Pathophysiological basis of low contrast visual acuity loss in multiple sclerosis

Triplett, James; Yiannikas, Con; Barnett, Michael; Parratt, John; Barton, Joshua; Graham, Stuart L.; You, Yuyi; Klistorner, Alexander

doi:10.1002/acn3.659

Cited by 8 publications

(12 citation statements)

References 38 publications

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“…The level and topography of demyelination in the visual pathways was assessed by the latency delay of mfVEP recorded using the Vision Search system (VisionSearch, Sydney, Australia) with standard stimulus conditions as described previously. 16,20 In brief, 4 gold-disc electrodes (Grass, West Warwick, RI) were used for bipolar recording with 2 electrodes positioned 4 cm on either side of the inion, one electrode 2.5 cm above and another 4.5 cm below the inion in the midline. Electrical signals were recorded along 2 channels, measured as the difference between superior and inferior and between the left and right electrodes.…”

Section: Multifocal Vep Recordingsmentioning

confidence: 99%

Chronic demyelination exacerbates neuroaxonal loss in patients with MS with unilateral optic neuritis

You¹,

Barnett²,

Yiannikas

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo examine the effect of chronic demyelination in the optic nerve of patients with MS on progressive loss of retinal ganglion cell (RGC) axons.MethodsProgressive retinal nerve fiber layer (RNFL) loss, as measured by optical coherence tomography, was longitudinally examined in 51 patients with MS with a history of unilateral optic neuritis (ON) and 25 normal controls. Patients were examined annually with a median of 4-year follow-up. Pairwise intereye comparison was performed between ON and fellow non-ON (NON) eyes of patients with MS using the linear mixed-effects model and survival analysis. The latency asymmetry of multifocal visual evoked potential (mfVEP) was used to determine the level of demyelination in the optic nerve.ResultsAlthough both ON and NON eyes demonstrate significantly faster loss of RGC axons compared with normal subjects, ON eyes with severe chronic demyelination show accelerated thinning in the RNFL in the temporal sector of the optic disc (temporal RNFL [tRNFL]) compared with fellow eyes (evidenced by both the linear mixed-effects model and survival analysis). Furthermore, progressive tRNFL thinning is associated with the degree of optic nerve demyelination and reflects the topography of pathology in the optic nerve. More rapid axonal loss in ON eyes is also functionally evidenced by mfVEP amplitude reduction, which correlates with the level of optic nerve demyelination.ConclusionsAlthough the effect of demyelination on axonal survival has been demonstrated in experimental studies, our results provide first clinically meaningful evidence that chronic demyelination is associated with progressive axonal loss in human MS.

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Section: Multifocal Vep Recordingsmentioning

confidence: 99%

Chronic demyelination exacerbates neuroaxonal loss in patients with MS with unilateral optic neuritis

You¹,

Barnett²,

Yiannikas

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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“…Interocular latency tended to be high in groups of patients with ON due to the functional differences between eyes in unilateral ON cases. Previous papers [48] found a significant increase in mfVEP latency in ON eyes compared to fellow (non-ON) eyes.…”

Section: Resultsmentioning

confidence: 90%

A computer-aided diagnosis of multiple sclerosis based on mfVEP recordings

et al. 2019

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Introduction The aim of this study is to develop a computer-aided diagnosis system to identify subjects at differing stages of development of multiple sclerosis (MS) using multifocal visual-evoked potentials (mfVEPs). Using an automatic classifier, diagnosis is performed first on the eyes and then on the subjects. Patients MfVEP signals were obtained from patients with Radiologically Isolated Syndrome (RIS) (n = 30 eyes), patients with Clinically Isolated Syndrome (CIS) (n = 62 eyes), patients with definite MS (n = 56 eyes) and 22 control subjects (n = 44 eyes). The CIS and MS groups were divided into two subgroups: those with eyes affected by optic neuritis (ON) and those without (non-ON). Methods For individual eye diagnosis, a feature vector was formed with information about the intensity, latency and singular values of the mfVEP signals. A flat multiclass classifier (FMC) and a hierarchical classifier (HC) were tested and both were implemented using the k-Nearest Neighbour (k-NN) algorithm. The output of the best eye classifier was used to classify the subjects. In the event of divergence, the eye with the best mfVEP recording was selected. Results In the eye classifier, the HC performed better than the FMC (accuracy = 0.74 and extended Matthew Correlation Coefficient (MCC) = 0.68). In the subject classification, accuracy = 0.95 and MCC = 0.93, confirming that it may be a promising tool for MS diagnosis. Conclusion In addition to amplitude (axonal loss) and latency (demyelination), it has shown that the singular values of the mfVEP signals provide discriminatory information that may be used to identify subjects with differing degrees of the disease.

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“…13 The substrate of LCVA damage in ON and MS is complex. Both pRNFL and mfVEP latency have been shown to correlate with LCVA in MS eyes with previous ON, 10 though the contribution of axonal damage seemed more pronounced. 10 The timing of the follow-up visit (⩾90 days) was a point of discussion between the co-authors.…”

Section: Discussionmentioning

confidence: 96%

“…Using inter-eye asymmetry measures may minimize the inherent risk of inter-person variability and possible effect of retrochiasmal demyelinating lesion load. 10 Inter-eye asymmetry measures were, therefore, used for LCVA, OCT and mfVEP measures in the correlation analyses. In healthy control subjects, the inter-eye asymmetry of mfVEP amplitudes and latencies were calculated as the absolute difference between eyes, since we did not expect laterality.…”

Section: Trial Subjectsmentioning

confidence: 99%

“…[4][5][6][7] GCLIPL thickness compared with pRNFL may be less confounded by gliosis and oedema 7 and correlates better with multifocal VEP (mfVEP) and LCVA in MS eyes with and without previous ON. 7,8 correlation with OCT signs of axonal loss and with remyelination in MS 10 and tends to show lasting deficits even in the case of complete recovery of highcontrast visual acuity (HCVA) following ON. 5 ffVEP measurements have been associated with visual outcome 11 and axonal loss 12,13 following ON in some studies although not in others.…”

Section: Introductionmentioning

confidence: 99%

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Multifocal visual evoked potential evaluation for diagnosis of acute optic neuritis and for prediction of visual outcome and ganglion cell layer thinning following optic neuritis

2020

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Background:: While damage to the optic nerve following optic neuritis (ON) is readily quantifiable, the evaluation of prognosis for visual function and neuroaxonal loss in the acute ON is challenging. Objective:: The objective of this study is to investigate the value of multifocal visual evoked potential (mfVEP) in acute ON, diagnostically for acute ON and prognostically for visual outcome and subsequent ganglion cell/inner plexiform layer thickness (GCLIPLt). Methods:: A prospective cohort study of mfVEP and full-field visual evoked potential (ffVEP) in acute, unilateral ON (onset < 31 days) was conducted. Comparisons with healthy controls ( n = 30) and association analysis with follow-up optical coherence tomography (OCT) measurements (of the GCLIPLt) and visual function (Sloan low-contrast visual acuity (LCVA)) were conducted. Results:: Seventy-nine ON patients were included (mean: 17 days from onset). Excluding measurements with conduction block, ffVEP ( n = 54) and mfVEP ( n = 44) showed sensitivities of 89% and 84% to a specificity of 97%. 65/79 patients were re-examined (mean: 200 days follow-up). mfVEP amplitude and latency inter-eye asymmetry in acute ON correlated with GCLIPLt ( r = 0.587 and Spearman’s ρ = 0.597, for both, p < 0.001). mfVEP amplitude correlated with LCVA inter-eye asymmetry at follow-up ( r = 0.421, p < 0.001), mfVEP latency did not. Conclusion: mfVEP may support the prognostic evaluation of acute ON patients and prove valuable in future neuroprotective and remyelinating trials. In acute ON, the increase in diagnostic value of mfVEP to ffVEP may be limited due to widespread conduction block.

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Pathophysiological basis of low contrast visual acuity loss in multiple sclerosis

Cited by 8 publications

References 38 publications

Chronic demyelination exacerbates neuroaxonal loss in patients with MS with unilateral optic neuritis

Chronic demyelination exacerbates neuroaxonal loss in patients with MS with unilateral optic neuritis

A computer-aided diagnosis of multiple sclerosis based on mfVEP recordings

Multifocal visual evoked potential evaluation for diagnosis of acute optic neuritis and for prediction of visual outcome and ganglion cell layer thinning following optic neuritis

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