<i>Background</i>. Multiple sclerosis (MS) patients of African ancestry have a more aggressive disease course than white patients and could be resistant to interferon-beta (INFB). <i>Methods</i>. We studied the impact of INFB in treatment-naive Afro-Caribbean (AC) with clinically definite MS using our European Database for Multiple Sclerosis (EDMUS) (2003&#8211;2010). Main outcome measures were annual relapse rate after 2 years of treatment, proportion of exacerbation-free subjects 48 weeks after initiating INFB, and time to first relapse. <i>Results</i>. 76 AC-MS (59F/17M) were identified. Annual relapse rate of 1.29 decreased to 0.83 (&#x2212;35.6&#37;) after 2 years of treatment. The proportion of relapse-free patients at 48 weeks was 46.2&#37;. Median time to first relapse was 52 weeks. <i>Conclusion</i>. INFB is not strong enough to control AC-MS patients in many cases which is problematic in a population of worse MS prognosis.

S. Jeannin

R. Deschamps

N. Chausson

P. Cabre

Response to Interferon-Beta Treatment in Afro-Caribbeans with Multiple Sclerosis

For patients with Relapsing Remitting Multiple Scierosis Beta Interfaerons and Glatiramer Acetate were the first to be licensed for treatment. This review deals with one major question: when to initiate therapy? Through exploring the unique characteristics of the disease and treatement we suggest an approach that should be helpful in the process of decision-making.

Mona Alkhawajah

Joel Oger

When to Initiate Disease-Modifying Drugs for Relapsing Remitting Multiple Sclerosis in Adults?

Following emerging evidence that neurodegenerative processes in multiple sclerosis (MS) are present from its early stages, an intensive scientific interest has been directed to biomarkers of neuro-axonal damage in body fluids of MS patients. Recent research has introduced new candidate biomarkers but also elucidated pathogenetic and clinical relevance of the well-known ones. This paper reviews the existing data on blood and cerebrospinal fluid biomarkers of neuroaxonal damage in MS and highlights their relation to clinical parameters, as well as their potential predictive value to estimate future disease course, disability, and treatment response. Strategies for future research in this field are suggested.

Irena Dujmovic

Cerebrospinal Fluid and Blood Biomarkers of Neuroaxonal Damage in Multiple Sclerosis

<i  >Background</i>. Disability in multiple sclerosis (MS) is related to neuroaxonal degeneration. A reliable blood biomarker for neuroaxonal degeneration is needed. <i  >Objectives</i>. To explore the relationship between cerebrospinal fluid (CSF) and serum concentrations of a protein biomarker for neuroaxonal degeneration, the neurofilaments heavy chain (NfH). <i  >Methods</i>. An exploratory cross-sectional (<svg     style="vertical-align:-0.1638pt;width:44.400002px;" id="M1" height="11.125" version="1.1" viewBox="0 0 44.400002 11.125" width="44.400002"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,10.862)"><path id="x1D45B" d="M495 86q-46 -47 -87 -72.5t-63 -25.5q-43 0 -16 107l49 210q7 34 8 50.5t-3 21t-13 4.5q-35 0 -109.5 -72.5t-115.5 -140.5q-21 -75 -38 -159q-50 -10 -76 -21l-6 8l84 340q8 35 -4 35q-17 0 -67 -46l-15 26q44 44 85.5 70.5t64.5 26.5q35 0 10 -103l-24 -98h2&#xA;q42 56 97 103.5t96 71.5q46 26 74 26q9 0 16 -2.5t14 -11.5t9.5 -24.5t-1 -44t-13.5 -68.5q-30 -117 -47 -200q-4 -19 -3.5 -25t6.5 -6q21 0 70 48z" /></g><g transform="matrix(.017,-0,0,-.017,13.305,10.862)"><path id="x3D" d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z" /></g><g transform="matrix(.017,-0,0,-.017,28.008,10.862)"><path id="x35" d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8&#xA;l-26 -65h-233z" /></g><g transform="matrix(.017,-0,0,-.017,36.168,10.862)"><path id="x31" d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z" /></g>

		
	
</svg>) and longitudinal (<svg     style="vertical-align:-0.1638pt;width:44.400002px;" id="M2" height="11.125" version="1.1" viewBox="0 0 44.400002 11.125" width="44.400002"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,10.862)"><use xlink:href="#x1D45B"/></g><g transform="matrix(.017,-0,0,-.017,13.305,10.862)"><use xlink:href="#x3D"/></g><g transform="matrix(.017,-0,0,-.017,28.008,10.862)"><path id="x33" d="M285 378v-2q65 -13 102 -54.5t37 -97.5q0 -57 -30.5 -104.5t-74 -75t-85.5 -42t-72 -14.5q-31 0 -59.5 11t-40.5 23q-19 18 -16 36q1 16 23 33q13 10 24 0q58 -51 124 -51q55 0 88 40t33 112q0 64 -39 96.5t-88 32.5q-29 0 -64 -11l-6 29q77 25 118 57.5t41 84.5&#xA;q0 45 -26.5 69.5t-68.5 24.5q-67 0 -120 -79l-20 20l43 63q51 56 127 56h1q66 0 107 -37t41 -95q0 -42 -31 -71q-22 -23 -68 -54z" /></g><g transform="matrix(.017,-0,0,-.017,36.168,10.862)"><path id="x34" d="M456 178h-96v-72q0 -51 12.5 -62.5t72.5 -16.5v-27h-256v27q65 5 78 17t13 62v72h-260v28q182 271 300 426h40v-407h96v-47zM280 225v295h-2q-107 -148 -196 -295h198z" /></g>

		
	
</svg>) study on cerebrospinal fluid (CSF) and serum NfH phosphoform levels in patients with MS. The expanded disability status scale (EDSS), CSF, and serum levels of NfH-SMI34 and NfH-SMI35 were quantified at baseline. Disability progression was assessed at 3-year followup. <i  >Results</i>. At baseline, patients with primary progressive MS (PPMS, EDSS 6) and secondary progressive MS (SPMS, EDSS 6) were more disabled compared to patients with relapsing remitting MS (RRMS, EDSS 2, <svg     style="vertical-align:-0.1638pt;width:66.875px;" id="M3" height="11.375" version="1.1" viewBox="0 0 66.875 11.375" width="66.875"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x1D443" d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5&#xA;t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" /></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><path id="x3C" d="M512 -3l-437 233v51l437 233v-58l-378 -200v-2l378 -199v-58z" /></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><path id="x2E" d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" /></g><g transform="matrix(.017,-0,0,-.017,34.162,11.112)"><path id="x30" d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105&#xA;q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" /></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,58.64,11.112)"><use xlink:href="#x31"/></g>

		
	
</svg>). Serum and CSF NfH phosphoform levels were not correlated. Baseline serum levels of the NfH-SMI34 were significantly (<svg     style="vertical-align:-0.1638pt;width:50.549999px;" id="M4" height="11.375" version="1.1" viewBox="0 0 50.549999 11.375" width="50.549999"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3C"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,34.162,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x35"/></g>

		
	
</svg>) higher in patients with PPMS (2.05&#x2009;ng/mL) compared to SPMS (0.03&#x2009;ng/mL) and RRMS (1.56&#x2009;ng/mL). In SPMS higher serum than CSF NfH-SMI34 levels predicted disability progression from baseline (<svg     style="vertical-align:-0.20473pt;width:49.287498px;" id="M5" height="11.6875" version="1.1" viewBox="0 0 49.287498 11.6875" width="49.287498"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.363)"><path id="x394" d="M600 0h-557v24l268 633l28 8l261 -641v-24zM497 50l-194 489l-196 -489h390z" /></g><g transform="matrix(.017,-0,0,-.017,10.959,11.363)"><path id="x45" d="M517 162l29 -4q-18 -100 -35 -158h-482v28q68 5 83.5 20t15.5 77v398q0 66 -13 80t-73 19v28h446q0 -8 8 -144l-29 -4q-11 51 -32 85q-11 17 -35 23t-78 6h-76q-23 0 -28 -5t-5 -27v-228h94q67 0 83 12t25 63h29v-191h-29q-10 54 -26 65.5t-81 11.5h-95v-189&#xA;q0 -65 24 -81q19 -13 104 -13q57 0 83 7t43 27q28 33 50 94z" /></g><g transform="matrix(.017,-0,0,-.017,20.614,11.363)"><path id="x44" d="M43 650h280q194 0 282 -85q85 -82 85 -215q0 -173 -123 -267q-107 -83 -297 -83h-236v27q65 5 79.5 19.5t14.5 77.5v402q0 45 -6 62.5t-21.5 24t-57.5 9.5v28zM213 547v-416q0 -55 24.5 -75t81.5 -20q133 0 203 86t70 214q0 80 -30 143t-88 97q-66 41 -170 41&#xA;q-62 0 -78 -13q-13 -9 -13 -57z" /></g><g transform="matrix(.017,-0,0,-.017,33.108,11.363)"><path id="x53" d="M409 504l-29 -5q-16 60 -44.5 96t-86.5 36q-54 0 -82.5 -32t-28.5 -77q0 -51 30.5 -82.5t96.5 -65.5l35.5 -18t33 -19.5t33.5 -23.5l27 -25.5t24.5 -32t13.5 -36.5t6 -45q0 -80 -62 -134.5t-160 -54.5q-47 0 -98 15q-22 7 -50 21q-8 23 -27 155l30 7q7 -27 18 -52&#xA;t30 -51.5t49 -42.5t67 -16q56 0 88 32.5t32 87.5q0 51 -31.5 82t-98.5 67q-80 44 -110 73q-55 53 -55 124q0 75 56 126.5t150 51.5q53 0 126 -23z" /></g><g transform="matrix(.017,-0,0,-.017,41.165,11.363)"><use xlink:href="#x53"/></g>

		
	
</svg> 2, <svg     style="vertical-align:-0.1638pt;width:50.549999px;" id="M6" height="11.375" version="1.1" viewBox="0 0 50.549999 11.375" width="50.549999"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3C"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,34.162,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x35"/></g>

		
	
</svg>). In RRMS higher CSF than serum NfH-SMI35 levels predicted disability progression (<svg     style="vertical-align:-0.20473pt;width:49.287498px;" id="M7" height="11.6875" version="1.1" viewBox="0 0 49.287498 11.6875" width="49.287498"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.363)"><use xlink:href="#x394"/></g><g transform="matrix(.017,-0,0,-.017,10.959,11.363)"><use xlink:href="#x45"/></g><g transform="matrix(.017,-0,0,-.017,20.614,11.363)"><use xlink:href="#x44"/></g><g transform="matrix(.017,-0,0,-.017,33.108,11.363)"><use xlink:href="#x53"/></g><g transform="matrix(.017,-0,0,-.017,41.165,11.363)"><use xlink:href="#x53"/></g>

		
	
</svg> 2, <svg     style="vertical-align:-0.1638pt;width:50.549999px;" id="M8" height="11.375" version="1.1" viewBox="0 0 50.549999 11.375" width="50.549999"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3C"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,34.162,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x35"/></g>

		
	
</svg>). <i  >Conclusion</i>. Serum and CSF NfH-SMI34 and NfH-SMI35 levels did not correlate with each other in MS. The quantitative relationship of CSF and serum NfH levels suggests that neuroaxonal degeneration of the central nervous system is the likely cause for disability progression in RRMS. In more severely disabled patients with PP/SPMS, subtle pathology of the peripheral nervous system cannot be excluded as an alternative source for blood NfH levels. Therefore, the interpretation of blood protein biomarker data in diseases of the central nervous system (CNS) should consider the possibility that pathology of the peripheral nervous system (PNS) may influence the results.

M. J. Eikelenboom

B. M. J. Uitdehaag

A. Petzold

Blood and CSF Biomarker Dynamics in Multiple Sclerosis: Implications for Data Interpretation

Multiple sclerosis (MS) is an immune-mediated disorder; however, little is known about the triggering factors of the abnormal immune response. Different viruses from the herpes family have been mentioned as potential participants. Here, we review the evidences that support the association of varicella zoster virus (VZV) with MS. Epidemiological studies from geographical areas, where incidence of MS has increased in recent decades, pointed out a high frequency of varicella and zoster in the clinical antecedents of MS patients, and also laboratory investigations have found large quantities of DNA from VZV in leucocytes and cerebrospinal fluid of MS patients restricted to the ephemeral period of MS relapse, followed by disappearance of the virus during remission. The above observations and the peculiar features of VZV, mainly characterized by its neurotropism and long periods of latency followed by viral reactivation, support the idea on the participation of VZV in the etiology of MS. However, as with reports from studies with other viruses, particularly Epstein Barr virus, conflicting results on confirmatory studies about the presence of viral gene products in brain tissue indicate the need for further research on the potential participation of VZV in the etiology of MS.

Julio Sotelo

Teresa Corona

Varicella Zoster Virus and Relapsing Remitting Multiple Sclerosis

Multiple sclerosis is a chronic debilitating autoimmune disease of the central nervous system. The contribution of B cells in the pathoetiology of MS has recently been highlighted by the emergence of rituximab, an anti-CD20 monoclonal antibody that specifically depletes B cells, as a potent immunomodulatory therapy for the treatment of MS. However, a clearer understanding of the impact B cells have on the neuro-inflammatory component of MS pathogenesis is needed in order to develop novel therapeutics whose affects on B cells would be beneficial and not harmful. Since T cells are known mediators of the pathology of MS, the goal of this review is to summarize what is known about the interactions between B cells and T cells, and how current and emerging immunotherapies may impact B-T cell interactions in MS.

Sara Ireland

Nancy Monson

Potential Impact of B Cells on T Cell Function in Multiple Sclerosis

Optic neuritis (ON) is an inflammatory optic nerve injury, which is strongly associated with multiple sclerosis (MS). Axonal damage in the optic nerve manifests as retinal nerve fiber layer (RNFL) deficits, which can be readily quantified with optical coherence tomography (OCT).  The RNFL represents the most proximal region of the afferent visual pathway; and, as such, is a unique region of the central nervous system (CNS) because it lacks myelin. Changes in retinal integrity can be correlated with reliable and quantifiable visual outcomes to provide a structural-functional paradigm of CNS injury.  Because the eye provides a unique “view” into the effects of CNS inflammation, the ON “system model” may provide greater understanding about disease mechanisms, which underpin disability in MS.  This review addresses the applications of OCT in study of ON patients, with specific reference to the published reports to date.  The future role of OCT is discussed, both in terms of the potential gains and certain challenges associated with this evolving technology.

Fiona Costello

Evaluating the Use of Optical Coherence Tomography in Optic Neuritis

The focus of this paper is to summarize the current knowledge on visual pathway damage in neuromyelitis optica (NMO) assessed by magnetic resonance imaging (MRI) and optical coherence tomography (OCT).

Caspar F. Pfueller

Friedemann Paul

Imaging the Visual Pathway in Neuromyelitis Optica

Increased iron deposition might be implicated in multiple sclerosis (MS). Recent development of MRI enabled to determine brain iron levels in a quantitative manner, which has put more interest on studying the role of iron in MS. Evidence for abnormal iron homeostasis in MS comes also from analyses of iron and iron-related proteins in CSF and blood and postmortem MS brain sections. However, it is not yet clear if iron accumulation is implicated in MS pathology or merely reflects an epiphenomenon. Further interest has been generated by the idea of chronic cerebrospinal venous insufficiency that might be associated with brain iron accumulation due to a reduction in venous outflow, but its existence and etiologic role in MS are currently controversially debated. In future studies, combined approaches applying quantitative MRI together with CSF and serum analyses of iron and iron-related proteins in a clinical followup setting might help to elucidate the implication of iron accumulation in MS.

Michael Khalil

Charlotte Teunissen

Christian Langkammer

Iron and Neurodegeneration in Multiple Sclerosis

Biomarkers of axonal degeneration have the potential to improve our capacity to predict and monitor neurological outcome in multiple sclerosis (MS) patients. Neurofilament proteins, one of the major proteins expressed within neurons and axons, have been detected in cerebrospinal fluid and blood samples from MS patients and are now being actively investigated for their utility as prognostic indicators of disease progression in MS. In this paper, we summarize the current literature on neurofilament structure, assembly, and degeneration and discuss their potential utility as biomarkers for monitoring neurological decline in MS. We also discuss the need to further develop sensitive methods for assaying neurofilaments in blood to improve clinical applicability.

Melissa M. Gresle

Helmut Butzkueven

Gerry Shaw

Neurofilament Proteins as Body Fluid Biomarkers of Neurodegeneration in Multiple Sclerosis

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<p><em>Multiple Sclerosis International</em> publishes articles related to all aspects of multiple sclerosis, such as clinical neurology, neuroimaging, neuropathology, neuroimmunology, biomarkers, psychology and neurorehabilitation.</p>


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Multiple Sclerosis International - Table of contents 2011

Multiple Sclerosis International | Hindawi

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Multiple Sclerosis International publishes articles related to all aspects of multiple sclerosis, such as clinical neurology, neuroimaging, neuropathology, neuroimmunology, biomarkers, psychology and neurorehabilitation.

Multiple Sclerosis International