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Hernando Rafael

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Izumi Yamaguchi, Kyong-Hon Pooh, Mai Azumi and Yasushi Takagi

Temporal crescent syndrome is a monocular visual field defect involving the temporal crescent of one eye caused by a retrochiasmal lesion. The most anterior portion of the striate cortex is the only area where the retrochiasmal lesion produces a monocular visual field defect. The authors present the case of a 9-year-old boy who presented with mild headache. MRI revealed a cyst with cerebrospinal fluid signal intensity, occupying the body and trigone of the right lateral ventricle. Conservative treatment with regular clinical and radiological follow-up was chosen because neurological examination findings were normal. Three years later, the patient experienced blurred vision with a temporal crescent defect in the left eye. Endoscopic cyst fenestration was performed, and the pathological findings indicated a glioependymal cyst. After surgery, the monocular temporal crescent disorder was resolved. MRI indicated shrinkage of the cyst and improvement in the narrowing of the anterior calcarine sulcus. These findings suggested that the temporal crescent syndrome was caused by a lateral ventricular glioependymal cyst. This is the first known report of temporal crescent syndrome caused by a lateral ventricular glioependymal cyst. In patients with monocular temporal crescent disorder without intraocular disease, a retrochiasmal lesion in the most anterior portion of the striate cortex should be considered.

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Toru Iwama, Nobuo Hashimoto, Yasushi Takagi, Michihiro Tanaka, Satoshi Yamamoto, Shogo Nishi and Kohei Hayashida

✓ In patients with intracranial dural arteriovenous fistulas (AVFs), clinical symptoms and angiographic findings vary. The relevance of disturbed venous drainage to clinical symptoms and prognosis has been recognized. However, the roles of cerebral hemodynamics and metabolism, which are impaired by shunt flow or disturbed venous drainage, have not been fully evaluated. The authors studied the cerebral hemodynamic and metabolic status in 10 patients with intracranial dural AVFs using positron emission tomography (PET) scanning. Ten patients with dural AVFs underwent a PET study before treatment. The regional cerebral blood flow (rCBF), regional oxygen extraction fraction (rOEF), regional cerebral metabolic rate of oxygen (rCMRO2), and regional cerebral blood volume (rCBV) were measured using the 15O-labeled gas inhalation steady-state method. The PET parameters that were obtained were analyzed and compared with the patients' neurological and angiographic findings. In six of the 10 patients, a PET study was also performed after treatment. Before treatments, all four patients with cerebral symptoms showed a severe reduction in rCBF and a mild elevation in the rOEF. The areas showing reduced rCBF corresponded with areas in which retrograde venous drainage into the cortical veins and delayed parenchymal circulation were seen on angiograms. In another two patients with occlusion of the affected sinus and/or retrograde drainage into the cortical veins, mild abnormalities were demonstrated in rCBF mapping. In the remaining four patients, all PET parameters except rCBV were within normal limits and venous flow was not impaired on the angiograms. In four patients who underwent surgical excision or transvenous embolization of the affected sinus, the cerebral hemodynamics and metabolism were improved, as were the clinical symptoms. In two patients who underwent transarterial embolization of the feeding vessels only or craniotomy, no hemodynamic improvement was achieved. Our results indicate that hemodynamic insufficiency detected by the PET study corresponded well with cerebral symptoms and angiographic findings of retrograde venous drainage into the cortical veins and delayed parenchymal circulation, but not with sinus occlusion or arterial blood supply. Eradication or prevention of retrograde venous drainage from the affected sinus into the cortical veins should be a treatment goal in patients with dural AVFs.

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Kazuhiko Nozaki, Takaaki Inomoto, Yasushi Takagi and Nobuo Hashimoto

✓ The spinal intradural extramedullary cavernous angioma is a rare clinical entity. Only 20 surgically treated cases have been reported. The authors report on an additional case in which the lesion was located in the cervical region, and they summarize its unique clinical features. Intradural extramedullary cavernous angiomas occur predominantly in males, in the lower thoracolumbar region, exhibit a relatively high association with subarachnoid hemorrhage, and mostly adhere to the nerve root or spinal cord. Because resection is possible without causing morbidity and because outcome depends on the severity of preoperative neurological dysfunction, precise diagnosis and timely treatment are mandatory.

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Shigeki Yamada, Yasushi Takagi, Kazuhiko Nozaki, Ken-ichiro Kikuta and Nobuo Hashimoto

Object

The aim of this study was to identify the natural history of untreated cerebral arteriovenous malformations (AVMs) and the risk factors for subsequent hemorrhage after an initial AVM diagnosis.

Methods

The authors studied 305 consecutive patients with AVMs at the Kyoto University Hospital between 1983 and 2005. These patients were followed up until the first subsequent hemorrhage, the start of any treatment, or the end of 2005. Possible risk factors that were investigated included age at initial diagnosis, sex, type of initial presentation, size and location of the AVM nidus, and the venous drainage pattern. Subsequent hemorrhage occurred in 26 patients from the hemorrhagic group during 380 patient–years, and in 16 patients from the nonhemorrhagic group during 512 patient–years.

Results

The annual bleeding rate in the hemorrhagic group was 6.84% after the initial hemorrhage; however, that rate decreased in the first 5 years (15.42% in the first year, 5.32% in the subsequent 4 years, and 1.72% in more than 5 years). In the nonhemorrhagic group (annual bleeding rate of 3.12%), the patients initially presenting with headaches (annual bleeding rate of 6.48%) or asymptomatic presentations (annual bleeding rate of 6.44%) had a higher risk for subsequent hemorrhage. Conversely, those patients presenting with seizures (annual bleeding rate of 2.20%) or neurological deficits (annual bleeding rate of 1.73%) had a lower risk. A significantly increased risk (p < 0.05) of rebleeding was found among children (hazard ratio [HR] = 2.69), females (HR = 2.93), or patients with deep-seated AVMs (HR = 3.07).

Conclusions

Children, females, and patients with deep-seated AVMs had a threefold increased risk of rebleeding after an initial cerebral AVM. This increased risk was highest in the first year after the initial hemorrhage, and thereafter gradually decreased.

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Yasushi Takagi, Ken-Ichiro Kikuta, Kazuhiko Nozaki, Motoaki Fujimoto, Junya Hayashi and Nobuo Hashimoto

Object

The expression and localization of phosphorylated Fas-associated death domain protein (pFADD) and cleaved caspase-8 was examined in human cerebral arteriovenous malformations (AVMs). The authors focused on the perinidal parenchyma to clarify the effect of AVMs on perinidal brain tissue.

Methods

Seventeen cerebral AVMs were analyzed using immunohistochemical methods. Specimens were removed from patients during surgical procedures. The characteristics of the areas that stained positively for pFADD or cleaved caspase-8 were also assessed using an image analysis system. Eleven (65%) of the 17 lesions demonstrated anti-pFADD immunoreactivity and 12 (71%) showed anti–cleaved caspase-8 immunoreactivity. The immunoreactive cells in the perinidal parenchyma demonstrated obvious neuronal morphological characteristics.

The characteristics of pFADD-positive and cleaved caspase-8–positive areas were assessed using the image analysis system. The mean distance from the nidus adjacent to either area was not affected by preoperative hemorrhage. The neuronal densities of pFADD-positive and cleaved caspase-8–positive areas were analyzed using the same system. The density of the control area (samples that were pFADD-negative and cleaved caspase-8 negative) was significantly higher when compared with that of pFADD-positive and cleaved caspase-8–positive areas (p < 0.05). The expressions of cleaved caspase-9, cleaved poly(adenosine diphosphate–ribose) polymerase, and apoptotic cells were analyzed using the terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling method.

Conclusions

Neuronal areas that stained positively for pFADD and cleaved caspase-8 existed around the nidus of AVMs. In these areas, the neuronal density was lower than that in the other parenchyma around the AVM. Neuronal loss around the nidus may be the origin of brain dysfunction around AVMs.

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Tomohiro Aoki, Masaki Nishimura, Ryota Ishibashi, Hiroharu Kataoka, Yasushi Takagi and Nobuo Hashimoto

Object

The pathophysiological origin of cerebral aneurysms is closely associated with chronic inflammation in arterial walls. Recently, the authors identified nuclear factor–kappa B (NF-κB) as a key mediator of cerebral aneurysm formation and progression. Because Toll-like receptor 4 (TLR4) stimulates NF-κB activation in arterial walls in atherosclerosis, the authors hypothesize that TLR4 expresses in cerebral aneurysms and contributes to the activation of NF-κB in cerebral aneurysm walls.

Methods

Cerebral aneurysms were induced in male Sprague-Dawley rats. Expression of TLRs in cerebral aneurysm walls was assessed using reverse transcriptase polymerase chain reaction (RT-PCR). The expression of TLR4 was examined using RT-PCR, immunohistochemical studies, and Western blotting. To assess TLR4 dependency on NF-κB activation, double immunostaining and a study using NF-κB–deficient mice were done. Finally, TLR4 expression in human cerebral aneurysm walls was assessed using immunohistochemical studies.

Results

In cerebral aneurysm walls, TLR1, -4, -5, -6, -10, and -11 were expressed. Among them, TLR4 and TLR10 expression changed during cerebral aneurysm formation. Expression of TLR4 was predominantly in the endothelial cell layer of cerebral aneurysm walls, and was transitionally upregulated at the early stage of cerebral aneurysm formation. The TLR4 expression coincided well with NF-κB activation. In human cerebral aneurysms, TLR4 was also expressed in the endothelial cell layer, as it was in rats.

Conclusions

Toll-like receptor 4 was expressed in cerebral aneurysm walls both in rats and humans. This receptor may play a crucial role in cerebral aneurysm formation through NF-κB activation in endothelial cells. The results of the present study will shed new light on the pathogenesis of cerebral aneurysm formation.

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Yasushi Takagi, Masaki Nishimura, Asuka Morizane, Jun Takahashi, Kazuhiko Nozaki, Junya Hayashi and Nobuo Hashimoto

Object. Cell replacement therapy including the use of embryonic stem cells (ESCs) may represent a novel treatment for damage from stroke. In this study, the authors transplanted neural progenitor cells (NPCs) derived from ESCs into ischemic brain and analyzed their survival and differentiation.

Methods. Multipotential NPCs were generated from ESCs by using the stromal cell—derived inducing activity method. These cells could differentiate in vitro into neurons, glia, and oligodendrocytes, thus revealing them to be neural stem cells. The NPCs were then transplanted into ischemic brain. At 2 weeks postischemia, the transplanted cells occupied 18.8 ± 2.5% of the hemispheric area; by 4 weeks postischemia, 26.5 ± 4% of the hemisphere. At 4 weeks after transplantation, green fluorescent protein (GFP)—positive transplanted cells showed mature neuronal morphological features. The authors also investigated the expression of differentiation markers and various neurotransmitters. Transplanted cells were immunopositive for neuronal nuclei, β-tubulin-III, and glial fibrillary acidic protein. Of the GFP-positive cells, 33.3 ± 11.5% were positive for glutamate decarboxylase, 13.3 ± 5.8% for glutamate, 2.1 ± 2.5% for tyrosine hydroxylase, 1.8 ± 2% for serotonin, and 0.4 ± 0.2% for choline acetyltransferase.

Conclusions. The authors confirmed the survival and differentiation of ESC-derived NPCs transplanted into the ischemic brain. Surviving transplanted cells expressed several neural markers and neurotransmitters. These findings indicate that these cells can function in the brain.

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Yasushi Takagi, Ken-ichiro Kikuta, Kazuhiko Nozaki, Keiko Sawamura and Nobuo Hashimoto

✓With the use of indocyanine green (ICG) as a novel fluorescent dye, and its integration into a compact system that takes advantage of modern video technology, fluorescence angiography has recently reemerged as a viable option. In this report, the authors show the efficacy of ICG videoangiography in the case of a child with a cerebral arteriovenous malformation (AVM). In this case, the ICG videoangiography shows residual nidus of diffuse-type AVM. This is a safe and simple method that can be used to assess the microcirculation of the brain. The ICG videoangiography is helpful in resecting residual cerebral AVM, especially in cases of diffuse-type AVM.

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Ken-ichiro Kikuta, Yasushi Takagi, Yoshiki Arakawa, Susumu Miyamoto and Nobuo Hashimoto

✓ The authors present the case of a 6-year-old girl with typical absence epilepsy induced by hyperventilation associated with moyamoya disease (MMD). A diffuse 3-Hz spike-and-wave complex induced by hyperventilation was apparent on an electroencephalogram, and her seizures were intractable to medication. Significant ischemia in the bilateral frontal lobes was present. The epilepsy disappeared after superficial temporal artery–middle cerebral artery anastomosis with encephalomyosynangiosis on both sides. In the treatment of children with intractable absence epilepsy, the possibility of underlying MMD and indications that revascularization surgery may be needed should be taken into consideration.