Cell Death in Acute Spinal Cord Injury

OBJECTIVE: In acute spinal cord injury, biomechanical and pathological changes in the cord may worsen after injury. To explain these phenomena, the concept of the secondary injury has evolved and numerous pathophysiological mechanisms have postulated. These, however, have mainly focused only on the cell necrosis. The aim of present study is to verify whether apoptosis plays a role in the animal model of secondary injury of spinal cord. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were laminectomized and spinal cord injury was induced using NYU spinal impactor at T9 segment. The animals were sacrificed periodically and tissue specimen was obtained at the injury segment, adjacent segments, and remote segments to observe the secondary injury ultimately for the observation of the spatial and temporal distribution and the related cells for the appearance of apoptosis, if present. RESULTS: In the spatial distribution of apoptosis, the apoptotic cells were located at gray matter of spinal cord and the number of apoptotic cells were significantly higher in adjacent segments than in the injured segment. In the temporal distribution of apoptosis, the number of apoptotic cells were maximal at 4 hours after injury and decreased subsequently. No apoptotic cells were found at remote segments which implies that there were no influence of apoptosis on transneuronal degeneration. CONCLUSION: These results suggest that the lesioned area of spinal cord expanded over time in acute spinal cord injury and apoptosis contributed to the spinal cord neuronal and glial cell loss. In conclusion, apoptosis is thought to have an important role in secondary injury of acute spinal cord injury.ope

Traumatic Aneurysm of the Pericallosal artery -A Case Report-

Traumatic intracranial aneurysms are rare, compromising less than 1% of intracranial aneurysms. The case of 20-year-old man suffered from delayed frontal intracerebral hematoma, subarachnoid hemorrhage and intraventricular hemorrhage from traumatic pericallosal aneurysm 12 days after head injury is presented. Traumatic pericallosal artery aneurysm is always near the falcine edge, is unrelated to arterial branching point. Sudden movement of brain and artery causes vessel wall injury against the stationary edge of the falx. Because of high mortality rate of ruptured traumatic aneurysm, clinical suspicion must be focused on the prompt diagnostic work-up and early treatment.ope

Expression of the DNA repair gene, N-methylpurine-DNA glycosylase in astrocytic tumors

Objective：This study is designed to investigate the association of tumorigenesis with DNA repair gene, N-methylpurine-DNA-glycosylase(MPG) in astrocytic tumors. Methods：MPG mRNA expression and localization in the 30 astrocytic tumors and 7 tumor-adjacent brain tissues was examined by reverse transcriptase-polymerase chain reaction(RT-PCR) and RNA in situ hybridization. Expression and intracellular localization of MPG protein was determined by immunohistochemistry. Statistical analysis was performed by ANOVA with a p value<0.05 considered statistically significant. Results：MPG mRNA expression in RT-PCR was significantly higher in grade IV tumor tissues than in brain tissues adjacent to tumor or in grade II-III astrocytic tumor tissues(p<0.05). MPG mRNA in in situ hybridization was detected both in brain tissues adjacent to tumor and in astrocytic tumor tissues, regardless of the tumor grades. However, MPG protein localization in immunohistochemical study was detected only in the nucleus of all tumor tissues. In brain tissues adjacent to tumor, immunohistochemical study for MPG was not stained both in the nucleus and in cytoplasm. Conclusion：These results suggest MPG's role in human astrocytic tumors and raise the possibility that the increased mRNA level and intracellular localization could be associated with astrocytic tumorigenesis. Further studies about control of MPG gene expression in astrocytic tumors are warranted.ope

Atypical Meningioma in the Fourth Ventricle

the authors report a case of atypical meningioma in the fourth ventricle. Intraventricular meningioma is not uncommon intracranial neoplasm, especially that in the trigone of lateral ventricle, however, those in the third and fourth ventricle are very rare. There are only two cases of atypical meningiomas in the fourth ventricle among 29 cases of fourth ventricular meningiomas reported 17 literature. The clinical features, findings of magnetic resonance image and operation of our case, and review of literature are presented.ope

Endovascular Treatments of Traumatic Carotid and Vertebral Vascular Injuries

Objective：The purpose of this report is to determine the safety and efficacy of endovascular therapy in the management of craniocervical vascular injuries. Methods : Fifteen patients with traumatic carotid and vertebral lesions were treated using therapeutic endovascular methods. In 13 patients with blunt trauma, five patients had a carotid-cavernous fistula, 8 had a dissecting pseudoaneurysm or arterial dissection. One of two penetrating patients had complete transection of the vertebral artery, and the other had an internal carotid artery-internal jugular vein fistula with two pseudoaneurysms. Endovascular therapy was accomplished by implanting the balloons, porous or polytetrafluoroethylene covered stent, and/or embolic materials including coils or glue. Results : All fistulas and pseudoaneurysms were successfully embolized with coils, glue, or stents. Most of all parent arteries except two patients were preserved. Sacrifice of the parent artery was inevitable in cases of thrombus formation due to coil migration into the parent artery and the existing transaction of the parent artery. No additional surgical procedures for vascular lesions were required. There were no delayed neurological or vascular complications. Additionally, no lesions recurred during follow-up periods (mean 26.9 months). Conclusion : From the author's experiences, the endovascular therapy using stents, balloons, and coils is both feasible and safe in treatment of the traumatic vascular injuries. Long-term follow-up review of these repairs will be requisite to provide a full evaluation of the safety and efficacy of these devices.ope

Preventive Effect of Clazosentan against Cerebral Vasospasm after Clipping Surgery for Aneurysmal Subarachnoid Hemorrhage in Japanese and Korean Patients

BACKGROUND: Clazosentan has been explored worldwide for the prophylaxis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). In a dose-finding trial (CONSCIOUS-1) conducted in Israel, Europe, and North America, clazosentan (1, 5, and 15 mg/h) significantly reduced the incidence of cerebral vasospasm, but its efficacy in Japanese and Korean patients was unknown. We conducted a double-blind comparative study to evaluate the occurrence of cerebral vasospasm in Japanese and Korean patients with aSAH. METHODS: The aim of this multicenter, double-blind, randomized, placebo-controlled, dose-finding phase 2 clinical trial, was to evaluate the efficacy, pharmacokinetics, and safety of clazosentan (5 and 10 mg/h) against cerebral vasospasm after clipping surgery in Japanese and Korean patients with aSAH. Patients aged between 20 and 75 years were administered the study drug within 56 h after the aneurysm rupture and up to day 14 post-aSAH. The incidence of vasospasm, defined as an inner artery diameter reduction of major intracranial arteries ≥34% based on catheter angiography, was compared between each treatment group. Cerebral infarction due to vasospasm at 6 weeks and patients' outcome at 3 months was also compared. RESULTS: Among 181 enrolled patients, 158 completed the study and were analyzed. The incidence of vasospasm up to day 14 after aSAH onset was 80.0% in the placebo group (95% CI 67.0-89.6), 38.5% in the 5 mg/h clazosentan group (95% CI 25.3-53.0), and 35.3% in the 10 mg/h clazosentan group (95% CI 22.4-49.9), indicating that the incidence of vasospasm was significantly reduced by clazosentan treatment (placebo vs. 5 mg/h clazosentan, p < 0.0001; placebo vs. 10 mg/h clazosentan, p < 0.0001). The occurrence of cerebral infarction due to vasospasm was 20.8% in the placebo group (95% CI 10.8-34.1), 3.8% in the 5 mg/h clazosentan group (95% CI 0.5-13.2), and 4.2% in the 10 mg/h clazosentan group (95% CI 0.5-14.3), indicating that clazosentan significantly reduced the occurrence of cerebral infarctions caused by vasospasm (placebo vs. 5 mg/h clazosentan, p = 0.0151; placebo vs. 10 mg/h clazosentan, p = 0.0165). The overall incidence of all-cause death and/or vasospasm-related morbidity/mortality was significantly reduced in the 10 mg/h clazosentan group compared with the placebo group (p = 0.0003). CONCLUSION: These results suggest that clazosentan prevents cerebral vasospasm and subsequent cerebral infarction, and could thereby improve outcomes after performing a clipping surgery for aSAH in Japanese and Korean patients.ope

Surgical Management of Middle Cerebral Artery Aneurysms

Middle cerebral artery (MCA) aneurysms account for approximately one-fifth of aneurysmal subarachnoid hemorrhage. The preferred treatment of these aneuryms is microsurgical clipping because of their peripheral location, large neck-to-fundus ratio, incorporation of major branches into the aneurysmal wall, and high incidence of intracerebral hematoma. MCA aneurysms can be approached surgically using one or two of three basic techniques; medial transsylvian, lateral transsylvian and superior temporal gyrus approach. In this presentation, selection of surgical approaches and the surgical techniques to minimize the neurovascular structures are described. Management outcomes by using these techniques is also presented.ope

Genetic Mutation of 5, 10-Methylenetetrahydrofolate Reductase in the Brain Neoplasms

Objective：Recent epidermiologic studies suggested that alterations in folate metabolism as a result of polymorphism in the enzyme 5,10-methylenetetrahydrofolate reductase(MTHFR) have been frequently associated with neural tube defects, vascular disease, and some cancers. A common 677C→T polymorphism in the MTHFR gene results in thermolability and reduced MTHFR activity that decreases the pool of 5-methyltetrahydrofolate and increases the pool of 5,10-methylenetetrahydrofolate. A possible cause underlying altered DNA methylation could be an insufficient level of S-adenosylmethionine as a consequence of weaker alleles of MTHFR gene. Therefore, the weak MTHFR activity may underlie susceptibility to brain neoplasms. We now report the associations of MTHFR polymorphisms in three groups of adult brain tumors：gliomas, meningiomas and schwannomas. Methods：We analyzed DNA of 71 brain tumors and 254 age- and sex-matched controls with a case-control study. MTHFR variant alleles were determined by a PCR-restriction fragment length polymorphism assay. Results：The incidence of the MTHFR 677TT genotype was higher among 20 schwannoma cases compared with that of 254 controls, conferring a 5-fold increase of the risk of schwannomas(odds ratio, OR=4.75；95% confidence index, CI=1.05-21.50). The homozygous mutant group had half the risk of meningioma(OR=0.42；95% CI = 0.11-1.58) compared with the homozygous normal or heterozygous genotypes. There was no significant difference in MTHFR 677TT genotype frequency between glioma group(19 cases) and control group(254 cases)(OR = 1.53；95% CI = 0.30-7.73). Conclusion：The data indicate that the homozygous 677TT MTHFR genotype confers the significantly higher risk of schwannoma and the lower risk of meningioma. However, our study had limited a statistical power because of the small sample size, which is reflected in the wide CIs. Hence, these findings need to be confirmed in larger populations.ope

Multiple Separate Aneurysms on Anterior Communicating Artery

Multiple cerebral aneurysms reportedly account for 14-33 % of all cerebral aneurysms. The incidence of multiple aneurysms has been increasing with development of radiological diagnostic tools such as magnetic resonance angiography, digital subtraction angiography and three dimension computed tomography. However, multiple aneurysms arising from same parent artery are uncommon. We have found only a few references as to diagnosis and surgical treatment of such lesions in the literature. Multiple separate aneurysms on same parent artery have been found most frequently on internal carotid artery 2, and then from middle cerebral artery (MCA). Those lesions arising from anterior communicating artery (ACoA) are rare. We report 7 cases (5.21%) of multiple aneurysms developed separately on ACoA and describe angiographic and operative finding of these rare lesions. One hundred and thirty four ACoA aneurysms were operated in our hospital from May 1997 to November 2004. There were only 7 patients with multiple aneurysms on ACoA. Out of 7 cases, four were diagnosed preoperatively and the other 2 were found intraoperatively. Multiple aneurysms may be associated with familiar aneurysms or arteriovenous malformations, however, there was no such case in our series. All patients were treated successfully with single or multiple clippings. Despite the advanced technology in radiological examinations, these lesions may not be detected on preoperative study. Close proximity or smaller size of the lesion may be responsible for the preoperative false negative angiographic findings. It is recommended to keep this possibility in mind during aneurysm surgery. Careful dissection is mandatory to ensure the completeness of aneurysm surgery.ope

Surgery of Parasplenial Arteriovenous Malformation with Preservation of vision

Parasplenial arteriovenous malformations(AVMs) are rare vascular malformations which have distinct clinical and anatomical features. They are situated at the confluence of the hippocampus, isthmus of the cingulate gyrus and the gyrus occipitotemporalis medialis. These lesions are anterior to the calcarine sulcus and their apex extends towards the medial surface of the trigonum. Posterolaterally, these lesions are in close proximity to the visual cortex and optic radiation. The objectives in the surgery of parasplenial AVMs are complete resection of the lesions and preservation of vision. These objectives must be achieved with comprehensive understanding of the following anatomical features：1) the deep central location of the lesions within eloquent brain tissue；2) the lack of cortical representation of the AVMs that requires retraction of visual cortex；3) deep arterial supply；4) deep venous drainage； 5) juxtaposition to the choroid plexus with which arterial supply and venous drainage are shared. A 16-year-old female student presented with intraventricular hemorrhage from a right parasplenial-subtrigonal AVM. The lesion, fed by posterior cerebral artery and drained into the vein of Galen, was successfully treated by the inter-hemispheric parietooccipital approach. To avoid visual field defect a small incision was made on precuneus anterior to the calcarine sulcus. In this report, the authors describe a surgical approach with special consideration on preservation of visual field.ope