Takefumi Hitomi’s research while affiliated with Kyoto University and other places

Introduction: The aim was to examine the differences in electroencephalography (EEG) findings by visual and automated quantitative analyses between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). Methods: EEG data of 20 patients with AD and 24 with DLB/PDD (12 DLB and 12 PDD) were retrospectively analyzed. Based on the awake EEG, the posterior dominant rhythm frequency and proportion of patients who showed intermittent focal and diffuse slow waves (IDS) were visually and automatically compared between the AD and DLB/PDD groups. Results: On visual analysis, patients with DLB/PDD showed a lower PDR frequency than patients with AD. In patients with PDR <8 Hz and occipital slow waves or patients with PDR <8 Hz and IDS, DLB/PDD was highly suspected (PPV 100%) and AD was unlikely (PPV 0%). On automatic analysis, the findings of the PDR were similar to those on visual analysis. Comparisons between visual and automatic analysis showed an overlap in the focal slow wave commonly detected by both methods in 10 of 44 patients, and concordant presence or absence of IDS in 29 of 43 patients. With respect to PDR <8 Hz and the combination of PDR <8 Hz and IDS, PPV and NPV in DLB/PDD and AD were not different between visual and automatic analysis. Conclusions: As the noninvasive, widely available clinical tool of low expense, visual analysis of EEG findings provided highly sufficient information to delineate different brain dysfunction in AD and DLB/PDD, and automatic EEG analysis could support visual analysis especially about PD.

Objective Degree of indication for epilepsy surgery is determined by taking multiple factors into account. This study aimed to investigate the usefulness of the Specific Consistency Score (SCS), a proposed score for focal epilepsy to rate the indication for epilepsy focal resection. Methods This retrospective cohort study included patients considered for resective epilepsy surgery in Kyoto University Hospital from 2011 to 2022. Plausible epileptic focus was tentatively defined. Cardinal findings were scored based on specificity and consistency with the estimated laterality and lobe. The total points represented SCS. The association between SCS and the following clinical parameters was assessed by univariate and multivariate analysis: (1) probability of undergoing resective epilepsy surgery, (2) good postoperative seizure outcome (Engel I and II or Engel I only), and (3) lobar concordance between the noninvasively estimated focus and intracranial electroencephalographic (EEG) recordings. Results A total of 131 patients were evaluated. Univariate analysis revealed higher SCS in the (1) epilepsy surgery group (8.4 [95% confidence interval (CI) = 7.8–8.9] vs. 4.9 [95% CI = 4.3–5.5] points; p < .001), (2) good postoperative seizure outcome group (Engel I and II; 8.7 [95% CI = 8.2–9.3] vs. 6.4 [95% CI = 4.5–8.3] points; p = .008), and (3) patients whose focus defined by intracranial EEG matched the noninvasively estimated focus (8.3 [95% CI = 7.3–9.2] vs. 5.4 [95% CI = 3.5–7.3] points; p = .004). Multivariate analysis revealed areas under the curve of .843, .825, and .881 for Parameters 1, 2, and 3, respectively. Significance SCS provides a reliable index of good indication for resective epilepsy surgery and can be easily available in many institutions not necessarily specializing in epilepsy.

A 30-year-old man who received infliximab for treatment of Crohn’s disease developed Epstein–Barr virus (EBV) encephalitis, which responded well to therapy; however, he had left lower visual field loss following treatment. The patient noticed peculiar symptoms 9 months after recovery from encephalitis; objects in his view appeared smaller or larger than their actual size (micropsia/macropsia). Moreover, it appeared that objects outside moved faster or slower than their actual speed of movements and moving objects appeared as a series of many consecutive snap shots. His vision was blurred, and he had visual difficulties and a sensation that his body was floating. These symptoms mainly appeared following fatigue and persisted over approximately 10 years. Based on cerebrospinal fluid analysis, brain MRI, N-isopropyl-p-¹²³I-iodoamphetamine with single photon emission computed tomography, fluorodeoxyglucose positron emission tomography, and electroencephalography, we excluded both recurrent encephalitis and focal epileptic seizures. By taking all symptoms and other evaluation findings into account, the patient most likely suffered from “Alice in Wonderland syndrome” which is primarily associated with cortical dysfunction in the right temporo-parieto-occipital area as the consequence of previous acute EBV encephalitis.

The clinical diagnostic criteria for benign adult familial myoclonus epilepsy (BAFME) originally included (1) cortical tremor and infrequent generalized seizures, (2) autosomal dominant inheritance, (3) lack of cognitive decline and other neurological symptoms, (4) Electrophysiological findings of cortical reflex myoclonus, and (5) lack of clear clinical progression (BAFME criteria‐1). It was revised such that (1) included partial seizures, and (3) and (5) may develop among middle‐aged patients (Revised criteria‐2). The Japanese Ministry of Health, Labor and Welfare proposed their criteria, which included the EEG and MRI findings (MHLW criteria‐3). Recently, high‐frequency oscillations, superimposed on the giant somatosensory evoked potential (SEP) P25 component (P25‐HFOs) has been found useful as a biomarker for BAFME diagnosis. We examined the genetic diagnosis of BAFME type 1 and its consistency with the three diagnostic criteria and P25‐HFOs. Twenty‐four Japanese patients, who underwent BAFME genetic testing, were rated using three independent diagnostic criteria and P25‐HFOs. Twenty‐one patients were genetically diagnosed with BAFME type 1. Nineteen patients fulfilled BAFME‐1 (sensitivity 90%), and 21 fulfilled Revised‐2 and MHLW criteria‐3 (sensitivity 100%). We could evaluate P25‐HFOs in 19 of the 21 gene‐positive patients and 17 of the 19 patients showed P25‐HFOs. Three patients with negative genetic testing did not meet any of the criteria and had no P25‐HFOs. The three available clinical diagnostic criteria for BAFME were highly concordant with the positive result for genetic testing.

The association between neurocognitive function (NCF) impairment and brain cortical functional connectivity in glioma patients remains unclear. The correlations between brain oscillatory activity or functional connectivity and NCF measured by the Wechsler Adult Intelligence Scale full-scale intelligence quotient scores (WAIS FSIQ), the Wechsler Memory Scale-revised general memory scores (WMS-R GM), and the Western aphasia battery aphasia quotient scores (WAB AQ) were evaluated in 18 patients with left frontal glioma using resting-state electroencephalography (EEG). Current source density (CSD) and lagged phase synchronization (LPS) were analyzed using exact low-resolution electromagnetic tomography (eLORETA). Although 2 and 2 patients scored in the borderline range of WAIS FSIQ and WMS-R GM, respectively, the mean WAIS FSIQ, WMS-R GM, and WAB AQ values of all patients were within normal limits, and none had aphasia. In the correlation analysis, lower WMS-R GM was associated with a higher LPS value between the right anterior prefrontal cortex and the left superior parietal lobule in the beta1 band (13–20 Hz, R = − 0.802, P = 0.012). These findings suggest that LPS evaluated by scalp EEG is associated with memory function in patients with left frontal glioma and mild NCF disorders.

Identifying the minimal and optimal epileptogenic area to resect and cure is the goal of epilepsy surgery. To achieve this, EEG analysis is recognized as the most direct way to detect epileptogenic lesions from spatiotemporal perspectives. Although ictal direct-current shifts (icDCs; below 1 Hz) and ictal high-frequency oscillations (icHFOs; above 80 Hz) have received increasing attention as good indicators that can add more specific information to the conventionally defined seizure-onset zone, large cohort studies on postoperative outcomes are still lacking. This work aimed to clarify whether this additional information, particularly icDCs which is assumed to reflect extracellular potassium concentration, really improve postoperative outcomes. To assess the usefulness in epilepsy surgery, we collected unique EEG datasets recorded with a longer time constant of 10 sec using an alternate current amplifier. 61 patients [15 with mesial temporal lobe epilepsy and 46 with neocortical epilepsy] who had undergone invasive presurgical evaluation for medically refractory seizures at five institutes in Japan, were retrospectively enrolled in this study. Among intracranially implanted electrodes, the two core electrodes of both icDCs and icHFOs were independently identified by board-certified clinicians based on unified methods. The occurrence patterns, such as their onset time, duration, and amplitude (power) were evaluated to extract the features of both icDCs and icHFOs. Additionally, we examined whether the resection ratio of the core electrodes of icDCs and icHFOs independently correlated with favorable outcomes. A total of 53 patients with 327 seizures were analyzed for wide-band EEG analysis, and 49 patients were analyzed for outcome analysis. icDCs were detected in the seizure-onset zone more frequently than icHFOs among both patients (92% vs. 71%) and seizures (86% vs. 62%). Additionally, icDCs significantly preceded icHFOs in patients exhibiting both biomarkers, and icDCs occurred more frequently in neocortical epilepsy patients than in mesial temporal lobe epilepsy patients. Finally, although a low corresponding rate was observed for icDCs and icHFOs (39%) at the electrode level, complete resection of the core area of icDCs significantly correlated with favorable outcomes, similar to icHFO outcomes. Our results provide a proof of concept that the independent significance of icDCs from icHFOs should be considered as reliable biomarkers to achieve favorable outcomes in epilepsy surgery. Moreover, the different distribution of the core areas of icDCs and icHFOs may provide new insights into the underlying mechanisms of epilepsy, in which not only neurons but also glial cells may be actively involved via extracellular potassium levels.