Masako Kinoshita

Low-frequency repetitive transcranial magnetic stimulation for seizure suppression in patients with extratemporal lobe epilepsy-—A pilot study

We evaluated the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on seizure frequency in adult patients with medically intractable extratemporal lobe epilepsy (ETLE). Seven patients with medically intractable ETLE received low-frequency rTMS at 0.9 Hz, basically two sets of 15 min stimulation per day for five days in a week, with the stimulus intensity of 90% of resting motor threshold (RMT). The number of seizures during two weeks before and after the stimulation of one week was compared. Furthermore, RMT and active motor threshold (AMT) were measured before and after rTMS for each daily session. After low-frequency rTMS of one week, the frequency of all seizure types, complex partial seizures (CPSs) and simple partial seizures was reduced by 19.1, 35.9 and 7.4%, respectively. The patients with smaller difference between RMT and AMT before rTMS had higher reduction rate of CPSs. A favorable tendency of seizure reduction, though not statistically significant, during two weeks after low-frequency rTMS was demonstrated in medically intractable ETLE patients. As far as CPSs are concerned, smaller decrease of motor threshold by voluntary muscle contraction was associated with better response to rTMS.

Electric Stimulation on Human Cortex Suppresses Fast Cortical Activity and Epileptic Spikes

Summary:  Purpose: To investigate underlying mechanisms and adequate parameters for electric cortical stimulation to inhibit epileptic focus in humans.

Improved cerebral function in mesial temporal lobe epilepsy after subtemporal amygdalohippocampectomy

The functional changes that occur throughout the human brain after the selective removal of an epileptogenic lesion remain unclear. Subtemporal selective amygdalohippocampectomy (SAH) has been advocated as a minimally invasive surgical procedure for patients with medically intractable mesial temporal lobe epilepsy (MTLE). We evaluated the effects of subtemporal SAH on cerebral glucose metabolism and memory function in 15 patients with medically intractable MTLE with hippocampal sclerosis using [(18)F]-fluorodeoxyglucose PET (FDG-PET) and the Wechsler Memory Scale-Revised. The patients were evaluated before and 1-5 years (mean 2.6 years) after surgery. In patients with MTLE of the language-dominant hemisphere, the basal temporal language area was preserved by this surgical approach. Voxel-wise comparison of FDG-PET images was conducted using SPM5 to identify the brain regions showing postoperative changes in glucose metabolism (height threshold, P = 0.01 corrected for multiple comparisons; extent threshold, 100 voxels). During spatial normalization of the postoperative FDG-PET images, we used cost-function masking to minimize any inappropriate image distortion as a result of the abnormal signal within the surgically resected region. Postoperative glucose metabolism increased in extratemporal areas ipsilateral to the affected side, such as the dorsolateral prefrontal cortex, and the dorsomedial and ventromedial frontal cortices. Glucose metabolism also increased in the bilateral inferior parietal lobules and in the remaining temporal lobe regions remote from the resected mesial temporal region, such as the superior temporal gyrus and the temporal pole. By contrast, postoperative glucose metabolism decreased only in the mesial temporal area adjacent to the resected region. Postoperative verbal memory, delayed recall and attention/concentration scores were significantly better than preoperative scores regardless of the resected side. This study suggests that the selective removal of the epileptogenic region in MTLE using a subtemporal approach improved cerebral glucose metabolism in the areas receiving projections from the affected mesial temporal lobe. Cognitive improvement might result from a combination of good seizure control and minimizing the regions of the brain with postoperative functional impairment.

In vivo epileptogenicity of focal cortical dysplasia: a direct cortical paired stimulation study.

Summary:  Purpose: Alternation of the intracortical inhibitory and excitatory mechanisms in focal cortical dysplasia (FCD) has not been well elucidated in vivo in humans. We investigated in vivo alternation of these mechanisms in epileptogenesis of FCD by means of paired‐pulse direct cortical electrical stimulation.

Low-frequency electric cortical stimulation decreases interictal and ictal activity in human epilepsy

We previously reported that low-frequency electric cortical stimulation (LFECS) directly applied to the epileptic focus by means of subdural electrodes decreased the number of interictal epileptiform discharges in patients with intractable partial epilepsy. In the present study, LFECS was applied to the epileptic foci directly in four patients with medically intractable partial epilepsy through subdural electrodes and evaluated its effect on the number of interictal epileptiform discharges as well as simple partial seizures. We used alternating electric current of 0.3 ms duration presented at 0.9 Hz frequency for 250 s. LFECS did not induce seizures in any of the four patients. In one patient, the number of interictal epileptiform discharge decreased significantly by LFECS, which is in conformity with our previous report. In addition, LFECS applied to the seizure onset zone decreased the frequency of simple partial seizures in one patient. These results suggest that LFECS has an inhibitory effect not only on the interictal but also the ictal activities in patients with intractable partial epilepsy. Further study is required to determine the inhibitory effect of LFECS more in details.

Negative motor seizure arising from the negative motor area: Is it ictal apraxia?

Purpose:  Seizure manifesting motor arrest, that is, negative motor seizure (NMS), is a rare epileptic condition in which only inability to conduct voluntary movements or praxis is produced, although consciousness is preserved. The negative motor area (NMA) seems to be responsible, but its generator mechanism has not yet been clarified.

Efficacy of low-dose, add-on therapy of clobazam (CLB) is produced by its major metabolite, N-desmethyl-CLB

We evaluated the efficacy of low-dose, add-on therapy of CLB in adults with refractory epilepsy. 28 patients were included: 12 with temporal lobe epilepsy (TLE), 14 with extratemporal lobe epilepsy (ETLE) and 2 with symptomatic generalized epilepsy (SGE). CLB was added with the initial dose of 2.5 mg/day and increased to the optimal dose (mean, 5.6 mg/day). The mean observation period was 7.9 months. As compared with the baseline period, 14 out of 28 patients (50%) obtained an obviously good seizure control: 6 seizure free and 8 more than 50% of seizure reduction. The 14 patients comprised of 4 TLE, 8 ETLE and 2 SGE. In seizure type analysis, 26% of complex partial seizures (CPS), 64% of simple partial seizures (SPS) and 86% of generalized tonic-clonic seizures (GTC) showed a good control. Blood level of N-desmethyl-CLB in the steady state was higher in seizure-free group of 6 patients, and N-desmethyl-CLB blood level/dose per kg body weight correlated significantly to seizure control (p=0.0167). Our data show that even in low dose CLB was effective to patients with refractory epilepsy who had higher blood level of N-desmethyl-CLB.

Generators and temporal succession of giant somatosensory evoked potentials in cortical reflex myoclonus: Epicortical recording from sensorimotor cortex

OBJECTIVE To clarify the generator mechanism of giant somatosensory evoked potentials (giant SEPs) and the hyperexcitability of primary somatosensory and motor cortices (SI and MI). METHODS In a patient with intractable focal seizures manifesting cortical reflex myoclonus of the left foot, giant SEPs to left tibial nerve stimulation were epicortically recorded as a part of presurgical evaluation with subdural electrodes. RESULTS In the single pulse SEPs, enlarged P1-N1 components were observed at the foot area of the SI and MI (86.5-258.8 microV, respectively), and the peak latencies were always shorter at SI than at MI by 6 ms. Similar findings were obtained for peroneal and sural nerve stimulation. In the paired pulse SEPs, the second response was less suppressed, as compared to other interstimulus intervals (ISIs), with ISIs of 40 and 200 ms both at SI and MI. CONCLUSIONS In this particular patient, cortical hyperexcitability to somatosensory stimuli seems to originate from SI but subsequently both SI and MI are responsible for the generation of giant SEPs and cortical reflex myoclonus. SIGNIFICANCE Somatosensory and primary motor cortices both generated enhanced early cortical components of SEPs, most likely by enhancing the latter by the former.

Corticosteroid and tacrolimus treatment in neuromyelitis optica related disorders

Nervous tissue damage in neuromyelitis optica (NMO) is mediated by anti-aquaporin (AQP) 4 antibodies with activated complements. Patients with NMO require long-term immunosuppressive therapy, including oral corticosteroids (prednisolone, PSL), azathioprine (AZP), and rituximab. Tacrolimus, a macrolide immunosuppressant that inhibits the intracellular calcineurin pathway required for T lymphocyte activation, is commonly used in patients with organ transplantation or autoimmune disorders. Tacrolimus is preferable to cyclosporine in the context of adverse effects on renal function and lipid profiles.1

Methionine adenosyltransferase I/III deficiency: Neurological manifestations and relevance of S-adenosylmethionine

Methionine adenosyltransferase I/III (MAT I/III) deficiency, caused by mutations in the MAT1A gene, is an inherited metabolic disorder characterized by persistent hypermethioninemia, usually detected by newborn mass screening. There is a wide range of clinical manifestations, from completely asymptomatic to neurological problems associated with brain demyelination. Physiological role of S-adenosylmethionine (SAM), the metabolic product of methionine catalyzed by MAT, in the central nervous system has been investigated in vivo and in vitro, and case reports demonstrated an effectiveness of supplementary treatment of SAM in the improvement of neurological development and myelination. Methionine restriction can be an additional therapeutic strategy because hypermethioninemia alone may be neurotoxic; however, lowering methionine carries a risk to decrease the synthesis of SAM.