Young Seok Park

Association of the Single Nucleotide Polymorphisms in microRNAs 130b, 200b, and 495 with Ischemic Stroke Susceptibility and Post-Stroke Mortality.

The microRNA (miRNA) is a small non-coding RNA molecule that modulates gene expression at the posttranscriptional level. Platelets have a crucial role in both hemostasis and thrombosis, a condition that can occlude a cerebral artery and cause ischemic stroke. miR-130b, miR-200b, and miR-495 are potential genetic modulators involving platelet production and activation. We hypothesized that single nucleotide polymorphisms (SNPs) in these miRNAs might potentially contribute to the susceptibility to ischemic stroke and post-stroke mortality. This study included 523 ischemic stroke patients and 400 control subjects. We investigated the association of three miRNA SNPs (miR-130bT>C, miR-200bT>C, and miR-495A>C) with ischemic stroke prevalence and post-stroke mortality. In the multivariate logistic regression, there was no statistically significant difference in the distribution of miR-130bT>C, miR-200bT>C, or miR-495A>C between the ischemic stroke and control groups. In the subgroup analysis based on ischemic stroke subtype, the miR-200b CC genotype was less frequently found in the large-artery atherosclerosis stroke subtype compared with controls (TT+CT vs CC; adjusted odds ratio for CC, 0.506; 95% confidence interval, 0.265–0.965). During a mean follow-up period of 4.80 ± 2.11 years after stroke onset, there were 106 all-cause deaths among the 523 stroke patients. Multivariate Cox regression analysis did not find a significant association between post-stroke mortality and three miRNA SNPs. Our findings suggest that the functional SNP of miR-200b might be responsible for the susceptibility to large-artery atherosclerotic stroke.

Comparison of 7 T and 3 T MRI in patients with moyamoya disease

Magnetic resonance imaging and magnetic resonance angiography (MRI/MRA) are widely used for evaluating the moyamoya disease (MMD). This study compared the diagnostic accuracy of 7Tesla (T) and 3T MRI/MRA in MMD. In this case control study, 12 patients [median age: 34years; range (10-66years)] with MMD and 12 healthy controls [median age: 25years; range (22-59years)] underwent both 7T and 3T MRI/MRA. To evaluate the accuracy of MRI/MRA in MMD, five criteria were compared between imaging systems of 7T and 3T: Suzuki grading system, internal carotid artery (ICA) diameter, ivy sign, flow void of the basal ganglia on T2-weighted images, and high signal intensity areas of the basal ganglia on time-of-flight (TOF) source images. No difference was observed between 7T and 3T MRI/MRA in Suzuki stage, ICA diameter, and ivy sign score; while, 7T MRI/MRA showed a higher detection rate in the flow void on T2-weighted images and TOF source images (p<0.001). Receiver operating characteristic curves of both T2 and TOF criteria showed that 7T MRI/MRA had higher sensitivity and specificity than 3T MRI/MRA. Our findings indicate that 7T MRI/MRA is superior to 3T MRI/MRA for the diagnosis of MMD in point of detecting the flow void in basal ganglia by T2-weighted and TOF images.

Spontaneous Resolution of a Large Chronic Subdural Hematoma Which Required Surgical Decompression

We report on a case of an 87-year-old woman who showed spontaneous resolution of a large chronic subdural hematoma which required surgical decompression. She had suffered from confused mentality and right side weakness of motor grade II for 10 days. The initial brain CT scan showed a 22 mm thick low density lesion located in the left fronto-temporo-parietal region with midline shift (12 mm) which required emergency decompression. However, because she and her family did not want surgery, she was followed up in the outpatient clinic. Five months later, follow up brain CT showed that the CSDH had disappeared and the patient became neurologically normal. The reasons for spontaneous resolution of CSDH remain unclear. We discuss the possible relation between mechanisms of physio-pathogenesis and spontaneous resolution of a large chronic subdural hematoma (CSH) in an elderly patient.

Correlating Parkinson’s disease motor symptoms with three-dimensional [18F]FP-CIT PET

PurposeTo investigate the correlation between the striatal three-dimensional location and the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score in the context of idiopathic Parkinson’s disease (PD) through radiolabeled N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane positron emission tomography/computed tomography (FP-CIT PET/CT).Materials and methodsIn this cross-sectional study, we assessed the UPDRS motor score and performed FP-CIT PET/CT in patients with PD. Thirty-eight patients with idiopathic PD [average 70xa0years of age (range 49–86); male:female ratio 12:26] were enrolled. The correlation between FP-CIT PET/CT and the UPDRS III scores was investigated after the transformation of PET images by an alternative method using MATLAB.ResultsLeft caudate nucleus uptake negatively correlated with UPDRS items 18, 20 (face), 22 (right arm and leg), 23, 24 (right side), 26 (right side), 27, 30, and 31, while right caudate nucleus uptake positively correlated with items 18, 22 (left arm), 26, and 29. Putamen uptake correlated with items 22 and 25. Left caudate nucleus uptake positively correlated with axial and akinetic-rigidity symptoms.ConclusionsFP-CIT uptake in specific basal ganglia structures strongly correlated with the UPDRS III motor score. Among these, the left caudate nucleus exhibited the strongest relationship with axial and akinetic-rigidity PD symptoms.

Second-stage transsphenoidal approach (TSA) for highly vascular pituicytomas in children.

IntroductionA pituicytoma in the sellar area is extremely rare in children and, due to its highly vascularized nature, can be difficult to address using the transsphenoid approach (TSA) to surgery. Here, we report a rare case of a pituicytoma that was completely removed from a child through a staged operation using the TSA.Case summaryA 13-year-old girl was admitted with a 1-year history of visual disturbance and amenorrhea. Visual field examination showed left total blindness and right temporal hemianopsia. Laboratory results revealed hormonal levels all within normal ranges. Brain magnetic resonance imaging (MRI) showed a homogeneous, highly enhancing sellar and suprasellar mass, typically suggestive of a pituitary adenoma. TSA surgery revealed the tumor had a rubbery-firm consistency, hypervascularity, and profuse bleeding. We removed the tumor partially and planned a second-stage operation.DiscussionGross total removal is the treatment of choice for this type of tumor. Attempted resection of these presumed adenomas or meningiomas using the TSA often results in unexpectedly heavy intraoperative bleeding due to the high vascularity of this rare tumor, making surgery challenging, especially in children where the tumor is within a relatively narrow corridor. While pituicytomas are a rare differential diagnosis for sellar or parasellar tumors in children, total removal by second-stage TSA surgery is indicated in the case of profuse bleeding or uncertainty of biopsy. Following first-stage TSA surgery and pathologic confirmation of pituicytoma, the strategy is typically gross total removal during second-stage TSA surgery.ConclusionsAlthough very rare in children, a pituicytoma should be included in the differential diagnosis of a mass in the sellar area if the tumor is highly enhancing or very vascular. Second-stage TSA surgery is another strategy when the pathology is not clear during the first-stage TSA surgery.

Suppressed GABAergic signaling in the zona incerta causes neuropathic pain in a thoracic hemisection spinal cord injury rat model

OBJECTIVEnSuppression of the gamma-aminobutyric acid (GABA)ergic activity of the zona incerta (ZI) reportedly plays a role in neuropathic pain after spinal cord injury (SCI). A reduction in GABAergic signaling in the ZI of a thoracic hemisection-SCI rat model has been suggested, but not clearly demonstrated. Accordingly, our objective was to investigate whether GABAergic signals influence SCI-induced neuropathic pain.nnnMETHODSnIn vivo, we recorded and compared single-unit, neuronal activity between hemisection-SCI and sham-operated rat models. Furthermore, we analyzed neuronal activity in both models following treatment with either a GABAA receptor agonist (muscimol) or antagonist (bicuculline).nnnRESULTSnRats that underwent hemisection SCI exhibited reduced hindpaw withdrawal thresholds, latencies, and decreased ZI neuronal activity compared with sham-operated controls. Importantly, muscimol treatment increased, whereas bicuculline decreased, the firing rates of the ZI neurons. The muscimol treated, hemisection-SCI rats also exhibited increased hindpaw withdrawal thresholds and latencies.nnnCONCLUSIONSnThese data provide evidence that neuropathic pain after SCI is caused by decreased GABAergic signaling in the ZI. Furthermore, our data demonstrate that infusion of a GABAergic drug into the ZI could restore its inhibitory action and improve neuropathic pain behaviors.

Cerebral-perfusion-based single-photon emission computed tomography (SPECT) staging using NeuroGam® in patients with moyamoya disease

Background and purposeCerebral angiography (CA) is the gold standard for moyamoya disease (MMD) staging and diagnosis, but CA findings are not well correlated with clinical symptoms. The purpose of this study was to establish novel cerebral-perfusion-based staging for MMD that is well correlated with clinical symptoms.Materials and methodsFrom 2010 to 2015, regional cerebrovascular reserve (rCVR) was examined by single-photon emission computed tomography (SPECT) using NeuroGam® (Segamicorp, Houston, TX, USA) in 30 patients (17 women, 13 men; 60 hemispheres; mean 42.0xa0years old [range 5–60xa0years old]) with MMD, which was diagnosed by CA and magnetic resonance angiography (MRA). Brain CT or brain magnetic resonance imaging (MRI) was used to evaluate neurological conditions such as transient ischemic attack (TIA), cerebral hemorrhage, and cerebral infarction. A novel staging system for MMD was developed by combining findings from CA, MRI, and SPECT with NeuroGam®.ResultsOur novel staging system was strongly associated with clinical symptoms. Twenty-two hemispheres out of 60 were categorized as stage I, 24 hemispheres were categorized as stage II, and 14 hemispheres were categorized as stage III. Hemispheres with higher scores exhibited a higher incidence of clinical symptoms. These findings indicate that cerebral-perfusion-based staging is predictive of MMD clinical symptoms.ConclusionPerfusion-based SPECT staging correlates well with clinical symptoms and may be a reliable alternative to the Suzuki staging by CA.

Association of reduced folate carrier-1 (RFC-1) polymorphisms with ischemic stroke and silent brain infarction.

Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke.

The roles of methylenetetrahydrofolate reductase 677C>T and 1298A>C polymorphisms in moyamoya disease patients

PurposeThe methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C polymorphisms, which are associated with hyperhomocysteinemia and nitric oxide (NO) deficiency (which is related to atherothrombosis and cerebral ischemia), have not been studied in moyamoya disease. A case-control study was performed to investigate whether the MTHFR 677C>T and 1298A>C polymorphisms contribute to moyamoya disease (MMD).MethodsOne hundred and seven Korean patients with MMD (mean age, 20.85u2009±u200915.89xa0years; 66.4xa0% female) and 232 healthy control subjects (mean age, 23.99u2009±u200916.16xa0years; 56.8xa0% female) were included. Genotyping for the MTHFR 677C>T and 1298A>C polymorphisms and measurements of homocysteine, folate, vitamin B12, and NO in the cerebrospinal fluid (CSF) were performed. The statistical analysis was performed by multivariate linear regression and logistic regression.ResultThe MTHFR 677CT+TT genotype frequency was significantly increased with early-onset MMD (<10xa0years) compared with late-onset MMD (≥10xa0years) (adjusted odds ratio, 3.392; 95xa0% confidence interval, 1.294–8.893, Pu2009=u20090.013). The MTHFR 677C-1298C/677T-1298A diplotype (1.71u2009±u20091.23 arbitrary units) presented significantly lower NO levels in the CSF compared with the 677C-1298A/677C-1298A diplotype (11.40u2009±u200912.24 arbitrary units).ConclusionThe MTHFR 677C>T and 1298A>C polymorphisms have restricted roles in the Korean MMD population. Therefore, further studies involving larger and more heterogeneous cohorts are needed to extend our understanding of the influence of polymorphisms in MTHFR and other thrombophilic genes on MMD.

The GC + CC genotype at position -418 in TIMP-2 promoter and the -1575GA/-1306CC genotype in MMP-2 is genetic predisposing factors for prevalence of moyamoya disease

BackgroundTo investigate the association of single-nucleotide polymorphisms (SNPs) in matrix metalloproteinases (MMPs)-2, -3, and -9 and tissue inhibitor of metalloproteinase (TIMP)-2 with moyamoya disease (MMD). We conducted a case-control study of MMD patients by assessing the prevalence of six SNPs of MMP-2 -1575G > A [rs243866], MMP-2 -1306C > T [rs243865], MMP-3 -1171 5a/6a [rs3025058], MMP-9 -1562C > T [rs3918242], MMP-9 Q279R [rs17576], and TIMP-2 -418G > C [rs8179090].MethodsKorean patients with MMD (n = 107, mean age, 20.9 ± 15.9 years; 66.4% female) and 243 healthy control subjects (mean age, 23.0 ± 16.1 years; 56.8% female) were included. The subjects were divided into pediatric and adult groups. The genotyping of six well-known SNPs (MMP-2 -1575G > A, MMP-2 -1306C > T, MMP-3 -1171 5a/6a, MMP-9 -1562C > T, MMP-9 Q279R, and TIMP-2 -418G > C) in MMP and TIMP genes was performed by polymerase chain reaction-restriction fragment length polymorphism assays.ResultsA significantly higher frequency of the GC genotype for TIMP-2 -418 G > C was found in MMD patients. The MMP-9 Q279R GA + AA genotype showed a protective effect for MMD. The GA/CC MMP-2 -1575/-1306 genotype was significantly more prevalent in MMD patients.ConclusionsOur findings demonstrate that TIMP-2 -418 GC + CC and MMP-2 -1575GA/-1306CC genotypes could be genetic predisposing factors for MMD development.