Takamichi Yamamoto

Phenotypic Spectrum of COL4A1 Mutations: Porencephaly to Schizencephaly

Recently, COL4A1 mutations have been reported in porencephaly and other cerebral vascular diseases, often associated with ocular, renal, and muscular features. In this study, we aimed to clarify the phenotypic spectrum and incidence of COL4A1 mutations.

Comparison of dense array EEG with simultaneous intracranial EEG for Interictal spike detection and localization

PURPOSEnTo evaluate the clinical utility of dense array electroencephalography (dEEG) for the detection yield and localization of interictal spikes in mesial temporal lobe epilepsy.nnnMETHODSnWe simultaneously recorded 256-channel dEEG and intracranial electroencephalography (icEEG) implanted over the lateral and mesial temporal lobe in patients with intractable epilepsy. We calculated the dEEG spike detection rate for mesial temporal spikes which were confirmed by icEEG and applied source estimation to dEEG to compare noninvasive localization to the invasive recordings.nnnRESULTSn339 of 760 interictal spikes (45%) were detected by dEEG examining the 256-channel head surface array. The average icEEG amplitude of dEEG detectable spikes was 1083 μV, and that of dEEG undetectable spikes was 780 μV (P<0.05). All spikes detected in dEEG were localized to the temporal lobe. 295 of 339 spikes (87%) were well localized in mesial temporal lobe, close to the position confirmed by subdural electrodes.nnnSIGNIFICANCEn256-channel dEEG may provide more precise information for the localization of interictal epileptiform discharges than conventional EEG or MEG in patients with deep spike foci. 256-channel dEEG may be clinically useful in the presurgical work-up for epilepsy, providing accurate noninvasive guidance for the placement of intracranial electrodes.

Dense array EEG source estimation in neocortical epilepsy.

Rationale: Dense array EEG (dEEG) evenly covers the whole head surface with over 100 channels contributing to more accurate electrical source imaging due to the higher spatial and temporal resolution. Several studies have shown the clinical utility of dEEG in presurgical clinical evaluation of epilepsy. However validation studies measuring the accuracy of dEEG source imaging are still needed. This can be achieved through simultaneously recording both scalp dEEG with intracranial electrodes (icEEG), which is considered as the true measure of cortical activity at the source. The purpose of this study is to evaluate the accuracy of 256-channel dEEG electrical source estimation for interictal spikes. Methods: Four patients with medically refractory neocortical epilepsy, all surgical candidates, underwent subdural electrode implantation to determine ictal onset and define functional areas. One patient showed a lesion on the magnetic resonance imaging in the right parietal lobe. The patient underwent simultaneous recording of interictal spikes by both scalp 256-channelsvdEEG and icEEG. The dEEG was used to non-invasively estimate the source of the interictal spikes detected by the 256-channel dEEG array, which was then compared to the activity measured directly at the source by the icEEG. Results: From the four patients, a total of 287 interictal spikes were measured with the icEEG. One hundred fifty-five of the 287 spikes (54%) were visually detected by the dEEG upon examination of the 256 channel head surface array. The spike amplitudes detected by the 256-channel dEEG correlated with icEEG spike amplitudes (pu2009<u20090.01). All spikes detected in dEEG were localized to the same lobe correctly. Conclusion: Our study demonstrates that 256-channel dEEG can reliably detect interictal spikes and localize them with reasonable accuracy. Two hundred fifty-six-channel dEEG may be clinically useful in the presurgical workup for epilepsy and also reduce the need for invasive EEG evaluation.

Integrating Dense Array EEG in the Presurgical Evaluation of Temporal Lobe Epilepsy

Purpose. To evaluate the clinical utility of dense array electroencephalography (dEEG) for detecting and localizing interictal spikes in temporal lobe epilepsy. Methods. Simultaneous invasive and noninvasive recordings were performed across two different groups. (1) The first group underwent both noninvasive recording with 128 channels of (scalp) dEEG and invasive sphenoidal electrode recording. (2) The second group underwent both noninvasive recording with 256 channels of (scalp) dEEG and invasive intracranial EEG (icEEG) involving coverage with grids and strips over the lateral and mesial temporal lobe. A noninvasive to noninvasive comparison was made comparing the overall spike detection rate of the dEEG to that of conventional 10/20 EEG. A noninvasive to invasive comparison was made comparing the spike detection rate of dEEG to that of conventional 10/20 EEG plus sphenoidal electrodes. And finally, a noninvasive to invasive evaluation measuring the source localization ability of the dEEG using the icEEG as validation. Results. In the 128-channel dEEG study (1), 90.4% of the interictal spikes detected by the dEEG were not detected in the 10/20 montage. 91% of the dEEG-detected spikes were accurately localized to the medial temporal lobe. In the 256-channel dEEG study (2), 218 of 519 interictal spikes (42%) were detected by dEEG. 85% of these spikes were accurately localized to the medial temporal lobe, close to the position confirmed by subdural electrodes. Conclusion. Dense array EEG may provide more precise information than conventional EEG and has a potential for providing an alternative to sphenoidal electrode monitoring in patients with temporal lobe epilepsy.

Vagus Nerve Stimulation Therapy: Indications, Programing, and Outcomes

Vagus nerve stimulation (VNS) provides palliation of seizure reduction for patients with medically refractory epilepsy. VNS is indicated for symptomatic localization-related epilepsy with multiple and bilateral independent foci, symptomatic generalized epilepsy with diffuse epileptogenic abnormalities, refractory idiopathic generalized epilepsy, failed intracranial epilepsy surgery, and other several reasons of contraindications to epilepsy surgery. Programing of the parameters is a principal part in VNS. Output current and duty cycle should be adjusted to higher settings particularly when a patient does not respond to the initial setting, since the pivotal randomized trials performed in the United States demonstrated high stimulation made better responses in seizure frequency. These trials revealed that a ≥ 50% seizure reduction occurred in 36.8% of patients at 1 year, in 43.2% at 2 years, and in 42.7% at 3 years in 440 patients. Safety of VNS was also confirmed because side effects including hoarseness, throat discomfort, cough, paresthesia, and headache improved progressively during the period of 3 years. The largest retrospective study with 436 patients demonstrated the mean seizure reduction of 55.8% in nearly 5 years, and also found 75.5% at 10 years in 65 consecutive patients. The intermediate analysis report of the Japan VNS Registry showed that 60% of 164 cases got a ≥ 50% seizure reduction in 12 months. In addition to seizure reduction, VNS has positive effects in mood and improves energy level, memory difficulties, social aspects, and fear of seizures. VNS is an effective and safe option for patients who are not suitable candidates for intracranial epilepsy surgery.

Clinical utility of vagus nerve stimulation for progressive myoclonic epilepsy.

Progressive myoclonic epilepsy (PME) is a group of disorders in which myoclonus is a major component. Patients with PME typically have generalized tonic–clonic or clonic seizures, mental retardation culminating in dementia, and a neurologic syndrome that almost always includes cerebellar dysfunction. It comprises a heterogeneous group of inherited disorders. Conditions inwhich PME is seen include Unverricht–Lundborg disease, sialidosis, Gaucher’s disease, mitochondrial encephalomyelopathy with ragged-red fibers (MERRF), Lafora’s disease, neuronal ceroid lipofuscinosis, and Dentato-Rubro-Pallido Luysian Atrophy (DRPLA). The intensity of the various clinical features varies depending on the etiology. Although valproate, benzodiazepines, piracetam, zonisamide, topiramate, and levetiracetam have had a positive impact on the control of the epilepsy, the prognosis of this syndrome is poor. PME is also not responsive to open surgical resection. Among complimentary treatment options for epilepsy resistant tomedical and open surgical treatments, most patients so far have been treated by vagus nerve stimulation (VNS). VNS is a widely used neurostimulation for treatment-resistant epilepsy. Its components are a pulse generator and a bipolar vagus nerve lead. The generator is designed to be implanted in the patient’s chest on the upper left side. This pulse generator produces charge-balanced waveforms at a constant current. The effectiveness of VNS for PME has rarely been reported. The purpose of this study was to evaluate the efficacy of VNS for PME.

New-onset refractory status epilepticus treated with vagus nerve stimulation: A case report

Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Hamamatsu, Shizuoka 430-8558, Japan Department of Neurophysiology, Seirei Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Hamamatsu, Shizuoka 430-8558, Japan Department of Neurology and Stroke, Japanese Red Cross Kyoto Daiichi Hospital, 15-749 Motomachi, Kyoto, 605-0981, Japan Department of Neurology, Kyoto Prefectural University of Medicine, 465 Kajimachi, Kyouto, 602-0841, Japan

Outcome of vagus nerve stimulation for drug-resistant epilepsy: the first three years of a prospective Japanese registry

Vagus nerve stimulation (VNS) is an established option of adjunctive treatment for patients with drug-resistant epilepsy, however, evidence for long-term efficacy is still limited. Studies on clinical outcomes of VNS in Asia are also limited. We report the overall outcome of a national, prospective registry that included all patients implanted in Japan. The registry included patients of all ages with all seizure types who underwent VNS implantation for drug-resistant epilepsy in the first three years after approval of VNS in 2010. The registry excluded patients who were expected to benefit from resective surgery. Efficacy analysis was assessed based on the change in frequency of all seizure types and the rate of responders. Changes in cognitive, behavioural and social status, quality of life (QOL), antiepileptic drug (AED) use, and overall AED burden were analysed as other efficacy indices. A total of 385 patients were initially registered. Efficacy analyses included data from 362 patients. Age range at the time of VNS implantation was 12 months to 72 years; 21.5% of patients were under 12 years of age and 49.7% had prior epilepsy surgery. Follow-up rate was >90%, even at 36 months. Seizure control improved over time with median seizure reduction of 25.0%, 40.9%, 53.3%, 60.0%, and 66.2%, and responder rates of 38.9%, 46.8%, 55.8%, 57.7%, and 58.8% at three, six, 12, 24, and 36 months of VNS therapy, respectively. There were no substantial changes in other indices throughout the three years of the study, except for self/family-accessed QOL which improved over time. No new safety issues were identified. Although this was not a controlled comparative study, this prospective national registry of Japanese patients with drug-resistant epilepsy, with >90% follow-up rate, indicates long-term efficacy of VNS therapy which increased over time, over a period of up to three years. The limits of such trials, in terms of AED modifications and during follow-up and difficulties in seizure counting are also discussed.

Wolf–Hirschhorn (4p-) syndrome with West syndrome

Wolf–Hirschhorn syndrome (WHS) is a chromosome disorder (4p-syndrome) which is characterized by craniofacial features and epileptic seizures. Here, we report a case of WHS with West syndrome, in whom the seizures were refractory to several antiepileptic drugs but were responsive to the addition of lamotrigine. The patient had epileptic spasms at age seven months. The interictal electroencephalogram was hypsarrhythmic. After adding lamotrigine, seizures decreased remarkably, and spasms disappeared. We have identified and described the very rare case of a girl with WHS who also developed West syndrome. In this case, adding lamotrigine to her medications effectively treated the spasms.

Total corpus callosotomy for epileptic spasms after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) in a case with tuberous sclerosis complex

Corpus callosotomy is a palliative therapy for refractory epilepsy, including West syndrome, without a resectable epileptic focus. The surgical outcome of corpus callosotomy is relatively favorable in cryptogenic (non-lesional) West syndrome. Tuberous sclerosis complex (TSC) is a disorder that frequently leads to the development of refractory seizures by multiple cortical tubers. The multiple cortical tubers cause multiple or wide epileptic networks in these cases. Most of West syndrome cases in TSC with multiple tubers need additional resective surgery after corpus callosotomy. We describe a case of TSC in a boy aged 4years and 8months. He had multiple cortical tubers on his brain and developed epileptic spasms. The seizures were controlled with valproate. At the age of 1year and 4months, he presented with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), and had relapsed epileptic spasms one month after the onset of the encephalopathy. The seizures were refractory to multiple antiepileptic drugs. A total corpus callosotomy was performed at the age of 3years and 8months. The patient did not show any seizures after the surgery. During 12months of the follow-up, the patient was free from any seizures. Even in cases of symptomatic WS with multiple lesions, total corpus callosotomy may be a good strategy if the patients have secondary diffuse brain insults.