Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease affecting the central nervous system (CNS), often characterized by the accumulation of irreversible ...clinical disability over time. During last years, there has been a dramatic evolution in several key concepts of immune pathophysiology of MS and in the treatment of this disease. The demonstration of the strong efficacy and good safety profile of selective B-cell-depleting therapies (such as anti-CD20 monoclonal antibodies) has significantly expanded the therapeutic scenario for both relapsing and progressive MS patients with the identification of a new therapeutic target. The key role of B cells in triggering MS disease has been also pointed out, determining a shift from the traditional view of MS activity as largely being ‘T-cell mediated’ to the notion that MS-related pathological processes involve bi-directional interactions between several immune cell types, including B cells, both in the periphery and in the CNS. This review provides an updated overview of the involvement of B cells in the immune pathophysiology and pathology of MS. We summarize the rationale regarding the use of anti-CD20 therapies and the results of the main randomized controlled trials and observational studies investigating the efficacy and safety profile of rituximab, ocrelizumab, ofatumumab and ublituximab. Suggestions regarding vaccinations and management of MS patients during COVID-19 pandemic with anti-CD20 therapies are also discussed. Finally, therapies under investigation and future perspectives of anti-CD20 therapies are taken into consideration.
The current review summarizes the current knowledge on longitudinal cortical and subcortical grey and white matter MRI findings assessed using T1-weighted and one-tensor diffusion-weighted MRI in ...Parkinson’s disease (PD) patients. Results were reviewed according to disease duration, disease severity and cognitive impairment. The most consistent findings are those showing a progressive cortical atrophy accumulation in caudate, putamen, temporal/hippocampal, frontal and parietal areas in de novo PD cases and in the early/middle phase of the disease, with the achievement of a plateau in the later stage. Analyzing results according to the patient cognitive status, only a few studies used longitudinal MRI metrics to predict mild cognitive impairment or dementia conversion in PD patients, suggesting that atrophy of the hippocampus, fronto-temporal areas, caudate, thalamus and accumbens might play a role in this process. Stratifying patients according to disease severity, findings appear partially controversial, although showing a progressive atrophy of basal ganglia over 1 year of follow up and a widespread cortical thinning over 3–6 years in mild to moderate PD patients. Finally, microstructural damage of the main motor and associative WM tracts seems to be present, and rapidly progress, even in the early phase of PD. The utility of structural MRI metrics as biomarkers of PD progression and their role in improving the accuracy of disease progression prediction is still debated.
We built and validated a deep learning algorithm predicting the individual diagnosis of Alzheimer's disease (AD) and mild cognitive impairment who will convert to AD (c-MCI) based on a single ...cross-sectional brain structural MRI scan. Convolutional neural networks (CNNs) were applied on 3D T1-weighted images from ADNI and subjects recruited at our Institute (407 healthy controls HC, 418 AD, 280 c-MCI, 533 stable MCI s-MCI). CNN performance was tested in distinguishing AD, c-MCI and s-MCI. High levels of accuracy were achieved in all the classifications, with the highest rates achieved in the AD vs HC classification tests using both the ADNI dataset only (99%) and the combined ADNI + non-ADNI dataset (98%). CNNs discriminated c-MCI from s-MCI patients with an accuracy up to 75% and no difference between ADNI and non-ADNI images. CNNs provide a powerful tool for the automatic individual patient diagnosis along the AD continuum. Our method performed well without any prior feature engineering and regardless the variability of imaging protocols and scanners, demonstrating that it is exploitable by not-trained operators and likely to be generalizable to unseen patient data. CNNs may accelerate the adoption of structural MRI in routine practice to help assessment and management of patients.
•CNNs predict AD and MCI with high accuracy based on a single T1-weighted image•CNNs discriminate c-MCI from s-MCI patients with an accuracy up to 75%•CNNs are exploitable by not-trained operators•CNNs are likely to be generalizable to unseen patient data
Summary In patients presenting with a clinically isolated syndrome, MRI can support and substitute clinical information in the diagnosis of multiple sclerosis by showing disease dissemination in ...space and time and by helping to exclude disorders that can mimic multiple sclerosis. MRI criteria were first included in the diagnostic work-up for multiple sclerosis in 2001, and since then several modifications to the criteria have been proposed in an attempt to simplify lesion-count models for showing disease dissemination in space, change the timing of MRI scanning to show dissemination in time, and increase the value of spinal cord imaging. Since the last update of these criteria, new data on the use of MRI to establish dissemination in space and time have become available, and MRI technology has improved. State-of-the-art MRI findings in these patients were discussed in a MAGNIMS workshop, the goal of which was to provide an evidence-based and expert-opinion consensus on proposed modifications to MRI criteria for the diagnosis of multiple sclerosis.
Summary In patients with multiple sclerosis (MS), grey matter damage is widespread and might underlie many of the clinical symptoms, especially cognitive impairment. This relation between grey matter ...damage and cognitive impairment has been lent support by findings from clinical and MRI studies. However, many aspects of cognitive impairment in patients with MS still need to be characterised. Standardised neuropsychological tests that are easy to administer and sensitive to disease-related abnormalities are needed to gain a better understanding of the factors affecting cognitive performance in patients with MS than exists at present. Imaging measures of the grey matter are necessary, but not sufficient to fully characterise cognitive decline in MS. Imaging measures of both lesioned and normal-appearing white matter lend support to the hypothesis of the existence of an underlying disconnection syndrome that causes clinical symptoms to trigger. Findings on cortical reorganisation support the contribution of brain plasticity and cognitive reserve in limiting cognitive deficits. The development of clinical and imaging biomarkers that can monitor disease development and treatment response is crucial to allow early identification of patients with MS who are at risk of cognitive impairment.
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.
Abstract Schizophrenia has long been hypothesized to result from a disconnection syndrome due to a disruption of the association fibers of the brain. However, only with the advent of in vivo ...neuroimaging, a formal disconnectivity hypothesis for schizophrenia has been developed. Diffusion tensor MRI, a non-invasive technique which is sensitive to features of tissue microstructure and to the anatomy of the white matter fibers, has gained a crucial role in the field. Here, we provide a state-of-the-art review of structural connectivity abnormalities detected in schizophrenia and discuss the most relevant findings at preclinical, first episode drug-naïve, and chronic stages. Imaging studies showed white matter alterations from the preclinical to the chronic stage of the disease, which involve the corticospinal tracts, interhemispheric connections, long association white matter tracts, cerebello-thalamo-cortical circuit, and limbic system. Such abnormalities were found to be associated with the psychiatric and cognitive manifestations of the disease and to predict, at least partially, the patient clinical evolution and response to treatment.
Description of migraine pain is sometimes difficult for a patient. The simple words reported in the Classification of International Headache Society are not sufficient to explain both the patient’s ...sense of discomfort and the emotional point of view. We analyzed works by international writers and novelists in the last centuries to explore the connotation of migraine in literature. We evaluated the literary insight of migraine, the description of migraine experience and the therapies proposed in novels, essays and short stories. In literature, migraine has still the negative connotation of an untreatable disease. It is described as a barrier for social, familial, and work activities. In more recent works, new therapies are not mentioned, confirming that scientific improvements both in acute phase and in prophylaxis are not part of the literary cultural mainstream.
Longitudinal connectivity studies might guide our understanding of the underlying neurodegenerative processes. We report the results of a longitudinal study in patients at different stages of ...Parkinson's disease (PD), who performed motor and non-motor evaluations and serial resting state (RS) functional MRI (fMRI). Cluster analysis was applied to demographic and clinical data of 146 PD patients to define disease subtypes. Brain network functional alterations were assessed at baseline in PD relative to 60 healthy controls and every year for a maximum of 4 years in PD groups. Progression of brain network changes were compared between patient clusters using RS fMRI. The contribution of network changes in predicting clinical deterioration was explored. Two main PD clusters were identified: mild PD (86 patients) and moderate-to-severe PD (60 patients), with the latter group being older and having earlier onset, longer PD duration, more severe motor, non-motor and cognitive deficits. Within the mild patient cluster, two clinical subtypes were further identified: mild motor-predominant (43) and mild-diffuse (43), with the latter being older and having more frequent non-motor symptoms. Longitudinal functional connectivity changes vary across patients in different disease stages with the coexistence of hypo- and hyper-connectivity in all subtypes. RS fMRI changes were associated with motor, cognitive and non-motor evolution in PD patients. Baseline RS fMRI presaged clinical and cognitive evolution. Our network perspective was able to define trajectories of functional architecture changes according to PD stages and prognosis. RS fMRI may be an early biomarker of PD motor and non-motor progression.
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