Alterations in the multilayer network in patients with rapid eye movement sleep behaviour disorder.

This study aimed to reveal the pathophysiology of isolated rapid eye movement sleep behaviour disorder (RBD) in patients using multilayer network analysis. Participants eligible for isolated RBD were included and verified via polysomnography. Both iRBD patients and healthy controls underwent brain MRI, including T1-weighted imaging and diffusion tensor imaging. Grey matter matrix was derived from T1-weighted images using a morphometric similarity network. White matter matrix was formed from diffusion tensor imaging-based structural connectivity. Multilayer network analysis of grey and white matter was performed using graph theory. We studied 29 isolated RBD patients and 30 healthy controls. Patients exhibited a higher average overlap degree (27.921 vs. 23.734, p = 0.002) and average multilayer clustering coefficient (0.474 vs. 0.413, p = 0.002) compared with controls. Additionally, several regions showed significant differences in the degree of overlap and multilayer clustering coefficient between patients with isolated RBD and healthy controls at the nodal level. The degree of overlap in the left medial orbitofrontal, left posterior cingulate, and right paracentral nodes and the multilayer clustering coefficients in the left lateral occipital, left rostral middle frontal, right fusiform, right inferior posterior parietal, and right parahippocampal nodes were higher in patients with isolated RBD than in healthy controls. We found alterations in the multilayer network at the global and nodal levels in patients with isolated RBD, and these changes may be associated with the pathophysiology of isolated RBD. Multilayer network analysis can be used widely to explore the mechanisms underlying various neurological disorders.

Anti-seizure medication response and the glymphatic system in patients with focal epilepsy.

BACKGROUND AND PURPOSE: We aimed to evaluate (i) glymphatic system function in patients with focal epilepsy in comparison with healthy controls, and (ii) the association between anti-seizure medication (ASM) response and glymphatic system function by using diffusion tensor image analysis along the perivascular space (DTI-ALPS). METHODS: We retrospectively enrolled 100 patients with focal epilepsy who had normal brain magnetic resonance imaging (MRI) findings, and classified them as "poor" or "good" ASM responders according to their seizure control at the time of brain MRI. We also included 79 age- and sex-matched healthy controls. All patients and healthy controls underwent conventional brain MRI and diffusion tensor imaging. The DTI-ALPS index was calculated using the DSI studio program. RESULTS: Of the 100 patients with focal epilepsy, 38 and 62 were poor and good ASM responders, respectively. The DTI-ALPS index differed significantly between patients with focal epilepsy and healthy controls and was significantly lower in patients with focal epilepsy (1.55 vs. 1.70; p < 0.001). The DTI-ALPS index also differed significantly according to ASM response and was lower in poor ASM responders (1.48 vs. 1.59; p = 0.047). Furthermore, the DTI-ALPS index was negatively correlated with age (r = -0.234, p = 0.019) and duration of epilepsy (r = -0.240, p = 0.016) in patients with focal epilepsy. CONCLUSION: Our study is the first to identify, in focal epilepsy patients, a greater reduction in glymphatic system function among poor ASM responders compared to good responders. To confirm our results, further prospective multicenter studies with large sample sizes are needed.

Functional Connectivity Alterations in Patients with Post-stroke Epilepsy Based on Source-level EEG and Graph Theory.

We investigated the differences in functional connectivity based on the source-level electroencephalography (EEG) analysis between stroke patients with and without post-stroke epilepsy (PSE). Thirty stroke patients with PSE and 35 stroke patients without PSE were enrolled. EEG was conducted during a resting state period. We used a Brainstorm program for source estimation and the connectivity matrix. Data were processed according to EEG frequency bands. We used a BRAPH program to apply a graph theoretical analysis. In the beta band, radius and diameter were increased in patients with PSE than in those without PSE (2.699 vs. 2.579, adjusted p = 0.03; 2.261 vs. 2.171, adjusted p = 0.03). In the low gamma band, radius was increased in patients with PSE than in those without PSE (2.808 vs. 2.617, adjusted p = 0.03). In the high gamma band, the radius, diameter, average eccentricity, and characteristic path length were increased (1.828 vs. 1.559, adjusted p < 0.01; 2.653 vs. 2.306, adjusted p = 0.01; 2.212 vs. 1.913, adjusted p < 0.01; 1.425 vs. 1.286, adjusted p = 0.01), whereas average strength, mean clustering coefficient, and transitivity were decreased in patients with PSE than in those without PSE (49.955 vs. 55.055, adjusted p < 0.01; 0.727 vs. 0.810, adjusted p < 0.01; 1.091 vs. 1.215, adjusted p < 0.01). However, in the delta, theta, and alpha bands, none of the functional connectivity measures were different between groups. We demonstrated significant alterations of functional connectivity in patients with PSE, who have decreased segregation and integration in brain network, compared to those without PSE.

Structural connectivity as a predictive factor for responsiveness to levetiracetam treatment in epilepsy.

PURPOSE: To investigate whether structural connectivity or glymphatic system function is a potential predictive factor for levetiracetam (LEV) response in patients with newly diagnosed epilepsy. METHODS: We enrolled patients with newly diagnosed epilepsy who were administered LEV as initial monotherapy and underwent diffusion tensor imaging (DTI) at diagnosis. We categorized the patients into drug response. We used graph theory to calculate the network measures for structural connectivity based on the DTI scans in patients with epilepsy. Additionally, we evaluated glymphatic system function by calculating the DTI analysis along the perivascular space (DTI-ALPS) index based on DTI scans. RESULTS: We enrolled 84 patients with epilepsy. The clinical factors and DTI-ALPS index did not differ between the groups. However, some of the structural connectivity measures significantly differ between the groups. The poor responders exhibited a higher mean clustering coefficient, global efficiency, and small-worldness index than the good responders (p = 0.003, p = 0.048, and p = 0.038, respectively). In the receiver operating characteristic curve analysis, the mean clustering coefficient exhibited the highest performance in predicting the responsiveness to LEV (area under the curve of 0.677). In the multiple logistic regression analysis, the mean clustering coefficient of the structural connectivity measures was the only significant predictor of LEV response (p = 0.014). Furthermore, in the survival analysis, the mean clustering coefficient was the only significant predictor of LEV response (p = 0.026). CONCLUSION: We demonstrated that structural connectivity is a potential predictive factor for responsiveness to LEV treatment in patients with newly diagnosed epilepsy.

Multilayer network analysis in patients with juvenile myoclonic epilepsy.

INTRODUCTION: We conducted a multilayer network analysis in patients with juvenile myoclonic epilepsy (JME) and healthy controls, to investigate the gray matter layer using a morphometric similarity network and analyze the white matter layer using structural connectivity. METHODS: We enrolled 42 patients with newly diagnosed JME and 53 healthy controls. Brain magnetic resonance imaging (MRI) using a three-tesla MRI scanner, including T1-weighted imaging and diffusion tensor imaging (DTI) were performed. We created a gray matter layer matrix with a morphometric similarity network using T1-weighted imaging, and a white matter layer matrix with structural connectivity using the DTI. Subsequently, we performed a multilayer network analysis by applying graph theory. RESULTS: There were significant differences in network at the global level in the multilayer network analysis between the groups. The average multiplex participation of patients with JME was lower than that of healthy controls (0.858 vs. 0.878, p = 0.007). In addition, several regions showed significant differences in multiplex participation at the nodal level in the multilayer network analysis. Multiplex participation in the right entorhinal cortex was lower, whereas multiplex participation in the right supramarginal gyrus was higher at the nodal level in the multilayer network analysis of patients with JME compared to healthy controls. CONCLUSION: We demonstrated differences in network at the global and nodal levels in the multilayer network analysis between patients with JME and healthy controls. These features may be associated with the pathophysiology of JME and could help us understand the complex brain network in patients with JME.

Alteration of multilayer network perspective on gray and white matter connectivity in obstructive sleep apnea.

PURPOSE: The objective of this research was to examine changes in the neural networks of both gray and white matter in individuals with obstructive sleep apnea (OSA) in comparison to those without the condition, employing a comprehensive multilayer network analysis. METHODS: Patients meeting the criteria for OSA were recruited through polysomnography, while a control group of healthy individuals matched for age and sex was also assembled. Utilizing T1-weighted imaging, a morphometric similarity network was crafted to represent gray matter, while diffusion tensor imaging provided structural connectivity for constructing a white matter network. A multilayer network analysis was then performed, employing graph theory methodologies. RESULTS: We included 40 individuals diagnosed with OSA and 40 healthy participants in our study. Analysis revealed significant differences in various global network metrics between the two groups. Specifically, patients with OSA exhibited higher average degree overlap and average multilayer clustering coefficient (28.081 vs. 23.407, p < 0.001; 0.459 vs. 0.412, p = 0.004), but lower multilayer modularity (0.150 vs. 0.175, p = 0.001) compared to healthy controls. However, no significant differences were observed in average multiplex participation, average overlapping strength, or average weighted multiplex participation between the patients with OSA and healthy controls. Moreover, several brain regions displayed notable differences in degree overlap at the nodal level between patients with OSA and healthy controls. CONCLUSION: Remarkable alterations in the multilayer network, indicating shifts in both gray and white matter, were detected in patients with OSA in contrast to their healthy counterparts. Further examination at the nodal level unveiled notable changes in regions associated with cognition, underscoring the effectiveness of multilayer network analysis in exploring interactions across brain layers.

Cerebellar volumes and the intrinsic cerebellar network in patients with obstructive sleep apnea.

PURPOSE: This research aimed to explore changes in both cerebellar volume and the intrinsic cerebellar network in patients with obstructive sleep apnea (OSA). METHODS: Newly diagnosed OSA patients and healthy controls were included in the study. All participants underwent three-dimensional T1-weighted imaging using a 3-T MRI scanner. Cerebellar volumes, both overall and subdivided, were quantified using the ACAPULCO program. The intrinsic cerebellar network was assessed using the BRAPH program, which applied graph theory to the cerebellar volume subdivision. Comparisons were drawn between the patients with OSA and healthy controls. RESULTS: The study revealed that the 26 patients with OSA exhibited a notably lower total cerebellar volume compared to the 28 healthy controls (8.330 vs. 9.068%, p < 0.001). The volume of the left lobule VIIB was reduced in patients with OSA compared to healthy controls (0.339 vs. 0.407%, p = 0.001). Among patients with OSA, there was a negative correlation between the volume of the left lobule X and apnea-hypopnea index during non-rapid eye movement sleep (r = - 0.536, p = 0.005). However, no significant differences were observed in the intrinsic cerebellar network between patients and healthy controls. CONCLUSION: This study established that patients with OSA exhibited decreased total cerebellar volumes and particularly reduced volumes in subdivisions such as the left lobule VIIB compared to healthy controls. These findings suggest potential involvement of the cerebellum in the underlying mechanisms of OSA.

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.

Structural brain network analysis in occipital lobe epilepsy.

BACKGROUND: This study aimed to analyze the structural brain network in patients with occipital lobe epilepsy (OLE) and investigate the differences in structural brain networks between patients with OLE and healthy controls. METHODS: Patients with OLE and healthy controls with normal brain MRI findings were enrolled. They underwent diffusion tensor imaging using a 3.0T MRI scanner, and we computed the network measures of global and local structural networks in patients with OLE and healthy controls using the DSI studio program. We compared network measures between the groups. RESULTS: We enrolled 23 patients with OLE and 42 healthy controls. There were significant differences in the global structural network between patients with OLE and healthy controls. The assortativity coefficient (-0.0864 vs. -0.0814, p = 0.0214), mean clustering coefficient (0.0061 vs. 0.0064, p = 0.0203), global efficiency (0.0315 vs. 0.0353, p = 0.0086), and small-worldness index (0.0001 vs. 0.0001, p = 0.0175) were lower, whereas the characteristic path length (59.2724 vs. 53.4684, p = 0.0120) was higher in patients with OLE than those in the healthy controls. There were several nodes beyond the occipital lobe that showed significant differences in the local structural network between the groups. In addition, the assortativity coefficient was negatively correlated with the duration of epilepsy (r=-0.676, p = 0.001).

Involvement of the default mode network in patients with transient global amnesia: multilayer network.

INTRODUCTION: We aimed to investigate the alterations in the multilayer network in patients with transient global amnesia (TGA). METHODS: We enrolled 124 patients with TGA and 80 healthy controls. Both patients with TGA and healthy controls underwent a three-teslar brain magnetic resonance imaging (MRI). A gray matter layer matrix was created using a morphometric similarity network derived from the T1-weighted imaging, and a white matter layer matrix was constructed using structural connectivity based on the diffusion tensor imaging. A multilayer network analysis was performed by applying graph theoretical analysis. RESULTS: There were no significant differences in global network measures between the groups. However, several regions, related to the default mode network, showed significant differences in nodal network measures between the groups. Multi-richness in the left pars opercularis, multi-rich-club degree in the right posterior cingulate gyrus, and weighted multiplex participation in the right posterior cingulate gyrus were higher in patients with TGA compared with healthy controls (15.47 vs. 12.26, p = 0.0005; 41.68 vs. 37.16, p = 0.0005; 0.90 vs. 0.80, p = 0.0005; respectively). The multiplex core-periphery in the left precuneus was higher (0.96 vs. 0.84, p = 0.0005), whereas that in the transverse temporal gyrus was lower in patients with TGA compared with healthy controls (0.00 vs. 0.02, p = 0.0005). CONCLUSION: We newly find the alterations in the multilayer network in patients with TGA compared with healthy controls, which shows the involvement of the default mode network. These changes may be related to the pathophysiology of TGA.

Alterations of Limbic Structure Volumes in Patients with Obstructive Sleep Apnea.

OBJECTIVES: We investigated the change in limbic structure volumes and intrinsic limbic network in patients with obstructive sleep apnea (OSA) compared to healthy controls. METHODS: We enrolled 26 patients with OSA and 30 healthy controls. They underwent three-dimensional T1-weighted magnetic resonance imaging (MRI) on a 3 T MRI scanner. The limbic structures were analyzed volumetrically using the FreeSurfer program. We examined the intrinsic limbic network using the Brain Analysis with Graph Theory program and compared the groups' limbic structure volumes and intrinsic limbic network. RESULTS: There were significant differences in specific limbic structure volumes between the groups. The volumes in the right amygdala, right hippocampus, right hypothalamus, right nucleus accumbens, left amygdala, left basal forebrain, left hippocampus, left hypothalamus, and left nucleus accumbens in patients with OSA were lower than those in healthy controls (right amygdala, 0.102 vs. 0.113%, p = 0.004; right hippocampus, 0.253 vs. 0.281%, p = 0.002; right hypothalamus, 0.028 vs. 0.032%, p = 0.002; right nucleus accumbens, 0.021 vs. 0.024%, p = 0.019; left amygdala, 0.089 vs. 0.098%, p = 0.007; left basal forebrain, 0.020 vs. 0.022%, p = 0.027; left hippocampus, 0.245 vs. 0.265%, p = 0.021; left hypothalamus, 0.028 vs. 0.031%, p = 0.016; left nucleus accumbens, 0.023 vs. 0.027%, p = 0.002). However, there were no significant differences in network measures between the groups. CONCLUSION: We demonstrate that the volumes of several limbic structures in patients with OSA are significantly lower than those in healthy controls. However, there are no alterations to the intrinsic limbic network. These findings suggest that OSA is one of the risk factors for cognitive impairments.

Cerebellar Volume Reduction in Patients with Isolated REM Sleep Behavior Disorder: Evidence of a Potential Role of the Cerebellum.

INTRODUCTION: In this study, we aimed to investigate changes in the total cerebellar volume, subdivisions of the cerebellar volume, and intrinsic cerebellar network in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD) compared to healthy controls. METHODS: We enrolled patients with newly diagnosed iRBD and healthy controls who had no structural lesions according to their brain MRI. All participants underwent three-dimensional T1-weighted imaging. We obtained the total cerebellar volume and subdivisions of the cerebellar volume using the ACAPULCO program and calculated the intrinsic cerebellar network using a BRAPH program based on the subdivisions of the cerebellar volume by applying a graph theory. We compared the cerebellar volumes and intrinsic cerebellar network between the patients with iRBD and healthy controls. RESULTS: In total, we enrolled 43 patients with iRBD and 47 healthy controls. Total cerebellar volume in patients with iRBD was lower than that in the healthy controls (8.4637 vs. 9.0863%, p = 0.0001). There were significant differences in the subdivisions of cerebellar volume between the groups. The volumes of the right and left lobule VIIB in the patients with iRBD were lower than those in the healthy controls (right, 0.3495 vs. 0.4025%, p = 0.0009; left, 0.3561 vs. 0.4293%, p < 0.0001). However, the other cerebellar volumes, such as the corpus meullare and vermis, were not different between the groups. The intrinsic cerebellar network was not different between the patients with iRBD and healthy controls. CONCLUSION: We found decreased total cerebellar volumes and subdivisions of the cerebellar volume, particularly in the right and left lobule VIIB, in patients with iRBD compared to healthy controls. The present results suggest that the cerebellum may play a potential role in the pathogenesis of iRBD.

Difference in functional connectivity between end-stage renal disease patients with and without restless legs syndrome: A prospective study.

PURPOSE: The purpose of this study was to examine differences in functional connectivity between patients with end-stage renal disease (ESRD) with and without restless legs syndrome (RLS). In addition, the study aimed to identify any potential associations between RLS severity and functional connectivity. METHODS: We enrolled patients with ESRD who had been undergoing hemodialysis. Patients with and without RLS were separated into two groups. Using functional near-infrared spectroscopy (fNIRS) and a graph theory approach, we determined the functional connectivity of patients with ESRD. The data were collected during a 300-s resting state evaluation performed in the dialysis room prior to dialysis. RESULTS: Eighteen of 48 patients with ESRD were diagnosed with RLS, whereas 30 patients did not exhibit RLS symptoms. Notably, functional connectivity metrics differed significantly between patients with and without RLS. Specifically, patients with ESRD and RLS displayed higher values for mean clustering coefficient (0.474 vs. 0.352, p = 0.001), global efficiency (0.520 vs. 0.414, p = 0.001), strength (6.538 vs. 4.783, p = 0.001), and transitivity (0.714 vs. 0.521, p = 0.001), while values for diameter (5.451 vs. 7.338, p = 0.002), eccentricity (4.598 vs. 5.985, p = 0.004), and characteristic path length (2.520 vs. 3.271, p = 0.002) were lower in patients with ESRD and RLS compared to those without RLS. In addition, there were correlations between the RLS severity score and the assortative coefficient (r = 0.479, p = 0.044), the small-worldness index (r = -0.475, p = 0.046), and transitivity (r = 0.500, p = 0.034). CONCLUSIONS: We demonstrated differences in functional connectivity between patients with ESRD with and without RLS, which may shed light on the pathophysiology of RLS. Notably, a number of functional connectivity metrics demonstrated strong associations with RLS severity. Our study also confirmed the applicability of fNIRS as a tool for investigating functional connectivity in patients with RLS.

Changes in the glymphatic system before and after dialysis initiation in patients with end-stage kidney disease.

INTRODUCTION: The aims of this study were to evaluate 1) glymphatic system function in patients with end-stage kidney disease (ESKD) before initiating dialysis compared to healthy controls, and 2) changes in the glymphatic system function after kidney replacement therapy including dialysis in patients with ESKD using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. MATERIALS AND METHODS: This study was prospectively conducted at a single hospital. We enrolled 14 neurologically asymptomatic patients who first initiated hemodialysis or peritoneal dialysis for ESKD and 17 healthy controls. Patients had magnetic resonance imaging scans before initiating dialysis and again 3 months after initiating dialysis and the DTI-ALPS index was calculated. We compared the DTI-ALPS index before and after the initiation of dialysis and compared the DTI-ALPS index between the patients with ESKD and healthy control. RESULTS: There were differences in the DTI-ALPS index between ESKD patients before initiating dialysis and healthy controls (1.342 vs. 1.633, p = 0.003). DTI-ALPS index between ESKD patients before initiating dialysis and those after dialysis were not different (1.342 vs. 1.262, p = 0.386). There was a positive correlation between DTI-ALPS index and phosphate (r = 0.610, p = 0.020) in patients with ESKD. CONCLUSION: We confirmed the presence of glymphatic dysfunction in patients with ESKD. However, there was no difference in the glymphatic system before and after dialysis initiation. This finding may be related to uremic toxins that are not removed by dialysis in patients with ESKD. This study can be used for the development of pathophysiology of patients with ESKD.

Normal glymphatic system function in patients with migraine: A pilot study.

OBJECTIVE: No studies have evaluated the glymphatic system function in patients with migraine. In this pilot study, we evaluated and compared the alterations in the glymphatic system function in patients with migraine with healthy controls using a diffusion tensor imaging (DTI) analysis along the perivascular space (DTI-ALPS) method. We also investigated the differences in the glymphatic system function table between patients with migraine with and without aura using the ALPS method. METHODS: This field study used a cross-sectional study design. We prospectively enrolled patients with migraine and healthy controls. All brain magnetic resonance imaging (MRI), including DTI, in participants, patients with migraine, and healthy controls were obtained using the same MRI scanner. We calculated and compared the ALPS index between patients with migraine and healthy controls, and between patients with migraine with and without aura. In addition, we investigated the association between the glymphatic system function and the clinical characteristics of migraine. RESULTS: We enrolled 92 patients with migraine and 80 healthy controls. There were no significant differences in the ALPS index between patients with migraine and healthy controls (1.655 ± 0.335 [patients with migraine] vs. 1.713 ± 0.297 [controls], difference = 0.058, 95% confidence interval [CI] of difference = -0.037 to 0.154, p = 0.233), and between patients with migraine with and without aura (1.690 ± 0.380 [with aura] vs. 1.645 ± 0.323 [without aura], difference = -0.044, 95% CI of difference = -0.213 to 0.124, p = 0.601). There was no significant correlation between the ALPS index and clinical characteristics of migraine, including age (r = -0.07, p = 0.507), age at onset (r = 0.07, p = 0.552), disease duration (r = -0.12, p = 0.306), attack frequency (r = -0.05, p = 0.668), and headache intensity (r = 0.00, p = 0.976). CONCLUSIONS: There was no glymphatic system dysfunction in patients with migraine. Moreover, there were no differences in the glymphatic system function between patients with migraine with and without aura. We also demonstrated the feasibility of the ALPS method, which can be used for research on various neurological diseases. Further studies are needed to confirm our findings.

Glymphatic dysfunction in isolated REM sleep behavior disorder.

OBJECTIVES: This study aimed to evaluate glymphatic-system function in patients with isolated rapid eye movement sleep behavior disorder (iRBD) in comparison with healthy controls by using diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS) method. We hypothesized that patients with iRBD may show glymphatic-system dysfunction. METHODS: We retrospectively enrolled 18 patients with iRBD and 18 age- and sex-matched healthy controls. All participants underwent DTI magnetic resonance imaging (MRI) using the same 3T MRI scanner, and the DTI-ALPS index was calculated using DTI data. We evaluated the differences in the DTI-ALPS index between patients with iRBD and healthy controls. In addition, we evaluated the correlation between the DTI-ALPS index and demographic and polysomnographic characteristics. RESULTS: The DTI-ALPS index was significantly different between the groups; it was significantly lower in patients with iRBD than in healthy controls (1.5647 vs. 1.7612, p = .0157). The index did not correlate with demographic and polysomnographic characteristics, including age, Epworth Sleepiness Scale score, total sleep time, sleep efficiency, sleep stage N1 ratio, stage N2 ratio, stage N3 ratio, stage R ratio, and total apnea-hypopnea index. CONCLUSION: The DTI-ALPS index was significantly lower in patients with iRBD than in healthy controls, indicating the presence of glymphatic-system dysfunction in patients with iRBD. Our study also suggests that the DTI-ALPS index could serve as a biomarker for evaluating glymphatic-system function in neurological disorders.

Brain networks in migraine with and without aura: An exploratory arterial spin labeling MRI study.

OBJECTIVES: The aim of this exploratory study was to investigate the underlying pathomechanisms of migraine with aura (MA) and migraine without aura (MO) in the interictal phase using a connectivity analysis. METHODS: We prospectively enrolled patients who were newly diagnosed with migraine. All patients underwent brain MRI, including diffusion tensor imaging and arterial spin labeling perfusion MRI. We analyzed the differences between patients with MA and those with MO in structural connectivity based on diffusion tensor imaging and functional connectivity based on arterial spin labeling perfusion MRI using a graph theoretical analysis. RESULTS: We enrolled 58 patients with migraine (11 patients with MA and 47 patients with MO). There were no differences between patients with MA and those with MO in the network measures of global structural connectivity. However, differences in global functional connectivity were found between the two groups. The assortative coefficient was lower in patients with MA than in those with MO (-0.050 vs. -0.012, p = .017). There were no differences in local structural and functional connectivity between patients with MA and those with MO. CONCLUSION: We found differences in global functional connectivity between patients with MO and those with MA. The study of MA and MO using a connectivity analysis may shed light on migraine pathophysiology. We suggest it is worthwhile to investigate if changes in functional connectivity may serve as novel biomarkers in MA. In this regard, ASL MRI appears to be valuable in the context of network analysis, but further studies are needed to confirm our findings.

Glymphatic system impairment in patients with status epilepticus.

OBJECTIVE: The aim of this study was to compare the function of the glymphatic system in patients with status epilepticus (SE) with that in healthy controls by diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. We also investigated the association between glymphatic system function and the clinical characteristics of SE. METHODS: We retrospectively enrolled 28 patients with SE and 31 healthy controls matched for age and sex. All study participants underwent diffusion tensor imaging using the same 3-T MRI scanner, and the DTI-ALPS index was calculated. We compared the DTI-ALPS index between the SE group and the control group. We also evaluated the associations of the DTI-ALPS index with etiology and type of SE, age, putative duration of seizure, time interval until MRI, seizure-related changes on diffusion-weighted imaging, and any previous structural lesions. RESULTS: The DTI-ALPS index was significantly lower in the SE group than in the control group (1.462 ± 0.297 vs. 1.632 ± 0.270, p = 0.026) and was negatively correlated with age (r = - 0.280, p = 0.032) in the SE group. However, there were no significant between-group differences in the DTI-ALPS index according to other clinical factors. SIGNIFICANCE: The finding of a significantly lower DTI-ALPS index in the SE group suggests that the glymphatic system is impaired in patients with SE. DTI-ALPS is a useful tool for evaluation of the function of the glymphatic system in these patients.

Alterations of thalamic nuclei volumes in patients with cluster headache.

PURPOSE: This study aimed to compare the alterations of thalamic nuclei volumes and the intrinsic thalamic network in patients with cluster headache and healthy controls. METHODS: We retrospectively enrolled 24 patients with episodic cluster headache and 24 healthy controls. We calculated the thalamic nuclei volumes in the patients with cluster headache and healthy controls based on three-dimensional T1-weighted imaging with automated segmentation using the FreeSurfer program. We also investigated the intrinsic thalamic network using structural co-variance analysis based on the thalamic nuclei volumes and graph theory under the BRAPH program. We compared the thalamic nuclei volumes and intrinsic thalamic networks in patients with cluster headaches and healthy controls. RESULTS: The right and left whole thalamic volumes did not differ in the patients with cluster headaches and healthy controls (0.4199 vs. 0.4069%, p = 0.2008; 0.4386 vs. 0.4273%, p = 0.3437; respectively). However, there were significant alterations of right and left medial geniculate nuclei volumes in the patients with cluster headaches and the healthy controls. The right and left medial geniculate nuclei volumes of the patients with cluster headaches were greater than those of the healthy controls (0.0088 vs. 0.0075%, p < 0.0001; 0.0086 vs. 0.0072%, p < 0.0001; respectively). The intrinsic thalamic networks of the groups were not different. CONCLUSION: This study demonstrates significant alterations in the bilateral medial geniculate nuclei volumes in patients with cluster headache compared to healthy controls. These alterations may be related to the pathophysiology of cluster headache. However, there are no changes in the intrinsic thalamic network in patients with cluster headache.

Network differences based on arterial spin labeling related to anti-seizure medication response in focal epilepsy.

PURPOSE: The aim of this study was to determine whether anti-seizure medication (ASM) response is associated with structural connectivity in diffusion tensor imaging (DTI) or functional co-variance network in arterial spin labeling (ASL) magnetic resonance imaging (MRI) in patients with focal epilepsy. METHODS: In this retrospective study conducted at a tertiary hospital, we enrolled 105 patients with focal epilepsy, of which 64 patients were good ASM responders, and 41 patients were poor ASM responders. All patients showed normal MRI findings on visual inspection and underwent DTI and ASL MRI from August 2018 to July 2020, with regular follow-up for at least 12 months after epilepsy diagnosis while taking ASMs. We calculated the structural connectivity based on DTI and functional co-variance network based on ASL MRI by using graph theory and analyzed their differences in relation to the ASM response. RESULTS: No differences were observed in structural connectivity between the good and poor ASM responders. However, significant differences were observed in functional co-variance network between the good and poor ASM responders. In comparison with good ASM responders, poor ASM responders showed a significantly greater characteristic path length (2.557 vs. 1.753, p = 0.034) and a lower local efficiency (2.311 vs. 3.927, p = 0.048). CONCLUSION: Significant differences were observed in functional co-variance network based on ASL MRI between the good and poor ASM responders. These findings suggest that functional co-variance network could serve as a new biomarker of ASM response in focal epilepsy.