Current Immunotherapeutic Approaches for Malignant Gliomas

Glioblastoma is the most common malignant central nervous system (CNS) tumor (48.3%), with a median survival of only about 14.6 months. Although the CNS is an immune-privileged site, activated T cells can cross the blood-brain barrier. The recent successes of several immunotherapies for various cancers have drawn interest in immunotherapy for treatment of malignant glioma. There have been extensive attempts to evaluate the efficiency of immunotherapy against malignant glioma. Passive immunotherapy for malignant glioma includes monoclonal antibody-mediated immunotherapy, cytokine-mediated therapy, and adoptive cell transfer, also known as chimeric antigen receptor T cell treatment. On the other hand, active immunotherapy, which stimulates the patient’s adaptive immune system against specific tumor-associated antigens, includes cancer vaccines that are divided into peptide vaccines and cell-based vaccines. In addition, there is immune checkpoint blockade therapy, which increases the efficiency of immunotherapy by reducing the resistance of malignant glioma to immunotherapy. Despite centuries of efforts, immunotherapeutic successes for malignant glioma remain limited. However, many clinical trials of adoptive cell transfer immunotherapy on malignant glioma are ongoing, and the outcomes are eagerly awaited. In addition, although there are still several obstacles, current clinical trials using personalized neoantigen-based dendritic cell vaccines offer new hope to glioblastoma patients. Furthermore, immune checkpoint targeted therapy is expected to decipher the mechanism of immunotherapy resistance in malignant glioma in the near future. More studies are needed to increase the efficacy of immunotherapy in malignant glioma. We hope that immunotherapy will become a new treatment of malignant glioma.

Risk Factors of Delayed Intracranial Hemorrhage Following Ventriculoperitoneal Shunt / 대한신경손상학회지

OBJECTIVE: Placement of a ventriculoperitoneal (VP) shunt is a common neurosurgical procedure for cerebrospinal fluid diversion. A rare complication is delayed intracranial hemorrhage (ICH) secondary to VP shunting, and only a few patients with this complication have been reported. We investigate the incidence and risk factors of delayed ICH development following VP shunt placement. METHODS: Over an 11-year period, 167 patients received a VP shunt for hydrocephalus, and of these, 138 patients were eligible for this study. All medical records and computed tomography scans obtained within 48 h after the operation and at postoperative day 7 were reviewed. The risk factors of developing delayed ICH (≥48 hr after VP shunt placement) were analyzed according to the demographic data, including sex and age, original intracranial lesions, co-morbid diseases, and laboratory findings. RESULTS: Delayed ICH following VP shunt placement developed in 34 (24.6%) of the 138 patients. Risk factors for developing delayed ICH were age (p=0.037) and the partial thromboplastin time (PTT) (p=0.032). Intraventricular hemorrhage after VP shunting was the most common complication, occurring in 16 cases. Hemorrhagic volume was 1 mL in 6 cases. CONCLUSION: This study suggests that old age and delayed PTT are major risk factors for developing delayed ICH following VP shunting. Additionally, delayed ICH after VP shunting commonly occurs even when most patients are asymptomatic. Therefore, extra care should be taken to observe and follow-up with patients who have undergone VP shunt placement.

Postpartum Superior Sagittal Sinus Thrombosis: A Case Report / 대한신경손상학회지

Cerebral venous sinus thrombosis (CVST) is a rare disease. Early diagnosis and treatment are important, as CVST is potentially fatal. Pregnancy and puerperium are known risk factors for CVST. Here, we report the case of a patient who developed superior sagittal sinus thrombosis after a normal vaginal delivery. A 20-year-old woman presented with a headache and seizures two days after a normal vaginal delivery. Initially, brain computed tomography (CT) showed a subarachnoid hemorrhage in the right parietal lobe and sylvian fissure, together with mild cerebral edema. CT angiography revealed superior sagittal sinus thrombosis. Multiple micro-infarctions were seen on diffusion-weighted magnetic resonance images. An intravenous infusion of heparin and mannitol was administered immediately. Two days after treatment initiation, the patient showed sudden neurological deterioration, with left-sided hemiplegia. Brain CT showed moderate brain edema and hemorrhagic densities. Emergency decompressive craniectomy was performed, and heparin was re-administered on post-operative day (POD) 1. On POD 9, the patient's mental state improved from stupor to drowsy, but the left-sided hemiplegia persisted. CT angiography showed that the superior sinus thrombosis had decreased. Superior sagittal sinus thrombosis is an uncommon complication, with an unfavorable outcome, after delivery. Timely diagnosis and treatment are important for preventing neurological deterioration.

Radiologic Findings and Patient Factors Associated with 30-Day Mortality after Surgical Evacuation of Subdural Hematoma in Patients Less Than 65 Years Old

OBJECTIVE: The purpose of this study is to evaluate the associations between 30-day mortality and various radiological and clinical factors in patients with traumatic acute subdural hematoma (SDH). During the 11-year study period, young patients who underwent surgery for SDH were followed for 30 days. Patients who died due to other medical comorbidities or other organ problems were not included in the study population. METHODS: From January 1, 2004 to December 31, 2014, 318 consecutive surgically-treated traumatic acute SDH patients were registered for the study. The Kaplan–Meier method was used to analyze 30-day survival rates. We also estimated the hazard ratios of various variables in order to identify the independent predictors of 30-day mortality. RESULTS: We observed a negative correlation between 30-day mortality and Glasgow coma scale score (per 1-point score increase) (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.52–0.70; p<0.001). In addition, use of antithrombotics (HR, 2.34; 95% CI, 1.27–4.33; p=0.008), history of diabetes mellitus (HR, 2.28; 95% CI, 1.20–4.32; p=0.015), and accompanying traumatic subarachnoid hemorrhage (hazard ratio, 2.13; 95% CI, 1.27–3.58; p=0.005) were positively associated with 30-day mortality. CONCLUSION: We found significant associations between short-term mortality after surgery for traumatic acute SDH and lower Glasgow Coma Scale scores, use of antithrombotics, history of diabetes mellitus, and accompanying traumatic subarachnoid hemorrhage at admission. We expect these findings to be helpful for selecting patients for surgical treatment of traumatic acute SDH, and for making accurate prognoses.

Retrograde Stent-assisted Coil Embolization of Wide-neck or Branch-incorporated Posterior Communicating Artery Aneurysm

Endovascular coil embolization using a balloon- or stent-assisted technique for the treatment of wide-necked posterior communicating artery (PcomA) aneurysms is well established. However, complete aneurysm occlusion with preservation of the PcomA can be difficult in case of wide-neck aneurysms with a PcomA incorporation. We present two cases of stent-assisted coil embolization using a retrograde approach through the posterior circulation for wide-neck or branch-incorporated PcomA aneurysms. Retrograde stenting was successful without periprocedural complications. These aneurysms were completely occluded. The patency of the PcomA was maintained in all cases.

Multiple Meningocerebral Metastasis and Extensive Skull Metastasis from Squamous Cell Carcinoma of Esophagus: A Case Report and Review of Literature

Esophageal carcinoma rarely metastasizes to the brain. Although some studies have mentioned esophageal cancer with solitary brain metastasis or with meningocerebral metastasis or with skull metastasis, multiple meningocerebral metastasis and extensive skull metastasis from squamous cell carcinoma of esophagus has not been reported in the literature. We encountered a case of an extensive osteolytic change of the skull and multiple meningocerebral metastases from esophageal carcinoma.

Concomitant Subdural Hemorrhage and Intracerebral Hemorrhage due to Brain Metastasis of the Hepatocellular Carcinoma

Hemorrhagic metastatic brain tumors of hepatocellular carcinoma (HCC) are rare and have been mostly presented as intracranial hemorrhage (ICH). A 51-year-old male patient presented with sudden altered level of consciousness. He suffered from HCC since 2010 and transarterial chemoembolization was performed three times for HCC. The brain computed tomography (CT) scans revealed subdural hematoma (SDH) in the right fronto-temporal area and 6.0x3.5 cm sized ICH in the right parieto-occipital lobe. Brain angiographic CT scans demonstrated that the hemorrhagic lesions did not include any enhancing lesions and vascular abnormalities. We undertook a decompressive craniectomy and evacuation of the acute SDH and ICH. During evacuation of ICH, the yellowish mass was observed in the cortical surface of the right occipital lobe. Pathological examination displayed the findings of metastatic brain tumor from HCC. Metastatic brain tumors should be considered in the differential diagnosis as a cause of spontaneous SDH with ICH.

Bone Flap Resorption Following Cranioplasty after Decompressive Craniectomy: Preliminary Report / 대한신경손상학회지

OBJECTIVE: Resorption of autologous bone flap grafts is a known long-term complication of cranioplasty following decompressive craniectomy (DC). We analyzed our data to identify risk factors for bone flap resorption (BFR) following cranioplasty. METHODS: A total of 162 patients who underwent cranioplasty following DC due to life-threatening elevated intracranial pressure between October 2003 and December 2012, were included in our investigation. Follow-up exceeded one year. RESULTS: BFR occurred as a long-term complication in 9 of the 162 patients (5.6%). The affected patients consisted of individuals who had undergone DC for traumatic brain injury (TBI; n=4), for subarachnoid hemorrhage (SAH; n=3), for cerebral infarction (n=1), and intracerebral hemorrhage (n=1). Logistic regression analysis identified no significant risk factors for BFR. CONCLUSION: TBI and SAH as initial diagnoses are more often associated with BFR than other diagnoses. This finding may influence future surgical decision making, especially in patients with possible risk factors for BFR. A prospective study with a large number of patients is needed to identify potential predictors of BFR such as bone flap sterilization and preservation.

A Ruptured Dermoid Cyst of the Cavernous Sinus Extending into the Posterior Fossa

Supratentorial dermoid cysts are uncommon to develop in the cavernous sinus. We present a ruptured dermoid cyst of the cavernous sinus extending into the posterior fossa. The patient was a 32-year-old female who complained occipital headache, blurred vision, and tinnitus over 4 years. Brain magnetic resonance (MR) imaging revealed an enhanced tumor in the right cavernous sinus extending into the right temporal base and the posterior fossa with findings of ruptured cyst. Surgical resection was performed, and pathological findings were confirmed to be a dermoid cyst. We report a second case with ruptured dermoid cyst of the cavernous sinus extending into the posterior fossa.

Sporadic Hemangioblastoma in the Pituitary Stalk: A Case Report and Review of the Literature

Hemangioblastomas in the pituitary stalk are especially rare. Most pituitary stalk hemangioblastomas reported in the literature were associated with von Hippel-Lindau (VHL) disease. Here, we report only the 3rd case of sporadic pituitary stalk hemangioblastoma diagnosed in a 60-year-old woman. Despite the danger of potential complications due to excessive vascularity or proximity to important neural structures, the tumor in our case was successfully removed while preserving pituitary function. In this case, complete surgical excision was shown to be an effective treatment option for symptomatic pituitary stalk hemangioblastoma, and we suggest careful evaluation of any highly enhancing mass with a signal void in the pituitary stalk preoperatively, even if no VHL disease is evident.

A Primary Ossifying Intracranial Myxoma Arising from the Ethmoid Sinus

Myxomas are rare benign tumors that originate from mesenchymal tissue. They usually develop in the atrium of the heart, the skin, subcutaneous tissue, or bone. Involvement of the skull base with an intracranial extension is very rare and not well-described in the literature. We report a rare case of primary intracranial ossifying myxoma arising from the anterior skull base and mimicking a huge chondrosarcoma, and we review the relevant literature.

Extracranial Extension of Intracranial Atypical Meningioma En Plaque with Osteoblastic Change of the Skull

Meningioma is a common primary tumor of central nervous system. However, extracranial extension of the intracranial meningioma is unusual, and mostly accompanied the osteolytic change of the skull. We herein describe an atypical meningioma having extracranial extension with hyperostotic change of the skull. The patient was a 72-year-old woman who presented a large mass in the right frontal scalp and left hemiparesis. Brain magnetic resonance imaging and computed tomography scans revealed an intracranial mass, diffuse meningeal thickening, hyperostotic change of the skull with focal extension into the right frontal scalp. She underwent total removal of extracranial tumor, bifrontal craniectomy, and partial removal of intracranial tumor followed by cranioplasty. Tumor pathology was confirmed as atypical meningioma, and she received adjuvant radiotherapy. In this report, we present and discuss a meningioma en plaque of atypical histopathology having an extracranial extension with diffuse intracranial growth and hyperostotic change of the skull.

Evaluating the Differential Electrophysiological Effects of the Focal Vibrator on the Tendon and Muscle Belly in Healthy People

OBJECTIVE: To investigate the electrophysiological effects of focal vibration on the tendon and muscle belly in healthy people. METHODS: The miniaturized focal vibrator consisted of an unbalanced mass rotating offset and wireless controller. The parameters of vibratory stimulation were adjusted on a flat rigid surface as 65 microm at 70 Hz. Two consecutive tests on the different vibration sites were conducted in 10 healthy volunteers (test 1, the Achilles tendon; test 2, the muscle belly on the medial head of the gastrocnemius). The Hoffman (H)-reflex was measured 7 times during each test. The minimal H-reflex latency, maximal amplitude of H-reflex (Hmax), and maximal amplitude of the M-response (Mmax) were acquired. The ratio of Hmax and Mmax (HMR) and the vibratory inhibition index (VII: the ratio of the Hmax after vibration and Hmax before vibration) were calculated. The changes in parameters according to the time and site of stimulation were analyzed using the generalized estimating equation methods. RESULTS: All subjects completed the two tests without serious adverse effects. The minimal H-reflex latency did not show significant changes over time (Wald test: chi2=11.62, p=0.07), and between the two sites (chi2=0.42, p=0.52). The changes in Hmax (chi2=53.74, p<0.01), HMR (chi2=20.49, p<0.01), and VII (chi2=13.16, p=0.02) were significant over time with the adjustment of sites. These parameters were reduced at all time points compared to the baseline, but the decrements reverted instantly after the cessation of stimulation. When adjusted over time, a 1.99-mV decrease in the Hmax (chi2=4.02, p=0.04) and a 9.02% decrease in the VII (chi2=4.54, p=0.03) were observed when the muscle belly was vibrated compared to the tendon. CONCLUSION: The differential electrophysiological effects of focal vibration were verified. The muscle belly may be the more effective site for reducing the H-reflex compared to the tendon. This study provides the neurophysiological basis for a selective and safe rehabilitation program for spasticity management with focal vibration.

Clinical Outcome of Paraclinoid Internal Carotid Artery Aneurysms After Microsurgical Neck Clipping in Comparison with Endovascular Embolization

OBJECTIVE: Because of the complex anatomical association among vascular, dural, and bony structures, paraclinoid internal carotid artery (ICA) aneurysms remain a major challenge for vascular neurosurgeons. We studied the clinical outcomes of 61 paraclinoid ICA aneurysms after microsurgical clipping in comparison with endovascular coiling. MATERIALS AND METHODS: Between January 2008 and December 2012, we treated 61 paraclinoid ICA aneurysms created by surgical clipping or endovascular coiling. Preoperative neurologic status and postoperative outcome were evaluated using the Glasgow coma scale (GCS) and the modified Rankin scale (mRS). Postoperative hydrocephalus and vasospasm were reviewed using the patients' medical charts. RESULTS: Most patients were in good clinical condition before the operations and had good treatment outcomes. Clinical vasospasm was observed after the operation in five patients, and hydrocephalus occurred in six patients. No statistically significant difference regarding aneurysm size, sex, GCS score, H-H grade, and mRS was observed between the surgical clipping group and the endovascular coiling group. In addition, the treatment results and complications did not show statistically significant difference in either group. CONCLUSION: Surgical occlusion of paraclinoid ICA aneurysms is difficult; however, no significant differences were observed in the treatment results or complications when compared with coil embolization. In particular, use of an adequate surgical technique may lead to better outcomes than those for coil embolization in the treatment of large and/or wide-neck paraclinoid ICA aneurysms.

Adulthood Benign Triton Tumor Developed in the Orbit

Benign triton tumor (BTT) or neuromuscular hamartoma is an uncommon tumor composed of mature neural and well-differentiated striated muscular elements. Its development is exceptionally rare in the adult and head region. This report describes a case of adulthood BTT that occurred in the orbit. The patient was a 53-year-old woman who presented with right periorbital swelling and pain in eyeball over 2 months. Magnetic resonance imaging revealed a well-enhancing mass surrounding optic nerve and ocular muscles in the right retrobulbar area. The tumor was subtotally removed via transcranial approach. Its pathological diagnosis was confirmed to be a neuromuscular hamartoma. She developed diplopia postoperatively. Adulthood BTT should be considered in the differential diagnosis of head and neck tumors. It is also important to make adequate therapeutic strategy to avoid postoperative neural dysfunction.

Clinical Experiences of Unruptured Vertebral Artery Dissection / 대한신경손상학회지

OBJECTIVE: The natural course of unruptured vertebral artery dissection remains unclear. The clinical manifestation of unruptured vertebral artery dissection varies from headache, focal neurologic deficits caused by ischemia to subarachnoid hemorrhage with high mortality. The purpose of this study is to investigate the clinical course of unruptured vertebral artery dissection. METHODS: From March 2011 to April 2013, 7 patients with headache or nuchal pain by spontaneous vertebral artery dissection visited our institute were retrospectively reviewed. Their clinical data was obtained by medical records and radiologic studies including computed tomographic angiography, magnetic resonance imaging, magnetic resonance angiography and digital subtraction angiography. RESULTS: No patient experienced fatal outcome by subarachnoid hemorrhage or vertebrobasilar ischemia during follow-up period. Radiologic studies also did not show the evidence of subarachnoid hemorrhage or vertebrobasilar ischemia. Follow-up angiography showed the decreased size or disappearance of aneurysm in 3 patients. CONCLUSION: This study suggests that the natural course of unruptured vertebral artery dissection is not aggressive. Patients with unruptured vertebral artery dissection could be managed with conservative treatment including anticoagulants and/or antiplatelet agents.

Risk Factors for Developing Large Emboli Following Carotid Artery Stenting

OBJECTIVE: The introduction and development of the embolic protecting device (EPD) has resulted in a decreased rate of stroke after carotid artery stenting (CAS). The authors performed a retrospective study to investigate the risk factors for developing large emboli after CAS which can lead to ischemic events. METHODS: A total of 35 consecutive patients who underwent CAS between January 2009 and March 2012 were included in this study. Patients were divided into two groups including those with small emboli (group A; grade 1, 2) and those with large emboli (group B; grade 3, 4). The size and number of emboli were assigned one of four grades (1=no clots, 2=1 or 2 small clots, 3=more than 3 small clots, 4=large clots) by microscopic observation of the EPD after CAS. We compared demographic characteristics, medical history, and angiographic findings of each group. RESULTS: Thirty-five patients underwent CAS, and technical success was achieved in all cases. Twenty-three patients were included in group A and 12 patients in group B. Our results demonstrated that advanced age [odds ratio (OR) 1.24; 95% confidence interval (CI) 1.01-1.52; p=0.044] and smoking (OR 42.06; CI 2.828-625.65, p=0.006) were independent risk factors for developing large emboli after CAS. CONCLUSION: In patients with carotid artery stenosis treated with CAS, advanced age and smoking increased the number and size of emboli. Although use of an EPD is controversial, it may be useful in CAS in patients with risk factors for large emboli in order to reduce the risk of ischemic events.

Reperfusion Injury after Autologous Cranioplasty in a Patient with Sinking Skin Flap Syndrome

The sinking skin flap syndrome is a rare complication after a large craniectomy. It consists of a sunken skin above the bone defect with neurological symptoms such as severe headache, mental changes, focal deficits, or seizures. In patient with sinking skin flap syndrome, cerebral blood flow and cerebral metabolism are decreased by sinking skin flap syndrome, and it may cause the deterioration of autoregulation of brain. We report a case of a patient with sinking skin flap syndrome who suffered from reperfusion injury after cranioplasty with review of pertinent literature.

Migration of Sparganosis from the Brain to the Cervical Spinal Cord

Central nervous system (CNS) sparganosis is a rare parasitic infestation caused by ingestion of the raw or inadequately cooked snakes or frogs. Sparganum is well known for its ability of migrating though the tissue, therefore, it can cause various neurological symptoms if it involves neurological systems. A 51-year-old male patient visited our department of neurosurgery complaining of the motor weakness and radiating pain on both upper extremities over 4 months. He had a history of ingesting raw snakes untill his late twenties. The magnetic resonance (MR) images of cervical spine revealed an intramedullary ill-defined enhancing lesion with the aggregated cysts in the upper cervical spinal cord. Under presumptive diagnosis of sparganosis, we took brain MR image. The brain MR images revealed the signal change in right fronto-temporal lobe suggesting the trajectory of parasitic migration via ventricular systems. He underwent a midline myelotomy and granuloma removal followed by the posterior laminoplasty. Pathologic findings showed inflammatory changes and necrosis with keratinized tissue suggesting the CNS sparganosis. We report an uncommon case of CNS sparganosis migrated from the brain to the spinal cord with literature review.

Skull Perforation and Depressed Fracture Following Skull Fixation for Stereotactic Surgery / 대한신경손상학회지

We report an unusual case of skull perforation and depressed fracture with epidural hematoma in a 61-year-old woman who has been undertaken a skeletal fixation for stereotactic evacuation of intracerebral hematoma. Most neurosurgeons secure the patient's head in a skeletal fixation device with a three- or four-pronged pin-type headrest for stereotactic procedure or microsurgery. Although a variety of complications have been reported secondary to the use of head fixation devices, these potential complications of skull fixation have been infrequently described in the medical literatures. Consideration of calvarial thickness, tightening force, and adequate location of skull fixation may reduce the risk of skull perforation and depressed fracture.