Mamiko Ishitobi

Remote discharges in the posterior language area during basal temporal stimulation.

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.

Elevated plasma levels of transforming growth factor β1 in patients with muscular dystrophy

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 β1 (TGF-β1) promotes tissue fibrosis, we measured the plasma TGF-β1 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-β1 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.

Acute encephalopathy with bilateral striatal necrosis: favourable response to corticosteroid therapy

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.

Dynamic cortical activity during spasms in three patients with West syndrome: A multichannel near-infrared spectroscopic topography study

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).

Opercular to interhemispheric source distribution of benign rolandic spikes of childhood

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.

Mechanism of tonic spasms in West syndrome viewed from ictal SPECT findings

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.

Utility of subtraction ictal SPECT images in detecting focal leading activity and understanding the pathophysiology of spasms in patients with West syndrome

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.

The effects of copper-histidine therapy on brain metabolism in a patient with Menkes disease: a proton magnetic resonance spectroscopic study

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.

Successful treatment of a 2-year-old girl with intractable myasthenia gravis using tacrolimus

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.

Abnormal primary somatosensory function in unilateral polymicrogyria : an MEG study

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.