Pharmacological Management of Germinal Matrix-Intraventricular Hemorrhage

Germinal matrix-intraventricular hemorrhage (GM-IVH) is among the devastating neurological complications with mortality and neurodevelopmental disability rates ranging from 14.7% to 44.7% in preterm infants. The medical techniques have improved throughout the years, as the morbidity-free survival rate of very-low-birth-weight infants has increased; however, the neonatal and long-term morbidity rates have not significantly improved. To this date, there is no strong evidence on pharmacological management on GM-IVH, due to the limitation of well-designed randomized controlled studies. However, recombinant human erythropoietin administration in preterm infants seems to be the only effective pharmacological management in limited situations. Hence, further high-quality collaborative research studies are warranted in the future to ensure better outcomes among preterm infants with GM-IVH.

Importance of Differential Diagnosis of a Possible Brain Tumor in Patients with Cervical Radiculopathy

Lesions occurring simultaneously in the somatosensory or motor cortex of the brain and the cervical spine are rare. Brain tumors can cause similar symptoms to cervical lesions which can lead to confusion in treatment priorities. Moreover, if cervical disease is noticeably observed in radiologic findings of a patient complaining of cervical radiculopathy with non-specific electromyography results, it is common to no longer perform further evaluation. Here we introduce two cases where the cause of cervical radiculopathy was first considered to be the result of a degenerative cervical disease but was later discovered to be a result of a brain tumor.

High-accuracy quantitative principle of a new compact digital PCR equipment: Lab On An Array

Digital PCR (dPCR) is the third-generation PCR that enables real-time absolute quantification without reference materials. Recently, global diagnosis companies have developed new dPCR equipment. In line with the development, the Lab On An Array (LOAA) dPCR analyzer (Optolane) was launched last year. The LOAA dPCR is a semiconductor chip-based separation PCR type equipment. The LOAA dPCR includes Micro Electro Mechanical System that can be injected by partitioning the target gene into 56 to 20,000 wells. The amount of target gene per wells is digitized to 0 or 1 as the number of well gradually increases to 20,000 wells because its principle follows Poisson distribution, which allows the LOAA dPCR to perform precise absolute quantification. LOAA determined region of interest first prior to dPCR operation. To exclude invalid wells for the quantification, the LOAA dPCR has applied various filtering methods using brightness, slope, baseline, and noise filters. As the coronavirus disease 2019 has now spread around the world, needs for diagnostic equipment of point of care testing (POCT) are increasing. The LOAA dPCR is expected to be suitable for POCT diagnosis due to its compact size and high accuracy. Here, we describe the quantitative principle of the LOAA dPCR and suggest that it can be applied to various fields.

Structural Variation of Alu Element and Human Disease

Transposable elements are one of major sources to cause genomic instability through various mechanisms including de novo insertion, insertion-mediated genomic deletion, and recombination-associated genomic deletion. Among them is Alu element which is the most abundant element, composing ~10% of the human genome. The element emerged in the primate genome 65 million years ago and has since propagated successfully in the human and non-human primate genomes. Alu element is a non-autonomous retrotransposon and therefore retrotransposed using L1-enzyme machinery. The 'master gene' model has been generally accepted to explain Alu element amplification in primate genomes. According to the model, different subfamilies of Alu elements are created by mutations on the master gene and most Alu elements are amplified from the hyperactive master genes. Alu element is frequently involved in genomic rearrangements in the human genome due to its abundance and sequence identity between them. The genomic rearrangements caused by Alu elements could lead to genetic disorders such as hereditary disease, blood disorder, and neurological disorder. In fact, Alu elements are associated with approximately 0.1% of human genetic disorders. The first part of this review discusses mechanisms of Alu amplification and diversity among different Alu subfamilies. The second part discusses the particular role of Alu elements in generating genomic rearrangements as well as human genetic disorders.

Mutational Analysis of Extranodal NK/T-Cell Lymphoma Using Targeted Sequencing with a Comprehensive Cancer Panel

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.

Large Intracranial Aneurysm after Transsphenoidal Surgery for Pituitary Macroadenoma

Uncontrolled cerebrospinal fluid (CSF) leakage after transsphenoidal surgery (TSS) for pituitary adenoma can lead to meningitis. Intracranial mycotic pseudoaneurysm is a rare complication in central nervous system infection. Large single pseudoaneurysm is more uncommon. Most mycotic aneurysms occur due to endocarditis. The present patient had no heart problem and was infected by CSF leakage after transsphenoidal surgery. We present a case of large ruptured mycotic pseudoaneurysm as a complication of cerebral infection after TSS for pituitary macroadenoma.

Delayed Self-expansion Phenomenon as a Complication of Neuroform Stent Assisted Coiling for Ruptured Intracranial Aneurysm

Use of stent assisted coiling of intracranial aneurysms has shown a recent increase. Despite technical improvement and accumulated clinical experiences, due to insufficient study data, debate over short and long term durability and associated complication has continued. To the best of our knowledge, this case report, for the first time, demonstrates delayed self-expansion phenomenon occurring as an acute and unpredictable complication of Neuroform stent assisted coiling for treatment of a ruptured intracranial aneurysm.

Y-Stenting Endovascular Treatment for Ruptured Intracranial Aneurysms : A Single-Institution Experience in Korea

OBJECTIVE: Stent-assisted coiling on intracranial aneurysm has been considered as an effective technique and has made the complex aneurysms amenable to coiling. To achieve reconstruction of intracranial vessels with preservation of parent artery the use of stents has the greatest potential for assisted coiling. We report the results of our experiences in ruptured wide-necked intracranial aneurysms using Y-stent coiling. METHODS: From October 2003 to October 2011, 12 patients (3 men, 9 women; mean age, 62.6) harboring 12 complex ruptured aneurysms (3 middle cerebral artery, 9 basilar tip) were treated by Y-stent coiling by using self-expandable intracranial stents. Procedural complications, clinical outcome, and initial and midterm angiographic results were evaluated. The definition of broad-necked aneurysm is neck diameter over than 4 mm or an aneurysm with a neck diameter smaller than 4 mm in which the dome/neck ratio was less than 2. RESULTS: In all patients, the aneurysm was successfully occluded with no apparent procedure-related complication. There was no evidence of thromboembolic complication, arterial dissection and spasm during procedure. Follow-up studies showed stable and complete occlusion of the aneurysm in all patients with no neurologic deficits. CONCLUSION: The present study did show that the Y-stent coiling seemed to facilitate endovascular treatment of ruptured wide-necked intracranial aneurysms. More clinical data with longer follow-up are needed to establish the role of Y-stent coiling in ruptured aneurysms.

Experiences of Neuroform Stent Applications for Ruptured Anterior Communicating Artery Aneurysms with Small Parent Vessel

OBJECTIVE: The purpose of this study was to review the safety and durability of aneurysms treated with stent-assisted coiling of ruptured anterior communicating artery aneurysms with small parent vessels (< 2.0 mm). METHODS: Retrospective review of all ruptured aneurysm treated with stent assisted endovascular coiling between March 2005 and March 2009 at our institution was conducted. We report 11 cases of the Neuroform stent placement into cerebral vessels measuring less than 2.0 mm in diameter (range, 1.3-1.9 mm) in anterior cerebral artery. Clinical follow-up ranged from 3 to 12 months and imaging follow-up was performed with cerebral angiography at 6 months and 12 months after discharge. RESULTS: Complete occlusion was achieved in 10 patients, and a remnant neck was evident in one. No stent displacement or no dislodgement occurred during stent placement. There was no evidence of thromboembolic complication, arterial dissection and spasm during procedure. We performed follow-up angiography in all patients at 6 months and/or 12 months from the first procedure. The follow-up angiographic data showed successfully results except one in-stent stenosis case. All patients improved clinical performances except one patient with severe vasospasm who showed poor clinical condition initially. CONCLUSION: We have safely and successfully treated 11 vessels smaller than 2.0 mm in diameter with self-expanding stents with good short and intermediate term results. More clinical data with longer follow-ups are needed to establish the role of stent-assisted coiling in ruptured aneurysms with small parent vessels.

The Predisposing Causes Associated with a Poor Outcome for the Surgical Treatment of Ruptured Cerebral Aneurysms / 대한뇌혈관외과학회지

OBJECTIVE: We analyzed the main causes leading to a poor outcome (severe disability, a vegetative state and death) following surgical treatment for ruptured intracerbral aneurysms. METHODS: Between January 1994 and December 2007, we maintained a retrospective database of 339 patients who underwent surgical clipping. The various causes we investigated were the technical problems during operation, the initial SAH or ICH, vasospasm, hydrocephalus and the post-operative medical complications. The clinical outcome was assessed according to the Glasgow Coma Scale (GOS). RESULTS: There were 263 cases of good outcomes (77.6%) and 76 cases of poor outcomes (22.4%). The three main causes of a poor outcome were 1) preoperative causes such as the direct insult of the initial SAH and ICH in 21 cases (27.6%), 2) intra-operative causes such as the technical problems during dissection and clipping of the aneurysm neck in 29 cases (38.2%) and 3) postoperative causes such as clinical vasospasm in 16 cases (21.1%). The mean follow-up period was 17.6 months (range : 2 months to 9 years). CONCLUSION: A meticulous neck dissection and complete obliteration of the aneurysm preserving parent arteries and perforators are the most effective and prime methods that surgeons can employ to reduce the rate of poor outcomes when performing ruptured aneurysm surgery.

The Utility and Benefits of External Lumbar CSF Drainage after Endovascular Coiling on Aneurysmal ubarachnoid Hemorrhage

OBJECTIVE: Cerebral vasospasm still remains a major cause of the morbidity and mortality, despite the developments in treatment of aneurysmal subarachnoid hemorrhage. The authors measured the utility and benefits of external lumbar cerebrospinal fluid (CSF) drainage to prevent the clinical vasospasm and its sequelae after endovascular coiling on aneurysmal subarachnoid hemorrhage in this randomized study. METHODS: Between January 2004 and March 2006, 280 patients with aneurysmal subarachnoid hemorrhage were treated at our institution. Among them, 107 patients met our study criteria. The treatment group consisted of 47 patients who underwent lumbar CSF drainage during vasospasm risk period (about for 14 days after SAH), whereas the control group consisted of 60 patients who received the management according to conventional protocol without lumbar CSF drainage. We created our new modified Fisher grade on the basis of initial brain computed tomography (CT) scan at admission. The authors established five outcome criteria as follows : 1) clinical vasospasm; 2) GOS score at 1-month to 6-month follow-up; 3) shunt procedures for hydrocephalus; 4) the duration of stay in the ICU and total hospital stay; 5) mortality rate. RESULTS: The incidence of clinical vasospasm in the lumbar drain group showed 23.4% compared with 63.3% of individuals in the control group. Moreover, the risk of death in the lumbar drain group showed 2.1% compared with 15% of individuals in the control group. Within individual modified Fisher grade, there were similar favorable results. Also, lumbar drain group had twice more patients than the control group in good GOS score of 5. However, there were no statistical significances in mean hospital stay and shunt procedures between the two groups. IVH was an important factor for delayed hydrocephalus regardless of lumbar drain. CONCLUSION: Lumbar CSF drainage remains to play a prominent role to prevent clinical vasospasm and its sequelae after endovascular coiling on aneurysmal subarachnoid hemorrhage. Also, this technique shows favorable effects on numerous neurological outcomes and prognosis. The results of this study warrant clinical trials after endovascular treatment in patients with aneurysmal SAH.

Coil Embolization for Distal Middle Cerebral Artery Aneurysm

Middle cerebral artery (MCA) aneurysms are a common source of subarachnoid hemorrhage (SAH). But, ruptured distal MCA aneurysm is very rare, and their clinical and radiological features are poorly understood. Microsurgical repair remains the most common method used to treat distal MCA aneurysm, even though endovascular coiling has been favored recently. We report our experience of successful coiling for ruptured distal MCA aneurysm. In selected patients, coiling may be a good treatment option for ruptured distal MCA aneurysm.

'Y-stenting' for Endovascular Coiling of Small Basilar Tip Aneurysm

This 58-year-old woman was transferred from a local hospital due to symptoms of acute headache and decreased consciousness. Computed tomography revealed a subarachnoid hemorrhage with blood clot in prepontine cistern. On the first day in the hospital, diagnostic cerebral angiography revealed a basilar tip aneurysm. We performed basilar artery to bilateral posterior cerebral artery(PCA) stent placement to reconstruct the basilar artery apex.

LINAC Radiosurgery for Cerebral Arteriovenous Malformation

OBJECTIVE: The author conducts a retrospective study to analyze long-term outcome and complication of LINAC radiosurgery for cerebral arteriovenous malformation(AVM). METHODS: We performed a detailed long-term follow-up study of 31 patients who could be followed up more than 2 years, with AVM treated by LINAC radiosurgery during January, 1996 to July, 2001. At the time of radiosurgery, the mean age was 47 years (range: 13-68). The median follow up period after radiosurgery was 27.2 months (range: 24-36). In all patients, AVM were completely covered with a 50~90% isodose line. The margin dose delivered by the LINAC was 14~28Gy(mean: 20.9Gy) at the periphery. RESULTS: Angiographic complete obliteration rate was 74.2% at 2 years after radiosurgery. Hemorrhage occured in 2cases(6.5%) at 12 and 14months after radiosurgery retrospectively, and 1patient died. Radiation related complication was developed in 1case(3.2%). CONCLUSION: LINAC radiosurgery is safe and effective in the treatment of cerebral arteriovenous malformation.

Comparative Study of Treatment Results between Surgical Neck Clipping and Endovascular Coiling on the Ruptured Middle Cerebral Artery Aneurysms

OBJECTIVE: The treatment modalities of cerebral aneurysms mainly consist of surgical neck clipping of aneurysms and endovascular embolization. Through comparing of the treatment results between two methods especially focused on their complicatons, the authors present the efficacy of the treatment modality in ruptured middle cerebral artery aneurysms. METHODS: Patients who admitted due to ruptured middle cerebral artery aneurysm between January 1998 and December 2002 were selected. They have done surgical neck clipping or endovascular embolization which employed platinum coil. Treatment methods were chosen in random fashion. The patient's clinical state were determined before, during, and after the treatment by using Hunt and Hess grade and Glasgow outcome scale(GOS). According to Fisher grade was classified based on the amount of hemorrhage. Statistical analyses were done with Student t-test, Pearson's correlation coefficient, and Mann-Whitney U test. RESULTS: Average follow-up period was 24 months(5 days-36 months) in surgery group and 26 months(8 days-36 months) in endovascular embolization group. There was no statistical significance regard to sex, age, patient's Hunt and Hess grade on admission, the Fisher grade, and aneurysmal size. There was no significant difference between GOS of two groups in statistically(p>0.05). CONCLUSION: This comparative study of reveals no significant difference in neurologic outcomes between two treatment modalities.

Lymphocytic Hypophysitis: Case Report

The authors report two cases of lymphocytic hypophsitis: a 38-year-old male patient with headache and diabetes insipidus and in a 64-year-old female patient with headache. Magnetic resonance(MR) image of the patients showed mass-like lesions in the hypophysis as well as loss of high signal on T1-weighted MR images. There was evidence of hypopituitarism. Both patients underwent transsphenoidal approaches for histological diagnosis, which was compatable with lymphocytic hypophysitis. When MR image reveals a characteristic pituitary in the hypophysis lesion with relevant clinical symptoms in a patient, one should include "lymphocytic hypophysitis" as one of the diagnostic possibilities, since the therapeutic options are different from those of pituitary tumors.