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The recent findings on subtraction ictal SPECT and ictal near-infrared spectroscopic topography in patients with West syndrome were summarized and its availability for presurgical evaluation was discussed. The subtraction ictal SPECT study in patients with West syndrome demonstrated the cortical epileptic region and subcortical involvement, which may consist of epilepsy networks related to the spasms. Moreover, subtraction ictal SPECT may have predictive power for short-term seizure outcome. Patients with a symmetric hyperperfusion pattern are predicted to have a better seizure outcome, whereas patients with asymmetric hyperperfusion pattern may develop poor seizure control. Importantly, asymmetric MRI findings had no predictive power for seizure outcome. Multichannel near-infrared spectroscopic topography applied to the patients with West syndrome detected an increase in regional cerebral blood volume in multiple areas which were activated either simultaneously or sequentially during spasms. Topographic changes in cerebral blood volume were closely correlated with spasm phenotype, suggesting that the cortex is involved in the generation of spasms. In conclusion, subtraction ictal SPECT may be considered as a useful tool for presurgical evaluation of patients with West syndrome and investigation of the pathophysiology of spasms. The ictal near-infrared spectroscopic topography should be more investigated to see if this is useful tool for presurgical evaluation.

This report describes a patient with Gaucher disease type II who developed severe rhabdomy- olysis. We treated him successfully and meas- ured various cytokine and chemokine levels sequentially to elucidate the pathophysiology of rhabdomyolysis. The serum levels of interleukin- 6, − 8, − 10, granulocyte colony-stimulating fac- tor, interferon- γ , and monocyte chemoattractant protein-1 were markedly elevated in the early phase of rhabdomyolysis. These fi ndings indicate that cytokines and chemokines are related to the massive myolysis and regenerating process. A viral infection may have triggered rhabdomy- olysis through exaggerated activation of macro- phages in our patient. The profi les of cytokines and chemokines should be examined in further cases to increase our understanding of the patho- physiology of rhabdomyolysis.

Summary Purposes The aims of the study were to evaluate the detectability of focal leading activity in three cases of West syndrome having focal abnormal activity on EEG by comparing subtraction ictal images and raw ictal images, and to interpret the results in 16 cases. Methods Subtraction images were constructed using iNeurostat (revision 2). Results In three cases with focal abnormal activity on EEG, subtraction ictal images reflected the EEG findings; in contrast, raw ictal images did not. Diverse degrees of cortical hyperperfusion, ranging from zero to 10 sites, seen in the other 13 cases seemed to reflect spasm pathophysiology and rapid spasm propagation. Subtraction ictal images also allowed the ready detection of hyperperfusion of subcortical structures and of a tight cortico-subcortical relationship in a subset of cases. Conclusions We showed the superiority of subtraction ictal images in detecting the focal epileptic region and in showing propagation pathways from the cortex to subcortical structures. A subset of spasms in WS may be focal cortical-onset secondarily generalized seizures. We believe that subtraction analysis is valuable in patients with complex WS who have partial seizures and spasms simultaneously along with focal epileptic EEG activity, as they will likely be candidates for epilepsy surgery.

Objective To evaluate whether the orientation of interictal spikes, localized in major sulci by magnetoencephalography (MEG), predicts the epileptogenic side of the sulcal wall. Methods Sixteen epilepsy patients were analyzed in whom equivalent current dipoles (ECDs) of MEG spikes were localized on the central (four patients), interhemispheric (4), or sylvian fissure (8); and the epileptogenic side across the sulci had been confirmed by seizure semiology, structural lesions, or intracranial electroencephalography (EEG). ECD was classified as epileptogenic side or normal side oriented and correlated to the scalp EEG map. Results All central ( n =50) and interhemispheric ( n =83) spike ECDs were oriented toward the epileptogenic side at peak latency. In scalp EEG, 91% of the spikes showed radial pattern of broad negativity above the sulcus whereas 9% showed tangential pattern with positive maximum above the epileptogenic side. Sylvian spikes were only found in patients with temporal lobe epilepsy (TLE). In sylvian spikes ( n =220), 73% of ECDs were oriented toward the epileptogenic side, whereas 27% were oriented toward the normal side. Conclusions In central and interhemispheric spikes, epileptogenic side cortex may be gross surface negative through the sulcal wall to the adjacent gyrus. Inconsistent orientation of the sylvian spikes suggests a complex pattern of spike propagation in TLE. Significance ECD orientation of central and interhemispheric spikes in MEG may predict the epileptogenic side.

Interhemispheric time difference (ITD) measured by electroencephalography (EEG) and magnetoencephalography (MEG) was compared to seizure outcome after callosotomy. Two patients with frequent drop attacks underwent simultaneous EEG and MEG before and after total callosotomy. ITDs in 30 bilateral synchronized (BS) discharges were calculated independently by EEG and MEG. As minimum transcallosal conduction time was suggested to be approximately 20 msec, BS discharges were classified into five categories according to ITD and side: left- or right-leading long (300 to 80 msec), left- or right-leading moderate (80 to 20 msec), and negligible (

The purpose of this study is to investigate the primary somatosensory function in patients with unilateral polymicrogyria. Somatosensory evoked fields (SEFs) due to median and posterior tibial nerve stimulation were compared in the normal and dysplastic cortices of five patients with unilateral polymicrogyria. SEFs were observed in all five normal hemispheres and three dysplastic hemispheres. Latencies of N20m and P38m, the first cortical components of and SEFs for median nerve and tibial nerve stimulation, were all within the normal range in both normal and dysplastic hemispheres. The amplitudes of the N20m and P38m in the dysplastic hemispheres were smaller in one patient and larger in two patients compared to the normal hemispheres. Equivalent current dipoles of N20m and P38m were localized on the anatomical central sulcus of the normal hemispheres and over the central area of the dysplastic hemispheres. P38m dipoles were localized medial and upward to the N20m dipole in both normal and dysplastic hemispheres. N20m dipole orientation was normal in all normal hemispheres and in one dysplastic hemisphere, but abnormally inferior in two dysplastic hemispheres. P38m dipole had normal medial orientation in all hemispheres except one dysplastic hemisphere. Abnormality of the primary somatosensory function in the dysplastic cortex of patients with unilateral polymicrogyria was clearly demonstrated by magnetoencephalography with high resolution in time and space. The normal somatotopic arrangement was preserved.

To clarify the pathophysiology of tonic spasms, 21 patients with West syndrome were analyzed using ictal and interictal single photon emission computed tomography (SPECT). We focused on whether ictal perfusion changes were observed in the focal cortical region. Eight of the patients studied showed definite focal cortical ictal hyperperfusion, indicating that there is a unique subset of West syndrome that can be classified as infantile localization-related epilepsy. Of those eight patients, only two showed asymmetric spasms, suggesting that seizure symptomatology in infants gives only limited information on the localization-related nature of epilepsy. Furthermore, the activation of subcortical structures by focal cortical regions might be attributable to the symmetric seizure phenomena. Thirteen patients showed a diffuse pattern in their ictal SPECTs; this probably included patients with diffuse hyperperfusion and those with no changes. The following have yet to be determined: (1) whether West syndrome is divided into subgroups based on the origin of spasms, in that some patients have the origin in the cortical hemisphere and some have the origin in structures other than the cortical hemisphere, such as the brain stem; (2) whether differences in ictal SPECT patterns reflect a unique nature of tonic spasms in West syndrome, where tonic spasms appear in clusters and the interval of each spasm is different among each patient.

A 23-year-old woman with refractory complex partial seizures underwent implantation of subdural grid electrodes over the left hemisphere to map epileptic foci and language function. Aphasic symptoms occurred during stimulation of the basal temporal area, which were always associated with intrastimulus remote discharges (ISRDs) in the classical posterior language area. No sequential language deficits occurred after anterior temporal lobectomy including the basal temporal area. These results suggest a close functional relationship between the basal temporal area and posterior language area in patients with temporal lobe epilepsy. ISRDs may explain the paradoxical observation that resection of the basal temporal language area results in no language deficits.

We report on 3-year-old Japanese twin brothers suffering from ictal vomiting during infancy. Intractable seizures, including generalized tonic-clonic convulsions, and myoclonic seizures persisted in late infancy. The diagnosis of severe myoclonic epilepsy in infancy was confirmed by detecting a mutation in the voltage-gated sodium channel alpha subunit type gene. This is the first case report addressing ictal vomiting as the initial presentation of severe myoclonic epilepsy in infancy.

We used tacrolimus to successfully treat a patient with childhood-onset oropharyngeal myasthenia gravis (MG). A girl (2 years, 5 months old) with oropharyngeal MG responded partially to treatment including pyridostigmine bromide, intravenous immunoglobulin, and prednisolone (2 mg/kg/day) for 7 weeks, but this resulted in worsening of her eye symptoms. By contrast, tacrolimus at 2 mg/day resulted in complete remission of the MG, which made it possible to reduce the dose of prednisolone. This is a rare report of the use of tacrolimus as an effective treatment for patients with intractable childhood-onset MG.

A case of acute encephalopathy with selective bilateral symmetrical striatal lesions is reported. The patient was a previously healthy 4-year-old boy who became obtunded after a febrile illness and fell into a state of delirium with severe pain in the feet. He showed abnormal postures: hyperextension of the neck and upper limbs and extreme flexion of both lower limbs, and abnormal involuntary movements of the limbs: tremor, athetotic movement and right hemiballismus. Analysis of serum antibody titres suggested recent primary infection of herpes simplex type 1 (HSV-1). Cranial T2-weighted magnetic resonance imaging (MRI) demonstrated areas of high-signal intensity involving the whole basal ganglia bilaterally. He showed rapid clinical improvement after the initiation of corticosteroid therapy; complete clinical recovery was noted 3 months after the onset. Serial MRI studies demonstrated a rapid reduction of the lesions, resulting in only slight T2-hyperintense areas in both caudate nuclei. The pathogenesis of the disorder remains unknown, though an autoimmune mechanism has been speculated. The clinical and laboratory findings in this case suggested a possible role of HSV-1 in the pathomechanism of the disorder and a beneficial effect of early corticosteroid therapy.

An 11-year-old boy presented with acute dysautonomia manifesting as severe orthostatic hypotension following fever. Serial orthostatic tests with measurement of the coefficient of variation in the R-R intervals showed improvement after one course and complete recovery after two courses of intravenous high-dose immunoglobulin therapy (IVIg). Repeated courses of IVIg should be considered to treat this disorder if spontaneous remission does not occur.

We have successfully eliminated herpes simplex virus-2 from the central nervous system in a case of neonatal herpes simplex virus encephalitis with a continuous acyclovir infusion. A male infant delivered from a healthy 22-year-old woman without genital or systemic herpes symptoms around delivery began to develop fever and intractable seizures. He was started on intermittent intravenous acyclovir (20 mg/kg every 8 h) based on the diagnosis of herpes encephalitis. The virus was not eliminated with intermittent acyclovir and vidarabine, while continuous acyclovir was ultimately effective in eliminating herpes simplex virus from his central nervous system. This report demonstrates the efficacy of continuous acyclovir infusion in neonatal herpes simplex virus encephalitis.

Although magnetoencephalography (MEG) and electroencephalography (EEG) have been available for decades, their relative merits are still debated. We examined regional differences in signal-to-noise-ratios (SNRs) of cortical sources in MEG and EEG. Data from four subjects were used to simulate focal and extended sources located on the cortical surface reconstructed from high-resolution magnetic resonance images. The SNR maps for MEG and EEG were found to be complementary. The SNR of deep sources was larger in EEG than in MEG, whereas the opposite was typically the case for superficial sources. Overall, the SNR maps were more uniform for EEG than for MEG. When using a noise model based on uniformly distributed random sources on the cortex, the SNR in MEG was found to be underestimated, compared with the maps obtained with noise estimated from actual recorded MEG and EEG data. With extended sources, the total area of cortex in which the SNR was higher in EEG than in MEG was larger than with focal sources. Clinically, SNR maps in a patient explained differential sensitivity of MEG and EEG in detecting epileptic activity. Our results emphasize the benefits of recording MEG and EEG simultaneously.

Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare leukoencephalopathy presenting in the infantile period and characterized by diffuse cerebral hypomyelination, and atrophy of the basal ganglia and cerebellum. As patients with H-ABC lack remarkable laboratory findings, the diagnosis is based on brain magnetic resonance imaging findings alone. Only eight cases have been reported in the literature, and thus the natural course and treatment of this disease are not fully understood. We report a 35-month-old boy with H-ABC who had hemidystonia, hypomyelination, and cerebellar ataxia. We diagnosed H-ABC after considering a thorough differential diagnosis, excluding other diseases involving hemidystonia, hypomyelination, and cerebellar ataxia. Furthermore, technetium-99m ethyl cysteinate dimmer-single-photon emission computerized tomography (Tc-ECD-SPECT) and positron emission tomography with fluorodeoxyglucose (18)F (FDG-PET) revealed decreased blood flow and glucose metabolism in the bilateral lenticular nucleus, thalamus, and cerebellum. A peroral levodopa preparation containing carbidopa (levodopa-carbidopa) was effective at ameliorating and stopping the progression of the patient's dystonia (final effective doses: levodopa, 200 mg/day and carbidopa, 20 mg/day). This is the first case report of a Japanese patient with H-ABC and treatment for this disease. Levodopa-carbidopa may be an effective treatment for H-ABC.

Interhemispheric time difference (ITD) measured by electroencephalography (EEG) and magnetoencephalography (MEG) was compared to seizure outcome after callosotomy. Two patients with frequent drop attacks underwent simultaneous EEG and MEG before and after total callosotomy. ITDs in 30 bilateral synchronized (BS) discharges were calculated independently by EEG and MEG. As minimum transcallosal conduction time was suggested to be approximately 20 msec, BS discharges were classified into five categories according to ITD and side: left- or right-leading long (300 to 80 msec), left- or right-leading moderate (80 to 20 msec), and negligible (20 msec). In Case 1 before callosotomy, EEG detected 77% negligible and 23% right-leading moderate BS discharges, whereas MEG detected 30% and 63%, respectively. After callosotomy, drop attacks reduced remarkably and EEG and MEG detected no BS discharges. In Case 2 before callosotomy, EEG detected 77% negligible and 23% moderate BS discharges, whereas MEG detected 80% and 20%, respectively. After callosotomy, drop attacks recurred 2 months later and EEG and MEG detected left- and right-leading long BS discharges (63% by EEG and 56% by MEG). MEG detected a large number of BS discharges with moderate ITD before surgery in Case 1, suggesting that the transcallosal pathway was the main pathway for the synchronization, whereas the negligible ITD in Case 2 excludes transcallosal propagation. BS discharges with longer ITD after surgery in Case 2 suggest a persistent poly-synaptic non-transcallosal pathway. MEG with higher spatial resolution than EEG may provide surgical indications for callosotomy.

Summary: Purpose: To investigate spatial and temporal cortical activity during clusters of naturally occurring epileptic spasms in patients with West syndrome (WS) by using multichannel near-infrared spectroscopy (mNIRS). Methods: Conventional magnetic resonance imaging (MRI) and interictal and ictal single-photon emission computed tomography (SPECT) were carried out in three patients with WS. Thereafter, cortical hemodynamics during naturally occurring epileptic spasms were measured by mNIRS with simultaneous video/electroencephalographic (EEG) monitoring. Results: Ictal SPECT revealed multiple hyperperfused areas within the cortex. With the use of mNIRS, an increase in regional cerebral blood volume (CBV) was observed in these areas, which is representative of cortical activation. The increase in CBV was accompanied by an increase in the concentrations of both oxy- and deoxyhemoglobin. The following heterogeneous regional changes in CBV during ictus were observed: (a) transient increases that were synchronized with spasms; (b) a gradual increase during an ictal event that fluctuated in synchrony with spasms; and (c) a combination of transient and gradual increases. An increase in regional CBV occurred in multiple areas that were activated either simultaneously or sequentially during an ictal event. Topographic changes in CBV were closely correlated with the phenotype of the spasm. Conclusions: During ictal events, multiple cortical areas were activated simultaneously or sequentially. The pattern of cortical activation closely affected the phenotype of the spasm, which suggested that the cortex was involved in the generation of spasms.

We evaluated the source distribution of benign rolandic spikes of childhood along and across the central sulcus in 15 patients, aged between 7 and 15 years, who suffered from seizure disorders. Previous routine EEG showed centrotemporal spikes, but none of them had major abnormalities on brain magnetic resonance imaging or neurological deficits. The equivalent current dipoles (ECDs) of the spikes measured by whole-head magnetoencephalography (MEG) were compared to the spike distributions detected by simultaneous scalp EEG according to the international 10–20 system. Locations and orientations of the MEG spikes corresponded to the EEG spike distribution as follows: superiorly oriented spike MEG dipoles in the opercular area corresponded to T3/4 negative peaks (8 spike groups in 6 patients); anteriorly oriented spike dipoles in the rolandic area corresponded to C3/4 or P3/4 negative peaks (17 spike groups in 13 patients); laterally oriented spike dipoles in the interhemispheric area corresponded to Cz/Pz negative peaks (4 spike groups in 3 patients); and others (4 spike groups in 4 patients). Rolandic spikes include three main types according to the ECD location from the opercular to the interhemispheric areas. The functional anatomy of benign rolandic spikes was correlated with partial seizure semiology. All three rolandic spike types can be explained by a precentral origin, assuming that the surface negative potential is continuous from the gyral to fissural cortices.

We report on metabolic changes in the brain of a boy with Menkes disease. He was treated with parenteral copper (Cu)-histidine supplementation, from 5 months of age, and assessed with proton magnetic resonance spectroscopy ((1)H-MRS). The single-voxel (1)H-MRS before treatment revealed an accumulation of lactate and a reduced N-acetyl aspartate (NAA)/total creatine (tCr) ratio with a z-score of -3.0. During treatment, the lactate signal faded away, whereas the NAA signal gradually increased to a z-score of -1.5 at 120 days of treatment. The choline/tCr ratio did not deviate much initially (z-score +0.5), but the ratio increased markedly during treatment (z-score +4.8). Consequently, the Cu-histidine therapy initiated after the critical period still improved the neuronal metabolism, suggesting that some Cu was delivered to neurons. Nevertheless, the brain atrophy, impaired myelination, and severe neurological symptoms were not ameliorated.

The progression of muscular weakness of patients suffering from muscular dystrophies directly correlates with the progressive loss of myofibers, accompanied by fibrosis. Since transforming growth factor beta1 (TGF-beta1) promotes tissue fibrosis, we measured the plasma TGF-beta1 level in patients with various muscular dystrophies in order to determine whether the level is elevated in patients with muscular dystrophy and if the level reflects the severity of tissue fibrosis. The plasma TGF-beta1 level was significantly elevated in patients with Duchenne muscular dystrophy and congenital muscular dystrophy (CMD), but not in those with Becker muscular dystrophy. Growth factors related to muscle fiber regeneration and fibrosis might be a key factor in the progression of muscular dystrophy and could be a target for therapeutic studies.

Purpose: Attention has recently been directed to pediatric cases of a peculiar type of postencephalitic or encephalopathic epilepsy proposed by Awaya et al. This type is characterized by an abrupt onset of frequent refractory complex partial seizures followed by the development of partial epilepsy. There is no seizure-free interval, and the seizure-type is fundamentally the same as that in the acute phase. Therefore, it is hard to distinguish the encephalitis/encephalopathy-related seizures from epileptic ones as its sequela. The pathomechanism of this syndrome remains unknown, even though viral infection has been postulated. After studying our cases, we looked for those in this category to elucidate its clinical characteristics. Methods: Five cases (two boys and three girls) with this syndrome were selected for this study from 53 pediatric patients with acute encephalopathy or encephalitis. These patients had been treated at Sendai City Hospital during the years from 1986 to 1996. This is an incidence of 9.4%. Clinical features such as cerebrospinal fluid and EEG findings, neuroimaging, prognosis of epileptic seizures, and mental status were investigated. Results: The age at onset ranged from 4 to 14 years. All cases had no significant previous or family history. In all cases, there was an antecedent infection. Seizure type during the acute phase consisted of complex partial seizures with or without secondarily generalized tonic-clonic convulsions. All had a high fever during the acute stage. The interictal EEG revealed generalized high-voltage slow waves, and the ictal EEG showed diffuse spike-and-wave discharges developing from temporal or occipital spike foci. Mild cerebrospinal fluid pleocytosis was noted in two cases. The five cases were divided into two groups according to their clinical severity. In the severe group (three cases), the seizures during the acute phase were highly refractory. Pentobarbital (PTB) was administered to two of the three cases. The duration of the acute phase ranged from 1 to 5 months. The computed tomography (CT) and magnetic resonance imaging (MRI) showed diffuse cerebral atrophy. In one case, localized lesions also were detected in the right temporal and both occipital lobes. The lesions coincided with EEG spike foci, which persisted throughout the course. All three had profound mental deterioration and intractable partial epilepsy during the chronic phase. On the other hand, in the mild group (two cases), seizures during the acute phase were suppressed by intravenous midazolam (MDL) or lidocaine. The duration of the acute phase was shorter (12 and 24 days). Neither MRI abnormalities nor mental deterioration was observed. Epileptic seizures after the convalescent phase were rare. Conclusions: Among the three severe cases, one corresponded well to Awaya's description, and the others appeared to be more severe. The mild group apparently showed less severity. After reviewing the literature, previously reported patients were no less severe than Awaya's original cases. Therefore it is noteworthy that the two milder cases might indicate that this syndrome has a wider clinical spectrum than previously suspected. The pathogenesis of the disorder could not be clarified by this study. However, after judging the focal brain lesions detected on the MRI in one case, the focal encephalitic process and localization-related epilepsy as its sequela might offer a partial explanation for the pathogenesis of this disorder.