Elena Fraga-Pumar

Trans-Synaptic Axonal Degeneration in the Visual Pathway in Multiple Sclerosis

To evaluate the association between the damage to the anterior and posterior visual pathway as evidence of the presence of retrograde and anterograde trans‐synaptic degeneration in multiple sclerosis (MS).

Dynamics of retinal injury after acute optic neuritis

We set out to assess the dynamics of retinal injury after acute optic neuritis (ON) and their association with clinical visual outcomes.

The visual pathway as a model to understand brain damage in multiple sclerosis.

Patients with multiple sclerosis (MS) almost always experience effects in the visual pathway; and thus, visual dysfunction is not only common but also highly relevant. The visual pathway represents a model of acute focal central nervous system (CNS) damage, through acute optic neuritis and retinal periphlebitis, as well as a model of chronic, diffuse CNS damage through chronic retinopathy and optic neuropathy. The optic pathway can be accurately evaluated in detail, due to the availability of highly sensitive imaging techniques (e.g. magnetic resonance imaging or optical coherent tomography) or electrophysiological tests (multifocal visual evoked potentials or electroretinography). These techniques allow the interactions between the different processes at play to be evaluated, such as inflammation, demyelination, axonal damage and neurodegeneration. Moreover, these features mean that the visual pathway can be used as a model to test new neuroprotective or regenerative therapies.

Colour vision impairment is associated with disease severity in multiple sclerosis

Background: Colour vision assessment correlates with damage of the visual pathway and might be informative of overall brain damage in multiple sclerosis (MS). Objective: The objective of this paper is to investigate the association between impaired colour vision and disease severity. Methods: We performed neurological and ophthalmic examinations, as well as magnetic resonance imaging (MRI) and optical coherence tomography (OCT) analyses, on 108 MS patients, both at baseline and after a follow-up of one year. Colour vision was evaluated by Hardy, Rand and Rittler plates. Dyschromatopsia was defined if colour vision was impaired in either eye, except for participants with optic neuritis (ON), for whom only the unaffected eye was considered. We used general linear models adjusted for sex, age, disease duration and MS treatment for comparing presence of dyschromatopsia and disease severity. Results: Impaired colour vision in non-ON eyes was detected in 21 out of 108 patients at baseline. At baseline, patients with dyschromatopsia had lower Multiple Sclerosis Functional Composite (MSFC) scores and Brief Repeatable Battery-Neuropsychology executive function scores than those participants with normal colour vision. In addition, these patients had thinner retinal nerve fiber layer (RNFL), and smaller macular volume, normalized brain volume and normalized gray matter volume (NGMV) at baseline. Moreover, participants with incident dyschromatopsia after one-year follow-up had a greater disability measured by the Expanded Disability Status Scale and MSFC-20 and a greater decrease in NGMV than participants with normal colour vision. Conclusions: Colour vision impairment is associated with greater MS severity.

Retinal periphlebitis is associated with multiple sclerosis severity

Objectives: To assess the association of primary retinal inflammation, namely retinal periphlebitis (RP) and microcystic macular edema, with clinical, brain, and retinal imaging biomarkers of multiple sclerosis (MS) severity. Methods: One hundred patients with MS underwent a neurologic and ophthalmic examination, MRI, and optical coherence tomography. Disability was assessed using the Expanded Disability Status Scale at baseline and after a 1-year follow-up. The normalized brain volume, the normal-appearing gray matter volume, and T1 lesion volume were assessed at baseline as radiologic biomarkers of disease severity. Retinal nerve fiber layer thickness and macular volume at baseline were used as surrogate markers of axonal damage. We used general linear models adjusted for sex, age, disease duration, and MS treatment to compared adjusted means of these parameters among patients with RP and patients without primary retinal inflammation. Results: Five patients showed RP, 2 showed microcystic macular edema, and the retina was normal in the remaining 93. Patients with RP had a tendency toward a higher adjusted-mean Expanded Disability Status Scale score at baseline and disability progression after a 1-year follow-up compared with patients without primary retinal inflammation. These patients also had a higher adjusted-mean T1 lesion volume (adjusted differences: 10.4, 95% confidence interval [CI]: 0.6 to 20.2; p = 0.038) and lower T1 brain volume (adjusted differences: −68, 95% CI: −139 to 2; p = 0.059). Patients with RP had a lower adjusted-mean retinal nerve fiber layer thickness (adjusted differences: −13.4, 95% CI: −24.4 to −2.3; p = 0.018) and a trend toward lower macular volume. Conclusions: These results support the role of RP as a biomarker of MS severity.

Is the incidence of optic neuritis rising? Evidence from an epidemiological study in Barcelona (Spain), 2008–2012

Abstract It is currently believed that the incidence rate of optic neuritis (ON) ranges between 0.56 and 5.1 cases per 100,000 person-years. However, since these figures were generated, they have not been updated and there are suggestions that the incidence of ON is on the rise. When designing new therapies and clinical trials for ON, and to improve the management this disease, it is important to have accurate epidemiological data. Thus, we set out to obtain the prevalence and incidence rates of ON in Barcelona (Spain) from 2008 to 2012, by a retrospective evaluation of electronic hospital records at the Hospital Clinic of Barcelona (population of 300,000 in the catchment area) matching the following ICD-9-CM codes as search terms: 377.3-optic neuritis; 377.30-optic neuritis, unspecific; 377.31-optic papillitis; 377.32-retrobulbar neuritis, acute; 377.39-other optic neuritis and “optic neuropathy”. Demographic and clinical data were collected from records with a confirmed diagnosis of ON, including cases of idiopathic ON, multiple sclerosis, neuromyelitis optica and CRION. The prevalence of acute ON on 31 December 2012 was 2.75 cases per 100,000 people. The mean annual prevalence of acute ON during the 2008–2012 period was 7.87 cases per 100,000 person-year and the mean annual incidence rate was 5.36 cases per 100,000 person-years. The incidence of ON in Barcelona during 2008–2012 was higher than previously reported. This increase may reflect the evolution of diagnostic criteria, the use of a referral-center approach instead of a population-based approach, increased awareness of demyelinating diseases, latitude-related factors and possibly a true increase in its incidence.

The multiple sclerosis visual pathway cohort: understanding neurodegeneration in MS

BackgroundMultiple Sclerosis (MS) is an immune-mediated disease of the Central Nervous System with two major underlying etiopathogenic processes: inflammation and neurodegeneration. The latter determines the prognosis of this disease. MS is the main cause of non-traumatic disability in middle-aged populations.FindingsThe MS-VisualPath Cohort was set up to study the neurodegenerative component of MS using advanced imaging techniques by focusing on analysis of the visual pathway in a middle-aged MS population in Barcelona, Spain. We started the recruitment of patients in the early phase of MS in 2010 and it remains permanently open. All patients undergo a complete neurological and ophthalmological examination including measurements of physical and disability (Expanded Disability Status Scale; Multiple Sclerosis Functional Composite and neuropsychological tests), disease activity (relapses) and visual function testing (visual acuity, color vision and visual field). The MS-VisualPath protocol also assesses the presence of anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), general quality of life (SF-36) and visual quality of life (25-Item National Eye Institute Visual Function Questionnaire with the 10-Item Neuro-Ophthalmic Supplement). In addition, the imaging protocol includes both retinal (Optical Coherence Tomography and Wide-Field Fundus Imaging) and brain imaging (Magnetic Resonance Imaging). Finally, multifocal Visual Evoked Potentials are used to perform neurophysiological assessment of the visual pathway.DiscussionThe analysis of the visual pathway with advance imaging and electrophysilogical tools in parallel with clinical information will provide significant and new knowledge regarding neurodegeneration in MS and provide new clinical and imaging biomarkers to help monitor disease progression in these patients.

Retrograde retinal damage after acute optic tract lesion in MS

The anterior visual pathway is frequently affected in multiple sclerosis (MS), but how axonal damage extends from the site of the lesion to neuronal bodies in the retina or lateral geniculate nucleus is poorly understood. Thanks to optical coherence tomography (OCT), it is possible to map and quantify the retrograde diffusion of axonal damage to the retina.1 Lesions in the anterior optic pathway promote significant atrophy of retinal nerve fibre layer (RNFL), which develops in the first 3 months after damage and remains stable after 3 months. Moreover, it has been recently demonstrated that retinal damage in MS is complex and may distinctly affect retinal layers, combining either layer thinning (suggesting the presence of synapse loss and neuronal loss) or layer thickening (suggesting the presence of oedema and inflammation). In fact, the analysis of the ganglion cell/inner plexiform layer (ganglion cell layer (GCL)+inner plexiform layer complex (IPL)) and inner nuclear layer (INL) better correlates with functional disability and prognosis than with RNFL atrophy.2 Acute focal lesions of the optic tracts are infrequently recognised in MS, and they constitute an excellent opportunity to study retrograde axonal degeneration. Previous studies with OCT have shown the homonymous hemimacular atrophy ipsilateral to the optic tract lesion as a specific pattern of retinal atrophy in optic tract lesions,3 with a preferential impact on the GCL.4 A patient with relapsing–remitting MS presented with non-painful, new onset, acute bilateral visual deficit. Automated visual field tests demonstrated non-congruent bilateral homonymous right hemianopsia (figure 1A). Visual acuity (Snellen chart) and colour …