Radiologically isolated syndrome (RIS) describes asymptomatic individuals with incidental radiologic abnormalities suggestive of multiple sclerosis (MS). Much of RIS literature is about adult-onset ...cases. Treatment of RIS is controversial, especially in pediatric age, but early treatment in selected patients might improve long-term outcomes.
We report a single RIS patient who followed up for 18 years in our MS center. At first, she was only monitored with follow-up MRIs. Then, as the lesion load increased, she was treated with a first-line disease-modifying treatment (DMT) reaching MRI stability.
This report highlights how treatment can be an appropriate choice in pediatric forms of RIS.
Background:
Damage to the cerebellar sensorimotor and cognitive domains may underlie physical and cognitive disability.
Objective:
To investigate resting-state functional connectivity (FC) of ...sensorimotor and cognitive cerebellum, and clinical correlates in multiple sclerosis (MS).
Methods:
A total of 119 patients with MS and 42 healthy subjects underwent multimodal 3T-magnetic resonance imaging (MRI). Patients were evaluated using the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite Scale. After parcellation of sensorimotor (lobules I–V + VIII) and cognitive cerebellum (lobules VI, VII, IX, X), we calculated cerebellar resting-state FC using a seed-based approach.
Results:
In patients with MS, the sensorimotor cerebellum showed increased FC mainly with cerebellar, thalamic, and cortical (frontal, parietal, temporal) areas and decreased FC with insular areas; the cognitive cerebellum showed increased FC mainly with thalamic and cortical (temporal-occipital) areas, and decreased FC with frontal-insular areas. Both sensorimotor and cognitive cerebellar FC negatively correlated with disability, and positively with cognitive scores. Cerebellar structural damage only partially influenced results.
Conclusion:
The two neocerebellar circuits showed altered FC with subcortical and cortical areas. The association between increased sensorimotor and cognitive cerebellar FC and low levels of physical and cognitive disability suggests that altered FC might modulate the effects of cerebellar structural damage on clinical condition.
Brain and spinal cord imaging plays a pivotal role in aiding clinicians with the diagnosis and monitoring of multiple sclerosis. Nevertheless, the significance of magnetic resonance imaging in MS ...extends beyond its clinical utility. Advanced imaging modalities have facilitated the in vivo detection of various components of MS pathogenesis, and, in recent years, MRI biomarkers have been utilized to assess the response of patients with relapsing–remitting MS to the available treatments. Similarly, MRI indicators of neurodegeneration demonstrate potential as primary and secondary endpoints in clinical trials targeting progressive phenotypes. This review aims to provide an overview of the latest advancements in brain and spinal cord neuroimaging in MS.
Multiple sclerosis (MS) is a chronic, progressive neurological disease involving neuroinflammation, neurodegeneration, and demyelination. Cladribine tablets are approved for immune reconstitution ...therapy in patients with highly active relapsing–remitting MS based on favorable efficacy and tolerability results from the CLARITY study that have been confirmed in long-term extension studies. The approved 4-year dosing regimen foresees a cumulative dose of 3.5 mg/kg administered in two cycles administered 1 year apart, followed by 2 years of observation. Evidence on managing patients beyond year 4 is scarce; therefore, a group of 10 neurologists has assessed the available evidence and formulated an expert opinion on management of the growing population of patients now completing the approved 4-year regimen. We propose five patient categories based on response to treatment during the first 4-year regimen, and corresponding management pathways that envision close monitoring with clinical visits, magnetic resonance imaging (MRI) and/or biomarkers. At the first sign of clinical or radiological disease activity, patients should receive a highly effective disease-modifying therapy, comprising either a full cladribine regimen as described in regulatory documents (cumulative dose 7.0 mg/kg) or a comparably effective treatment. Re-treatment decisions should be based on the intensity and timing of onset of disease activity, clinical and radiological assessments, as well as patient eligibility for treatment and treatment preference.
As atrophy represents the most relevant driver of progression in multiple sclerosis (MS), we investigated the impact of different patterns of brain and spinal cord atrophy on disability worsening in ...MS. We acquired clinical and MRI data from 90 patients with relapsing–remitting MS and 24 healthy controls (HC). Clinical progression at follow-up (mean 3.7 years) was defined according to the Expanded Disability Status Scale-Plus. Brain and spinal cord volumes were computed on MRI brain scans. After normalizing each participants’ brain and spine volume to the mean of the HC, z-score cut-offs were applied to separate pathologically atrophic from normal brain and spine volumes (accepting a 2.5% error probability). Accordingly, MS patients were classified into four groups (Group I: no brain or spinal cord atrophy
N
= 40, Group II: brain atrophy/no spinal cord atrophy
N
= 11, Group III: no brain atrophy/ spinal cord atrophy
N
= 32, Group IV: both brain and spinal cord atrophy
N
= 7). All patients’ groups showed significantly lower brain volume than HC (
p
< 0.0001). Group III and IV showed lower spine volume than HC (
p
< 0.0001 for both). Higher brain lesion load was identified in Group II (
p
= 0.049) and Group IV (
p
= 0.023) vs Group I, and in Group IV (
p
= 0.048) vs Group III. Spinal cord atrophy (OR = 3.75,
p
= 0.018) and brain + spinal cord atrophy (OR = 5.71,
p
= 0.046) were significant predictors of disability progression. The presence of concomitant brain and spinal cord atrophy is the strongest correlate of progression over time. Isolated spinal cord atrophy exerts a similar effect, confirming the leading role of spinal cord atrophy in the determination of motor disability.
Background
Dimethyl fumarate (DMF) is an oral drug approved for Relapsing Multiple Sclerosis (RMS) patients. Grade III lymphopenia is reported in 5–10% DMF-treated patients. Data on lymphocyte count ...(ALC) recovery after DMF withdrawal following prolonged lymphopenia are still scarce.
Objectives
To characterize ALC recovery and to identify predictors of slower recovery after DMF interruption.
Methods
Multicenter data from RMS patients who started DMF and developed lymphopenia during treatment were collected. In patients with grade II–III lymphopenia, ALCs were evaluated from DMF withdrawal until reaching lymphocyte counts > 800/mm
3
.
Results
Among 1034 patients who started DMF, we found 198 (19.1%) patients with lymphopenia and 65 patients (6.3%) who discontinued DMF due to persistent grade II–III lymphopenia. Complete data were available for 51 patients. All patients recovered to ALC > 800 cells/mm
3
with a median time of 3.4 months. Lower ALCs at DMF suspension (HR 0.98;
p
= 0.005), longer disease duration (HR 1.29;
p
= 0.014) and prior exposure to MS treatments (HR 0.03;
p
= 0.025) were found predictive of delayed ALC recovery.
Conclusion
ALC recovery after DMF withdrawal is usually rapid, nevertheless it may require longer time in patients with lower ALC count at DMF interruption, longer disease duration and previous exposure to MS treatments, potentially leading to delayed initiation of a new therapy.
Physical fatigue is one of the most disabling symptoms in people with Multiple Sclerosis (PwMS). Several factors might influence the development of fatigue, such as gender, education, body mass index ...(BMI), Expanded Disability Status Scale (EDSS), disease duration, working status (Ws), physiotherapy (Ph), and disease-modifying therapies (DMTs). Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) is a patient-reported outcome (PRO) that allows one to define the impact of fatigue in PwMS clearly. This study aimed to assess fatigue impact on PwMS by using FSIQ-RMS.
The participants were enrolled from May to July 2021 in MS Centers of Sant'Andrea Hospital and Policlinico Umberto I Hospital in Rome. Fatigue was evaluated using the FSIQ-RMS, validated, and culturally adapted in Italian. Clinical and demographic data were collected at the same time.
We enrolled 178 PwMS Female 74.16%; RMS 82.58%, SPMS 17.52%. FSIQ-RMS scores were significantly correlated with EDSS (p-value < 0.01). Analysis of variance between means showed a statistically significant difference between the BMI groups at the 24hours_FSIQ-RMS score and the 7days_FSIQ-RMS score (p < 0.01), with the lower BMI group having the highest scores. Furthermore, perceived fatigue significantly improved both in subjects performing Ph (p < 0.05) and in those who actively work (p < 0.01).
The use of FSIQ-RMS in a real-world setting confirmed that underweight and high levels of disability are closely related to fatigue. In addition, Ph and active Ws are strongly correlated with fatigue in PwMS.
Author Affiliation: (1) Neurology Unit, MS Center, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy (2) Neurorehabilitation Unit, IRCCS San Raffaele Scientific ...Institute, Milan, Italy (3) Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy (4) Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy (5) Vita-Salute San Raffaele University, Milan, Italy (6) Multiple Sclerosis Center, Spedali Civili of Brescia, Montichiari, Brescia, Italy (7) Department of Systems Medicine, Tor Vergata University, Rome, Italy (8) Unit of Neurology, IRCCS Neuromed, Pozzilli, IS, Italy (9) Department of Neurosciences, San Camillo Forlanini Hospital, Rome, Italy (10) Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, University of Catania, Catania, Italy (11) Multiple Sclerosis Center, PO G Rodolico, University of Catania, Catania, Italy (12) Multiple Sclerosis Centre of the Veneto Region, Neurology Clinic, Department of Neurosciences (DNS), University of Padua, Padua, Italy (13) Multiple Sclerosis Center, 'S. Andrea' Hospital, Rome, Italy (14) Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy (15) Neurology and Neurophysiopathology Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro", Bari, Italy (a) filippi.massimo@hsr.it Article History: Registration Date: 02/11/2021 Received Date: 01/08/2021 Accepted Date: 02/11/2021 Online Date: 02/20/2021 Byline:
Purpose
In multiple sclerosis (MS), how brain functional changes relate to clinical conditions is still a matter of debate. The aim of this study was to investigate how functional connectivity (FC) ...reorganization at three different scales, ranging from local to whole brain, is related to tissue damage and disability.
Methods
One-hundred-nineteen patients with MS were clinically evaluated with the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite. Patients and 42 healthy controls underwent a multimodal 3 T MRI, including resting-state functional MRI.
Results
We identified 16 resting-state networks via independent component analysis and measured within-network, between-network, and whole-brain (global efficiency and degree centrality) FC. Within-network FC was higher in patients than in controls in default mode, frontoparietal, and executive-control networks, and corresponded to low clinical impairment (default mode network versus Expanded Disability Status Scale
r
= − 0.31,
p
< 0.01; right frontoparietal network versus Paced Auditory Serial Addition Test
r
= 0.33,
p
< 0.01). All measures of between-network and whole-brain FC, except default mode network global efficiency, were lower in patients than in controls, and corresponded to high disability (i.e., basal ganglia global efficiency versus Timed 25-Foot Walk
r
= − 0.25,
p
< 0.03; default mode global efficiency versus Expanded Disability Status Scale
r
= − 0.44,
p
< 0.001). Altered measures of within-network, between-network, and whole-brain FC were combined in functional indices that were linearly related to disease duration, Paced Auditory Serial Addition Test and lesion load and non-linearly related to Expanded Disability Status Scale.
Conclusion
We suggest that the combined evaluation of functional alterations occurring at different levels, from local to whole brain, could exhaustively describe neuroplastic changes in MS, while increased within-network FC likely represents adaptive compensatory processes, decreased between-network and whole-brain FC likely represent loss of functional network integration consequent to structural disruption.
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