Tacrolimus and Mini-dose Methotrexate for Prevention of Graft-Versus-Host Disease after Unrelated Hematopoietic Stem Cell Transplantation in Children: A Single-center Study in Korea / 임상소아혈액종양

BACKGROUND: Currently, data on the role of tacrolimus and mini-dose methotrexate (MTX) in pediatric unrelated hematopoietic stem cell transplantation (HSCT) is limited. We report the outcomes of unrelated hematopoietic stem cell recipients, evaluating engraftment status, incidence of acute and chronic graft-versus-host disease (GVHD) and toxicities after use of tacrolimus and mini-dose MTX for GVHD prophylaxis. METHODS: Thirty-five children who received tacrolimus and mini-dose MTX as prophylaxis from January 2004 to December 2013 were reviewed. All patients received tacrolimus beginning the day prior to transplant at a dose of 0.03 mg/kg/day by continuous intravenous infusion. MTX was administered at a dose of 5 mg/m2 IV on days 1, 3, 6 and 11. RESULTS: Median age at transplantation was 8.42 years (range 0.75-18.9 years). Seventeen patients received human leukocyte antigen (HLA) fully matched donor transplants and 18 received partially mismatched transplants. All but two patients who received unrelated cord blood transplants showed successful engraftment. The median time to ANC recovery was 12 days. The incidence of acute GVHD was 33.3% including 15.1% grade III-IV GVHD. Localized chronic GVHD developed in only 2 of 27 (7.4%) evaluable patients. Lower tacrolimus levels during days 1-21 were associated with a higher incidence of acute GVHD (P=0.033). The estimated 4-year event free survival and overall survival of the patients were 71.2% and 80.0%. CONCLUSION: Overall, the combination of tacrolimus and mini-dose MTX could be effectively administered in the setting of pediatric unrelated HSCT.

A Case of Blastic Plasmacytoid Dendritic Cell Neoplasm in a Child / 임상소아혈액종양

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare hematological malignancy in children that is characterized by bruise-like skin lesions, with or without bone marrow involvement. Because the clinical course of BPDCN is highly aggressive and fatal in adults, allogeneic hematopoietic stem cell transplantation (HSCT) is recommended as the optimal treatment. Due to its rarity, the pediatric experience with BPDCN is limited and standard treatment has so far not been defined. We report a case of a 14-year-old boy with BPDCN involving the skin, bone marrow and lymph nodes. The patient was treated with high-risk group acute lymphoblastic leukemia protocol. He achieved a complete remission after induction chemotherapy and still maintains clinical remission without HSCT for 17 months after initial diagnosis.

Tacrolimus and Mini-dose Methotrexate for Prevention of Graft-Versus-Host Disease after Unrelated Hematopoietic Stem Cell Transplantation in Children: A Single-center Study in Korea / 임상소아혈액종양

BACKGROUND: Currently, data on the role of tacrolimus and mini-dose methotrexate (MTX) in pediatric unrelated hematopoietic stem cell transplantation (HSCT) is limited. We report the outcomes of unrelated hematopoietic stem cell recipients, evaluating engraftment status, incidence of acute and chronic graft-versus-host disease (GVHD) and toxicities after use of tacrolimus and mini-dose MTX for GVHD prophylaxis.METHODS: Thirty-five children who received tacrolimus and mini-dose MTX as prophylaxis from January 2004 to December 2013 were reviewed. All patients received tacrolimus beginning the day prior to transplant at a dose of 0.03 mg/kg/day by continuous intravenous infusion. MTX was administered at a dose of 5 mg/m2 IV on days 1, 3, 6 and 11.RESULTS: Median age at transplantation was 8.42 years (range 0.75-18.9 years). Seventeen patients received human leukocyte antigen (HLA) fully matched donor transplants and 18 received partially mismatched transplants. All but two patients who received unrelated cord blood transplants showed successful engraftment. The median time to ANC recovery was 12 days. The incidence of acute GVHD was 33.3% including 15.1% grade III-IV GVHD. Localized chronic GVHD developed in only 2 of 27 (7.4%) evaluable patients. Lower tacrolimus levels during days 1-21 were associated with a higher incidence of acute GVHD (P=0.033). The estimated 4-year event free survival and overall survival of the patients were 71.2% and 80.0%.CONCLUSION: Overall, the combination of tacrolimus and mini-dose MTX could be effectively administered in the setting of pediatric unrelated HSCT.

A Case of Blastic Plasmacytoid Dendritic Cell Neoplasm in a Child / 임상소아혈액종양

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare hematological malignancy in children that is characterized by bruise-like skin lesions, with or without bone marrow involvement. Because the clinical course of BPDCN is highly aggressive and fatal in adults, allogeneic hematopoietic stem cell transplantation (HSCT) is recommended as the optimal treatment. Due to its rarity, the pediatric experience with BPDCN is limited and standard treatment has so far not been defined. We report a case of a 14-year-old boy with BPDCN involving the skin, bone marrow and lymph nodes. The patient was treated with high-risk group acute lymphoblastic leukemia protocol. He achieved a complete remission after induction chemotherapy and still maintains clinical remission without HSCT for 17 months after initial diagnosis.

Childhood acute lymphoblastic leukemia with hyperleukocytosis at presentation

BACKGROUND: Hyperleukocytosis caused by acute lymphoblastic leukemia (ALL) is associated with early morbidity and mortality due to hyperviscosity arising from the excessive number of leukocytes.This study was designed to assess the incidence of hyperleukocytosis, survival outcomes, and adverse features among pediatric ALL patients with hyperleukocytosis. METHODS: Between January 2001 and December 2010, 104 children with previously untreated ALL were enrolled at the Pusan National University Hospital. All of them were initially stratified based on the National Cancer Institute (NCI) risk; 48 (46.2%) were diagnosed with high-risk ALL. The medical charts of these patients were retrospectively reviewed. RESULTS: Twenty (19.2%) of the 104 children with ALL had initial leukocyte counts of >100x10(9)/L, and 11 patients had a leukocyte count of >200x10(9)/L. Male gender, T-cell phenotype, and massive splenomegaly were positively associated with hyperleukocytosis. Common early complications during induction therapy included renal dysfunction, and central nervous system hemorrhage. The complete remission (CR) rate for the pediatric ALL patients with hyperleukocytosis (94.1%) was similar to the overall CR rate (95.6%). The estimated 3-year event free survival (EFS) and overall survival of ALL children with hyperleukocytosis were 75.0% and 81.2%, respectively. However, patients with initial leukocyte counts >200x10(9)/L had a lower EFS than those with initial leukocyte counts 100-200x109/L (63.6% vs. 100%; P=0.046). CONCLUSION: The outcome of pediatric ALL cases with an initial leukocyte count >200x10(9)/L was very poor, probably due to early toxicity-related death during induction therapy.

A Case of Reticulohistiocytoma Mimicking Primary Cutaneous CD 4 Positive Small/medium T-cell Lymphoma / 임상소아혈액종양

Reticulohistiocytoma is a rare, benign histiocytic proliferation of the skin or soft tissue. A 5-month-old healthy girl visited our clinic for an enlarging nodule on the center of her right palm. The clinical differential diagnosis included xanthogranuloma and primary cutaneous CD4 positive small/medium T-cell lymphoma. Histopathology of the nodule showed abundant eosinophilic and glassy cytoplasm. The nuclei were round to oval shaped, with focal irregular nuclear membrane, and mitotic figures were absent. Immunohistochemical study determined that the cells were positive for CD68 but negative for CD1a. She was finally diagnosed with reticulohistiocytoma (solitary epithelioid histiocytoma).

A Case of Reticulohistiocytoma Mimicking Primary Cutaneous CD 4 Positive Small/medium T-cell Lymphoma / 임상소아혈액종양

Reticulohistiocytoma is a rare, benign histiocytic proliferation of the skin or soft tissue. A 5-month-old healthy girl visited our clinic for an enlarging nodule on the center of her right palm. The clinical differential diagnosis included xanthogranuloma and primary cutaneous CD4 positive small/medium T-cell lymphoma. Histopathology of the nodule showed abundant eosinophilic and glassy cytoplasm. The nuclei were round to oval shaped, with focal irregular nuclear membrane, and mitotic figures were absent. Immunohistochemical study determined that the cells were positive for CD68 but negative for CD1a. She was finally diagnosed with reticulohistiocytoma (solitary epithelioid histiocytoma).

Bone Strength of the Primary Compression Trabeculae in Human Calcaneus / 대한골다공증학회지

OBJECTIVES: The accuracy of bone strength can be improved for medically treating osteoporosis by diagnosing and predicting fracture risk. In this study, we calculated the material properties of calcaneus bone and evaluated the statistical correlation of the bone mineral density (BMD) with morphometry indices and bone strength. MATERIALS & METHODS: Twelve cored bone samples were obtained from the primary compressive trabeculae of human calcaneus. All samples were scanned with a Lunar PIXImus(R), and two-dimensional serial section images were obtained on a micro-computed tomography system. A mechanical test was performed with an Instron universal testing machine and finite element analysis (FEA) to determine material properties and bone strength. RESULTS: The material property of the samples was 2.97 GPA. BMD was significantly correlated with bone strength and morphometric indices except for Tb.Sp, DA, and Tb.N. The statistical relationship between bone strength and the morphometric indices was significant except for DA. CONCLUSIONS: FEA based on in vivo high resolution serial section images can be used to directly evaluate bone strength and will be a useful tool in clinical practice for diagnosing osteoporosis and predicting fracture risk.

Colonization Rate and Control of Vancomycin-Resistant Enterococci in the Neonatal Intensive Care Unit / 소아감염

PURPOSE: Recently, vancomycin-resistant enterococci (VRE) have become one of the major nosocomial pathogens in Korea. However, there have been few studies on the epidemiology of VRE colonization among neonates. In this study, we investigated the prevalence of VRE colonization, risk factors for VRE, and how to control the spread of VRE infection in the Neonatal Intensive Care Unit (NICU) of Pusan National University Hospital (PNUH). METHODS: We retrospectively reviewed medical records of 192 neonates who were admitted to the NICU of PNUH from March 2006 to March 2007. Surveillance cultures from rectal swabs for detecting VRE were obtained weekly during the study period. We analyzed the prevalence of VRE and various risk factors. RESULTS: The rate of VRE colonization among NICU patients was 25% (48/192). Thirty five of these VRE colonized patients were transferred to the NICU from other local hospitals. Compared with the non-VRE group, the risk factors associated with VRE colonization were lower birth weight, congenital heart disease, applied mechanical ventilation, use of a central venous catheter, chest tubing, a history of surgery, and use of antibiotics. CONCLUSION: VRE colonization among patients admitted to the NICU is rapidly increasing. Monitoring and managing premature neonates from the beginning of the birth process, avoiding many invasive procedures, avoiding antibiotics such as vancomycin and third generation cephalosporin are important for preventing the emergence and spread of VRE colonization in the NICU.

Clinical Features of Acute Pancreatitis in Children / 대한소아소화기영양학회지

PURPOSE: Since there are few studies involving acute pancreatitis in children, we reviewed our experience with this medical condition to describe the clinical features. METHODS: A retrospective analysis was conducted by reviewing the medical records of 41 patients with AP who were admitted to the Department of Pediatrics of Pusan National University Hospital between January 1996 and June 2007. RESULTS: Twenty males and 21 females (mean age, 8.7+/-4.5 years) were included. In 22 patients (53.7%), no definitive causes were found. The most common etiologies were choledochal cysts (22.0%). Necrotizing pancreatitis was diagnosed in 5 patients (12.2%), and recurrent acute pancreatitis in 4 patients (9.8%). CT findings included pancreatic swelling (43.9%), peripancreatic fluid collection (29.3%), ascites (24.4%), and peripancreatic fat necrosis (12.2%). Serum amylase and lipase levels at diagnosis were 535.3+/-553.2 and 766.2+/-723.6 U/L, respectively, and were normalized within 1 week in 22 and 14 patients, respectively. On the basis of the Balthazar scale, 2 patients were diagnosed with severe AP. In 4 patients (9.8%), a surgical procedure was indicated. Major complications included ascites (32.3%), sepsis (16.1%), and pseudocyst and renal impairments (12.9%). Two patients died from multi-organ failure. CONCLUSION: The etiologies of AP in children are varied. Most children have a single episode and a self-limited course. However, AP of childhood still carries significant morbidity and mortality. Early diagnosis, appropriate treatment according to disease severity, and management of complications are important.

Intramedullary Decompression for the Treatment of Unicameral Bone Cysts in Children / 대한정형외과학회잡지

PURPOSE: The present study aims at evaluating our results of intramedullary decompression of the unicameral bone cysts in children with using flexible nail(s) or titanium cannulated screws. MATERIALS AND METHODS: We treated fourteen children with unicameral bone cysts by intramedullary decompression. Eleven cases were in the metaphysis of long bones (seven in the proximal humerus amd four were in the proximal femur), which were all treated by flexible intramedullary nailing; while a cancellous screw was axially placed in three cysts of the short bones (all in the calcaneus). The mean age of the patients at the time of surgery was 11.8 years, and the mean duration of follow-up was 16.7 months. The final outcome was radiographically classified into the four categories of Capanna et al.,; completely healed, healed with residual radiolucency, recurred or having no response. RESULTS: All of the cysts In the long bones responded to treatment. Seven cysts healed completely, and three healed with residual radiolucent areas visible on radiographs. One cyst, which initially appeared completely healed, recurred after the removal of nails. The healing period varied from three to 36 months. For the calcaneal cysts, there was no definite sign of effective consolidation in all three cases. CONCLUSION: Intramedullary decompression by flexible nailing for the treatment of unicameral bone cyst of a long bone was effective in providing early stability and for accelerating consolidation of the cyst. Its surgical intervention is minimal, and the result is predictable. Our trial of placing a screw in the calcaneal cysts was unsuccessful according to the short term follow-up.

Association between Migraine with Aura and both Homocysteine and MTHFR C677T Polymorphism

BACKGROUND: The pathophysiology of migraine is not yet fully understood. Homocysteine acts as an excitatory amino acid in vivo and may influence the threshold of migraine. The previous studies have revealed strong association between the homozygous C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and hyperhomocysteinemia. In this study, we examined the association between both homocysteine and MTHFR C677T polymorphism and headache, such as migraine and tension headache. METHODS: We enrolled 148 headache patients (75 tension headache, 34 migraine with aura [MWA], and 39 migraine without aura [MOA]) and 121 normal controls; checked their fasting homocysteine levels and analyzed for the MTHFR C677T polymorphism. For the multivariate analysis, we used logistic regression to adjust for age and sex. RESULTS: Plasma homocysteine levels were significantly higher in patients with MWA than those in controls (adjusted odds ratio (AOR), 1.12; 95% confidence intervals (CI), 1.02~1.23). The AOR and 95% CI of the MTHFR 677TT genotype was significantly higher in patients with total migraine (AOR, 3.32; 95% CI, 1.30~9.55; p< 0.05) and with MWA (AOR, 4.70; 95% CI, 1.44~15.29; p<0.01) than the controls. However, the AOR was not significant in patients with tension headache (AOR, 0.93; 95% CI, 0.37~2.32) and with MOA (AOR, 2.77; 95% CI, 0.78~9.74). CONCLUSIONS: Our findings suggest that both elevated homocysteine level and the homozygous C677T mutation in the MTHFR gene are associated with migraine with aura.

The Prevalence of Childhood and Adolescent Obesity in Jeju and Clinical Characteristics according to the Degree of Obesity / 소아과

PURPOSE: Recently, childhood obesity has increased and became a major health concern in Korea. The aim of this study is to examine the prevalence of childhood and adolescent obesity in Jeju and to analyze clinical characteristics according to the degree of obesity. METHODS: A total of 3,643 students from April 2002 to August 2002 were studied. To examine the prevalence of childhood and adolescent obesity, obesity index, body mass index and Rholer index were used. To analyze clinical characteristics according to the degree of obesity, blood pressure and laboratory data from student health examination were used. RESULTS: Prevalence of childhood and adolescent obesity in Jeju was 9.9%(mild:5.1%, moderate:4.3%, severe:0.5%) by obesity index, 5.6% by body mass index, and 6.3% by Rholer index. Prevalence of obesity in males was significantly higher than in females, but prevalence of obesity according to age made no significant difference. Prevalence of hypertension, liver function test abnormality and hypercholesterolemia according to the degree of obesity were significantly increased, but that of anemia, hyperglucosemia showed no significant difference. CONCLUSION: By student health examination data, the prevalence of childhood and adolescent obesity in Jeju was identified. Because the prevalence of hypertension, liver function test abnormality and hypercholesterolemia according to the degree of obesity were significantly increased, we must pay more attention to childhood and adolescent obesity as an important student health issue.

A Case of Fetal Intracranial Hemorrhage Diagnosed by Antenatal Ultrasonogram / 대한산부인과학회잡지

Fetal intracranial hemorrhage is quite rare. It refers to the bleeding that occurs antenatally from a blood vessel into ventricles, subdural space, or parenchyme of the brain. Factors that may place the fetus at risk for intracranial hemorrhage include maternal drug exposure history, various maternal and fetal conditions. The majority of reported antenatally detected cases of intracranial hemorrhage have occurred during the third trimester. Residual changes may include development of a porencephalic cyst or ventricular enlargement. Intracranial hemorrhage has a broad spectrum of manifestations with diverse prognosis. We report a case of fetal intracranial hemorrhage that was diagnosed antenatally in the third trimester with a brief review of literatures.

Hyperhomocysteinemia as an Independent Risk Factor for Silent Brain Infarction: Inverse Correlation with Folate in Patients with MTHFR 677TT Genotype

BACKGROUND: Silent brain infarction (SBI) are common in elderly people and are associated with an increased risk of clinically apparent stroke. Hyperhomocysteinemia is also an independent risk factor for ischemic stroke. This study was undertaken to determine whether hyperhomocysteinemia was associated with SBI, and also to find prevention against SBI through correlation among homocysteine, folate, and vitamin B12. METHODS: We enrolled 103 SBI patients and 107 healthy individuals and checked their fasting plasma homocysteine levels and analyzed the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. RESULTS: The plasma homocysteine levels in subjects with SBI (12.91 +/- 5.84 micromoll/L) were significantly higher than those in subjects without SBI (10.21+/-3.92 micromol/L; p or =13.3 micromol/L), moderate (10.0 to 13.2 micromol/L), and low (< or =9.9 micromol/L) groups, the adjusted odds ratio (AOR) for SBI was significantly greater in subjects with high group compared with in subjects with low group (AOR, 3.58; 95% CI, 1.69 to 7.58: p = 0.0009). When we combined each MTHFR genotype with SBI patients and controls, the plasma homocysteine concentrations showed a significant inverse correlation with folate only in SBI patient with MTHFR 677 TT genotype (correlation coefficient: -0.495; p = 0.023). CONCLUSIONS: Hyperhomocysteinemia is an independent risk factor for SBI. Our findings show that reducing plasma hommocysteine level by folate intake may prevent SBI in patients with homozygous C677T mutation in the MTHFR gene.

Hepatitis B Surface Antigen and Antibody Positive Rates of Children and Adolescents in Jeju / 대한간학회지

BACKGROUND/AIMS: Korea has been an endemic area of Hepatitis B infection. Recently, the Hepatitis B carrier population has been significantly decreasing because of Hepatitis B vaccination. The aim of this study was to analyse the Hepatitis B surface antigen (HBsAg) and the Hepatitis B surface antibody (anti-HBs) positive rates of children and adolescents in Jeju. METHODS: From January 2000 to August 2002, seropositivity of HBsAg and anti-HBs were evaluated by enzyme immunoassay (EIA) in 1,653 pediatric patients. From April 2002 to August 2002, seropositivity of HBsAg and anti-HBs were evaluated by reversed passive hemaglutination (RPHA) in 2,532 students. From July 1994 to February 2003, seropositivity of HBsAg was evaluated by EIA in 1,013 pregnant women. RESULTS: The positive rates of HBsAg and anti-HBs of children and adolescents in Jeju were 2.1% and 70.9%, respectively. The positive rates of HBsAg of pregnant women in Jeju was 4.7% and that of HBeAg in HBsAg positive pregnant women was 38.1%. In children born after 1995, as age increased, HBsAg seropositivity increased significantly and anti-HBs seropositivity decreased significantly. There was no significant difference in testing HBsAg positivity between the RPHA and the EIA tests, but testing anti-HBs positivity by EIA was significantly higher than by RPHA. CONCLUSIONS: To reduce HBsAg positive rate, regular testing for anti-HBs by EIA may be indicated until at least 15 years after the primary vaccination schedule, and booster vaccination may be indicated in subjects whose anti-HBs titer was under 10 mIU/mL. 29.1% of children and adolescents in Jeju, therefore, may need to be revaccinated.

A Study for the Prevalence of High-risk HPV Subtype in Uterine Cervical Neoplasia of Korean Women / 대한산부인과학회잡지

OBJECTIVE: Many studies about Human Papilloma virus (HPV) that is a causative factor uterine cervical cancer have been established and more than 85 HPV types have been identified. The distributions of cancer-associated HPV types are different according to nations and region. To estimate the extent of infection with common HPVs among Korean women, we have examined specimens of various cervical lesion. METHODS: The samples were collected from 135 Korean women visiting the Department of Obstetrics and Gynecology, Chunan Hospital Soonchunhyang University, Chunan, Korea. DNA was extracted from the specimen and 112 samples were available. HPV subtype were identified using HPV DNA Chip and P-E ABI prism 310 DNA Autosequencer. RESULTS: HPV DNA was detected in 98 cervical sample (80.3%) out of 122 cases. HPV typing in the samples revealed the prevalence of HPV 16 in 56 cases (57.1%), followed by HPV 58 in 14 cases (14.3%) and HPV 18 were only 2 cases (2.0%) among 98 HPV (+) cases. HPV-negative case was 34.8% and HPV-positive case was 65.2% in CIN I group. HPV-negative case was significantly high in CIN I group. HPV-positive cases were 83 cases (83.8%) in the cases advanced more than CIN I. There were significant difference comparing CIN I group. The order of cervical neoplasia-associated type were HPV-16, -58, -52 and ect. The pattern is similar to the results reported in China and Japanese. CONCLUSION: The finding indicated that the overall prevalence of HPV among Korean women is similar to that in China and Japanese, the distinct high proportion of HPV 58 infection deserves attention. The prevalence of high-risk HPV in Korean women is different from the one in western women but accumulated data from larger population and different regions in Korea is needed.

Factors Affecting Development of Epilepsy and Postoperative Recurrence of Epilepsy in Primary Brain Tumor

BACKGROUND: A small but significant proportion of patients with brain tumors continued to have seizures postoperatively. All of them could not be explained simply by the failure to adequately resect the tumor mass. We investigated factors influencing seizure recurrence in primary brain tumors. METHODS: We analyzed 435 patients treated with tumor surgery and examined the differences between epileptic seizure group (ESG) and non-epileptic seizure group (NESG). Among ESG, we selected 99 patients confirmed by pathology. We divided patients into chronic epileptic seizure group (CESG; duration of seizure attack >or=1 year) and acute epileptic seizure group (AESG; < 1 year). We also investigated the differences between two groups. RESULTS: Of 435 patients, 104 were ESG and 331 NESG. Among various factors, male, favorable neurological state, fronto-temporal lobe origin, astrocytoma, oligodendroglioma were statistically significant in ESG compared with NESG (p<0.05). Of 99 patients, 43 were CESG and 56 AESG. Among various factors, seizure recurrence rate without residual tumor or tumor recurrences was significantly higher in CESG than in AESG (p<0.05). On the other hand, the laboratory abnormalities, and the rate of residual tumor or tumor recurrences on follow-up MRI were significantly higher in AESG than in CESG (p<0.05). CONCLUSIONS: Among many factors, sex, neurological state, location and pathology of tumors were significantly related to seizure attacks in brain tumor. There were the differences of epileptogenesis between AESG and CESG. We suggest that patients with brain tumor and chronic epilepsy have to be investigated with extensive work-up including invasive electrophyosiologic studies.

The Relationship between Hyperhomocysteinemia and C677T MTHFR Gene Polymorphism in Patients with Ischemic Stroke

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for cerebrovascular disease. MTHFR 677TT genotype can induce hyperhomocysteinemia. However, the association between this 677TT genotype and ischemic stroke still remains controversial. This study was undertaken to determine whether MTHFR 677TT genotype was associated with certain subtype of ischemic stroke. METHODS: The case group consisted of 129 patients with ischemic stroke and the control group consisted of 157 healthy individuals. We checked their fasting plasma homocysteine levels and analyzed the C677T mutation in the MTHFR gene. The relative risk of MTHFR 677TT genotype was assessed by odds ratios using multivariate logistic regression. RESULTS: Homocysteine levels in plasma were significantly higher in ischemic stroke patients (10.386.44 mol/L) than in controls (8.002.40) (P<0.05). In small-artery disease (11.366.01), the same result was found (P<0.05). On the other hand, the prevalence of the homozygote mutation was not significantly higher in ischemic stroke patients (20.2%) than in controls (13.4%) (adjusted OR 1.39, 95% CI 0.65 to 2.96). The adjusted OR and 95% CI was 2.59 (1.08 to 6.25) for the TT genotype in patients with small-artery disease compared to controls. The 677TT genotype was increased in small-artery disease compared to large-artery disease (adjusted OR 7.60, 95% CI 1.66 to 34.77). CONCLUSIONS: Our findings suggest that the homozygous C677T mutation in the MTHFR gene is a risk predictor in the subtype of ischemic stroke, such as small-artery disease.

The Significance of Homocysteine in Epileptic Patients / 대한간질학회지

PURPOSE: Hyperhomocysteinemia was observed in epileptic patients receiving anticonvulsants, especially homozygotes for mtehylenetetrahydrofolate reductase (MTHFR) gene 677C->T mutation. Hyperhomocysteinemia induce atherosclerosis, fetal anticonvulsant syndrome, etc. Therefore, we examined any other factors that might affect the level of homocysteine in epileptic patients. METHODS: We investigated the plasma total homocysteine level in 145 patients with epilepsy. And then we analyzed various factors (clinical findings, neuro-image finding, drugs, MTHFR gene, serum folate and vitamin B12 level) affecting the level of homocysteine. RESULTS: Among the various factors, male, present neurological deficits, frequent seizure attacks, MTHFR gene 677 TT genotype, polypharmacy, and conventional drug (phenytoin, carbamazepine, valproic acid, phenobarbital, primidone, benzodiazpines) than new drug (lamotrigine, vigabatrin, topiramate, oxcarbazepine zonisamide) were related with elevated homocysteine levels. CONCLUSION: We recommend monotherapy with new drugs and higher vitamin requirement in the male epileptic patients of MTHFR TT genotype with neurological deficits and frequent seizure attacks.