Neurofilaments and 10-year follow-up in multiple sclerosis

2018 ◽  
Vol 24 (10) ◽  
pp. 1301-1307 ◽  
Author(s):  
Alok Bhan ◽  
Cecilie Jacobsen ◽  
Kjell Morten Myhr ◽  
Ingvild Dalen ◽  
Kirsten Lode ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Outcome ◽  
Predictive Biomarker ◽  
Progressive Multiple Sclerosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Newly Diagnosed ◽  
Relapsing Remitting ◽  
Csf Levels ◽  
Relapsing Remitting Multiple Sclerosis

Background: The role of biomarkers to predict clinical outcome in multiple sclerosis (MS) is still debated. Objective: To test whether cerebrospinal fluid (CSF) light-chain neurofilament (NfL) levels in newly diagnosed patients with MS could predict clinical outcome over a 10-year period. Methods: Patients with newly diagnosed MS underwent standardized clinical assessments at baseline and 5 and 10 years of follow-up. Expanded Disability Status Scale (EDSS) progression between assessments was defined as an increase in one point or more if <6 and 0.5 or more if ≥6. CSF obtained at baseline was analyzed for levels of NfL using enzyme-linked immunosorbent assay technology. Results: A total of 44 patients were included. In all, 35 patients (80%) had relapsing–remitting multiple sclerosis (RRMS). Patients who progressed in EDSS showed a trend for higher median baseline CSF-NfL levels than patients who did not progress after 5 years (947 ng/L vs 246 ng/L, p = 0.05), and although not statistically significant, after 10 years (708 ng/L vs 265 ng/L, p = 0.28). Patients who converted from RRMS to secondary-progressive multiple sclerosis (SPMS) at 5 years had a statistical significant higher median CSF level of NfL (2122 ng/L vs 246 ng/L, p = 0.01). Conclusion: CSF levels of NfL at the time of diagnosis seems to be an early predictive biomarker of long-term clinical outcome and conversion from RRMS to SPMS.

scholarly journals CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis

2012 ◽  
Vol 19 (7) ◽  
pp. 877-884 ◽  
Author(s):  
Jeppe Romme Christensen ◽  
Lars Börnsen ◽  
Mohsen Khademi ◽  
Tomas Olsson ◽  
Poul Erik Jensen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Underlying Disease ◽  
Progressive Multiple Sclerosis ◽  
Axonal Damage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Csf Biomarkers ◽  
Relapsing Remitting ◽  
One Year

Background: The mechanism underlying disease progression in progressive multiple sclerosis (MS) is uncertain. Pathological studies found widespread inflammation in progressive MS brains correlating with disease progression and axonal damage. Objectives: To study cerebrospinal fluid (CSF) biomarkers and clarify whether inflammation and axonal damage are associated in progressive MS. Methods: Using enzyme-linked immunosorbent assay (ELISA), we analysed CSF from 40 secondary progressive (SPMS), 21 primary progressive (PPMS), and 36 relapsing–remitting (RRMS) and 20 non-inflammatory neurological disease (NIND) patients. Twenty-two of the SPMS patients participated in an MBP8298 peptide clinical trial and had CSF follow-up after one year. Results: Compared to NIND patients, inflammatory biomarkers osteopontin and matrix metalloproteinase-9 (MMP9) were increased in all MS patients while CXCL13 was increased in RRMS and SPMS patients. Biomarkers of axonal damage (NFL) and demyelination (MBP) were increased in all MS patients. In progressive MS patients CSF levels of osteopontin and CXCL13 correlated with NFL while osteopontin and MMP9 correlated with MBP. MBP8298 treatment did not affect the levels of the biomarkers after one year of treatment. All biomarkers were continuously increased after one year of follow-up except MBP, which decreased. Conclusion: CSF biomarkers of inflammation, axonal damage and demyelination are continuously increased in progressive MS patients and correlate. These findings parallel pathology studies, emphasise a relationship between inflammation, axonal damage and demyelination and support the use of CSF biomarkers in progressive MS clinical trials.

scholarly journals Monitoring cognitive change in multiple sclerosis using a computerized cognitive battery

2018 ◽  
Vol 4 (4) ◽  
pp. 205521731881551 ◽  
Author(s):  
L De Meijer ◽  
D Merlo ◽  
O Skibina ◽  
EJ Grobbee ◽  
J Gale ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Change ◽  
Progressive Multiple Sclerosis ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Serial Addition ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Cognitive Monitoring

Background Cognitive monitoring that can detect short-term change in multiple sclerosis is challenging. Computerized cognitive batteries such as the CogState Brief Battery can rapidly assess commonly affected cognitive domains. Objectives The purpose of this study was to establish the acceptability and sensitivity of the CogState Brief Battery in multiple sclerosis patients compared to controls. We compared the sensitivity of the CogState Brief Battery to that of the Paced Auditory Serial Addition Test over 12 months. Methods Demographics, Expanded Disability Status Scale scores, depression and anxiety scores were compared with CogState Brief Battery and Paced Auditory Serial Addition Test performances of 51 patients with relapsing–remitting multiple sclerosis, 19 with secondary progressive multiple sclerosis and 40 healthy controls. Longitudinal data in 37 relapsing–remitting multiple sclerosis patients were evaluated using linear mixed models. Results Both the CogState Brief Battery and the Paced Auditory Serial Addition Test discriminated between multiple sclerosis and healthy controls at baseline ( p<0.001). CogState Brief Battery tasks were more acceptable and caused less anxiety than the Paced Auditory Serial Addition Test ( p<0.001). In relapsing–remitting multiple sclerosis patients, reaction time slowed over 12 months ( p<0.001) for the CogState Brief Battery Detection (mean change –34.23 ms) and Identification (–25.31 ms) tasks. Paced Auditory Serial Addition Test scores did not change over this time. Conclusions The CogState Brief Battery is highly acceptable and better able to detect cognitive change than the Paced Auditory Serial Addition Test. The CogState Brief Battery could potentially be used as a practical cognitive monitoring tool in the multiple sclerosis clinic setting.

scholarly journals Cerebrospinal fluid mtDNA concentration is elevated in multiple sclerosis disease and responds to treatment

2017 ◽  
Vol 24 (4) ◽  
pp. 472-480 ◽  
Author(s):  
Cyra E Leurs ◽  
Petar Podlesniy ◽  
Ramon Trullas ◽  
Lisanne Balk ◽  
Martijn D Steenwijk ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Progression ◽  
Progressive Multiple Sclerosis ◽  
Neurologic Disease ◽  
Brain Volumes ◽  
Multiple Sclerosis Disease ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Digital Polymerase Chain Reaction

Background: Mitochondrial dysfunction is increasingly recognized as an important feature of multiple sclerosis (MS) pathology and may be relevant for clinical disease progression. However, it is unknown whether mitochondrial DNA (mtDNA) levels in the cerebrospinal fluid (CSF) associate with disease progression and therapeutic response. Objectives: To evaluate whether CSF concentrations of mtDNA in MS patients can serve as a marker of ongoing neuropathology and may be helpful to differentiate between MS disease subtypes. To explore the effect of disease-modifying therapies on mtDNA levels in the CSF. Methods: CSF mtDNA was measured using a digital polymerase chain reaction (PCR) CSF mtDNA in two independent MS cohorts. The cohorts included 92 relapsing-remitting multiple sclerosis (RRMS) patients, 40 progressive multiple sclerosis (PMS) patients (27 secondary progressive and 13 primary progressive), 50 various neurologic disease controls, and 5 healthy controls. Results: Patients with PMS showed a significant increase in CSF mtDNA compared to non-inflammatory neurologic disease controls. Patients with higher T2 lesion volumes and lower normalized brain volumes showed increased concentration of mtDNA. Patients treated with fingolimod had significantly lower mtDNA copy levels at follow-up compared to baseline. Conclusion: Our results showed a non-specific elevation of concentration of mtDNA in PMS patients. mtDNA concentrations respond to fingolimod and may be used to monitor biological effect of this treatment.

scholarly journals Onset of secondary progressive multiple sclerosis is not influenced by current relapsing multiple sclerosis therapies

2018 ◽  
Vol 4 (2) ◽  
pp. 205521731878334 ◽  
Author(s):  
Francisco Coret ◽  
Francisco C Pérez-Miralles ◽  
Francisco Gascón ◽  
Carmen Alcalá ◽  
Arantxa Navarré ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background Disease-modifying therapies are thought to reduce the conversion rate to secondary progressive multiple sclerosis. Objective To explore the rate, chronology, and contributing factors of conversion to the progressive phase in treated relapsing–remitting multiple sclerosis patients. Methods Our study included 204 patients treated for relapsing–remitting multiple sclerosis between 1995 and 2002, prospectively followed to date. Kaplan–Meier analysis was applied to estimate the time until secondary progressive multiple sclerosis conversion, and multivariate survival analysis with a Cox regression model was used to analyse prognostic factors. Results Relapsing–remitting multiple sclerosis patients were continuously treated for 13 years (SD 4.5); 36.3% converted to secondary progressive multiple sclerosis at a mean age of 42.6 years (SD 10.6), a mean time of 8.2 years (SD 5.2) and an estimated mean time of 17.2 years (range 17.1–18.1). A multifocal relapse, age older than 34 years at disease onset and treatment failure independently predicted conversion to secondary progressive multiple sclerosis but did not influence the time to reach an Expanded Disability Status Scale of 6.0. Conclusions The favourable influence of disease-modifying therapies on long-term disability in relapsing–remitting multiple sclerosis is well established. However, the time to progression onset and the subsequent clinical course in treated patients seem similar to those previously reported in natural history studies. More studies are needed to clarify the effect of disease-modifying therapies once the progressive phase has been reached.

scholarly journals Ocrelizumab-induced alopecia areata—A series of five patients from Ontario, Canada: A case report

2020 ◽  
Vol 8 ◽  
pp. 2050313X2091961
Author(s):  
Laura D Chin ◽  
Mohn’d AbuHilal
Keyword(s):  
Multiple Sclerosis ◽  
Alopecia Areata ◽  
Conventional Treatment ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Cd20 Antigen ◽  
Humanized Monoclonal Antibody ◽  
Relapsing Remitting ◽  
Topical Minoxidil ◽  
Relapsing Remitting Multiple Sclerosis

Background: Ocrelizumab is a humanized monoclonal antibody that targets the CD20 antigen found on B-cells. It is indicated in the treatment of both relapsing–remitting multiple sclerosis and primary progressive multiple sclerosis. Objective: The aim of this study is to report and describe the characteristics of alopecia areata following treatment with ocrelizumab for multiple sclerosis. Results: Five patients were reported, two female and three male. Four of the five patients had alopecia areata of the scalp, one of the five having alopecia to the beard area. All patients responded well to conventional treatment with topical and intralesional corticosteroids and topical minoxidil foam. Ocrelizumab can be associated with the development of alopecia areata. Initiation of proper treatment may lead to quick improvement or resolution of this potentially reversible adverse effect.

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