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Objective: Previous reports on the simultaneous recording of electroencephalography (EEG) and electrocorticography (ECoG) have demonstrated that, in patients with temporal lobe epilepsy (TLE), ictal ECoG discharges with an amplitude as high as 1000 μV originating from the medial temporal lobe could not be recorded on EEG. In contrast, ictal EEG discharges were recorded after ictal ECoG discharges propagated to the lateral temporal lobe. Here, we report a case of TLE in which the ictal EEG discharges, corresponding to ictal ECoG discharges confined to the medial temporal lobe, were recorded. Case report: In the present case, ictal EEG discharges were hardly recognized when the amplitude of the ECoG discharges was less than 1500 μV. During the evolution and burst suppression phase, corresponding to highly synchronized ECoG discharges with amplitudes greater than 1500 to 2000 μV, rhythmic negative waves with the same frequency were clearly recorded both on the lateral temporal lobe and scalp. The amplitude of the lateral temporal ECoG was approximately one-tenth of that of the medial temporal ECoG. The amplitude of the scalp EEG was approximately one-tenth of that of the lateral temporal ECoG. Conclusions: Highly synchronized ictal ECoG discharges with high amplitude of greater than 1500 to 2000 μV in the medial temporal lobe could be recorded on the scalp as ictal EEG discharges via volume conduction.

Patients with cortical reflex myoclonus manifest typical neurophysiologic characteristics due to primary sensorimotor cortex (S1/M1) hyperexcitability, namely, contralateral giant somatosensory-evoked potentials/fields and a C-reflex (CR) in the stimulated arm. Some patients show a CR in both arms in response to unilateral stimulation, with about 10-ms delay in the non-stimulated compared with the stimulated arm. This bilateral C-reflex (BCR) may reflect strong involvement of bilateral S1/M1. However, the significance and exact pathophysiology of BCR within 50 ms are yet to be established because it is difficult to identify a true ipsilateral response in the presence of the giant component in the contralateral hemisphere. We hypothesized that in patients with BCR, bilateral S1/M1 activity will be detected using MEG source localization and interhemispheric connectivity will be stronger than in healthy controls (HCs) between S1/M1 cortices. We recruited five patients with cortical reflex myoclonus with BCR and 15 HCs. All patients had benign adult familial myoclonus epilepsy. The median nerve was electrically stimulated unilaterally. Ipsilateral activity was investigated in functional regions of interest that were determined by the N20m response to contralateral stimulation. Functional connectivity was investigated using weighted phase-lag index (wPLI) in the time-frequency window of 30–50 ms and 30–100 Hz. Among seven of the 10 arms of the patients who showed BCR, the average onset-to-onset delay between the stimulated and the non-stimulated arm was 8.4 ms. Ipsilateral S1/M1 activity was prominent in patients. The average time difference between bilateral cortical activities was 9.4 ms. The average wPLI was significantly higher in the patients compared with HCs in specific cortico-cortical connections. These connections included precentral-precentral, postcentral-precentral, inferior parietal (IP)-precentral, and IP-postcentral cortices interhemispherically (contralateral region-ipsilateral region), and precentral-IP and postcentral-IP intrahemispherically (contralateral region-contralateral region). The ipsilateral response in patients with BCR may be a pathologically enhanced motor response homologous to the giant component, which was too weak to be reliably detected in HCs. Bilateral representation of sensorimotor responses is associated with disinhibition of the transcallosal inhibitory pathway within homologous motor cortices, which is mediated by the IP. IP may play a role in suppressing the inappropriate movements seen in cortical myoclonus.

OBJECTIVE To identify the risk factors for psychological distress in electroencephalography (EEG) technicians during the coronavirus disease 2019 (COVID-19) pandemic. METHOD In this national-level cross-sectional survey initiated by Japan Young Epilepsy Section (YES-Japan), which is a national chapter of The Young Epilepsy Section of the International League Against Epilepsy (ILAE-YES), a questionnaire was administered to 173 technicians engaged in EEG at four clinics specializing in epilepsy care and 20 hospitals accredited as (quasi-) epilepsy centers or epilepsy training facilities in Japan from March 1 to April 30, 2021. We collected data on participants' profiles, information about work, and psychological distress outcome measurements, such as the K-6 and Tokyo Metropolitan Distress Scale for Pandemic (TMDP). Linear regression analysis was used to identify the risk factors for psychological distress. Factors that were significantly associated with psychological distress in the univariate analysis were subjected to multivariate analysis. RESULTS Among the 142 respondents (response rate: 82%), 128 were included in the final analysis. As many as 35.2% of EEG technicians have been under psychological distress. In multivariate linear regression analysis for K-6, female sex, examination for patients (suspected) with COVID-19, and change in salary or bonus were independent associated factors for psychological distress. Contrastingly, in multivariate linear regression analysis for TMDP, female sex, presence of cohabitants who had to be separated from the respondent due to this pandemic, and change in salary or bonus were independent associated factors for psychological distress. CONCLUSION We successfully identified the risk factors associated with psychological distress in EEG technicians during the COVID-19 pandemic. Our results may help in understanding the psychological stress in EEG technicians during the COVID-19 pandemic and improving the work environment, which is necessary to maintain the mental health of EEG technicians.

Background: Temporal lobe epilepsy (TLE) associated with temporal lobe encephalocele is rare, and the precise epileptogenic mechanisms and surgical strategies for such cases are still unknown. Although the previous studies have reported good seizure outcomes following chronic subdural electrode recording through invasive craniotomy, only few studies have reported successful epilepsy surgery through endoscopic endonasal lesionectomy. Case Description: An 18-year-old man developed generalized convulsions at the age of 15 years. Despite treatment with optimal doses of antiepileptic drugs, episodes of speech and reading difficulties were observed 2–3 times per week. Long-term video electroencephalogram (EEG) revealed ictal activities starting from the left anterior temporal region. Magnetic resonance imaging revealed a temporal lobe encephalocele in the left lateral fossa of the sphenoidal sinus (sphenoidal encephalocele). Through the endoscopic endonasal approach, the tip of the encephalocele was exposed. A depth electrode was inserted into the encephalocele, which showed frequent spikes superimposed with high-frequency oscillations (HFOs) suggesting intrinsic epileptogenicity. The encephalocele was resected 8 mm from the tip. Twelve months postoperatively, the patient had no recurrence of seizures on tapering of the medication. Conclusion: TLE associated with sphenoidal encephalocele could be controlled with endoscopic endonasal lesionectomy, after confirming the high epileptogenicity with analysis of HFOs of intraoperative EEG recorded using an intralesional depth electrode.

Objectives The objectives of this study were to determine how hemispheric laterality of seizure activity influences periictal heart rate variability (HRV) and investigate the ability of HRV parameters to discriminate right- and left-sided seizures. Methods Long-term video electroencephalogram-electrocardiogram recordings of 54 focal seizures in 25 patients with focal epilepsy were reviewed. Using linear mixed models, we examined the effect of seizure laterality on linear (standard deviation of R-R intervals [SDNN], root mean square of successive differences [RMSSD], low frequency [LF] and high frequency [HF] power of HRV, and LF/HF) and nonlinear (standard deviation [SD]1, SD2, and SD2/SD1 derived from Poincare plots) periictal HRV parameters, the magnitude of heart rate (HR) changes, and the onset time of increased HR. Receiver operating characteristics (ROC) were used to determine the ability of these parameters to discriminate between right- and left-sided seizures. Results Postictal SDNN, RMSSD, LF, HF, SD1, and SD2 were higher in right- than left-sided seizures. Root mean square of successive difference and HF were decreased after left- but not right-sided seizures. Standard deviation of R-R intervals, LF, and SD1 were increased after right- but not left-sided seizures. Increased ictal HR was earlier and larger in right- than left-sided seizures. Postictal HF showed the greatest area under the ROC curve (AUC) (0.87) for discriminating right- and left-sided seizures. Conclusions Our data suggest that postictal parasympathetic activity is higher, whereas ictal HR increase is greater, in right- than left-sided seizures. Involvement of the right hemisphere may be associated with postictal autonomic instability. Postictal HRV parameters may provide useful information on hemispheric laterality of seizure activity.

It remains unclear whether epileptogenic networks in focal epilepsy develop on physiological networks. This work aimed to explore the association between the rapid spread of ictal fast activity (IFA), a proposed biomarker for epileptogenic networks, and the functional connectivity or networks of healthy subjects. We reviewed 45 patients with focal epilepsy who underwent electrocorticographic (ECoG) recordings to identify the patients showing the rapid spread of IFA. IFA power was quantified as normalized beta-gamma band power. Using published resting-state functional magnetic resonance imaging databases, we estimated resting-state functional connectivity of healthy subjects (RSFC-HS) and resting-state networks of healthy subjects (RSNs-HS) at the locations corresponding to the patients' electrodes. We predicted the IFA power of each electrode based on RSFC-HS between electrode locations (RSFC-HS-based prediction) using a recently developed method, termed activity flow mapping. RSNs-HS were identified using seed-based and atlas-based methods. We compared IFA power with RSFC-HS-based prediction or RSNs-HS using non-parametric correlation coefficients. RSFC and seed-based RSNs of each patient (RSFC-PT and seed-based RSNs-PT) were also estimated using interictal ECoG data and compared with IFA power in the same way as RSFC-HS and seed-based RSNs-HS. Spatial autocorrelation-preserving randomization tests were performed for significance testing. Nine patients met the inclusion criteria. None of the patients had reflex seizures. Six patients showed pathological evidence of a structural etiology. In total, we analyzed 49 seizures (2-13 seizures per patient). We observed significant correlations between IFA power and RSFC-HS-based prediction, seed-based RSNs-HS, or atlas-based RSNs-HS in 28 (57.1%), 21 (42.9%), and 28 (57.1%) seizures, respectively. Thirty-two (65.3%) seizures showed a significant correlation with either seed-based or atlas-based RSNs-HS, but this ratio varied across patients: 27 (93.1%) of 29 seizures in six patients correlated with either of them. Among atlas-based RSNs-HS, correlated RSNs-HS with IFA power included the default mode, control, dorsal attention, somatomotor, and temporal-parietal networks. We could not obtain RSFC-PT and RSNs-PT in one patient due to frequent interictal epileptiform discharges. In the remaining eight patients, most of the seizures showed significant correlations between IFA power and RSFC-PT-based prediction or seed-based RSNs-PT. Our study provides evidence that the rapid spread of IFA in focal epilepsy can arise from physiological RSNs. This finding suggests an overlap between epileptogenic and functional networks, which may explain why functional networks in patients with focal epilepsy frequently disrupt.

Objective Lateralized periodic discharges (LPDs), which constitute an abnormal electroencephalographic (EEG) pattern, are most often observed in critically ill patients with acute pathological conditions, and are less frequently observed in chronic conditions such as focal epilepsies, including temporal lobe epilepsy (TLE). Here we aim to explore the pathophysiological mechanism of LPD in TLE. Methods We retrospectively selected 3 patients with drug-resistant TLE who simultaneously underwent EEG and electrocorticography (ECoG) and demonstrated LPDs. We analyzed the correlation between the EEG and ECoG findings. Results In patients 1 and 2, LPDs were recorded in the temporal region of the scalp during the interictal periods, when repeated spikes followed by slow waves (spike-and-wave complexes; SWs) and periodic discharges (PDs) with amplitudes of >600 to 800 µV appeared in the lateral temporal lobe over a cortical area of >10 cm2. In patient 3, when the ictal discharges persisted and were confined to the medial temporal lobe, repeated SWs were provoked on the lateral temporal lobe. When repeated SWs with amplitudes of >800 µV appeared in an area of the lateral temporal lobe of >10 cm2, the corresponding EEG discharges appeared on the temporal scalp. Conclusions LPDs in patients with TLE originate from repeated SWs and PDs of the lateral temporal lobe, which might represent a highly irritable state of the lateral temporal cortex during both interictal and ictal periods.

Objective Our previous study of monaural auditory evoked magnetic fields (AEFs) demonstrated that hippocampal sclerosis significantly modulated auditory processing in patients with mesial temporal lobe epilepsy (mTLE). However, the small sample size (n = 17) and focus on the M100 response were insufficient to elucidate the lateralization of the epileptic focus. Therefore, we increased the number of patients with mTLE (n = 39) to examine whether neural synchronization induced by monaural pure tone stimulation provides useful diagnostic information about epileptic foci in patients with unilateral mTLE. Methods Twenty-five patients with left mTLE, 14 patients with right mTLE, and 32 healthy controls (HCs) were recruited. Auditory stimuli of 500-Hz tone burst were monaurally presented to subjects. The AEF data were analyzed with source estimation of M100 responses in bilateral auditory cortices (ACs). Neural synchronization within ACs and between ACs was evaluated with phase-locking factor (PLF) and phase-locking value (PLV), respectively. Linear discriminant analysis was performed for diagnosis and lateralization of epileptic focus. Results The M100 amplitude revealed that patients with right mTLE exhibited smaller M100 amplitude than patients with left mTLE and HCs. Interestingly, PLF was able to differentiate the groups with mTLE, with decreased PLFs in the alpha band observed in patients with right mTLE compared with those (PLFs) in patients with left mTLE. Right hemispheric predominance was confirmed in both HCs and patients with left mTLE while patients with right mTLE showed a lack of right hemispheric predominance. Functional connectivity between bilateral ACs (PLV) was reduced in both patients with right and left mTLE compared with that of HCs. The accuracy of diagnosis and lateralization was 80%–90%. Conclusion Auditory cortex subnormal function was more pronounced in patients with right mTLE compared with that in patients with left mTLE as well as HCs. Monaural AEFs can be used to reveal the pathophysiology of mTLE. Overall, our results indicate that altered neural synchronization may provide useful information about possible functional deterioration in patients with unilateral mTLE.

OBJECTIVE To determine the characteristics of olfactory dysfunction in patients with temporal lobe epilepsy (TLE). METHODS Odor identification was assessed using the odor stick identification test for Japanese (OSIT-J, full score 12 points) in 65 patients with TLE and in 74 controls. RESULTS The mean OSIT-J score was significantly lower in patients with TLE (mean ± SD = 8.1 ± 2.8; median = 9) than in the control subjects (mean ± SD = 10.6 ± 1.1; median = 11) (P

We report the case of a 17-year-old woman with paroxysmal sympathetic storm (PSS), which was successfully treated with clonidine hydrochloride. The patient was hospitalized for acute disseminated encephalomyelitis in June 2006. Dysphagia led to severe aspiration pneumonia in September 2006, and she suffered cardiopulmonary arrest. She survived but had severe brain damage, with her brain MRI showing diffuse hypoxic encephalopathy. From October 2006, she had several episodes of profound tachypnea (> 60/min), tachycardia (160 to 170 beats/min), hypertension (> 140 mmHg), hyperthermia (39°C), and decerebrate posturing. During the attacks, the levels of catecholamines in the patient's blood and urine were markedly elevated. Accordingly, a diagnosis of PSS associated with hypoxic encephalopathy was made. Her PSS clearly improved after the administration of clonidine hydrochloride (900 μg/day). This case suggests that clonidine hydrochloride, an α2 blocker, may be one therapeutic option for PSS.

Objective Patients with mesial temporal lobe epilepsy (mTLE) often exhibit central auditory processing (CAP) dysfunction. Monaural 40-Hz auditory steady-state magnetic responses (ASSRs) were recorded to explore the pathophysiology of mTLE. Methods Eighteen left mTLE patients, 11 right mTLE patients and 16 healthy controls (HCs) were examined. Monaural clicks were presented at a rate of 40 Hz. Phase-locking factor (PLF) and power values were analyzed within bilateral Heschl’s gyri. Results Monaural 40-Hz ASSR demonstrated temporal frequency dynamics in both PLF and power data. Symmetrical hemispheric contralaterality was revealed in HCs. However, predominant contralaterality was absent in mTLE patients. Specifically, right mTLE patients exhibited a lack of contralaterality in response to left ear but not right ear stimulation, and vice versa in left mTLE patients. Conclusion This is the first study to use monaural 40-Hz ASSR with unilateral mTLE patients to clarify the relationship between CAP and epileptic focus. CAP dysfunction was characterized by a lack of contralaterality corresponding to epileptic focus. Significance Monaural 40-Hz ASSR can provide useful information for localizing epileptic focus in mTLE patients.

Central pontine myelinolysis (CPM), which was originally considered to be the result of rapid correction of chronic hyponatremia, is not necessarily accompanied by hyponatremia or drastic changes in serum sodium level. Here, we report a case of an anorexic 55-year-old male with a history of pharyngo-laryngo-esophagogastrectomy, initially hospitalized with status epilepticus. Although his consciousness gradually recovered as we were controlling his convulsion, it deteriorated again with new onset of anisocoria, and magnetic resonance imaging (MRI) at this point revealed CPM. Rapid change of serum sodium or osmolarity, which is often associated with CPM, had not been apparent throughout his hospitalization. Instead, a review of the serum biochemistry test results showed that serum phosphate had drastically declined the day before the MRI first detected CPM. In this case, we suspect that hypophosphatemia induced by refeeding syndrome greatly contributed to the occurrence of CPM.

"Solitary" meningioangiomatosis (MA) is a rare, benign, hamartomatous lesion of the cerebral cortex and frequently leads to epilepsy. However, the source of the epileptogenicity in meningioangiomatosis remains controversial. We report two surgically-treated meningioangiomatosis cases with medically intractable epilepsy. In both cases, chronic subdural electrocorticogram (ECoG) recordings identified the ictal onset zone on apparently normal cortex, adjacent to and/or above the meningioangiomatosis lesion, not on the meningioangiomatosis lesion itself. The ictal onset zone was resected, along with the MA lesion, and good seizure outcome was achieved. Histological examination of the ictal onset zone revealed the presence of ILAE focal cortical dysplasia (FCD) type IIIc. Our case studies suggest that in the surgical management of epilepsy with meningioangiomatosis, it is important to identify undetected, but epileptogenic, ILAE FCD Type IIIc, using preoperative multimodal examinations, including chronic ECoG recordings.

Focal cortical dysplasia (FCD) is an important cause of intractable epilepsy. Previous rat studies have utilized freeze lesioning of neonatal animals to model FCD; however, such models are unable to demonstrate spontaneous seizures without seizure-provoking events. Therefore, we created an animal model with multiple FCD, produced during embryonic development, and observed whether spontaneous seizures occurred. Furthermore, we examined the relationship between FCD and epileptogenesis using immunohistochemistry. At 18 days postconception, a frozen metal probe was placed bilaterally on the scalps of Sprague-Dawley rat embryos through the uterus wall to produce multiple FCD. Electroencephalogram (EEG) and video recording were performed from postnatal day (P) 35 to P77. Brain tissues were examined immunohistochemically at P28 and P78 using semiquantitative densitometry. Eleven of 16 rats (68.8%) showed spontaneous seizures arising in the hippocampus from P47. Movement cessation followed by sniffing and mastication, culminating in wet-dog shaking, was seen during the hippocampal EEG discharges. FCD was observed in the bilateral frontoparietal lobes. The expression levels of N-methyl-d-aspartate receptor (NMDAR) subunits 1, 2A, 2B, the glutamate/aspartate transporter and the glial glutamate transporter 1 (GLT1) at FCD sites were increased at P28 and P78. There were no major histological abnormalities in the hippocampi compared with those in the cortex. However, the expression levels of NMDAR 2A and 2B were increased at P28. Levels of NMDAR1, 2A and 2B, the glutamate/aspartate transporter and GLT1 were also increased at P78. We created an animal model showing spontaneous seizures without a provoking event except for the existence of cortical dysplasia, and without a genetic or general systematic cause like MAM injection or irradiation. The seizures resembled human temporal lobe epilepsy both clinically and on EEG. Alterations in the levels of glutamatergic and GABAergic receptors were investigated during growth. This model should enable better clarification of the mechanisms underlying the development of human epilepsy.

Objectives To clarify the differences in multimodality evoked potential findings between patients with atopic myelitis (AM) and those with multiple sclerosis (MS). Methods A retrospective chart review of 70 consecutive AM patients and 93 MS patients was carried out. All patients were negative for serum anti-aquaporin-4 antibody. Visual- (VEP), somatosensory- (SEP) and motor-evoked potentials (MEP) recorded at first examination, and magnetic resonance imaging (MRI) findings from the first examination were compared between AM and MS patients. Results Compared with MS patients, AM patients showed male preponderance, lower the Expanded Disability Status Scale scores and less frequent spinal cord MRI lesions. Visual impairment and muscle weakness were also less severe in AM patients. Frequencies of abnormal VEP and prolonged central conduction time on lower limb MEP were significantly lower in AM patients than in MS patients (AM vs MS: 9.5% vs 55.6%, and 28.2% vs 54.4%, respectively), whereas frequencies of peripheral nerve involvement in upper and lower limb MEP and upper limb SEP were significantly higher in AM than in MS patients (AM vs MS: 12.8% vs 2.9%, 17.9% vs 2.9% and 33.3% vs 4.4%, respectively). When patients whose EP were examined within 5 years of disease onset were compared, lower frequencies of abnormal VEP and higher peripheral nerve involvement detected by MEP and SEP were observed in AM patients. Conclusions AM patients have distinct physiological features compared with MS patients, even at the first examination of evoked potentials, which might suggest distinct immunological mechanisms between the two conditions. Multimodality evoked potentials might contribute to the early discrimination of these two disorders.

Epilepsy is a frequent comorbidity in patients with focal cortical dysplasia (FCD). Recent studies utilizing massive sequencing data identified subsets of genes that are associated with epilepsy and FCD. AKT and mTOR-related signals have been recently implicated in the pathogenic processes of epilepsy and FCD. To clarify the functional roles of the AKT-mTOR pathway in the hippocampal neurons, we generated conditional knockout mice harboring the deletion of Pten (Pten-cKO) in Proopiomelanocortin-expressing neurons. The Pten-cKO mice developed normally until 8 weeks of age, then presented generalized seizures at 8-10 weeks of age. Video-monitored electroencephalograms detected paroxysmal discharges emerging from the cerebral cortex and hippocampus. These mice showed progressive hypertrophy of the dentate gyrus (DG) with increased expressions of excitatory synaptic markers (Psd95, Shank3 and Homer). In contrast, the expression of inhibitory neurons (Gad67) was decreased at 6-8 weeks of age. Immunofluorescence studies revealed the abnormal sprouting of mossy fibers in the DG of the Pten-cKO mice prior to the onset of seizures. The treatment of these mice with an mTOR inhibitor rapamycin successfully prevented the development of seizures and reversed these molecular phenotypes. These data indicate that the mTOR pathway regulates hippocampal excitability in the postnatal brain.

We report a case of primary central nervous system vasculitis (PCNSV) diagnosed by second brain biopsy. A 53-year-old man initially presented with left lateral gaze diplopia. Brain MRI revealed multiple enhanced lesions in the bilateral frontal lobe, bilateral basal ganglia, left cerebellum and brainstem. An initial brain biopsy of the right frontal lobe suggested immune-related encephalitis with angiocentric accumulation of chronic inflammatory cells, while malignant lymphoma could not be completely ruled out. The patient deteriorated despite being treated with repeated methylprednisolone pulse therapy, cyclophosphamide, and plasmapheresis. A second brain biopsy of the right temporal lobe was then performed. The biopsied specimens showed vascular wall disruption and fibrinoid necrosis with perivascular inflammatory infiltrates, mainly composed of CD8-positive T cells, and PCNSV was diagnosed. He was treated with high dose corticosteroids, in combination with methotrexate (8 mg/week), which reduced the brain lesions. As brain biopsy is an essential investigation for the histological diagnosis of PCNSV; subsequent biopsies may be required when a histopathological diagnosis has not been obtained by the first biopsy, and further aggressive therapy is being considered.

Objective To establish the first evidence-based diagnostic criteria for atopic myelitis (AM) enabling it to be discriminated from myelitis-onset multiple sclerosis (MS), which is a difficult differential diagnosis. Methods Sixty-nine consecutive AM patients examined from 1996 to 2010 at Kyushu University hospital, who fulfilled the empirical definition of AM (2003), and 51 myelitis-onset MS patients in whom allergen-specific IgE was measured, were enrolled. The first available brain MRI findings were compared between the two. Then, we compared the clinical and laboratory features between the 16 AM cases who did not meet the Barkhof brain MRI criteria for MS after more than 5 years follow-up and 51 myelitis-onset MS cases. Based on the discriminative findings, we established diagnostic criteria for AM and calculated the sensitivity and specificity. Results AM patients had a significantly lower frequency of Barkhof brain lesions on baseline MRI than myelitis-onset MS patients. AM patients had a significantly higher frequency of present and/or past history of atopic disease and hyperIgEemia, and higher cerebrospinal fluid levels of interleukin 9 and CCL11/eotaxin, but a lower frequency of oligoclonal IgG bands than myelitis-onset MS patients. Our proposed diagnostic criteria for AM demonstrated 93.3% sensitivity and 93.3% specificity for AM against myelitis-onset MS, with 82.4% positive predictive value and 97.7% negative predictive value. Conclusion Our first evidence-based criteria for AM show high sensitivity and specificity, and would be useful clinically.

A 24-year-old man was referred to our hospital emergency department due to a sudden onset of convulsions after drinking. On arrival he presented status epilepticus and was managed by artificial ventilation. He had no brainstem signs or meningeal irritation. Head MRI showed an old infarction-like lesion in the left occipital lobe, but no abnormal signals on diffusion-weighted images. The patient showed acute rhabdomyolysis (CK 18,000 IU/l) and renal failure, and hemodialysis was started. On 18 day after admission, he was transferred to our department with mild proximal limb muscle weakness and bilateral sensorineural hearing impairment. Electroencephalography demonstrated diffuse intermittent slow wave activities. We suspected a mitochondrial disease because of a significant increase in the lactate/pyruvate ratio (24.1) in the spinal fluid, and identified A3243G mutations in mitochondrial DNA (heteroplasmy 20%) in peripheral white blood cells. We diagnosed his illness as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). This is a rare case presenting an acute onset of rhabdomyolysis following alcohol intake related to A3243G mitochondrial mutation without preceding stroke-like episodes.

Epilepsy is a common disease with a high incidence of about one percent. Knowledge of seizure semiology and correct reading of EEG findings are important for diagnosis of epilepsy. Because the primary therapy for epilepsy is antiepileptic drugs (AEDs), including several ones that are newly permitted in Japan, we need to prescribe them based on an understanding of their actions and interaction mechanisms. However, we also need to consider early surgical treatment for temporal lobe epilepsy with hippocampal sclerosis. In the therapeutic decision for adult epilepsy patients many factors such as employment, marriage, child bearing, and co-existent disease need to be considered. The present review provides an overview of the basis of epilepsy practice for neurologists treating adults with epilepsy, including a discussion of new AEDs, epilepsy surgery, women with epilepsy, and epilepsy in the elderly.

We report a case of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) concomitant with acquired von Willebrand syndrome. A 33-year-old man developed motor and sensory polyneuropathy with electrophysiological conduction slowing. At this time, M-protein was absent He was diagnosed with CIDP and received intravenous immunoglobulin and subsequent oral corticosteroids, which resulted in almost complete remission for over 10 years. At the age of 44, he presented with chronic anemia. Laboratory tests and colonoscopy revealed that he had acquired von Willebrand syndrome with monoclonal gammopathy of undetermined significance (IgG lambda type) and colon cancer. Bleeding symptoms were.resolved with intravenous immunoglobulin, but not with supplementation of factor VIII. Shortly after successful excision of the cancer, CIDP and acquired von Willebrand syndrome simultaneously recurred. Intravenous immunoglobulin produced rapid improvement of both neurological and hematological abnormalities. Concurring CIDP and acquired von Willebrand syndrome in the present case may indicate that the conditions have a partly common immunological background including monoclonal gammopathy and a potential common autoantibody-mediated mechanism. Alternatively, dysfunction of von Willebrand factor may increase blood-nerve barrier permeability, inducing the recurrence of CIDP.

We report a 78-year-old woman who had episodes of nonconvulsive status epilepticus (NCSE) with dizziness. At 75 years of age, she had first seizure, but was not well examined. At 78 years of age, she had brief myoclonic jerks of her arms, soon after awakening, in May. She suffered from strong dizziness and was admitted in our hospital at the end of June. The symptoms regressed with bed rest in few days and she was discharged. However, she was admitted again with dizziness in the middle of July. There were no myoclonic jerks of her arms or legs and she could converse and interact normally, but was slightly disoriented (JCS: 2). Blood test, Cerebrospinal fluid analyses and brain MRI were normal. An EEG showed frequent intermittent generalized multiple spikes and slow wave complexes and a 3-4 Hz generalized spike and slow wave complexes every 2-4 seconds during whole 20 minutes record. Intravenous injection of 5 mg diazepam terminated status immediately. Thereafter, she was treated with sodium valproate (400 mg/day). Her symptoms improved, and interictal epileptic discharges extremely decreased. Late-onset NCSE of generalized epilepsy is rare. We discussed this case as an important case for diagnosis of NCSE with subtle symptom of dizziness.

Recent resting-state functional MRI (rs-fMRI) studies have demonstrated that the human brain is composed of several essential large-scale functional brain networks, including the "default-mode network". We analyzed electrocorticogram data from four patients with intractable focal epilepsy and compared the extent of these large-scale functional brain networks with propagation pathways of ictal discharge. We found that large-scale functional brain networks had markedly similar spatial patterns compared with multisite ictal fast activity, suggesting that some epileptic activity propagates along large-scale functional brain networks. Given that decreased functional connectivity in large-scale functional brain networks has been reported in patients with focal epilepsy, ictal propagation may lead to chronic alteration of normal functional networks in the brain.

Focal cortical dysplasia (FCD) is of increasing interest as a cause of focal epilepsy. We aimed to determine whether the existence of FCD influences the epileptogenicity induced by electrical kindling stimulation of the cortices. We created an FCD rat model by focal contact of a frozen metal probe on the scalp immediately after birth. To produce afterdischarges (ADs), electrical stimulation was applied to the frontal cortices once daily for 20 consecutive days from postnatal day 38 (P38). Thresholds and durations of ADs were measured. Brains were exposed and examined histologically at P58. We observed mild FCD, which consisted of disorganized cortices with extra sulci; however, there was no statistical difference in the thresholds or durations of ADs between FCD rats and control animals. These results suggest that FCD might not influence vulnerability to epileptogenicity, at least in some patients with mild FCD.

Summary Purpose: Focal cortical dysplasia (FCD) is thought to be an important cause of intractable epilepsy. However, its epileptogenicity remains unclear. Therefore, we created a novel rat model by freeze lesioning during the late embryonic stage to verify whether FCD influences seizure activities. Methods: At 18 days postconception, a frozen probe was placed on the left scalp of a Sprague–Dawley rat embryo through the uterus wall. For 40 consecutive days from postnatal day 38 (P38), electrical kindling stimulation was applied to the frontal lobes of male rat pups. Afterdischarges (ADs) were measured in both the cortex and hippocampus. Brain tissues were examined by immunohistochemistry. Results: All brains from prenatally freeze-lesioned rats displayed severe disorganization of the cortical layers with randomly oriented dendrites/axons. In addition, heterotopic cortices were observed in 42.1% of cases. ADs in the cortex and hippocampus were significantly prolonged in freeze-lesioned rats compared with those in sham-operated and control rats. FCD rats also revealed early development of hippocampal kindling and spontaneous cortico-hippocampal spikes, even in the chronic EEG recordings. Immunoreactivities for N-methyl-D-aspartate receptor (NMDAR) subunit 2B and glutamate/aspartate transporter in the lesions were significantly enhanced compared with the nonlesioned side, even in the absence of electrical stimulation. After electrical stimulation, NMDAR1 and 2B were markedly upregulated not only in the FCD, but also in the hippocampus. Conclusions: Prenatal freeze lesioning of the brain produces a severe neuronal migration disorder, closely mimicking human FCD. Our model suggests that FCD is associated with vulnerability to epilepsy, and may augment hippocampal epileptogenicity.

We report a 72-year-old man with eosinophilic myositis (EM). At age 71 he noticed a painful nodule in his left calf. A biopsy (first biopsy) showed marked infiltration of mononucleated cells and necrotic muscle fibers. Several phagocytosed fibers were also seen. He was diagnosed as having myositis. The painful nodule disappeared spontaneously. At age 72, he again had a painful nodule, but this time in his right calf; again, this disappeared spontaneously on the first admission. Just after discharge, he noted painful nodules in the left thigh and right anterior tibial muscles and was again admitted (second admission). Neurological examination revealed mild proximal-dominant weakness in all four extremities but no other abnormalities. Laboratory studies showed elevated creatine kinase (CK) level (38,803 U/l; normal 62-287) and positive Jo-1 antibody, but no eosinophilia. Needle electromyography of the limb muscles showed myogenic patterns. Magnetic resonance imaging of the lower limbs demonstrated several T2-high and gadolinium (Gd)-enhanced lesions. Muscle biopsy (second biopsy) from the left quadriceps femoris showed marked infiltration of eosinophils; he was diagnosed as having EM. Administration of prednisolone was initiated at 60 mg/day and then gradually tapered. After starting treatment with steroids, his muscle weakness gradually ameliorated, CK level dramatically decreased, and the nodules disappeared. Clinically, the patient had developed localized nodular myositis (LNM), but pathologically it was EM without peripheral blood eosinophilia and positive Jo-1 antibody that is occasionally found in polymyositis (PM). Thus, this patient demonstrated overlapping characteristics of EM, LNM, and possibly PM, suggesting that a common mechanism underlay these conditions. As discussed, the involvement of eosinophils in three inflammatory myopathies was indicated.

Focal cortical dysplasia (FCD) is an important cause of intractable epilepsy. Previous rat studies have utilized freeze lesioning of neonatal animals to model FCD; however, such models are unable to demonstrate spontaneous seizures without seizure-provoking events. Therefore, we created an animal model with multiple FCD, produced during embryonic development, and observed whether spontaneous seizures occurred. Furthermore, we examined the relationship between FCD and epileptogenesis using immunohistochemistry. At 18 days postconception, a frozen metal probe was placed bilaterally on the scalps of Sprague-Dawley rat embryos through the uterus wall to produce multiple FCD. Eleven of 16 rats showed spontaneous seizures arising in the hippocampus from postnatal day47. Movement cessation followed by sniffing and mastication, culminating in wet-dog shaking, was seen during the hippocampal EEG discharges. Alterations in the levels of glutamatergic and GABA-ergic receptors were investigated during growth. We created an animal model showing spontaneous seizures without a provoking event except for the existence of cortical dysplasia, and without a genetic or general systematic cause like MAM injection or irradiation. The seizures resembled human temporal lobe epilepsy both clinically and on EEG. This model should enable better clarification of the mechanisms underlying the development of human epilepsy.

Adult neurologists routinely encounter cases of epilepsy. Appropriate therapy based on a correct diagnosis is very important, and is aided by knowledge of seizure semiology and the correct reading of EEG findings. Many factors need to be considered when deciding upon a treatment regime for adult epilepsy patients, such as employment, marriage, child bearing status, and co-existent disease in elderly patients. Four new antiepileptic drugs (AEDs), which have been used in other countries for more than 10 years, have been authorized for use over the past few years in Japan. Because new AEDs also have interactions and side effects, administration to patients must be carried out based on an understanding of drug actions and interaction mechanisms. Surgical treatment should be considered for drug resistant patients, especially for those suffering from temporal lobe epilepsy with hippocampal sclerosis. For drug resistant patients who are not candidates for resection therapy, we can undertake vagus nerve stimulation therapy, which has recently been authorized for use in Japan. Other electrical stimulation therapies, targeting the anterior nucleus of thalamus, hippocampus and epileptic neo-cortex, have been investigated and are now under study in the USA. Neurologists should be aware of such newly introduced therapies in giving a better quality of life for epilepsy patients.

cle spasms were frequently experienced. Her neck, trunk and extremities showed rigido-spasticity. Painful spasms were easily elicited by auditory, visual and tactile stimuli. Reflex myoclonus was also observed. Hyper-reflexia was seen in 4 limbs and pathological reflexes were bilaterally positive. Sensation was normal. Blood cell counts and serum chemistry revealed no abnormalities. The anti-glutamic acid decarboxylase (GAD) antibody level was 9,020 U/ml in serum and 109 U/ml in cerebrospinal fluid (normal 1.5). Anti-acetylcholine receptor antibody was positive at a titer of 11.9 nmol/l (normal 0.2). Serum anti-amphiphysin antibody was negative. Cerebrospinal fluid analysis showed no abnormality. Head and spinal cord MRI was normal. There was no slowing in electroencephalography. Nerve conduction study was normal. There was no decrease in compound muscle action po tential on repetitive stimulation of the median nerve. Needle electromyography revealed continuous contraction of both agonist and antagonist muscles in the extremities ( fig. 1 A). Thoracic CT depicted the presence of thymoma in the anterior mediastinum ( fig. 1 B).

We report the case of a 30-year-old man who developed severe dysphagia owing to neuroborreliosis. He showed dysphagia, diplopia, hiccups, and walking difficulty Neurological examination revealed mild disturbance of consciousness, diplopia on left lateral gaze, left-side-dominant blephaloptosis, gaze-evoked horizontal nystagmus on left lateral gaze, mild bilateral muscle weakness, palatoplegia, dysphagia, dysarthria, and truncal ataxia An increased pharyngeal reflex caused dysphagia in this patient. An EEG revealed intermittent high amplitude slow wave activity. However, head MRI, blood count, serum chemistry, and cerebrospinal fluid examination showed no abnormality. Initially, brainstem encephalitis with unknown etiology was diagnosed. The hiccups, diplopia, and ptosis were improved by corticosteroid therapy, but other symptoms were refractory to corticosteroid therapy and IVIg. After these immunotherapies, anti-Borrelia IgG and IgM antibodies were found to be positive, and symptoms, including dysphagia, were improved by doxycycline and cefotaxime. Because the clinical symptoms of Borrelia infection are widely variable, neuroborreliosis should be considered in patients with brainstem encephalitis refractory to conventional immunotherapies.

We report a case of mononeuropathy multiplex with idiopathic thrombocytopenic purpura (ITP). A 78-year-old man developed patches of purpura on his left forearm. His platelet count was 11,000/microl and platelet-associated IgG was elevated. He was diagnosed as having ITP. At the beginning of the following month, he noticed dysesthesia and weakness of his left finger and left lower limb, as well as dysesthesia of his bilateral lower thighs. Neurological examination revealed weakness in the area of the left ulnar nerve and of the left anterior tibial muscle. Dysesthesia presented in the area of the left ulnar nerve and bilateral superficial peroneal nerves. Nerve conduction studies revealed asymmetric axonal sensorimotor neuropathy (mononeuropathy multiplex). A cerebrospinal fluid specimen showed a normal cell count and normal protein level Serum anti-ganglioside antibody was negative. The platelet count gradually increased after the introduction of corticosteroid therapy. His neurological deficits and electrophysiological findings also improved. Immune-mediated neuropathy was suggested as the cause of his mononeuropathy multiplex with ITP.

Magnetoencephalographic (MEG) activities were recorded in five patients with cerebral arteriovenous malformation (AVM) who presented with epilepsy and no clinical history of intracranial hemorrhage, using a 37-channel DC superconducting quantum interference device (SQUID) system. While scalp-recorded electroencephalograms (EEG) failed to reveal paroxysmal discharge, MEGs demonstrated localized high frequency magnetic activity (HFMA). Magnetic source imaging (MSI) depicted the accumulation of equivalent current dipole (ECD) originating from HFMA around the nidus, and the ECD localization agreed well with spike localization on intraoperative electrocorticography (ECoG). These areas corresponded with the areas of hypoperfusion on single photon emission tomography and the intraoperative laser Doppler flow meter. We discussed the application of MEG in estimating interictal paroxysmal activity sources in patients with AVM and addressed the questions of its reliability and validity in source localization.

Focal cortical dysplasia (FCD) is often associated with severe partial epilepsy. In this study, we performed magnetoencephalography (MEG) and electrocorticogrsphy (ECoG) on four patients with FCD-associated epilepsy to confirm the 'intrinsic' epileptogenicity of FCD. In all patients, we determined the three-dimensional locations of the magnetic sources of the interictal paroxysmal activities by a single dipole model, and then the estimated dipole localization was superimposed on the magnetic resonance image. The dipole clusters were located in the T2-prolonged lesions, namely in the FCD lesions themselves. All patients underwent surgery for their medically intractable epilepsy, and the acute and/or chronic ECoG were thereafter recorded. Either frequent or continuous paroxysmal activities were recorded from the ECoG electrodes which were placed over the surface of the FCD lesion, while few paroxysmal activities were observed on the normal appearing adjacent cortex. Intraoperative depth recordings were performed in a patient with the needle electrode inserted into the FCD lesion and they revealed these paroxysmal foci to be located not on the cortical surface but at a depth of 15 mm from the cortical surface where both abnormal giant neurons and bizarre large eosinophilic cells (so-called balloon cells) were also prominently observed on the postoperative histological sections. Following a lesionectomy combined with the removal of the underlying white matter, three patients demonstrated a favorable seizure outcome. Our findings thus suggest the FCD lesions to be highly and intrinsically epileptogenic lesions.

BACKGROUND Although magnetoencephalography (MEG) provides accurate information on the spatial distribution and temporal patterns of the “interictal” epileptic activities, it is interictal in nature and therefore also prone to all the problems associated with interictal data. METHODS We investigated the subclinical “ictal” epileptic activity with a 37-channel, large-array biomagnetometer and mapped the data onto a three-dimensional image in a patient with intractable frontal lobe epilepsy. Dipole source localization was calculated based on magnetic fields for both the interictal and subclinical ictal activities. RESULTS The current dipoles of the interictal MEG spikes (MEG irritative zone) were revealed to be scattered in the left anterior frontal lobe, whereas that of the subclinical ictal onset (MEG subclinical ictal onset zone) was surrounded by the interictal dipole cluster. The dipole source localization of the propagating activities was not calculated with a single dipole model. The MEG subclinical ictal onset zone correlated well with the ictal onset zone subsequently recorded by invasive subdural electrophysiological monitoring. After multiple subpial transection of the deduced epileptogenic area, a dramatic reduction of the seizures occurred. CONCLUSION These results illustrate the potential of MEG for localizing the epileptogenic foci with high spatial and temporal resolution.

Surgery for lesions either within or close to the central sulcus of the brain always carries the risk of inducing iatrogenic motor or sensory deficits. We performed advanced magnetic source imaging (MSI) of the somatosensory cortex combined with 3-dimensional (3-D) surface anatomy scanning (SAS) of magnetic resonance imaging on 9 patients who had peri-Rolandic lesions, including 7 tumor cases, 1 arteriovenous malformation and 1 focal cortical dysplasia. 3-D MSI mapped out the entire somatosensory homunculus and localized the lesion on a cortical surface image. The results were then used for developing an appropriate surgical strategy and also as a reference in the operating room. This relationship and deduced localization were both confirmed by a cortical recording of the somatosensory evoked potentials at the time of surgery. Case histories of selected patients are briefly reported to demonstrate how the method can be used to improve the safety of surgical excisions of peri-Rolandic lesions. MSI on SAS including the cortical veins, was thus found to provide a readily interpretable presurgical road map of the cortical surface which compares favorably to that of intraoperative brain mapping.

In order to localize the generator site of epileptiform discharges, we applied the techniques of jerk-locked back averaging (JBA) of magnetoencephalographic (MEG) activities and dipole source localization in a patient with epilepsia partialis continua (EPC), who showed continuous, focal myoclonic jerks in the right arm. The myoclonic discharges in the right muscle were used as a trigger pulse. JBA revealed consistent EEG and MEG transients that coincided consistently and constantly preceded the myoclonic jerks. The estimated dipoles of MEG were localized in a restricted area in the left precentral area, which closely correlated with the area of epileptic discharges recorded in electrocorticography. Therefore, JBA of MEG is considered to be a useful non-invasive method for localizing the epileptogenic area in EPC.