Optical Coherence Tomography and Visual Evoked Potentials as Prognostic and Monitoring Tools in Progressive Multiple Sclerosis

Guerrieri, Simone; Comi, Giancarlo; Leocani, Letizia

doi:10.3389/fnins.2021.692599

Cited by 19 publications

(11 citation statements)

References 92 publications

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“…In fact, 21% of our 181 patients at diagnosis showed a prolonged P100 latency in non–ON eyes, and irrespectively from a history of contralateral ON. Seven (18%) patients with abnormal VEPs in clinically unaffected eyes showed a progressive MS course at diagnosis, according to previous data [ 14 ]. A role of VEPs in progressive MS was suggested by Sater et al that presented P100 latency as a tool for monitoring disease course in 11 patients [ 15 ].…”

Section: Discussionsupporting

confidence: 66%

Prognostic Role of Visual Evoked Potentials in Non-Neuritic Eyes at Multiple Sclerosis Diagnosis

Vecchio

Barbero

Galli

et al. 2023

JCM

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Introduction: This study aimed to assess the prognostic role of visual evoked potentials (VEPs) of the non-neuritic eye at the diagnosis of multiple sclerosis (MS). Patients and methods: We enrolled 181 MS patients (62% females, mean age at diagnosis: 38 years, standard deviation: 12) at the time of the first diagnostic work-up, including VEPs. We collected P100 latency and N75-P100 amplitude of non-neuritic eyes at diagnosis, and then we calculated the mean values in 127 patients with no history of optic neuritis (ON) or considered the unaffected eye in the remaining. At last follow-up (minimum: one year), disability was evaluated according to MS Severity Score or MSSS (median: 2.44, range: 0.18–9.63). Statistical analysis included Mann–Whitney descriptive analysis, Spearman correlation for independent samples, and linear regression for significant predictors of MSSS. Results: 38/181 patients had P100 latency >115 ms, and 63/181 showed N75-P100 amplitude < 5 microV in the unaffected eyes at MS diagnosis. At last follow-up, MSSS correlated with P100 latency (rho = 0.21, p = 0.004) and N75-P100 amplitude (rho = 0.19, p = 0.009) collected at diagnosis. P100 latency (not N75-P100 amplitude) resulted in a predictor for disability over time (MSSS) in the regression model (along with age at onset, MS course, and disease-modifying treatments). Conclusions: Our study showed a prognostic value of VEPs in clinically unaffected eyes at MS diagnosis to predict future disability, independently from a history of ON.

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Section: Discussionsupporting

confidence: 66%

Prognostic Role of Visual Evoked Potentials in Non-Neuritic Eyes at Multiple Sclerosis Diagnosis

Vecchio

Barbero

Galli

et al. 2023

JCM

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“…In addition, the 9-HPT score, which is more sensitive than EDSS in identifying a worsening in more advanced stages of the disease, showed a worsening in the 2-year follow-up. Despite pRNFL thickness being considered a potential biomarker of neuroaxonal loss, representing a reliable objective tool to assess novel neuroprotective therapies in PMS 17 , our patients did not show significant pRNFL variation over time. Cognitive dysfunction with impaired information processing speed significantly contributes to disability in PMS 18 .…”

Section: Discussioncontrasting

confidence: 64%

“…Despite pRNFL thickness being considered a potential biomarker of neuroaxonal loss, representing a reliable objective tool to assess novel neuroprotective therapies in PMS 17 , our patients did not show significant pRNFL variation over time. Cognitive dysfunction with impaired information processing speed significantly contributes to disability in PMS 18 .…”

Section: Discussioncontrasting

confidence: 64%

Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study

Genchi

Brambilla

Sangalli

et al. 2023

Nat Med

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Innovative pro-regenerative treatment strategies for progressive multiple sclerosis (PMS), combining neuroprotection and immunomodulation, represent an unmet need. Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis have shown preclinical efficacy by promoting neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. Here we present the results of STEMS, a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial (NCT03269071, EudraCT 2016-002020-86), performed at San Raffaele Hospital in Milan, Italy, evaluating the feasibility, safety and tolerability of intrathecally transplanted human fetal NPCs (hfNPCs) in 12 patients with PMS (with evidence of disease progression, Expanded Disability Status Scale ≥6.5, age 18–55 years, disease duration 2–20 years, without any alternative approved therapy). The safety primary outcome was reached, with no severe adverse reactions related to hfNPCs at 2-year follow-up, clearly demonstrating that hfNPC therapy in PMS is feasible, safe and tolerable. Exploratory secondary analyses showed a lower rate of brain atrophy in patients receiving the highest dosage of hfNPCs and increased cerebrospinal fluid levels of anti-inflammatory and neuroprotective molecules. Although preliminary, these results support the rationale and value of future clinical studies with the highest dose of hfNPCs in a larger cohort of patients.

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“…The abnormalities in electrical conduction may be measured using evoked potentials (EPs) (Leocani and Comi, 2014). In particular, the visual system offers a unique opportunity to study non-invasively the effects of subclinical relapses in patients with MS over time, through the combination of functional information from visual EPs and structural information from optical coherence tomography (OCT) (Costello and Burton, 2018;Guerrieri et al, 2021). These tools were revealed to be useful in testing remyelinating treatments in clinical trials (Cadavid et al, 2017), and are feasible in pre-clinical settings (Marenna et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Visual Evoked Potentials to Monitor Myelin Cuprizone-Induced Functional Changes

et al. 2022

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The visual system is one of the most accessible routes to study the central nervous system under pathological conditions, such as in multiple sclerosis (MS). Non-invasive visual evoked potential (VEP) and optical coherence tomography (OCT) were used to assess visual function and neuroretinal thickness in C57BL/6 taking 0.2% cuprizone for 7 weeks and at 5, 8, 12, and 15 days after returning to a normal diet. VEPs were significantly delayed starting from 4 weeks on cuprizone, with progressive recovery off cuprizone, becoming significant at day 8, complete at day 15. In contrast, OCT and neurofilament staining showed no significant axonal thinning. Optic nerve histology indicated that whilst there was significant myelin loss at 7 weeks on the cuprizone diet compared with healthy mice, at 15 days off cuprizone diet demyelination was significantly less severe. The number of Iba 1+ cells was found increased in cuprizone mice at 7 weeks on and 15 days off cuprizone. The combined use of VEPs and OCT allowed us to characterize non-invasively, in vivo, the functional and structural changes associated with demyelination and remyelination in a preclinical model of MS. This approach contributes to the non-invasive study of possible effective treatments to promote remyelination in demyelinating pathologies.

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Optical Coherence Tomography and Visual Evoked Potentials as Prognostic and Monitoring Tools in Progressive Multiple Sclerosis

Cited by 19 publications

References 92 publications

Prognostic Role of Visual Evoked Potentials in Non-Neuritic Eyes at Multiple Sclerosis Diagnosis

Prognostic Role of Visual Evoked Potentials in Non-Neuritic Eyes at Multiple Sclerosis Diagnosis

Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study

Visual Evoked Potentials to Monitor Myelin Cuprizone-Induced Functional Changes

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