Kazuya Itomi

The somatosensory evoked magnetic fields.

Averaged magnetoencephalography (MEG) following somatosensory stimulation, somatosensory evoked magnetic field(s) (SEF), in humans are reviewed. The equivalent current dipole(s) (ECD) of the primary and the following middle-latency components of SEF following electrical stimulation within 80-100 ms are estimated in area 3b of the primary somatosensory cortex (SI), the posterior bank of the central sulcus, in the hemisphere contralateral to the stimulated site. Their sites are generally compatible with the homunculus which was reported by Penfield using direct cortical stimulation during surgery. SEF to passive finger movement is generated in area 3a or 2 of SI, unlike with electrical stimulation. Long-latency components with peaks of approximately 80-120 ms are recorded in the bilateral hemispheres and their ECD are estimated in the secondary somatosensory cortex (SII) in the bilateral hemispheres. We also summarized (1) the gating effects on SEF by interference tactile stimulation or movement applied to the stimulus site, (2) clinical applications of SEF in the fields of neurosurgery and neurology and (3) cortical plasticity (reorganization) of the SI. SEF specific to painful stimulation is also recorded following painful stimulation by CO(2) laser beam. Pain-specific components are recorded over 150 ms after the stimulus and their ECD are estimated in the bilateral SII and the limbic system. We introduced a newly-developed multi (12)-channel gradiometer system with the smallest and highest quality superconducting quantum interference device (micro-SQUID) available to non-invasively detect the magnetic fields of a human peripheral nerve. Clear nerve action fields (NAFs) were consistently recorded from all subjects.

Combination of neonatal electroencephalography and ultrasonography: sensitive means of early diagnosis of periventricular leukomalacia

This study was performed to assess the predictive value of ultrasonography and electroencephalography (EEG) in order to identify infants with periventricular leukomalacia (PVL) during the early neonatal period, especially non-cystic cases, and to clarify the combination of ultrasonographic and EEG findings that are the most useful. We studied 288 eligible infants, whose gestational ages ranged between 27 and 32 weeks. PVL was observed in 49 infants (26 cystic PVL and 23 non-cystic PVL). On ultrasonography, 31 infants with PVL were detected on the basis of definite periventricular echodensity (PVE). Thirty-seven infants had at least one of equivocal or definite PVE or cystic changes, but the other 12 did not have any of them. The sensitivity and specificity were 0.76 and 0.81, respectively. In EEG findings, acute stage abnormalities (ASA) of grade II or more were recognized in 31 infants with PVL. The sensitivity and specificity were 0.63 and 0.91, respectively. Equivocal or definite chronic stage abnormalities (CSA) were seen in 43 infants, the sensitivity and specificity being 0.88 and 0.84. The sensitivity of CSA was higher than that of ASA, and the specificity of ASA was higher than that of CSA. When these EEG findings were combined, 45 infants with PVL were detected. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.92, 0.77, 0.45, and 0.98, respectively. Moreover, ultrasonographic and EEG findings were combined, 46 out of the 49 infants with PVL were detected with a sensitivity of 0.94 and a specificity of 0.64. The results indicated that EEG may be suitable for detecting infants at risk for development of PVL on the basis of its high sensitivity, and ultrasonography may be useful for confirming the presence of PVL on the grounds of its high specificity. Appropriate use of these measurements will make an early diagnosis of infants with PVL possible, even in non-cystic cases.

PCDH19 mutation in Japanese females with epilepsy

PURPOSE To determine the significance of PCDH19 mutations in Japanese females with epilepsy and to delineate their phenotypes. METHODS PCDH19 sequencing analysis was performed in 116 females with various epilepsies, including 97 with Dravet syndrome (83.6%). They were referred for SCN1A analysis, and 52 carried SCN1A mutations. RESULTS Seven heterozygous mutations in exon 1 were identified in 7 patients (6.0%): 2 frameshift, 2 nonsense, and 3 missense mutations. One patient was a monozygotic twin, and her sister with mild phenotype carried the same mutation. The main clinical features among these 8 patients included early seizure onset (≤25 months of age), seizure clusters (7/8), fever-associated seizures (7/8), single seizure type (6/8), and late deterioration of intellect (5/8). Seizure durations were generally up to a few minutes, and only one patient developed status epilepticus once. The main seizure types were generalized tonic-clonic (4/8), tonic (3/8) and focal seizures, with (2/8) or without secondary generalization (3/8). Myoclonic, atonic and absence seizures were extremely rare. Two patients had Dravet syndrome (25%), and this proportion was significantly smaller than that in the total subjects (p<0.01). CONCLUSION PCDH19 mutation is a relatively frequent cause of epilepsy in Japanese females. Dravet syndrome was rare in our cohort.

Dermatome versus homunculus; detailed topography of the primary somatosensory cortex following trunk stimulation

OBJECTIVE Identification of a detailed topography of the receptive area for each of the thoracic dermatomes in humans using somatosensory evoked magnetic fields (SEF). METHODS We analyzed the location of the equivalent current dipole (ECD) of SEF following electrical stimulation of the skin at Th4, Th6, Th8, Th10 and Th12 dermatomes in 14 normal subjects. RESULTS Three deflections, M18, M25 and M40, were obtained within 60 ms of stimulation of Th6, Th8 and Th10 dermatomes. No consistent deflection could be identified following Th4 and Th12 dermatomal stimulation, probably due to a poor signal-to-noise ratio and difficulty in fixing the stimulation electrodes. M18 was absent or small in amplitude. The latency of M25 ranged from short to long in the order Th6, Th8 and Th10 (P<0.05). ECDs of all components for each site stimulation were located in the truncal area of the primary somatosensory cortex. Although the locations of the ECDs tend to be arranged from lateral to medial in the sequence Th6, Th8 and Th10, the difference was not significant. CONCLUSION The representation area of the trunk is small, and the receptive areas for the stimulation of Th6, Th8 and Th10 dermatomes are considered to be very close or to overlap.

Prognostic value of positron emission tomography in cryptogenic West syndrome

The relationship between positron emission tomography (PET) findings and developmental or seizure outcome was examined in 17 infants (11 males, six females; mean age at onset of spasms 7 months, range 3 to 26 months) with newly diagnosed cryptogenic West syndrome. The predictive value of PET in these infants was assessed. PET was performed in the infants at the onset of spasms and 3 months after initial therapy using 18F‐labelled 2‐deoxy‐2‐fluoro‐D‐glucose. A third PET was performed at 18 months of age if the second scan was abnormal. All infants were followed up until at least 3 years of age. Cortical hypometabolism was detected in 11 infants on the first PET and in five infants on the second. Rate of developmental delay at the last follow‐up was significantly higher in infants with hypometabolism on the second PET than in those without PET abnormalities (p<0.05). Rate of seizure occurrence after initial treatment was higher in infants with cortical hypometabolism on the second PET, but the difference was not statistically significant. Results suggest that when PET after the initial treatment shows no abnormalities, even though the first PET shows hypometabolism, infants with cryptogenic West syndrome may have a favourable developmental or seizure outcome. PET may be a useful tool in evaluating the prognosis in infants with cryptogenic West syndrome.

Relation between the date of cyst formation observable on ultrasonography and the timing of injury determined by serial electroencephalography in preterm infants with periventricular leukomalacia

The aim of this study was to clarify the relation between the date of cyst formation and the timing of injury in preterm infants with periventricular leukomalacia in order to address the issue of whether or not we can determine the timing of injury on the basis of ultrasonographic findings. We studied 33 preterm infants with cystic periventricular leukomalacia, the gestational ages being 32 weeks or less. As 27 of them exhibited either acute or chronic stage abnormalities in the initial electroencephalogram, the timing of injury was presumed to be before or around birth. For the remaining six infants, the timing of injury was considered to be postnatal in two infants, and was not determined in another four. The median date of cyst formation was 18 days of age (range, 10-39 days) in the 27 infants with abnormal initial electroencephalograms. For these 27 infants, the gestational age did not influence the date of cyst formation. In contrast, the date of cyst formation was significantly earlier in infants with widespread cysts than in those with localized cysts. In conclusion, it is difficult to determine the timing of injury from ultrasonographic findings, because the range of the date of cyst formation on ultrasonography was very wide among infants whose timing of injury was not greatly different.

Epileptic Spasms Preceded by Partial Seizures with a Close Temporal Association

Summary: Purpose: To investigate the distinctive features of patients with West syndrome who had partial seizures followed by epileptic spasms (PS‐ES).

The Predictive Value of Electroencephalogram during Early Infancy for Later Development of West Syndrome in Infants with Cystic Periventricular Leukomalacia

Summary:  Purpose: The aim of this study was to elucidate a predictive value of electroencephalogram (EEG) during early infancy for later development of West syndrome (WS) in premature infants with cystic periventricular leukomalacia (PVL).

Immediate suppression of seizure clusters by corticosteroids in PCDH19 female epilepsy

PURPOSE The pathomechanism and treatment of PCDH19 female epilepsy (PCDH19-FE) remain unclear. Here, we report that corticosteroids are effective for control of the seizure clusters or other acute symptoms of PCDH19-FE and argue for the possible involvement of a compromised blood-brain barrier (BBB) in its pathogenesis. METHODS The efficacy of corticosteroids was retrospectively reviewed in five Japanese patients with PCDH19-FE. The results of antibody assays against the N-methyl-d-aspartate-type glutamate receptor (abs-NR) in serum/cerebrospinal fluid were also compiled. RESULTS Corticosteroid treatments significantly improved the acute symptoms, including seizure clusters, in all cases, most often immediately after the initial administration. However, the effect was transient, and some seizures recurred within a few weeks, especially in association with fever. Serum and/or cerebrospinal fluid abs-NR were detected in all patients. Target sequences of the detected antibodies were multiple, and the titers tended to decrease over time. In one patient, immunohistochemical analysis using rat hippocampal slices also revealed serum antibodies targeting an unknown epitope in neuronal cytoplasm. CONCLUSION Our findings imply an involvement of inflammatory processes in the pathogenesis of PCDH19-FE and therapeutic utility for corticosteroids as an adjunctive option in acute treatment. PCDH19 is well expressed in brain microvascular endothelial cells and thus its impairment may cause BBB vulnerability, which may be ameliorated by corticosteroids. The abs-NR detected in our patients may not indicate an autoimmune pathomechanism, but may rather represent non-specific sensitization to degraded neuronal components entering the general circulation, the latter process facilitated by the BBB vulnerability.

A Unique Area of the Homonculus: The Topography of the Primary Somatosensory Cortex in Humans Following Posterior Scalp and Shoulder Stimulation

We recorded somatosensory evoked magnetic field (SEF) to investigate the differentiation in the receptive area for the face, lower part of the posterior scalp (mastoid) and shoulder, which occupy an unique area in the homunculus. We analyzed the location of the equivalent current dipole (ECD) of SEF following electrical stimulation of the skin at the face, mastoid and shoulder in 20 normal subjects. Three deflections (1M, 2M and 3M) were obtained within 50 ms of the stimulation in 16 of 20 subjects. The peak latency of the 1M and 2M was not significantly different at any stimulus sites. The amplitude of the 1M was significantly larger following the face than mastoid stimulation (p < 0.05). The 16 subjects were classified according to the locations of the ECD on stimulation of the mastoid: close to that for shoulder stimulation, but significantly (p < 0.05) more superior and medial to that following the face stimulation (Type 1, eleven subjects); close to that for face stimulation, but significantly (P < 0.05) more inferior and lateral to that following the shoulder stimulation (Type 2, five subjects). The site of the receptive area for the posterior scalp shows interindividual variation, possibly due to anatomical differences.