This week in Neurology

This AudioScholar briefing is generated by artificial intelligence for healthcare professionals and trainees. It is not medical advice.

Welcome to This Week in Neurology. This week we're covering 10 notable papers spanning acute stroke reperfusion, stroke diagnosis and secondary prevention, and refractory epilepsy, with a closing look at delirium and long-term cognition. Let's dive in.

Reperfusion therapy keeps expanding, and this week's papers ask a sharper question: which patients actually benefit, and when does more treatment start to harm? Grotta, writing a review in the New England Journal of Medicine, sets the scene [1]. He describes the shift from alteplase toward tenecteplase, the broadening indications for intravenous thrombolysis, and the unresolved challenge of integrating thrombolysis with thrombectomy for large vessel occlusion. Two secondary analyses in Stroke then probe the edges of that integration. Zhang and colleagues reported a prespecified analysis of the ANGEL-TNK trial, in which patients with anterior circulation large vessel occlusion who achieved at least partial reperfusion after thrombectomy were randomized to intra-arterial tenecteplase at 0.125 milligrams per kilogram or standard care [2]. The benefit concentrated entirely in patients with incomplete reperfusion, those graded eTICI 2b50 to 67, where an excellent 90-day outcome roughly doubled, from about one in five patients to just under half. In patients with near-complete or complete reperfusion there was no benefit, and any intracranial hemorrhage became more common, although symptomatic hemorrhage and death did not differ. This is a subgroup analysis of one open-label trial of 253 patients, so it generates a hypothesis about selecting patients by residual perfusion rather than settling the question. Kurmann and colleagues, also in Stroke, turned to medium and distal vessel occlusion, where the DISTAL trial found no net benefit of thrombectomy [3]. Using a machine learning model trained on a Bernese registry to predict who would recover well on medical therapy alone, they found that in patients predicted to do well, thrombectomy was associated with roughly halved odds of a better 90-day disability score, meaning harm, while patients predicted to do poorly saw no effect either way. Strikingly, a simple cutoff of an admission NIH Stroke Scale score of 4 or less performed about as well as the model. As a post hoc analysis, this cannot prove harm, but it strengthens the argument that the neutral DISTAL result may conceal real damage in mildly affected patients.

One population almost always excluded from these trials is pregnant patients, and Payne and colleagues in Neurology pooled 216 published cases of thrombolysis during pregnancy, 85 for ischemic stroke [4]. Of 32 fetal deaths, six were judged likely caused by the thrombolytic, three of them in stroke. Miscarriage and stillbirth rates ran somewhat higher than general population benchmarks, but symptomatic intracerebral hemorrhage in mothers was similar to young nonpregnant patients. Published case series carry obvious reporting bias, and the authors themselves caution that disease and drug effects are hard to separate, but they conclude the data broadly support thrombolysis in otherwise eligible pregnant patients with careful risk-benefit discussion.

Our second theme moves from the hyperacute window to the diagnostic workup and secondary prevention that follow. Tanaka and colleagues in Stroke pooled individual data from three cohorts, about two thousand patients with transient neurological events and a normal examination, to ask whether the ABCD2 score still adds anything once diffusion-weighted imaging is known [5]. In patients with a positive scan, ABCD2 did not meaningfully separate risk, with 90-day stroke rates around 3 to 4 percent across all score bands. In patients with a negative scan, the score did discriminate, and those with low scores and negative imaging had a 90-day stroke risk of about one percent. With only 53 strokes in total, the estimates are imprecise, but the findings suggest ABCD2 is most informative when imaging is negative and adds little once a lesion is seen.

For intracerebral hemorrhage, Beaufort and colleagues in Neurology tested whether arterial spin labeling MRI, a noninvasive perfusion sequence, can rule out arteriovenous shunts, the leading secondary cause of hemorrhage [6]. In a prospective study of 277 consecutive adults across three French centers, 24 patients had a confirmed shunt, almost all arteriovenous malformations. Arterial spin labeling detected all but one, and its negative predictive value was close to perfect, at about 99.6 percent. Every shunt seen on initial angiography was caught, and three shunts were visible on arterial spin labeling before angiography found them. The positive predictive value was modest, at about six in ten, so false positives remain common, and the cohort included only one dural fistula. The authors propose arterial spin labeling as a gatekeeper to catheter angiography, explicitly pending external validation.

On secondary prevention, Papageorgiou and colleagues in Stroke conducted a network meta-analysis of six trials covering more than eighteen thousand patients with atrial fibrillation and prior stroke or transient ischemic attack [7]. Compared with warfarin, apixaban was the only agent to reduce both any stroke and major bleeding, each by roughly a quarter, while edoxaban was the only one linked to lower cardiovascular and all-cause mortality. Dabigatran, apixaban, and edoxaban all reduced intracranial hemorrhage, rivaroxaban did not reach significance on bleeding outcomes, and importantly, indirect comparisons showed no significant differences between the direct oral anticoagulants themselves. Because each drug rests on a single warfarin-controlled trial, the paper reinforces the class advantage over warfarin without establishing a winner within the class.

Turning to epilepsy, two Neurology papers address patients whose seizures resist standard approaches. Campos-Fernandez and colleagues described 31 adults with focal refractory or super-refractory status epilepticus who received cenobamate, typically after five other antiseizure medications had failed, starting at a median dose of 50 milligrams a day [8]. Sustained resolution occurred in about 84 percent of patients, including all 17 with refractory status and about two thirds of those with super-refractory status, with response after a median of two days. In a propensity-matched comparison, resolution was more frequent with cenobamate, about 82 versus 57 percent, and there were no serious drug-related adverse events, though somnolence was common. This is retrospective Class IV evidence from a small cohort, and the slow titration usually required for cenobamate makes prospective confirmation important before it moves into status protocols.

Ivaniuk and colleagues pooled 272 patients with germline genetic epilepsies, excluding tuberous sclerosis, who underwent resection or laser ablation [9]. Outcomes split cleanly by biological pathway: roughly two thirds or more of patients with vascular disorders or GATOR pathway variants became seizure free, compared with about 30 percent of patients with channelopathies and about 22 percent with synaptopathies. That gap persisted even when MRI lesions were present. The data are largely from published case reports with variable follow-up, but they suggest genotype may refine surgical counseling beyond imaging alone, and the authors call for genotype-aware surgical registries.

Finally, in JAMA Neurology, Palmer and colleagues used the Mayo Clinic Study of Aging to follow about 3,500 hospitalized adults without dementia for a median of seven years [10]. Delirium, identified by a natural language processing algorithm in clinical notes, was documented in only 75 participants, but it was associated with roughly a fourfold higher risk of mild cognitive impairment and about a fivefold higher risk of dementia, along with faster decline on serial neuropsychological testing. The observational design cannot show causation, and the low detection rate suggests many delirium episodes went uncaptured, but the strength of the association in cognitively unimpaired adults adds weight to delirium as a marker, and possibly a driver, of long-term decline.

If you only have time for one paper this week, make it the arterial spin labeling study in Neurology [6]. It offers prospective, blinded evidence that a widely available MRI sequence can reliably exclude arteriovenous shunts after intracerebral hemorrhage, reopening the question of which patients truly need catheter angiography.

That's your roundup for This Week in Neurology. The full transcript and references are available on the episode page. See you next week.

If this weekly briefing is useful, follow the show in your podcast app so new episodes arrive automatically. And if you have a paper you have been meaning to read, upload the PDF, or paste any link, at audioscholar dot C C. We will turn it into audio like this one, in any of thirty-one languages.

This is an automated summary generated by artificial intelligence, which can make mistakes. Always review the original source materials.