Shin-ichiro Osawa

Optogenetically Induced Seizure and the Longitudinal Hippocampal Network Dynamics

Epileptic seizure is a paroxysmal and self-limited phenomenon characterized by abnormal hypersynchrony of a large population of neurons. However, our current understanding of seizure dynamics is still limited. Here we propose a novel in vivo model of seizure-like afterdischarges using optogenetics, and report on investigation of directional network dynamics during seizure along the septo-temporal (ST) axis of hippocampus. Repetitive pulse photostimulation was applied to the rodent hippocampus, in which channelrhodopsin-2 (ChR2) was expressed, under simultaneous recording of local field potentials (LFPs). Seizure-like afterdischarges were successfully induced after the stimulation in both W-TChR2V4 transgenic (ChR2V-TG) rats and in wild type rats transfected with adeno-associated virus (AAV) vectors carrying ChR2. Pulse frequency at 10 and 20 Hz, and a 0.05 duty ratio were optimal for afterdischarge induction. Immunohistochemical c-Fos staining after a single induced afterdischarge confirmed neuronal activation of the entire hippocampus. LFPs were recorded during seizure-like afterdischarges with a multi-contact array electrode inserted along the ST axis of hippocampus. Granger causality analysis of the LFPs showed a bidirectional but asymmetric increase in signal flow along the ST direction. State space presentation of the causality and coherence revealed three discrete states of the seizure-like afterdischarge phenomenon: 1) resting state; 2) afterdischarge initiation with moderate coherence and dominant septal-to-temporal causality; and 3) afterdischarge termination with increased coherence and dominant temporal-to-septal causality. A novel in vivo model of seizure-like afterdischarge was developed using optogenetics, which was advantageous in its reproducibility and artifact-free electrophysiological observations. Our results provide additional evidence for the potential role of hippocampal septo-temporal interactions in seizure dynamics in vivo. Bidirectional networks work hierarchically along the ST hippocampus in the genesis and termination of epileptic seizures.

Complete remission of seizures after corpus callosotomy

OBJECT Corpus callosotomy is usually intended to alleviate-not to achieve total control of-epileptic seizures. A few patients experience complete seizure control after callosotomy, but the associated clinical factors are unknown. The object of this study was to investigate clinical factors associated with long-term seizure remission after total corpus callosotomy in patients with infantile or early childhood onset epilepsy. METHODS Thirteen consecutive patients with infantile or early childhood onset epilepsy underwent 1-stage total corpus callosotomy for alleviation of seizures. Their age at surgery ranged from 1 year and 5 months to 24 years (median 7 years). Eleven patients had West syndrome at the onset of disease, and the other 2 had Lennox-Gastaut syndrome. All patients suffered from spasms, axial tonic seizures, or atonic seizures. Six patients had proven etiology of epilepsy, including tuberous sclerosis, polymicrogyria, trauma, and Smith-Magenis syndrome. The association between postoperative seizure freedom and preoperative factors including age at surgery, no MRI abnormalities, proven etiology, and focal electroencephalographic epileptiform discharges was examined. RESULTS Postoperative seizure freedom was achieved in 4 of 13 patients for a minimum of 12 months. All 4 patients had no MRI abnormalities and no identified etiology. None of the 8 patients with MRI abnormality, 6 patients with known etiology of epilepsy, or 4 patients aged older than 10 years at surgery achieved seizure freedom. Two of the 7 patients with focal electroencephalographic abnormalities became seizure free. Absence of MRI abnormalities was significantly associated with postoperative seizure freedom (p < 0.01). CONCLUSIONS Complete seizure remission is achieved after total corpus callosotomy in a subgroup of patients with intractable epilepsy following West syndrome or Lennox-Gastaut syndrome. One-stage total corpus callosotomy at a young age may provide a higher rate of seizure freedom, especially for patients with no MRI abnormalities and no identified etiology of epilepsy.

Increase in the number of patients with seizures following the Great East-Japan Earthquake

In the afternoon of March 11, 2011, Kesennuma City was hit by the Great East‐Japan Earthquake and a devastating tsunami. The purpose of this retrospective study is to document possible changes in the number of patients with distinct neurologic diseases seeking treatment following this disaster. Because of Kesennumas unique geographical location, the city was isolated by the disaster, allowing for a study with relatively limited population selection bias. Patients admitted for neurologic emergencies from January 14 to May 5 in 2011 (n = 117) were compared with patients in the corresponding 16‐week periods in 2008–2010 (n = 323). The number of patients with unprovoked seizures was significantly higher during the 8‐week period after the earthquake (n = 13) than during the same periods in 2008 (n = 6), 2009 (n = 3), and 2010 (no patients) (p = 0.0062). In contrast, the number of patients treated for other neurologic diseases such as stroke, trauma, and tumors remained unchanged. To our knowledge, this is the first report of an increase in the number of patients with seizures following a life‐threatening natural disaster. We suggest that stress associated with life‐threatening situations may enhance seizure generation.

Predicting human performance by channelized Hotelling observer in discriminating between Alzheimer's dementia and controls using statistically processed brain perfusion SPECT

ObjectiveWe compared the diagnostic accuracy achieved by a human observer (nuclear medicine physician) and a channelized Hotelling (CH) observer on the basis of receiver-operating characteristics (ROC) curve for the differential diagnosis of Alzheimer’s disease (AD) from SPECT images.MethodsThe I-123-IMP brain perfusion SPECT images of 42 subjects (21 AD patients and 21 healthy controls) were used for an interpretation study and those of 10 healthy subjects were for a normal database. SPECT images were processed into four types: original SPECT images, three-dimensional stereotactic surface projection (3DSSP) images derived from them, Z-scores of SPECT images, and Z-scores of 3DSSP images. Five nuclear medicine physicians evaluated the test dataset sequentially as to whether the presented images were those of AD patients, which were rated using five categories of certainty: definitely, possibly, equivocally, possibly not, and definitely not. The test statistics (λ) of the dataset generated by the CH observer were rated for ROC analysis. The areas under the ROC curves (Az) for the four image types interpreted by the human and CH observers were estimated and compared.ResultsAmong the four image types, the best performance based on Az obtained by both the CH and human observers was observed for the Z-score of 3DSSP images, and the lowest was for the original SPECT images.ConclusionsThe performance of the CH observer was similar to that of the human observers, and both were dependent on the image type. This indicates that the CH observer may predict human performance in discriminating Alzheimer’s dementia and can be useful for comparing and optimizing image processing methods of brain perfusion SPECT without human observers.

Parental satisfaction and seizure outcome after corpus callosotomy in patients with infantile or early childhood onset epilepsy

PURPOSE To elucidate the benefit of corpus callosotmy in terms of parental satisfaction and seizure outcome. METHOD This study included 16 consecutive patients with infantile or early childhood onset epilepsy who underwent total corpus callosotomy for alleviation of seizures. Questionnaires were sent anonymously to the parents asking about relative changes in seizures and about parental satisfaction for the post-operative outcome. RESULTS The improvements in frequency, intensity, and duration of seizures were correlated with the level of satisfaction (Spearmans rank-order correlation coefficient, ρ=0.87, 0.93, and 0.75, respectively). The highest level of satisfaction was only seen in patients who achieved freedom from all seizures or drop attacks. CONCLUSION Complete seizure freedom and freedom from drop attacks are important goals of corpus callosotomy for parental satisfaction. These factors should be considered in assessing post-operative outcome after corpus callosotomy.

Time-varying inter-hemispheric coherence during corpus callosotomy

OBJECTIVE Corpus callosotomy limits the bilateral synchrony of epileptic discharges. However, the instantaneous changes in bilateral synchrony during corpus callosotomy are unclear. The present study investigated how and when bilateral synchrony is suppressed in the anterior and then posterior steps of corpus callosotomy. METHODS Intra-operative scalp electroencephalography (EEG) was recorded simultaneously with surgical video for six patients who underwent total corpus callosotomy for medically intractable drop attacks. The time-varying EEG inter-hemispheric coherence was quantified by wavelet transform coherence and trend analysis. RESULTS The 4-13 Hz coherence decreased after corpus callosotomy in five patients. Significant decrease in coherence was observed only during the posterior step of callosal sectioning in three patients, but throughout both steps in two patients. CONCLUSIONS Decrease in inter-hemispheric coherence is not always correlated with the stages of callosal sectioning. Inter-hemispheric coherence is decreased during the final stage of corpus callosotomy and the effect is maximized after sectioning is completed. SIGNIFICANCE Various patterns of coherence decrease suggest individual variations in the participation of the corpus callosum in the genesis of bilateral synchrony. Time-varying inter-hemispheric EEG coherence is useful to monitor the physiological completeness of corpus callosotomy.

Ruptured Cerebral Microaneurysm Diagnosed by 3-Dimensional Fast Spin-Echo T1 Imaging with Variable Flip Angles.

Cerebral microaneurysms, which are 2 mm or small in size, are a rare cause of subarachnoid hemorrhage (SAH). The authors present 2 cases with ruptured microaneurysms, in which 3-dimensional (3D) fast spin-echo T1 imaging with variable flip angles (CUBE T1) using gadolinium-diethylenetriaminepentaacetic acid (Gd) enhancement was useful in diagnosing the microaneurysms as the source of bleeding. Case 1 was a 61-year-old woman who had an SAH localized to the left Sylvian fissure. A small bulge (1.4 mm) at the bifurcation of left middle cerebral artery (MCA), which was detected by 3D angiography, was well enhanced by CUBE T1 with Gd enhancement. The patient was successfully treated by trapping of the lower division of the left M2 segment with superficial temporal artery-M3 bypass. The intraoperative findings indicated that the microaneurysm at the bifurcation of the left MCA was the ruptured site. Case 2 was a 41-year-old man who had a diffuse SAH. A small bulge (1.5 mm) at the inferolateral wall of the left internal carotid artery (ICA), which was detected by 3D angiography, was well enhanced by CUBE T1 with Gd enhancement. The patient was treated by trapping of the left ICA with external carotid artery-saphenous vein graft-M2 bypass without complications. The intraoperative findings indicated that the microaneurysm at the inferolateral wall of the left ICA was the ruptured site. CUBE T1 with Gd enhancement was useful as an adjunctive tool for the diagnosis of ruptured cerebral microaneurysms. This sequence might enable neurosurgeons to perform curative surgery with certainty for ruptured microaneurysms.

Interhemispheric Vertical Hemispherotomy: A Single Center Experience.

Purpose: Hemispheric epileptogenic lesions such as hemimegalencephaly often manifest as intractable epilepsy in early infancy. Hemispherotomy is the treatment of choice for controlling intractable hemispheric epilepsy. Less invasive procedures are desirable for surgery on infants with low body weight. This study compared our experience with interhemispheric vertical hemispherotomy (IVH) and peri-insular lateral hemispherotomy (PIH). Methods: Thirteen consecutive patients underwent hemispherotomy for treatment of intractable epilepsy in our institution between 2001 and 2012. The etiology of epilepsy included hemimegalencephaly in 7 patients and cortical dysplasia in 3. PIH was performed on the first 5 patients and IVH on the last 8 patients. In the latter procedure, complete section of the corpus callosum was first performed via the interhemispheric approach. After removing part of the cingulate gyrus, section of the descending fibers was performed anterolaterally to the thalamus. Clinical characteristics, duration of operation and amount of blood transfusion were compared between the PIH and IVH groups. Results: There was no difference in age at surgery, body weight and age of epilepsy onset between the two groups. No surgery-related death was observed. No patients required shunt operation. One patient who underwent IVH required reoperation for incomplete disconnection. The amount of intraoperative blood transfusion was smaller and the total duration of operation was shorter in the IVH group than in the PIH group. Conclusion: The interhemispheric approach minimizes cortical resection and may be less invasive than PIH. IVH is advantageous for treating infants with low body weight.

A case of intravascular epithelioid hemangioendothelioma occurring 14 years after coil embolization for an extracranial internal carotid artery aneurysm

Epithelioid hemangioendothelioma (EHE) is a rare neoplasm originating from various organs. The clinical outcome mostly depends on surgical resectability. The authors report an EHE of the extracranial internal carotid artery developed in a 59-year-old male patient 14 years after the intravascular coil embolization for a carotid aneurysm at the same site. Because the lesion was initially diagnosed as regrowth of the thrombosed aneurysm, decision for radical resection was delayed, and the patient died from rapid tumor progression. Differential diagnosis of atypical vascular mass lesions should include neoplasm, because initial radical resection may be the key to achieve a better prognosis.

Occult dual pathology in mesial temporal lobe epilepsy

Keywords Dual pathology ´Temporal lobe epilepsy Ganglioglioma Negative magnetic resonance imagingDear Sir,Hippocampal sclerosis (HS) can appear secondary to neo-cortical epileptogenic lesion in medically refractoryepilepsy, called dual pathology. In the dual pathology, re-moval of both the primary lesion and HS is necessary toachieve better seizure outcome. However, if the primarylesion is not apparent in pre-operative imaging studies,selective surgery to hippocampus may be performed andfollowed by inadequate seizure control. Here, we report acase of dual pathology which was not diagnosed pre-operatively.A 50-year-old man with drug-resistant temporal lobeepilepsy (TLE) was referred to our department forevaluation of surgical treatment. Seizures had started atage 10 years and had become intractable to multiplemedications at age 22 years. He had aura of fear or deja`-vu followed by complex partial seizures 2–3 times amonth despite antiepileptic medications including carba-mazepine and lamotrigine. Previously, he was treatedwith valproic acid, levetiracetam and zonisamide. Com-prehensive presurgical evaluation including video-elec-troencephalography (EEG), ‘‘epilepsy protocol’’ high-fieldmagnetic resonance imaging (MRI), fluoro-deoxy-glucosepositron emission tomography (FDG-PET), neuropsycho-logical testing, was performed. 3.0-T MRI revealed in-creased T2 signal intensity and volume loss of the righthippocampus (Fig. 1). No cystic lesions or other neo-cortical abnormalities were observed by neuroradi-ologists. Gadolinium enhancement was not performed. Nocalcifying lesions were seen in computed tomographyscans. Video-EEG monitoring revealed that complexpartial seizures with automatisms were associated withrhythmic EEG changes in the right anterior temporalregion. FDG-PET showed glucose hypometabolism in theright antero-basal temporal region. Neuropsychologically,mild impairment of verbal memory function was noted.Under a diagnosis of right TLE with hippocampal scle-rosis, trans-sylvian selective amygdalo-hippocampectomywas performed. Histological examination revealed bothType 1b HS (Fig. 2a) and ganglioglioma in the subiculum(Fig. 2b, c) [1]. He has suffered no additional neuro-logical deficits post-operatively. The patient was seizurefree for 2 years with continuing medication. Follow-upMRI at 1 year showed no evidence for recurrence oftumor.Neocortical epileptogenic lesion occasionally coexistswith HS, and is called ‘‘dual pathology.’’ Surgical re-moval of both neocortical lesion and hippocampus isbetter for the achievement of seizure freedom [2]. In thepresent case, the subicular tumor was not identified pre-