Publications by authors named "Midori Nakajima"

10 Publications

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Adrenal function during long-term ACTH therapy for patients with developmental and epileptic encephalopathy.

Epilepsia Open 2022 03 14;7(1):194-200. Epub 2021 Dec 14.

Department of Pediatrics, Hokkaido University Hospital, Sapporo, Japan.

Some patients with developmental and epileptic encephalopathy (DEE) respond to adrenocorticotropic hormone (ACTH) therapy but relapse soon after. While long-term ACTH therapy (LT-ACTH) has been attempted for these patients, no previous studies have carefully assessed adrenal function during LT-ACTH. We evaluated the effectiveness of LT-ACTH, as well as adverse effects (AE), including their adrenal function in three DEE patients. Patients underwent a corticotropin-releasing hormone (CRH) stimulation test during LT-ACTH, and those with peak serum cortisol below 15 μg/dL were considered to be at high risk of adrenal insufficiency (AI). Two of three responded, and their life-threatening seizures with postgeneralized electroencephalogram (EEG) suppression decreased. Although no individuals had serious AE, CRH stimulation test revealed relatively weak responses, without reaching normal cortisol peak level (18 μg/dL). Hydrocortisone replacement during stress was prepared in a case with lower cortisol peak than our cutoff level. LT-ACTH could be a promising treatment option for cases of DEE that relapse soon after effective ACTH treatment. The longer duration and larger cumulative dosage in LT-ACTH than in conventional ACTH could increase the relative risk of AI. Careful evaluation with pediatric endocrinologists, including hormonal stimulation tests, might be useful for continuing this treatment safely.
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March 2022

Reinterpretation of magnetic resonance imaging findings with magnetoencephalography can improve the accuracy of detecting epileptogenic cortical lesions.

Epilepsy Behav 2021 01 13;114(Pt A):107516. Epub 2020 Dec 13.

Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan. Electronic address:

Objective: This study examined whether the application of magnetoencephalography (MEG) to interpret magnetic resonance imaging (MRI) findings can aid the diagnosis of intractable epilepsy caused by organic brain lesions.

Methods: This study included 51 patients with epilepsy who had MEG clusters but whose initial MRI findings were interpreted as being negative for organic lesions. Three board-certified radiologists reinterpreted the MRI findings, utilizing the MEG findings as a guide. The degree to which the reinterpretation of the imaging results identified an organic lesion was rated on a 5-point scale.

Results: Reinterpretation of the MRI data with MEG guidance helped detect an abnormality by at least one radiologist in 18 of the 51 patients (35.2%) with symptomatic localization-related epilepsy. A surgery was performed in 7 of the 51 patients, and histopathological analysis results identified focal cortical dysplasia in 5 patients (Ia: 1, IIa: 2, unknown: 2), hippocampal sclerosis in 1 patient, and dysplastic neurons/gliosis in 1 patient.

Conclusions: The results of this study highlight the potential diagnostic applications of MEG to detect organic epileptogenic lesions, particularly when radiological visualization is difficult with MRI alone.
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January 2021

Detection of epileptogenic focus using advanced dynamic statistical parametric mapping with magnetoencephalography in a patient with MRI-negative focal cortical dysplasia type IIB.

J Neurosurg Pediatr 2019 Oct 11:1-5. Epub 2019 Oct 11.

1Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.

Advanced dynamic statistical parametric mapping (AdSPM) with magnetoencephalography (MEG) was used to identify MRI-negative epileptogenic lesions in this report. A 15-year-old girl had MRI-negative and pharmacology-resistant focal-onset epilepsy. She experienced two types of seizures. Type I consisted of her arousal from sleep, staring, and a forced head-turning movement to the left, followed by secondary generalization. Type II began with an aura of dizziness followed by staring and postictal headache with fatigue. Scalp video-electroencephalography (EEG) captured two type I seizures originating from the right frontocentral region. MEG showed scattered dipoles over the right frontal region. AdSPM identified the spike source at the bottom of the right inferior frontal sulcus. Intracranial video-EEG captured one type I seizure, which originated from the depth electrode at the bottom of the sulcus and correlated with the AdSPM spike source. Accordingly, the patient underwent resection of the middle and inferior frontal gyri, including the AdSPM-identified spike source. Histopathological examination revealed that the patient had focal cortical dysplasia type IIB. To date, the patient has been seizure free for 2 years while receiving topiramate treatment. This is the first preliminary report to identify MRI-negative epilepsy using AdSPM. Further investigation of AdSPM would be valuable for cases of MRI-negative focal epilepsy.
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October 2019

Advanced dynamic statistical parametric mapping with MEG in localizing epileptogenicity of the bottom of sulcus dysplasia.

Clin Neurophysiol 2018 06 30;129(6):1182-1191. Epub 2018 Mar 30.

Division of Neurology, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address:

Objective: To investigate whether advanced dynamic statistical parametric mapping (AdSPM) using magnetoencephalography (MEG) can better localize focal cortical dysplasia at bottom of sulcus (FCDB).

Methods: We analyzed 15 children with diagnosis of FCDB in surgical specimen and 3 T MRI by using MEG. Using AdSPM, we analyzed a ±50 ms epoch relative to each single moving dipole (SMD) and applied summation technique to estimate the source activity. The most active area in AdSPM was defined as the location of AdSPM spike source. We compared spatial congruence between MRI-visible FCDB and (1) dipole cluster in SMD method; and (2) AdSPM spike source.

Results: AdSPM localized FCDB in 12 (80%) of 15 children whereas dipole cluster localized six (40%). AdSPM spike source was concordant within seizure onset zone in nine (82%) of 11 children with intracranial video EEG. Eleven children with resective surgery achieved seizure freedom with follow-up period of 1.9 ± 1.5 years. Ten (91%) of them had an AdSPM spike source in the resection area.

Conclusion: AdSPM can noninvasively and neurophysiologically localize epileptogenic FCDB, whether it overlaps with the dipole cluster or not.

Significance: This is the first study to localize epileptogenic FCDB using MEG.
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June 2018

Promoting Role Clarity for Health Professional Students Participating in an Interprofessional Behavior Change Counseling Workshop.

J Allied Health 2017 ;46(2):e35-e37

School of Nursing, University of California San Francisco, 2 Koret Way, Box 0608, San Francisco, CA 94143-2218, USA. Tel 415-502-6615, fax 415-476-6042.

Interprofessional role clarity is linked to improving team collaboration and clinical care, yet there are barriers to implementing interprofessional curricula targeted to learner achievement of this competency. A behavior change counseling skills workshop for first-year advanced practice nursing (APN) (n=153) and third-year pharmacy (PharmD) (n=127) students was modified to include learning experiences for enhancing interprofessional role clarity. Students rated the importance of each profession's contributions in nine patient care activities before and after the workshop. APN and PharmD students increased their ratings of the merit of each profession in counseling patients in several care activities. Findings suggest that providing interprofessional students an opportunity to learn core skills together can also foster an understanding of each other's professional roles and responsibilities.
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April 2018

Increased subcortical oligodendroglia-like cells in pharmacoresistant focal epilepsy in children correlate with extensive epileptogenic zones.

Epilepsia 2016 12 8;57(12):2031-2038. Epub 2016 Nov 8.

Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Objective: Cortical resections in epilepsy surgery tend to involve multiple lobes in children, compared to adults, partly due to underlying pathology. Oligodendroglia-like cells (OLCs) have been observed in surgical specimens from children with pharmacoresistant epilepsy. We hypothesize that OLCs recruit multiple-lobe epileptogenic zones in pediatric pharmacoresistant focal epilepsy.

Methods: We examined the surgical specimens from 30 children who underwent epilepsy surgery (1.8- to 16.9-years-old; mean age 9.7 years). Immunohistochemical assays of OLCs were performed using Olig2, which is a marker of OLC. OLC populations in three sites (gray matter, gray-white matter junction, and white matter) were counted. We also performed immunohistochemical staining with neuronal nuclear antigen (NeuN) and glial fibrillary acidic protein (GFAP) for neuronal and astroglial markers, respectively. NeuN- and GFAP-positive cells were distinguished from OLCs. OLC results were compared with seizure types, scalp and intracranial video-electroencephalography (EEG), magnetic resonance imaging (MRI), surgical resection area, histopathologic diagnosis, and seizure outcome.

Results: Histopathologic diagnosis consisted of 14 cases of focal cortical dysplasia (FCD; type I; 4, type II; 9, type III; one); 6 cases of oligodendrogliosis; 6 cases of astrocytic gliosis; 2 cases of hyaline protoplasmic astrocytopathy; and 2 cases of tuberous sclerosis. Fifteen children (50%) underwent multiple-lobe resections after intracranial video-EEG. There was a positive correlation between the number of resected electrodes and the OLC population in the white matter (correlation coefficient 0.581, p = 0.001) and at the gray-white matter junction- (correlation coefficient 0.426, p = 0.027). OLC populations in both areas were increased significantly in nine children with epileptic spasms (ES) (gray-white matter junction [p = 0.021] and white matter [p = 0.025]), and nine nonfocal ictal scalp EEG findings (gray-white matter junction [p = 0.04] and white matter [p = 0.042]). The OLC population in white matter was significantly increased in children with 11 nonfocal interictal scalp EEG findings (p = 0.01), with 15 multiple-lobe resections (p = 0.028).

Significance: Pharmacoresistant epilepsy in children with increased OLCs presented with nonfocal epileptiform discharges on scalp EEG and ES, and they required multiple-lobe resections. We found increased populations of subcortical OLCs in the extensive epileptogenic zone.
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December 2016

Magnetoencephalography spike sources interrelate the extensive epileptogenic zone of tuberous sclerosis complex.

Epilepsy Res 2016 11 6;127:302-310. Epub 2016 Sep 6.

Division of Neurology, The Hospital for Sick Children, PO Box M5G, 1X8, Toronto, Ontario, Canada.

Objective: We hypothesized that the extensive epileptic network in patients with tuberous sclerosis complex (TSC) manifests as clustered and scattered distributions of magnetoencephalography spike sources (MEGSS).

Methods: We retrospectively analyzed pre-surgical MEG in 15 patients with TSC. We performed single moving dipole analysis to localize and classify clustered and scattered MEGSS. We compared the number of electrodes within the resected area (RA) and the proportions of clustered and scattered MEGSS within RA with the seizure outcome.

Results: The number of electrodes within RA ranged from 29 to 83 (mean=51). The MEGSS were distributed over multiple lobes (3-8; mean=5.9) and bilaterally in 14 patients. Clusters of MEGSS ranged from 1 to 4 (mean=1.4). The number of MEGSS ranged in total from 28 to 139 (mean=70); in the clusters, 10-128 (mean=49); and in the scatters, 0-45 (mean=21). Four patients achieved an Engel class I surgical outcome, four, a class II outcome; five, a class III outcome; and two, a class IV outcome. The proportion of MEGSS ranged in total from 0 to 92% (mean=57%) within RA; 0-100% (mean=67%) in the resection hemisphere; 0-100% (mean=63%) in the clusters; and 0-81% (mean=28%) in the scatters. Univariate ordinal logistic regression analyses showed that the proportion of scattered MEGSS within RA (p=0.049) significantly correlated with seizure outcomes. Multivariate analyses using three covariates (number of electrodes, proportions of clustered and scattered MEGSS within RA) showed that only the proportion of scattered MEGSS within RA significantly correlated with seizure outcomes (p=0.016).

Significance: MEG data showed a wide distribution of multilobar MEGSS in patients with TSC. The seizure outcome was not related to the clustered MEGSS within RA, since the grids were essentially planned to cover and resect the clustered MEGSS surrounding tubers. The maximal possible resection of scattered MEGSS correlated with improved seizure outcome in TSC. Some parts of the epileptogenic zone disrupted by multiple tubers did not have a sufficiently large area to produce clustered MEGSS. Although the wide distribution of scattered MEGSS is not interpreted as epileptogenic, they might be interrelated with clustered MEGSS to project a complex epilepsy network and be part of the extensive epileptogenic zones found in TSC.
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November 2016

Remote MEG dipoles in focal cortical dysplasia at bottom of sulcus.

Epilepsia 2016 07 2;57(7):1169-78. Epub 2016 Jun 2.

Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Objective: To investigate whether the magnetoencephalography (MEG) single moving dipole (SMD) method could delineate the epileptic zone of focal cortical dysplasia (FCD) at the bottom of sulcus (FCDB).

Methods: We retrospectively analyzed 17 children (11 male; mean age 8.8 years, range 3-17 years) with FCD type II who underwent epilepsy surgery. We compared spatial congruence between the following: (1) MEG cluster and FCDB and (2) MEG cluster and FCD at the brain surface (FCDS). We measured the volume and depth of magnetic resonance imaging (MRI)-visible lesions to investigate whether they affect spatial congruence between MEG cluster and MRI-visible lesion.

Results: Eight children had FCDB and the other nine children had FCDS. The volume of MRI-visible lesions for FCDB ranged from 1,632 to 4,707 mm(3) (mean ± standard deviation [SD] 3,095 ± 1,211 mm(3) ). The depth of FCDB ranged from 19 to 33 mm (mean ± SD 26 ± 4 mm). The volume of MRI-visible lesion for FCDS ranged from 2,375 to 57,331 mm(3) (15,470 ± 18,455 mm(3) ). There was a tendency for a smaller volume of MRI-visible lesion for FCDB, relative to FCDS(p = 0.079). In FCDB, six children showed clusters of MEG dipoles and two children showed scattered MEG dipoles for interictal spikes. The spatial congruence between the MEG result and FCDB was partially overlapping in four children and discordant in another four children. In FCDS, eight children had MEG cluster and one child had MEG scatter alone. The spatial congruence between MEG result and FCDS was overlapping in eight of nine children (fully two; partially six) and discordant in one of nine children. Fifteen children (88%; FCDB eight; FCDS seven) became seizure-free after resective surgery. MEG spike dipole resection ratio in the cluster ranged from 4-100% (mean 67%) in 6 FCDB and 23-99% (mean 77%) in 8 FCDS.

Significance: The SMD method may drift MEG spike dipoles for FCDB. Lesionectomy can control seizures for four of eight patients in FCDB despite the remote MEG dipoles. The FCDB or FCDS partially overlapped with MEG cluster may have an extending/invisible epileptogenic zone consecutive to the MRI-visible lesion.
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July 2016

The presence of short and sharp MEG spikes implies focal cortical dysplasia.

Epilepsy Res 2015 Aug 12;114:141-6. Epub 2015 May 12.

Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo, Japan. Electronic address:

Purpose: This study focused on the characteristic needle-like epileptic spikes of short duration and steep shape seen on magnetoencephalography (MEG) in patients diagnosed with focal cortical dysplasia (FCD) morphologically. We aimed to validate the analysis of MEG spike morphology as a noninvasive method of identifying the presence and location of FCD.

Methods: MEG was collected by 204-channel helmet-shaped gradiometers. We analyzed MEG spike sources for 282 patients with symptomatic localization-related epilepsy. MEG showed clustered equivalent current dipoles when superimposed on their three-dimensional-magnetic resonance images (MRI) in 85 patients. Fifty-seven patients were excluded from our study, because they had destructive brain lesions or an insufficient number of spikes for statistical analysis. Twenty-eight patients (18 males, 10 females; aged 1-34 years) were finally matched to our inclusion criteria, and were categorized into three groups: FCD (7 patients), non-FCD (10 patients), and non-lesion (11 patients), based on the MRI findings. We measured the duration, amplitude, and tilt manually for at least 15 spikes per patient, and compared the three groups using a one-way analysis of variance, followed by the Tukey test when statistically significant (p < 0.05). In 17 patients with visible MRI lesions, we investigated the correlation between the depth of the lesion and the tilt using the Pearson product moment correlation.

Results: The average spike duration was significantly shorter in the FCD and non-lesion groups than in the non-FCD group (p < 0.05). The average amplitude was not significantly different between the three groups. The average spike tilt was significantly steeper in the FCD group than in the non-FCD group (p = 0.0058). There was no significant difference between FCD and non-lesion patients in both duration and tilt. Our additional study revealed a significant negative correlation between the depth of the lesion and the average tilt (p = 0.0009).

Significance: MEG epileptiform discharges of short duration and steep tilt characterize FCD, especially when located at the superficial neocortical gyrus. We speculate that this particular spike morphology results from the intrinsic epileptogenicity of FCD. Morphological analysis of MEG spikes can evaluate the etiology of epileptogenic lesions and detect a strong, localized epileptogenic focus such as that typically observed in FCD.
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August 2015