underwent clinical and cognitive assessment. Grey matter (GM) integrity was measured using voxel-based morphometry (VBM). VBM findings served as basis to localize midbrain damage, and were further used as a seed region for investigating whole-brain FC alterations using rs-fMRI. Results: In rs-fMRI, patients with PD and FOG demonstrated significant decrease of midbrain-cortical FC levels in the R PCG, right postcentral, and supramarginal gyri compared to controls and the middle cingulate compared to noFOG group. Based on the regression analysis, MOCA, UPDRS-III total score, and FOG severity scores were associated with FC levels in several frontal, parietal and temporal regions. Discussion: The present results suggest that midbrain structural damage as well as decreased FC within the brainstem functional network might contribute to FOG occurrence in PD patients.

Dynamic functional networks in idiopathic normal pressure hydrocephalus: Alterations and reversibility by CSF tap test.

Idiopathic Normal Pressure Hydrocephalus (iNPH)-the leading cause of reversible dementia in aging-is characterized by ventriculomegaly and gait, cognitive and urinary impairments. Despite its high prevalence estimated at 6% among the elderlies, iNPH remains underdiagnosed and undertreated due to the lack of iNPH-specific diagnostic markers and limited understanding of pathophysiological mechanisms. INPH diagnosis is also complicated by the frequent occurrence of comorbidities, the most common one being Alzheimer's disease (AD). Here we investigate the resting-state functional magnetic resonance imaging dynamics of 26 iNPH patients before and after a CSF tap test, and of 48 normal older adults. Alzheimer's pathology was evaluated by CSF biomarkers. We show that the interactions between the default mode, and the executive-control, salience and attention networks are impaired in iNPH, explain gait and executive disturbances in patients, and are not driven by AD-pathology. In particular, AD molecular biomarkers are associated with functional changes distinct from iNPH functional alterations. Finally, we demonstrate a partial normalization of brain dynamics 24 hr after a CSF tap test, indicating functional plasticity mechanisms. We conclude that functional changes involving the default mode cross-network interactions reflect iNPH pathophysiological mechanisms and track treatment response, possibly contributing to iNPH differential diagnosis and better clinical management.

Position Sense Deficits at the Lower Limbs in Early Multiple Sclerosis: Clinical and Neural Correlates.

Background/Objective. Position sense, defined as the ability to identify joint and limb position in space, is crucial for balance and gait but has received limited attention in patients with multiple sclerosis (MS). We investigated lower limb position sense deficits, their neural correlates, and their effects on standing balance in patients with early MS. Methods. A total of 24 patients with early relapsing-remitting MS and 24 healthy controls performed ipsilateral and contralateral matching tasks with the right foot during functional magnetic resonance imaging. Corpus callosum (CC) integrity was estimated with diffusion tensor imaging. Patients also underwent an assessment of balance during quiet standing. We investigated differences between the 2 groups and the relations among proprioceptive errors, balance performance, and functional/structural correlates. Results. During the contralateral matching task, patients demonstrated a higher matching error than controls, which correlated with the microstructural damage of the CC and with balance ability. In contrast, during the ipsilateral task, the 2 groups showed a similar matching performance, but patients displayed a functional reorganization involving the parietal areas. Neural activity in the frontoparietal regions correlated with the performance during both proprioceptive matching tasks and quiet standing. Conclusion. Patients with early MS had subtle, clinically undetectable, position sense deficits at the lower limbs that, nevertheless, affected standing balance. Functional changes allowed correct proprioception processing during the ipsilateral matching task but not during the more demanding bilateral task, possibly because of damage to the CC. These findings provide new insights into the mechanisms underlying disability in MS and could influence the design of neurorehabilitation protocols.

Functional Correlates of Action Observation of Gait in Patients with Parkinson's Disease.

Background: Action observation (AO) relies on the mirror neuron system (MNS) and has been proposed as a rehabilitation tool in Parkinson's disease (PD), in particular for gait disorder such as freezing of gait (FOG). In this study, we aimed to explore the brain functional correlates of the observation of human gait in PD patients with (FOG+) and without (FOG-) FOG and to investigate a possible relationship between AO-induced brain activation and gait performance. Methods: Fifty-four participants were enrolled in the study (15 PD FOG+; 18 PD FOG-; 21 healthy subjects (HS)) which consisted of two tasks in two separate days: (i) gait assessment and (ii) task-fMRI during AO of gait. Differences between patients with PD (FOG+ and FOG-) and HS were assessed at the level of behavioral and functional analysis. Results: Gait parameters, including gait velocity, stride length, and their coefficients of variability (CV), were different in PD patients compared to HS, whereas gait performance was similar between FOG+ and FOG-. The PD group, compared to HS, presented reduced functional activation in the frontal, cingulum, and parietooccipital regions. Reduced activity was more pronounced in the FOG+ group, compared to both HS and FOG- groups. Gait variability positively correlated with precuneus neural activity in the FOG+ group. Discussion. Patients with PD present a reduced functional activity during AO of gait, especially if FOG+. A baseline knowledge of the neural correlates of AO of gait in the clinical routine "on" status would help for the design of future AO rehabilitative interventions.

Relationship between retinal inner nuclear layer, age, and disease activity in progressive MS.

OBJECTIVE: To investigate whether inner nuclear layer (INL) thickness as assessed with optical coherence tomography differs between patients with progressive MS (P-MS) according to age and disease activity. METHODS: In this retrospective longitudinal analysis, differences in terms of peripapillary retinal nerve fiber layer (pRNFL), ganglion cell layer + inner plexiform layer (GCIPL), INL and T1/T2 lesion volumes (T1LV/T2LV) were assessed between 84 patients with P-MS and 36 sex- and age-matched healthy controls (HCs) and between patients stratified according to age (cut-off: 51 years) and evidence of clinical/MRI activity in the previous 12 months RESULTS: pRNFL and GCIPL thickness were significantly lower in patients with P-MS than in HCs (p = 0.003 and p < 0.0001, respectively). INL was significantly thicker in patients aged < 51 years compared to the older ones and HCs (38.2 vs 36.5 and 36.7 µm; p = 0.038 and p = 0.04, respectively) and in those who presented MRI activity (new T2/gadolinium-enhancing lesions) in the previous 12 months compared to the ones who did not and HCs (39.5 vs 36.4 and 36.7 µm; p = 0.003 and p = 0.008, respectively). Recent MRI activity was significantly predicted by greater INL thickness (Nagelkerke R2 0.36, p = 0.001). CONCLUSIONS: INL thickness was higher in younger patients with P-MS with recent MRI activity, a criterion used in previous studies to identify a specific subset of patients with P-MS who best responded to disease-modifying treatment. If this finding is confirmed, we suggest that INL thickness might be a useful tool in stratification of patients with P-MS for current and experimental treatment choice.

A two alternative forced choice method for assessing vibrotactile discrimination thresholds in the lower limb.

The development of an easy to implement, quantitative measure to examine vibration perception would be useful for future application in clinical settings. Vibration sense in the lower limb of younger and older adults was examined using the method of constant stimuli (MCS) and the two-alternative forced choice paradigm. The focus of this experiment was to determine an appropriate stimulation site on the lower limb (tendon versus bone) to assess vibration threshold and to determine if the left and right legs have varying thresholds. Discrimination thresholds obtained at two stimulation sites in the left and right lower limbs showed differences in vibration threshold across the two ages groups, but not across sides of the body nor between stimulation sites within each limb. Overall, the MCS can be implemented simply, reliably, and with minimal time. It can also easily be implemented with low-cost technology. Therefore, it could be a good candidate method to assess the presence of specific deep sensitivity deficits in clinical practice, particularly in populations likely to show the onset of sensory deficits.

CSF oligoclonal bands and normal appearing white matter periventricular damage in patients with clinically isolated syndrome suggestive of MS.

BACKGROUND: A periventricular gradient of normal appearing white matter (NAWM) damage has been described in multiple sclerosis (MS), including subjects with clinically isolated syndrome (CIS). The pathological mechanisms underlying this gradient is not currently understood. METHODS: 34 CIS subjects were enrolled and underwent cerebrospinal fluid oligo-clonal bands (CSF-OCB) evaluation. Moreover, all CIS subjects and 24 healthy controls underwent a brain MRI scan. Diffusion weighted imaging was used to compute mean diffusivity (MD) values in periventricular and deep NAWM for all groups. RESULTS: CSF-OCB were present in 24 CIS subjects (CSF-OCB+) out of 34 tested. Periventricular NAWM MD values were significantly higher in CIS subjects with than in those without CSF-OCB (0.78 ± 0.06 mm3/10-3 vs. 0.72 ± 0.06 mm3/10-3; p = 0.01), while there was no difference between groups in deep NAWM MD values. The periventricular gradient of damage, expressed in z score based on healthy controls data, was more marked in CSF-OCB+ than in CSF-OCB- (0.65 ± 0.05 vs. 0.17 ± 0.04 p < 0.001). There was no difference in periventricular lesion load between the two groups. CONCLUSIONS: In CIS, the presence of CSF-OCB is associated with the severity of periventricular NAWM damage gradient. Intrathecal inflammation could play a role in NAWM damage distribution.

How much do periventricular lesions assist in distinguishing migraine with aura from CIS?

OBJECTIVE: To evaluate in clinically isolated syndrome (CIS) and migraine with aura (MA) how the number of periventricular lesions (PVLs) detected at MRI influences diagnostic performance when the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) or the 2017 revised criteria are applied. METHODS: In this retrospective study, white matter hyperintensities (WMH) of 84 patients with MA and 79 patients with CIS were assessed using manual segmentation technique. Lesion probability maps (LPMs) and voxel-wise analysis of lesion distribution by diagnosis were obtained. Furthermore, we performed a logistic regression analysis based on lesion locations and volumes. RESULTS: Compared to patients with MA, patients with CIS showed a significant overall higher T2 WMH mean number and volume (17.9 ± 16.9 vs 6.2 ± 11.9 and 3.1 ± 4.2 vs 0.3 ± 0.6 mL; p < 0.0001) and a significantly higher T2 WMH mean number in infratentorial, periventricular, and juxtacortical areas (p < 0.0001). LPMs identified the periventricular regions as the sites with the highest probability of detecting T2 WMH in patients with CIS. Voxel-wise analysis of lesion distribution by diagnosis revealed a statistically significant association exclusively between the diagnosis of CIS and the PVLs. MAGNIMS criteria demonstrated the highest specificity in differentiating patients with CIS from patients with MA (100% vs 87%) against a predictable lower sensitivity (63% vs 72%). CONCLUSIONS: PVLs play a key role in the differential diagnosis between MA and CIS, particularly when there are more than 3. Future studies on multiple sclerosis criteria might reconsider the 3 PVLs to minimize the risk of misdiagnosis. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the presence at least 3 PVLs increases the specificity in distinguishing MA from CIS.

Exploring mania-associated white matter injury by comparison with multiple sclerosis: a diffusion tensor imaging study.

Bipolar disorder (BD), especially in its active phases, has shown some neuroimaging and immunological similarities with multiple sclerosis (MS). The objective of this study was to compare white matter (WM) alterations in BD patients in manic phase (M-BD) and MS patients at early stage of disease and with low lesion burden. We compared diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) in a priori selected WM regions (i.e., corpus callosum and cingulum) betwixt 23 M-BD, 23 MS patients and 46 healthy controls. Both M-BD and MS showed WM changes in the corpus callosum, which, however, showed a greater impairment in MS patients. However, considering the different sub-regions of corpus callosum separately (i.e., genu, body, splenium), M-BD and MS presented an opposite pattern in spatial distribution of WM microstructure alterations, with a greater impairment in the anterior region in M-BD and in the posterior region in MS. Common features as well as divergent patterns in DTI changes are detected in M-BD and early MS, prompting a deeper investigation of analogies and differences in WM and immunological alterations of these disorders.

Monitoring Progressive Multiple Sclerosis with Novel Imaging Techniques.

Imaging markers for monitoring disease progression in progressive multiple sclerosis (PMS) are scarce, thereby limiting the possibility to monitor disease evolution and to test effective treatments in clinical trials. Advanced imaging techniques that have the advantage of metrics with increased sensitivity to short-term tissue changes and increased specificity to the structural abnormalities characteristic of PMS have recently been applied in clinical trials of PMS. In this review, we (1) provide an overview of the pathological features of PMS, (2) summarize the findings of research and clinical trials conducted in PMS which have applied conventional and advanced magnetic resonance imaging techniques and (3) discuss recent advancements and future perspectives in monitoring PMS with imaging techniques.

Radiotherapy in acromegaly: Long-term brain parenchymal and vascular magnetic resonance changes.

BACKGROUND: Radiation therapy (RT) effectiveness on hormonal reduction is proven in acromegaly; however, collateral long-term effects are still undetermined. This transversal neuroimaging study on a large cohort of acromegalic patients aimed to investigate the rate of parenchymal and vascular changes after RT. MATERIALS AND METHODS: Thirty-six acromegalic patients underwent RT (RT+) after unsuccessful surgery and were compared to RT- acromegalic patients matched for age, gender, adenoma features, clinical and surgical history. All patients underwent magnetic resonance angiography (MRA) to investigate intracranial artery abnormalities and FLAIR sequence to assess white matter changes according to the Wahlund scale. RESULTS: RT+ acromegalic patients had a higher rate of controlled disease (29/36 vs. 12/36, P<0.001). RT+ acromegalic patients had MRI/MRA evaluation 15.3±9.6 years after RT. RT+ acromegalic patients had a significantly higher Wahlund score than RT- acromegalic patients (6.03±6.41 vs. 2.53±3.66, P=0.006) due to increased white matter signal abnormalities at the level of the temporal lobes, the basal ganglia (insula) and the infratentorial regions, bilaterally. Among RT+ patients one died because of temporo-polar anaplastic astrocytoma, one suffered from a stroke due to right internal carotid artery occlusion, one presented with cystic degeneration of the temporal poles. Long-dated RT (>10 years before MR evaluation) was associated with a higher rate of RT-related white matter changes (P=0.0004). CONCLUSIONS: RT seems to have created a cohort of patients with brain parenchymal changes whose clinical and cognitive impact is still unknown. These patients might require a prolonged MRI and MRA follow-up to promptly detect delayed RT-related complications and minimize their clinical consequences.