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1.  Failed First Craniotomy and Tumor Removal of Parasagittal Meningioma with Severe Peritumoral Brain Edema 
Parasagittal meningioma often presents as peritumoral brain edema (PTBE). The risk of edema increases when the tumor occludes the superior sagittal sinus (SSS). Although PTBE may be expected based on the patient’s symptoms or radiologic findings, extensive brain swelling and extracranial herniation during elective surgery are rare. Herniation during surgery could lead to irreversible neurological damage and even brain rupture. We report a case of a failed routine craniotomy for a parasagittal meningioma with complete occlusion of the posterior third of the SSS in a 30-year-old male patient. The patient developed extensive brain swelling and extracranial herniation during surgery.
PMCID: PMC5114183  PMID: 27867923
Meningioma; Brain edema; Craniotomy
2.  Penetration and Splitting of Optic Nerve by Tuberculum Sellae Meningioma 
Preservation of the optic nerves is an important issue in the resection of tuberculum sellae meningiomas. We report the case of a patient whose optic nerve was penetrated by a tuberculum sellae meningioma. During surgery, a bulging tumor was found to penetrate the right optic nerve. The tumor was gross totally removed, including tumors bulging through the optic nerve. Two trunks of the split optic nerve were preserved. The penetrated shape of the optic nerve may lead to misjudgment and its damage. Divided trunks of optic nerves are difficult to recognize and may be confused for the tumor capsule, because they may be thinned and seem to contain tumors. In addition, a single trunk may be confused for the whole nerve; thus, the other trunk may be easily damaged if not dissected cautiously. Treatment strategy according to the remnant visual acuity was suggested.
PMCID: PMC5028616  PMID: 27651874
Meningioma; Optic nerve; Penetration; Visual acuity
3.  Post-Carotid Endarterectomy Cerebral Hyperperfusion Syndrome : Is It Preventable by Strict Blood Pressure Control? 
Cerebral hyperperfusion syndrome (CHS) is a serious complication after carotid endarterectomy (CEA). However, the prevalence of CHS has decreased as techniques have improved. This study evaluates the role of strict blood pressure (BP) control for the prevention of CHS.
All 18 patients who received CEA from February 2009 through November 2012 were retrospectively reviewed. All patients were routinely managed in an intensive care unit by a same protocol. The cerebral perfusion state was evaluated on the basis of the regional cerebral blood flow (rCBF) study by perfusion computed tomography (pCT) and mean velocity by transcranial doppler (TCD). BP was strictly controlled (<140/90 mm Hg) for 7 days. When either post-CEA hyperperfusion (>100% increase in the rCBF by pCT or in the mean velocity by TCD compared with preoperative values) or CHS was detected, BP was maintained below 120/80 mm Hg.
TCD and pCT data on the patients were analyzed. Ipsilateral rCBF was significantly increased after CEA in the pCT (p=0.049). Post-CEA hyperperfusion was observed in 3 patients (18.7%) in the pCT and 2 patients (12.5%) in the TCD study. No patients developed clinical CHS for one month after CEA. Furthermore, no patients developed additional neurological deficits related to postoperative cerebrovascular complications.
Intensive care with strict BP control (<140/90 mm Hg) achieved a low prevalence of post-CEA hyperperfusion and prevented CHS. This study suggests that intensive care with strict BP control can prevent the prevalence of post-CEA CHS.
PMCID: PMC3836920  PMID: 24278642
Carotid endarterectomy; Hyperperfusion; Cerebral blood flow; Blood pressure; Cerebral hyperperfusion syndrome
4.  Slowly Recovering Isolated Bilateral Abducens Nerve Palsy after Embolization of Ruptured Anterior Communicating Artery Aneurysm 
Bilateral abducens nerve palsy related to ruptured aneurysm of the anterior communicating artery (ACoA) has only been reported in four patients. Three cases were treated by surgical clipping. No report has described the clinical course of the isolated bilateral abducens nerve palsy following ruptured ACoA aneurysm obliterated with coil. A 32-year-old man was transferred to our institution after three days of diplopia, dizziness and headache after the onset of a 5-minute generalized tonic-clonic seizure. Computed tomographic angiography revealed an aneurysm of the ACoA. Magnetic resonance imaging showed focal intraventricular hemorrhage without brain stem abnormalities including infarction or space-occupying lesion. Endovascular coil embolization was conducted to obliterate an aneurysmal sac followed by lumbar cerebrospinal fluid (CSF) drainage. Bilateral paresis of abducens nerve completely recovered 9 weeks after ictus. In conclusion, isolated bilateral abducens nerve palsy associated with ruptured ACoA aneurysm may be resolved successfully by coil embolization and lumbar CSF drainage without directly relieving cerebrospinal fluid pressure by opening Lillequist's membrane and prepontine cistern.
PMCID: PMC3611054  PMID: 23560176
Anterior communicating artery; Subarachnoid hemorrhage; Abducens nerve palsy
5.  Mobile Computed Tomography : Three Year Clinical Experience in Korea 
Obtaining real-time image is essential for neurosurgeons to minimize invasion of normal brain tissue and to prompt diagnosis of intracranial event. The aim of this study was to report our three-year experience with a mobile computed tomography (mCT) for intraoperative and bedside scanning.
A total of 357 mCT (297 patients) scans from January 2009 to December 2011 in single institution were reviewed. After excluding post-operative routine follow-up, 202 mCT were included for analysis. Their medical records such as diagnosis, clinical application, impact on decision making, times, image quality and radiologic findings were assessed.
Two-hundred-two mCT scans were performed in the operation room (n=192, 95%) or intensive care unit (ICU) (n=10, 5%). Regarding intraoperative images, extent of resection of tumor (n=55, 27.2%), degree of hematoma removal (n=42, 20.8%), confirmation of catheter placement (n=91, 45.0%) and monitoring unexpected complications (n=4, 2.0%) were evaluated. A total of 14 additional procedures were introduced after confirmation of residual tumor (n=7, 50%), hematoma (n=2, 14.3%), malpositioned catheter (n=3, 21.4%) and newly developed intracranial events (n=2, 14.3%). Every image was obtained within 15 minutes and image quality was sufficient for interpretation.
mCT is feasible for prompt intraoperative and ICU monitoring with enhanced diagnostic certainty, safety and efficiency.
PMCID: PMC3579080  PMID: 23440939
Computed tomography; Intensive care unit
6.  Spinal Epidural Arteriovenous Hemangioma Mimicking Lumbar Disc Herniation 
A spinal epidural hemangioma is rare. In this case, a 51 year-old female patient had low back pain and right thigh numbness. She was initially misdiagnosed as having a ruptured disc with possible sequestration of granulation tissue formation due to the limited number of spinal epidural hemangiomas and little-known radiological findings. Because there are no effective diagnostic tools to verify the hemangioma, more effort should be put into preoperative imaging tests to avoid misdiagnosis and poor decisions).
PMCID: PMC3488653  PMID: 23133733
Spinal hemangioma; Indocyanine green videoangiography; Spinal cavernous; Hemangioma; Spinal epidural hemangioma
7.  Mobile Computed Tomography : Early Experience in Korea 
With improved technology, the values of intraoperative computed tomography (iCT) have been reevaluated. We describe our early clinical experience with a mobile CT (mCT) system for iCT and discuss its clinical applications, advantages and limitations.
Compared with intraoperative magnetic resonance imaging, this mCT system has no need for major reconstruction of a preexisting operating room for shielding, or for specialized instruments or equipment. Patients are placed on a radiolucent head clamp that fits within the gantry. Because it consists simply of a scanner and a workstation, it can be moved between locations such as an operating room, an intensive care unit (ICU) or an emergency room without difficulty. Furthermore, it can achieve nearly all types of CT scanning procedures such as enhancement, temporal bone imaging, angiography and three-dimensional reconstruction.
For intracranial surgery, mCT can be used for intraoperative real-time neuronavigation by interacting with preoperative images. It can also be used for intraoperative confirmation of the extent of resection of intracranial lesions and for immediate checks for preventing intraoperative unexpected accidents. Therefore, the goals of maximal resection or optimal treatment can be achieved without any guesswork. Furthermore, mCT can achieve improved patient care with safety and faster diagnosis for patients in an ICU who might be subjected to a ventilator and/or various monitoring devices.
Our initial experience demonstrates that mCT with high-quality imaging offers very useful information in various clinical situations.
PMCID: PMC2916145  PMID: 20717509
Intraoperative computed tomography; Mobile computed tomography
8.  Hydrocephalus as a Presenting Manifestation of Neurosarcoidosis : Easy to Misdiagnose as Tuberculosis 
We present a case of hydrocephalus as the primary manifestation of neurosarcoidosis. Sarcoidosis is a rare disease in Korea and its incidence is much lower than that of tuberculosis. Diagnosis is made by pathologic findings and by exclusion of other granulomatous disorders. Neurosarcoidosis is observed in approximately 5% of sarcoidosis. Its common manifestations are facial palsy (50% of patients with neurosarcoidosis) and optic neuritis. Hydrocephalus is a very uncommon reported finding. Although the typical presentation of sarcoidosis such as facial palsy is not a diagnostic dilemma, more atypical presentations such as hydrocephalus with altered mentality in a tuberculosis patient can lead to a misdiagnosis.
PMCID: PMC2916154  PMID: 20717518
Sarcoidosis; Neurosarcoidosis; Tuberculosis; Hydrocephalus
10.  Expression of Epidermal c-Kit+ of Vitiligo Lesions Is Related to Responses to Excimer Laser 
Annals of Dermatology  2016;28(4):457-463.
The survival and growth of melanocytes are controlled by the binding of stem cell factor to its cell surface receptor c-kit+ (CD117). We have observed that c-kit+ melanocytes existed in some lesions of vitiligo, while Melan A+ cells were absent.
To verify possible relation between c-kit+ expression and treatment response in non-segmental vitiligo lesions
Skin biopsies were done from the center of the 47 lesions from the 47 patients with non-segmental vitiligo. Expression of c-kit+ and Melan A, and amounts of melanin in the epidermis were assessed in each lesion, and treatment responses to excimer laser were evaluated.
Thirty-five of the 47 lesions (74.5%) had c-kit+ phenotypes. There was significant difference of c-kit staining value between good responders in 3 months of excimer laser treatment (average of 24 sessions) and the others.
c-Kit expression in vitiliginous epidermis may be related to better treatment responses to excimer laser.
PMCID: PMC4969475  PMID: 27489428
c-Kit receptor; Excimer laser; Vitiligo
11.  Incidence and Risk Factors Associated With Hospitalization for Variant Angina in Korea 
Medicine  2016;95(13):e3237.
This study aimed to determine the incidence and the risk factors of hospitalization for variant angina (VA) in Korean patients. Using the National Inpatient Sample (NIS) database, manufactured and released by the Health Insurance Review and Assessment Service (HIRA) in Korea, the incidence of hospitalization and rehospitalization for VA were calculated. The numbers of patients hospitalized for VA were estimated to be 14,362 in 2009, 17,492 in 2010, and 20,592 in 2011. The standardized incidence rates of hospitalization for VA were 31.4% in 2009, 36.5% in 2010, and 41.7% in 2011 (relative increase rate from 2009 to 2011, 33.0%, P for trend < 0.0001). VA patients predominantly belonged to the middle-age group between 40 and 69 years (75.5%), and there were 54.3% male. Based on the hospitalization episodes, the number of rehospitalization was calculated to be 879, 1141, and 1446 patients out of 1867, 2274, and 2677 patients from 2009, 2010, and 2011, respectively. The rates of rehospitalization for VA were 47.1% in 2009, 50.2% in 2010, and 54.0% in 2011 (P for trend < 0.0001). Age was an independent factor associated with rehospitalization for VA. Hospitalization for VA occurred most frequently in fall from 2009 to 2011. In conclusion, hospitalization rates for VA steadily increased from 2009 to 2011 in Korea, and about a half of VA patients was hospitalized more than once a year in 2009 to 2011. Proper health policy and patient education are warranted to control the high rate of hospitalization for VA.
PMCID: PMC4998556  PMID: 27043695
13.  Usefulness of Fracture Risk Assessment Tool Using Lumbar Bone Mineral Density in Prediction of Osteoporotic Vertebral Fracture 
To investigate the value of lumbar bone mineral density (BMD) in fracture risk assessment (FRAX) tool.
One hundred and ten patients aged over 60 years were enrolled and divided into 2 groups as non-osteoporotic vertebral fracture (OVF) and OVF groups. The 10-year-risk of major osteoporotic vertebral fracture of each group was calculated by FRAX tool with femoral and lumbar spine BMDs to compare the usefulness of lumbar spine BMD in prediction of OVF. The blood level of osteocalcin and C-terminal telopeptide (CTX) as markers of activities of osteoblast and osteoclast, respectively were analyzed using the institutional database.
In the OVF group, the ratio of patients with previous fracture history or use of glucocorticoid was higher than those in non-OVF group (p=0.000 and 0.030, respectively). The levels of T-score of femur neck and lumbar spine in OVF group were significantly lower than those in non-OVF group (p=0.001 and 0.000, respectively). The risk of OVF in FRAX using femur BMD in non-OVF and OVF groups was 6.7±6.13 and 11.4±10.06, respectively (p=0.007). The risk of using lumbar BMD in the 2 groups was 6.9±8.91 and 15.1±15.08, respectively (p=0.002). The areas under the receiver operator characteristic curve in the FRAX risk with lumbar and femur neck BMD were 0.726 and 0.684, respectively. The comparison of osteocalcin and CTX was not significant (p=0.162 and 0.369, respectively).
In our study, the 10-year risk of major osteoporotic fracture in the OVF group of our study was lower than the recommended threshold of intervention for osteoporosis. Hence, a lower threshold for the treatment of osteoporosis may be set for the Korean population to prevent OVF. In the prediction of symptomatic OVF, FRAX tool using lumbar spine BMD may be more useful than that using femur neck BMD.
PMCID: PMC4651995  PMID: 26587188
Osteoporosis; Spine; Fracture; Femur
14.  Large Spinal Meningioma with Hemorrhage after Selective Root Block in the Thoraco-Lumbar Spine 
Korean Journal of Spine  2013;10(4):255-257.
Spinal meningioma accounts for 25% of all spinal cord tumors and occurs mostly in the thoracic region. Spontaneous intraspinal bleeding associated with spinal meningioma has rarely been reported. Most cases of hemorrhage associated with meningiomas are extratumoral and subarachnoid, whereas subdural and intratumoral hemorrhage cases have been reported to occur rarely. We experienced a case of a 58-year-old woman with thoracolumbar spinal meningioma accompanied by intraspinal subdural hematoma. She presented with progressively worsened back pain and newly developed weakness in the right lower extremity after a selective nerve root block in the lumbar spine. She underwent the operation and progressively showed neurological recovery during the postoperative course. We report a thoracolumbarspinal meningioma with subdural and intratumoral hemorrhage after a spinal procedure that caused a sudden neurological deterioration.
PMCID: PMC4040649  PMID: 24891860
Spinal meningioma; Hemorrhage
15.  The Impact of Menopause on Bone Fusion after the Single-Level Anterior Cervical Discectomy and Fusion 
To evaluate the successful fusion rate in postmenopausal women with single-level anterior cervical discectomy and successful fusion (ACDF) and identify the significant factors related to bone successful fusion in pre- and postmenopausal women.
From July 2004 to December 2010, 108 consecutive patients who underwent single-level ACDF were prospectively selected as candidates. Among these, the charts and radiological data of 39 women were reviewed retrospectively. These 39 women were divided into two groups : a premenopausal group (n=11) and a postmenopausal group (n=28). To evaluate the significant factors affecting the successful fusion rate, the following were analyzed : the presence of successful fusion, successful fusion type, age, operated level, bone mineral density, graft materials, stand-alone cage or plating with autologous iliac bone, subsidence, adjacent segment degeneration, smoking, diabetes mellitus, and renal disease.
The successful fusion rates of the pre- and postmenopausal groups were 90.9% and 89.2%, respectively. There was no significant difference in the successful fusion rate or successful fusion type between the two groups. In the postmenopausal group, three patients (10.8%) had successful fusion failure. In the postmenopausal group, age and subsidence significantly affected the successful fusion rate (p=0.016 and 0.011, respectively), and the incidence of subsidence in patients with a cage was higher than that in patients with a plate (p=0.030).
Menopausal status did not significantly affect bone successful fusion in patients with single-level ACDF. However, in older women with single-level ACDF, the combination of use of a cage and subsidence may unfavorably affect successful fusion.
PMCID: PMC3921277  PMID: 24527192
Menopause; Cervical; Discectomy; Successful fusion; Bone mineral density
16.  Quantitative Evaluation of Median Nerve Motor Function in Carpal Tunnel Syndrome Using Load Cell : Correlation with Clinical, Electrodiagnostic, and Ultrasonographic Findings 
Major complaints of carpal tunnel syndrome (CTS) are sensory components. However, motor deficit also impedes functional status of hand. Contrary to evaluation of sensory function, the objective, quantitative evaluation of median nerve motor function is not easy. The motor function of median was evaluated quantitatively using load cell and its correlation with findings of electrodiagnostic study (EDS) was evaluated.
Objective motor function of median nerve was evaluated by load cell and personal computer-based measurement system. All of the measurement was done in patients diagnosed as having idiopathic CTS by clinical features and EDS findings. The strength of thumb abduction and index finger flexion was measured in each hand three times, and the average value was used to calculate thumb index ratio (TIR). The correlation of TIR with clinical, EDS, and ultrasonographic findings were evaluated.
The TIR was evaluated in 67 patients (119 hands). There were 14 males and 53 females, mean age were 57.6 years (range 28 to 81). The higher preoperative nerve conductive studies grade of the patients, the lower TIR was observed [p<0.001, analysis of variance (ANOVA)]. TIR of cases with thenar atrophy were significantly lower than those without (p<0.001, t-test). TIR were significantly lower in patients with severe median nerve swelling in ultrasonography (p=0.042, ANOVA).
Measurements of median nerve motor function using load cell is a valuable evaluation tool in CTS. It might be helpful in detecting subclinical motor dysfunction before muscle atrophy develops.
PMCID: PMC3836931  PMID: 24278653
Carpal tunnel syndrome; Thumb abduction strength; Load cell; Electrodiagnostic study; Ultrasonography
17.  Quantitative Analysis of Intraoperative Indocyanine Green Video Angiography in Aneurysm Surgery 
Indocyanine green (ICG) videoangiography (VA) is being used in assessment of blood flow during cerebrovascular surgery. However, data collected during ICG angiography are usually interpreted qualitatively. In this study, quantitative analysis of ICG angiogram was attempted.
Materials and Methods
ICG VA, performed during aneurysm surgery was analyzed retrospectively. The angiogram was captured serially in regular time interval. The stacked images were then fed into an image analysis program, ImageJ. The selected areas of interest were as follows: parent and branch vessels, and dome of aneurysm. Changes of signals of measurement points were plotted. The time to peak, washout time, and the peak intensity between areas were compared.
Among the 16 cases enrolled in this study, five cases were anterior communicating artery aneurysms, and 11 cases were middle cerebral artery bifurcation aneurysms. There was no signal intensity of aneurysm dome in our series. No difference in time to peak or maximum signal intensity was observed between vessels in each case. The average time to peak was 9.0 and washout time was 31.3 seconds. No significant difference in time profile was observed between anterior communicating artery aneurysms and middle cerebral artery bifurcation aneurysms.
Findings of this study demonstrate that quantitative analysis is possible using a personal computer and common video capture and analysis software. It can be a good adjunctive to evaluation of vascular status during aneurysm surgery. It displays time profiles of multiple points of interest over time, and is helpful in objective evaluation of changes of blood flow over time. It might be helpful in various fields of cerebrovascular surgery.
PMCID: PMC3704998  PMID: 23844351
Indocyanine green video angiography; Aneurysm; Quantitative analysis; ImageJ
18.  Medial Loop of V2 Segment of Vertebral Artery Causing Compression of Proximal Cervical Root 
It is rare that the medial loop in the V2 segment of the vertebral artery (VA) causes compression of the proximal cervical root of the spinal cord without leading to bony erosion and an enlarged foramen. We evaluated the clinical significance and incidence of the medial loop in the V2 segment of the VA.
We reviewed the records from 1000 consecutive patients who had undergone magnetic resonance imaging evaluation of the cervical spine between January 2005 and January 2008. The inclusion criteria were that over a third of the axial aspect of the VA located in the intervertebral foramen was inside the line between the most ventral points of the bilateral lateral mass, and that the ipsilateral proximal root deviated dorsally because of the medial loop of the VA. We excluded cases of bone erosion, a widened foramen at the medial loop of the VA, any bony abnormalities, tumors displacing VA, or vertebral fractures. The medical records were reviewed retrospectively to search for factors of clinical significance.
In six patients (0.6%), the VA formed a medial loop that caused compression of the proximal cervical root. One of these patients had the cervical radiculopathy that developed after minor trauma but the others did not present with cervical radiculopathy related to the medial loop of the VA.
The medial loop of the VA might have a direct effect on cervical radiculopathy. Therefore, this feature should be of critical consideration in preoperative planning and during surgery.
PMCID: PMC3550417  PMID: 23346321
Vertebral artery; Medial loop; Spine
19.  Outcomes of Instrumented Posterolateral Fusion for Patients Over 70 Years with Degenerative Lumbar Spinal Disease: A Minimum of 2 Years Follow-up 
Korean Journal of Spine  2012;9(2):74-78.
To determine the outcome of posterolateral fusion (PLF) for patients over 70 years of age with degenerative lumbar spinal disease.
The authors reviewed 18 patients (13 women and 5 men) over 70 years of age who underwent PLF with a minimum 2-years follow-up at a single institution. The parameters for analysis were clinical outcome, intraoperative bleeding, operating time, transfusion amount, fusion rate, decreased disc height at the operated level, and the incidence of adjacent disc degeneration.
The mean age and follow-up duration were 74.1 years and 44.7 months, respectively. The mean fusion level was 2.5 levels. 12 patients (66.7%) reported good or excellent outcomes, and 4 patients complained of poor outcomes. The fusion rate was 61.1%. The rate of adjacent segment degeneration was 61.1%. Among all of the patients, 5 had decreased intervertebral disc heights compared to their initial statuses. In correlative comparison analyses of parameters, a significant correlation was observed between a "good" or better clinical outcome and fusion (p=0.034). Also, there were significant relationships between a "fair" or better clinical outcome and fusion (p=0.045) and decreased disc height at the operated level (p=0.017). Other factors did not have a significant relationship with the clinical outcome.
Before performing instrumented PLF in patients over 70 years old, problems related to the low fusion rate and adjacent segment degeneration should be considered and relevant information should be provided to the patients and the family.
PMCID: PMC4432364  PMID: 25983792
Aged; Spine; Lumbar Vertebrae
20.  The Effect of Vertebroplasty on Costal Pain Related to Osteoporotic Thoracic Compression Fractures in Elderly Patients 
Korean Journal of Spine  2012;9(2):98-101.
To analyze the effect of vertebroplasty on costal pain which develops following osteoporotic thoracic compression fractures (OTCFs).
The authors reviewed the medical records of 35 patients who underwent vertebral augmentation for the treatment of OTCFs over a five year period. The patients were divided into two groups: the costalgia group included patientswho had costal pain after a vertebral fracture and the non-costalgia group included patients without costalgia. To evaluate the effect of vertebroplasty on costal pain and factors related to costal pain, several factors including: vertebral body fracture type, pedicle injury, bone mineral density, the fracture level and clinical outcome were confirmed with magnetic resonance imaging and chart reviews.
Among 35 patients, ten patients (28.6%) complained of costal pain with back pain. Only five of the ten patients (50%) had improved costal pain after a vertebroplasty. In the remaining 5 patients, the costal pain was improved through the use of medication including pain killers or a costal block during the follow-up period. Although the incidence of wedge deformity in the costal group was low(10%), there was no significant relationship to the incidence of costal pain statistically. Pedicle injury, bone mineral density and the fracture level had no significant relation to costal pain.
The patients with wedge type, OTCFs may have a low incidence of costal pain as compared to those patients with bi-concave and crush deformities. The vertebroplasty effect on costal pain may not be effective. Therefore, before doing vertebroplasty, the surgeon should advise patients of this potential outcome in those treated for OTCFs.
PMCID: PMC4432368  PMID: 25983796
Osteoporosis; Vertebroplasty; Spinal Fractures; Intercostal Nerves
21.  Toxoplasma gondii Infection in the Brain Inhibits Neuronal Degeneration and Learning and Memory Impairments in a Murine Model of Alzheimer's Disease 
PLoS ONE  2012;7(3):e33312.
Immunosuppression is a characteristic feature of Toxoplasma gondii-infected murine hosts. The present study aimed to determine the effect of the immunosuppression induced by T. gondii infection on the pathogenesis and progression of Alzheimer's disease (AD) in Tg2576 AD mice. Mice were infected with a cyst-forming strain (ME49) of T. gondii, and levels of inflammatory mediators (IFN-γ and nitric oxide), anti-inflammatory cytokines (IL-10 and TGF-β), neuronal damage, and β-amyloid plaque deposition were examined in brain tissues and/or in BV-2 microglial cells. In addition, behavioral tests, including the water maze and Y-maze tests, were performed on T. gondii-infected and uninfected Tg2576 mice. Results revealed that whereas the level of IFN-γ was unchanged, the levels of anti-inflammatory cytokines were significantly higher in T. gondii-infected mice than in uninfected mice, and in BV-2 cells treated with T. gondii lysate antigen. Furthermore, nitrite production from primary cultured brain microglial cells and BV-2 cells was reduced by the addition of T. gondii lysate antigen (TLA), and β-amyloid plaque deposition in the cortex and hippocampus of Tg2576 mouse brains was remarkably lower in T. gondii-infected AD mice than in uninfected controls. In addition, water maze and Y-maze test results revealed retarded cognitive capacities in uninfected mice as compared with infected mice. These findings demonstrate the favorable effects of the immunosuppression induced by T. gondii infection on the pathogenesis and progression of AD in Tg2576 mice.
PMCID: PMC3310043  PMID: 22470449
22.  Analysis of Complications Following Decompressive Craniectomy for Traumatic Brain Injury 
Adequate management of increased intracranial pressure (ICP) is critical in patients with traumatic brain injury (TBI), and decompressive craniectomy is widely used to treat refractory increased ICP. The authors reviewed and analyzed complications following decompressive craniectomy for the management of TBI.
A total of 89 consecutive patients who underwent decompressive craniectomy for TBI between February 2004 and February 2009 were reviewed retrospectively. Incidence rates of complications secondary to decompressive craniectomy were determined, and analyses were performed to identify clinical factors associated with the development of complications and the poor outcome.
Complications secondary to decompressive craniectomy occurred in 48 of the 89 (53.9%) patients. Furthermore, these complications occurred in a sequential fashion at specific times after surgical intervention; cerebral contusion expansion (2.2 ± 1.2 days), newly appearing subdural or epidural hematoma contralateral to the craniectomy defect (1.5 ± 0.9 days), epilepsy (2.7 ± 1.5 days), cerebrospinal fluid leakage through the scalp incision (7.0 ± 4.2 days), and external cerebral herniation (5.5 ± 3.3 days). Subdural effusion (10.8 ± 5.2 days) and postoperative infection (9.8 ± 3.1 days) developed between one and four weeks postoperatively. Trephined and post-traumatic hydrocephalus syndromes developed after one month postoperatively (at 79.5 ± 23.6 and 49.2 ± 14.1 days, respectively).
A poor GCS score (≤ 8) and an age of ≥ 65 were found to be related to the occurrence of one of the above-mentioned complications. These results should help neurosurgeons anticipate these complications, to adopt management strategies that reduce the risks of complications, and to improve clinical outcomes.
PMCID: PMC2966727  PMID: 21082053
Decompressive craniectomy; Traumatic brain injury; Complication
23.  Amyloid Precursor Protein Binding Protein-1 Is Up-regulated in Brains of Tg2576 Mice 
Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of amyloid precursor protein and serves as a bipartite activation enzyme for the ubiquitin-like protein, NEDD8. Previously, it has been reported that APP-BP1 rescues the cell cycle S-M checkpoint defect in Ts41 hamster cells, that this rescue is dependent on the interaction of APP-BP1 with hUba3. The exogenous expression of APP-BP1 in neurons has been reported to cause DNA synthesis and apoptosis via a signaling pathway that is dependent on APP-BP1 binding to APP. These results suggest that APP-BP1 overexpression contributes to neurodegeneration. In the present study, we explored whether APP-BP1 expression was altered in the brains of Tg2576 mice, which is an animal model of Alzheimer's disease. APP-BP1 was found to be up-regulated in the hippocampus and cortex of 12 month-old Tg2576 mice compared to age-matched wild-type mice. In addition, APP-BP1 knockdown by siRNA treatment reduced cullin-1 neddylation in fetal neural stem cells, suggesting that APP-BP1 plays a role in cell cycle progression in the cells. Collectively, these results suggest that increased expression of APP-BP1, which has a role in cell cycle progression in neuronal cells, contributes to the pathogenesis of Alzheimer's disease.
PMCID: PMC2933439  PMID: 20827337
Amyloid precursor protein binding protein-1; Amyloid precursor protein; Alzheimer's disease; cell cycle; Tg2576 mice
24.  Activation of PERK Signaling Attenuates Aβ-Mediated ER Stress 
PLoS ONE  2010;5(5):e10489.
Alzheimer's disease (AD) is characterized by the deposition of aggregated beta-amyloid (Aβ), which triggers a cellular stress response called the unfolded protein response (UPR). The UPR signaling pathway is a cellular defense system for dealing with the accumulation of misfolded proteins but switches to apoptosis when endoplasmic reticulum (ER) stress is prolonged. ER stress is involved in neurodegenerative diseases including AD, but the molecular mechanisms of ER stress-mediated Aβ neurotoxicity still remain unknown. Here, we show that treatment of Aβ triggers the UPR in the SK-N-SH human neuroblastoma cells. Aβ mediated UPR pathway accompanies the activation of protective pathways such as Grp78/Bip and PERK-eIF2α pathway, as well as the apoptotic pathways of the UPR such as CHOP and caspase-4. Knockdown of PERK enhances Aβ neurotoxicity through reducing the activation of eIF2α and Grp8/Bip in neurons. Salubrinal, an activator of the eIF2α pathway, significantly increased the Grp78/Bip ER chaperone resulted in attenuating caspase-4 dependent apoptosis in Aβ treated neurons. These results indicate that PERK-eIF2α pathway is a potential target for therapeutic applications in neurodegenerative diseases including AD.
PMCID: PMC2864758  PMID: 20463975
25.  Pressure Measurement in Carpal Tunnel Syndrome : Correlation with Electrodiagnostic and Ultrasonographic Findings 
This study was done to evaluate the correlation between carpal tunnel pressure (CTP), electrodiagnostic and ultrasonographic findings in patients with carpal tunnel syndrome (CTS).
CTP was measured during endoscopic carpal tunnel release (ECTR) for CTS using Spiegelberg ICP monitoring device with parenchymal type catheter. Neurophysiologic severity and nerve cross sectional area were evaluated using nerve conductive study and ultrasonography (USG) before ECTR in all patients.
Tests were performed in a total of 48 wrists in 39 patients (9 cases bilateral). Maximum CTP was 56.7 ± 19.3 mmHg (Mean ± SD) and 7.4 ± 3.3 mmHg before and after ECTR, respectively. No correlation was found between maximum CTP and either neurophysiologic severity or nerve cross sectional area, whereas we found a significant correlation between the latter two parameters.
CTP was not correlated with neurophysiologic severity and nerve cross sectional area. Dynamic, rather than static, pressure in carpal tunnel might account for the basic pathophysiology of CTS better.
PMCID: PMC2764016  PMID: 19844618
Carpal tunnel syndrome; Pressure; Ultrasonography; Electrodiagnosis

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