scholarly journals CSF Levels of CXCL12 and Osteopontin as Early Markers of Primary Progressive Multiple Sclerosis

2021 ◽  
Vol 8 (6) ◽  
pp. e1083
Author(s):  
Damiano Marastoni ◽  
Roberta Magliozzi ◽  
Anna Bolzan ◽  
Anna Isabella Pisani ◽  
Stefania Rossi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Protein Profile ◽  
Brain Mri ◽  
Cortical Lesion ◽  
Primary Progressive Multiple Sclerosis ◽  
Class Iii ◽  
Primary Progressive ◽  
Lesion Number ◽  
Inflammatory Processes ◽  
Csf Levels

Background and ObjectivesTo evaluate the extent of intrathecal inflammation in patients with primary progressive MS (PPMS) at the time of diagnosis and to define markers and a specific inflammatory profile capable of distinguishing progressive from relapsing-remitting multiple sclerosis (RRMS).MethodsLevels of 34 pro- and anti-inflammatory cytokines and chemokines in the CSF were evaluated at the diagnosis in 16 patients with PPMS and 80 with RRMS. All patients underwent clinical evaluation, including Expanded Disability Status Scale assessment and a 3T brain MRI to detect white matter and cortical lesion number and volume and global and regional cortical thickness.ResultsHigher levels of CXCL12 (odds ratio [OR] = 3.97, 95% CI [1.34–11.7]) and the monocyte-related osteopontin (OR = 2.24, 95% CI [1.01–4.99]) were detected in patients with PPMS, whereas levels of interleukin-10 (IL10) (OR = 0.28, 95% CI [0.09–0.96]) were significantly increased in those with RRMS. High CXCL12 levels were detected in patients with increased gray matter lesion number and volume (p = 0.001, r = 0.832 and r = 0.821, respectively). Pathway analysis confirmed the chronic inflammatory processes occurring in PPMS.ConclusionsAt the time of diagnosis, a specific CSF protein profile can recognize the presence of early intrathecal inflammatory processes, possibly stratifying PPMS with respect to RRMS. Elevated CSF levels of CXCL12 and osteopontin suggested a key role of brain innate immunity and glia activity in MS. These molecules could represent useful candidate markers of MS progression, with implications for the pathogenesis and treatment of progressive MS.Classification of EvidenceThis study provides Class III evidence that CXCL12 and monocyte-related osteopontin may be correlated with PPMS, and IL-10 may be related to RRMS. It is may be correlated due to Bonferroni correction negating the statistical correlations found in the study.

Preferential spinal cord volume loss in primary progressive multiple sclerosis

2018 ◽  
Vol 25 (7) ◽  
pp. 947-957 ◽  
Author(s):  
Charidimos Tsagkas ◽  
Stefano Magon ◽  
Laura Gaetano ◽  
Simon Pezold ◽  
Yvonne Naegelin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Clinical Outcomes ◽  
Brain Mri ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Over Time ◽  
Spinal Cord Volume

Background: Little is known on longer term changes of spinal cord volume (SCV) in primary progressive multiple sclerosis (PPMS). Objective: Longitudinal evaluation of SCV loss in PPMS and its correlation to clinical outcomes, compared to relapse-onset multiple sclerosis (MS) subtypes. Methods: A total of 60 MS age-, sex- and disease duration-matched patients (12 PPMS, each 24 relapsing-remitting (RRMS) and secondary progressive MS (SPMS)) were analysed annually over 6 years of follow-up. The upper cervical SCV was measured on 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images using a semi-automatic software (CORDIAL), along with the total brain volume (TBV), brain T2 lesion volume (T2LV) and Expanded Disability Status Scale (EDSS). Results: PPMS showed faster SCV loss over time than RRMS ( p < 0.01) and by trend ( p = 0.066) compared with SPMS. In contrast to relapse-onset MS, in PPMS SCV loss progressed independent of TBV and T2LV changes. Moreover, in PPMS, SCV was the only magnetic resonance imaging (MRI) measurement associated with EDSS increase over time ( p < 0.01), as opposed to RRMS and SPMS. Conclusion: SCV loss is a strong predictor of clinical outcomes in PPMS and has shown to be faster and independent of brain MRI metrics compared to relapse-onset MS.

scholarly journals Ongoing microstructural changes in the cervical cord underpin disability progression in early primary progressive multiple sclerosis

2020 ◽  
Vol 27 (1) ◽  
pp. 28-38 ◽  
Author(s):  
Rosa Cortese ◽  
Carmen Tur ◽  
Ferran Prados ◽  
Torben Schneider ◽  
Baris Kanber ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Brain Mri ◽  
Progressive Multiple Sclerosis ◽  
Cervical Cord ◽  
Primary Progressive Multiple Sclerosis ◽  
Disability Progression ◽  
Mixed Effect ◽  
Primary Progressive ◽  
Over Time

Background: Pathology in the spinal cord of patients with primary progressive multiple sclerosis (PPMS) contributes to disability progression. We previously reported abnormal Q-space imaging (QSI)-derived indices in the spinal cord at baseline in patients with early PPMS, suggesting early neurodegeneration. Objective: The aim was to investigate whether changes in spinal cord QSI over 3 years in the same cohort are associated with disability progression and if baseline QSI metrics predict clinical outcome. Methods: Twenty-three PPMS patients and 23 healthy controls recruited at baseline were invited for follow-up cervical cord 3T magnetic resonance imaging (MRI) and clinical assessment after 1 year and 3 years. Cord cross-sectional area (CSA) and QSI measures were obtained, together with standard brain MRI measures. Mixed-effect models assessed MRI changes over time and their association with clinical changes. Linear regression identified baseline MRI indices associated with disability at 3 years. Results: Over time, patients deteriorated clinically and showed an increase in cord QSI indices of perpendicular diffusivity that was associated with disability worsening, independently of the decrease in CSA. Higher perpendicular diffusivity and lower CSA at baseline predicted worse disability at 3 years. Conclusion: Increasing spinal cord perpendicular diffusivity may indicate ongoing neurodegeneration, which underpins disability progression in PPMS, independently of the development of spinal cord atrophy.

Retinal degeneration in primary-progressive multiple sclerosis: A role for cortical lesions?

2016 ◽  
Vol 23 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Maria Petracca ◽  
Christian Cordano ◽  
Maria Cellerino ◽  
Julia Button ◽  
Stephen Krieger ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Visual Pathway ◽  
Progressive Multiple Sclerosis ◽  
Lesion Volume ◽  
Primary Progressive Multiple Sclerosis ◽  
Inner Plexiform Layer ◽  
Cortical Lesions ◽  
Fiber Layer ◽  
Primary Progressive ◽  
Lesion Number

Background: Retinal atrophy in multiple sclerosis (MS) is secondary to optic nerve focal inflammation and to injury of the posterior visual pathway. Objectives: To investigate the contribution of cortical lesions (CLs) to retinal pathology in primary-progressive multiple sclerosis (PPMS). Methods: We performed a cross-sectional evaluation of 25 patients and 20 controls, relating magnetic resonance imaging (MRI) metrics of visual pathway integrity with parameters derived from spectral-domain optical coherence tomography (peripapillary retinal nerve fiber layer (RNFL) thickness, ganglion cell + inner plexiform layer (GCIPL) thickness, and macular volume (MV)). Results: Mean RNFL, GCIPL thickness, and MV were significantly reduced in patients compared to controls. MV and GCIPL thickness were significantly correlated with visual acuity. RNFL thinning was associated with thalamus and visual cortex volume (respectively, p = 0.01 and p < 0.05). In addition to thalamic volume, GCIPL thinning was associated with CLs and intracortical lesion number and volume, leucocortical lesion volume (all p ⩽ 0.05) while MV decrease was associated with CLs volume ( p = 0.05) and intracortical lesion number and volume ( p < 0.05). Conclusion: Our results suggest that RNFL thinning and GCIPL thinning/MV decrease may be explained by alternative mechanisms including retrograde trans-synaptic degeneration and/or a common pathophysiologic process affecting both the brain with CLs and the retina with neuronal loss.

Diagnostic brain MRI findings in primary progressive multiple sclerosis

2000 ◽  
Vol 6 (2) ◽  
pp. 81-85 ◽  
Author(s):  
M Kremenchutzky ◽  
D Lee ◽  
G P A Rice ◽  
G C Ebers
Keyword(s):  
Multiple Sclerosis ◽  
Age Of Onset ◽  
Brain Mri ◽  
Diagnostic Value ◽  
Progressive Multiple Sclerosis ◽  
Normal Brain ◽  
Primary Progressive Multiple Sclerosis ◽  
Mri Findings ◽  
Primary Progressive ◽  
Mri Scans

The clinical course of multiple sclerosis can be classified as relapsing from onset (relapsing-remitting), or progressive from onset (primary progressive -PPMS). These clinical phenotypes have been based on historical and clinical observations. It has been reported that PPMS patients tend to have quantitatively less MRI activity and disease burden. We evaluated the sensitivity and diagnostic value of conventional brain MRI scan in 143 PPMS patients. Brain MRIs were blindly evaluated to determine if they satisfied Paty and/or Fazekas diagnostic criteria. Patient were divided into those with typical atypical or normal scans. They satisfied brain MRI criteria in 92% cases. Findings included: 131 typical four atypical, and eight normal scans. All 12 non-typical scans' subject had spinal onset; spinal MRI scans were positive in four of seven cases. Sex, age of onset, site and number of symptoms involved at onset among those groups were not significantly different but accumulation of disability had a tendency to be slower in these few individuals with normal or atypical head MRI's. Although there may be quantitative differences in lesion activity/burden, MRI scanning in PPMS unexpectedly has diagnostic sensitivity very similar to that seen in RRMS. A normal brain MRI is unusual in PPMS patients.

scholarly journals Safety of Ocrelizumab in Patients With Relapsing and Primary Progressive Multiple Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012700
Author(s):  
Stephen L Hauser ◽  
Ludwig Kappos ◽  
Xavier Montalban ◽  
Licinio Craveiro ◽  
Cathy Chognot ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Real World ◽  
Safety Profile ◽  
Progressive Multiple Sclerosis ◽  
Continuous Treatment ◽  
Primary Progressive Multiple Sclerosis ◽  
Class Iii ◽  
Primary Progressive ◽  
Controlled Treatment

ObjectiveTo report safety of ocrelizumab (OCR) up to 7 years in patients with relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS) enrolled in clinical trials or treated in real-world postmarketing settings.MethodsSafety analyses are based on integrated clinical and laboratory data for all patients who received OCR in 11 clinical trials, including the controlled treatment and open-label extension (OLE) periods of the phase 2 and 3 trials, plus the phase 3b trials VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, CONSONANCE, and LIBERTO. For selected adverse events (AEs), additional postmarketing data were used. Incidence rates of serious infections (SIs) and malignancies were contextualized using multiple epidemiologic sources.ResultsAt data cut-off (January 2020), 5,680 patients with multiple sclerosis (MS) received OCR (18,218 patient years [PY] of exposure) in clinical trials. Rates per 100 PY (95% CI) of AEs (248; 246–251), serious AEs (7.3; 7.0–7.7), infusion-related reactions (25.9; 25.1–26.6), and infections (76.2; 74.9–77.4) were similar to those within the controlled treatment period of the phase 3 trials. Rates of the most common serious AEs, including SIs (2.01; 1.81–2.23) and malignancies (0.46; 0.37–0.57), were consistent with the ranges reported in epidemiologic data.ConclusionContinuous administration of OCR for up to 7 years in clinical trials, as well as its broader use for more than 3 years in the real-world setting, are associated with a favorable and manageable safety profile, without emerging safety concerns in a heterogeneous MS population.Classification of evidenceThis analysis provides Class III evidence that long-term, continuous treatment with OCR has a consistent and favorable safety profile in patients with RMS and PPMS. This study is rated Class III because of the use of OLE data and historical controls.

scholarly journals The Critical Role of Imaging in Primary Progressive Multiple Sclerosis

2020 ◽  
Vol 8 (C) ◽  
pp. 195-200
Author(s):  
Yuyun Yueniwati ◽  
Dotti Inggrianita
Keyword(s):  
Multiple Sclerosis ◽  
Physical Examination ◽  
Cranial Nerve ◽  
Brain Mri ◽  
Critical Role ◽  
Disease Onset ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
The Past ◽  
Cranial Nerve Palsies

BACKGROUND: Multiple sclerosis (MS) is an autoimmune-related neurological disorder as a result of chronic inflammation and demyelination which affect the central nervous system. The number of MS cases in Indonesia is about 1–5/100.000 people. This disease causes disability and requires immense treatment costs. One of the MS subtypes is primary progressive which is marked by the decline of neurological functions since the disease onset, without any period of relapse attacks. CASE REPORT: A 59-year-old female came with complaints on spinning dizziness, accompanied by vomiting and waddling for the past month before hospital administration. Based on physical examination, we found multiple cranial nerve palsies on the cranial nerve III, IV, V, VI, and VII on the left side. Initially, it suspected as an intracranial lesion in the cerebellopontine angle. However, brain computed tomography scan showed a normal result. Brain magnetic resonance imaging (MRI) was conducted and we found multiple lesions on the supratentorial and infratentorial region. The second patient was a 24-year-old female complained about waddling gait for the past year, which grew heavier. Based on physical examination, we found a cerebellar sign on the left side, cerebellar ataxia, paraparesis of lower extremity, and paresthesia. Brain MRI with contrast displayed white matter periventricular and infratentorial lesion. CONCLUSION: In both cases, radiological imaging examination, which was MRI with contrast, was beneficial in the establishment of patient’s diagnosis, which made therapeutic management suitable as needed.

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