Anticonvulsant and antioxidant effects of lamotrigine on pilocarpine-induced status epilepticus in mice.

OBJECTIVES: The anticonvulsant and antioxidant effects of lamotrigine on status epilepticus (SE) are incompletely understood. We assessed these effects of lamotrigine on pilocarpine (Pilo)-induced SE in mice. METHODS: Male C57BL/J6 mice were assigned to three groups: the control group, Pilo (400 mg/kg, s.c.)-induced SE (Pilo group) and lamotrigine (20 mg/kg, i.p.) treated (Pilo/lamotrigine group). The latency to SE of Racine's stage 3 or higher, the mortality rate within 2 h of Pilo administration, and the duration of SE until sacrifice were examined. Nitric oxide (NO), malondialdehyde and glutathione of oxidative stress biomarkers were detected in the hippocampus of the sacrificed animals in the above groups. NO was also detected in the cultured rat hippocampal neurons treated with 4 µM Pilo, Pilo+100 µM lamotrigine (Pilo/lamotrigine) and Pilo/lamotrigine+ N-methyl-D-aspartic acid (NMDA) receptor antagonist (10 µM MK-801, 3 µM ifenprodil) to examine the antioxidant effects of lamotrigine via non-NMDA-related pathways. RESULTS: lamotrigine prolonged the latency to SE, the SE duration until sacrifice, and decreased the mortality rate in mice with Pilo-induced SE. Lamotrigine also decreased hippocampal concentrations of NO and malondialdehyde and increased the concentrations of glutathione in the SE model. Furthermore, there were significant differences in NO concentrations between groups of cultured rat hippocampal neurons treated with Pilo and Pilo/lamotrigine, and with Pilo/lamotrigine and Pilo/lamotrigine+MK-801. CONCLUSION: Our findings suggest that lamotrigine exerts anticonvulsant and antioxidant effects on SE, but its antioxidant activity may not be fully exerted via NMDA-related pathways.

An adult case of cerebral malakoplakia successfully cured by treatment with antibiotics, bethanechol and ascorbic acid.

Cerebral malakoplakia is a very rare chronic inflammatory disease. We herein report the case of a 49-year-old female who presented with a slowly progressive speech disturbance and right hemiparesis. Computed tomography and magnetic resonance imaging showed irregular enhanced mass lesions with numerous scattered areas of calcification in the left insula, thalamus and basal ganglia. Histopathologically, the biopsy specimen showed basophilic laminated inclusion bodies and intracellular and extracellular calculospherules, usually with a typical targetoid appearance (Michaelis-Gutmann bodies). Treatment with antibiotics, bethanechol and ascorbic acid improved her symptoms in association with a decrease in the abnormal calcification and enhancement. The cerebral malakoplakia mimicked a brain tumor in terms of the patient's clinical course and neuroradiological image findings; however, it was successfully cured with medical treatment. This case provides evidence that the pathogenesis of cerebral malakoplakia is deeply tied to bacterial infection and that medical treatment is effective in cases of this disease.

Cathodal transcranial direct current stimulation affects seizures and cognition in fully amygdala-kindled rats.

This study evaluated the effects of weak transcranial direct current stimulation (tDCS), a new non-invasive brain stimulation technique, on amygdala-kindled rats. The seizure severity, i.e. seizure stage, afterdischarge duration (ADD), and AD threshold (ADT) in the animals were measured one day after the last cathodal tDCS session, comparing with those of pre-treatment controls. Furthermore, the effects of cathodal tDCS on cognitive function were also studied by a water maze test (WMT) two days after the last tDCS session. Cathodal tDCS treatment significantly improved the seizure stage and decreased ADD together with elevated ADT one day after the last tDCS session. The treatment also showed significant improvement in the performance of WMT. The findings suggest that cathodal tDCS has anticonvulsive after-effects last at least for one day on the amygdala-kindled rats and positively affects cognitive performance.

Transcranial direct current stimulation decreases convulsions and spatial memory deficits following pilocarpine-induced status epilepticus in immature rats.

PURPOSE: Transcranial direct current stimulation (tDCS) is a recently available, noninvasive brain stimulation technique. The effects of cathodal tDCS on convulsions and spatial memory after status epilepticus (SE) in immature animals were investigated. METHODS: Rats underwent lithium-pilocarpine-induced SE at postnatal day (P) 20-21 and received daily 30-min cathodal tDCS for 2 weeks at P23-36 through a unilateral epicranial electrode at 200µA. After tDCS, convulsions over 2 weeks were estimated by 20-h/day video monitoring. The rats were tested in a water maze for spatial learning at P50-53 and the brains were examined for cell loss and mossy fiber sprouting. RESULTS: Long-term treatment with weak cathodal tDCS reduced SE-induced hippocampal cell loss, supragranular and CA3 mossy fiber sprouting, and convulsions (reduction of 21%) in immature rats. The tDCS treatment also rescued cognitive impairment following SE. CONCLUSIONS: These findings suggested that cathodal tDCS has neuroprotective effects on the immature rat hippocampus after pilocarpine-induced SE, including reduced sprouting and subsequent improvements in cognitive performance. Such treatment might also have an antiepileptic effect.

Cerebral vasculitis associated with amyloid angiopathy: case report.

A 78-year-old female presented with coexisting primary angiitis of the central nervous system (CNS) and cerebral amyloid angiopathy (CAA) manifesting as motor aphasia caused by a left frontal lobe lesion. Magnetic resonance imaging revealed an enhanced lesion with moderate surrounding edema.Technetium-99m propylene amine oxime single-photon emission computed tomography showed decreased cerebral blood flow (CBF) in the lesions, and high serum soluble-interleukin-2 level was detected, suggesting intravascular lymphoma of the CNS. Cerebral biopsy revealed CAA with secondary florid vasculitic appearance. The CBF and neurological symptoms, such as aphasia and dementia, recovered following steroid treatment. Cerebral vasculitis associated with CAA should be included in the differential diagnosis of an unusually enhanced lesion, because timely diagnosis and aggressive treatment are critical to successful recovery in such elderly patients.

Visualization of subdural electrodes with fusion CT scan/MRI during neuronavigation-guided epilepsy surgery.

Neuronavigation in epilepsy surgery enables surgeons to accurately resect deep targets inside the brain, especially lesions that are unable to be visually differentiated from adjacent normal brain. The usefulness of visualizing subdural electrodes with postimplantation fusion CT/MRI was investigated. The use of platinum subdural electrodes made it possible to obtain postimplantation MRI. The postimplantation MRI and CT scans were fused on the surgical navigation system workstation to form three-dimensional (3D) images, and the epileptogenic regions were marked using the visualized electrodes. Immediately after a craniotomy was performed, the subdural electrodes were removed and the epileptogenic region was successfully resected using the neuronavigation guide. During neuronavigation-guided surgery to target deep brain epileptogenic lesions adjacent to eloquent areas, which are often invisible, we found visualization of the subdural electrodes with postimplantation fusion CT/MRI very useful.

Increasing high-frequency oscillations (HFOs) in patients with brain tumours: implication for increasing amplitude of N20.

OBJECTIVE: The N20 and high-frequency oscillations (HFOs) of somatosensory evoked potentials (SEPs) were recorded in patients with brain tumours. This study sought to estimate how a brain tumour could increase the peak amplitude of N20, while also illustrating the clinical significance of this condition. METHODS: Median nerve SEPs were recorded in 34 conscious patients, who were admitted to the hospital owing to the presence of a circumscribed unilateral brain tumour. Eleven patients showed an increasing peak amplitude of N20 on the affected side (AS). HFOs were used to analyse the underlying mechanism. RESULTS: While the amplitude of N20 in AS was higher than that on the normal side (NS), the latency of N20 showed no difference on either side. The amplitude of the early components of HFOs on the AS was higher than that on the NS (p=0.015), but the latency was not significantly different. The amplitude of late HFOs on the AS was also higher than on the NS (p=0.041), and the latency was also not significantly different. Our findings proved an increasing amplitude of HFOs to be a discrete character in AS>NS group, thereby indicating that a sensory disturbance was not commonly expressed in AS>NS groups. CONCLUSIONS: These results suggested that the hyperexcitability in the thalamocortical pathway were responsible for this condition. Hyperexcitability was presumably caused by the influence of the corticothalamic feedback and the neural interactions between the relay neurons and the reticular neurons. The clinically significant finding was that an increasing amplitude of N20 thus indicated the presence of a sub-clinical change. SIGNIFICANCE: A brain tumour could increase the amplitude of N20 due to the hyperexcitability in the thalamocortical pathway. An increasing amplitude of N20 thus indicated the presence of a sub-clinical change in the thalamocortical pathway on the side of the tumour.

Malignant fibrous histiocytosis after high-dose proton radiation therapy for anaplastic astrocytoma.

This report presents a 70-year-old male who presented with a rare malignant fibrous histiocytosis after high-dose proton radiation therapy for anaplastic astrocytoma. To our knowledge, malignant fibrous histiocytosis caused by proton therapy has not been reported, therefore the clinical features of this complication are described and previous cases are reviewed.

A hemispherotomy for intractable startle epilepsy characterized by infantile hemiplegia and drop attacks.

Startle epilepsy is provoked by unexpected sensory stimuli, mainly auditory, and reveals subsequent tonic posturing of the limbs. We present a case of intractable startle epilepsy with infantile hemiplegia and discuss the indications for a hemispherotomy.

Functional motor recovery of an infant after a huge ependymoma resection.

Huge supratentorial ependymomas are rarely encountered tumors, even in the infant population. A recovery from complete hemiplegia following a tumor resection including the primary motor cortex was observed. A 5-month-old girl presented with a conjugate deviation to the right and a head circumference that had gradually expanded since birth. Magnetic resonance imaging (MRI) demonstrated a well-enhanced huge mass extending into the right hemisphere. A subtotal removal with the primary motor cortex was performed. However, a regrowth of the residual tumor was observed and, thereafter, the patient underwent a subsequent surgical intervention 5 months later. The histological findings demonstrated an ependymoma. Her motor function was dramatically improved after rehabilitation and no tumor recurrence was detected for 10 years. A diffusion tensor imaging study showed that the motor fibers arose from the residual frontal lobe. The successful surgical management of ependymoma may depend on a total microscopic resection. In a case demonstrating a huge ependymoma, we had to remove a very thin motor cortex with the tumor. However, the motor function recovered completely. The motor damage inflicted at an early developmental age may be fully compensated due to the neuroplasticity of the residual brain.

Intracranial infiltration by recurrent scalp dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) of the scalp is a rare soft tissue sarcoma. A 22-year-old male with DFSP, who had undergone several surgical excisions and radiotherapy, presented with a mild left lower-limb paresis. An MRI scan demonstrated a huge mass extending throughout the frontoparietal convexity. A macroscopically complete removal of the mass was performed. Despite this, there were several recurrences; thereafter, the patient underwent surgery, stereotactic radiosurgery and chemotherapy. The histological findings demonstrated a DFSP that both abutted and occasionally invaded the adjacent brain cortex, while extending along the Virchow-Robin spaces. Due to the highly infiltrating characteristics of DFSP, another approach, such as the use of molecular-targeted agents, will be required to significantly improve the clinical outcome.

Edaravone, a free radical scavenger, retards the development of amygdala kindling in rats.

This study evaluated the antiepileptogenic effects of edaravone, a newly developed radical scavenger, on the amygdala kindling rats. The afterdischarge duration (ADD), AD threshold (ADT), and seizure severity in animals were measured to study the anticonvulsant effects of edaravone (2mg/kg or 20mg/kg i.p. for 7 days) on fully kindled seizures. Furthermore, for the study of antiepileptogenesis effects of the drug (2mg/kg or 20mg/kg i.p. for 7 days), not only ADD and seizure severity during kindling but also both the pre- and post-kindling ADT were measured. Edaravone neither induces nor inhibits fully kindled seizures regardless of the dose; however high-dose edaravone (20mg/kg) retarded kindling development together with shortened ADD and elevated ADT. The present data suggest that high-dose edaravone has an antiepileptogenic drug effect for the prevention of epilepsy. However, other chronic models and clinical trials are needed to confirm the effects of edaravone on the prevention of human epilepsy.

Induction of collateral circulation by hypoxia-inducible factor 1alpha decreased cerebral infarction in the rat.

BACKGROUND: We recently reported that hypoxia-inducible factor 1alpha (HIF-1alpha), HIF-2alpha and cyclooxygenase 2 naked DNA induced angiogenesis in a rat indirect bypass model. In this work, we investigated whether the collateral circulation induced by HIF-1alpha DNA affected the cerebral infarction. METHODS: We utilized a rat encephalomyosynangiosis (EMS) model and inoculated HIF-1alpha DNA onto the brain surface. These treatments were performed before the cerebral infarction occurred. We thereafter performed middle cerebral artery occlusion on the fifth or tenth day after EMS. RESULTS: A histological section treated with HIF-1alpha DNA for 10 days showed a well-developed collateral circulation (p<0.05) and a reduction in the infarction volume in comparison to the control DNA (p<0.01). CONCLUSION: These results suggest the feasibility of a novel approach for the treatment of cerebral ischemia via the development of therapeutic collateral circulation, in which neovascularization may be indirectly achieved using a transcriptional regulatory strategy.

Possible involvement of interferon beta in post-operative vasculitis restricted to the tumour bed: a case report.

Cerebral vasculitis is a very rare complication after brain tumour surgery. We herein report a case and discuss the origins of this complication. A 52-year-old female was admitted because of motor aphasia due to a left frontal lobe brain tumour. The magnetic resonance imaging (MRI) study revealed a non-enhanced tumour. A partial resection of the tumour and the placement of an Ommaya's reservoir were performed. The pathological diagnosis was an oligoastrocytoma. The patient recovered well without any neurological deficits. Post-operative radiotherapy and the intravenous injection of interferon beta were performed. During these treatments, the patient showed a continued high fever. An MRI scan revealed multiple enhanced lesions in the residual tumour, thus raising suspicions about a post-operative infection. We therefore performed a tumour biopsy and the removal of the exogenous materials. The histopathological diagnosis was vasculitis in the residual tumour. The patient's consciousness and neurological symptoms recovered quickly with the steroid treatment. Following the radiotherapy (50 Gy total), complete remission of the tumour was rapidly obtained and no recurrence was observed. Cerebral vasculitis confined to the tumour bed is an unusual complication; however, this special condition was of critical importance for a successful tumour regression in this patient.

Neuroprotective and antiamnesic effect of donepezil, a nicotinic acetylcholine-receptor activator, on rats with concussive mild traumatic brain injury.

In this study we evaluated the effect of donepezil on the neurodegeneration and behavioral impairments induced by mild traumatic brain injury (MTBI). Donepezil is an acetylcholinesterase inhibitor that is used to treat Alzheimer's disease. Donepezil was given orally to rats subjected to MTBI. Treatment with a single oral dose of donepezil (12mg/kg) immediately after injury significantly attenuated MTBI-induced neuronal death and cognitive impairment as measured by preservation of neurons in the CA1 region of the hippocampus and a water maze test respectively. However, these neuroprotective effects were prevented by concomitant injection of mecamylamine, a nicotinic acetylcholine-receptor (nAChR) antagonist, indicating that protection is mediated by nAChR activation.

Severe postoperative vasculitis of the central nervous system in a child with arteriovenous malformation: case report.

BACKGROUND: Cerebral vasculitis is very rare complication after craniotomy. We report a case and discuss the etiology, diagnosis, and treatment of this complication. CASE DESCRIPTION: A 12-year-old boy was admitted because of a consciousness disturbance due to a ruptured AVM. Computed tomography revealed a left parietal subcortical hematoma. No apparent nidus was detected on the angiography findings, but AVM was suspected. After resection of the hematoma, the patient did not recover consciousness, and his high fever continued. Despite postoperative induced hypothermia, progressive multiple cerebral infarctions occurred. Postoperative angiography showed multiple arterial narrowing, and a "string of beads" phenomenon was observed in the anterior and posterior circulation in addition to the residual AVM. After administering steroid therapy, he recovered consciousness, but had a severe disability. After angiography, which was performed 1 year after onset, an improvement of the vasculitis and the complete occlusion of AVM were observed. CONCLUSION: We should therefore include cerebral vasculitis in the differential diagnosis when encountering a case with an unusual progressive stroke because a timely diagnosis and aggressive treatment are of critical importance for a successful recovery in such patients.

Unique infiltrating morphology of a meningioma-a case report.

BACKGROUND: We report on the case of a patient with meningioma that was correctly identified through biopsy. CASE DESCRIPTION: A 69-year-old woman presented with slight headache and was then examined at our hospital. Neurologic and physical examinations found no abnormality. Magnetic resonance imaging demonstrated a well-enhanced huge, dural-based, and plaque-like mass extending throughout the parietooccipital convexity and the posterior fossa. Tumors pressed the adjacent brain cortex while extending along the Virchow-Robin space. A CT scan also showed hyperostosis on the parietooccipital bone. Angiography demonstrated a vascular blush that appeared to be of a tumor-like shape. A biopsy was performed to confirm the diagnosis. The histologic findings demonstrated meningothelial meningioma with infiltration into the Virchow-Robin space. CONCLUSIONS: Many radiographic patterns of meningioma have been reported, but the present case is quite rare. The radiographic and pathologic findings in our patient are discussed.