Helen Kim

Publications (37) View all

• Article: G Protein-Coupled Receptor 124 (GPR124) Gene Polymorphisms and Risk of Brain Arteriovenous Malformation.

  Shantel Weinsheimer, Ari D Brettman, Ludmila Pawlikowska, D Christine Wu, Michael R Mancuso, Frank Kuhnert, Michael T Lawton, Stephen Sidney, Jonathan G Zaroff, Charles E McCulloch, William L Young, Calvin Kuo, Helen Kim
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  ABSTRACT: Abnormal endothelial proliferation and angiogenesis may contribute to brain arteriovenous malformation (BAVM) formation. G protein-coupled receptor 124 (GPR124) mediates embryonic CNS angiogenesis; thus we investigated the association of single nucleotide polymorphisms (SNPs) and haplotypes in GPR124 with risk of BAVM. Ten tagging SNPs spanning 39 kb of GPR124 were genotyped in 195 Caucasian BAVM patients and 243 Caucasian controls. SNP and haplotype association with risk of BAVM was screened using χ(2) analysis. Associated variants were further evaluated using multivariable logistic regression, adjusting for age and sex. The minor alleles of 3 GPR124 SNPs adjacent to exon 2 and localized to a 16 kb region of high linkage disequilibrium were associated with reduced risk of BAVM (rs7015566 A, P=0.001; rs7823249 T, P=0.014; rs12676965 C, P=0.007). SNP rs7015566 (intron 1) remained associated after permutation testing (additive model P=0.033). Haplotype analysis revealed a significant overall association (χ(2)=12.55, 4 df, P=0.014); 2 haplotypes (ATCC, P=0.006 and GGCT, P=0.008) were associated with risk of BAVM. We genotyped a known synonymous SNP (rs16887051) in exon 2, however genotype frequency did not differ between cases and controls. Sequencing of conserved GPR124 regions revealed a novel indel polymorphism in intron 2. Immunohistochemistry confirmed GPR124 expression in the endothelium with no qualitative difference in expression between BAVM cases and controls. SNP rs7015566 mapping to intron 1 of GPR124 was associated with BAVM susceptibility among Caucasians. Future work is focused on investigating this gene region.
  Translational stroke research. 12/2012; 3(4):418-427.
• Article: Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: Gene-phenotype correlations.

  Takeo Nishida, Marie E Faughnan, Timo Krings, Murali Chakinala, James R Gossage, William L Young, Helen Kim, Tony Pourmohamad, Katharine J Henderson, Stacy D Schrum, Melissa James, Nancy Quinnine, Aditya Bharatha, Karel G Terbrugge, Robert I White
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  ABSTRACT: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disease with a wide spectrum of vascular malformations (VMs) involving multiple organs. Nine to 16% of patients with HHT harbor brain arteriovenous malformations (AVMs), which can cause intracranial hemorrhage (ICH). Our objective was to study clinical manifestations of brain AVMs in patients with HHT and correlate these with the specific gene mutated. We reviewed records of 171 patients with HHT and brain AVMs. A history of ICH was found in 27% (41/152) patients, with a mean age of 26 ± 18 range, (0-68) years. All of patients with ICH were neurologically asymptomatic prior to ICH. Multiple brain AVMs were found in 23% (170/39) of patients on initial examination. Genetic test results were available in 109 (64%) patients. Mutations in ENG, ACVRL1, and SMAD4 were present in 75 (69%), 18 (17%), and 2 (2%), respectively. A history of ICH was reported in 24% of patients with an ENG mutation and 27% of patients with an ACVRL1 mutation, with a mean age of 26 ± 16 (range, 2-50) and 18 ± 21 (0-48) years, respectively. No statistically significant differences in age at first brain AVM diagnosis, prevalence of ICH history, age at ICH, or other manifestations of brain AVMs were observed among gene groups. In conclusion, no evidence for differences in brain AVM characteristics was observed among HHT gene groups, although we cannot exclude clinically important differences. Larger studies are needed to further guide brain AVM screening decisions in patients with HHT. © 2012 Wiley Periodicals, Inc.
  American Journal of Medical Genetics Part A 09/2012; 158A(11):2829-34. · 2.39 Impact Factor
• Article: Cerebellar Arteriovenous Malformations: Anatomical Subtypes, Surgical Results, and Increased Predictive Accuracy of the Supplementary Grading System.

  Ana Rodríguez-Hernández, Helen Kim, Tony Pourmohamad, William L Young, Michael T Lawton
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  ABSTRACT: BACKGROUND:: Anatomical diversity amongst cerebellar AVMs calls for a classification that is intuitive and surgically informative. Selection tools like the Spetzler-Martin grading system are designed to work best with cerebral AVMs, but have shortcomings with cerebellar AVMs. OBJECTIVE:: To define subtypes of cerebellar AVMs that clarify anatomy and surgical management, determine results according to subtypes, and compare predictive accuracies of Spetzler-Martin and supplementary systems. METHODS:: From a consecutive surgical series of 500 patients, 60 had cerebellar AVMs, 39 had brain stem AVMs and were excluded, and 401 had cerebral AVMs. RESULTS:: Cerebellar AVM subtypes were: 18 vermian, 13 suboccipital, 12 tentorial, 12 petrosal, and 5 tonsillar. Patients with tonsillar and tentorial AVMs fared best. Cerebellar AVMs presented with hemorrhage more than cerebral AVMs (p<0.001). Cerebellar AVMs were more likely to drain deep (p=0.036) and less likely eloquent (p<0.001). The predictive accuracy of supplementary grade was better than that of Spetzler-Martin grade with cerebellar AVMs (areas under the ROC curve 0.74 and 0.59, respectively). The predictive accuracy of the supplementary system was consistent for cerebral and cerebellar AVMs, whereas that of the Spetzler-Martin system was greater with cerebral AVMs. CONCLUSION:: Patients with cerebellar AVMs present with hemorrhage more than patients with cerebral AVMs, justifying an aggressive treatment posture. The supplementary system is better than the Spetzler-Martin system at predicting outcomes after cerebellar AVM resection. Key components of the Spetzler-Martin system, like venous drainage and eloquence, are distorted by cerebellar anatomy in ways that components of the supplementary system are not.
  Neurosurgery 09/2012; · 2.79 Impact Factor
• Article: Evaluating performance of the spetzler-martin supplemented model in selecting patients with brain arteriovenous malformation for surgery.

  Helen Kim, Tony Pourmohamad, Erick M Westbroek, Charles E McCulloch, Michael T Lawton, William L Young
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  ABSTRACT: Our recently proposed point scoring model includes the widely-used Spetzler-Martin (SM)-5 variables, along with age, unruptured presentation, and diffuse border (SM-Supp). Here we evaluate the SM-Supp model performance compared with SM-5, SM-3, and Toronto prediction models using net reclassification index, which quantifies the correct movement in risk reclassification, and validate the model in an independent data set. Bad outcome was defined as worsening between preoperative and final postoperative modified Rankin Scale score. Point scores for each model were used as predictors in logistic regression and predictions evaluated using net reclassification index at varying thresholds (10%-30%) and any threshold (continuous net reclassification index >0). Performance was validated in an independent data set (n=117). Net gain in risk reclassification was better using the SM-Supp model over a range of threshold values (net reclassification index=9%-25%) and significantly improved overall predictions for outcomes in the development data set, yielding a continuous net reclassification index of 64% versus SM-5, 67% versus SM-3, and 61% versus Toronto (all P<0.001). In the validation data set, the SM-Supp model again correctly reclassified a greater proportion of patients versus SM-5 (82%), SM-3 (85%), and Toronto models (69%). The SM-Supp model demonstrated better discrimination and risk reclassification than several existing models and should be considered for clinical practice to estimate surgical risk in patients with brain arteriovenous malformation.
  Stroke 07/2012; 43(9):2497-9. · 5.73 Impact Factor
• Article: Brain-derived neurotrophic factor Val66Met polymorphism predicts worse functional outcome after surgery in patients with unruptured brain arteriovenous malformation.

  Erick M Westbroek, Ludmila Pawlikowska, Michael T Lawton, Charles E McCulloch, William L Young, Helen Kim
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  ABSTRACT: The Val66Met polymorphism of brain-derived neurotrophic factor is associated with decreased brain-derived neurotrophic factor secretion and poor outcome after acute neurological injury. We hypothesized that the Met allele is associated with worsening of functional outcome after brain arteriovenous malformation resection. Three hundred forty-one surgically treated patients with brain arteriovenous malformation with outcome data were genotyped for Val66Met. Outcome was change in modified Rankin Scale preoperatively versus postoperatively, dichotomized into poor (change >0) or good outcome (change ≤0). Likelihood ratio tests for interactions and logistic regression analysis were performed. A significant interaction (P=0.03) of Val66Met genotype and hemorrhagic presentation existed; thus, ruptured and unruptured patients were considered separately. The Met allele was associated with increased risk of poor outcome among patients presenting unruptured (OR, 2.15; 95% CI, 1.02-4.55; P=0.045) but not ruptured (OR, 0.54; 95% CI, 0.19-1.53; P=0.25), adjusting for covariates. The Val66Met polymorphism is associated with worsened surgical outcome in patients with unruptured brain arteriovenous malformation, a group that currently has no good risk predictors. Further studies replicating these findings are needed.
  Stroke 07/2012; 43(8):2255-7. · 5.73 Impact Factor