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

Objective. To correlate visual and neurologic
clinical scores and treatment of optic neuritis and multiple
sclerosis (MS) patients with assays of serum phosphorylated
neurofilament heavy chain (pNF-H) and optical coherence tomography
(OCT) measurements of axonal loss. 
Design/Methods. The Optic Neuritis Treatment
Trial (ONTT) randomized 457 patients with acute optic neuritis to
intravenous methylprednisolone (IVMP) followed by oral prednisone,
oral prednisone or placebo treatment arms. We quantified serum
pNF-H levels in 175 ONTT patients 5 years after study entry. We
performed OCT measurements of macular volume and the retinal nerve
fiber layer (RNFL) in a subset of 51 patients at year 15. 
Results. Elevated pNF-H levels at year 5
correlated to poorer visual function at study entry. Lower 15 year
macular volumes and RNFL thickness correlated better with
follow-up than with baseline visual function measures. With IVMP
treatment, 15 year RNFL differences of the fellow eye (FE) minus
the affected eye (SE) RNFLFEmSE correlated with five-year pNF-H
levels. PNF-H was reduced by half with IVMP relative to placebo or
by 40&#x25; relative to prednisone. 
Conclusions/Relevance. Acute optic neuritis
patients who have more severe visual loss during initial
presentation have a higher incidence of axonal loss that was
slightly suppressed with IVMP treatment.

Joshua Pasol

William Feuer

Cui Yang

Gerry Shaw

Randy Kardon

John Guy

Phosphorylated 
                        Neurofilament Heavy Chain Correlations to 
                        Visual Function, Optical Coherence 
                        Tomography, and Treatment

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

Neurofilament Proteins as Body Fluid Biomarkers of Neurodegeneration in Multiple Sclerosis

Immunosuppressive therapy is an established therapeutic option in patients suffering from multiple sclerosis (MS). In an open nonrandomized study we serially assessed cardiac function in 30 consecutive patients with MS before, during, and after mitoxantrone therapy. Mitoxantrone (12&#x2009;mg/m2) was administered intravenously at 3-month intervals. Before each infusion, cardiac function was assessed by history taking, resting electrocardiogram, and echocardiography. Whereas no patient experienced clinical signs of heart failure, left ventricular pump function decreased continuously during mitoxantrone therapy and did not recover after cessation. The presented data suggest a dose-dependent and long-lasting toxic cardiac effect of low-dose mitoxantrone therapy in MS.

Damian Franzen

Angelika Haus

Martin Hellmich

Serial Assessment of Cardiac Function during and  following Mitoxantrone Infusion in 30 Consecutive  Patients with Multiple Sclerosis

Online health information and services for patients were suggested to improve symptom management and treatment adherence, thereby contributing to healthcare optimization. This paper aimed to characterize multiple sclerosis (MS) patients Internet usage. Information regarding browsing habits, Internet reliability, and the medical team's attitude to information collected online was obtained by questionnaires from MS patients. Data was compared between nonbrowsers, browsers on MS topics, and browsers on non-MS topics only. From the 96 patients recruited, 61 (63.5&#37;) performed MS-related searches. The most viewed topics were &#x0201c;understanding the disease&#x0201d; and &#x0201c;treatments&#x0201d;. Patients reported that the information helped coping with MS and assured them of the appropriateness of their therapy. Shorter disease duration was correlated with higher Internet activity. Disabled patients were more interested in online interaction with specialists and support groups. This paper suggests that MS patients benefit from online information, and it emphasizes the importance of resources tailored to patients needs.

Izabella Lejbkowicz

Tamar Paperna

Nili Stein

Sara Dishon

Ariel Miller

Internet Usage by Patients with Multiple Sclerosis: Implications to Participatory Medicine and Personalized Healthcare

About this journal

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

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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