Time matters in multiple sclerosis: can early treatment and long-term follow-up ensure everyone benefits from the latest advances in multiple sclerosis?

Cerqueira, João José; Compston, D. A. S.; Geraldes, Ruth; Rosa, Mário Miguel; Schmierer, Klaus; Thompson, Alan J.; Tinelli, Michela; Palace, Jacqueline

doi:10.1136/jnnp-2017-317509

Cited by 117 publications

(89 citation statements)

References 93 publications

(69 reference statements)

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“…Prevention can be recommended to those patients who are susceptible to disease development based on genetic analysis and family history, or to those with cognitive decline which appears long before walking disability starts to be pronounced. 28 Evidence indicate that patients who received interferon-beta had improvement in mortality if they start receiving the drug early. 29 Consequently, it is highly important to understand how DMTs work and when is the best time of using them in order to efficiently interfere with disease progression.…”

Section: Discussionmentioning

confidence: 99%

<p>Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens</p>

Al‐Ani¹,

Raju²,

Hachim³

et al. 2020

JIR

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Objective: To investigate, in detail, the effects of rituximab (RTX), an off-label drug for treating multiple sclerosis (MS) disease on preventing and/or ameliorating experimental autoimmune encephalomyelitis (EAE). Methods: Using bioinformatics analysis of publicly available transcriptomics data, we determined the accumulation of B cells, plasma cells and T cells in different compartments of multiple sclerosis patients (MS) and healthy individual brains. Based on these observations and on the literature search, we dosed RTX in EAE mice either orally, or injected intraperitoneally (IP). The latter route was used either prophylactically (asymptomatic stage; upon the induction of the disease), or therapeutically (acute stage; upon the appearance of the first sign of the disease). Further, we used RTX as a preventive drug either as a single agent or in combination with other routes of administration. Results: Because no complete recovery was observed when RTX was used prophylactically or therapeutically, we devised another protocol of injecting this drug before the onset of the disease and designated this regiment as prevention. We demonstrated that the 20 μg/mouse prevention completely reduced the EAE clinical score, impaired infiltration of T and B cells into the perivascular space of mice brains, along with inhibiting the inflammation and demyelination. However, the 5 and 10 μg/mouse doses although reduced all aspects of inflammation in these mice, their effects were not as potent as the 20 μg/mouse RTX dose. Finally, we combined the 5 μg/mouse prevention treatment with either the prophylactic or therapeutic regimen and observed a robust effect. Conclusion: We observed that combinatorial regimens resulted in further reduction of inflammation, T and B cell extravasation into the brains of EAE mice and improved the remyelination.

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Section: Discussionmentioning

confidence: 99%

<p>Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens</p>

Al‐Ani¹,

Raju²,

Hachim³

et al. 2020

JIR

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“…The characterization of a prodromal phase is necessary to understanding the natural history of MS, not only to provide a better understanding of the pathophysiology of MS but also to identify opportunities for early treatment interventions to attenuate disease progression. Importantly, earlier treatment in MS has been associated with a better clinical outcome, in addition to decrease degeneration and cognitive decline …”

Section: Discussionmentioning

confidence: 99%

“…Importantly, earlier treatment in MS has been associated with a better clinical outcome, in addition to decrease degeneration and cognitive decline. 30,31 We do acknowledge limitations to our data. following the first demyelinating event (CIS).…”

Section: Post-cis Gimentioning

confidence: 99%

Bowel symptoms predate the diagnosis among many patients with multiple sclerosis: A 14‐year cohort study

Almeida

Silvernale

Kuo

et al. 2019

Neurogastroenterology Motil

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Background Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease frequently complicated by bowel symptoms. Multiple sclerosis typically first manifests with a demyelination event, also known as a clinically isolated syndrome (CIS). We sought to examine the prevalence of prodromal bowel symptoms predating a CIS in patients with MS as part of a recently characterized prodromal phase of disease. Methods We constructed a retrospective cohort of MS patients with bowel symptoms and an identifiable CIS at two tertiary care centers over 14 years using administrative and billing data. We determined the date of onset of reported bowel symptoms in comparison with the date of first CIS and determined the overall prevalence of prediagnosis bowel symptoms within 1, 2, 3, and >3 years from a CIS. We used multivariable modeling to determine demographic and clinical risk factors for prediagnosis bowel symptoms. Key Results Among 385 MS patients with reported bowel symptoms, 122 (31.6%) reported bowel symptoms prior to CIS. The most common first bowel symptom was constipation (50.0%), followed by diarrhea (29.5%). The average lead time between a first bowel symptom and a CIS event was 3.7 ± 3.4 years. Pre‐CIS fatigue (OR 4.48, 95% CI: 2.68‐7.51, P < 0.001) and pre‐CIS sensory disturbances (OR 1.88, 95% CI: 1.15‐3.08, P < 0.05) were all associated with bowel symptoms prior to a CIS event. Conclusions and Inferences Nearly a third of MS patients with bowel symptoms reported bowel symptoms prior to a demyelinating event/CIS. Characterization of a prodromal phase of disease may provide important insights into understanding disease progression.

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“…Die Prädiktion klinischer Parameter ist hingegen noch nicht so weit fortgeschritten. Ein früher Therapiebeginn gilt bei MS als besonders wichtig [44,45], daher könnte eine zuverlässige frühe Vorhersage des zu erwartenden Verlaufs Therapieentscheidungen beeinflussen. Angesichts eines immer breiter werdenden Arsenals an verfügbaren Medikamenten [46] wäre es außerdem besonders interessant, inwiefern Maschinenlernen dazu beitragen kann, für einzelne Patientinnen und Patienten die jeweils individuell am besten geeignete Therapie zu identifizieren.…”

Section: Diskussion Und Ausblickunclassified

AI in Radiology: Where are we today in Multiple Sclerosis Imaging?

Eichinger

Zimmer

Wiestler

2020

Rofo

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Background MR imaging is an essential component in managing patients with Multiple sclerosis (MS). This holds true for the initial diagnosis as well as for assessing the clinical course of MS. In recent years, a growing number of computer tools were developed to analyze imaging data in MS. This review gives an overview of the most important applications with special emphasis on artificial intelligence (AI). Methods Relevant studies were identified through a literature search in recognized databases, and through parsing the references in studies found this way. Literature published as of November 2019 was included with a special focus on recent studies from 2018 and 2019. Results There are a number of studies which focus on optimizing lesion visualization and lesion segmentation. Some of these studies accomplished these tasks with high accuracy, enabling a reproducible quantitative analysis of lesion loads. Some studies took a radiomics approach and aimed at predicting clinical endpoints such as the conversion from a clinically isolated syndrome to definite MS. Moreover, recent studies investigated synthetic imaging, i. e. imaging data that is not measured during an MR scan but generated by a computer algorithm to optimize the contrast between MS lesions and brain parenchyma. Conclusion Computer-based image analysis and AI are hot topics in imaging MS. Some applications are ready for use in clinical routine. A major challenge for the future is to improve prediction of expected disease courses and thereby helping to find optimal treatment decisions on an individual level. With technical improvements, more questions arise about the integration of new tools into the radiological workflow. Key Points: Citation Format

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Time matters in multiple sclerosis: can early treatment and long-term follow-up ensure everyone benefits from the latest advances in multiple sclerosis?

Cited by 117 publications

References 93 publications

<p>Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens</p>

<p>Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens</p>

Bowel symptoms predate the diagnosis among many patients with multiple sclerosis: A 14‐year cohort study

AI in Radiology: Where are we today in Multiple Sclerosis Imaging?

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