Background

The visual pathway has emerged as an elective platform to study the interaction between demyelination and neurodegeneration in multiple sclerosis (MS)

Objectives

We specifically assessed neural damage at this level in progressive MS (PMS), also exploring the evolution over time of functional (trough visual evoked potentials - VEPs) and structural (trough optical coherence tomography - OCT) parameters, as well as their relations with disease course and clinical disability.

Methods

We performed a prospective longitudinal study enrolling 350 PMS patients (228 secondary progressive MS - SPMS, 122 primary progressive MS - PPMS) who underwent a cross-sectional evaluation comprehensive of Expanded Disability Statur Scale (EDSS) assessment, high (HCVA)- and low-contrast (LCLA) visual acuity test, full-field (ff-VEPs) as well as multifocal (mf-VEPs) VEPs, and OCT. We performed a follow-up assessment (mean interval 2.0±0.9 years) in 147 patients (52 PPMS and 95 SPMS); a parallel collection of clinical records (including reports MRI scans, performed as per clinical practice) has been also obtained.

Results

Independently from previous optic neuritis (ON), we found visual conduction to be slower among SPMS compared to PPMS patients, particularly for mf-VEPs: mean latency 168.9 ms (95% CI 166.2-171.1) vs 163.8 ms (95% CI 160.7-166.9) respectively, p=0.019. Retinal Nerve Fiber Layer (RNFL) was also found to be thinner among SPMS in comparison to PPMS patients: mean 83.4 μm (95% CI 81.4-85.4) vs 87.0 μm (95% CI 84.4-89.6), p=0.040, with similar results for Ganglion Cell-Inner Plexiform Layer (GCIPL). Considering the evolution over time of functional and structural parameters, we found no significant differences comparing PPMS and SPMS patients. Reclassifying our cohort according to EDSS status (“stable” vs “worsened”) we found a significant between-groups difference in terms of RNFL evolution: mean annualized percent change -0.163 %/year (95% CI -0.467 - -0.141) vs -0.854 %/year (95% CI -1.188 - -0.521) respectively, p=0.003. Similar findings were obtained for GCIPL change. In both cases, these observations were independent from the evidence of MRI activity during follow-up.

Conclusions

our results suggest the presence of a greater functional and structural involvement of the visual system among SPMS compared to PPMS patients, independently from previous ON history; follow-up data suggest however neurodegeneration accrual over time to be similar between these two clinical subgroups. The longitudinal relation between RNFL - GCIPL thinning and EDSS worsening, even in the absence of overt MRI activity and/or clinical relapses, suggests OCT to represent a useful tool to monitor disease progression and to assess neuroprotection in PMS.

Background

Cognitive impairment (CI) affects nearly 30% of paediatric patients with Multiple Sclerosis (MS) and has a negative impact on school performance and participation in social activities. This study is a re-appraisal of cognitive functioning and socio-professional attainment in adulthood in an Italian cohort of paediatric MS patients after 10 years from baseline neuropsychological assessment.

Objectives

To re-assess cognitive performance and its impact on socio-professional attainment in our cohort of paediatric MS patients after 10 years from baseline evaluation and to determine predictors of the individual outcomes.

Methods

Sixty-three paediatric patients were assessed at baseline and 48 followed-up after five years. To date, 31 out of these 48 patients (17 females, mean age 27.9±2.5 years, mean EDSS 1.7±1.6) were reassessed on an extensive neuropsychological battery and compared with a matched group of 31 healthy controls. CI was defined as the failure of > 2 tests. Socio-professional attainment was evaluated on the Work and Social Assessment Scale (WSAS). Predictors of CI and WSAS score were assessed through multivariable logistic and linear models.

Results

After a mean follow-up of 12.5±2.3 years, 15 (54%) subjects were classified as cognitively impaired. Patients with CI compared with those cognitively preserved at follow-up had higher Expanded Disability Status Scale (EDSS) score (1.9±1.4 vs 1.0±0.7; p = 0.046), lower baseline intelligence quotient (IQ) (86.2±23.8 vs 103.6±14.7; p = 0.025) and were less frequently treated with disease modifying therapy (DMT) at baseline [6 (35.3%) vs 11 (78.6%); p = 0.016]. In the regression model, CI after 10 years was related to lower IQ (OR 0.93, 95% CI 0.87-0.99, p = 0. 027) and absence of DMT at baseline assessment (OR 17.78 95%; 1.72-183.65, p = 0.017).

Baseline predictors of worse socio-professional attainment on the WSAS in adulthood were CI (B=6.3, p=0.016), higher EDSS (B=2.2, p=0.023) and higher age at onset (B=0.6, p=0.041). As for 10-year correlates, only CI was associated to poor functional outcome (B=5.2, p=0.006).

Conclusions

Complete data collection is ongoing; available findings to date show that in paediatric onset subjects CI remains significant in adulthood, is related to lower cognitive reserve, higher levels of neurological impairment and delay in DMT initiation. Moreover, CI plays a key role in predicting the subject social performance and professional outcome. Early treatment and promotion of strategies aimed at enhancing cognitive reserve are recommended in paediatric patients with MS.