Related Experiment Video
Updated: May 5, 2026
09:46
Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines
Published on: September 21, 2021
4.6K
Intrathecal Inflammatory Profile and Gray Matter Damage Predict Progression Independent of Relapse Activity in Early
Damiano Marastoni1, Elisa Colato1,2,3, Matteo Foschi4,5
1Neurology B, Department of Neurosciences, University of Verona, Italy.
Neurology(R) Neuroimmunology & Neuroinflammation
|May 1, 2025
Summary
Early multiple sclerosis patients with specific inflammatory markers in cerebrospinal fluid (CSF) and MRI findings indicating brain atrophy are at higher risk for progression independent of relapse activity (PIRA). This profile aids in predicting disease worsening at diagnosis.
Area of Science:
- Neuroimmunology
- Neurology
- Radiology
Background:
- Relapsing-remitting multiple sclerosis (RRMS) is characterized by unpredictable relapses and progressive disability.
- Progression independent of relapse activity (PIRA) represents a significant challenge in managing MS, as it indicates disability accumulation unrelated to clinical relapses.
- Identifying early predictors of PIRA is crucial for timely therapeutic intervention and personalized treatment strategies.
Purpose of the Study:
- To identify a predictive profile for Progression Independent of Relapse Activity (PIRA) in early relapsing-remitting multiple sclerosis (RRMS) at the time of diagnosis.
- To correlate cerebrospinal fluid (CSF) inflammatory markers and Magnetic Resonance Imaging (MRI) features with PIRA development.
- To establish an early diagnostic tool for predicting long-term disability in RRMS patients.
Main Methods:
- A five-year prospective study involving 80 treatment-naïve RRMS patients.
- Collection of CSF for analysis of 68 inflammatory molecules, alongside regular neurological assessments (including EDSS) and annual 3T brain MRIs.
- Definition of PIRA as confirmed disability progression independent of relapse activity.
Main Results:
- 28.8% of RRMS patients developed PIRA within five years.
- Older age and higher baseline EDSS scores were associated with PIRA.
- Key CSF markers (e.g., sTNFR1, sTNFR2, LIGHT) and MRI findings (thalamus volume, middle frontal gyrus thickness, cortical lesion number) predicted PIRA development.
Conclusions:
- A distinct intrathecal inflammatory profile, including TNF superfamily markers, combined with MRI-detected white matter lesions and gray matter atrophy, can predict PIRA in early MS.
- These findings highlight the importance of assessing both inflammatory markers and structural brain changes at diagnosis.
- The identified profile offers a potential tool for early risk stratification and personalized management of RRMS patients.
Related Concept Videos
01:21Myocarditis I: Introduction
645
Myocarditis is inflammation of the myocardium, which is the muscular layer of the heart.EtiologyMyocarditis has a diverse etiology, including a wide range of infectious and non-infectious causes:Infectious CausesViral: Common viruses include Coxsackie A and B, adenovirus, parvovirus B19, enteroviruses, and influenza A.Bacterial: Examples include infections caused by Streptococcus, Staphylococcus, and Mycoplasma species.Rickettsial: Infections like Rocky Mountain spotted fever can result in...
645
01:29Acute Kidney Injury III: Clinical Manifestations
1.8K
Acute Kidney Injury (AKI) progresses through distinct clinical phases: the oliguric, diuretic, and recovery phases, each marked by unique manifestations and challenges.Oliguric Phase:The oliguric phase is the initial stage of AKI, typically lasting 10 to 14 days. This phase is marked by a significant reduction in urine output, usually less than 400 mL per day, indicating decreased kidney function. Fluid retention is a prominent feature, leading to symptoms such as edema, hypertension, and...
1.8K
01:12Chronic Inflammation: Introduction
41
Chronic inflammation is a prolonged, dysregulated immune response that persists for weeks to years when the inciting stimulus is difficult to eradicate or when self‑antigens drive ongoing reactivity. Morphologically, it is defined by mononuclear cell infiltration, progressive tissue destruction, and concurrent attempts at healing via angiogenesis and fibrosis. Compared with acute inflammation, edema is less prominent while cellular infiltration predominates; triggers include persistent...
41
01:24Healing II: Complications
37
Complications during healing arise when tissue repair is altered by local or systemic factors. These changes involve abnormal collagen deposition, altered biomechanics, and reduced vascular supply, impairing restoration of normal structure and function.Loss of FunctionScar tissue differs significantly from the original tissue it replaces. In the skin, fibrosis lacks adnexal structures such as hair follicles, sebaceous glands, and sweat glands. Their absence reduces tactile sensitivity, impairs...
37
01:14Spinal Cord Injury ll: Pathophysiology
25
Spinal cord injury progresses through two interconnected phases: primary injury and secondary injury.Primary InjuryPrimary injury happens at the moment of trauma and involves immediate mechanical damage to the spinal cord.Compression happens when broken vertebrae, herniated discs, or accumulating blood (such as a hematoma) press directly against the spinal cord, distorting its normal shape and function. In cases of contusion, the cord is bruised by a blunt force (like penetrating injuries or...
25
01:25Secondary Spinal Cord Injury llI: Pathophysiology
52
Early Ischemia and Ionic ImbalanceWithin minutes of spinal cord injury, a secondary cascade begins, progressing over hours to weeks. Vascular damage reduces blood flow, causing ischemia and mitochondrial dysfunction. ATP depletion leads to ion pump failure, membrane depolarization, sodium influx, potassium efflux, and water accumulation, resulting in cellular swelling. Increased intracellular calcium further disrupts mitochondria and accelerates cellular injury.Excitotoxicity and Neuronal...
52