Kazuyori Yagyu

Dried Umbilical Cords in the Retrospective Diagnosis of Congenital Cytomegalovirus Infection as a Cause of Developmental Delays

To clarify the impact of congenital cytomegalovirus (CMV) infection on developmental disabilities, 20 children with disabilities of unknown cause were analyzed. Five children were CMV positive and had no clinical manifestations at birth. Intracranial calcification was observed in 4 cases. Thus, congenital CMV infection is a significant cause of developmental disabilities.

The applications of time-frequency analyses to ictal magnetoencephalography in neocortical epilepsy

PURPOSE Ictal magenetoencephalographic (MEG) discharges convey significant information about ictal onset and propagation, but there is no established method for analyzing ictal MEG. This study sought to clarify the usefulness of time-frequency analyses using short-time Fourier transform (STFT) for ictal onset and propagation of ictal MEG activity in patients with neocortical epilepsy. METHODS Four ictal MEG discharges in two patients with perirolandic epilepsy and one with frontal lobe epilepsy (FLE) were evaluated by time-frequency analyses using STFT. Prominent oscillation bands were collected manually and the magnitudes of those specific bands were superimposed on individual 3D-magnetic resonance images. RESULTS STFT showed specific rhythmic activities from alpha to beta bands at the magnetological onset in all four ictal MEG records. Those activities were located at the vicinity of interictal spike sources, as estimated by the single dipole method (SDM), and two of the four ictal rhythmic activities promptly propagated to ipsilateral or bilateral cerebral cortices. The patients with FLE and perirolandic epilepsy underwent frontal lobectomy and resection of primary motor area, respectively including the origin of high-magnitude areas of a specific band indicated by STFT, and have been seizure free after the surgery. CONCLUSIONS STFT for ictal MEG discharges readily demonstrated the ictal onset and propagation. These data were important for decisions on surgical procedure and extent of resection. Ictal MEG analyses using STFT could provide a powerful tool for noninvasive evaluation of ictal onset zone.

Direct correlation between the facial nerve nucleus and hemifacial seizures associated with a gangliocytoma of the floor of the fourth ventricle: A case report

A dysplastic neuronal lesion of the floor of the fourth ventricle (DNFFV) causes hemifacial seizures (HFS) from early infancy. However, it is still controversial whether HFS is generated by the facial nerve nucleus or cerebellar cortex. In this study, we confirm a direct correlation between the rhythmic activities in the DNFFV and HFS using intraoperative electroencephalography (EEG) and electromyography (EMG) monitoring. Our results support the theory that a DNFFV provokes ipsilateral HFS via the facial nerve nucleus.

Molecular genetic analysis of 30 families with Joubert syndrome

Joubert syndrome (JS) is rare recessive disorders characterized by the combination of hypoplasia/aplasia of the cerebellar vermis, thickened and elongated superior cerebellar peduncles, and a deep interpeduncular fossa which is defined by neuroimaging and is termed the ‘molar tooth sign’. JS is genetically highly heterogeneous, with at least 29 disease genes being involved. To further understand the genetic causes of JS, we performed whole‐exome sequencing in 24 newly recruited JS families. Together with six previously reported families, we identified causative mutations in 25 out of 30 (24 + 6) families (83.3%). We identified eight mutated genes in 27 (21 + 6) Japanese families, TMEM67 (7/27, 25.9%) and CEP290 (6/27, 22.2%) were the most commonly mutated. Interestingly, 9 of 12 CEP290 disease alleles were c.6012‐12T>A (75.0%), an allele that has not been reported in non‐Japanese populations. Therefore c.6012‐12T>A is a common allele in the Japanese population. Importantly, one Japanese and one Omani families carried compound biallelic mutations in two distinct genes (TMEM67/RPGRIP1L and TMEM138/BBS1, respectively). BBS1 is the causative gene in Bardet–Biedl syndrome. These concomitant mutations led to severe and/or complex clinical features in the patients, suggesting combined effects of different mutant genes.

Advantageous information provided by magnetoencephalography for patients with neocortical epilepsy.

PURPOSE We evaluated whether magnetoencephalography (MEG), in addition to surgery, was valuable for the diagnosis and management of epileptic syndromes in patients with neocortical epilepsy (NE). METHODS We studied MEG in 73 patients (29 females; aged 1-26years; mean 10.3years) for the clinical diagnosis of epilepsy and for preoperative evaluation. MEG data were recorded by 204-channel whole head gradiometers with a 600Hz sampling rate. MEG spike sources were localized on magnetic resonance images (MRI) using a single dipole model to project equivalent current dipoles. RESULTS MEG localized an epileptic focus with single clustered dipoles in 24 (33%) of 73 NE patients: 16 (25%) of 64 symptomatic localization-related epilepsy (SLRE) patients and eight (89%) of nine idiopathic localization-related epilepsy (ILRE) patients. MEG provided advantageous information in 12 (50%) of 24 patients with clustered dipoles and confirmed the diagnosis in the remaining 12 (50%). Furthermore, the use of MEG resulted in changes to surgical treatments in nine (38%) patients and in medical management in eight (33%). MEG confirmed the diagnosis in eight (16%) of 49 patients with scattered dipoles. MRI identified a single lesion (28 patients, 38%), multiple lesions (5, 7%), and no lesion (40, 55%). MRI provided confirming information in 19 of 28 patients with a single lesion and 18 of them required surgical resections. MRI did not provide any supportive information in 54 (74%) patients with a single (9), multiple (5) and no lesion (40). CONCLUSION Our study shows that MEG provides fundamental information to aid the choice of diagnostic and therapeutic procedures including changes in medication in addition to surgical treatments for NE.

Childhood-onset anti-MuSK antibody positive myasthenia gravis demonstrates a distinct clinical course.

Anti-muscle-specific tyrosine kinase antibody (MuSK-Ab) is the second most frequent autoantibody identified in adult patients with myasthenia gravis (MG). Adult patients with MuSK-Ab demonstrate characteristic clinical features but very little information is available for childhood-onset patients with MuSK-positive MG. We report a childhood-onset female patient with MuSK-positive MG. This patient showed basic clinical features compatible with adult-onset MuSK-positive MG, but some features, including spontaneous improvement, are distinct from those in adult patients. Serial examination of MuSK-Ab titers revealed a gross correlation with clinical severity despite significantly high titers throughout the clinical course. Therefore, childhood-onset MuSK-positive MG may demonstrate a distinct clinical characteristics in the early period of illness.

Magnetoencephalographic analysis of paroxysmal fast activity in patients with epileptic spasms.

PURPOSE This study sought to demonstrate the origin and propagation of paroxysmal fast activity (PFA) in patients with epileptic spasms (ESs), using time-frequency analyses of magnetoencephalogram (MEG) PFA recordings. METHODS A 204-channel helmet-shaped MEG, with a 600Hz sampling rate, was used to examine PFA in 3 children with ESs. We analyzed MEG recordings of PFA by short-time Fourier transform and the aberrant area or high-power spectrum was superimposed onto reconstructed three-dimensional magnetic resonance images as moving images. One ictal discharge was collected. One child and one adult with PFA due to Lennox-Gastaut syndrome were also examined for comparison. RESULTS All four PFAs in Patient 1 and five PFAs in Patient 3 were generated from one hemisphere. In Patient 2, four of seven PFAs were generated from one hemisphere and the remaining three were generated from both hemispheres. In Patient 3, one ictal MEG showed ictal discharges that were generated from the same area as the PFA, although the electroencephalogram showed no discharge. In Patients with Lennox-Gastaut syndrome, all 10 PFAs were generated from bilateral hemispheres simultaneously. CONCLUSION Short-time Fourier transform analyses of MEG PFA can show the origin and form of propagation of PFA. These results suggest that ESs are representative of focal seizures and the mechanism of PFA is different between ESs and Lennox-Gastaut syndrome.

Modulation of stimulus-induced 20-Hz activity for the tongue and hard palate during tongue movement in humans.

OBJECTIVE Modulation of 20-Hz activity in the primary sensorimotor cortex (SM1) may be important for oral functions. Here, we show that 20-Hz event-related desynchronization/synchronization (20-Hz ERD/ERS) is modulated by sensory input and motor output in the oral region. METHODS Magnetic 20-Hz activity was recorded following right-sided tongue stimulation during rest (Rest) and self-paced repetitive tongue movement (Move). To exclude proprioception effects, 20-Hz activity induced by right-sided hard palate stimulation was also recorded. The 20-Hz activity in the two conditions was compared via temporal spectral evolution analyses. RESULTS 20-Hz ERD/ERS was detected over bilateral temporoparietal areas in the Rest condition for both regions. Moreover, 20-Hz ERS was significantly suppressed in the Move condition for both regions. CONCLUSIONS Detection of 20-Hz ERD/ERS during the Rest condition for both regions suggests that the SM1 functional state may be modulated by oral stimulation, with or without proprioceptive effects. Moreover, the suppression of 20-Hz ERS for the hard palate during the Move condition suggests that the stimulation-induced functional state of SM1 may have been modulated by the movement, even though the movement and stimulation areas were different. SIGNIFICANCE Sensorimotor function of the general oral region may be finely coordinated through 20-Hz cortical oscillation.

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

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.

4. Malfunction of a sense of agency in schizophrenia patients: Evidence from somatosensory evoked potentials and fields

The aim of this study was to examine a sense of agency in schizophrenia patients using somatosensory evoked potentials (SEP) and fields (SEF). The subjects were 15 right-handed schizophrenia patients and 14 healthy controls. SEP and SEF were conducted with electrical stimuli to the left median nerve at intervals of 1–3 s. In ‘auto’ condition, the stimuli were externally induced. In ‘self’ condition, the stimuli were induced by tapping with their own right index finger. Peak to peak amplitude at C4 in SEP and root mean square (RMS) in 10 channels on right primary somatosensory area in SEF were analyzed. In SEP, the amplitude in ‘self’ was decreased with N33-P45, P45-N55, N55-P85 and P85N140 in control, while significant reduction was shown only with N33-P45 in schizophrenia. In SEF, there was no significant difference between ‘auto’ and ‘self’ condition in both groups about the RMS at N20m. However, at P30m, the RMS in ‘self’ was significantly decreased compared with that in ‘auto’ in control group only. Moreover, the RMS at P30m in ‘self’ in schizophrenia group was positively correlated with PANSS positive scale. These results suggest that positive symptom in schizophrenia patents may be caused by a malfunction of sense of agency.