Showing papers by "Maria A. Rocca published in 2020"

MAGNIMS consensus recommendations on the use of brain and spinal cord atrophy measures in clinical practice

Abstract: Early evaluation of treatment response and prediction of disease evolution are key issues in the management of people with multiple sclerosis (MS). In the past 20 years, MRI has become the most useful paraclinical tool in both situations and is used clinically to assess the inflammatory component of the disease, particularly the presence and evolution of focal lesions - the pathological hallmark of MS. However, diffuse neurodegenerative processes that are at least partly independent of inflammatory mechanisms can develop early in people with MS and are closely related to disability. The effects of these neurodegenerative processes at a macroscopic level can be quantified by estimation of brain and spinal cord atrophy with MRI. MRI measurements of atrophy in MS have also been proposed as a complementary approach to lesion assessment to facilitate the prediction of clinical outcomes and to assess treatment responses. In this Consensus statement, the Magnetic Resonance Imaging in MS (MAGNIMS) study group critically review the application of brain and spinal cord atrophy in clinical practice in the management of MS, considering the role of atrophy measures in prognosis and treatment monitoring and the barriers to clinical use of these measures. On the basis of this review, the group makes consensus statements and recommendations for future research.

Longitudinal Assessment of Multiple Sclerosis with the Brain-Age Paradigm

Abstract: Objective: During the natural course of multiple sclerosis (MS), the brain is exposed to aging as well as disease effects. Brain aging can be modeled statistically; the so-called “brain-age” paradigm. Here, we evaluated whether brain-predicted age difference (brain-PAD) was sensitive to the presence of MS, clinical progression, and future outcomes. Methods: In a longitudinal, multicenter sample of 3,565 magnetic resonance imaging (MRI) scans, in 1,204 patients with MS and clinically isolated syndrome (CIS) and 150 healthy controls (mean follow-up time: patients 3.41 years, healthy controls 1.97 years), we measured “brain-predicted age” using T1-weighted MRI. We compared brain-PAD among patients with MS and patients with CIS and healthy controls, and between disease subtypes. Relationships between brain-PAD and Expanded Disability Status Scale (EDSS) were explored. Results: Patients with MS had markedly higher brain-PAD than healthy controls (mean brain-PAD +10.3 years; 95% confidence interval [CI] = 8.5–12.1] versus 4.3 years; 95% CI = 2.1 to 6.4; p < 0.001). The highest brain-PADs were in secondary-progressive MS (+13.3 years; 95% CI = 11.3–15.3). Brain-PAD at study entry predicted time-to-disability progression (hazard ratio 1.02; 95% CI = 1.01–1.03; p < 0.001); although normalized brain volume was a stronger predictor. Greater annualized brain-PAD increases were associated with greater annualized EDSS score (r = 0.26; p < 0.001). Interpretation: The brain-age paradigm is sensitive to MS-related atrophy and clinical progression. A higher brain-PAD at baseline was associated with more rapid disability progression and the rate of change in brain-PAD related to worsening disability. Potentially, “brain-age” could be used as a prognostic biomarker in early-stage MS, to track disease progression or stratify patients for clinical trial enrollment. ANN NEUROL 2020 ANN NEUROL 2020;88:93–105.

Identifying Progression In Multiple Sclerosis : New Perspectives

Abstract: The identification of progression in multiple sclerosis is typically retrospective. Given the profound burden of progressive multiple sclerosis, and the recent development of effective treatments for these patients, there is a need to establish measures capable of identifying progressive multiple sclerosis early in the disease course. Starting from recent pathological findings, this review assesses the state of the art of potential measures able to predict progressive multiple sclerosis. Future promising biomarkers that might shed light on mechanisms of progression are also discussed. Finally, expansion of the concept of progressive multiple sclerosis, by including an assessment of cognition, patient-reported outcomes, and comorbidities, is considered. ANN NEUROL 2020;88:438-452.

Reduced dynamics of functional connectivity and cognitive impairment in multiple sclerosis

Abstract: Background:In multiple sclerosis (MS), abnormalities of brain network dynamics and their relevance for cognitive impairment have never been investigated.Objectives:The aim of this study was to asse...

Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability.

Abstract: Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites Lesions were segmented on both brain (T2-FLAIR or T2-weighted) and cervical (axial T2- or T2*-weighted) MRI scans Data were processed using an automated and publicly available pipeline Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 36 ± 27% and 29 ± 24%), compared to relapsing-remitting patients (16 ± 21%, both P < 00001) Voxel-wise analyses confirmed that lesion frequency was higher in progressive compared to relapsing-remitting patients, with significant bilateral clusters in the spinal cord corticospinal tracts (P < 001) The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 031, P < 00001), brainstem (r = 045, P < 00001) and spinal cord (r = 057, P < 00001) corticospinal tracts The spinal cord corticospinal tracts lesion volume fraction remained the strongest factor in the multiple linear regression model, independently from cord atrophy Baseline spinal cord corticospinal tracts lesion volume fraction was also associated with disability progression at 2-year follow-up (P = 0003) Our results suggest a cumulative effect of lesions within the corticospinal tracts along the brain, brainstem and spinal cord portions to explain physical disability in multiple sclerosis patients, with a predominant impact of intramedullary lesions

Structural connectivity in multiple sclerosis and modeling of disconnection.

Abstract: Background:Multiple sclerosis (MS) is characterized by focal white matter damage, and when the brain is modeled as a network, lesions can be treated as disconnection events.Objective:To evaluate wh...

Study protocol: improving cognition in people with progressive multiple sclerosis: a multi-arm, randomized, blinded, sham-controlled trial of cognitive rehabilitation and aerobic exercise (COGEx)

Abstract: Cognitive dysfunction affects up to 70% of people with progressive MS (PMS). It can exert a deleterious effect on activities of daily living, employment and relationships. Preliminary evidence suggests that performance can improve with cognitive rehabilitation (CR) and aerobic exercise (EX), but existing data are predominantly from people with relapsing-remitting MS without cognitive impairment. There is therefore a need to investigate whether this is also the case in people with progressive forms of the disease who have objectively identified cognitive impairment. It is hypothesized that CR and EX are effective treatments for people with PMS who have cognitive impairment, in particular processing speed (PS) deficits, and that a combination of these two treatments is more effective than each individual treatment given alone. We further hypothesize that improvements in PS will be associated with modifications of functional and/or structural plasticity within specific brain networks/regions involved in PS measured with advanced MRI techniques. This study is a multisite, randomized, double-blinded, sham controlled clinical trial of CR and aerobic exercise. Three hundred and sixty subjects from 11 sites will be randomly assigned into one of four groups: CR plus aerobic exercise; CR plus sham exercise; CR sham plus aerobic exercise and CR sham plus sham exercise. Subjects will participate in the assigned treatments for 12 weeks, twice a week. All subjects will have a cognitive and physical assessment at baseline, 12 weeks and 24 weeks. In an embedded sub-study, approximately 30% of subjects will undergo structural and functional MRI to investigate the neural mechanisms underlying the behavioral response. The primary outcome is the Symbol Digit Modalities Test (SDMT) measuring PS. Secondary outcome measures include: indices of verbal and non-verbal memory, depression, walking speed and a dual cognitive-motor task and MRI. The study is being undertaken in 6 countries (11 centres) in multiple languages (English, Italian, Danish, Dutch); with testing material validated and standardized in these languages. The rationale for this approach is to obtain a robustly powered sample size and to demonstrate that these two interventions can be given effectively in multiple countries and in different languages. The trial was registered on September 20th 2018 at www.clinicaltrials.gov having identifier NCT03679468 . Registration was performed before recruitment was initiated.

Clinical Relevance of Multiparametric MRI Assessment of Cervical Cord Damage in Multiple Sclerosis

Abstract: Cervical cord damage assessed with multiparametric MRI explains a substantial proportion of disease course in multiple sclerosis

Fatigue in multiple sclerosis patients with different clinical phenotypes: a clinical and magnetic resonance imaging study

Abstract: BACKGROUND AND PURPOSE The prevalence of fatigue and its relation with clinical, neuropsychological and brain magnetic resonance imaging (MRI) variables in a large cohort of multiple sclerosis (MS) patients was investigated. METHOD The Modified Fatigue Impact Scale and its subdomains were collected from 725 healthy controls and 366 MS patients [238 relapsing-remitting (RRMS) and 128 progressive (PMS)]. For the Modified Fatigue Impact Scale global and subdomains, MS patients were classified as fatigued (F-MS) or non-fatigued (NF-MS) according to cut-off values provided by logistic regression models with a specificity of 90% (i.e. a 10% false-positive rate in classifying healthy controls). MS patients underwent neurological, neuropsychological and MRI evaluations. Clinical and MRI measures were compared between F-MS and NF-MS patients using age-, sex- and phenotype-adjusted linear models. Heterogeneities between phenotypes were tested with specific interaction terms. RESULTS Global fatigue affected 174 (47.5%) MS patients, being more prevalent in PMS (PMS 64.1% vs. RRMS 38.7%, P < 0.001). For all dichotomizations, F-MS were older (P from <0.001 to 0.012) and more depressed (P < 0.001) than NF-MS patients. Compared to NF-MS, cognitive F-MS patients had lower education (P = 0.035). Compared to NF-MS, patients with global and physical fatigue had higher Expanded Disability Status Scale only for RRMS (P < 0.001). Only RRMS patients with physical fatigue had lower brain (P = 0.05), white matter (P = 0.039) and thalamic volumes (P = 0.022) compared to NF-MS patients. CONCLUSIONS In MS, fatigue is associated with older age, lower education and higher depression. Only in RRMS, fatigue is associated with Expanded Disability Status Scale and brain atrophy. A plateauing effect of disability and structural damage can explain the lack of associations in PMS.

Two-year dynamic functional network connectivity in clinically isolated syndrome

Abstract: Background:The features of functional network connectivity reorganization at the earliest stages of MS have not been investigated yet.Objective:To combine static and dynamic analysis of resting sta...

Current state-of-art of the application of serum neurofilaments in multiple sclerosis diagnosis and monitoring

Abstract: Neurodegenerative processes occur from the beginning of multiple sclerosis, contribute to irreversible clinical disability and are only partially addressed by current disease-modifying therapies. R...

Structural and functional brain connectomes in patients with systemic lupus erythematosus.

Abstract: BACKGROUND AND PURPOSE Systemic lupus erythematosus (SLE) is an immune-mediated disease that may affect the nervous system. We explored the topographical organization of structural and functional brain connectivity in patients with SLE and its correlation with neuropsychiatric (NP) involvement and autoantibody profiles. METHODS Graph theoretical analysis was applied to diffusion tensor magnetic resonance imaging (MRI) and resting-state functional MRI data from 32 patients with SLE and 32 age- and sex-matched healthy controls. Structural and functional connectivity matrices between 116 cortical/subcortical brain regions were estimated using a bivariate correlation analysis, and global and nodal network metrics were calculated. RESULTS Structural, but not functional, global network properties (strength, transitivity, global efficiency and path length) were abnormal in patients with SLE versus controls (P < 0.0001), especially in patients with anti-double-stranded DNA (ADNA) autoantibodies (P = 0.03). No difference was found according to NP involvement or anti-phospholipid autoantibody status. Patients with SLE and controls shared identical structural hubs and the majority of functional hubs. In patients with SLE, all structural hubs showed reduced strength and clustering coefficient compared with controls (P from 0.001 to <0.0001), especially in patients with ADNA autoantibodies. Only a few differences in functional hub properties were found between patients with SLE and controls. Structural and functional hub measures did not differ according to NP involvement or anti-phospholipid autoantibody status. Significant correlations were found between clinical, MRI and network measures (r from -0.56 to 0.60, P from 0.0003 to 0.05). CONCLUSIONS Abnormalities of global and nodal structural connectivity occur in patients with SLE, especially with ADNA autoantibodies, with a diffuse disruption of structural integrity. Functional network integrity may contribute to preserve clinical functions.

What role should spinal cord MRI take in the future of multiple sclerosis surveillance

Abstract: In multiple sclerosis (MS), inflammatory, demyelinating, and neurodegenerative phenomena affect the spinal cord, with detrimental effects on patients’ clinical disability. Although spinal cord imag...

Functional brain connectivity abnormalities and cognitive deficits in neuromyelitis optica spectrum disorder.

Abstract: Background:Functional magnetic resonance imaging (fMRI) correlates of cognitive deficits have not been thoroughly studied in patients with neuromyelitis optica spectrum disorders (NMOSDs).Objective...

Cognitive impairment in benign multiple sclerosis: a multiparametric structural and functional MRI study.

Abstract: The substrates of cognitive impairment in benign MS (BMS) still need to be identified. We investigated whether cognitive impairment in BMS patients is associated with specific patterns of brain structural and functional abnormalities. Thirty-seven BMS patients (EDSS score ≤ 3.0 and disease duration ≥ 15 years) and 50 healthy controls (HC) were studied. In BMS patients, a cognitive impairment index (CII) was derived. Gray matter (GM) volumes, white matter (WM) fractional anisotropy (FA) and resting-state (RS) functional connectivity (FC) were investigated for whole-brain relevant regions (cortex, lobes, subcortical nuclei, fiber tracts) and functional networks. Univariate and multivariate analyses identified independent predictors of cognitive impairment. In BMS, median CII was 9 (IQR: 4–16). Compared to HC, BMS patients showed reduced WM FA, GM atrophy and increased RS FC in fronto-temporo-parietal regions. At multivariate analysis, percentage of T2-lesions of the corpus callosum, reduced posterior corona radiata (PCR) FA and caudate nucleus atrophy were independent predictors of worse CII. A multivariate model identified reduced PCR FA (R2 = 0.39; p = 0.001) as the only predictor of CII. Cognitive impairment in BMS is associated with structural damage of relevant brain areas. WM damage of parietal regions was the predominant predictor of worse cognitive performance in these patients.

Imaging correlates of hand motor performance in multiple sclerosis: A multiparametric structural and functional MRI study.

Abstract: Background:Hand motor impairment has considerable effects on daily-life activities of patients with multiple sclerosis (pwMS). Understanding its anatomo-functional substrates is relevant to provide...

Dysregulation of multisensory processing stands out from an early stage of migraine: a study in pediatric patients.

Abstract: Resting state (RS) functional connectivity (FC) abnormalities of brain networks involved in pain- and multisensory processing have been disclosed in adult-migraine patients. We explored RS FC of large-scale brain networks in pediatric-migraine patients and their correlation with patients' clinical characteristics. RS functional MRI data was acquired from 13 pediatric-migraine patients and 14 age- and sex-matched controls. Intra- and inter-network RS FC differences between patients and controls were evaluated. Correlations between RS FC abnormalities and patients' clinical characteristics were also assessed. Compared to controls, pediatric-migraine patients had a decreased RS FC of the left parieto-occipital junction of the default mode network (DMN) and left-dorsolateral prefrontal cortex of the executive control network (ECN). They also experienced an increased RS FC of the right frontopolar cortex of the right frontoparietal network (FPN) and the right-middle occipital gyrus of the secondary visual network. A significant stronger connectivity between the ECN and primary visual network and between the right FPN and primary sensorimotor, primary visual and auditory networks were found in migraine patients compared to controls. A significant weaker connectivity between the DMN and right FPN was revealed in migraineurs compared to controls. No correlation was found between intra- and inter-network RS FC abnormalities and patients' clinical characteristics. Pediatric-migraine patients harbor significant RS FC abnormalities in brain networks involved in multisensory processing and in the cognitive control of pain. An early dysregulation of multisensory processing, including pain, might represent a phenotypic biomarker of the disease.

Are Machine Learning Approaches the Future to Study Patients With Migraine

Abstract: One of the most exciting developments in modern neuroscience has been the expansion of imaging techniques that can provide insights into human brain structures and networks that could be involved in the pathophysiology of diseases. A series of MRI techniques have been extensively applied to the study of patients with migraine. It is now widely accepted that migraine should be viewed as a complex brain network disorder with a strong genetic basis that involves the interplay of multiple neuronal systems to account for the pain and the wide constellation of symptoms characterizing the migraine attack.1 Widespread structural and functional abnormalities in cortical and subcortical areas involved in multisensory processing, including pain, occur in patients with migraine, both in the course of an acute attack and during the interictal phase.2,3 Whether such alterations represent a potential migraine biomarker that can help to discriminate patients with migraine from controls and from patients with other chronic pain conditions is still a matter of debate.

Influence of CNS T2-focal lesions on cervical cord atrophy and disability in multiple sclerosis

Abstract: Background:Mechanisms associated with cervical spinal cord (CSC) and upper thoracic spinal cord (TSC) atrophy in multiple sclerosis (MS) are poorly understood.Objective:To assess the influence of b...

COVID-19 will change MS care forever - No.

Abstract: During these weeks, these concerns have pushed to promptly adopt specific strategies for the management of PwMSs, in addition to the recommendations provided by the World Health Organization. Neurologic visits have been significantly reduced and replaced by telemedicine services; treatment start, switch, escalation, or re-treatment with some oral (fingolimod and cladribine) and infusional therapies (ocrelizumab and alemtuzumab) have been postponed or replaced by other treatment options, in some cases less effective in controlling disease activity; and patients with leukopenia or lymphopenia have been often asked to temporarily discontinue or modify DMT posology (e.g. fingolimod or dimethyl fumarate).

Moving beyond anti-aquaporin-4 antibodies: emerging biomarkers in the spectrum of neuromyelitis optica

Abstract: With the advent of targeted drugs, a correct identification of patients with neuromyelitis optica spectrum disorders (NMOSD) is fundamental. Moreover, to assess treatment efficacy, sensitive biomar...

Two-year regional grey and white matter volume changes with natalizumab and fingolimod.

Abstract: Objective To compare the efficacy of fingolimod and natalizumab in preventing regional grey matter (GM) and white matter (WM) atrophy in relapsing-remitting multiple sclerosis (RRMS) over 2 years. Methods Patients with RRMS starting fingolimod (n=25) or natalizumab (n=30) underwent clinical examination and 3T MRI scans at baseline (month (M) 0), M6, M12 and M24. Seventeen healthy controls were also scanned at M0 and M24. Tensor-based morphometry and SPM12 were used to assess the longitudinal regional GM/WM volume changes. Results At M0, no clinical or GM/WM volume differences were found between treatment groups. At M24, both drugs reduced relapse rate (p Conclusions Natalizumab and fingolimod are associated with heterogeneous temporal and regional patterns of GM and WM atrophy progression. Compared with natalizumab, fingolimod-treated patients experience accelerated GM and WM atrophy in the cerebellum, while both drugs show minimal regional volumetric differences in supratentorial regions.

Spinal Cord Atrophy in Neuromyelitis Optica Spectrum Disorders Is Spatially Related to Cord Lesions and Disability

Abstract: Background The spinal cord is commonly involved in patients with neuromyelitis optica spectrum disorders (NMOSDs). However, the relationship between inflammation and atrophy remains unclear. Purpose To characterize the spatial distribution of T1-hypointense lesions in the spinal cord at MRI, its association with cord atrophy, and its correlation with disability in participants with NMOSDs. Materials and Methods This prospective study evaluated three-dimensional T1-weighted spinal cord MRI scans in seropositive participants with NMOSDs and in age-matched healthy control participants acquired between February 2010 and July 2018. Binary masks of T1-hypointense lesions and lesion probability maps were produced. Cross-sectional area of the cervical and upper thoracic cord (down to T3 level) was calculated with the active-surface method. Full factorial models were used to assess cord atrophy in participants with NMOSDs. Correlations between cord atrophy and clinical and brain MRI measures were investigated with multiple regression models. Results A total of 52 participants with NMOSDs (mean age ± standard deviation, 44 years ± 15; 45 women) and 28 age-matched healthy control participants (mean age, 44 years ± 13; 16 women) were evaluated. Thirty-eight of 52 (73%) participants with NMOSDs had T1-hypointense cord lesions. No cord lesions were detected in the healthy control participants. Lesion probability maps showed a predominant involvement of the upper cervical (C2-C4) and upper thoracic (T1-T3 level) cord. The greater involvement of C1-C4 survived Bonferroni correction (P value range, .007-.04), with a higher percentage lesion extent in the gray matter (P < .001). Atrophy colocalized with focal cord lesions and correlated with pyramidal subscore (r ranging from -0.53 to -0.40; P < .001) and sensitive subscore (r ranging from -0.48 to -0.46; P = .001) of the Expanded Disability Status Scale. Participants without cord lesions had no cord atrophy. Conclusion In participants with neuromyelitis optica spectrum disorders, focal areas of spinal cord atrophy at MRI were topographically associated with lesions and correlated to motor and sensory disability. Participants without visible cord lesions had no atrophy. © RSNA, 2020 Online supplemental material is available for this article.

Quantitative MRI adds to neuropsychiatric lupus diagnostics.

Abstract: OBJECTIVE Attributing neuropsychiatric manifestations to SLE is often challenging. Brain white matter lesions are frequent in SLE at MRI, but their diagnostic role is unclear. Here, we assessed whether white matter lesions count, volume and distribution measurement can help in the diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS Brain dual-echo and 3D T1-weighted sequences were acquired from 32 patients with SLE and 32 healthy controls with a 3 T-scanner and employed to derive T2-hyperintense lesion volume (T2LV), number (T2LN) and probability maps (LPM) using a semi-automatic local thresholding segmentation technique. NPSLE was classified as per the ACR nomenclature, the Italian Society for Rheumatology algorithm and by clinical impression. Clinical descriptors including the SLE International Collaborating Clinics/ACR damage index (SDI) were also recorded. RESULTS Higher T2LV were observed in SLE vs healthy controls (P < 0.001) and in NPSLE vs other SLE (P =0.006). Patients with NPSLE also had higher T2LN (P =0.003) compared with other SLE. In SLE, T2LPM revealed a high prevalence of lesions in the splenium of the corpus callosum, right superior longitudinal fasciculus and right corona radiata. T2LV and T2LN correlated with SLE duration (rho = 0.606; P <0.001 and rho = 0.483; P =0.005, respectively) and age (rho = 0.478; P =0.006 and rho = 0.362; P = 0.042, respectively). T2LV also correlated with SDI (rho = 0.352; P =0.048). SLE patients with fatigue had lower T2LN (P =0.038) compared with patients without fatigue. Thresholds of T2LV ≥ 0.423 cm3 or of T2LN ≥ 12 were associated with definite NPSLE and improved the classification of patients with possible NPSLE per clinical impression. CONCLUSION Brain white matter lesions (WML) quantitation adds to NPSLE diagnostics.

Neural precursor cells contribute to decision-making by tuning striatal connectivity via secretion of IGFBPL-1

Abstract: The adult brain retains endogenous neural stem/precursors cells (eNPCs) in two major neurogenic niches, the subgranular zone (SGZ) in the hippocampus and the subventricular zone (SVZ). While in humans and rodents the SGZ contributes to memory functions by generating new neurons that integrate into hippocampal circuitry, the role of eNPCs of the SVZ is less clear. SVZ-eNPCs contribute to the generation of new neurons fated to the olfactory bulb (OB) in rodents but not in humans where they are thought to contribute to striatal neurogenesis as a result of tissue damage. Here, we show in mice and humans a novel non-neurogenic physiological role of adult SVZ-eNPCs in supporting cognitive functions by regulating striatal neuronal activity. We first provide evidence that GABAergic transmission between parvalbumin-expressing fast-spiking interneurons (FSIs) and medium spiny neurons (MSNs) is tuned by SVZ-eNPCs via secretion of Insulin-Like Growth Factor Binding Protein Like 1 (IGFBPL-1) that, in turn, regulates the Insulin-Like Growth Factor (IGF-1) signalling cascade. Consistently, selective ablation of SVZ-eNPCs and in vivo disruption of the IGF-signalling determine the impairment of intrastriatal coherence. A finding associated with a higher failure rate of GABAergic transmission mediated by FSIs and with striatum-related behavioural dysfunctions impairing decision making. Human validation studies revealed IGFBPL-1 expression in the SVZ and in foetal and induced-pluripotent stem cell-derived NPCs as well as a strong correlation in neurological patients between SVZ pathological damage, reduction of striatum volume and impairment of information processing speed. All in all, our results highlight a novel non-neurogenic homeostatic role exerted by SVZ-eNPCs on striatal GABAergic neurons that might contribute to cognitive processes involving decisions-making tasks.

Neuromyelitis Optica Spectrum Disorders

Abstract: Neuromyelitis optica spectrum disorders (NMOSD) are a heterogeneous group of inflammatory, demyelinating and antibody-mediated diseases of the central nervous system (CNS). The anti-aquaporin-4-IgG (AQP4-IgG) seems to be the pathogenetic agent, being present in the large majority of patients, although seronegative forms can occur. Clinical manifestations include core features, such as myelitis, optic neuritis, and area postrema syndrome, possibly associated with collateral symptoms like pain, dystonic movements, and pruritus. Diagnosis is based on both clinical presentation and anti-AQP4-IgG testing. MRI features provide supportive elements in seronegative patients. The most effective therapy in acute attacks is plasma exchange, whereas multiple drugs are used for chronic maintenance (azathioprine, mycophenolate mofetil, rituximab and eculizumab).