Selected highlights from the European Academy of Neurology annual meeting, Vienna, Austria, June 25-28, 2022.
NfL, GFAP elevated post-COVID
Long-term data for anti-CD20 agents
Improved cognitive processing speed with ofatumumab
Cognitive impairment may predict physical disability
B cell kinetics during pregnancy
Clinical tip of the day
CONGRESS HIGHLIGHTS – THURSDAY EDITION
Fluid biomarkers of neuroaxonal damage are elevated in hospitalized COVID patients without a history of neurological disorders (Plantone et al. EAN 2022; OPR-034). Mean serum neurofilament light (sNfL) level was significantly higher in COVID patients (38.02 pg/mL) compared to that of patients with non-COVID pneumonia (13.63 pg/mL) or healthy controls (6.65 pg/mL). Mean serum glial fibrillary acidic protein (GFAP) was also elevated (232.98 vs. 145.32 and 84.12, respectively). The authors concluded that COVID infection may be associated with neuronal and glial degeneration that is independent of neurological disease.
A separate study looked at the use of sNfL and sGFAP in 259 progressive MS patients seen in clinical practice (Barro et al. EAN 2022; OPR-136). Patients were examined within six months of their first EDSS score >3.0. Baseline sNfL or sGFAP level was not useful for discriminating between patients with active vs. non-active disease. A higher baseline sNfL level was predictive of inflammatory disease activity over the next two years and was associated with future cognitive decline. A higher sGFAP level was associated with a higher risk of six-month confirmed disability progression (HR 1.71); interestingly, this association was stronger in patients with lower sNfL levels (HR 2.44).
An analysis of the OPERA I/II long-term extension reported good outcomes in the subgroup of newly-diagnosed patients (n=756) (Cerqueira et al. EAN 2022; OPR-135). In the continuous ocrelizumab group, 50.97% had no evidence of disease activity (NEDA) at week 286 (5.5 years); MRI was rebaselined at week 24. The proportion with 24-week confirmed disability progression at year 7 (week 364) was about 22%. Time to 24-week CDP was not significantly different in the continuous ocrelizumab vs. IFN/ocrelizumab groups.
In the long-term extension of the ASCLEPIOS trials, annualized relapse rate remained low in the group on continuous ofatumumab after four years (0.05); the cumulative rate of three-month confirmed disability progression was 18% (Kappos et al. EAN 2022; EPR-161). The mean number of Gd+ lesions and new T2 lesions was 0.01 and 0.07, respectively. The NEDA rate at four years was 31.5% with continuous ofatumumab.
An analysis of data (N=1882) from the ASCLEPIOS trials reported that ofatumumab significantly improved cognitive processing speed as assessed by the Symbol Digit Modalities Test (SDMT) compared to teriflunomide (Benedict et al. EAN 2022; OPR-130). The mean change from baseline in SDMT score was 3.50 with ofatumumab compared to 2.39 with teriflunomide at month 24. Mean change in the newly-diagnosed subgroup was 4.29 and 2.56, respectively, at month 24. The proportion of patients with clinically significant sustained improvement (>4-point change) was 25.0% with ofatumumab vs. 19.6% with teriflunomide. The proportion showing cognitive improvement was somewhat higher (26.9%) in younger recently-diagnosed patients. The authors concluded that earlier use of high-efficacy therapy may preserve cognitive function.
MS patients with worse SDMT scores had worse EDSS disability outcomes, according to an analysis of the EXPAND trial of siponimod (Penner et al. EAN 2022; OPR-120). Patients were stratified by baseline SDMT score and on-study SDMT change. The risk of reaching EDSS >7 was higher for patients in the worst vs. best quartile both in the full study group and in the siponimod-treated arm. The authors concluded that changes in cognitive processing speed may help to identify patients at risk of disability progression.
The BABIES study examined changes in B cell subsets in untreated MS patients during pregnancy and postpartum (Landi et al. EAN 2022; EPR-095). The preliminary results indicated a reduction in the number and percentage of CD19+ B cells during pregnancy. Reductions were seen in naïve transitional immature B cells (CD24+CD38+) and memory cells (CD27+). Mature naïve B cells (CD27-) increased. Antibody-producing plasmablasts significantly increased in peripheral blood. IgG/IgA switched memory cells increased while IgM cells decreased. All changes were rapidly reversed after childbirth. The authors noted that B cell changes during pregnancy may provide a clue as to the more pathogenic subsets in MS.
Screening for depression may be advised in patients presenting with persistent cognitive symptoms after COVID-19 hospitalization (Cristillo et al. EAN 2022; EPO-541). An Italian study reported that at one year post-hospitalization, 22% of patients had subjective cognitive complaints (SCC, ‘brain fog’), including difficulty focusing, confusion and forgetfulness. Objective findings included lower scores on the Montreal Cognitive Assessment (MoCA) scale and higher scores on the impact of event scale and Fatigue Symptom Scale. However, depression scale scores were most strongly correlated with brain fog.