Brain network reconstruction of abnormal functional connectivity in Lennox-Gastaut syndrome according to drug responsiveness: A retrospective study.

OBJECTIVE: Functional network effects of resective or palliative epilepsy surgery in Lennox-Gastaut syndrome (LGS) patients are different according to the seizure outcome. This study aimed to clarify whether the response to antiseizure medications (ASM) can affect to alteration of brain network connectivity. METHODS: In this retrospective study, 37 patients with LGS who underwent 1st electroencephalography (EEG) and 40 healthy controls were enrolled. Among them, 24 LGS patients had follow-up EEG data and were classified as drug responders and non-responders according to the ASM response. Graphical theoretical analysis was used to assess functional connectivity using resting-state EEG. RESULTS: The 1st EEG showed a decreased radius in patients with LGS compared with that in healthy controls (3.987 vs. 4.279, P = 0.003). Follow-up EEG data of patients with LGS revealed significant differences in functional connectivity depending on the ASM response. On follow-up EEG, non-responders (n = 11) demonstrated significant increases in global network parameters, whereas responders (n = 13) showed no significant difference in functional connectivity compared with healthy controls. CONCLUSIONS: The functional connectivity patterns in patients with LGS differed from those in healthy controls. Functional connectivity in drug-responsive patients with LGS tended to preserve the network of brain connections in a pattern similar to that in healthy controls, whereas non-responders showed more disrupted functional connectivity.

Structural brain network changes in patients with neurofibromatosis type 1: A retrospective study.

We investigated the changes in structural connectivity (using diffusion tensor imaging [DTI]) and the structural covariance network based on structural volume using graph theory in patients with neurofibromatosis type 1 (NF1) compared to a healthy control group. We included 14 patients with NF1, according to international consensus recommendations, and 16 healthy individuals formed the control group. This was retrospectively observational study followed STROBE guideline. Both groups underwent brain magnetic resonance imaging including DTI and 3-dimensional T1-weighted imaging. We analyzed structural connectivity using DTI and Diffusion Spectrum Imaging Studio software and evaluated the structural covariance network based on the structural volumes using FreeSurfer and Brain Analysis Using Graph Theory software. There were no differences in the global structural connectivity between the 2 groups, but several brain regions showed significant differences in local structural connectivity. Additionally, there were differences between the global structural covariance networks. The characteristic path length was longer and the small-worldness index was lower in patients with NF1. Furthermore, several regions showed significant differences in the local structural covariance networks. We observed changes in structural connectivity and covariance networks in patients with NF1 compared to a healthy control group. We found that global structural efficiency is decreased in the brains of patients with NF1, and widespread changes in the local structural network were found. These results suggest that NF1 is a brain network disease, and our study provides direction for further research to elucidate the biological processes of NF1.

The effects of the dialysis on the white matter tracts in patients with end-stage renal disease using differential tractography study.

This study aimed to determine whether white matter tracts correlate with kidney function using correlation tractography, and to investigate the effects of dialysis on white matter tracts in patients with end-stage renal disease (ESRD) using differential tractography. Ten patients with ESRD, who had a glomerular filtration rate of < 15 mL/min/1.73 m2, were enrolled in this prospective study. Diffusion tensor imaging (DTI) was performed both before and after dialysis. We discovered that white matter tracts correlated with the estimated glomerular filtration rate based on pre- and post-dialysis DTI using correlation tractography and investigated the differences in the white matter tracts between pre- and post-dialysis DTI in patients with ESRD using differential tractography. Correlation tractography revealed no quantitative anisotropy of the white matter tracts that correlated with the estimated glomerular filtration rate in pre- and post-dialysis patients with ESRD. Differential tractography revealed significant differences in several white matter tracts, particularly the cingulum, thalamic radiation, corpus callosum, and superior longitudinal fasciculus, between pre- and post-dialysis DTI, which revealed increased diffusion density after dialysis. We demonstrated the significant effects of dialysis on several white matter tracts in patients with ESRD using differential tractography, which showed increased diffusion density after dialysis. In this study, we confirmed the effects of dialysis on brain structure, especially white matter tracts.

Metabolic network is related to surgical outcome in temporal lobe epilepsy with hippocampal sclerosis: A brain FDG-PET study.

BACKGROUND AND PURPOSE: The aim of this study was to investigate differences in metabolic networks based on preoperative fluorodeoxyglucose (FDG)-positron emission tomography (PET) in temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) between patients with complete seizure-free (SF) and those with noncomplete seizure-free (non-SF) after anterior temporal lobectomy. METHODS: This study was retrospectively performed at a tertiary hospital. We recruited pathologically confirmed 75 TLE patients with HS who underwent preoperative FDG-PET. All patients underwent a standard anterior temporal lobectomy. The surgical outcome was evaluated at least 12 months after surgery, and we divided the subjects into patients with SF (International League Against Epilepsy [ILAE] class I) and those with non-SF (ILAE class II-VI). We evaluated the metabolic network using graph theoretical analysis based on FDG-PET. We investigated the differences in network measures between the two groups. RESULTS: Of the 75 TLE patients with HS, 32 patients (42.6%) had SF, whereas 43 patients (57.3%) had non-SF. There were significant differences in global metabolic networks according to surgical outcomes. The patients with SF had a lower assortative coefficient than those with non-SF (-0.020 vs. -0.009, p = .044). We also found widespread regional differences in local metabolic networks according to surgical outcomes. CONCLUSION: Our study demonstrates significant differences in preoperative metabolic networks based on FDG-PET in TLE patients with HS according to surgical outcomes. This work introduces a metabolic network based on FDG-PET and can be used as a potential tool for predicting surgical outcome in TLE patients with HS.

Intrinsic Thalamic Network in Temporal Lobe Epilepsy With Hippocampal Sclerosis According to Surgical Outcomes.

Background: The aim of this study was to identify the differences of intrinsic amygdala, hippocampal, or thalamic networks according to surgical outcomes in temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (HS). Methods: We enrolled 69 pathologically confirmed TLE patients with HS. All patients had pre-operative three-dimensional T1-weighted MRI using a 3.0 T scanner. We obtained the structural volumes of the amygdala nuclei, hippocampal subfields, and thalamic nuclei. Then, we investigated the intrinsic networks based on volumes of these structures using structural covariance and graph theoretical analysis. Results: Of the 69 TLE patients with HS, 21 patients (42.1%) had poor surgical outcomes, whereas 40 patients (57.9%) had good surgical outcomes. The volumes in the amygdala nuclei, hippocampal subfields, and thalamic nuclei were not different according to surgical outcome. In addition, the intrinsic amygdala and hippocampal networks were not different between the patients with poor and good surgical outcomes. However, there was a significant difference in the intrinsic thalamic network in the ipsilateral hemisphere between them. The eccentricity and small-worldness index were significantly increased, whereas the characteristic path length was decreased in the patients with poor surgical outcomes compared to those with good surgical outcomes. Conclusion: We successfully demonstrated significant differences in the intrinsic thalamic network in the ipsilateral hemisphere between TLE patients with HS with poor and good surgical outcomes. This result suggests that the pre-operative intrinsic thalamic network can be related with surgical outcomes in TLE patients with HS.

Alterations of structural connectivity and structural co-variance network in focal cortical dysplasia.

BACKGROUND: The aim of this study was to investigate alterations in structural connectivity and structural co-variance network in patients with focal cortical dysplasia (FCD). METHODS: We enrolled 37 patients with FCD and 35 healthy controls. All subjects underwent brain MRI with the same scanner and with the same protocol, which included diffusion tensor imaging (DTI) and T1-weighted imaging. We analyzed the structural connectivity based on DTI, and structural co-variance network based on the structural volume with T1-weighted imaging. We created a connectivity matrix and obtained network measures from the matrix using the graph theory. We tested the difference in network measure between patients with FCD and healthy controls. RESULTS: In the structural connectivity analysis, we found that the local efficiency in patients with FCD was significantly lower than in healthy controls (2.390 vs. 2.578, p = 0.031). Structural co-variance network analysis revealed that the mean clustering coefficient, global efficiency, local efficiency, and transitivity were significantly decreased in patients with FCD compared to those in healthy controls (0.527 vs. 0.635, p = 0.036; 0.545 vs. 0.648, p = 0.026; 2.699 vs. 3.801, p = 0.019; 0.791 vs. 0.954, p = 0.026, respectively). CONCLUSIONS: We demonstrate that there are significant alterations in structural connectivity, based on DTI, and structural co-variance network, based on the structural volume, in patients with FCD compared to healthy controls. These findings suggest that focal lesions with FCD could affect the whole-brain network and that FCD is a network disease.

Artificial intelligence with kidney disease: A scoping review with bibliometric analysis, PRISMA-ScR.

BACKGROUND: Artificial intelligence (AI) has had a significant impact on our lives and plays many roles in various fields. By analyzing the past 30 years of AI trends in the field of nephrology, using a bibliography, we wanted to know the areas of interest and future direction of AI in research related to the kidney. METHODS: Using the Institute for Scientific Information Web of Knowledge database, we searched for articles published from 1990 to 2019 in January 2020 using the keywords AI; deep learning; machine learning; and kidney (or renal). The selected articles were reviewed manually at the points of citation analysis. RESULTS: From 218 related articles, we selected the top fifty with 1188 citations in total. The most-cited article was cited 84 times and the least-cited one was cited 12 times. These articles were published in 40 journals. Expert Systems with Applications (three articles) and Kidney International (three articles) were the most cited journals. Forty articles were published in the 2010s, and seven articles were published in the 2000s. The top-fifty most cited articles originated from 17 countries; the USA contributed 16 articles, followed by Turkey with four articles. The main topics in the top fifty consisted of tumors (11), acute kidney injury (10), dialysis-related (5), kidney-transplant related (4), nephrotoxicity (4), glomerular disease (4), chronic kidney disease (3), polycystic kidney disease (2), kidney stone (2), kidney image (2), renal pathology (2), and glomerular filtration rate measure (1). CONCLUSIONS: After 2010, the interest in AI and its achievements increased enormously. To date, AIs have been investigated using data that are relatively easy to access, for example, radiologic images and laboratory results in the fields of tumor and acute kidney injury. In the near future, a deeper and wider range of information, such as genetic and personalized database, will help enrich nephrology fields with AI technology.

Alterations of gray matter volumes and connectivity in patients with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an inherited genetic disorder caused by mutations in the TSC1 or TSC2 genes, encoding hamartin and tuberin. We aimed to evaluate structural volumes and connectivity of patients with TSC compared to those of healthy subjects. We consecutively enrolled 13 patients with a diagnosis of TSC and 15 age- and sex-matched healthy control subjects. Subjects underwent three-dimensional volumetric T1-weighted imaging, suitable for a quantitative analysis. Structural volumes were investigated using FreeSurfer image analysis software, and structural connectivity was calculated from a connectivity matrix, which was estimated from the correlation analysis of structural volumes using the Brain Analysis using Graph Theory software package. Differences in structural volumes and connectivity were analyzed between patients with TSC and healthy subjects. There were no differences of cortical volumes between the patients with TSC and healthy controls. However, we found decreased gray matter volumes in several subcortical regions in the patients with TSC compared to those in healthy controls, specifically in the putamen (0.3212 vs. 0.3841%, p = 0.001), even after multiple corrections. Regarding global structural connectivity, the small-worldness index was significantly decreased in patients with TSC compared to that in healthy controls (0.907 vs. 0.977, p = 0.049). This study revealed structural volumes and connectivity in patients with TSC that are significantly different from those in healthy controls. These alterations have implications for the pathogenesis of TSC.

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.

Top 100 cited articles on epilepsy and status epilepticus: A bibliometric analysis.

The purpose of this study is to identify the top 100-cited articles dedicated to epilepsy and status epilepticus published in journals from January, 1950 through February, 2016 that have made key contributions in the field. We performed a search of journals and selected the top 100-cited articles on epilepsy and status epilepticus, respectively, by utilizing the Institute for Scientific Information database available under the banner of the Web of Science. The top-cited articles on epilepsy and status epilepticus were all published in 24 journals, respectively. In both fields of epilepsy and status epilepticus, the most frequently cited journal was Epilepsia (26 articles on epilepsy and 19 articles on status epilepticus). The 100 most-cited articles in the field of both epilepsy and status epilepticus mainly originated from institutions in the United States of America. The articles on epilepsy included 25 laboratory studies, 15 pharmacotherapy studies, 13 general review studies, 12 surgery studies, 11 neuroimaging studies, eight epidemiology studies, eight neuropsychiatry studies, six genetic studies, and two electrophysiology studies, whereas 41 laboratory studies, 21 epidemiology studies, 16 pharmacotherapy studies, nine electrophysiology studies, nine general review studies, and four neuroimaging studies were included in the field of status epilepticus. We demonstrate that neuroimaging, genetics, and surgery are emerging topics in the field of epilepsy over the past decades. Moreover, we found that the majority of top-cited articles on epilepsy and status epilepticus originated from institutions in the United States of America and most were published in Epilepsia.

Polyomavirus Nephropathy in Native Kidneys of an Immunocompetent Individual.

BACKGROUND Polyomavirus nephropathy has emerged as an important cause of graft loss in kidney transplant recipients. Polyomavirus rarely affects the native kidneys of an immunocompetent individual. Until now, polyomavirus nephropathy in native kidneys of an immunocompetent individual has not been reported, as far as we know. CASE REPORT A 34-year-old man was transferred from a local clinic to be evaluated for the cause of azotemia. Serum creatinine was 2.85 mg/dL. We performed renal biopsy to identify the cause of azotemia. The result of kidney biopsy was consisted to polyomavirus nephropathy. CONCLUSIONS We report the first case of polyomavirus nephropathy in native kidneys of an immunocompetent individual.

Coombs negative autoimmune hemolytic anemia in Crohn's disease.

BACKGROUND: Anemia is a common, important extraintestinal complication of Crohn's disease. The main types of anemia in patients with Crohn's disease are iron deficiency anemia and anemia of chronic disease. Although patients with Crohn's disease may experience various type of anemia, autoimmune hemolytic anemia (AIHA) in patients with Crohn's disease, especially Coombs-negative AIHA, is very rare. CASE REPORT: A 41-year-old woman with Crohn's disease presented to our emergency room (ER) with dark urine, dizziness, and shortness of breath. The activity of Crohn's disease had been controlled, with Crohn's disease activity index (CDAI) score below 100 point. On physical examination, the patient had pale conjunctivae and mildly icteric sclerae. Serum bilirubin was raised at 3.1 mg/dL, lactate dehydrogenase (LDH) level was 1418 U/L and the haptoglobin level was <3 mg/dL. Results of direct and the indirect Coombs tests were all negative. We then measured the RBC-IgG to evaluate the possibility of Coombs-negative AIHA. The result revealed that RBC-IgG level was 352 IgG molecules/cell, with the cut-off value at 78.5 IgG molecules/cell. CONCLUSIONS: We report a case of Coombs-negative AIHA in a patient with Crohn's disease with chronic anemia, diagnosed by red blood cell-bound immunoglobulin G (RBC-IgG) and treated with steroids therapy.

Response to antiepileptic drugs in partial epilepsy with structural lesions on MRI.

OBJECTIVE: Although partial epilepsy with structural lesions on MRI (lesional epilepsy) is less favorably responsive to antiepileptics than those without structural lesions on MRI, the response to antiepileptics in lesional epilepsy is a heterogeneous condition. There is growing evidence that the extent of epileptic network beyond the visible lesion on MRI may be related with the response to antiepileptics. The aims of this study are to clarify whether (1) the epilepsy network beyond the visible lesion on MRI, or (2) duration of lesional epilepsy on MRI are related with the response to antiepileptics or not. METHODS: The inclusion criteria for this study were (1) having structural lesions on MRI, (2) taking antiepileptics for at least 1 year, and (3) age ≥13 years old. The definition for drug-resistance epilepsy was a failure of adequate trials of two tolerated, appropriately chosen and used antiepileptics to achieve sustained seizure freedom. The duration was defined as the interval between the start of antiepileptics and the last follow-up. We defined the lesion-plus group as the structural lesions on MRI that has wider spread of epileptic network beyond the visible lesions on MRI, such as hippocampal sclerosis and malformation of cortical development. Lesion-restriction group was defined as the epileptic network being believed to be limited on the structural lesions. RESULTS: We found 234 patients with lesional epilepsy, who met the inclusion criteria. Of these 234 patients, 115 patients were male (49%) and 119 patients were female (51%). The median age was 22 years old (range 13-78 years old) and the median duration was 131 months (range 12-516 months). Forty percent (90/234 patients) were intractable to antiepileptics. Of the structural lesions on MRI, hippocampal sclerosis was most frequent (N=90). Other structural lesions were malformation of cortical development (N=38), cerebromalatic lesions related with trauma (N=34), tumor (N=19), cystic lesion (N=15), cerebral infarction (N=11), vascular malformation (N=10), and other miscellaneous lesion (N=24). Lesion-plus group had significantly higher drug-resistance epilepsy than cystic lesions on MRI (60/128 vs. 2/15, p=0.013 by Fisher's exact test). There was a tendency of having more drug-resistance epilepsy in the lesion-plus group than the lesion-restriction group (56/121 vs. 30/89, p=0.09 by Chi-square test). The median duration in drug-resistance epilepsy was significantly longer than that of medically controlled epilepsy (178 months (range 23-516 months) vs 102 months (range 12-479 months), p<0.0001 by Mann-Whitney test). In addition, duration was only the significant variable associated with drug-resistance epilepsy in lesional epilepsy by multiple logistic regression analysis (p=0.02 for overall model fit). CONCLUSION: In lesional epilepsy, hippocampal sclerosis and malformation of cortical development are more intractable to antiepileptics, reflecting wider epileptic network beyond the visible lesion. In addition, the response to antiepileptics may be expected to decrease when the duration is prolonged.