Journal of Neurology最新文献

Background: Multiple sclerosis (MS) involves a complex interplay between immune-mediated inflammation and neurodegeneration. Recent advances in biomarker research have provided new insights into the molecular underpinnings of MS, including ferritin, neurogranin, Triggering Receptor Expressed on Myeloid cells 2 (TREM2), and neurofilaments light chain.

Objectives: This pilot study aims to investigate the levels of these biomarkers in the cerebrospinal fluid (CSF) of MS patients and explore their associations with clinical, cognitive, and optical coherence tomography (OCT) parameters.

Methods: This cross-sectional pilot study included 26 patients with relapsing MS (RMS) and 13 symptomatic controls (SCs). Clinical, cognitive, and OCT assessments were performed, and CSF samples were analyzed for ferritin, neurogranin, TREM2, and neurofilaments.

Results: Neurogranin levels were significantly higher in RMS patients compared to SCs (p = 0.04), and the receiver-operating characteristic (ROC) analysis indicated that neurogranin could be considered a disease biomarker (AUC = 0.733, p = 0.01). Ferritin and neurogranin showed a strong positive correlation (r = 0.690, p < 0.01), and both were inversely correlated with retinal ganglion cell layer (GCL) thickness. TREM2 was positively associated with baseline Expanded Disability Status Scale score.

Conclusion: This pilot study suggests that neurogranin may be a potential biomarker at the time of MS diagnosis, and the interplay between ferritin, neurogranin, and TREM2 highlights the complex relationship between inflammation, oxidative stress, and neuronal damage in MS. The inverse association of ferritin and neurogranin with GCL thickness warrants further investigation into the role of iron metabolism and synaptic damage in the early stages of the disease.

Background and purpose: Endothelial dysfunction is considered an emerging therapeutic target to prevent complications during acute stroke and to prevent recurrent stroke. This review aims to provide an overview of the current knowledge on endothelial dysfunction, outline the diagnostic methods used to measure it and highlight the drugs currently being investigated for the treatment of endothelial dysfunction in acute ischemic stroke.

Methods:  The PubMed® and ClinicalTrials.gov electronic databases were searched for eligible articles/studies dealing with endothelial dysfunction and stroke. The references of the articles were screened to identify additional sources. The data were abstracted and summarized.

Findings and discussion: Endothelial dysfunction can be measured by serum biomarkers as well as by ultrasound or plethysmography techniques. Drugs targeting endothelial dysfunction include widely used agents such as angiotensin-converting enzyme inhibitors or isosorbide mononitrate, but also experimental therapies such as endothelial progenitor cells.

Conclusion: The role of endothelial dysfunction in acute ischemic stroke has been studied increasingly in recent years. It has been shown that there is a correlation between endothelial dysfunction and parenchymal hematoma after endovascular thrombectomy. Also, early clinical trials are conducted investigating, e.g., endothelial progenitor cells in the treatment of endothelial dysfunction in ischemic stroke. Current research focuses on the integration of novel markers of endothelial dysfunction into routine clinical practice to support decision making in the treatment of acute ischemic stroke.

Background: Idiopathic intracranial hypertension (IIH) is increasingly prevalent, yet longitudinal outcome data are scarce. This study aimed to characterise demographic and longitudinal clinical changes in a cohort of patients with IIH.

Methods: Retrospective cohort analysis on adult patients diagnosed with IIH (Friedman criteria) enrolled in the neuro-ophthalmology database (NODE) across two tertiary centres. Baseline demographic data was obtained at first assessment, with clinical and paraclinical outcomes collected longitudinally. Multivariable statistical analysis identified factors associated with poorer visual outcomes.

Results: A total of 221 patients were included. 91.8% were female (ratio 11:1). Mean age at presentation was 29.2 ± 8.1 years with mean body mass index (kg/m²) at diagnosis of 38.7 ± 9.4. Headache was the most common symptom. Papilloedema was found in 95.5% of patients at baseline. Mean CSF opening pressure was 32.67 ± 6.85cmCSF (range 25-76). Visual outcomes remained stable over time. Trajectory plots showed no deviations in visual acuity, while regression models found no associations with sex, site or age. A higher retinal nerve fibre layer thickness and greater baseline Frisen grade were associated with worse outcomes. Baseline papilloedema grade and CSF opening pressure emerged as early prognostic indicators, aiding risk stratification for those with a greater probability of persistent optic nerve abnormalities including higher retinal nerve fibre layer elevation and sustained atrophic changes over time.

Conclusions: This study offers insights into visual outcomes in IIH, emphasising the importance of early recognition, risk stratification, and intervention in those with a more severe clinical phenotype at presentation.

Background: Alpha-synuclein (ɑ-syn) plays a key role in Parkinson's disease (PD) pathogenesis, but existing studies have found mixed results regarding the associations between plasma ɑ-syn and the development of cognitive impairment. We aim to clarify the potentially important relationship between ɑ-syn level in plasma and development of cognitive impairment in PD through systematic review and meta-analysis.

Methods: A systematic search was conducted in the PubMed, Embase and Web of Science databases for studies reporting plasma ɑ-syn concentrations and cognitive impairment in PD. Effect directions were plotted to investigate methodological factors, and a meta-analysis was performed comparing PD patients with dementia (PDD) to PD patients with normal cognition (PDNC).

Results: Twenty-five studies were identified for the systematic review, involving 1,888 PD patients. Studies using the clinical diagnostic Movement Disorder Society (MDS) criteria for PD with mild cognitive impairment and PDD found consistently positive associations with plasma ɑ-syn level. This was further supported by a meta-analysis which found a significant standardised mean difference (g = 1.770, 95% CI: 0.749-2.790, p < 0.001) between PDD and PDNC patients in 10 studies. Furthermore, studies using emerging immunomagnetic reduction or single-molecule array techniques to quantify ɑ-syn reported strong positive associations. In contrast, studies using enzyme-linked immunoassay and cognitive screening tests alone found mixed results.

Conclusion: There is an overall positive effect between plasma ɑ-syn levels and cognitive impairment in PD. As methodological factors can significantly affect associations, future studies should carefully select ɑ-syn immunoassays and utilise the MDS diagnostic criteria for cognitive impairment in PD.

Background: In multiple sclerosis (MS), susceptibility-weighted imaging (SWI) may reveal white matter lesions (WML) with a paramagnetic rim ("paramagnetic rim lesions" [PRLs]) or diffuse hypointensity ("core-sign lesions"), reflecting different stages of WML evolution.

Objective: Using the soma and neurite density imaging (SANDI) model on diffusion-weighted magnetic resonance imaging (MRI), we characterized microstructural abnormalities of MS PRLs and core-sign lesions and their clinical relevance.

Methods: Forty MS patients and 20 healthy controls (HC) underwent a 3 T brain MRI. Using SANDI, the fractions of neurite (f_neurite) and soma (f_soma) and size of soma (r_soma) were quantified in PRLs (including their core and rim separately), and core-sign lesions identified on SWI-phase.

Results: Among 1811 WMLs, 122 (6.7%) core-sign lesions and 97 (5.4%) PRLs were identified. Compared to HC and MS normal-appearing white matter, all MS WML showed significantly lower f_neurite and f_soma and higher r_soma (FDR-p < 0.001). Compared to SWI-isointense WML, core-sign lesions showed a significantly higher f_neurite, and lower f_soma and r_soma (FDR-p ≤ 0.005). Compared to SWI-isointense WML and core-sign lesions, PRLs showed a significantly lower f_neurite, higher f_soma, and higher r_soma (FDR-p ≤ 0.001). The PRL-core showed significantly lower f_neurite, and higher r_soma than PRL-rim (FDR-p < 0.001). Lower PRL f_neurite (β ≤ -0.006, FDR-p ≤ 0.015) and higher r_soma (β ≥ 0.032, FDR-p ≤ 0.024) were significantly associated with a longer disease duration and more severe disability.

Conclusions: In PRLs, the significant and clinically relevant neurite loss and increased soma fraction and size possibly reflect increased astrogliosis and activated microglia. Core-sign lesions exhibit milder axonal loss, microglia density and astrogliosis, supporting their less destructive nature.

Background: The diagnosis of isolated REM sleep behavior disorder (IRBD) requires video polysomnography (V-PSG) showing increased muscle activity and abnormal behaviors in REM sleep.

Objective: To describe in IRBD the behavioral manifestations occurring during REM sleep in the diagnostic V-PSG.

Methods: This is a systematic audiovisual V-PSG analysis of consecutive IRBD patients. According to the International RBD Study Group recommendations, REM sleep movements and vocalizations were classified into categories and severity.

Results: We analyzed the V-PSG of 62 IRBD patients with a mean age of 67.6 ± 8.1 years. Of 6,330 30-s epochs of REM sleep, 55.1% epochs exhibited motor events, 5.5% contained vocalizations and 39.4% were silent. Among the epochs with motor manifestations, 66.1% contained simple minor movements, 25.0% simple major and 8.9% complex movements. Motor severity of the epochs was mild in 82.2%, moderate in 13.2% and severe in 4.6%. Most movements were bilateral (62.4%) and located in the upper limbs (42.5%). Of the epochs with vocalizations, 61.5% were simple minor, 20.7% complex and 17.8% simple major of mild (72.7%), moderate (23.0%) and severe (4.3%) severity. Complex movements occurred in 87.1% of the patients and complex vocalizations in 38.7%.

Conclusions: In IRBD, the most common manifestations in REM sleep are simple minor movements and vocalizations of mild intensity. Complex movements are observed during REM sleep in most patients but are much less frequent than simple minor and major motor events. These findings should be considered for the routine diagnosis of IRBD when reviewing the V-PSG studies.

Research on the cerebellum and its functional organization has significantly expanded over the last decades, expanding our comprehension of its role far beyond motor control, including critical contributions to cognition and affective processing. Notably, the cerebellar lateralization mirrors contralateral brain lateralization, a complex phenomenon that remains unexplored, especially across different stages of life. The present work aims to bridge this gap by providing a comprehensive scoping review of the lateralization of motor, cognitive, and affective functioning within the cerebellum across the lifespan. A methodical search in electronic databases (i.e., PubMed, Embase, and PsycINFO) was conducted up to October 2024, focusing on neuroimaging studies with healthy participants of all ages performing motor, cognitive, or affective tasks. Our selection process, which involved multiple independent reviewers, identified 128 studies reporting cerebellar asymmetries in individuals from early childhood to older age, with a significant portion of studies regarding young-middle adults (19-45 years old). The majority of the findings confirmed established lateralization patterns in motor and language processing, such as ipsilateral motor control and right-lateralized language functions. However, less attention has been paid to other cognitive functions and affective processing where more heterogeneous and less consistent asymmetries have been observed. To the best of our knowledge, this scoping review is the first to comprehensively investigate the motor, cognitive, and affective functional lateralization of the cerebellum across lifespan, highlighting previously overlooked dimensions of cerebellar contributions.

Background: Circadian disruptions are increasingly recognized in Alzheimer's disease (AD) patients and may influence disease onset and progression. This study examines how AD pathology affects blood-borne factors that regulate circadian rhythms.

Methods: Eighty-five participants from the Sino Longitudinal Study on Cognitive Decline were enrolled: 35 amyloid-beta negative normal controls (Aβ- NCs), 23 amyloid-beta positive normal controls (Aβ+ NCs), 15 patients with amnestic mild cognitive impairment (aMCI), and 12 with Alzheimer's disease dementia (ADD). Patients with aMCI and ADD were grouped as cognitively impaired (CI). Cellular circadian period length was assessed using a serum-based assay. Expression levels of clock genes in serum-treated cells and in leukocytes of participants were measured via real-time PCR. Plasma biomarkers were quantified using a single-molecule array immunoassay. Pineal parenchymal and hippocampal volumes were determined by magnetic resonance imaging.

Results: The cellular circadian period length was significantly extended by serum from CI patients than by that from Aβ- NCs (p < 0.01). Treatment of cells with serum from the CI patients resulted in suppressed expression of the clock genes Bmal1 and Nr1d1. Strong relationships between the expression levels of clock genes observed in leukocytes of the Aβ- NC group did not appear in those of the Aβ+ NC or CI groups. The significant correlation of cellular circadian period length and the pineal volume was only observed in the Aβ- NC group, but not in the Aβ+ NC or CI groups.

Conclusions: This study indicates the presence of significant changes in blood-borne factors that could affect the circadian rhythms in AD, starting even at preclinical stages. These alterations could precede cognitive decline and contribute to AD pathogenesis.

Trial registration: The cohort is registered at ClinicalTrials.gov (SILCODE: NCT03370744; Registered on Mar 15^th, 2017).

Objectives: Granulomatous myositis (GM) is a rare entity whose precise clinical features and therapeutic outcomes have not yet been well defined. Given the limited evidence, data from a large cohort of patients is needed to aid in the recognition and management of this condition.

Methods: We retrospectively analyzed our institutional databases to identify patients who had myositis and non-caseating granuloma on muscle biopsy (GM). We collected data on clinical and diagnostic features, management, and outcomes of these cases and compared them with inclusion body myositis (IBM) controls.

Results: 22 GM patients were identified and subdivided into 3 main groups: 13 patients with GM and sarcoidosis (6 of whom subsequently developed suspected or confirmed IBM), 7 patients with idiopathic isolated GM (2 of whom subsequently developed confirmed IBM), 2 patients with GM and Crohn's disease. Patients with GM and sarcoidosis without IBM, as well as patients with isolated GM, exhibited variable clinical presentation ranging from myalgia to mostly symmetrical proximo-distal weakness, with most showing complete or at least partial response to therapies. Patients with GM associated with Crohn's disease had only mild clinical impairment and good therapeutic outcomes. Conversely, patients with GM and IBM presented more severe asymmetric proximo-distal muscle weakness, increased occurrence of dysphagia and poor treatment response, similar to IBM controls.

Conclusions: A frequent association of GM with IBM and/or sarcoidosis was demonstrated in our cohort. When associated with IBM, GM led to treatment refractoriness and more severe clinical impairment, unlike the other GM groups which showed satisfactory outcomes in most cases.