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.

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.

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.

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.

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.

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.

Neural correlates of lower limbs proprioception: An fMRI study of foot position matching.

Little is known about the neural correlates of lower limbs position sense, despite the impact that proprioceptive deficits have on everyday life activities, such as posture and gait control. We used fMRI to investigate in 30 healthy right-handed and right-footed subjects the regional distribution of brain activity during position matching tasks performed with the right dominant and the left nondominant foot. Along with the brain activation, we assessed the performance during both ipsilateral and contralateral matching tasks. Subjects had lower errors when matching was performed by the left nondominant foot. The fMRI analysis suggested that the significant regions responsible for position sense are in the right parietal and frontal cortex, providing a first characterization of the neural correlates of foot position matching.

Composite MRI measures and short-term disability in patients with clinically isolated syndrome suggestive of MS.

BACKGROUND: The use of composite magnetic resonance imaging (MRI) measures has been suggested to better explain disability in patients with multiple sclerosis (MS). However, little is known about the utility of composite scores at the earliest stages of the disease. OBJECTIVE: To investigate whether, in patients with clinically isolated syndrome (CIS), a composite MRI measure, rather than the single metrics, would explain conversion to MS and would better correlate with disability at baseline and at 1 year of follow-up. METHODS: Corticospinal tract (CST), corpus callosum (CC) and optic radiation (OR) volume, fractional anisotropy (FA), and mean diffusivity (MD) values were measured in 27 CIS patients and 24 healthy controls (HCs). Z-scores of FA, MD, and tract volume measures were calculated in patients, based on the corresponding measures obtained from HCs, and then combined in a composite score for each tract. Correlations between Z-scores at baseline and both the Expanded Disability Status Scale (EDSS) at baseline and at follow-up (FU-EDSS) were investigated. RESULTS: Only CST, CC, and OR composite scores as well as the CST volume were significantly associated with FU-EDSS ( p = 0.005, p = 0.007, p = 0.020, and p = 0.010, respectively). CONCLUSION: The combination of MRI measures rather than the individual metrics better captured the association between tissue damage in both the CC, OR and CST and short-term follow-up disability.

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.

Resting-state functional connectivity and motor imagery brain activation.

Motor imagery (MI) relies on the mental simulation of an action without any overt motor execution (ME), and can facilitate motor learning and enhance the effect of rehabilitation in patients with neurological conditions. While functional magnetic resonance imaging (fMRI) during MI and ME reveals shared cortical representations, the role and functional relevance of the resting-state functional connectivity (RSFC) of brain regions involved in MI is yet unknown. Here, we performed resting-state fMRI followed by fMRI during ME and MI with the dominant hand. We used a behavioral chronometry test to measure ME and MI movement duration and compute an index of performance (IP). Then, we analyzed the voxel-matched correlation between the individual MI parameter estimates and seed-based RSFC maps in the MI network to measure the correspondence between RSFC and MI fMRI activation. We found that inter-individual differences in intrinsic connectivity in the MI network predicted several clusters of activation. Taken together, present findings provide first evidence that RSFC within the MI network is predictive of the activation of MI brain regions, including those associated with behavioral performance, thus suggesting a role for RSFC in obtaining a deeper understanding of neural substrates of MI and of MI ability. Hum Brain Mapp 37:3847-3857, 2016. © 2016 Wiley Periodicals, Inc.

Cingulum bundle alterations underlie subjective fatigue in multiple sclerosis.

OBJECTIVE: To evaluate the neural basis of subjective fatigue in subjects with multiple sclerosis (MS) using a connectionist framework. METHODS: Seventy seven subjects with relapsing-remitting MS were recruited in the study and underwent subjective fatigue evaluations and a diffusion MRI scan. Firstly, local white matter Fractional Anisotropy values were correlated with subjective fatigue scores using a voxel-wise approach. The long-range loss of connectivity due to structural damage in the white matter voxels thus associated with subjective fatigue was then assessed using the Network Modification (NeMo) package. RESULTS: A voxel-wise regression analysis with fatigue scores revealed a significant association between structural damage and fatigue levels in two discrete white matter clusters, both included in the left cingulate bundle. The connectivity analysis revealed that damage in these clusters was associated with loss of structural connectivity in the anterior and medial cingulate cortices, dorsolateral prefrontal areas and in the left caudate. DISCUSSION: Our data point to the cingulum bundle and its projections as the key network involved in subjective fatigue perception in MS. More generally, these results suggest the potential of the connectionist framework to generate coherent models of the neural basis of complex symptomatology in MS.

Structural correlates of subjective and objective memory performance in multiple sclerosis.

Subjective and objective memory deficits represent a frequent and ill-understood aspect of multiple sclerosis (MS), and a significant cause of disability and quality of life reduction. The aim of the study is to verify the role of hippocampal and temporal associative fibers' damage in MS-related memory complaints. To reach this aim, 25 patients with low disability relapsing-remitting MS and 19 healthy controls were included in the study. All subjects underwent 3D T1 structural imaging and Diffusion Tensor Imaging. Additionally, MS patients underwent neuropsychological evaluation of objective (Selective Reminding Test and Spatial Recall Test) and of subjective (Perceived Deficit Questionnaire, Retrospective and Prospective Memory Subscales) memory deficits. Normalized hippocampal volume (NHV) and mean Fractional Anisotropy (FA) for the uncinate fasciculus (UF) and for the ventral division of the cingulum bundle (VCB) were calculated for all subjects. We showed that, compared to controls, MS subjects presented with reduced right NHV and with reduced mean FA bilaterally in the UF and the VCB. In the MS group, verbal memory scores correlated with left NHV, spatial memory scores correlated with right NHV, while perceived retrospective and prospective memory deficits correlated with left VCB and left UF mean FA respectively. Our data confirm an early involvement of memory-related brain structures in MS patients. Our data suggest that verbal and nonverbal memory as well as perceived retrospective and prospective memory deficits are related to alterations of discrete anatomical structures in the low-disability phase of MS.

Intracranial internal carotid artery changes in acromegaly: a quantitative magnetic resonance angiography study.

PURPOSE: Although cerebrovascular mortality is increased up to eightfold in acromegaly, intracranial internal carotid artery (ICA) changes have not been well investigated. This is a magnetic resonance angiography (MRA) quantitative cross-sectional study of ICA tortuosity, ectasia and intercarotid distance in acromegalic patients with subsequent analysis of concomitant clinical, laboratory and neuroimaging findings. METHODS: One hundred seventy six acromegalic patients (mean-age 55 ± 14 years, age range 21-88, 92 females) and 104 subjects with headache or transient neurological deficits underwent MRA with the same 1.5 T scanner. Clinical data, laboratory and pituitary adenoma imaging findings were recorded. Using a commercially available software, we measured the tortuosity index [(curved/linear ICA length from C3-midpoint to intracranial bifurcation) - 1], ICA ectasia index (intracavernous/petrous ICA diameter) and intercarotid distance at C3 and C4 levels. RESULTS: Mean ICA tortuosity and ectasia indices were increased in acromegalic patients compared with controls (1.06 ± 0.29 vs 0.93 ± 0.26, p < 0.001; 1.02 ± 0.10 vs 0.92 ± 0.09, p < 0.001). Mean intercarotid distance was reduced at C3 and increased at C4 in acromegalic patients (16.7 ± 3.4 vs 17.9 ± 2.5 mm, p < 0.001; 16.7 ± 4.6 vs 15.4 ± 4.1 mm, p < 0.05; t test). ICA tortuosity and ectasia correlated neither with laboratory findings nor with previous or current treatment. On multivariate analysis, C3 intercarotid distance was reduced in patients on dopamine agonist treatment (p < 0.01) and increased in patients with GH-deficit (p = 0.01), while C4 intercarotid distance was increased with macroadenoma (p = 0.01) and reduced in patients under dopamine agonist (p < 0.01) or somatostatin analogue (p < 0.05) treatment. CONCLUSIONS: Intracranial ICA changes are common findings in acromegaly, and further studies focused on their possible clinical impact are needed.

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.

Herniation of cerebellar tonsils in acromegaly: prevalence, pathogenesis and clinical impact.

Herniation of cerebellar tonsils (CTH) might occur in acromegaly patients and improve after acromegaly treatment. Our study investigated CTH prevalence in acromegaly, its relationship with clinical, laboratory and neuroimaging findings and its possible pathogenesis and clinical impact. 150 acromegaly patients (median-age 56 years, age-range 21-88, 83 females) underwent brain magnetic resonance imaging (MRI). Clinical data, laboratory and pituitary adenoma imaging findings were recorded. CTH, posterior cranial fossa area, tentorial angle, clivus, supraocciput and Twining's line length were measured in acromegaly patients and controls, who included MRI of 115 consecutive subjects with headache or transient neurological deficits (control group-1) and 24 symptomatic classic Chiari 1 malformation patients (control group-2). Acromegaly patients were interviewed for symptoms known to be related with CTH. 22/150 acromegaly patients (15 %) and 8/115 control group-1 subjects presented with CTH (p = 0.04). In acromegaly patients, CTH correlated positively with younger age and inversely with GH-receptor antagonist treatment. Control group-2 had a shorter clivus than CTH acromegaly patients (40.4 ± 3.2 mm vs 42.5 ± 3.3 mm, p < 0.05), while posterior fossa measures did not differ among acromegaly subgroups (with and without CTH) and control group-1. Headache and vision problems were more frequent in CTH acromegaly patients (p < 0.05); two acromegaly patients presented with imaging and neurological signs of syringomyelia. Despite no signs of posterior fossa underdevelopment or cranial constriction, CTH is more frequent in acromegaly patients and seems to contribute to some disabling neurological symptoms.

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.

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.