Takanobu Kaido

Protective effect of C1 esterase inhibitor on reperfusion injury in the rat middle cerebral artery occlusion model.

OBJECTIVEThe complement system is thought to play a major role in initiating some of the inflammatory events that occur during reperfusion injury. The aim of this study was to assess the effects of C1 esterase inhibitor (C1-INH) on ischemic injury in the rat model of middle cerebral artery suture occlusion and reperfusion. METHODSThirty-six male Wistar rats were used. Intraluminal middle cerebral artery occlusion was performed for 60 minutes. Just before reperfusion, C1-INH (50 international units/kg) (C1-INH group, n = 19) or saline solution (control group, n = 17) was administered. Physiological parameters (arterial blood gas values, mean arterial blood pressure, and heart rate) and local cerebral blood flow were recorded during the experiment. Forty-eight hours after reperfusion, all rats were killed, and assessments of leukocyte infiltration with a myeloperoxidase activity assay and histological analyses with 2,3,5-triphenyl tetrazolium chloride staining were performed. RESULTSThe physiological parameters and local cerebral blood flow values were not significantly different in the two groups. The infarction volume was significantly smaller and the myeloperoxidase activity was significantly lower in the C1-INH group (84.9 ± 69.1 mm3 and 0.40 ± 0.29 units/g, respectively) than in the control group (202.3 ± 98.3 mm3 and 1.41 ± 0.44 units/g, respectively) (P < 0.01). Myeloperoxidase activities were strongly correlated with infarction volumes (r = 0.73, P < 0.01). CONCLUSIONThe results of this study indicated that C1-INH reduced polymorphonuclear leukocyte accumulation and neuronal damage in focal ischemia and reperfusion.

Complex behavioral automatism arising from insular cortex

We describe two cases of complex partial seizures with ictal violent movements arising from the insular cortex. The first patient, a 14-year-old girl, presented with hyperkinetic behavior such as rolling, thrashing, and pedaling, and the second case, a 38-year-old woman, had been suffering from frequent daytime hyperkinetic seizures characterized by bizarre vocalization, jumping, and violent bimanual movements. Both patients showed a slight high signal change in the right posterior ventral insular cortex in fluid-attenuated inversion recovery (FLAIR) studies involving magnetic resonance imaging, and extensive subdural electroencephalographic monitoring revealed EEG seizure onset from the temporal lobe. The posterior ventral insular and lateral temporal cortices were resected, resulting in complete seizure freedom in both cases. The histological diagnoses were focal cortical dysplasia in the first case and gliosis in the second case. There may exist a group of patients with complex partial seizures with ictal violent automatism that can be ameliorated by the resection of epileptogenic lesions in the insular cortex. Careful inspection of the insular cortex is necessary to diagnose this type of epileptic seizure.

Deep Brain Stimulation for Tourette Syndrome: A Prospective Pilot Study in Japan

Objective:  Refractory Tourette syndrome (TS) disturbs the social life of patients. Deep brain stimulation (DBS) has recently been applied to relieve severe tics. We report a prospective open‐labeled case series of DBS for TS as a pilot study.

Delayed maturation and differentiation of neurons in focal cortical dysplasia with the transmantle sign: analysis of layer-specific marker expression.

Abstract Transmantle dysplasia is a rare type of focal cortical dysplasia (FCD) characterized by expansion of the cortex from the deep white matter to the surface and in which there is a FCD IIA or IIB pathologic pattern. To characterize possible mechanisms underlying this regional disorder of radial migrating cells, we studied the expression patterns of neocortical layer-specific markers using immunohistochemistry in surgical specimens from 5 FCD IIA and 4 FCD IIB cases in children. All neuronal cells expressed the mature neuron marker MAP2/2B but not the microglia markers Iba-1 and CD68. Some layer-specific markers showed distinct expression patterns. TBR1-positive, SATB2-positive, and FOXP1-positive cells were diffusely distributed in the cortex and/or the white matter. TBR1-positive and FOXP1-positive cells were generally more numerous in FCD IIB than in FCD IIA and were mostly in the cortical molecular and upper layers. FOXP1-, FOXP2-, and CUTL1-positive cells also expressed the immature neuron marker, Nestin/PROX1, whereas TBR1-, CTIP2-, and SATB2-positive cells only expressed MAP2/2B. These data highlight differences between FCD IIB and FCD IIA with more cells having the immature marker in upper layer markers in the former. By analyzing layer-specific marker expression patterns, we identified apparent neuronal maturation differences between FCD IIA and FCD IIB in cases of transmantle dysplasia.

Long-term developmental outcome after early hemispherotomy for hemimegalencephaly in infants with epileptic encephalopathy

This study aimed to identify the effect of early hemispherotomy on development in a consecutive series of 12 infants with hemimegalencephaly (HME) demonstrating epileptic encephalopathy. Mean age at onset was 20.4 days (range, 1-140), mean age at surgery was 4.3 months (range, 2-9), and mean follow-up time was 78.8 months (range, 36-121). Eleven patients had a history of early infantile epileptic encephalopathy. Vertical parasagittal hemispherotomy was performed without mortality or severe morbidities. At follow-up, seizure freedom was obtained in 8 patients (66.7%), who showed significantly higher postoperative developmental quotient (DQ) (mean, 31.3; range, 7-61) than those with seizures (mean, 5.5; range, 3-8) (p=0.02). Within the seizure-free group, postoperative DQ correlated with preoperative seizure duration (r=-0.811, p=0.01). Our results showed that shorter seizure duration during early infancy could provide better postoperative DQ in infants with HME and epileptic encephalopathy.

Secondary spinal cord hypoperfusion of circumscribed areas after injury in rats

Abstract Objectives: The evaluation of the spatial spread of ischemia following spinal cord injury (SCI) is important for planning therapeutic strategies for secondary injury. The purpose of this study was to investigate in detail the change in regional spinal cord blood flow (rSCBF) after SCI. Methods: Thirty-four male Wistar rats were used, for which laminectomies of the T11–13 vertebrae were performed. SCI was produced by a directed impact through a laminectomy site at the level of the Th12 using a pneumatic impact device. We measured the sequential and spatial changes of rSCBF using a laser Doppler scanning technique before and after SCI in rats not only at the injured myelomere but also at the circumferent myelomeres. SCBF mapping was carried out before and after SCI on each site. Results: After SCI, the rSCBF value gradually decreased for each site for the SCI group (n=26), while it globally decreased at the epicenter. Moreover, a decrease in SCBF was observed at the caudal and rostral sites. The mean value of the %SCBF 120 minutes after SCI for each site was 63.6±2.3% (Th11), 74.4±4.5% (Th12), 75.8±3.2% (Th13), and was significantly lower for the rostral site compared with the caudal site (p<0.05, one-way analysis of variance). Discussion: This study found that SCBF is significantly decreased not only at the injured myelomere but also at the circumferent myelomeres. Circumferentially extending ischemia after SCI is related to secondary injury after SCI. The improvement in SCBF after SCI, therefore, can be attributed to the treatment of SCI.

Surgical management of cortical dysplasia in infancy and early childhood

PURPOSE To describe operative procedures, seizure control and complications of surgery for cortical dysplasia (CD) causing intractable epilepsy in infancy and early childhood. METHODS Fifty-six consecutive children (less than 6years old) underwent resective epilepsy surgery for CD from December 2000 to August 2011. Age at surgery ranged from 2 to 69months (mean 23months) and the follow-up was from 1 to 11years (mean 4years 4months). RESULTS Half of the children underwent surgery during infancy at an age less than 10months, and the majority (80%) of these infants needed extensive surgical procedures, such as hemispherotomy and multi-lobar disconnection. Seizure free (ILAE class 1) outcome was obtained in 66% of the cases (class 1a; 55%): 85% with focal resection (n=13), 50% with lobar resection (n=18), 71% with multilobar disconnection (n=7) and 67% with hemispherotomy (n=18). Peri-ventricular and insular structures were resected in 23% of focal and 61% of lobar resections. Repeated surgery was performed in 9 children and 5 (56%) became seizure free. Histological subtypes included hemimegalencephaly (16 patients), polymicrogyria (5 patients), and FCD type I (6 patients), type IIA (19 patients), type IIB (10 patients). Polymicrogyria had the worst seizure outcome compared to other pathologies. Surgical complications included 1 post-operative hydrocephalus, 1 chronic subdural hematoma, 2 intracranial cysts, and 1 case of meningitis. No mortality or severe morbidities occurred. CONCLUSIONS Early surgical intervention in children with CD and intractable seizures in infancy and early childhood can yield favorable seizure outcome without mortality or severe morbidities although younger children often need extensive surgical procedures.

Imbalance of interneuron distribution between neocortex and basal ganglia: Consideration of epileptogenesis of focal cortical dysplasia

AIM The balance of excitation and inhibition of neurons and neuronal network is very important to perform complete neuronal function. Damage or loss of inhibitory γ-aminobutyric acid (GABA)-ergic interneuron is associated with impaired inhibitory control of cortical pyramidal neurons, leading to hyperexcitability and epileptogenesis. Ectopic neurons in the basal ganglia are to be one of the pathological features of epileptogenesis. In the present study, we investigated distribution of interneuron subtypes between neocortex and caudate nucleus. METHODS We performed immunohistochemistry of GABA, glutamic acid decarboxylase (GAD), calretinin (CR), calbindin (CB), parvalbumin (PV) and neuropeptide. We used surgical materials of four focal cortical dysplasia (FCD) cases, having lesions of neocortex and caudate nucleus, and eight age-matched autopsy controls. RESULTS The pathology showed three FCD IIa, containing dysmorphic neurons, and one FCD IIb, balloon cells. In the neocortex, the concentrations (each positive cell number/all cell numbers in the evaluated field) of GAD+, CR+ and CB+ cells were significantly lower in FCD than in controls. On the contrary, in the caudate nucleus those of CR+ and CB+ cells were significantly more in FCD than in controls. CONCLUSION The interneuron imbalance between the neocortex and basal ganglia may affect the epileptogenesis of FCD.

Abnormal maturation and differentiation of neocortical neurons in epileptogenic cortical malformation: unique distribution of layer-specific marker cells of focal cortical dysplasia and hemimegalencephaly.

Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are major causes of intractable epilepsy in children. The probable pathogenesis of FCD and HMG is the abnormal migration and differentiation of neurons. The aim of the present study was to clarify the abnormal cytoarchitecture, based on neuronal immaturation. Tissue samples were obtained from 16 FCD and seven HME patients, aged between 2 months and 12 years, who had been diagnosed as typical FCD and HME, following surgical treatment for intractable epilepsy. Paraffin-embedded sections were stained with the antibodies of three layer-markers that are usually present only during the fetal period, namely SATB2 (expressed in the upper layer of the normal fetal neocortex), FOXP1 (expressed in the 5th layer), and TBR1 (expressed in the 6th layer). In FCD, SATB2-positive (+) cells located in the middle and deep regions of FCD Ia and Ib, but only in the superficial region of FCD IIa and IIb. FOXP1+ cells diffusely located in the neocortex, especially the upper layer of FCD IIa and IIb. TBR1+ cells mainly located in the middle and deep regions, and also white matter. In FCD IIb, TBR1+ cells were in the superficial region. In HME, SATB2+ and FOXP1+ cells were found diffusely. TBR1+ cells were in the middle and deep regions. On the basis of continued expression of fetal cortical layer-specific markers in FCD and HME brains, the abnormal neocortical formation in both is likely to be the result of disrupted neuronal migration and dysmaturation. The expression pattern is different between FCD and HME.

Effect of corpus callosotomy on attention deficit and behavioral problems in pediatric patients with intractable epilepsy.

To evaluate the effect of corpus callosotomy (CC) on attention deficit and behavioral problems in pediatric patients with intractable epilepsy, we retrospectively investigated sequential patients who had undergone CC to control seizures. Between August 2005 and April 2010, a total of 15 patients aged between 3.1 and 17.9 years underwent CC at our institute. All the patients experienced either drop attacks or head nodding, which were considered to be therapeutic targets of CC. A standardized instrument, the Child Behavior Checklist (CBCL), was used to assess behavioral and emotional problems before and after surgery. On postoperative EEGs, 8 (53%) showed improvement and 7 (47%) showed no change in epileptiform discharges. The Attention Problems scale and total score on the CBCL significantly improved in patients whose postoperative EEGs showed improvement. In addition to amelioration of target seizures, CC can improve attention impairments in association with improvement in the postoperative EEG.