European Journal of Neurology最新文献

{"title":"New-Onset Headache After SARS-CoV-2 Infection and Vaccination: Results From Three Population-Based Cohorts in Norway","authors":"Kristine Blix,&nbsp;Ida Laake,&nbsp;Ida Henriette Caspersen,&nbsp;Berit Feiring,&nbsp;Anna Hayman Robertson,&nbsp;Siri N. Skodvin,&nbsp;Siri Mjaaland,&nbsp;Per Magnus,&nbsp;Anker Stubberud,&nbsp;Marte-Helene Bjørk,&nbsp;Lill Trogstad","doi":"10.1111/ene.70437","DOIUrl":"10.1111/ene.70437","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Persistent headache after SARS-CoV-2 infections and vaccination has been reported. However, limited data exist on the risk of new-onset headache after these exposures compared to unexposed periods in the general population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used data from three population-based cohorts (<i>N</i> = 85,774, age 19–81 years). SARS-CoV-2 infections and vaccinations were obtained from national registries and questionnaires. Before and after Omicron emergence, participants stated whether they had been suffering from headache during the past year, reported headache characteristics, and time of onset. Time-dependent exposures were used to investigate the impact of SARS-CoV-2 infection and vaccination on the risk of new-onset headache. Headache subtypes were secondary outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SARS-CoV-2 infection and first and second vaccine doses were associated with increased risk of new-onset headache. The three cohorts, representing different age groups, were analyzed separately. For pre-Omicron infections, the hazard ratio (HR) was 6.7 (95% confidence interval (CI) 4.8–9.2) and 6.5 (95% CI 3.8–11.1) among middle-aged women and men, respectively. For Omicron infection, HRs were 4.7 (95% CI 4.1–5.4) and 4.5 (95% CI 3.7–5.4), respectively. The risk increased with infection severity. Corresponding HRs for first and second vaccine doses, administered during low transmission, were 1.6 and 1.7, respectively, in women, and 1.5 for both doses in men. The third dose, given before the Omicron surge, was associated with 20%–40% protection against new-onset headache.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SARS-CoV-2 infection was strongly associated with new-onset headache. Primary vaccination was associated with a small increased risk of headache during a low-transmission period, whereas booster vaccination offered protection during high-transmission.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12675824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Profiling of Annexins in Neuromuscular Disorders Reveals a Unique Signature in Dysferlinopathy","authors":"Qi-Fang He,&nbsp;Yu-hua Lin,&nbsp;Ze-ling Zheng,&nbsp;Ming-hui Zeng,&nbsp;Xin Lin,&nbsp;Xin-yi Liu,&nbsp; Kang-yang,&nbsp;Q I-jie Zhang,&nbsp;Min-ting Lin,&nbsp;Ning Wang,&nbsp;Zhi-qiang Wang,&nbsp;Feng Lin","doi":"10.1111/ene.70442","DOIUrl":"10.1111/ene.70442","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Annexins are a family of calcium-dependent membrane-binding proteins implicated in membrane repair and inflammation, yet their immunoreactivity patterns in neuromuscular disorders remain poorly characterized. This study systematically examined the immunoreactivity profiles of annexins A1, A2, A4, A5, A6, A7, and A11 across various muscular dystrophies, including muscular dystrophies, inflammatory myopathies, lipid storage myopathy (LSM), and amyotrophic lateral sclerosis (ALS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Muscle biopsies from patients with dysferlinopathy, Duchenne/Becker muscular dystrophy (DMD/BMD), myotonic dystrophy type 1 (DM1), oculopharyngeal muscular dystrophy (OPMD), facioscapulohumeral muscular dystrophy (FSHD), LSM, inflammatory myopathies, and ALS, along with controls, were analyzed. Immunofluorescence and immunoblot assays were used to assess annexin localization and abundance, and quantitative immunoreactivity levels were statistically compared with controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Dysferlinopathy showed a distinct upregulation of multiple annexins (A1, A2, A4, A5, A6, and A7). These annexins were primarily localized to the extracellular matrix, with additional cytoplasmic accumulation in atrophied fibers. Annexin A6 was strongly associated with the sarcolemma, while annexin A7 was diffusely distributed. In contrast, other myopathies such as OPMD and FSHD exhibited reduced or unchanged annexin immunoreactivity. Inflammatory myopathies partially mirrored the dysferlinopathy pattern, though annexin A2 levels were lower. ALS samples displayed minimal immunoreactivity, restricted to focal cytoplasmic annexin A1 and sparse sarcolemmal annexin A6.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings reveal a unique annexin signature in dysferlinopathy, suggesting a potential involvement in membrane repair and inflammatory modulation. The differential expression across disorders highlights the diverse roles of annexins in muscle pathophysiology and supports their utility as diagnostic biomarkers and therapeutic targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12669908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI-DTI Biomarkers Along the Continuum of Behavioral Variant Frontotemporal Dementia","authors":"Marco Michelutti,&nbsp;Hans-Jürgen Huppertz,&nbsp;Sarah Anderl-Straub,&nbsp;Heiko Volkmann,&nbsp;Daniele Urso,&nbsp;Benedetta Tafuri,&nbsp;Salvatore Nigro,&nbsp;Paolo Manganotti,&nbsp;Angela Rosenbohm,&nbsp;Albert C. Ludolph,&nbsp;Markus Otto,&nbsp;Giancarlo Logroscino,&nbsp;Hans-Peter Müller,&nbsp;Jan Kassubek","doi":"10.1111/ene.70438","DOIUrl":"10.1111/ene.70438","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>We investigated whether diffusion tensor imaging (DTI) and atlas-based volumetry (ABV) could track specific patterns of brain white matter (WM) microstructure and gray matter (GM) volumes in behavioral variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis with frontotemporal dementia (ALS-FTD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MRI datasets from 65 bvFTD (including 19 with longitudinal MRI), 18ALS-FTD, and 39 controls were analyzed. White matter fractional anisotropy (FA) differences were assessed using unbiased Whole Brain-based Spatial Statistics (WBSS) and a hypothesis-driven complementary approach consisting of Tract-Wise FA Statistics (TFAS) in Tracts of Interest (TOIs) and ABV in Structures of Interest (SOIs). FA maps were correlated with disease severity (FTLD-CDR sum of boxes). A random forest algorithm classified participants employing TOI and SOI data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At baseline, both bvFTD and ALS-FTD exhibited WM changes in several tracts including the uncinate fasciculi, tracts originating in the corpus callosum, and the inferior and superior longitudinal fasciculi. Atrophy was most pronounced in the frontal lobes and caudate nuclei. Longitudinally, bvFTD demonstrated an antero-posterior spread of WM degeneration, particularly along the corpus callosum and inferior longitudinal fasciculus, with relatively modest cortical atrophy progression. Random forest analysis identified the most discriminative TOIs and SOIs including the uncinate fasciculus and the amygdala.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrate a similar pattern of structural and microstructural changes in bvFTD and ALS-FTD, with a specific involvement of the corticospinal tract for ALS-FTD, and support the utility of combined DTI and ABV in tracking disease progression across the FTLD spectrum.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dermal Alpha-Synuclein Aggregation in Seed Amplification Assays for Parkinson's Disease Subtype Differentiation","authors":"Magdalena Vieregge,&nbsp;Anastasia Kuzkina,&nbsp;Annette Janzen,&nbsp;Wolfgang H. Oertel,&nbsp;Michael Sommerauer,&nbsp;Jens Volkmann,&nbsp;Kathrin Doppler","doi":"10.1111/ene.70453","DOIUrl":"https://doi.org/10.1111/ene.70453","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Skin biopsies and seed amplification assays (SAA) provide a sensitive and potentially quantitative method to detect alpha-synuclein (a-syn) aggregation in peripheral nerve fibers in Parkinson's disease (PD). Relating to the previously published hypothesis that PD may either originate in the peripheral (body-first) or central (brain-first) nervous system, we investigated whether patients with clinical features that have been reported to be associated with a suspected body-first subtype of PD exhibit higher levels of a-syn aggregation in dermal nerve fibers compared to those without these features. Patients with isolated REM sleep behavior disorder (iRBD) representing a suspected premotor stage of body-first PD were studied in comparison to the PD cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients were categorized on the basis of clinical features, and SAA parameters such as lag time, number of positive curves, and titers were analyzed and correlated with clinical features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Although patients with clinical features of suspected body-first PD showed slightly higher titers, significant differences were mainly observed between iRBD patients and PD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data suggest that widespread α-syn aggregation in advanced PD limits the use of SAA in skin biopsies for subtype differentiation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70453","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Letter to the Editor: Headache After Sealing of Cerebrospinal Fluid Leaks in Patients With Spontaneous Intracranial Hypotension","authors":"Adrian Scutelnic,&nbsp;Nedelina Slavova,&nbsp;Eric Morel,&nbsp;Franz Riederer,&nbsp;Tomas Dobrocky,&nbsp;Eike I. Piechowiak,&nbsp;Ralph T. Schär,&nbsp;Christoph J. Schankin","doi":"10.1111/ene.70431","DOIUrl":"https://doi.org/10.1111/ene.70431","url":null,"abstract":"&lt;p&gt;We thank Irshad and Nizami for their letter to the editors commenting on our article “Headache After Sealing of Cerebrospinal Fluid Leaks in Patients With Spontaneous Intracranial Hypotension.”&lt;/p&gt;&lt;p&gt;We agree that rebound intracranial hypertension is a well-known complication in SIH patients following successful sealing of a CSF leak. However, there is no consensus on how to approach these patients. Fortunately, rebound hypertension has been found to be self-limited in most cases. Consequently, lumbar punctures are not warranted for these patients. Indeed, a repeat lumbar puncture might actually be harmful by causing a second lumbar leak with subsequent post-punctional headache or even worse complications in subjects who are just recovering from intracranial hypotension.&lt;/p&gt;&lt;p&gt;It is true that from a purely methodological point of view, a control population of untreated SIH patients would most certainly strengthen our findings. However, given the known risks of persisting CSF leaks such as superficial siderosis, subdural hematoma and bibrachial atrophy [&lt;span&gt;1&lt;/span&gt;], we strongly recommend treating every SIH patient with a proven CSF leak. A control group with primary headache disorders such as migraine would not be adequate since they are both fundamentally different in respect to clinical and pathophysiological mechanisms. In our study, we were able to explore pre-existing primary headache and other co-morbidities (e.g., medication overuse) as potential risk factors for persistent headache despite successful sealing of the CSF leak.&lt;/p&gt;&lt;p&gt;It is true that we did not elaborate in detail on our treatment protocol for sealing CSF leaks in SIH patients, which have been described elsewhere [&lt;span&gt;2, 3&lt;/span&gt;]. Rather than classifying CSF leaks as high- vs. low- flow leaks, as suggested by Nizami and Irshad, anatomical location and type of the CSF have proven to be the key determinants in selecting the appropriate management strategy (microsurgical repair vs. endovascular embolization).&lt;/p&gt;&lt;p&gt;As detailed in the method section, this is a retrospective study of a large population of a rare disorder. This comes with inherent limitations, such as no standardized follow-up and the lack of psychometric- and headache-related scores as listed by the authors of the comment. Similarly, we did not explore central pain sensitization using methods such as cutaneous allodynia or “permanent pain pathways changes.” Although being interesting, data on central sensitization would not allow assessing whether headaches are due to ongoing CSF disturbances, as central sensitization is not specific with regard to the etiologies of chronic pain syndromes.&lt;/p&gt;&lt;p&gt;Still, we agree that such patient-reported outcomes, scores and measures of central sensitization would be interesting, and we encourage the authors and other researchers worldwide to set up prospective and controlled studies to better understand and treat patients with SIH.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Adrian Scutelnic:&lt;/b&gt; conceptu","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor: “Headache After Sealing of Cerebrospinal Fluid Leaks in Patients With Spontaneous Intracranial Hypotension”","authors":"Yixin Fu,&nbsp;Jianghao Yu,&nbsp;Qingshan Deng","doi":"10.1111/ene.70439","DOIUrl":"https://doi.org/10.1111/ene.70439","url":null,"abstract":"<p>I recently read the article titled “Headache After Sealing of Cerebrospinal Fluid Leaks in Patients With Spontaneous Intracranial Hypotension” published in <i>European Journal of Neurology</i> [<span>1</span>]. I commend the authors for their important work in investigating the long-term outcomes of patients with persistent headache following the sealing of cerebrospinal fluid (CSF) leaks.</p><p>However, I would like to suggest a few considerations that could strengthen the study's findings. The study mentions the correlation between various clinical features and persistent headaches, but does not perform a more detailed regression analysis to better control for potential confounding factors [<span>2</span>]. A more robust statistical analysis could help identify the most significant predictors of persistent headaches and improve the interpretability of the results.</p><p>Additionally, the article highlights the occurrence of recurrent or new CSF leaks in some patients, which suggests a possible risk of missed diagnoses or recurrence. A comparison of the characteristics of these patients with those who did not experience recurrence could help identify potential risk factors for such leaks [<span>3</span>].</p><p>Lastly, as this is an observational study without a control group or randomization, the findings may be influenced by selection bias. The absence of a control group makes it challenging to attribute changes in headache outcomes directly to the sealing treatment, as other factors such as treatment delays or coexisting conditions may also play a role [<span>4</span>].</p><p>In conclusion, while the study provides valuable insights, addressing these statistical aspects in future research could enhance the understanding of persistent headaches in SIH patients and guide clinical practice more effectively.</p><p><b>Yixin Fu:</b> conceptualization, writing – original draft. <b>Jianghao Yu:</b> conducted a literature review and reference validation. <b>Qingshan Deng:</b> supervised the commentary, finalized recommendations and manuscript as corresponding author.</p><p>The authors declare no conflicts of interest.</p><p>This article is linked to Scutelnic et al. papers. To view this article, visit https://doi.org/10.1111/ene.70431 and Nizami and Irshad papers. To view this article, visit https://doi.org/10.1111/ene.70436.</p><p>The authors have nothing to report.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning Analysis Applied to Prediction of Early Progression Independent of Relapse Activity in Multiple Sclerosis Patients","authors":"Valentina Poretto,&nbsp;Walter Endrizzi,&nbsp;Matteo Betti,&nbsp;Stefano Bovo,&nbsp;Angelo Bellinvia,&nbsp;Flavio Ragni,&nbsp;Caterina Lapucci,&nbsp;Monica Moroni,&nbsp;Sabrina Marangoni,&nbsp;Emilio Portaccio,&nbsp;Chiara Longo,&nbsp;Lorenzo Gios,&nbsp;Marco Chierici,&nbsp;Giuseppe Jurman,&nbsp;Bruno Giometto,&nbsp;Matilde Inglese,&nbsp;Venet Osmani,&nbsp;Manuela Marenco,&nbsp;Antonio Uccelli,&nbsp;Maria Pia Amato","doi":"10.1111/ene.70417","DOIUrl":"https://doi.org/10.1111/ene.70417","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Predicting prognosis in people with multiple sclerosis (pwMS) at early disease stages still remains an unmet need. Machine learning (ML) strategies demonstrated good reliability when applied for prediction in medicine. This study aimed at developing a predictive algorithm comparing different ML approaches, by using routine demographic, clinical and radiological data from a large multicentric cohort of newly diagnosed pwMS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Demographic, clinical, radiological and biochemical data were retrospectively collected at three Italian MS centers at baseline and four timepoints thereafter (6, 12, 24, and 36 months). Data from the first evaluation and subsequent 2-year follow-up were analyzed, comparing different ML models (Random Forest, Extra Trees, XGBoost, Logistic Regression and Support Vector Classifier) to predict progression independent of relapse activity (PIRA) at year 3. To understand how features impacted the selected model's output, a ML explainability analysis was performed on the whole cohort and on specific subsets of patients, those aged under 45 and those NEDA-3 at the 2-year follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data from 719 pwMS (age 34.6 ± 11.2 years); female sex 501 (70%) were analyzed. Ninety-two pwMS (13%) developed PIRA at year 3. Random Forest achieved the highest score, with a test set area under the ROC curve (AUC) of 0.75 ± 0.06. Features with the highest predictive impact were Expanded Disability Status Scale at 24 months, age at symptom onset and disease duration at baseline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results showed the feasibility of applying ML techniques to predict short-term PIRA in newly diagnosed pwMS by using routine clinical practice data, paving the way for tailored and personalized approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70417","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor: Headache After Sealing of Cerebrospinal Fluid Leaks in Patients With Spontaneous Intracranial Hypotension","authors":"Hafiza Aimal Nizami,&nbsp;Noor un nisa Irshad","doi":"10.1111/ene.70436","DOIUrl":"https://doi.org/10.1111/ene.70436","url":null,"abstract":"&lt;p&gt;The recent study by Scutelnic et al. [&lt;span&gt;1&lt;/span&gt;] evaluating headaches following CSF leak repair in patients with Spontaneous Intracranial Hypotension (SIH) provides valuable insights; however, several key factors appear to have been overlooked and merit discussion.&lt;/p&gt;&lt;p&gt;First of all, the study's operational definition of successful leak sealing is based exclusively on imaging resolution, without incorporating CSF pressure measurement (lumbar puncture or manometry). This omission is critical because post-procedural rebound intracranial hypertension is recognized complication after SIH treatment [&lt;span&gt;2&lt;/span&gt;]. According to ICHD-3, headache attributed to raised CSF pressure requires objective evidence of elevated CSF pressure [&lt;span&gt;3&lt;/span&gt;]. Without such measurements, anatomical sealing may be mistaken for functional recovery, as rebound intracranial hypertension and other CSF pressure dysregulations occur in a notable proportion of treated patients [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The lack of a control group in this study fundamentally compromises its conclusions. Post-repair persistent headache was not compared to untreated SIH patients or individuals with primary headache disorders such as migraine, making it difficult to determine its origin. This omission is critical, as many of the reported new phenotype headaches may in fact represent unrelated primary disorders rather than sequelae of SIH [&lt;span&gt;4&lt;/span&gt;]. Without having an appropriate control group, it is impossible to determine whether post-repair headache arises from the natural course of CSF pressure dysregulation, incomplete leak closure, or unrelated primary headache syndromes.&lt;/p&gt;&lt;p&gt;The study did not evaluate psychological comorbidities, behavioral drivers, and quality of life (QoL) impacts. Despite documenting that 36% of refractory patients had pre-existing primary headache, the authors didn't assess depression and anxiety (a known factor amplifying pain perception), sleep disturbances (an established barrier to recovery), and QoL burden, for example, via HIT-6 or MIDAS scores. Future studies should incorporate HADS (Hospital Anxiety/Depression Scale), Pain Catastrophizing Scale, and HEADWORK (headache-specific productivity tool) to better integrate psychological and functional assessment.&lt;/p&gt;&lt;p&gt;Despite meticulously documenting leak locations and types, the study did not consider CSF flow dynamics (high-flow vs. low-flow), which are increasingly recognized as influencing treatment strategy [&lt;span&gt;5&lt;/span&gt;]. For instance, CSF-venous fistulas often require embolization or ligation, while dural tears may respond to epidural blood patches. Consequently, uniform protocols were applied, and patients received blood patches or surgery regardless of flow, without correlating leak type, size, and location with outcomes.&lt;/p&gt;&lt;p&gt;Another gap is the lack of systemic evaluation of central pain sensitization, such as cutaneous allodynia or other validated markers. Chronic SIH may induce permane","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Sleep Puzzle: Linking Glymphatic Function to Cognitive Decline","authors":"Matti Einari Ahlström,&nbsp;Aleksi Johannes Sihvonen","doi":"10.1111/ene.70451","DOIUrl":"https://doi.org/10.1111/ene.70451","url":null,"abstract":"&lt;p&gt;It has been almost 200 years since the first medical description of cerebral small vessel disease (cSVD). Beginning in the 1830s, several French physicians, most notably Maxime Durand-Fardel and Pierre Marie, reported distinct clinicopathological observations of patients with cognitive decline, gait disturbances and stroke episodes. Marie, appearing almost prescient, associated his patients' clinical symptoms with what would later become the radiological hallmarks of cSVD—lacunar infarcts, enlarged perivascular spaces, white matter tissue abnormalities and atrophy, as well as intracerebral haemorrhaging [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Despite this rich history, cSVD remains a global health concern and a major cause of cognitive impairment, with recent ESO guidelines highlighting the scarcity and generally low-quality evidence to support existing therapeutic interventions [&lt;span&gt;2&lt;/span&gt;]. Additionally, the pathophysiology of cSVD has remained elusive, with earlier models of chronic hypertensive hypoperfusion-induced ischemia appearing too rigid to account for the apparent heterogeneity among cSVD patients. Neurovascular unit dysfunction, blood–brain barrier leakage, inflammation and oligodendrocyte dysfunction have all been implicated in the cellular-level pathogenesis of cSVD [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The discovery of the glymphatic system in 2012 introduced a striking new viewpoint to the debate on brain health. A fluid and waste clearance system in the brain that had previously been completely hidden from pathologists, radiologists and clinicians alike? The notion seemed as preposterous as it was exciting. The glymphatic system has been proposed to permeate the brain parenchyma utilising perivascular spaces and has been speculated to be defective in a variety of neurological disorders [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;As the glymphatic pathways appear to be most active during deep sleep, there has been renewed interest in assessing sleep quality not only as an indicator of subjective well-being, but as a predictor of later neurodegeneration [&lt;span&gt;4&lt;/span&gt;]. This seems especially pertinent with cSVD, as the major anatomical features involved in the glymphatic system are also areas of impairment in cSVD. It has indeed recently been proposed that glymphatic dysfunction and sleep disturbances can be contributing factors in the pathology of cSVD [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;While most of our data on the glymphatic system comes from rodent models, waste removal certainly seems like an obvious and important element of maintaining health through senescence in the mammalian brain. Could a lack of deep, cleansing sleep be the missing link to explain why some patients with similar risk factors develop neurodegenerative disorders like Alzheimer's disease, while others don't? It has already been demonstrated that a single night of sleep deprivation impedes molecular clearance in the human brain, with the contrast marker used interpreted by the authors as a surrogate for amyloi","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Laboratory Predictors of Poor Neurological Outcomes Following Infectious Encephalitis: Systematic Review and Meta-Analysis","authors":"Thomas Johnson,&nbsp;Mia Venables,&nbsp;Babak Soleimani,&nbsp;Laurissa Havins,&nbsp;Annapoorna Kannan,&nbsp;Gregory Holt,&nbsp;Jonathan Cleaver,&nbsp;Adam E. Handel,&nbsp;Ava Easton,&nbsp;Defne Saatci,&nbsp;Lahiru Handunnetthi","doi":"10.1111/ene.70445","DOIUrl":"https://doi.org/10.1111/ene.70445","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Infectious encephalitis is a serious global health problem linked to high rates of mortality and morbidity. However, clinical and laboratory factors that impact neurological outcomes following infectious encephalitis remain poorly understood. Accordingly, we undertook a systematic review and meta-analysis of clinical and laboratory factors influencing neurological outcomes following infectious encephalitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We searched MEDLINE and EMBASE from inception to 25th September 2023 for observational studies that reported on neurological outcomes at discharge or at ≥ 6 months. We assessed the prognostic value of a priori selected clinical and laboratory-based features by estimating pooled risk ratios (RRs) through a random-effects meta-analysis. The <i>I</i>² statistic was used to assess heterogeneity. This study is registered with PROSPERO (CRD42023485045).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were several key findings. First, immunocompromised status, status epilepticus, and Glasgow coma scale of &lt; 8 during initial admission were significantly associated with poor neurological outcomes both at discharge and ≥ 6 months after infectious encephalitis onset. Second, CSF leucocytosis [RR: 0.83 95% CI: 0.69–0.98, <i>p</i> = 0.03, <i>n</i> = 5, <i>I</i>² = 0%] conferred better neurological outcomes while elevated CSF protein [RR: 1.25 95% CI: 1.07–1.46, <i>p</i> = 0.006, <i>n</i> = 7, <i>I</i>² = 0%] was linked to worse neurological outcomes at discharge. Third, there was no significant association between adjunct steroid therapy and neurological outcomes at discharge and ≥ 6 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>This is the first systematic review and meta-analysis to investigate prognostic factors linked to neurological outcomes following infectious encephalitis. The results highlight the prognostic value of a range of easily accessible clinical and laboratory parameters.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"32 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}