Annals of Neurology最新文献

{"title":"Frequency and Early Predictors of Cognitive Deterioration in Amyotrophic Lateral Sclerosis: A Longitudinal Population-Based Study","authors":"Barbara Iazzolino PsyD,&nbsp;Francesca Palumbo MD,&nbsp;Cristina Moglia MD, PhD,&nbsp;Umberto Manera MD, PhD,&nbsp;Maurizio Grassano MD, PhD,&nbsp;Enrico Matteoni MD,&nbsp;Sara Cabras MD,&nbsp;Maura Brunetti BsC,&nbsp;Rosario Vasta MD, PhD,&nbsp;Marco Pagani MD,&nbsp;Gabriele Mora MD,&nbsp;Antonio Canosa MD, PhD,&nbsp;Andrea Calvo MD, PhD, FAAN, FEAN,&nbsp;Adriano Chiò MD, FAAN","doi":"10.1002/ana.27194","DOIUrl":"10.1002/ana.27194","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective is to evaluate cognitive and behavioral progression and identify early predictors of these changes in a cohort of amyotrophic lateral sclerosis (ALS) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 161 ALS patients were tested at diagnosis (T0), and 107 were re-tested after 1 year (T1) using cognitive/behavioral tests. All patients underwent whole-genome sequencing, and 46 patients (ALS-normal cognition [CN]) underwent [18F]Fluorodeoxyglucose positron emission tomography.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 161 patients, 107 were re-rested at T1; non-retested patients included 10 with frontotemporal dementia and 44 who were either non-testable or deceased. At T0, 67 patients (62.6%) were classified as ALS-CN, whereas 40 (38.4%) showed some degree of cognitive/behavioral impairment. Eighteen ALS-CN patients (26.9%) experienced cognitive decline at T1. Phenoconverters had lower baseline scores in letter fluency (Letter Fluency Test [FAS]) (<i>p</i> &lt; 0.001), Edinburgh Cognitive and Behavioral ALS Screen (ECAS) verbal fluency score (<i>p</i> = 0.017). Both tests were independently predictive of phenoconversion in binary logistic regression models, with optimal cut-off scores of 28.75 and 14.2, with good sensitivity and specificity. Other predictors included older age, lower education, and ALS-related genetic variants. Phenoconverters were hypometabolic in the left temporal lobe. Thirteen (32.5%) of the 40 patients with cognitive impairment at T0 worsened by T1, with FAS (<i>p</i> = 0.02) and the ECAS verbal fluency score (<i>p</i> = 0.023) predicting further decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Approximately 30% of ALS patients experienced cognitive/behavioral decline within the first year after diagnosis. FAS and ECAS verbal fluency were predictive of cognitive phenoconversion. Our findings highlight the importance of early detection of at-risk individuals and the need for longitudinal cognitive assessments to monitor disease progression. ANN NEUROL 2025;97:1122–1133</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 6","pages":"1122-1133"},"PeriodicalIF":8.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Perforators Collateral in Middle Cerebral Artery Occlusion","authors":"Ying Yu MD,&nbsp;Ning Ma MD","doi":"10.1002/ana.27199","DOIUrl":"10.1002/ana.27199","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 5","pages":"961-962"},"PeriodicalIF":8.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerated Cellular Senescence in Progressive Multiple Sclerosis: A Histopathological Study","authors":"Dimitrios Papadopoulos MD, PhD,&nbsp;Roberta Magliozzi PhD,&nbsp;Sara Bandiera PhD,&nbsp;Ilaria Cimignolo MSc,&nbsp;Elena Barusolo MSc,&nbsp;Lesley Probert PhD,&nbsp;Vassilis Gorgoulis MD, PhD,&nbsp;Richard Reynolds PhD,&nbsp;Richard Nicholas FRCP, PhD","doi":"10.1002/ana.27195","DOIUrl":"10.1002/ana.27195","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The neurodegenerative processes driving the build-up of disability in progressive multiple sclerosis (P-MS) have not been fully elucidated. Recent data link cellular senescence (CS) to neurodegeneration. We investigated for evidence of CS in P-MS and sought to determine its pattern.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used 53BP1, p16, and lipofuscin as markers of CS in white matter lesions (WMLs), normal appearing white matter (NAWM), normal appearing cortical gray matter (NAGM), control white matter (CWM), and control gray matter (CGM) on autopsy material from patient with P-MS and healthy controls. Senescence-associated secretory phenotype (SASP) factors were quantified in cerebrospinal fluid (CSF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>P16⁺ cell counts were significantly increased in WMLs and GMLs, compared with NAWM, CWM, NAGM, and CGM and lipofuscin⁺ cells were significantly increased in WMLs, compared with NAWM and CWM, indicating more abundant CS in demyelinated lesions. The 53BP1⁺ cells in WMLs were significantly increased compared with NAWM and CWM. The 53BP1⁺ and p16⁺ cells were found significantly more abundant in acute active WMLs and GMLs, compared with chronic inactive lesions. Co-localization studies showed evidence of CS in neurons, astrocytes, oligodendrocytes, microglia, and macrophages. Among the quantified CSF SASP factors, IL-6, MIF, and MIP1a levels correlated with 53BP1⁺ cell counts in NAGM, whereas IL-10 levels correlated with p16⁺ cell counts in NAWM. P16⁺ cell counts in WMLs exhibited an inverse correlation with time to requiring a wheelchair and with age at death.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our data indicates that CS primarily affects actively demyelinating gray and WMLs. A higher senescent cell load in P-MS is associated with faster disability progression and death. ANN NEUROL 2025;97:1074–1087</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 6","pages":"1074-1087"},"PeriodicalIF":8.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimaging Predictors of Cognitive Resilience against Alzheimer's Disease Pathology","authors":"McKenna E. Williams MS,&nbsp;Christine Fennema-Notestine PhD,&nbsp;Tyler R. Bell PhD,&nbsp;Shu-Ju Lin PhD,&nbsp;Stephen J. Glatt PhD,&nbsp;William S. Kremen PhD,&nbsp;Jeremy A. Elman PhD,&nbsp;for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/ana.27186","DOIUrl":"10.1002/ana.27186","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Some individuals demonstrate greater cognitive resilience—the ability to maintain cognitive performance despite adverse brain-related changes—through as yet unknown mechanisms. We examined whether cortical thickness in several brain regions confers resilience against cognitive decline in amyloid-positive adults by moderating the effects of thinner cortex in Alzheimer's disease (AD)-related brain regions and of higher levels of tau.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Amyloid-positive participants from the Alzheimer's Disease Neuroimaging Initiative with relevant imaging data were included (n = 160, observations = 473). Risk factors included an AD brain signature and cerebrospinal fluid phosphorylated tau. Cognitive measures were episodic memory and executive function composites. Mixed effects models tested whether region-specific cortical thickness moderated relationships between markers of AD risk and memory or executive function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cross-sectionally, thicker cortex in 8 regions minimized the negative impact of thinner cortex/smaller volume in AD signature regions on executive function. Longitudinally, higher baseline thickness in a composite of these 8 regions predicted less memory decline (<i>p</i> = 0.007) and weakened negative effects of phosphorylated tau on memory decline (<i>p</i> = 0.014), independent of baseline cognition and risk markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>We identified 8 cortical regions that appear to confer cognitive resilience cross-sectionally and longitudinally in the face of established indicators of AD pathology. Brain regions fostering executive function may enable compensation in later memory performance and confer cognitive resilience against effects of phosphorylated tau and AD-related cortical changes. These “resilience” regions suggest the value of focusing on brain regions beyond only those determined to be AD-related and may partially explain variability in AD-related cognitive trajectories. ANN NEUROL 2025;97:1038–1050</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 6","pages":"1038-1050"},"PeriodicalIF":8.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle Hypermetabolism and Pruritus in Amphiphysin-IgG-Positive Stiff-Person Syndrome","authors":"Samir Alkabie MD, MSc,&nbsp;Janet Yeh MD,&nbsp;Sabina Hajiyeva MD,&nbsp;Souhel Najjar MD","doi":"10.1002/ana.27191","DOIUrl":"10.1002/ana.27191","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 5","pages":"976-978"},"PeriodicalIF":8.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spiking Patterns in the Globus Pallidus Highlight Convergent Neural Dynamics across Diverse Genetic Dystonia Syndromes","authors":"Ahmet Kaymak PhD,&nbsp;Fabiana Colucci MD, PhD,&nbsp;Mahboubeh Ahmadipour PhD,&nbsp;Nico Golfrè Andreasi MD,&nbsp;Sara Rinaldo Tch,&nbsp;Zvi Israel MD,&nbsp;David Arkadir MD, PhD,&nbsp;Roberta Telese MD,&nbsp;Vincenzo Levi MD,&nbsp;Giovanna Zorzi MD,&nbsp;Jacopo Carpaneto PhD,&nbsp;Miryam Carecchio MD, PhD,&nbsp;Holger Prokisch PhD,&nbsp;Michael Zech MD, PhD,&nbsp;Barbara Garavaglia PhD,&nbsp;Hagai Bergman MD, PhD,&nbsp;Roberto Eleopra MD,&nbsp;Alberto Mazzoni PhD,&nbsp;Luigi M. Romito MD, PhD","doi":"10.1002/ana.27185","DOIUrl":"10.1002/ana.27185","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Genetic dystonia is a complex movement disorder with diverse clinical manifestations resulting from pathogenic mutations in associated genes. A recent paradigm shift emphasizes the functional convergence among dystonia genes, hinting at a shared pathomechanism. However, the neural dynamics supporting this convergence remain largely unexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Herein, we analyzed microelectrode recordings acquired during pallidal deep brain stimulation surgery from 31 dystonia patients with pathogenic mutations in the <i>AOPEP</i>, <i>GNAL</i>, <i>KMT2B</i>, <i>PANK2</i>, <i>PLA2G6</i>, <i>SGCE</i>, <i>THAP1</i>, <i>TOR1A</i>, and <i>VPS16</i> genes. We identified 1,694 single units whose activity was characterized by a broad set of neural features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>AOPEP</i>, <i>PANK2</i>, and <i>THAP1</i> displayed higher firing regularity, whereas <i>GNAL</i>, <i>PLA2G6</i>, <i>KMT2B</i>, and <i>SGCE</i> shared a large fraction of bursting neurons (&gt; 26.6%), significantly exceeding the rate in other genes. <i>TOR1A</i> and <i>VPS16</i> genes constituted an intermediate group, bridging these 2 groups, due to having the highest degree of spiking irregularity. Hierarchical clustering algorithms based on these dynamics confirmed the results obtained with first-order comparisons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Despite lacking common molecular pathways, dystonia genes share largely overlapping structures of neural patterns, in particular the degree of pallidal spiking regularity and bursting activity. We propose that the degree of desynchronization facilitated by pallidal neural bursts may explain the variability in deep brain stimulation (DBS) of the globus pallidus internus (GPi) surgery outcomes across genetic dystonia syndromes. Lastly, investigating the effects of genetic mutations on low-frequency pallidal activity could optimize personalized adaptive DBS treatments in patients with genetic dystonia. ANN NEUROL 2025;97:826–844</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 5","pages":"826-844"},"PeriodicalIF":8.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vertebral Artery Pseudoaneurysm: Novel Marker of Bow Hunter's Syndrome","authors":"Joseph Y. Yoon MD, MSc, MAEd,&nbsp;Mehrdad Emami MD,&nbsp;J Mocco MD, MS,&nbsp;M. Travis Caton Jr MD","doi":"10.1002/ana.27188","DOIUrl":"10.1002/ana.27188","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 5","pages":"959-960"},"PeriodicalIF":8.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling Sporadic Progressive Supranuclear Palsy in 3D Midbrain Organoids: Recapitulating Disease Features for In Vitro Diagnosis and Drug Discovery","authors":"Elvira Immacolata Parrotta PhD,&nbsp;Valeria Lucchino PhD,&nbsp;Clara Zannino PhD,&nbsp;Desirèe Valente PhD,&nbsp;Stefania Scalise PhD,&nbsp;Davide Bressan PhD,&nbsp;Giorgia Lucia Benedetto PhD,&nbsp;Maria Roberta Iazzetta PhD,&nbsp;Mariagrazia Talarico PhD,&nbsp;Monica Gagliardi PhD,&nbsp;Francesco Conforti PhD,&nbsp;Silvia Di Agostino PhD,&nbsp;Alessandro Fiorenzano PhD,&nbsp;Aldo Quattrone MD,&nbsp;Giovanni Cuda MD,&nbsp;Andrea Quattrone MD, PhD","doi":"10.1002/ana.27172","DOIUrl":"10.1002/ana.27172","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Progressive Supranuclear Palsy (PSP) is a severe neurodegenerative disease characterized by tangles of hyperphosphorylated tau protein and tufted astrocytes. Developing treatments for PSP is challenging due to the lack of disease models reproducing its key pathological features. This study aimed to model sporadic PSP-Richardson's syndrome (PSP-RS) using multi-donor midbrain organoids (MOs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The MOs were generated by pooling induced pluripotent stem cells (iPSCs) from 4 patients with sporadic probable PSP-RS and compared them with MOs from 3 healthy control (HC) subjects. We performed comprehensive analyses of MOs over 120 days to assess neuronal death, reactive gliosis, and the accumulation of 4R-tau and hyperphosphorylated tau forms (pThr231, pSer396, pThr181, and pSer202/pThr205 [AT8]) using immunofluorescence microscopy and Western blot. On day 90, immunohistochemical analysis using pSer396 and AT8 antibodies was conducted to assess disease pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PSP-derived MOs showed progressive size reduction compared with HC-derived MOs, linked to upregulated apoptosis-related mRNA markers. Dopaminergic neuron degeneration was marked by decreased tyrosine hydroxylase (TH) and increased neurofilament light chain (NfL). Immunofluorescence and Western blot revealed accumulation of all investigated tau forms with a peak at 90 days, along with a significant rise in GFAP-positive cells in PSP-derived MOs. Immunochemistry confirmed typical PSP histological alterations, such as neurofibrillary tangles and tufted-shaped astrocytes, absent in HC-derived organoids.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>We developed a robust in vitro PSP model reproducing the key molecular and histologic features of the disease. This result holds promise for advancing basic and clinical research in PSP, paving the way for in vitro molecular diagnosis and identification of novel therapeutic targets. ANN NEUROL 2025;97:845–859</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 5","pages":"845-859"},"PeriodicalIF":8.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heparin-Binding Protein in Cerebrospinal Fluid as a Biomarker for Bacterial Meningitis: A Study of Diagnostic Accuracy","authors":"Sabine E. Olie MD,&nbsp;Steven L. Staal MD,&nbsp;Ana C. da Cruz Campos,&nbsp;Jacob Bodilsen MD, PhD,&nbsp;Henrik Nielsen MD, PhD,&nbsp;Diederik van de Beek MD, PhD,&nbsp;Matthijs C. Brouwer MD, PhD","doi":"10.1002/ana.27193","DOIUrl":"10.1002/ana.27193","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We aimed to evaluate the diagnostic accuracy of heparin-binding protein (HBP) in cerebrospinal fluid for the diagnosis of bacterial meningitis in patients with a suspected central nervous system infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective multicenter cohort study determined the diagnostic accuracy of HBP in cerebrospinal fluid (CSF) for bacterial meningitis among a cohort of consecutive patients with a suspected central nervous infection. The final clinical diagnosis was considered the reference standard. The results were validated in a separate cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 631 Dutch patients were evaluated for the current study, of which 73 (12%) had a final diagnosis of bacterial meningitis. For the differentiation of bacterial meningitis from all other disorders, diagnostic accuracy was high with an area under the curve (AUC) of 0.98 (95% confidence interval [CI] 0.96–1.00). With the proposed cutoff of 5.2 ng/ml, sensitivity was 97% with a specificity of 96%. In the population of patients with a CSF leukocyte count of 5-1,000/mm³, the AUC was 0.96 (95% CI 0.87–1.00), outperforming CSF leukocytes (AUC 0.88 [95% CI 0.79–0.97]). Combining HBP with CSF C-reactive protein (CRP) significantly increased accuracy in this population and reached a 100% sensitivity (AUC 1.00 [95% CI 0.99–1.00], cutoff 0.07, sensitivity 100%, specificity 96%). These results remained robust in an external validation cohort of 120 Danish patients (AUC 0.97 [95% CI 0.93–1.00]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>HBP can correctly distinguish bacterial meningitis from other disorders. It can be of additional value to current diagnostics in cases where CSF leukocyte count is relatively low, particularly when combined with CSF CRP. ANN NEUROL 2025;97:1088–1095</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 6","pages":"1088-1095"},"PeriodicalIF":8.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged Febrile Seizure and Long-Term Neurological Sequelae in Otherwise Healthy Children","authors":"Takenori Suga MD,&nbsp;Takeshi Yoshida MD, PhD,&nbsp;Atsushi Yokoyama MD, PhD,&nbsp;Yotaro Hanami MD,&nbsp;Kazushige Ashina MD,&nbsp;Natsumi Nakamura MD,&nbsp;Koji Kawakami MD, PhD,&nbsp;Junko Takita MD, PhD,&nbsp;Masato Takeuchi MD, MPH, PhD","doi":"10.1002/ana.27192","DOIUrl":"10.1002/ana.27192","url":null,"abstract":"<p>The association between prolonged febrile seizure and long-term neurological sequelae in otherwise healthy children remains unclear. We conducted a retrospective cohort study using a Japanese nationwide medical database. In the cohort of 38,465 children with febrile seizures, 610 and 31,157 were classified into the prolonged and non-prolonged groups, respectively. Within a median of 2.70 years of follow-up, the risk of subsequent epilepsy was significantly higher in the prolonged febrile seizure group (hazard ratio, 3.99; 95% confidence interval, 2.40–6.64). The risk of neurodevelopmental disorders was similar between the two groups (hazard ratio, 1.39; 95% confidence interval, 1.00–1.79). ANN NEUROL 2025;97:688–693</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 4","pages":"688-693"},"PeriodicalIF":8.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}