This Week in Neurology — May 28, 2026

Welcome to This Week in Neurology. This week we're covering 8 notable papers spanning advances in acute stroke care, the rapidly evolving diagnostic landscape for neurodegenerative diseases, and new therapeutic options for conditions like Duchenne muscular dystrophy and Tourette syndrome. Let's dive in.

First, in stroke, two papers explore optimizing care at different stages of the patient journey, from pre-hospital management to specific in-hospital interventions. A study in the journal *Stroke* evaluated the impact of mobile stroke units, or MSUs, on the management of intracerebral hemorrhage [5]. While MSUs are well-studied for ischemic stroke, their role in ICH has been less clear. This retrospective analysis from the Cleveland Clinic and Stony Brook University compared 218 patients with ICH managed by an MSU to 192 managed by conventional emergency medical services. The results showed a significant time savings with MSU deployment. Time to diagnosis via CT scan was reduced by 28 percent. More critically, MSUs enabled much faster blood pressure control. Antihypertensive medications were administered 54 percent sooner to patients in the MSU group. This led to 87 percent of MSU patients achieving their goal blood pressure within one hour from last known well, compared to only 60 percent in the conventional EMS group. This provides strong evidence that the benefits of MSUs extend to hemorrhagic stroke, facilitating faster diagnosis and goal-directed medical therapy.

Moving from pre-hospital to in-hospital care, a paper in *Neurology* addresses a common clinical question: the role of IV thrombolysis before thrombectomy for large vessel occlusions caused by carotid artery dissection [3]. The benefit of this bridging therapy has been uncertain. Using data from two large registries, investigators analyzed 1,091 patients with anterior circulation LVO from carotid artery dissection. About half received IV thrombolysis, or IVT, before their thrombectomy, while the other half proceeded directly to thrombectomy. After adjusting for baseline differences, the group that received IVT had a higher likelihood of a favorable functional outcome at 3 months, with an adjusted risk ratio of 1.16. They were also significantly more likely to achieve successful reperfusion. Importantly, this benefit came without an associated increase in symptomatic intracranial hemorrhage. A subgroup analysis suggested the functional benefit was most pronounced in patients presenting with more severe strokes, as indicated by higher admission NIH Stroke Scale scores. This study provides reassurance that for patients with LVO from carotid dissection, bridging with IVT before thrombectomy is not only safe but is associated with improved reperfusion and functional outcomes.

Next, we turn to neurodegeneration, where a major theme this week is the quest for better biomarkers to diagnose and stage disease, moving from invasive methods toward blood tests and advanced imaging.

Leading the way is a report in *JAMA Neurology* on a new plasma-based model for the biological staging of Alzheimer disease [8]. Current staging often requires PET imaging or CSF analysis. This study sought to develop a more accessible blood-based approach. Using data from the BioFINDER-2 and Knight ADRC cohorts, researchers developed a model based on two plasma markers: the percentage of p-tau217, and a novel marker called eMTBR-tau243. This two-marker model demonstrated high concordance with established PET-based staging, with a C index of 0.91. This was superior to a model using p-tau217 alone, particularly for classifying intermediate stages of tau pathology. The plasma-based staging also correlated well with clinical severity and, in a subsample with brain autopsies, was strongly aligned with confirmed Alzheimer disease neuropathologic changes. This work represents a significant step toward a scalable, minimally invasive approach that could bring biological staging of Alzheimer's into routine clinical practice.

While that paper tackles Alzheimer's, two others address the challenge of diagnosing synucleinopathies. A common problem is differentiating multiple system atrophy, or MSA, from Parkinson's disease. A paper in *Cell* reports a potentially breakthrough biomarker that offers specificity [6]. While alpha-synuclein seed amplification assays can detect synucleinopathy, they don't reliably distinguish between disorders. This research team identified a different protein, tubulin polymerization promoting protein, or TPPP/p25. They found that in MSA, this protein misfolds and forms amyloid seeds. Based on this, they developed a seed amplification assay using a portion of the TPPP/p25 protein, which they tested on cerebrospinal fluid. The assay robustly differentiated patients with MSA from those with Parkinson's disease and other neurodegenerative conditions. This establishes misfolded TPPP/p25 as a promising and highly specific biomarker for the diagnosis of MSA.

Complementing this fluid biomarker work, a third paper in *Science Translational Medicine* describes the first-in-human evaluation of a PET tracer designed to visualize alpha-synuclein aggregates in the brain [4]. The tracer, called [C]MODAG-005, showed high affinity for alpha-synuclein fibrils in preclinical studies. In this first-in-human study, PET imaging demonstrated tracer binding in brain regions known to be affected by alpha-synuclein pathology in patients with both MSA and Parkinson's disease. While still early, the development of a reliable alpha-synuclein PET tracer would be revolutionary for early diagnosis, tracking disease progression, and measuring the effects of new therapies for these devastating disorders.

In therapeutics, two studies offer new options for challenging movement and neuromuscular disorders, focusing on maintaining efficacy while improving side effect profiles.

First, a phase 3 randomized clinical trial in *JAMA Neurology* evaluated ecopipam for Tourette syndrome [7]. Ecopipam is a selective dopamine D1 receptor antagonist, differing from many current therapies that target D2 receptors. The study used a randomized withdrawal design. After an open-label period where patients were started on the drug, those who responded were randomized to either continue ecopipam or switch to placebo. The primary outcome was time to relapse. In pediatric participants, aged 6 to 18, continuing ecopipam significantly reduced the risk of relapse by about half compared to placebo. While a similar trend was seen in adults, the result was not statistically significant due to the small number of adult participants. Critically, the side effect profile was favorable. The most common adverse events were somnolence, anxiety, and headache. Importantly, there was no clinically meaningful impact on weight or metabolic parameters, and no drug-induced movement disorders were observed, which are major limitations of current treatments. This positions ecopipam as a promising alternative for Tourette syndrome with a distinct safety profile.

Next, in *Neurology*, a study provides a cross-trial comparison of vamorolone versus classic corticosteroids for Duchenne muscular dystrophy, or DMD [2]. Vamorolone was developed to retain the anti-inflammatory benefits of steroids while reducing their side effects. This analysis used a statistical weighting method to compare boys treated with vamorolone in the VISION-DMD trial to those treated with daily prednisone or deflazacort in the FOR-DMD trial. At 12 months, vamorolone demonstrated numerically similar improvements in motor function, as measured by time-to-stand velocity, compared to both prednisone and deflazacort. However, the confidence intervals were wide, limiting definitive conclusions about non-inferiority. The major difference was in side effects. While all treatments were associated with an increased body mass index, boys treated with prednisone and deflazacort experienced a slowdown in growth. This was not seen in the vamorolone group, which showed a significant growth-protective effect. This evidence suggests vamorolone may serve as an alternative to classic corticosteroids, offering comparable motor efficacy with the key advantage of preserving linear growth.

Finally, we highlight a report from *The New England Journal of Medicine* detailing a successful treatment for progressive multifocal leukoencephalopathy, or PML [1]. The abstract describes a case where a patient with this devastating JC virus-related demyelinating disease experienced resolution of PML after receiving treatment with virus-specific T cells followed by a hematopoietic cell transplant. While this is a single case, it provides a powerful proof-of-concept for a cellular therapy-based approach to a condition with historically poor outcomes, offering a new potential avenue for future investigation.

Editor's Pick If you only have time for one paper this week, make it the study in *JAMA Neurology* on a plasma-based biological staging model for Alzheimer disease [8]. This two-marker blood test shows high concordance with PET and autopsy findings, representing a major step toward making accurate, biological staging of Alzheimer's accessible in routine clinical practice.

Clinical Bottom Line Here are the key takeaways from this week in Neurology:

First, in acute stroke care: For intracerebral hemorrhage, mobile stroke units can dramatically speed up diagnosis and blood pressure control [5]. And for large vessel occlusions due to carotid dissection, bridging with IV thrombolysis before thrombectomy appears safe and improves outcomes, particularly in patients with severe strokes [3].

Second, in neurodegeneration diagnostics: A new plasma test combining p-tau217 and eMTBR-tau243 can accurately stage Alzheimer's disease biologically [8]. In parallel, a novel CSF assay for the protein TPPP/p25 shows high specificity for diagnosing multiple system atrophy [6], while a new PET tracer shows early promise for imaging alpha-synuclein in vivo [4].

Third, in therapeutics: For pediatric Tourette syndrome, the D1 antagonist ecopipam effectively maintains tic improvement without the metabolic or extrapyramidal side effects common with other agents [7]. For Duchenne muscular dystrophy, vamorolone offers motor efficacy similar to classic steroids but spares patients from the associated growth stunting [2].

Finally, a proof-of-concept report suggests that virus-specific T-cell therapy followed by hematopoietic cell transplant may be a viable strategy for treating progressive multifocal leukoencephalopathy [1].

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.