Citations

ABSTRACT Among 9457 aquaporin‐4 (AQP4) immunoglobulin G‐positive patients, 2071 underwent autoimmune encephalitis antibody testing and 85 (4%) had coexisting antibodies, most commonly cerebrospinal fluid glial fibrillary acidic protein‐IgG and N‐methyl‐D‐aspartate receptor‐IgG, or serum high‐titer GAD65‐IgG. Compared with AQP4‐IgG positive neuromyelitis optica spectrum disorder controls, dual‐positive patients were younger and more frequently exhibited encephalopathy, psychiatric symptoms, seizures, ovarian teratomas, and deep gray matter, temporal lobe, or diencephalic MRI abnormalities. GAD65‐IgG‐positive patients developed stiff‐person syndrome. These findings define a distinct mixed glial‐neuronal autoimmune phenotype and support additional neural antibody testing in atypical AQP4‐IgG‐positive presentations.

Background: Assessing craniocervical fibromuscular dysplasia (cc-FMD) can be challenging using cross-sectional imaging. We hypothesize that photon-counting detector CT (PCD-CT), owing to its superior spatial resolution over conventional energy-integrating detector CT (EID-CT), may better help appreciate changes in cc-FMD. Materials and Methods: In this retrospective cohort, 24 patients with radiologically reported cc-FMD (mean age: 54 y; 75% women) underwent both PCD-CT and EID-CT within 180 days (median: 52 d). Bilateral internal carotid (ICA) and vertebral artery (VA) segments without dissection/occlusion were graded on a 3-point scale (absent/likely present/present). Intermodality agreement was evaluated with weighted Cohen κ, and radiation dose metrics (CTDIvol) were compared using the paired Wilcoxon signed-rank tests. Results: Eighty-seven paired segments were analyzed. PCD-CT detected FMD in 48 segments (55.1%) versus 30 (34.5%) on EID-CT. The mean reader confidence scores were consistently higher with PCD-CT compared with EID-CT, for both ICAs (2.16±0.95 vs. 1.93±0.99) and VAs (1.86±0.95 vs. 1.36±0.75). Intermodality agreement was almost perfect for ICAs (κ=0.807) and substantial for VAs (κ=0.662). Under our institutional protocols, median CTDIvol was lower with PCD-CT (16.6 mGy) than EID-CT (21.5 mGy; P =0.0112). Conclusion: PCD-CT demonstrated more frequent reader categorization of cc-FMD features than EID-CT, particularly in the VAs, and had a lower median CTDIvol under our institutional protocols. These preliminary findings suggest improved cc-FMD detection with PCD-CT as compared with EID-CT and require prospective, reference-standard validation to establish accuracy and clinical impact.

Abstract: Amyloidosis is a heterogeneous group of diseases characterized by extracellular deposition of insoluble proteins. Glucagon-like peptide-1 analog (AGLP1)-type amyloidosis is a rare iatrogenic form of amyloidosis localized to areas of glucagon-like peptide-1 analog injections. In this study, we describe a case of AGLP1-type amyloidosis presenting as a subcutaneous mass on the abdomen of a 71-year-old woman with a history of liraglutide, semaglutide, and tirzepatide use. Biopsy, including Congo red stain, was consistent with an amyloid deposit. Amyloid protein identification by liquid chromatography tandem mass spectrometry showed a typical amyloid profile with low spectra for liraglutide. Immunohistochemistry, subsequently performed, showed that the amyloid deposits were positive for glucagon; there is an extensive peptide homology between liraglutide and glucagon. Only 3 cases of AGLP1-type amyloidosis have been previously reported. It is vital for clinicians and pathologists to be aware of AGLP1-type amyloidosis given the increasing worldwide use of GLP-1 agonists, as well as the potential for misdiagnosis of systemic amyloidosis, which has profound therapeutic and prognostic implications.

Chimeric antigen receptor T-cell (CAR-T) and CD20xCD3 bispecific antibody (BsAb) therapies are both effective for relapsed/refractory (R/R) follicular lymphoma (FL), but comparative real-world survival outcomes and time toxicity have not been characterized. We performed a multicenter retrospective study of 228 patients with R/R FL treated with standard-of-care CAR-T (n = 141) or BsAb (n = 87) across 17 U.S. academic centers in the third-line or later setting. Progression-free survival (PFS) and overall survival (OS) were stratified by 2 or ≥3 prior lines of therapy (LOT2 or LOT3+), including propensity matching. Time toxicity was measured by physical health care contact days. Median PFS was not reached (NR) with CAR-T and 581 days with BsAb in the LOT2 cohort (p < .0001), and was NR with CAR-T and 584 days with BsAb in the LOT3+ cohort (p = .0064). CAR-T recipients were younger (p < .0001) and had better performance status (p = .007) but were more refractory to prior LOT (p = .017). PFS advantages of CAR-T were independent of these differences. OS did not differ between treatment groups. CAR-T had significantly greater time toxicity over the first year, with higher mean contact days than BsAb in both the LOT2 (58 vs 44) and LOT3+ (69 vs 49) cohorts. In this large multicenter cohort of patients with R/R FL, CAR-T was associated with superior PFS but greater time toxicity compared with BsAb therapy. These findings provide real-world outcomes data and time toxicity benchmarks to support treatment sequencing decision-making in R/R FL.

A thorough understanding of hand and wrist vascular anatomy and disease patterns, combined with strategic use of multimodality imaging, enables radiologists to diagnose vascular diseases, guide clinical management, and help preserve limb function.

Background Rhabdomyolysis is a complex and potentially life-threatening syndrome characterized by the rapid breakdown of damaged skeletal muscle. Despite its clinical significance, universally accepted diagnostic criteria and standardized management guidelines are lacking. Methods A cross-sectional online survey about the current diagnostic approach, assessment of risk factors and severity, and management of follow-up of rhabdomyolysis was conducted among clinicians across Europe, Australia, and the USA. Results Fifty-four respondents from 16 countries completed the survey. Results revealed considerable variability in hospital admission practices, and patient follow-up. Some agreement was found in the frequent use of genetic and neurophysiological testing in as diagnostic tools. The survey revealed no consensus on which CK-level would be considered cut-off levels for rhabdomyolysis. Conclusions The survey found little to no coherent approach to diagnosing, assessment of severity, nor follow-up of rhabdomyolysis among respondents who were primarily neurologists and pediatric neurologists. It highlights the need for international guidelines in the diagnostic process, treatment and follow-up of rhabdomyolysis as well as a universally agreed definition of rhabdomyolysis.

Background & Aims: To evaluate safety and efficacy of FGFR1–3 kinase inhibitor derazantinib, in advanced intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions or rearrangements ( FGFR2 F ), mutations ( FGFR2 M ), or amplifications ( FGFR2 A ), previously treated with chemotherapy. Approach & Results: Open-label, non-controlled Phase 2 trial. Patients with advanced iCCA, ≥1 prior chemotherapy, and FGFR2 F (Substudy 1) or FGFR2 M /FGFR A (Substudy 2), received once-daily oral derazantinib 300 mg until disease progression, unacceptable toxicity, consent withdrawal or investigator decision to stop. Efficacy was assessed by central radiology review using RECIST v1.1. Primary endpoints were objective response rate (ORR; Substudy 1) and 3-month progression-free survival (PFS3; Substudy 2). Other endpoints were PFS, ORR (Substudy 2), disease control rate (DCR), duration of response (DOR), and overall survival (OS). In Substudy 1, ORR and DCR were 22.3% (23/103 partial responses) and 75.7%, respectively; median (95% CI) PFS was 8.1 (5.5,8.3) months, DOR was 6.5 (4.6,9.2) months, and OS was 17.2 (12.5,22.4) months. In Substudy 2, PFS3 was 63% (27/43), ORR was 9.3% (3 partial, 1 complete response), DCR was 69.8%, and OS was 11.9 (8.4,15.9) months. There were no Grade 4 or 5 drug-related events. FGFR inhibitor class-specific toxicities included drug-related hyperphosphataemia (38%, Grade 3: 3%) and dry eye (36%). Nail disorders (10%, any grade or causality), stomatitis (5%), retinal events (5%), and palmar-plantar erythrodysesthesia (1%) were infrequent. Conclusions: In previously chemotherapy treated, FGFR-inhibitor-naïve patients with iCCA harboring FGFR2 fusions, mutations, or amplifications, derazantinib showed clinically meaningful efficacy with durable objective responses, and a manageable safety profile.

Abstract Emotional experiences during focal seizures are often misinterpreted as psychiatric disorders. We aimed to evaluate symptoms involving affective symptoms at seizure onset. We aimed to identify the most prevalent affective symptoms at seizure onset and characterize their localizing and lateralizing value. We performed a scoping review based on Preferred Reporting Items for Systematic reviews and Meta‐Analyses–extension for Scoping Reviews guidelines. A systematic search identified records from 4 databases: PubMed, Embase, CINAHL (via EBSCOhost), and Web of Science. Two reviewers independently screened titles/abstracts and full texts; discrepancies were resolved by consensus. This review focused on patients with focal seizures, as affective symptoms may occur in generalized epilepsies. The affective symptoms: fear, anxiety, panic, sadness, mystic, ecstatic, sexual, and mirth were identified, and semiology was evaluated in accordance with ILAE guidelines. Symptom onset, frequency, brain localization, and video‐EEG monitoring technique were evaluated to assess localization and lateralization of regional networks. Scalp EEG, invasive EEG recordings, and electrical stimulation were analyzed. A total of 1276 documents were identified, with 98 studies included for review. Fear was the most frequently reported ictal emotion, identified in 274 patients (66%), predominantly in temporal lobe epilepsy. Sadness and sexual, ecstatic symptoms were also consistently associated with temporal networks. Mirth was more frequently reported with frontal onset seizures. Evidence, primarily from Class IV studies, reported right hemispheric predominance for ecstasy, mystic, and sexual symptoms at seizure onset. Ictal affective symptoms at seizure onset yield localizing information. The limbic system, especially the temporal lobe, followed by the frontal lobe, was the most common site of origin. Fear was the most common spontaneous and electrically elicited symptom, followed by anxiety. While bi‐hemispheric lateralization occurred, right lateralization predominated. Recognizing paroxysmal affective symptoms as ictal phenomena may reduce misdiagnosis and aid presurgical evaluation in drug‐resistant focal epilepsy.