Faculty Bibliography

INTRODUCTION/BACKGROUND:Measuring plasma biomarkers effectively assesses early-stage Alzheimer's disease. METHODS:Subjects were categorized as cognitively unimpaired (CU) (n = 66), CU with subjective cognitive decline (SCD) (n = 100), and mild cognitive impairment (MCI) (n = 25). Plasma biomarkers measured were amyloid beta (Aβ) 40, Aβ42, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau phosphorylated at threonine 181 (pTau181), neuroinflammatory biomarkers, and blood-brain barrier biomarkers. Amyloid and tau positron emission tomography (PET) imaging was performed in 186 and 144 subjects, respectively. RESULTS:Comparing those having MCI, both CU and SCD participants had significantly lower amyloid PET standardized uptake value ratio (SUVR) (p < 0.001; p = 0.005). Higher amyloid PET SUVR was significantly associated with higher pTau181 (p = 0.001) and a higher pTau181/Aβ42 ratio (p < 0.001). Higher tau PET SUVR was associated with lower plasma Aβ42 (p = 0.020), older age (p = 0.005), higher GFAP (p = 0.020), and lower interleukin-8 levels (p < 0.001). DISCUSSION/CONCLUSIONS:Our study supports plasma biomarker monitoring of at-risk patients at various stages of pre-dementia.

OBJECTIVE:Interictal epileptiform discharges (IEDs) are transients observed on the electroencephalogram (EEG) of patients with epilepsy. IEDs have traditionally been recorded from scalp or intracranial EEG macrocontacts, which coarsely sample neural activity. Here, we investigated the use of flexible, high-resolution microelectrocorticographic (μECoG) arrays for measuring IEDs with greater spatiotemporal precision to test whether there exist microscale patterns of IED activity that may be missed on standard intracranial EEG. METHODS:) to record from seven patients undergoing surgical treatment of epilepsy. We identified IEDs by a combination of expert review and automated detection. We quantified the spatial extent of IEDs, mapped patterns of repeated IED activity, and quantified IED propagation direction using multilinear fit models. We also compared IED detection rates and propagation measurements between μECoG arrays and simulated macroarrays (10-mm spacing, 2.3-mm diameter). RESULTS:We demonstrated successful use of μECoG arrays to map intraoperative microscale patterns of IEDs. The majority of patients (5/7) exhibited elevated IED activity that was highly localized (subcentimeter localization). Across all patients, 40% of detected IEDs were observed within a 4-mm radius of cortex. μECoG arrays also mapped the direction of IED propagation. An average of 39% (range = 4.2%-96.5%, SD = ±36.8%) of the IED events captured by the μECoG arrays were not detectable by simulated macrocontacts. SIGNIFICANCE/CONCLUSIONS:These intraoperative data demonstrate that μECoG arrays can map the microscale spatiotemporal activity of IEDs. These patterns of IEDs may be poorly captured by standard, macroscale recording devices. Our findings support the use of high-resolution, large area coverage μECoG arrays for the presurgical and intraoperative mapping of epileptic cortex.

Polyaminopathies are a recently described family of rare genetic neurodevelopmental disorders. Polyaminopathies disrupt the biosynthesis of the primary polyamines: putrescine, spermidine, and spermine. Snyder-Robinson syndrome results from hemizygous loss-of-function variants in the spermine synthase (SMS) gene, resulting in decreased or complete loss of spermine synthase enzyme activity. Bachmann-Bupp syndrome results from heterozygous gain-of-function variants in the ornithine decarboxylase 1 (ODC1) gene, resulting in increased ornithine decarboxylase enzyme activity. Faundes-Banka syndrome results from heterozygous loss-of-function variants in the eukaryotic translation initiation factor 5A (EIF5A) gene, impairing eIF5A protein function. DHPS (deoxyhypusine synthase) deficiency is an autosomal recessive disease and results from bi-allelic hypomorphic variants in the deoxyhypusine synthase (DHPS) gene, which results in reduced deoxyhypusine synthase enzyme activity. Finally, DOHH (deoxyhypusine hydroxylase) disorder is an autosomal recessive disorder caused by bi-allelic loss-of-function variants in the deoxyhypusine hydroxylase (DOHH) gene, which causes decreased deoxyhypusine hydroxylase enzyme activity. Snyder-Robinson syndrome was first described in 1969, while the other four syndromes have only been identified in the past 7 years. A comprehensive phenotypic and genotypic description of these five syndromes is needed. We review the clinical and genetic features of these five polyaminopathies to create an inclusive clinical resource. A systematic keyword search strategy was used to identify all published cases in PubMed, Web of Science, and Scopus databases. The five known syndromes associated with the polyamine pathway share many similar clinical phenotypes, and yet patients with each syndrome present with distinctive syndromic features. This review will serve as a valuable resource for clinicians diagnosing and caring for patients with these rare polyaminopathies.

BACKGROUND:Carotid webs are increasingly recognized as a cause of ischemic stroke, but less is known about morphologically similar lesions in other arteries. We present the first study characterizing the clinical and radiographic features of extra-carotid arterial webs through a single-center case series and systematic review. METHODS:Patients with possible extra-carotid webs were identified from 2017 to 2025 using a natural language processing search of radiology reports at our institution. Candidate cases underwent imaging review with multiplanar and 3-dimensional reconstructions to distinguish webs from fenestrations, vessel tortuosity, dissection, or atherosclerotic plaque. In parallel, we performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review (Web of Science and PubMed, inception to September 2025) to identify published cases of extra-carotid web. Data on demographics, vascular location, imaging modality, clinical presentation, treatment, and outcomes were extracted and synthesized descriptively. RESULTS:Four extra-carotid webs were identified at our institution (3 basilar and 1 subclavian). None were associated with stroke, and all patients remained stable on conservative management during 9 months to 4 years of follow-up. Across 16 published studies, 22 additional extra-carotid webs were identified, yielding 26 patients in aggregate (mean age, 52.7 years; 61.5% male). The vertebral artery was the most common site (53.8%), followed by the basilar (30.8%) and subclavian (15.4%) arteries. Ten patients with vertebral or basilar web presented with posterior circulation ischemic stroke, with recurrent events in 4 patients. Most patients were managed with antiplatelet therapy or observation, while 3 vertebral webs with recurrent stroke were successfully treated with stenting. CONCLUSIONS:Extra-carotid webs share morphological and clinical features with carotid webs and may represent a unified disease spectrum of cervical artery webs. Vertebral and basilar webs, though rare, may be an underrecognized source of posterior circulation stroke. Recognition of these lesions may broaden the differential for cryptogenic stroke though the lack of histopathologic visualization remains a critical limitation of our study.

The frequency and nature of neurological exams (neuro-checks) in patients with severe acquired brain injury resulting in coma or disorders of consciousness (DoC) remain variable, with limited evidence guiding practice and poor understanding of their role in predicting and preventing neurological deterioration, functional recovery and adverse effects such as delirium. This scoping review aims to explore the frequency of bedside neurological exams within the first 7 days of injury impact on clinical outcomes in adult patients with severe acquired brain injury including mortality, neurological deterioration, long-term function, and delirium. METHODS: A comprehensive literature search was conducted using the PubMed, CINAHL, Medline and EMBASE databases from 2003 to 2023. Search terms captured a range of acute brain injuries and neuro-assessment tools. Eligible studies included adult patients with severe traumatic or non-traumatic brain injury or stroke that addressed frequency of bedside neurological exams within the first 7 days of admission. RESULTS: Of 1327 studies screened, 20 met inclusion criteria, representing over 16,000 patients across 14 countries. Assessment tools varied, but use of the Glasgow Coma Scale was prevalent. Frequency of neuro-checks ranged from hourly to daily. Multiple outcome measures were utilized. Some studies found that continuing hourly neuro-checks beyond the first 48 hours did not provide additional clinical benefit. Others associated excessive assessment with increased stress or delirium. CONCLUSION: There is very low evidence supporting an association between the frequency of neuro-checks and functional outcomes, mortality, length of stay, or delirium. Although early assessments may aid prognostication, excessive exams may not improve outcomes and may contribute to harm. The heterogeneity, lack of evidence, and limited standardization of neuro-check frequency highlight the need for clinical research to guide future practice.

BACKGROUND:Carotid webs are increasingly recognized as a significant cause of cryptogenic stroke in young adults, yet they remain frequently underdiagnosed due to their subtle radiographic appearance and atypical presentations. The natural history of untreated carotid webs includes high rates of recurrent ipsilateral ischemic events despite optimal medical therapy. OBSERVATIONS/METHODS:The authors present the case of a 44-year-old man with four recurrent right hemispheric ischemic events over 5 years. Despite multiple angiographic studies, an underlying carotid web was initially misinterpreted. Digital subtraction angiography ultimately revealed a subtle posterolateral carotid web. Prior to endarterectomy, intraoperative ultrasound uniquely visualized a large thrombus adherent to the web, a critical finding not appreciated on preoperative angiography. Successful en bloc removal of the web and thrombus was performed with histopathological confirmation. The patient remained stroke free at the 1-year follow-up. LESSONS/CONCLUSIONS:Atypical carotid webs may lack classic radiographic features and can be misclassified on noninvasive imaging. Intraoperative ultrasound provides real-time assessment of thrombus burden not visible on preoperative angiography, allowing for improved surgical planning. This case demonstrates that web-associated thrombi are dynamic and may not be apparent even on high-resolution angiography performed shortly before surgery. Surgical intervention with intraoperative ultrasound guidance offers definitive treatment and excellent long-term outcomes. https://thejns.org/doi/10.3171/CASE2610.

IMPORTANCE/UNASSIGNED:Seizure-induced brain injury is central to the treatment urgency of new-onset refractory status epilepticus (NORSE). Identifying biomarkers that reflect ongoing neuronal damage could inform therapeutic timing and improve outcomes. OBJECTIVE/UNASSIGNED:To quantify acute brain injury in patients with cryptogenic NORSE (cNORSE), etiology-defined status epilepticus (eSE), and chronic epilepsy. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This was an international cross-sectional study conducted between 2013 and 2025. Patients were enrolled at 36 hospitals in the US, 2 in Canada, and 1 in Italy, France, and Belgium. Patients with cNORSE and eSE for which biological samples were obtained during ongoing seizure activity were enrolled in the study. Comparison groups without status epilepticus comprised individuals with chronic epilepsy and healthy participants. None were excluded. EXPOSURES/UNASSIGNED:Neurofilament light chain (NfL) and S100-beta (S100B) protein concentrations in serum and cerebrospinal fluid (CSF). MAIN OUTCOMES AND MEASURES/UNASSIGNED:Degree of neuronal and glial damage, indexed by NfL and S100B levels, and their association with short-term functional outcomes. RESULTS/UNASSIGNED:A total of 78 patients with cNORSE (mean [95% CI] age, 37 [30-41] years; 44 female [56%]) and 2 independent cohorts of 211 patients (mean [95% CI] age, 69 [66-71] years; 128 female [61%]) and 73 patients (mean [95% CI] age, 56 [45-65] years; 39 male [53%]) with eSE were included. NfL concentrations were markedly elevated in cNORSE-approximately 10-fold higher in CSF and 4-fold higher in serum-compared with the eSE cohorts (CSF: median [IQR], 6408 [1503-22 963] pg/mL compared with 694 [219-2389] pg/mL; serum: median [IQR], 231 [99-855] pg/mL compared with 55 [20-135] pg/mL; P <.001). Serum NfL levels were nearly 20-fold higher in cNORSE than in the cohort with epilepsy and in healthy controls (median [IQR], 11 [7-19 ] and 7 [5-14 ] pg/mL, respectively). Serum and CSF NfL levels were strongly correlated (Spearman ρ = 0.75; P < .001) and rose sharply between week 1 (median [IQR], 101 [51-137] pg/mL), week 2 (median [IQR], 197 [117-324] pg/mL), and week 3 (median [IQR], 598 [163-1000] pg/mL) after onset (P < .001). In contrast, S100B concentrations did not differ between groups and showed no consistent temporal pattern. NfL discriminated cNORSE from eSE (area under the receiver operating characteristic curve [AUROC], 0.79; 95% CI, 0.68-0.90) and from cohorts without status epilepticus (AUROC, 0.99; 95% CI, 0.78-1.00). Higher serum NfL was independently associated with poor functional outcome at discharge (Glasgow Outcome Scale extended score, 1-4; odds ratio, 1.01; 95% CI, 1.00-1.03; P = .03). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Results of this cross-sectional study suggest that acute neuroaxonal injury, as reflected by elevated NfL levels, was substantially greater in cNORSE than in the cohorts with eSE and in controls without status epilepticus. The rapid early rise in NfL highlights a narrow therapeutic window, emphasizing the need for prompt, effective, and potentially neuroprotective interventions in cNORSE.

Rasmussen syndrome (RS) includes a well-described constellation of refractory focal seizures, often including epilepsia partialis continua, hemiplegia with progressive unilateral cortical atrophy, and cognitive/language decline. However, the precise early pathogenesis and reliable biomarkers remain elusive. In addition, we lack operational management guidelines, including diagnostic evaluation, disease-monitoring assessments, and medical and surgical treatment approaches. We aimed to create an expert consensus statement to guide and standardize the treatment of RS, with the goal of providing recommendations applicable to a global population. An expert panel was convened to complete three rounds of a modified Delphi procedure given the lack of high-level evidence, with a focus on workup to exclude mimicking diagnoses, disease-activity metrics, and treatment. Consensus was defined as ≥75% of responses being agree/strongly agree in either two subsequent rounds or in the third and final round. A total of 122 of 143 statements met consensus. Proposed diagnostic evaluation in patients with possible RS is outlined, including physical examination, blood/cerebrospinal fluid analyses, neuroimaging, electroencephalography (EEG), and biopsy. Suggested disease-monitoring assessments include neuropsychological testing and serial magnetic resonance imaging (MRI). Intravenous corticosteroids are recommended as first-line, acute immunotherapy for seizure exacerbations and status epilepticus, with or without the addition of intravenous immunoglobulin. Options for maintenance immunotherapy are outlined, with lack of evidence noted for comparing efficacy of these treatments. Hemispheric disconnection remains the most effective seizure treatment, with parameters including age, function, seizure burden, and patient values influencing candidacy for surgery. This consensus statement offers a guideline to standardize management, as well as suggests future directions to further elucidate underlying pathophysiology and target more-effective, better-tolerated treatments.

BACKGROUND/OBJECTIVES/OBJECTIVE:Characterizing spinal cord multiple sclerosis (MS) lesions in MRI is critical for diagnosis, monitoring, and treatment evaluation. However, current automated approaches for lesion detection and segmentation are typically designed for specific MRI contrasts or acquisition sites, limiting their generalizability in real-world clinical settings where imaging protocols vary widely. This work proposes a robust multi-site, multi-contrast segmentation framework for spinal cord lesions. METHODS:The segmentation model was trained and evaluated on a large-scale dataset comprising 4428 annotated images from 1849 persons with MS across 23 imaging centers, encompassing six MRI contrasts (T1w, T2w, T2*w, PSIR, STIR, and UNIT1) acquired at 1.5 tesla (T), 3 T, and 7 T. RESULTS: < 0.01). Additional experiments evaluated robustness across spinal levels, acquisition resolutions, binarization thresholds, and quantitative evaluation on external labeled datasets. CONCLUSIONS:https://github.com/ivadomed/seg-sc-ms-lesion-multicontrast.