VKORC1 and CYP2C9 Genotype Variations in Relation to Warfarin Dosing in Korean Stroke Patients / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Variant alleles of CYP2C9 and VKORC1 account for differences in anticoagulation response. We sought to establish a warfarin dosing formula for individualized target International Normalization Ratio of Prothrombin Times (INRs) using data from single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 in Korean patients. METHODS: Ischemic stroke patients displaying stable target INR for at least 3 months before enrollment were analyzed. Warfarin and vitamin K levels were measured to adjust for confounders. Phenotypes were defined using the 'warfarin response index' (WRI) defined as INR divided by the daily maintenance warfarin dose. We tested SNPs in CYP2C9 (3 sites: 430C>T (rs1799853), 1075A>C (rs1057910), 1076T>C) and VKORC1 (14 sites: 381C>T, 861C>A (rs17880887), 2653G>C, 3673A>G, 5496G>T, 5808T>G (r17882154), 6009C>T, 6484T>C (rs9934438), 6853C>T (rs17886369), 7566T>C, 8767G>C, 8814T>C, 9041G>A (rs17880624), and 9071G>T) using a standard sequencing method. Multivariate linear regression analysis was applied to establish the formula for warfarin dosage. RESULTS: All 204 patients had excellent drug compliance. The mean INR was 2.22 (+0.56) and mean daily maintenance dose of warfarin was 3.92 mg (+1.54). Patients with low WRI were younger (PC, PC, 3673G>A, 6484T>C, 6853C>G. 7566C>T, 9041G>A) (r2=1). Based on these data, a warfarin dosing formula was established. CONCLUSIONS: WRI is influenced by age, body mass index and SNPs in VKORC1 and CYP2C9 in Korean stroke patients. The obtained warfarin dosing formula may be clinically applicable.

Subclavian Steal Syndrome Treated by Axilloaxillary Bypass Surgery : The Role of Duplex Sonography

We report herein a case of subclavian steal syndrome due to occlusive disease in multiple branches of the aortic arch, which was successfully treated by axilloaxillary bypass and subclavian stent insertion. The hemodynamic changes were evaluated using duplex sonography and transcranial Doppler before and after each procedure. The waveform and parameters of blood flow revealed an objective improvement in cerebral perfusion. These findings correlated well with clinical outcome. Neurosonologic evaluation can provide objective evidence for improved hemodynamic status after treatment.

The Effect of the MTHFR C677T Single Nucleotide Polymorphism on Plasma Homocysteine Lowering Therapy with Vitamins in the Ischemic Stroke Patients

BACKGROUND: C677T single nucleotide polymorphism (SNP) of Methylentetrahydrofolate reductase (MTHFR) has been known to be associated with plasma homocysteine (Hcy) levels, which is an independent risk factor for stroke. However, recent large clinical trials did not show any benefits of Hcy lowering therapy with vitamins on the prevention of stroke. We hypothesized that the Hcy lowering effect by vitamins would be different according to the MTHFR C677T SNP types (CC, CT or TT), which may influence the benefits of vitamins by Hcy lowering on stroke prevention. METHODS: The authors retrospectively studied acute stroke patients with information of the genotype of MTHFR and serial levels of Hcy during a recent 4 year period (July 2002 - Dec 2005). Vitamins (folic acid 1 mg, and/or cobalamin 750 microgram and pyridoxine 75 mg) were prescribed to the patients whose basal plasma Hcy levels were above 12 umol/L. RESULTS: Among 172 patients, 68 patients took vitamins. The mean basal Hcy level was significantly higher in the TT type than the others, and was decreased by vitamin therapy. Distribution of homocysteine grading (normal, intermediate or high) in follow up was not significantly different according to these SNP types. CONCLUSIONS: The Hcy lowering effect by vitamins was not different by MTHFR genetic polymorphism. Considering the higher prevalence of certain gene types in stroke and our study results, genetic factors such as MTHFR polymorphism may play an important role on the development of stroke rather than the plasma Hcy levels.

Cerebral Air Embolism Following Pneumopyelography

No abstract available.

Ictal Spitting in a Patient with Dominant Temporal Lobe Epilepsy: Discrepancy between Epileptogenic and Symptomatogenic Areas for Spitting Automatism

Ictal spitting is an unusual manifestation that originates from the non-dominant hemisphere, but rarely from the dominant hemisphere. In the latter case, it has not been well defined as to whether symptomatogenic area for ictal spitting originates from the dominant hemisphere. We present a patient with ictal spitting. Intracranial EEG demonstrated a left hippocampal onset with propagation to the right hemisphere, and subsequent ictal spitting development. Even in dominant hemispheric seizures, the non-dominant hemisphere is a symptomatogenic area for ictal spitting.

A Case of Lateral Medullary Infraction Presenting with Thoracic Sensory Level

Loss of pain and temperature sensation due to lateral medullary infarction are well known and classically involve the ipsilateral side of the face and the lower part of the body on the controlateral side. This pattern of sensory loss below a certain level on the trunk, usually a sign of spinal cord disease, may also appear following a lesion in the lateral medullar, due to damage to the spinothalamic tract. A 72-year-old hypertensive man developed sudden dizziness, headache, and gait ataxia. On neurologic examination, he had left limb and gait ataxia. Five days later he noted loss of pain and temperature sensation on the right leg and trunk with a sensory level at T4 with preservation of touch, vibration, and joint position sense in all limbs. Brain MRI showed a small infarct in the left lower lateral medulla. Brain MR angiography showed stenosis of the right proximal carotid artery, left distal vertebral artery, and mid-basilar artery. We report a case of sensory defects with a sensory level on the trunk that occured as the result of lesion of the lower lateral medulla.