In epilepsy-aphasia spectrum (EAS) disorders, mutations in the glutamate receptor ionotropic N-methyl-D-aspartate type subunit 2A (GRIN2A) have become important for screening the disease. Research into the phenotypic variability of several types of neurologic impairment involving these mutations is in progress. However, the non-neurological problems related to these mutations are poorly understood. EAS disorders usually have epileptic, cognitive, or behavioral manifestations. In this case report, we present a female patient with epilepsy, delay in expressive language and social development, and intellectual disability with low intelligence quotient and memory quotient, but normal motor development. Through genetic analysis, she was found to have a missense and a nonsense mutation in GRIN2A (c.1770A>C; p.Lys509Asn and c.3187G>T; p.Glu1063∗, respectively) and we consider the nonsense mutation as 'pathogenic variant'. She was also discovered to have congenital hypothyroidism, growth hormone deficiency and Rathke's cleft cyst in the brain, which were previously unknown features of GRIN2A mutation. Our findings should widen understanding of the spectrum of GRIN2A phenotypes, and emphasize the need for more research into the association between GRIN2A mutations and non-neurologic clinical presentations.
Objective : We aimed to analyze clinical and radiological outcomes retrospectively in patients with basilar apex aneurysms treated by coiling or clipping. Methods : Outcomes of basilar bifurcation aneurysms were assessed retrospectively in 77 consecutive patients (61 women, 16 men), ranging in age from 25 to 79 years (mean, 53.7 years) from 1999 to 2007. Results : Forty-nine patients out of 77 patients (63.6%) presented with subarachnoid hemorrhages of the 49 patients treated with coiling, 27 (55.1 %) showed complete occlusion of the aneurysm sac. Of these, 13 patients (26.5%) developed coil compaction on angiographic or MRI follow-up, with recoiling required in 9 patients (18.4%). Procedural complications of coiling were acute infarction in nine patients and the bleeding of the aneurysms in six patients. The remaining 28 patients underwent microsurgery : twenty-six of these (92.9%) with microsurgery followed up with conventional angiography. Complete occlusion of the aneurysm sac was achieved in 19 patients (73.1%). Operation-related complications of microsurgery were thalamoperforating artery injuries in three patients, retraction venous injury in two, postoperative epidural hemorrhage (EDH) in one, and transient partial or complete occulomotor palsy in 14 patients. Glasgow Outcome Scores (GOS) were 4 or 5 in 21 of 28 (75%) patients treated with microsurgery at discharge, and at 6 month follow-up, 20 of 28 (70.9%) maintained the same GOS. In comparison, GOS of four or 5 was observed in 36 of 49 (73.5%) patients treated with coiling at discharge and at 6 month follow-up, 33 of 49 patients (67.3%) maintained the GOS from discharge. Conclusion : Basilar top aneurysms were still challenging lesions based on our series. Endovascular or microsurgery endowed with its inborn risks and procedural complications for the treatment of basilar apex aneurysms individually. Microsurgery provided better outcome in some specific basilar apex aneurysms. For reaching the most favorable outcome, endovascular modality as well as microsurgery was inevitably considered for each specific basilar apex aneurysm.
Objective: To analyze the correlations between intraoperative ultrasound and MRI metrics of the spinal cord in degenerative cervical myelopathy and identify novel potential predictive ultrasonic indicators of neurological recovery for degenerative cervical myelopathy. Materials and Methods: Twenty-two patients who underwent French-door laminoplasty for multilevel degenerative cervical myelopathy were followed up for 12 months. The Japanese Orthopedic Association (JOA) scores were assessed preoperatively and 12 months postoperatively. Maximum spinal cord compression and compression rates were measured and calculated using both intraoperative ultrasound imaging and preoperative T2-weight (T2W) MRI. Signal change rates of the spinal cord on preoperative T2W MRI and gray value ratios of dorsal and ventral spinal cord hyperechogenicity on intraoperative ultrasound imaging were measured and calculated. Correlations between intraoperative ultrasound metrics, MRI metrics, and the recovery rate JOA scores were analyzed using Spearman correlation analysis. Results: The postoperative JOA scores improved significantly, with a mean recovery rate of 65.0 ± 20.3% (p < 0.001). No significant correlations were found between the operative ultrasound metrics and MRI metrics. The gray value ratios of the spinal cord hyperechogenicity was negatively correlated with the recovery rate of JOA scores (ρ = -0.638, p = 0.001), while the ventral and dorsal gray value ratios of spinal cord hyperechogenicity were negatively correlated with the recovery rate of JOA-motor scores (ρ = -0.582, p = 0.004) and JOA-sensory scores (ρ = -0.452, p = 0.035), respectively. The dorsal gray value ratio was significantly higher than the ventral gray value ratio (p < 0.001), while the recovery rate of JOA-motor scores was better than that of JOA-sensory scores at 12 months post-surgery (p = 0.028). Conclusion: For degenerative cervical myelopathy, the correlations between intraoperative ultrasound and preoperative T2W MRI metrics were not significant. Gray value ratios of the spinal cord hyperechogenicity and dorsal and ventral spinal cord hyperechogenicity were significantly correlated with neurological recovery at 12 months postoperatively.
Objectives : The authors present a retrospective analysis of 14 patients treated for spinal cord hemangioblastoma (SCH) between Dec. 1986 and Mar. 2000. This study was conducted to evaluate and compare the difference of the functional outcomes associated with the extent of surgical removal of SCH. Methods : Eleven patients were male and three patients were female. Their mean age was 37.2 years that ranged from 19 to 62 years. Preoperative magnetic resonance(MR) imaging of the spine was performed in all cases, and preoperative angiography in eleven cases. They were followed from 15 months to 161 months(median follow-up period, 47 months), and we investigated the change of neurological symptoms and functional outcomes with radiological features, especially on MR imaging. Results : Six patients were accompanied by von Hippel-Lindau disease, and three of them had multiple CNS tumors. Thirteen patients had intramedullary tumor, and the remaining one had extradural. Syringomyelia around the tumor was observed in ten cases. All patients underwent surgical removal, and gross total removal(GTR) was achieved in ten cases. Preoperative embolization was performed in four cases. In four patients who were treated with preoperative embolization, intraoperative loss of blood was minimal and GTR was possible. One patient developed a transient swallowing difficulty postoperatively without permanent postoperative neurological deficits. In three of four patients in whom GTR was not possible, their functional outcomes were worsened postoperatively. The functional status at discharge was improved in seven patients, stationary in four patients, and worse in three. At the last follow-up(15-161 months), one of four patients who had been stationary at discharge showed improvement but, the rest did not show any change. All patients who showed neurological improvement were patients with GTR, and the patients with GTR had significant better outcome than those without GTR(p=0.015). Conclusion : Surgical treatment, and especially, GTR is considered as treatment of choice for spinal cord hemangioblastoma. Preoperative embolization may prevent intraoperative bleeding and improve surgical outcome.
Objective : In this study, we investigated the relationship between the histologic grading of meningiomas and proliferative potentials determined by the Ki-67, proliferating cell nuclear antigen(PCNA) and flow cytometry (FCM) with the aim of determining whether these potentials can be used as a parameter to the proliferative activity, in particular of atypical and malignant meningiomas. Methods : This study consisted of 47 meningiomas(6 malignant, 14 atypical, and random sampled 27 benign meningiomas). By immunohistochemical staining of Ki-67 and PCNA on formalin-fixed, paraffin-embedded sections, the anti-human rabbit polyclonal antibody against Ki-67 antigen and anti-PCNA monoclonal antibody(PC10) scores were counted. FCM was also performed on paraffin-embedded tissue using a selective staining technique for DNA. DNA ploidy, S-phase fraction, and proliferative index(PI)) were determined. Results : The results are summarized as follows ; 1) Proliferation rates as assessed by Ki-67 and PCNA closely correlated with the degree of anaplastic histologic features. 2) Proliferative potentials determined by FCM(S-phase fraction and PI) were not able to distinguish between benign and atypical/malignant meningiomas. 3) DNA ploidy was not a useful indicator of histologic grade in these tumors. 4) Proliferative potentials such as Ki-67 staining index(SI) and PCNA SI did not correlate with the ploidy pattern. 5) There was a linear correlation between Ki-67 SI and PCNA SI, but we could not find a correlation between Ki-67 SI and S-phase fraction or PI. Our results also did not show a statistically signficant correlation between PCNA SI and S-phse fraction or PI. Conclusions : We conclude that evaluation of the proliferative potentials with Ki-67 and PCNA is important as an additional factor for the prediction of malignancy in meningiomas. A dual study of Ki-67 and PCNA SIs on the same tissue might improve the accuracy with which the proliferative potential of a tumor can be predicted. We demonstrated that FCM in meningiomas is not valuable in predicting the behavior of these neoplasms, but we did observe a trend toward more malignancy with higher percent S-phase fraction and higher PI. Analysis of the S-phase fraction and PI might therefore be a useful tool to discriminate among histologic grades of meningiomas.
Objective : The brain is dependent on glucose as an energy source. Intricate homeostatic mechanisms have been implicated in maintaining the blood glucose concentration in the brain. The aim of this study is to find the way to identify the metabolic proteins regulating the glucose in rat hypothalamus. Methods : In this study, we analysed the secretome from rat hypothalamus in vivo. We introduced 500 nM of insulin into the rat hypothalamus. The chromatographic patterns of the secretome were identified, after which Mass Spectrometry-Mass Spectrometry (MS-MS) analysis was performed. Results : In Liquid Chromatography-Mass Spectrometry (LC-MS) analysis, 60 proteins were identified in the secretome. Among them, 8 novel proteins were unveiled and were associated with the energy metabolism of insulin signaling in mitochondria of rat hypothalamic neuron. Nineteen other proteins have unknown functions. These ligands were confirmed to be secreting from the rat hypothalmus on insulin signaling by western blotting. Conclusion : The hypothalamus is the master endocrine gland responsible for the regulation of various physiological and metabolic processes. Proteomics using LC-MS analysis offer a efficient means for generating a comprehensive analysis of hypothalamic protein expression by insulin signaling.
Woo, Won Cheol;Song, Shi Hun;Koh, Hyeon Song;Yeom, Jin Young;Kim, Seong Ho;Kim, Youn
Journal of Korean Neurosurgical Society
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제29권11호
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pp.1445-1450
/
2000
Objectives : The Objective of this study was to analyze the prognostic factors affecting survival in the patients with glioblastomas. Methods : We retrospectively studied 55 consecutive patients with glioblastomas who were admitted to neurosurgery department from January 1988 to March 1998. Fifteen pateients were excluded from the analysis because of follow-up loss and surgical motality. There were 24 male and 16 female patients, with a mean age of 51 years. Surgery consisted of biopsy in 4(10.0%) patients, subtotal resection in 9(22.5%) patients and gross total resection in 27(67.5%) patients. Nine(22.5%) patients received second operation. Twenty-eight(70%) received postoperative radiation therapy. Various levels of radiation dose were used, 6,000 rad over 7 weeks in most cases. The variable factors were examined for their relationship with survival ; age at the time of diagnosis, gender, duration of neurological symptoms, preoperative neurological state(Karnofsky performance score), extent of surgical resection, location of tumor, reoperation, and postoperative radiotherapy and chemotherapy. Result : The mean survival time was 55 weeks, three(7.5%) of the 40 patients survived more than two years. Survival time with biopsy only cases was 24 weeks, for those with subtotal resection 43 weeks, and for those with gross total resection 67 weeks. A mean survival time from the time of reoperation was 42 weeks. Statistically significant survival factors in glioblastoma were extent of surgical resection, postoperative radiotherapy and reoperation. Summary : Results of our series support the views that the extent of surgery, reoperation and postoperative radiation are important prognostic factors. We also recommend radical tumor removal, postoperative radiotherapy and reoperation, if possible.
Objective: This study aimed to investigate the occurrence and types of the adverse events (AEs) associated with oral fluconazole and itraconazole and factors associated with specific types of AEs. Methods: We analyzed AEs reported by community pharmacies nationwide over 10 years using the Korea Adverse Event Reporting System database. Various AE terms were categorized into 18 types, and concomitant medications were classified by drug-drug interaction (DDI) severity. The relationship between the specific type of AE and age, sex, and number of concomitant medications was investigated using multiple logistic regression analysis. Results: A total of 879 AE reports of fluconazole and 401 reports of itraconazole were analyzed; of these reports, 321 and 83 reports of fluconazole and itraconazole, respectively, described concomitant drug administration categorized as DDI severity of contraindicated or major. Women had a higher risk of psychiatric AEs associated with fluconazole use (OR, 1.587; p=0.042). Polypharmacy increased the risk for psychiatric AEs (OR, 3.598; p<0.001 for fluconazole and OR, 2.308; p=0.046 for itraconazole). In dermatologic AEs, the mean age of patients who received itraconazole was lower than that of patients who received fluconazole (46.3±16.8 vs. 54.9±15.4; p<0.001). Co-administration of fluconazole with 1-3 drugs increased the risk of neurological AEs (OR, 1.764; p=0.028). Conclusion: When using fluconazole and itraconazole, psychiatric AEs should be noted, particularly in women and in case of polypharmacy; moreover, when fluconazole is co-administered with other drugs, attention should be paid to the occurrence of neurological AEs.
Hyoung-Won Seo;Jeong-Min Lee;Hae-Boem Lee;Yoon-Ho Roh;Tae-Sung Hwang;Kun-Ho Song;Joong-Hyun Song
Journal of Veterinary Clinics
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제40권1호
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pp.56-61
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2023
A 5-month-old female domestic short-haired cat presented with a history of seizure episodes for two months following an animal bite injury to the head. There were no remarkable findings on physical and neurological examination or blood analysis. Computed tomography revealed a fracture of the left parietal bone with an inward displacement of the bone fragment while magnetic resonance imaging revealed an enlarged temporal horn of the left lateral ventricle and a pseudomeningocele compressing the adjacent cerebral parenchyma. Subsequently, cerebrospinal fluid analysis results were normal. The patient was diagnosed with traumatic brain injury (TBI), with subsequent post-traumatic hydrocephalus (PTH) and pseudomeningocele. Despite treatment with phenobarbital and levetiracetam, seizures were not sufficiently controlled. Craniectomy for bone fragment removal and duraplasty were performed after a week. The patient then returned to normal condition with no further seizure activity. On repeated MRI two months after discharge, the hydrocephalus of the lateral ventricle and pseudomeningocele were enlarged; however, the patient maintained a good clinical status without any neurological signs. To the best of our knowledge, PTH and intracranial pseudomeningoceles have not yet been reported in cats. PTH and pseudomeningocele are among the complications of TBI and may not have any significant relevance with the clinical signs in this case. Thus, to broaden our knowledge about PTH and pseudomeningocele in cats, we describe serial changes in the clinical findings of this cat over the treatment period.
Background: This study was aimed to identify the safety signals of metoclopramide in Korea Adverse Event Reporting System (KAERS) database by proportionality analysis methods. Methods: The study was conducted using Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD) reported from January 2013 to December 2017 through KAERS. Signals of metoclopramide that satisfied the data-mining indices of proportional reporting ratio (PRR), reporting odds ratio (ROR) and information component (IC) were defined. The detected signals were checked whether they included in drug labels in the Ministry of Food and Drug Safety (MFDS), U.S. Food and Drug Administration (FDA) and Micromedex®. Results: A total number of drug AE reports associated with all drugs of data in this study was 2,665,429. Among them, the number of AE reports associated with metoclopramide was 22,583. Forty-two meaningful signals of metoclopramide were detected that satisfied with the criteria of data-mining indicies. Especially neurological signals including extrapyramidal reactions, represented in the safety letter of regulatory agencies were identified in this study. Conclusion: Neurological signals of metoclopramide including extrapyramidal reactions were detected. It is believed that this search for signals can contribute to ensuring safety in the use of metoclopramide.
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