This Week in Neurology — Sep 16, 2026

Welcome to This Week in Neurology. This week we're covering 10 notable papers spanning secondary stroke prevention and the limits of revascularization, the diagnosis and outcomes of treatable cognitive syndromes, and a cluster of trials and cohorts in epilepsy and neuromuscular disease. Let's dive in.

We start with cerebrovascular disease, where one paper expands what we can offer and another closes a door. In Neurology, Katsanos and colleagues pooled three randomized trials of factor XIa inhibitors added to standard antiplatelet therapy after noncardioembolic ischemic stroke or transient ischemic attack, covering just over fourteen thousand participants, though the estimates are largely driven by a single large phase 3 trial of more than twelve thousand patients [1]. Adding a factor XIa inhibitor cut the risk of any stroke by about a quarter, with a similar reduction in ischemic stroke and a smaller but real reduction in composite cardiovascular events. Crucially, there was no signal of harm: major bleeding, hemorrhagic stroke, intracranial hemorrhage, any bleeding and all-cause mortality were all statistically indistinguishable from placebo. That is the whole premise of this drug class made good on in humans, decoupling thrombosis from hemostasis. For now this is not a prescription you can write, but it is the shape of secondary prevention to come, and it is worth knowing which of your recurrent-stroke patients might be trial candidates.

The counterpoint comes from JAMA, where Marshall and colleagues report CREST-H, the cognitive substudy nested inside the CREST-2 trial [2]. The hypothesis was attractive: if asymptomatic high-grade carotid stenosis impairs cognition through chronic hypoperfusion, then the patients with measurable hemodynamic impairment on perfusion imaging should be the ones whose thinking improves after revascularization. Nearly four hundred participants were enrolled across sixty-one North American sites, with time-to-peak delay used to grade hemodynamic impairment, and the key analysis focused on the roughly fifty participants who had reduced cognition at baseline. Over one year there was no difference in the composite cognitive score between revascularization plus intensive medical management and intensive medical management alone, and no interaction with hemodynamic status. Both groups drifted slightly upward, consistent with practice effects rather than treatment. The honest reading is that restoring flow does not fix cognition in chronic asymptomatic carotid disease, and the subgroup carrying the primary analysis was small. When a patient or a referring surgeon raises cognitive decline as an indication for carotid intervention, you now have randomized data to say no.

Our second theme is cognitive syndromes we are still under-diagnosing. JAMA also published a comprehensive review of idiopathic normal pressure hydrocephalus by Maroufi and colleagues, and the epidemiology alone justifies attention: somewhere between one and four percent of adults over sixty-five, rising to six to eight percent of those over eighty [3]. Gait disturbance is the earliest and most consistent feature, present in the large majority of patients, with urinary dysfunction and a frontal-subcortical cognitive profile following. The practical message is that imaging establishes the diagnosis but does not predict who will respond. The review is emphatic that patients under evaluation should undergo large-volume lumbar puncture with removal of thirty to fifty millilitres of cerebrospinal fluid, with objective gait measures repeated within hours, and that extended lumbar drainage of two hundred to three hundred millilitres over several days gives better prognostic accuracy when clinical suspicion is high but the tap result is equivocal. After shunting, roughly three quarters of patients gain gait velocity and around half to two thirds improve cognitively or urologically, against shunt complication rates in the ten to thirty percent range for over- and under-drainage. And because shorter symptom duration predicts better outcome, delay is itself a treatment decision.

Under-recognition is also the theme of a JAMA Neurology cohort from Coffi and colleagues, who used the clinical data warehouse of the Greater Paris hospital system to assemble more than thirteen hundred adults diagnosed with Korsakoff syndrome [4]. Two findings should change how you think about these patients. First, among the well-documented subgroup, only about one in five had any recorded history of Wernicke encephalopathy, which means the acute, treatable phase is being missed almost routinely. Second, this is not a static amnestic condition to be parked in long-term care: about thirty percent OF PATIENTS died over a median follow-up of just over three years, with malnutrition, alcoholic liver disease, male sex and advanced age each independently associated with mortality. On imaging, abnormalities in the Papez circuit and vascular leukoencephalopathy were each seen in a little over forty percent OF THOSE SCANNED, underlining the vascular comorbidity burden. The practice implication is aggressive thiamine repletion and nutritional management in anyone with alcohol use disorder and confusion, long before amnesia becomes fixed.

Turning to epilepsy, three papers address timing, prevention and prognosis. In Epilepsia, Pelliccia and colleagues studied two hundred and fourteen patients with focal structural epilepsy from focal cortical dysplasia type two, hippocampal sclerosis or low-grade epilepsy-associated tumours, comparing drug-sensitive patients who went to surgery, drug-resistant patients who went to surgery, and drug-resistant patients managed medically [5]. Drug-sensitive patients operated on early achieved complete seizure freedom in eighty-six percent of cases, against sixty-nine percent in the drug-resistant surgical group. Just as important, the drug-sensitive patients started with fewer cognitive deficits and better quality of life, and those measures stayed stable after surgery, while the medically managed drug-resistant group showed a mild decline in verbal and visuospatial memory. This is a prospective-retrospective design with one year of follow-up, not a randomized trial, so causal claims are limited, but it argues for referring patients with a clear structural lesion for surgical evaluation before pharmacoresistance is formally established.

Also in Epilepsia, Orlandi and colleagues asked whether statins act as antiepileptogenic agents after status epilepticus, using a prospectively maintained registry of three hundred and fourteen adults surviving a first-ever episode [6]. About one in five developed a remote unprovoked seizure, with cumulative risk rising to roughly a third by five years and most events occurring within the first year. After adjustment, patients taking statins after the index event had about half the risk of a remote seizure. This is retrospective and confounding by indication cuts both ways, so nobody should start a statin for seizure prevention, but it is a hypothesis worth a proper trial. And in Neurology, Tokatly Latzer and colleagues analysed one hundred and fifty-two longitudinal EEGs from forty-eight infants with CDKL5 deficiency disorder [7]. The background worsens progressively across the first two years, with nine months emerging as the age that best discriminates high-severity epileptiform burden. Epileptic spasms and tonic seizures dominate, often occurring in sequence, and parieto-occipital paroxysmal fast activity, while not specific, is highly suggestive of the diagnosis and correlated with worse developmental scores.

Finally, therapeutics and diagnostics in neuromuscular and degenerative disease. JAMA Neurology reports a double-blind randomized trial from Özkaynar and colleagues testing three cycles of intravenous immunoglobulin added to standard high-dose prednisone in adults with newly diagnosed idiopathic inflammatory myopathy [8]. Forty-two patients reached the primary endpoint, and the mean Total Improvement Score at twelve weeks was sixty in the immunoglobulin arm against about forty-three on placebo. Moderate improvement was reached by ninety-one percent of the immunoglobulin group versus roughly half of the placebo group, major improvement by seventy percent versus about a quarter, and the median time to response was four weeks rather than twelve. One asymptomatic deep vein thrombosis was the notable safety event. It is a single tertiary centre and a small sample, but it supports front-loading immunoglobulin in newly diagnosed myositis rather than reserving it for steroid failure. In Movement Disorders, Shen and colleagues randomized one hundred and sixteen patients with spinocerebellar ataxia type three to oral DL-3-n-butylphthalide or placebo for twelve months [9]. Both primary endpoints favoured treatment, but the ataxia scale difference was under one point, which is of uncertain clinical meaning; adverse events were not significantly different and no serious events occurred. Call it preliminary evidence deserving replication. And in Brain, Benatar and colleagues offer a corrective on amyotrophic lateral sclerosis biomarkers, arguing that almost all diagnostic biomarker studies in the field test samples from patients in whom the diagnosis is already obvious, which tells you nothing about predictive value in the uncertain cases where a test would actually help [10]. If you referee or read biomarker papers, that framing is worth internalising.

If you only have time for one paper this week, make it the factor XIa inhibitor meta-analysis in Neurology [1]. It is the first credible sign in years that we can add anticoagulant efficacy to antiplatelet therapy after noncardioembolic stroke without paying for it in bleeding, and it will shape the secondary prevention conversation for the rest of the decade.

Here are the key takeaways from this week in Neurology. Factor XIa inhibition after noncardioembolic stroke cut recurrent stroke by about a quarter with no excess bleeding, but remains investigational. Carotid revascularization does not improve cognition in asymptomatic stenosis, even in patients with measurable hemodynamic impairment, so stop offering it on that basis. In suspected normal pressure hydrocephalus, imaging does not predict shunt response, so proceed to large-volume lumbar puncture with objective gait testing, and do it early. Wernicke encephalopathy is being missed in most patients who go on to develop Korsakoff syndrome, and those patients face substantial mortality driven by malnutrition and liver disease. And in focal structural epilepsy, earlier surgical referral is associated with better seizure freedom and preserved cognition, while add-on immunoglobulin produces faster, larger improvement in newly diagnosed inflammatory myopathy.

That's your roundup for This Week in Neurology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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