PFAPA syndrome is the most common autoinflammatory disorder in childhood with unknown etiology. The aim of our study was clinical evaluation of PFAPA patients from a single tertiary care center and to determine whether variations of AIM2, MEFV, NLRP3, and MVK genes are involved in PFAPA pathogenesis. Clinical and laboratory data of consecutive patients with PFAPA syndrome followed up at the University Children's Hospital, Ljubljana, were collected from 2008 to 2014. All four genes were PCR amplified and directly sequenced. Eighty-one patients fulfilled criteria for PFAPA syndrome, 50 (63%) boys and 31 (37%) girls, with mean age at disease onset of 2.1 ± 1.5 years. Adenitis, pharyngitis, and aphthae were present in 94%, 98%, and 56%, respectively. Family history of recurrent fevers in childhood was positive in 78%. Nineteen variants were found in 17/62 (27%) patients, 4 different variants in NLRP3 gene in 13 patients, and 6 different variants in MEFV gene in 5 patients, and 2 patients had 2 different variants. No variants of clinical significance were found in MVK and AIM2 genes. Our data suggest that PFAPA could be the result of multiple low-penetrant variants in different genes in combination with epigenetic and environmental factors leading to uniform clinical picture.

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Our study showed that systemic endothelial function is not impaired in migraine patients without comorbidities, neither in those with or without aura. Considering these findings, the investigation of cerebral endothelial function would be useful in a further investigation of the role of endothelial (dys)function in migraine pathophysiology.

OBJECTIVE - Cerebral infarction preferentially affects the posterior cerebral artery distribution in migraine patients. The results obtained from the few known studies that have compared the anterior and posterior cerebral endothelial function are contradictory. To the best of our knowledge, cerebrovascular reactivity to L-arginine (CVR), measured by transcranial Doppler sonography (TCD), has not been previously used to determine the posterior cerebral endothelial function in migraine patients with (MwA) and without aura (MwoA). MATERIALS AND METHODS -  Forty migraine patients without comorbidities (20 MwA, 20 MwoA) and 20 healthy subjects were included. By employing strict inclusion criteria, we avoided the possible vascular risk factors. Mean arterial velocity in the middle cerebral artery (MCA) and the posterior cerebral artery (PCA) was measured by TCD before and after infusion of L-arginine, and CVR to L-arginine was then calculated. RESULTS - All migraine patients had lower CVR to L-arginine in PCA (P = 0.002) and similar in MCA (P = 0.29) compared to healthy subjects. This difference was also present in MwA and MwoA compared to healthy subjects (P = 0.003). CONCLUSIONS -  Lower CVR to L-arginine in PCA in migraine patients could associate migraine and cerebral infarcts that are more common in the posterior cerebral artery distribution.

Background: Cerebral endothelial function might be different in distinct cerebrovascular territory, thereby making these areas more susceptible to ischemia and stroke. Higher incidence and prevalence of stroke in males suggest that gender could have a strong influence on this difference. In order to evaluate cerebral endothelial function, we compared cerebrovascular reactivity (CVR) to L-arginine in the anterior and posterior cerebral circulation in healthy young males and females. Methods: Thirty healthy subjects, 15 females (32.1 ± 7.1 years) and 15 males (32.2 ± 6.3 years), were included. The mean arterial velocity in the middle cerebral artery (MCA) and the posterior cerebral artery (PCA) was measured by transcranial Doppler sonography before and after intravenous infusion of L-arginine, and CVR to L-arginine was then calculated. Results: CVR to L-arginine was significantly higher in PCA than in MCA in all subjects (19.2 ± 8.2 vs. 13.6 ± 7.1%, p ≤ 0.01). In addition, CVR to L-arginine was significantly more pronounced in females compared to males in PCA (22.7 ± 8.3 vs. 15.8 ± 6.7%, p ≤ 0.01) and MCA (16.8 ± 6.4 vs. 10.4 ± 6.4%, p < 0.05). Conclusions: Lower CVR to L-arginine and therefore lower cerebral endothelial function in the anterior cerebral circulation and in males might be related to the higher incidence of ischemia and stroke in the anterior cerebral circulation, particularly in males.