Renan Flávio de França Nunes, Thiago Junqueira Ribeiro de Rezende, Guilherme Soares de Oliveira Wertheimer, Wilson Marques Junior, Marcondes Cavalcante França Junior
Background
Hereditary Transthyretin Amyloidosis with polyneuropathy (ATTRv-PN) is an autosomal dominant disorder characterized by TTR gene mutations, causing amyloid fibril deposition in peripheral nerves. Significant CNS involvement has been noted, emphasizing the necessity for advanced neuroimaging tools for early detection of CNS damage in ATTRv.
Methods
Comprehensive clinical assessments and multimodal MRI techniques, including FreeSurfer, TBSS and microbleed analysis, were utilized. The cohorts comprised 30 symptomatic patients (ATTRv-PN), 19 presymptomatic patients (pre-ATTRv-PN), classified based on neuropathic signs, and 44 age- and sex-matched controls. For cognitive assessment, we utilized the Addenbrooke's Cognitive Examination-Revised.
Results
The ATTRv-PN group had an average age of 51 years, while the pre-ATTRv-PN group averaged 41 years, with a sex ratio of 35% men to 65% women. Symptomatic patients experienced an average disease duration of 5 years, predominantly featuring the p.Val50Met genotype (73%). Brain imaging showed diffuse subcortical white matter alterations in ATTRv-PN, while cortical thinning and microbleeds were infrequent. Cognitive assessments revealed significant differences, with symptomatic scoring lower in memory and verbal fluency than presymptomatic.
Conclusion
ATTRv-PN involves cerebral white matter microstructural damage from early stages. Multimodal MRI serves as an accurate, non-invasive tool for detecting CNS damage, improving our understanding of the disease spectrum.
{"title":"Early Detection of Central Nervous System Involvement in ATTRv Using Multimodal MRI and Cognitive Assessments","authors":"Renan Flávio de França Nunes, Thiago Junqueira Ribeiro de Rezende, Guilherme Soares de Oliveira Wertheimer, Wilson Marques Junior, Marcondes Cavalcante França Junior","doi":"10.1111/ene.70427","DOIUrl":"10.1111/ene.70427","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary Transthyretin Amyloidosis with polyneuropathy (ATTRv-PN) is an autosomal dominant disorder characterized by <i>TTR</i> gene mutations, causing amyloid fibril deposition in peripheral nerves. Significant CNS involvement has been noted, emphasizing the necessity for advanced neuroimaging tools for early detection of CNS damage in ATTRv.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Comprehensive clinical assessments and multimodal MRI techniques, including FreeSurfer, TBSS and microbleed analysis, were utilized. The cohorts comprised 30 symptomatic patients (ATTRv-PN), 19 presymptomatic patients (pre-ATTRv-PN), classified based on neuropathic signs, and 44 age- and sex-matched controls. For cognitive assessment, we utilized the Addenbrooke's Cognitive Examination-Revised.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The ATTRv-PN group had an average age of 51 years, while the pre-ATTRv-PN group averaged 41 years, with a sex ratio of 35% men to 65% women. Symptomatic patients experienced an average disease duration of 5 years, predominantly featuring the p.Val50Met genotype (73%). Brain imaging showed diffuse subcortical white matter alterations in ATTRv-PN, while cortical thinning and microbleeds were infrequent. Cognitive assessments revealed significant differences, with symptomatic scoring lower in memory and verbal fluency than presymptomatic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ATTRv-PN involves cerebral white matter microstructural damage from early stages. Multimodal MRI serves as an accurate, non-invasive tool for detecting CNS damage, improving our understanding of the disease spectrum.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12780865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917250","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}
Sefa Ozturk, Duygu Dolen, Cafer Ikbal Gulsever, Huseyin Emre Dagdeviren, Onur Ozturk, Eren Andıc, Senem Kılıc Ozturk, Ahmet Muhammet Kocabıyık, Pulat Akın Sabancı
Objective
Parkinson's disease (PD) affects both motor and non-motor functions, including facial expressivity. While subthalamic nucleus deep brain stimulation (STN-DBS) is effective for motor symptoms, its impact on facial expression remains unclear. This study aimed to objectively assess the impact of DBS on facial movement timing and amplitude using objective facial landmark-based motion analysis.
Methods
We analyzed 10 PD patients with STN-DBS (≥ 3 years) and 10 age- and sex-matched controls. Standardized video recordings were obtained using a fixed camera setup. Facial movements were analyzed using objective facial landmark-based motion analysis implemented via a pre-trained facial landmark detection framework (Mediapipe), extracting 468 facial landmarks across approximately 1800 frames per recording. Key facial parameters, including smile completion time and region-specific ranges of motion (ROM), were quantified.
Results
DBS significantly increased oral commissure and frontal ROM (p < 0.05) while reducing smile completion time (p = 0.003). However, PD patients' smiles remained slower than those of controls (0.64 ± 0.21 s vs. 0.49 ± 0.09 s; p = 0.019), indicating incomplete normalization of facial expressivity. Medial eyebrow and palpebral movements showed no significant differences (p > 0.05).
Conclusion
STN-DBS enhances the amplitude of some facial movements but does not fully restore temporal dynamics of facial expression. Persistent delays in smile execution suggest that aspects of facial motor control may remain impaired despite effective stimulation. Objective facial landmark-based motion analysis provides a sensitive tool for detecting subtle alterations in facial motor dynamics and may support future studies investigating complementary strategies to optimize motor expressivity in PD.
{"title":"Objective Assessment of Facial Expressions in Parkinson's Disease During Deep Brain Stimulation ON and OFF States: A Pilot Study","authors":"Sefa Ozturk, Duygu Dolen, Cafer Ikbal Gulsever, Huseyin Emre Dagdeviren, Onur Ozturk, Eren Andıc, Senem Kılıc Ozturk, Ahmet Muhammet Kocabıyık, Pulat Akın Sabancı","doi":"10.1111/ene.70497","DOIUrl":"10.1111/ene.70497","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Parkinson's disease (PD) affects both motor and non-motor functions, including facial expressivity. While subthalamic nucleus deep brain stimulation (STN-DBS) is effective for motor symptoms, its impact on facial expression remains unclear. This study aimed to objectively assess the impact of DBS on facial movement timing and amplitude using objective facial landmark-based motion analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed 10 PD patients with STN-DBS (≥ 3 years) and 10 age- and sex-matched controls. Standardized video recordings were obtained using a fixed camera setup. Facial movements were analyzed using objective facial landmark-based motion analysis implemented via a pre-trained facial landmark detection framework (Mediapipe), extracting 468 facial landmarks across approximately 1800 frames per recording. Key facial parameters, including smile completion time and region-specific ranges of motion (ROM), were quantified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DBS significantly increased oral commissure and frontal ROM (<i>p</i> < 0.05) while reducing smile completion time (<i>p</i> = 0.003). However, PD patients' smiles remained slower than those of controls (0.64 ± 0.21 s vs. 0.49 ± 0.09 s; <i>p</i> = 0.019), indicating incomplete normalization of facial expressivity. Medial eyebrow and palpebral movements showed no significant differences (<i>p</i> > 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>STN-DBS enhances the amplitude of some facial movements but does not fully restore temporal dynamics of facial expression. Persistent delays in smile execution suggest that aspects of facial motor control may remain impaired despite effective stimulation. Objective facial landmark-based motion analysis provides a sensitive tool for detecting subtle alterations in facial motor dynamics and may support future studies investigating complementary strategies to optimize motor expressivity in PD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12780872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917326","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}
Nicola Rifino, Anne Hege Aamodt, Markus Wiedmann, Markus Kramer, Jana Becker, Stéphanie Guey, Francesco Acerbi, Dominique Herve, Anna Bersano
<p>We thank Drs. Gaul and Naegel for their thoughtful comments on our recent consensus review addressing the spectrum of headaches in Moyamoya angiopathy (MMA). We fully agree that the management of headache in this rare and complex cerebrovascular disorder should be guided by prudence, individualized assessment, and a deep understanding of the disease's unique hemodynamic fragility.</p><p>As the authors rightly emphasize, MMA represents a condition in which cerebral perfusion critically depends on compensatory vasodilatory mechanisms that may be highly sensitive to pharmacological modulation [<span>1</span>]. From this perspective, any therapeutic approach acting on vascular tone requires careful consideration, especially when its vascular effects are incompletely understood in such a context.</p><p>We would like to clarify that our review did not suggest or encourage the use of calcitonin gene–related peptide (CGRP)–targeted therapies in patients with MMA. Our intention was indeed to acknowledge their relevance in the broader landscape of migraine management, while underscoring that, in the specific setting of MMA, the absence of clinical data and the theoretical implications on cerebrovascular autoregulation call for particular caution.</p><p>In fact, as also mentioned by Drs. Gaul and Naegel, the study by Mulder and colleagues [<span>2</span>] provides relevant experimental evidence in this regard. In their murine model of middle cerebral artery occlusion, the authors demonstrated that exposure to small-molecule CGRP receptor antagonists led to higher rates of cerebral infarction compared with placebo and resulted in larger infarct volumes with longer durations of occlusion. These findings suggest that while CGRP receptor blockade may not independently induce ischemic events, it could potentially exacerbate outcomes when cerebral perfusion is already compromised.</p><p>For this reason, pivotal clinical trials of anti-CGRP therapies systematically excluded patients with cerebrovascular disease, and post-marketing surveillance has identified occasional cardiovascular adverse events [<span>3, 4</span>].</p><p>On the other hand, to thoroughly examine the effect of erenumab on cerebral hemodynamics, one study evaluated cerebral vasomotor reactivity and endothelial function in 60 patients with migraine without aura [<span>5</span>]. The findings revealed no significant alterations following treatment, indicating that in certain contexts, anti-CGRP antibodies preserve cerebral vasomotor reactivity in migraineurs without aura.</p><p>Moreover, current evidence from large randomized controlled trials does not indicate an increased risk of stroke associated with CGRP-targeted therapies, but data regarding their safety in individuals with preexisting cerebrovascular or cardiovascular disease remain very limited [<span>6</span>].</p><p>However, it should be noted that results obtained under physiological conditions may not be generalizable to patients wit
我们感谢dr。Gaul和Naegel对我们最近关于烟雾血管病（MMA）头痛频谱的共识评论进行了深思熟虑的评论。我们完全同意，在这种罕见而复杂的脑血管疾病中，头痛的治疗应以谨慎、个体化评估和对疾病独特的血液动力学脆弱性的深刻理解为指导。正如作者正确地强调的那样，MMA代表了脑灌注严重依赖代偿性血管舒张机制的一种情况，这种机制可能对药物调节[1]高度敏感。从这个角度来看，任何作用于血管张力的治疗方法都需要仔细考虑，特别是当其血管作用在这种情况下不完全了解时。我们想澄清的是，我们的综述并不建议或鼓励在MMA患者中使用降钙素基因相关肽（CGRP）靶向治疗。我们的目的确实是承认它们在更广泛的偏头痛管理领域的相关性，同时强调，在MMA的特定背景下，缺乏临床数据和脑血管自动调节的理论意义需要特别谨慎。事实上，正如dr。Gaul和Naegel， Mulder及其同事b[2]的研究在这方面提供了相关的实验证据。在他们的小鼠大脑中动脉闭塞模型中，作者证明，与安慰剂相比，暴露于小分子CGRP受体拮抗剂会导致更高的脑梗死率，并导致更大的梗死体积和更长的闭塞时间。这些发现表明，虽然CGRP受体阻断可能不会独立诱导缺血事件，但当脑灌注已经受损时，它可能会加剧结果。因此，抗cgrp治疗的关键临床试验系统地排除了脑血管疾病患者，上市后监测也发现了偶尔的心血管不良事件[3,4]。另一方面，为了全面研究erenumab对脑血流动力学的影响，一项研究评估了60例无先兆偏头痛患者的脑血管舒缩反应性和内皮功能。研究结果显示，治疗后无显著改变，表明在某些情况下，抗cgrp抗体保留了无先兆偏头痛患者的脑血管运动反应性。此外，目前来自大型随机对照试验的证据并未表明cgrp靶向治疗与卒中风险增加相关，但关于其在既往存在脑血管或心血管疾病的个体中的安全性的数据仍然非常有限。然而，应该注意的是，在生理条件下获得的结果可能不适用于MMA患者。总之，我们同意同事的观点，在考虑对MMA患者进行cgrp靶向治疗时，需要非常谨慎。我们完全同意不能低估损害代偿性血管舒张的理论风险。然而，在明确建议禁用这些药物之前，需要更多的证据来确定它们对这一特定人群的实际脑血管影响。在获得这些数据之前，如我们的综述所述，抗cgrp治疗在MMA中不能被推荐使用，临床决策仍应以个体化、多学科的风险和获益评估为指导。真诚的，Nicola Rifino， MDon代表共同作者francesco Acerbi：验证，写作-审查和编辑。安娜·贝尔萨诺：验证，写作-审查和编辑。Anne Hege Aamodt：写作-审查和编辑，验证。Nicola Rifino, Markus Wiedmann, Markus Kramer, Jana Becker, Stephanie Guey， Dominique Herve：写作-审查和编辑，验证。作者声明无利益冲突。数据共享不适用于本文，因为在当前研究中没有生成或分析数据集。
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<p>We read with great interest the comment by Zhang et al. on our recently published paper entitled “Compound Muscle Action Potential (CMAP) Amplitude Trajectories and Patterns in Adults with 5q-Spinal Muscular Atrophy Receiving Nusinersen Therapy: A Multicenter, Binational Observational Study.” In that paper, we concluded that although CMAP amplitude correlates with disease severity, it may not serve as a sensitive biomarker of treatment response in adult SMA patients, as CMAP amplitudes remained largely stable during nusinersen treatment and no differences in trajectories between SMA subgroups were observed.</p><p>Zhang et al. commented that the observed population-level stability could potentially mask important heterogeneity in treatment response. We fully agree with this observation and thank the authors for highlighting this important aspect. Indeed, in the first paragraph of the Discussion section of our paper, we described a non-significant trend toward an increase in median and peroneal nerve CMAP amplitudes up to month 18, which may have paralleled observed clinical improvements [<span>1</span>]. However, our data do not support using CMAP amplitude alone for clinical decision-making regarding nusinersen efficacy in adults with SMA, and we therefore recommend relying on validated motor outcome measures. As discussed in the Discussion section of our paper, “in the context of slowly progressive denervation, such as in SMA, surviving motor units can expand their territories to reinnervate muscle fibers that have lost synaptic input. This reinnervation may adequately restore the CMAP response to near-normal levels, rendering CMAP a less sensitive measure.” In our dataset, some patients demonstrated motor function improvement despite worsening CMAP amplitudes (data not shown), suggesting that factors beyond CMAP amplitude contribute to functional outcomes. Nevertheless, we fully agree with Zhang et al. that population-level stability may mask meaningful inter-individual variability, and we encourage further investigation of this issue in larger multicenter studies. Importantly, the linear mixed-effects models used in our study were specifically chosen to account for inter-individual heterogeneity by allowing for random intercepts and slopes. This approach explicitly models variability in baseline CMAP values as well as individual longitudinal trajectories [<span>2</span>], thereby at least at some point, addressing the concern that population-level analyses may obscure clinically relevant individual or subgroup-specific treatment responses.</p><p>Zhang et al. also suggested that exploring whether early CMAP trends correlate with baseline characteristics or long-term functional outcomes might provide additional insights into treatment dynamics. In our study, we examined whether CMAP trajectories differed between SMA type 2 and type 3 patients and found no significant differences. We also assessed correlations between changes in motor scores (
我们饶有兴趣地阅读了Zhang等人对我们最近发表的论文的评论，题为“接受Nusinersen治疗的5q型脊髓性肌萎缩症患者的复合肌肉动作电位（CMAP）振幅轨迹和模式：一项多中心、两国观察研究”。在这篇论文中，我们得出结论，尽管CMAP振幅与疾病严重程度相关，但它可能不能作为成人SMA患者治疗反应的敏感生物标志物，因为CMAP振幅在nusinersen治疗期间基本保持稳定，并且在SMA亚组之间没有观察到差异。Zhang等人评论说，观察到的人群水平的稳定性可能潜在地掩盖了治疗反应的重要异质性。我们完全同意这一观点，并感谢作者强调了这一重要方面。事实上，在我们论文讨论部分的第一段中，我们描述了到第18个月，正中神经和腓神经CMAP振幅增加的非显著趋势，这可能与观察到的临床改善是平行的。然而，我们的数据并不支持仅使用CMAP振幅来对成人SMA患者的nusinersen疗效进行临床决策，因此我们建议依赖于经过验证的运动结果测量。正如我们论文的讨论部分所讨论的那样，“在缓慢进行性去神经支配的背景下，例如在SMA中，幸存的运动单元可以扩大其领土，以重新支配失去突触输入的肌肉纤维。”这种神经再生可以充分地将CMAP反应恢复到接近正常水平，使CMAP成为不那么敏感的测量方法。”在我们的数据集中，尽管CMAP振幅恶化，但一些患者表现出运动功能改善（数据未显示），这表明CMAP振幅以外的因素有助于功能预后。然而，我们完全同意Zhang等人的观点，即种群水平的稳定性可能掩盖了有意义的个体间变异性，我们鼓励在更大的多中心研究中进一步研究这一问题。重要的是，我们研究中使用的线性混合效应模型是专门选择的，通过允许随机截点和斜率来解释个体间的异质性。这种方法明确地模拟了基线CMAP值和个体纵向轨迹的可变性，因此，至少在某种程度上，解决了人群水平分析可能模糊临床相关的个体或亚组特异性治疗反应的担忧。Zhang等人还建议，探索早期CMAP趋势是否与基线特征或长期功能结果相关，可能会为治疗动态提供额外的见解。在我们的研究中，我们检查了2型和3型SMA患者的CMAP轨迹是否存在差异，发现没有显著差异。我们还评估了运动评分（HFMSE和RULM）在整个治疗期间的变化与CMAP振幅的变化之间的相关性，但经过多次比较校正后，没有显著的相关性。为了控制I型误差，我们采用了Bonferroni校正，这是一种高度保守的方法。值得注意的是，在未经调整的分析中，我们观察到第10个月时RULM和正中神经CMAP的变化呈正相关（ρ = 0.38; p = 0.016），与上述早期趋势一致（数据见我们论文[1]的表S4）。最后，我们恳请作者在评论中审阅参考文献4和5，因为它们无法在索引数据库中识别。总之，我们感谢Zhang等人深思熟虑和建设性的意见，这些意见突出了治疗异质性的重要方面。我们希望这一反应能充分解决所提出的问题，并刺激对成人SMA治疗反应的个体化生物标志物的进一步研究。Bogdan Bjelica：构思，写作-原稿，写作-审查和编辑。作者声明无利益冲突。数据共享不适用于本文，因为在当前研究中没有生成或分析数据集。
{"title":"Reply to the Comment by Zhang et al","authors":"Bogdan Bjelica","doi":"10.1111/ene.70496","DOIUrl":"10.1111/ene.70496","url":null,"abstract":"<p>We read with great interest the comment by Zhang et al. on our recently published paper entitled “Compound Muscle Action Potential (CMAP) Amplitude Trajectories and Patterns in Adults with 5q-Spinal Muscular Atrophy Receiving Nusinersen Therapy: A Multicenter, Binational Observational Study.” In that paper, we concluded that although CMAP amplitude correlates with disease severity, it may not serve as a sensitive biomarker of treatment response in adult SMA patients, as CMAP amplitudes remained largely stable during nusinersen treatment and no differences in trajectories between SMA subgroups were observed.</p><p>Zhang et al. commented that the observed population-level stability could potentially mask important heterogeneity in treatment response. We fully agree with this observation and thank the authors for highlighting this important aspect. Indeed, in the first paragraph of the Discussion section of our paper, we described a non-significant trend toward an increase in median and peroneal nerve CMAP amplitudes up to month 18, which may have paralleled observed clinical improvements [<span>1</span>]. However, our data do not support using CMAP amplitude alone for clinical decision-making regarding nusinersen efficacy in adults with SMA, and we therefore recommend relying on validated motor outcome measures. As discussed in the Discussion section of our paper, “in the context of slowly progressive denervation, such as in SMA, surviving motor units can expand their territories to reinnervate muscle fibers that have lost synaptic input. This reinnervation may adequately restore the CMAP response to near-normal levels, rendering CMAP a less sensitive measure.” In our dataset, some patients demonstrated motor function improvement despite worsening CMAP amplitudes (data not shown), suggesting that factors beyond CMAP amplitude contribute to functional outcomes. Nevertheless, we fully agree with Zhang et al. that population-level stability may mask meaningful inter-individual variability, and we encourage further investigation of this issue in larger multicenter studies. Importantly, the linear mixed-effects models used in our study were specifically chosen to account for inter-individual heterogeneity by allowing for random intercepts and slopes. This approach explicitly models variability in baseline CMAP values as well as individual longitudinal trajectories [<span>2</span>], thereby at least at some point, addressing the concern that population-level analyses may obscure clinically relevant individual or subgroup-specific treatment responses.</p><p>Zhang et al. also suggested that exploring whether early CMAP trends correlate with baseline characteristics or long-term functional outcomes might provide additional insights into treatment dynamics. In our study, we examined whether CMAP trajectories differed between SMA type 2 and type 3 patients and found no significant differences. We also assessed correlations between changes in motor scores (","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12772632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145910843","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}
E. Vallès, A. B. Garcia, E. Giralt-Steinhauer, M. Ble, J. I. Jiménez, B. Casteigt, C. E. González-Matos, E. Cuadrado-Godia, A. González, F. Zaraket, O. Rodriguez, G. Guelfand, M. A. Guijo, M. Cainzos-Achirica
Background
Cryptogenic strokes (CS) represent one third of admissions for stroke. Silent paroxysmal atrial fibrillation (PAF) is the underlying cause of a significant proportion of cases. The use of internal loop recorders (ILR) after CS has shown controversial results, remaining unclear in guidelines. Subtle ultrasound left atrium (LA) anomalies may help select patients more prone to suffer from silent PAF who can benefit from an ILR.
Methods
Randomized, controlled, parallel-arm, open-label trial of patients with CS. We evaluated the efficacy of early ILR for detection of silent PAF episodes compared to standard care. Clinical/ultrasound predictors of PAF were studied. The presence of subtle LA anomalies (any of: LA dilatation, maximum systolic global longitudinal strain < 21%, atrial contraction strain < 13%, atrial ejection fraction < 55%) was used in a pre-specified subgroup analysis.
Results
Fifty-nine CS patients were included (52.5% to ILR and 47.5% to standard care). There were no statistically significant differences among groups regarding baseline characteristics. Median follow-up was 377 days. The diagnosis of silent PAF was made in 43.3% in the ILR group compared to 7.1% in the control group (HR 7.47, 95% CI 1.68–31.19, p = 0.008). Most PAF events were detected in the 100 days following ILR implantation. In patients with normal LA, PAF was observed in 23% versus 7%, while in patients with abnormal LA, PAF was diagnosed in 58.8% versus 7.7%.
Conclusions
An ILR implanted early after CS improves the detection of PAF compared to standard care. Individuals with abnormal LA features may benefit the most from ILR.
背景：隐源性卒中（CS）占卒中入院患者的三分之一。无症状阵发性心房颤动（PAF）是一个重要比例的病例的根本原因。CS后使用内循环记录仪（ILR）显示出有争议的结果，在指南中仍不明确。微妙的超声左心房（LA）异常可能有助于选择更容易遭受无症状PAF的患者，这些患者可以从ILR中受益。方法对CS患者进行随机、对照、平行、开放标签试验。与标准治疗相比，我们评估了早期ILR检测无症状PAF发作的疗效。研究了PAF的临床/超声预测因素。在预先指定的亚组分析中，存在细微的左室异常（左室扩张，最大收缩总纵向应变<； 21%，心房收缩应变<； 13%，心房射血分数<； 55%）。结果纳入59例CS患者，其中接受ILR治疗的占52.5%，接受标准治疗的占47.5%。各组间基线特征无统计学差异。中位随访时间为377天。ILR组诊断为无症状PAF的比例为43.3%，对照组为7.1% （HR 7.47, 95% CI 1.68-31.19, p = 0.008）。大多数PAF事件在ILR植入后100天检测到。在LA正常的患者中，PAF的诊断率为23%比7%，而在LA异常的患者中，PAF的诊断率为58.8%比7.7%。结论与标准治疗相比，CS术后早期植入ILR可提高PAF的检出率。具有异常LA特征的个体可能从ILR中获益最多。
{"title":"Ultra-Early Continuous ECG Monitoring for Silent Atrial Fibrillation Diagnosis in Cryptogenic Stroke: The CRIPTOFAST Randomized Controlled Trial","authors":"E. Vallès, A. B. Garcia, E. Giralt-Steinhauer, M. Ble, J. I. Jiménez, B. Casteigt, C. E. González-Matos, E. Cuadrado-Godia, A. González, F. Zaraket, O. Rodriguez, G. Guelfand, M. A. Guijo, M. Cainzos-Achirica","doi":"10.1111/ene.70482","DOIUrl":"https://doi.org/10.1111/ene.70482","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cryptogenic strokes (CS) represent one third of admissions for stroke. Silent paroxysmal atrial fibrillation (PAF) is the underlying cause of a significant proportion of cases. The use of internal loop recorders (ILR) after CS has shown controversial results, remaining unclear in guidelines. Subtle ultrasound left atrium (LA) anomalies may help select patients more prone to suffer from silent PAF who can benefit from an ILR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Randomized, controlled, parallel-arm, open-label trial of patients with CS. We evaluated the efficacy of early ILR for detection of silent PAF episodes compared to standard care. Clinical/ultrasound predictors of PAF were studied. The presence of subtle LA anomalies (any of: LA dilatation, maximum systolic global longitudinal strain < 21%, atrial contraction strain < 13%, atrial ejection fraction < 55%) was used in a pre-specified subgroup analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-nine CS patients were included (52.5% to ILR and 47.5% to standard care). There were no statistically significant differences among groups regarding baseline characteristics. Median follow-up was 377 days. The diagnosis of silent PAF was made in 43.3% in the ILR group compared to 7.1% in the control group (HR 7.47, 95% CI 1.68–31.19, <i>p</i> = 0.008). Most PAF events were detected in the 100 days following ILR implantation. In patients with normal LA, PAF was observed in 23% versus 7%, while in patients with abnormal LA, PAF was diagnosed in 58.8% versus 7.7%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>An ILR implanted early after CS improves the detection of PAF compared to standard care. Individuals with abnormal LA features may benefit the most from ILR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70482","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145887439","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}
<p>We thank Dr. Noor un nisa Irshad et al. for their interest in our study “Signs of Intracranial Hypertension in Chronic Inflammatory Polyradiculoneuropathies—A Cross-Sectional Cohort Study” [<span>1</span>]. In response, we wish to convey some key considerations:</p><p>Our study aimed to identify the prevalence and potential associations of intracranial hypertension (IH) signs in patients with inflammatory polyradiculoneuropathy (IPN), which previously was reported only anecdotally. With the benefit of hindsight, a longitudinal follow-up would naturally increase the ability to gauge the clinical relevance of subclinical IH in IPN, particularly regarding visual outcomes, CIDP course, headache, and potentially also cognition. Now, we agree that a prospective longitudinal study over a longer term is needed to determine whether the frequent finding of subclinical IH is relevant in this population.</p><p>We recognize the importance of exploring how immunomodulatory and immunosuppressive therapies might influence IH risk. While most patients in our cohort were receiving treatment at the time of assessment, the heterogeneity in treatment regimens precluded reliable analysis of treatment-IH interactions. Future prospective studies in larger cohorts might enable us to explore this further, especially in light of case-based evidence suggesting therapeutic modulation of ICP [<span>2-4</span>].</p><p>Subtyping CIDP based on antibody-positivity (e.g., anti-NF155, CNTN1) or other biomarker profiles, while completely hypothetically, could be relevant for stratifying IH risk. Naturally, such subtyping requires much larger sample sizes than available in our study, creating an important avenue for future research to identify mechanistically distinct subgroups potentially more vulnerable to IH.</p><p>Indeed, our analysis did not systematically account for metabolic or vascular comorbidities (e.g., diabetes, dyslipidemia, or steroid-induced changes), although patients with known secondary causes of IH (e.g., sinus vein thrombosis, etc.) were excluded. While higher BMI is likely the most relevant cofactor for IH, we concur that metabolic comorbidities may modulate IH risk, and that their inclusion in future analyses would enhance our ability to construct individualized risk profiles.</p><p>In conclusion, we appreciate the authors' insights, which underscore key next steps for research in this emerging area. Our study represents an initial effort to identify and characterize IH in IPN, suggesting a non-negligible prevalence and a possible association with elevated CSF protein. However, as rightly noted, the clinical significance, pathophysiological underpinnings, and therapeutic implications remain to be clarified through prospective, multimodal, and biomarker-integrated studies.</p><p>Stefan Macher: has participated in meetings sponsored by, received speaker honoraria or travel funding from Novartis, AbbVie, and Merz. Berthold Pemp: has received honoraria for consu
我们感谢Dr. Noor un nisa Irshad等人对我们的研究“慢性炎症性多根神经病变颅内高压的体征-横断面队列研究”的兴趣。作为回应，我们希望传达一些关键的注意事项：我们的研究旨在确定炎症性多根神经病变（IPN）患者颅内高压（IH）体征的患病率和潜在关联，这在以前的报道中只是轶事。事后看来，纵向随访自然会增加衡量IPN中亚临床IH临床相关性的能力，特别是在视觉结果、CIDP病程、头痛和潜在的认知方面。现在，我们同意需要一项长期的前瞻性纵向研究来确定亚临床IH的频繁发现是否与该人群相关。我们认识到探索免疫调节和免疫抑制疗法如何影响IH风险的重要性。虽然我们队列中的大多数患者在评估时正在接受治疗，但治疗方案的异质性妨碍了对治疗- ih相互作用的可靠分析。未来更大规模的前瞻性研究可能使我们能够进一步探索这一点，特别是考虑到基于病例的证据表明治疗性调节ICP[2-4]。基于抗体阳性（例如，抗nf155， CNTN1）或其他生物标志物特征对CIDP进行亚型分型，虽然完全是假设的，但可能与IH风险分层有关。当然，这种亚型需要比我们的研究更大的样本量，为未来的研究创造了一个重要的途径，以确定机械上不同的亚群，可能更容易受到IH的影响。的确，我们的分析没有系统地考虑代谢或血管合并症（如糖尿病、血脂异常或类固醇引起的改变），尽管已知继发原因的IH患者（如窦静脉血栓形成等）被排除在外。虽然较高的BMI可能是IH最相关的辅助因素，但我们同意代谢合并症可能会调节IH风险，并且将其纳入未来的分析将增强我们构建个性化风险概况的能力。总之，我们赞赏作者的见解，这些见解强调了这一新兴领域研究的关键下一步。我们的研究代表了在IPN中识别和表征IH的初步努力，表明不可忽视的患病率和可能与脑脊液蛋白升高有关。然而，正如正确指出的那样，临床意义、病理生理基础和治疗意义仍需通过前瞻性、多模式和生物标志物整合研究来阐明。Stefan Macher：参加了由诺华、艾伯维和Merz赞助的会议，并获得了演讲者荣誉或旅行资助。Berthold Pemp：获得Chiesi， GenSight， Novartis和Santen的咨询/演讲荣誉。Gabriel Bsteh：曾参加由Biogen、Celgene/Bristol Meyers Squibb、Janssen、Lilly、Medwhizz、Merck、Novartis、Roche、Sanofi-Genzyme和Teva主办的会议，并获得了演讲者酬金或差旅资金，并获得了Biogen、Celgene/Bristol Meyers Squibb、Janssen、Merck、Novartis、Roche、Sanofi-Genzyme和Teva的咨询酬金。他曾获得Celgene/Bristol Meyers Squibb和Novartis的无限制研究资助。他是欧洲多发性硬化症治疗和研究委员会（ECTRIMS）的执行委员会成员。支持本研究结果的数据可根据通讯作者的合理要求提供。
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We thank Gao et al. for their thoughtful commentary [1]. We share their view that advancing psychometrically informed care for persistent postural-perceptual dizziness (PPPD) requires longitudinal and mechanistic designs supported by precise self-report instruments.
We affirm our mediation result as hypothesis-generating. Perceived injustice may serve as an accessible marker of psychological processes influencing functional symptom severity in PPPD. As Gao et al. [1] note, our mediation analysis between PPPD and healthy controls was cross-sectional and should be interpreted cautiously. Future studies should establish temporal precedence through prospective designs such as latent-growth or cross-lagged panel models and apply penalised regression with bootstrap optimism correction to reduce overfitting. Within this framework, perceived injustice, capturing unfairness, invalidation and loss of agency, remains a plausible indicator of cognitive-affective mechanisms that may identify patients less responsive to standard care.
Testing such mechanisms requires reliable self-report instruments. A coordinated effort is needed to refine and isolate constructs in PPPD. Gao et al. [1] correctly highlight the absence of measurement-invariance testing. We add that reliance on simple composite scoring also constrains psychometric precision. Although our study did not examine item loadings directly, prior validations of the Dizziness Handicap Inventory (DHI) report inconsistent factor structures and subscale performance, suggesting that the equal-loading assumption may not be met. Despite being the most widely used measure in clinical vestibular research [2], the DHI shows variable content validity and subscale definitions [3] and was excluded from our analyses due to unacceptable variance-inflation factors.
Poor construct reliability hinders downstream analysis and limits the accuracy of brain–behaviour models [4]. These psychometric constraints impede mechanistic testing in PPPD. To address this, future work should establish reliable self-report frameworks guided by international standards such as the COSMIN guidelines [5].
We appreciate this exchange and support continued efforts to align measurement precision with mechanistic insight.
Ariel Sereda: conceptualization, methodology, writing – review and editing, writing – original draft. Diego Kaski: writing – review and editing, supervision, conceptualization.
The authors declare no conflicts of interest.
Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.
我们感谢高等人对b[1]的周到评论。我们同意他们的观点，即推进对持续性体位知觉眩晕（PPPD）的心理测量学知情护理需要纵向和机械设计支持精确的自我报告工具。我们确认我们的中介结果为假设生成。感知不公正可能是影响PPPD功能症状严重程度的心理过程的一个可访问的标记。正如Gao等人所指出的那样，我们对PPPD与健康对照之间的中介分析是横断面的，应谨慎解释。未来的研究应该通过前瞻性设计，如潜在增长或交叉滞后面板模型，建立时间优先性，并应用惩罚回归与自举乐观修正，以减少过拟合。在这个框架内，感知到的不公正，捕捉不公平，无效和代理丧失，仍然是认知-情感机制的一个合理指标，可以识别对标准治疗反应较差的患者。测试这种机制需要可靠的自我报告工具。需要协调一致的努力来改进和隔离PPPD中的构造。Gao et al.[1]正确地强调了测量不变性测试的缺失。我们补充说，依赖简单的综合评分也限制了心理测量的精度。虽然我们的研究没有直接检查项目负荷，但先前对头晕障碍量表（DHI）的验证报告了不一致的因素结构和子量表的表现，这表明等负荷假设可能不符合。尽管是临床前庭研究中使用最广泛的测量方法，但DHI显示出可变的内容效度和子量表定义[3]，并且由于不可接受的方差膨胀因素而被排除在我们的分析之外。较差的构建可靠性阻碍了下游分析并限制了脑行为模型的准确性[10]。这些心理测量限制阻碍了PPPD的机制测试。为了解决这个问题，未来的工作应该建立可靠的自我报告框架，以国际标准为指导，如COSMIN准则[5]。我们赞赏这种交流，并支持将测量精度与机械洞察力结合起来的持续努力。Ariel Sereda：概念，方法论，写作-审查和编辑，写作-原稿。迭戈卡斯基：写作-审查和编辑，监督，概念化。作者声明无利益冲突。数据共享不适用于本文，因为在当前研究期间没有生成或分析数据集。
{"title":"The Importance of Reliable Self-Report Measures to Test PPPD Mechanisms","authors":"Ariel Sereda, Diego Kaski","doi":"10.1111/ene.70487","DOIUrl":"10.1111/ene.70487","url":null,"abstract":"<p>We thank Gao et al. for their thoughtful commentary [<span>1</span>]. We share their view that advancing psychometrically informed care for persistent postural-perceptual dizziness (PPPD) requires longitudinal and mechanistic designs supported by precise self-report instruments.</p><p>We affirm our mediation result as hypothesis-generating. Perceived injustice may serve as an accessible marker of psychological processes influencing functional symptom severity in PPPD. As Gao et al. [<span>1</span>] note, our mediation analysis between PPPD and healthy controls was cross-sectional and should be interpreted cautiously. Future studies should establish temporal precedence through prospective designs such as latent-growth or cross-lagged panel models and apply penalised regression with bootstrap optimism correction to reduce overfitting. Within this framework, perceived injustice, capturing unfairness, invalidation and loss of agency, remains a plausible indicator of cognitive-affective mechanisms that may identify patients less responsive to standard care.</p><p>Testing such mechanisms requires reliable self-report instruments. A coordinated effort is needed to refine and isolate constructs in PPPD. Gao et al. [<span>1</span>] correctly highlight the absence of measurement-invariance testing. We add that reliance on simple composite scoring also constrains psychometric precision. Although our study did not examine item loadings directly, prior validations of the Dizziness Handicap Inventory (DHI) report inconsistent factor structures and subscale performance, suggesting that the equal-loading assumption may not be met. Despite being the most widely used measure in clinical vestibular research [<span>2</span>], the DHI shows variable content validity and subscale definitions [<span>3</span>] and was excluded from our analyses due to unacceptable variance-inflation factors.</p><p>Poor construct reliability hinders downstream analysis and limits the accuracy of brain–behaviour models [<span>4</span>]. These psychometric constraints impede mechanistic testing in PPPD. To address this, future work should establish reliable self-report frameworks guided by international standards such as the COSMIN guidelines [<span>5</span>].</p><p>We appreciate this exchange and support continued efforts to align measurement precision with mechanistic insight.</p><p><b>Ariel Sereda:</b> conceptualization, methodology, writing – review and editing, writing – original draft. <b>Diego Kaski:</b> writing – review and editing, supervision, conceptualization.</p><p>The authors declare no conflicts of interest.</p><p>Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70487","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888201","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}
Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is a newly recognized autoimmune disorder of the central nervous system, characterized by the presence of GFAP-IgG in the cerebrospinal fluid. Although corticosteroid therapy typically yields favorable responses, limited therapeutic efficacy is observed in some patients who subsequently develop poor clinical outcomes. This study aimed to identify prognostic factors using clinical data of patients with GFAP-A.
Methods
This retrospective cohort study included 233 patients with GFAP-A, who were followed up for more than 6 months. At 6 months after admission, patients were classified into unfavorable outcome [modified Rankin Scale (mRS) score ≥ 3] and favorable outcome (mRS ≤ 2) groups. Clinical data were compared between the two groups using univariate analysis. Variables that showed statistically significant differences were subsequently analyzed using multiple regression analysis to identify the individual contribution of each predictor to the unfavorable outcomes at 6 months after admission.
Results
In the multiple regression analysis, age (p < 0.001), seizures (p = 0.050), motor paralysis (p = 0.042), and mRS scores at admission (p = 0.001) were positively associated with unfavorable outcomes. In contrast, fever (p = 0.020) was negatively associated with unfavorable outcomes.
Conclusions
In conclusion, advanced age, comorbid seizures, comorbid motor paralysis, lack of febrile episodes, and higher mRS scores at admission were associated with unfavorable outcomes in our cohort. These findings highlight the need for future studies to elucidate the underlying pathophysiological mechanisms associated with these clinical characteristics and to develop effective alternatives to corticosteroid therapy.
{"title":"Investigation of Prognostic Factors in Patients With Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy","authors":"Akio Kimura, Akira Takekoshi, Yoichi Maekawa, Keiko Tanaka, Yoshihisa Yamano, Kuniaki Saito, Masao Takemura, Takayoshi Shimohata","doi":"10.1111/ene.70489","DOIUrl":"10.1111/ene.70489","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is a newly recognized autoimmune disorder of the central nervous system, characterized by the presence of GFAP-IgG in the cerebrospinal fluid. Although corticosteroid therapy typically yields favorable responses, limited therapeutic efficacy is observed in some patients who subsequently develop poor clinical outcomes. This study aimed to identify prognostic factors using clinical data of patients with GFAP-A.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective cohort study included 233 patients with GFAP-A, who were followed up for more than 6 months. At 6 months after admission, patients were classified into unfavorable outcome [modified Rankin Scale (mRS) score ≥ 3] and favorable outcome (mRS ≤ 2) groups. Clinical data were compared between the two groups using univariate analysis. Variables that showed statistically significant differences were subsequently analyzed using multiple regression analysis to identify the individual contribution of each predictor to the unfavorable outcomes at 6 months after admission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the multiple regression analysis, age (<i>p</i> < 0.001), seizures (<i>p</i> = 0.050), motor paralysis (<i>p</i> = 0.042), and mRS scores at admission (<i>p</i> = 0.001) were positively associated with unfavorable outcomes. In contrast, fever (<i>p</i> = 0.020) was negatively associated with unfavorable outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In conclusion, advanced age, comorbid seizures, comorbid motor paralysis, lack of febrile episodes, and higher mRS scores at admission were associated with unfavorable outcomes in our cohort. These findings highlight the need for future studies to elucidate the underlying pathophysiological mechanisms associated with these clinical characteristics and to develop effective alternatives to corticosteroid therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.70489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888152","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}
Christoph Theyer, Johannes Kirchmair, Frank Jagusch, Simon Leiter, Atbin Djamshidian, Beatrice Heim, Corinne Horlings, Alessandra Fanciulli, Werner Poewe, Klaus Seppi, Philipp Mahlknecht, Florian Krismer
Background
Hyposmia is present in most patients with Parkinson's disease (PD), whereas olfaction is usually preserved in its diagnostic mimics. To address the limited evidence from smaller studies, we conducted a meta-analysis on the diagnostic accuracy of olfactory testing in differentiating PD from clinical look-alikes.
Methods
A systematic search was performed in PubMed and Web of Science according to the PRISMA guidelines. Studies describing results of validated smell tests in PD patients and at least one differential diagnosis were included. The risk of bias and applicability was assessed with the QUADAS-2 tool. For data synthesis, a hierarchical regression model was employed.
Results
Of 787 publications, 23 studies describing 1957 PD patients, 462 patients with atypical parkinsonian disorders, 239 patients with essential tremor, and 43 patients with secondary parkinsonism were included. The meta-analysis demonstrated a sensitivity of 79% (95% confidence interval [CI]: 72%–84%) and a specificity of 81% (95% CI: 73%–86%) for olfactory dysfunction to differentiate PD from all other disorders combined. Additional analyses showed consistent sensitivities across sub-analyses, with lowest specificities for the distinction from progressive supranuclear palsy, 64% (95% CI: 55%–72%), and highest from essential tremor, 92% (95% CI: 84%–96%).
Conclusion
Our findings indicate that olfactory testing shows moderate to good diagnostic accuracy in differentiating PD from its main differential diagnoses. While results of olfactory testing alone are insufficient for a definite distinction of PD from non-PD parkinsonism, it represents an easy-to-use and inexpensive test that may be used in combination with other diagnostic tools.
{"title":"The Utility of Olfactory Testing to Discriminate Parkinson's Disease From Diagnostic Mimics: A Systematic Review and Meta-Analysis","authors":"Christoph Theyer, Johannes Kirchmair, Frank Jagusch, Simon Leiter, Atbin Djamshidian, Beatrice Heim, Corinne Horlings, Alessandra Fanciulli, Werner Poewe, Klaus Seppi, Philipp Mahlknecht, Florian Krismer","doi":"10.1111/ene.70473","DOIUrl":"10.1111/ene.70473","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hyposmia is present in most patients with Parkinson's disease (PD), whereas olfaction is usually preserved in its diagnostic mimics. To address the limited evidence from smaller studies, we conducted a meta-analysis on the diagnostic accuracy of olfactory testing in differentiating PD from clinical look-alikes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search was performed in PubMed and Web of Science according to the PRISMA guidelines. Studies describing results of validated smell tests in PD patients and at least one differential diagnosis were included. The risk of bias and applicability was assessed with the QUADAS-2 tool. For data synthesis, a hierarchical regression model was employed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 787 publications, 23 studies describing 1957 PD patients, 462 patients with atypical parkinsonian disorders, 239 patients with essential tremor, and 43 patients with secondary parkinsonism were included. The meta-analysis demonstrated a sensitivity of 79% (95% confidence interval [CI]: 72%–84%) and a specificity of 81% (95% CI: 73%–86%) for olfactory dysfunction to differentiate PD from all other disorders combined. Additional analyses showed consistent sensitivities across sub-analyses, with lowest specificities for the distinction from progressive supranuclear palsy, 64% (95% CI: 55%–72%), and highest from essential tremor, 92% (95% CI: 84%–96%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings indicate that olfactory testing shows moderate to good diagnostic accuracy in differentiating PD from its main differential diagnoses. While results of olfactory testing alone are insufficient for a definite distinction of PD from non-PD parkinsonism, it represents an easy-to-use and inexpensive test that may be used in combination with other diagnostic tools.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12750508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145855041","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}
Disorders of consciousness (DoC) pose significant challenges in clinical diagnosis and treatment. This study aims to investigate the relationship between consciousness levels and the brainstem-cortical white matter tracts in DoC patients resulting from focal brainstem injury using diffusion tensor imaging (DTI).
Methods
DTI data of DoC patients with focal brainstem injury and healthy volunteers were retrospectively collected. White matter tractography was performed to reconstruct brainstem-cortical projections. The number of streamlines, total volume, and fractional anisotropy (FA) were analyzed from the perspective of global brain, physiological pathways, and functional networks. The relationship between these measurements and consciousness levels was investigated.
Results
A cohort of 28 DoC patients and 32 healthy controls were included in the analysis. DoC patients exhibited significant reductions in the number of streamlines in global brainstem-cortical projections compared to controls. However, the total volume and FA of these fibers were relatively preserved. Specific pathways such as the corticospinal tract and frontoparietal tract showed marked reductions in streamline counts. Significant reductions in streamline counts were also observed in the somatomotor and frontoparietal networks. No significant changes in mean FA were observed across different physiological pathways and brain networks. Correlation analyses revealed significant associations between consciousness levels and structural connections in the frontoparietal tract and frontoparietal network.
Conclusion
This study highlights the impact of focal brainstem injury on global brain structural connectivity in DoC patients. Despite significant reductions in streamline counts, the preservation of FA suggests maintained microstructural integrity in surviving fibers.
{"title":"Global White Matter Damage in Focal Brainstem Injury Patients With Disorders of Consciousness: A Diffusion Tensor Tractography Study","authors":"Miao Wang, Qiheng He, Sipeng Zhu, Tianqing Cao, Nan Wang, Yitong Jia, Hongbin Wu, Jianfeng Liang, Hongchuan Niu, Zongsheng Xu, Zaixu Cui, Yi Yang, Jizong Zhao","doi":"10.1111/ene.70476","DOIUrl":"10.1111/ene.70476","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Disorders of consciousness (DoC) pose significant challenges in clinical diagnosis and treatment. This study aims to investigate the relationship between consciousness levels and the brainstem-cortical white matter tracts in DoC patients resulting from focal brainstem injury using diffusion tensor imaging (DTI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>DTI data of DoC patients with focal brainstem injury and healthy volunteers were retrospectively collected. White matter tractography was performed to reconstruct brainstem-cortical projections. The number of streamlines, total volume, and fractional anisotropy (FA) were analyzed from the perspective of global brain, physiological pathways, and functional networks. The relationship between these measurements and consciousness levels was investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A cohort of 28 DoC patients and 32 healthy controls were included in the analysis. DoC patients exhibited significant reductions in the number of streamlines in global brainstem-cortical projections compared to controls. However, the total volume and FA of these fibers were relatively preserved. Specific pathways such as the corticospinal tract and frontoparietal tract showed marked reductions in streamline counts. Significant reductions in streamline counts were also observed in the somatomotor and frontoparietal networks. No significant changes in mean FA were observed across different physiological pathways and brain networks. Correlation analyses revealed significant associations between consciousness levels and structural connections in the frontoparietal tract and frontoparietal network.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study highlights the impact of focal brainstem injury on global brain structural connectivity in DoC patients. Despite significant reductions in streamline counts, the preservation of FA suggests maintained microstructural integrity in surviving fibers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":"33 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12750513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145854960","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}
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