Utility of quantitative MRI metrics in brain ageing research

19 May

Multicentre analysis of seizure outcome predicted by removal of high-frequency oscillations

In drug-resistant focal epilepsy, planning surgical resection can involve presurgical intracranial EEG (iEEG) recordings to detect seizures and other iEEG patterns to improve postsurgical seizure outcome. We hypothesized that resection of tissue generating interictal high-frequency oscillations (HFOs, 80-500 Hz) in the iEEG predicts surgical outcome. In eight international epilepsy centres, iEEG was recorded during the presurgical evaluation of patients. The patients were of all ages, had epilepsy of all types, and underwent surgical resection of a single focus aiming at seizure freedom. In a prospective analysis, we applied a fully automated definition of HFO that was independent of the dataset. Using an observational cohort design that was blinded to postsurgical seizure outcome, we analysed HFO rates during non-rapid-eye-movement sleep. If channels had consistently high rates over multiple epochs, they were labelled the 'HFO area'. After HFO analysis, centres provided the electrode contacts located in the resected volume and the seizure outcome at follow-up ≥24 months after surgery. The study was registered at www.clinicaltrials.gov (NCT05332990). We received 160 iEEG datasets. In 146 datasets (91%), the HFO area could be defined. The patients with a completely resected HFO area were more likely to achieve seizure freedom in comparison to those without [odds ratio 2.61, 95% confidence interval (CI) 1.15-5.91, P = 0.02]. 

19 May

Subcutaneous Ocrelizumab in Patients With Multiple Sclerosis: Results of the Phase 3 OCARINA II Study

Background and objectives: IV-administered ocrelizumab (OCR) is approved for the treatment of relapsing and primary progressive multiple sclerosis (RMS/PPMS). OCARINA II (NCT05232825) was designed to demonstrate noninferiority in drug exposure of OCR subcutaneous (SC) vs IV administration.

Methods: This phase 3, randomized, open-label study enrolled OCR-naive patients aged 18-65 years with RMS/PPMS and an Expanded Disability Status Scale score of 0-6.5. Patients received OCR IV 600 mg or OCR SC 920 mg (controlled period), followed by OCR SC 920 mg every 24 weeks, up to week 96 (OCR IV/SC and OCR SC/SC). The primary end point was OCR area under the serum concentration-time curve from day 1 to week 12 (AUC_W1‒12); other end points included clinical, biomarker, and pharmacodynamic outcomes and safety data.

Results: Baseline demographics were balanced across OCR IV/SC and OCR SC/SC arms (N = 118/118, 40.0 ± 11.9/39.9 ± 11.4 years, 59.3%/65.3% female, 89.0%/89.0% with RMS). The study demonstrated noninferiority of OCR SC 920 mg to OCR IV 600 mg for the primary end point AUC_W1-12 and also over the dosing interval for AUC_W1‒24 (geometric mean ratios [90% CI] 1.29 [1.23-1.35] and 1.27 [1.21-1.34], respectively). At week 48, 111 of 118 (OCR IV/SC) and 114 of 118 (OCR SC/SC) had received OCR SC.