Neurology最新文献

The differentials for rapidly progressive dementia are broad, encompassing structural, infectious, inflammatory, neoplastic, and neurodegenerative etiologies. The presence of abnormal movements further complicates the diagnostic approach. We describe a 69-year-old man presenting with a diverse array of neurologic symptoms, starting with rapidly progressive cognitive impairment, later developing abnormal movements, sleep disruption, and constitutional symptoms. Despite extensive investigations and empirical treatment, the diagnosis remained elusive until postmortem evaluation. This case highlights the challenges inherent in neurologic diagnostic odysseys, offering insight into the diagnostic reasoning process and unveiling novel clinical findings that may aid earlier recognition of this rare disorder.

Background and objectives: Neurofibrillary tangles (NFTs) progressively damage gray matter in Alzheimer disease (AD). Resulting cortical microstructural alterations might not be detectable using macrostructural metrics but may be studied using isotropic water diffusion, as it reflects extracellular free water content. The aim of this study was to examine the effect of NFTs on cortical microstructure by investigating whether cortical free water increases as a function of tau load. We also investigated whether phosphorylated tau in blood plasma also indicated cortical microstructural abnormalities.

Methods: For this cross-sectional study, we sampled participants with T1 MRI, multishell diffusion-weighted MRI, amyloid PET ([¹⁸F]AZD4694), tau PET, and plasma phosphorylated tau 217+ (p-tau217) from the Translational biomarkers in Aging and Dementia cohort at McGill University; participants were recruited between 2017 and 2024. We used the Neurite Orientation Dispersion and Density Imaging algorithm to calculate isotropic free water images ("free water"). FreeSurfer was used to calculate cortical thickness in the entorhinal, fusiform, inferior temporal, and middle temporal gyri regions of interest ("meta-ROI"); Automatic Segmentation of Hippocampal Subfields was used to calculate hippocampal volumes. We grouped participants by amyloid PET positivity (A), plasma p-tau217 positivity (T1), and tau PET positivity (T2). We performed voxel-wise correlation analyses between free water and these proteinopathy markers, as well as ROI-based analyses in the meta-ROI.

Results: A total of 303 participants (mean age 67 years, 58.7% female) were included in this study (168 cognitively normal individuals, 43 with mild cognitive impairment, 23 with AD dementia, 68 not diagnosed). Tau PET was positively correlated with free water in gray matter predominantly in the temporal lobe (partial R² = 0.39, p < 0.001), and the correlation of p-tau217 with the meta-ROI free water was entirely mediated by tau PET (p < 0.001). In addition, medial temporal and hippocampal free water was negatively correlated with Montreal Cognitive Assessment scores in the A-T₁+ and A+T₂+ groups. The strongest ROI-based multilinear models for predicting temporal gray matter and hippocampal tau PET burden used both cortical thickness and free water as predictors (temporal gray matter partial R² = 0.62; hippocampal partial R² = 0.64).

Discussion: In AD-relevant regions, increased free water correlates with tau load independently of macrostructural metrics or amyloid load. Free water may serve as an imaging marker for microstructural changes in gray matter resulting from NFT accumulation, complementary to macrostructural metrics.

In 2025, international neurology celebrates the bicentenary of J.-M. Charcot's birth. As a major medical scientist in Paris and the founder of modern clinical neurology, Charcot became friends with the celebrated literary figure Alphonse Daudet. Discord subsequently intervened, as Daudet, afflicted with tabes dorsalis, was treated by Charcot without success and even underwent suspension therapy that led to serious side effects. Daudet's son, Léon, blamed Charcot for his own failure in medical school and became a bitter social critic of the French medical system, condemning the hospital hierarchy, including Charcot. Further family discord occurred when Léon married the granddaughter of Victor Hugo, instead of Charcot's own daughter. Within this background, after Charcot's death in 1893, Alphonse Daudet incorporated Charcot into a fictional account, A la Salpêtrière, one of 3 short stories in his Trois Souvenirs (3 Recollections). This study dissects Daudet's Charcot depiction where he presents Charcot as mostly silent, passive, and distant within a circus-like atmosphere of disruptive patients, foreign visitors, and interns. The portrait is a striking contrast to the many other first-hand descriptions of Charcot's domineering, autocratic, and patronizing manner. However, the depiction of a quiet and distantly bland master in the fictional office consultation setting is historically anchored in Daudet's life experiences, which included visits to the Salpêtrière, first-hand knowledge of Charcot over many years, and the experience of being a patient with unremitting neurologic disease. The veracity of the actual events is questionable, given the personal antagonism that colored the last years of their lives, but it is also conceivable to see in Charcot a Janus-like figure of dominance and theatrical authority in the teaching amphitheater interfaced with a more passive, reflective observer in the intimacy of an office setting.

Background and objectives: Although etiology is considered central to outcomes in status epilepticus (SE), previous studies often lacked standardized classification and adjustment for confounders, particularly withdrawal of life-sustaining treatment (WLST). This study examined the association between SE etiology, mortality, and neurologic recovery using the International League Against Epilepsy (ILAE) classification while accounting for confounders and WLST.

Methods: This 2-center observational study included adults (≥18 years) with SE treated at the University Hospitals of Basel and Geneva from 2015 to 2023. Etiologies were classified as acute symptomatic, remote symptomatic-unprovoked, progressive CNS disorders, epilepsy without additional triggers, or cryptogenic. Demographics, SE type, SE severity score, Charlson Comorbidity Index, treatment data, complications, and WLST were assessed. The primary outcome was in-hospital mortality; secondary outcomes were 30-day mortality and recovery to premorbid neurologic function at discharge. Associations were assessed using Poisson regression with robust error variance, adjusted for age, nonconvulsive SE (NCSE) with coma, comorbidity, and center.

Results: Among 967 patients (median age 67 years, interquartile range 54-78; 46.5% female), SE was terminated in 95%, with 48.5% of patients recovering to premorbid function. Acute symptomatic SE accounted for 34.2%, remote symptomatic SE for 27.6%, SE due to progressive CNS disorders for 14.4%, epilepsy without additional triggers for 16.7%, and cryptogenic SE for 7.1%. In-hospital and 30-day mortality were 7.9% and 13.9%, respectively, while 48.5% recovered to premorbid function. Etiology was associated with neurologic recovery, with intracranial hemorrhage (relative risk [RR] 0.49, 95% CI 0.35-0.67) and acute symptomatic SE (RR 0.71, 95% CI 0.60-0.83) being associated with reduced likelihood of recovery, whereas known epilepsy was associated with increased likelihood of recovery (RR 1.40, 95% CI 1.23-1.60). NCSE with coma (11.9%) was independently associated with higher in-hospital and 30-day mortality and reduced recovery across all ILAE etiology groups. WLST did not significantly alter these associations.

Discussion: Etiology was associated with neurologic recovery but not with short-term mortality after adjustment for confounders and WLST. By contrast, NCSE with coma showed the strongest association with adverse outcomes. This suggests that while etiology informs prognosis for recovery, SE type, particularly NCSE with coma, is the more critical determinant of survival.

Background and objectives: Peri-ictal apnea is common in persons with epilepsy (PWE) and may contribute to sudden unexpected death in epilepsy (SUDEP). It is not yet known whether brainstem respiratory centers in PWE respond differently to voluntary apnea. We addressed this issue using breath-holding (BH) functional MRI (fMRI).

Methods: Adult PWE were recruited from a single outpatient clinic with the aim of achieving a comparable proportion of patients with and without generalized or focal-to-bilateral tonic-clonic seizures. Age-matched and sex-matched healthy controls were recruited through public advertisements. Exclusion criteria included physiologic and medical conditions known to alter respiration. All participants underwent fMRI while performing voluntary inspiratory and expiratory BH tasks. Respiratory rate, oxygen saturation, and end-tidal O₂ and CO₂ were recorded. Functional data were analyzed using a standard general linear model, as well as seed-to-voxel and ROI-to-ROI connectivity analyses targeting predefined brainstem regions of interest.

Results: The study included 31 PWE (mean age 34.0 ± 11.6 years, 51.6% female) and 21 controls (mean age 32.8 ± 9.9, 52.4% female). At the group level, PWE had significantly lower brainstem activation than controls during both expiratory BH (Cohen d = 1.43, 95% CI 0.81-2.05, p = 0.005) and inspiratory BH (Cohen d = 1.31, 95% CI 0.70-1.92, p = 0.006). Decreased activations in PWE were observed in regions corresponding to the cuneiform nucleus during expiratory BH and the median raphe nucleus during the inspiratory BH. BH-triggered fMRI changes at the individual level showed a significant brainstem activation during expiratory BH in 61% of PWE vs 90% of controls. When comparing each participant with the control group, 35% of PWE demonstrated a significantly decreased brainstem activation, vs none of the controls. Intrinsic connectivity during self-paced breathing and BH showed reduced brainstem-cortical connectivity in PWE.

Discussion: A significant proportion of PWE seem to suffer from interictal dysfunction of brainstem regions involved in respiratory control. These abnormalities could be detected at the individual level using a simple BH fMRI paradigm, suggesting potential for translation into a clinical biomarker. Future studies are needed to confirm these findings in larger populations and investigate their relation to SUDEP.

Background and objectives: Ischemic stroke remains a leading cause of death and disability worldwide, with large vessel occlusion (LVO) accounting for a disproportionate share of poststroke morbidity. Early identification of LVO is essential for timely intervention with endovascular thrombectomy; however, the clinical scales currently used for triage vary widely in their application and accuracy. This study assesses the diagnostic performance of clinical stroke scales in predicting LVO.

Methods: A systematic review was conducted to identify studies evaluating the diagnostic accuracy of prehospital stroke scales for detecting LVO. Pooled sensitivity and specificity were estimated using a bivariate random-effects model, with diagnostic performance further assessed through summary receiver operating characteristic (ROC) curves and area under the curve (AUC) analysis. A Bayesian network meta-analysis was conducted to rank the scales using surface under the cumulative ranking (SUCRA) probabilities, and post hoc analyses were performed to evaluate publication bias.

Results: A total of 58 studies comprising 58,381 patients and 33 unique stroke scales were included in the final analysis. The studies, published between 2014 and 2023, were primarily conducted in North America (50%) and Europe (26%), with a median sample size of 473 participants. Pooled sensitivity ranged from 0.30 (HEMIPARESIS) to 0.99 (LARIO) while specificity varied from 0.34 (FANG) to 0.94 (HEMIPLEGIA). Among the highest-performing scales overall were LARIO (AUC = 0.983), FPSS (AUC = 0.896), FACE2AD (AUC = 0.876), and ACT-FAST (AUC = 0.873). In prehospital settings, FPSS (AUC = 0.896), FAST VAN (AUC = 0.878), and FACE2AD (AUC = 0.876) demonstrated strong performance while LARIO (AUC = 0.983) and ACT-FAST (AUC = 0.883) showed the highest accuracy in hospital settings. Bayesian network meta-analysis identified POMONA (SUCRA = 0.877), NIHSS (0.856), sNIHSS EMS (0.854), G-FAST (0.823), and SAFE (0.788) as the top-ranked scales. Funnel plot analysis revealed minimal publication bias among the most frequently evaluated tools, including RACE, CPSS, and NIHSS.

Discussion: Numerous clinical scales are available for detecting LVO in the prehospital setting. While several demonstrate strong performance in specific contexts, there remains a clear need for a simple, accurate, and generalizable tool to reliably identify patients with LVO across diverse clinical environments.