• Title/Summary/Keyword: Journal of Korean neurosurgical society

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Long-Term Outcomes of Stenting on Non-Acute Phase Extracranial Supra-Aortic Dissections

  • Jiang, Yeqing;Di, Ruoyu;Lu, Gang;Huang, Lei;Wan, Hailin;Ge, Liang;Zhang, Xiaolong
    • Journal of Korean Neurosurgical Society
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    • v.65 no.3
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    • pp.422-429
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    • 2022
  • Objective : Extracranial supra-aortic dissections (ESADs) with severe stenosis, occlusion and/or pseudoaneurysm presents potential risk of stroke. Endovascular stenting to reconstruct non acute phase ESADs (NAP-ESADs) is an alternative to anticoagulant or antiplatelet therapy. However, its feasibility, safety and efficacy of stenting in NAP-ESADs is unclear. This study aims to investigate the long-term outcomes of the feasibility, safety and efficacy of stenting in NAP-ESADs. Methods : Seventy-four patients with 91 NAP-ESAD vessels with severe stenosis, occlusion and/or pseudoaneurysm presents potential risk of stroke who underwent stent remodeling were enrolled into this respective study from December 2008 to March 2020. Technical success rate, complications, clinical and angiographic results were harvested and analyzed. Results : Success rate of stent deployment was 99% (90/91) with no procedural mortality or morbidity. Transient ischemic attack occurred in three patients during operation (4.1%, 3/74). Asymptomatic embolisms of distal intracranial vessels were found in two patients (2.7%, 2/74). One hundred and forty-two stents deployed at 85 carotid (135 stents) and six vertebral (seven stents) vessels. Six stent types (Wingspan, 28/135, 20.7%; Solitaire, 10/135, 7.4%; Neuroform, 8/135, 5.9%; LVIS, 2/135, 1.5%; Precise, 75/135, 55.6%; Acculink, 12/135, 8.9%) were deployed at carotid arterial dissection while two types (Wingspan, 5/7, 71.4%; Solitaire 2/7, 28.6%) at vertebral arterial dissection. Digital subtracted angiography (56%, 51/91), computational tomography angiography (41.8%, 38/91) and high resolution magnetic resonance imaging (2.2%, 2/91) were adopted for follow up, with a mean time of 17.2±15.4 months (5-77). All patient modified Rankin Scale scores showed no increase at discharge or follow-up. Angiographically, dissections in 86 vessels in 69 patients (94.5%, 86/91) were completely reconstructed with only minor remnant dissections in four vessels in four patients (4.4%, 4/91). Severe re-stenosis in the stented segment required re-stenting in one patient (1.1%, 1/91). Conclusion : Stent remodeling technique provides feasible, safe and efficacious treatment of ESADs patients with severe stenosis, occlusion and/or pseudoaneurysm.

The Treatment Outcome of Elderly Patients with Idiopathic Trigeminal Neuralgia : Micro-Vascular Decompression versus Gamma Knife Radiosurgery

  • Oh, In-Ho;Choi, Seok-Keun;Park, Bong-Jin;Kim, Tae-Sung;Rhee, Bong-Arm;Lim, Young-Jin
    • Journal of Korean Neurosurgical Society
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    • v.44 no.4
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    • pp.199-204
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    • 2008
  • Objective : This study was designed to compare the efficacy of micro-vascular decompression (MVD) and Gamma knife radiosurgery (GKRS) for elderly idiopathic trigeminal neuralgia patients by analyzing the clinical outcome. Methods : In the past 10 years, 27 elderly patients were treated with MVD while 18 patients were treated with GKRS (>65-years-old). We reviewed their clinical characteristics and clinical courses after treatment as well as the treatment outcomes. For patients who were treated with MVD, additional treatment methods such as rhizotomy were combined in some areas. In GKRS, we radiated the root entry zone (REZ) with the mean maximum dose of 77.8 (70-84.3) Gy and one 4 mm collimator. Results : The mean age was 68.1 years for MVD, and 71.1 years for GKS group. The average time interval between first presenting symptom and surgery was 84.1 (1-361) months, and 51.4 (1-120) months, respectively. The mean follow-up period after the surgery was 35.9 months for MVD, and 33.1 months for GKRS. According to Pain Intensity Scale, MVD group showed better prognosis with 17 (63%) cases in grade I-II versus 10 (55.6%) cases in GKRS group after the treatment. The pain recurrence rate during follow up did not show much difference with 3 (11.1%) in MVD, and 2 (11.1%) in GKRS. After the treatment, 2 cases of facial numbness, and 1 case each of herpes zoster, cerebrospinal fluid (CSF) leakage, hearing disturbance, and subdural hematoma occurred in MVD Group. In GKRS, there was 1 (5.6%) case of dysesthesia but was not permanent. Three cases were retreated by GKRS but the prognosis was not as good as when the surgery was used as primary treatment, with 1 case of grade I-II, and 1 case of recurrence. The maximal relieve of pain was seen just after surgery in MVD group, and 1 year after treatment in GKRS group. Conclusion : For trigeminal neuralgia patients with advanced age, MVD showed advantages in immediately relieving the pain. However, in overall, GKRS was preferable, despite the delayed pain relief, due to the lower rate of surgical complications that arise owing to the old age.

Compare the Intracranial Pressure Trend after the Decompressive Craniectomy between Massive Intracerebral Hemorrhagic and Major Ischemic Stroke Patients

  • Huh, Joon;Yang, Seo-Yeon;Huh, Han-Yong;Ahn, Jae-Kun;Cho, Kwang-Wook;Kim, Young-Woo;Kim, Sung-Lim;Kim, Jong-Tae;Yoo, Do-Sung;Park, Hae-Kwan;Ji, Cheol
    • Journal of Korean Neurosurgical Society
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    • v.61 no.1
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    • pp.42-50
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    • 2018
  • Objective : Massive intracerebral hemorrhage (ICH) and major infarction (MI) are devastating cerebral vascular diseases. Decompression craniectomy (DC) is a common treatment approach for these diseases and acceptable clinical results have been reported. Author experienced the postoperative intracranaial pressure (ICP) trend is somewhat different between the ICH and MI patients. In this study, we compare the ICP trend following DC and evaluate the clinical significance. Methods : One hundred forty-three patients who underwent DC following massive ICH (81 cases) or MI (62 cases) were analyzed retrospectively. The mean age was $56.3{\pm}14.3$ (median=57, male : female=89 : 54). DC was applied using consistent criteria in both diseases patients; Glasgow coma scale (GCS) score less than 8 and a midline shift more than 6 mm on brain computed tomography. In all patients, ventricular puncture was done before the DC and ICP trends were monitored during and after the surgery. Outcome comparisons included the ictus to operation time (OP-time), postoperative ICP trend, favorable outcomes and mortality. Results : Initial GCS (p=0.364) and initial ventricular ICP (p=0.783) were similar among the ICH and MI patients. The postoperative ICP of ICH patients were drop rapidly and maintained within physiological range if greater than 80% of the hematoma was removed. While in MI patients, the postoperative ICP were not drop rapidly and maintained above the physiologic range (MI=18.8 vs. ICH=13.6 mmHg, p=0.000). The OP-times were faster in ICH patients (ICH=7.3 vs. MI=40.9 hours, p=0.000) and the mortality rate was higher in MI patients (MI=37.1% vs. ICH=17.3%, p=0.007). Conclusion : The results of this study suggest that if greater than 80% of the hematoma was removed in ICH patients, the postoperative ICP rarely over the physiologic range. But in MI patients, the postoperative ICP was above the physiologic range for several days after the DC. Authors propose that DC is no need for the massive ICH patient if a significant portion of their hematoma is removed. But DC might be essential to improve the MI patients' outcome and timely treatment decision.

Comparative Analysis of Spontaneous Infectious Spondylitis : Pyogenic versus Tuberculous

  • Lee, Yangwon;Kim, Bum-Joon;Kim, Se-Hoon;Lee, Seung-Hwan;Kim, Won-Hyung;Jin, Sung-Won
    • Journal of Korean Neurosurgical Society
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    • v.61 no.1
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    • pp.81-88
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    • 2018
  • Objective : Spondylitis is often chemotherapy resistant and requires long-term treatment. Without adequate chemotherapy, the outcome can be fatal or result in severe neurologic damage. Therefore, differentiating the etiology of spondylitis is very important, particularly in spontaneous cases. As the prevalence of tuberculosis in Korea has decreased in recent years, updated clinical research about spondylitis is warranted. Methods : From April 2010 to March 2016, data from spondylitis patients were collected retrospectively. In total, 69 patients (51 with pyogenic spondylitis and 18 with tuberculous spondylitis) were included. Clinical data, laboratory findings including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level, measurements of Cobb angles at the initial and final follow-up, and radiologic features on magnetic resonance imaging (MRI) scans were evaluated. To test differences between the pyogenic and tuberculous groups, numerical data were compared using the student's t-test and Mann-Whitney U test, and categorical data were compared using the chi-square test and Fisher's exact test. Results : The patients' mean age was 60.0 years. Male sex was slightly predominant (56.5%). There was no difference in mean age and sex between the two groups. The pyogenic group had a relatively higher proportion of immunocompromised patients. The peak CRP value was higher in the pyogenic group than in the tuberculous group (14.08 mg/dL and 8.50 mg/dL, respectively, p=0.009), whereas the ESR was not significantly different between the groups (81.5 mm/h and 75.6 mm/h, respectively, p=0.442). Radiologically, the presence of disc space sparing and vertebral body collapse differed between the groups. In the tuberculous group, the disc was more commonly preserved on contrast-enhanced MRI (50% and 23.5%, respectively, p=0.044), and vertebral body collapse was more common (66.6% and 15.7%, respectively, p<0.001). The mean length of hospitalization was longer in the pyogenic group (56.5 days and 41.2 days, respectively, p=0.001). Four mortality cases were observed only in the pyogenic group. The most commonly isolated microorganism in the pyogenic group was Staphylococcus aureus(S. aureus) (methicillin susceptible S. aureus and methicillin resistant S. aureus [MRSA] in 8 and 4 cases, respectively). Conclusion : The clinical and radiological manifestations of spontaneous spondylitis differ based on the causative organism. Pyogenic spondylitis patients tend to have a higher CRP level and a more severe clinical course, whereas tuberculous spondylitis patients present with destruction of the vertebral body with disc sparing more frequently. The presence of MRSA is increasing in community-acquired spondylitis cases.

Impact of Time Interval between Index Event and Stenting on Periprocedural Risk in Patients with Symptomatic Carotid Stenosis

  • Han, Wonsuck;Hwang, Gyojun;Oh, Sung Han;Lee, Jong Joo;Kim, Mi Kyung;Chung, Bong Sub;Rhim, Jong Kook;Sheen, Seung Hun;Kim, Taehyung
    • Journal of Korean Neurosurgical Society
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    • v.63 no.5
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    • pp.598-606
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    • 2020
  • Objective : The purpose of this study was to evaluate the impact of time interval between index event and stenting on the periprocedural risk of stenting for symptomatic carotid stenosis and to determine the optimal timing of stenting. Methods : This retrospective study included 491 (322 symptomatic [65.6%] and 169 asymptomatic [34.4%]) patients undergoing carotid stenting. The symptomatic patients were categorized into Day 0-3, 4-7, 8-10, 11-14, 15-21, and >21 groups according to the time interval between index event and stenting. Periprocedural (≤30 days) risk for clinical (any neurological deterioration) and radiological (new infarction on postprocedural diffusion-weighted imaging) events of stenting in each time interval versus asymptomatic stenosis was calculated with logistic regression analysis adjusted for confounders, and provided as odds ratio (OR) and 95% confidence interval (CI). Results : Overall clinical event rate (4.3%) of stenting for symptomatic carotid stenosis was higher than that for asymptomatic stenosis (1.2%; OR, 3.979 [95% CI, 1.093-14.489]; p=0.036). Stenting in Day 0-3 (13.2%; OR, 10.997 [95% CI, 2.333-51.826]; p=0.002) and Day 4-7 (8.3%; OR, 6.775 [95% CI, 1.382-33.227]; p=0.018) was associated with high risk for clinical events. However, the clinical event rates in stenting after 7 days from index event (Day 8-10, 1.8%; Day 11-14, 2.5%; Day 15-21, 0%; Day >21, 2.9%) were not different from that in stenting for asymptomatic stenosis. Overall radiological event rate (55.6%) in symptomatic stenosis was also higher than that in asymptomatic stenosis (35.5%; OR, 2.274 [95% CI, 1.553-3.352]; p<0.001). The high risk for radiological events was maintained in all time intervals (Day 0-3 : 55.3%; OR, 2.224 [95% CI, 1.103-4.627]; p=0.026; Day 4-7 : 58.3%; OR, 2.543 [95% CI, 1.329-4.949]; p=0.005; Day 8-10 : 53.6%; OR, 2.096 [95% CI, 1.138-3.889]; p=0.018; Day 11-14 : 57.5%; OR, 2.458 [95% CI, 1.225-5.021]; p=0.012; Day 15-21 : 55.6%; OR, 2.271 [95% CI, 1.099-4.764]; p=0.028; Day >21 : 54.8%; OR, 2.203 [95% CI, 1.342-3.641]; p=0.002). Conclusion : This study showed that as stenting was delayed, the periprocedural risk for clinical events decreased. The clinical event risk was high only in stenting within 7 days and comparable with that for asymptomatic stenosis in stenting after 7 days from index event, although the radiological event risk was not affected by stenting timing. Therefore, our results suggest that delayed stenting after 7 days from symptom onset is a safe strategy for symptomatic stenosis.

Resection and Observation for Brain Metastasis without Prompt Postoperative Radiation Therapy

  • Song, Tae-Wook;Kim, In-Young;Jung, Shin;Jung, Tae-Young;Moon, Kyung-Sub;Jang, Woo-Youl
    • Journal of Korean Neurosurgical Society
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    • v.60 no.6
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    • pp.667-675
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    • 2017
  • Objective : Total resection without consecutive postoperative whole brain radiation therapy is indicated for patients with a single or two sites of brain metastasis, with close follow-up by serial magnetic resonance imaging (MRI). In this study, we explored the effectiveness, usefulness, and safety of this follow-up regimen. Methods : From January 2006 to December 2015, a total of 109 patients (76 males, 33 females) underwent tumor resection as the first treatment for brain metastases (97 patients with single metastases, 12 with two metastases). The mean age was 59.8 years (range 27-80). The location of the 121 tumors in the 109 patients was supratentorial (n=98) and in the cerebellum (n=23). The origin of the primary cancers was lung (n=45), breast (n=17), gastrointestinal tract (n=18), hepatobiliary system (n=8), kidney (n=7), others (n=11), and unknown origin (n=3). The 121 tumors were totally resected. Follow-up involved regular clinical and MRI assessments. Recurrence-free survival (RFS) and overall survival (OS) after tumor resection were analyzed by Kaplan-Meier methods based on clinical prognostic factors. Results : During the follow-up, MRI scans were done for 85 patients (78%) with 97 tumors. Fifty-six of the 97 tumors showed no recurrence without adjuvant local treatment, representing a numerical tumor recurrence-free rate of 57.7%. Mean and median RFS was 13.6 and 5.3 months, respectively. Kaplan-Meier analysis revealed the cerebellar location of the tumor as the only statistically significant prognostic factor related to RFS (p=0.020). Mean and median OS was 15.2 and 8.1 months, respectively. There were no significant prognostic factors related to OS. The survival rate at one year was 8.2% (9 of 109). Conclusion : With close and regular clinical and image follow-up, initial postoperative observation without prompt postoperative radiation therapy can be applied in patients of brain metastasi(e)s when both the tumor(s) are completely resected.

Which One Is Better to Reduce the Infection Rate, Early or Late Cranioplasty?

  • Oh, Jae-Sang;Lee, Kyeong-Seok;Shim, Jai-Joon;Yoon, Seok-Mann;Doh, Jae-Won;Bae, Hack-Gun
    • Journal of Korean Neurosurgical Society
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    • v.59 no.5
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    • pp.492-497
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    • 2016
  • Objective : Decompressive craniectomy is an effective therapy to relieve high intracranial pressure after acute brain damage. However, the optimal timing for cranioplasty after decompression is still controversial. Many authors reported that early cranioplasty may contribute to improve the cerebral blood flow and brain metabolism. However, despite all the advantages, there always remains a concern that early cranioplasty may increase the chance of infection. The purpose of this retrospective study is to investigate whether the early cranioplasty increase the infection rate. We also evaluated the risk factors of infection following cranioplasty. Methods : We retrospectively examined the results of 131 patients who underwent cranioplasty in our institution between January 2008 and June 2015. We divided them into early (${\leq}90days$) and late (>90 days after craniectomy) groups. We examined the risk factors of infection after cranioplasty. We analyzed the infection rate between two groups. Results : There were more male patients (62%) than female (38%). The mean age was 49 years. Infection occurred in 17 patients (13%) after cranioplasty. The infection rate of early cranioplasty was lower than that of late cranioplasty (7% vs. 20%; p=0.02). Early cranioplasty, non-metal allograft materials, re-operation before cranioplasty and younger age were the significant factors in the infection rate after cranioplasty (p<0.05). Especially allograft was a significant risk factor of infection (odds ratio, 12.4; 95% confidence interval, 3.24-47.33; p<0.01). Younger age was also a significant risk factor of infection after cranioplasty by multivariable analysis (odds ratio, 0.96; 95% confidence interval, 0.96-0.99; p=0.02). Conclusion : Early cranioplasty did not increase the infection rate in this study. The use of non-metal allograft materials influenced a more important role in infection in cranioplasty. Actually, timing itself was not a significant risk factor in multivariate analysis. So the early cranioplasty may bring better outcomes in cognitive functions or wound without raising the infection rate.

Rutin Improves Bone Histomorphometric Values by Reduction of Osteoclastic Activity in Osteoporosis Mouse Model Induced by Bilateral Ovariectomy

  • Lee, Hye-Hwa;Jang, Jae-Won;Lee, Jung-Kil;Park, Choon-Keun
    • Journal of Korean Neurosurgical Society
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    • v.63 no.4
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    • pp.433-443
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    • 2020
  • Objective : Osteoporosis is a disease of unbalanced bone metabolism that results in low bone mineral density with increased bone fragility and propensity for fractures. The increased rate of bone fracture due to osteoporosis places a significant burden on public health care expenditures. Therefore, numerous studies have been designed and performed to identify the drugs or health foods that can improve the bone quality or quantity. This study was designed to evaluate and analyze the therapeutic effects of rutin on histomorphometric values of the spine and femur in an osteoporotic mouse model induced by bilateral ovariectomy. Methods : Thirty female ICR mice (8 weeks old) underwent either a sham operation (only abdominal incision, sham group, n=10) or bilateral ovariectomy (n=20). The ovariectomized (OVX) animals were randomly divided into two groups : untreated OVX group (OVX-C, n=10), or rutin-administered group (OVX-R, n=10). The OVX-C group received weight-adjusted doses of saline vehicle and the OVX-R group received 50 mg/kg of rutin intraperitoneally, starting 1 day after surgery. At 4 and 8 weeks after surgery, serum estrogen, osteocalcin, alkaline phosphatase (ALP), and the telopeptide fragment of type I collagen C-terminus (CTX-1) were analyzed. Interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor (TNF)-α were also analyzed. Bone histomorphometric parameters of the 4th lumbar vertebra and femur were determined by micro-computed tomography. Results : In OVX-C group, ALP, osteocalcin, CTX-1, IL-1β, IL-6, and TNF-α levels were significantly increased at 4 and 8 weeks compared to sham operation group. Rutin administration after OVX statistically significantly reduced ALP, CTX-1, IL-1β, IL-6, and TNF-α levels at 4 and 8 weeks. Rutin administration also improves bone histomorphometric parameters including trabecular bone volume fraction, trabecular thickness, and trabecular number. Trabecular separation was also decreased in OVX-R group compared to OVX-C group. Conclusion : The present study demonstrated that rutin has therapeutic effects on improving bone histomorphometric values in an OVX mouse model. The improvement in histomorphometric values may be associated with the reduction of osteoclastic activity via inhibition of IL-1β, IL-6, and TNF-α. In future studies, the mechanism for the effect of rutin on osteoporosis should be demonstrated more clearly to use rutin in human osteoporosis.

Biomechanical Comparison of Inter-fragmentary Compression Pressures : Lag Screw versus Herbert Screw for Anterior Odontoid Screw Fixation

  • Park, Jin-Woo;Kim, Kyoung-Tae;Sung, Joo-Kyung;Park, Seong-Hyun;Seong, Ki-Woong;Cho, Dae-Chul
    • Journal of Korean Neurosurgical Society
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    • v.60 no.5
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    • pp.498-503
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    • 2017
  • Objective : The purpose of the present study was to compare inter-fragmentary compression pressures after fixation of a simulated type II odontoid fracture with the headless compression Herbert screw and a half threaded cannulated lag screw. Methods : We compared inter-fragmentary compression pressures between 40- and 45-mm long 4.5-mm Herbert screws (n=8 and n=9, respectively) and 40- and 45-mm long 4.0-mm cannulated lag screws (n=7 and n=10, respectively) after insertion into rigid polyurethane foam test blocks (Sawbones, Vashon, WA, USA). A washer load cell was placed between the two segments of test blocks to measure the compression force. Because the total length of each foam block was 42 mm, the 40-mm screws were embedded in the cancellous foam, while the 45-mm screws penetrated the denser cortical foam at the bottom. This enabled us to compare inter-fragmentary compression pressures as they are affected by the penetration of the apical dens tip by the screws. Results : The mean compression pressures of the 40- and 45-mm long cannulated lag screws were $50.48{\pm}1.20N$ and $53.88{\pm}1.02N$, respectively, which was not statistically significant (p=0.0551). The mean compression pressures of the 40-mm long Herbert screw was $52.82{\pm}2.17N$, and was not statistically significant compared with the 40-mm long cannulated lag screw (p=0.3679). However, 45-mm Herbert screw had significantly higher mean compression pressure ($60.68{\pm}2.03N$) than both the 45-mm cannulated lag screw and the 40-mm Herbert screw (p=0.0049 and p=0.0246, respectively). Conclusion : Our results showed that inter-fragmentary compression pressures of the Herbert screw were significantly increased when the screw tip penetrated the opposite dens cortical foam. This can support the generally recommended surgical technique that, in order to facilitate maximal reduction of the fracture gap using anterior odontoid screws, it is essential to penetrate the apical dens tip with the screw.

The Protective Effects of Statins towards Vessel Wall Injury Caused by a Stent Retrieving Mechanical Thrombectomy Device : A Histological Analysis of the Rabbit Carotid Artery Model

  • Lee, Seung Hwan;Shin, Hee Sup;Oh, Inho
    • Journal of Korean Neurosurgical Society
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    • v.64 no.5
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    • pp.693-704
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    • 2021
  • Objective : Endovascular mechanical thrombectomy (MT) has been regarded as one of the standard treatments for acute ischemic stroke caused by large vessel occlusion. Despite the wide use of stent retrievers for MT, arterial intimal damage caused when deployed stent is pulled has been a certain disadvantage. We hypothesized that statin could protect and stabilize vessel damage after endovascular MT using a stent retriever. In this animal study, we observed the protective effects of the statins towards MT-induced vessel wall injury. Methods : Twenty-eight carotid arteries of fourteen rabbits were used in the experiments with MT using stent retriever. We divided the rabbits into four groups as follows : group 1, negative control; group 2, positive control; group 3, statin before MT; and group 4, statin after MT. After MT procedures, we harvested the carotid arteries and performed histomorphological and immunohistochemical analyses. Results : In histomorphological analysis with hematoxylin and eosin and Masson's trichrome stain, significant intimal thickening (p<0.05) was observed in the positive control (group 2), compared to in the negative control (group 1). Intimal thickening was improved in the statin-administered groups (groups 3 and 4 vs. group 2, p<0.05). We also observed that statin administration after MT (group 4) resulted in a more effective decrease in intimal thickness than statin administration before MT (group 3) (p<0.05). We performed immunohistochemical analysis with the antibodies for tumor necrosis factor-alpha (TNF-α), cluster of differentiation (CD)11b, and CD163. In contrast to the negative control (group 1), the stained percentage areas of all immunological markers were markedly increased in the positive control (group 2) (p<0.05). Based on statin administration, the percentage area of TNF-α staining was significantly reduced (p<0.05) in group 3, compared to the positive control group (group 2). However, significant differences were not observed for CD11b and CD163 staining. In group 4, no significant differences were observed for TNF-α, CD11b, and CD163 staining (p≥0.05). The differences in the percentage areas of the different markers between the statin-administered groups (groups 3 and 4) were also not revealed. Conclusion : We presented that statin administration before and after MT exerted protective effects towards vessel wall injury. The efficacy of statins was greater post-administration than pre-administration. Thus, statin administration in routine prescriptions in the peri-procedural period is strongly advised.