Meletti S, Hanin A, Giovannini G
… +30 more, Bedin R, Burani M, Taruffi L, Orlandi N, Urbano T, D'Achille F, Malerba M, Basha MM, Eschbach K, Foreman B, Farias-Moeller R, Gaspard N, Gerard EE, Gofton T, Gopaul MT, Haider HA, Hantus ST, Herman S, Kang P, Day GS, Kandula P, Steriade C, Struck AF, Taraschenko O, Wainwright M, Yoo JY, Zhou DJ, Lattanzi S, Navarro V, Hirsch LJ
JAMA Neurol
· 2026 Jun · PMID 42043830
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IMPORTANCE: 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...IMPORTANCE: 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: To quantify acute brain injury in patients with cryptogenic NORSE (cNORSE), etiology-defined status epilepticus (eSE), and chronic epilepsy. DESIGN, SETTING, AND PARTICIPANTS: 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: Neurofilament light chain (NfL) and S100-beta (S100B) protein concentrations in serum and cerebrospinal fluid (CSF). MAIN OUTCOMES AND MEASURES: Degree of neuronal and glial damage, indexed by NfL and S100B levels, and their association with short-term functional outcomes. RESULTS: 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: 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.
JAMA Neurol
· 2026 Jun · PMID 42043826
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IMPORTANCE: Seizures are a known complication of cancer, but whether they may be the first sign of undiagnosed neurological and nonneurological cancer remains unclear. OBJECTIVE: To examine neurological and nonneurologic...IMPORTANCE: Seizures are a known complication of cancer, but whether they may be the first sign of undiagnosed neurological and nonneurological cancer remains unclear. OBJECTIVE: To examine neurological and nonneurological cancer risk in patients with first-time seizures vs the general population. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study was conducted using nationwide Danish medical registries from January 1996 through December 2022. Follow-up extended until cancer diagnosis (excluding nonmelanoma skin cancer), emigration, death, or December 31, 2022. Analyses were performed from January 2025 through December 2025. All persons aged 18 years or older with a first-time hospital diagnosis of seizure and no preceding cancer were included. EXPOSURE: First-time seizure diagnosis. MAIN OUTCOMES AND MEASURES: The primary outcomes were absolute risks (ARs) of cancer and standardized incidence ratios (SIRs) relative to the general Danish population with 95% confidence intervals, which were computed for all cancers, neurological and nonneurological cancers, and site-specific cancer within 1 year, from 1 to less than 5 years, and from 5 to 20 years after the first seizure. RESULTS: Among 49 894 adults with first-time seizure (median [IQR] age at seizure diagnosis, 51.5 [35.6-67.8] years; 20 648 [41.4%] women), a total of 1172 neurological and 850 nonneurological cancers were observed within the first year of follow-up; 87 neurological and 1226 nonneurological cancers were observed during the period from 1 to less than 5 years; and 112 neurological and 2120 nonneurological cancers were observed during the period from 5 to 20 years. In these time periods, the ARs for any cancer were 4.1%, 3.5%, and 13.4%, with SIRs of 5.30 (95% CI, 5.07-5.54), 1.18 (95% CI, 1.12-1.25), and 1.34 (95% CI, 1.28-1.40). ARs for neurological cancers were 2.4%, 0.2%, and 0.7%, with SIRs of 76.1 (95% CI, 71.8-80.6), 1.85 (95% CI, 1.48-2.28), and 1.46 (95% CI, 1.20-1.75). ARs for nonneurological cancers were 1.7%, 3.3%, and 12.8%, with SIRs of 2.32 (95% CI, 2.17-2.48), 1.15 (95% CI, 1.09-1.22), and 1.33 (95% CI, 1.28-1.39). CONCLUSIONS AND RELEVANCE: Per the results of this cohort study, first-time seizures were associated with clearly elevated short-term relative risk of cancer and slightly elevated long-term risk, indicating they may be an early clinical sign of both neurological and nonneurological occult cancers. These findings highlight the importance of considering broader diagnostic assessments after first-time seizures in select patients.
Saccà F, Gialdini G, Howard JF
… +13 more, Vu TH, Meisel A, Peric S, Lünemann JD, Sgarzi M, Shaibani A, Bril V, Yeh JH, Reyes-Garrido V, Liao S, Metais C, van der Valk RJP, ALXN2050-MG-201 Investigators
JAMA Neurol
· 2026 Jun · PMID 42043793
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IMPORTANCE: Inhibition of terminal complement component 5 has proven effective in acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG) but requires intravenous or daily subcutaneous adm...IMPORTANCE: Inhibition of terminal complement component 5 has proven effective in acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG) but requires intravenous or daily subcutaneous administration and is associated with an increased meningococcal infection risk. Targeting the complement alternative pathway (AP) may offer similar benefits while sparing the classical and lectin pathways, preserving some immune responses against infection. OBJECTIVE: To evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of vemircopan, an oral, selective factor D inhibitor that blocks AP-mediated complement activation and amplification, in adults with AChR-Ab+ gMG. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, parallel-group, placebo-controlled phase 2 randomized clinical trial was conducted between April 14, 2022, and April 3, 2024, at 60 sites across 8 countries. Adults with AChR-Ab+ gMG, Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 5 or greater, and Myasthenia Gravis Foundation of America classes II through IV classification were eligible for inclusion. Data were unblinded in June 2024; final analysis was completed October 2024. INTERVENTION: Randomization 2:1:2 to twice-daily oral vemircopan, 180 mg or 120 mg, or placebo. MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of participants achieving a 2-point or greater reduction in MG-ADL total score from baseline for 4 consecutive weeks, without rescue therapy, during the 8-week, double-blind primary evaluation period. Secondary end points were change from baseline to week 8 in MG-ADL total score, Quantitative Myasthenia Gravis total score, and Neurological Disorders Fatigue questionnaire score. RESULTS: Of 99 individuals screened, 70 met eligibility criteria, and 29 were excluded. Of 70 participants randomized (vemircopan, 180 mg: n = 28; vemircopan, 120 mg: n = 14; placebo: n = 28), 38 participants (54%) were female; mean (SD) age at diagnosis was 45.4 (18.5) years. The proportion of participants achieving the primary end point did not differ significantly between placebo (18 of 28 [64%]; 90% CI, 47%-79%) and either vemircopan group (180 mg: 16 of 28 [57%]; 90% CI, 40%-73%; 120 mg: 8 of 14 [57%]; 90% CI, 33%-79%). No significant differences were observed for the secondary end points. No cases of meningococcal infection were reported; 1 participant died due to hepatic failure and 1 discontinued study treatment due to herpes simplex meningitis. CONCLUSIONS AND RELEVANCE: In this double-blind, parallel-group, placebo-controlled phase 2 randomized clinical trial, vemircopan did not meet the prespecified threshold for efficacy, and consequently, the study was terminated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05218096.
Chen W, Yang B, Bai X
… +43 more, Yi T, Wang H, Wen C, Liu Y, Ma L, Wu S, Liu S, Zhang L, Peng Y, Zhao Y, Song C, Cai X, Zhang G, Zheng W, Cheng T, Wei L, Xu L, Liu W, Han H, Cao H, Chang W, Fang P, Xu C, Ju D, Liu Y, Zhang J, Li J, Wang E, Zhang G, Yu J, Zeng G, Chen F, Li X, Dai Y, Guo X, Wu Y, Nguyen TN, Fischer U, Qureshi AI, Nogueira RG, Ji X, Jiao L, IAT-TOP Investigators
JAMA Neurol
· 2026 Apr · PMID 42026933
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IMPORTANCE: The impact of adjunctive intra-arterial alteplase after successful endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) in the posterior circulation r...IMPORTANCE: The impact of adjunctive intra-arterial alteplase after successful endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) in the posterior circulation requires further investigation. OBJECTIVE: To assess the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, prospective, randomized, open-label, blinded-end point (PROBE design) clinical trial. The study was conducted between September 5, 2023, and November 29, 2024, with the 3-month follow-up completed on February 18, 2025. The trial was conducted in 37 comprehensive stroke centers in China. Patients in China with acute basilar artery occlusion presenting within 24 hours of the time last known well were randomly assigned to the treatment group or control group. Eligible participants were adults who achieved successful recanalization after EVT. INTERVENTIONS: Eligible patients were randomly assigned to the intra-arterial alteplase group (0.225 mg/kg, maximum dose limit 22.5 mg infused at a concentration of 1.0 mg/mL within 15 minutes distal to the origin of posterior inferior cerebellar artery) or control group (no intra-arterial thrombolysis). MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the proportion of patients achieving functional independence (modified Rankin Scale score of 0-2) at 90 days. The primary safety outcomes were mortality at 90 days and incidence of symptomatic intracranial hemorrhage within 48 hours. RESULTS: A total of 247 patients were enrolled, and 1 patient was excluded from the full analysis set due to basilar artery reocclusion before intra-arterial alteplase. The remaining 246 patients (median [IQR] age, 65.0 [56.0-72.0] years; 176 male [71.5%]) were included in this analysis, 124 (50.4%) in the treatment group and 122 (49.6%) in the control group. Among the patients recruited and followed up, functional independence at 90 days was achieved in 52 (41.9%) in the intra-arterial alteplase group and 57 (46.7%) in the control group (adjusted risk ratio, 0.93; 95% CI, 0.73-1.18; P = .55). Mortality at 90 days (29.6% vs 27.0%, respectively; adjusted hazard ratio, 1.07; 95% CI, 0.71-1.61; P = .75) and incidence of symptomatic intracranial hemorrhage (2.4% vs 2.5%, respectively; unadjusted risk ratio, 0.98; 95% CI, 0.20-4.74; P = .97) were similar across groups. CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial reveal that in patients with posterior circulation stroke due to acute basilar artery occlusion, intra-arterial alteplase after successful endovascular recanalization appeared to be safe but was not associated with improvement of functional outcomes at 90 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05897554.
Anastasiou A, Corbaz H, Christodoulou E
… +18 more, Albers GW, Heit JJ, Tsivgoulis G, Müller L, van Es A, Kruyt ND, Staals J, van Zwam W, Dassen S, Dobrocky T, Hajdu SD, van den Bergh F, Rommers N, Aebischer V, Brehm A, Fischer U, Psychogios M, DISTAL investigators
JAMA Neurol
· 2026 Jun · PMID 42008259
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IMPORTANCE: Imaging-based end points may enhance the understanding of endovascular treatment (EVT) outcomes in patients with medium- or distal-vessel occlusion stroke. OBJECTIVE: To investigate the outcomes of endovascul...IMPORTANCE: Imaging-based end points may enhance the understanding of endovascular treatment (EVT) outcomes in patients with medium- or distal-vessel occlusion stroke. OBJECTIVE: To investigate the outcomes of endovascular treatment (EVT) in addition to best medical treatment (BMT) compared with BMT alone on the volume of brain tissue initially at risk preserved in patients with a medium or distal vessel occlusion stroke. DESIGN, SETTING, AND PARTICIPANTS: Post hoc imaging analysis of the Endovascular Treatment for Stroke Due to Occlusion of Medium or Distal Vessels (DISTAL) trial, a multicenter randomized clinical trial with blinded end point assessment conducted at 55 hospitals in 11 countries from December 2021 through July 2024, with clinical follow-up at 90 days. Patients with baseline perfusion imaging and follow-up imaging at 24 hours were included. INTERVENTIONS: EVT plus BMT compared with BMT alone. MAIN OUTCOMES AND MEASURES: Primary outcome was calculated as the difference in volume of tissue at risk and the final infarct volume divided by the tissue at risk (change in Vrel). We defined a Vrel of 0.8 or greater as a good imaging outcome, meaning that at least 80% of the brain tissue initially at risk was not infarcted at 24 hours. Additionally, the association between brain tissue preserved and clinical outcome at 90 days was investigated. RESULTS: From the 447 patients (252 [56.4%] male; median [IQR] age, 77.0 [68.0-84.0] years) included in this secondary analysis, 226 received EVT plus BMT and 221 received BMT alone. Median (IQR) time of the follow-up imaging was 22.9 (19.2-25.5) hours. Median (IQR) Time to maximum less than 6 seconds (Tmax6) volume was 34.0 (20.0-50.0) mL. Median follow-up infarct volume was 7.0 (1.0-22.9) mL. The median (IQR) change in absolute volume in the EVT plus BMT group was 23.6 (5.7-38.9) mL and 14.8 (0-30.3) mL in the BMT group. Median (IQR) change in Vrel was 0.8 (0.2-1.0) in the EVT plus BMT group and 0.6 (0-0.9) in the BMT group. Odds for reaching a change in Vrel of 0.8 or greater were higher in the EVT plus BMT group compared with BMT (adjusted odds ratio [aOR], 1.6; 95% CI, 1.1-2.3) and with successful reperfusion compared with no successful reperfusion (aOR, 2.5; 95% CI, 1.3-4.8). Patients with a change in Vrel of 0.8 or greater had a better clinical outcome at 90 days. CONCLUSIONS AND RELEVANCE: In this post hoc analysis of the DISTAL trial data, EVT plus BMT was associated with a higher likelihood of achieving a good imaging outcome compared with BMT alone. A good imaging outcome was associated with a better clinical outcome in both treatment groups.
Ridha M, Hailat R, Stanton R
… +9 more, Merkler AE, Elkind MSV, Longstreth WT, Tirschwell DL, Kronmal RA, Hannawi Y, Kamel H, Burke J, Woo D
JAMA Neurol
· 2026 Jun · PMID 42008258
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IMPORTANCE: Multiple trials have found no difference in secondary stroke prevention between anticoagulation and antiplatelet therapy after cryptogenic stroke. Due to limitations of current stroke mechanism classification...IMPORTANCE: Multiple trials have found no difference in secondary stroke prevention between anticoagulation and antiplatelet therapy after cryptogenic stroke. Due to limitations of current stroke mechanism classification, one possible explanation is the failure to exclude patients with hypertension-related cerebrovascular disease. OBJECTIVE: To determine whether hypertension with high-risk features is associated with treatment effect modification of anticoagulation vs antiplatelet therapy. DESIGN, SETTING, AND PARTICIPANTS: This exploratory analysis of the Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy (ARCADIA) randomized clinical trial was conducted between April and August 2025. The original trial was conducted from February 2018 to February 2023 at 185 sites in North America. From 1015 randomized patients with a recent cryptogenic stroke and atrial cardiopathy, 945 with available hypertension data were included in this analysis after exclusions for missing blood pressure and echocardiography data. INTERVENTIONS: Apixaban, 5 mg or 2.5 mg, twice daily vs aspirin, 81 mg, once daily. MAIN OUTCOMES AND MEASURES: The primary outcome was recurrent ischemic stroke or systemic embolism. Hypertension with high-risk features was defined as systolic blood pressure ≥160 mm Hg at enrollment, left ventricular hypertrophy on echocardiography, or both. Cox proportional hazards models evaluated treatment interaction with hypertension with high-risk features and estimated hazard ratios within hypertension with high-risk features subgroups. RESULTS: Among 945 patients (mean [SD] age, 68.0 [10.8] years; 513 [54.3%] female), 351 (37.1%) met criteria for hypertension with high-risk features. Over a median (IQR) follow-up of 1.6 (0.7-3.0) years within the analytic cohort, 67 patients experienced a recurrent ischemic stroke or systemic embolism. A significant interaction between hypertension with high-risk features and antithrombotic treatment was observed. In 594 patients without hypertension with high-risk features, apixaban was associated with lower risk compared to aspirin (hazard ratio [HR], 0.43; 95% CI, 0.22-0.85; annualized rate difference: -3.4%), whereas no significant association was observed in patients with hypertension with high-risk features (HR, 1.68; 95% CI, 0.78-3.62; annualized rate difference: 2.4%). CONCLUSIONS AND RELEVANCE: The findings in this study indicate that hypertension with high-risk features may be associated with modifications in the effect of antithrombotic treatment in patients with cryptogenic stroke. An unappreciated inclusion of strokes due to hypertensive arteriopathy may account for the lack of benefit with anticoagulation in prior trials of embolic stroke of undetermined source. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03192215.
Harrison TM, Harvey DJ, Chadwick T
… +19 more, Chao Y, Taggett J, Maillard P, Lovato L, Farias ST, Papp KV, Lockhart SN, Toga AW, Koeppe RA, Jung Y, Jagust WJ, Whitmer RA, Snyder HM, Carrillo MC, Baker LD, Espeland MA, Vemuri P, DeCarli C, Landau SM
JAMA Neurol
· 2026 Jun · PMID 42008251
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IMPORTANCE: Brain imaging biomarkers may (1) identify underlying mechanisms of intervention effects and (2) define brain characteristics of those most likely to benefit cognitively from the intervention. OBJECTIVE: To te...IMPORTANCE: Brain imaging biomarkers may (1) identify underlying mechanisms of intervention effects and (2) define brain characteristics of those most likely to benefit cognitively from the intervention. OBJECTIVE: To test whether (1) a lifestyle intervention is related to brain changes, (2) brain changes are correlated with intervention-specific cognition changes, and (3) brain imaging biomarkers provide information about who is likely to benefit from a lifestyle intervention. DESIGN, SETTING, AND PARTICIPANTS: In this randomized clinical trial, the POINTER Imaging study was an ancillary study of the 2-year, single-blind multicenter US POINTER clinical trial in which neuroimaging data were collected on eligible enrolled participants. The study was conducted from May 2019 to March 2023 (final follow-up, May 14, 2025). Participants were enrolled into the POINTER Imaging study following a standard procedure at 5 clinical sites in the US. Participant eligibility criteria included an age of 60 to 79 years, sedentary lifestyle, and suboptimal diet, plus at least 2 additional risk criteria for cognitive decline and no contraindications for neuroimaging. INTERVENTIONS: Participants were randomly assigned to receive the structured or self-guided intervention. Both interventions emphasized increased physical and cognitive activity, healthy nutrition, social engagement, and cardiovascular health monitoring, but they differed in intensity and accountability. MAIN OUTCOMES AND MEASURES: There were 4 primary imaging outcomes: global β-amyloid (Aβ) burden, tau burden in the entorhinal cortex (ERC), hippocampal (HC) volume, and white matter hyperintensity volume. The primary cognitive measure was a global cognitive composite. RESULTS: Among 1943 parent trial participants who were assessed for eligibility, 983 underwent at least 1 magnetic resonance imaging or positron emission tomography scanning session. The mean (SD) age was 68.4 (5.2) years; 605 participants (61.5%) were female and 378 male (38.5%). Five hundred sixteen participants received the structured intervention and 467 the self-guided intervention. There were no intervention group differences in longitudinal cognitive or imaging outcomes. Intervention group differences were not associated with or moderated by Aβ status or accumulation. There was a negative association between change in ERC tau and change in global cognition in the self-guided group that was attenuated in the structured group (difference in association: 0.289; 95% CI, 0.029 to 0.550; interaction P = .03). Lower baseline HC volume was associated with greater cognitive benefit for participants in the structured group vs the self-guided group (lower HC: 0.077 SD; 95% CI, 0.022 to 0.132; higher HC: 0.002 SD; 95% CI, -0.037 to 0.041; interaction P = .03). CONCLUSION AND RELEVANCE: This study found that a high-intensity multidomain lifestyle intervention did not affect brain biomarker trajectories and was not associated with Aβ pathology, but older adults with specific at-risk brain characteristics, including lower baseline HC volume, showed a greater cognitive benefit of the structured intervention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03688126.
Petutschnigg T, Aschwanden S, Descombes C
… +11 more, Nasiri D, Bervini D, Murek M, Häni L, Jesse CM, Schär RT, Zubak I, Z'Graggen WJ, Raabe A, Schucht P, Goldberg J
JAMA Neurol
· 2026 Jun · PMID 41973454
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IMPORTANCE: Chronic subdural hematoma (cSDH) is among the most common neurosurgical disorders in older adults. Although short-term outcomes after surgery are favorable, long-term survival and health-related quality of li...IMPORTANCE: Chronic subdural hematoma (cSDH) is among the most common neurosurgical disorders in older adults. Although short-term outcomes after surgery are favorable, long-term survival and health-related quality of life (HRQoL) remain poorly characterized. OBJECTIVE: To evaluate long-term survival, excess mortality, and HRQoL 10 years after surgical treatment of cSDH. DESIGN, SETTING, AND PARTICIPANTS: This population-matched cohort study was conducted at a single tertiary referral center in Switzerland, with mortality follow-up through December 31, 2023 (mean [SD] follow-up, 9.55 [1.24] years), and cross-sectional HRQoL assessment through December 31, 2024 (mean [SD] follow-up, 10.05 [1.16] years). Analyses were conducted from October to December 2025. Adults surgically treated for cSDH between June 2012 and August 2016 were included, matched with the Swiss general population by age, sex, and birth month for mortality analysis. Among survivors, those completing HRQoL assessment were compared with age- and sex-weighted European reference values. EXPOSURE: Surgically treated cSDH. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality, estimated using Kaplan-Meier analysis, with excess mortality expressed as absolute survival differences and standardized mortality ratios (SMRs). Secondary outcomes were the following HRQoL domains: cognitive functioning (CF), physical functioning (PF), role functioning (RF), emotional functioning (EF), social functioning (SF), and global QoL, compared using 2-sided z tests. RESULTS: A total of 359 adults surgically treated for cSDH were included; among survivors, 147 completed HRQoL assessment and were compared with age- and sex-weighted European reference values. Among 359 patients (mean [SD] age, 73.4 [11.0] years; 117 female patients [32.6%]), overall survival was significantly lower than matched controls (hazard ratio [cohort vs control], 2.02; 95% CI, 1.73-2.37; log-rank P < .001). One-year survival in the cSDH cohort was 92.8% (95% CI, 90.1%-95.5%) vs 98.8% (95% CI, 98.7%-98.8%) in controls, representing an excess mortality of 6.0 percentage points (SMR, 3.22; 95% CI, 2.10-4.72); 5-year survival was 76.6% (95% CI, 72.3%-81.1%) vs 88.2% (95% CI, 88.2%-88.3%), representing an excess of 11.6 percentage points (SMR, 1.19; 95% CI, 0.95-1.47); and 10-year survival was 55.5% (95% CI, 50.3%-61.3%) vs 73.5% (95% CI, 73.4%-73.6%), representing an excess of 18.0 percentage points (SMR, 1.12; 95% CI, 0.94-1.31). Men reported significantly lower mean (SD) PF scores (75.9 [26.8] vs control mean score, 83.22; P < .001), RF scores (74.9 [32.0] vs 84.87; P < .001), CF scores (77.6 [22.6] vs 87.38; P < .001), and SF scores (84.3 [24.0] vs 90.00; P = .02) than controls, and women reported lower mean (SD) RF (69.0 [30.9] vs 80.91; P = .02) and CF scores (70.2 [24.8] vs 86.50; P < .001). EF and global QoL did not differ significantly from European reference values. CONCLUSIONS AND RELEVANCE: In this population-matched cohort study, patients surgically treated for cSDH experienced sustained excess mortality and clinically relevant HRQoL deficits 10 years after surgery. These findings call for structured postoperative and rehabilitative care beyond the acute phase.
Behrens JR, Kaffes M, Aigner A
… +23 more, Herm J, Erdur H, Siepmann T, Barlinn J, Hubert G, Wiestler H, Gumbinger C, Ranta A, von Weitzel-Mudersbach P, Rocco A, Hofmann-Shen C, Muhn F, Liman T, Rozanski M, Litmeier S, Riegler C, Hellwig S, Geran R, Koschützke L, Ditsche H, Kotlarz-Böttcher M, Kinze S, Audebert H
JAMA Neurol
· 2026 Apr · PMID 41941227
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IMPORTANCE: Telestroke networks provide coverage of neurological expertise in rural areas. While most teleneurological consultations focus on acute stroke care in emergency departments, neurological expertise remains cru...IMPORTANCE: Telestroke networks provide coverage of neurological expertise in rural areas. While most teleneurological consultations focus on acute stroke care in emergency departments, neurological expertise remains crucial in the subacute phase. However, teleneurological ward rounds have not yet been systematically investigated for feasibility and quality. OBJECTIVE: To assess noninferiority of teleneurological ward rounds compared with conventional on-site ward rounds during subacute inpatient stroke care, focusing on adherence to guideline-based quality indicators. DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter, nonrandomized, noninferiority study was conducted at 15 primary care hospitals within 4 German telestroke networks from October 2022 to December 2024. Adults (18 years or older) hospitalized with suspected acute ischemic or hemorrhagic stroke or transient ischemic attack were eligible. A total of 1908 patients were screened. These data were analyzed from January 2025 to May 2025. EXPOSURES: Patients received both a teleneurological and an on-site neurological ward round. Teleneurological ward rounds were performed by network neurologists via video consultation; on-site consultations were performed by local neurologists. Documentation from both consultations was evaluated by blinded external neurovascular experts. MAIN OUTCOMES AND MEASURES: The primary outcome was complete fulfillment of 6 predefined, guideline-based quality domains: etiological classification, neurological examination, risk assessment, diagnostic recommendations, secondary prevention, and recommended aftercare. Noninferiority was defined as a maximum difference in proportions of correct assessments of 5 percentage points. Secondary outcomes included correctness of individual domains and expert quality ratings on a visual analoge scale. RESULTS: A total of 518 patients were enrolled (median age, 71 years; 222 female [44%] and 296 male [56%]) and 501 were included in the final analysis. Complete adherence to all quality criteria was achieved in 92% (95% CI, 90%-94%) of teleneurological ward rounds compared with 54% (95% CI, 49%-58%) of on-site ward rounds (absolute difference, 38 percentage points; 90% CI, 34-42). Superiority of teleneurological ward rounds was consistent across all quality domains with the most pronounced differences observed for secondary prevention (absolute difference, 21% percentage points; 90% CI, 17-24). CONCLUSIONS AND RELEVANCE: Teleneurological ward rounds in subacute stroke care were noninferior and even superior when compared with on-site consultations, with respect to guideline adherence across all quality domains. These findings support the integration of telemedicine into routine inpatient stroke care, particularly in regions with limited access to neurological expertise.
Banerjee G, Mok TH, Hyare H
… +4 more, Cousins O, Jaunmuktane Z, Mead S, Collinge J
JAMA Neurol
· 2026 May · PMID 41910964
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IMPORTANCE: Alzheimer disease (AD) is pathologically characterized by the deposition of amyloid-β (Aβ) and hyperphosphorylated tau. Human transmission of Aβ pathology in a prion-like fashion has resulted in iatrogenic ce...IMPORTANCE: Alzheimer disease (AD) is pathologically characterized by the deposition of amyloid-β (Aβ) and hyperphosphorylated tau. Human transmission of Aβ pathology in a prion-like fashion has resulted in iatrogenic cerebral amyloid angiopathy. More recently, iatrogenic Alzheimer disease (iAD) was described in recipients of cadaveric pituitary-derived human growth hormone (c-hGH) contaminated with Aβ amyloid seeds. OBJECTIVE: To describe the clinical and postmortem findings in iAD. DESIGN, SETTING, AND PARTICIPANTS: This case series describes 4 c-hGH recipients who were referred to the UK National Prion Clinic. Between February 2024 and February 2025, 14 c-hGH recipients had been referred to this service, with clinical assessments ongoing. The current study included 4 of 14 people treated with c-hGH who were referred since the original report. These data were analyzed during February and March 2025. EXPOSURE: c-hGH contaminated with Aβ amyloid seeds. MAIN OUTCOMES AND MEASURES: Clinical and histopathological description. RESULTS: The study describes 4 males who developed dementia following confirmed or suspected c-hGH treatment in childhood (age at symptom onset between 47 and 60 years) with cognitive syndromes characterized by prominent language involvement. Results include clinical and postmortem findings for 1 patient (onset at age 47 years) in whom postmortem examination (at age 57 years) showed unequivocal neuropathological features of AD, including severe tauopathy. Brief descriptions of 3 additional patients with prominent language involvement are also provided. CONCLUSIONS AND RELEVANCE: These results demonstrate that patients with iAD can have histopathological findings classically found in sporadic AD and that prominent language involvement might be an important phenotypic feature in this AD subtype.