Role of a Burr Hole and Calvarial Bone Marrow-Derived Stem Cells in the Ischemic Rat Brain: A Possible Mechanism for the Efficacy of Multiple Burr Hole Surgery in Moyamoya Disease

OBJECTIVE: This study investigates the role of a burr hole and calvarial bone marrow-derived stem cells (BMSCs) in a transient ischemic brain injury model in the rat and postulates a possible mechanism for the efficacy of multiple cranial burr hole (MCBH) surgery in moyamoya disease (MMD). METHODS: Twenty Sprague-Dawley rats (250 g, male) were divided into four groups : normal control group (n=5), burr hole group (n=5), ischemia group (n=5), and ischemia+burr hole group (n=5). Focal ischemia was induced by the transient middle cerebral artery occlusion (MCAO). At one week after the ischemic injury, a 2 mm-sized cranial burr hole with small cortical incision was made on the ipsilateral (left) parietal area. Bromodeoxyuridine (BrdU, 50 mg/kg) was injected intraperitoneally, 2 times a day for 6 days after the burr hole trephination. At one week after the burr hole trephination, brains were harvested. Immunohistochemical stainings for BrdU, CD34, VEGF, and Doublecortin and Nestin were done. RESULTS: In the ischemia+burr hole group, BrdU (+), CD34 (+), and Doublecortin (+) cells were found in the cortical incision site below the burr hole. A number of cells with Nestin (+) or VEGF (+) were found in the cerebral parenchyma around the cortical incision site. In the other groups, BrdU (+), CD34 (+), Doublecortin (+), and Nestin (+) cells were not detected in the corresponding area. These findings suggest that BrdU (+) and CD34 (+) cells are bone marrow-derived stem cells, which may be derived from the calvarial bone marrow through the burr hole. The existence of CD34 (+) and VEGF (+) cells indicates increased angiogenesis, while the existence of Doublecortin (+), Nestin (+) cells indicates increased neurogenesis. CONCLUSION: Based on these findings, the BMSCs through burr holes seem to play an important role for the therapeutic effect of the MCBH surgery in MMD.

Locations and Clinical Significance of Non-Hemorrhagic Brain Lesions in Diffuse Axonal Injuries

OBJECTIVE: Detection of focal non-hemorrhagic lesion (NHL) has become more efficient in diffuse axonal injury (DAI) patients using an MRI. The aims of this study are to find out the radiological distribution, progress of NHL and its clinical significance. METHODS: Between September 2005 and October 2011, 32 individuals with NHLs on brain MRI were enrolled. NHLs were classified by brain location into 4 major districts and 13 detailed locations including cortical and subcortical, corpus callosum, deep nuclei and adjacent area, and brainstem. The severity of NHL was scored from grades 1 to 4, according to the number of districts involved. Fourteen patients with NHL were available for MRI follow-up and an investigation of the changes was conducted. RESULTS: Thirty-two patients had 59 NHLs. The most common district of NHL was cortical and subcortical area; 15 patients had 20 NHSs. However the most common specific location was the splenium of the corpus callosum; 14 patients had 14 lesions. The more lesions patients had, the lower the GCS, however, this was not a statistically meaningful difference. On follow-up MRI in 14 patients, out of 24 lesions, 13 NHLs resolved, 5 showed cystic change, and 6 showed atrophic changes. CONCLUSION: NHLs were located most commonly in the splenium and occur frequently in the thalamus and the mesial temporal lobe. Because most NHS occur concomitantly with hemorrhagic lesions, it was difficult to determine their effects on prognosis. Since most NHLs resolve completely, they are probably less significant to prognosis than hemorrhagic lesions.

Remote Cerebellar Hemorrhage after Lumbar Spinal Surgery

Remote cerebellar hemorrhage (RCH) is rare but potentially lethal as a complication of spinal surgery. We recently experienced a case of RCH in a 61-year-old man who showed mental deterioration after lumbar spinal surgery. There was dural tearing with subsequent cerebrospinal fluid (CSF) loss during the surgery. Brain computed tomography scan revealed cerebellar hemorrhage, 3rd and 4th ventricular hemorrhage and pneumocephalus. He underwent suboccipital craniectomy and hematoma removal. The most important pathomechanism leading to RCH after spinal surgery has been known to be venous bleeding due to caudal sagging of cerebellum by rapid leak of large amount of CSF which seems to be related with this case. Dural repair and minimizing CSF loss after intraoperative dural tearing would be helpful to prevent postoperative RCH.

Detection of Traumatic Cerebral Microbleeds by Susceptibility-Weighted Image of MRI

OBJECTIVE: Susceptibility-weighted image (SWI) is a sensitive magnetic resonance image (MRI) technique to detect cerebral microbleeds (MBLs), which would not be detected by conventional MRI. We performed SWI to detect MBLs and investigated its usefulness in the evaluation of mild traumatic brain injury (MTBI) patients. METHODS: From December 2006 to June 2007, twenty-one MTBI patients without any parenchymal hemorrhage on conventional MRI were selected. Forty-two patients without trauma were selected for control group. According to the presence of MBLs, we divided the MTBI group into MBLs positive [SWI (+)] and negative [SWI (-)] group. Regional distribution of MBLs and clinical factors were compared between groups. RESULTS: Fifty-one MBLs appeared in 16 patients of SWI (+) group and 16 MBLs in 10 patients of control group [control (+)], respectively. In SWI (+) group, MBLs were located more frequently in white matters than in deep nucleus different from the control (+) group (p < 0.05). Nine patients (56.3%) of SWI (+) group had various neurological deficits (disorientation in 4, visual field defect in 2, hearing difficulty in 2 and Parkinson syndrome in 1). Initial Glasgow Coma Scale (GCS)/mean Glasgow Outcome Scale (GOS) were 13.9 +/- 1.5 / 4.7 +/- 0.8 and 15.0 +/- 0.0 / 5.0 +/- 0.0 in SWI (+) and SWI (-) groups, respectively (p < 0.05). CONCLUSION: Traumatic cerebral MBLs showed characteristic regional distribution, and seemed to have an importance on the initial neurological status and the prognosis. SWI is useful for detection of traumatic cerebral MBLs, and can provide etiologic evidences for some post-traumatic neurologic deficits which were unexplainable with conventional MRI.

The Effect of Barbiturate Coma Therapy for the Patients with Severe Intracranial Hypertension : A 10-Year Experience

OBJECTIVE: Barbiturate coma therapy (BCT) has been known to be an useful method to control increased intracranial pressure (IICP) refractory to medical and surgical treatments. We have used BCT for patients with severe IICP during the past 10 years, and analyzed our results with review of literatures. METHODS: We analyzed 92 semicomatose or comatose patients with Glasgow coma scale (GCS) of 7 or less with severe IICP due to cerebral edema secondary to parenchymal damages irrespective of their causes. Forty patients who had received BCT with ICP monitoring from January 1997 to December 2006 were included in BCT group, and fifty-two patients who had been managed without BCT from January 1991 to December 1995 were divided into control group. We compared outcomes with Glasgow outcome scale (GOS) and survival rate between the two groups. RESULTS: Good outcome (GOS=4 and 5) rates at 3-month after insult were 27.5% and 5.8% in BCT and control group, respectively (p<0.01). One-year survival rates were 35.9% and 12.5% in BCT and control group, respectively (p<0.01). In BCT group, the mean age of good outcome patients (37.1 +/- 14.9) was significantly lower than that of poor outcome patients (48.1 +/- 13.5) (p<0.05). CONCLUSION: With our 10-year experience, we suggest that BCT is an effective treatment method for severe IICP patients for better survival and GOS, especially for younger patients.

Predictable Risk Factors for Adjacent Segment Degeneration After Lumbar Fusion

OBJECTIVE: The aim of this study is to investigate predictable risk factors for radiologic degeneration of adjacent segment after lumbar fusion and preoperative radiologic features of patients who underwent additional surgery with adjacent segment degeneration. METHODS: Between January 1995 and December 2002, 201 patients who underwent lumbar fusion for degenerative conditions of lumbar spine were evaluated. We studied radiologic features, the method of operation, the length of fusion, age, sex, osteoporosis, and body mass index. Special attention was focused on, preoperative radiologic features of patients who required additional surgery were studied to detect risk factors for clinical deterioration. RESULTS: Follow-up period ranged from 3 to 11 years. In our study, 61 (30%) patients developed adjacent segment degeneration, and 15 (7%) patients required additional surgery for neurologic deterioration. Age, the postoperative delay, facet volume, motion range, laminar inclination, facet tropism, and preexisting disc degeneration of adjacent segment considered as possible risk factors. Among these, laminar inclination and preexisting disc degeneration of adjacent segment were significantly correlated with clinical deterioration. CONCLUSION: The radiologic degeneration of adjacent segment after lumbar fusion can be predicted in terms of each preoperative radiologic factor, age and the postoperative delay. Laminar inclination and preexisting disc degeneration of adjacent segment have shown as strong risk factors for neurologic deterioration. Thus, careful consideration is warranted when these risk factors are present.

What are the Differences in Outcome among Various Fusion Methods of the Lumbar Spine?

OBJECTIVE: For Posterior lumbar interbody fusion(PLIF) various cages or iliac bone dowels are used with or without pedicle screw fixation(PSF). To evaluate and compare the clinical and radiological results of different fusion methods, we intend to verify the effect of added PSF on PLIF, the effect of bone cages and several factors which are thought to be related with the postoperative prognosis. METHODS: One hundred and ninety seven patients with lumbar spinal stenosis and instability or spondylolisthesis underwent various fusion operations from May 1993 to May 2003. The patients were divided into five groups, group A (PLIF with autologous bone dowels, N=24), group B (PLIF with bone cages, N=13), group C (PLIF with bone dowels and PSF, N=37), group D (PLIF with bone cages and PSF, N=30) and group E (PSF with intertransverse bone graft, N=93) for comparison and analyzed for the outcome and fusion rate. RESULTS: Outcome was not significantly different among the five groups. In intervertebral height (IVH) changes between pre- and post-operation, Group B (2.42+/-2.20mm) was better than Group A (-1.33+/-2.05mm). But in the Group C, D and E, the IVH changes were not different statistically. Fusion rate of group C, D was higher than that of Group A and B. But the intervertebral height(IVH) increased significantly in group B(2.42+/-2.20mm). Fusion rate of group C and D were higher than that of group A and D. CONCLUSION: Intervertebral cages are superior to autologous iliac bone dowels for maintaining intervertebral height in PLIF. The additional pedicle screw fixation seems to stabilize the graft and improve fusion rates.

Effect on Varying the Impact Velocity in the Controlled Cortical Impact Injury Model: Injury Severity and Impact Velocity

OBJECTIVE: A study of the histopathologic and neurobehavioral correlates of cortical impact injury produced by increasing impact velocity using the controlled cortical impact(CCI) injury model is studied. METHODS: Twenty-four Sprague-Dawley rats (200~250g) were given CCI injury using a pneumatically driven piston. Effect of impact velocity on a 3mm deformation was assessed at 2.5m/sec (n=6), 3.0m/sec (n=6), 3.5m/sec (n=6), and no injury (n=6). After postoperative 24hours the rats were evaluated using several neurobehavioral tests including the rotarod test, beam-balance performance, and postural reflex test. Contusion volume and histopathologic findings were evaluated for each of the impact velocities. RESULTS: On the rotarod test, all the injured rats exhibited a significant difference compared to the sham-operated rats and increased velocity correlated with increased deficit (P<0.001). Contusion volume increased with increasing impact velocity. For the 2.5, 3.0, and 3.5m/sec groups, injured volumes were 18.8+/-2.3mm3, 26.8+/-3.1mm3, and 32.5+/-3.5mm3, respectively. In addition, neuronal loss in the hippocampal sub-region increased with increasing impact velocity. In the TUNEL staining, all the injured groups exhibited definitely positive cells at pericontusional area. However, there were no significant differences in the number of positive cells among the injured groups. CONCLUSION: Cortical impact velocity is a critical parameter in producing cortical contusion. Severity of cortical injury is proportional to increasing impact velocity of cortical injury.

p53 Protein Expression Area as a Molecular Penumbra of Focal Cerebral Infarction in Rats

OBJECTIVE: The authors investigate the spatial characteristics of apoptotic genes expressed around the focal cerebral infarction, and attempted to explain the penumbra with them. METHODS: A delayed focal cerebral infarction was created in twelve adult Sprague-Dawley rats. We performed the immunohistochemical staining for the apoptosis, bcl-2 and p53 proteins and measured the local cerebral blood flow (CBF) at the infarction core area and peri-infarct area pre- and intra-operatively. The peri-infarct area was divided into six sectors by distance from the infarction border. RESULTS: The size (mm2) of apoptosis, bcl-2, and p53 areas were 3.1+/-1.2, 4.7+/-2.1, and 6.8+/-2.4, respectively. Apoptosis, bcl-2 or p53 positive cells were concentrated at the peri-infarct area adjacent to the infarction core. Their numbers reduced peripherally, which was inversely proportional to the local CBF. The p53 area seems to overlap with and larger than the ischemic penumbra. CONCLUSION: The p53 positive area provides a substitutive method defining the penumbra under the molecular base of knowledge.

Efficacy of Unilateral Laminectomy for Bilateral Decompression in Elderly Lumbar Spinal Stenosis

OBJECTIVE: The aim of our study is to evaluate the effectiveness of unilateral hemilaminectomy for bilateral decompression in elderly patients with degenerative spinal stenosis. For this purpose, we studied the co-morbid condition and clinical outcome of patients who underwent decompressive surgery using the unilateral approach technique. METHODS: Thirty-four patients over 65years of age who underwent unilateral partial laminectomy for bilateral decompression from January 2000 to October 2003 were analyzed. These patients were studied for preoperative co-morbid condition and physical status according to the American Society of Anesthesiologists(ASA) classification, postoperative morphometrical change, and clinical outcomes, including visual analogue scale(VAS) score. The mean follow-up was 23months (range 6-48months). RESULTS: A patient's physical status was recorded as class I, II, or III by ASA classification, which correlated to 41.2%, 44.1%, and 14.7% of patients, respectively. The cross-sectional area of the pre- and postoperative dural sac at the level of the stenosis was 52.5+/-19.9mm2 and 110.6+/-18.2mm2, respectively. The outcome was excellent in 8.8%, good in 58.8%, fair in 23.6%, and poor in 8.8% of the patients. The VAS was changed postoperatively to 3.1+/-1.2. There was no operation-related transfusion yet there was no evidence of postoperative instability at the follow-up examination. CONCLUSION: Unilateral laminectomy for bilateral decompression, in spite of the limited exposure, can result in satisfactory decompression of the lumbar spinal stenosis and tolerable clinical outcome. This approach is thought to be appropriate for elderly patients who have a greater surgical burden.

Neuroprotective Effect of Ginseng Total Saponins in Experimental Traumatic Brain Injury

In the present study, we investigated whether ginseng total saponins (GTSs) protect hippocampal neurons after experimental traumatic brain injury (TBI) in rats. A moderate-grade TBI was made with the aid of a controlled cortical impact (CCI) device set at a velocity of 3.0 m/sec, a deformation of 3.0 mm, and a compression time of 0.2 sec at the right parietal area for adult male Sprague-Dawley rats. Shamoperated rats that underwent craniectomy without impact served as controls. GTSs (100 and 200 mg/kg) or saline was injected intraperitoneally into the rats immediately post-injury. Twenty-four hours after the injury, the rats underwent neurological evaluation. Contusion volume and the number of hippocampal neurons were calculated with apoptosis evaluated by TUNEL staining. 24 hr post-injury, salineinjected rats showed a significant loss of neuronal cells in the CA2 region of the right hippocampus (53.4%, p<0.05) and CA3 (34.6%, p<0.05) compared with contralateral hippocampal region, a significant increase in contusion volume (34 +/-8microliter), and significant increase in neurologic deficits compared with the GTSs groups. Treating rats with GTSs seemed to protect the CCI-induced neuronal loss in the hippocampus, decrease cortical contusion volume, and improve neurological deficits.

Development of a Rat Model of Graded Contusive Spinal Cord Injury Using a Pneumatic Impact Device

An animal model of spinal cord trauma is essential for understanding the injury mechanisms, cord regeneration, and to aid the development of new therapeutic modalities. This study focused on the development of a graded experimental contusion model for spinal cord injury (SCI) using a pneumatic impact device made in Korea. A contusive injury was made to the dorsal aspect of the cord. Three trauma groups were defined according to the impact velocity (IV). A control group (n=6), received laminectomy only. Group 1 (n=10), 2 (n=10), and 3 (n=10) had IVs of 1.5 m/sec, 2.0 m/sec, and 3.5 m/sec respectively. Functional assessments were made up to the 14th day after injury. The cord was removed at the 14th post-injury day and prepared for histopathologic examination. Significant behavioral and histopathological abnormalities were found in control and each trauma group. All trauma groups showed severe functional impairment immediately after injury but following different rates of functional recovery (Fig. 5). As the impact velocity and impulse increased, the depth of contusive lesion revealed to be profound the results show that the rat model reproduces spinal cord lesions consistently, has a distinctive value in assessing the effects of impact energy.

Coexistence of Cerebral Amyloid Angiopathy and an Arteriovenous Malformation in a Young Adult

The prevalence and cerebral hemorrhage of cerebral amyloid angiopathy(CAA) are age-related. It is rare in young adults. The authors report on CAA coexisting with an arteriovenous malformation(AVM) in a 30-year-old male, who present with the sudden onset of headache and vomiting. Magnetic resonance imaging revealed a cerebral hemorrhage with an AVM. The AVM was completely removed through the hematoma and the histological section obtained from the periphery of the hematoma showed the typical findings of CAA. The epsilon4 allele of apoprotein E(apoE) was identified in genotype determination.

Esthesioneuroblastoma Treated by Craniofacial Resection: Case Report

The authors report a case of esthesioneuroblastoma with intracranial extension treated by craniofacial resection. The tumor was resected by transbasal approach and repaired the dural defect using pericranial flap. The defect of floor of anterior cranial fossa was repaired with splitted calvarium and pericranial flap. Otorhinolaryngologist removed the residual tumor mass located at paranasal sinuses using lateral rhinotomy. Using cranifacial resection, the authors could remove the mass completely. The patient was referred to hemato-oncologist for chemotherapy.

Differences in Biomechanical Factors for Fusion Transition Syndrome of Lumbar Spine between Pedicle Screw Fixation and Posterior Lumbar Interbody Fusion Groups

OBJECTIVE: We present the investigation of the biomechanical factors of the degeneration process after lumbar fusion. METHODS: Thirty-five patients underwent L4-5 fusion operation. We measured radius(cm), top angle(TA)(degree), and flexion-extension angle(FEA) at L3-4 joint in pedicle screw fixation(PSF)(n=27) and posterior lumbar interbody fusion(PLIF)(n=8)groups. They were divided into early(3 to 6 months) and late(over 1 year) groups according to post-operative period. RESULTS: The pre-operative radius, TA and FEA in PSF were 6.2+/-0.4, 9.0+/-0.8, and 8.2+/-0.8. The early and late post-operative radius, TA and FEA in PSF were 6.4+/-0.5, 6.9+/-0.8, 6.8+/-0.8, and 5.5+/-0.7, 12.1+/-0.9, 11.0+/-0.9, respectively. The pre-operative radius, TA and FEA in PLIF were 5.4+/-0.5, 8.9+/-0.8, and 9.5+/-1.2. The early and late post-operative Radius, TA and FEA in PLIF were 5.0+/-0.4, 5.8+/-0.9, 5.2+/-0.7, and 5.0+/-0.5, 8.4+/-0.9, 7.6+/-0.8, respectively. In late PSF, TA and FEA were significantly increased(p<0.05)but radius was significantly decreased (p<0.05) compared with pre-operative ones. But in late PLIF, all the factors were decreased compared with pre-operative ones. CONCLUSION: Biomechanical factors of chronic complications were different between PSF and PLIF. Increased FEA seems to be an important factor for post-operative degeneration in PSF, whereas increased stiffness and stress seems more important in PLIF.

The Level of Cerebral Blood Flow, p53 and p21 Expression at the Penumbric Area of Cerebral Infarction in Rats

OBJECTIVE: We report an investigation of cerebral blood flow(CBF) and the expression of p53 and p21 at peri-infarct area of focal cerebral infarction in rats. METHODS: Adult Sprague-Dawley male rats were used for the experiment. In Group 1(n=7), the right middle cerebral artery(MCA) was coagulated. In Group 2(n=11), the right MCA and common carotid artery(CCA) were coagulated, and the left CCA was occluded for 30 minutes. Cerebral blood flow was measured at two areas, 2mm and 8mm distal to the MCA coagulation site. The rats were killed after 24 hours. After immunohistochemical staining, the width of the p53 or p21 positive area was measured. The p53 and p21 positive glial cells were counted at the peri-infarct area adjacent to the infarction core in Group 2. RESULTS: A focal infarction was found invariably in Group 2. CBF's at 2 mm and 8 mm areas were 8.3+/-2.1, 36.4+/-4.2 in Group 1 and 0.0+/-0.0, 6.7+/-1.5ml/100g/min in Group 2, respectively. All of the measured CBF's except that of the 8mm site in Group 1 were significantly lower than preoperative level(p<0.001), which were between 20.8+/-4.5% and 16.3+/-3.3% of preoperative CBF. The ratio of p21 and p53 positive cells was 1.0+/-0.1. CONCLUSION: We could note that the expression of p53 and p21 was the highest at an adjacent peri-infarct area. The degree of CBF reduction is more responsible for infarction than CBF itself.

Spontaneous Resolution of Dissecting Aneurysm of the Vertebral Artery / 대한뇌혈관외과학회지

Although dissecting aneurysm of vertebral artery were once thought to be extremely rare, they are now recognized with increasing frequency by dint of aggressive work-up using sophisticated imaging techniques. Vertebral dissection most commonly result from cervical hyperextension and lateral cervical rotation. Our two cases followed suit respectively and presented with ischemic symptoms. The vertebral angiogram demonstrated a pseudoaneurysm at the site of dissection in both cases. Presence or absence of SAH, size of dissection and incorporation of the PICA into dissection greatly have influence upon the outcome after treatment. The authors report two cases of dissecting aneurysm of vertebral artery, in which complete resolution of the pseudoaneurysm was spontaneously achieved following conservative management.

Differences in p53 Protein Expression between Delayed and Completed Focal Cerebral Infarction in Rats

OBJECTIVE: We investigate and compare geometric patterns and degree of p53 protein expression in a peri-infarction area between two different types of cerebral infarction, delayed and completed focal cerebral infarctions. METHODS: For the delayed focal cerebral infarction group(Group 1 ; n=8), right middle cerebral artery(MCA) and bilateral common carotid artery(CCA) were ligated temporarily for thirty minutes, and their brains were obtained after 72 hours. For the completed focal cerebral infarction group(Group2 ; n=11), right MCA and CCA were occluded permanently, and contralateral CCA was occluded for thirty minutes, and their brains were obtained after 24 hours. RESULTS: The infarction volume was significantly larger in Group 2(267.2+/-29.6mm3) than that of Group 1(10.4+/-2.7mm3)(p<0.001). The width of p53 protein positive area was significantly longer in Group 1(107.8+/-60.5micro meter) than that in Group 2(75.0+/-7.1micro meter)(p<0.05). The density of p53 positive cell was more compact in group 2(48.2+/-1.7cells/HPF) than group 1(28.3+/-9.1cells/HPF)(p<0.001). CONCLUSION: It is suggested that the decreased p53 protein expression in the delayed infarction has certain roles other than apoptosis. The degree of p53 protein expression in the completed focal cerebral infarction seems to be closer to a critical level of gene expression that might determine cell death.

Pleomorphic Xanthoastrocytoma: Report of 3 Cases

Pleomorphic xanthoastrocytoma(PXA) is a rare neoplasm with favorable prognosis despite of its aggressive histological features. The authors report three cases of pleomorphic xanthoastrocytomas. The masses were in the temporal or parietal lobe of children or adolscence and presented as complex partial seizures. Total removal of mass was performed in all three cases and the seizure was abscent postoperatively. It is important to differentiate of pleomorphic xanthoastrocytoma from other malignant brain tumors and identify this type of glioma as a distinct entity.

Angiographically Occult Arteriovenous Malformation Mimicking Brain Tumor: Case Report

The authors report a case of angiographycally occult intracranial vascular malformation. The patient had huge calcified mass at left frontoparietal area. The preoperative diagnosis was a slowly growing benign tumor. The mass was very hard and so vascular malformation was not suspected even during the operation. Pathologic report revealed arteriovenous malformation.