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Multiple Sclerosis: Diagnosis, Treatment and Clinical Management
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Multiple Sclerosis: Diagnosis, Treatment and Clinical Management

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: closed (31 March 2025) | Viewed by 7886

Special Issue Editor

Prof. Dr. Carlo Avolio

E-Mail Website
Guest Editor
Department of Medical and Surgical Sciences, Multiple Sclerosis Center, University of Foggia, Foggia, Italy
Interests: neuroimmunology; clinical neurology

Special Issue Information

Dear Colleagues,

It is a great pleasure and honor to invite you to contribute a paper to this Special Issue of the Journal of Clinical Medicine on Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease of the central nervous system characterized by chronic inflammatory demyelination and axonal transection. MS typically presents during young adulthood and can lead to physical disability and cognitive impairment resulting in a general reduction in patients’ quality of life. The McDonald Criteria (2017) enable the early diagnosis of MS if compared to the past,  based on a combination of signs and symptoms, MRI and laboratory findings. This provides an opportunity to commence treatment that evidences high efficacy from the very beginning. The advanced and correct clinical management of the disease could improve the outcomes and quality of life of MS patients.

The aim of this JCM Special Issue, entitled “Multiple Sclerosis: Diagnosis, Treatment and Clinical Management”, is to provide an overview of the latest advancements in the diagnosis and treatment of this disease.

Prof. Dr. Carlo Avolio
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • multiple sclerosis
  • MRI
  • cerebrospinal fluid
  • diagnosis
  • biomarkers
  • treatment
  • disease modifying treatment (DMT)
  • disease management

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Published Papers (6 papers)

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Research

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13 pages, 1199 KiB  
Article
The Role of the Cerebellum in Multiple Sclerosis-Related Fatigue and Disability
by Nicola Manocchio, Ornella Argento, Michela Bossa, Barbara Spanò, Leonardo Pellicciari, Calogero Foti and Ugo Nocentini
J. Clin. Med. 2025, 14(8), 2840; https://doi.org/10.3390/jcm14082840 - 20 Apr 2025
Viewed by 134
Abstract
Background: Fatigue is a prevalent and debilitating symptom in people with multiple sclerosis (pwMS), significantly impairing quality of life. While the cerebellum is traditionally associated with motor control, emerging evidence suggests its involvement in cognitive, emotional, and integrative functions. This study aimed [...] Read more.
Background: Fatigue is a prevalent and debilitating symptom in people with multiple sclerosis (pwMS), significantly impairing quality of life. While the cerebellum is traditionally associated with motor control, emerging evidence suggests its involvement in cognitive, emotional, and integrative functions. This study aimed to explore the relationship between fatigue components (physical, cognitive, and psychosocial), clinical disability, and cerebellar structural changes in pwMS acquired via magnetic resonance imaging (MRI). Methods: Participants of this cross-sectional study underwent clinical assessments for fatigue (Modified Fatigue Impact Scale) and disability (Expanded Disability Status Scale). Cerebellar volumes were measured using high-resolution MRI and voxel-based morphometry (VBM) to identify correlations between fatigue subdomains and specific cerebellar subregions. Statistical analyses included group comparisons and correlation tests. Results: Forty-four pwMS were included. Fatigued MS patients exhibited reduced sensorimotor cerebellar volumes compared to non-fatigued counterparts. Physical fatigue correlated negatively with sensorimotor cerebellum volume, while cognitive fatigue showed an inverse relationship with limbic cerebellum regions. Interestingly, psychosocial fatigue was positively associated with limbic cerebellum volume, contrary to initial hypotheses. Higher disability scores were linked to atrophy in cognitive and limbic cerebellar regions. Conclusions: The findings highlight the cerebellum’s multifaceted role in MS-related fatigue, with distinct subregions contributing to physical, cognitive, and psychosocial fatigue components. These results underscore the cerebellum’s critical function as a hub for motor, cognitive, and emotional integration. Future longitudinal studies incorporating objective measures and advanced imaging are essential to elucidate these relationships further and inform targeted therapeutic strategies for pwMS. Full article
(This article belongs to the Special Issue Multiple Sclerosis: Diagnosis, Treatment and Clinical Management)
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12 pages, 1195 KiB  
Article
Picturing the Multiple Sclerosis Patient Journey: A Symptomatic Overview
by Inês Correia, Catarina Bernardes, Carolina Cunha, Carla Nunes, Carmo Macário, Lívia Sousa and Sónia Batista
J. Clin. Med. 2024, 13(19), 5687; https://doi.org/10.3390/jcm13195687 - 25 Sep 2024
Viewed by 1901
Abstract
Background: Multiple sclerosis (MS) presents a wide range of clinical symptoms, historically understood through long-term studies of earlier patient cohorts. However, due to improved diagnostic criteria, modern patients are diagnosed earlier and benefit from effective treatments, altering the disease’s natural history. This [...] Read more.
Background: Multiple sclerosis (MS) presents a wide range of clinical symptoms, historically understood through long-term studies of earlier patient cohorts. However, due to improved diagnostic criteria, modern patients are diagnosed earlier and benefit from effective treatments, altering the disease’s natural history. This study aimed to assess the clinical symptoms of MS patients in a modern population at various stages: before diagnosis, at diagnosis, during the disease course, and at the time of the survey. Methods: This was an observational study with retrospective and cross-sectional components; patients that fulfilled the 2017 revised McDonald criteria for MS completed a survey evaluating demographic and clinical data. Results: We included 163 patients, 69.9% female, with a mean age of 48.21 years; 87.1% had relapsing–remitting MS (RRMS), with a median EDSS of 2.0. Before diagnosis, 74.2% of patients experienced symptoms, mainly sensory issues (39.3%), fatigue (29.4%), and imbalance (27%). Motor and coordination symptoms were more common in progressive forms. At diagnosis, sensory (46.6%) and motor complaints (36.8%) were most prevalent. In RRMS and secondary progressive MS (SPMS), sensory and motor complaints predominated alongside imbalance, while primary progressive MS (PPMS) was characterized by motor, imbalance, and genitourinary symptoms. Throughout the disease, sensory symptoms were most common (76.1%), with fatigue (73%) and motor issues (62.6%) more prevalent in progressive forms. At the time of the survey, 50.7% of RRMS patients were asymptomatic, while progressive patients continued to experience motor symptoms, imbalance, and fatigue. Conclusions: The study reflects the modern spectrum of MS symptoms, consistent with previous research. Full article
(This article belongs to the Special Issue Multiple Sclerosis: Diagnosis, Treatment and Clinical Management)
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12 pages, 397 KiB  
Article
Can International Classification of Functioning, Disability and Health (ICF) Be Used for Prediction of Work Capacity and Employment Status in Multiple Sclerosis?
by Daiva Valadkevičienė, Dalius Jatužis, Irena Žukauskaitė and Indre Bileviciute-Ljungar
J. Clin. Med. 2024, 13(14), 4195; https://doi.org/10.3390/jcm13144195 - 18 Jul 2024
Viewed by 1231
Abstract
Background: Multiple sclerosis (MS) affects many body functions and activities, including work capacity and ability to work. An evaluation of work-related parameters is important to understand the barriers to maintaining the job. The aim of this study was to evaluate if a Comprehensive [...] Read more.
Background: Multiple sclerosis (MS) affects many body functions and activities, including work capacity and ability to work. An evaluation of work-related parameters is important to understand the barriers to maintaining the job. The aim of this study was to evaluate if a Comprehensive International Classification of Functioning, Disability and Health (ICF) core set for MS can be used to predict work capacity and employment status. Methods: The cohort included 151 participants with MS (99 female/52 male, mean age 49 years) referred for a work capacity evaluation. Results: 71 (47.0%) were employed and a major part (131, 86.7%) had a work capacity between 20 and 40% with no difference between those who were employed and those who were unemployed. The analysis revealed that age and the following categories explained 68.8% of the work capacity: b770 Gait pattern functions; b730 Muscle power functions; b134 Sleep functions; d845 Acquiring, keeping and terminating a job; and b620 Urination functions. The following categories in 79.5% predicted ability to work: b164 Higher-level cognitive functions; d510 Washing oneself; d630; Preparing meals; and d870 Economic self-sufficiency. Conclusions: Here, we show that different functions/activities predicted work capacity in comparison with employment status in MS. Therefore, ICF should be implemented when assessing work ability. Full article
(This article belongs to the Special Issue Multiple Sclerosis: Diagnosis, Treatment and Clinical Management)
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9 pages, 241 KiB  
Article
Effectiveness, Safety and Patients’ Satisfaction of Nabiximols (Sativex®) on Multiple Sclerosis Spasticity and Related Symptoms in a Swiss Multicenter Study
by Rosaria Sacco, Gianna Carla Riccitelli, Giulio Disanto, Julien Bogousslavsky, Ariane Cavelti, David Czell, Christian Philipp Kamm, Uta Kliesch, Simon Peter Ramseier, Claudio Gobbi and Chiara Zecca
J. Clin. Med. 2024, 13(10), 2907; https://doi.org/10.3390/jcm13102907 - 14 May 2024
Viewed by 1561
Abstract
Background: Cannabinoid oro-mucosal spray nabiximols is approved for patients with moderate to severe multiple sclerosis spasticity (MSS) resistant to other antispastic medications. Few real-world data are available on the effectiveness, safety and patients’ satisfaction in MS patients treated with nabiximols as monotherapy. Methods: [...] Read more.
Background: Cannabinoid oro-mucosal spray nabiximols is approved for patients with moderate to severe multiple sclerosis spasticity (MSS) resistant to other antispastic medications. Few real-world data are available on the effectiveness, safety and patients’ satisfaction in MS patients treated with nabiximols as monotherapy. Methods: To investigate the effectiveness, tolerability and satisfaction of nabiximols in a real-life multicentric Swiss cohort as monotherapy or with stable doses of other antispastic medications, and explore clinical features which may predict treatment response. The following data were collected at treatment start (baseline) and 12 weeks thereafter: Modified Ashworth scale (MAS), scores at numerical rating scales ranging from 0 (absent) to 10 (considerable) for effect on spasticity (sNRS), pain (pNRS), gait (gNRS), urinary symptoms (uNRS), tolerability (tNRS) as assessed by the treating neurologist, and overall treatment satisfaction (TsNRS) and tolerability (tNRS) as assessed by the patient. Results: Ninety-five patients (44 relapsing remitting, 37 secondary progressive and 14 primary progressive MS; median age = 53 (IQR 45–62); female 70%; median EDSS 6 (IQR 4–6), concomitant antispastic treatments in 54% of patients) were included. From baseline to week 12, median MAS score decreased from 3.0 to 2.0 (p < 0.001). Median scores of the each NRS also significantly decreased (p < 0.001 for all comparisons). At week 12, the median TsNRS and tTS scores were 8/10 (IQR: 6–9) and 9/10 (IQR: 7–10), respectively, and 93.7% of patients continued to use nabiximols at the average dose of six sprays/day. No clinical factors, including use of nabiximols as add on vs. monotherapy, were associated with responder status. Conclusions: Our first Swiss, multicentric, observational, real-life study supports and enhances previous finding of nabiximols as monotherapy and as add-on therapy, being an effective, safe and well-tolerated treatment option for resistant MS spasticity and spasticity-related symptoms (pain, bladder dysfunction and gait). Full article
(This article belongs to the Special Issue Multiple Sclerosis: Diagnosis, Treatment and Clinical Management)

Review

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25 pages, 696 KiB  
Review
The Potential of Transcranial Direct Current Stimulation (tDCS) in Improving Quality of Life in Patients with Multiple Sclerosis: A Review and Discussion of Mechanisms of Action
by James Chmiel, Donata Kurpas and Marta Stępień-Słodkowska
J. Clin. Med. 2025, 14(2), 373; https://doi.org/10.3390/jcm14020373 - 9 Jan 2025
Cited by 2 | Viewed by 1219
Abstract
Background/Objectives: Multiple sclerosis (MS) is the most prevalent incurable nontraumatic neurological disability in young individuals. It causes numerous symptoms, including tingling, fatigue, muscle spasms, cognitive deficits, and neuropsychiatric disorders. This disease significantly worsens quality of life (QoL), and this dimension of general [...] Read more.
Background/Objectives: Multiple sclerosis (MS) is the most prevalent incurable nontraumatic neurological disability in young individuals. It causes numerous symptoms, including tingling, fatigue, muscle spasms, cognitive deficits, and neuropsychiatric disorders. This disease significantly worsens quality of life (QoL), and this dimension of general functioning provides valuable information about the effectiveness of treatment and well-being. There are psychological interventions that can improve QoL, but their number is limited. Therefore, searching for new methods that are as effective and safe as possible is ongoing. Methods: This review examines the potential effectiveness of transcranial direct current stimulation (tDCS) in improving the quality of life in patients with MS. Searches were conducted in the PubMed/Medline, Research Gate, and Cochrane databases. Results: The search yielded seven studies in which QoL was a primary or secondary outcome. Stimulation protocols displayed heterogeneity, especially concerning the choice of the stimulation site. Four studies demonstrated the effectiveness of tDCS in improving QoL, all of which (two) used anodal stimulation of the left DLPFC. Stimulation of the motor cortex has produced mixed results. The potential mechanisms of action of tDCS in improving QoL in MS are explained. These include improved synaptic plasticity, increased cerebral blood flow, salience network engagement through tDCS, and reduction of beta-amyloid deposition. The limitations are also detailed, and recommendations for future research are made. Conclusions: While the evidence is limited, tDCS has shown potential to improve QoL in MS patients in some studies. Prefrontal stimulation appears promising, and further research is recommended to explore this approach. Full article
(This article belongs to the Special Issue Multiple Sclerosis: Diagnosis, Treatment and Clinical Management)
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26 pages, 1026 KiB  
Review
Efficacy of Transcranial Direct Current Stimulation (tDCS) on Neuropsychiatric Symptoms in Multiple Sclerosis (MS)—A Review and Insight into Possible Mechanisms of Action
by James Chmiel and Marta Stępień-Słodkowska
J. Clin. Med. 2024, 13(24), 7793; https://doi.org/10.3390/jcm13247793 - 20 Dec 2024
Viewed by 1089
Abstract
Introduction: Neuropsychiatric symptoms such as depression and anxiety are a significant burden on patients with multiple sclerosis (MS). Their pathophysiology is complex and yet to be fully understood. There is an urgent need for non-invasive treatments that directly target the brain and [...] Read more.
Introduction: Neuropsychiatric symptoms such as depression and anxiety are a significant burden on patients with multiple sclerosis (MS). Their pathophysiology is complex and yet to be fully understood. There is an urgent need for non-invasive treatments that directly target the brain and help patients with MS. One such possible treatment is transcranial direct current stimulation (tDCS), a popular and effective non-invasive brain stimulation technique. Methods: This mechanistic review explores the efficacy of tDCS in treating depression and anxiety in MS while focusing on the underlying mechanisms of action. Understanding these mechanisms is crucial, as neuropsychiatric symptoms in MS arise from complex neuroinflammatory and neurodegenerative processes. This review offers insights that may direct more focused and efficient therapeutic approaches by investigating the ways in which tDCS affects inflammation, brain plasticity, and neural connections. Searches were conducted using the PubMed/Medline, ResearchGate, Cochrane, and Google Scholar databases. Results: The literature search yielded 11 studies to be included in this review, with a total of 175 patients participating in the included studies. In most studies, tDCS did not significantly reduce depression or anxiety scores as the studied patients did not have elevated scores indicating depression and anxiety. In the few studies where the patients had scores indicating mild/moderate dysfunction, tDCS was more effective. The risk of bias in the included studies was assessed as moderate. Despite the null or near-null results, tDCS may still prove to be an effective treatment option for depression and anxiety in MS, because tDCS produces a neurobiological effect on the brain and nervous system. To facilitate further work, several possible mechanisms of action of tDCS have been reported, such as the modulation of the frontal–midline theta, reductions in neuroinflammation, the modulation of the HPA axis, and cerebral blood flow regulation. Conclusions: Although tDCS did not overall demonstrate positive effects in reducing depression and anxiety in the studied MS patients, the role of tDCS in this area should not be underestimated. Evidence from other studies indicates the effectiveness of tDCS in reducing depression and anxiety, but the studies included in this review did not include patients with sufficient depression or anxiety. Future studies are needed to confirm the effectiveness of tDCS in neuropsychiatric dysfunctions in MS. Full article
(This article belongs to the Special Issue Multiple Sclerosis: Diagnosis, Treatment and Clinical Management)
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