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Background. Atypical HUS (aHUS) is thought to be caused by predisposing mutations in genes encoding complement (regulating) proteins, such as Factor H (CFH), Factor I (IF), membrane co-factor protein (MCP) and Factor B (FB), or by auto-antibodies against CFH (αFH) in combination with a homozygous polymorphic deletion of the genes encoding Complement Factor H-related 1 and 3 (ΔCFHR1/3). The clinical impact of this knowledge is high, as it might be a prognostic factor for the outcome of renal transplantations and kidney donations. Methods. Mutational screening, by means of PCR and DNA sequencing, is performed in the above-mentioned genes in a group of 72 aHUS patients. Also, the presence of αFH and ΔCFHR1/3 was tested in patients and controls. Results. In 23 patients, a genetic aberration in at least one gene or the presence of αFH was found. A heterozygous mutation was observed in CFH in nine patients, in IF in seven patients and in MCP in three patients. No mutations were observed in FB. Seven patients presented αFH, of whom five also carried ΔCFHR1/3. Three patients carried a combined mutation (two patients: IF and MCP; one patient: IF, αFH and ΔCFHR1/3). A significant difference between patients and controls was detected for the presence of all three associated polymorphisms in CFH. Conclusions. Genetic abnormalities or the presence of αFH were detected in 31.9% of the aHUS patients. Furthermore, bigenic mutations were present, indicating that routine DNA mutation analysis of all complement factors associated with aHUS is important.

In 20 patients with pure menstrual migraine either Estraderm TTS 50 patches (E) or placebo (P) patches were applied during three successive menstrual cycles, randomly allocated to the treatment sequences E-P-E or P-E-P. Clinical neurophysiological tests, contingent negative variation (CNV) and exteroceptive temporalis muscle suppression test (ETST) were performed before treatment. The predictive value of these tests regarding the efficacy of Estraderm TTS was studied. Neither the number, duration and severity of the migraine attacks, nor the consumption of analgesics and ergotamine differed significantly during Estraderm TTS and placebo treatment. The ETST was consistent with migraine in 35% (95% confidence interval 15.4 to 59.2) of the patients. The CNV in 55% (31.5 to 76.9), and both tests in 25% (8.7 to 49.1%). Regarding the prediction of the Estraderm TTS effect on the migraine attacks, the specificity of the ETST, CNV and the combination of ETST with CNV, calculated for the first two cycles, was respectively 81.8% (48.2 to 97.7), 45.5% (16.8 to 76.6) and 80% (28.4 to 99.5). For the last two cycles these values were respectively 75% (42.8 to 94.5), 50.0% (21.1 to 87.9) and 71.4% (29.0 to 96.3). The sensitivity of the tests was respectively 62.5% (24.5 to 91.5), 62.5% (24.5 to 91.5) and 66.7% (22.3 to 95.7) in the first 2 cycles. In the last 2 cycles 50.0% (15.1 to 84.3), 62.5% (24.5 to 91.5) and 60% (14.7 to 94.7). This study did not demonstrate an effectiveness of Estraderm TTS in perimenstrual migraine, except for the subgroup of perimenstrual migraine patients in whom the ETST test results were consistent with migraine.

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