Recurrent ATP1A2 mutations in Portuguese families with familial hemiplegic migraine.

Familial hemiplegic migraine is a rare autosomal dominant subtype of migraine with aura. Three genes have been identified, all involved in ion transport. There is considerable clinical variation associated with FHM mutations. Genotype-phenotype correlation studies are needed, but are challenging mainly because the number of carriers of individual mutations is low. One exception is the recurrent T666M mutation in the FHM1 CACNA1A gene that was identified in almost one-third of FHM families and showed variable associated clinical features and severity, both within and among FHM families. Similar studies in the FHM2 ATP1A2 gene have not been performed because of the low number of carriers with individual mutations. Here we report on the recurrence of ATP1A2 mutations M731T and T376M that affect sodium-potassium pump functioning in two Portuguese FHM families. Considerably increasing the number of mutation carriers with these mutations indicated a clear genotype-phenotype correlation: both mutations are associated with pure FHM. In addition, we show that recurrent mutations for ATP1A2 are more frequent than previously thought, which has implications for genotype-phenotype correlations and genetic testing.

Cluster headache without autonomic symptoms: why is it different?

BACKGROUND: Some patients with otherwise typical cluster headache (CH) have persistent attacks free of cranial autonomic symptoms (CAS). The factors responsible for this atypical presentation are not known. OBJECTIVES: To identify factors associated to the absence of CAS in patients with CH. METHODS: A prospective series of 157 patients with the diagnosis of CH was analyzed, comparing 148 typical CH patients with 9 CH patients without CAS. RESULTS: Patients without CAS reported significantly less intense attacks (P = .003) when compared to those with CAS. There was also a tendency (not reaching statistical significance) for a higher frequency of females and chronic CH among those without CAS. Otherwise, there were no differences between the two groups (in age, duration of illness, follow-up time, attack duration or frequency, nor side or site of pain). A logistic regression analysis showed that only pain intensity could explain the difference between the two groups, since the other explanatory variables were also associated with different intensity of attacks. CONCLUSIONS: These results support the hypothesis that CH without cranial autonomic symptoms represents a milder form of CH.