Perivascular spaces (PVS) are fluid-filled structures that form the immediate peripheral environment of small cerebral vessels. They are a central component of the glymphatic system, which plays a crucial role in maintaining cerebral homeostasis. Their involvement in central nervous system diseases is currently a major focus of research, particularly in neuroimaging. Pathological enhancement of PVS on post-contrast MRI sequences creates a distinctive pattern due to their topography. As with other intracranial enhancement patterns, a differential diagnosis approach can be applied to perivascular enhancement (PVE). However, it is particularly challenging due to the rarity and complexity of the conditions involved. This article aims to facilitate the recognition of PVE pattern, to highlight the various causal conditions and to propose a practical diagnostic approach.

Objectives: Nonenhanced T-1-w sequences such as magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) and derived fluid and white matter suppression (FLAWS) have demonstrated high performance for detecting brain parenchymal and cervical spine demyelinating lesions in multiple sclerosis. However, their potential for identifying optic nerve (ON) demyelination remains unexplored. The aim of this study was to evaluate the performance of compressed sensing-accelerated (CS) MP2RAGE-FLAWS imaging for detection of ON demyelination lesions compared with T2-w fat-saturated (FS) TSE imaging in a clinical setting. Materials and Methods: We conducted a retrospective study of magnetic resonance scans acquired on patients with central nervous system demyelinating disorders between January and December 2022. Inclusion criteria were the acquisition in the same session of a brain CS-MP2RAGE-FLAWS imaging and a combination of axial + coronal T2-w FS orbital sequences. A 4-step radiological analysis-including blinded and consensus readings-assessed ON lesion detection. The reference standard was the final reading session of radiologists using the entire patient file. Sensitivities and specificities of both sequences were computed and compared using McNemar chi(2) tests. Results: Thirty-nine patients (mean age: 43 +/- 14 years; 25 women) were analyzed, including 34 with multiple sclerosis, 2 with MOGAD (myelin oligodendrocyte glycoprotein antibody-associated disease), 1 with NMOSD (neuromyelitis optica spectrum disorder), and 2 with indeterminate demyelinating disease. Among the 78 ONs analyzed, 64 lesions were detected with CS-MP2RAGE-FLAWS as opposed to 37 with 2D T2-w FS imaging, corresponding to a total of 41 and 27 affected nerves, respectively. CS-MP2RAGE-FLAWS exhibited higher sensitivity for overall detection of ON lesions compared with 2D T2-w FS imaging (97.5% vs 67.5%, P = 0.001) without reducing the specificity. Improved lesion detectability with CS-MP2RAGE-FLAWS was significant compared with 2D T2-w FS in intraorbital and intracanalicular segments (respectively, 92.3% vs 50% and 96.3% vs 66.7%; P < 0.05). There was no difference in sensitivity (P = 0.69) or specificity (P = 0.99) regarding the intracranial segment analysis. Conclusions: CS-MP2RAGE-FLAWS sequence improves ON lesion detection compared with conventional 2D T2-w FS, especially in the intraorbital segment, while simultaneously providing whole-brain and cervical spinal cord imaging at no additional time cost.

The prevalent belief that individuals with Huntington's disease exhibit selfish behaviour, disregarding the thoughts, feelings and actions of others, has been challenged by patient organizations and clinical experts. To further investigate this issue and study whether participants with Huntington's disease can pay attention to others, a joint memory task was carried out in patients with Huntington's disease with and without a partner. This study involved 69 participants at an early stage of Huntington's disease and 56 healthy controls from the UK, France and Germany, who participated in the international Repair-HD multicentre study (NCT03119246). Participants completed a semantic categorization task across three categories: animals, fruits and vegetables and manufactured objects. They performed the task either alone (Alone condition) or with the examiner acting as a partner (Pair condition). In the Pair condition, the participant was assigned one category, their partner was assigned another and one category was left unassigned. Afterwards, participants engaged in a surprise free recall task to remember as many words as possible. Words not assigned to anyone were considered socially irrelevant in contrast to the ones assigned to the participant and to the partner. Both groups demonstrated the expected self-prioritization effect, recalling their assigned words better than their partner's or unassigned words in both conditions. Additionally, a joint memory effect was observed, with better recall for the partner's assigned words than the unassigned words in the Pair condition (controls: difference = 0.45, P < 0.001; participants with Huntington's disease: difference = 0.34, P < 0.001). Socially relevant words were thus better recalled than irrelevant words. The number of recalled words correlated with cognitive performance (all P-values < 0.05) and MRI analysis revealed a negative correlation between the joint memory effect and right orbitofrontal grey matter density in participants with Huntington's disease. These findings challenge the notion that individuals with Huntington's disease display selfish behaviours because of disinterest in others. They show the ability to process information about their partners, implying that their social difficulties may arise from factors other than social cognition deficits. This opens the door for more ecological assessments of social cognition in patients with Huntington's disease.

Impaired motor function is a major cause of disability in multiple sclerosis (MS), involving various neuroplasticity processes typically assessed by neuroimaging. This study aimed to determine whether navigated transcranial magnetic stimulation (nTMS) could also provide biomarkers of motor cortex plasticity in patients with MS (pwMS). nTMS motor mapping was performed for hand and leg muscles bilaterally. nTMS variables included the amplitude and latency of motor evoked potentials (MEPs), corticospinal excitability measures, and the size of cortical motor maps (CMMs). Clinical assessment included disability (Expanded Disability Status Scale, EDSS), strength (MRC scale, pinch and grip), and dexterity (9-hole Pegboard Test). nTMS motor mapping was performed in 68 pwMS. PwMS with high disability (EDSS ≥ 3) had enlarged CMMs with less dense distribution of MEPs and various MEP parameter changes compared to pwMS with low disability (EDSS < 3). Patients with progressive MS had also various MEP parameter changes compared to pwMS with relapsing remitting form. MRC score correlated positively with MEP amplitude and negatively with MEP latency, pinch strength correlated negatively with CMM volume and dexterity with MEP latency. This is the first study to perform 4-limb cortical motor mapping in pwMS using a dedicated nTMS procedure. By quantifying the cortical surface representation of a given muscle and the variability of MEP within this representation, nTMS can provide new biomarkers of motor function impairment in pwMS. Our study opens perspectives for the use of nTMS as an objective method for assessing pwMS disability in clinical practice.

BackgroundComorbidities, particularly vascular comorbidities, have been shown to exacerbate the progression of disability in multiple sclerosis (MS). Metabolic syndrome (MetS) is a cluster of conditions including abdominal obesity, insulin resistance, atherogenic dyslipidemia, and vascular dysfunction, which contribute to vascular morbidity and chronic inflammation.ObjectiveTo describe the characteristics of MetS in a cohort of MS patients and evaluate its relationship with the MS phenotype.MethodsA monocentric cohort study was conducted on MS patients, collecting demographic, clinical, radiological, and therapeutic data, as well as metabolic data including waist circumference, blood pressure, serum triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose.ResultsAmong the 84 patients included in the study, 27% were diagnosed with MetS. MetS was found to be associated with secondary progressive MS (SPMS). Patients with SPMS had a higher prevalence of MetS compared to those with relapsing-remitting MS (RRMS), even after adjusting for disease duration. While MetS was associated with Expanded Disability Status Scale (EDSS) progression in the 3-year period according to univariate analysis, it did not show a significant association with disease activity.ConclusionThis study provides evidence supporting the connection between MetS and the progression of disability in MS, independent of disease relapse activity.

Malignant peripheral nerve sheath tumors (MPNST) are the leading cause of death in Neurofibromatosis type 1 (NF1). They can result from premalignant neurofibromas (NF) including NF with atypia and atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP). Some phenotypic characteristics have been described as associated with their development. The aim was to outline our use of whole-body 18F-FDG-PET/MRI in adults with NF1, especially in the screening of asymptomatic individuals with a higher risk of developing a MPNST, and to study its impact on NF classification (malignant vs premalignant) and MPNST staging over time. Individuals with NF1 who underwent a 18F-FDG-PET/MRI between 2017 to 2021 were included, analyzing separately the screened population. Maximum standard uptake value and diffusion-weighed imaging were assessed. Biopsy/surgery confirmed the diagnosis. In all, 345 18F-FDG-PET/MRI were performed in 241 patients including 149 asymptomatic (62%), but at risk. Eight MPNST in 8 screened individuals (5%), 6 NF with atypia in 4 (3%) and 29 ANNUBP in 23 (15%) were diagnosed. Over time, the proportion of grade 3 MPNST and the malignant/premalignant ratio in screened individuals significantly decreased (p=0.03 and p<0.001, respectively). This study emphasizes the diagnostic and screening performances of whole-body 18F-FDG-PET/MRI in adults with NF1.

Abstract The occurrence of severe intracranial hemorrhage under venovenous extracorporeal membrane oxygenation (VV-ECMO) is a diagnostic and therapeutic challenge. The aim of this retrospective study is to determine factors associated with the occurrence of severe intracranial hemorrhage under VV-ECMO in patients with SARS-CoV-2 infection. Among the 43 COVID-19 VV-ECMO patients included (seven women, median age: 55 years), eight patients(19%) presented an intracranial hemorrhage during VV-ECMO treatment, and 10 patients didn’t show any signs of intracranial hemorrhage on brain imaging. Twenty-five patients didn’t have imaging during or after VV-ECMO treatment. Kaplan-Meier analysis showed that the delay from hospital admission to VV-ECMO initiation was longer in patients with intracranial hemorrhage than in patients without intracranial hemorrhage(log-rank test P=0.03). Minute ventilation before cannulation was significantly lower in patients with intracranial hemorrhage compared to patients without intracranial hemorrhage: median(range)= 7.7L/min (3.9–14.0) vs. 12.1L/min(8.3–16.0);P=0.04. Arterial lactate values were higher in patients with intracranial hemorrhage compared to patients without intracranial hemorrhage: median(range)= 3.0mmol/L(1.1–6.6) vs. 1.9mmol/L(1.1–2.8);P=0.03. The occurrence of intracranial hemorrhage was associated with a longer period from hospitalization to VV-ECMO initiation, as well as hypoventilation and higher arterial lactate levels before VV-ECMO treatment.

Purpose: The purpose of this study was to compare a highly-accelerated double inversion recovery (fast-DIR) sequence using a recent parallel imaging technique (CAIPIRINHA) with a conventional DIR (cony-DIR) sequence for image quality and the detection of juxtacortical and infratentorial multiple sclerosis (MS) lesions. Materials and methods: A total of 38 patients with MS who underwent brain MRI at 3 T between 2020 and 2021 were included. There were 27 women and 12 men with a mean age of 40 +/- 12.8 (standard deviation) years (range: 20-59 years). All patients underwent cony-DIR sequence and fast-DIR sequence. Fast-DIR was obtained with a T2-preparation module to improve contrast and an iterative denoising algorithm to compensate noise enhancement. Two blinded readers reported the number of juxtacortical and infratentorial MS lesions for fastDIR and cony-DIR, confirmed by further consensus reading that was used as the standard of reference. Image quality and contrast were evaluated for fast-DIR and cony-DIR sequences. Comparisons between fast-DIR and cony-DIR sequences were performed using Wilcoxon test and Lin concordance correlation coefficient. Results: Thirty-eight patients were analyzed. Fast-DIR imaging allowed detection of 289 juxtacortical lesions vs. 238 with cony-DIR, corresponding to a significant improved detection rate with fast-DIR (P < 0.001). Conversely, 117 infratentorial lesions were detected with cony-DIR sequence vs. 80 with fast-DIR sequence (P < 0.001). Inter-observer agreement for lesion detection with fast-DIR and cony-DIR was very high (Lin concordance correlation coefficient ranging between 0.86 and 0.96). Conclusion: Fast-DIR improves the detection of juxtacortical MS lesions, but is limited for the detection of infratentorial MS lesions. (c) 2023 Societe francaise de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Purpose: MP2RAGE parameter optimization is redefined to allow more time-efficient MR acquisitions, whereas the T-1 -based synthetic imaging framework is used to obtain on-demand T-1 -weighted contrasts. Our aim was to validate this concept on healthy volunteers and patients with multiple sclerosis, using plug-and-play parallel-transmission brain imaging at 7 T.Methods: A "time-efficient" MP2RAGE sequence was designed with optimized parameters including TI and TR set as small as possible. Extended phase graph formalism was used to set flip-angle values to maximize the gray-to-white-matter contrast-to-noise ratio (CNR). Several synthetic contrasts (UNI, EDGE, FGATIR, FLAWS(MIN) , FLAWS(HCO) ) were generated online based on the acquired T-1 maps. Experimental validation was performed on 4 healthy volunteers at various spatial resolutions. Clinical applicability was evaluated on 6 patients with multiple sclerosis, scanned with both time-efficient and conventional MP2RAGE parameterizations.Results: The proposed time-efficient MP2RAGE protocols reduced acquisition time by 40%, 30%, and 19% for brain imaging at (1 mm)(3) , (0.80 mm)(3) and (0.65 mm)(3) , respectively, when compared with conventional parameterizations. They also provided all synthetic contrasts and comparable contrast-to-noise ratio on UNI images. The flexibility in parameter selection allowed us to obtain a whole-brain (0.45 mm)(3) acquisition in 19 min 56 s. On patients with multiple sclerosis, a (0.67 mm)(3) time-efficient acquisition enhanced cortical lesion visualization compared with a conventional (0.80 mm)(3) protocol, while decreasing the scan time by 15%.Conclusion: The proposed optimization, associated with T-1 -based synthetic contrasts, enabled substantial decrease of the acquisition time or higher spatial resolution scans for a given time budget, while generating all typical brain contrasts derived from MP2RAGE.

Purpose: Patient-induced inhomogeneities in the static magnetic field cause distortions and blurring (off-resonance artifacts) during acquisitions with long readouts such as in SWI. Conventional versatile correction methods based on extended Fourier models are too slow for clinical practice in computationally demanding cases such as 3D high-resolution non- Cartesian multi-coil acquisitions. Theory: Most reconstruction methods can be accelerated when performing off-resonance correction by reducing the number of iterations, compressed coils, and correction components. Recent state- of-the-art unrolled deep learning architectures could help but are generally not adapted to corrupted measurements as they rely on the standard Fourier operator in the data consistency term. The combination of correction models and neural networks is therefore necessary to reduce reconstruction times. Methods: Hybrid pipelines using UNets were trained stack-by-stack over 99 SWI 3D SPARKLING 20-fold accelerated acquisitions at 0.6mm isotropic resolution using different off-resonance correction methods. Target images were obtained using slow model-based corrections based on self-estimated.B0 field maps. The proposed strategies, tested over 11 volumes, are compared to model-only and network-only pipelines. Results: The proposed hybrid pipelines achieved scores competing with two to three times slower baselinemethods, and neural networkswere observed to contribute both as pre-conditioner and through inter-iterationmemory by allowing more degrees of freedom over the model design. Conclusion: A combination of model-based and network-based off-resonance correction was proposed to significantly accelerate conventional methods.Different promising synergies were observed between acceleration factors (iterations, coils, correction) and model/network that could be expanded in the future.

Cognitive deficits represent a hallmark of neurodegenerative diseases, but evaluating their progression is complex. Most current evaluations involve lengthy paper-and-pencil tasks which are subject to learning effects dependent on the mode of response (motor or verbal), the countries' language or the examiners. To address these limitations, we hypothesized that applying neuroscience principles may offer a fruitful alternative. We thus developed the SelfCog, a digitized battery that tests motor, executive, visuospatial, language and memory functions in 15 min. All cognitive functions are tested according to the same paradigm, and a randomization algorithm provides a new test at each assessment with a constant level of difficulty. Here, we assessed its validity, reliability and sensitivity to detect decline in early-stage Huntington's disease in a prospective and international multilingual study (France, the UK and Germany). Fifty-one out of 85 participants with Huntington's disease and 40 of 52 healthy controls included at baseline were followed up for 1 year. Assessments included a comprehensive clinical assessment battery including currently standard cognitive assessments alongside the SelfCog. We estimated associations between each of the clinical assessments and SelfCog using Spearman's correlation and proneness to retest effects and sensitivity to decline through linear mixed models. Longitudinal effect sizes were estimated for each cognitive score. Voxel-based morphometry and tract-based spatial statistics analyses were conducted to assess the consistency between performance on the SelfCog and MRI 3D-T1 and diffusion-weighted imaging in a subgroup that underwent MRI at baseline and after 12 months. The SelfCog detected the decline of patients with Huntington's disease in a 1-year follow-up period with satisfactory psychometric properties. Huntington's disease patients are correctly differentiated from controls. The SelfCog showed larger effect sizes than the classical cognitive assessments. Its scores were associated with grey and white matter damage at baseline and over 1 year. Given its good performance in longitudinal analyses of the Huntington's disease cohort, it should likely become a very useful tool for measuring cognition in Huntington's disease in the future. It highlights the value of moving the field along the neuroscience principles and eventually applying them to the evaluation of all neurodegenerative diseases. Lunven et al. developed a brief digitized cognitive battery, assessing cognitive functions following a similar procedure in Huntington's disease. Cognitive decline over 1 year with greater sensitivity than traditional tests was observed in a multicentric study. It will likely improve patients' follow-up by detecting eventual heterogeneous progression of cognitive performance.

The unified model of time processing suggests that the striatum is a central structure involved in all tasks that require the processing of temporal durations. Patients with Huntington's disease exhibit striatal degeneration and a deficit in time perception in interval timing tasks (i.e. for duration ranging from hundreds of milliseconds to minutes), but whether this deficit extends to time production remains unclear. In this study, we investigated whether symptomatic patients (HD, N = 101) or presymptomatic gene carriers (Pre-HD, N = 31) of Huntington's disease had a deficit in time production for durations between 4 and 10 s compared to healthy controls and whether this deficit developed over a year for patients. We found a clear deficit in temporal production for HD patients, whereas Pre-HD performed similarly to Controls. For HD patients and Pre-HD participants, task per-formance was correlated with grey matter volume in the amygdala and caudate, bilaterally. These results confirm that the striatum is involved in interval timing not only in perception but also in production, in accordance with the unified model of time processing. Furthermore, exploratory factor analyses on our data indicated that temporal production was associated with clinical assessments of psychomotor and executive functions. Finally, when retested twelve months later, the deficit of HD patients remained stable, although striatal degeneration was more pronounced. Thus, the simple, short and language-independent temporal production task may be a useful clinical tool to detect striatal degeneration in patients in early stages of Huntington's disease. However, its usefulness to detect presymptomatic stages or for monitoring the evolution of HD over a year seems limited.

Objectives The precise location of multiple sclerosis (MS) cortical lesions can be very challenging at 3 T, yet distinguishing them from subcortical lesions is essential for the diagnosis and prognosis of the disease. Compressed sensing–accelerated fluid and white matter suppression imaging (CS-FLAWS) is a new magnetic resonance imaging sequence derived from magnetization-prepared 2 rapid acquisition gradient echo with promising features for the detection and classification of MS lesions. The objective of this study was to compare the diagnostic performances of CS-FLAWS (evaluated imaging) and phase sensitive inversion recovery (PSIR; reference imaging) for classification of cortical lesions (primary objective) and infratentorial lesions (secondary objective) in MS, in combination with 3-dimensional (3D) double inversion recovery (DIR). Materials and Methods Prospective 3 T scans (MS first diagnosis or follow-up) acquired between March and August 2021 were retrospectively analyzed. All underwent 3D CS-FLAWS, axial 2D PSIR, and 3D DIR. Double-blinded reading sessions exclusively in axial plane and final consensual reading were performed to assess the number of cortical and infratentorial lesions. Wilcoxon test was used to compare the 2 imaging datasets (FLAWS + DIR and PSIR + DIR), and intraobserver and interobserver agreement was assessed using the intraclass correlation coefficient. Results Forty-two patients were analyzed (38 with relapsing-remitting MS, 29 women, 42.7 ± 12.6 years old). Compressed sensing–accelerated FLAWS allowed the identification of 263 cortical lesions versus 251 with PSIR (P = 0.74) and 123 infratentorial lesions versus 109 with PSIR (P = 0.63), corresponding to a nonsignificant difference between the 2 sequences. Compressed sensing–accelerated FLAWS exhibited fewer false-negative findings than PSIR either for cortical lesions (1 vs 13; P < 0.01) or infratentorial lesions (1 vs 15; P < 0.01). No false-positive findings were found with any of the 2 sequences. Diagnostic confidence was high for each contrast. Conclusion Three-dimensional CS-FLAWS is as accurate as 2D PSIR imaging for classification of cortical and infratentorial MS lesions, with fewer false-negative findings, opening the way to a reliable full brain MS exploration in a clinically acceptable duration (5 minutes 15 seconds).

Objectives Fluid and white matter suppression (FLAWS) is a recently proposed magnetic resonance sequence derived from magnetization-prepared 2 rapid acquisition gradient-echo providing 2 coregistered datasets with white matter– and cerebrospinal fluid–suppressed signal, enabling synthetic imaging with amplified contrast. Although these features are high potential for brain multiple sclerosis (MS) imaging, spinal cord has never been evaluated with this sequence to date. The objective of this work was therefore to assess diagnostic performance and self-confidence provided by compressed-sensing (CS) 3-dimensional (3D) FLAWS for cervical MS lesion detection on a head scan that includes the cervical cord without changing standard procedures. Materials and Methods Prospective 3 T scans (MS first diagnosis or follow-up) acquired between 2019 and 2020 were retrospectively analyzed. All patients underwent 3D CS-FLAWS (duration: 5 minutes 40 seconds), axial T2 turbo spin echo covering cervical spine from cervicomedullary junction to the same inferior level as FLAWS, and sagittal cervical T2/short tau inversion recovery imaging. Two readers performed a 2-stage double-blind reading, followed by consensus reading. Wilcoxon tests were used to compare the number of detected spinal cord lesions and the reader's diagnostic self-confidence when using FLAWS versus the reference 2D T2-weighted imaging. Results Fifty-eight patients were included (mean age, 40 ± 13 years, 46 women, 7 ± 6 years mean disease duration). The CS-FLAWS detected significantly more lesions than the reference T2-weighted imaging (197 vs 152 detected lesions, P < 0.001), with a sensitivity of 98% (T2-weighted imaging sensitivity: 90%) after consensual reading. Considering the subgroup of patients who underwent sagittal T2 + short tau inversion recovery imaging (Magnetic Resonance Imaging for Multiple Sclerosis subgroup), +250% lesions were detected with FLAWS (63 vs 25 lesions detected, P < 0.001). Mean reading self-confidence was significantly better with CS-FLAWS (median, 5 [interquartile range, 1] [no doubt for diagnosis] vs 4 [interquartile range, 1] [high confidence]; P < 0.001). Conclusions Imaging with CS-FLAWS provides an improved cervical spinal cord exploration for MS with increased self-confidence compared with conventional T2-weighted imaging, in a clinically acceptable time.

BACKGROUND:Neurological disorders associated with SARS-CoV-2 infection represent a clinical challenge because they encompass a broad neurological spectrum and may occur before the diagnosis of COVID-19. METHODS:In this monocentric retrospective case series, medical records from patients with acute neurological disorders associated with SARS-CoV-2 infection from medicine departments of an academic center in Paris area were collected between March 15th and May 15th 2020. Diagnosis of SARS-CoV-2 was ascertained through specific RT-PCR in nasopharyngeal swabs or based on circulating serum IgG antibodies. RESULTS:Twenty-six patients diagnosed with SARS-CoV-2 infection presented with neurological disorders: encephalitis (N=8), encephalopathy (N=6), cerebrovascular events (ischemic strokes N=4 and vein thromboses N=2), other central nervous system (CNS) disorders (N=4), and Guillain-Barré syndrome (N=2). The diagnosis of SARS-CoV-2 was delayed on average 1.6 days after the onset of neurological disorder, especially in case of encephalitis 3.9 days, encephalopathy 1.0 day, and cerebrovascular event 2.7 days. CONCLUSIONS:Our study confirms that COVID-19 can yield a broad spectrum of neurological disorders. Because neurological presentations of COVID-19 often occur a few days before the diagnosis of SARS-COV-2 infection, clinicians should take preventive measures such as patient isolation and masks for any new admission to avoid nosocomial infections. Anti-SARS-CoV2 antibody detection in RT-PCR SARS CoV-2 negative suspected cases is useful to confirm a posteriori the diagnosis of atypical COVID-19 presentations.

The supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus undergo structural and functional changes over the course of healthy aging. These nuclei and their connections are also heterogeneously affected by several different neurodegenerative diseases. This chapter reviews the involvement of the SON and PVN, the hypothalamic–pituitary axes, and the peptide hormones produced in both nuclei in healthy aging and in neurodegeneration, with a focus on Alzheimer's disease (AD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis, progressive supranuclear palsy, Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy, and Huntington's disease.Although age-related changes occur in several regions of the hypothalamus, the SON and PVN are relatively preserved during aging and in many neurodegenerative disorders. With aging, these nuclei do undergo some sexually dimorphic changes including changes in size and levels of vasopressin and corticotropin-releasing hormone, likely due to age-related changes in sex hormones. In contrast, oxytocinergic cells and circulating levels of thyrotropin-releasing hormone remain stable.A relative resistance to many forms of neurodegenerative pathology is also observed, in comparison to other hypothalamic and brain regions. Mirroring the pattern observed in aging, pathologic hallmarks of AD, and some subtypes of FTD are observed in the PVN, though to a milder degree than are observed in other brain regions, while the SON is relatively spared. In contrast, the SON appears more vulnerable to alpha-synuclein pathology of DLB and PD. The consequences of these alterations may help to inform several of the physiologic changes observed in aging and neurodegenerative disease.

BACKGROUND:Efficient cognitive tasks sensitive to longitudinal deterioration in small cohorts of Huntington's disease (HD) patients are lacking in HD research. We thus developed and assessed the digitized arithmetic task (DAT), which combines inner language and executive functions in approximately 4 minutes. METHODS:We assessed the psychometric properties of DAT in three languages, across four European sites, in 77 early-stage HD patients (age: 52 ± 11 years; 27 females), and 57 controls (age: 50 ± 10, 31 females). Forty-eight HD patients and 34 controls were followed up to one year with 96 participants who underwent MRI brain imaging (HD patients = 46) at baseline and 50 participants (HD patients = 22) at one year. Linear mixed models and Pearson correlations were used to assess associations with clinical assessment. RESULTS:At baseline, HD patients were less accurate (p = 0.0002) with increased response time (p<0.0001) when compared to DAT in controls. Test-retest reliability in HD patients ranged from good to excellent for response time (range: 0.63-0.79) and from questionable to acceptable for accuracy (range: r = 0.52-0.69). Only DAT, the Mattis Dementia Rating Scale, the Symbol Digit Modalities Test, and Total Functional Capacity scores were able to detect a decline within a one-year follow-up in HD patients (all p< 0.05). In contrast with all the other cognitive tasks, DAT correlated with striatal atrophy over time (p = 0.037) but not with motor impairment. CONCLUSIONS:DAT is fast, reliable, motor-free, applicable in several languages, and able to unmask cognitive decline correlated with striatal atrophy in small cohorts of HD patients. This likely makes it a useful endpoint in future trials for HD and other neurodegenerative diseases.

Background: Maximum safe resection of infiltrative brain tumors in eloquent area is the primary objective in surgical neuro-oncology. This goal can be achieved with direct electrical stimulation (DES) to perform a functional mapping of the brain in patients awake intraoperatively. When awake surgery is not possible, we propose a pipeline procedure that combines advanced techniques aiming at performing a dissection that respects the anatomo-functional connectivity of the peritumoral region. This procedure can benefit from intraoperative monitoring with computerized tomography scan (iCT-scan) and brain shift correction. Associated with this intraoperative monitoring, the additional value of preoperative investigation combining brain mapping by navigated transcranial magnetic stimulation (nTMS) with various neuroimaging modalities (tractography and resting state functional MRI) has not yet been reported. Case Report: A 42-year-old left-handed man had increased intracranial pressure (IICP), left hand muscle deficit, and dysarthria, related to an infiltrative tumor of the right frontal lobe with large mass effect and circumscribed contrast enhancement in motor and premotor cortical areas. Spectroscopy profile and intratumoral calcifications on CT-scan suggested an WHO grade III glioma, later confirmed by histology. The aforementioned surgical procedure was considered, since standard awake surgery was not appropriate for this patient. In preoperative time, nTMS mapping of motor function (deltoid, first interosseous, and tibialis anterior muscles) was performed, combined with magnetic resonance imaging (MRI)-based tractography reconstruction of 6 neural tracts (arcuate, corticospinal, inferior fronto-occipital, uncinate and superior and inferior longitudinal fasciculi) and resting-state functional MRI connectivity (rs-fMRI) of sensorimotor and language networks. In intraoperative time, DES mapping was performed with motor evoked response recording and tumor resection was optimized using non-rigid image transformation of the preoperative data (nTMS, tractography, and rs-fMRI) to iCT data. Image guidance was updated with correction for brain shift and tissue deformation using biomechanical modeling taking into account brain elastic properties. This correction was done at crucial surgical steps, i.e., when tumor bulged through the craniotomy after dura mater opening and when approaching the presumed eloquent brain regions. This procedure allowed a total resection of the tumor region with contrast enhancement as well as a complete regression of IICP and dysarthria. Hand paresis remained stable with no additional deficit. Postoperative nTMS mapping confirmed the good functional outcome. Conclusion: This case report and technical note highlights the value of preoperative functional evaluation by nTMS updated intraoperatively with correction of brain deformation by iCT. This multimodal approach may become the optimized technique of reference for patients with brain tumors in eloquent areas that are unsuitable for awake brain surgery.