by Viktoria Papp
Each month the EANpages editorial team reviews the scientific press for recently published papers of outstanding interest to neurologists. Below we present our selection for November 2024.
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1) Tenecteplase versus alteplase for acute stroke within 4.5 h of onset (ATTEST-2): a randomised, parallel group, open-label trial (Lancet Neurol.)
The results of the ATTEST-2 study may shape the future of acute stroke treatment. This large, prospective, randomised, parallel-group, open-label, non-inferiority trial from the UK compared the effect of tenecteplase, a modified plasminogen activator, to the current standard treatment with alteplase within 4.5 hours after stroke onset. The longer half-time of tenecteplase allows the administration of a single bolus, providing several practical advantages. Data obtained from 1,777 1:1 randomised patients showed that the functional outcome (distribution of modified Rankin Scale at day 90, proportion of patients with excellent recovery) in the tenecteplase-treated group was non-inferior to the alteplase-treated group but did not reach the superiority margin. There was no significant difference between the groups in adverse events. These non-inferiority data suggest that tenecteplase with its easier administration may be the preferred choice for clinical use over alteplase. The results of the ATTEST-2 study may shape the future of acute stroke treatment.
2) Antiseizure Medications and Cardiovascular Events in Older People With Epilepsy (JAMA Neurol.)
This large Canadian prospective cohort study, with 6 years of follow-up on 51,338 individuals between the ages of 45 and 85, evaluated the implication of epilepsy and enzyme-inducing antiseizure medications on the risk of new-onset cardiovascular events. Of the 27,230 individuals included, 431 had a history of epilepsy. Data revealed that individuals in this age group with epilepsy had 2.2 times higher odds of new-onset cardiovascular events compared to those without epilepsy, and one third of these events are linked to the use of enzyme-inducing antiseizure medications. Therefore, when initiating antiseizure medicines in older patients at risk of cardiovascular events, carefulness is necessary.
3) High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity (Nat Med)
This is a prospective ex vivo study on profiling drug responses in single-cell maps in tissue samples from 27 patients diagnosed with glioblastoma. Using complex model systems and machine learning, the study group discovered a convergent drug–target connectivity trademark predictive of anti-glioblastoma efficacy in drugs. This pathway was AP-1/BTG-driven glioblastoma suppression, also confirmed by deep multimodal profiling. They found that the most promising drug, an anti-depressant, vortioxetine, targeting this neural activity-like signalling, caused considerable neurophysiological and transcriptional response and resulted in cell death in glioblastoma. The hopeful result of vortioxetine should be tested in the clinical world as an add-on to the current standard care.
4) Acetyl-DL-leucine in two individuals with REM sleep behavior disorder improves symptoms, reverses loss of striatal dopamine-transporter binding and stabilizes pathological metabolic brain pattern—case reports (Nat Commun)
This is an encouraging case report of two patients with REM sleep behaviour, a potential prodroma of Parkinson’s disease (PD), who were treated with the modified amino acid acetyl-D-leucine (ADLL). The mechanism of action is repairing metabolic dysfunction and improving adenosine triphosphate (ATP) production. Clinical evaluation and imaging techniques such as dopamine-transporter (DAT) ligand-binding imaging (DAT-SPECT) and 18F-Fluorodeoxyglucose PET showed improvements in the patient’s symptoms, recovery of the loss of dopamine-transporter binding in the nigrostriatal system and prevention of further deterioration in the pathological brain metabolism. These findings may provide a foundation for further evaluation of possible disease-modifying effects of ADLL in prodromal PD.
