BACKGROUND:Right to left shunting, usually caused by a patent foramen ovale (PFO), is associated with migraine and visual aura. It is unknown if patients who present with visual aura without headache behave similarly to those experiencing typical migraine headache with aura. The purpose of this study was to assess the prevalence of right to left shunting in patients who present with migraine aura without headache and evaluate the response to PFO closure. METHODS:The records of patients referred to the Interventional Cardiology program at the University of California at Los Angeles for suspected intracardiac right to left shunt were reviewed. Individuals with visual auras with or without migraine headaches were divided into three groups: group A (aura + migraine), migraine aura during or within 60 minutes of headache; group B (migraine aura unrelated to headache), migraine aura and headache temporally unrelated; and group C (migraine aura only), isolated migraine visual aura without a history of headaches. The presence of right to left shunt was assessed using transcranial Doppler with an agitated saline test. PFO closure was performed in 80 patients. Residual headache and migraine visual aura were assessed 3 and 12 months after the procedure. The control group consisted of 200 patients referred for diagnostic cardiac catheterization. RESULTS:Of 590 referred patients, 225 had migraine visual aura with or without headache. The prevalence of right to left shunt was similar (P = 0.66) in groups B (21/29, 72%) and C (14/21, 67%). Group A patients had a higher prevalence of right to left shunt (168/175, 96%) due to selection bias. The prevalence of right to left shunt in the control group was significantly (P < 0.0001) lower (36/200, 18%) than in groups A, B, and C. At 12 months after PFO closure, visual aura was resolved in 52%, 75%, and 80% of patients in groups A, B, and C, respectively (difference not statistically significant). CONCLUSION:There is an increased prevalence of PFO among patients with migraine aura without headache. The closure of PFO correlates with improvement of the visual aura, suggesting a causative association between the presence of PFO and both visual aura and migraine headaches. Ophthalmologists should be aware of the association of right to left shunts with visual aura.

Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are killer lymphocytes that provide defense against viral infections and tumor transformation. Analogous to that of CTL, interactions of killer-cell immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands calibrate NK cell education and response. Gene families encoding KIRs and HLA ligands are located on different chromosomes, and feature variation in the number and type of genes. The independent segregation of KIR and HLA genes results in variable KIR-HLA interactions in individuals, which may impact disease susceptibility. We tested whether KIR-HLA combinations are associated with Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis that has strong association with HLA-DR4. We present a case control study of 196 VKH patients and 209 controls from a highly homogeneous native population of Japan. KIR and HLA class I genes were typed using oligonucleotide hybridization method and analyzed using two-tailed Fisher's exact probabilities. The incidence of Bx-KIR genotypes was decreased in VKH patients (odds ratio [OR] 0.58, P = 0.007), due primarily to a decrease in centromeric B-KIR motif and its associated KIRs 2DS2, 2DL2, 2DS3, and 2DL5B. HLA-B22, implicated in poor immune response, was increased in VKH (OR = 4.25, P = 0.0001). HLA-Bw4, the ligand for KIR3DL1, was decreased in VKH (OR = 0.59, P = 0.01). The KIR-HLA combinations 2DL2+C1/C2 and 3DL1+Bw4, which function in NK education, were also decreased in VKH (OR = 0.49, P = 0.012; OR = 0.59, P = 0.013). Genotypes missing these two inhibitory KIR-HLA combinations in addition to missing activating KIRs 2DS2 and 2DS3 were more common in VKH (OR = 1.90, P = 0.002). These results suggest that synergistic hyporesponsiveness of NK cells (due to poor NK education along with missing of activating KIRs) and CTL (due to HLA-B22 restriction) fail to mount an effective immune response against viral-infection that may trigger VKH pathogenesis in genetically susceptible individuals, such as HLA-DR4 carriers.