Keisuke Toda

Visualization of DNA double strand breaks in the gerbil hippocampal CA1 following transient ischemia

To clarify the relationship between delayed neuronal death and apoptosis, we made an attempt to detect DNA strand breaks in the gerbil hippocampal CA1 pyramidal neurons following transient ischemia by an in situ DNA double strand breaks staining. The condensed nuclei of neurons in CA1 were occasionally seen and positively stained 3 days after ischemia. The degenerating dark neurons with condensed nuclei in CA1 markedly increased in number and were clearly stained for DNA strand breaks 5 days after ischemia, whereas normal-looking nuclei remained unstained. No neurons were stained in other hippocampal subfields and dentate gyrus. The present study strongly indicates that the CA1 pyramidal neurons die through an apoptotic process.

Brain surface spindle cell glioma in a patient with medically intractable partial epilepsy : A variant of monomorphous angiocentric glioma?

We report a case of brain surface angiocentric glioma in a 6‐year‐old Japanese boy with medically intractable partial epilepsy. MRI showed somewhat ill‐defined high‐signal lesions on fluid‐attenuated inversion recovery and T2‐weighted imagings of the right occipitoparietal cortex. At surgery, a yellowish tumor was localized in the superficial cortex. Histologically, the tumor was predominantly composed of elongated astrocytic cells forming rings around blood vessels. Tumor cells circumferential to vessels predominanted in low cellurarity areas, whereas radial alignment with perivascular pseudorosettes was observed in more cellular regions. These perivascular pseudorosettes closely resembled those of ependymoma. The tumor cells showed variable cytoplasmic immunoreactivity with GFAP. These findings were more likely monomorphous angiocentric glioma, which was first described by Wang et al. in 2005. However, in our case the tumor had a small foci of polymorphous appearance and a comparatively high MIB‐1 labeling index (8%). Therefore, the present case may be an atypical form of monomorphous angiocentric glioma. However, no de novo anaplastic monomorphous angiocentric glioma similar to our case has yet been reported in the literature. It remains to be determined whether the behavior of monomorphous angiocentric glioma is an example of benign biological characteristics or whether it more closely resembles a low‐grade malignant tumor.

Callosotomy and subsequent surgery for children with refractory epilepsy

Callosotomy has been considered as a palliative therapy for refractory epilepsy patients with non-focal onset seizures. Residual partial seizures and unilateral epileptiform discharges on electroencephalography (EEG) are sometimes observed after callosotomy. These findings suggest that some patients may be candidates for subsequent resective surgery. Of 149 children who received a callosotomy, resective/disconnective surgery was subsequently performed in 19 patients. Most patients had generalized seizures and epileptiform discharges on EEG before callosotomy. Two-third had normal neuroimaging studies at initial presurgical evaluation. After callosotomy, ictal symptoms evolved into asymmetric features suggesting partial onset seizures. Post-callosotomy EEG showed completely lateralized or localized epileptiform discharges responsible for residual partial seizures in 16 of 19 patients. Fifteen patients underwent resective surgery of the unilateral frontal lobe, and the remaining received hemispherotomy or posterior quadrantectomy. After subsequent surgery, favorable seizure outcomes were obtained in 11 patients (57.9%). Favorable seizure outcomes may be achieved with callosotomy and subsequent surgery in selected patients who are not candidates for a conventional resective surgery at initial presurgical evaluation.

Pediatric moyamoya disease presenting with intracerebral hemorrhage—Report of three cases and review of the literature

Intracerebral hemorrhage in patients with moyamoya disease is rare in children. We report three unique cases of pediatric moyamoya disease with hemorrhagic onset. Two 7-year-old girls and a 9-year-old girl were admitted to our hospital because of intracerebral hemorrhage associated with angiographically verified moyamoya disease. Two of them did not demonstrate either an ischemic episode or cerebral infarct on the magnetic resonance images. A decreased regional cerebral blood flow was revealed on single photon emission computed tomography in two patients, who developed cerebral infarction in the acute stage following hemorrhage. They underwent superficial temporal artery-middle cerebral artery anastomoses combined with encephalo-myo-synangiosis, and have not experienced any further ischemic episodes thereafter. Hemodynamic insufficiency associated with moyamoya disease could cause intracerebral hemorrhage even in children. Adequate management in the acute stage of hemorrhage and revascularization surgery are recommended to prevent cerebral infarction, which may easily occur in pediatric patients with moyamoya disease.

Hemispheric asymmetry of callosal neuronal participation in bilaterally synchronous epileptiform discharges

PURPOSE Callosal compound action potentials (CCAPs) recorded from the corpus callosum can reveal callosal neuronal activity. In this study, hemisphere-specific activity of callosal neurons during bilateral synchrony was evaluated in relation to the postoperative EEG. METHODS In 19 patients undergoing callosotomy for intractable epilepsy, intraoperative electrocorticograms (ECoGs) and CCAPs were simultaneously recorded prior to callosal bisection. Hemisphere-specific CCAPs during bilateral synchrony were estimated through an averaging-based method. The degree of asymmetry in hemisphere-specific CCAPs was evaluated with a laterality index (LI), and correlated with post-callosotomy outcomes. RESULTS Despite preoperative frequency of bilateral synchrony, postoperative EEG outcomes were mostly categorized as either unilaterally lateralized discharge group or bilaterally asynchronous discharge group. The LI of the former group was significantly higher than that of the latter group. In addition, higher amplitudes of the hemisphere-specific CCAP coincided with the side on which epileptiform discharges persisted postoperatively in most patients of the unilaterally lateralized discharge group. CONCLUSIONS Electrophysiologic analysis with CCAPs revealed hemispheric asymmetry of callosal neuronal participation in bilateral synchrony. More callosal neurons fire together in the more epileptogenic hemisphere during bilateral synchrony even if preoperative EEG features are virtually symmetric. This suggests transcallosal dynamic actions on the bi-hemispheric epileptogenesis maintenance.

Epstein–Barr virus and methotrexate-related CNS lymphoma in a patient with rheumatoid arthritis

Patients with rheumatoid arthritis (RA), especially those treated with methotrexate (MTX), might have an increased risk of lymphoproliferative disorders that are associated with Epstein–Barr virus (EBV). We describe a case of EBV-associated central nervous system (CNS) lymphoma (diffuse large B-cell lymphoma) in a patient with RA on a short course of MTX treatment. The neoplastic cells express the B-cell surface markers (CD20, Pax-5 and CD30), and EBV-encoded RNA was demonstrated by in situ hybridization. The patient’s lymphoma did not recur for the 8-year follow-up period after the tumor resection and cessation of MTX. MTX may promote EBV-positive CNS lymphoma in RA patient due to its immunosuppressive properties as well as reactivating latent EBV infection.

Radiological findings of orbital infarction syndrome following intracranial aneurysm surgery.

Orbital infarction syndrome is a rare disorder resulting from cclusion of the ophthalmic artery and its branches. Zimmerman t al. first reported six patients with proptosis, opthalmoplegia nd blindness immediately after intracranial aneurysm surgery as rbital infarction syndrome [1]. To present, only ten cases (3 litertures) of orbital infarction syndrome after intracranial aneurysm urgery have been reported [1–3]. However two of three literaures were described by ophthalmologists. Neurosurgeons should ay attention to this rare but devastating complication. In order to ssist the early diagnosis of this complication, we report upon two ases of orbital infarction syndrome after intracranial aneurysm urgery.

Factors affecting rapid growth of unruptured cerebral aneurysms during the acute stage of subarachnoid hemorrhage.

Abstract Background and purpose: Several unruptured cerebral aneurysms have been reported to grow and rupture. To determine which factors affect the growth of these aneurysms during the acute stage of subarachnoid hemorrhage (SAH), a retrospective review was performed. Methods: Between January 2000 and January 2003, 130 patients with angiographically proven ruptured cerebral aneurysms were treated at our institution. Of these patients, 32 also had simultaneous unruptured aneurysms, and the total number of the unruptured aneurysms was 40, including two neck remnants which had remained since the past clipping. Seventeen patients had 17 unruptured aneurysms and two neck remnants. The unruptured aneurysms were not treated during the acute stage of SAH but had received a complete short term follow-up. Results: The rapid growth of one unruptured aneurysm and two neck remnants was confirmed by a second angiogram performed on average40 days after the first angiogram. Several candidate factors responsible for the growth of aneurysm were selected, and the results of a statistical analysis indicate that a systolic blood pressure above 200 mmHg during the acute stage of SAH and vasospasm, confirmed by transcranial Doppler ultrasound (TCD) or neurological examination, and neck remnants, are risk factors that affect the growth. Conclusions: Short term follow-up angiography is thus important for patients with untreated unruptured cerebral aneurysms after the acute stage of SAH.

Early total corpus callosotomy in a patient with cryptogenic West syndrome.

West syndrome is a generalized epileptic syndrome of infancy, that is characterized by clinical spasms and hypsarrhythmia and usually has an onset age before two years old. Children affected by West syndrome have a high risk of severe psychomotor developmental delay. Infants with West syndrome without identification of underlying neurological disorder after adequate investigations are classified as ‘‘cryptogenic’’ and usually have better prognoses than children with ‘‘symptomatic’’ West syndrome. Early seizure cessation, particularly among cryptogenic cases, may cure the disease and allow a good neurodevelopmental outcome. Corpus callosotomy was first introduced as a palliative treatment for epilepsy in 1940 and is performed in patients whose seizures are not amenable to surgical focal resection. West syndrome is often medically intractable and has features of ‘‘generalized’’ epilepsy, but corpus callosotomy has not been discussed widely as a treatment strategy. Given the catastrophic nature of West syndrome, an early indication for total corpus callosotomy may be appropriate. Here, we describe a case that was diagnosed as cryptogenic West syndrome, in which the epileptogenic focus was defined after total corpus callosotomy.

Dolichoectasic Anterior Cerebral Artery and Hemodynamics

Dolichoectasia of the intracranial arteries is a rare condition, and the vertebrobasilar system and the internal carotid artery are the most commonly involved structures. We report a rare case of idiopathic dolichoectasia of the anterior cerebral artery in a 22-year-old female. The patient caused an automobile accident and was brought to our hospital in an ambulance. A computed tomography scan and magnetic resonance imaging revealed no fresh lesions, but showed a prominent serpentine structure with calcification and flow void in the region of the interhemispheric fissure, which was suspicious for arteriovenous malformation or arteriovenous fistula. Cerebral angiography demonstrated extensive dilatation of the anterior cerebral artery, but no evidence of arteriovenous malformation or arteriovenous fistula. Single photon emission computed tomography revealed hypoperfusion of the right frontal lobe at rest. Electroencephalography showed no epileptic discharge. The patients course was uneventful, and she was discharged with no neurologic deficit. There are few reports of hemodynamic changes in cases of dolichoectasia. In the diagnosis of cerebral dolichoectasia, cerebral hemodynamics should be examined carefully in addition to evaluating vascular disease by angiography.