Increased Thalamic Connectivity in Juvenile Myoclonic Epilepsy Based on Electroencephalography Source-Level Analysis.

Background: This study investigated alterations in the intrinsic thalamic network of patients with juvenile myoclonic epilepsy (JME) based on an electroencephalography (EEG) source-level analysis. Materials and Methods: We enrolled patients newly diagnosed with JME as well as healthy controls. The assessments were conducted in the resting state. We computed sources based on the scalp electrical potentials using a minimum-norm imaging method and a standardized, low-resolution, brain electromagnetic tomography approach. To create a functional connectivity matrix, we used the Talairach atlas to define thalamic nodes and applied the coherence method to measure brain synchronization as edges. We then calculated the intrinsic thalamic network using graph theory. We compared the intrinsic thalamic network of patients with JME with those of healthy controls. Results: This study included 67 patients with JME and 66 healthy controls. EEG source-level analysis revealed significant differences in the intrinsic thalamic networks between patients with JME and healthy controls. The measures of functional connectivity (radius, diameter, and characteristic path length) were significantly lower in patients with JME than in healthy controls (radius: 2.769 vs. 3.544, p = 0.015; diameter: 4.464 vs. 5.443, p = 0.024; and characteristic path length: 2.248 vs. 2.616, p = 0.046). Conclusions: We demonstrated alterations in the intrinsic thalamic network in patients with JME compared with those in healthy controls based on the EEG source-level analysis. These findings indicated increased thalamic connectivity in the JME group. These intrinsic thalamic network changes may be related to the pathophysiology of JME.

Thalamic nuclei volumes and intrinsic thalamic network in patients with occipital lobe epilepsy.

INTRODUCTION: This study aimed to investigate the alterations in individual thalamic nuclei volumes in patients with occipital lobe epilepsy (OLE) compared with those of healthy controls, and to analyze the intrinsic thalamic network based on these volumes using graph theory. METHODS: Thirty adult patients with newly diagnosed OLE and 42 healthy controls were retrospectively enrolled (mean age, 33.8 ± 17.0 and 32.2 ± 6.6 years, respectively). The study participants underwent brain magnetic resonance imaging with three-dimensional T1-weighted imaging. The right and left total thalamic and individual thalamic nuclei volumes were obtained using the FreeSurfer program. Then, the intrinsic thalamic network was calculated based on the individual thalamic nuclei volumes and graph theory using a BRAPH program. RESULTS: There were no differences in the right and left whole-thalamic volumes between the two groups (0.445% vs. 0.469%, p = .142 and 0.481% vs. 0.490%, p = .575, respectively). However, significant differences were observed in the volumes of several thalamic nuclei between the two groups. The right medial geniculate and right suprageniculate nuclei volumes were increased (0.0077% vs. 0.0064%, p = .0003 and 0.0013% vs. 0.0010%, p = .0004, respectively), whereas the right and left parafascicular nuclei volumes were decreased in patients with OLE compared with those in healthy controls (0.0038% vs. 0.0048%, p < .0001 and 0.0037% vs. 0.0045%, p = .0001, respectively). There were no differences in the network measures regarding intrinsic thalamic network between the two groups. CONCLUSION: We successfully demonstrated the alterations in individual thalamic nuclei volumes, especially the increased medial geniculate and suprageniculate, and decreased parafascicular nuclei volumes in patients with OLE compared with those of healthy controls despite no changes in the whole-thalamic volumes. These findings suggest an important role of the thalamus in the epileptic network of OLE.

Alterations of the thalamic nuclei volumes and intrinsic thalamic network in patients with restless legs syndrome.

We aimed to investigate the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with primary restless legs syndrome (RLS) compared to healthy controls. Seventy-one patients with primary RLS and 55 healthy controls were recruited. They underwent brain MRI using a three-tesla MRI scanner, including three-dimensional T1-weighted images. The intrinsic thalamic network was determined using graph theoretical analysis. The right and left whole thalamic volumes, and the right pulvinar inferior, left ventral posterolateral, left medial ventral, and left pulvinar inferior nuclei volumes in the patients with RLS were lower than those in healthy controls (0.433 vs. 0.447%, p = 0.034; 0.482 vs. 0.502%, p = 0.016; 0.013 vs. 0.015%, p = 0.031; 0.062 vs. 0.065%, p = 0.035; 0.001 vs. 0.001%, p = 0.034; 0.018 vs. 0.020%, p = 0.043; respectively). There was also a difference in the intrinsic thalamic network between the groups. The assortative coefficient in patients with RLS was higher than that in healthy controls (0.0318 vs. - 0.0358, p = 0.048). We demonstrated the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with RLS compared to healthy controls. These changes might be related to RLS pathophysiology and suggest the pivotal role of the thalamus in RLS symptoms.

Alterations of limbic structure volumes and limbic covariance network in patients with cluster headache.

The aim of this study was to compare the limbic structures and covariance network in patients with cluster headache to those of healthy controls. We enrolled 23 patients with newly diagnosed cluster headache and 31 healthy controls. They underwent three-dimensional T1-weighted imaging utilizing a 3.0 Tesla MRI scanner. Volumetric analysis of the subcortical limbic structures, including the hippocampus, amygdala, thalamus, mammillary body, hypothalamus, basal forebrain, septal nuclei, fornix, and nucleus accumbens, was performed. We examined the limbic covariance network using a graph theory. The volumes of the limbic structures between patients with cluster headache and healthy controls were significantly different. The volume of the left hippocampus in patients with cluster headache was significantly lower than that in healthy controls (0.256 vs 0.291 %, p = 0.002). Patients with cluster headache showed significant alterations of the limbic covariance network. The average strength, global efficiency, local efficiency, mean clustering coefficient, and transitivity were lower (5.238 vs 10.322, p = 0.030; 0.355 vs 0.608, p = 0.020; 0.547 vs 1.553, p = 0.020; 0.424 vs 0.895, p = 0.016; respectively), whereas the characteristic path length was higher (3.314 vs 1.752, p = 0.040) in patients with cluster headache than in healthy controls. We detected alterations of limbic structure volumes in patients with cluster headache compared to healthy controls, especially in the hippocampus. We also found significant alterations in the limbic covariance network in patients with cluster headache who showed decreased segregation and integration. These abnormalities could be related to the pathophysiology of cluster headache.

Alterations in the structural covariance network of the hypothalamus in patients with narcolepsy.

PURPOSE: The hypothalamus plays a pivotal role in the pathogenesis of narcolepsy. This study aimed to evaluate the differences in the structural covariance network of thehypothalamus based on volume differences between patients with narcolepsy and healthy controls. METHODS: We retrospectively enrolled 15 patients with narcolepsy and 19 healthy controls.All subjects underwent three-dimensional T1-weighted imaging using a 3-T magnetic resonance imaging scanner. Hypothalamic subunits were segmented, and the volumes of individual hypothalamic subunits were obtained using the FreeSurfer program. Subsequently, we conducted a structural covariance network analysis of the subunit volumes with graph theory using the BRAPH program in patients with narcolepsy and in healthy controls. RESULTS: There were no significant differences in the volumes of the entire right and left hypothalamus nor in the hypothalamic subunit between patients with narcolepsy and healthy controls. However, we found significant differences in the structural covariance network in the hypothalamus between these groups. The characteristic path length was significantly lower in patients with narcolepsy than in healthy controls (1.698 vs. 2.831, p = 0.001). However, other network measures did not differ between patients with narcolepsy and healthy controls. CONCLUSION: We found that the structural covariance network of the hypothalamus, as assessed from the subunit volumes of hypothalamic regions using a graph theoretical analysis, is different in patients with narcolepsy compared to healthy controls. These findings may contribute to the understanding of the pathogenesis of narcolepsy.

Alterations of the structural covariance network in the hypothalamus of patients with cluster headache.

OBJECTIVE: The hypothalamus is one of the key structures involved in the pathophysiology of cluster headaches. This study aimed to analyze the volume of hypothalamic subunits and structural covariance networks in the hypothalamus of patients with cluster headache. METHODS: We retrospectively enrolled 18 patients with episodic cluster headache and 18 age- and sex-matched healthy controls. We calculated individual structural volumes in ten hypothalamic subunits using three-dimensional T1-weighted imaging and the FreeSurfer program, which conducted an automated segmentation based on deep convolutional neural networks. We also performed an analysis of the structural covariance network in the hypothalamus using graph theory and the BRAPH program. We compared the volumes of hypothalamic subunits and structural covariance networks in the hypothalamus of patients with cluster headache versus those of healthy controls. RESULTS: There were no significant differences in the structural volumes of the whole hypothalamus and hypothalamic subunits between patients with cluster headache and healthy controls. However, patients with cluster headache had significant alterations of the structural covariance network in the hypothalamus compared to that of healthy controls. The network measure of small-worldness index in patients with cluster headache was lower than that in healthy controls (0.844 vs. 0.955, p = 0.004). CONCLUSION: We demonstrated a significant difference in the structural covariance network in the hypothalamus of patients with cluster headache versus those of healthy controls. These findings could be related to the pathogenesis of cluster headache.

A Case of Seizure Revealing Fahr's Syndrome with Primary Hypoparathyroidism.

BACKGROUND Idiopathic basal ganglia calcification, also known as Fahr's disease or Fahr's syndrome, is a rare neurological disorder characterized by abnormal calcified deposits in the basal ganglia. Here, we report a case of Fahr's syndrome with calcification of the basal ganglia due to hypoparathyroidism in a patient with seizures. CASE REPORT A 52-year-old male patient visited our clinic with seizures. Brain computed tomography (CT) showed bilateral symmetrical calcifications in cerebellar white matter, the corpus striatum, the posterior thalami, and the centrum semiovale of both cerebral hemispheres. He had symptoms of hypocalcemia and low parathyroid hormone levels. The patient was diagnosed with Fahr's syndrome due to primary hypoparathyroidism. He underwent calcium supplementation and calcifediol treatment. His symptoms improved, and he was discharged from the hospital. CONCLUSIONS In patients with hypocalcemia accompanied by parathyroid dysfunction, neurological examination and CT should be performed to confirm abnormal intracranial calcification.

Reduction of ipsilateral thalamic volume in temporal lobe epilepsy with hippocampal sclerosis.

The thalamus plays an important role in the modulation of both focal and generalized seizures, but the mechanisms related to seizures may be different among epilepsy syndromes. The aim of this study is to investigate the thalamic atrophy in different epilepsy syndromes. We enrolled a total of 72 patients with epilepsy (22 patients with temporal lobe epilepsy with hippocampal sclerosis, 21 patients with extra-temporal lobe epilepsy, and 29 patients with juvenile myoclonic epilepsy). We analyzed structural volumes of the brain with FreeSurfer 5.1 software, and compared them among subgroups of epilepsy and normal control subjects. Moreover, we quantified correlations between the duration of epilepsy and the structural volumes with age and sex as covariates. The volumes of the ipsilateral hippocampus in temporal lobe epilepsy with hippocampal sclerosis were significantly smaller than those in extra-temporal lobe epilepsy and normal control subjects [analysis of variance (ANOVA), p < 0.001]. Although the volumes of the ipsilateral thalamus were not different from those of normal control subjects, the volumes of the ipsilateral thalamus were negatively correlated with duration of epilepsy in temporal lobe epilepsy with hippocampal sclerosis (r = -0.5, p = 0.02). However, the volumes of interest in extra-temporal lobe epilepsy and juvenile myoclonic epilepsy were not different from those in normal control subjects, and none of these structures were correlated with duration of epilepsy. These findings suggest that the role of the thalamus may be different in thalamo-limbic circuits among epilepsy syndromes.

Juvenile myoclonic epilepsy may be a disorder of cortex rather than thalamus: An effective connectivity analysis.

Although juvenile myoclonic epilepsy has been considered as a disorder of thalamo-cortical circuit, it is not determined the causality relationship between thalamus and cortex. The aim of this study was to evaluate whether juvenile myoclonic epilepsy is a disorder of thalamus or cortex. Twenty-nine patients with juvenile myoclonic epilepsy and 20 normal controls were enrolled in this study. In addition, we included 10 patients with childhood absence epilepsy as a disease control group. Using whole-brain T1-weighted MRIs, we analyzed the volumes of the structures, including hippocampus, thalamus, and total cortex, with FreeSurfer 5.1. We also investigated the effective connectivity among these structures using SPSS Amos 21 based on these volumetric measures. The structural volumes in juvenile myoclonic epilepsy were not different from those in normal controls. There was a statistically significant effective connectivity from the total cortex to the thalamus in the patients with juvenile myoclonic epilepsy. In addition, a significant effective connectivity from the hippocampus to the ipsilateral thalamus was revealed. Unlike the patients with juvenile myoclonic epilepsy, neither the patients with childhood absence epilepsy nor normal controls had a significant effective connectivity from the total cortex to the thalamus or from the thalamus to the cortex. The connectivity of brain in patients with juvenile myoclonic epilepsy could be different from that in patients with childhood absence epilepsy, and the cortex rather than the thalamus might play a critical role in the pathogenesis of juvenile myoclonic epilepsy.

Modification of electrophysiological activity pattern after anterior thalamic deep brain stimulation for intractable epilepsy: report of 3 cases.

OBJECTIVE Thalamic stimulation can provoke electroencephalography (EEG) synchronization or desynchronization, which can help to reduce the occurrence of seizures in intractable epilepsy, though the underlying mechanism is not fully understood. Therefore, the authors investigated changes in EEG electrical activity to better understand the seizure-reducing effects of deep brain stimulation (DBS) in patients with intractable epilepsy. METHODS Electrical activation patterns in the epileptogenic brains of 3 patients were analyzed using classical low-resolution electromagnetic tomography analysis recursively applied (CLARA). Electrical activity recorded during thalamic stimulation was compared with that recorded during the preoperative and postoperative off-stimulation states in patients who underwent anterior thalamic nucleus DBS for intractable epilepsy. RESULTS Interictal EEG was fully synchronized to the ß frequency in the postoperative on-stimulation period. The CLARA showed that electrical activity during preoperative and postoperative off-stimulation states was localized in cortical and subcortical areas, including the insular, middle frontal, mesial temporal, and precentral areas. No electrical activity was localized in deep nucleus structures. However, with CLARA, electrical activity in the postoperative on-stimulation period was localized in the anterior cingulate area, basal ganglia, and midbrain. CONCLUSIONS Anterior thalamic stimulation could spread electrical current to the underlying neuronal networks that connect with the thalamus, which functions as a cortical pacemaker. Consequently, the thalamus could modify electrical activity within these neuronal networks and influence cortical EEG activity by inducing neuronal synchronization between the thalamus and cortical structures.

Cerebellar white matter changes in patients with newly diagnosed partial epilepsy of unknown etiology.

OBJECTIVE: We hypothesize that pre-existing susceptible structures in the brain may be associated with the development of newly diagnosed partial epilepsy of unknown etiology. METHODS: Twenty-two patients with newly diagnosed partial epilepsy of unknown etiology and 36 healthy controls were enrolled in this study. In addition, we included 24 patients with chronic partial epilepsy of unknown etiology as a disease control group. We analyzed whole-brain T1-weighted MRIs using FreeSurfer 5.1. The volumes of the hippocampus, amygdala, thalamus, caudate, putamen, pallidum, brainstem, cerebellar gray and white matter, as well as cerebral gray and white matter were compared between the groups. We also analyzed the changes in brain volumes associated with the chronicity of epilepsy in the patients with chronic epilepsy compared to newly diagnosed epilepsy. RESULTS: The volume of cerebellar white matter in patients with newly diagnosed epilepsy was significantly smaller than that which was observed in the healthy controls (p=0.0001). This finding was also observed in patients with chronic epilepsy (p<0.0001). Cerebral white matter volume was negatively correlated with the duration of epilepsy (r=-0.4, p=0.04). CONCLUSION: These findings support our hypothesis that cerebellar white matter changes may constitute a pre-existing susceptible structure in the brain that is associated with the development of partial epilepsy of unknown etiology. In addition, cerebral white matter was the structure that was the most vulnerable to the progression of epilepsy.