The following are some of the highlights of research presented at the 7th Congress of the European Academy of Neurology, held 19-22 June 2021.
DMTs in development
CNS/PNS complications: A Danish study reported that 28 of 61 consecutive COVID-19 patients admitted to hospital had CNS/PNS complications (Nersesjan et al. EAN 2021; OPR-140). The most common complication was encephalopathy (31%); other complications included ischemic stroke, acute necrotizing encephalitis and transverse myelitis. The most common PNS complication was polyneuromyopathy. Most complications were secondary to critical illness or other causes. There was no evidence of CNS infection by CoV-2; laboratory changes implicated autoimmune-mediated mechanisms in some cases.
A survey of patients hospitalized for COVID-19 found that 77% reported at least one neurological sequela, such as insomnia (65.9%), daytime somnolence (46.3%), walking difficulties (31.7%), headache (15.1%), hyposmia/hypogeusia (15.1%) and tremor (9.4%) (Pozzato et al. EAN 2021; EPR-131).
No CNS infection with CoV-2: An analysis of CSF samples of COVID-19 patients with neurological complications vs. neurological controls reported no evidence of CoV-2 invasion of the CNS (Bernard-Valnet et al. EAN 2021; OPR-053). In the COVID group, CoV-2 RNA was found in 0 of 17 CSF samples; intrathecal synthesis of CoV-2 antibodies was found in 2 of 16 samples.
COVID and MS: A study in Belgium of 28 MS patients (mean age 36.4 years) on DMTs reported a good overall outcome after COVID infection (Elands et al. EAN 2021; EPR-070). An Austrian study of 73 MS patients (mean age 41 years) with COVID-19 found no association between DMT use and COVID severity after adjusting for known risk factors (age, comorbidity, disability) (Guger et al. EAN 2021; EPR-066). There was a trend to greater COVID severity with DMT exposure (odds ratio 1.6) that did not achieve significance. Overall, 87.5% had a mild COVID course and 9.7% had a severe course. The mortality rate was 2.8%. A separate study by the Milan group found that COVID risk factors in MS patients were lower premorbid vitamin D levels (31 vs 40 ng/mL) and a slightly higher neutrophil count (3.80 vs 3.18 x 109/L).
Effects on MS disease course: A preliminary analysis of MS patients who developed COVID found no clinical/radiological worsening at 6-month follow-up (Chyzhyk et al. EAN 2021; EPO-084). In one patient hospitalized with severe COVID, there were no signs of MS disease activity on contrast-enhanced MRI at 6 months.
Effect on cognition: An Italian study performed neurocognitive testing on 38 patients (aged 22-74 years) about five months after hospitalization for severe COVID-19 (Dini et al. EAN 2021; EPO-227). Overall, 42.1% had processing speed deficits on SDMT. Acute respiratory distress syndrome in hospital was associated with delayed verbal recall deficits on SRT-D and worse verbal long-term memory performance.
Leptomeningeal contrast enhancement (LMCE): Meningeal inflammation is associated with cortical demyelination and disability progression in MS and the presence of LMCE on 3D-FLAIR MRI has been proposed as an imaging biomarker of meningeal inflammation (Titelbaum et al. J Neuroimaging 2020;30:917-929). Less is known about more common meningeal enhancement patterns, such as dura mater (DME) and vessel wall enhancement (VWE) (Hildesheim et al. Mult Scler Relat Disord 2021;47:102653).
A new study retrospectively examined the MRIs of 70 patients (mean age 47 years) with RRMS or PPMS treated with anti-CD20 therapies (Friedli et al. EAN 2021; OPR-114). Overall, 83% had no LMCE, 10% had persistent LMCE and 7% (4 RRMS patients) had resolution of LMCE during treatment with ocrelizumab. While this may indicate a treatment effect, it should be noted that LMCE has also been reported to resolve spontaneously or following corticosteroid therapy (Bonnan et al. Neurol Sci 2021;42:1959-1961. Titelbaum 2020).
Ublituximab: The ULTIMATE I/II trials reported results for ublituximab, an anti-CD20 therapy administered in a 1-hour infusion every 24 weeks (Steinman et al. EAN 2021; OPR-086). The studies randomized 1094 RRMS patients to ublituximab or teriflunomide for 96 weeks. Ublituximab was associated with a significant 60% and 50% reduction in annualized relapse rate vs. teriflunomide in the two studies.
NfL: A European study examined factors influencing serum neurofilament-light chain (sNfL) levels in 292 subjects (Pirpamer et al. EAN 2021; EPR-077). Age was the most important predictor of sNfL levels. In individuals aged 38-60 years, body-mass index (BMI) was an independent predictor. Predictors in other age groups were BMI, glomerular filtration rate and lactate dehydrogenase in those aged 60-69 years; and creatinine and erythrocyte count in those aged >70 years.
CXCL12/osteopontin: A CSF analysis reported elevated levels of the chemokine CXCL12 (odds ratio 3.97) and osteopontin (OR 2.24) in PPMS vs. RRMS patients (Marastoni et al. EAN 2021; OPR-010). CXCL12 levels were correlated with grey-matter lesion number and volume. The authors proposed that CXCL12 and osteopontin, as indicators of innate immune activation in the CNS, may be useful biomarkers of progression in MS.
GFAP: Levels of glial fibrillary acidic protein (GFAP), a filament expressed by astrocytes, were assessed in a post-hoc analysis of the SUNBEAM trial of ozanimod vs. IFN-beta-1a IM (Harris et al. EAN 2021; OPR-087). At baseline, GFAP levels were unrelated to relapse history and weakly correlated with NfL. During treatment, GFAP was weakly related to relapses, lesion counts and whole-brain volume.