Prognosis prediction and immunotherapy optimisation for cryptogenic new-onset refractory status epilepticus.

BACKGROUND: Cryptogenic new-onset refractory status epilepticus (cNORSE) currently lacks comprehensive knowledge regarding its clinical dynamics, prognostic factors and treatment guidance. Here we present the longitudinal clinical profiles, predictive factors for outcomes and the optimal duration of immunotherapy in patients with cNORSE. METHODS: This retrospective secondary endpoint analysis investigated patients with cNORSE identified from a prospective autoimmune encephalitis cohort at a national referral centre in Korea. The main outcomes included longitudinal functional scales, seizure frequency and the number of antiseizure medications. Measures encompassed NORSE-related clinical parameters such as the duration of unconsciousness, immunotherapy profiles, cytokine/chemokine analysis, and serial MRI scans. RESULTS: A total of 74 patients with cNORSE were finally analysed (mean age: 38.0±18.2; 36 (48.6%) male). All patients received first-line immunotherapy, and 91.9% (68/74) received second-line immunotherapy. A total of 83.8% (62/74) regained consciousness within a median duration of 30 days (14-56), and 50% (31/62) achieved good outcome (mRS ≤2) at 2 years. Poor 1-year outcomes (mRS ≥3) were predicted by the presence of mesial temporal lobe (mTL) and extra-mTL lesions at 3-month MRI, and prolonged unconsciousness (≥60 days). Those with mTL atrophy exhibited a higher seizure burden post-NORSE. The optimal duration of immunotherapy appeared to be between 18 weeks and 1-year post-NORSE onset. CONCLUSIONS: This study elucidates longitudinal clinical dynamics, functional outcomes, prognostic factors and immunotherapy response in patients with cNORSE. These findings might contribute to a more standardised understanding and clinical decision-making for cNORSE.

Improving inter-session performance via relevant session-transfer for multi-session motor imagery classification.

Motor imagery (MI)-based brain-computer interfaces (BCIs) using electroencephalography (EEG) have found practical applications in external device control. However, the non-stationary nature of EEG signals remains to obstruct BCI performance across multiple sessions, even for the same user. In this study, we aim to address the impact of non-stationarity, also known as inter-session variability, on multi-session MI classification performance by introducing a novel approach, the relevant session-transfer (RST) method. Leveraging the cosine similarity as a benchmark, the RST method transfers relevant EEG data from the previous session to the current one. The effectiveness of the proposed RST method was investigated through performance comparisons with the self-calibrating method, which uses only the data from the current session, and the whole-session transfer method, which utilizes data from all prior sessions. We validated the effectiveness of these methods using two datasets: a large MI public dataset (Shu Dataset) and our own dataset of gait-related MI, which includes both healthy participants and individuals with spinal cord injuries. Our experimental results revealed that the proposed RST method leads to a 2.29 % improvement (p < 0.001) in the Shu Dataset and up to a 6.37 % improvement in our dataset when compared to the self-calibrating method. Moreover, our method surpassed the performance of the recent highest-performing method that utilized the Shu Dataset, providing further support for the efficacy of the RST method in improving multi-session MI classification performance. Consequently, our findings confirm that the proposed RST method can improve classification performance across multiple sessions in practical MI-BCIs.

Alterations in functional brain connectivity following treatment for restless legs syndrome: The role of symptom improvement in restoring functional connectivity.

The pathophysiology of restless legs syndrome (RLS) remains incompletely understood. Although several studies have investigated the alterations of brain connectivity as one of the pathophysiological mechanisms of RLS, there are only few reports on functional connectivity changes after RLS treatment. Forty-nine patients with newly diagnosed RLS and 50 healthy controls were prospectively enrolled. The patients underwent resting-state functional magnetic resonance imaging (rs-fMRI) at baseline, and 39 patients underwent follow-up rs-fMRI, 3 months after treatment with pramipexole or pregabalin. Patients were divided into good or poor medication response groups. Functional brain connectivity was analysed using rs-fMRI and graph theoretical analysis. Significant differences in functional connectivity were observed between the RLS patients and healthy controls. The average path length, clustering coefficient, transitivity, and local efficiency were lower (2.02 vs. 2.30, p < 0.001; 0.45 vs. 0.56, p < 0.001; 3.08 vs. 4.21, p < 0.001; and 0.71 vs. 0.76, p < 0.001, respectively) and the global efficiency was higher (0.53 vs. 0.50, p < 0.001) in patients with RLS than in healthy controls. Differences in functional connectivity at the global level were also observed between post- and pre-treatment RLS patients who showed a good medication response. Transitivity in the post-treatment group was higher than that in the pre-treatment group (3.22 vs. 3.04, p = 0.007). Global efficiency was positively correlated with RLS severity (r = 0.377, p = 0.007). This study demonstrates that RLS is associated with distinct alterations in brain connectivity, which can be partially normalised following symptom management. These findings suggest that therapeutic interventions for RLS modulate brain function, emphasising the importance of symptom-focussed treatment in managing RLS.

Atezolizumab- and bevacizumab -induced encephalitis in a patient with advanced hepatocellular carcinoma: a case report and literature review.

Treatment with atezolizumab and bevacizumab is the first-line therapy for unresectable hepatocellular carcinoma. Although immune checkpoint inhibitors are novel and effective treatments, they can induce immune-related adverse events. However, neurological immune-related adverse events have rarely been reported. We report the case of a man in his 40s with hepatocellular carcinoma who developed life-threatening encephalitis after atezolizumab plus bevacizumab was administered. The patient presented with fever, headache, altered mentality, and general epileptic seizures, ten days after administration. Cerebrospinal fluid analysis showed elevated white blood cells and elevated protein levels, but revealed no infection or malignancy. Brain magnetic resonance imaging showed diffuse leptomeningeal enhancement in both the cerebrum and cerebellum. As immune checkpoint inhibitor-induced encephalitis was strongly suspected, steroid pulse therapy was initiated and neurological symptoms quickly improved. The patient was discharged after 66 days of hospitalization, and administration of sorafenib and radiotherapy was started for the hepatocellular carcinoma on an outpatient basis. This case demonstrates the importance of recognizing neurological immune-related adverse events following atezolizumab and bevacizumab treatment for early intervention. We discuss this case in comparison to available literature and previous two cases of Atezolizumab- and bevacizumab- induced encephalitis in hepatocellular carcinoma.

Ocular vestibular-evoked myogenic potential assists in differentiation of multiple system atrophy from Parkinson's disease.

Vestibular-evoked myogenic potentials (VEMPs) can help assess otolithic neural pathway in the brainstem that may also participate in cardiovascular autonomic function. Parkinson's disease (PD) is associated with altered VEMP responses; however, the association between VEMP abnormalities and multiple system atrophy (MSA) remains unknown. Therefore, we compared the extent of otolith dysfunction using ocular (oVEMP) and cervical VEMP (cVEMP) between MSA and PD. We analyzed the clinical features and VEMP and head-up tilt table test (HUT) findings using the Finometer in 24 patients with MSA and 52 with de-novo PD, who had undergone neurotologic evaluation in a referral-based university hospital in South Korea from January 2021 to March 2023. MSA was associated with bilateral oVEMP abnormality (odds ratio [95% confidence interval] = 9.19 [1.77-47.76], p=0.008). n1-p1 amplitude was negatively correlated with Unified Multiple System Atrophy Rating Scale I-II scores in patients with MSA (r=-0.571, p=0.033), whereas it did not correlate with Movement Disorder Society-Unified Parkinson's Disease Rating Scale-III scores in patients with PD (r=-0.051, p=0.687). n1 latency was negatively correlated with maximum changes in systolic blood pressure within 15 s during HUT in patients with PD (r=-0.335, p=0.040) but not in those with MSA (r=0.277, p=0.299). In conclusion, bilaterally abnormal oVEMP responses may indicate the extent of brainstem dysfunction in MSA. oVEMP reflects the integrity of otolith-autonomic interplay, reliably assists in differentiating between MSA and PD, and helps infer clinical decline.

Developing a device for simultaneously investigating pivoting neuromuscular control and muscle properties toward a multi-axis rehabilitation.

Understanding the pivoting neuromuscular control of the lower limb and its associated muscle properties is critical for developing diagnostic and rehabilitation tools. However, to the best of our knowledge, a device that can evaluate these factors simultaneously remains lacking. To address this gap, a device that can investigate pivoting neuromuscular control and associated muscle properties was developed in this study. The proposed device consisted of a pivoting mechanism and height-adjustable chair with a brace interface. The device can control a footplate at various speeds to facilitate pivoting stretching and quantify neuromuscular control. Time-synchronized ultrasonographic images can be acquired simultaneously to quantify muscle properties during both active and passive pivoting movements. The muscle displacement, fascicle length/displacement, pennation angle, pivoting stiffness, and pivoting instability were investigated using the proposed device. Further, the feasibility of the device was demonstrated through a cross-sectional study with healthy subjects. The proposed device successfully quantified changes in muscle displacement during passive and active pivoting movements, pivoting stiffness during passive movements, and neuromuscular control during active movements. Therefore, the proposed device is expected to be used as a research and therapeutic tool for improving pivoting neuromuscular control and muscle functions and investigating the underlying mechanisms associated between muscle properties and joint movement in the transverse plane.

Differentiating loss of consciousness causes through artificial intelligence-enabled decoding of functional connectivity.

Differential diagnosis of acute loss of consciousness (LOC) is crucial due to the need for different therapeutic strategies despite similar clinical presentations among etiologies such as nonconvulsive status epilepticus, metabolic encephalopathy, and benzodiazepine intoxication. While altered functional connectivity (FC) plays a pivotal role in the pathophysiology of LOC, there has been a lack of efforts to develop differential diagnosis artificial intelligence (AI) models that feature the distinctive FC change patterns specific to each LOC cause. Three approaches were applied for extracting features for the AI models: three-dimensional FC adjacency matrices, vectorized FC values, and graph theoretical measurements. Deep learning using convolutional neural networks (CNN) and various machine learning algorithms were implemented to compare classification accuracy using electroencephalography (EEG) data with different epoch sizes. The CNN model using FC adjacency matrices achieved the highest accuracy with an AUC of 0.905, with 20-s epoch data being optimal for classifying the different LOC causes. The high accuracy of the CNN model was maintained in a prospective cohort. Key distinguishing features among the LOC causes were found in the delta and theta brain wave bands. This research advances the understanding of LOC's underlying mechanisms and shows promise for enhancing diagnosis and treatment selection. Moreover, the AI models can provide accurate LOC differentiation with a relatively small amount of EEG data in 20-s epochs, which may be clinically useful.

Four-hour-delayed 3D-FLAIR MRIs in patients with acute unilateral peripheral vestibulopathy.

OBJECTIVE: Conventionally, MRI aids in differentiating acute unilateral peripheral vestibulopathy/vestibular neuritis (AUPV/VN) from mimickers. Meanwhile, the diagnostic utility of MRIs dedicated to the inner ear remains to be elucidated for diagnosing AUPV/VN. METHODS: We prospectively recruited 53 patients with AUPV/VN (mean age ± SD = 60 ± 15 years, 29 men). Initial MRIs were performed with a standard protocol, and an additional axial 3D-fluid-attenuated inversion recovery (3D-FLAIR) sequence was obtained 4 h after intravenous injection of gadoterate meglumine. Abnormal enhancement was defined as a signal intensity that exceeded the mean + 2SD value on the healthy side. The findings of neurotologic evaluation and MRIs were compared. RESULTS: Overall, the inter-rater agreement for gadolinium enhancement was 0.886 (Cohen's kappa coefficient). Enhancement was observed in 26 patients (49%), most frequently in the vestibule (n = 20), followed by the anterior (n = 12), horizontal (HC, n = 8), posterior canal (n = 5), and superior (n = 3) and inferior (n = 1) vestibular nerves. In multivariable logistic regression analysis, the enhancement was associated with decreased HC gain in video head-impulse tests (p = 0.036), increased interaural difference in ocular vestibular-evoked myogenic potentials (p = 0.001), and a longer onset-to-MRI time span (p = 0.024). The sensitivity and specificity were 92.3% and 81.5%, respectively, with an area under the curve of 0.90 for predicting gadolinium enhancement. INTERPRETATION: Robust gadolinium enhancement was observed on 4-hour-delayed 3D-FLAIR images in nearly half of the patients with AUPV/VN, with a good correlation with the results of neurotologic evaluation. The positivity may be determined by the extent of vestibular deficit, timing of imaging acquisition, and possibly by the underlying etiology causing AUPV/VN. MRIs may aid in delineating the involved structures in AUPV/VN.

Grapefruit-Inspired Polymeric Capsule with Hierarchical Microstructure: Advanced Nanomaterial Carrier Platform for Energy Storage, Drug Delivery, Catalysis, and Environmental Applications.

Efficient support materials are crucial for maximizing the efficacy of nanomaterials in various applications such as energy storage, drug delivery, catalysis, and environmental remediation. However, traditional supports often hinder nanomaterial performance due to their high weight ratio and limited manageability, leading to issues like tube blocking and secondary pollution. To address this, a novel grapefruit-inspired polymeric capsule (GPC) as a promising carrier platform is introduced. The millimeter-scale GPC features a hydrophilic shell and an internal hierarchical microstructure with 80% void volume, providing ample space for encapsulating diverse nanomaterials including metals, polymers, metal-organic frameworks, and silica. Through liquid-phase bottom-up methods, it is successfully loaded Fe2O3, SiO2, polyacrylic acid, and Prussian blue nanomaterials onto the GPC, achieving high mass ratio (1776, 488, 898, and 634 wt.%, respectively). The GPC shell prevents nanomaterial leakage and the influx of suspended solids, while its internal framework enhances structural stability and mass transfer rates. With long-term storage stability, high carrying capacity, and versatile applicability, the GPC significantly enhances the field applicability of nanomaterials.

Multi-Task Heterogeneous Ensemble Learning-Based Cross-Subject EEG Classification Under Stroke Patients.

Robot-assisted motor training is applied for neurorehabilitation in stroke patients, using motor imagery (MI) as a representative paradigm of brain-computer interfaces to offer real-life assistance to individuals facing movement challenges. However, the effectiveness of training with MI may vary depending on the location of the stroke lesion, which should be considered. This paper introduces a multi-task electroencephalogram-based heterogeneous ensemble learning (MEEG-HEL) specifically designed for cross-subject training. In the proposed framework, common spatial patterns were used for feature extraction, and the features according to stroke lesions are shared and selected through sequential forward floating selection. The heterogeneous ensembles were used as classifiers. Nine patients with chronic ischemic stroke participated, engaging in MI and motor execution (ME) paradigms involving finger tapping. The classification criteria for the multi-task were established in two ways, taking into account the characteristics of stroke patients. In the cross-subject session, the first involved a direction recognition task for two-handed classification, achieving a performance of 0.7419 (±0.0811) in MI and 0.7061 (±0.1270) in ME. The second task focused on motor assessment for lesion location, resulting in a performance of 0.7457 (±0.1317) in MI and 0.6791 (±0.1253) in ME. Comparing the specific-subject session, except for ME on the motor assessment task, performance on both tasks was significantly higher than the cross-subject session. Furthermore, classification performance was similar to or statistically higher in cross-subject sessions compared to baseline models. The proposed MEEG-HEL holds promise in improving the practicality of neurorehabilitation in clinical settings and facilitating the detection of lesions.

Crosstalk between Signaling Pathways and Energy Metabolism in Pluripotency.

The sequential change from totipotency to multipotency occurs during early mammalian embryo development. However, due to the lack of cellular models to recapitulate the distinct potency of stem cells at each stage, their molecular and cellular characteristics remain ambiguous. The establishment of isogenic naïve and primed pluripotent stem cells to represent the pluripotency in the inner cell mass of the pre-implantation blastocyst and in the epiblast from the post-implantation embryo allows the understanding of the distinctive characteristics of two different states of pluripotent stem cells. This review discusses the prominent disparities between naïve and primed pluripotency, including signaling pathways, metabolism, and epigenetic status, ultimately facilitating a comprehensive understanding of their significance during early mammalian embryonic development.

Erectile dysfunction in patient with obstructive sleep apnea: effects of continuous positive airway pressure.

BACKGROUND: Obstructive sleep apnea (OSA) is linked to various health complications, including erectile dysfunction (ED), which is more prevalent in individuals with OSA. This study explored ED in Korean OSA patients and assessed the impact of continuous positive airway pressure (CPAP) therapy on ED. METHODS: A total of 87 male patients with OSA from four different sleep centers underwent physical measurements and completed sleep and mental health (MH) questionnaires, including the Korean version of the International index of erectile function (IIEF), before and three months after initiating CPAP therapy. RESULTS: After three months of CPAP therapy, the patients demonstrated a significant improvement in ED as measured on the IIEF. However, the study found no significant correlation between the duration of CPAP use and the improvement in IIEF score. It did identify the SF36 quality of life assessment as a significant factor influencing ED improvement after CPAP. CONCLUSIONS: ED is a prevalent issue that escalates with age and is associated with OSA. CPAP therapy has shown potential in alleviating ED symptoms, particularly in those with underlying psychological conditions, although further research is required to confirm these findings and understand the underlying mechanisms.

Differentiating changes in movement-related EEG response induced by transcranial direct current stimulation using convolutional neural network.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that can modulate neuronal excitability and induce brain plasticity. Although tDCS has been studied with various methods, more research is needed on the movement-related electroencephalography (EEG) changes induced by tDCS. Moreover, it is necessary to investigate whether these changes can be distinguished through a convolutional neural network (CNN)-based classifier. In this study, we measured the EEG during the voluntary foot-tapping task of participants who received tDCS or sham stimulation and evaluated the classification performance. As a result, significantly higher classification accuracy was shown using the ß band (88.7±9.4%), which is more related to motor function, than in the other bands (71.4±10.6% for δ band, 64.1±13.4% for θ band, and 65.7±10.9% for α band). Consequently, EEG changes during the voluntary foot-tapping task induced by tDCS appeared large in the ß band, implying that it is effective in classifying whether tDCS was given or not, and plays an important role in identifying the effect of tDCS.

Association Between Electronic Device Use at Bedtime and COVID-19 Vaccine-Related Adverse Events During the COVID-19 Pandemic in Korean Adults: A Nationwide Cross-Sectional Population-Based Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to heightened mood disturbances linked to increased electronic device use at bedtime (EUB). General anxiety may contribute to an increased likelihood of experiencing nocebo responses, which have been reported to be associated with COVID-19 vaccine-related adverse events (CAEs). However, no related studies have been conducted to examine this association to date. METHODS: We executed a nationwide cross-sectional study to explore these correlations during the pandemic. Using data from the 2022 National Sleep Survey of South Korea, we analyzed the sleep health of 4,000 adults aged 20-69 years between January and February 2022. Shift workers and those with severe sleep disorders were excluded. Participants with EUB more than four days a week were labeled as high frequency EUB, and those reporting CAEs after both vaccine doses were marked as having a presence of CAEs. The survey also included details about anthropometric data, socioeconomic status, and sleep status. RESULTS: Of the 3,702 participants, 92.6% had received two or more vaccine doses, with 41.2% experiencing CAEs. Furthermore, 73.7% had a high EUB frequency. Factors associated with CAE reporting included younger age, female sex, and high EUB frequency, while heavy alcohol use was found to be less likely to be associated with CAE reporting. Notably, a high EUB frequency was significantly associated with reported CAEs (odds ratio, 1.223; 95% confidence interval, 1.028-1.455; P = 0.023). CONCLUSION: A nationwide online survey conducted in South Korea during the pandemic found that individuals who engaged in the relatively frequent use of electronic devices during bedtime had worse sleep quality and increased COVID-19-related adverse events compared with those using these devices less frequently. These findings have the potential to enhance our understanding of the impact of the use of electronic devices at bedtime on health.

Structural and functional multilayer network analysis in restless legs syndrome patients.

The combination of brain structural and functional connectivity offers complementary insights into its organisation. Multilayer network analysis explores various relationships across different layers within a single system. We aimed to investigate changes in the structural and functional multilayer network in 69 patients with primary restless legs syndrome (RLS) compared with 50 healthy controls. Participants underwent diffusion tensor imaging (DTI) and resting state-functional magnetic resonance imaging (rs-fMRI) using a three-tesla MRI scanner. We constructed a structural connectivity matrix derived from DTI using a DSI program and made a functional connectivity matrix based on rs-fMRI using an SPM program and CONN toolbox. A multilayer network analysis, using BRAPH program, was then conducted to assess the connectivity patterns in both groups. At the global level, significant differences there were between the patients with RLS and healthy controls. The average multiplex participation was lower in patients with RLS than in healthy controls (0.804 vs. 0.821, p = 0.042). Additionally, several regions showed significant differences in the nodal level in multiplex participation between patients with RLS and healthy controls, particularly the frontal and temporal lobes. The regions affected included the inferior frontal gyrus, medial orbital gyrus, precentral gyrus, rectus gyrus, insula, superior and inferior temporal gyrus, medial and lateral occipitotemporal gyrus, and temporal pole. These results represent evidence of diversity in interactions between structural and functional connectivity in patients with RLS, providing a more comprehensive understanding of the brain network in RLS. This may contribute to a precise diagnosis of RLS, and aid the development of a biomarker to track treatment effectiveness.

Partial in vivo reprogramming enables injury-free intestinal regeneration via autonomous Ptgs1 induction.

Tissue regeneration after injury involves the dedifferentiation of somatic cells, a natural adaptive reprogramming that leads to the emergence of injury-responsive cells with fetal-like characteristics. However, there is no direct evidence that adaptive reprogramming involves a shared molecular mechanism with direct cellular reprogramming. Here, we induced dedifferentiation of intestinal epithelial cells using OSKM (Oct4, Sox2, Klf4, and c-Myc) in vivo. The OSKM-induced forced dedifferentiation showed similar molecular features of intestinal regeneration, including a transition from homeostatic cell types to injury-responsive-like cell types. These injury-responsive-like cells, sharing gene signatures of revival stem cells and atrophy-induced villus epithelial cells, actively assisted tissue regeneration following damage. In contrast to normal intestinal regeneration involving Ptgs2 induction, the OSKM promotes autonomous production of prostaglandin E2 via epithelial Ptgs1 expression. These results indicate prostaglandin synthesis is a common mechanism for intestinal regeneration but involves a different enzyme when partial reprogramming is applied to the intestinal epithelium.

Correlation of Diffusion Tensor Tractography with Restless Legs Syndrome Severity.

This prospective study investigated white matter tracts associated with restless legs syndrome (RLS) severity in 69 patients with primary RLS using correlational tractography based on diffusion tensor imaging. Fractional anisotropy (FA) and quantitative anisotropy (QA) were analyzed separately to understand white matter abnormalities in RLS patients. Connectometry analysis revealed positive correlations between RLS severity and FA values in various white matter tracts, including the left and right cerebellum, corpus callosum forceps minor and major, corpus callosum body, right cingulum, and frontoparietal tract. In addition, connectometry analysis revealed that the FA of the middle cerebellar peduncle, left inferior longitudinal fasciculus, left corticospinal tract, corpus callosum forceps minor, right cerebellum, left frontal aslant tract, left dentatorubrothalamic tract, right inferior longitudinal fasciculus, left corticostriatal tract superior, and left cingulum parahippocampoparietal tract was negatively correlated with RLS severity in patients with RLS. However, there were no significant correlations between QA values and RLS severity. It is implied that RLS symptoms may be potentially reversible with appropriate treatment. This study highlights the importance of considering white matter alterations in understanding the pathophysiology of RLS and in developing effective treatment strategies.

Redefining the role of the cerebellum in restless legs syndrome.

OBJECTIVES: We aimed to investigate alterations in cerebellar volume and the intrinsic cerebellar network in patients with restless legs syndrome (RLS). METHODS: We recruited 69 patients with RLS and 50 healthy controls who underwent brain magnetic resonance imaging (MRI), including three-dimensional T1-weighted imaging. The total cerebellar volume and cerebellar volume subdivisions were analyzed through automatic cerebellum anatomical parcellation using U-Net with locally constrained optimization program. The intrinsic cerebellar network was calculated through brain analysis using a graph theory program based on the cerebellar volume subdivisions. The cerebellar volumes and intrinsic cerebellar networks were compared between patients with RLS and healthy controls. RESULTS: The cerebellar volume and subdivisions in patients with RLS did not show significant differences compared to those in healthy controls. However, significant alterations were observed in the intrinsic cerebellar network of patients with RLS. Increased mean clustering coefficient (0.185 vs. 0.114; p = 0.047) and small-worldness index (0.927 vs. 0.800; p = 0.047) were observed in patients with RLS. Additionally, total cerebellar volume was negatively correlated with the Pittsburgh Sleep Quality Index (r = -0.398; p = 0.020) and Insomnia Severity Index (ISI; r = -0.396; p = 0.011). Negative correlations were additionally observed between the right X lobule volume and the International Restless Legs Syndrome Severity Scale (r = -0.425; p = 0.008) and between the vermis VIII volume and ISI score (r = -0.399; p = 0.011). CONCLUSION: We demonstrated alterations in the intrinsic cerebellar network in patients with RLS compared with healthy controls, showing increased connectivity with increased segregation in patients with RLS. This suggests a potential role of the cerebellum in RLS pathophysiology.

Glymphatic system dysfunction in restless legs syndrome: evidenced by diffusion tensor imaging along the perivascular space.

STUDY OBJECTIVES: There is growing evidence pointing at glymphatic system dysfunction in diseases with circadian disruption, such as sleep disorders. Lower diffusivity in the direction of perivascular space has been shown in several neurological and sleep-related disorders; however, its role in restless legs syndrome (RLS) is unclear. We hypothesized that similarly, in RLS the diffusivity in glymphatic system is decreased. Here, we aimed to evaluate glymphatic system functionality in patients with RLS, compare it to healthy controls, and analyze the correlation between its function and clinical characteristics. METHODS: Sixty-nine patients with primary RLS and 51 healthy controls were recruited at a tertiary hospital. All participants underwent diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI) using a 3T MRI scanner, and the DTI along the perivascular space (DTI-ALPS) index was calculated using DTI data. We compared the DTI-ALPS index between the patients with RLS and healthy controls. We also conducted the correlation analysis between the DTI-ALPS index and clinical characteristics, including age, age of onset, symptom duration, and RLS severity. RESULTS: DTI-ALPS index differed significantly between the patients with RLS and healthy controls; the DTI-ALPS index in the patients with RLS was lower than that in the healthy controls (1.48 vs. 0.60, p = 0.008). There was no significant correlation between the DTI-ALPS index and clinical characteristics. CONCLUSION: A significantly lower DTI-ALPS index in patients with RLS suggests that the glymphatic system function is impaired in patients with RLS.

Clinical Features and Neurotologic Findings in Patients With Acute Unilateral Peripheral Vestibulopathy Associated With Antiganglioside Antibody.

BACKGROUND AND OBJECTIVES: Anecdotal studies have reported the presence of antiganglioside antibodies in acute unilateral peripheral vestibulopathy (AUPV). This study aimed to determine the prevalence, clinical characteristics, and neurotologic findings of AUPV associated with antiganglioside antibodies. METHODS: Serum antigangliosides were measured in consecutive patients with AUPV according to the Bárány Society criteria during the acute and recovery phases in a referral-based university hospital in South Korea from September 2019 to January 2023. Clinical characteristics and neurotologic findings were compared between those with and without antiganglioside antibodies. The results of video-oculography, video head impulse and bithermal caloric tests, and other neurotologic evaluations including ocular and cervical vestibular-evoked myogenic potentials and subjective visual vertical were compared between the 2. MRIs dedicated to the inner ear were also conducted when considered necessary. RESULTS: One hundred five patients (mean age ± SD = 60 ± 13 years, 57 male) were included for analyses. During the acute phase, 12 patients (12/105, 11%) were tested positive for serum antiganglioside antibodies, including anti-GQ1b immunoglobulin (Ig) G (n = 5) or IgM (n = 4), anti-GM1 IgM (n = 3), and anti-GD1a IgG (n = 1, including 1 patient with a positive anti-GQ1b antibody). Patients with antiganglioside antibodies showed lesser intensity of spontaneous nystagmus (median [interquartile range] = 1.8 [1.2-2.1] vs 3.4 [1.5-9.5], p = 0.003) and a lesser degree of canal paresis (30 [17-47] vs 58 [34-79], p = 0.028) and gain asymmetry of the vestibulo-ocular reflex for the horizontal semicircular canal during head impulse tests (0.07 [-0.04 to 0.61] vs 0.36 [0.18-0.47], p = 0.032) than those without antibodies. Negative conversion of antibodies and vestibular recovery were observed in most patients (6/8, 75%). Among 30 patients with AUPV with 4-hour delayed 3D fluid-attenuated inversion recovery dedicated to the inner ear, gadolinium enhancement was observed in 18 (18/30, 60%), either in the vestibule (n = 9), semicircular canal (n = 6), or vestibular nerve (n = 5). The positivity rates based on specific antibodies could not be determined due to limited sample sizes. DISCUSSION: The association between antiganglioside antibodies and AUPV suggests an immune-mediated mechanism in acute vestibular failure and extends the clinical spectrum of antiganglioside antibody syndrome.