Persistently reduced humoral and sustained cellular immune response from first to third SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients.

OBJECTIVE: To examine humoral and cellular response in multiple sclerosis patients on anti-CD20 therapy after third BNT162b2 mRNA SARS-CoV-2 vaccination. METHODS: A prospective longitudinal study design from first throughout third vaccination in Danish and American MS centers. All participants were treated with ocrelizumab. Antibody (Ab) levels were assessed before and after third vaccination using SARS-CoV-2 IgG II Quant assay (Abbott Laboratories). B- and T-lymphocytes enumeration was done with BD Multitest™6-color TBNK reagent. Spike-specific T-cell responses were measured through PBMC stimulation with spike peptide pools (JPT Peptide Technologies). RESULTS: We found that 14.0%, 37.7%, and 33.3% were seropositive after first, second and third vaccination. The median Ab-levels were 74.2 BAU/mL (range: 8.5-2427) after second vaccination, as well as 43.7 BAU/ml (range: 7.8-366.1) and 31.3 BAU/mL (range: 7.9-507.0) before and after third vaccination, respectively. No difference was found in levels after second and third vaccination (p = 0.1475). Seropositivity dropped to 25.0% of participants before the third vaccination, a relative reduction of 33.3% (p = 0.0020). No difference was found between frequencies of spike reactive CD4+and CD8+ T-cells after second (0.65 ± 0.08% and 0.95 ± 0.20%, respectively) and third vaccination (0.99 ± 0.22% and 1.3 ± 0.34%, respectively). CONCLUSION: In this longitudinal cohort we found no significant increased humoral or cellular response with administration of a third SARS-CoV-2 mRNA vaccination. These findings suggest the need for clinical strategies to include allowance of B cell reconstitution before repeat vaccination and/or provision of pre-exposure prophylactic monoclonal antibodies.

The operational definition of epileptiform discharges significantly improves diagnostic accuracy and inter-rater agreement of trainees in EEG reading.

To assess whether trainees can learn and implement the operational definition of interictal epileptiform discharges (IEDs) of the International Federation of Clinical Neurophysiology (IFCN), based on six morphological criteria, and whether its implementation improves their diagnostic performance and inter-rater agreement (IRA). Seven trainees evaluated a balanced dataset of 70 EEG samples containing sharp transients (35 from patients with epilepsy and 35 from patients with non-epileptic paroxysmal events). The gold standard was derived from video-EEG recordings of the habitual clinical episodes. The trainees individually reviewed the EEGs, blinded to all other data, in two successive training sessions, three months apart. The second session was preceded by a teaching module about the IFCN criteria, and the trainees implemented them during the second reading session. By implementing the IFCN criteria, trainees significantly improved their specificity (94.29% vs. 77.14%; p=0.01) and overall accuracy (81.43% vs. 64.29%; p=0.01) for identifying IEDs. Sensitivity also improved but did not reach the level of statistical significance (77.14% vs. 60%; p=0.07). IRA improved significantly from fair (k=0.31; 95% CI: 0.22-0.40) to high-moderate (k=0.56; 95% CI:0.46-0.67) beyond-chance agreement. Implementing the IFCN criteria significantly improves the diagnostic performance and IRA of trainees in identifying IEDs. Teaching the IFCN criteria for IEDs will increase specificity in clinical EEG and avoid over-reading, the most common cause of misdiagnosing epilepsy.

Reducing delay of carotid endarterectomy in acute ischemic stroke patients: a nationwide initiative.

BACKGROUND AND PURPOSE: Guidelines recommend carotid endarterectomy (CEA) within 2 weeks from an ischemic event. However, previous studies have shown that only a minority of patients undergo CEA within this period. The aim of this study was to examine the effect of a multidisciplinary nationwide initiative aimed at reducing time to CEA after acute ischemic stroke. METHODS: We examined a historic population-based observational cohort based on individual patient-level records from the Danish Stroke Registry and the Danish Vascular Registry. The implementation of early ultrasound examination of the carotids (within 4 days from admission) in medical departments coupled with fast CEA after referral to a department of vascular surgery were monitored and audited systematically from 2008 and onward. RESULTS: A total of 813 acute ischemic stroke patients underwent CEA during 2007-2010. The percentage of patients undergoing CEA within 2 weeks increased from 13% in 2007 to 47% in 2010 (adjusted odds ratio, 5.8 [95% CI, 3.4-10.1]). The overall median time decreased from 31 days to 16 days. The percentage of relevant acute ischemic stroke patients receiving early ultrasound examination of the carotids increased from 41% in 2008 to 72% in 2010. The time from referral to operation at a vascular department was reduced by ≈40%. CONCLUSIONS: Establishing time limits of 4 days to ultrasound examination of the carotids and of 2 weeks to CEA from onset of stroke followed by a systematic multidisciplinary monitoring and auditing of processes was associated with a substantial increase in the proportion of acute ischemic stroke patients who undergo CEA within 2 weeks in Denmark.